The study aimed to explore the prognostic value of fear-avoidance beliefs (FABs) on

postoperative pain and back-specific function for patients with lumbar degenerative
disk disease (LDDD). FABs have been proven to be a predictorof pain and disability
for patients with low back pain. However, whether FABs are a predictor of surgical
outcomes for LDDD is a matter of debate. PubMed, Cochrane library, EMBASE, and
EBSCO were searched for eligible cohort studies or secondary analyses of randomized
controlled trials. Fixed-effect meta-analysis models were used to estimate odds
ratios (OR) because of absent or low heterogeneity (I-2 < 50%). Subgroup analyses
were conducted according to different follow-up durations. Forest plots were used
for graphical representation. Six studies with a total of 829 participants were
included in the meta-analyses. Risk of bias was high for three studies and moderate
for the other three studies. For patients with LDDD, meta-analyses showed that FABs
were a predictor of postoperative pain intensity [OR 2.88; 95% confidence interval
(CI), 2.76-3.00] and back-specific function (OR 3.13; 95% CI, 3.02-3.24). Patients
with FABs are less likely to report improvement in pain (OR 2.56; 95% CI, 1.73-
3.86) and function (OR 2.81; 95% CI, 2.57-3.07). In conclusion, FABs were a
predictor of postoperative pain and back-specific function for patients with LDDD.
This prognostic value is sustained for a long period after surgery (>12 months).
Clinicians are advised to initiate targeted interventions for patients with FABs at
different stages after surgery. Due to the limited number and low quality of
included studies, the results of this meta-analysis should be interpreted with
caution.
Cyberloafing is one of the areas that researchers have been following with interest
and has been extensively studied with its causes and results. In the studies
conducted, it has been argued that personality is one of the factors affecting
cyberloafing and in these studies personality is generally discussed in terms of
five factor personality traits. Although the growing body of research about the
relationship among cyberloafing and personality traits, many important questions
remain unanswered. In particular, it is still unclear whether FoMO is related to
cyberloafing, and what the mechanism behind the cyberloafing-personality traits
link is. The present study addresses this gap by examining the mediator role of
fear of missing out (FoMO) on the relationship between cyberloafing and personality
traits within the context of need to belong thory and social comparison theory. To
this end, suvey data, collected from 443 employees working in state-owned banks and
private banks, was used to test hypotheses. Results showed that FoMO mediates the
negative relationship between conscientiousness and cyberloafing. Furthermore, it
was found that FoMO is negatively associated with cyberloafing.
Background and objectives: Panic disorder is defined by recurring and unexpected
panic attacks, accompanied by anticipatory anxiety about future attacks and their
consequences. This generally involves avoiding situations and behaviors that can
produce panic attacks (American Psychiatric Association [APA], 2013). Among anxiety
dis-orders, panic disorder is associated with some of the greatest burdens in terms
of personal suffering, occupational disability, and societal cost. The objective of
this article is to systematically identify and review the empirical literature on
emotional management processes and strategies associated with panic disorder, with
the aim of evaluating their role in the development and maintenance of panic
disorder, in order to better understand the pathogenesis of the disorder and guide
clinicians to improve their current treatments.Methods: Four databases were
searched for studies which were based on self-reported questionnaires or a
methodology based on an experimental procedure.Results: Of the 1719 articles
identified, 61 referred to different aspects of emotional management. People living
with PD are characterized by low emotional intelligence levels, excessive use of
suppression, impaired cognitive reappraisal, high levels of alexithymia and
maladaptive coping strategies.Limitations: Most of the reviewed studies used
measures of emotional management in cross-sectional models and were based on self-
assessment reports.Conclusions: Improving emotional intelligence levels is key to
increasing emotion regulation flexibility for people living with PD. Automatic
cognitive reappraisal impairment in these people indicates low importance of
cognitive restructuring in psychotherapeutic treatment.
Objectives: The aim of this study was to explore the impact of the 2020-2022
pandemic on the levels of fear and anxiety in pregnant women and to identify risk
and protective factors.Methods: A systematic review was conducted. Electronic
databases were consulted for studies published between January 2020 and August
2022. The methodological quality was assessed using a critical appraisal tool for
non-randomised studies.Results: Seventeen studies were included in the review. A
high prevalence of levels of fear and anxiety were observed. Risk factors such as
unplanned pregnancy, poor support from partners, or intolerance of uncertainty were
identified for high levels of fear. Regarding anxiety, risk factors such as
maternal age, social support, financial status, or concern about being able to
maintain antenatal follow-ups were identified.Conclusion: The COVID-19 pandemic had
a significant impact on the mental health of pregnant women through increased
levels of fear and anxiety. It has not been possible to establish a relationship
between significant factors such as gestational age or health emergency control
measures with high levels of fear or anxiety.
Aim. The aim of this review is to find out what levels of anxiety and fear have
been shown by nurses during the COVID-19 pandemic. Background. Health security
crises affect not only physical health but also the mental health and wellbeing of
healthcare professionals due to a higher level of exposure. Evaluation. A
systematic review was carried out following the PRISMA statement. Methodological
quality was assessed using the Joanna Briggs Institute critical appraisal tools.
The literature search was carried out in the PubMed, Scopus, and Web of Science
(WoS) electronic databases based on the keywords that the research question yielded
following the PECOT strategy. For the selection of articles, original articles,
meta-analyses, systematic reviews, short communication articles, and case reports
were included. Then, a series of inclusion and exclusion criteria were applied,
screening the results to obtain a total of 18 articles, which were used to
elaborate the study. Key Issues. Fear and anxiety levels were described in a total
of 18 selected studies. The main fear-related concerns of the nurses were
associated with the fear of infecting their family or friends and the fear of the
death of a family member or friend. Conclusions. The main psychological impact on
nurses during the COVID-19 pandemic was related to fear, anxiety, stress, and
depression. Fear of infecting family members or of being infected were the main
impacts perceived by nurses. Implications for Nursing Management. In general, high
scores were found for levels of fear and anxiety, although the figures varied by
country and time of data collection. Resilience was considered the main tool for
coping with the loss and trauma experienced by nurses.
Objectives This systematic review was to compare the effects of interventions for
the management of fear and anxiety for dental treatments. Methods This research
project was applied to PubMed, CENTRAL, Web of Science, Cochrane library databases.
The last search was run on March 31st, 2021. A list of references of relevant
articles and previous reviews were checked. Qualitative and quantitative analyses
were performed. Results A total of 20 eligible randomized controlled trials were
included, and 969 participations in experimental group and 892 participations in
the control group were involved. Anxiety levels decreased more in intervention
groups than in control groups (Z = 3.47, P = 0.0005, SMD = - 0.62, 95% CI - 0.98 to
- 0.27). For adults, there was statistical difference between experimental and
control groups [Z = 2.14, P = 0.03, 95% CI - 0.54 (- 1.03, - 0.04)], while there
was not no such statistical difference in children and adolescents [Z = 1.62, P =
0.11, 95% CI - 0.60 (- 1.32, 0.13)]. Patients experienced a significant decrease in
anxiety level using sedation drugs [Z = 2.44, P = 0.01, 95% CI - 0.61 (- 1.10, -
0.12)] and audio-visual distractions [Z = 3.1, P = 0.002, 95% CI - 0.86 (- 1.40, -
0.32)]. For the informative intervention groups, patients did not show significant
difference than control groups [Z = 1.22, P = 0.22, 95% CI - 0.55 (- 1.43, 0. 33)].
There was no statistical difference in vital signs [Z = 1.39, P = 0.16, 95% CI -
0.25 (- 0.61, 0.10)] and pain levels [Z = 0.69, P = 0.49; SMD = - 0.06, 95% CI
(0.27, 0.11)] between intervention and control groups. Conclusions Interventions
should be used in managing anxiety and fear for dental treatment. It might be
effective for anxiety alleviating for adults, but there was a low certainty of
evidence that interventions could reduce anxiety level in children and adolescents.
Sedation drugs and audio-visual distractions might be useful for managing dental
fear and anxiety. Pain levels and vital signs could not be improved form our study.
High-quality randomized clinical trials are required for further study.
The current narrative review summarizes and examines several theories of panic
disorder (PD) including biological theories, encompassing neurochemical factors,
metabolic and genetic theories, respiratory and hyperventilation theories and
cognitive theory. Biological theories have informed the development of
psychopharmacological treatments; however, they may be limited in their utility
given the efficacy of psychological treatments. In particular, behavioral and, more
recently, cognitive models have garnered support due to the efficacy of cognitive-
behavior therapy (CBT) in treating PD. The role of combination treatments has been
found to be superior in the treatment of PD in particular cases, lending support
for the need for an integrated approach and model for PD given that the etiology of
PD is complex and multifactorial.
Aims To evaluate the effectiveness of virtual reality (VR) intervention in the
management of pain, anxiety and fear in paediatric patients undergoing needle-
related procedures. Design A systematic review and meta-analysis of randomized
controlled trials (RCTs). Data sources A librarian-designed search of the Cochrane
Library, PubMed, Web of Science, EMBASE, CINAHL, CBM, CNKI, and Wanfang databases
was conducted to identify research articles in English or Chinese on RCTs up to
February 28, 2022. Review methods Two researchers independently screened eligible
articles. The Cochrane Handbook for Systematic Reviews was used to assess the risk
of bias in the included studies. A fixed- or random-effects meta-analysis model was
used to determine the pooled mean difference based on the results of the
heterogeneity test. Results A total of 2269 articles were initially screened. The
meta-analysis included data from 27 studies representing 2224 participants.
Compared with the non-VR group, the VR intervention group significantly reduced
pain, anxiety, and fear in paediatric patients who underwent puncture-related
procedures. Subgroup analysis showed that VR has advantages over conventional and
other distraction methods. Conclusion Paediatric patients undergoing needle-related
procedures would benefit from VR interventions for pain, anxiety and fear
management. Impact VR intervention has the potential to reduce pain, anxiety and
fear in paediatric patients undergoing puncture-related procedures. Future clinical
interventions could incorporate VR into puncture procedures as an effective method
to reduce negative emotions in children eligible for VR distractions. Patient or
Public Contribution Our paper is a systematic review and meta-analysis and such
details don't apply to our work.
COVID-19 is the latest pandemic form and, as usual, it also opened gates for new
avenues in consumer behavior research. Panic buying among consumers due to the
current pandemic is the focus of this study. This study adopts a bibliometric
approach to analyze the studies published in the last three years (2020-2022)
(obviously, there is no research before 2020). Seventy-nine studies are included
based on the Web of Science database. First, a general analysis is conducted to
understand the current state of research by mapping countries, authors, publication
outlets, citations, institutions, etc. It provides the association or linkage of
the mentioned variables related to the mentioned studies. Second, insights and
recommendations are provided based on specific keyword analysis and deep diving.
The findings indicate that panic-buying behavior is a fact during COVID-19,
especially in the first year, and specific factors were responsible for the same.
In the second year, it ebbed substantially. This study provides recommendations for
practitioners to deal with panic buying behaviors in future pandemics.
Objective To consolidate the evidence on the effect of physical exercise on fear of
falling in individuals with stroke. Data Sources PubMed, CINAHL, Cochrane Database
and MEDLINE Methods An extensive database search was conducted to identify the
randomised controlled trials that examined the effect of physical exercise on fear
of falling post-stroke. Grading of Recommendation, Assessment, Development and
Evaluation (GRADE) was used to assess the quality of evidence for each meta-
analysis. Results Fourteen trials totalling 1211 participants were included in this
review. Thirteen of these (1180 participants) were included in the meta-analyses.
In the primary analysis, very low-quality evidence suggested that exercise reduced
fear of falling post-stroke (standardized mean difference (SMD) 0.48; 95%
confidence interval (CI) 0.23 to 0.72). The effect was diminished at three- to six-
month follow-up after exercise training ended (SMD -0.09; 95% CI -0.27 to 0.10;
high-quality evidence). In the sensitivity analyses, the treatment effect was more
pronounced in individuals with a lower baseline Berg balance score (BBS <= 45; SMD
0.53; 95%CI 0.17 to 0.88) and for those trials with exercise frequency of >= 3
sessions per week (SMD 0.70; 95%CI 0.39 to 1.01). Compared with circuit-based
training consisting of a combination of walking, balance and strengthening
exercises (SMD 0.27; 95% CI -0.09 to 0.63), walking programmes seemed to generate a
larger effect on fear of falling (SMD 1.06; 95%CI 0.43 to 1.70). Conclusion
Physical exercise was beneficial for reducing fear of falling in individuals with
stroke, particularly those with poorer balance ability.
BackgroundFear of falling (FoF) affects a large number of older people, whether
they have a history of falls or not. This has an impact on their lives. FoF is a
potentially modifiable factor, which has been identified as one of the most
important threats to older people's autonomy. ObjectivesTo gain a comprehensive
understanding of the phenomenon, we conducted a systematic review and meta-summary.
The available evidence from qualitative research exploring how people experience
FoF and how FoF affects daily living was aggregated. MethodsWe followed the
approach by Sandelowski and Barroso (2007) as a method to aggregate knowledge based
on an exhaustive literature search. We searched the databases CINAHL, MEDLINE,
PsycINFO and SSCI systematically for relevant articles as well as grey literature
until September 2020. Out of the included studies, findings were extracted, edited,
grouped and abstracted into meta-findings. Finally, the manifest frequency effect
size of each abstracted meta-finding was calculated. ResultsOut of 2978 identified
studies, 15 met our inclusion criteria, which were published between 1993 and 2017
and included a total of 276 participants. We extracted 578 findings, and the
abstraction process resulted in 183 meta-findings. We identified three main topics:
'Triggers and reasons for FoF identified by affected people', 'Consequences
attributed to FoF' and 'Strategies to manage FoF in daily life'. ConclusionOur
findings demonstrate that FoF has a far-reaching impact on the lives of those
affected. With the aggregation of the existing qualitative data with the
application of the frequency effect size, we were able to identify three areas of
particular importance to those affected: (1) controlling the risk, (2) creating a
safe environment and (3) staying independent. Implications for practice these three
areas of particular importance to those affected should be taken into account when
revisiting or creating new interventions to prevent or reduce FoF.
Introduction Fears of relapse in people diagnosed with schizophrenia have long been
recognised as an impediment to recovery and wellbeing. However, the extent of the
empirical basis for the fear of relapse concept is unclear. A systematic review is
required to collate available evidence and define future research directions.
Methods A pre-registered systematic search (PROSPERO CRD42020196964) of four
databases (PubMED, MEDLINE-Ovid, PsycINFO-Ovid, and Cochrane Central Register of
Controlled Trials) was conducted from their inception to 05/04/2021. Results We
found nine eligible studies. Five were quantitative (4 descriptive and 1 randomised
controlled trial), and four were qualitative. The available quantitative evidence
suggests that fear of relapse may have concurrent positive relationships with
depression (r = 0.72) and suicide ideation (r = 0.48), and negative relationship
with self-esteem (r = 0.67). Qualitative synthesis suggests that fear of relapse is
a complex phenomenon with behavioural and emotional components which has both
direct and indirect effects on wellbeing. Conclusions Evidence in this area is
limited and research with explicit service user and carer involvement is urgently
needed to develop new and/or refine existing measurement tools, and to measure
wellbeing rather than psychopathology. Nonetheless, clinicians should be aware that
fear of relapse exists and appears to be positively associated with depression and
suicide ideation, and negatively associated with self-esteem. Fear of relapse can
include fears of losing personal autonomy and/or social/occupational functioning.
It appears to impact carers as well as those diagnosed with schizophrenia.
The purpose of this review was to explore the correlation between patients' fear of
cancer recurrence (KR) and radiotherapy. National Knowledge Infrastructure, Wanfang
Database, China Science and Technology Journal Database, SinoMed, PubMed, Web of
Science, EBSCO-CINAHL, Cochrane Library, and Ovid Embase were searched to identify
relevant studies. Thirty-five eligible studies were included in the systematic
review, and 22 of them were included in further meta-analysis. The results of the
meta-analysis showed that the level of patients' FCR was positively correlated with
radiotherapy, but the correlation was weak (overall r = 0.075; 95% confidence
interval [CI], 0.046-0.103; P = .000). In terms of subgroup analysis based on
cancer site (breast cancer vs other types of cancer), the breast cancer group (r =
0.086; 95% CI, 0.027-0.143; P= .004), the mixed-type group (r = 0.073; 95% CI,
0.033-0.112; P = .000), and the other-type group (r = 0.071; 95% CI, 0.015-0.126; P
= .013) have a positive correlation with radiotherapy. Patients' FCR positively
correlated with the receipt of radiotherapy. However, because of the variability
among the studies, the results have limitations. Therefore, longitudinal studies
are needed to verify the trajectory of FCR over radiation therapy.
Background: This study investigated the lifetime suicide attempt and ideation rates
among patients with panic disorder (PD). Methods: Online databases regarding
lifetime suicide attempt and ideation rates in patients with PD were searched up to
May 2021. Results: The suicide attempt and ideation rates were 0.17 (95% CI: 0.16,
0.18) and 0.23 (95% CI: 0.22, 0.25). The suicide attempt rates among female and
male patients were 0.17 (95% CI: 0.14, 0.20) and 0.15 (95% CI: 0.12, 0.19). When PD
was comorbid with anxiety, depression, substance abuse, and personality disorders,
the suicide attempt rates increased to 0.23 (95% CI: 0.20, 0.26), 0.23 (95% CI:
0.18, 0.27), 0.25 (95% CI: 0.20, 0.31), and 0.25 (95% CI: 0.23, 0.28),
respectively. Limitations: The suicide attempt and ideation by age, suicide
ideation by sex, and suicide ideation by comorbidity with other mental disorders
were passed in our meta-analysis as sample size was small. Stratification analysis
on ethnicity, marital status, education levels, resident location, and severity of
PD should be considered in the future. Conclusion: The lifetime suicide ideation
and attempt rates in patients with PD were higher than general populations but
lower than patients with bipolar or depression. The lifetime suicide attempt rate
in female patients was slightly higher than male patients. When PD was comorbid
with one other mental illness, the lifetime suicide attempt rate increased by about
50%.
Objective: To remove the phobic psychological situation of Chinese college students
who were in school lockdowns during the COVID-19 outbreak, and to provide a
theoretical basis for college student psychological intervention.Methods: Online
survey conducted from December 9, 2021, to December 11, 2021. The seven-item Fcv-
19s was employed to assess fear of COVID-19 on a Likert five-point scale.
Categorical data were reported as number and percentage, whereas continuous data
were reported as mean +/- standard deviation. Multivariate logistic regres-sion
models were used to assess the association between different factors and anxiety
symptoms.Results: The study population consisted of 26.02% (268) male and 73.98%
(762) female, of whom approximately 84% were undergraduates. The overall mean score
of the questionnaire was 16.04 +/- 5.28. Significantly more study populations
reported high levels of fear (54.8%), while age, cost of life, professional
category, education background (P < 0.05) revealed significant differences based on
fear levels.Conclusions: More than half of the Chinese college students developed
fear symptoms during the COVID-19 epidemic. Appropriate psychological interventions
for college students should be implemented promptly to reduce the psychological
harm induced by the COVID-19 epidemic.
Problem: Fear of hypoglycemia is a significant concern for parents of children/
adolescents with type 1 diabetes. Although some studies have explained the parental
fear of hypoglycemia, the related factors were yet to be determined. This
systematic review aims to identify the related factors of fear of hypoglycemia in
the parents of children and adolescents with type 1 diabetes and provide a
theoretical basis for further intervention. Eligibility criteria: PubMed, MEDLINE,
EMBASE, Scopus, CINAHL, EBSCO, Web of Science, and Cochrane Library were
systematically searched from 2010 to 2021. Studies evaluating the fear of
hypoglycemia of parents and its associated factors were included. Sample: Twenty-
three observational articles met the criteria. Results: Significant associations
were found between fear of hypoglycemia and specific factors, including motherhood,
nocturnal hypoglycemia, and the number of blood glucose monitoring. Psychological
factors, including anxiety, depression, pediatric parenting stress, mindfulness,
self-efficacy, quality of life, and sleep disorders, were conclusive and
associations with parental fear of hypoglycemia. Conclusions: Understanding
parental fear of hypoglycemia can help parents prevent potential problems in
diabetes management, thus promoting children's growth. According to current
evidence, effective targeted interventions based on modifiable relevant factors can
be developed to reduce the fear of hypoglycemia in parents while maintaining
optimal blood glucose control in children/ adolescents. Implications: Health
professionals should pay more attention to the mental health of parents, and
parents should be involved in the care plan and have the opportunity to discuss
their fear of hypoglycemia in the most appropriate way to manage type 1 diabetes.
(c) 2022 Elsevier Inc. All rights reserved.
Background. Cognitive-behavioral therapy (CBT) is commonly adopted in pain
management programs for patients with chronic low back pain (CLBP). However, the
benefits of CBT are still unclear. Objectives. This review investigated the
effectiveness of CBT on pain, disability, fear avoidance, and self-efficacy in
patients with CLBP. Methods. Databases including PubMed, EMBASE, Web of Science,
Cochrane Library, and PsycINFO were searched. RCTs examining the effects of CBT in
adults with CLBP were included. The data about the outcome of pain, disability,
fear avoidance, and self-efficacy were retained. Subgroup analysis about the
effects of CBT on posttreatment was conducted according to CBT versus control
groups (waiting list/usual care, active therapy) and concurrent CBT versus CBT
alone. A random-effects model was used, and statistical heterogeneity was explored.
Results. 22 articles were included. The results indicated that CBT was superior to
other therapies in improving disability (SMD -0.44, 95% CI -0.71 to -0.17, P <
0.05), pain (SMD -0.32, 95% CI -0.57 to -0.06, P < 0.05), fear avoidance (SMD -
1.24, 95% CI -2.25 to -0.23, P < 0.05), and self-efficacy (SMD 0.27, 95% CI 0.15 to
0.40, P < 0.05) after intervention. No different effect was observed between CBT
and other therapies in all the follow-up terms. Subgroup analysis suggested that
CBT in conjunction with other interventions was in favor of other interventions
alone to reduce pain and disability (P < 0.05). Conclusion. CBT is beneficial in
patients with CLBP for improving pain, disability, fear avoidance, and self-
efficacy in CLBP patients. Further study is recommended to investigate the long-
term benefits of CBT. This meta-analysis is registered with Prospero (registration
number CRD42021224837).
Objective Even though 32%-83% for fear of falling (FoF) in patients with stroke,
very little is known about the predictors of the problems. Therefore, we
systematically reviewed the literature on risk factors for FoF in patients with
stroke. Design A systematic review and meta-analysis Data sources PubMed, Embase,
Cochrane Library database, Web of Science, CINAHL, PsycINFO, Grey literature and
other relevant databases for related publications were searched (from inception to
17 July 2021). Results Eight studies involving 1597 participants were selected to
analyse risk factors for patients with stroke with FoF. The quality of all included
studies was assessed and categorised as medium or high quality. Review Manager
V.5.3 merged the OR value and 95% CI of the potential risk factors. Meta-regression
and Egger's test were performed by Stata V.15.1. The risk factors for FoF in
patients with stroke were women (OR=2.13, 95% CI 1.47 to 3.09), impaired balance
ability (OR=5.54; 95% CI 3.48 to 8.81), lower mobility (OR=1.12; 95% CI 1.05 to
1.19), history of falls (OR=2.33; 95% CI 1.54 to 3.53) and walking aid (OR=1.98;
95% CI 1.37 to 2.88), anxiety (OR=2.29; 95% CI 1.43 to 3.67), depression (OR=1.80;
95% CI 1.22 to 2.67), poor lower limb motor function (OR=1.14; 95% CI 1.00 to 1.29)
and physically inactiveness (OR=2.04; 95% CI 1.01 to 4.12). Measurement of
heterogeneity between studies was high for all outcomes (I-2=0%-93%), indicating
that the substantial interstudy heterogeneity in estimated proportions was not
attributed to the sampling error. Sensitivity analysis (leave-one-out method)
showed that the pooled estimate was stable. Conclusion This meta-analysis indicated
that female population, impaired balance ability, lower mobility, history of falls
and walking aid in patients with stroke might be at greater risk for FoF. Future
studies are recommended to determine other risk factors specific to patients with
stroke.
Background: Currently, evidence regarding fear avoidance beliefs as potential
predictors for lumbar surgery outcomes seems insufficient and strong conclusions
are not yet available. Objective: This systematic review aimed to evaluate the
predictive value of preoperative fear avoidance beliefs for postoperative pain
intensity, functional status, and health-related quality of life following surgery
for lumbar degenerative disease. Study Design: Systematic review and best evidence
synthesis. Methods: An extensive search was performed in PubMed/Medline, EMBASE,
PsycINFO, CINAHL and the Cochrane library for articles published up until October
2021. Two independent reviewers performed the screening, data extraction, and
quality assessment, with a third independent reviewer consulting to resolve any
disagreement. Observational studies that included patients undergoing surgery for
lumbar degenerative disease, as well as evaluated fear avoidance beliefs (i.e.,
pain-related fear, pain catastrophizing, pain anxiety) in relation to a surgical
outcome measure (i.e., pain intensity, functional status and health-related quality
of life) were included in the review. The CHARMS-and QUIPS-tools were used for data
extraction and quality assessment, respectively. A best evidence synthesis was
performed resulting in conclusions regarding strong, moderate, conflicting, and
limited levels of evidence. Results: A total of 24 studies (n = 17,881) were
included in this review. Following best evidence synthesis, 3 included studies
reported no significant predictive value of preoperative pain-related fear for
postoperative pain intensity resulting in moderate evidence for this relationship.
Moderate evidence was also found indicating no significant predictive value of
preoperative pain-related fear for postoperative functional status, as 6 out of 8
relevant studies reported this result. Only one study reported on the predictive
value of preoperative pain catastrophizing for postoperative health -related
quality of life, resulting in limited evidence for the absence of this predictive
relationship. All other relationships were found to have conflicting evidence.
Limitations: To evaluate surgical outcome, only patient-reported outcome measures
as used by spine registries were included. Thus, our findings cannot be
extrapolated to all surgery outcomes following lumbar degenerative disease and
should only be interpreted in relation to postoperative pain intensity, functional
status, or health-related quality of life. Conclusion: Best evidence synthesis
showed moderate evidence indicating that preoperative pain-related fear is not a
significant predictor for postoperative pain and function following surgery for
lumbar degenerative disease. Additionally, limited evidence was found for a lack of
predictive value of preoperative pain catastrophizing for postoperative health-
related quality of life. As current evidence regarding the predictive value of
preoperative fear avoidance beliefs following such a surgery is mixed, further
research is required before more definitive conclusions can be made.
In the early stages of the COVID-19 pandemic, the public has been experiencing
severe stress and feelings of anxiety. Social media in particular has been shown in
the literature to be a major contributing medium for the widespread distribution of
misinformation concerning COVID-19. The rapid dissemination of fake news concerning
supply shortages of certain essential items has increased pandemic-related
behaviours such as panic buying. Factors that have led to panic buying include:
perceived threat of an event, perceived product scarcity, fear of the unknown, and
coping methods to gain control. Although these factors are prevalent reasons that
induce panic buying behaviours, they do not explain the mechanisms of perception
formation. It is possible that heuristics (i.e. availability, and affect), which
are reinforced by social media posts, aid in the development of the illusory truth
effect. This psychological phenomenon may be the root cause of the public's false
perceptions of pandemic-related events. This paper reviews the impact of the
illusory truth effect as a mediator in processing misinformation from social media
and the news as truths that inevitably encourages panic buying behaviour.
Furthermore, this paper examines the persistence of the illusory truth effect due
to herd mentality and confirmation bias in the perpetual cycle of irrational
decision making. In conclusion, the illusory truth effect has been demonstrated to
be a key cognitive bias that strengthens with repetitive exposure to adverse
sentiments related to COVID-19, and is likely to be maintained through herd
mentality and confirmation bias in social situations. Although more research must
be conducted to solidify this theory, the current review aims to serve as a basis
for further research on the illusory truth effect and potentiate solutions in the
prevention of adherence to this effect.
This report investigated the effectiveness of non-pharmacological interventions for
reducing dental fear and anxiety in patients undergoing third molar extraction
under local anesthesia. In November 2020, multiple electronic databases (Cochrane,
EMBASE, MEDLINE, PsycInfo, PsycArticles, PubMed, and Web of Science) were searched
for articles published in English. Inclusion criteria were randomized-controlled
trials reporting the effectiveness of any non-pharmacological interventions in
reducing fear or anxiety levels in patients with third molar extraction. A total of
3015 studies by electronic search and 2 studies by hand search were identified.
After screening, 21 studies were eligible for systematic review. Seven studies were
included in the meta-analysis. Study selection, data extraction, and quality
assessment of the included studies were performed by two independent investigators.
The anxiety levels after intervention in each study were pooled and meta-analyzed
by the random-effect model. A significant reduction in anxiety level was observed
in non-pharmacological intervention groups (SMD = -0.32; 95% CI -0.57 to -0.07; p =
0.01). Subgroup analyses showed that a significant anxiety reduction by non-
pharmacological interventions could be demonstrated by pooled data from studies
using psychometric assessments, but not from studies using physiological
assessments. Non-pharmacological interventions appear to reduce fear and anxiety
levels in patients undergoing third molar extraction under local anesthesia.
Anxiety and trauma-related disorders, such as post-traumatic stress disorder
(PTSD), are debilitating mental illnesses with great personal and socioeconomic
costs. Examining memory formation and relevant behavioural responding associated
with aversive stimuli may improve our understanding of the neurobiology underlying
fear memory processing and PTSD treatment. The neurocircuitry underpinning learned
fear and its inhibition through extinction is complex, involving synergistic
interactions between different neurotransmitter systems in inter-connected brain
areas. Endocannabinoid and noradrenergic transmission have both been implicated
separately in fear memory processing and PTSD, but potential interactions between
these systems in relation to fear extinction have received little attention to
date. Their receptors are expressed together in brain areas crucial for fear
extinction, which is enhanced by both cannabinoid and noradrenergic receptor
activation in these areas. Moreover, cannabinoid signalling modulates the activity
of locus coeruleus noradrenaline (NA) neurons and the release of NA in the medial
prefrontal cortex, a brain area that is crucial for fear extinction. Interestingly,
endocannabinoid-noradrenergic system interactions have been shown to regulate the
encoding and retrieval of fear memory. Thus, noradrenergic regulation of fear
extinction may also be driven indirectly in part via cannabinoid receptor
signalling. In this perspective paper, we collate the available relevant literature
and propose a synergistic role for the endocannabinoid and noradrenergic systems in
regulating fear extinction, the study of which may further our understanding of the
neurobiological substrates of PTSD and its treatment.
Background: Needle-related pain, fear, and anxiety can be a deterrent to treatments
in children and adolescents. Virtual reality (VR) can be used to manage the poor
experience of needle procedures. Objective: This meta-analysis aimed to examine the
effects of VR on pain, fear, and anxiety related to needle procedures in children
and adolescents. Methods: PubMed, EMBASE, and the Cochrane Library were searched
for potentially eligible studies published up to June 2021. The outcomes were pain
assessed by the Wong-Baker Faces Pain Scale (WBS) or Faces Pain Scale-Revised (FPS-
R), and Visual Analog Scale (VAS), fear assessed by Children's Fear Scale (CFS),
and anxiety assessed by Children's Anxiety Meter (CAM), VAS, or CFS. Because of
expected heterogeneity among studies, all analyses were conducted using the random-
effects model. Results: Ten studies were included (571 children in the VR group and
575 in the control group). Based on the WBS, VR reduced pain, either self-reported
(WMD = -2.17, 95%CI: -3.37, -0.97), parent-reported (WMD = -3.52, 95%CI: -4.62, -
2.42), nurse-reported (WMD = -3.29, 95%CI: -5.59, -0.99), and
physician/investigator-reported (WMD = -3.48, 95%CI: -5.93, -1.04). Using the FPS-
R, VR reduced needle-related pain compared with controls (WMD = -0.85, 95%CI: -
1.64, -0.06). Similar results were observed for fear (children/adolescents: WMD = -
1.52, 95%CI: -2.18, -0.86; parents: WMD = -1.71, 95%CI: -2.30, -1.13; nurses: WMD =
-1.55, 95%CI: -2.47, -0.63; physicians/investigators: WMD = -0.59, 95%CI: -1.00, -
0.18) and anxiety (self-reported: WMD = -2.79, 95%CI: -4.07, -1.54; parent-
reported: WMD = -3.87, 95%CI: -5.58, -2.15; nurse-reported: WMD = -4.64, 95%CI: -
6.56, -2.71; physician/investigator-reported: WMD = -2.06, 95%CI: -4.13, -0.00).
Conclusion: A VR-based intervention could reduce needle-related pain, fear, and
anxiety in children and adolescents.
Background: Mental health issue among college students is routinely a major public
health concern, and coronavirus disease 2019 (COVID-19) pandemic may have
exacerbated the students' mental health issues which include psychological
distress, panic disorder, insomnia, and posttraumatic stress symptoms. However, few
studies reached a consensus on the impact of COVID-19 fear on mental health among
college students. Therefore, we aimed to conduct a systematic review and meta-
analysis that quantitatively synthesized the fear among college students during the
COVID-19 pandemic. Methods: PubMed, EMBASE, CINAHL, and PsycINFO electronic
databases were systematically searched to identify cross-sectional study reporting
the state of COVID-19 fear examined by the Fear of COVID-19 Scale (FCV-19S)
published up until November 20, 2021. Methodological quality was complied with the
evaluation criteria of the Agency for Healthcare Research and Quality. The random
effects model was employed to estimate the pooled mean of FCV-19S score. Subgroup
analysis and meta-regression analysis were also conducted. Publication bias was
assessed by Begg's test and funnel plot. Results: A total of 16 studies with a
sample size of 11,872 were included. A pooled mean of FCV-19S score was 17.60 [95%
confidence interval (CI): 16.41-18.78]. The mean of COVID-19 fear in women (17.11,
95% CI: 16.59-17.64) was higher than that in men (15.21, 95% CI: 14.33-16.08). The
highest and lowest pooled means of FCV-19S score were observed in the studies
conducted in multiple countries that include Israel, Russian, and Belarus (21.55,
95% CI: 20.77-22.33) and in Europe (16.52, 95% CI: 15.26-17.77), respectively. No
significant publication bias was detected by Begg's test. Conclusions: College
students experienced a moderate level of fear caused by COVID-19 pandemic. It is
necessary to design and implement prevention programs that target the mental health
of college students.
Purpose of review Dysfunction of fear memory systems underlie a cluster of
clinically important and highly prevalent psychological morbidities seen in
perioperative and critical care patients, most archetypally posttraumatic stress
disorder (PTSD). Several sedative-hypnotics and analgesics are known to modulate
fear systems, and it is theoretically plausible that clinical decisions of the
anesthesiologist could impact psychological outcomes. This review aims to provide a
focused synthesis of relevant literature from multiple fields of research. Recent
findings There is evidence in some contexts that unconscious fear memory systems
are less sensitive to anesthetics than are conscious memory systems. Opiates may
suppress the activation of fear systems and have benefit in the prevention of PTSD
following trauma. There is inconsistent evidence that the use of propofol and
benzodiazepines for sedation following trauma may potentiate the development of
PTSD relative to other drugs. The benefits of ketamine seen in the treatment of
major depression are not clearly replicated in PTSD-cluster psychopathologies, and
its effects on fear processes are complex. There are multiple theoretical
mechanisms by which anesthetic drugs can modulate fear systems and clinically
important fear-based psychopathologies. The current state of research provides some
evidence to support further hypothesis investigation. However, the absence of
effectiveness studies and the inconsistent signals from smaller studies provide
insufficient evidence to currently offer firm clinical guidance.
Healthy brain functioning in mammals requires a continuous fine-tuning of gene
expression. Accumulating evidence over the last three decades demonstrates that
epigenetic mechanisms and dynamic changes in chromatin organization are critical
components during the control of gene transcription in neural cells. Recent genome-
wide analyses show that the regulation of brain genes requires the contribution of
both promoter and long-distance enhancer elements, which must functionally interact
with upregulated gene expression in response to physiological cues. Hence, a deep
comprehension of the mechanisms mediating these enhancer-promoter interactions
(EPIs) is critical if we are to understand the processes associated with learning,
memory and recall. Moreover, the onset and progression of several neurodegenerative
diseases and neurological alterations are found to be strongly associated with
changes in the components that support and/or modulate the dynamics of these EPIs.
Here, we overview relevant discoveries in the field supporting the role of the
chromatin organization and of specific epigenetic mechanisms during the control of
gene transcription in neural cells from healthy mice subjected to the fear
conditioning paradigm, a relevant model to study memory ensemble. Additionally,
special consideration is dedicated to revising recent results generated by
investigators working with animal models and human postmortem brain tissue to
address how changes in the epigenome and chromatin architecture contribute to
transcriptional dysregulation in Alzheimer's disease, a widely studied
neurodegenerative disease. We also discuss recent developments of potential new
therapeutic strategies involving epigenetic editing and small chromatin-modifying
molecules (or epidrugs).
(Non-)selective non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used
for musculoskeletal related pain. These cheap and easily accessible drugs may be of
great value for hemophilia patients in developing countries and countries with a
high rate of opioid poisoning, but also in developed countries due to potential
joint protective effects. However, fear for adverse bleeding and cardiovascular
events during the use of these drugs restrains prescription within this population.
To give a complete overview of all publications reporting on safety, a systematic
search till March 2021 was performed. All studies were reviewed and critically
appraised and this resulted in 19 studies eligible for inclusion. Most studies with
(non-)selective NSAIDs showed no evident risk for relevant adverse bleeding or
cardiovascular events. However, some studies had a high risk of bias and studies
reporting on cardiovascular events were limited. Future studies with longitudinal
follow-up in well-defined large patient populations, including older patients,
focusing on both adverse bleeding and cardiovascular events are required to confirm
the alleged safe use.
For 23 years, Charles V "The Wise" of France suffered from a mysterious fistula on
his left arm that continuously drained pus. For all this time, he believed that as
soon as the fistula ceased to weep, he would have a mere 15 days before death
followed. His death in 1380, at the young age of 42, seemingly proved this
assumption correct. This paper explores the possible explanations from arsenic
poisoning at the hands of his longtime nemesis Charles II, as many of his
contemporaries believed, to an undiagnosed case of hidradenitis suppurativa, to an
underlying tuberculosis infection, to the possibility that his condition was
entirely self-inflicted. While it is impossible to determine a definitive cause, it
is highly unlikely that Charles II "The Bad" of Navarre had anything to do with his
rival's strange condition.
In a matter of mere months, humanity was unexpectedly struck by the appearance of
SARS-CoV-2, shifting our perception as medical practitioners regarding our day-to-
day activity. One especially disconcerting change was patient addressability to
medical facilities, as well as access to proper healthcare in various fields. As
these changes occurred rapidly, dermatologists too had to adapt by means of
teledermatology, giving us back the ability to reach, treat, and comfort our
patients. Among the individuals requiring special dermatological attention are
those suffering from psoriasis, especially considering that the biological
therapies employed in treating this debilitating disease become questionable in the
circumstance of the current pandemic. As more evidence surfaces concerning the
pathophysiology of SARS-CoV-2, we become closer to understanding which therapies
may interfere with its clearance, and which are actually safe to use. This review
aims to answer the question, are biological therapies warranted in the treatment of
psoriasis during the COVID-19 outbreak, or should they be discontinued?
BackgroundThe most common complications related to the closure of abdominal wall
incisions are surgical site infections, wound dehiscence and the development of an
incisional hernia. Several factors relating to the surgical technique and the
materials used have been identified and analysed over the years, as mirrored in the
current recommendations of the European Hernia Society, but some misconceptions
still remain that hinder wide implementation. MethodA literature search was
performed in the PubMed and GoogleScholar databases on 15 July 2021 and
additionally on 30 March 2022 to include recent updates. The goal was to describe
the scientific background behind the optimal strategies for reducing incisional
hernia risk after closure of abdominal wall incisions in a narrative style review
ResultsAn aponeurosis alone, small bites/small steps continuous suture technique
should be used, using a slowly resorbable USP 2/0 or alternatively USP 0 suture
loaded in a small 1/2 circle needle. The fascial edges should be properly
visualised and tension should be moderate. ConclusionDespite the reproducibility,
low risk and effectiveness in reducing wound complications following abdominal wall
incisions, utilisation of the recommendation of the guidelines of the European
Hernia Society remain relatively limited. More work is needed to clear
misconceptions and disseminate the established knowledge and technique especially
to younger surgeons
Recent emergence of the SARS-CoV-2 variant as OMICRON has become a global concern.
This short note highlights the identification and global spread of OMICRON which
has spread over 77 nations by now, which resulted in many hypotheses about its
origin and degree of infectivity. The detection of mutations in the RBD region of
Spike protein is a concern by surpassing vaccine immunity. The ahead will speak
about its transmission potentiality, infectivity, disease morbidity as well as its
effect on COVID-19 vaccines.
Mental health problems often involve clusters of symptoms that include subjective
(conscious) experiences as well as behavioral and/or physiological responses.
Because the bodily responses are readily measured objectively, these have come to
be emphasized when developing treatments and assessing their effectiveness. On the
other hand, the subjective experience of the patient reported during a clinical
interview is often viewed as a weak correlate of psychopathology. To the extent
that subjective symptoms are related to the underlying problem, it is often assumed
that they will be taken care of if the more objective behavioral and physiological
symptoms are properly treated. Decades of research on anxiety disorders, however,
show that behavioral and physiological symptoms do not correlate as strongly with
subjective experiences as is typically assumed. Further, the treatments developed
using more objective symptoms as a marker of psychopathology have mostly been
disappointing in effectiveness. Given that "mental" disorders are named for, and
defined by, their subjective mental qualities, it is perhaps not surprising, in
retrospect, that treatments that have sidelined mental qualities have not been
especially effective. These negative attitudes about subjective experience took
root in psychiatry and allied fields decades ago when there were few avenues for
scientifically studying subjective experience. Today, however, cognitive
neuroscience research on consciousness is thriving, and offers a viable and novel
scientific approach that could help achieve a deeper understanding of mental
disorders and their treatment.
Fear memory recruits various brain regions with long-lasting brain-wide subcellular
events. The medial prefrontal cortex processes the emo-tional and cognitive
functions required for adequately handling fear memory. Several studies have
indicated that subdivisions within the medial prefrontal cortex, namely the
prelimbic, infralimbic, and anterior cingulate cortices, may play different roles
across fear memory states. Through a dedicated cytoarchitecture and connectivity,
the three different regions of the medial prefrontal cortex play a specific role in
maintaining and extin-guishing fear memory. Furthermore, synaptic plasticity and
maturation of neural circuits within the medial prefrontal cortex suggest that
remote memories undergo structural and functional reorganization. Finally, recent
technical advances have enabled genetic access to transiently activated neuronal
ensembles within these regions, suggesting that memory trace cells in these regions
may preferentially contribute to processing specific fear memory. We reviewed
recently published reports and summarize the molecular, synaptic and cellular
events occurring within the medial pre-frontal cortex during various memory stages.
For decades, Izquierdo and colleagues contributed to building the notion that
declarative memory requires different processes at the molecular and systems
levels. This review aims to discuss part of Izquierdo's legacy, mainly but not
exclusively that related to fear memory. First, some of the philosophical and
evolutionary issues that arise from declarative memory definition are presented.
Then, the underlying processes of declarative memory are depicted, discussing the
formation, the nature and the progression of the memory trace in short-term and
long-term memory, and describing the involvement of some molecular cascades in the
hippocampal formation, mesocortex and frontal areas. Potential contributions to
therapy or understanding cognitive processes are mentioned. (C) 2022 IBRO.
Published by Elsevier Ltd. All rights reserved.
Pain management in trauma or surgery with a high risk of developing compartment
syndrome (CS) is always challenging due to fears of masking symptoms that could
delay diagnosis and treatment. Regional anesthesia/analgesia (RA) can facilitate
enhanced postoperative recovery and improve patient satisfaction by providing
excellent postoperative analgesia. However, its consideration in surgeries with a
high risk of developing CS remains controversial and contentious. Studies suggest
focusing more on early diagnosis through regular vigilant monitoring with a high
index of suspicion rather than discontinuing the analgesic method alone. The most
consistent features in all reported cases of CS were altered sensation in the
affected limb, disproportionate pain in the presence of a functional nerve block,
and an escalating need for analgesics.Several extrinsic or intrinsic factors are
responsible for the progressive increase in compartment pressure that can lead to
vascular compromise and subsequent ischemic changes in muscles, tissues, and
nerves. Measurement of intracompartmental pressure (ICP) has always been considered
the gold standard for diagnosing CS. An ICP of 30 mm Hg is considered the cut-off
point for fasciotomy that helps restore muscle perfusion and avoid irreversible
tissue damage. The chronology of symptoms can sometimes provide clues to the
severity of CS, the pathophysiology involved, and the management required.
Therefore, it is necessary to look for warning signs, further investigate the
causes, and make quick decisions to diagnose and treat CS and its complications on
time. Any delay in the diagnosis and treatment of CS can result in high morbidity
and poor outcomes. A well-integrated interprofessional team of health professionals
can deliver the required complexity of care through a holistic and
multidisciplinary approach.This review article highlights the symptoms, risk
factors, and pathophysiology involved in CS. It can guide readers in choosing
various options to diagnose, prevent, and treat CS. It also discusses the role of
RA in patients or surgeries prone to developing CS.
Global climate change awareness is increasing, but efforts to convey information
can trigger undesirable behaviors, including denial, skepticism, and increased
resource consumption. It is therefore essential to more fully investigate social-
psychological responses to climate information and messaging if we are to prompt,
support, and sustain pro-environmental behaviors. Yet consideration of these
responses is typically absent from interdisciplinary environmental study designs.
Of specific relevance is research using social psychology's Terror Management
Theory (TMT) showing that people's efforts to repress mortality salience (MS) or
awareness significantly influence their attitudes, beliefs, and behaviors. Research
on MS's influence on climate change beliefs is progressing but, to date, a
systematic scoping review of the literature has been unavailable. Here, we provide
such a review. We propose that TMT insights and methods should be better integrated
into research designs to guide climate communications and to generate the
comprehensive cultural and behavioral changes needed to address societies' climate
problems. We introduce a methodological framework for interdisciplinary researchers
to incorporate TMT into their research designs and to help practitioners anticipate
how their mortality-laden messaging could trigger unintentional social-
psychological responses that degrade climate communication strategies. This article
is categorized under: Perceptions, Behavior, and Communication of Climate Change >
Behavior Change and Responses
Purpose Fear of cancer recurrence (FCR) may be equally prevalent, persistent and
burdensome in cancer caregivers as in survivors. This systematic review evaluated
FCR prevalence, severity, correlates, course, impact and interventions in cancer
caregivers. Methods Electronic databases were searched from 1997 to May 2021. Two
reviewers identified eligible peer-reviewed qualitative or quantitative studies on
FCR in adult caregivers or family members of adult cancer survivors. The risk of
bias was assessed using the Cochrane Risk of Bias tools for randomised and non-
randomised studies and the Mixed-Methods Appraisal Tool. A narrative synthesis and
thematic synthesis occurred on quantitative and qualitative studies, respectively.
Results Of 2418 papers identified, 70 reports (59 peer-reviewed articles, 11
postgraduate theses) from 63 studies were included. Approximately 50% of caregivers
experienced FCR. Younger caregivers and those caring for survivors with worse FCR
or overall health reported higher FCR. Most studies found caregivers' FCR levels
were equal to or greater than survivors'. Caregivers' FCR was persistently elevated
but peaked approaching survivor follow-up appointments. Caregivers' FCR was
associated with poorer quality of life in caregivers and survivors. Three studies
found couple-based FCR interventions were acceptable, but had limited efficacy.
Conclusions FCR in caregivers is prevalent, persistent and burdensome. Younger
caregivers of survivors with worse overall health or FCR are at the greatest risk.
Further research on identifying and treating caregivers' FCR is required.
Implications for Cancer Survivors Caregiver and survivor FCR are similarly
impactful and appear interrelated. Addressing FCR may improve outcomes for both
cancer caregivers and survivors.
Purpose The threat of national and international terrorism remains high.
Preparation is the key requirement for the resilience of hospitals and out-of-
hospital rescue forces. The scientific evidence for defining medical and tactical
strategies often feeds on the analysis of real incidents and the lessons learned
derived from them. This systematic review of the literature aims to identify and
systematically report lessons learned from terrorist attacks since 2001. Methods
PubMed was used as a database using predefined search strategies and eligibility
criteria. All countries that are part of the Organization for Economic Cooperation
and Development (OECD) were included. The time frame was set between 2001 and 2018.
Results Finally 68 articles were included in the review. From these, 616 lessons
learned were extracted and summarized into 15 categories. The data shows that
despite the difference in attacks, countries, and casualties involved, many of the
lessons learned are similar. We also found that the pattern of lessons learned is
repeated continuously over the time period studied. Conclusions The lessons from
terrorist attacks since 2001 follow a certain pattern and remained constant over
time. Therefore, it seems to be more accurate to talk about lessons identified
rather than lessons learned. To save as many victims as possible, protect rescue
forces from harm, and to prepare hospitals at the best possible level it is
important to implement the lessons identified in training and preparation.
Monkeypox is a zoonotic Orthopoxvirus called human Monkeypox. It has symptoms that
resemble or are pretty similar to smallpox. Monkeypox virus belongs to the genus
Orthopoxvirus, which also includes cowpox, vaccinia, and variola viruses. The World
Health Organization confirmed in 1970 that the primary virus is the Orthopoxvirus
infecting humans after smallpox elimination. Clinically distinguishing the
condition from varicella and smallpox is challenging for a clinician. Although the
mortality rate of this disease is low, new tests are being tried and studied, which
are required for a more accurate and quick diagnosis because the lab diagnosis is
the key to the detection of illness and its monitoring. The illness or the virus is
endemic to parts of western and central Africa. Surveillance in underdeveloped
rural regions is challenging but manageable with evidence-based techniques and
training materials for public health professionals. However, as in the present
scenario, the disease is having a worldwide outbreak in various countries, and
recently India detected its first case on 15 July 2022 in New Delhi. The widespread
disease is due to trading exotic pets and international travel. Since smallpox
vaccinations are not administered to people regularly, epidemiological studies are
required. New medications and vaccines provide hope for treating and preventing
Monkeypox; however, further study is required before they can be used effectively.
Also, there is a requirement for advanced scientific studies in the etiology,
epidemiology, and biological structure of the virus in the endemic zones to know
and halt the spread of infection to humans.
Purpose The aim of this study was to systematically review the literature to answer
the question: Can children's drawings represent a helping tool so the dentist can
better understand the children's pain, fear, anxiety or stress/distress and their
perception concerning the dentist and/or dental treatment? Methods A scoping review
was done. Cochrane Library, EMBASE, LILACS, LIVIVO, PsycINFO, PubMed, Scopus, Web
of Science, and Grey literature was searched. Cross-sectional, quasi-experimental
and qualitative studies in which patients were children and adolescents were
included. Two authors independently selected studies to extract data and evaluate
methodological quality by using Joanna Briggs Institute tools. Data collected
included: characteristics of the studies, drawing evaluation/scales, main results
and conclusion. Results Out of 1037 papers were identified in search, 25 studies
verified the emotional state and the children's perceptions regarding dental
environment and the dentist and were included in the narrative synthesis. The
spontaneous drawings were useful to identify the children's emotions. Drawings
might be considered a helping tool to identify children and adolescents' perception
in relation to dental treatment. Few studies used validated instruments. There were
methodological disparities among studies. Conclusions The drawings can be
considered a useful tool in identifying children's pain, fear, anxiety or
stress/distress and perceptions about the dentist and/or dental treatment. Future
studies with standardized analysis of the drawings are recommended. Code
.https://doi.org/ 10.17605/OSF.IO/U5BJH. "Retrospectively registered".
The amygdala is a key brain region involved in emotional memory formation. It is
also responsible for memory modulation in other brain areas. Under extreme
conditions, amygdala modulation may lead to the generation of abnormal plasticity
and trauma-related psychopathologies. However, the amygdala itself is a dynamic
brain region, which is amenable to long-term plasticity and is affected by
emotional experiences. These alterations may modify the way the amygdala modulates
activity and plasticity in other related brain regions, which in turn may alter the
animal's response to subsequent challenges in what could be termed as "Behavioral
metaplasticity."Because of the reciprocal interactions between the amygdala and
other emotion processing regions, such as the medial prefrontal cortex (mPFC) or
the hippocampus, experience-induced intra-amygdala metaplasticity could lead to
alterations in mPFC-dependent or hippocampus-dependent behaviors. While initiated
by alterations within the basolateral amygdala (BLA), such alterations in other
brain regions may come to be independent of BLA modulation, thus establishing what
may be termed "Trans-regional metaplasticity." In this article, we review evidence
supporting the notions of intra-BLA metaplasticity and how this may develop into
"Trans-regional metaplasticity." Future research is needed to understand how such
dynamic metaplastic alterations contribute to developing psychopathologies, and how
this knowledge may be translated into promoting novel interventions in
psychopathologies associated with fear, stress, and trauma.
Hyperexcitability in fear circuits is suggested to be important for development of
pathological anxiety and trauma from adaptive mechanisms of fear. Hyperexcitability
is proposed to be due to acquired sensitization in fear circuits that progressively
becomes more severe over time causing changing symptoms in early and late
pathology. We use the metaphor and mechanisms of kindling to examine gains and
losses in function of one excitatory and one inhibitory neuropeptide,
corticotrophin releasing factor and somatostatin, respectively, to explore this
sensitization hypothesis. We suggest amygdala kindling induced hyperexcitability,
hyper-inhibition and loss of inhibition provide clues to mechanisms for
hyperexcitability and progressive changes in function initiated by stress and
trauma.
Background and objective Biopsychosocial conceptualizations of clinical pain
conditions recognize the multi-faceted nature of pain experience and its
intersection with mental health. A primary cognitive-behavioural framework is the
Fear-Avoidance Model, which posits that pain catastrophizing and fear of pain
(including avoidance, cognitions and physiological reactivity) are key antecedents
to, and drivers of, pain intensity and disability, in addition to pain-related
psychological distress. This study aimed to provide a comprehensive analysis of the
magnitude of the cross-sectional association between the primary components of the
Fear-Avoidance Model (pain catastrophizing, fear of pain, pain vigilance) with
negative affect, anxiety, depression, pain intensity and disabilities in studies of
clinical pain. Databases and data treatment A search of MEDLINE and PubMed
databases resulted in 335 studies that were evaluated in this meta-analytic review,
which represented 65,340 participants. Results Results from the random effect
models indicated a positive, medium- to large-sized association between fear of
pain, pain catastrophizing, and pain vigilance measures and outcomes (pain-related
negative affect, anxiety, depression and pain-related disability) and medium-sized
associations with pain intensity. Fear of pain measurement type was a significant
moderator of effects across all outcomes. Conclusions These findings provide
empirical support, aligned with the components of the fear-avoidance (FA) model,
for the relevance of both pain catastrophizing and fear of pain to the pain
experience and its intersection with mental health. Implications for the
conceptualization of the pain catastrophizing and fear of pain construct and its
measurement are discussed. Significance This meta-analysis reveals that, among
individuals with various pain conditions, pain catastrophizing, fear of pain, and
pain vigilance have medium to large associations with pain- related negative
affect, anxiety, and depression, pain intensity and disability. Differences in the
strength of the associations depend on the type of self-report tool used to assess
fear of pain.
Falling and fear of falling (FOF) are significant concerns for people with
Parkinson's disease (PD). FOF can lead to activity avoidance behavior, a risk
factor for increased falls and further functional decline. The significant
implications of fear of falling avoidance behavior (FFAB) among PD warrant a
literature review. The objective of this review was to explore existing literature
on FFAB and identify what is known about this phenomenon in people with PD. This
scoping review considered studies including adults 18 years and older diagnosed
with PD experiencing FFAB. Using Joanna Briggs Institute methodology and the PRISMA
extension for scoping reviews, we performed a scoping review searching MEDLINE,
Embase, Scopus, APA PsycInfo, CINAHL, Papers First, and ProQuest Dissertations and
Theses for studies examining FFAB among people with PD with no limit on publication
date. A three-step search strategy was followed and data extraction was performed
by two independent reviewers. A total of 9 articles met eligibility criteria. Seven
studies were quantitative and two were qualitative. The results identified that
FFAB has a significant impact on daily life and is associated with downstream
consequences of physical and psychological decline. The symptoms and severity of PD
uniquely influence FFAB. Multiple assessments were utilized, but only two measured
the impact of FOF and how this fear translates into avoidance behavior. There is a
paucity of literature on interventions targeting FFAB among PD. In summary, this
review demonstrated that FFAB is complex, multifactorial, and significantly impacts
everyday life for people with PD. Evaluation and treatment should begin in the
early stages of the disease. PD adds disease-specific symptoms and progression that
directly impact FFAB, possibly in a bidirectional or cyclical manner. Further
research is required to explore assessment and interventions for FFAB among people
with PD.
Fear of falling is a geriatric condition that must be understood from both a
clinical perspective and from the environment in which older adults live. This
review aimed to describe the scientific evidence reported in the last 5 years
regarding the fear of falling in older adults and its relationship with
environmental factors. The relationships between fear of falling and environmental
factors are mainly evidenced in the built environment. Older adults with a fear of
falling are described as perceiving the built environment as dangerous when they do
not meet the requirements of safety, accessibility, and comfort; they also report
the importance of living in communities with controlled crime levels and available
social support for older adults to improve their insecurity and feelings of
vulnerability.
Background: Panic disorder is a common and disabling psychiatric condition marked
by sudden onset of physiological sensations that are appraised as dangerous. A
number of studies and reviews have examined the efficacy of psychosocial treatments
for PD; however, there is a lack of overarching reports that discuss the strength
of evidence for the different psychosocial treatments for PD. This umbrella review
provides an overview of systematic reviews and meta-analyses on psychosocial
treatments for PD. Methods: A systematic search and review of the literature was
conducted according to PRISMA guidelines. Results: A total of 38 reviews (31 meta-
analyses and 7 systematic reviews) were included in the umbrella review. Most of
the 38 reviews were focused on the use of CBT, both in-person and internet-based,
to treat PD among adults, generally finding it to be an efficacious treatment
compared to control conditions. A limited number of the 38 reviews included other
age ranges or examined other forms of psychosocial treatments. The methodological
quality of most included reviews was rated as critically low according to the
AMSTAR-2 rating system. Conclusions: Future reviews should focus on improving their
methodological quality. Although the included reviews supported CBT as an
efficacious treatment for reducing panic symptoms among adults, future research
could focus on how CBT compares to other psychosocial treatments and the efficacy
of CBT for PD among other populations (e.g., children and adolescents) and among
diverse cultural groups.
Aim To synthesise knowledge on the relative efficacies of non-pharmacological
strategies for managing dental fear and anxiety (DFA) in children and adolescents,
specifically their effects on behaviour, anxiety levels and pain perception.
Materials and methods An umbrella review on non-pharmacological strategies used to
manage DFA in children and adolescents was conducted based the Joanna Briggs
Institute methodology. Searches were performed in 5 main electronic databases and
the grey-literature. Two independent reviewers selected and appraised the included
studies using the AMSTAR2 tool. Disagreements were resolved by a third reviewer.
Results From 191 studies, 13 systematic reviews (SRs) were included and the
majority were of low or critically low quality. Findings from the SRs suggest that
audio-visual distraction was the most effective strategy for reducing anxiety, but
effects on pain perception and behaviour were inconclusive. Traditional behaviour
management techniques and audio distraction had mixed outcomes. Other strategies
like aromatherapy and cognitive behaviour therapy were found to be effective for
reducing anxiety but the evidence was weak. Conclusions Audio-visual distraction
was effective in reducing anxiety during a variety of dental procedures including
those requiring local anaesthesia. A combination of techniques may be more
effective in managing DFA in children and adolescents, possibly improving pain
perception and cooperative behaviour.
Introduction Fear of hypoglycemia (FOH) is a phenomenon that affects people with
diabetes experiencing hypoglycemia. On the one hand, FOH is an adaptive mechanism
that helps to protect patients from hypoglycemia and its consequences. On the other
hand, the non-normative level of FOH causes anxiety and tension, disturbs normal
functioning, and makes normoglycemia maintenance difficult. Objective The main
objective of this review was to describe factors influencing FOH and methods of
measurement of FOH levels. Moreover, we highlighted the impact of the new
technologies used in diabetes therapy on FOH and different therapeutic
possibilities helping patients cope with excessive levels of FOH. We also presented
clinical cases of patients with high FOH levels met in clinical practice and
discussed methods to better diagnose and assist people with this kind of problem.
Methods We searched for studies and articles via PubMed using the keywords fear of
hypoglycemia, diabetes, and hypoglycemia. From screened documents identified from
literature search, 67 articles were included in our review. Results We divided
results from literature screening into five parts: fear of hypoglycemia and
hypoglycemia definition, risk factors for the FOH, methods of measuring levels of
FOH, therapies for the FOH, and modern technologies. We also described clinical
examples of abnormal fear of hypoglycemia in patients. Conclusion The review
highlights the importance of taking into consideration fear of hypoglycemia
phenomenon in diabetic patients in everyday clinical practice.
Purpose of review Fear of cancer recurrence (FCR) is a common concern among cancer
survivors and support for FCR is one of the most cited unmet needs. High FCR was
found to be related to increased use of healthcare services, specifically primary
healthcare and medical consultations, and lower quality of life. In the past decade
screening instruments for FCR and interventions have been developed and proven
effective. Recent findings Systematic reviews and meta-analyses have shown that
psychological treatments are effective for reducing FCR. The cost-effectiveness of
FCR interventions could be increased by considering stepped or matched models for
supportive care. Despite availability of evidence-based interventions, the proposed
care models are not implemented and most cancer survivors still do not benefit from
supportive care. The time is right to focus on implementation of FCR interventions
into clinical practice. The complexity of optimizing FCR care is characterized by
barriers and facilitators in the domains of patients, healthcare professionals,
healthcare organizations and the broader economic, and political context. The main
challenge for future research is to address these issues so that former investments
in high-quality FCR intervention research will pay out in actual practice changes
in the benefit of cancer survivors.
Learning to identify and predict threats is a basic skill that allows animals to
avoid harm. Studies in invertebrates like Aplysia californica, Drosophila
melanogaster, and Caenorhabditis elegans have revealed that the basic mechanisms of
learning and memory are conserved. We will summarize these studies and highlight
the common pathways and mechanisms in invertebrate fear-associated behavioral
changes. Fear conditioning studies utilizing electric shock in Aplysia and
Drosophila have demonstrated that serotonin or dopamine are typically involved in
relaying aversive stimuli, leading to changes in intracellular calcium levels and
increased presynaptic neurotransmitter release and short-term changes in behavior.
Long-term changes in behavior typically require multiple, spaced trials, and
involve changes in gene expression. C. elegans studies have demonstrated these
basic aversive learning principles as well; however, fear conditioning has yet to
be explicitly demonstrated in this model due to stimulus choice. Because predator-
prey relationships can be used to study learned fear in a naturalistic context,
this review also summarizes what is known about predator-induced behaviors in these
three organisms, and their potential applications for future investigations into
fear conditioning.
Fear memory generalisation is a central hallmark in the broad range of anxiety and
trauma-related disorders. Recent findings suggest that fear generalisation is
closely related to hippocampal dependency during retrieval. In this review, we
describe the current understanding about memory generalisation and its potential
influence in fear attenuation through pharmacological and behavioural
interventions. In light of systems consolidation framework, we propose that keeping
memory precision could be a key step to enhance therapeutic outcomes.
Background: Fear of cancer recurrence (FCR) has been addressed as a cause of
emotional distress among breast cancer survivors (BCSs). This study aimed to
systematically review the evidence on randomized controlled trials (RCTs) of
cognitive behavioral therapy (CBT) designed to reduce FCR among BCSs. Methods: A
systematic review of published original research articles meeting the inclusion
criteria was conducted. Five electronic databases, including the Cochrane Library,
CINAHL, PubMed, PsycINFO, and Web of Science, were independently searched to
identify relevant articles. The Consolidated Standards of Reporting Trials
(CONSORT) 2010 checklist was used to evaluate the quality of the eligible studies.
Results: Through a database search and a manual review process, seventeen
quantitative studies with an RCT study design were included in the current
systematic review. The interventions varied greatly in length and intensity, but
the study designs and methodologies were similar. RCTs with face-to-face
interventions of at least 1 month seemed to be more effective in reducing FCR
outcomes and complying with than the CONSORT 2010 criteria than those with a brief
online or telephone format of interventions; nevertheless, most RCT interventions
appeared to be effective. Conclusions: These findings highlight the importance of
conducting well-designed CBT interventions to reduce FCR in BCSs with diverse
populations at multiple sites, thereby improving the quality of research in this
area.
Fear memory helps animals and humans avoid harm from certain stimuli and coordinate
adaptive behavior. However, excessive consolidation of fear memory, caused by the
dysfunction of cellular mechanisms and neural circuits in the brain, is responsible
for post-traumatic stress disorder and anxiety-related disorders. Dysregulation of
specific brain regions and neural circuits, particularly the hippocampus, amygdala,
and medial prefrontal cortex, have been demonstrated in patients with these
disorders. These regions are involved in learning, memory, consolidation, and
extinction. These are also the brain regions where new neurons are generated and
are crucial for memory formation and integration. Therefore, these three brain
regions and neural circuits have contributed greatly to studies on neural
plasticity and structural remodeling in patients with psychiatric disorders. In
this review, we provide an understanding of fear memory and its underlying cellular
mechanisms and describe how neural circuits are involved in fear memory.
Additionally, we discuss therapeutic interventions for these disorders based on
their proneurogenic efficacy and the neural circuits involved in fear memory.
Background Psychotherapies are the treatment of choice for panic disorder, but
which should be considered as first-line treatment is yet to be substantiated by
evidence. Aims To examine the most effective and accepted psychotherapy for the
acute phase of panic disorder with or without agoraphobia via a network meta-
analysis. Method We conducted a systematic review and network meta-analysis of
randomised controlled trials (RCTs) to examine the most effective and accepted
psychotherapy for the acute phase of panic disorder. We searched MEDLINE, Embase,
PsycInfo and CENTRAL, from inception to 1 Jan 2021 for RCTs. Cochrane and PRISMA
guidelines were used. Pairwise and network meta-analyses were conducted using a
random-effects model. Confidence in the evidence was assessed using Confidence in
Network Meta-Analysis (CINeMA). The protocol was published in a peer-reviewed
journal and in PROSPERO (CRD42020206258). Results We included 136 RCTs in the
systematic review. Taking into consideration efficacy (7352 participants),
acceptability (6862 participants) and the CINeMA confidence in evidence appraisal,
the best interventions in comparison with treatment as usual (TAU) were cognitive-
behavioural therapy (CBT) (for efficacy: standardised mean differences s.m.d. = -
0.67, 95% CI -0.95 to -0.39; CINeMA: moderate; for acceptability: relative risk RR
= 1.21, 95% CI -0.94 to 1.56; CINeMA: moderate) and short-term psychodynamic
therapy (for efficacy: s.m.d. = -0.61, 95% CI -1.15 to -0.07; CINeMA: low; for
acceptability: RR = 0.92, 95% CI 0.54-1.54; CINeMA: moderate). After removing RCTs
at high risk of bias only CBT remained more efficacious than TAU. Conclusions CBT
and short-term psychodynamic therapy are reasonable first-line choices. Studies
with high risk of bias tend to inflate the overall efficacy of treatments. Results
from this systematic review and network meta-analysis should inform clinicians and
guidelines.
The landscape of fear (LOF) concept posits that prey navigate spatial heterogeneity
in perceived predation risk, balancing risk mitigation against other activities
necessary for survival and reproduction. These proactive behavioral responses to
risk can affect individual fitness, population dynamics, species interactions, and
coexistence. Yet, antipredator responses in free-ranging prey often contradict
expectations, raising questions about the generality and scalability of the LOF
framework and suggesting that a purely spatial, static LOF conceptualization may be
inadequate. Here, we outline a 'dynamic' LOF framework that explicitly incorporates
time to account for predictable spatiotemporal variation in risk-resource trade-
offs. This integrated approach suggests novel predictions about predator effects on
prey behaviors to refine understanding of the role predators play in ecological
communities.
Objectives. - Panic disorder (PD) is defined by recurring and unexpected panic
attacks accompanied by anticipatory anxiety about future attacks and their
consequences. This generally involves avoiding situations and behaviors that can
produce panic attacks (American Psychiatric Association [APA], 2013). Among anxiety
disorders, PD is associated with some of the greatest burdens in terms of personal
suffering, occupational disability, and societal cost. Since the introduction of PD
in the DSM-III (1980) and the distinction of PD from generalized anxiety disorder
following the work of Klein (1964), several biological and psychological theories
of PD have been developed. These theories have highlighted several risk factors
(for the onset, maintenance and relapse associated with the disorder) that have
strongly influenced research on PD and have guided its treatment. However, a
comprehensive and universally accepted theoretical framework of PD to guide its
treatment is lacking. This article reviews the previously described theoretical
frameworks of PD and related treatments while examining the strength of the
scientific evidence supporting their validity as well as their limitations.
Methodology. - A review of the literature was undertaken by searching PsycINFO
database to list all the articles published between January 2000 and November 2020
and referring to a theoretical model or a conceptual framework of PD. The
conceptual frameworks identified were reviewed based on the recent scientific
researches to determine the strength of the evidence supporting their validity.
Results. - Of the 928 articles initially identified, 54 referred to fourteen
different conceptual frameworks relating to PD. Two models are exclusively
biological: the false suffocation alarm and the neuroanatomical hypothesis of PD.
Six models are psychological, one of which is psychodynamic and five are derived
from the cognitive-behavioral paradigm. Finally, six models are integrative: triple
vulnerability of Barlow, integrated cognitive vulnerability of Schmidt & Woolaway-
Bickel, unified model of vulnerability of McGinn, causal model of Fava & Morton,
causal model based on the evidence by Pilecki and integrated model of Busch. These
models highlight biological, environmental, developmental and psychological
vulnerability factors. Conclusion. - The analysis of these different models shows
that few conceptual frameworks have been used consistently to guide the treatment
of PD, and that not all frameworks are empirically well supported. The theoretical
approaches that have strongly influenced the treatment of PD are the cognitive
model of Clark, the expectation model of Reiss as well as the triple vulnerability
model of Barlow. Although treatments based on these models benefit a large
percentage of patients, at least 25% of patients are classified as resistant to
these treatments. In addition, relapses and persistence of symptoms remain common
results of these treatments. This suggests that other vulnerability factors such as
emotional regulation skills should be taken into consideration and integrated into
these models especially as several studies have suggested that research focused on
emotion regulation may improve our understanding of panic. (C) 2021 Published by
Elsevier Masson SAS.
Purpose To describe expectant mothers' experiences of fear of childbirth after a
previous traumatic birth. Method Qualitative, individual, in-depth interviews were
conducted with eight expectant mothers between September and November 2020. Data
were analysed using a descriptive phenomenological approach. Results We identified
four interconnected constituents: Suboptimal midwifery care, loss of control and
agency; insufficient time and capacity to process a traumatic birth experience;
"The baby has to be delivered!", and finally, the path to a new childbirth with the
hope of mastering fears. Conclusion Findings reveal an association between a
previous history of traumatic birth and a fear of childbirth in expectant mothers.
The trauma they experienced whilst giving birth strongly impacted their subsequent
pregnancy, making it difficult for them to deal with the new pregnancy and
impending birth. Women who have experienced a traumatic birth need to have the
opportunity to process the trauma. Routines must therefore be developed that
identify, support and follow up with the women. If these women are identified and
given the help they need, this may help prevent and/or alleviate fear of childbirth
in their subsequent pregnancy.
This article discusses the treatment of panic disorder in terms of cognitive
behavioral psychotherapy. Panic disorder is one of the most common anxiety
disorders. The etiology of panic disorder assumes the coexistence of genetic and
environmental factors. Panic attacks of-ten accompany other mental and somatic
diseases. The constant feeling of intense anxiety with a number of somatic symptoms
affects the deterioration of every-day functioning, significantly reducing one's
quality of life. The global situation caused by SARS-CoV-2 may correlate with the
increase in the incidence of panic disorder. The introduction of appropriate ther-
apeutic interventions at the earliest possible stage of the disease gives patients
a chance for long-term re-mission. So far, it has been proven that the best results
of pharmacological treatment are achieved thanks to the antidepressant and
benzodiazepine drug groups. One of the non-pharmacological interventions with the
highest clinical effectiveness is cognitive -behavio-ral psychotherapy. Compared to
other trends, cogni-tive-behavioral therapy is characterized by the most reliable
research proving its high effectiveness. Psycho-therapy of panic disorders in the
cognitive-behavioral approach includes a complete conceptualization of the
patient's problem, taking into account individual the-oretical models. Treatment of
panic attacks is based on a protocol which takes into account both cognitive and
behavioral interventions, e.g. psychoeducation, cognitive restructuring, breathing
training, relaxation exercises and both interoceptive and in vivo exposures.
Research results indicate that this therapy is an alter-native form of treatment
for panic disorders. Sources indicate that the effectiveness of interventions based
on cognitive-behavioral therapy is comparable to that of pharmacotherapy.
Extreme stress can cause long-lasting changes in affective behavior manifesting in
conditions such as post -traumatic stress disorder (PTSD). Understanding the
biological mechanisms that govern trauma-induced behavioral dysregulation requires
reliable and rigorous pre-clinical models that recapitulate multiple facets of this
complex disease. For decades, Pavlovian fear conditioning has been a dominant
paradigm for studying the effects of trauma through an associative learning
framework. However, severe stress also causes long-lasting nonassociative fear
sensitization, which is often overlooked in Pavlovian fear conditioning studies.
This paper synthesizes recent research on the stress-enhanced fear learning (SEFL)
paradigm, a valuable rodent model that can dissociate associative and
nonassociative effects of stress. We discuss evidence that the SEFL paradigm
produces nonassociative fear sensitization that is distinguishable from Pavlovian
fear conditioning. We also discuss key biological variables, such as age and sex,
neural circuit mechanisms, and crucial gaps in knowledge. We argue that
nonassociative fear sensitization deserves more attention within current PTSD
models and that SEFL provides a valuable complement to Pavlovian conditioning
research on trauma-related pathology.
A growing literature has sought to combine fear conditioning paradigms with the
trauma film paradigm to study the associative learning properties of intrusive re-
experiencing in PTSD. We review this innovative approach and the recent findings by
highlighting their relevance to cognitive and conditioning theories of PTSD. We
also conduct a meta-analysis of the available studies to demonstrate that, for most
outcome measures, fear learning using a traumatic film clip unconditional stimulus
yields results similar to those seen with an electm-tactile unconditional stimulus,
which implies that the combined paradigm shares at least some properties of more
standard fear conditioning paradigms. We argue that careful use of this combined
paradigm will provide important new insights into the mechanisms underlying memory
symptoms of PTSD and will allow rigorous testing of cognitive theories of the
disorder.
Some previous research has shown stronger acquisition and impaired extinction of
fear conditioned to angry or fearful compared to happy or neutral face conditional
stimuli (CS) - a difference attributed to biological 'pre-paredness'. A systematic
review and meta-analysis of fear conditioning studies comparing face CSs of
differing expressions identified thirty studies, eighteen of which were eligible
for meta-analysis. Skin conductance re-sponses were larger to angry or fearful
faces compared to happy or neutral faces during habituation, acquisition and
extinction. Significant differences in differential conditioning between angry,
fearful, neutral, and happy face CSs were also found, but differences were more
prominent between angry and neutral faces compared to angry/fearful and happy
faces. This is likely due to lower arousal elicited by neutral compared to happy
faces, which may be more salient as CSs. The findings suggest there are small to
moderate differences in differential conditioning when angry or fearful compared to
happy or neutral faces are used as CSs. These findings have implications for fear
conditioning study design and the preparedness theory.
Objective: The current review aims to (1) investigate the effectiveness of
Internet-based psychological intervention in reducing depressive, anxiety, and
stress symptoms and fear of childbirth among pregnant women at post-intervention
and follow-up; (2) compare the effects of the intervention using different
psychological principles; and (3) explore potential covariates on the intervention
effect.& nbsp;Methods: A literature search of seven databases was carried out to
identify published and unpublished randomized controlled trials (RCTs) in English
without any time limitation up to February 2021. Meta-analysis and meta-regression
were conducted using Comprehensive Meta-analysis software. This review protocol was
registered on PROSPERO (CRD42021235565).& nbsp;Results: Sixteen RCTs involving 3894
pregnant women were included from more than 23 countries. Internet-delivered
psychological interventions were found to significantly (p < 0.05) reduce
depressive (g =-0.16 to-0.32) and anxiety (g =-0.22 to-0.33) symptoms with small
effect sizes at post-intervention and follow-up during 6 to 8 weeks postpartum
compared with those in the comparator group. However, there was insufficient
evidence for fear of childbirth and stress symptoms. Our subgroup analyses found
that psychological interventions adopting component of cognitive behavioral therapy
(g =-0.29) or mindfulness therapy (g =-0.62) showed beneficial effects to improve
depressive symptoms among pregnant women. Univariate random-effect regression
analyses showed that the attrition rate was a significant covariate (Z =-2.33, p =
0.02) on depressive symptoms. The certainty of main outcomes was graded from low to
very low in accordance with the GRADE criteria.& nbsp;Conclusions: Our reviews
suggested that Internet-delivered psychological intervention may complement usual
antenatal care in the improvement of depressive and anxiety symptoms. Future trials
involving a large-scale sample are needed to improve the methodological quality.
Estimated rates of co-occurrence between obsessive and compulsive disorder (OCD)
and panic disorder (PD) are notable, but vary considerably, with rates from
epidemiological and clinical studies ranging from 1.8% to 22% (Rector et al.,
2017). We reviewed the current empirical literature on the etiology, treatment,
diagnostic assessment, and differential diagnosis of co-occurring OCD/PD. Best
practices for cognitive-behavioral treatment, including identifying and addressing
treatment barriers are also addressed. Although it is acknowledged in current
literature that co-occurring OCD and PD levels may be clinically significant, there
remains a need to thoroughly examine the possible consequences and future research
directions of this overlap. Future research must continue to elucidate the
biological and environmental causes of OCD/PD co-occurrence.
Over the past decades, studies of fear learning and extinction have advanced our
understanding of the neurobiology of threat and safety learning. Animal studies can
provide mechanistic/causal insights into human brain regions and their functional
connectivity involved in fear learning and extinction. Findings in humans,
conversely, may further enrich our understanding of neural circuits in animals by
providing macroscopic insights at the level of brain-wide networks. Nevertheless,
there is still much room for improvement in translation between basic and clinical
research on fear learning and extinction. Through the lens of neural circuits, in
this article, we aim to review the current knowledge of fear learning and
extinction in both animals and humans, and to propose strategies to fill in the
current knowledge gap for the purpose of enhancing clinical benefits.
Activation of the fear system is adaptive, and protects individuals from impending
harm; yet, exacerbation of the fear system is at the source of anxiety-related
disorders. Here, we briefly review the 'why' and 'how' of fear, with an emphasis on
models that encapsulate the elegant complexity of rodents' behavioral responding in
the face of impending harm, and its relevance to developing treatment
interventions.
Studies conducted during the pandemic revealed strong associations between gender
and COVID-19 related fear and anxiety. Females perceive coronavirus as a greater
threat to personal health and population than males. The aim of the current meta-
analysis is to estimate gender difference in COVID-19 related fear and anxiety. The
second purpose of this study is to clarify the role of potential moderators in
COVID-19 fear and anxiety. For these reasons, studies published between March 2020
and October 2021 were searched in various databases (Web of Science, SCOPUS,
PubMed, and Google Scholar). In total, 315 studies met the inclusion criteria, and
60 studies for COVID-19 related fear and 23 studies for COVID-19 related anxiety
were included in the current study. Cohen's d effect size values were calculated
based on these individual studies showing the difference between males and females
in terms of COVID-19 related fear and anxiety. Results revealed that gender has a
moderate and statistically significant effect on COVID-19 related fear (ES = 0.307)
and anxiety (ES = 0.316) in favor of females. Moderator analyses showed that
continent variable was a statistically significant moderator of gender difference
in COVID-19 related fear and anxiety. The highest effect size of gender differences
in COVID-related fear and anxiety were obtained from the studies conducted in
Europe. However, other moderators (the average age of sample, culture, timing, and
population) were not statistically significant. Although this meta-analysis has a
few limitations, the findings showed that COVID-19 outbreak negatively affected
females more.
Panic disorder (PD) is unique among anxiety disorders in that the emotional
symptoms (e.g., fear and anxiety) associated with panic are strongly linked to body
sensations indicative of threats to physiological homeostasis. For example, panic
attacks often present with feelings of suffocation that evoke hyperventilation,
breathlessness, or air hunger. Due to the somatic underpinnings of PD, a major
focus has been placed on interoceptive signaling and it is recognized that
dysfunctional body-to-brain communication pathways promote the initiation and
maintenance of PD symptomatology. While body-to-brain signaling can occur via
several pathways, immune and humoral pathways play an important role in
communicating bodily physiological state to the brain. Accumulating evidence
suggests that neuroimmune mediators play a role in fear and panic-associated
disorders, although this has not been systematically investigated. Currently, our
understanding of the role of immune mechanisms in the etiology and maintenance of
PD remains limited. In the current review, we attempt to summarize findings that
support a role of immune dysregulation in PD symptomology. We compile evidence from
human studies and panic-relevant rodent paradigms that indicate a role of systemic
and brain immune signaling in the regulation of fear and panic-relevant behavior
and physiology. Specifically, we discuss how immune signaling can contribute to
maladaptive body-to-brain communication and conditioned fear that are relevant to
spontaneous and conditioned symptoms of PD and identify putative avenues warranting
future investigation.
The mortality rate of patients affected with oral squamous cell carcinoma (OSCC)
has been stable in recent decades due to several factors, especially diagnostic
delay, which is often associated with a late stage diagnosis and poor prognosis.
The aims of this paper were to: analyze diagnostic delay in OSCC and to discuss the
various psychological factors of patients with OSCC, with particular attention to
the patient's fear of receiving news regarding their health; and the professional
dynamics related to the decision-making processes in cases of suspected OSCC. A
preliminary review of literature focusing on OSCC diagnostic delay was performed.
Seven articles were included with the diagnostic delay ranging from 45 days to
approximately 6 months. Patients' fears and, to a lesser degree, the concerns of
dentists, were found to be still poorly investigated. On the basis of the authors'
professional experience, the development of oral lesions of unknown origin may
generate different behaviors in the decision-making processes by patients and
clinicians, and fear may play a key role in the distinct steps of this process. It
is crucial to increase awareness and inform patients about the onset of OSCC, and
contemporaneously encourage experimental studies on patients' fear and professional
behaviors with respect to communication regarding OSCC.
Therapeutic interventions for disorders of fear and anxiety rely on behavioral
approaches that reduce pathological fear memories. For example, learning that
threat-predictive stimuli are no longer associated with aversive outcomes is
central to the extinction of conditioned fear responses. Unfortunately, fear
memories are durable, long-lasting, and resistant to extinction, particularly under
high levels of stress. This is illustrated by the "immediate extinction deficit,"
which is characterized by a poor long-term reduction of conditioned fear when
extinction procedures are attempted within hours of fear conditioning. Here, I will
review recent work that has provided new insight into the neural mechanisms
underlying resistance to fear extinction. Emerging studies reveal that locus
coeruleus norepinephrine modulates amygdala-prefrontal cortical circuits that are
critical for extinction learning. These data suggest that stress-induced activation
of brain neuromodulatory systems biases fear memory at the expense of extinction
learning. Behavioral and pharmacological strategies to reduce stress in patients
undergoing exposure therapy might improve therapeutic outcomes.
The under-or misdiagnosis, and symptomatic treatment of the panic disorder (PD),
despite high prevalent medical illness, is common among non-psychiatric physicians.
The non-psychiatrist physician's role is vital in the care of PD as most patients
initially approach general medical settings for medical help. including primary
care. However, a significant proportion is undiagnosed and undergoes either
unnecessary investigation, misdiagnosed, or mismanaged even among post-Coronary
Artery Bypass Grafting patients, which profoundly affects the patients functioning
and quality of life. This article aims to provide overviews of relevant
epidemiological aspects, presenting features across medical specialties with
respective diagnostic dilemmas, assessment, and management of the PD in their
general medical settings, including emergency visits. Apart from psychiatrists,
this will also assist non-psychiatrist physicians across all medical specialties,
including general practitioners, to understand, identify, and provide the first
line evidence-based pharmacotherapy and address the unmet need of patients with PD
in their day-to-day busy clinical practice. This paper also provides a referral
guide for non-psychiatrist physicians to refer to psychiatrists for further
management after their first-line management.
Background: Dyspepsia is one of the most common complaints in gastroenterology.
While its etiology is usually benign, rare cases of malignancy have to be
identified. Individualized risk stratification is essential for cost-effective
management of dyspepsia. Here, we discuss the challenges of investigating dyspepsia
at the specialist level and provide a framework for rational workup and
surveillance strategies. Summary: Causes of dyspepsia can be functional or organic,
including gastritis, peptic ulcers, or malignancy. H. pylori gastritis represents a
specific entity of dyspepsia and increases the risk of gastric cancer. H. pylori
eradication can improve symptoms in a subset of patients and reduce gastric cancer
risk. In young patients without alarm features, malignancy is rare, and noninvasive
testing for H. pylori is appropriate. In elder patients and those with alarm
features, high-quality endoscopy is the method of choice to rule out malignancy.
Advanced corpus-predominant atrophic gastritis with or without intestinal
metaplasia represent precancerous lesions. Key Messages: Symptom assessment
requires to distinguish dyspepsia of functional or organic origin. Risk
stratification in dyspeptic patients is based on age, alarm features, and H. pylori
status. Noninvasive test-and-treat is recommended in patients with low gastric
cancer risk, while endoscopy is recommended in individuals at increased risk. H.
pylori infection should be eradicated in order to obtain a symptomatic benefit and
reduce gastric cancer risk. Advanced preneoplastic lesions require endoscopic
surveillance.
Introduction In the last few decades, exercise has been explored as a potential
tool to reduce symptoms experienced by patients with panic disorder (PD). This
systematic review aims to assess the effects of regular exercise interventions on
panic severity, global anxiety, and depression symptoms of these patients. Areas
covered A search was conducted on PubMed, ISI Web of Science, and Cochrane Central
Register of Controlled Trials using search terms related to PD and exercise. Eight
trials were included, Furthermore, regular exercise programs presented different
methodological characteristics. There is o clear evidence indicating that regular
exercise programs (at least two 20-minute sessions per week for at least 6 weeks)
reduce panic-related symptoms. Regular exercise is effective in improving global
anxiety measures and depression. Expert opinion Continuous aerobic exercise is the
main type of intervention in the literature, generally providing a limited
prescription. Currently, it is recommended the interval training, with intense and
shorter stimuli, and long-term duration trials. However, despite the use of self-
selected intensities and control based on the internal load be interesting as
recommendation to increase adherence, careful is needed regarding training
prescription due to scarce evidence.
Aim To evaluate the effectiveness of psychological interventions in reducing fear
of cancer recurrence in breast cancer survivors. Design A systematic review and
meta-analysis. Data Sources PubMed, Embase, Cochrane Central Register of Controlled
Trials, CINAHL, Scopus, PsycINFO, Web of Science and were searched for relevant
studies published from 1 January 1976 to 28 November 2020. Methods Eligible
randomized controlled trials on psychological interventions for reducing fear of
cancer recurrence in breast cancer survivors were included in meta-analysis. Review
Manager 5.4 was used to conduct the meta-analysis, and the fear of cancer
recurrence score was calculated by using standardized mean differences and 95%
confidence intervals. Risk of bias was assessed with the Cochrane risk-of-bias
tool. Quality of evidence, sensitivity analyses, and subgroup analyses were also
conducted. Results This systematic review included 16 randomized controlled trials.
We found psychological interventions significantly reduced fear of cancer
recurrence. Subgroup analyses indicated that mindfulness and acceptance therapy-
based interventions reduced fear of cancer recurrence, whereas cognitive-
behavioural therapy combined with psychoeducation did not. Interventions with three
to eight sessions were effective, while interventions with nine or more sessions
were not. Face-to-face interventions were effective, whereas online interventions
were not. The quality of evidence for fear of cancer recurrence was evaluated as
moderate due to moderate heterogeneity in the included studies. Conclusions
Psychological interventions were effective in reducing fear of cancer recurrence in
breast cancer survivors. Mindfulness and acceptance therapy-based interventions and
short-term interventions are recommended. Future well-designed randomized
controlled trials aiming to examine the effectiveness of psychological
interventions in reducing fear of cancer recurrence are needed. Impact The findings
of this systematic review may guide the development of psychological interventions
and encourage the use of psychological interventions for reducing fear of cancer
recurrence in breast cancer survivors.
In 1 year, COVID-19 spread rapidly worldwide affecting all societies and most age-
groups. It has taken not only a toll of human lives (approaching 220 million people
infected with 4.55 million reported deaths at time of writing) but also decimated
every economy as countries struggle to control infection rates by introducing
draconian lockdown and social distancing measures, bringing great suffering well
beyond medical effects of the disease. A parallel pandemic has resulted in a deluge
of information emanating from both scientific as well as international news media
including social media platforms. Fact and fiction, reality, and perception have
become entangled; the only realistic solution, both medically as well as
politically, is concerted global vaccination (which is currently underway) to
reduce further infection by introducing universal immunity. However, public
controversy rages due to widespread apprehension regarding necessity, immediate
risks, and long-term safety of what is perceived as "fast-tracked" medication.
While some concerns may be justified, much is due to misconception and
misunderstanding. This review highlights some of the issues concerning the handling
of the COVID-19 crisis by governments worldwide, the medical and scientific
communities, and the media and how this may have laid the foundations for a far
greater medical, social, and economic burden in the coming years. We present
comparative data to challenge current conceptions of this disease in the more
general con- text of human health to provide a perspective that seems to have been
lost in the general panic. We need more rational approaches to the handling of a
disease which is unlikely to disappear from our spectrum of afflictions even after
the magnifying glass has been removed. (C) 2021 The Author(s).
Objective Care for fear of cancer recurrence (FCR) is considered the most common
unmet need among cancer survivors. Yet the prevalence of FCR and predisposing
factors remain inconclusive. To support targeted care, we provide a comprehensive
overview of the prevalence and severity of FCR among cancer survivors and patients,
as measured using the short form of the validated Fear of Cancer Recurrence
Inventory (FCRI-SF). We also report on associations between FCR and clinical and
demographic characteristics. Methods This is a systematic review and individual
participant data (IPD) meta-analysis on the prevalence of FCR. In the review, we
included all studies that used the FCRI-SF with adult (>= 18 years) cancer
survivors and patients. Date of search: 7 February 2020. Risk of bias was assessed
using the Joanna Briggs Institute critical appraisal tool. Results IPD were
requested from 87 unique studies and provided for 46 studies comprising 11,226
participants from 13 countries. 9311 respondents were included for the main
analyses. On the FCRI-SF (range 0-36), 58.8% of respondents scored >= 13, 45.1%
scored >= 16 and 19.2% scored >= 22. FCR decreased with age and women reported more
FCR than men. FCR was found across cancer types and continents and for all time
periods since cancer diagnosis. Conclusions FCR affects a considerable number of
cancer survivors and patients. It is therefore important that healthcare providers
discuss this issue with their patients and provide treatment when needed. Further
research is needed to investigate how best to prevent and treat FCR and to identify
other factors associated with FCR. The protocol was prospectively registered
(PROSPERO CRD42020142185).
Background: Virtual reality (VR) is used as a distraction measure during painful
clinical procedures associated with the use of needles. These procedures include
vaccinations, blood draws, or the administration of medications, which can cause
children to feel increased levels of pain and fear. Objective: The objective of
this study was to collect and analyze the current evidence regarding the
effectiveness of VR as a tool to distract children from pain and fear during needle
procedures as compared to that of standard techniques. Methods: A systematic review
and meta-analysis was performed. We included randomized clinical trials (RCTs) or
quasi-RCTs with participants younger than 21 years who underwent needle procedures
in which the main distraction measure used was VR and where the main outcome
measure was pain. The databases searched included the PubMed, Web of Science,
Scopus, PsycINFO, CINAHL, and Cochrane libraries. In this systematic review, the
studies were analyzed by applying the Critical Appraisal Skills Program guide in
Spanish and the Jadad scale. In the meta-analysis, the effect size of the studies
was analyzed based on the results for pain and fear in children. Results: From 665
unique search results, 21 studies were included in this systematic review, most of
which reported low methodological quality. The study sample cohorts ranged from a
minimum of 15 participants to a maximum of 220 participants. Ten studies were
included in the meta-analysis. The global effect of using VR as a distraction
measure was a significant reduction in pain (inverse variance [IV] -2.37, 95% CI -
3.20 to -1.54; Z=5.58; P<.001) and fear (IV -1.26, 95% CI -1.89 to -0.63; Z=3.92;
P<.001) in children in the experimental groups. Conclusions: The quality of the
studies was mostly low. The main limitations were the impossibility of blinding the
participants and health care personnel to the VR intervention. Nonetheless, the use
of VR as a distraction measure was effective in reducing pain and fear in children
during procedures involving needles.
Objective To synthesize recent empirical evidence for the prevention and management
of falls and fear of falling in patients with Parkinson's disease (PD). Data source
Database from PubMed, Cochrane Library, and EMBASE. Study design Systematic review.
Data collection We searched the PubMed, Cochrane Library, and EMBASE databases for
studies published from inception to February 27, 2021. Inclusion criteria were
nonreview articles on prevention and management measures related to falls and fall
prevention in Parkinson's disease patients. Principal findings We selected 45
articles and conducted in-depth research and discussion. According to the causes of
falls in PD patients, they were divided into five directions, namely physical
status, pre-existing conditions, environment, medical care, and cognition. In the
cognitive domain, we focused on the fear of falling. On the above basis, we
constructed a fall prevention model, which is a tertiary prevention health care
network, based on The Johns Hopkins Fall Risk Assessment Tool to provide ideas for
the prevention and management of falling and fear of falling in PD patients in
clinical practice Conclusions Falls and fear of falls in patients with Parkinson's
disease can be reduced by effective clinical prevention and management. Future
studies are needed to explore the efficacy of treatment and prevention of falls and
fear of falls.
Post-traumatic stress disorder (PTSD) is a unique clinical mental abnormality
presenting a cluster of symptoms in which patients primarily experience flashbacks,
nightmares and uncontrollable thoughts about the event that triggered their PTSD.
Patients with PTSD may also have comorbid depression and anxiety in an intractable
and long-term course, which makes establishing a comprehensive treatment plan
difficult and complicated. The present article reviews current pharmacological
manipulations for adjusting abnormal fear memory. The roles of the central
monoaminergic systems (including serotonin, norepinephrine and dopamine) within the
fear circuit areas and the involvement of the hypothalamic-pituitary-adrenal (HPA)
axis and glucocorticoid receptor (GR) are explored based on attempts to integrate
current clinical and preclinical basic studies. In this review, we explain how
these therapeutic paradigms function based on their connections to stages of the
abnormal fear memory process from condition to extinction. This may provide useful
translational interpretations for clinicians to manage PTSD.
Fear of falling (FoF) results in social, functional, physical, and psychological
symptoms, including secondary disorders, such as depression and general anxiety
disorder (GAD). A vicious cycle develops, where symptoms maintain and reinforce FoF
and its consequences, including increasing the risk of falling. In this position
paper, we suggest screening for FoF using the falls efficacy scale international
(FES-I) questionnaire. The presence of a high score (> 23) warrants an
investigation into frailty and exclusion of depression and GAD, during the clinical
interview. Stratifying frailty, based on the Fried frailty criteria will guide
treatment options based on the most significant health concerns. Frail older adults
should first receive physiotherapy and exercise interventions, as physical
disabilities are their most significant characteristic, while pre-frail and non-
frail older adults should receive multicomponent interventions, consisting of
cognitive behavioral therapy (CBT) with physical exercise. The non-frail with
predominantly GAD and depression should receive specialized CBT interventions.
Currently, only exercise interventions are available for FoF treatment in
Switzerland. Although some exercise interventions use CBT elements, such as goal
setting and reflections on behavior and feelings, they are not systematically used,
are not part of a quality-assured procedure, and do not address the psychological-
cognitive aspects of FoF. As the pre-frail and non-frail are the largest groups to
use these services, adapting current exercise programs by incorporating a CBT
component would be the most practical means to provide optimized care.
Purpose Fear of falling (FoF) is a common and debilitating problem for older
people. Most multicomponent interventions show only moderate effects. Exploring the
effective components may help in the optimization of treatments for FoF. Materials
and methods In a systematic review of five scientific literature databases, we
identified randomized controlled trials with older community-dwelling people that
included FoF as an outcome. There was no restriction on types of interventions. Two
reviewers extracted information about outcomes and content of interventions.
Intervention content was coded with a coding scheme of 68 intervention components.
We compared all studies with a component to those without using univariate meta-
regressions. Results Sixty-six studies, reporting on 85 interventions, were
included in the systematic review. In the meta-regressions (n = 49), few components
were associated with intervention effects at the first available follow up after
the intervention, but interventions with meditation, holistic exercises (such as
Tai Chi or Pilates) or body awareness were significantly more effective than
interventions without these components. Interventions with self-monitoring, balance
exercises, or tailoring were less effective compared to those without these
components. Conclusions The identified components may be important for the design
and optimization of treatments to reduce FoF.
Fear of specific stimuli is thought to develop through associative learning
mechanisms and research indicates that a form of observational (vicarious) learning
known as positive modelling can counter these effects. This systematic review
examined and synthesised the experimental positive modelling literature to
establish its efficacy for reducing fear. Psych Info, Medline and the Psychology
and Behavioural Science Collection databases were systematically searched until
August 2021. Of the 1,677 papers identified, 18 experiments across 14 articles met
the inclusion criteria. In the majority of these, positive modelling was found to
lower fear levels in one or more of three procedures: fear prevention, fear
reduction and fear reversal. Procedures inform prevention and treatment initiatives
for specific phobias in several ways. The overall efficacy of positive modelling
techniques and the ease in which they can be implemented highlight the importance
of further research to evaluate their inclusion in prevention and treatment
interventions. More research is required to establish the longevity and
transferability of positive modelling.
Background: Caffeine has been purported to have anxiogenic and panicogenic
properties, specifically salient in patients with panic disorder (PD). However,
compilations of the magnitude of the effect of caffeine on anxiety and panic
attacks are lacking and potential dose-response relationships have not been
examined. Objectives: In the present systematic review and meta-analysis, we aimed
to examine the acute effects of placebo-controlled caffeine challenge on occurrence
of panic attacks and subjective anxiety in patients with PD and healthy controls
(HC), including dose-response relationships. Methods: Systematic searches were
performed in six databases. We included blinded placebo-controlled studies of acute
caffeine challenge on panic attacks and/or subjective anxiety in adult patients
with PD. Results: Of the 1893 identified articles, ten met our inclusion criteria.
The 9 studies investigating panic attacks included 237 patients, of which 51.1% had
a panic attack following caffeine, but none after placebo. Six of these studies
compared 128 patients with 115 healthy controls (HC), finding that patients (53.9%)
were more vulnerable than HC (1.7%) for panic attacks following caffeine (log RR:
3.47; 95% CI 2.06-4.87). Six studies investigated subjective anxiety in 121
patients and 111 HC following caffeine, with an overall effect indicating increased
sensitivity to the anxiogenic effects of caffeine in the patient group (Hedges' g =
1.02 [95% CI: 0.09-1.96]). The restricted range of caffeine employed [400-750 mg]
and few studies (3) not using 480 mg prevented any meaningful analysis of a dose-
response relationship. Limitations: Of the ten studies included, only 2 reported
anxiety data for the placebo condition, precluding a proper meta-analysis comparing
anxiogenic effects of caffeine and placebo. The restricted dose range used
prevented assessment of dose-response relationships. Conclusions: The results
confirm that caffeine at doses roughly equivalent to 5 cups of coffee induces panic
attacks in a large proportion of PD patients and highly discriminates this
population from healthy adults. Caffeine also increases anxiety in PD patients as
well as among healthy adults at these doses although the exact relationship between
caffeine-induced anxiety and panic attacks remains uncertain. The results suggest
that caffeine targets important mechanisms related to the pathophysiology of PD.
Fear of cancer recurrence (FCR) is a normal response in cancer survivors and one of
the most prevalent reactions reported by up to 87% of them. However, elevated
levels of FCR impair well-being, quality of life and professional functioning, and
lead to anxiety, depression or PTSD. COVID-19 pandemic can exacerbate FCR symptoms,
given the restricting access to follow-up investigations and treatment, the
isolation restrictions imposed and the possibility of the medical system becoming
overworked. This scoping review's objective was to synthesize the literature
investigating the factors associated with higher levels of FCR in cancer survivors
during the COVID-19 pandemic. The focus was on FCR in breast cancer patients,
including most of the studies (5 out of 9) on this topic. However, given the
novelty of the subject, the increased interest in it, and the fact that there are
few studies in this field, the review included 4 other studies with mixed samples
of patients with breast cancer and other oncological pathologies. Following
rigorous methodological criteria, 9 studies with quantitative or mixed methodology
were included (N = 4831 patients). The results indicate that high levels of FCR are
associated with distress and concerns regarding the pandemic impact, with most
common concerns of patients being changes in treatment plan (delays and
interruptions), dysfunctional communication with medical staff or difficult access
to food or medicine. The most common correlates of FCR during the pandemic are
marital status, childlessness, low financial status, level of education, type of
cancer diagnosis, generalized anxiety and depression.
Purpose The impact of prostate cancer on the mental wellbeing of patients is
increasingly being appreciated. Two important aspects of this include fear of
cancer recurrence (FCR) and prostate-specific antigen (PSA) anxiety. However, their
prevalence, severity and associating factors remain poorly understood. Therefore,
this review aims to evaluate the current evidence for the prevalence, severity and
associating features of PSA anxiety and FCR. Methods A systematic search of
MEDLINE, EMBASE and PsycINFO databases was conducted by two independent reviewers.
Observational studies measuring FCR and PSA anxiety in prostate cancer using
validated measures were included. Outcome measures were prevalence of significant
levels, mean scores and significant correlations of FCR and PSA anxiety scores with
patient, disease, treatment or other mental health and quality of life outcomes.
Results One thousand one hundred forty-eight individual records underwent screening
with 32 studies included. Median prevalence of significant FCR and PSA anxiety was
16% and 22% respectively across all studies. Longitudinal studies demonstrated
severity of both symptoms peaks at diagnosis, with little variability, even several
years following this. Evaluating associating factors revealed younger age,
generalised quality of life and mental health symptoms to be important factors for
both outcomes. Few studies evaluated associations and differences between other
patient, disease and treatment characteristics. Conclusion FCR and PSA anxiety are
prominent symptoms for prostate cancer patients and importantly when present, are
associated with poorer quality of life and mental health symptoms. Screening for
these constructs and referral to appropriate services should form part of routine
follow-up care.
Purpose Molar Incisor Hypomineralization (MIH) are first molars with developmental
enamel defects and are common findings in many child populations. The porous nature
of MIH enamel and the presence of post-eruptive enamel breakdown leads to the
presence of hypersensitivity and pain, which is often the patient's main complaint
and can result in dental fear and affect the quality of life. The present review
aims to summarise the evidence for the ability of MIH to cause problems, such as
dental fear and anxiety (DFA) and to summarise the evidence for a possibly negative
impact on the oral health-related quality of life (OHRQoL) of MIH affected children
and adolescents, in a systematic review. Method Two searches, (1) MIH AND dental
anxiety and (2) MIH AND Quality of life, were performed in MEDLINE/PubMed and
Scopus. Selection demands were fulfilling the MIH diagnosis criteria using
validated instruments and questionnaires for assessing DFA and OHRQoL,
respectively. Results After removing duplicates and articles not fulfilling the
selection demands, 6 studies concerning MIH and DFA and 8 studies concerning MIH
and OHRQoL remained. Conclusion Children and adolescents with diagnosed MIH did not
seem to suffer from increased dental fear and anxiety, but indicated an impaired
oral health-related quality of life.
This review aims to shed light on the symptoms of obsessive-compulsive disorder
(OCD) with a focus on contamination fears. In addition, we will briefly review the
current therapies for OCD and detail what their limitations are. A key focus will
be on discussing how smartphone solutions may provide approaches to novel
treatments, especially when considering global mental health and the challenges
imposed by rural environments and limited resources; as well as restrictions
imposed by world-wide pandemics such as COVID-19. In brief, research that questions
this review will seek to address include: (1) What are the symptoms of
contamination-related OCD? (2) How effective are current OCD therapies and what are
their limitations? (3) How can novel technologies help mitigate challenges imposed
by global mental health and pandemics/COVID-19.
Introduction Low back pain and neck pain are leading causes of disability. Although
several studies have examined the effect of exercise on fear of movement in people
with spine-related pain, the overall evidence supporting the beneficial effect of
different forms of exercise on fear of movement remains unknown. This systematic
review will determine the strength of evidence for the effect of exercise/physical
activity on fear of movement in people with non-specific spine-related pain.
Methods/analysis This review protocol was developed following the Preferred
Reporting Items for Systematic Reviews and Meta-Analysis Protocols. The review will
include randomised controlled trials and non-randomised studies that recruited
adults (>= 18 years) with chronic non-specific spine-related pain and where a
validated measure of fear of movement/kinesiophobia such as the Tampa Scale of
Kinesiophobia (TSK) and the Fear Avoidance Behaviour Questionnaire (FABQ) or any
other validated measures to ascertain fear of movement/kinesiophobia was employed.
Bibliographic databases include MEDLINE, PsycINFO, EMBASE, CINAHL, ZETOC, Web of
Science, PubMed and Google Scholar as well as key journals/grey literature will be
searched from inception to 31 January 2022. Only articles published in English will
be considered eligible. Two independent reviewers will search, screen studies,
extract data and assess risk of bias. Preintervention and postintervention mean and
SD with 95% CI of the outcome data (TSK or FABQ) will be extracted or estimated
where possible. If possible, study results will be pooled into a meta-analysis. A
narrative synthesis of the results will be presented if heterogeneity is high. The
overall quality of evidence and risk of bias will be assessed using the Grading of
Recommendations Assessment, Development and Evaluation and Risk Of Bias in Non-
randomised Studies of Interventions guidelines. Ethics and dissemination This
systematic review does not require ethical approval as existing data will be used.
The results will be disseminated through a peer-reviewed journal and via national
and international conferences. PROSPERO registration number CRD42021295755.
Objective To review concepts, definitions, and findings about fear of childbirth
(FOC). Methods A bibliographic review was carried out through the main scientific
databases in 2020. Results All 32 articles considered potentially relevant were
analyzed. A recent study suggests that the global prevalence of FOC can reach up to
14%. Factors such as parity, gestational age, previous birth experience, age and
nationality of the woman seem to influence FOC. Conclusion Fear of childbirth could
be related to an increased risk of adverse obstetric outcomes such as maternal
request for cesarean delivery, preterm birth, prolonged labor, postpartum
depression, and post-traumatic stress. These evidence highlight the importance of
the discussion regarding this topic.
Disorders of arousal (DOA) is an umbrella term initially covering classical
sleepwalking, sleep terrors, and confusional arousals, and now including a wider
spectrum of specialised forms of non rapid eye movement (non REM) parasomnias such
as sexsomnia, sleep-related eating disorder, and sleep-related choking syndrome.
Growing evidence has shown that DOA are not restricted to children but are also
prevalent in adults (2%-4% of the adult population). While DOA run in family,
genetics studies remain scarce and inconclusive. In addition to the risk of injury
on themselves and others (including sexual assaults in sexsomnia), adults with DOA
frequently suffer from excessive daytime sleepiness, pain, and altered quality of
life. The widespread view of DOA as automatic and amnesiac behaviours has now been
challenged by subjective (dream reports) and objective (dream-enacting behaviours
documented on video-polysomnography) observations, suggesting that sleepwalkers are
'dream walking' during their episodes. Behavioural, experiential, cognitive, and
brain (scalp electroencephalography [EEG], stereo-EEG, high density-EEG, functional
brain imaging) data converge in showing a dissociated pattern during the episodes.
This dissociated pattern resembles the new concept of local arousal with a wake-
like activation in motor and limbic regions and a preserved (or even increased)
sleep intensity over a frontoparietal network. EEG and behavioural criteria
supporting the DOA diagnosis with high sensitivity and specificity are now
available. However, treatment is still based on controlling priming and
precipitating factors, as well as on clinicians' personal experience with sedative
drugs. Placebo-controlled trials are needed to improve patients' treatment. DOA
deserve more attention from sleep researchers and clinicians.
Accumulating evidence indicates that the cerebellum is critically involved in
modulating non-motor behaviors, including cognition and emotional processing. Both
imaging and lesion studies strongly suggest that the cerebellum is a component of
the fear memory network. Given the well-established role of the cerebellum in
adaptive prediction of movement and cognition, the cerebellum is likely to be
engaged in the prediction of learned threats. The cerebellum is activated by fear
learning, and fear learning induces changes at multiple synaptic sites in the
cerebellum. Furthermore, recent technological advances have enabled the
investigation of causal relationships between intra- and extra-cerebellar circuits
and fear-related behaviors such as freezing. Here, we review the literature on the
mechanisms underlying the modulation of cerebellar circuits in a mammalian brain by
fear conditioning at the cellular and synaptic levels to elucidate the
contributions of distinct cerebellar structures to fear learning and memory. This
knowledge may facilitate a deeper understanding and development of more effective
treatment strategies for fear-related affective disorders including post-traumatic
stress or anxiety related disorders.
Recent work has revealed that social support cues are powerful inhibitors of the
fear response. They are endowed with a unique combination of inhibitory properties,
enabling them to both inhibit fear in the short term and reduce fear in the long
term. While these findings had previously been thought to suggest that social
support cues belong to a category of prepared safety stimuli, mounting evidence
clearly shows that the mechanisms underlying safety signaling cannot account for
the unique effects of social support cues. Here, we propose a reclassification of
social support cues as members of a prepared fear suppressor category. We present
an argument for the prepared fear suppressor classification, discuss potential
mechanisms underlying the unique effects of prepared fear suppressors, and outline
next steps to build an understanding of this category and its clinical
implications. This review is meant to serve as a roadmap for exploring this novel
category of prepared fear suppressors, whose never-before-seen range of inhibitory
effects makes them an important and impactful discovery with implications for both
fear learning theory and clinical application.
New neurons are continuously generated and functionally integrated into the dentate
gyrus (DG) network during the adult lifespan of most mammals. The hippocampus is a
crucial structure for spatial learning and memory, and the addition of new neurons
into the DG circuitry of rodents seems to be a key element for these processes to
occur. The Morris water maze (MWM) and contextual fear conditioning (CFC) are among
the most commonly used hippocampus-dependent behavioral tasks to study episodic-
like learning and memory in rodents. While the functional contribution of adult
hippocampal neurogenesis (AHN) through these paradigms has been widely addressed,
results have generated controversial findings. In this review, we analyze and
discuss possible factors in the experimental methods that could explain the
inconsistent results among AHN studies; moreover, we provide specific suggestions
for the design of more sensitive protocols to assess AHN-mediated learning and
memory functions.
Few topics have drawn more attention nor elicited as much debate within the fields
of Atlantic History, Slavery Studies, and African Diaspora Studies than slave
resistance and rebellion. Since at least the 1940s, scholars have argued about what
constitutes resistance, what motivated slave rebels, agency, and how best to
approach the documentary record among many other topics. More so than in most
subfields, scholarship on slave resistance often resonates with contemporary
political and cultural movements for racial equity. This review essay considers
three new works on slave resistance.
Background: Parental dental fear and anxiety (DFA) is an important factor, which
has an impact on adolescence receiving dental treatment and maintenance of their
oral health. It is necessary to recognize and know how parental DFA affects the
dental treatment of children and adolescents. Aim: This narrative review was
planned with the objective of evaluating parental DFA influence on adolescent
dental treatment. Materials and Methods: A broad search of literature published
between 2005 and 2021 from electronic databases through Scopus, PubMed, Web of
Science, Google Scholar was performed. We included the studies in which parental
dental anxiety was a major criterion affecting different dental health conditions.
Articles referring to adolescents facing different oral health problems were also
included. This narrative review included 12 articles of which 8 cross-sectional
studies, 3 longitudinal studies, and 1 descriptive study, all of which met the
inclusion criteria and the specified age group of adolescents ranging between 10
and 19 years. Results: After screening 83 abstracts, 12 articles were selected,
which included all the inclusion criteria. In this study, we found that parental
DFA showed a positive association with their adolescent's DFA, which hinders the
dental treatment received. Conclusion: Parental DFA influences the adolescent
behavior and can impact the seeking of dental treatment. Hence, it is important to
address parental DFA prior to the intervention and treatment. An appropriate
address will facilitate in reducing or eliminating DFA in adolescents.
The aim of this review is to synthesize qualitative research on the lived
experiences of grandchildren of Holocaust survivors (GHSs). A systematic search
yielded 18 studies covering a period of two decades. Four main themes emerged; (i)
the responsibility to teach and transfer the Holocaust legacy to future
generations, (ii) experiences of family life, (iii) struggles integrating the
Holocaust-related past into current life and (iv) fears and anxieties. Findings
highlight the role of trauma related communication within families of survivors in
the transmission of the trauma narratives. Implications for trauma informed
practice are discussed.
Background Fear of cancer recurrence (FCR) is the most prevalent need among breast
cancer survivors. Age is the most consistent predictor of higher FCR, with
prevalence rates as high as 70% among young adults. Although the association
between age and higher FCR is well established, a more comprehensive understanding
of the factors contributing to higher FCR among young adult breast cancer survivors
is needed. Objective The purpose of this integrative review was to explore the
factors associated with higher FCR among young adult breast cancer survivors (<= 45
years old). Methods A literature search was conducted using PubMed, CINAHL,
PsycINFO, and EMBASE databases with specific Medical Subject Headings terms
delimited to FCR, diagnosis, sex, and age range. The initial search yielded 378
studies, 13 of which met the eligibility criteria. Results Themes include
motherhood status, health behaviors and decision making (eg, surveillance behaviors
and surgical decision making), psychological morbidity, and social support.
Cognitive behavioral factors include cognitive processing, metacognition, illness
intrusiveness, and self-efficacy. Conclusion Fear of cancer recurrence among young
adult breast cancer survivors is a unique construct requiring further exploration
and tailored interventions to improve the health-related quality of life for this
population. Implications for Practice Oncology nurses should screen all cancer
survivors for FCR, with particular attention to the unique needs of young adults.
Future research should address the role of age-appropriate support and increased
levels of FCR during surveillance periods.
Fear-related disorders, mainly phobias and post-traumatic stress disorder, are
highly prevalent, debilitating disorders that pose a significant public health
problem. They are characterized by aberrant processing of aversive experiences and
dysregulated fear extinction, leading to excessive expression of fear and
diminished quality of life. The gold standard for treating fear-related disorders
is extinction-based exposure therapy (ET), shown to be ineffective for up to 35% of
subjects. Moreover, ET combined with traditional pharmacological treatments for
fear-related disorders, such as selective serotonin reuptake inhibitors, offers no
further advantage to patients. This prompted the search for ways to improve ET
outcomes, with current research focused on pharmacological agents that can augment
ET by strengthening fear extinction learning. Hallucinogenic drugs promote
reprocessing of fear-imbued memories and induce positive mood and openness,
relieving anxiety and enabling the necessary emotional engagement during
psychotherapeutic interventions. Mechanistically, hallucinogens induce dynamic
structural and functional neuroplastic changes across the fear extinction circuitry
and temper amygdala's hyperreactivity to threat-related stimuli, effectively
mitigating one of the hallmarks of fear-related disorders. This paper provides the
first comprehensive review of hallucinogens' potential to alleviate symptoms of
fear-related disorders by focusing on their effects on fear extinction and the
underlying molecular mechanisms. We overview both preclinical and clinical studies
and emphasize the advantages of hallucinogenic drugs over current first-line
treatments. We highlight 3,4-methylenedioxymethamphetamine and ketamine as the most
effective therapeutics for fear-related disorders and discuss the potential
molecular mechanisms responsible for their potency with implications for improving
hallucinogen-assisted psychotherapy.
Background The negative effects of bullying, discrimination, harassment, and sexual
harassment (BDHS) on well-being and productivity of surgical residents in training
have been well documented. Despite this, little has changed over the past decade
and these behaviors continue. The purpose of this study was to determine the
prevalence of each abusive behavior experienced by residents, identify the
perpetrators, and examine the reporting tendency. Methods A systematic review of
articles published between 2010 and 2020 in the MEDLINE, EMBASE, and Cochrane
databases was performed following PRISMA guidelines. The following search terms
were used: bullying, harassment, sexual harassment, discrimination, abuse,
residency, surgery, orthopedic surgery, general surgery, otolaryngology,
obstetrics, gynecology, urology, plastic surgery, and training. Results Twenty-five
studies with 29,980 surgical residents were included. Sixty-three percent, 43, 29,
and 27% of surgical residents experienced BDHS, respectively. Female residents
reported experiencing all BDHS behaviors more often. Thirty-seven percent of
resident respondents reported burnout, and 33% reported anxiety/depression.
Attending surgeons, followed by senior co-residents, were the most common
perpetrators. Seventy-one percent did not report the behavior to their institution.
Fifty-one percent stated this was due to fear of retaliation. Of those who reported
their experiences, 56% stated they had a negative experience reporting. Conclusion
Our review demonstrates high prevalence rates of BDHS experienced by residents
during surgical training, which have been associated with burnout, anxiety, and
depression. The majority of residents did not report BDHS due to fear of
retaliation. Residency programs need to devise methods to have a platform for
residents to safely voice their complaints.
Objectives Fear of falling is common among older adults and can increase fall-risk
through premature activity restriction. Exergames, an emerging tool in fall
prevention, combine exercise with interactive and adaptive game elements. This
review examines the extent to which exergame interventions reduce fear of falling
among community-dwelling older adults. Method: Guided by the PRISMA methodology, we
reviewed peer-reviewed studies that were published in English between 2006 and 2019
and employed a comparative design to test the effect of exergames on fear of
falling in community-dwelling older adults. Two reviewers screened the literature
and extracted data on the exergame platform, participants, study design, and
results. A modified PEDro scale was used to assess study quality. Disagreements
were resolved through discussion with the third reviewer. Results: Our literature
search resulted in 23 eligible studies on exergame interventions where fear of
falling was the primary or secondary outcome. Most interventions (35%) occurred
within hospitals and were delivered via a Wii-based system (61%). Fear of falling
was most commonly measured using the Falls Efficacy Scale, the Activities-specific
Balance Scale and their modified versions. A total of 15 of the 23 studies reported
statistically significant changes in fear of falling. Quality assessment showed 10
studies to be rated as 'good.' Conclusion: This review showed that exergame may
have a positive effect in reducing fear of falling in community-dwelling older
adults. The finding provides a direction for clinical practice in the research area
of intervention on fear of falling in older adults.
The aim was to systematically review the effects of gaming on pain-related fear,
pain catastrophizing, anxiety, and depression in patients with chronic
musculoskeletal pain. Databases (Medline, EMBASE, PsycInfo, CINAHL, Cochrane
Central Register for Controlled Trials [CENTRAL], Web of Science, and SCOPUS) were
searched from inception up to October 2021. Two reviewers independently selected
randomized controlled trials that compared the effects of any gaming modality with
other interventions or no treatment on pain-related fear, pain catastrophizing,
anxiety, and depression. For data synthesis, Standardized Mean Differences (SMDs)
and 95% confidence interval (CI) were calculated using a random-effects inverse
variance model for meta-analysis according to the outcome of interest, comparison
group, and follow-up period. The level of evidence was synthesized using Grading of
Recommendations, Assessment, Development, and Evaluations (GRADE). Thirteen studies
were included with a total sample of 680 patients. Gaming was superior to other
treatments and no treatment on reducing pain-related fear (SMD: -1.23; 95% CI: -
2.02 to -0.44) and anxiety (SMD: -0.55; 95% CI: -1.01 to -0.09), respectively.
Gaming was not superior to other treatments on reducing pain catastrophizing,
anxiety, and depression, and it was not superior to no treatment on reducing pain-
related fear, pain catastrophizing, and depression. Those findings were based on
very low or low-quality evidence. In a conclusion, gaming modalities may have
positive effects on some mental health outcomes. However, there were conflicting
results with low-quality evidence, which indicates that more high-quality
randomized controlled trials are needed.
Introduction: Depression rates in older people worldwide vary from 10% to 15% of
community-dwelling older persons. There are two others problems related to
depression in old age, namely the high incidence of falls and the so-called fear of
falling (FOF), with a prevalence ranging from 20% to 85%; it was initially
considered a postfall syndrome, which later as a fall-independent event. Aims:
Study aims to conduct a systematic review and meta-analysis to bridge the existing
gap in literature about the association between depressive symptomatology, FOF, use
of antidepressant therapy and falls, also identifying a possible effect of the
study quality on the outcome. Methods: The selection of studies was carried out
between May 20, 2020, and July 27, 2020 and only observational clinical trials,
written in English, with participants aged more or equal to 60 years affected by
diagnosis of depression or treatment for depression mentioned both as a clinical
diagnosis in older patient, and as a predictor/consequence of falls were included.
The systematic review was performed according to the Preferred Reporting Items for
Systematic Reviews and Meta-Analysis (PRISMA) guidelines for reporting systematic
reviews and meta-analysis, and the protocol was recorded in the International
Prospective Register of Systematic Reviews (PROSPERO). Results and discussion: The
screening process ultimately led to the inclusion of 18 articles. Many of the
included studies showed that depressive symptoms caused the subsequent increase in
the number of falls. Results from the meta-analysis had no highlighted association
between depression and falls, in contrast to other review and metaanalysis works:
our work includes a substantial number of studies, with a relatively recent
publication date, including patients diagnosed with depression, clearly evaluating
the association between depression and falls. Results all seem to confirm the
hypothesis of an interdependent association between the presence of FOF and the
risk of fall, despite the high percentage of cross-sectional studies prevents
inferring on the direction of the association. Therapeutic interventions aimed at
decrease rate of falls reducing depressive symptoms and FOF.
It is a defining feature of anxiety disorders that fear is elicited by a
circumscribed class of stimuli rather than by only one specific exemplar of that
class. Therefore, fear generalization, a mechanism by which associative fear
extends from one conditioned stimulus to similar cues, has been central to theories
on anxiety. Yet, experimental evidence for the link between generalization and
pathological anxiety, as well as its moderators, has not been formally integrated.
This systematic review and meta-analysis of empirical findings clarifies the
relationship between fear generalization and pathological anxiety. In conclusion,
enhanced fear generalization is associated with several anxiety disorders and
stress-related disorders, which is supported statistically by a small, but robust
effect size of g = 0.44 for risk ratings as an index of fear generalization.
However, empirical results are inconsistent across disorders and they rarely allow
for conclusions on their causality in the disorders' etiology. Therefore, based on
theoretical considerations, we recommend directions for intensified research,
especially on the causal relationship between overgeneralization and pathological
fear.
Objective Fear of falling (FOF) contributes to activity restriction and
institutionalization among older adults, and exercise interventions are linked to
reduction in FOF. Adhering to exercise principles and adapting optimal exercise
parameters are fundamental to optimizing the effectiveness of exercise
interventions. The purpose of this review was to describe FOF exercise
interventions in community-dwelling older adults, evaluate the extent to which
these interventions followed the exercise principles and reported exercise
parameters, and quantify the effect of these interventions on reducing FOF. Methods
Randomized controlled trials (RCTs) of FOF exercise interventions in older adults
(>= 65 years) were identified from 4 databases. The methodological quality of RCTs
was assessed using the Physiotherapy Evidence Database scale. A random-effect model
was used in the meta-analysis. Results Seventy-five RCTs were included in this
review. With regard to reporting exercise principles, specificity was reported in
92% of trials, progression in 72%, reversibility in 32%, overload in 31%,
diminished return in 21%, and initial value in 8%. For exercise parameters, 97% of
RCTs reported exercise type; 89%, frequency; and 85%, time. Only 25% reported the
intensity. The pooled effect of exercise interventions on FOF among all included
studies was a standard mean difference of -0.34 (95% CI = -0.44 to -0.23).
Conclusion This study showed a significant small to moderate effect size of
exercise interventions in reducing FOF among community-dwelling older adults. Most
exercise principles and intensity of exercises were not adequately reported in
included trials. Impact These inadequate reports could undermine efforts to examine
the optimal dosage for exercise prescription. More attention must be given to
designing and reporting components of therapeutic exercise programs to facilitate
evidence-based practice.
In research spanning three decades we have estimated brain monoamine turnover
(approximately equating with synthesis rate) with sampling from the internal
jugular veins and measurement of trans-cerebral plasma monoamine metabolite
concentration gradients. Here we report indices of brain noradrenaline and
serotonin turnover in patients with major depressive illness (MDD) and panic
disorder (PD). Brain noradrenaline turnover was assessed from the combined flux
into the internal jugular veins of the metabolites dihydroxyphenylglycol (DHPG) and
3-hydroxy-4-methoxyphenylglycol (MHPG), and brain serotonin turnover from the
overflow of the primary metabolite, 5-hydroxyindole acetic acid (5HIAA). Comparison
was made with matched healthy research participants. In both MD and PD the estimate
of brain noradrenaline turnover provided by metabolite overflow was unremarkable.
In contrast, in both patient groups the estimate of brain serotonin turnover
provided by 5HIAA overflow was increased 3-4-fold (P < 0.01). This neurotransmitter
abnormality was normalized in MDD and PD in clinical remission, during selective
serotonin reuptake blocker (SSRI) dosing. We cannot be sure if the brain
serotonergic abnormality we find in MDD and PD is causal or a correlate.
Measurements in PD were not made during a panic attack. The increased estimated
serotonin turnover here may possibly be a substrate for panic attacks; serotonergic
raphe nuclei participate in anxiety responses in experimental animals. It is
puzzling that the findings were identical in MDD and PD, although it may be
pertinent that these psychiatric diagnoses are commonly comorbid. It is unlikely
that activation of brain serotonergic neurons is driving the sympathetic nervous
activation present, which contributes to cardiovascular risk, persistent
sympathetic activation in MDD and episodic activation in PD during panic attacks.
We have previously demonstrated that the mechanism of activation of human central
sympathetic outflow in other contexts (hypertension, heart failure) is activation
of noradrenergic brainstem neurons projecting to the hypothalamus and amygdala.
Background Health care workers (HCWs) have been engaged in fighting dangerous
epidemics for hundreds of years, more recently in severe acute respiratory
syndrome, H1N1, Middle East respiratory syndrome, and now coronavirus disease 2019.
A consistent feature of epidemic disease results is that health care systems and
HCWs are placed under immense strain. Methods A focused narrative review was
conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses
guidelines to examine the main concerns and anxieties faced by HCWs during recent
epidemics and to determine the supports deemed most important to those HCWs to keep
them at the frontline. PubMed, Web of Science, and the Cochrane Library were
searched in March 2020 using terms "Healthcare" OR "Medical" AND "Staff" OR
"Workers" OR "Front line" AND "Concerns" OR "Anxiety" OR "Stress" AND "Pandemic" Or
"Epidemic." Results Twenty-five studies that reported the concerns and expectations
of an estimated 13,793 HCWs in 10 countries (Canada, China, Greece, Hong Kong,
Japan, Liberia, Netherlands, Saudi Arabia, Singapore and Taiwan) during pandemic
situations were identified. Health care workers identified personal and family
safety, appreciation, and the provision of personal protective equipment and
adequate rest as primary concerns. Informal psychological supports were favored
over formal employment-based group interventions. Discussion Despite being hailed
by the media as heroes, HCWs face social stigmatization and experienced high levels
of anxiety and fear regarding personal safety and the health of their colleagues
and family. Health care workers are more likely to seek peer-to-peer psychological
support but also benefit from knowing that formal psychological supports are
available to them.
We all want to be right in our thinking. Vaccine hesitancy and global warming
denial share much in common: (1) both are threats to personal, community and global
health, (2) action is contingent on co-operation and social policy, and (3) public
support relies on trust in science. The irony is, however, as the science has
become more convincing, public opinion has become more divided. A number of early
polls showed that ~70% of people supported COVID-19 vaccine use and global warming,
~20% adopted a wait-and-see approach, and ~10% were staunch objectors. Although
these percentages are approximate, what factors are responsible for the differences
in engagement, doubt and distrust? How can we reduce the consensus gap? One
approach is to return to grass roots and provide a brief history of the issues,
understand the difference between fact and opinion, truth and falsehood, the
problem of certainty, and how scientific consensus is reached. To doubt is a
healthy response to new information, and it too has a scientific basis. Doubt and
distrust reside in that region of the brain called the dorsolateral prefrontal
cortex, which is responsible for suppressing unwanted representations. Bridging the
consensus gap requires shifting human thinking patterns from doubt to belief, and
belief to action. Education and improved public messaging are key, and social media
providers require urgent oversight or regulation to remove false and
harmful/dangerous content from our digital lives. Delays to vaccinate and failure
to reduce greenhouse gases will dramatically change the way we live. The new norm
may be more deadly COVID variants, strained healthcare systems, extreme weather
patterns, diminished food supply, delays in goods and services, damage to world's
economies and widespread global instability.
Objective:The objective of this review was to map and analyze midwives'
interventions for reducing fear of childbirth in pregnant women. Introduction:Fear
of childbirth is a phenomenon negatively affecting women's health and well-being
before and during pregnancy. Over the past few decades, there has been growing
research interest in interventions for reducing fear of childbirth in pregnant
women. One of the challenges in midwifery care is to provide an appropriate model
of care for pregnant women with fear of childbirth. Further research efforts are
needed to identify midwives' interventions for reducing fear of childbirth in
pregnant women and to examine their characteristics. Inclusion criteria:This
scoping review considered studies that included midwives' interventions for
reducing fear of childbirth in pregnant women. Specifically, interventions were led
and/or implemented by midwives during the antenatal period, and integrating all
possible midwifery practice settings. Quantitative, qualitative, and mixed methods
studies were included. This review also considered systematic reviews, text and
opinion papers, and conference abstracts. Methods:The JBI methodology for
conducting scoping reviews was used. Published and unpublished literature in
English, Portuguese, and Spanish from January 1981 to October 2020 was included.
MEDLINE (PubMed), CINAHL Complete, APA PsycINFO, Scopus, Embase, Web of Science,
SciELO, MedicLatina, Academic Search Complete, ERIC, Psychology and Behavioral
Sciences Collection, and the Cochrane Library databases were searched. Searches for
gray literature were also undertaken on the Repositorio Cientifico de Acesso Aberto
de Portugal, ProQuest Dissertations and Theses, British Library EThOS, OvidSP
Resource Center, Banco de Teses da CAPES, and OpenGrey. A three-step search
strategy was followed, and the Preferred Reporting Items for Systematic Reviews and
Meta-Analysis extension for Scoping Reviews checklist was used. Two independent
reviewers extracted the data using a data extraction tool developed specifically
for this scoping review. Results:A total of 3704 articles were identified and
screened, of which 34 articles were included. The majority of studies had been
published in the past 10 years (88%) in Scandinavian countries or Australia (79%).
Several midwives' antenatal interventions were found, such as midwife-led team
models of care. Midwives played a facilitator role that varied across the included
studies. In 20 studies (59%), midwives led and implemented the interventions alone
(n = 13; 38%) or with the participation of other health professionals (n = 7; 21%).
In the remaining 14 studies (41%), midwives were part of a multidisciplinary team
that included different health professionals (mainly obstetricians and
psychologists) who had been involved in delivering interventions alongside midwives
or with minor participation from midwives. Counseling (n = 12; 35%) and
psychoeducation (n = 8; 24%) were the most common midwife interventions for
reducing fear of childbirth in pregnant women. Conclusions:Midwives working across
their full scope of practice play a pivotal role in reducing fear of childbirth,
which may explain the variety of midwives' antenatal interventions. Reducing fear
of childbirth in pregnant women and promoting normal childbirth as a positive
experience are key features of midwives' interventions, which should include
women's empowerment measures. Evidence-based midwife-led intervention programs for
pregnant women with fear of childbirth should be designed and tested to improve
clinical practice as well as women's reproductive outcomes and perinatal
experiences.
Objective We sought to determine whether acute delta 9-tetrahyrdrocannabidol (THC)
administration would facilitate fear extinction in young occasional cannabis users,
given that animal models indicate THC facilitates extinction learning, and recent
studies indicate THC administration may also enhance threat memory extinction in
humans. Methods On each of the 2 days, 24+ hour THC-deprived participants were
conditioned to fear visual stimuli in a delay conditioning and extinction paradigm.
Both CS+ and CS- were faces of negative emotional valence, with the CS+ paired with
mild electric shock. Throughout both conditioning and extinction paradigms, EEG was
measured to quantify event-related potentials for these learning processes.
Following conditioning, individuals, in a randomized and counter-balanced order,
smoked either an active THC cigarette (26.25 mg/2.7% THC) or a placebo marijuana
cigarette (0.002% THC) on 1 day and the opposite cigarette on the second day. After
smoking, CS+ and CS- were presented without shock, resulting in extinction of
conditioned fear. Results Relative to placebo, THC facilitated extinction of the
conditioned response to the CS+, as reflected by reductions in late positive
potential amplitude during extinction learning. Conclusions The results indicate
that acute THC administration may facilitate extinction of the conditioned fear
response in humans.
Metformin, a molecule belonging to the biguanide family, represents one of the most
commonly prescribed medications for the treatment of diabetes mellitus in the
world. Over the sixty years during which it has been used, many benefits have been
described, which are not limited to the treatment of diabetes mellitus. However,
since metformin is similar to other members of the same drug family, there is still
much concern regarding the risk of lactic acidosis. This article aims to highlight
the correlation between the use of metformin and the onset of renal damage or
lactic acidosis. Metformin-associated lactic acidosis exists; however, it is rare.
The appropriate use of the drug, under safe conditions, induces benefits without
risks.
Background/Objective: Fear of falling (FoF) and frailty are common problems in
older adults. FoF can lead to self-imposed restriction of activities and then
further decline in physical capacities that predispose older adults to frailty.
Evaluating the association of these two geriatric syndromes may be the first step
for understanding their complex relationship and might ultimately lead to
establishing therapeutic goals and guiding treatments for older adults with
frailty. This systematic review was conducted to provide evidence regarding the
association between FoF and frailty. Methods: All the articles that provided
information on the association between FoF and frailty were selected from PubMed,
Scopus, CINAHL, and EMBASE in search of relevant papers. Articles reporting
information on the association between FoF (exposure) and frailty (outcome), with
older adults (age >= 60 years) living in the community (ie, living either at home
or in places of residence that do not provide nursing care or rehabilitation) were
included. Only original articles with observational design (cross-sectional or
longitudinal/cohort) were included. The methodological quality of included articles
was evaluated independently by the two assessors through the Newcastle-Ottawa Scale
(NOS) and the Joanna Briggs Institute (JBI) critical appraisal checklist for
longitudinal and crosssectional studies, respectively. Results: The initial
searches found 4,342 articles, of which 10 articles were included in this review: 7
cross-sectional and 2 longitudinal studies, and 1 study with cross-sectional and
longitudinal analyses. The total sample was composed of 6,294 community-dwelling
older adults (61.8% women). Among the longitudinal studies, adjusted odds ratios
ranged from 1.18 (95% CI = 1.02; 1.36) to 9.87 (95% CI = 5.22; 18.68), while the
adjusted odds ratios of the cross-sectional studies ranged from 1.04 (95% CI =
1.02; 1.07) to 7.16 (95% CI = 2.34; 21.89). Conclusion: FoF increases the risk of
frailty in community-dwelling older adults. The knowledge of this association is of
utmost importance in clinical practice, since it can help health professionals in
the development of rehabilitation, prevention, and health promotion protocols. In
addition, these findings can contribute to the development of public health
policies and actions aimed at reducing the FoF and consequently the frailty.
Aim: The aim of this systematic review and meta-analysis was to evaluate the
association between sense of coherence (SOC) and dental fear/dental anxiety.
Methods: Computerized searches were performed in six databases. Gray literature and
manual searches were also conducted. Study selection, risk of bias assessment, and
meta-analyses were performed. The results of meta-analyses were reported in odds
ratio (OR), mean difference (MD), and confidence interval (CI). Results: After
removing duplicates, 131 references were retrieved and the full texts of 12 were
evaluated. Nine references met the eligibility criteria and were included. The
results of meta-analyses demonstrated that individuals with a weaker SOC had a
score in the dental anxiety/dental fear scale 6.04 times higher than individuals
with a stronger SOC (OR = 6.04, CI = 2.62-13.91). Individuals with no dental
anxiety/dental fear had a mean score of the SOC scale higher than individuals with
dental anxiety/dental fear (MD = 5.39, CI = 2.21-8.56). Sensitivity analysis
demonstrated that the result of a higher mean score of the SOC scale among
individuals with no dental anxiety/dental fear remained (MD = 7.38, CI = 3.79-
10.98). Risk of bias ranged from low to high. The certainty of evidence was very
low. Conclusion: Individuals with stronger SOC have lower levels of dental
fear/dental anxiety.
BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an FDA-approved,
noninvasive modality for treating major depressive disorder and obsessive-
compulsive disorder. Earlier studies evaluating therapeutic effects of rTMS on
symptom scores of patients with generalized anxiety disorder (GAD) and panic
disorder (PD) have yielded inconsistent findings. METHODS: We performed a
systematic review and meta-analysis of interventional studies assessing the effect
of rTMS on symptom scores in patients with GAD or PD with or without psychiatric
comorbidities using studies published up to April 2021. We used DerSimonian-Laird
random effects models to obtain pooled standardized mean difference (SMD) and 95%
CI. RESULTS: A total of 13 studies consisting of 677 participants (404 treated with
rTMS and 273 without rTMS) were included in this meta-analysis. In GAD patients
with or without any comorbidities, rTMS therapy demonstrated significant
improvements in anxiety (SMD = 1.45; P < .001) and depression (SMD = 1.65; P
< .001) scores regardless of rTMS parameters. Overall anxiety (SMD = 0.24; P = .48)
and panic severity (SMD = 1.19; P = .054) scores did not significantly improve
after rTMS therapy in patients with PD. CONCLUSIONS: rTMS is safe and improves
anxiety and depression scores only in GAD patients, regardless of underlying
comorbidities or rTMS parameters.
Context: Cognitive theories of anxiety-and fear-related pathology suggest that
individuals with these forms of pathology (versus those without) exhibit greater
threat-related attentional bias (AB). However, there are a multitude of mixed and
null findings in this area of research. Unlike other commonly used measures of AB,
eye tracking indices of AB exhibit acceptable reliability, and thus, may help
clarify the relationship between AB and anxiety-and fear-related symptoms.
Objective: The purpose of this study was to conduct a meta-analysis, to determine
whether there is evidence of a relationship between anxiety and fear-related
symptoms and expressions of threat-related AB (i.e., reflexive orienting and
maintenance) measured via free-viewing eye-tracking tasks. Data synthesis: A total
of 40 articles were retained for this meta-analysis. Significant relations were
observed between anxiety and fear-related symptoms and both reflexive orienting
toward threat (r = 0.13, 95% CI: 0.03, 0.22) and maintenance of attention on threat
(r = 0.15, 95% CI: 0.05, 0.25). Conclusions: Results from the present study
suggests that it may be important to develop attention bias modification
interventions that target AB at both early (bottom-up) and later (top-down) stages
of information processing to reduce anxiety-and fear-related pathology.
Background: Patients with cancer and survivors may experience the fear of cancer
recurrence (FCR), a preoccupation with the progression or recurrence of cancer.
During the spread of COVID-19 in 2019, patients and survivors experienced increased
levels of FCR. Hence, there is a greater need to identify effective evidence-based
treatments to help people cope with FCR. Remotely delivered interventions might
provide a valuable means to address FCR in patients with cancer. Objective: The aim
of this study is to first discuss the available psychological interventions for FCR
based on traditional cognitive behavioral therapies (CBTs) or contemporary CBTs, in
particular, mindfulness and acceptance and commitment therapy, and then propose a
possible approach based on the retrieved literature. Methods: We searched key
electronic databases to identify studies that evaluated the effect of psychological
interventions such as CBT on FCR among patients with cancer and survivors. Results:
Current evidence suggests that face-to-face psychological interventions for FCR are
feasible, acceptable, and efficacious for managing FCR. However, there are no
specific data on the interventions that are most effective when delivered remotely.
Conclusions: CBT interventions can be efficacious in managing FCR, especially at
posttreatment, regardless of whether it is delivered face to face, on the web, or
using a blended approach. To date, no study has simultaneously compared the
effectiveness of face-to-face, web-based, and blended interventions. On the basis
of the retrieved evidence, we propose the hypothetical program of an intervention
for FCR based on both traditional CBT and contemporary CBT, named Change Of
Recurrence, which aims to improve the management of FCR in patients with cancer and
survivors.
Objectives The COVID-19 pandemic has negatively affected the lives of millions of
individuals physiologically, behaviorally, socially, and/or psychologically.
Moreover, there is now much empirical evidence that mental health problems have
increased during the pandemic period and these problems have various consequences.
The changes in the mood states of individuals due to the pandemic underpins the
rationale of the present study. The aim of the study was to identify the cross-
sectional associations between fear of COVID-19, stress, anxiety, and depression by
using two stage-meta-analytic structural equation modeling (TS-MASEM). Design This
is a meta-analytic structural equation modelling study. Method A systematic
literature review initially identified 4840 studies. As a result of applying
inclusion and exclusion criteria, 25 studies comprising 28 samples (reporting 120
effect sizes) were eligible for inclusion in the current TS-MASEM (N = 16,452).
Results The results showed significant associations between fear of COVID-19,
stress, anxiety, and depression. Additionally, the mediation role of anxiety in the
association between depression and fear of COVID-19 and stress was explored.
Conclusions Although the results did not allow for causal inferences regarding
depression, they provide insight into the possible consequences of fear of COVID-19
and comorbid problems for clinicians and researchers.
This paper presents a brief overview of current knowl-edge regarding the
neuroscientific and biological back-ground of anxiety and fear. The
conceptualisation of the "two-system" framework is described in detail. In terms of
terminology, the terms fear and anxiety are limited in this framework to mental
states connected with consciously experiencing emotions as opposed to nonconscious
autonomic nervous system reactions. The introduced terminology may have practical
impli-cations in psychotherapy as people seek help mainly because of subjective
experiences of fear and anxiety and the effectiveness of mental health
interventions is also evaluated on the basis of experiencing these men-tal states.
The background of developing anxiety dis-orders is briefly described, emphasising
the key role of sympathetic and parasympathetic systems. As nowa-days anxiety
disorders are prevalent among adolescents and adults, it is necessary to implement
interventions preventing development of full-blown disorders in people suffering
from excessive or sub-threshold anxie-ty levels. Acceptance and commitment therapy
(ACT) is suggested as the evidence-based prevention model. ACT promotes building
psychological flexibility, incor-porates mindfulness techniques which enable
alteration of the anoetic form of consciousness, and introduces breathing exercises
that may stimulate the sympathet-ic system through the vagus nerve. Thus ACT model
as a preventive tool has the implications to bridge the psychological and
neuroscientific research and theory with practical usage.
Anxiety disorders are the most common comorbid psychiatric disorders in patients
with bipolar disorder. Managing anxiety symptoms in comorbid conditions is
challenging and has received little research interest. The findings from
preclinical research on fear conditioning, an animal model of anxiety disorder,
have suggested that memory reconsolidation updating (exposure-based therapy)
combined with val-proate might facilitate the amelioration of fear memories. Here,
three cases of successful amelioration of agoraphobia and panic symptoms through
valproate adjuvant therapy for cognitive behavioral therapy in patients who failed
to respond to two to three consecutive stan-dard pharmacotherapy trials over
several years are described. To the best of the author's knowledge, this is the
first attempt to combine CBT with valproate in patients with panic disorder,
agoraphobia, and comorbid bipolar disorder. Additionally, the background
preclinical re-search on this combination therapy based on the reconsolidation-
updating mechanism, the inhibition of histone deacetylase 2, and critical period
reopening, off-label use of valproate in panic disorder, plasticity-augmented
psychotherapy, and how to combine valproate with CBT is discussed. Psychiatry
Investig 2022;19(8):614-625
Because ungulates are important contributors to ecosystem function, understanding
the "ecology of fear" could be important to the conservation of ecosystems.
Although studying ungulate ecology of fear is common, knowledge from ungulate
systems is highly contested among ecologists. Here, we review the available
literature on the ecology of fear in ungulates to generalize our current knowledge
and how we can leverage it for conservation. Four general focus areas emerged from
the 275 papers included in our literature search (and some papers were included in
multiple categories): behavioral responses to predation risk (79%), physiological
responses to predation risk (15%), trophic cascades resulting from ungulate
responses to predation risk (20%), and manipulation of predation risk (1%). Of
papers focused on behavior, 75% were about movement and habitat selection. Studies
were biased toward North America (53%), tended to be focused on elk (Cervus
canadensis; 29%), and were dominated by gray wolves (40%) or humans (39%) as
predators of interest. Emerging literature suggests that we can utilize predation
risk for conservation with top-down (i.e., increasing predation risk) and bottom-up
(i.e., manipulating landscape characteristics to increase risk or risk perception)
approaches. It is less clear whether fear-related changes in physiology have
population-level fitness consequences or cascading effects, which could be fruitful
avenues for future research. Conflicting evidence of trait-mediated trophic
cascades might be improved with better replication across systems and accounting
for confounding effects of ungulate density. Improving our understanding of
mechanisms modulating the nature of trophic cascades likely is most important to
ensure desirable conservation outcomes. We recommend future work embrace the
complexity of natural systems by attempting to link together the focal areas of
study identified herein.
Pathological anxiety is among the most difficult neuropsychiatric diseases to treat
pharmacologically, and it represents a major societal problem. Studies have
implicated structural changes within the prefrontal cortex (PFC) and functional
changes in the communication of the PFC with distal brain structures in anxiety
disorders. Treatments that affect the activity of the PFC, including cognitive
therapies and transcranial magnetic stimulation, reverse anxiety- and fear-
associated circuit abnormalities through mechanisms that remain largely unclear.
While the subjective experience of a rodent cannot be precisely determined, rodent
models hold great promise in dissecting well-conserved circuits. Newly developed
genetic and viral tools and optogenetic and chemogenetic techniques have revealed
the intricacies of neural circuits underlying anxiety and fear by allowing direct
examination of hypotheses drawn from existing psychological concepts. This review
focuses on studies that have used these circuit-based approaches to gain a more
detailed, more comprehensive, and more integrated view on how the PFC governs
anxiety and fear and orchestrates adaptive defensive behaviors to hopefully provide
a roadmap for the future development of therapies for pathological anxiety.
Introduction: The lack of any definitive treatment or preventive method, and the
prediction of some epidemiologists that most of the population will infected with
Covid-19, has caused a lot of stress and anxiety in people. So study aimed to
review the prevalence of fear and anxiety due to Covid-19 in medical staff and non-
medical population. Method: in this study the databases including PubMed, Web of
Science (ISI), Scopus, PsycINFO, EMBASE, Google Scholar, and national databases
such as Irandoc, Civilica, Maglran SID, using the keywords of fear, anxiety,
prevalence, and covid-19 from the start of Covid-19 pandemic at December 2019 until
July 2022 were searched in order to find the related articles. Results: Anxiety
prevalence in women was higher than in men, in people who follow the news related
to Covid-19 was more than those who didn't follow, among younger people was higher
than older, in people in the region with the high epidemic of covid-19 was more
than a low epidemic region, and in people who had an unchanging residence was
higher than those who change. Also, anxiety prevalence among medical staff was
higher than the non-medical. Conclusion: The prevalence of anxiety in most people
especially in medical staff was high. Special measures should be taken to reduce
anxiety among the medical staff and non-medical population.
Finite element analysis (FEA) incorporates the principles of erudite engineering to
scrutinize stresses that cause deformation in structural units. This technique uses
computer-assisted design software and FEA analysis software for modeling structural
units established on their geometry, loading, boundaries, and converts the data
into algebraic equations to find solutions for different applications. In
dentistry, this computer-based simulation method is deemed revolutionary in
forecasting and quantifying stress in investigational biological tissues, dental
prostheses, and restorations. This review is designed to explicate the significance
of FEA in diverse facets of dentistry with special consideration to orthodontics.
OBJECTIVE To identify drug classes and individual selective serotonin reuptake
inhibitors (SSRIs) with high rates of remission and low risk of adverse events in
the treatment of panic disorder with or without agoraphobia. DESIGN Systematic
review and network meta-analysis. DATA SOURCES Embase, Medline, and
ClinicalTrials.gov from inception to 17 June 2021. ELIGIBILITY CRITERIA FOR STUDY
SELECTION Randomised controlled trials that included adults aged >= 18 years with a
diagnosis of panic disorder, compared drugs used to treat the panic disorder, and
measured the outcomes of interest, including remissions, dropouts, and adverse
events. METHODS Risk of bias in the included studies was assessed using the revised
Cochrane risk of bias tool for randomised trials. Direct meta-analyses were
performed using random effects models. A two stage network meta-analysis with
surface under the cumulative ranking curve (SUCRA) was used to estimate the
comparative efficacy of drug classes and individual SSRIs. RESULTS 87 studies
including a total of 12 800 participants and 12 drug classes were eligible for
inclusion. Almost all the studies (86/87) had some concern or were at high risk of
bias. Network meta-analysis of remission with consistent results indicated that
tricyclic antidepressants, benzodiazepines, monoamine oxidase inhibitors, SSRIs,
and serotonin-noradrenaline reuptake inhibitors (SNRIs) were associated with
significantly higher remission rates than placebo, with risk ratios of 1.39 (95%
confidence interval 1.26 to 1.54), 1.47 (1.36 to 1.60), 1.30 (1.00 to 1.69), 1.38
(1.26 to 1.50), and 1.27 (1.12 to 1.45), respectively. SUCRAs identified
benzodiazepines (84.5%, mean rank=2.4), tricyclic antidepressants (68.7%, 3.8), and
SSRIs (66.4%, 4.0) as the top three best treatments for remission. However,
tricyclic antidepressants, benzodiazepines, and SSRIs were also significantly
associated with increased risk of adverse events compared with placebo, with risk
ratios of 1.79 (1.47 to 2.19), 1.76 (1.50 to 2.06), and 1.19 (1.01 to 1.41),
respectively. Consistency assumption of adverse events was upheld but could still
be present on removal of studies with high percentages of women participants and
those with agoraphobia. A SUCRA cluster ranking plot considering both remission and
adverse events among all drug classes indicated that SSRIs were associated with
high remission and low risk of adverse events. Among individual SSRIs, sertraline
and escitalopram provided high remission with an acceptable risk of adverse events.
CONCLUSION The findings suggest that SSRIs provide high rates of remission with low
risk of adverse events for the treatment of panic disorder. Among SSRIs, sertraline
and escitalopram were associated with high remission and low risk of adverse
events. The findings were, however, based on studies of moderate to very low
certainty levels of evidence, mostly as a result of within study bias,
inconsistency, and imprecision of the findings reported. SYSTEMATIC REVIEW
REGISTRATION PROSPERO CRD42020180638.
Background Childhood epilepsy is a serious and common neurological condition and
can have life-long consequences and its impact can pervade all aspects of family
life. Whilst the medical management of seizures is important, much of the day-to-
day home management of epilepsy is invisible to people external to the family,
including health care professionals, and parents'/caregivers' fears and concerns
can go unacknowledged and unaddressed by health care professionals. Objective This
objective of this review was to examine parents'/caregivers' fears and concerns
regarding their child's epilepsy, the impact of these fears and concerns on family
life, the social and emotional well-being of parents/caregivers and any factors
which mitigate these fears and concerns. Design Scoping review using a modified
version of Arksey and O'Malley's framework. Data sources Relevant studies were
identified using key search terms in Scopus, Medline, CINAHL and PsychInfo
databases in March 2021 with hand checking of reference lists. Search terms were
developed using population (parents/caregivers of children aged <= 18 years with
epilepsy, families); concept (parents'/caregivers' fears, concerns, anxiety about
their child's epilepsy); and context (any setting). A further search was run in
April 2022. Other inclusion criteria: English language empirical studies, 2010-
2021. Study appraisal methods A minimum of two reviewers independently screened
articles and undertook data extraction and decisions were consensually made.
Methodological quality appraisal was undertaken using the Mixed Methods Appraisal
Tool v2018. A data extraction table was created to chart all studies. The conduct
and reporting of this study followed the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses (PRISMA) guidance for Systematic reviews and Meta-
Analyses extension for Scoping Reviews (PRISMA-ScR) (S1 Table). There is no
published copy of the review protocol. Main findings The search identified a total
of 4077 papers (after duplicates were removed) of which 110 were assessed for
eligibility. Twenty-four papers published between 2010-2021 were included in the
review and each paper was treated as a separate study. The review findings indicate
that parents'/caregivers' fears and concerns stem from more than their child's
seizures and relate to many wider aspects of family life. These fears and concerns
had far-reaching influences on their parenting/caregiving, and on the lifestyle and
activities of their child and their family. What was less evident was what
parents/caregivers wanted in terms of support or how they thought health
professionals could acknowledge and/or allay their fears and concerns. The
discussion is framed within the compassion-focused therapy model as a basis for
generating new thinking about the impact of these fears and concerns and the need
for a new agenda for clinical consultations in childhood epilepsy. Conclusions The
review concludes with a proposal that a more compassionate agenda underpins the
dialogue between parents/caregivers and clinicians to encompass and mitigate the
wider emotional, psychosocial, and societal threats that impact on the
parent/caregivers of children with epilepsy.
Simple Summary Attitudes toward animal welfare have changed considerably over
recent decades. Avoiding the experience of undue fear or stress in animals is a
goal across many sectors including production animals, captive zoo species, and
companion animals. Husbandry and veterinary procedures have the potential for
generating fear and stress in animals; however, this can be mitigated through the
types of handling techniques used, and by undertaking training to adequately
prepare the animal for all aspects of the procedure. The companion animal sector
and the zoo sector have made significant strides towards recognizing and reducing
fear during health care. This review discusses the potential for improving horse
experiences during husbandry and veterinary procedures. Husbandry and veterinary
procedures have the potential to generate fear and stress in animals. In horses,
the associated responses can pose a significant safety risk to the human personnel
involved in the procedure, as well as to the animal itself. Traditionally, physical
restraint, punishment, and/or threat of an aversive, have been the most common
strategies used to achieve compliance from the horse. However, from a welfare
perspective, this is less than ideal. This approach also has the potential for
creating a more dangerous response from the horse in future similar situations.
When caring for companion animals, and captive animals within zoological
facilities, there has been a steady transition away from this approach, and toward
strategies aimed at reducing fear and stress during veterinary visits and when
undertaking routine husbandry procedures. This review discusses the current
approaches to horse care and training, the strategies being used in other animal
sectors, and potential strategies for improving human safety, as well as the
horse's experience, during husbandry and veterinary procedures.
The spiral of silence theory suggests that those who hold a contrary opinion to the
majority tend to remain silent; however, social media may be flipping this upside
down. The majority may remain silent to the hardcore vocal minority, implying a
self-censoring majority. This study examines the spiral of silence theory, and the
effect of political identity and ideology has on the willingness to self-censor and
the fear of isolation with social media use. Through a survey distributed through a
Qualtrics panel to participants that mirror the US census (N= 1,047), this study
investigates political identity and ideology by examining self-censorship and fear
of isolation of social media users. Results identify significant differences with
self-censorship and identity politics between strong conservatives and liberals in
comparison to the majority in the middle. Differing political ideologies seem to
have an impact on fear of isolation between democrats and conservatives.
Background To improve the understanding of the psychological impacts of anterior
cruciate ligament (ACL) injury, a systematic review synthesizing the evidence on
knee self-efficacy, fear avoidance beliefs and kinesiophobia following ACL injury
is needed. Objective The aim of this systematic review was to investigate knee
self-efficacy, fear avoidance beliefs and kinesiophobia following ACL injury, and
compare these outcomes following management with rehabilitation alone, early and
delayed ACL reconstruction (ACLR). Methods Seven databases were searched from
inception to April 14, 2022. Articles were included if they assessed Tampa Scale of
Kinesiophobia (TSK), Knee Self-Efficacy Scale (KSES), or Fear Avoidance Beliefs
Questionnaire (FABQ). Risk of bias (RoB) was assessed using domain-based RoB tools
(ROBINS-1, RoB 2, RoBANS), and GRADE-assessed certainty of evidence. Random-effects
meta-analyses pooled outcomes, stratified by time post-injury (pre-operative, 3-6
months, 7-12 months, > 1-2 years, > 2-5 years, > 5 years). Results Seventy-three
studies (70% high RoB) were included (study outcomes: TSK: 55; KSES: 22; FABQ: 5).
Meta-analysis demonstrated worse kinesiophobia and self-efficacy pre-operatively
(pooled mean [95% CI], TSK-11: 23.8 [22.2-25.3]; KSES: 5.0 [4.4-5.5]) compared with
3-6 months following ACLR (TSK-11: 19.6 [18.7-20.6]; KSES: 19.6 [18.6-20.6]). Meta-
analysis suggests similar kinesiophobia > 3-6 months following early ACLR (19.8
[4.9]) versus delayed ACLR (17.2 [5.0]). Only one study assessed outcomes comparing
ACLR with rehabilitation only. Conclusions Knee self-efficacy and kinesiophobia
improved from pre-ACLR to 3-6 months following ACLR, with similar outcomes after 6
months. Since the overall evidence was weak, there is a need for high-quality
observational and intervention studies focusing on psychological outcomes following
ACL injury.
In ICD-11, catatonia is a complex syndrome that includes psychomotor disorders
(negativity, catalepsy, wax flexibility, mutism, automatism, mannerisms, or
echolalia) and volitional processes affect modulation and action planning, which
leads to hypofunctional, hyperfunctional, or parafunctional motor action. This is a
very important clue that this state can be associated with both mental and somatic
diseases. In order to create a narrative review, authors analyzed the diagnostic
criteria of ICD-10 and ICD-11 and searched the PubMed medical base for articles on
the diagnosis and different approaches to the treatment of catatonia. The treatment
of catatonia is not standardized. It is based on the use of benzodiazepines, GABAa
receptor antagonists, NMDA receptor antagonists, D2 receptor antagonist, and
electroconvulsive therapy (ECT). The authors also would like to present the case of
a patient in whom the diagnosis of catatonia was not so clear according to the
diagnostic criteria, emphasizing the importance of the key diagnosis for the
patient's recovery. The authors would also like to point out that the topic of
catatonia should be of interest not only to psychiatrists, but also to doctors of
other specialties, who may encounter cases of catatonia complicating somatic states
in hospital wards.
It has only been recently that fear of crime scholars have shifted their attention
to online contexts. The current systematic review provides an overview of available
studies on measurement, intensity and determinants of fear of cybercrime. While
matters of measurement and conceptualisation has sprung a sizeable and vivid debate
in the general fear of crime literature, we aim to scope this debate for the online
context by scrutinizing the available knowledge base. At the same time, and by
providing an overview of correlates of fear of cybercrime, we aim to provide a
fertile ground for theory building specific to the online context. A comprehensive
literature search was conducted, yielding a total of 28 relevant studies from a
range of (sub)disciplines, using a variety of measures in terms of the particular
emotion measured (fear, worry, anxiety) and the type of cybercrime it related to.
We find considerable agreement between studies on classic fear of crime indicators
such as gender, victimization and risk perception. At the same time, various
studies report a relationship between fear of cybercrime and what is termed
'constrained behavior', as outcome measure. Implications of these findings, and
future directions for fear of cybercrime research are discussed.
Background: Although there is no standard definition for eco-anxiety, most authors
define it as people's emotional reaction of concern, worry, anxiety, and fear in
view of global Climate Change (CC) threats and concurrent environmental
degradation. This systematic review was carried out to critically evaluate the
evidence on eco-anxiety related to CC and its health implications in general
populations. Methods: We performed a search for scientific articles in PubMed,
Scopus, Embase, Web of Science, and Cochrane Central. Studies were included if they
complied with the study objective. Selection of articles and data extraction were
carried out independently by 2 reviewers. We used the Axis tool and JBI critical
appraisal checklist to assess the quality of the studies. Results: A final sample
of 12 articles was included in this review. The methodological quality of the
studies was limited. A wide variety of eco-anxiety definitions was used in the
different studies but further research is needed to provide conceptual clarity of
the term eco-anxiety. Eco-anxiety was associated with functional impairment,
symptoms of depression, anxiety, PTSD, stress and insomnia, lower self-rated mental
health, and reluctance to have children. Moreover, habitual worry about global
warming was associated with a pro-ecological worldview, a green self-identity and
pro-environmental behavior, strongly suggesting a constructive nature. Indeed, pro
-environmental behavior in the form of climate activism would buffer the impact of
CCA cognitive-emotional impairment on MDD symptoms. However, sometimes engaging in
pro-environmental behavior might not be successful in dealing with eco-anxiety,
since individuals might perceive that their efforts do not help to mitigate the CC
crisis. Conclusions: Results have to be interpreted with caution since the
methodological quality of the studies was limited. However, they do suggest a link
between eco-anxiety and negative mental health outcomes, mainly in younger
generations, women, and poorer countries in the "Global South". Eco-anxiety may
constitute a stressor to mental health, particularly if coping mechanisms are not
successfully developed.
The Terror and Disaster Surgical Care (TDSC (R)) course on mass casualty incident
management was formulated in Germany by military medical personnel, who have been
deployed to conflict areas, but also work in hospitals open for the lay public. In
this manuscript we discuss different concepts and ideas taught in this course as
these are described in a focused issue recently published in the European Journal
of Trauma and Emergency Surgery. We provide reinforcement for some of the ideas
conveyed. We provide alternative views for others. Injuries following explosions
are different from blunt and penetrating trauma and at times demand a different
approach. There are probably several ways to manage a mass casualty incident
depending on the setup of the organization. An open discussion on the topics
presented in the manuscripts included in the focused issue on military and disaster
surgery should enrich everyone.
Background: Panic buying has been reported during a period of crisis when people
buy an extra amount of essential commodities and hoard them anticipating their
future utility. As a newer entity, a bibliometric analysis would reveal the
research gaps for further studies. We aimed to do a bibliometric analysis of
researches published on panic buying over the past two decades.Methods: A
literature search was conducted in the SCOPUS database using the keyword "panic
buying". All published research in the English language between 1st January 2001 to
1st August 2021 was included in the analysis of this study.Results: We identified a
total of 142 articles on panic buying published over the past two decades. There is
an exponential increase in the publication on this topic during the COVID-19
pandemic (n=127). Majority of the articles were published from the United States
(n=23), followed by the United Kingdom (n=20), and China (n=20). The Frontiers in
Public Health and Journal of Retailing and Consumer Services published the highest
number of articles (eight each). Arafat SMY published the highest number of
publications as a single author (n=10) and Enam Medical College and Hospital,
Bangladesh has the highest number of papers as an institution (n=10). Among all the
publishers, Elsevier has published the maximum number of papers (n=38).Conclusion:
There is an exponential growth of panic buying research during 2020-21. The global
crisis of the COVID-19 pandemic has been attributed to the recent rise in panic
buying research.
BackgroundAtrial fibrillation occurs when rapid and disorganized electrical signals
cause the atria in the heart to beat irregularly and is associated with an
increased risk for stroke. Despite medical advancements, first and second line
atrial fibrillation treatments exhibit significant recurrence rates. Because of
this, atrial fibrillation patients often experience disease-specific fears that are
not routinely assessed and targeted in clinical management. Fear of recurrence
models in cancer research and other cardiac-specific fears have paved the way for a
patient-centric approach to disease intervention. PurposeClinical assessment
focused solely on the taxonomy of anxiety disorders may miss key components unique
to the atrial fibrillation patient experience. An anxiety disorder diagnosis in the
presence of an arrhythmia could be misleading and ultimately fail to address
patient needs. Modeled from the cancer literature, providers may benefit from a
broader disease specific conceptualization for AF patients that differs from a
general DSM-5 diagnosis. AimsThe objectives of this paper are: (1) to review the
medical aspects of atrial fibrillation, (2) to examine the comparability of fear of
recurrence concept from cancer literature to the atrial fibrillation patient, and
(3) to suggest considerations of these novel concepts in patient care. Future
DirectionsIncreased understanding of fear of recurrence among atrial fibrillation
patients aims to define and assess fear of recurrence components, determine
treatment targets, and ultimately improve patient outcomes.
A scoping review was performed to examine the extent and nature of research
activity on kinesiophobia and fear avoidance in older adults and summarize research
findings. Four databases were searched from January 2006 to May 2021. Eleven papers
were selected for inclusion, with a predominance of cross-sectional design (54.5%;
n = 6). Most of the studies were associated with chronic pain (n = 9; 81.8%).
Higher levels of kinesiophobia were found among frailer and older people,
predominantly living in care homes. Kinesiophobia and fear avoidance have been
related to other constructs of the fear avoidance model, and the conclusions
partially support the assumptions derived from it in older adults. Nevertheless,
kinesiophobia proved to be a more dominant factor in determining the level of
physical activity than pain in this population. None of the studies aimed to test
the effectiveness of interventions directly targeting kinesiophobia or fear
avoidance.
Background and Purpose: In light of the fear avoidance model, kinesiophobia and
fear avoidance (FA) can lead to physical inactivity and disability. Previous
studies regarding kinesiophobia and FA in older adults have reported conflicting
results. The purpose of this review was to identify the reported constructs and
assessment instruments used in published studies on kinesiophobia and FA in older
adults and to verify the alignment between the instruments used and the constructs
under study. Methods: Following the Preferred Reporting Items for Systematic
reviews and Meta-Analyses 2020 statement (PRISMA-2020), 4 databases were searched
from January 2005 to March 2020. All study types, except qualitative, were eligible
for inclusion. The participants were 65 years and older. Studies were excluded in
the absence of sufficient data on participant age. Study characteristics,
constructs related to kinesiophobia, fear and/or avoidance, and instruments used
were extracted independently by 2 reviewers. Results: Fourteen articles were
selected for inclusion in the study, in which 7 constructs were identified. The
most reported constructs were "fear avoidance beliefs" (FAB) (50%; n = 7),
"kinesiophobia" (35.7%; n = 5), and "fear of falling" (14.3%; n = 2). The remaining
constructs were only approached, each in 7.1% (n = 1) of the included studies.
Seven instruments were used to assess the constructs. The Fear Avoidance Beliefs
Questionnaire (FABQ) was the most used instrument (n = 3) to evaluate "FAB," and
the Tampa Scale for Kinesiophobia-11 (TSK-11) was the most reported (n = 3) to
assess "kinesiophobia." Conclusion: This review identified a large diversity in the
constructs and instruments used to study kinesiophobia and FA among older adults.
Some constructs are used interchangeably although they do not share the same
conceptual definition. There is poor standardization in the use of assessment tools
in accordance with the construct under study. Clinical evaluation and study results
can be biased owing to this ambiguity.
Background The severity of COVID-19 remains high worldwide. Therefore, millions of
individuals are likely to suffer from fear of COVID-19 and related mental health
factors. Aims The present systematic review and meta-analysis aimed to synthesize
empirical evidence to understand fear of COVID-19 and its associations with mental
health-related problems during this pandemic period. Method Relevant studies were
searched for on five databases (Scopus, ProQuest, EMBASE, PubMed Central, and ISI
Web of Knowledge), using relevant terms (COVID-19-related fear, anxiety,
depression, mental health-related factors, mental well-being and sleep problems).
All studies were included for analyses irrespective of their methodological
quality, and the impact of quality on pooled effect size was examined by subgroup
analysis. Results The meta-analysis pooled data from 91 studies comprising 88 320
participants (mean age 38.88 years; 60.66% females) from 36 countries. The pooled
estimated mean of fear of COVID-19 was 13.11 (out of 35), using the Fear of COVID-
19 Scale. The associations between fear of COVID-19 and mental health-related
factors were mostly moderate (Fisher's z = 0.56 for mental health-related factors;
0.54 for anxiety; 0.42 for stress; 0.40 for depression; 0.29 for sleep problems and
-0.24 for mental well-being). Methodological quality did not affect these
associations. Conclusions Fear of COVID-19 has associations with various mental
health-related factors. Therefore, programmes for reducing fear of COVID-19 and
improving mental health are needed.
Background: The COVID-19 pandemic is still ongoing and is not yet under control.
Evidence regarding the impacts of COVID-19 on psychological distress has been
widely reported worldwide, and one of the primary concerns regarding psychological
distress is fear (ie, fear of COVID-19). Therefore, having a robust instrument for
assessing fear of COVID-19 is important. The present systematic review aimed to
synthesize the psychometric evidence evaluated using item response theory (IRT) on
the Fear of COVID-19 Scale (FCV-19S). Methods: Utilizing the Preferred Reporting
Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, four academic
databases (Scopus, PubMed Central, ProQuest, and ISI Web of Knowledge) were used to
search target papers. Keywords used for search were "Fear of COVID-19 Scale" and
its abbreviation (ie, "FCV-19S") and IRT-related terms. The COnsensus-based
Standards for the selection of health status Measurement INstruments (COSMIN)
checklist was then applied to evaluate the methodological quality of the reviewed
papers. Moreover, psychometric properties using IRT methods were synthesized using
a qualitative method. Results: The initial search resulted in 552 papers (73
duplicates) and 479 were screened based on their titles and abstracts. Finally, 16
papers were included for review regarding their methodological quality (via COSMIN)
to synthesize the psychometric evidence for FCV-19S. The 16 papers included 21
countries with 16 language versions of FCV-19S. Conclusion: All the psychometric
evidence indicated that the seven items in the FCV-19S fit with the concept of
fear. The FCV-19S is a strong and valid instrument for assessing fear across
different languages. The seven items in the FCV-19S appear to be unidimensional in
assessing fear, which indicates that all items are necessary in the FCV-19S.
Objective: This review aimed to measure the degree of placebo response in panic
disorder. Data Sources: We searched major databases up to 31 January 2021, for
randomized pharmacotherapy trials published in English. Study Selection: A total of
43 studies met inclusion criteria to be in the analysis (with 174 separate outcome
measurements). Data Extraction: Changes in outcome measures from baseline in the
placebo group were used to estimate modified Cohen's d effect size. Results: A
total of 43 trials (2392 subjects, 174 outcomes using 27 rating scales) were
included in the meta-analysis. Overall placebo effect size was 0.57 (95% confidence
interval = [0.50, 0.64]), heterogeneity (I-2: 96.3%). Higher placebo effect size
was observed among clinician-rated scales compared to patient reports (0.75 vs
0.35) and among general symptom and anxiety scales compared to panic symptoms and
depression scales (0.92 and 0.64 vs 0.56 and 0.54, respectively). There was an
upward trend in effect size over the publication period (r = 0.02, p = 0.002) that
was only significant among clinician-rated scales (r = 0.02, p = 0.011). There was
no significant publication bias, Egger's test (p = 0.08). Conclusion: We observed a
substantial placebo effect size in panic disorder. This effect was more prominent
for some aspects of panic disorder psychopathology than for others and was
correlated with the source of the assessment and publication year. This finding has
implications both for research design, to address the heterogeneity and diversity
in placebo responses, and for clinical practice to ensure optimal quality of care.
Systematic review registration number: PROSPERO, CRD42019125979.
BACKGROUND: Panic disorder (PD) is a devastating illness, with numer-ous patients
experiencing significant functional disability and many not achieving full
remission with first-line pharmacologic and psychothera-peutic treatments. METHODS:
A search of PubMed, Cochrane Library, and PsychINFO data-bases was used to identify
publications focused on evidence-based treat-ment of PD. RESULTS: Selective
serotonin reuptake inhibitors (SSRIs) and benzodiaze-pines are standard first-line
pharmacologic treatments for PD. Many other antidepressants can be considered as
alternatives to SSRIs, including sero-tonin-norepinephrine reuptake inhibitors,
serotonin multimodal agents, tricyclic antidepressants, monoamine oxidase
inhibitors, and mirtazap-ine. Certain anticonvulsants and antipsychotics may be
helpful; however, the evidence base is limited. Buspirone, beta blockers, and
hydroxyzine can be considered third-line agents. Currently, there is minimal data
sup-port the use of electroconvulsive therapy or repetitive transcranial mag-netic
stimulation (rTMS). There is very little evidence justifying the use of medical
cannabis or over-the-counter supplements for PD, and these treatments have risk for
adverse effects. Research strongly supports the use of cognitive-behavioral therapy
(CBT) for PD. CONCLUSIONS: Many options exist for the management of PD. Treatments
with the strongest evidence include SSRIs, other antidepressants, and CBT. Newer
interventions approved for the treatment of depression, such as serotonin
multimodal agents, esketamine, and rTMS, merit further investigation for use in PD.
Aims and objectives To summarise and thematise fear of hypoglycaemia (FOH) in
individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D) to provide a
theoretical basis for the development of effective interventions. Background FOH is
common in this population and can reduce quality of life (QOL) and adversely impact
upon diabetes self-care management. Design A systematic review. Methods Articles
published between 2000-2019 were searched in PubMed, MEDLINE, EMBASE, Web of
Science and three Chinese databases (CNKI, Wan-fang data and VIP). Eligible
articles were selected using the Preferred Reporting Item for Systematic Review and
Meta-analysis (PRISMA) guidelines. The quality of all articles finally included was
evaluated by the Joanna Briggs Institute (JBI) Critical Appraisal tools. Results
Eighteen studies from 8654 papers were included. The sample size of each study
ranged from 48-3812 subjects. FOH negatively impacted QOL, particularly
psychosocial functioning, daily life and sleep quality. Conclusions FOH is a common
and serious problem for patients, leading to poor QOL. It has been suggested that
psychological concerns, QOL and effective countermeasures in individuals with T1D
and T2D should be taken seriously. Advanced technology should be evaluated for its
benefits before being used by patients. Relevance to Clinical Practice The review
highlights that FOH negatively impacts QOL, including psychosocial factors, daily
life and sleep quality. Healthcare providers should develop targeted and
professional assessment tools for FOH and QOL for patients with T2D, especially for
patients who are about 60 years old. Advanced technology should be evaluated for
its benefits before being used by patients.
Objective Fear of cancer recurrence (FCR) is a common and burdensome psychological
condition affecting cancer survivors. This systematic review aims to synthesise
current evidence regarding: (1) FCR-related healthcare usage and costs and (2) the
cost-effectiveness of FCR treatments. Methods We searched MEDLINE, CINAHL, Cochrane
and other electronic databases using MeSH headings and keywords for cancer, FCR and
costs from their inception to September 2019. Identified studies were screened for
eligibility. Original, peer-reviewed journal articles reporting quantitative data
from samples of adults treated for cancer written in English were included. Quality
was appraised using the Drummond checklist for economic evaluations or the relevant
Joanna Briggs Institute Critical Appraisal Tool. Results Data from 11 studies were
extracted and synthesised. Seven studies addressed the costs of FCR and suggested
an increase in the use of primary and secondary healthcare. Four studies addressed
the cost-effectiveness of different FCR treatments and suggest that some treatments
may cost-effectively reduce FCR and improve quality of life. Reviewed treatments
had an incremental cost-effectiveness ratio between AU$3,233 and AU$152,050 per
quality-adjusted life year gained when adjusted to 2019 Australian dollars. All
studies were of sufficient quality to be synthesised in this review. Conclusions
FCR appears to be associated with greater use of certain healthcare resources, and
FCR may be treated cost-effectively. Thus, appropriate FCR treatments may not only
reduce the individual burden, but also the strain on the healthcare system. Further
high-quality research is needed to confirm this and ensure the future
implementation of efficient and sustainable FCR treatments.
Trauma-induced insomnia is a symptom of posttraumatic stress disorder (PTSD), and
is reported to be particularly distressing and often persists even after remission
of the core symptoms of PTSD. Recently, it has been suggested that fear of sleep
plays an important role in the development and maintenance of trauma-induced
insomnia. The aim of this review is to propose a conceptual model of fear of sleep
as a maintaining factor of trauma-induced insomnia. After a brief overview of the
role of sleep in PTSD, the concept of fear of sleep is introduced. Theoretical
considerations and empirical findings on the role of fear of sleep for trauma-
induced insomnia in the context of PTSD are summarized and integrated.
Specifically, links between PTSD symptoms and fear of sleep are presented, as well
as possible consequences of fear of sleep leading to trauma-induced insomnia.
Finally, we highlight methodological issues, identify areas for future research,
and discuss potential clinical implications. (C) 2020 Elsevier Ltd. All rights
reserved.
Fear generalization to stimuli resembling a conditioned danger-cue (CS+) is a
fundamental dynamic of classical fear-conditioning. Despite the ubiquity of fear
generalization in human experience and its known pathogenic contribution to
clinical anxiety, neural investigations of human generalization have only recently
begun. The present work provides the first meta-analysis of this growing literature
to delineate brain substrates of conditioned fear-generalization and formulate a
working neural model. Included studies (K = 6, N = 176) reported whole-brain fMRI
results and applied generalization-gradient methodology to identify brain
activations that gradually strengthen (positive generalization) or weaken (negative
generalization) as presented stimuli increase in CS+ resemblance. Positive
generalization was instantiated in cingulo-opercular, frontoparietal,
striatalthalamic, and midbrain regions (locus coeruleus, periaqueductal grey,
ventral tegmental area), while negative generalization was implemented in default-
mode network nodes (ventromedial prefrontal cortex, hippocampus, middle temporal
gyrus, angular gyrus) and amygdala. Findings are integrated within an updated
neural account of generalization centering on the hippocampus, its modulation by
locus coeruleus and basolateral amygdala, and the excitation of threat- or safety-
related loci by the hippocampus.
Background Between 5% and 14% of women suffer from fear of childbirth (FOC) which
is associated with difficulties during birth and in postnatal psychological
adjustment. Therefore, effective interventions are needed to improve outcomes for
women. A systematic review and meta-analysis was used to identify effective
interventions for treating women with FOC. Methods Literature searches were
undertaken on online databases. Hand searches of reference lists were also carried
out. Studies were included in the review if they recruited women with FOC and aimed
to reduce FOC and/or improve birth outcomes. Data were synthesised qualitatively
and quantitatively using meta-analysis. The literature searches provided a total of
4474 citations. Results After removing duplicates and screening through abstracts,
titles and full texts, 66 papers from 48 studies were identified for inclusion in
the review. Methodological quality was mixed with 30 out of 48 studies having a
medium risk of bias. Interventions were categorised into six broad groups:
cognitive behavioural therapy, other talking therapies, antenatal education,
enhanced midwifery care, alternative interventions and interventions during labour.
Results from the meta-analysis showed that most interventions reduced FOC,
regardless of the approach (mean effect size = -1.27; z = -4.53, p < 0.0001) and
that other talking therapies may reduce caesarean section rates (OR 0.48, 95% CI
0.48-0.90). Conclusions Poor methodological quality of studies limits conclusions
that can be drawn; however, evidence suggests that most interventions investigated
reduce FOC. Future high-quality randomised controlled trials are needed so that
clear conclusions can be made.
Background: The paradox of similar diagnostic criteria but potentially different
neuropathologies in panic disorder (PD) and social anxiety disorder (SAD) needs to
be clarified. Methods: We performed a qualitative systematic review and a
quantitative whole-brain voxel-based morphometry (VBM) meta-analysis with an
anisotropic effect-size version of seed-based D mapping (AES-SDM) to explore
whether the alterations of grey matter volume (GMV) in PD are similar to or
different from those in SAD, together with potential confounding factors. Results:
A total of thirty-one studies were eligible for inclusion, eighteen of which were
included in the meta analysis. Compared to the respective healthy controls (HC),
qualitative and quantitative analyses revealed smaller cortical-subcortical GMVs in
PD patients in brain areas including the prefrontal and temporal-parietal cortices,
striatum, thalamus and brainstem, predominantly right-lateralized regions, and
larger GMVs in the prefrontal and temporal-parietal-occipital cortices, and smaller
striatum and thalamus in SAD patients. Quantitatively, the right inferior frontal
gyrus (IFG) deficit was specifically implicated in PD patients, whereas left
striatum-thalamus deficits were specific to SAD patients, without shared GMV
alterations in both disorders. Sex, the severity of clinical symptoms, psychiatric
comorbidity, and concomitant medication use were negatively correlated with smaller
regional GMV alterations in PD patients. Conclusion: PD and SAD may represent
different anxiety sub-entities at the neuroanatomical phenotypes level, with
different specific neurostructural deficits in the right IFG of PD patients, and
the left striatum and thalamus of SAD patients. This combination of differences and
specificities can potentially be used to guide the development of diagnostic
biomarkers for these disorders.
Background: Painful pokes, buzzing drills, uncomfortable pressure, foreign tastes,
and disturbing noises are all events that a child can experience in a single dental
appointment. Each event has the potential to trigger dental fear and anxiety in
pediatric patients. Dental fear and anxiety are common for children and can lead to
the neglect of dental care into adulthood. Many behavioral interventions currently
in practice focus on immediate behavior changes rather than long-term psychosocial
well-being of children. Objective: The purpose of this paper was to review the
literature of pediatric dental fear and anxiety and provide reasoning for child
life specialist intervention in the pediatric dental clinic. Results: Rooted in
developmental theory, child life specialists advocate for the psychosocial care of
children in various healthcare environments, including dental clinics. Child life
specialists work to minimize pediatric fear and anxiety using various strategies,
including psychological preparation. Psychological preparation is accomplished by
the provision of developmentally appropriate education, therapeutic or medical
play, and preparation books. Conclusions: Further research is needed to establish
the effectiveness of child life specialist intervention, such as psychological
preparation, in pediatric dentistry at reducing pediatric dental fear and anxiety.
(C) 2021 Japanese Society of Pediatric Dentistry. Published by Elsevier Ltd. All
rights reserved.
Pandemics are associated with panic buying (PB) of groceries and other supplies.
During the COVID-19 pandemic, community leaders expressed frustration and
bewilderment about PB. Psychological explanatory concepts, including those from
social learning theory and the concept of the behavioral immune system, along with
recent research, suggests the following account of pandemic-related PB. PB arises
when people are told to go into self-isolation as part of pandemic containment
interventions. Empirically, episodes of PB typically last 7?10 days and are likely
initiated by highly fearful people. PB by an anxious minority of shoppers leads to
fear contagion among other shoppers, amplified by widespread dissemination, via
social media, of images and videos of PB and empty shelves in stores. Thus, a snow-
balling effect arises where fear of scarcity creates real but shortterm scarcity.
People who are highly frightened of infection tend to have heightened disgust
proneness. Toilet paper is a means of escaping disgust stimuli, and for this and
other reasons, toilet paper became a target of PB for people frightened of
contracting COVID-19. Exploitative or selfish over-purchasing also occurred,
motivated by ?dark? (e.g., psychopathic) personality traits. ?Don?t panic!?
messages from community leaders were ineffective or counter-productive. Alternative
forms of messaging are discussed.
Purpose Research examining the "fear of missing out" (FoMO) is increasingly
prominent, with a growing number of studies exploring this phenomenon. Despite the
increased academic interest, no attempts have been made to synthesize extant
knowledge on FoMO. There is limited holistic understanding of its conceptualization
and operationalization. To address this gap, an exhaustive systematic literature
review (SLR) on FoMO is presented. Design/methodology/approach Systematic review
protocols and content analysis was used to analyze and synthesize insights from 58
empirical studies obtained from four academic databases: Scopus, Web of Science,
PubMed and PsycINFO. Findings Significant diversity in prior research on FoMO was
encapsulated in four themes. There are significant limitations in conceptualization
of FoMO, along with narrow focus on geographic, methodological and contextual foci
of prior studies. The authors propose a comprehensive framework and extensive gap-
specific research directions to aid future research. Research
limitations/implications The SLR is limited in its consideration of empirical
studies published in academic journal articles obtained from four databases. Social
implications The authors imply the critical need to ascertain motives for
individuals' excessive engagement with social media and the subsequent impact on
well-being indicators (e.g. sleep quality) and functional impairments (e.g.
addiction). Originality/value This study magnifies and expands the intellectual
boundaries of FoMO and suggests the adoption of a multidisciplinary perspective for
further investigation. The use of novel theoretical lenses can further ascertain
FoMO's effect on different cultures and social media users.
Context: Injury-related fear has recently been recognized to exist in ankle sprain
populations. It is unclear, however, if injury-related fear levels differ between
those who develop chronic ankle instability (CAI) and those who do not and the best
tools for assessing these differences. Objective: The purpose of this study was to
conduct a comprehensive systematic review investigating differences in injury-
related fear between individuals with and without CAI. Evidence Acquisition:
Relevant studies from CINAHL Plus with full text, PubMed, and SPORTDiscus through
November 2020 were included. All studies used the Tampa Scale of Kinesiophobia,
Fear-Avoidance Beliefs Questionnaire, or Athlete Fear Avoidance Questionnaire as
either a descriptor or a main outcome and provided comparison data between a CAI
group and ankle sprain copers (COP) or controls (CON). The authors independently
assessed methodological quality using the modified Downs and Black Quality Index.
Studies were then grouped by between-group comparisons including CAI and CON, CAI
and COP, and COP and CON. The authors calculated Hedge g effect sizes and 95%
confidence intervals to examine group differences. Evidence Synthesis: A total of
11 studies were included in this review. In total, 8 studies provided data for the
CAI and CON comparison, 7 for CAI and COP comparisons, and 4 for COP and CON
comparisons. Methodological quality scores ranged from 60.0% to 86.7%, with 2
high-, and 9 moderate-quality studies. Overall, the evidence suggests that
physically active individuals with CAI report higher levels of injury-related fear
when compared with both COP and CON. Although limited, ankle sprain COP do not seem
to differ from CON. Conclusion: Available evidence emphasizes the importance of
injury-related fear in individuals who develop chronicity after ankle sprain
injury. The Fear-Avoidance Beliefs Questionnaire and Tampa Scale of Kinesiophobia
are useful for the identification of injury-related fear in individuals after
sustaining an ankle sprain and should be used to inform rehabilitation strategies
and to monitor efficacy in fear reduction.
Anxiety disorders are the most common form of mental illness and are more likely to
emerge during childhood compared with most other psychiatric disorders. While
research on children is the gold standard for understanding the behavioral
expression of anxiety and its neural circuitry, the ethical and technical
limitations in exploring neural underpinnings limit our understanding of the child?
s developing brain. Instead, we must rely on animal models to build strong
methodological bridges for bidirectional translation to child development research.
Using the caregiver?infant context, we review the rodent literature on early-life
fear development to characterize developmental transitions in amygdala function
underlying age-specific behavioral transitions. We then describe how this system
can be per-turbed by early-life adversity, including reduced efficacy of the
caregiver as a safe haven. We suggest that greater integration of clinically
informed animal research enhances bidirectional translation to permit new
approaches to therapeutics for children with early onset anxiety disorders.
Learning to associate certain contexts with threat and adapting to changing
environmental contingencies by learning that such contexts are no longer associated
with threat are both crucial for survival. Research over the last few decades has
made considerable progress in determining the brain areas involved in the encoding,
retrieval and extinction of contextual fear. These studies have identified the
hippocampus and amygdala, along with the prefrontal cortex and other inter-
connected brain areas, as key players in contextual fear processing. In contrast to
the neural circuit basis of contextual fear, the neurochemical mechanisms involved
in its regulation remain poorly understood. Dopamine is well known for its role in
appetitive learning but this neurotransmitter is also important for other types of
learning, including spatial and aversive memory processing. Dopamine is ideally
positioned to regulate contextual fear given that the areas involved receive
dopamine input and express dopamine receptors. Moreover, neuronal activity,
functional connectivity and synaptic plasticity in this neural circuitry are
modulated by dopamine receptor signalling. Here, we review the evidence indicating
that dopamine regulates various contextual fear processes, along with the more
recent studies that have begun to elucidate the brain areas and neurophysiological
mechanisms involved. From a fundamental research perspective, understanding how
dopamine regulates contextual fear will lead to novel insights on the neurochemical
modulation of neural circuit function underlying memory processing. This research
may also have translational relevance given that contextual fear conditioning and
extinction also provide useful preclinical models of certain aspects of anxiety-
related disorders and their treatment.
Few researches have considered fear of crime as a context-specific experience. This
article promotes a place-based theoretical framework for studying crime perceptions
through presenting app-based and crowdsourcing measures of perception of crime and
place as a robust methodological framework. A systematic review of published
studies that use crowdsourced or app-based measures to explore perceptions of crime
was conducted. From the 27 studies that met our inclusion criteria, reported
strengths and limitations were synthesized to determine key developments and common
issues, illustrated with data from three app-based studies. We found consensus that
app-based and crowdsourcing measures of fear of crime capture more precise spatial
and temporal data alongside auxiliary information about the individual and the
environment. Practical benefits, such as reduced cost of data collection and
implementable outputs that are useful to practitioners were also highlighted.
However, limitations around sampling biases, generalizability of findings, and the
under-representation of certain areas persist.
Purpose of Review There is a growing body of work that documents the impact of 9/11
and the war on terror on Arab and Muslim children and families. This review is
designed to provide a brief overview and suggest new ways to better understand this
understudied population. Recent Findings Several studies show anti-Arab and anti-
Muslim sentiments at its highest levels since 9/11. There is strong evidence that
Arab and Muslim children and families experience some of the highest levels of
discrimination, and as a result, they report higher levels of mental health
symptoms. Given the limited data, we need future studies (a) to focus on
populations outside of the USA and Europe; (b) to use longitudinal designs; (c) to
pay attention to within group variations by race, gender, social class, and
immigration status; and (d) to use culturally validated instruments.
Contextual fear conditioning (CFC) in rodents is the most widely used behavioural
paradigm in neuroscience research to elucidate the neurobiological mechanisms
underlying learning and memory. It is based on the pairing of an aversive
unconditioned stimulus (US; e.g. mild footshock) with a neutral conditioned
stimulus (CS; e.g. context of the test chamber) in order to acquire associative
long-term memory (LTM), which persists for days and even months. Using genome-wide
analysis, several studies have generated lists of genes modulated in response to
CFC in an attempt to identify the "memory genes", which orchestrate memory
formation. Yet, most studies use naive animals as a baseline for assessing gene-
expression changes, while only few studies have examined the effect of the US
alone, without pairing to context, using genome-wide analysis of gene-expression.
Herein, using the ribosome profiling methodology, we show that in male mice an
immediate shock, which does not lead to LTM formation, elicits pervasive
translational and transcriptional changes in the expression of Immediate Early
Genes (IEGs) in dorsal hippocampus (such as Fos and Arc), a fact which has been
disregarded by the majority of CFC studies. By removing the effect of the immediate
shock, we identify and validate a new set of genes, which are translationally and
transcriptionally responsive to the association of context-to-footshock in CFC, and
thus constitute salient "memory genes".
Objectives: To systematically review the literature about: ?What is the global
estimated prevalence of dental fear in adults??. Data/sources: Inclusion criteria
were observational population-based studies reporting the prevalence or raw data of
dental fear in adults (>18 years). Five electronic databases (Embase, PubMed,
Scopus, Virtual Health Library and Web of Science) were searched without language
restrictions up to March 2020. Two researchers independently performed the study
selection, data extraction and quality assessment of the included studies. Risk of
bias was performed using the Joanna Briggs Critical Appraisal Checklist for
Prevalence and Incidence studies. The prevalence pooled estimates of dental fear
were calculated using fixed- and random-effect models. Subgroup analyses were
performed. Study selection: The search strategy identified 4,486 studies. After
removal of duplicates (1,722), title and abstract screening (2,764) and full-text
reading (108), 31 publications were deemed eligible for this systematic review.
Three studies presented low risk of bias and 28 studies presented high risk of
bias. A total of 72,577 individuals 18 years of age or older composed the sample of
this systematic review. The global estimated prevalence of dental fear and anxiety
(DFA), high DFA and severe DFA in adults were 15.3 % (95 %CI 10.2-21.2), 12.4 % (95
% CI 9.5?15.6) and 3.3 % (95 %CI 0.9?7.1), respectively. Subgroup analyses showed a
higher prevalence of DFA, high DFA and severe DFA among women and younger adults.
The instruments used to measure dental fear also affected its prevalence.
Conclusions: Dental fear and high dental fear are prevalent in adults worldwide,
being more prevalent among women. Clinical significance: Evidence suggests fear
negatively impacts dental care pattern, clinical and subjective oral health
conditions. A better knowledge of the global prevalence and the factors associated
with this problem will allow that prevention or even behavior modulation strategies
of the fearful individual?s in dental setting being carried out.
Today people have a few unanswered questions in their mind, such as "Do negative
emotions will co-survive with the COVID-19 pandemic? Which one is worse? Which one
will disappear quicker? Is there any connection between negative emotions and being
infected by COVID-19 or the severity of infected individuals' symptoms? How are we
supposed to live with COVID-19 and adapt our emotional system to the virus for more
than one upcoming year? These uncertainties could result in massive pressure on
people. While there is no clear consensus regarding what establishes psychological
stress on an individual, the effect of negative affect and psychological stress on
increased susceptibility to disease due to altered immune functions is well
established. Here we are going through the possible effect of emotions associated
with the present pandemic on COVID-19 course of disease and severity of symptoms.
Celiac disease (CD) primarily affects the small intestine. Previous studies have
identified higher incidences of neuropsychiatric diseases among CD patients
compared to non-CD controls. Genome-wide association studies have identified >60
non-human leukocyte antigen (HLA) genes associated with CD, where estimated 15%
genes have role in neurological health. We carried out a systematic review and
meta-analysis to estimate the potential risk conferred by CD in developing
neuropsychiatric diseases. Literature search was performed till June 2019.
Incidences of neuropsychiatric diseases were compared among CD and non-CD controls.
Funnel plots and Egger's tests were used to evaluate publication bias and estimate
study effects. Qualities of the included studies were estimated using Newcastle-
Ottawa Scale. Quality of evidence was graded using the Grading of Recommendations
Assessment, Development and Evaluation (GRADE) approach. Odds of developing
neuropsychiatric diseases among CD were evaluated by computing meta-odds ratio
(Manten-Haenszel method) and Z test p-value using random and fixed effect models
based on the degree of study heterogeneity. Thirteen non-randomized case-control
studies were found eligible. Subjects suffering from CD were found to have
significantly more risk to develop depression (p<1.00E-05; OR=1.60 [1.37-1.86]),
anxiety (p=0.05; OR=1.41 [1.00-1.97]), headache (p<0.1.00E-05; OR=3.27 [2.46-
4.34]), epilepsy (p<1.00E-04; OR=11.90 [3.78-37.43]), panic disorder (p<1.00E-04;
OR=4.64 [2.22-9.70]), and dysthymia (p=2.00E-03; OR=5.27 [1.83-15.22]). CD is a
major predisposing factor in developing array of common neuropsychiatric diseases.
Shared biological processes and molecular networks could play a crucial role in
disease co-occurrence. Detailed molecular evidences are needed to establish the
cause-effect relationship between these diseases.
Introduction: Fear of falling (FOF) is a widespread problem affecting about 60% of
people with multiple sclerosis (pwMS). Inflammatory lesions in the brain that are
caused by the disease result in gait deficits and increase the risk of fall. Falls
induce fear of falling and trigger a vicious circle, which in turn increases the
likelihood of falling. Objective of this review was to provide an overview of
existing research on the effects of FOF and therapy options in multiple sclerosis.
Methods: A systematic search at Web of Science and PubMed was conducted. The search
included the terms (fear of falling) OR (concern about falling) OR (fall anxiety)
AND (multiple sclerosis). Results: In included studies, FOF was measured by
different instruments. The Falls Efficacy Scale-International (FES-I) was the most
frequently used instrument for pwMS. Patients with a higher FOF score fell more
frequently, had lower walking speed, shorter stride length, larger ellipse sway
area and a more severe disability. At present, therapeutic offers exist mainly in
the field of physiotherapy. For reducing FOF, assisted vibration (d(z) = 0.68), VR
(d(z) =0.87) and bicycle training (d(z) = 1.23) were the most effective methods.
Conclusion: It is advisable to develop therapies that incorporate both physical and
psychological aspects in neurorehabilitation, like in a cognitive behavioral
therapy. Moreover, FOF monitoring should be integrated into the clinical routine.
A common assumption in human fear conditioning research is that findings are
informative for the etiology and treatment of clinical anxiety. One way to
empirically evaluate the external validity of fear conditioning is by prospective
studies. We review available prospective research investigating whether individual
performance in fear conditioning predicts individual differences in anxiety levels
and exposure-based treatment outcome. We focus on fear extinction, generalization,
acquisition, and avoidance. Results suggest that reduced extinction and broader
generalization predict higher anxiety levels. Results with respect to the
predictive value of acquisition for anxiety levels are mixed. With regard to
predicting exposurebased treatment outcome, some studies do find an association
with extinction whereas others do not. The majority of studies does not find an
association with acquisition. Evidence on extinction recall is limited and not
consistent. The interpretation of these results requires caution. The number of
available studies is limited. It is possible that not all work, in particular
studies with only null effects, has found its way to publication. Future research
on this topic will benefit from large sample sizes, preregistered hypotheses, full
transparency about the conducted analyses and the publication of high-quality
studies with null effects.
Sleep may contribute to the long-lasting consolidation and processing of emotional
memories. Experimental fear conditioning and extinction paradigms model the
development, maintenance, and treatment of anxiety disorders. The literature
provides compelling evidence for the involvement of rapid eye movement (REM) sleep
in the consolidation of such memories. This meta-analysis correlated poly-
somnographic sleep findings with psychophysiological reactivity to the danger
(CSthorn) and safety stimuli (CS-), to clarify the specific role of sleep stages
before and after fear conditioning, extinction learning and extinction recall.
Overall, there was evidence that more pre-learning sleep stage two and less slow
wave sleep was associated with higher psychophysiological reactivity to the safety
stimulus during extinction learning. Preliminary evidence found here support the
role of REM sleep during the post-extinction consolidation sleep phase in clinical
populations with disrupted sleep, but not in healthy controls. Furthermore, the
meta-regressions found that sex moderated the associations between sleep and psy-
chophysiological reactivity throughout the paradigm providing evidence for
diverging correlations in male and females. Specifically, increased post-extinction
REM was associated with poorer extinction and safety recall in females while the
opposite was found in males. These results have implications for future research in
the role of sleep in emotional memory processing. (C) 2021 Elsevier Ltd. All rights
reserved.
The ability to extinguish fear memories when threats are no longer present is
critical for adaptive behavior. Fear extinction represents a new learning process
that eventually leads to the formation of extinction memories. Understanding the
neural basis of fear extinction has considerable clinical significance as deficits
in extinction learning are the hallmark of human anxiety disorders. In recent
years, the dopamine (DA) system has emerged as one of the key regulators of fear
extinction. In this review article, we highlight recent advances that have
demonstrated the crucial role DA plays in mediating different phases of fear
extinction. Emerging concepts and outstanding questions for future research are
also discussed.
COVID-19, the global pandemic of the decade was declared as an overall health
emergency of national and international concern on 30th of January 2020 by World
Health Organization.It created a worldwide panic during the recent times. Millions
of new cases were being reported daily and considerable mortality was reported.The
psychological trauma of loss of near and dear ones and fear and anxiety of
isolation affected the attitude of general population towards healthcare workers
and professionals.This COVID-19 pandemic is provoking social stigma big time and
peculiar behaviour against person of a particular kind of background and also as
somebody thought to have being with contact of the virus.In some instance when in
the pandemic like condition the incidence of psychosocially morbid are always seems
much more than in comparison to normal. The present condition which has been
because of former virus, pandemic is causing some increasing worry, emotional
stress and fright within population and various groups across the world. This study
has attempted to compile the episodes of discrimination against COVID warriors and
different aspects of managing psychosocial influences.
A bioterror event using an infectious bacterium may lead to catastrophic outcomes
involving morbidity and mortality as well as social and psychological stress.
Moreover, a bioterror event using an antibiotic resistance engineered bacterial
agent may raise additional concerns. Thus, preparedness is essential to preclude
and control the dissemination of the bacterial agent as well as to appropriately
and promptly treat potentially exposed individuals or patients. Rates of morbidity,
death, and social anxiety can be drastically reduced if the rapid delivery of
antimicrobial agents for post-exposure prophylaxis and treatment is initiated as
soon as possible. Availability of rapid antibiotic susceptibility tests that may
provide key recommendations to targeted antibiotic treatment is mandatory, yet,
such tests are only at the development stage. In this review, we describe the
recently published rapid antibiotic susceptibility tests implemented on bioterror
bacterial agents and discuss their assimilation in clinical and environmental
samples.
Purpose: A diagnosis of testicular cancer (TC) at a relatively young age can have a
dramatic impact on the psychological well-being of those affected. The aim of this
review was to synthesize recent evidence to provide an updated account of the
prevalence, severity and correlates of anxiety, depression, fear of cancer
recurrence (FCR) and distress in TC survivors. Patients and Methods: A systematic
literature review was conducted from September 2017 until June 2020 using
electronic databases including Embase, MEDLINE, PsycINFO, Scopus and Web of
Science. Study eligibility and quality were independently assessed by two
reviewers. Narrative synthesis was used to depict the severity (mean/median
scores), prevalence (proportions above standard clinical thresholds) and correlates
of study outcomes. Results: A total of 988 articles were identified for screening
after duplicate removal. Fiftysix full-text articles were screened, and eight
articles met the inclusion criteria. The reported prevalence of the outcomes varied
across studies (clinical levels of anxiety ranged from 6.9% to 21.1%, depression
varied from 4.7% to 7%, distress was found between 25% and 41.4%, prevalence of FCR
was not reported). Few studies compared TC survivors with other populations.
Correlates of poorer psychological outcomes included younger age, relationship
status, employment status, poorer sexual functioning, impaired masculinity and
coping strategies. Conclusion: Anxiety seems to be the most common issue for TC
survivors. Men who are single or unemployed appear most at risk of poorer
psychological outcomes, which seem associated with impaired masculinity and sexual
function. More research is needed to identify TC survivors most likely to need one
of the increasing number of psychological interventions being developed for TC
survivors.
Simple Summary The majority of dogs and cats are fearful during veterinary visits,
and some individuals may show aggression as a result. We review ways to avoid
negative experiences and promote positive emotions in animals visiting the
veterinarian. Whenever an animal is in the practice, the veterinary team should
endeavour to make the visit as pleasant as possible, by using non-threatening body
language and by creating positive associations. High-value food (unless an animal
needs to be fasted) or toys should be used generously throughout the visit. In the
interaction with the animals, low-stress handling methods, brief pauses and
adjusting the procedure based on the animal's body language help them to feel
secure. Distractions can be used to minimise perceived pain such as from
injections. If a known painful area needs to be treated, pain killers are advised.
For animals that are very fearful, several medication options are available that
can be given prior to the veterinary visit to help them with their fears. With
reward-based training, animals can learn to accept veterinary procedures. A stress-
free veterinary visit benefits all involved parties-the animals, their owners, as
well as the veterinary team. A high proportion of dogs and cats are fearful during
veterinary visits, which in some cases may escalate into aggression. Here, we
discuss factors that contribute to negative emotions in a veterinary setting and
how these can be addressed. We briefly summarise the available evidence for the
interventions discussed. The set-up of the waiting area (e.g., spatial dividers;
elevated places for cat carriers), tailoring the examination and the treatment to
the individual, considerate handling (minimal restraint when possible, avoiding
leaning over or cornering animals) and offering high-value food or toys throughout
the visit can promote security and, ideally, positive associations. Desensitisation
and counterconditioning are highly recommended, both to prevent and address
existing negative emotions. Short-term pain from injections can be minimised by
using tactile and cognitive distractions and topical analgesics, which are also
indicated for painful procedures such as ear cleanings. Recommendations for
handling fearful animals to minimise aggressive responses are discussed. However,
anxiolytics or sedation should be used whenever there is a risk of traumatising an
animal or for safety reasons. Stress-reducing measures can decrease fear and stress
in patients and consequently their owners, thus strengthening the relationship with
the clients as well as increasing the professional satisfaction of veterinary
staff.
Objective: The objective of this review is to explore existing literature related
to fear of falling activity avoidance behavior and identify what is known about
this phenomenon in people with Parkinson's disease. Introduction: Falling and fear
of falling are significant concerns for persons with Parkinson's disease. Fear of
falling is a significant problem over and above falling itself and can lead to
activity avoidance. Activity-avoidance behavior is a risk factor for increased
falls and can lead to further functional decline. A better understanding of the
fear of falling and the associated avoidance behavior can inform screening,
evaluation, and interventions to decrease fall risk and improve activity engagement
and quality of life for persons with Parkinson's disease. Inclusion criteria: This
review will consider studies published in English that include individuals
diagnosed with Parkinson's disease experiencing fear of falling that impacts
activity engagement with no limit on participant age or time of publication.
Methods: JBI methodology will be used to conduct this scoping review. A three-step
search strategy will be utilized. The databases to be searched include MEDLINE
(PubMed), Embase (Elsevier), Scopus (Elsevier), APA PsycINFO (EBSCO), CINAHL
(EBSCO), Papers First (OCLC), and ProQuest Dissertations and Theses (ProQuest). Two
independent reviewers will screen the titles, abstracts, and full text of the
selected studies. Data collection will be performed with a tool developed by the
researchers based on the standardized tool from JBI SUMARI. Data will be presented
in a comprehensive narrative summary.
The classic gut hormone cholecystokinin (CCK) and its CCK2-receptor are expressed
in almost all regions of the brain. This widespread expression makes CCK by far the
most abundant peptidergic transmitter system in the brain. This CNS-ubiquity has,
however, complicated the delineation of the roles of CCK peptides in normal brain
functions and neuropsychiatric diseases. Nevertheless, the common panic disorder
disease is apparently associated with CCK in the brain. Thus, the C-terminal
tetrapeptide fragment of CCK (CCK-4) induces, by intravenous administration in a
dose-related manner, panic attacks that are similar to the endogenous attacks in
panic disorder patients. This review describes the history behind the discovery of
the panicogenic effect of CCK-4. Subsequently, the review discusses three unsettled
questions about the involvement of cerebral CCK in the pathogenesis of anxiety and
panic disorder, including therapeutic attempts with CCK2-receptor antagonists.
The global COVID-19 pandemic has focused the attention of researchers, civil
authority and the general public on the phenomenon of "panic buying," characterized
by the excessive purchase of specific materials-particularly food and hygiene-
related products-in anticipation of an expected shortage. This phenomenon has been
well-documented in response to several natural and man-made disasters, but its
global scope and severity in the context of COVID-19 are unprecedented. This
response can negatively impact health, food security, and disease prevention
efforts. Attempts to modify such behaviors are more likely to succeed if they are
based on insights from both the biomedical and the social sciences. From a
biological perspective, the phenomenological overlap between panic buying and
psychological disorders such as hoarding disorder and compulsive buying raises the
possibility of a shared neurobiological underpinning. Evolutionary models suggest
that these behaviors represent an attempt to enhance individual and group survival
in the face of a threatened scarcity of resources. These phenomena may be
influenced by specific genetic variants which are also implicated in hoarding-
related psychological disorders. From a psychological perspective, attachment
theory provides a conceptual framework that serves as a bridge between prior life
adversity, current deprivation, and an increased attachment to material objects.
Such a framework is of relevance when considering panic buying during the COVID-19
pandemic, which has been associated with significant disruptions in attachment
bonds. From a social-anthropological perspective, hoarding and related behaviors
have been associated with social exclusion and rejection, as well a lack of social
support. These risk factors have affected large sections of the general population
in the context of the COVID-19 pandemic and the governmental responses to it. This
perspective also emphasizes the symbolic significance of the hoarded objects
themselves. In this paper, an attempt is made to integrate these three perspectives
and thereby formulate a biopsychosocial model of panic buying in response to this
global health crisis. The existing scientific literature on panic buying is
examined in the light of this model. Finally, suggestions are proposed as to how
this model might inform social strategies aimed at preventing or reducing panic
buying.
The coronavirus disease 2019 (COVID-19) pandemic has had different effects on
different occupations. The present study was designed to systematically review the
available evidence to investigate the pandemic on occupational effects. The
academic databases of Scopus, PubMed Central, ProQuest, Science Direct, and ISI Web
of Knowledge were searched systematically between December 2019 and February 2021.
COVID-19-related fear, concern, worry, anxiety, and stress in combination with job-
related MeSH terms were used to search the databases. The methodological quality of
included papers was assessed using the Newcastle Ottawa Scale checklist. To
synthesize data, a qualitative synthesis of findings was performed due to the small
number of included studies (n = 4) and the heterogeneity of the assessed outcomes.
Four studies were included in the final analysis. All four studies were cross-
sectional, collected the data online, and comprised 1654 participants from four
different countries. Fear of COVID-19 was associated with increased future career
anxiety, perceived job insecurity, organizational and professional turnover
intentions, and decreased job satisfaction. COVID-19 Anxiety Syndrome was
associated with scores on the Work and Social Adjustment Scale. As so few studies
have been conducted, there are no conclusive findings. More studies using valid and
reliable measures to assess fear/anxiety related to COVID-19 and its' association
with job attributes are needed. It is also recommended that these associations are
examined in variety of different jobs.
Background: Psychological stressors like panic, fear, phobia, etc., are being
substantially reported during the COVID-19 outbreak. In the prior outbreaks, fear
of being infected was reported as the prominent suicide stressor. Therefore, fear
of infection has become a concern in the context of the COVID-19 pandemic because
it worsens emotion, cognition, and behavioral responses. Understanding the extent
of fear of COVID-19 infection in various cohorts would aid in gauging the mental
health services, which was a remedy in the present review.</p> Methods: Adhering to
Arksey and O'Malley's framework for conducting a scoping review, a systematic
search was performed in the month of September 2020 in several databases, including
Scopus, PubMed, Web of Science, etc. Considering the inclusion criteria, a total of
14 articles were included in the present review.</p> Results: All of the included
studies were conducted via online platforms, whereas all but one of the studies
were cross-sectional in nature (including a mixed-method study, and a comparative
study). Most of the studies were conducted among the general population (n = 12),
within March and May 2020 (n = 9), from Asian countries (n = 7), and considered a
self-developed item for fear of COVID-19 assessment (n = 8; whereas the Fear of
COVID-19 Scale was used in 6-studies). The prevalence of fear of COVID-19 was
reported to be 18.1-45.2%, although no cutoff point or criteria was mentioned for
such a prevalence estimation of the Fear of COVID-19 Scale. However, females,
younger adults, urban residents, divorcees, healthcare workers, those in quarantine
settings, those in suspicion of being infected, and those with mental health
problems, etc., were found to be at an increased risk of COVID-19 fear.</p>
Conclusions: Being one of the first reviews in this context, the findings are
anticipated to be helpful to predict the possible solutions for reducing fear of
COVID-19 and facilitate further studies on strategies of how to alleviate such a
stressful situation.</p>
Background: Fear of cancer recurrence or progression (FCR) is common amongst cancer
survivors and an important minority develop clinically significant levels of FCR.
However, it is unclear how current clinical services might best support the growing
numbers of cancer survivors. Purpose: The aim of this study is to develop
recommendations for future research in the management of FCR and propose a model of
care to help manage FCR in the growing population of cancer survivors. Methods:
This is a narrative review and synthesis of empirical research relevant to managing
FCR. We reviewed meta-analyses, systematic reviews and individual studies that had
investigated interventions for FCR. Results: A recent, well-conducted meta-analysis
confirmed a range of moderately effective treatments for FCR. However, many
survivors continued to experience clinical levels of FCR after treatment,
indicating a clear need to improve the gold standard treatments. Accessibility of
interventions is arguably a greater concern. The majority of FCR treatments require
face-to-face therapy, with highly skilled psycho-oncologists to produce moderate
changes in FCR. With increasing numbers of cancer survivors, we need to consider
how to meet the unmet need of cancer survivors in relation to FCR. Although there
have been attempts to develop minimal interventions, these are not yet sufficiently
well supported to warrant implementation. Attempts to help clinicians to provide
information which might prevent the development of clinically significant FCR have
shown some early promise, but research is needed to confirm efficacy. Conclusion:
The next decade of research needs to focus on developing preventative approaches
for FCR, and minimal interventions for those with mild-to-moderate symptoms. When
evidence-based approaches to prevent FCR or manage moderate levels of FCR are
available, stepped care approaches that could meet the needs of survivors could be
implemented. However, we also need to improve existing interventions for severe
FCR.
Background: A significant concern for patients treated for cancer is fear of cancer
recurrence (FCR). Although a common experience, some patients report high levels of
FCR that are difficult to manage and result in over vigilant checking and high use
of health services. There has been speculation about the relationship of FCR with
gender with mixed reports from several systematic reviews. Aims: To determine the
association of FCR with gender in previous reported studies and investigate the
strength of this relationship with various moderators including year of
publication, type of cancer and measurement attributes of self-reported FCR
instruments. Methods: A systematic review was conducted with searches of the
literature from the MEDLINE, PubMed, Embase, and PsycINFO databases following
PRISMA guidelines. All the included papers were divided into two groups, namely:
"pure" that comprise only of patients with cancer types that both men and women can
contract and "mixed" that report on patients with a variety of cancer types. The
association between gender and FCR level was assessed by meta-analysis. A meta-
regression was performed to investigate the moderating effects of factors
including: the year of publication, cancer type, mean age of the sample and the
length of the FCR scale measurement. This review was registered with PROSPERO, ID:
CRD42020184812. Results: Finally, 29 studies were included. The N size of pooled
participants was 33,339. The meta-analysis showed females to have an overall higher
level of FCR than males (ES = 0.30; 95% CI, 0.23, 0.36). The meta-regression of
moderating or control variables found little, if any, systematic variation in
effect-sizes. Conclusion: This systematic review has clarified a potentially
confused pattern of previous results in understanding the relationship between
gender and FCR. Women report higher levels of FCR than men and this feature is one
that clinicians and researchers can factor into their practice and future studies.
The effect size is moderate, hence there is ample variation in FCR level,
independent of gender, that requires further investigation.
Background: Panic Disorder (PD) is mainly characterized by recurrent unexpected
panic attacks. Although the presence of emotional functioning deficits in PD is
well established, their neuronal bases are still less known. Therefore, in this
review, we aim to summarize the available functional Magnetic Resonance Imaging
(fMRI) studies investigating the neural correlates associated with the processing
of facial emotional expressions in patients with PD. Methods: A comprehensive
search on PubMed was performed and 10 fMRI studies meeting our inclusion criteria
were included in this review. Results: The majority of the studies reported
selective deficits in key brain regions within the prefronto-limbic network in PD
patients. Specifically, a mixed picture of hyperactivation and hypoactivation
patterns were observed in limbic regions, including the amygdala and the anterior
cingulate cortex (ACC), as well as in areas within the prefrontal cortex (PFC),
either during negative or positive valenced stimuli, as compared to healthy
controls (HC) or other anxiety disorders. Limitations: The limited number of
studies and the clinical and methodological heterogeneity make it difficult to draw
definite conclusions on the neural mechanism of emotional processing associated
with PD. Conclusion: Although the results of the available evidence suggest the
presence of selective dysfunctions in regions within the cortico-limbic network in
PD patients during processing of emotional stimuli, the direction of these
abnormalities is still unclear. Therefore, future larger and more homogeneous
studies are needed to elucidate the neural mechanisms underpinning the emotional
processing dysfunctions often observed in PD patients.
Adolescence is a peak time for the onset of psychiatric disorders, with anxiety
disorders being the most common and affecting as many as 30% of youths. A core
feature of anxiety disorders is difficulty regulating fear, with evidence
suggesting deficits in extinction learning and corresponding alterations in
frontolimbic circuitry. Despite marked changes in this neural circuitry and
extinction learning throughout development, interventions for anxious youths are
largely based on principles of extinction learning studied in adulthood. Safety
signal learning, based on conditioned inhibition of fear in the presence of a cue
that indicates safety, has been shown to effectively reduce anxiety-like behavior
in animal models and attenuate fear responses in healthy adults. Cross-species
evidence suggests that safety signal learning involves connections between the
ventral hippocampus and the prelimbic cortex in rodents or the dorsal anterior
cingulate cortex in humans. Particularly because this pathway follows a different
developmental trajectory than Pronto-amygdala circuitry involved in traditional
extinction learning, safety cues may provide a novel approach to reducing fear in
youths. In this review, the authors leverage a translational framework to bring
together findings from studies in animal models and humans and to bridge the gap
between research on basic neuroscience and clinical treatment. The authors consider
the potential application of safety signal learning for optimizing interventions
for anxious youths by targeting the biological state of the developing brain. Based
on the existing cross-species literature on safety signal learning, they propose
that the judicious use of safety cues may be an effective and neurodevelopmentally
optimized approach to enhancing treatment outcomes for youths with anxiety
disorders.
Cataract surgery is one of the most frequently performed surgical procedures
worldwide. Patients usually experience strong negative emotions, such as fear and
anxiety. A systematic review of the recent literature regarding the emotional
states experienced during cataract surgery under local anaesthesia was performed
based on the PubMed and Scopus databases. The objective of this review was to
determine the causes and frequency of fear and anxiety, as well as methods for
improving intraoperative experience and supporting the patient prior to surgery.
Anxiety is mainly caused by fear of the surgery itself, fright of pain, and loss of
vision. Abstaining and visual sensations experienced during cataract surgery also
increased the preoperative anxiety. Women and hypochondriacs showed higher levels
of anxiety. The greatest intensity of negative emotions occurred on the day of the
cataract surgery. Patients operated on both eyes experienced greater fear and
anxiety before the operation of the first eye surgery. In order to reduce patients'
negative experiences, pharmacological sedation, preoperative education and
counselling, manual massage immediately before surgery, and listening to music
during surgery are used. Taking this information into consideration allows the
introduction of effective methods of eliminating the patient's negative feelings in
connection with cataract surgery, which leads to an improvement in the results of
the operation and an increase in the patients' sense of satisfaction and quality of
life.
Objective: Fear of cancer recurrence (FCR) is a significant concern for family
caregivers of cancer survivors and is associated with many adverse outcomes,
including increased emotional distress and poorer quality of life. Although several
theoretical models have been proposed to account for FCR in cancer survivors, their
applicability to caregivers is unknown. The aim of this review was to identify
clinical, demographic and psychological factors that are associated with, and
predict, FCR in caregivers of cancer survivors. Method: AMED, CINAHL, Medline,
PsycINFO, and Scopus were systematically searched for relevant studies reporting
quantitative data on factors associated with FCR or similar constructs (e.g., worry
or anxiety about cancer recurrence) in family caregivers of adult cancer survivors.
Included studies were assessed for methodological quality using a standardized
checklist adapted from the Agency for Healthcare Research and Quality. Results:
Sixteen studies, half of which were cross-sectional, were included and summarized
narratively. Non-modifiable factors, including age (n = 6) and treatment modality
(n = 4), were found to be associated with increased FCR. Significant positive
associations were also reported between illness perceptions and FCR (n = 3).
However, there was heterogeneity across included studies with regards to factors
examined and most were conducted in the USA. There were also several methodological
limitations to the included studies. Conclusions: Research examining FCR in
caregivers of cancer survivors has predominantly focused on demographic and
clinical factors. Given the paucity of research exploring the psychological
mechanisms underpinning FCR, future research should investigate theoretical
underpinnings of FCR in caregivers of cancer survivors to support the development
of psychological interventions for this population.
To review the anxiety and fear risk factors, pathophysiology, symptoms, screening
and diagnosis while highlighting treatment considerations for women undergoing a
pelvic examination. Methods: We reviewed the literature pertaining to anxiety and
fear surrounding the pelvic examination to help guide health care providers' on
available screening options and to review options for individualized patient
management. Results: Anxiety and fear are common before and during the pelvic
examination. In fact, the pelvic exam is one of the most common anxiety-provoking
medical procedures. This exam can provoke negative physical and emotional symptoms
such as pain, discomfort, anxiety, fear, embarrassment, and irritability. These
negative symptoms can interfere with preventative health screening compliance
resulting in delayed or avoided care and significant health consequences.
Conclusion: Assessing women for anxiety related to pelvic examinations may help
decrease a delay or avoidance of examinations. Risk factor and symptom
identification is also a key component in this. General anxiety questionnaires can
help identify women with anxiety related to pelvic examinations. Strategies to
reduce anxiety, fear and pain during a pelvic examination should routinely be
implemented, particularly in women with high-risk factors or those identified with
screening techniques as having anxiety, fear or pain with examinations. Treatment
options should be targeted at understanding the patient's concerns, starting
conversations about pelvic examinations early, educating patient's about the
examination and offering the presence of a chaperone or support person. During an
examination providers should ensure the patient is comfortable, negative phrases
are avoided, the correct speculum size is utilized and proper lubrication, draping,
dressing and positioning are performed. Treating underlying gynecologic or mental
health conditions, consideration of cognitive behavioral therapy and complementary
techniques such as lavender aromatherapy and music therapy should also be
considered when appropriate.
Background Many women experience fear of childbirth (FOC). While fears about
childbirth may be normal during pregnancy, some women experience high to severe
FOC. At the extreme end of the fear spectrum is tocophobia, which is considered a
specific condition that may cause distress, affect well-being during pregnancy and
impede the transition to parenthood. Various interventions have been trialled,
which support women to reduce and manage high to severe FOC, including tocophobia.
Objectives To investigate the effectiveness of non-pharmacological interventions
for reducing fear of childbirth (FOC) compared with standard maternity care in
pregnant women with high to severe FOC, including tocophobia. Search methods In
July 2020, we searched Cochrane Pregnancy and Childbirth's Trials Register,
ClinicalTrials.gov , the World Health Organization (WHO) International Clinical
Trials Registry Platform (ICTRP), and reference lists of retrieved studies. We
contacted researchers of trials which were registered and appeared to be ongoing.
Selection criteria We included randomised clinical trials which recruited pregnant
women with high or severe FOC (as defined by the individual trial), for treatment
intended to reduce FOC. Two review authors independently screened and selected
titles and abstracts for inclusion. We excluded quasi-randomised and cross-over
trials. Data collection and analysis We used standard methodological approaches as
recommended by Cochrane. Two review authors independently extracted data and
assessed the studies for risk of bias. A third review author checked the data
analysis for accuracy. We used GRADE to assess the certainty of the evidence. The
primary outcome was a reduction in FOC. Secondary outcomes were caesarean section,
depression, birth preference for caesarean section or spontaneous vaginal delivery,
and epidural use. Main results We included seven trials with a total of 1357
participants. The interventions included psychoeducation, cognitive behavioural
therapy, group discussion, peer education and art therapy. We judged four studies
as high or unclear risk of bias in terms of allocation concealment; we judged three
studies as high risk in terms of incomplete outcome data; and in all studies, there
was a high risk of bias due to lack of blinding. We downgraded the certainty of the
evidence due to concerns about risk of bias, imprecision and inconsistency. None of
the studies reported data about women's anxiety. Participating in non-
pharmacological interventions may reduce levels of fear of childbirth, as measured
by the Wij ma Delivery Expectancy Questionnaire (W-DEQ), but the reduction may not
be clinically meaningful (mean difference (MD) -7.08, 95% confidence interval (CI)
-12.19 to -1.97; 7 studies, 828 women; low-certainty evidence). The W-DEQ toot is
scored from 0 to 165 (higher score = greater fear). Non-pharmacological
interventions probably reduce the number of women having a caesarean section (RR
0.70, 95% CI 0.55 to 0.89; 5 studies, 557 women; moderate-certainty evidence).
There may be little to no difference between non-pharmacological interventions and
usual care in depression scores measured with the Edinburgh Postnatal Depression
Scale (EPDS) (MD 0.09, 95% CI -1.23 to 1.40; 2 studies, 399 women; low-certainty
evidence). The EPDS tool is scored from 0 to 30 (higher score = greater
depression). Non-pharmacological interventions probably lead to fewer women
preferring a caesarean section (RR 0.37, 95% CI 0.15 to 0.89; 3 studies, 276 women;
moderate-certainty evidence). Non-pharmacological interventions may increase
epidural use compared with usual care, but the 95% CI includes the possibility of a
slight reduction in epidural use (RR 1.21, 95% CI 0.98 to 1.48; 2 studies, 380
women; low-certainty evidence). . Authors' conclusions The effect of non-
pharmacological interventions for women with high to severe fear of childbirth in
terms of reducing fear is uncertain. Fear of childbirth, as measured by W-DEQ, may
be reduced but it is not certain if this represents a meaningful clinical reduction
of fear. There may be little or no difference in depression, but there may be a
reduction in caesarean section delivery. Future trials should recruit adequate
numbers of women and measure birth satisfaction and anxiety
There currently exist few frameworks for common neurobiology between reexperiencing
and negative cognitions and mood symptoms of PTSD. Adopting a dopaminergic
framework for PTSD unites many aspects of unique symptom clusters, and this
approach also links PTSD symptomology to common comorbidities with a common
neurobiological deficiency. Here we review the dopamine literature and incorporate
it with a growing field of research that describes both the contribution of
endocannabinoids to fear extinction and PTSD, as well as the interactions between
dopaminergic and endocannabinoid systems underlying this disorder. Based on current
evidence, we outline an early, preliminary model that links re-experiencing and
negative cognitions and mood in PTSD by invoking the interaction between
endocannabinoid and dopaminergic signalling in the brain. These interactions
between PTSD, dopamine and endocannabinoids may have implications for future
therapies for treatment-resistant and comorbid PTSD patients.
Background The COVID-19 pandemic has become a source of fear across the world.
Measuring the level or significance of fear in different populations may help
identify populations and areas in need of public health and education campaigns. We
were interested in diagnostic tests developed to assess or diagnose COVID-19-
related fear or phobia. Methods We performed a systematic review of studies that
examined instruments diagnosing or assessing fear or phobia of COVID-19 (PROSPERO
registration: CRD42020197100). We utilized the Norwegian Institute of Public
Health's Live map of covid-19 evidence, a database of pre-screened and pre-
categorized studies. The Live map of covid-19 evidence identified references
published since 1 December 2019 in MEDLINE, Embase, and the Centers for Disease
Control and Prevention. Following biweekly searches, two researchers independently
categorized all studies according to topic (seven main topics, 52 subordinate
topics), population (41 available groups), study design, and publication type. For
this review, we assessed for eligibility all studies that had been categorized to
the topic "Experiences and perceptions, consequences; social, political, economic
aspects" as of 25 September 2020, in addition to hand-searching included studies'
reference lists. We meta-analyzed correlation coefficients of fear scores to the
most common reference tests (self-reports of anxiety, depression, and stress), and
reported additional concurrent validity to other reference tests such as specific
phobias. We assessed study quality using the QUADAS-2 for the minority of studies
that presented diagnostic accuracy statistics. Results We found 18 studies that
validated fear instruments. Fifteen validated the Fear of COVID-19 scale (FCV-19S).
We found no studies that proposed a diagnosis of fear of COVID-19 or a threshold of
significant/clinical versus non-significant/subclinical fear. Study quality was
low, with the most common potential biases related to sampling strategy and un-
blinded data analysis. The FSV-19S total score correlated strongly with severe
phobia (r = 0.703, 95%CI 0.634-0.761) in one study, and moderately with anxiety in
a meta-analysis. Conclusions The accuracy of the FSV-19S needs to be measured
further using fear-related reference instruments, and future studies need to
provide cut-off scores and normative values. Further evaluation of the remaining
three instruments is required.
The present work aims to explain FoMO, anxiety and social media, identifying
categories and related variables through a systematic review of exploratory
literature in the respective databases: Scopus, PubMed, Web of Science, PsycINFO
and Lilacs, using only empirical articles published in Portuguese and English in
the last 10 years. It is concluded, based on the databases used in this research,
that the personality is understood as a predictor of the engagement and problematic
use of social media, in addition, it is verified that the association with the FoMO
is direct, since such traits provoke a need of the individuals to remain online and
connected, independently of any cost or consequence, generating anxiety.
Background: This study aimed to assess factors affecting panic buying and
strategies to deal with them during COVID-19 with a scoping review. Method: The
review was performed based on Arksey and O'Malley. PubMed, Embase, Scopus,
ProQuest, and Science Direct databases were selected to search. All English
language full-text articles from Jan 2020 to May 2021 were included. Initially, the
titles and abstracts of the retrieved articles were read and screening was
accomplished based on the research question. After that, the full text of eligible
studies was examined. A third reviewer was resolved disagreements at any stage by a
consensus meeting. A self-assessment form was designed for data extraction. The
causes of panic buying were assessed as a descriptive study. Results: The search
process returned 23 articles after deletion for complete data extraction and
analysis. Through thematic analysis, the factors influencing panic buying were
divided into six categories including cognitive, emotional, behavioral, social, and
economic factors as well as government action, and finally, the recommended
strategies were categorized in two categories included psychosocial and economic.
Conclusion: A holistic view of panic buying's causes allows planners and decision-
makers to design categorized strategies beyond the suggested strategies. Increasing
customer awareness and monitoring the flow of information through social media and
mass media, psychotherapy, counseling, and economic strategies are considered by
planners to combat panic buying.
As the number of patients infected with the 2019 novel coronavirus disease (nCOVID-
19) increases, the number of deaths has also been increasing. According to World
Health Organization (WHO), as of 4 October 2020, 34,804,348 cases had tested
positive for nCOVID-19 globally, which among them, 1,030,738 confirmed deaths had
occurred, equivalent to a case-fatality rate of 2.96%. However, in comparison with
global statistics, the incidence and mortality of the nCOVID-19 infection are
higher in Iran. As reported by the National Committee on COVID-19 Epidemiology of
Ministry of Health of Iran, the total number of patients with confirmed COVID-19
infection has reached 468,119, of which 26,746 have died, equivalent to a case-
fatality rate of 5.71%. Currently, there is solid evidence that older adults are at
a higher risk of severe disease following infection from COVID-19.
Background: It is estimated that approximately 13% of expectant fathers experience
a pathological and debilitating fear of childbirth. Objective: The aim of this
integrative review was to examine and synthesise the current body of research
relating to paternal experience of fear of childbirth. Methods: A systematic
literature search of five databases-CINAHL, Cochrane Library, MEDLINE, PsycArticles
and PsycInfo-identified seventeen papers. Methodological quality of studies was
assessed using the Crowe Critical Appraisal Tool. Results: Thematic data analysis
identified three themes: the focus of fathers' childbirth-related fears, the impact
of fear of childbirth on health and wellbeing, and fear of childbirth as a private
burden. Discussion: Fear of childbirth is a significant and distressing experience
for expectant fathers who may benefit from an opportunity to express their
childbirth-related fears in an environment where they feel validated and supported.
Antenatal education is recommended to enhance fathers' childbirth-related self-
efficacy to reduce fear of childbirth. Conclusions: Fear of childbirth may
negatively impact the lives of men and consequently their families. Further
investigation into methods and models for identifying and supporting men at risk of
or experiencing fear of childbirth is required to improve outcomes for this
population of men.
Animal behavior is greatly shaped by the 'landscape of fear', induced by predation
risk, and the equivalent 'landscape of disgust', induced by parasitism or infection
risk. However, the role that carrion may play in these landscapes of peril has been
largely overlooked. Here, we aim to emphasize that animal carcasses likely
represent ubiquitous hotspots for both predation and infection risk, thus being an
outstanding paradigm of how predation and parasitism pressures can concur in space
and time. By conducting a literature review, we highlight the manifold inter- and
intra-specific interactions linked to carrion via predation and parasitism risks,
which may affect not only scavengers, but also non-scavengers. However, we
identified major knowledge gaps, as reviewed articles were highly biased towards
fear, terrestrial environments, vertebrates, and behavioral responses. Based on the
reviewed literature, we provide a conceptual framework on the main fear- and
disgust-based interaction pathways associated with carrion resources. This
framework may be used to formulate predictions about how the landscape of fear and
disgust around carcasses might influence animals' individual behavior and
ecological processes, from population to ecosystem functioning. We encourage
ecologists, evolutionary biologists, epidemiologists, forensic scientists, and
conservation biologists to explore the promising research avenues associated with
the scary and disgusting facets of carrion. Acknowledging the multiple trophic and
non-trophic interactions among dead and live animals, including both herbivores and
carnivores, will notably improve our understanding of the overlapping pressures
that shape the landscape of fear and disgust.
Endocannabinoids are involved in various physiological functions, including
synaptic plasticity and memory, and some psychiatric disorders, such as
posttraumatic stress disorder (PTSD), through the activation of cannabinoid (CB)
receptors. Patients with PTSD often show excessive fear memory and impairment of
fear extinction (FE). It has been reported that the stability of acquired fear
memory is altered through multiple memory stages, such as consolidation and
reconsolidation. FE also affects the stability of fear memory. Each stage of fear
memory formation and FE are regulated by different molecular mechanisms, including
the CB system. However, to the best of our knowledge, no review summarizes the role
of the CB system during each stage of fear memory formation and FE. In this review,
we summarize the roles of endocannabinoids in fear memory formation and FE.
Moreover, based on the summary, we propose a new hypothesis for the role of
endocannabinoids in fear regulation, and discuss treatment for PTSD using CB
system-related drugs.
Background: As the remission rate of panic disorder (PD) achieved with conventional
pharmacotherapy ranges between 20% and 50%, alternative psychopharmacological
strategies are needed. We aimed to firstly review data regarding use of
antipsychotic and non-benzodiazepine anticonvulsant medication in PD patients with
or without comorbidities; secondly, to review data concerning reduction of panic
symptoms during treatment of another psychiatric disorder with the same
medications; and thirdly, to examine reports of anticonvulsant- or antipsychotic-
induced new-onset panic symptomatology. Methods: We performed a PubMed search (last
day: 28 April 2020) of English-language studies only, combining psychopathological
terms (e.g. 'panic disorder') and terms referring either to categories of
psychotropic medications (e.g. 'anticonvulsants') or to specific drugs (e.g.
'carbamazepine'). All duplications were eliminated. All studies included in the
review met certain inclusion/exclusion criteria. The level of evidence for the
efficacy of each drug was defined according to widely accepted criteria. Results:
In treatment-resistant PD, beneficial effects have been reported after treatment
(mostly augmentation therapy) with a range of anticonvulsant (carbamazepine,
gabapentin, lamotrigine, levetiracetam, oxcarbamazepine, valproate, vigabatrin,
tiagabine) and antipsychotic (aripiprazole, olanzapine, risperidone, sulpiride)
medications: overall, most medications appear generally well tolerated.
Additionally, bipolar patients receiving valproate or quetiapine-XR (but not
risperidone or ziprasidone) demonstrated reductions of comorbid panic-related
symptoms. There are case reports of new-onset panic symptoms associated with
clozapine, haloperidol, olanzapine and topiramate, in patients with conditions
other than PD. The small-to-modest sample size, the lack of control groups and the
open-label and short-term nature of most of the reviewed studies hinder definitive
conclusions regarding either the short-term and long-term efficacy of antipsychotic
and anticonvulsant medications or their potential long-term side effects.
Conclusion: Some atypical antipsychotic and anticonvulsant medications may have a
role in the treatment of some PD patients, mostly when more conventional approaches
have not been successful, but the quality of supporting evidence is limited.
Objective. This systematic review aimed to evaluate the effectiveness of different
interventions at reducing pain-related fear in people with fibromyalgia and to
analyze whether the included trials reported their interventions in full detail.
Design. Systematic review. Setting. No restrictions. Methods. The Cochrane Library,
CINAHL, EMBASE, PsycINFO, PubMed, and Scopus were searched from their inception to
April 2020, along with manual searches and a gray literature search. Randomized
clinical trials were included if they assessed pain-related fear constructs as the
primary or secondary outcome in adults with fibromyalgia. Two reviewers
independently performed the study selection, data extraction, risk-of-bias
assessment, Template for Intervention Description and Replication (TIDieR)
checklist assessment, and grading the quality of evidence. Results. Twelve
randomized clinical trials satisfied the eligibility criteria, including 11 cohorts
with a total sample of 1,441 participants. Exercise, multicomponent, and
psychological interventions were more effective than controls were in reducing
kinesiophobia. However, there were no differences in decreasing kinesiophobia when
self-management and electrotherapy were used. There were also no differences
between groups with regard to the rest of the interventions and pain-related
constructs (fear-avoidance beliefs, fear of pain, and pain-related anxiety).
However, a serious risk of bias and a very serious risk of imprecision were
detected across the included trials. This caused the overall certainty of the
judged evidence to be low and very low. Additionally, the included trials reported
insufficient details to allow the full replication of their interventions.
Conclusions. This systematic review shows that there are promising interventions,
such as exercise, multicomponent, and psychological therapies, that may decrease
one specific type of fear in people with fibromyalgia, i.e., kinesiophobia.
However, because of the low-very low certainty of the evidence found, a call for
action is needed to improve the quality of randomized clinical trials, which will
lead to more definitive information about the clinical efficacy of interventions in
this field.
Anxiety disorders are among the most prevalent mental disorders. Present treatments
such as cognitive behavior therapy and pharmacological treatments show only
moderate success, which emphasizes the importance for the development of new
treatment protocols. Non-invasive brain stimulation methods such as repetitive
transcranial magnetic stimulation (rTMS) and transcranial direct current
stimulation (tDCS) have been probed as therapeutic option for anxiety disorders in
recent years. Mechanistic information about their mode of action, and most
efficient protocols is however limited. Here the fear extinction model can serve as
a model of exposure therapies for studying therapeutic mechanisms, and development
of appropriate intervention protocols. We systematically reviewed 30 research
articles that investigated the impact of rTMS and tDCS on fear memory and
extinction in animal models and humans, in clinical and healthy populations. The
results of these studies suggest that tDCS and rTMS can be efficient methods to
modulate fear memory and extinction. Furthermore, excitability-enhancing
stimulation applied over the vmPFC showed the strongest potential to enhance fear
extinction. We further discuss factors that determine the efficacy of rTMS and tDCS
in the context of the fear extinction model and provide future directions to
optimize parameters and protocols of stimulation for research and treatment.
There is increasing evidence for species using information from heterospecifics to
assess predation risk or habitat quality. Notably, a series of influential studies,
using geometric symbols added to nest boxes, has shown that migratory flycatchers
copy tits' apparent nest-site preferences and settle in nest boxes bearing the same
symbol as tits' nest boxes. This "Selective Interspecific Information Use"
hypothesis was recently challenged by the "Owner Aggression" hypothesis, stating
that nest occupancy patterns are instead driven by tits aggressively excluding
flycatchers from particular empty boxes to use as potential re-nesting sites after
nest predation. Here, I propose the "Adaptive Interspecific Information Use"
hypothesis, which outlines the predicted fitness benefits of nest-site copying or
rejecting, and, importantly, provides an explanation for inconsistent experimental
results to date. Indeed, neither previous hypotheses satisfactorily explains why
flycatchers switch from copying to avoiding tits' preferences, when tits' clutch
sizes are small or tits are at the laying stage. Adding to the recent debate, I
show how predictable changes in nest predators' search image and tits' anti-
predator behaviour may explain this variation. Indeed, incubating tit species
aggressively defend their nest against nest predators, including by emitting snake-
like vocalisations, which may generally deter predators from boxes bearing a tit
nest symbol. By contrast, the undefended tit nests-which occur during laying before
incubation starts, or potentially in individuals with small clutches-are easy prey
that predators may specifically target. If predators cue on tit nests' symbol, I
therefore predict that, to reduce predation risk throughout the season, flycatchers
may switch from avoiding the symbol of undefended tit nests to preferring the
symbol of tits incubating large clutches. I propose experiments to test these
predictions. Overall, considering nest-site copying in the landscape of fear
framework, rather than invalidating the Selective Interspecific Information Use
hypothesis, may be key to understand its evolution.
Objective: Fear of Cancer Recurrence (FCR), Health Anxiety (HA), worry, and
uncertainty in illness are psychological concerns commonly faced by cancer
patients. In survivorship research, these similar, yet different constructs are
frequently used interchangeably and multiple instruments are used in to measure
them. The lack of clear and consistent conceptualization and measurement can lead
to diverse or contradictory interpretations. The purpose of this scoping review was
to review, compare, and analyze the current conceptualization and measurements used
for FCR, HA, worry, and uncertainty in the breast cancer survivorship literature to
improve research and practice. Inclusion Criteria: We considered quantitative,
qualitative, and mixed methods studies of breast cancer survivors that examined
FCR, HA, worry, or uncertainty in illness as a main topic and included a definition
or assessment of the constructs. Methods and Analysis: The six-staged framework was
used to guide the scoping review process. Searches of PubMed, CINAHL, and PsycINFO
databases were conducted. The principle-based qualitative analysis and simultaneous
content analysis procedures were employed to synthesize and map the findings.
Findings: After duplicate removal, the search revealed 3,299 articles, of which 82
studies met the inclusion criteria. Several critical attributes overlapped the four
constructs, for example, all were triggered by internal somatic and external cues.
However, several unique attributes were found (e.g., a sense of loss of security in
the body is observed only among survivors experiencing FCR). Overall, findings
showed that FCR and uncertainty in illness are more likely to be triggered by
cancer-specific factors, while worry and HA have more trait-like in terms of
characteristics, theoretical features, and correlates. We found that the measures
used to assess each construct were on par with their intended constructs. Eighteen
approaches were used to measure FCR, 15 for HA, 8 for worry, and 4 for uncertainty.
Conclusion: While consensus on the conceptualization and measurement of the four
constructs has not yet been reached, this scoping review identifies key
similarities and differences to aid in their selection and measurement. Considering
the observed overlap between the four studied constructs, further research
delineating the unique attributes for each construct is warranted.
Background Fear of falling (FOF) is prevalent among older adults and associated
with adverse health outcomes. Over recent years a substantial body of research has
emerged on its epidemiology, associated factors, and consequences. This scoping
review summarizes the FOF literature published between April 2015 and March 2020 in
order to inform current practice and identify gaps in the literature. Methods A
total of 439 articles related to FOF in older adults were identified, 56 selected
for full-text review, and 46 retained for data extraction and synthesis. Results
The majority of included studies were cross-sectional. Older age, female sex,
previous falls, worse physical performance, and depressive symptoms were the
factors most consistently associated with FOF. Studies that measured FOF with a
single question reported a significantly lower prevalence of FOF than those using
the Falls Efficacy Scale, a continuous measure. FOF was associated with higher
likelihoods of future falls, short-term mortality, and functional decline.
Conclusions Comparisons between studies were limited by inconsistent definition and
measurement of FOF, falls, and other characteristics. Consensus on how to measure
FOF and which participant characteristics to evaluate would address this issue.
Gaps in the literature include clarifying the relationships between FOF and
cognitive, psychological, social, and environmental factors.
Background: Due to lack of preparedness of health systems, fast spread of the new
virus, high mortality rates, and lack of a definite treatment, the outbreak of
Coronavirus disease (COVID-19) led to high levels of fear and anxiety in different
populations. In addition, isolation, mental disorders, and limitations in social
interactions as a result of lockdown and travel ban increased the fear of the new
coronavirus. Methods: International databases, including Scopus, PubMed, Web of
Science, and Google scholar, were searched without any time limitation, and all
observational studies published in English reporting the mean of fear of COVID-19
based on the Fear of COVID-19 scale (FCV-19S) were included in the analysis.
Methodological quality was assessed using the Strengthening the Reporting of
Observational Studies in Epidemiology (STROBE) guidelines. Random effects model,
subgroup analysis, and meta-regression analysis were used to analyze the data.
Heterogeneity across studies was examined using Cochran's Q test and I-2 statistic.
All the statistical analyses were conducted using R software v4.0.3. Results: A
total of 44 articles with a sample size of 52,462 were reviewed. A pooled mean of
18.57 was found for fear of COVID-19. The mean of fear of COVID-19 was higher in
women than in men (20.67 vs. 18.21). The highest and lowest means of fear of COVID-
19 had been found in Asia (18.36) and Australia (17.43) based on continent, and in
hospital staff (19.51) and college students (17.95) based on target population,
respectively. In addition, the highest and lowest means of fear of COVID-19 were
related to items #1 and #3 of the scale, respectively. According to the results of
meta-regression analysis, there was no significant association between the mean of
fear of COVID-19 and sample size and participants' age. In addition, publication
error was not significant (P = 0.721). Conclusion: The mean of fear of COVID-19 was
high around the world; therefore, it seems necessary to pay more attention to the
negative effects of the COVID-19 pandemic on mental health.
The prevalence of fear of movement (kinesiophobia) in persistent pain ranges from
50 to 70%, and it may hinder the subsequent rehabilitation interventions.
Therefore, the evaluation of fear of movement/(re)injury plays a crucial role in
making clinical treatment decisions conducive to the promotion of rehabilitation
and prognosis. In the decision-making process of pain treatment, the assessment of
fear of movement/(re)injury is mainly completed by scale/questionnaire.
Scale/questionnaire is the most widely used instrument for measuring fear of
movement/(re)injury in the decision-making process of pain treatment. At present,
the most commonly used scale/questionnaire are the Tampa Scale for Kinesiophobia
(TSK), the Fear-Avoidance Beliefs Questionnaire (FABQ), the Kinesiophobia Causes
Scale (KCS), the Athlete Fear-Avoidance Questionnaire (AFAQ), and the Fear-
Avoidance Components Scale (FACS). In order to provide necessary tools and
references for related research and rehabilitation treatment, this descriptive
review is designed as an introduction to the background and content, score system,
available language versions, variants of the original questionnaire, and
psychometric properties of these scales/questionnaries.
Background: Accumulating evidence has shown the important role of the inflammatory
process in the pathophysiology of mental disorders. However, the relative levels of
inflammatory markers in patients with panic disorder (PD) have rarely been
evaluated. The aim of the present study was to conduct a systematic review to
determine the correlation of peripheral C-reactive protein (CRP) and inflammatory
cytokine profiles with PD. Methods: This study followed the Preferred Reporting
Items for Systematic Reviews and Meta-Analyses guidelines. We searched for
quantitative research studies published up to July 31, 2021 that measured
peripheral levels of CRP and inflammatory cytokines in people with PD compared with
controls. Meta-analysis using a random-effects model was performed for the levels
of CRP and inflammatory cytokines with data from three or more studies. Results:
Fourteen identified studies met the inclusion criteria. In total, 18 cytokines were
evaluated. Markers that were reported in more than 3 studies were included in this
metaanalysis. The results showed that peripheral levels of CRP, IL-6, IL-2 and TNF-
alpha were significantly higher in PD patients than in healthy controls, while
there was no significant difference in peripheral levels of IL-1 beta, IL-10 and
IFN-gamma between groups. Notably, the relevant studies involving IL-6, IL-1 beta,
IL-10 and IFN-gamma in PD patients were highly heterogeneous. Similar to meta-
analyses of other inflammatory factors in mental disorders, our meta-analysis also
reflected differences in participant medication use, comorbid anxiety or
depression, sampling methods and detection methods. Eight inflammatory cytokines
were reported in only one study, and their expression levels were higher, lower, or
unchanged compared with those in healthy controls. Conclusion: There is preliminary
evidence to suggest a significant inflammatory response in PD patients, but the
role of inflammatory markers in PD remains unclear. Studying inflammatory markers
in PD will help to clarify the etiology and pathophysiological mechanisms of the
disorder.
Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes
mellitus. Our objective was to evaluate the efficacy of exercise interventions in
DPN patients from randomized controlled trials. The primary outcomes were the risk
of falls, fear of falling, balance and quality of life. Two reviewers independently
selected studies from Embase, Medline, LILACS, CENTRAL, and PEDro. They assessed
the risk of bias and extracted data from the trials. The relative risk (RR) and the
differences between means (MD) were calculated with a 95% confidence interval (CI)
and used as the effect size. We used a random-effects model to pool results across
studies, and the Grading of Recommendations Assessment, Development, and Evaluation
system to evaluate the certainty of evidence. Eight trials were included. No clear
effect was observed in the risk of falls (RR: 0.93, 95% CI: 0.41 to 2.09, 79
participants, 1 trial, low- certainty evidence). Regarding fear of falling, using
the Falls Efficacy Scale, a small difference in favor of the intervention was
observed (MD: -2.42, 95%, CI: -4.7 to -0.15, 3 trials, 185 participants, low-
certainty evidence). The meta-analysis of balance using the unipedal stance test
showed a small difference in favor of the intervention. One study evaluated quality
of life, and in the mental score there was a MD in favor of the intervention. In
DPN patients, a combination of gait, balance, and functional training improved
balance, the fear of falling, quality of life in the mental score, but not the risk
of falls.
Nighttime fears in children are common, interfere with daily functioning, and
result in considerable disruption in the family. The aim of the present review was
to examine empirical literature from the past 25 years that investigated the
assessment of nighttime fears in young children and the efficacy and effectiveness
of psychosocial treatments for children's nighttime fears. The last review of this
literature was in 1997 and examined studies conducted in and prior to 1995 (King et
al. in Clin Psychol Rev 17:431-443, 1997). Using the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic
review of the literature aimed at providing a synthesis of the Randomized Control
Trials (RCTs) and controlled single-case multiple baseline design studies (MBLs) on
the treatment of nighttime fears in children. A search of the literature identified
12 articles, with nine studies utilizing a between-group randomized controlled
trial design and three studies utilizing a multiple baseline design. Results
demonstrated significant improvements in children's nighttime fears and reductions
in disruptive nighttime behaviors using behavioral interventions and cognitive-
behavioral strategies. This review provides a commentary on the effectiveness and
limitations of the assessment and treatment approaches for nighttime fears in
children and suggests directions for future research.
Safety learning occurs when an otherwise neutral stimulus comes to signal the
absence of threat, allowing organisms to use safety information to inhibit fear and
anxiety in nonthreatening environments. Although it continues to emerge as a topic
of relevance in biological and clinical psychology, safety learning remains
inconsistently defined and under-researched. Here, we analyse the Pavlovian
conditioned inhibition paradigm and its application to the study of safety learning
in humans. We discuss existing studies; address outstanding theoretical
considerations; and identify prospects for its further application. Though
Pavlovian conditioned inhibition presents a theoretically sound model of safety
learning, it has been investigated infrequently, with decade-long interims between
some studies, and notable methodological variability. Consequently, we argue that
the full potential of conditioned inhibition as a model for human safety learning
remains untapped, and propose that it could be revisited as a framework for
addressing timely questions in the behavioural and clinical sciences.
Background and Objectives: Fear of falling (FoF) is associated with decreased
physical functioning and an increased fall risk. Interventions generally
demonstrate moderate effects and optimized interventions are needed. Intervention
characteristics, such as setting or delivery method may vary. We investigated which
overarching intervention characteristics are associated with a reduction in FoF in
community-dwelling older people. Research Design and Methods: A systematic review
and meta-analysis of randomized controlled trials (RCTs) in community-dwelling
older people without specific diseases was performed. Associations between
intervention characteristics and standardized mean differences (SMD) were
determined by univariate meta-regression. Sensitivity analyses were performed.
Results: Data on 62 RCTs were extracted, 50 intervention groups were included in
the meta-analysis. Most intervention characteristics and intervention types were
not associated with the intervention effect. Supervision by a tai chi instructor
(SMD: -1.047, 95% confidence interval [CI]: -1.598; -0.496) and delivery in a
community setting (SMD: -0.528, 95% CI: -0.894; -0.161) were-compared to
interventions without these characteristics-associated with a greater reduction in
FoF. Holistic exercise, such as Pilates or yoga (SMD: -0.823, 95% CI: -1.255; -
0.392), was also associated with a greater reduction in FoF. Delivery at home (SMD:
0.384, 95% CI: 0.002; 0.766) or with written materials (SMD: 0.452, 95% CI: 0.088;
0.815) and tailoring were less effective in reducing FoF (SMD: 0.687, 95% CI:
0.364; 1.011). Discussion and Implications: Holistic exercise, delivery with
written materials, the setting and tailoring potentially represent characteristics
to take into account when designing and improving interventions for FoF in
community-dwelling older people. PROSPERO international prospective register of
systematic reviews, registration ID CRD42018080483.
Background Innovations in virtual reality (VR) technologies have improved the
adaptability of its use in therapeutic settings, and VR has shown to be a promising
treatment for fear of medical procedures, with research increasing in this area in
recent years. Purpose This review aims to collate evidence for the impact of VR on
fear of medical procedures. Methods CENTRAL (Cochrane), MEDLINE, EMBASE, and
PsychINFO databases were searched up to October 2020. A mix of experimental and
case-control studies were included for review, which evaluated the effectiveness of
VR for fear, anxiety, and pain of medical procedures for people with needle phobia,
dental phobia, claustrophobia of medical scans, and burn wound care anxiety. Risk
of bias (RoB) was assessed by Cochrane and ROBINS-I tools. Results Twenty-eight
studies were selected. Some studies included mixed participant groups of young
people adults. The interventions varied, with VR used for distraction, hypnosis, or
exposure. These were shown to be effective for reducing fear of medical procedures.
However, effectiveness for blood-injection-injury phobias and burn wound care
patients was unclear. Conclusions Evidence on the effectiveness of VR suggests that
it does decrease fear of medical procedures in some situations. However, the RoB
assessment illustrated a poor quality of studies across those included in this
review, limiting the ability to draw firm general conclusions from the study
findings. There is a need for further research exploring the use of VR technologies
in the management of anxiety in physical health care settings.
Fear and anxiety disorders are prevalent in dogs. These disorders are not
adequately resolved by current interventions, which urges exploration of additional
interventions. In humans, fear and anxiety disorders such as post-traumatic stress
disorder (PTSD), are effectively treated by Eye Movement Desensitization and
Reprocessing (EMDR). EMDR is a non-invasive and non pharmacological intervention
involving bilateral sensory stimulation while memorizing the traumatic event,
resulting in decreased emotionality of the memory. We argue EMDR might be applied
as an intervention for fear and anxiety disorders in dogs, adding to the currently
available interventions for the field of Clinical Ethology. Particularly nonverbal
EMDR protocols used in preverbal children can be applied and the setup can be
adapted for dogs. Future research should focus on the development of nonverbal EMDR
protocols including proper controls, and on clinical effectiveness of such EMDR
protocols for dogs. Apart from behavioural measures, psychophysiological variables
should be incorporated as well.
Objective: To systematically review the effectiveness of manual therapy on fear-
avoidance, kinesiophobia, and pain catastrophizing in patients with chronic
musculoskeletal pain. Literature search: Databases (Medline, EMBASE, CINAHL, PEDro,
CENTRAL, Web of Science, and SCOPUS) were searched from inception up to March 2020.
Study selection criteria: Two reviewers independently selected randomized
controlled trials that investigated the effects of manual therapy associated or not
with other interventions on fear-avoidance, kinesiophobia and pain catastrophizing
in patients with chronic musculoskeletal pain. Data synthesis: Standardized Mean
Differences (SMD) and 95% confidence interval (CI) were calculated using a random-
effects inverse variance model for meta-analysis according to the outcome of
interest, comparison group and follow-up period. The level of evidence was
synthesized using GRADE. Results: Eleven studies were included with a total sample
of 717 individuals. Manual therapy was not superior to no treatment on reducing
fear-avoidance at short-term (low quality of evidence; SMD = -0.45, 95% CI -0.99 to
0.09), and intermediate-term (low quality of evidence; SMD = -0.48, 95% CI -1.0 to
0.04). Based on very-low quality of evidence, manual therapy was not better than
other treatments (SMD = 0.10, 95% CI -0.56 to 0.77) on reducing fear-avoidance,
kinesiophobia (SMD = -0.12, 95% CI -0.87 to 0.63) and pain catastrophizing (SMD = -
0.16, 95% CI -0.48 to 0.17) at short-term. Conclusion: Manual therapy may not be
superior to no treatment or other treatments on improving fear-avoidance,
kinesiophobia and pain catastrophizing, based on very low or low quality of
evidence. More studies are necessary to strengthen the evidence of effects of
manual therapy on pain-related fear outcomes.
The purpose of this study is to provide insight into the lead-lag relationships
between the BRIC stock index and its constituents. In addition, we assess the
comovements between the US volatility index (VIX) as a measure of investor
uncertainty and fear and stock returns of BRIC economies. Therefore, the bi-wavelet
and wavelet multiple correlations approaches are utilised. Findings from the bi-
wavelet technique indicate that there are high interdependencies between the BRIC
index and its constituents throughout the time-frequency domain. In addition,
comovements between the BRIC index and its constituents was positive and
significant. Notwithstanding, we find the BRIC index to be the first variable to
respond to shocks when all the study variables were considered in the wavelet
multiple cross-correlations. Similarly, the stock market of Brazil is the next to
respond to shocks. On the other hand, the stock market of Russia lags in the long-
term when the BRIC index was excluded from the wavelet multiple cross-correlations.
We also find a uni-directional causality between the VIX and the BRIC stocks in the
medium-, and long-terms. Specifically, the US VIX significantly drives the BRIC
stocks and considered to be negative. Findings from the study imply that global
investors can select any of the stock markets in BRIC to allocate their investments
due to their strong interdependencies which may facilitate trade and investments.
However, portfolio diversification, safe haven or hedge benefits within this region
may be minimal due to their high integration with the BRIC index which demonstrates
positive significant comovements. The findings present relevant inferences for
portfolio diversification, policy decisions, and risk management schemes. It is
recommended that investors hedge against volatilities in the BRIC stock markets
using the US VIX.
Although the "panic" word has been abundantly linked to the SARS-CoV-2 (severe
acute respiratory syndrome coronavirus 2) pandemic in the press, in the scientific
literature very few studies have considered whether the current epidemic could
predispose to the onset or the aggravation of panic attacks or panic disorder.
Indeed, most studies thus far have focused on the risk of increase and aggravation
of other psychiatric disorders as a consequence of the SARS-CoV-2 epidemic, such as
obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and
generalized anxiety disorder (GAD). Yet, risk of onset or aggravation of panic
disorder, especially the subtype with prominent respiratory symptoms, which is
characterized by a fear response conditioning to interoceptive sensations (e.g.,
respiratory), and hypervigilance to these interoceptive signals, could be expected
in the current situation. Indeed, respiratory symptoms, such as coughs and dyspnea,
are among the most commonly associated with the SARS-CoV-2 (59-82% and 31-55%,
respectively), and respiratory symptoms are associated with a poor illness
prognosis. Hence, given that some etiological and maintenance factors associated
with panic disorder - i.e., fear conditioning to abnormal breathing patterns
attributable or not to the COVID-19 (coronavirus disease 2019), as well as
hypervigilance towards breathing abnormalities - are supposedly more prevalent, one
could expect an increased risk of panic disorder onset or aggravation following the
COVID-19 pandemic in people who were affected by the virus, but also those who were
not. In people with the comorbidity (i.e., panic disorder or panic attacks and the
COVID-19), it is particularly important to be aware of the risk of hypokalemia in
specific at-risk situations or prescriptions. For instance, in the case of
salbutamol prescription, which might be overly used in patients with anxiety
disorders and COVID-19, or in patients presenting with diarrhea and vomiting.
Hypokalemia is associated with an increased risk of torsade de pointe; thus,
caution is required when prescribing specific psychotropic drugs, such as the
antidepressants citalopram and escitalopram, which are first-line treatments for
panic disorder, but also hydroxyzine, aiming at anxiety relief. The results
reviewed here highlight the importance of considering and further investigating the
impact of the current pandemic on the diagnosis and treatment of panic disorder
(alone or comorbid with the COVID-19). (C) 2020 L'Encephale, Paris.
Introduction: Using an ambulance as an attack modality offers many advantages to a
terrorist organization. Ambulances can carry more explosives than most vehicles and
can often bypass security. Yet, studies examining how terrorist organizations have
incorporated ambulances into their attacks are lacking. Study Objective: This
article seeks to identify and analyze known instances in which an ambulance has
been used in a terrorist attack. Methods: The Global Terrorism Database (GTD) was
searched for terrorist events that involved the use of an ambulance from the years
1970-2018. Variables of event time, location, and loss of life were analyzed.
Results: Twenty instances where an ambulance had been used in a terrorist attack
were identified from the GTD. Fifteen of the attacks occurred in the Middle East,
while the remaining five occurred in Southeast Asia. All attacks except one had
occurred after 2001, and 13 had occurred within the past decade. Most attacks
(12/20) resulted in up to three people killed, while six attacks had 10-20
casualties. The deadliest attack occurred in Kabul, Afghanistan in 2018 and caused
over 100 casualties. One event did not have casualty information in the GTD. In all
cases, ambulances were used as vehicle-borne improvised explosive devices (VBIED)
by terrorist organizations. Conclusion: This study shows that terrorists are
increasingly acquiring and utilizing ambulances in their attacks, often with deadly
consequences. Security and public health experts must be aware of this hazard and
work to deny terrorists access to these vehicles.
Treatment non-response, drop-out, and relapse have led researchers to examine if
issues related to the "self" contribute to obsessive-compulsive disorder. The
present systematic review investigated whether self-beliefs relate to obsessive-
compulsive symptoms and related phenomena, and if these beliefs contribute to the
concealment of personal and symptom-relevant information. Ninety-nine papers (103
studies; cumulative N = 21,701) met inclusion criteria. Self was broadly
conceptualized, including self-esteem (n = 18 studies), selfconcept (n = 5), self-
perception (n = 2), negative self-statements (n = 2), self-ambivalence and self-
concept clarity (n = 8), feared self (n = 13), self in autogenous and reactive
obsessions (n = 4), self-worth (n = 8), sensitivity of self (n = 2), moral self-
perceptions (n = 4), early maladaptive schemas (n = 5), egodystonicity and
egosyntonicity (n = 10), self-concealment (n = 1), self-disclosure (n = 1), and
symptom concealment (n = 20). Overall, while the more general experience of low
self-esteem does not appear to differentiate OCD from other psychiatric conditions,
self-beliefs encompassing particular egodystonic themes tend to accompany related
obsessional concerns or compulsive behaviors. There is consistent evidence that a
perceived morally deficient, fractured or feared self plays a role in these
phenomena. Owing to methodological constraints of the included studies, the
specific function of concealment behaviors in OCD is less clear. The present
findings add to growing evidence suggesting the importance of understanding the
idiosyncratic nature of self-beliefs in clinical presentations. Future studies
should aim to clarify the conceptual overlap across the self-themes examined in
this review, and the importance of self-themes for psychological treatments.
Psychopathic traits have been linked to anomalies in experiencing fear and anxiety.
It remains unclear, however, to what extent fear and anxiety levels are useful
parameters to effectively distinguish between subtypes of psychopathy. Therefore,
we aimed to elucidate whether different psychopathic phenotypes (primary and
secondary psychopathy) can be delineated based on fear/anxiety levels. To
investigate associations between psychopathic traits and conscious experiences of
fear and/or anxiety a systematic qualitative review of studies was conducted
following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
guidelines. Seventeen studies were included in the review. We found some evidence
for attenuated fear/anxiety levels in primary psychopathy. In secondary
psychopathy, the experience of fear/anxiety seemed rather intact. Moreover, primary
psychopathy might be associated with a more positive appraisal of the conscious
feeling of fear. We reason that consciously experienced fear and anxiety are
distinctly related to primary and secondary psychopathy. Due to a lack of
consistent and comprehensive operationalizations of fear and anxiety, however,
conclusions about their potential to differentiate psychopathic subtypes should be
drawn with caution.
Introduction. The outbreak of Coronavirus Disease 2019 (COVID-19) have changed into
a global crisis. Psychologically, this process of alteration can lead to feelings
of fear, insecurity, and anxiety. This fear and anxiety can be caused by a variety
of factors. However, due to the lack of extensive studies at this time, there are
little data on these conditions related to COVID-19. Therefore, in this narrative
review, we have tried to identify the most important possible causes of anxiety and
fear due to this disease, based on logical shreds of evidence. Then we tried to
discuss the consequences and ways to manage and prevent them. Methods. The current
focus was on three major axes of corona-phobia, fear and anxiety. PubMed, Science
Direct, Scopus, Google Scholar and authoritative news and information sources were
considered as the data sources. Results. Findings from the analysis of the results
revealed that, in addition to the real and the logical reasons which belong to the
intrinsic properties of SARS-CoV-2, some misleadings and misconceptions induced by
media, governmental policies, public awareness level, and non-scientific
speculations and contradictory data expressed by experts, researchers and
scientific societies, could provide the way for the development of corona-phobia,
and fear. Conclusions. Each of these causal components, in its place, leads to some
degrees of psychological disorders and subsequent consequences and complications.
Finally, here we reviewed, summarized the previous research findings on how to
prevent and manage this type of psychological disorder, and made comparisons.
Physical activity is a health behavior contributing to successful weight
management. Adults with overweight and obesity find it challenging to meet
recommended activity guidelines because of a range of barriers, some of which are
not yet fully understood. A barrier receiving limited consideration, compared with
other literature within this field, is that of fear. The purpose of this scoping
review was to establish the extent of literature on fear-related barriers to
physical activity in adults with overweight or obesity and to identify gaps in this
literature. The review followed the scoping review framework outlined by Arksey and
O'Malley and adhered to the Preferred Reporting Items for Systematic reviews and
Meta-Analyses extension for Scoping Reviews guidelines. The findings of the
identified papers were charted thematically using a framework of fears and age
group. In total, 34 studies were included that identified nine different fears
related to barriers to activity in this population. However, only a small number of
studies (n = 5) had explicitly intended to explore fear-related barriers. There
were notable knowledge gaps including activity-related fear of pain and movement in
adults under 45 years of age. There is a strong rationale to further explore these
fears because they may restrict health promoting behavior.
Fear of missing out (FoMO) is a unique term introduced in 2004 to describe a
phenomenon observed on social networking sites. FoMO includes two processes;
firstly, perception of missing out, followed up with a compulsive behavior to
maintain these social connections. We are interested in understanding the complex
construct of FoMO and its relations to the need to belong and form stable
interpersonal relationships. It is associated with a range of negative life
experiences and feelings, due to it being considered a problematic attachment to
social media. We have provided a general review of the literature and have
summarized the findings in relation to mental health, social functioning, sleep,
academic performance and productivity, neuro-developmental disorders, and physical
well-being. We have also discussed the treatment options available for FoMo based
on cognitive behavior therapy. It imperative that new findings on FoMO are
communicated to the clinical community as it has diagnostic implications and could
be a confounding variable in those who do not respond to treatment as usual.
Posttraumatic stress disorder (PTSD) is a persistent, trauma induced psychiatric
condition characterized by lifelong complex cognitive, emotional and behavioral
phenotype. Although many individuals that experience trauma are able to gradually
diminish their emotional responding to trauma-related stimuli over time, known as
extinction learning, individuals suffering from PTSD are impaired in this capacity.
An inability to decline this initially normal and adaptive fear response, can be
confronted with exposure-based therapies, often in combination with pharmacological
treatments. Due to the complexity of PTSD, currently available pharmacotherapeutics
are inadequate in treating the deficient extinction observed in many PTSD patients.
To develop novel therapeutics, researchers have exploited the conserved nature of
fear and stress-associated behavioral responses and neurocircuits across species in
an attempt to translate knowledge gained from preclinical studies into the clinic.
There is growing evidence on the endocannabinoid modulation of fear and stress due
to their 'on demand' synthesis and degradation. Involvement of the endocannabinoids
in fear extinction makes the endocannabinoid system very attractive for finding
effective therapeutics for trauma and stress related disorders. In this review, a
brief introduction on neuroanatomy and circuitry of fear extinction will be
provided as a model to study PTSD. Then, the endocannabinoid system will be
discussed as an important component of extinction modulation. In this regard,
anandamide degrading enzyme, fatty acid amide hydrolase (FAAH) will be exemplified
as a target identified and validated strongly from preclinical to clinical
translational studies of enhancing extinction.
Background: Panic disorder (PD) is an anxiety disorder characterized by recurrent
panic attacks whose aetiology might be associated with alterations of the
prefrontal-amygdala circuitry. The prefrontal cortex is a key region involved in
executive functioning (EF) whose disturbance may imply harsh consequences over
personal, social, and working aspects of PD patients. Indeed, defining the real
involvement of EF in PD could lead to early assessment, better treatment, and
rehabilitation options. These could have a substantial impact on the quality of
life of these patients and their caregivers, thus reducing long-term health care
needs. Methods: We reviewed findings from different studies that investigated
executive functioning in PD patients using standardized neuropsychological
measures. The review was conducted with the Preferred Reported Items for Systematic
Reviews and Meta-Analysis (PRISMA). In addition, peer-reviewed human-based research
articles were selected and twelve studies were retrieved through a search on
PubMed. Four uniquely focused on PD patients, two also included a sample of first-
degree relatives, while six included a mixed sample of different psychiatric
illnesses, including PD. Results: The majority of the studies found no alterations
in PD patients, suggesting that EF might not be a core deficit in this disorder.
However, some studies (N = 4) found EF deficits in selective domains, which
included attention and set-shifting processes, cognitive flexibility, decision-
making abilities, and working memory in PD patients and/or in their first-degree
relatives. Limitations: Unbalanced and small samples, unmonitored therapies, and
the heterogeneity of cognitive and diagnostic assessment measures might have
limited the generalizability of the results. Conclusions: Overall, the results
point towards the hypothesis that PD patients had preserved EF. However, future
studies with standardized methodological procedures and with a gold standard
assessment of EF will be required to finally exclude its involvement in the
disease.
Aim: To investigate clinical trials affecting anxiety, stress and fear of
childbirth in fathers. Design: A systematic literature search was conducted based
on Cochrane Collaboration statement recommendation and Preferred Reporting Items
for Systematic reviews and Meta-Analyses checklist. Methods: With assistance of
Medical Subject Headings, keywords were employed to search for relevant trials.
Articles published between November 2000-November 2019 were searched in five
electronic databases including PubMed, Web of Science, Google Scholar, Scopus and
Cochrane as well as Iranian databases. The risk of bias was assessed by Cochrane
Risk of Bias Scale. Results: A total of eight studies met the inclusion criteria.
Interventions were classified into four categories including pre-natal education,
music therapy, massage therapy and relaxation training. The results showed that
there is no evidence of a best intervention, but it showed that non-pharmacological
interventions can decrease anxiety, stress and fear of childbirth and increase the
positive experience of childbirth in the expectant fathers.
Research on the ecology of fear has highlighted the importance of perceived risk
from predators and humans in shaping animal behavior and physiology, with potential
demographic and ecosystem-wide consequences. Despite recent conceptual advances and
potential management implications of the ecology of fear, theory and conservation
practices have rarely been linked. Many challenges in animal conservation may be
alleviated by actively harnessing or compensating for risk perception and risk
avoidance behavior in wild animal populations. Integration of the ecology of fear
into conservation and management practice can contribute to the recovery of
threatened populations, human-wildlife conflict mitigation, invasive species
management, maintenance of sustainable harvest and species reintroduction plans.
Here, we present an applied framework that links conservation interventions to
desired outcomes by manipulating ecology of fear dynamics. We discuss how to reduce
or amplify fear in wild animals by manipulating habitat structure, sensory stimuli,
animal experience (previous exposure to risk) and food safety trade-offs to achieve
management objectives. Changing the optimal decision-making of individuals in
managed populations can then further conservation goals by shaping the
spatiotemporal distribution of animals, changing predation rates and altering risk
effects that scale up to demographic consequences. We also outline future
directions for applied research on fear ecology that will better inform
conservation practices. Our framework can help scientists and practitioners
anticipate and mitigate unintended consequences of management decisions, and
highlight new levers for multi-species conservation strategies that promote human-
wildlife coexistence.
Objectives: Phobia of natural childbirth is one of the most important and
influencing factors leading women to request cesarean sections. The present study
aimed to prepare a systematic review and meta-analysis to investigate the type of
interventions related to fear of childbirth (FOC). Materials and Methods: The data
collection was based on an extensive search of articles related to clinical trials
(1990-2019) posted on Google Scholar, Cochran, SID, Magiran, Web of Science,
Scopus, and PubMed electronic databases. In general, 109 abstracts were selected
after eliminating similar publications. As a result of the qualitative evaluations
of these articles, 11 studies were kept for investigation. Results: The studies
were categorized into three groups including prenatal education with childbirth
counseling, yoga courses, and psychoeducational-based interventions. Based on the
meta-analysis, psychoeducational interventions have a significant effect on
childbirth fears and anxiety in comparison with the control group (mean difference:
0.85, 95% CI: -1.20-0.45, P < 0.0001, I-2 = 82%). Conclusions: Psychologically-
based interventions, can creatively play an essential role in reducing the FOC
during pregnancy and even childbirth. It can also create a pleasant and traumatic-
free experience which is essential for encouraging women to have a natural
childbirth.
Objective: verify the bibliometrics indicators regarding to the scientific
production available in online journals related to balance and fear of falling in
aged. Method: a bibliometric study, whose sample was composed by 51 articles,
published between 2008 and 2018, written in English and/or Portuguese, available in
national and international databases. Results: the peak of productions was verified
in the year of 2016 (21.6%). It predominated publications written in English
(96.1%). Journals categorized as QUALIS A1 (52.9%) were the majority. Regarding to
the subject of the studies, it prevailed those related to accidents by fall;
prevention and treatment; morbidities; and studies emphasizing the measures used in
tests and evaluations. Conclusion: bibliometric indicators regarding the subject
balance and fear of falling expresses a scientific production under development.
This topic has been a recent focus of health researchers working in the care and
rehabilitation of the elderly.
A growing body of research has examined the potential effects of the Fear of
Missing Out (FoMO) on Social Networking Site (SNS) use and Problematic SNS use
(PSNSU). The aim of the current meta-analysis is to summarize findings on the
relationship between FoMO levels and (i) SNS use and (ii) PSNSU. Furthermore, we
metaanalyzed results on the associations between FoMO and some individual
characteristics. The sample included 33 independent samples with a total of 21,473
participants. The results of the random-effects meta-analysis show a positive
correlation between FoMO and SNS use and between FoMO and PSNSU, with effect sizes
indicating robust associations. Age, sex, and geographic area of the samples did
not moderate the associations. FoMO was positively correlated with depression,
anxiety, and neuroticism and negatively correlated with consciousness. These
results give robustness to the construct validity of FoMO itself, as this concept
was introduced to explain why some people might be especially attracted to social
media. Moreover, concerns that others might be having rewarding experiences that
one is absent from seem to be a trigger for a compulsive use of social platforms,
driven by the need to get in touch with others, or as tool to develop social
competence.
Stress can negatively impact brain function and behaviors across the lifespan.
However, stressors during adolescence have particularly harmful effects on brain
maturation, and on fear and social behaviors that extend beyond adolescence.
Throughout development, social behaviors are refined and the ability to suppress
fear increases, both of which are dependent on amygdala activity. We review rodent
literature focusing on developmental changes in social and fear behaviors, cortico-
amygdala circuits underlying these changes, and how this circuitry is altered by
stress. We first describe changes in fear and social behaviors from adolescence to
adulthood and parallel developmental changes in cortico-amygdala circuitry. We
propose a framework in which maturation of cortical inputs to the amygdala promote
changes in social drive and fear regulation, and the particularly damaging effects
of stress during adolescence may occur through lasting changes in this circuit.
This framework may explain why anxiety and social pathologies commonly co-occur,
adolescents are especially vulnerable to stressors impacting social and fear
behaviors, and predisposed towards psychiatric disorders related to abnormal
cortico-amygdala circuits.
Background: Type 1 diabetes mellitus is one of the most common chronic childhood
illnesses and, despite ongoing technological advances, hypoglycaemia remains an
inevitable therapeutic risk. Hypoglycaemia results in unpleasant physiological
outcomes, social embarrassment and - in extremis - life-threatening consequences.
Overlying this inescapable clinical risk is a fear of this risk, ranging from
fleeting to overwhelming, and substantially impacting the trajectory of diabetes.
Aim: The aim of this literature review is to identify, summarise and critically
appraise works pertaining to the development, impact and management of paediatric
fear of hypoglycaemia (FoH). Methods: A search was conducted on Embase, MEDLINE and
PsycINFO for studies published between 2000 and 2020, with cross-referencing
searches for articles not detected in the original keyword search. Study quality
was assessed using recognised tools, and relevant data were extracted
systematically. Results: Forty-three studies met the inclusion criteria. FoH was a
moderate problem throughout the studies, increased by a history of hypoglycaemia
and predisposition to psychological stress. There was conflicting evidence on the
influence of age, diabetes duration, technology and parental demographics. Some
studies showed a significant impact on glycaemic control and quality of life (QoL),
more consistently for the latter. Only 13 intervention trials were included,
showing mixed success with cutting-edge technology, and decent gains with
psychological interventions. Conclusions: FoH is clearly a ubiquitous issue among
some families with type 1 diabetes. Prospective longitudinal studies are required
to assess potential risk factors at diagnosis, monitor for the development of FoH
at regular intervals, and enable a more comprehensive assessment of the long-term
impact on glycaemic control and QoL. Further randomised controlled trials must
demonstrate the value of technological and psychological therapies in order to make
such interventions commonplace offerings for families suffering from intractable
fear.
Posttraumatic stress disorder (PTSD) is a mental health condition triggered by
experiencing or witnessing a terrifying event that can lead to lifelong burden that
increases mortality and adverse health outcomes. Yet, no new treatments have
reached the market in two decades. Thus, screening potential interventions for PTSD
is of high priority. Animal models often serve as a critical translational tool to
bring new therapeutics from bench to bedside. However, the lack of concordance of
some human clinical trial outcomes with preclinical animal efficacy findings has
led to a questioning of the methods of how animal studies are conducted and
translational validity established. Thus, we conducted a systematic review to
determine methodological variability in studies that applied a prominent animal
model of trauma-like stress, single prolonged stress (SPS). The SPS model has been
utilized to evaluate a myriad of PTSD-relevant outcomes including extinction
retention. Rodents exposed to SPS express an extinction retention deficit, a
phenotype identified in humans with PTSD, in which fear memory is aberrantly
retained after fear memory extinction. The current systematic review examines
methodological variation across all phases of the SPS paradigm, as well as
strategies for behavioral coding, data processing, statistical approach, and the
depiction of data. Solutions for key challenges and sources of variation within
these domains are discussed. In response to methodological variation in SPS
studies, an expert panel was convened to generate methodological considerations to
guide researchers in the application of SPS and the evaluation of extinction
retention as a test for a PTSD-like phenotype. Many of these guidelines are
applicable to all rodent paradigms developed to model trauma effects or learned
fear processes relevant to PTSD, and not limited to SPS. Efforts toward optimizing
preclinical model application are essential for enhancing the reproducibility and
translational validity of preclinical findings, and should be conducted for all
preclinical psychiatric research models.
This review focuses on pre-appointment medications used to decrease fear and
anxiety in dogs and cats related to veterinary visits. A review of the literature
revealed data on 4 medications from 4 medication classes that have been used to
ameliorate acute situational fear and anxiety in dogs and cats: gabapentin,
trazodone, oral transmucosal dexmedetomidine, and alprazolam. The available
information on use, mechanism of action, and pharmacokinetics is reviewed.
Social networks have become a very important part of human life in recent years.
This situation has led to new definitions such as the Fear of Missing Out (FOMO).
FOMO can be defined as the concern that others can have a good experience when the
person is absent and therefore the person wants to stay on social networks
constantly to avoid missing anything. It is especially common in young people.
Problematic internet use, psychosocial factors, social network use and anxiety are
blamed in its etiology. Family conflicts, loneliness, depression, and low self-
efficacy can be said as risk factors. People constantly want to spend time on
social networks, daily life activities are blocked and the person's productivity
decreases. It has no place in diagnostic classifications. For FOMO, the fear of
missing out scale developed by Przybylski can be used. It is reported that FOMO has
a significant positive relationship with nomophobia. There is no specific treatment
method. There is a need for extensive research on FOMO.
This article discusses the fear of missing out (FOMO) on rewarding experiences, an
important psychological construct in contemporary times. We present an overview of
the FOMO construct and its operational definition and measurement. Then, we review
recent empirical research on FOMO's relationship with levels of online social
engagement, problematic technology and internet communication use, negative
affectivity, and sociodemographic variables. Additionally, we discuss theoretical
conceptualizations regarding possible causes of FOMO and how FOMO may drive
problematic internet technology use. Finally, we discuss future directions for the
empirical study of FOMO.
Cognitive behavioral therapy (CBT) is an established treatment for panic disorder
(PD). Remote CBT (RCBT) is becoming increasingly popular and has the potential to
enhance access to this treatment. The aim of this study was to examine the efficacy
of RCBT for PD using a meta-analytic approach. An electronic database search was
used to identify relevant articles and the references of previously completed
reviews. Twenty-one studies (n = 1,604; mean age range: 31.9?43.9; mean female
representation = 71 %) were included in the meta-analysis. 14/21 (67 %; n = 817 of
the included studies were randomised controlled trials and 7/21 (33 %; n = 787)
were open trials or non-randomised controlled trials. Pooled within-group effect
sizes across all remote treatments for PD symptoms were large from pre-treatment to
post-treatment (Hedges? g = 1.18; 95 % CI: 0.99?1.36) and pretreatment to follow-up
(Hedges? g = 1.51; 95 % CI: 1.22?1.79). Pooled between-group findings indicate that
remote CBT treatments are more effective than passive control (Hedges? g = 1.17; 95
% CI: 0.85?1.50), but are similar to other active treatments on measures of PD
symptoms (e.g., face-to-face CBT) (Hedges? g = 0.02; 95 % CI: -0.43 to 0.48).
Internet-delivered CBT (Hedges? g = 1.10, 95 % CI: 0.91?1.30), videoconferencing-
delivered CBT (Hedges? g = 1.40, 95 % CI: 0.85?1.95) and bibliotherapy-delivered
CBT (Hedges? g = 1.51, 95 % CI: 0.95?2.06) each produce large effect sizes on
measures of PD symptoms. The results have important implications for the
dissemination of entirely remote stepped-care treatments for PD.
Background Little is known about the prevalence and best management of needle fear
in adults with chronic disease, who may experience frequent and long-term exposure
to needles for lifesaving therapies such as renal dialysis and cancer treatment.
Identifying interventions that assist in management of needle fear and associated
distress is essential to support these patients with repeated needle and cannula
exposure. Method We followed the PRISMA methodology for scoping reviews and
systematically searched PsychINFO, PubMed (MEDLINE), ProQuest, Embase and grey
literature and reference lists between 1989 and October 2020 for articles related
to needle discomfort, distress, anxiety, fear or phobia. The following chronic
diseases were included: arthritis, asthma, chronic back pain, cancer,
cardiovascular disease, chronic obstructive pulmonary disease, diabetes, and mental
illness, or kidney failure. Literature concerning dentistry, vaccination,
intravenous drug users and paediatric populations were excluded. Results We
identified 32 papers reporting prevalence (n = 24), management (n = 5) or both (n =
3). Needle fear prevalence varied in disease cohorts: 17-52% (cancer), 25-47%
(chronic kidney disease) and 0.2-80% (diabetes). Assessment methods varied across
studies. Management strategies had poor evidence-base, but included needle-specific
education, decorated devices, cognitive-behavioural stress management techniques,
distraction, and changing the therapy environment or modality. Conclusion Although
needle fear is common there is a paucity of evidence regarding interventions to
address it among adults living with chronic disease. This scoping review has
highlighted the need for improved identification of needle fear in adults and
development of interventions are required for these cohorts.
Objective: This systematic review aims to assess the efficacy and acceptability of
the different types of antidepressants and benzodiazepines for the treatment of
panic disorder (PD) in adult patients. Methods: PubMed, Web of Science, EMBASE,
MEDLINE, the Cochrane Library, and ClinicalTrials.gov were searched for randomized
controlled trials (RCTs) published between 1995 and 2020 on the use of
antidepressants and benzodiazepines for the treatment of PD. A systematic review
and network meta-analysis were performed. Results: 42 RCTs were included in the
network meta-analysis, with a comparison of 11 interventions.Escitalopram (odds
ratios OR 1.52, 95 % credible interval CI 1.09-2.10), venlafaxine (OR 1.33, 95 % CI
1.16-1.51) and benzodiazepines (OR 1.50, 95 % CI 1.29-1.75) had greater efficacy
and acceptability than the placebo. Imipramine(OR 1.43, 95 % CI 1.15-1.79) was also
demonstrated to be efficacious and tolerated but the results were restricted to
small sample size. Moreover, paroxetine, sertraline, fluoxetine, citalopram and
clomipramine (OR 1.37, 1.36, 1.45, 1.33 and 1.36, respectively) were more
efficacious, although the acceptability of paroxetine and sertraline were
significantly less tolerated than benzodiazepines. Notably, the efficacy of
reboxetine and fluvoxamine were merely as equal as that of the placebo. Outcomes:
This is the first systematic review of antidepressants and benzodiazepines for the
treatment of PD to use a network analysis. Escitalopram and venlafaxine as well as
benzodiazepines may be effective choices as treatments for PD with relatively good
acceptability, which still needs to be confirmed byhigh-quality RCTs.
It is becoming increasingly apparent that long-term memory formation relies on a
distributed network of brain areas. While the hippocampus has been at the center of
attention for decades, it is now clear that other regions, in particular the medial
prefrontal cortex (mPFC), are taking an active part as well. Recent evidence
suggests that the mPFC-traditionally implicated in the long-term storage of
memories-is already critical for the early phases of memory formation such as
encoding. In this review, we summarize these findings, relate them to the
functional importance of the mPFC connectivity, and discuss the role of the mPFC
during memory consolidation with respect to the different theories of memory
storage. Owing to its high functional connectivity to other brain areas subserving
memory formation and storage, the mPFC emerges as a central hub across the lifetime
of a memory, although much still remains to be discovered.
Purpose Head and neck cancer (HNC) patients may experience fears regarding cancer
recurrence (FoR) and of catching COVID-19. There could be unease for attending
hospital clinics for face to face (F2F) examination. F2F benefit in cancer
surveillance has to be balanced against the risk of virus transmission. This study
aimed to report perceptions of fear of cancer and fear of COVID-19 and to report
patient preference for follow-up consultation in HNC survivors during the COVID-19
pandemic. Methods The study ran from lockdown in England on 24th March to 29th July
2020. Patients were offered preference to postpone their consultation, to have it
by telephone, or F2F. A postal survey was undertaken in the 2 weeks post-
consultation (actual or postponed). Results There were 103 patients. Initial action
by consultant and patient resulted in 51 postponed consultations, 35 telephone
consultations and 17 F2F meetings, with 10 F2F triggered by the patient. There were
58 responders to the survey and most (39) had a clear preference for one mode of
follow-up consultation during the COVID-19 pandemic, with half (19) preferring F2F.
A similar response was seen regarding their consultations in general to address
unmet needs and concerns, with 38 having a preferred mode, 29 preferring F2F.
Serious fears about recurrence and COVID-19 were at relatively low levels with a
tendency to be more concerned about recurrence. Conclusion Any redesign of mode and
frequency of out-patient follow-up in light of COVID-19 should be undertaken in
discussion with patient groups and with individual patients.
INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder whose
rising incidence suggests the epidemic proportions of the disease. Impaired fasting
glucose (IFG) and Impaired Glucose Tolerance (IGT) - alone or combined - represent
two intermediate metabolic condition between Normal Glucose Tolerance (NGT) and
overt T2DM. EVIDENCE ACQUISITION: Databases were systematically screened using the
following MeSH terms combination as follows: 1. prediabetes, 2. prediabetic state,
3. prevention, 4. lifestyle, 5. diet, 6. nutrition, 7. pharmacotherapy, 8.
metformin, 9. thiazolidinediones, 10. sodium glucose cotransporter 2 inhibitors,
11. GLP 1 receptor agonists, 12. alpha glucosidase inhibitors, 13. insulin, 14. DPP
IV inhibitors. EVIDENCE SYNTHESIS: Several studies have demonstrated that insulin
resistance and beta-cell impairment can be identified even in normoglycemic
prediabetic individuals. Worsening of these two conditions may lead to progression
of IGT and/or IFG status to overt diabetes. Starting from these assumptions, it
seems logical to suppose that interventions aimed at improving metabolic
conditions, even in prediabetes, could represent an effective target to halt
transition from IGT/IFG to manifest T2DM. Starting from pathophysiological
knowledge, in this review we evaluate two possible interventions (lifestyle
modifications and pharmacological agents) eligible as prediabetes therapy since
they have been demonstrated to improve insulin resistance and beta-cell impairment.
CONCLUSIONS: Detecting high-risk people and treating them could represent an
effective strategy to slow down progression to overt diabetes, normalize glucose
tolerance, and even prevent micro- and macrovascular complications.
COVID-19 (Coronavirus disease 2019) is a novel coronavirus which was first detected
in late December 2019 in the Wuhan Province of China. This novel coronavirus,
caused by a zoonotic beta-coronavirus (SARS-CoV-), is described as highly
infectious. The World Health Organization (WHO) named the novel coronavirus as
COVID-19 on February 11, 2020, and declared it as a "pandemic." Almost all
countries have undertaken wide-scale precautions so as to prevent or limit the
spread of the virus, with most having practiced some form of "lockdown" along with
"social distancing," as well as dispensed recommendations for proper hand washing,
avoiding touching the face, wearing facemasks, and using disposable tissues when
either coughing or sneezing. Whereas it is well known that slowing the spread of
this new epidemic requires the cooperation of all citizens, some people still seem
to willfully disregard the rules and guidelines, and thereby ignore the health
risks posed to both themselves and to others they come into contact with. People
have responded differently to lockdown rules and social distancing practices.
Whilst the majority follow the rules and recommendations with great care, others
are more lax or simply refuse to comply. These differences might be accounted for
according to a number of factors including personal, social, cultural, mental, and
economic variables. Being persuaded to comply with preventive rules, especially
those concerned with health-related behaviors, also bring certain other factors
into play. Fear is one of those factors, and is one of the most powerful. It is
well known that fear-based appeals can be effective in inculcating health
behaviors, with many theories having been developed in this area. However, both the
content of the message (the level of the fear it contains) and certain personal
variables can determine the persuasive power of the fear appeal. It can even have
an adverse effect if not properly applied. Many theories have been developed to
address the persuasive effectiveness of the fear appeal (e.g., fear-drive theory,
protection-motivation theory), and this study aims to discuss these individual
differences in precautionary and preventive measures for the COVID-19 pandemic
within the framework of the basic assumptions of these theoretical approaches.
Background The presence of parents during the dental appointment can affect the
child's behaviour and, consequently, the success of the treatment. Aim This
systematic review aimed to evaluate whether parents' presence in the operatory room
influences children's behaviour, anxiety and fear during dental treatment. Design
EMBASE, Cochrane Library, LILACS, PubMed, PsycINFO, Scopus, Web of Science, Google
Scholar, OpenGrey and ProQuest Dissertations and Theses Databases were searched.
Randomized and non-randomized clinical trials in which some measure assessing
children's behaviour and/or anxiety and fear during dental treatment with the
presence and absence of parents were included. Two reviewers assessed studies for
selection, extracted data, evaluated bias (Joanna Briggs Institute) and graded the
certainty of evidence (Grading of Recommendations, Assessment, Development and
Evaluation). Random-effects meta-analyses using mean difference (MD) and narrative
synthesis were performed. Results A total of 2846 papers were identified, and after
a 2-phase selection, sixteen studies were included (five in meta-analyses). There
was no difference in children's behaviour in the presence or absence of parents (P
= .23, P = .40, P = .60 and P = .89, respectively). The presence or absence of
parents did not influence children's anxiety (P = .94 and P = .97) or fear (DM: -
0.08; CI:-0.34-0.19, P = .24). All included studies presented a high risk of bias,
and the certainty of evidence was considered to be very low. Conclusion It is
concluded that parents' presence in the operation room does not influence
children's (up to 12 years old) behaviour, anxiety and fear during dental treatment
with very low certainty of evidence. Methodological limitations of included
studies, however, suggest that better designed trials are needed to adequately
understand this issue.
Research on the 'ecology of fear' posits that defensive prey responses to avoid
predation can cause non-lethal effects across ecological scales. Parasites also
elicit defensive responses in hosts with associated non-lethal effects, which
raises the longstanding, yet unresolved question of how non-lethal effects of
parasites compare with those of predators. We developed a framework for
systematically answering this question for all types of predator-prey and host-
parasite systems. Our framework reveals likely differences in non-lethal effects
not only between predators and parasites, but also between different types of
predators and parasites. Trait responses should be strongest towards predators,
parasitoids and parasitic castrators, but more numerous and perhaps more frequent
for parasites than for predators. In a case study of larval amphibians, whose trait
responses to both predators and parasites have been relatively well studied,
existing data indicate that individuals generally respond more strongly and
proactively to short-term predation risks than to parasitism. Apart from studies
using amphibians, there have been few direct comparisons of responses to predation
and parasitism, and none have incorporated responses to micropredators, parasitoids
or parasitic castrators, or examined their long-term consequences. Addressing these
and other data gaps highlighted by our framework can advance the field towards
understanding how non-lethal effects impact prey/host population dynamics and shape
food webs that contain multiple predator and parasite species.
Needle-related procedures are often a source of pain, anxiety and fear in young
patients. This systematic review aimed to investigate the effectiveness of virtual
reality (VR) on reducing pain, fear and anxiety in pediatric patients undergoing
needle-related procedures. Pain, anxiety, fear, changes in blood pressure and heart
rate as well as satisfaction were evaluated as outcomes during needle-related
procedures in VR compared with standard care conditions. A meta-analysis was
performed, taking into account online databases. Two authors independently
conducted literature searches in December 2020. The last search was conducted in
March 2021 from a total of 106 records, 7 met our inclusion criteria. One study was
excluded from the meta-analysis due to insufficient data. VR was applied as a
distractor during venous access. Statistically significant benefits of using VR
were shown in children's pain scores, where VR significantly decreased symptoms (n
= 3204 patients, MD = -2.85; 95% CI -3.57, -2.14, for the Wong-Baker Faces Pain
Rating Scale and n = 2240 patients, MD = -0.19; 95% CI -0.58, 0.20, for the Faces
Pain Scale-Revised). The analysis of fear, anxiety and satisfaction scores revealed
no significant differences between the conditions, as the studies were too
heterogeneous to be pooled. Distraction using virtual reality may be an effective
intervention for reducing pain in children undergoing needle-related medical
procedures. However, further research in the implementation of VR as a distractor
for children and adolescents is required, due to the limited research into this
field.
Laboratory experiments using fear conditioning and extinction protocols help lay
the groundwork for designing, testing, and optimizing innovative treatments for
anxiety-related disorders. Yet, there is limited basic research on fear
conditioning and extinction in obsessive-compulsive disorder (OCD). This is
surprising because exposure based treatments based on associative learning
principles are among the most popular and effective treatment options for OCD.
Here, we systematically review and critically assess existing aversive conditioning
and extinction studies of OCD. Across 12 studies, there was moderate evidence that
OCD is associated with abnormal acquisition of conditioned responses that differ
from comparison groups. There was relatively stronger evidence of OCD's association
with impaired extinction processes. This included multiple studies finding elevated
conditioned responses during extinction learning and poorer threat/safety
discrimination during recall, although a minority of studies yielded results
inconsistent with this conclusion. Overall, the conditioning model holds value for
OCD research, but more work is necessary to clarify emerging patterns of results
and increase clinical translational utility to the level seen in other anxiety-
related disorders. We detail limitations in the literature and suggest next steps,
including modeling OCD with more complex conditioning methodology (e.g., semantic/
conceptual generalization, avoidance) and improving individual-differences
assessment with dimensional techniques.
Objective Panic disorder is a debilitating psychiatric disorder that often co-
occurs with substance use disorders. Given the current opioid epidemic, the high
reported rates of comorbid panic disorder and opioid use disorder are particularly
concerning. In this narrative review, we describe the literature on panic disorder
and opioid use disorder co-occurrence. Methods: 86 studies, 26 reviews, 2
commentaries, and 5 guidelines pertaining to opioid use disorder, panic disorder,
and their comorbidity were identified using all EBSCO databases, PubMed, and Google
Scholar. Results: First, we review epidemiological literature on the prevalence of
the comorbid condition above and beyond each disorder on its own. Additionally, we
discuss the challenges that complicate the differential diagnosis of panic disorder
and opioid use disorder and contribute to difficulties establishing rates of
comorbidity. Second, we review three theoretical models that have been proposed to
explain high rates of co-occurring panic disorder and opioid use disorder: the
precipitation hypothesis, the self-medication hypothesis, and the shared
vulnerability hypothesis. Third, we outline how co-occurring panic and opioid use
disorder may impact treatment for each condition. Conclusion: Based on findings in
the field, we provide recommendations for future research as well as treatment
considerations for co-occurring panic and opioid use disorders.
Purpose - The purpose of this paper is to examine how crises impact overall tourist
behaviour and travel preferences in times of crisis events, both man-made and
natural disasters. In doing so, the present paper has been designed to provide a
new conceptualization of travellers' shifting preferences in terms of the selection
of holiday destinations through the new concept of tourophobia and to classify this
as a new type of tourist behaviour. Design/methodology/approach - The present study
uses a literature review as a qualitative deductive content analysis of 58 field
studies published by major hospitality and tourism journals. By using a deductive
content analysis approach, the current paper is designed to delineate tourist
behaviour through a generic review of relevant literature detailing travellers'
preferences in times of crisis. Findings - The developed concept of tourophobia and
the suggested model, which proposes two possible scenarios, shows that traveller
behaviour is heterogeneous in terms of the destination selection process; this
finding is based on a content analysis of the articles chosen. Further, by using
the developed model, the decline in travel and tourism can also be explained by an
increase in what is termed in this paper "tourophobia", which results from the
various devastating effects of crises. Research limitations/implications - The
proposed model is expected to help destination managers and marketers to segment
and forecast the future market demand of tourist travel preferences, thereby
enabling them to form effective marketing strategies and increase their
responsiveness during difficult times. Only articles from hospitality and tourism
journals were subjected to content analysis; this is a major limitation of the
study. Originality/value - The present research contributes to current knowledge by
describing the concept of tourophobia as a tourist behaviour in times of crisis. As
an emerging phenomenon, it is also introduced as being one criterion for the
selection of destinations and, therefore, is regarded as a driver for tourist
behaviour, thus generating the originality of the paper. This study strives to
provide a new direction for future studies on tourist behaviour, rather than
offering new empirical data.
Background The aesthetic treatment based on fillers with hyaluronic acid presents
an increasing demand in the present day because it is considered a safe and
minimally invasive procedure. In the management of adverse effects or more severe
complications of hyaluronic acid-based fillers, hyaluronidase is the treatment of
choice. Aims To demonstrate efficacy in reversibility and safety in the treatment
of HA complications. Patients/Methods It is a retrospective study article that
reports the use of hyaluronidase in the main undesirable effects of fillers in 114
patients in a private dermatological clinic from 2015 to 2018. Results The target
of the application was 51 cases of overcorrection (45%), 50 cases of Tyndall effect
(44%), and 13 late nodules (11%). When we evaluated the areas where HYAL was
injected, we found that the area with the most indication of the application of the
product was the eyelid region (58 injections). Conclusion This study concluded that
HYAL is a safe and effective drug in the management of mild adverse events of HA
applications with no severe side effects in our protocol of use.
Background: Panic Disorder (PD) is characterized by unexpected and repeated moments
of intense fear or anxiety, which manifest themselves through strong cognitive and
behavioural symptoms. However, a clear picture of how impairments in recognition
and processing of facial emotions affect the everyday life of PD patients has yet
to be delineated. This review attempts to provide an overview of behavioural
studies of emotion detection from facial stimuli in PD patients. Methods: A
bibliographic research on PubMed of all studies investigating the recognition and
processing of facial emotion stimuli in patients with PD and in high-risk offspring
was performed, and nine articles (yrs: 2000 to 2019) were discovered. Results: In
several of the reviewed studies, PD patients showed significant deficits in
detecting (particularly negative) emotions in facial stimuli. These impairments
were also found in the offspring of parents with PD and high-risk individuals.
Limitations: Inferences are constrained by methodological heterogeneity, included
but not limited to cross-study variability in the stimuli employed, and in the
clinical characterization of PD patients. Conclusions: In general, the results of
this survey confirm that deficits in processing facially conveyed negative emotions
should be considered a core impairment in PD. However, future larger and more
homogenous studies are warranted to better highlight the connection between emotion
recognition and PD.
The acquisition of fear associative memory requires brain processes of coordinated
neural activity within the amygdala, prefrontal cortex (PFC), hippocampus, thalamus
and brainstem. After fear consolidation, a suppression of fear memory in the
absence of danger is crucial to permit adaptive coping behavior. Acquisition and
maintenance of fear extinction critically depend on amygdala-PFC projections. The
robust correspondence between the brain networks encompassed cortical and
subcortical hubs involved into fear processing in humans and in other species
underscores the potential utility of comparing the modulation of brain circuitry in
humans and animals, as a crucial step to inform the comprehension of fear
mechanisms and the development of treatments for fear-related disorders. The
present review is aimed at providing a comprehensive description of the literature
on recent clinical and experimental researches regarding the noninvasive brain
stimulation and optogenetics. These innovative manipulations applied over specific
hubs of fear matrix during fear acquisition, consolidation, reconsolidation and
extinction allow an accurate characterization of specific brain circuits and their
peculiar interaction within the specific fear processing.
Little is known about why people behave the way they do in threatening situations.
Some theories invoke a transfer of responses from unconditioned stimuli (US) to
conditioned stimuli (CS), but this principle goes astray because responses to the
US and CS can differ substantially. The idea that we introduce here is that the
pattern of responses to a newly established CS does not come from the US but (at
least partly) transfers from how one (learned to) respond(s) to previously
encountered stimuli with threat value. So, we conceptualize threat value as a
stimulus feature that allows responses to transfer between stimuli that share this
feature (in the same way as, for example, overlap in color or shape can support
transfer). In contrast to prevailing views, this new perspective focuses on the
relation between the CS and already established threat signals rather than on the
relation between the CS and the US. We discuss how this shared features perspective
on human fear responding can inspire future directions in both the laboratory and
clinical practice.
Despite exposure-based treatments being recommended for anxiety disorders, these
treatments are ineffective for over half of all adolescents who receive them. The
limited efficacy of exposure during adolescence may be driven by a deficit in
extinction. Although indications of diminished extinction learning during
adolescence were first reported over 10 years ago, these findings have yet to be
reviewed and compared. This review (k = 34) found a stark inter-species difference
in extinction performance: studies of adolescent mice reported deficits in
extinction learning and retention of both cued and context fear. In contrast,
studies of adolescent rats only reported poor extinction retention specific to cued
fear. Adolescent mice and rats appeared to have only one behavioral outcome in
common, being poor extinction retention of cued fear. These findings suggest that
different behavioral phenotypes are present across rodent species in adolescence
and highlight that preclinical work in rats and mice is not interchangeable.
Further investigation of these differences offers the opportunity to better
understand the etiology, maintenance, and treatment of fear-based disorders.
Panic buying has re-emerged as a 'new' normal consumer behaviour and has become a
coping mechanism for real and perceived dangers associated with COVID-19. Despite
the need for a better understanding of the panic buying phenomenon, there has been
a lack of scholarly research on this topic. This study seeks to fill this gap. In
this article, we systematically review extant studies in panic buying from the last
two decades. We analyse and categorize them according to Callahan's 4W (2014)
review structure and Paul and Rosado-Serrano's (2019) TCCM framework. We found that
the existing publications in panic buying are fragmented across multiple
disciplines. Due to the nature of the panic-induced behaviour, most of them have
been written as a reaction to the pandemic crisis. We contribute to marketing
research by providing theoretical, contextual and methodological insights into the
field of panic buying. Furthermore, we develop a research agenda related to
retailer and consumer perspectives. Additionally, we identify research issues
related to policymaking and governance, as well as broader societal impacts that
need to be addressed in the future.
Translational research on post-traumatic stress disorder (PTSD) has produced
limited improvements in clinical practice. Fear conditioning (FC) is one of the
dominant animal models of PTSD. In fact, FC is used in many different ways to model
PTSD. The variety of FC-based models is ill defined, creating confusion and
conceptual vagueness, which in turn impedes translation into the clinic. This
article takes a historical and conceptual approach to provide a comprehensive
picture of current research and help reorient the research focus. This work
historically reviews the variety of models that have emerged from the initial
association of PTSD with FC, highlighting conceptual pitfalls that have limited the
translation of animal research into clinical advances. We then provide some
guidance on how future translational research could benefit from conceptual and
technological improvements to translate basic findings in patients. This objective
will require transdisciplinary approaches and should involve physicians, engineers,
philosophers, and neuroscientists.
Hypoglycemia limits optimal glycemic management of patients with type 1 diabetes
mellitus (T1DM). Fear of hypoglycemia (FoH) is a significant psycho-social
consequence that negatively impacts the willingness of T1DM patients to engage in
and profit from the health benefits of regular physical activity (e.g.,
cardiometabolic health, improved body composition, cardiovascular fitness, quality
of life). Technological advances, improved insulin regimens, and a better
understanding of the physiology of various types of exercise could help ameliorate
FoH. This narrative review summarizes the available literature on FoH in children
and adults and tools to avoid it.
Attentional biases to threat exist in panic disorder (PD), probably related to
altered subliminal processing. We systematically reviewed studies investigating
subliminal processing in PD. Studies were retrieved from MEDLINE and Scopus (R). We
meta-analytically compared PD (n = 167) and healthy controls (HC, n = 165) for
processing of masked panic-related and neutral words. We also compared subliminal
and supraliminal presentations of panic-related words relative to neutral words
within PD subjects and HC. We found a significantly enhanced Stroop interference to
masked panic-related words in PD vs HC (Hedges' g = 0.60, p = 0.03; Q = 14.83, I-2
= 66.3 %, p = 0.01). While both PD subjects and HC tended to be slower to respond
to supraliminal threat words than to neutral words, PD subjects only showed a
marginally significant slower response to subliminal panic-related words vs neutral
words. Findings remain inconclusive regarding comparison to other mental disorders,
neural correlates, and the effect of psychotherapy. Even if possibly flawed by
methodological weaknesses, our findings support the existence of a sensitivity to
subliminal threat cues in PD, which could be targeted to improve treatment.
The pandemic resulting from COVID-19 has led to the collapse of the health system
in dozens of countries. Parallel to clinical risk, the appearance or
intensification of psychiatric symptoms has also been documented. The
identification of groups at risk is essential for the establishment of preventive
and therapeutic strategies. Cancer patients appear to be especially vulnerable both
from a clinical and psychiatric perspective. Problems related to contamination and
the cancer treatments themselves are intertwined, causing a sum of patients' fears
to arise, which can cause mental effects. This study aims to review and investigate
the impact of COVID-19 on the mental health of cancer patients and indicate
possible support strategies.
Several psychiatric conditions such as phobias, generalized anxiety, and post-
traumatic stress disorder (PTSD) are characterized by pathological fear and
anxiety. The main therapeutic approach used in the management of these disorders is
exposure-based therapy, which is conceptually based upon fear extinction with the
formation of a new safe memory association, allowing the reduction in behavioral
conditioned fear responses. Nevertheless, this approach is only partially
resolutive, since many patients have difficulty following the demanding and long
process, and relapses are frequently observed over time. One strategy to improve
the efficacy of the cognitive therapy is the combination with pharmacological
agents. Therefore, the identification of compounds able to strengthen the formation
and persistence of the inhibitory associations is a key goal. Recently, growing
interest has been aroused by the neuropeptide oxytocin (OXT), which has been shown
to have anxiolytic effects. Furthermore, OXT receptors and binding sites have been
found in the critical brain structures involved in fear extinction. In this review,
the recent literature addressing the complex effects of OXT on fear extinction at
preclinical and clinical levels is discussed. These studies suggest that the OXT
roles in fear behavior are due to its local effects in several brain regions, most
notably, distinct amygdaloid regions.
Background: Due to the fear of childbirth (FOC) and failure to provide painless
delivery in Iran, the prevalence rate of elective cesarean section (C-section)
performed on request by pregnant women is on the rise. However, no systematic
review assessing the results of studies in this respect has been thus far
developed. Objective: To systematically review published psychological intervention
research reflecting on FOC in Iran. Materials and Methods: In this systematic
review, the databases of PubMed, MEDLINE, PsycINFO, Wiley, ISI Web of Science,
Scopus, Science Direct, Cochrane Library, Google Scholar, and Scientific
Information Database were searched to retrieve the relevant studies. Manual
searches were performed to find the relevant articles and finally 21 intervention
studies were reviewed. Results: Based on the modified Jadad Scale, a methodological
quality (risk of bias) assessment tool, 14 and 7 studies had acceptable or good and
low quality, respectively. The included articles covered fear, fear of childbirth,
pregnancy, and psychological intervention in Iran. Cognitive behavioral therapy,
relaxation techniques, psychological counseling, childbirth preparation classes
(CPCs), mindfulness programs, and psychoeducation had been also practiced as the
main types of psychological interventions for reducing FOC in pregnant women.
Conclusion: There was no clear evidence to establish the most effective method for
minimizing levels of FOC in pregnant women. Based on the assessment tool and since
most of the studies had moderate or low quality, conducting standard and high-
quality randomized controlled trials focusing on FOC in pregnant women is of most
importance in Iranian population.
While cancer survivors commonly experience fear and anxiety, a substantial minority
experience an enduring and debilitating fear that their cancer will return; a
condition commonly referred to as fear of cancer recurrence (FCR). Despite recent
advances in this area, little is known about FCR among people from Indigenous or
other ethnic and racial minority populations. Given the high prevalence and poor
outcomes of cancer among people from these populations, a robust understanding of
FCR among people from these groups is critical. The current review identified and
aggregated existing literature on FCR amongst adult cancer survivors from
Indigenous and minority populations. The protocol of this review was registered
with PROSPERO in July 2020 (Registration number: CRD42020161655). A systematic
search of bibliographic databases was conducted for relevant articles published
from 1997 to November 2019. Data from eligible articles were extracted and
appraised for quality by two independent reviewers. Nineteen articles from four
countries (United States of America, Canada, Australia and the United Kingdom) met
the inclusion criteria, including 14 quantitative, 4 qualitative and 1 mixed-
methods study. Only one article reported on an Indigenous population. Few studies
reported on FCR prevalence (n = 3) or severity (n = 9). While the variation in
tools used to measure FCR hindered a robust estimate of severity, results suggested
some differences in FCR severity between minority and dominant populations,
although these may have been due to study metholodological differences. Few factors
were reported as being associated with FCR in minorities across multiple studies.
The qualitative synthesis found five themes associated with the lived experience of
FCR: (i) variations in the lived experience of FCR; (ii) spirituality and worldview
impacting on FCR; (iii) the importance of staying positive; (iv) complexities
around support; and (v) increasing cancer knowledge. The findings of this review
highlight differences in FCR across cultures and contexts, which reinforces the
need for culturally-specific approaches to this condition. The dearth of research
in this area is of concern given the significant burden of cancer in these
populations. A deeper understanding of this condition among Indigenous and minority
populations is critical to developing and delivering appropriate and effective
psychosocial care for cancer survivors from these groups. Systematic Review
Registration: identifier [CRD42020161655].
Fear of cancer recurrence (FoR) is an important yet underestimated long term
sequela that many cancer survivors suffer from. The continuous state of uncertainty
the survivors might go through can lead to a serious impact on their quality of
life (QoL), which is collectively referred to as Damocles syndrome. Given the
increasing numbers of cancer survivors, it is crucial to understand the different
psychological issues that face them, including Damocles syndrome. Herein, we review
the current literature of Damocles syndrome specifically in hematologic cancer
survivors. Although with inconsistent terms, current literature demonstrates the
impact and the prevalence of Damocles syndrome on QoL of survivors of leukemia,
lymphoma, and hematopoietic cell transplant. Interventional studies are very
limited in this area. Moreover, hematologic malignancy survivors can also meet the
diagnostic criteria of other psychiatric diseases, including depression, anxiety,
and post-traumatic stress disorder, wherein they should be managed accordingly. It
is important to increase the awareness about Damocles syndrome and screen patients
for it and other related psychological disorders. Additionally, this review has
shown the need for standardization of Damocles syndrome definitions. Finally, the
lack of interventional studies that target survivors' psychosocial challenges calls
for prospective research to better address this rising problem.
Few days after Nigeria attained the sexagenarian status on October 1, 2020, the
country has once again become a subject of unusual discourse both home and abroad.
This is due to the protests by disgruntled youths against the activities of the
Special Anti-Robbery Squad; a unit of the Nigeria Police Force, which has been
accused of brutality, human rights violation, sexual abuse, torture, and
extrajudicial killings among others. This study adopts a qualitative approach which
draws data from reports of reputable international organisations, juried scholarly
articles, working papers, and newspaper articles. The study concludes that the
police adopts brutality, abuse, and violations as its tactics due to its inadequate
equipment for investigation which makes officers deploy torture as a means of
extracting the truth. This is further complicated by an ingrained culture of
corruption, inadequate funding, political interference, inadequate personnel, and a
pro-elite orientation. As a result, it is recommended that a sincere and
comprehensive reform of the police be carried out to improve the welfare of the
police; encourage the use of extensive technology, and improve police-community
relations.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that includes
specific problems in many developmental areas. There are various studies on reflex,
motor development and sensory functionality in ASD. However, the studies on Fear
Paralysis Reflex (FPR) and Moro reflex are limited. FPR and Moro are important as
they are two of the initially developing ones that imply reflex harmony and the
main gateway to subsequent reflexes. The problems in these can cause impairment
among development areas, especially in motor development. They may cause or
accompany ASD, dyspraxia, epilepsy, allergies, dyslexia. Many problems occur
related with ASD as a result of the deterioration in these reflexes as part of
sensory-motor development. Some tests may detect the deterioration in Moro reflex
and offer exercise-based solutions to ensure the reflex integration. In conclusion,
the problems in FPR and Moro should be taken into account in the diagnosis and
intervention in terms of the development of these reflexes.
Background and aims: FoMO has been considered a predisposing factor toward
excessive internet use, and a great deal of literature has investigated the link
between FoMO and internet use. However, there is still a lack of cohesion in the
literature. Methods: The current study have been conducted and reported in
accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses
(PRISMA). Results: In the current systematic review and meta-analysis of 86 effect-
sizes, representative of 55,134 participants (Mean(age) = 22.07, SD = 6.15, females
= 58.37%), we found that the strength of the trait FoMO- internet use association
significantly varies from r = 0.11 to r = 0.63. In some populations, FoMO appears
to increase with age and it is reverse in other populations. Facebook use was
unrelated to FoMO in some populations, and higher FoMO was linked with stopping
Instagram use for some individuals. The FoMO- internet use association was
independent of their severity, as the interaction was not significant, and this
association was neither linear nor curvilinear. The FoMO-internet use association
does not appear to be associated with depressive, anxiety, and stress symptoms or
level of life satisfaction. The COVID-19 pandemic was the only significant
moderator of the FoMO-internet use association, strengthening this relationship.
Discussion and Conclusions: FoMO demonstrates a considerable role in internet use;
however, there is no evidence of interaction or bi-directional association between
the mentioned. Overall, we still don't know what factors contribute to individuals
exhibiting distinct patterns in the FoMO-internet use association.
Objective This review aims to identify non-medical interventions that may reduce
the fear of childbirth, directly or indirectly (through its factors). Methods This
review followed the PRISMA guidance and a rigorous protocol that was registered in
PROSPERO. Searches were done in ProQuest, the International Clinical Trials
Registry Platform, and Google Scholar. All RCTs published in the last 5 years, in
English or Spanish, regarding women with a low-risk pregnancy and without mental
disorders were included. Results From 5147 articles found, only 69 were full-text
assessed. Finally, 18 studies were included suggesting that prenatal education,
psychoeducation, and counseling might be effective, whereas cognitive-behavioral
therapy and some alternative therapies require more research. The results of
relaxation techniques were contradictory. Results also suggest that social support
and exposure (through education) might have an important role in the efficacy of
interventions. Conclusions More appropriately randomized and blinded trials are
necessary that use a prespecified definition of fear of childbirth and
comprehensive measurement tools specific for pregnant women.
Background: This review aimed to evaluate whether patients with panic disorder (PD)
exhibit different heart rate variability (HRV) compared to healthy controls and to
determine whether HRV is different in patients with PD after treatment. Methods:
Literature databases were searched for studies comparing resting-state HRV between
drug-naive patients with PD and healthy controls. Parameters from the short-term
frequency-domain and long-term time domain were included. Results: In the low
frequency (LF) analysis, no significant association was found between LF and PD
(standardised mean difference [SMD] = - 0.0443, 95% confidence interval [CI]: -
0.1765 to 0.0879). In the high frequency (HF) analysis, no significant association
was found between HF and PD (SMD = - 0.1269, 95% CI: - 0.2598 to 0.0059). In the
LF/HF analysis, a significantly higher LF/HF ratio was found in cases than in
controls, but the effect was moderate (SMD = 0.1390, 95% CI: 0.0180 to 0.2600). For
the standard deviation of normal-to-normal intervals, a significantly lower value
was observed in cases than in controls (SMD = - 0.3133, 95% CI: - 0.5459 to -
0.0808). Limitations: Limited sample size in the time-domain and treatment effect
analyses. Conclusions: Patients with PD had a higher short-term LF/HF ratio,
indicating impaired sympathovagal balance. The LF/HF ratio findings were more
consistent compared with LF and HF alone, making it a better parameter to interpret
the LF and HF in conjunction. HRV may be a promising biomarker for predicting
antidepressant response.
Objective To explore the short-term efficacy and tolerability of paroxetine in the
treatment of panic disorder in adults. Methods Multiple electronic databases were
searched to find randomized controlled trials (RCTs) on paroxetine and panic
disorder. The primary efficacy outcomes were: the mean change compared to the
baseline in the total number of full panic attacks, Clinical Global Impression-
Severity of Illness (CGI-S) score, and the proportion of participants with zero
full panic attacks and with a 50% or greater reduction in the number of full panic
attacks. The tolerability outcomes included withdrawal rate and the incidence of
adverse events (AEs). Results 13RCTs were included. The pooled analyses showed
patients who received paroxetine experienced greater improvements in the number of
full panic attacks (total: MD=-1.96, 95%CI -3.45 to -0.47, P=0.010; >= 50%
reduction: OR=1.66, 95%CI 1.08 to 2.55, P=0.02; zero full panic attacks: OR=1.70,
95%CI 1.42 to 2.03, P < 0.00001) and CGI-S (MD=-0.37, 95%CI -0.74 to -0.01, P=0.05)
than placebo. There was no evident difference in the total withdrawal rate
(OR=0.91, 95%CI 0.76 to 1.08, P=0.26) and withdrawal rate due to AEs (OR=1.29,
95%CI 0.97 to 1.72, P=0.07) between the two groups. Withdrawal rate due to lack of
efficacy or relapse (OR=0.44, 95%CI 0.31 to 0.63, P < 0.00001) and the incidence of
serious AEs (OR=0.42, 95%CI 0.23 to 0.79, P=0.007) in the paroxetine group was
lower than the placebo group. Meanwhile, the incidence of any treatment-emergent
adverse events (TEAEs) (OR=1.32, 95%CI 1.05 to 1.64, P=0.02) in the paroxetine
group was higher in comparison with the placebo. Conclusions Paroxetine is an
effective and well-tolerated short-term treatment for adults with panic disorder.
Attributed to the recent COVID-19 pandemic, panic buying is now a frequent
occurrence in many countries, leading to stockouts and supply chain disruptions.
Consequently, it has received much attention from academics and the retail
industry. The aim of this study is to review, identify, and synthesise the
psychological causes of panic buying, which is a relatively new and unexplored area
in consumer behaviour research. A systematic review of the related literature is
conducted. The review suggests that panic buying is influenced by (1) individuals'
perception of the threat of the health crisis and scarcity of products; (2) fear of
the unknown, which is caused by negative emotions and uncertainty; (3) coping
behaviour, which views panic buying as a venue to relieve anxiety and regain
control over the crisis; and (4) social psychological factors, which account for
the influence of the social network of an individual. This study contributes to the
literature by consolidating the scarce and scattered research on the causes of
panic buying, drawing greater theoretical insights into each cause and also offers
some implications for health professionals, policy makers, and retailers on
implementing appropriate policies and strategies to manage panic buying.
Recommendations for future research are also provided.
Fear and anxiety constitute an important theme in dentistry, especially with
children. Anxiety and the fear of pain during dental treatment can lead to
avoidance behaviour, which contributes to perpetuating fear and anxiety of dental
care. Understanding and assessing dental fear and anxiety in children is important
for delivering successful dental care with high satisfaction in this age group.
Among the vast assessment method options available today, self-report assessment,
parental proxy assessment, observation-based assessment, and physiological
assessment are the four major types for dental fear and anxiety in children. Each
method has its own merits and limitations. The selection of a method should be
based on the objectives, validity, and setting of the assessment. The aim of this
paper is to review and discuss the assessment methods for dental fear and anxiety
in children.
Falls in older adults are a major health concern, yet the "fear of falling", a
common psychosocial response that can occur post-fall, has seldom been
investigated. A scoping review was conducted to identify and map interventions that
occupational therapists can use to manage the fear of falling psychosocial response
(FoFPR) among older adults. Thirteen electronic databases were searched and 22
studies were retrieved. Cognitive behavioral therapy, guided imagery, and Tai Chi
were interventions found to help older adults deal with their FoFPRs. Occupational
therapists assisting older adults in this area can play a significant role.
Fear of self has been proposed as a transdiagnostic construct, playing a role in
not only obsessive compulsive disorder (OCD), but in related disorders as well. In
this article, empirical support for the association between eating disorders (EDs)
and the fear of self will be reviewed. Support for the fear of self in EDs will be
contextualized within the theory of possible selves, self-discrepancy theory, and
motivation frameworks. Most of the research that will be presented pertains to a
feared overweight self. The relevance of broadening the scope of feared self-
domains attributed to EDs beyond weight to include those pertaining to character
will be advocated. Furthermore, risk factors theorized to lead to the development
and investment in a feared self in OCD are examined and evidence for their
applicability to EDs is presented. Treatment strategies targeting self-concept and
the fear of self in EDs are also described, highlighting the clinical relevance of
integrating this construct into the conceptualization of EDs. Finally,
recommendations for future research are proposed.
Background: The aim of the present systematic meta-analytical review was to
quantify the effects of different mind-body interventions (MBI) involving
meditative movements on relevant psychological health outcomes (i.e., quality of
life (QoL), depressive symptoms, fear of falling (FoF) and sleep quality) in older
adults without mental disorders.Methods: A structured literature search was
conducted in five databases (Ovid, PsycINFO, PubMed, SPORTDiscus, Web of Science).
Inclusion criteria were: (i) the study was a (cluster) randomized controlled trial,
(ii) the subjects were aged >= 59 years without mental illnesses, (iii) an
intervention arm performing MBI compared to a non-exercise control group (e.g.,
wait-list or usual care), (iv) psychological health outcomes related to QoL,
depressive symptoms, FoF or sleep quality were assessed and (v) a PEDro score of >=
5. The interventions of the included studies were sub-grouped into Tai Chi/Qigong
(TCQ) and Yoga/Pilates (YP). Statistical analyses were conducted using a random-
effects inverse-variance model.Results: Thirty-seven randomized controlled trials
(RCTs) (comprising 3224 participants) were included. Small to moderate-but-
significant overall effect sizes favoring experimental groups (Hedges'g: 0.25 to
0.71) compared to non-exercise control groups were observed in all outcomes
(allpvalues <= 0.007), apart from one subdomain of quality of life (i.e., social
functioning,p= 0.15). Interestingly, a significant larger effect on QoL and
depressive symptoms with increasing training frequency was found for TCQ (p=
0.03;p= 0.004).Conclusions: MBI involving meditative movements may serve as a
promising opportunity to improve psychological health domains such as QoL,
depressive symptoms, FoF and sleep quality in older adults. Hence, these forms of
exercise may represent potential preventive measures regarding the increase of
late-life mental disorders, which need to be further confirmed by future research.
Social fear and avoidance of social partners and social situations represent the
core behavioral symptom of Social Anxiety Disorder (SAD), a prevalent psychiatric
disorder worldwide. The pathological mechanism of SAD remains elusive and there are
no specific and satisfactory therapeutic options currently available. With the
development of appropriate animal models, growing studies start to unravel neuronal
circuit mechanisms underlying social fear, and underscore a fundamental role of the
prefrontal cortex (PFC). Prefrontal cortical functions are implemented by a finely
wired microcircuit composed of excitatory principal neurons (PNs) and diverse
subtypes of inhibitory interneurons (INs). Disinhibition, defined as a break in
inhibition via interactions between IN subtypes that enhances the output of
excitatory PNs, has recently been discovered to serve as an efficient strategy in
cortical information processing. Here, we review the rodent animal models of social
fear, the prefrontal IN diversity, and their circuits with a particular emphasis on
a novel disinhibitory microcircuit mediated by somatostatin-expressing INs in
gating social fear behavior. The INs subtype distinct and microcircuit-based
mechanism advances our understanding of the etiology of social fear and sheds light
on developing future treatment of neuropsychiatric disorders associated with social
fear.
Decreasing the greenhouse gas (GHG) emissions from the residential sector is
critical to the low-carbon transition. Applying information and communication
technologies to power systems makes it possible to reduce GHG emissions in the
residential sector, for example through the development of smart homes. Smart homes
are more energy efficient and thus, they may be prone to the rebound effect (RE),
(i.e., an increase in demand following the introduction of more efficient
technology). Moreover, because the electricity's environmental impacts, cost and
demand all vary over time, the potential for RE may also fluctuate. Accounting for
these temporal aspects could therefore provide more insights into how and why
potential RE may occur in smart homes, especially with regard to households'
behaviours. In this study, an agent-based model is used to simulate standard and
smart home electricity consumption. Life cycle assessment and environmentally
extended input-output tables are used to calculate the households' electricity
consumption and RE GHG emissions during the simulations. Results show that, while
indirect RE in smart homes is low (about 5% in the simulations), the choice of
metric used for smart electricity management is key to maximize the GHG emissions
reductions of smart homes. When smart homes perform load shifting based on an
economic rather than environmental signal, RE increases by almost five-fold.
Moreover, certain periods, such as weekdays or the winter season, lead to more
significant RE. Thus, considering factors that decrease RE could enable smart homes
to reach their full potential contribution to sustainability.
y The novel Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2, which is
the causative agent of a potentially fatal disease that is of great global public
health concern. The outbreak of COVID-19 is wreaking havoc worldwide due to
inadequate risk assessment regarding the urgency of the situation. The COVID-19
pandemic has entered a dangerous new phase. When compared with SARS and MERS,
COVID-19 has spread more rapidly, due to increased globalization and adaptation of
the virus in every environment. Slowing the spread of the COVID-19 caseswill
significantly reduce the strain on the healthcare system of the country by limiting
the number of people who are severely sick by COVID-19 and need hospital care.
Hence, the recent outburst of COVID-19 highlights an urgent need for therapeutics
targeting SARS-CoV-2. Here, we have discussed the structure of virus; varying
symptoms among COVID-19, SARS, MERS and common flu; the probable mechanism behind
the infection and its immune response. Further, the current treatment options,
drugs available, ongoing trials and recent diagnostics for COVID-19 have been
discussed. We suggest traditional Indian medicinal plants as possible novel
therapeutic approaches, exclusively targeting SARS-CoV-2 and its pathways. (C) 2020
Elsevier B.V. All rights reserved.
Many studies in preclinical animal models have described fear-reducing effects of
the neuropeptide oxytocin in the central nucleus of the amygdala. However, recent
studies have refined the role of oxytocin in the central amygdala, which may extend
to the selection of an active defensive coping style in the face of immediate
threat, and also fear-enhancing effects have been reported. On top of this,
oxytocin enables the discrimination of unfamiliar conspecifics on the basis of
their emotional state, which could allow for the selection of an appropriate coping
style. This is in line with many observations that support the hypothesis that the
precise outcome of oxytocin signaling in the central amygdala or other brain
regions depends on the emotional or physiological state of an animal. In this
review, we highlight a number of studies to exemplify the diverse effects oxytocin
exerts on fear in the central amygdala of rodents. These are discussed in the
context of the organization of the neural network within the central amygdala and
in relation to the oxytocin-synthesizing neurons in the hypothalamus.
Post-traumatic stress disorder (PTSD) is a psychopathological response that
develops after exposure to an extreme life-threatening traumatic event. Its
prevalence ranges from 0.5% to 14.5% worldwide. Due to the complex pathophysiology
of PTSD, currently available treatment approaches are associated with high chances
of failure, thus further research to identify better pharmacotherapeutic approaches
is needed. The traumatic event associated with fear memories plays an important
role in the development of PTSD and could be considered as the main culprit. PTSD
patient feels frightened in a safe environment as the memories of the traumatic
event are revisited. Neurocircuit involving normal processing of fear memories get
disturbed in PTSD hence making a fear memory to remain to dominate even after years
of trauma. Persistence of fear memories could be explained by acquisition, re-
(consolidation) and extinction triad as all of these processes have been widely
explored in preclinical as well as clinical studies and set a therapeutic platform
for fear memory associated disorders. This review focuses on neurocircuit and
pathophysiology of PTSD in context to fear memories and pharmacological targeting
of fear memory for the management of PTSD.
(1) Background: Although panic disorder (PD) is one of the most common anxiety
disorders severely impacting quality of life, no effective genetic testing exists;
known data on possible genetic biomarkers is often scattered and unsystematic which
complicates further studies. (2) Methods: We used PathwayStudio 12.3 (Elsevier, The
Netherlands) to acquire literature data for further manual review and analysis. 229
articles were extracted, 55 articles reporting associations, and 32 articles
reporting no associations were finally selected. (3) Results: We provide exhaustive
information on genetic biomarkers associated with PD known in the scientific
literature. Data is presented in two tables. Genes COMT and SLC6A4 may be
considered the most promising for PD diagnostic to date. (4) Conclusions: This
review illustrates current progress in association studies of PD and may indicate
possible molecular mechanisms of its pathogenesis. This is a possible basis for
data analysis, novel experimental studies, or developing test systems and
personalized treatment approaches.
Burkholderia cepacia (formerly Pseudomonas cepacia) was once thought to be a single
bacterial species but has expanded to the Burkholderia cepacia complex (Bcc),
comprising 24 closely related opportunistic pathogenic species. These bacteria have
a widespread environmental distribution, an extraordinary metabolic versatility, a
complex genome with three chromosomes, and a high capacity for rapid mutation and
adaptation. Additionally, they present an inherent resistance to antibiotics and
antiseptics, as well as the abilities to survive under nutrient-limited conditions
and to metabolize the organic matter present in oligotrophic aquatic environments,
even using certain antimicrobials as carbon sources. These traits constitute the
reason that Bcc bacteria are considered feared contaminants of aqueous
pharmaceutical and personal care products and the frequent reason behind nonsterile
product recalls. Contamination with Bcc has caused numerous nosocomial outbreaks in
health care facilities, presenting a health threat, particularly for patients with
cystic fibrosis and chronic granulomatous disease and for immunocompromised
individuals. This review addresses the role of Bcc bacteria as a potential public
health problem, the mechanisms behind their success as contaminants of pharma-
ceutical products, particularly in the presence of biocides, the difficulties
encountered in their detection, and the preventive measures applied during
manufacturing processes to control contamination with these objectionable
microorganisms. A summary of Bcc-related outbreaks in different clinical settings,
due to contamination of diverse types of pharmaceutical products, is provided.
The current systematic review and meta-analysis examined the efficacy and
effectiveness of internet-delivered cognitive behavioral therapy (iCBT) on panic
disorder and agoraphobia symptom severity. Twenty-seven studies were identified.
Results from nine randomised controlled trials (RCTs) showed that iCBT outperformed
waiting list and information controls for panic (g = 1.22) and agoraphobia (g
= .91) symptoms, but the quality of RCTs varied and heterogeneity was high. Results
from three RCTs suggested iCBT may have similar outcomes to face-to-face CBT in
reducing panic and agoraphobia symptoms. Within-group effect sizes between baseline
and post-treatment were large for panic (n = 29, g = 1.16) and medium for
agoraphobia symptom severity (n = 18, g = .73). Subgroup analyses of within-group
pre/post treatment effect sizes showed larger within-group effect sizes for
efficacy studies (n = 15) compared to effectiveness studies (n = 14) for panic
severity (g = 1.38 vs. g = .98) but not agoraphobia severity. There was no impact
of program length, inclusion or arousal reduction techniques, or degree of
clinician support. Within-group effects of iCBT suggest the reduction in panic and
agoraphobia symptom severity is maintained at 3-6 month follow-up (n = 12).
Fear is an important physiological function for survival. It appears when animals
or humans are confronted with an environmental threat. The amygdala has been shown
to play a highly important role in emergence of fear. Hypothalamic orexin neurons
are activated by fearful stimuli to evoke a 'defense reaction' with an increase in
arousal level and sympathetic outflow to deal with the imminent danger. However,
how this system contributes to the emergence of fear-related behavior is not well
understood. Orexin neurons in the hypothalamus send excitatory innervations to
noradrenergic neurons in the locus coeruleus (NALC) which express orexin receptor 1
(OX1R) and send projections to the lateral amygdala (LA). Inhibition of this di-
synaptic orexin -> NA(LC) -> LA pathway by pharmacological or opto/chemogenetic
methods reduces cue-induced fear expression. Excitatory manipulation of this
pathway induces freezing, a fear-related behavior that only occurs when the
environment contains some elements suggestive of danger. Although, fear memory
helps animals respond to a context or cue previously paired with an aversive
stimulus, fear-related behavior is sometimes evoked even in a distinct context
containing some similar elements, which is known as fear generalization. Our recent
observation suggests that the orexin -> NA(LC) -> LA pathway might contribute to
this response. This review focuses on recent advances regarding the role of
hypothalamic orexin neurons in behavioral fear expression. We also discuss the
potential effectiveness of orexin receptor antagonists for treating excessive fear
response or overgeneralization seen in anxiety disorder and post-traumatic stress
disorder (PTSD).
Translational models of fear have greatly informed our understanding of PTSD and
its underlying fear circuitry. One of the most replicated findings in the field is
the two-fold higher PTSD incidence in females compared to males. While
sociocultural factors play a role, the most robust biological influencers to date
are gonadal hormones, such as estradiol and progesterone, which fluctuate across
the menstrual cycle. Among studies that account for these hormones, most do so in
isolation or collect both and only report one. Variation in study findings suggests
that the ratio between these two hormones (the P/E ratio) may be an important and
missing variable to further understand gonadal hormone influences on fear. Here we
review cross-species examinations of fear and PTSD, within the contexts of
estradiol and progesterone as well as P/E ratios that were calculated based on
extant literature. We then provide recommendations for best practices in assay
methods and reporting to improve research on the P/E ratio in fear and PTSD.
Ultimately, greater understanding of this important variable will advance efforts
to characterize gonadal hormone influences on fear learning processes in humans and
animals.
Fear is a fundamental evolutionary process for survival. However, excess or
irrational fear hampers normal activity and leads to phobia. The amygdala is the
primary brain region associated with fear learning and conditioning. There, Rho
GTPases are molecular switches that act as signaling molecules for further
downstream processes that modulate, among others, dendritic spine morphogenesis and
thereby play a role in fear conditioning. The three main Rho GTPases-RhoA, Rac1,
and Cdc42, together with their modulators, are known to be involved in many
psychiatric disorders that affect the amygdala ' s fear conditioning mechanism.
Rich2, a RhoGAP mainly for Rac1 and Cdc42, has been studied extensively in such
regard. Here, we will discuss these effectors, along with Rich2, as a molecular
switch for fears, especially in the amygdala. Understanding the role of Rho GTPases
in fear controlling could be beneficial for the development of therapeutic
strategies targeting conditions with abnormal fear/anxiety-like behaviors.
This study aims to evaluate the association of body weight (BW) and age on welfare
indicators and fear response (tonic immobility (TI) duration and number of TI
induction trials) and the relationships among welfare indicators. At 50 and 72
weeks of age, 100 laying hens (Novogen brown) from barn systems were weighed and
tested for tonic immobility (TI). After that, a physical examination was carried
out to evaluate health condition, hygiene status, feather damage and claw length.
Most welfare problems detected at 50 weeks had increased by 72 weeks of age. A
higher score for keel bone protrusion was observed in lighter (BW <= 1.9 kg, P =
0.014) and older hens (72 weeks, P = 0.004). Heavier hens (BW > 1.9 kg) showed
longer TI durations (P = 0.022) and older hens required fewer TI inductions (P =
0.025), indicating that heavier and older hens were more fearful. Feather damage
score on wings was positively correlated with feather damage scores on back, rump
and tail (P < 0.001). Hens with higher feather damage scores on the head, back and
tail showed a higher probability of having longer TI durations. Hens with skin
injuries (W = 4.100, P = 0.043) were more likely to be induced into TI on the first
attempt. Hens with higher feather damage scores on head, back and tail and
increased skin injuries were considered more fearful. Additionally, high cumulative
mortality rates (23-26%), keel bone deformations (57%) and keel bone protrusion
(89%) should be considered relevant welfare indicators in laying hens from barn
systems.
Objectives: Severe fear of childbirth (FOC) has adverse consequences for mother and
child. This study aimed to update the global prevalence of severe FOC in low-risk
pregnant women. Materials and Methods: Observational studies published in English
were obtained through PubMed, Scopus, Science Direct, Wiley Online, and Google
Scholar databases up to April 2020. After reviewing the title and introduction, the
quality of the articles that had full text and met the inclusion criteria of the
study was checked with the JBI checklist. Then, the final extracted data were
entered into the STATA software. The overall prevalence of severe FOC and fear in
subgroups were obtained using meta-analysis. Tests of publication bias and
sensitivity analysis were also performed. Results: Overall, 27 observational
studies were included (26014 participants). The global prevalence of severe FOC was
16% (95% CI: 14%-19%). The subgroup analysis showed that after 2015, the prevalence
of fear was higher than before (%18 versus %14). The results also showed a higher
prevalence of fear in women with a diploma and lower compared to women with a
university education (%19 versus %13), in single/divorced women compared to
married/cohabitation women (%21 versus %15), in nulliparous women compared to
multiparous women (%17 versus %14) and in women experiencing the second trimester
of pregnancy compared to women in the third trimester of pregnancy (%23 versus
%14). Conclusions: The global prevalence of severe FOC was 16%. Diagnostic,
preventive, therapeutic and follow-up strategies are needed to reduce fear in all
countries.
Every day we are bombarded by stimuli that must be assessed for their potential for
harm or benefit. Once a stimulus is learned to predict harm, it can elicit fear
responses. Such learning can last a lifetime but is not always beneficial for an
organism. For an organism to thrive in its environment, it must know when to engage
in defensive, avoidance behaviors and when to engage in non-defensive, approach
behaviors. Fear should be suppressed in situations that are not dangerous: when a
novel, innocuous stimulus resembles a feared stimulus, when a feared stimulus no
longer predicts harm, or when there is an option to avoid harm. A cardinal feature
of anxiety disorders is the inability to suppress fear adaptively. In PTSD, for
instance, learned fear is expressed inappropriately in safe situations and is
resistant to extinction. In this review, we discuss mechanisms of suppressing fear
responses during stimulus discrimination, fear extinction, and active avoidance,
focusing on the well-studied tripartite circuit consisting of the amygdala, medial
prefrontal cortex and hippocampus.
Purpose of Review The purpose of this review is to summarize the role of avoidance
behavior in headache-related disability and overview relevant clinical
implications. Recent Findings Avoidance occupies a central role in contemporary
psychological perspectives on headache disorders and other chronic pain conditions.
Several cognitive constructs of relevance to headache are influenced and maintained
by avoidance behavior. A growing body of literature attests to the notion that
avoidance of headache triggers, of stimuli that exacerbate headache, and of broader
life domains can negatively affect headache progression, disability/quality of
life, and comorbid psychiatric symptoms. Interventions targeting avoidance
behavior, such as therapeutic exposure to headache triggers, mindfulness, and
acceptance and commitment therapy (ACT), hold promise for headache disorders but
need to be tested in larger trials. Researchers and clinicians are encouraged to
attend to functional impairment as a critically important treatment outcome.
Comprehensive understanding of headache disorders necessitates attention not merely
to diagnostic symptoms and their reduction, but to patterns of avoidance behavior
that inadvertently exacerbate headache and contribute to functional impairment.
This review examines the current literature focused on nomophobia (objectives,
methodological design, main variables, sample details, and measurement methods) in
the Scopus and Web of Science databases. To this end, we conducted a systematic
literature review in accordance with the Preferred Reporting Items for Systematic
Reviews (PRISMA) guidelines. The initial sample consisted of 142 articles, of which
42 met the inclusion criteria and were analyzed in detail. The findings show that
the current research is in an exploratory phase, with a greater predominance of
descriptive, nonexperimental, and cross-sectional studies that explore the
prevalence of nomophobia mainly in adolescents and university students. The most
widely used measurement instrument is the Nomophobia Questionnaire (NMP-Q) proposed
by Yildrim and Correia. In addition, the research suggests that nomophobia
negatively affects personality, self-esteem, anxiety, stress, academic performance,
and other physical and mental health problems. We are therefore faced with a health
problem, which negatively affects a person, causing psychological problems and
physical and behavioral changes.
Anxiety and fear-related disorders are common and disabling, and they significantly
increase risk for suicide and other causes of morbidity and mortality. However,
there is tremendous potential for translational neuroscience to advance our
understanding of these disorders, leading to novel and powerful interventions and
even to preventing their initial development. This overview examines the general
circuits and processes thought to underlie fear and anxiety, along with the promise
of translational research. It then examines some of the data-driven "next-
generation" approaches that are needed for discovery and understanding but that do
not always fit neatly into established models. From one perspective, these
disorders offer among the most tractable problems in psychiatry, with a great deal
of accumulated understanding, across species, of neurocircuit, behavioral, and,
increasingly, genetic mechanisms, of how dysregulation of fear and threat processes
contributes to anxiety-related disorders. One example is the progressively
sophisticated understanding of how extinction underlies the exposure therapy
component of cognitive-behavioral therapy approaches, which are ubiquitously used
across anxiety and fear-related disorders. However, it is also critical to examine
gaps in our understanding between reasonably well-replicated examples of successful
translation, areas of significant deficits in knowledge, and the role of large-
scale data-driven approaches in future progress and discovery. Although a
tremendous amount of progress is still needed, translational approaches to
understanding, treating, and even preventing anxiety and fear-related disorders
offer great opportunities for successfully bridging neuroscience discovery to
clinical practice.
The current corona virus disease 2019 outbreak caused by severe acute respiratory
syndrome coronavirus 2 started in Wuhan, China in December 2019 and has put the
world on alert. To safeguard Chinese citizens and to strengthen global health
security, China has made great efforts to control the epidemic. Many in the global
community have joined China to limit the epidemic. However, discrimination and
prejudice driven by fear or misinformation have been flowing globally, superseding
evidence and jeopardizing the anti-severe acute respiratory syndrome coronavirus 2
efforts. We analyze this phenomenon and its underlying causes and suggest practical
solutions.
Stress and fear are two fields of research that have evolved simultaneously. It was
not until the eighties that these domains converged in order to better characterize
the impact of stress on fear memory formation. Here, we reviewed the effects of
stress occurring before fear acquisition on the main phases of fear conditioning
protocols (acquisition training, extinction training, extinction retention test),
with a specific focus on sex and sex hormones. We also paid close attention to
methodological aspects in order to better understand and characterize discrepant
findings across studies. In men, stress appears to potentiate fear acquisition at a
physiological level but induces lower activations of fear-related brain regions. In
women, results are inconsistent. Although some studies have shown that stress
lowers physiological fear responses and heightens brain activations in women during
fear acquisition, many studies report no significant effects. Irrespective of sex,
pre-acquisition stress seems to induce fear extinction learning resistance.
Overall, few studies have taken into account sex hormones, despite their impact on
both the fear and stress brain networks. As methodological variability makes it
complex to draw strong conclusions, several methodological aspects are discussed
with the aim of orienting future research.
The pathophysiology of insomnia remains poorly understood, yet emerging cross-
disciplinary approaches integrating natural history, observational studies in
traditional populations, gene-phenotype expression and experiments are opening up
new avenues to investigate the evolutionary origins of sleep disorders, with the
potential to inform innovations in treatment. Previous authors have supported that
acute insomnia is a normal biopsychosocial response to a perceived or real threat
and may thus represent an adaptive response to stress. We further extend this
hypothesis by claiming that insomnia reflects a fear-related evolutionary survival
mechanism, which becomes persistent in some vulnerable individuals due to failure
of the fear extinction function. Possible treatments targeting fear extinction are
proposed, such as pharmacotherapy and emotion-based cognitive behavioral therapy.
(C) 2020 Elsevier Ltd. All rights reserved.
Background: The wearing of respiratory protective devices (RPDs) correctly and
continually in situations where people are at risk of respiratory infections is
crucial for infection prevention. Certain people are poorly compliant with RPDs due
to RPD-related annoyance, including respiratory discomfort. We hypothesized that
individuals vulnerable to panic attacks are included in this group. No published
studies on this topic are available. The evidence for our hypothesis was reviewed
in this study as a starting point for future research. Methods: We selected a set
of experimental studies that measured the respiratory physiological burden in RPD
wearers through objective and validated methods. We conducted a bibliographic
search of publications in the PubMed database (January 2000-May 2020) to identify
representative studies that may be of interest for panic respiratory
pathophysiology. Results: Five studies were included. Wearing RPDs exerted
significant respiratory effects, including increased breathing resistance, CO2
rebreathing due to CO2 accumulation in the RPD cavity, and decreased inhaled O-2
concentration. We discussed the implications of these effects on the respiratory
pathophysiology of panic. Limitations: Most studies had a small sample size, with a
preponderance of young participants. Different methodologies were used across the
studies. Furthermore, differences in physical responses between wearing RPDs in
experimental settings or daily life cannot be excluded. Conclusions: This research
supports the idea that panic-prone individuals may be at higher risk of respiratory
discomfort when wearing RPDs, thereby reducing their tolerance for these devices.
Strategies to decrease dis-comfort should be identified to overcome the risk of
poor compliance.
Approximately half of older adults experience fear of falling (FoF) but the
aetiology is unclear. The aim is to review the literature on physiological, mood
and cognitive factors associated with FoF and to interpret these findings in the
context of a fear-avoidance model that provides a causal framework for the
development of FoF. There is growing evidence that the development of FoF is
influenced by balance problems and falls, and emerging evidence for a role for
cognitive factors, particularly attention and processing of sensory information.
While there may also be a role for mood/temperament in the development of FoF,
current evidence is weak. We argue that these factors co-exist and interact, which
complicates assessment and design of the most appropriate intervention. The fear
avoidance model offers a novel framework for explaining the mechanism of developing
FoF and the discrepancy between experienced and perceived fall risk. This model
specifically capitalizes on recent insights into fundamental learning mechanisms
underlying emotion and fear. The proposed models provide hypotheses for future
research and indications for improving efficacy of existing treatment programs.
The liver is the most commonly affected solid organ in cases of abdominal trauma.
Management of penetrating liver trauma is a challenge for surgeons but with the
introduction of the concept of damage control surgery accompanied by significant
technological advancements in radiologic imaging and endovascular techniques, the
focus on treatment has changed significantly. The use of immediately accessible
computed tomography as an integral tool for trauma evaluations for the precise
staging of liver trauma has significantly increased the incidence of conservative
non-operative management in hemodynamically stable trauma victims with liver
injuries. However, complex liver injuries accompanied by hemodynamic instability
are still associated with high mortality rates due to ongoing hemorrhage. The aim
of this article is to perform an extensive review of the literature and to propose
a management algorithm for hemodynamically unstable patients with penetrating liver
injury, via an expert consensus. It is important to establish a multidisciplinary
approach towards the management of patients with penetrating liver trauma and
hemodynamic instability. The appropriate triage of these patients, the early
activation of an institutional massive transfusion protocol, and the early control
of hemorrhage are essential landmarks in lowering the overall mortality of these
severely injured patients. To fear is to fear the unknown, and with the management
algorithm proposed in this manuscript, we aim to shed light on the unknown
regarding the management of the patient with a severely injured liver.
The nonapeptide, oxytocin (OT), known for its role in social bonding and attachment
formation, has demonstrated anxiolytic properties in animal models and human
studies. However, its role in the regulation of fear responses appears more
complex, brain site-specific, sex-specific, and dependent on a prior stress
history. Studies have shown that OT neurons in the hypothalamus are activated
during cued and contextual fear conditioning and during fear recall, highlighting
the recruitment of endogenous oxytocin system in fear learning. OT is released into
the extended amygdala, which contains the central nucleus of the amygdala (CeA) and
the bed nucleus of the stria terminalis (BNST), both critical for the regulation of
fear and anxiety-like behaviors. Behavioral studies report that OT in the CeA
reduces contextual fear responses; whereas in the BNST, OT receptor (OTR)
neurotransmission facilitates cued fear and reduces fear responses to un-signaled,
diffuse threats. These ostensibly contrasting behavioral effects support growing
evidence that OT works to promote fear discrimination by reducing contextual fear
or fear of diffuse threats, yet strengthening fear responses to imminent and
predictable threats. Recent studies from the basolateral nucleus of the amygdala
(BLA) support this notion and show that activation of OTR in the BLA facilitates
fear discrimination by increasing fear responses to discrete cues. Also, OTR
transmission in the CeA has been shown to mediate a switch from passive freezing to
active escape behaviors in confrontation with an imminent, yet escapable threat but
reduce reactivity to distant threats. Therefore, OT appears to increase the
salience of relevant threat-signaling cues yet reduce fear responses to un-
signaled, distant, or diffuse threats. Lastly, OTR signaling has been shown to
underlie emotional discrimination between conspecifics during time of distress,
social transmission of fear, and social buffering of fear. As OT has been shown to
enhance salience of both positive and negative social experiences, it can also
serve as a warning system against potential threats in social networks. Here, we
extend the social salience hypothesis by proposing that OT enhances the salience of
relevant environmental cues also in non-social contexts, and as such promotes
active defensive behaviors.
The fear of charm is a commonplace in the sociopolitical and economic life of many
Nigerians. Notably, researchers are yet to develop a measure that will assess fear
of charm in Nigeria and within the African population in general. In this regard,
this paper reports the development of the Fear of Charm Scale (FCS) among Nigerian
adults and demonstrates its reliability and validity evidences. The development of
the FCS entails item generation, content validity, determining its underlying
factor structure, internal consistency and construct validity. Exploratory and
confirmatory factor analyses indicated three-factor structures for the FCS. The
scale demonstrated good psychometric properties in terms of adequate reliability,
convergence and discriminant validity. By using the FCS, social science researchers
can now reliably and validly measure the construct of fear of charm and assess its
influence on other psychological variables such as self-efficacy, psychotic
symptoms, work performance, psychological well-being etc.
Adolescents are spending an increasing amount of their time online and connected to
each other via digital technologies. Mobile device ownership and social media usage
have reached unprecedented levels, and concerns have been raised that this constant
connectivity is harming adolescents' mental health. This review synthesized data
from three sources: (a) narrative reviews and meta-analyses conducted between 2014
and 2019, (b) large-scale preregistered cohort studies and (c) intensive
longitudinal and ecological momentary assessment studies, to summarize what is
known about linkages between digital technology usage and adolescent mental health,
with a specific focus on depression and anxiety. The review highlights that most
research to date has been correlational, focused on adults versus adolescents, and
has generated a mix of often conflicting small positive, negative and null
associations. The most recent and rigorous large-scale preregistered studies report
small associations between the amount of daily digital technology usage and
adolescents' well-being that do not offer a way of distinguishing cause from effect
and, as estimated, are unlikely to be of clinical or practical significance.
Implications for improving future research and for supporting adolescents' mental
health in the digital age are discussed.
Brain-derived neurotrophic factor (BDNF) is widely accepted for its involvement in
resilience and antidepressant drug action, is a common genetic locus of risk for
mental illnesses, and remains one of the most prominently studied molecules within
psychiatry. Stress, which arguably remains the "lowest common denominator" risk
factor for several mental illnesses, targets BDNF in disease-implicated brain
regions and circuits. Altered stress-related responses have also been observed in
animal models of BDNF deficiency in vivo, and BDNF is a common downstream
intermediary for environmental factors that potentiate anxiety- and depressive-like
behavior. However, BDNF's broad functionality has manifested a heterogeneous
literature; likely reflecting that BDNF plays a hitherto under-recognized
multifactorial role as both a regulator and target of stress hormone signaling
within the brain. The role of BDNF in vulnerability to stress and stress-related
disorders, such as posttraumatic stress disorder (PTSD), is a prominent example
where inconsistent effects have emerged across numerous models, labs, and
disciplines. In the current review we provide a contemporary update on the
neurobiology of BDNF including new data from the behavioral neuroscience and
neuropsychiatry literature on fear memory consolidation and extinction, stress, and
PTSD. First we present an overview of recent advances in knowledge on the role of
BDNF within the fear circuitry, as well as address mounting evidence whereby stress
hormones interact with endogenous BDNF-TrkB signaling to alter brain homeostasis.
Glucocorticoid signaling also acutely recruits BDNF to enhance the expression of
fear memory. We then include observations that the functional common BDNF Val66Met
polymorphism modulates stress susceptibility as well as stress-related and stress-
inducible neuropsychiatric endophenotypes in both man and mouse. We conclude by
proposing a BDNF stress-sensitivity hypothesis, which posits that disruption of
endogenous BDNF activity by common factors (such as the BDNF Val66Met variant)
potentiates sensitivity to stress and, by extension, vulnerability to stress-
inducible illnesses. Thus, BDNF may induce plasticity to deleteriously promote the
encoding of fear and trauma but, conversely, also enable adaptive plasticity during
extinction learning to suppress PTSD-like fear responses. Ergo regulators of BDNF
availability, such as the Val66Met polymorphism, may orchestrate sensitivity to
stress, trauma, and risk of stress-induced disorders such as PTSD. Given an
increasing interest in personalized psychiatry and clinically complex cases, this
model provides a framework from which to experimentally disentangle the causal
actions of BDNF in stress responses, which likely interact to potentiate, produce,
and impair treatment of, stress-related psychiatric disorders.
In cross-cultural communication and adjunct disciplines such as cross-cultural
management and international business, there is a negativity bias of seeing
cultural differences as a source of potential issues. The emergence of Positive
Organizational Scholarship (POS) questions this problem-focused approach. This
paper contributes to the ongoing discussion from neuroscience's perspectives in
several ways. Firstly, it provides a neurological look at this bias. Secondly, it
proposes that the problem-focused approach may (1) give us a biased outlook of
cross-cultural encounters rather than a reality, (2) hinder creativity, (3) lead to
the rebound effect, and (4) turn belief into reality. Finally, based on insight
from neuroscience and adopting the POS lens with the connection between POS and
creativity, it's recommended that future research takes three directions: (1) Using
similarity as the starting point; (2) strategize body language, context and
theories; and (3) develop a multicultural mind. In essence, the paper contributes
to existing knowledge of the field by employing an interdisciplinary approach,
aiming to gain a more holistic view, provoke thoughts, and trigger future empirical
studies.
Introduction: Dental anxiety refers to a set of complex psychological issues
bearing a significant impact in individual's lives reflecting in the form of dental
visit avoidance, poor dental health status and decreases oral health related
quality of life. Hence, it is imperative to consider those factors associated with
dental anxiety so as to treat and promote better oral health. The review aimed to
assess various factors associated with dental fear and anxiety. Materials and
Methods: Literature search was done from Pubmed and Google scholar search engines
to identify publications which explored factors associated with dental fear and
anxiety. Results: Research evidence pointed a significant relationship of age,
gender, maternal anxiety, previous dental experience, and number of siblings with
dental fear and anxiety (DFA). Conclusion: Findings of the review clearly suggest
that a better understanding of factors causing dental anxiety and phobia will help
preventing dental avoidance and providing better care.
Panic disorder (PD) is a common and debilitating neuropsychiatric disorder
characterized by panic attacks coupled with excessive anxiety. Both genetic factors
and environmental factors play an important role in PD pathogenesis and response to
treatment. However, PD is clinically heterogeneous and genetically complex, and the
exact genetic or environmental causes of this disorder remain unclear. Various
approaches for detecting disease-causing genes have recently been made available.
In particular, genome-wide association studies (GWAS) have attracted attention for
the identification of disease-associated loci of multifactorial disorders. This
review introduces GWAS of PD, followed by a discussion about the limitations of
GWAS and the major challenges facing geneticists in the post-GWAS era. Alternative
strategies to address these challenges are then proposed, such as epigenome-wide
association studies (EWAS) and rare variant association studies (RVAS) using next-
generation sequencing. To date, however, few reports have described these analyses,
and the evidence remains insufficient to confidently identify or exclude rare
variants or epigenetic changes in PD. Further analyses are therefore required,
using sample sizes in the tens of thousands, extensive functional annotations, and
highly targeted hypothesis testing.
Background: Fear of childbirth is a common feeling among expectant mothers.
Although it represents a physiological expression of women's concerns, it can
become a clinical condition compromising the woman's daily activities as well as
her coping strategies during labour and delivery. Research has focused on adverse
intrapartum and postpartum outcomes of fear of childbirth. As regards intrapartum
outcomes, some studies have investigated the association between fear of childbirth
and type of delivery, with contrasting results. Objective: This study aimed at
reviewing the literature on the association between fear of childbirth and
emergency caesarean section delivery. Method: This systematic review was based on
an electronic search of English-language published studies through 31 December
2018. Following the search process, 14 studies were included. Studies were analysed
specifically considering the sample parity and tools for evaluating fears. Results:
These studies revealed that both sample characteristics and assessment instruments
are not criteria for explaining the different result. Conclusions: The importance
of distinguishing between fear and severe fear was highlighted because the effect
of fear on the type of delivery was present only for clinical fear. However, the
different cut-off values did not make it possible to reach a clear result, making
further investigation necessary.
Naturalistic observations show that decisions to avoid or escape predators occur at
different spatiotemporal scales and that they are supported by different
computations and neural circuits. At their extremes, proximal threats are addressed
by a limited repertoire of reflexive and myopic actions, reflecting reduced
decision and state spaces and model-free (MF) architectures. Conversely, distal
threats allow increased information processing supported by model-based (MB)
operations, including affective prospection, replay, and planning. However, MF and
MB computations are often intertwined, and under conditions of safety the
foundations for future effective reactive execution can be laid through MB
instruction of MF control. Together, these computations are associated with
distinct population codes embedded within a distributed defensive circuitry whose
goal is to determine and realize the best policy.
Context: Within only 30 days after the first announcement of infection with "SARS-
CoV-2" in Wuhan, it spread to more than 20 countries and become a pandemic by WHO
as a "high alarming level of infection" with 136,343 involved cases all over the
world. Methods: To uncover more about the probable gastrointestinal transmission
and its clinical manifestations, we reviewed all research publications with
keywords including: "COVID-19", "SARS-CoV-2", "Coronavirus", "outbreak", "ARAS-CoV"
in Medline, Scopus, Google Scholar as well as all news in social media about "novel
COVID-19 pandemic". Out of 40 recent publications,10 articles were studied by 2
authors. Results: Although the SARS-CoV-2 tends to infect respiratory epithelial
cells through the respiratory tracts, recent investigations detected the virus in
the stool specimen, raising the question of the fecal-oral transmission route.
Different studies showed that almost all gastrointestinal signs and symptoms were
seen in elderly patients (more than 65 years old). including anorexia (40%),
nonspecific abdominal pains (8%), diarrhea (10%) and nausea and Vomiting in about
8% of patients. Anorexia and generalized abdominal pain suffer many treated cases
even10 - 20 days after negative blood tests (like CRP, lymphopenia) and negative
PCR of respiratory samples. The main reason for this prolonged anorexia and
abdominal pain may be due to the long persistence of COVID-19 in the
gastrointestinal tracts after primary treatment. Conclusions: Comparing to SARS,
patients with COVID-19 showed less diarrhea, nausea, vomiting and/or abdominal
discomfort before respiratory symptoms. Feces as a potential contagious source of
Viral RNA can last even after viral clearance in the respiratory tract. We strongly
recommend all cured patients of COVID-19 to disinfect and clean their toilets
until17- 20 days after negative blood tests and solving their respiratory
disorders. Gastrointestinal manifestations have seen in all men while no women
referred with GI signs.
In this paper, the bibliometric approach was used for the investigation of the
research field organized around the concept of moral panic. To examine the current
condition of the moral panic field, we analyzed the papers published in the WoS
from 1972-2019. As a result of our study, the thematic areas, and the most
influential actors in the field were revealed and described. Today, the moral panic
filed is dominated by sociologists. Among the leaders in terms of citations are
authors from financially-developed countries. This shows that there is an economic
inequality in the production of papers. The most cited are publications devoted to
online studies. The results of this research demonstrate that there is no
noticeable erosion among the empirical contexts, where the concept is used because
children and youth are still the most popular object of moral panic studies. They
are the classical objects for moral panic papers. At the same time, it could be
argued that this field is still in the process of development because the
theoretical and empirical papers that prevail are connected with the integration of
the moral panic theory with other theories and concepts. We suppose this approach
to the conceptual analysis developed in this paper could be useful for the revision
of other fields developed around controversial concepts in sociology.
Since the seminal 'Little Albert' study by Watson and Rayner (1920), fear
conditioning has become one of the most commonly used paradigms for studying the
etiology of anxiety-related disorders. In a fear conditioning procedure, a
(neutral) conditioned stimulus (CS) is paired with an aversive unconditioned
stimulus (US), resulting in fear-related conditioned responses (CRs) to the CS.
Whereas fear conditioning research initially focused on observable elements in the
environment (i.e., CSs, USs, and their contingency) and their effects (i.e., CRs),
subsequent research indicated that attention should also be given to unobservable
mental events (e.g., intrusive memories of aversive outcomes) to more fully account
for the symptomatology of anxiety disorders. In this paper, we review the research
relating to four major research questions on the relationship between mental
imagery and fear conditioning: (1) Can mental imagery substitute for actual
stimulus administration? (2) Can mental imagery inflate CRs? (3) Can fear
conditioning result in the installment of mental images as CRs (Le., intrusions)?
(4) Can mental imagery-based interventions reduce CRs? For all these research
questions, tentative confirmatory evidence has been found and these findings
corroborate contemporary conditioning theories. Nonetheless, we point to several
open questions and methodological issues that require further research.
Whether fear conditioning can take place without contingency awareness is a topic
of continuing debate and conflicting findings have been reported in the literature.
This systematic review provides a critical assessment of the available evidence.
Specifically, a search was conducted to identify articles reporting fear
conditioning studies in which the contingency between conditioned stimuli (CS) and
the unconditioned stimulus (US) was masked, and in which CS-US contingency
awareness was assessed. A systematic assessment of the methodological quality of
the included studies (k = 41) indicated that most studies suffered from
methodological limitations (i.e., poor masking procedures, poor awareness measures,
researcher degrees of freedom, and trial-order effects), and that higher quality
predicted lower odds of studies concluding in favor of contingency unaware fear
conditioning. Furthermore, meta-analytic moderation analyses indicated no evidence
for a specific set of conditions under which contingency unaware fear conditioning
can be observed. Finally, funnel plot asymmetry and p-curve analysis indicated
evidence for publication bias. We conclude that there is no convincing evidence for
contingency unaware fear conditioning.
The amygdala is a central hub for fear learning assessed by Pavlovian fear
conditioning. Indeed, the prevailing hypothesis that learning and memory are
mediated by changes in synaptic strength was shown most convincingly at thalamic
and cortical afferents to the lateral amygdala. The neurotrophin brain-derived
neurotrophic factor (BDNF) is known to regulate synaptic plasticity and memory
formation in many areas of the mammalian brain including the amygdala, where BDNF
signalling via tropomyosin-related kinase B (TrkB) receptors is prominently
involved in fear learning. This review updates the current understanding of
BDNF/TrkB signalling in the amygdala related to fear learning and extinction. In
addition, actions of proBDNF/p75NTR and NGF/TrkA as well as NT-3/TrkC signalling in
the amygdala are introduced.
The emergence of the COVID-19 and its consequences has led to fears, worries, and
anxiety among individuals worldwide. Recently, Ahorsu et al. (2020) developed the
Fear of COVID-19 Scale (FCV-19S). The present study aimed to translate and validate
the FCV-19S in Spanish university students. The sample comprised 606
Spanishundergraduates with a mean age of 21.59 years old. We also used a six items
from the State Trait Anxiety Inventory (STAI) by van Knippenberg, Duivenvoorden,
Bonke & Passchiner (1990). The Fear of COVID-19 scale used for the present survey
evidenced a good alpha measure of internal con-sistency or reliability analysis
with ordinal alpha and ordinal omega. Seven items with acceptable corrected item-
total correlation were retained and further confirmed by significant and strong
factor loadings. Concurrent validity was supported by the six items of the State
Trait Anxiety Inventory (STAI). The Fear of COVID-19 Scale, a seven-item scale, has
a stable unidimensional structure with robust psychometric properties. It is
reliable and valid in assessing fear of COVID-19 among the Spanish university
students.
Objective: To systematically review and critically appraise the effectiveness of
conservative and surgical interventions to reduce fear in studies of people with
chronic low back pain, based on the analysis of randomized controlled trials for
which fear was a primary or secondary outcome. Data Sources: Electronic databases
PubMed, CINAHL, PsycINFO, PEDro, and CENTRAL, as well as manual searches and grey
literature were searched from inception until May 2019. Study Selection: Randomized
controlled trials analyzing the effectiveness of conservative and surgical
interventions to reduce fear were included. Data Extraction: Two reviewers
independently conducted the search strategy, study selection, data extraction, risk
of bias assessment, and quality of the evidence judgment. Data Synthesis: Sixty-one
studies (n =7201) were included. A large number of fear-related search terms were
used but only 3 fear constructs (kinesiophobia, fear-avoidance beliefs, fear of
falling) were measured in the included studies. Multidisciplinary and psychological
interventions as well as exercise reduced kinesiophobia. Fear-avoidance beliefs
were reduced by the aforementioned interventions, manual therapy, and
electrotherapy. A multidisciplinary intervention reduced the fear of falling. There
was moderate evidence of multidisciplinary interventions and exercise to reduce
kinesiophobia. There was moderate evidence of manual therapy and electrotherapy to
reduce fear-avoidance beliefs. Conclusions: The present systematic review
highlights the potential effectiveness of conservative interventions to reduce
kinesiophobia and fearavoidance beliefs in individuals with chronic low back pain.
This information can help health professionals to reduce fear when treating
patients with this condition. (C) 2019 by the American Congress of Rehabilitation
Medicine
The fear avoidance model (FAM) represents a cognitive-behavioral explanatory
approach for pain chronification. The core assumption is that fear of pain (FOP)
following an acute pain experience facilitates the development of pain
chronification, disability, and receding functionality. Thus, the model predicts a
positive association between FOP and pain intensity in pain patients, which was
frequently investigated; however, results were inconsistent. To highlight
inconsistencies, we performed integrative statistical analysis aimed at evaluating
the strength of the cross-sectional relation between FOP and pain intensity in
clinical research and reviewing its moderation through demographic, pain-specific
and psychosocial characteristics. To this end, we searched the databases PsycINFO,
PubMed, and Web of Science and included 253 independent effect size estimates (N =
42 463). The overall mean effect size was computed based on a random-effects model.
By utilizing the artifact distribution method, we supplemented it with an analysis
correcting for artifacts. The magnitude of the positive association equated to the
threshold between a small to medium effect size, which was expected as the FAM
predicts an indirect relation only. The association turned out to be stable across
different FOP measures, but was significantly moderated by age, pain localization,
first-time pain episode, pain onset, treatment status, and anxiety sensitivity. A
potentially necessary differentiation of patient subgroups and suggestions for an
adjusted methodological approach of future research are discussed.
Background Literature, film and news media reflect and shape social perceptions of
dementia which in turn impact on dementia stigma. The aim of this paper is to
systematically review papers on the depiction and frames for dementia in
literature, film, mass media and social media in order to better understand
cultural stigma related to dementia. Methods A systematic search of electronic
databases was undertaken combining phrases relating to dementia, popular culture
and representations, and phrases relating to dementia and stigma. We searched for
scientific English language papers which included original analysis on the
representation or depiction of dementia in popular culture (i.e. in film and
television, literature, news, social media and language). Articles published
between 1989-2018 were included. The search was conducted in December 2017 and
updated in January 2019. Inductive thematic synthesis was undertaken. Results A
total of 60 articles were included from an initial sample of 37022. Dementia was
almost always depicted in conjunction with ageing, and often equated with
Alzheimer's disease. Common frames for dementia were biomedical - dementia involves
the deterioration of the brain for which there is no current cure; natural disaster
or epidemic - dementia is a force of nature which will overwhelm mankind; and
living dead - people with dementia lose their brains, memories, minds and
consequently their personhood and human rights. There were examples of more
positive depictions of dementia including expressing love and individual agency and
experiencing personal growth. Feelings commonly associated with dementia were fear,
shame, compassion and guilt, and depictions often resulted in a sense of social
distance. Conclusions Depictions of dementia in popular culture are associated with
negative images and feelings, and social distance between people with dementia and
those without. These correspond to dementia stigma in the public and as experienced
by people with dementia. Further research is needed into the impact of literature,
news and social media on dementia stigma and these cultural mediums might be used
to reduce stigma.
Background: Reports have suggested that sexual dysfunction is an underestimated
complication of panic disorder, but little research has focused on sexual
dysfunction associated specifically with panic disorder. The purpose of this
systematic review was to investigate whether patients with panic disorder who are
not currently receiving treatment had a higher risk of sexual dysfunction than
healthy people, as well as to clarify the appropriate treatment for this patient
group. Methods: Articles that reported panic disorder complicated with sexual
dysfunction were identified by a systematic literature search of electronic
databases, including PubMed, the Cochrane databases, EMBASE, and PsycINFO. Results:
Six articles were included in the review. Patients with panic disorder showed a
high prevalence of sexual aversion (35.7% to 64%) and sexual infrequency (36% to
44%). One cohort study indicated that untreated patients with panic disorders had a
higher risk of erectile dysfunction than controls. Another article that focused
specifically on female patients reported that the patients with panic disorder
exhibited decreased frequency of sexual behavior and decreased sexual desire
compared with the controls. However, 2 studies found conflicting results after
adjustment for confounding factors. Conclusions: Although the results were mixed,
it appears that patients with panic disorder tended to be more susceptible to
sexual dysfunction than the general population. Further trials with larger sample
sizes and rigorous research designs are needed to establish the relationship
between sexual dysfunction and panic disorder.
In this paper, the theory of "Fear injury kidney" in traditional Chinese medicine
is systematically re-viewed, and it is found that long-term or excessive
psychological changes of fear are likely to damage kidney qi and kidney essence. On
this basis, the psychological studies of patients, medical staff and the public
during the COVID-19 epidemic in China were analyzed, and fear psychology was found
to be preva-lent among all kinds of people. Modern researches on "Fear injury
kidney" have also found that long-term or excessive fear could cause changes in the
neuro-endocrine-immune system, which can induce diseases or susceptibility to some
diseases. Therefore, during or after the prevalence of COVID-19, different groups
of people may have emotional reactions such as stress and fear, which should be
paid long-term atten-tion, and the influence of fear on the body cannot be ignored.
According to the change rule of psycholog-ical state under stress reaction, we
should actively respond to and take psychological crisis intervention measures in
time to reduce the harm of psychological stress to the body. (C) 2020 Published by
Elsevier B.V. on behalf of World Journal of Acupuncture Moxibustion House.
BackgroundFears of cancer recurrence (FCR) is one of the most prevalent concerns
and a common unmet need reported by cancer patients. Patient age is a demographic
variable that has been linked to FCR, among others. Although it is recognised by
researchers that age and FCR may be negatively correlated, the strength of this
correlation has yet to be established. AimThe aims of this study were to (a)
conduct a meta-analysis to investigate the overall association of patient age in
years with FCR across studies from 2009 to February 2019 and (b) scrutinise for
patterns of these effect sizes across studies. Methods and ResultsPeer-reviewed
papers were gathered from the literature via online databases (PubMed, EMBASE,
MEDLINE, and PsycINFO). Systematic review guidelines including a quality assessment
were applied to the 31 selected studies (pooled participant N size = 19777). The
meta-analysis demonstrated a significant negative association between age and FCR
(ES = -0.12; 95% CI, -0.17, -0.07). Meta-regression revealed the association of
patient age and FCR significantly reduced over the last decade. A significant
effect (beta = -0.17, P = 0.005) of breast cancer versus other cancers on this age
by FCR association was also identified. ConclusionThe reliable and readily
accessible personal information of age of patient can be utilised as a weak
indicator of FCR level especially in the breast cancer field, where the majority of
studies were drawn. The suggestion that age and FCR association may be attenuated
in recent years requires confirmation.
Background: Sleep terrors are common, frightening, but fortunately benign events.
Familiarity with this condition is important so that an accurate diagnosis can be
made. Objective: To familiarize physicians with the clinical manifestations,
diagnosis, and management of children with sleep terrors. Methods: A PubMed search
was completed in Clinical Queries using the key terms " sleep terrors" OR " night
terrors". The search strategy included meta-analyses, randomized controlled trials,
clinical trials, observational studies, and reviews. Only papers published in the
English literature were included in this review. The information retrieved from the
above search was used in the compilation of the present article. Results: It is
estimated that sleep tenors occur in 1 to 6.5% of children 1 to 12 years of age.
Sleep terrors typically occur in children between 4 and 12 years of age, with a
peak between 5 and 7 years of age. The exact etiology is not known. Developmental,
environmental, organic, psychological, and genetic factors have been identified as
a potential cause of sleep terrors. Sleep terrors tend to occur within the first
three hours of the major sleep episode, during arousal from stage three or four
non-rapid eye movement (NREM) sleep. In a typical attack, the child awakens
abruptly from sleep, sits upright in bed or jumps out of bed, screams in terror and
intense fear, is panicky, and has a frightened expression. The child is confused
and incoherent: verbalization is generally present but disorganized. Autonomic
hyperactivity is manifested by tachycardia, tachypnea, diaphoresis, flushed face,
dilated pupils, agitation, tremulousness, and increased muscle tone. The child is
difficult to arouse and console and may express feelings of anxiety or doom. In the
majority of cases, the patient does not awaken fully and settles back to quiet and
deep sleep. There is retrograde amnesia for the attack the following morning.
Attempts to interrupt a sleep tenor episode should be avoided. As sleep deprivation
can predispose to sleep tenors, it is important that the child has good sleep
hygiene and an appropriate sleeping environment. Medical intervention is usually
not necessary, but clonazepam may be considered on a short-term basis at bedtime if
sleep tenors are frequent and severe or center dot are associated with functional
impairment, such as fatigue, daytime sleepiness, and distress. Anticipatory
awakening, performed approximately half an hour before the child is most likely to
experience a sleep tenor episode, is often effective for center dot the treatment
of frequently occurring sleep terrors. Conclusion: Most children outgrow the
disorder by late adolescence. In the majority of cases, there is no specific
treatment other than reassurance and parental education. Underlying conditions,
however, should be treated if possible and precipitating factors should be avoided.
Background Patients with chronic diseases commonly report fears of illness or
symptoms recurring or worsening. These fears have been addressed from an illness-
specific perspective (e.g., fear of cancer recurrence), a generic illness
perspective (e.g., fear of progression), and a psychiatric perspective (DSM-5
illness anxiety disorder and somatic symptom disorder). The broader concept of
health anxiety (HA) can also be applied to patients with a chronic disease. This
review was conducted to investigate the conceptual, theoretical, measurement-
overlap, and differences between these distinct perspectives. We also aimed to
summarize prevalence, course, and correlates of these fears in different chronic
illnesses. Methods We used PsycINFO, PubMED, CINAHL, Web of Science, SCOPUS, and
PSYNDEX to conduct a systematic review of studies pertaining to these fears in
chronic illness published from January 1996 to October 2017. A total of 401
articles were retained. Results There were commonalities across different
conceptualizations and diseases: a high prevalence of clinical levels of fears
(>20%), a stable course over time, and a deleterious impact on quality of life.
Reviewed studies used definitions, models, and measures that were illness-specific,
with only a minority employing a psychiatric perspective, limiting cross-disease
generalizability. There appears to be some applicability of DSM-5 disorders to the
experience of fear of illness/symptoms in patients with a chronic illness. While
conceptualizing HA on a continuum ranging from mild and transient to severe may be
appropriate, there is a lack of agreement about when the level of fear becomes
'excessive.' The definitions, models, and measures of HA across chronic illnesses
involve affective, cognitive, behavioral, and perceptual features. Conclusions The
concept of HA may offer a unifying conceptual perspective on the fears of
illness/symptoms worsening or returning commonly experienced by those with chronic
disease.
Background: Panic disorder (PD) is a kind of anxiety disorder that impacts the life
quality and functional perspectives in patients. However, the pathophysiological
study of PD seems still inadequate and many unresolved issues need to be clarified.
Objectives: In this review article of biomarkers in PD, the investigator will focus
on the findings of magnetic resonance imaging (MRI) of the brain in the
pathophysiology study. The MRI biomarkers would be divided into several categories,
on the basis of structural and functional perspectives. Methods: The structural
category would include the gray matter and white matter tract studies. The
functional category would consist of functional MRI (fMRI), resting-state fMRI (Rs-
fMRI), and magnetic resonance spectroscopy (MRS). The PD biomarkers revealed by the
above methodologies would be discussed in this article. Results: For the gray
matter perspectives, the PD patients would have alterations in the volumes of fear
network structures, such as the amygdala, parahippocampal gyrus, thalamus, anterior
cingulate cortex, insula, and frontal regions. For the white matter tract studies,
the PD patients seemed to have alterations in the fasciculus linking the fear
network regions, such as the anterior thalamic radiation, uncinate fasciculus,
fronto-occipital fasciculus, and superior longitudinal fasciculus. For the fMRI
studies in PD, the significant results also focused on the fear network regions,
such as the amygdala, hippocampus, thalamus, insula, and frontal regions. For the
Rs-fMRI studies, PD patients seemed to have alterations in the regions of the
default mode network and fear network model. At last, the MRS results showed
alterations in neuron metabolites of the hippocampus, amygdala, occipital cortex,
and frontal regions. Conclusion: The MRI biomarkers in PD might be compatible with
the extended fear network model hypothesis in PD, which included the amygdala,
hippocampus, thalamus, insula, frontal regions, and sensory-related cortex.
The aim of the article is to summarize the current knowledge on the phenomenon of
fear of hypoglycaemia and its impact on the metabolic control and well-being of the
population of diabetic patients. The article proposes a description of clinical
criteria useful for the diagnosis of the fear of hypoglycaemia in a non-normative
and harmful form. Therapeutic directions are presented that have been proven
effective in the recent years in reducing the level of maladaptive fear of
hypoglycaemia, while also protecting the mental health of the patients. Despite
extensive knowledge and numerous clinical trials undertaken in other countries,
further research on diabetes-related anxiety disorders in Polish patients is
needed. It is also advisable to create a database of culturally adapted management
protocols for specialists that could increase the quality and effectiveness of the
assistance provided in the outpatient health care.
Psychosocial stress has a profound impact on well-being and health. The response to
stress is associated mainly with the amygdala, a crucial structure of the fear-
defense system, essential for social cognition and emotion regulation. Recent
neuroimaging-studies demonstrated how an increased metabolic activity of the
amygdala enhances inflammation, and leads to cardiometabolic disease. The
development of therapeutic strategies depends on our understanding of both which
factors activate the fear-defense system and the subsequent molecular mechanisms
that translate emotional stress into cell damage. Fear of emotions as an aftermath
of attachment trauma is the most important trigger of the maladaptive activation of
the fear-defense system. The central molecular pathways are enhanced myelopoiesis
and upregulated proinflammatory gene expression, glucocorticoid and insulin
resistance, and oxidative stress. Therapeutic strategies may benefit from holistic
approaches. Psychotherapy can reduce the maladaptively increased activation of the
fear-defense system. Biological interventions can buffer the detrimental effects of
oxidative stress in the organism.
Although the "panic" word has been abundantly linked to the SARS-CoV-2 (severe
acute respiratory syndrome coronavirus 2) pandemic in the press, in the scientific
literature very few studies have considered whether the current epidemic could
predispose to the onset or the aggravation of panic attacks or panic disorder.
Indeed, most studies thus far have focused on the risk of increase and aggravation
of other psychiatric disorders as a consequence of the SARS-CoV-2 epidemic, such as
obsessive -compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and
generalized anxiety disorder (GAD). Yet, risk of onset or aggravation of panic
disorder, especially the subtype with prominent respiratory symptoms, which is
characterized by a fear response conditioning to interoceptive sensations (e.g.,
respiratory), and hypervigilance to these interoceptive signals, could be expected
in the current situation. Indeed, respiratory symptoms, such as coughs and dyspnea,
are among the most commonly associated with the SARS-CoV-2 (59-82% and 31-55%,
respectively), and respiratory symptoms are associated with a poor illness
prognosis. Hence given that some etiological and maintenance factors associated
with panic disorder - i.e., fear conditioning to abnormal breathing patterns
attributable or not to the COVID-19 (coronavirus disease 2019), as well as
hypervigilance towards breathing abnormalities - are supposedly more prevalent, one
could expect an increased risk of panic disorder onset or aggravation following the
COVID-19 epidemic in people who were affected by the virus, but also those who were
not. In people with the comorbidity (i.e., panic disorder or panic attacks and the
COVID-19), it is particularly important to be aware of the risk of hypokalemia in
specific at-risk situations or prescriptions. For instance, in the case of
salbutamol prescription, which might be overly used in patients with anxiety
disorders and COVID19, or in patients presenting with diarrhea and vomiting.
Hypokalemia is associated with an increased risk of torsade de pointe, thus caution
is required when prescribing specific psychotropic drugs, such as the
antidepressants citalopram and escitalopram, which are first-line treatments for
panic disorder, but also hydroxyzine, aiming at anxiety reduction. The results
reviewed here highlight the importance of considering and further investigating the
impact of the current pandemic on the diagnosis and treatment of panic disorder
(alone or comorbid with the COVID-19). (C) 2020 L'Encephale, Paris.
Background Fear of pain and movement is an important factor in the development of
hypervigilance and avoidance behaviours. Objective We examined the effectiveness of
exercise training on improving fear-avoidance beliefs. Methods A systematic review
(data sources: MEDLINE, CINAHL, SPORTDiscus, EMBASE, CENTRAL) and metaanalysis of
randomised controlled/clinical trials of exercise training in adults versus
relevant nonexercise comparators that quantified fear-avoidance was conducted.
Results After screening 4603 identified records, 17 (2014 participants) and 13
(1152 participants) studies were eligible for qualitative and quantitative
synthesis, respectively. Pairwise meta-analysis showed exercise training was more
effective than all non-exercise comparators (standardised mean difference (SMD)
[95% CI] - 0.378 [- 0.623, - 0.133],P = 0.002, Grading of Recommendations
Assessment, Development and Evaluation [GRADE]: very low) for reducing fear-
avoidance. Exercise training was more effective than true control for reducing fear
avoidance (- 0.407 [- 0.750, - 0.065],P = 0.020, GRADE: very low), however it was
not more effective than other interventions (- 0.243 [- 0.614, 0.128],P = 0.199,
GRADE: very low). In people with low back pain, exercise training was more
effective than non-exercise comparator groups for reducing fear-avoidance (- 0.530
[- 0.755, - 0.304],P < 0.001, GRADE: very low). For individuals with neck pain,
exercise training was not more effective than non-exercise comparator groups for
reducing fear-avoidance (0.061 [- 0.360, 0.482],P = 0.777, GRADE: very low).
Conclusion There is very low to low-quality evidence that exercise training is
effective for reducing fear-avoidance, including in people with low back pain.
Exercise training may be more effective than no intervention for reducing fear
avoidance, but there is very low-quality evidence that non-exercise interventions
are as effective as exercise for fear avoidance. Few studies with low risk of bias
is a limitation. Trail Registration PROSPERO Registration Number: CRD42019139678.
Might COVID-19 vaccines sensitize humans to antibody-dependent enhanced (ADE)
breakthrough infections? This is unlikely because coronavirus diseases in humans
lack the clinical, epidemiological, biological, or pathological attributes of ADE
disease exemplified by dengue viruses (DENV). In contrast to DENV, SARS and MERS
CoVs predominantly infect respiratory epithelium, not macrophages. Severe disease
centers on older persons with preexisting conditions and not infants or individuals
with previous coronavirus infections. Live virus challenge of animals given SARS or
MERS vaccines resulted in vaccine hypersensitivity reactions (VAH), similar to
those in humans given inactivated measles or respiratory syncytial virus vaccines.
Safe and effective COVID-19 vaccines must avoid VAH.
In two important books, the French philosopher Jacob Rogozinski analyses the logic
of hatred underlying the great witch-hunt at the beginning of modern times, the
period of terror following the French and the Russian Revolution and present-day
djihadism. According to his analysis, the same logic of hatred is at work in these
historical phenomena. The confrontation with the martyrs-murderers of djihadism,
challenges the self-understanding of the defenders of democracy. Just as, on the
level of religion, one must give up the dream of a reformation that would make
Islam more << moderate >>, and help the Islamic believers become more radical, but
otherwise than more fanatical, by rediscovering their forgotten treasures, on a
political level, democracy too needs to be radicalized.
Obsessive-compulsive disorder (OCD) is one of the most debilitating health
conditions in the world. There has been a vast amount of research into factors that
increase the likelihood of developing OCD, and there are several explanatory
models. Current cognitive models of OCD can be split into appraisal-based and self-
doubt models. To date, cognitive-behavioural therapy for OCD (grounded in
appraisal-based models) is the recommended treatment approach, and research into
the importance of self-doubt beliefs has been somewhat neglected. This paper
therefore aims to consolidate current research, utilizing a systematic review
approach, to establish the relationship between fear of self, self-ambivalence, and
obsessive-compulsive symptomatology. A systematic search was conducted based on
inclusion criteria identified for this review. Papers were then individually
appraised for quality and key data extracted from each paper. A total of 11 studies
were included in the final sample. Fear of self and self-ambivalence were both
consistently found to be significant predictors of obsessive-compulsive
symptomatology. In particular, research suggests that there is a strong link
between self-doubt beliefs and obsessions and obsessional beliefs related to OCD.
Limitations of the review and suggestions for future research are made and
applications to clinical practice discussed.
The coronavirus disease 2019 (COVID-19) pandemic has produced a world-wide collapse
of social and economic infrastructure, as well as constrained our freedom of
movement. This respiratory tract infection is nefarious in how it targets the most
distal and highly vulnerable aspect of the human bronchopulmonary tree,
specifically, the delicate yet irreplaceable alveoli that are responsible for the
loading of oxygen upon red cell hemoglobin for use by all of the body's tissues. In
most symptomatic individuals, the disease is a mild immune-mediated syndrome, with
limited damage to the lung tissues. About 20% of those affected experience a
disease course characterized by a cataclysmic set of immune activation responses
that can culminate in the diffuse and irreversible obliteration of the distal
alveoli, leading to a virtual collapse of the gas-exchange apparatus. Here, in Part
I of a duology on the characterization and potential treatment for COVID-19, we
define severe COVID-19 as a consequence of the ability of the severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) to trigger what we now designate
for the first time as a 'Prolific Activation of a Network-Immune-Inflammatory
Crisis', or 'PANIC' Attack, in the alveolar tree. In Part II we describe an
immunotherapeutic hypothesis worthy of the organization of a randomized clinical
trial in order to ascertain whether a repurposed, generic, inexpensive, and widely
available agent is capable of abolishing 'PANIC'; thereby preventing or mitigating
severe COVID-19, with monumental ramifications for world health, and the global
pandemic that continues to threaten it.
Here, in Part II of a duology on the characterization and potential treatment for
COVID-19, we characterize the application of an innovative treatment regimen for
the prevention of the transition from mild to severe COVID-19, as well as detail an
intensive immunotherapy intervention hypothesis. We propose as a putative
randomized controlled trial that high-dose methotrexate with leucovorin (HDMTX-LR)
rescue can abolish 'PANIC', thereby 'left-shifting' severe COVID-19 patients to the
group majority of those infected with SARS-CoV-2, who are designated as having
mild, even asymptomatic, disease. HDMTX-LR is endowed with broadly pleiotropic
properties and is a repurposed, generic, inexpensive, and widely available agent
which can be administered early in the course of severe COVID-19 thus rescuing the
critical and irreplaceable gas-exchange alveoli. Further, we describe a
preventative treatment intervention regimen for those designated as having mild to
moderate COVID-19 disease, but who exhibit features which herald the transition to
the severe variant of this disease. Both of our proposed hypothesis-driven
questions should be urgently subjected to rigorous assessment in the context of
randomized controlled trials, in order to confirm or refute the contention that the
approaches characterized herein, are in fact capable of exerting mitigating, if not
abolishing, effects upon SARS-CoV-2 triggered 'PANIC Attack'. Confirmation of our
immunotherapy hypothesis would have far-reaching ramifications for the current
pandemic, along with yielding invaluable lessons which could be leveraged to more
effectively prepare for the next challenge to global health.
Background: Although fear of negative evaluation (FNE) has long been recognized as
a core cognitive bias in social anxiety, fear of positive evaluation (FPE) has
received considerable attention over the past several years. The literature would
benefit from a synthesis of the current state of the research in order to
contribute to our understanding of FPE. Methods: A systematic review of the
literature was conducted in order to address several questions: (a) Is self-
reported FPE distinct from self-reported FNE? (b) Is self-reported FPE related to
social anxiety symptomatology? and (c) Is self-reported FPE uniquely related to
social anxiety symptomatology when accounting for self-reported FNE? Inclusion
criteria included studies published in English, testing FPE and FNE with trait-
based measures, and testing social anxiety with either self-report or diagnostic
interviews. Results: There were 33 studies identified in this review that provided
convincing empirical support for each of these questions across community and
clinical samples of adolescents, undergraduates, and adults. Limitations: The
systematic review did not have access to null results, present meta-analytic
results, or include studies that evaluated FPE or social anxiety with experimental
designs. Conclusions: The findings from the systematic review support updated
theoritical models of social anxiety and highlight the importance of assessing and
treating FPE in clinical interventions.
Fear of driving is common in the general population and can lead to serious
constraints in everyday life. There has been increased attention to this area of
research and clinical practice over the past few decades, and a summary of the
literature on treatment approaches is timely. This article gives an overview of the
current state of research on driving fear and its treatment. First, the main
findings about the construct and diagnosis are summarized, including understandings
of the epidemiology and etiology of driving fear. Second, existing treatment
studies of cognitive and behavioral therapy, virtual reality therapy, trauma-
focused and hypnosis-based interventions and treatment approaches using
technological aids such as driving-simulators are presented. Until now, no
randomized controlled trials (RCT) on the treatment of driving fear have been
conducted. Suggestions for future research are made, especially with regard to
further exploration of diagnostic features of driving fear and the need for RCTs
and robust treatment procedures.
Background: Panic attacks affect a sizeable proportion of the population. The
neurocircuitry of panic remains incompletely understood. Objective: To investigate
the neuroanatomical underpinnings of panic attacks induced by deep brain
stimulation (DBS) through (1) connectomic analysis of an obsessive-compulsive
disorder patient who experienced panic attacks during inferior thalamic peduncle
DBS; (2) appraisal of existing clinical reports on DBS-induced panic attacks.
Methods: Panicogenic, ventral contact stimulation was compared with benign
stimulation at other contacts using volume of tissue activated (VTA) modelling.
Networks associated with the panicogenic zone were investigated using state-of-the-
art normative connectivity mapping. In addition, a literature search for prior
reports of DBS-induced panic attacks was conducted. Results: Panicogenic VTAs
impinged primarily on the tuberal hypothalamus. Compared to non-panicogenic VTAs,
panicogenic loci were significantly functionally coupled to limbic and brainstem
structures, including periaqueductal grey and amygdala. Previous studies found
stimulation of these areas can also provoke panic attacks. Conclusions: DBS in the
region of the tuberal hypothalamus elicited panic attacks in a single obsessive-
compulsive disorder patient and recruited a network of structures previously
implicated in panic pathophysiology, reinforcing the importance of the hypothalamus
as a hub of panicogenic circuitry. (c) 2019 Elsevier Inc. This is an open access
article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-
nd/4.0/).
Inter-individual differences in defensive responding are widely established but
their morphological correlates in humans have not been investigated exhaustively.
Previous studies reported associations with cortical thickness of the dorsal
anterior cingulate cortex, insula and medial orbitofrontal cortex as well as
amygdala volume in fear conditioning studies. However, these associations are
partly inconsistent and often derived from small samples. The current study aimed
to replicate previously reported associations between physiological and subjective
measures of fear acquisition and extinction and brain morphology. Structural
magnetic resonance imaging was performed on 107 healthy adults who completed a
differential cued fear conditioning paradigm with 24 h delayed extinction while
skin conductance response (SCR) and fear ratings were recorded. Cortical thickness
and subcortical volume were obtained using the software Freesurfer. Results
obtained by traditional null hypothesis significance testing and Bayesians
statistics do not support structural brain-behavior relationships: Neither
differential SCR nor fear ratings during fear acquisition or extinction training
could be predicted by cortical thickness or subcortical volume in regions
previously reported. In summary, the current pre-registered study does not
corroborate associations between brain morphology and inter-individual differences
in defensive responding but differences in experimental design and analyses
approaches compared to previous work should be acknowledged.
AimThe aim of this systematic review is to evaluate and synthesize published and
unpublished literature on the effectiveness of a diverse range of exercise programs
on back shape/posture, balance, falling and fear of falling in older people with
hyperkyphosis. ObjectivesThe objective of this systematic review is to determine
the effects of difference exercise programs on back shape/posture, balance, falling
and fear of falling in older adults with hyperkyphosis.
Purpose of Review To review mechanisms of blushing and fear of blushing from
physiological, neuropharmacological and psychological viewpoints, and to evaluate
current forms of treatment for blushing-related fear. Recent Findings Blushing
appears to be driven primarily by sympathetic adrenomedullary and neural
vasodilator discharge, possibly in association with secondary neurovascular
inflammation. Psychological risk factors for fear of blushing include social
anxiety, coupled with heightened self-focused attention and inflated beliefs about
the likelihood and social costs of blushing. In addition, schemas of emotional
inhibition, social isolation and alienation may underlie blushing-related fears.
Established psychological treatments for fear of blushing include task
concentration training, exposure, cognitive therapy, social skills training,
psychoeducation and applied relaxation. More novel approaches include mindfulness
and mindful self-compassion, video feedback and imagery rescripting. There are no
established pharmacological treatments specifically for fear of blushing. However,
selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake
inhibitors are effective treatments for social anxiety disorder and may thus help
some patients manage their fear of blushing. A reactive sympathetic nervous system
may interact with psychological predispositions to intensify fear of blushing.
These physiological and psychological risk factors could be promising targets for
treatment.
Background: There is no meta-analysis that specifically evaluates the effectiveness
of Internetand mobile-based interventions (IMIs) in adults with diagnosed panic
disorder and/or agoraphobia (PD/A) so far. The current meta-analysis aims to fill
this gap (PROSPERO CRD 42016034016). Methods: Systematic literature searches in six
databases for randomised and controlled clinical trials investigating IMIs in
adults, who met diagnostic criteria for PD/A. Study selection and data extraction
were conducted independently by two reviewers. Random-effects meta-analyses, pre-
planned subgroup and sensitivity analyses were conducted when appropriate. Primary
outcomes were PD and A symptom severity. In addition, adherence, response,
remission, quality of life, anxiety and depression symptom severity were examined.
Results: A total of 16 trials (1015 patients), with 21 comparisons (9 IMI vs.
waitlist; 7 IMI vs. IMI; 5 IMI vs. active treatment condition), were included. IMIs
revealed beneficial effects on panic (Hedges' g range -2.61 to -0.25) and
agoraphobia symptom severity when compared to waitlist (pooled g = -1.15, [95%-CI =
-1.56; -0.74]). Studies comparing IMIs to active controls (i.e., face-to-face CBT
and applied relaxation) did not find significant differences for reductions in
panic (g = -0.02, [95%-CI = -0.25; 0.21]) and agoraphobia symptom severity (g = -
0.10, [95%-CI = -0.39; 0.19]). Furthermore, IMIs were superior to waitlist controls
regarding anxiety and depression symptom severity and quality of life. Limitations:
Tests for publication bias were not feasible due to the limited number of trials
per comparison, and the risk of bias assessment indicated some methodological
shortcomings. Conclusions: Findings from this meta-analytic review provide support
for the effectiveness of IMIs in patients with verified PD/A. However, before IMIs
can be included in treatment guidelines for PD/A, future high quality research is
needed that substantiates and extends the evidence base, especially in regard to
intervention safety.
Objective: The objective of the review is to map and analyze midwifery
interventions to reduce fear of childbirth in pregnant women. Introduction: Fear of
childbirth is a phenomenon negatively affecting women's health and well-being
before and during pregnancy, as well as after childbirth. During the previous few
decades, there has been a growing interest in research into interventions to reduce
the fear of childbirth in childbearing women. Currently, providing an appropriate
model of care for pregnant women with fear of childbirth is a challenge in
midwifery care. Therefore, further efforts are needed to identify and examine the
characteristics of different midwifery interventions to reduce fear of childbirth
in pregnant women. Inclusion criteria: This scoping review will consider studies
that include interventions to reduce fear of childbirth in pregnant women, led and
implemented by midwives, during the antenatal period, in all possible birth
scenarios. Quantitative, qualitative, and mixed methods studies will be included.
Methods: The JBI methodology for conducting scoping reviews will be employed.
Published and unpublished literature in English, Portuguese, and Spanish, from 1981
to the present, will be included. MEDLINE, CINAHL Complete, Scopus, Web of Science,
Embase, and Cochrane Library databases will be searched. Searches for gray
literature will be performed. Data will be extracted using a tool developed
specifically for the scoping review objectives.
Objective The aim of the study was to investigate alterations in motor behavior
related to pain-related beliefs in persons with peripheral joint conditions. Design
This is a systematic review. Results Our database search (PubMed, Web of Science,
Embase, PsycINFO) identified 7390 articles (until September 2019), and nine
articles (344 participants) were selected based on the eligibility criteria for
selecting studies, i.e., studies in adults with primary peripheral joint
conditions, assessing the influence of fear of movement, catastrophizing or anxiety
on motor behavior in terms of kinematics, kinetics, and muscle activity during
active movements. In the acute stage after knee or radius surgery, more
catastrophizing and fear were associated with less active joint motion in the
operated and adjacent joints. In knee patients in the chronic stage after surgery,
increased hip adduction and knee valgus were linked to increased fear of movement
during the performance of challenging tasks. Similar results were found in persons
with nonsurgical chronic knee pain. During gait, no relation between lower limb
kinematics and fear of movement was observed. Conclusions Kinematic alterations
appear in tandem with pain-related perceptions in acute stages after surgery.
Altered kinematics influenced by pain-related beliefs are also seen in persons with
chronic nonsurgical and surgical knee pain, when challenging tasks are performed.
Learning that certain cues or environments predict threat enhances survival by
promoting appropriate fear and the resulting defensive responses. Adapting to
changing stimulus contingencies by learning that such cues no longer predict
threat, or distinguishing between these threat-related and other innocuous stimuli,
also enhances survival by limiting fear responding in an appropriate manner to
conserve resources. Importantly, a failure to inhibit fear in response to harmless
stimuli is a feature of certain anxiety and trauma-related disorders, which are
also associated with dysfunction of the neural circuitry underlying learned fear
and its inhibition. Interestingly, these disorders are up to twice as common in
women, compared to men. Despite this striking sex difference in disease prevalence,
the neurobiological factors involved remain poorly understood. This is due in part
to the majority of relevant preclinical studies having neglected to include female
subjects alongside males, which has greatly hindered progress in this field.
However, more recent studies have begun to redress this imbalance and emerging
evidence indicates that there are significant sex differences in the inhibition of
learned fear and associated neural circuit function. This paper provides a
narrative review on sex differences in learned fear and its inhibition through
extinction and discrimination, along with the key gonadal hormone and brain
mechanisms involved. Understanding the endocrine and neural basis of sex
differences in learned fear inhibition may lead to novel insights on the
neurobiological mechanisms underlying the enhanced vulnerability to develop
anxiety-related disorders that are observed in women.
During the last 10 years, a large body of studies have used fear conditioning
paradigms to study the role of sleep in the consolidation of fear and safety
learning. This line of research could allow us to answer if it is adaptive or not
to sleep in the aftermath of a negative experience, and if sleep has a role in
consolidating extinction learning. This field has so far produced several
contrasting findings. Thus, this review will not deliver many clear conclusions,
but will instead be an attempt to summarize what we know at the moment, to describe
the potential clinical applications of this research, and to discuss where to go
from here.
Emergencies that occur during natural disasters, such as avalanches, earthquakes,
and floods, tend to be sudden, unexpected, and ephemeral and recruit defensive
responses, similar to the ones recruited when faced with dangerous animals.
Defensive behaviors are triggered by activity in survival circuits that detects
imminent threats and fear is the conscious emotion of that follows immediately. But
this particular threat (COVID-19) is useable and mysterious, triggering anxieties
much more than fear. We conducted a literature search on May 1, 2020 in Google
Scholar, PsychInfo, and PubMed with search terms related to COVID-19 fears and
found 28 relevant articles. We categorized the papers into six groups based on the
content and implications: fear of the unknown, social isolation, hypochondriasis,
disgust, information-driven fears, and compliance. Considering the nature of fear
and anxiety, combined with the characteristics of the present COVID-19 situation,
we contemplate that physicians and other health care workers of several
specialties, as well as police officers, fire-fighters, and rescue personnel, and
first responders might be more able to deal with COVID-19 if they have (a) some
tolerance of the unknown, (b) low illness anxiety disorder, (c) tolerance to social
isolation; (d) low levels of disgust sensitivity; (e) be granted financial support,
(f) have priority if needed medical assistance (g) use caution relatively to the
COVID-19 media coverage and (h) be trained to have high levels of efficacy.
Possibilities for preventive and therapeutic interventions that can help both
health care personnel and the general population are also discussed.
Ketamine, a multimodal anesthetic drug, has become increasingly popular in the
treatment of pain following traumatic injury as well as treatment-resistant major
depressive disorders. However, the psychological impact of this dissociative
medication on the development of stress-related disorders such as post-traumatic
stress disorder (PTSD) remains controversial. To address these concerns,
preclinical studies have investigated the effects of ketamine administration on
fear memory and stress-related behaviors in laboratory animals. Despite a well-
documented line of research examining the effects of ketamine on fear memory, there
is a lack of literature reviews on this important topic. Therefore, this review
article summarizes the current preclinical literature on ketamine and fear memory
with a particular emphasis on the route, dose, and timing of ketamine
administration in rodent fear conditioning studies. Additionally, this review
describes the molecular mechanisms by which ketamine may impact fear memory and
stress-related behaviors. Overall, findings from previous studies are inconsistent
in that fear memory may be increased, decreased, or unaltered following ketamine
administration in rodents. These conflicting results can be explained by factors
such as the route, dose, and timing of ketamine administration; the interaction
between ketamine and stress; and individual variability in the rodent response to
ketamine. This review also recommends that future preclinical studies utilize a
clinically relevant route of administration and account for biological sex
differences to improve translation between preclinical and clinical investigations.
Anxiety disorders impose substantial costs upon public health and productivity in
the USA and worldwide. At present, these conditions are quantified by self-report
questionnaires that only apply to behaviors that are accessible to consciousness,
or by the timing of responses to fear- and anxiety-related words that are indirect
since they do not produce fear, e.g., Dot Probe Test and emotional Stroop. We now
review the conditioned responses (CRs) to fear produced by a neutral stimulus
(conditioned stimulus CS+) when it cues a painful laser unconditioned stimulus
(US). These CRs include autonomic (Skin Conductance Response) and ratings of the
CS+ unpleasantness, ability to command attention, and the recognition of the
association of CS+ with US (expectancy). These CRs are directly related to fear,
and some measure behaviors that are minimally accessible to consciousness e.g.,
economic scales. Fear-related CRs include non-phase-locked phase changes in
oscillatory EEG power defined by frequency and time post-stimulus over baseline,
and changes in phase-locked visual and laser evoked responses both of which include
late potentials reflecting attention or expectancy, like the P300, or contingent
negative variation. Increases (ERS) and decreases (ERD) in oscillatory power post-
stimulus may be generalizable given their consistency across healthy subjects. ERS
and ERD are related to the ratings above as well as to anxious personalities and
clinical anxiety and can resolve activity over short time intervals like those for
some moods and emotions. These results could be incorporated into an objective
instrumented test that measures EEG and CRs of autonomic activity and psychological
ratings related to conditioned fear, some of which are subliminal. As in the case
of instrumented tests of vigilance, these results could be useful for the direct,
objective measurement of multiple aspects of the risk, diagnosis, and monitoring of
therapies for anxiety disorders and anxious personalities.
Anxiety disorders, mainly panic and agoraphobic disorders, are pathologies that
undermine postmodern society. For this reason, effective and short-term treatment
is needed. The purpose of this review is to identify the investigations that
associate treatments in agoraphobia and panic disorders, that apply the systemic
model in psychotherapy and that use the paradoxical prescriptions. A systematic
review of the literature has been carried out following the PRISMA guidelines
(Urrutia & Bonfill 2010). The databases used were: Scielo, Redalyc and Google
academic. The search was configured through the intersection of the descriptors as
"panic", "agoraphobia", "paradoxical prescriptions". After carrying out the
progression of the concepts in the three search engines and having limited the
results to the last 5 years and in Spanish, 2749 articles were obtained. This
result was restricted to the discipline "psychology" leaving a total of 190
articles that, suppressing the repetitions and with a manual review to select the
relevant ones for the subject, were totaled 8 articles that referred to the search.
It was observed that the use of paradoxical prescriptions are not of great
application, and that given the results in the investigations we have studied, they
would deserve further development given their effectiveness.
Introduction A substantial number of patients with PD experience relapse after the
discontinuation of effective pharmacotherapy, leading to detrimental effects on the
individuals and considerable societal costs. This suggests the need to optimize
pharmacotherapy to minimize relapse risk. Area covered The present systematic
review examines randomized, double-blind, placebo-controlled relapse prevention
studies published over the last 20 years involving recommended medications. The
authors aim to provide an overview of this topic and evaluate whether recent
advances were achieved. Only seven studies were included, providing limited
results. One-year maintenance pharmacotherapy with constant doses had protective
effects against relapse in patients who had previously exhibited satisfactory
responses to the same medication at the same doses. The duration of maintenance
treatment did not influence relapse risk. No data were available concerning the use
of lower doses or the predictors of relapse. Expert opinion Relapse prevention in
PD has received limited attention. Recent progress and conclusive indications are
lacking. Rethinking pharmacological research in PD may be productive. Collecting a
wide range of clinical and individual features/biomarkers in large-scale,
multicenter long-term naturalistic studies, and implementing recent technological
innovations (e.g., electronic medical records/'big data' platforms, wearable
devices, and machine learning techniques) may help identify reliable predictive
models.
Introduction: Painful sexual intercourse or dyspareunia is a common complaint among
women, affecting 12-21% of premenopausal women. Recent studies have begun to focus
on the role of fear avoidance and pain catastrophizing (PC) in genital pain and
have consistently highlighted the importance of psych-affective factors in sexual
pain. Aim: To establish the importance of PC, fear of pain, and depression for the
development and maintenance of female sexual pain. Methods: This longitudinal study
was conducted in the United Kingdom to assess sexual pain at 2 different time
points, in 2009 and 2013, in a convenience sample of N = 979 British women. Main
Outcome Measure: Well-validated questionnaires including the Pain Catastrophizing
Scale, the Pain Anxiety Symptom Scale, and the Female Sexual Function Index (recent
and lifelong version) were applied. Results: Multilevel modeling showed a strong
increase of short-lived sexual pain over the 4 years (pi(01) = -0.33; P < .001).
According to the moderation analyses, only depression influenced the change in
short-lived pain over the 4 years (pi(11) = 0.46; P = .016). Similarly, only
depression turned out to be independently associated with sexual pain when entered
into the multiple regression model, as women reporting higher depression levels
also reported more sexual pain (P < 0.05). Clinical Implications: Clinicians should
be aware that the mechanisms influencing short-lived sexual pain and changes in
sexual pain seem to be different from the more enduring psychological factors that
lead to the development and maintenance of "chronic" sexual pain. Strengths &
Limitations: A very generic and unidimensional definition of sexual pain was used
without information on pain frequency or intensity, and no information on the
possible underlying (medical or psychological or both) causes was available.
However, as far as we know this represents the first study to use repeated measures
to assess how pain changes over a 4-year period and to explore the role of
potential psychoaffective risk factors. Conclusion: Among the variables studied,
symptoms of depression seemed to be the only independent predictor of lifelong
sexual pain, overriding potential influences of pain catastrophizing or fear of
pain. Copyright (C) 2019, International Society for Sexual Medicine. Published by
Elsevier Inc. All rights reserved.
Background Fear of infertility (FOI) is often reported in studies about
reproductive health but this literature not yet mapped. The aim of this rapid
scoping review of qualitative studies was to describe the nature of FOI in Africa.
Methods Eligibility criteria were qualitative data from Africa reporting views of
women and men of any age. MEDLINE and CINAHL databases were searched for English
language citations to February 2019 using keywords related to fear, infertility and
Africa. Two independent reviewers screened texts for inclusion. Results Of 248
citations identified, 38 qualitative and six review papers were included. FOI was
reported in diverse groups (e.g., men, women, fertile, infertile, married,
unmarried, teachers, religious leaders). Two types of fears were identified: (1)
fear of triggering infertility due to specific reproductive choices and (2) fear of
the dire future consequences of infertility. Choices were perceived to affect
fertility via internal accumulation and blockage (e.g., of menstrual blood),
structural damage (e.g., burnt eggs), internal movement of contraceptive material,
deliberate toxicity preventing population growth and behavioral effects impeding
sexual activity. Diverse feared consequences of infertility were reported (e.g.,
polygamy, economic hardships). Fears were reported to affect reproductive behaviour
(e.g., stopping contraception), help-seeking and social behaviour. Conclusion FOI
is a phenomenon that should be studied in its own right. Fears could originate from
genuine threats, incorrect knowledge, distortions of truths, or dissemination of
false information. Rigorous studies are needed to better understand FOI and
integrate it in health education, client counselling and family planning service
provision.
For decades already, the human fear conditioning paradigm has been used to study
and develop treatments for anxiety disorders. This research is guided by
theoretical assumptions that, in some cases indirectly, stem from the tradition of
association formation models (e.g., the Rescorla-Wagner model). We argue that one
of these assumptions - fear responding as a monotonic function of the associative
activation of aversive memory representations - restricts the types of treatment
that the research community currently considers. We discuss the importance of this
assumption in the context of research on extinction-enhancing and reconsolidation
interference techniques. While acknowledging the merit of this research, we argue
that unstrapping the straitjacket of this assumption can lead to exploring new
directions for utilizing fear conditioning procedures in treatment research. We
discuss two determinants of fear responding other than associative memory
activation. First, fear responding might also depend on relational information.
Second, a recent goal-directed emotion theory suggests that goals might be the
primary determinant of the response pattern characterized as fear.
Compared to the field of anxiety research, the use of fear conditioning paradigms
for studying chronic pain is relatively novel. Developments in identifying the
neural correlates of pain-related fear are important for understanding the
mechanisms underlying chronic pain and warrant synthesis to establish the state-of-
the-art. Using effect-size signed differential mapping, this meta-analysis combined
nine MRI studies and compared the overlap in these correlates of pain-related fear
to those of other non-pain-related conditioned fears (55 studies). Pain-related
fear was characterized by neural activation of the supramarginal gyrus, middle
temporal gyrus, inferior/middle frontal gyri, frontal operculum and insula,
pre-/post-central gyri, medial frontal and (para-) cingulate cortex, hippocampus,
thalamus, and putamen. There were differences with other non-pain-related
conditioned fears, specifically in the inferior frontal gyrus, medial superior
frontal gyrus, post-central gyrus, middle temporal gyrus, parieto-occipital sulcus,
and striatum. We conclude that pain-related and non-pain related conditioned fears
recruit overlapping but distinguishable networks, with potential implications for
understanding the mechanisms underlying different psychopathologies.
Fear of cancer recurrence (FCR) is a pervasive concern for people living with
cancer. The rapidly expanding FCR literature has been weakened somewhat by use of
miscellaneous FCR measures of varying quality. The Fear of Cancer Recurrence
Inventory (FCRI) has been widely used in observational and intervention studies and
the FCRI severity subscale, also known as the FCRI-Short Form (FCRI-SF), is often
used to identify potential cases of clinically significant FCR. Given the FCRI's
increasing use in research and clinical practice, we aimed to provide an overview,
critique, and suggested improvements of the FCRI. Studies citing the original FCRI
validation paper were identified and synthesised using narrative and meta-analytic
methods. The 42-item FCRI has demonstrated a reasonably robust 7-factor structure
across evaluations in multiple languages, although certain subscales (eg, Coping)
demonstrate suboptimal reliability. Confirmation of the cross-cultural equivalence
of several FCRI translations is needed. Meta-analysis of FCRI-SF scores revealed a
combined weighted mean score of 15.7/36, a little above the lowest proposed cut-off
score (>= 13) for clinical FCR. Depending on the FCRI-SF cut-off used, between
30.0% and 53.9% of the cancer population (ie, patients and survivors) appear to
experience sub-clinical or clinical FCR. Higher FCRI scores were associated with
younger age and female gender, pain/physical symptoms and psychological morbidity,
consistent with the FCR literature generally. Issues regarding the application and
interpretation of the FCRI remain. Whether the FCRI is well suited to assessing
fear of progression as well as recurrence is unclear, the meaningfulness of the
FCRI total score is debatable, and the use of the FCRI-SF to screen for clinical
FCR is problematic, as items do not reflect established characteristics of clinical
FCR. Refinement of the FCRI is needed for it to remain a key FCR assessment tool in
future research and clinical practice.
The aim of this review is to give a synopsis on the coronavirus disease 2019
(COVID-19) pandemic, with major focus on the preventive measures. Ever since the
influenza pandemic of 1918, and the second world war of (1939-1945), the world has
not been faced with a common problem in recent memory like the COVID-19 pandemic.
The unprecedented COVID-19 pandemic is caused by infection with a viral pathogen,
the nascent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and is
characterized by respiratory failure in severe cases. The communicability period of
COVID-19 varies, but it is usually between 2-14 days, and the major signs and
symptoms of COVID-19 are high temperature (fever), severe and consistent cough, and
serious breathing problems in severe cases, however, complications result in the
serious inflammation of the lungs, and organ malfunction occurs in patients with
comorbidities and health conditions especially diabetes, heart disease and obesity.
With high virulence and contagious nature of SARS-CoV-2, over 11.4 million
confirmed cases and over 533,780 deaths have occurred as a result of COVID-19
globally, with over 6.1 million recoveries as of 6th July 2020. Presently, there is
no known cure for COVID-19, however, remdesivir has been approved for emergency use
for the treatment of COVID-19 patients by the Food and Drug Administration, a
United States federal regulatory body (FDA), while various clinical trial
treatments and vaccines are being tried globally. The world is faced with
containing the spread of the infection, and this review revealed that thorough hand
washing with antiseptic soap and running water and usage of alcohol hand sanitizer,
frequent surfaces cleaning, strict adherence to social distancing, regular
respiratory hygiene, wearing of protective face masks, frequent testing, self-
isolation, quarantine and rigorous contact tracing will help to prevent further
spread, and control the transmission of the viral pathogen. It is however strongly
recommended that only the strict compliance to the mitigative and preventive
measures provided above will yield the desired results in the prevention,
management and control of the COVID-19 pandemic.
The new coronavirus pandemic poses question and challenges for dermatologists. One
of question is if psoriasis patients treated with immunomodulating and
immunosuppressive drugs have to discontinue their treatment in the midst of fears
for the infection and its consequences. One of the challenges is how can we support
our patients in this critical time. Previous coronaviruses outbreaks reports,
current published evidences on pathogenesis and on clinical reports of COVID
infection in immunosuppressed patients are used to make a scientifically based
decision.
Objective: Psychoeducation is an evidence-based therapeutic intervention for women
that provide information, support for a better understanding and coping with fear
of childbirth (FOC). Although there have been some studies examining the effects of
psychoeducation on FOC and cesarean section (CS), there is no high quality
evidence. This systematic review and meta-analysis study aimed to investigate the
effects of psychoeducation on FOC and CS rate. Methods: Literature research was
performed in CINAHL, PubMed, Science Direct, OVID, Medline, Science Citation Index
(Web of Science) and Cochrane Central Register of Controlled Trials until April
2018. This study is based on the recommendations of the Cochrane guidelines. The
analysis was conducted using the Comprehensive Meta-Analysis Program Version 3.
Results: Four randomized controlled studies and three non-randomized controlled
studies were selected; six studies were combined for FOC and four studies were
combined for CS rate. Meta-analysis revealed that psychoeducation is effective in
reducing pregnant women's FOC (hedges' g 0.59, 95% Confidence Interval (CI) 0.46-
0.72, p = .000; 931 women) and the CS rate (Odds Ratio 1.730, 95% CI 1.285-2.330, p
= .000; 682 women). Conclusion: This study provides sufficient evidence that
psychoeducation is an effective to reduce FOC and CS rate.
This study examined factors underlying collective action tendencies in a context of
severe disadvantage and high repression. Drawing on the Social Identity Model of
Collective Action (SIMCA; van Zomeren, Postmes, & Spears, 2008), we tested the
roles of group-based anger, participative efficacy, group identity-SIMCA variables-
but also fear. Although SIMCA has been widely used in various social contexts,
little is known about how well it applies to severely disadvantaged groups in
highly repressive situations. In the study of female Filipina domestic workers (N =
123) in Beirut, Lebanon, results provided partial support for SIMCA, such that
identity indirectly and positively predicted collective action intentions via
efficacy, but not anger. Importantly, fear modulated the paths from anger and
efficacy to collective action intentions. Efficacy and anger positively predicted
collective action tendencies among individuals low, but not high, in fear. These
findings attest to the importance of studying political actions among
underrepresented populations.
Dopamine producing neurons of the ventral tegmental area (VTA) are an important
modulator of fear-related behavior and aversive motivations. Increasing evidence
suggests that disruption of the mesolimbic dopamine system contributes to fear
generalization. The neural substrates of fear generalization and the mechanism(s)
by which dopamine modulates the formation and updating of these aberrant engrams
are only beginning to be resolved. The purpose of this review is to highlight key
findings in the study of dopamine and fear processing and to provide a model of
fear generalization based on a stress-induced impairment in learning that results
in uncertainty in threat prediction.
Panic disorder (PD) being one of the most intensively investigated anxiety
disorders is considered a heterogeneous psychiatric disease which has difficulties
with early diagnosis. The disorder is recurrent and usually associated with low
remission rates and high rates of relapse which may exacerbated social and quality
of life, causes unnecessary cost and increased risk for complication and suicide.
Current pharmacotherapy for PD are available but these drugs have slow therapeutic
onset, several side effects and most patients do not fully respond to these
standard pharmacological treatments. Ongoing investigations indicate the need for
new and promising agents for the treatment of PD. This article will cover the
importance of immediate and proper treatment, the gap in the current management of
PD with special emphasis on pharmacotherapy, and evidence regarding the novel anti-
panic drugs including the drugs in developments such as metabotropic glutamate
(mGlu 2/3) agonist and levetiracetam. Preliminary results suggest the anti-panic
properties and the efficacy of duloxetine, reboxetine, mirtazapine, nefazodone,
risperidone and inositol as a monotherapy drug. Apart for their effectiveness, the
aforementioned compounds were generally well tolerated compared to the standard
available pharmacotherapy drugs, indicating their potential therapeutic usefulness
for ambivalent and hypervigilance patient. Further strong clinical trials will
provide an ample support to these novel compounds as an alternative monotherapy for
PD treatment-resistant patient.
Objective Treatment for panic disorder (PD) have evolved, although there is still a
strong unmet need for more effective and tolerable options. The present study
summarizes and discusses recent evidence regarding the pharmacological and
neuromodulatory treatment of PD. Methods MEDLINE, Cochrane Library, PsycINFO and
Thomson Reuters's Web of Science were searched for clinical trials published
between 2010 and 2018. We included all prospective experimental studies including
randomized controlled trials (RCT) and other clinical trials with more than 10
patients. Results Only 11 articles met the inclusion criteria, including 4 RCT, 3
open clinical trials and 5 comparative clinical trials. RCT demonstrated efficacy
of transcranial magnetic stimulation (TMS) in only one of two trials. Neither
pindolol nor d-fenfluramine were effective in blocking flumazenil-induced panic
attacks. Augmentation with quetiapine was not superior to placebo. Open trials
indicated that escitalopram, vortioxetine and TMS may be effective. Comparative
trials did not demonstrate superiority from any drug, but confirmed
tranylcypromine, paroxetine, clonazepam and alprazolam as effective options.
Conclusion The current study confirmed the efficacy of tranylcypromine, paroxetine,
clonazepam, alprazolam and escitalopram. Vortioxetine and TMS, with duration of 4
or more weeks, also seems to be effective. Quetiapine, pindolol and d-fenfluramine
were not considered effective compounds.
Anxiety disorders that develop in adolescence represent a significant burden and
are particularly challenging to treat, due in no small part to the high occurrence
of relapse in this age group following exposure therapy. This pattern of persistent
fear is preserved across species; relative to those younger and older, adolescents
consistently show poorer extinction, a key process underpinning exposure therapy.
This suggests that the neural processes underlying fear extinction are temporarily
but profoundly compromised during adolescence. The formation, retrieval, and
modification of fear- and extinction-associated memories are regulated by a
forebrain network consisting of the prefrontal cortex (PFC), the amygdala, and the
hippocampus. These regions undergo robust maturational changes in early life, with
unique alterations in structure and function occurring throughout adolescence. In
this review, we focus primarily on two of these regions-the PFC and the amygdala-
and discuss how changes in plasticity, synaptic transmission,
inhibition/excitation, and connectivity (including modulation by hippocampal
afferents to the PFC) may contribute to transient deficits in extinction retention.
We end with a brief consideration of how exposure to stress during this adolescent
window of vulnerability can permanently disrupt neurodevelopment, leading to
lasting impairments in pathways of emotional regulation.
Intensifying fear and fear of pain may lead to some diseases such as panic
disorder, phobias, post-traumatic stress disorder (PTSD), anxiety disorders,
depression, etc. A number of studies indicated positive effect of transcranial
direct current stimulation (tDCS) on controlling fear and some studies did not
observe any effect or even negative effect on decreasing fear. Due to lack of
consensus in the findings of research, we aimed to systematically review studies,
which investigated the effect of tDCS on fear. A literature search was conducted
using the databases of PubMed, Science Direct, OVID, CINAHL, PEDro, Cochrane,
Scopus and MEDLINE. Fear, fear memory, fear of pain, anxiety, post-traumatic stress
disorder, electrical brain stimulation were applied as keywords. The valid
assessment scale was used to evaluate the methodological quality of the included
studies. The results of this systematic review revealed that the cathodal tDCS (c-
tDCS) on the left dorsolateral prefrontal cortex (DLPFC) as compared to anodal tDCS
(a-tDCS) could significantly reduce fear and modulate the fear memory. In addition,
the findings of this study showed that the c-tDCS has positive effect on
behavioural parameters of fear, while it cannot change biochemical parameters of
fear during limited sessions of intervention. Application of c-tDCS on the left
DLPFC could significantly reduce fear and modulate the fear memory. (C) 2019
Elsevier Ltd. All rights reserved.
Objective The current systematic review aims to provide an overview of fear of
cancer recurrence (FCR) in adolescent and young adult cancer survivors (15-39 years
at cancer diagnosis, AYAs). Methods MEDLINE, PubMed, PsycINFO, and Embase databases
were independently searched to identify relevant quantitative articles. PRISMA
systematic review procedures were followed with quality assessment. Results
Seventeen studies were included in the current review. All were quantitative
studies that utilized a cross-sectional study design. Seven articles reported
results of FCR prevalence, six studied determinants related to FCR, and 11 articles
provided information about consequences of FCR. Prevalence of FCR ranged from 31%
to 85.2% among AYA survivors. Associations between sociodemographic/clinical
variables and FCR were inconsistent. Psychological distress and higher treatment
intensity were positively associated with higher FCR levels. Lower scores on levels
of physical, psychological functioning, and overall health-related quality of life
(QoL) were identified as consequences of increased FCR. Conclusion FCR appears to
be a prevalent concern among adolescent and young adult cancer populations.
Adequate assessment to determine need for support and intervention is still
required. Longitudinal studies in AYAs are warranted to understand the development
and potential influence of FCR. Age-appropriate and flexible psychological care
would be more successful potentially with this crucial background information.
In the recent decade, fear conditioning has evolved as a standard procedure for
testing cognitive abilities such as memory acquisition, consolidation, recall,
reconsolidation, and extinction, preferentially in genetically modified mice. The
reasons for the popularity of this powerful approach are its ease to perform, the
short duration of training and testing, and its well-described neural basis. So why
to bother about flaws in standardization of test procedures and analytical
routines? Simplicity does not preclude the existence of fallacies. A short survey
of the literature revealed an indifferent use of acoustic stimuli in terms of
quality (i.e., white noise vs. sine wave), duration, and intensity. The same
applies to the shock procedures. In the present article, I will provide evidence
for the importance of qualitative and quantitative parameters of conditioned and
unconditioned stimuli for the experimental outcome. Moreover, I will challenge
frequently applied interpretations of short-term vs. long-term extinction and
spontaneous recovery. On the basis of these concerns, I suggest a guideline for
standardization of fear conditioning experiments in mice to improve the
comparability of the experimental data.
Laboratory measures have played an integral role in diagnosing pathology; however,
compared to traditional medicine, psychiatric medicine has lagged behind in using
such measures. A growing body of literature has begun to examine the viability and
development of different laboratory measures in order to diagnose
psychopathologies. The present review examines the current state of development of
both sodium lactate infusion and CO2-35% inhalation as potential ancillary measures
to diagnose panic disorder (PD). A previously established 3-step approach to
identifying laboratory-based diagnostic tests was applied to available literature
assessing the ability of both sodium lactate infusion or CO2-35% inhalation to
induce panic attacks in PD patients, healthy controls, and individuals with other
psychiatric conditions. Results suggest that across the literature reviewed,
individuals with PD were more likely to exhibit panic attacks following
administration of sodium lactate or CO2-35% compared to control participants. The
majority of the studies examined only compared individuals with PD to healthy
controls, suggesting that these ancillary measures are underdeveloped. In order to
further determine the utility of these ancillary measures, research is needed to
determine if panic attacks following administration of these chemical agents are
unique to PD, or if individuals with related pathologies also respond, which may be
indicative of transdiagnostic characteristics found across disorders. (C) 2019 S.
Karger AG, Basel
The earthquake of 62/63 ce was a catastrophic event for Pompeii and Campania. The
destruction and death toll were extensive and it is clear that the city of Pompeii
was still recovering and rebuilding when the eruption of Vesuvius happened. This
article takes into consideration the mental and emotional damage that the
earthquake caused and the way in which Seneca and the archaeological record help us
to perceive strategies of consolation and therapy. Seneca discusses this earthquake
in Book 6 of his Naturales quaestiones and hopes to lead his reader from the shock
of the earthquake to a more comprehensive understanding of the physical causes of
the tremor. The cultural memory of events not witnessed directly (such as Seneca's
write-up of the Pompeii earthquake) makes us all survivors and 'turn[s] history
into a memory in which we can all participate'. If trauma 'spreads via language and
representation', Seneca wants to limit what exactly is traumatic about this event
and employs his creative rhetoric to do so. His account demonstrates how Stoic
physics and ethics are connected and moves the reader from his or her fear of
earthquakes to the fear of death at the root of the anxiety. Seneca carefully
alters the valence of certain terms as well as selected memories of the earthquake
to encourage his reader to transcend his or her fear and view earthquakes as
natural occurrences, not anomalies to be dreaded. He does this through strategies
identified in modern trauma theory as useful for post-traumatic stress disorder
(PTSD), and this article investigates how contemporary trauma theory can help us
understand aspects of Seneca's remedy. Seneca's repetitions of certain events and
terminology works to reassess and renovate them from a philosophical angle - in
essence it turns potential 'flashbacks' and 'triggers' into beneficial sites of
memory and the means of recovery. Survivors often relive the trauma again and again
- Seneca's work alludes to this, but now makes the victim actively revise how to
make such iterations part of the recovery.
Despite the exponential increase in fear research during the last years, few
studies have included female subjects in their design. The need to include females
arises from the knowledge gap of mechanistic processes underlying the behavioral
and neural differences observed in fear extinction. Moreover, the exact
contribution of sex and hormones in relation to learning and behavior is still
largely unknown. Insights from this field could be beneficial as fear-related
disorders are twice as prevalent in women compared to men. Here, we review an up-
to-date summary of animal and human studies in adulthood that report sex
differences in fear extinction from a structural and functional approach.
Furthermore, we describe how these factors could contribute to the observed sex
differences in fear extinction during normal and pathological conditions.
Emerging research demonstrates that a pattern of overlapping but distinct molecular
and circuit mechanisms are engaged by males and females during memory tasks.
Importantly, sex differences in neural mechanisms and behavioral strategies are
evident even when performance on amemory task is similar between females and males.
We propose that sex differences in memory may be best understood within a dynamic
memory systems framework. Specifically, sex differences in hormonal influences and
neural circuit development result in biases in the circuits engaged and the
information preferentially stored or retrieved in males and females. By using
animal models to understand the neural networks and molecular mechanisms required
for memory in both sexes, we can gain crucial insights into sex and gender biases
in disorders including post-traumatic stress disorder (PTSD) in humans.
The extinction of conditioned fear responses entrains the formation of safe new
memories to decrease those behavioral responses. The knowledge in neuronal
mechanisms of extinction is fundamental in the treatment of anxiety and fear
disorders. Interestingly, the use of pharmacological compounds that reduce anxiety
and fear has been shown as a potent co-adjuvant in extinction therapy. However, the
efficiency and mechanisms by which pharmacological compounds promote extinction of
fear memories remains still largely unknown and would benefit from a validation
based on functional neuronal circuits, and the neurotransmitters that modulate
them. From this perspective, oxytocin receptor signaling, which has been shown in
cortical and limbic areas to modulate numerous functions (Eliava et al. Neuron
89(6):1291-1304, 2016), among them fear and anxiety circuits, and to enhance the
salience of social stimuli (Stoop Neuron 76(1):142-59, 2012), may offer an
interesting perspective. Experiments in animals and humans suggest that oxytocin
could be a promising pharmacological agent at adjusting memory consolidation to
boost fear extinction. Additionally, it is possible that long-term changes in
endogenous oxytocin signaling can also play a role in reducing expression of fear
at different brain targets. In this review, we summarize the effects reported for
oxytocin in cortico-limbic circuits and on fear behavior that are of relevance for
the modulation and potential extinction of fear memories.
Psoriasis is a chronic, multifactorial inflammatory disease; its clinical severity
can vary widely. Treatment of severe cases during pregnancy is of special interest.
To date there is scarce information available and most data comes from other
medical specialties that use similar treatments. Immunosuppressors are strongly
discouraged during pregnancy and breastfeeding. Amongst biologic agents, anti-TNF
alpha having been the longest on the market has allowed for the most experience. It
is known that transplacental transport of these drugs does not occur until
gestational week 22, once organogenesis is completed. Within this group
certolizumab pegol, seems to be the safest choice, as its molecular structure does
not cross the placental barrier. Beyond pregnancy, it is important to take into
account these drugs' half-life and passage to breast milk, as well as its impact on
neonatal immunization.
Background: Subjects with panic disorder are nearly 4 times as likely to attempt
suicide as compared to subjects without this condition. Methods: We searched the
literature from Jan 1, 1960 to May, 4, 2019. Articles that reported a dichotomous
sample of patients with panic disorder with and without suicidal behavior were
included. Outcomes: Twelve studies with 1958 participants were included. Comorbid
depression (k = 3, ES = 4.47 [2.63; 7.60]), depressive symptoms (k = 2, ES = 1.98
[1.26; 3.11]), older age (k = 3, ES = 1.66 [1.32; 2.10]), younger age of panic
disorder onset (k = 2, ES = 0.65 [0.45; 0.94]), and history of alcohol dependence
(k = 2, ES = 8.70 [1.20; 63.04]) were associated with suicide attempt in panic
disorder. Depressive symptoms (k = 2, ES = 2.29 (1.60; 3.37]), anxiety symptoms (k
= 2, ES = 1.90 [1.33; 2.69]), longer illness duration (k = 2, ES = 3.31 [1.90;
5.74]), comorbid depressive disorder (k = 4, ES = 3.88 [2.03; 7.41]), agoraphobia
(k = 2, ES = 4.60 [1.47; 14.42]) and younger age of onset (k = 2, ES = 0.60 [0.38;
0.96]) were associated with suicidal ideation in panic disorder. Interpretation Our
findings provide a framework for the development of suicide prevention strategies
in this population.
Autism Spectrum Disorder (ASD) is a developmental condition characterized by
impaired communication and obsessive behavior that affects 1 in 59 children. ASD is
expected to affect 1 in about 40 children by 2020, but there is still no distinct
pathogenesis or effective treatments. Prenatal stress has been associated with
higher risk of developing ASD in the offspring. Moreover, children with ASD cannot
handle anxiety and respond disproportionately even to otherwise benign triggers.
Stress and environmental stimuli trigger the unique immune cells, mast cells, which
could then trigger microglia leading to abnormal synaptic pruning and dysfunctional
neuronal connectivity. This process could alter the fear threshold in the amygdala
and lead to an exaggerated fight-or-flight reaction. The combination of
corticotropin-releasing hormone (CRH), secreted under stress, together with
environmental stimuli could be major contributors to the pathogenesis of ASD.
Recognizing these associations and preventing stimulation of mast cells and/or
microglia could greatly benefit ASD patients.
PURPOSE Fear of cancer recurrence (FCR) is a significantly distressing problem that
affects a substantial number of patients with and survivors of cancer; however, the
overall efficacy of available psychological interventions on FCR remains unknown.
We therefore evaluated this in the present systematic review and meta-analysis.
METHODS We searched key electronic databases to identify trials that evaluated the
effect of psychological interventions on FCR among patients with and survivors of
cancer. Controlled trials were subjected to meta-analysis, and the moderating
influence of study characteristics on the effect were examined. Overall quality of
evidence was evaluated using the GRADE system. Open trials were narratively
reviewed to explore ongoing developments in the field (PROSPERO registration no.:
CRD42017076514). RESULTS A total of 23 controlled trials (21 randomized controlled
trials) and nine open trials were included. Small effects (Hedges's g) were found
both at postintervention (g = 0.33; 95% CI, 0.20 to 0.46; P < .001) and at follow-
up (g = 0.28; 95% CI, 0.17 to 0.40; P < .001). Effects at postintervention of
contemporary cognitive behavioral therapies (CBTs; g = 0.42) were larger than those
of traditional CBTs (g = 0.24; beta = .22; 95% CI, .04 to .41; P = .018). At
follow-up, larger effects were associated with shorter time to follow-up (beta =
-.01; 95% CI, -.01 to -.00; P = .027) and group-based formats (beta = .18; 95%
CI, .01 to .36; P = .041). A GRADE evaluation indicated evidence of moderate
strength for effects of psychological intervention for FCR. CONCLUSION
Psychological interventions for FCR revealed a small but robust effect at
postintervention, which was largely maintained at follow-up. Larger
postintervention effects were found for contemporary CBTs that were focused on
processes of cognition?for example, worry, rumination, and attentional bias-rather
than the content, and aimed to change the way in which the individual relates to
his or her inner experiences. Future trials could investigate how to further
optimize and tailor interventions to individual patients' FCR presentation. (C)
2019 by American Society of Clinical Oncology
Anxiety disorders pose one of the greatest threats to mental health. Modern
treatment methods exist but are hindered by relapse, toxicity, and low efficacy.
The use of neuromodulation to treat anxiety disorders has shown promising results,
yet its underpinning mechanisms remain poorly understood. In this review, we make
the case for further development of neuromodulation techniques to alter fear
memories, with particular regard to future clinical applications in treating
anxiety disorders. We start by briefly summarizing the neural circuitry of fear
while identifying the pros and cons of possible neuromodulation targets. We then
highlight recent advances in neuromodulation techniques that have been used to
alter fear memories. Next, we apply a novel network-based approach to elucidate
possible mechanisms of neuromodulation which may disrupt the consolidation of fear
memory. Finally, we emphasize the need for more systematic neuromodulation studies
on animal models and the developing brain. Overall, we aim to provide an integrated
framework for future action, identifying key research priorities that must be
addressed before effective neuromodulation-based treatments can be developed for
practical use.
The review essay concerns the book: Bhushan and Garfield, Minds Without Fear. The
book, in my view, accomplishes well the task of providing a philosophically
coherent interpretation of the main episodes of the modern Indian intellectual
tradition. In this essay, I describe the importance of the work and comment on the
cosmopolitan nature of the period of Indian thought under consideration.
Objectives This systematic review and meta-analysis aimed to critically appraise
the evidence on the relationship of oral health beliefs with dental fear and
anxiety in distinct patient groups. Materials and methods Observational studies
were retrieved by Cochrane, Embase Search, Portal BVS, Clinical Trials, Ovid, Open
Gray, PubMed, Scopus, and Web of Science, and they were manually checked for the
inclusion of additional articles of interest. The assessment of quality of studies
was performed by the application of three different versions of the Newcastle-
Ottawa Scale, for cohort, case-control, and cross-sectional studies. Only studies
with low or unclear/moderate risk of bias contributed to meta-analyses, regarding
the analysis of random effects of mean differences of dental beliefs scores between
dental fear/anxiety and control groups, and the correlation of dental beliefs with
dental fear and anxiety measures. Results Of 276 articles initially retrieved, 10
were included in the systematic review, while only 6 studies with unclear/moderate
risk of bias were considered in meta-analyses. The mean difference of dental
beliefs effects was higher in patients with dental fear and anxiety compared to
controls (1.20; 95% CI 0.27-2.14; P = 0.01). Additionally, a moderate positive
correlation was observed between dental beliefs and dental fear measures (r = 0.54,
95% CI 0.47-0.60;P< 0.001). Conclusions Based on these results, the presence of
negative health beliefs is directly related to the increase of dental fear and
anxiety; however, these findings are supported in studies with unclear/moderate
risk of bias.
Background: Despite the historical employment of boron-containing compounds (BCCs)
with medicinal purposes, the reported cases of BCC toxicity in humans during the
twentieth-century drived us towards a "boron-withdrawal" period. Fortunately, the
use of boric acid for specific purposes remains, and the discovery of natural BCCs
with biological action attractive for therapeutic purposes as well as the
introduction of some new BCCs for clinical use has reactivated the interest in
studying the properties of these BCCs. Methods: We carried out a structured search
of bibliographic databases for scientific peer-reviewed research literature
regarding boron toxicity and linked that information to that of BCCs in drug design
and development. A deductive qualitative content analysis methodology was applied
to analyse the interventions and findings of the included studies using a
theoretical outline. Results: This review recapitulates the following on a
timeline: the boron uses in medicine, the data known about the toxicological
profiles of some BCCs, the pharmacological properties of some BCCs that are
employed in cancer and infectious disease therapies, and the known properties of
BCCs recently introduced into clinical assays as well as the identification of
their structure-activity relationships for toxicity and therapeutic use. Then, we
discuss the use of new approaches taking advantage of some toxicological data to
identify potent and efficient BCCs for prevention and therapy while limiting their
toxic effects. Conclusion: Data for boron toxicity can be strategically used for
boron-containing drug design.
Concern has been expressed globally over rising caesarean birth rates. Recently,
the International Federation of Gynaecology and Obstetrics (FIGO) called for help
from governmental bodies, professional organisations, women's groups, and other
stakeholders to reduce unnecessary caesareans. As part of a wider research
initiative, we conducted an overview of systematic reviews of antenatal and
intrapartum interventions, and reports of evidence based recommendations, to
identify and highlight those that have been shown to be effective for reducing
caesarean birth, promoting vaginal birth and reducing fear of childbirth. Following
registration of the review protocol, (PROSPERO 2018 CRD42018090681), we searched
The Cochrane Database of Systematic Reviews, PubMed, CINAHL and EMBASE (Jan 2000-
Jan 2018) and searched for grey literature in PROSPERO, and on websites of health
professional and other relevant bodies. Screening and selection of reviews, quality
appraisal using AMSTAR-2, and data extraction were performed independently by pairs
of at least two reviewers. Excluding reviews assessed as 'critically low' on
AMSTAR-2 (n = 54), 101 systematic reviews, and 10 reports of evidence based
recommendations were included in the overview. Narrative synthesis was performed,
due to heterogeneity of review methodology and topics. The results highlight
twenty-five interventions, across 17 reviews, that reduced the risk of caesarean,
nine interventions across eight reviews that increased the risk of caesarean, eight
interventions that reduced instrumental vaginal birth, four interventions that
increased spontaneous vaginal birth, and two interventions that reduced fear of
childbirth. This overview of reviews identifies and highlights interventions that
have been shown to be effective for reducing caesarean birth, promoting vaginal
births and reducing fear of childbirth. In recognising that clinical practices
change over time, this overview includes reviews published from 2000 onwards only,
thus providing contemporary evidence, and a valuable resource for clinicians when
making decisions on practices that should be implemented for reducing unnecessary
caesarean births safely.
The measurement of Pavlovian forms of fear extinction offers a relatively simple
behavioral preparation that is nonetheless tractable, from a translational
perspective, as an approach to study mechanisms of exposure therapy and biological
underpinnings of anxiety and trauma-related disorders such as post-traumatic stress
disorder (PTSD). Deficient fear extinction is considered a robust clinical
endophenotype for these disorders and, as such, has particular significance in the
current age of RDoC (research domain criteria). Various rodent models of impaired
extinction have thus been generated with the objective of approximating this
clinical, relapse prone aberrant extinction learning. These models have helped to
reveal neurobiological correlates of extinction circuitry failure, gene variants,
and other mechanisms underlying deficient fear extinction. In addition, they are
increasingly serving as tools to investigate ways to therapeutically overcome poor
extinction to support long-term retention of extinction memory and thus protection
against various forms of fear relapse; modeled in the laboratory by measuring
spontaneous recovery, reinstatement and renewal of fear. In the current article, we
review models of impaired extinction built around (1) experimentally induced brain
region and neural circuit disruptions (2) spontaneously-arising and laboratory-
induced genetic modifications, or (3) exposure to environmental insults, including
stress, drugs of abuse, and unhealthy diet. Collectively, these models have been
instrumental in advancing in our understanding of extinction failure and underlying
susceptibilities at the neural, genetic, molecular, and neurochemical levels;
generating renewed interest in developing novel, targeted and effective therapeutic
treatments for anxiety and trauma-related disorders.
Rationale The experience of strong traumata leads to the formation of enduring fear
memories that may degenerate into post-traumatic stress disorder. One of the most
successful treatments for this condition consists of extinction training during
which the repeated exposure to trauma-inducing stimuli in a safe environment
results in an attenuation of the fearful component of trauma-related memories.
While numerous studies have investigated the neural substrates of recent (e.g., 1-
day-old) fear memory attenuation, much less is known about the neural networks
mediating the attenuation of remote (e.g., 30-day-old) fear memories. Since
extinction training becomes less effective when applied long after the original
encoding of the traumatic memory, this represents an important gap in memory
research. Objectives Here, we aimed to generate a comprehensive map of brain
activation upon effective remote fear memory attenuation in the mouse. Methods We
developed an efficient extinction training paradigm for 1-month-old contextual fear
memory attenuation and performed cFos immunohistochemistry and network connectivity
analyses on a set of cortical, amygdalar, thalamic, and hippocampal regions.
Results Remote fear memory attenuation induced cFos in the prelimbic cortex, the
basolateral amygdala, the nucleus reuniens of the thalamus, and the ventral fields
of the hippocampal CA1 and CA3. All these structures were equally recruited by
remote fear memory recall, but not by the recall of a familiar neutral context.
Conclusion These results suggest that progressive fear attenuation mediated by
repetitive exposure is accompanied by sustained neuronal activation and not
reverted to a pre-conditioning brain state. These findings contribute to the
identification of brain areas as targets for therapeutic approaches against
traumatic memories.
Background: Anxious personality characteristics form a risk factor for anxiety
disorders. A proposed mechanistic pathway is that anxious personality could lead to
greater vulnerability by increasing fear generalization. Here, we investigate if
there is evidence for this relationship before the onset of pathological anxiety,
with a metaanalysis in healthy subjects. Methods: Our search (anxious personality &
fear generalization) was performed in PubMed, PsychInfo, and Embase and via
snowballing. Results: In total, 4892 studies were screened and 19 studies (1348
participants) were included in the current review (meta-analysis: 18 studies, 1310
participants). The meta-analysis showed a significant, small, positive relationship
between anxious personality and fear generalization (r g .19, 95%CI [.126, .260], p
< .001). No moderators of the relationship were identified. Conclusions: The
identified robust relation suggests that people who score high on anxious
personality have a somewhat stronger tendency to generalize fear to safe or novel
situations. This might explain their vulnerability to anxiety disorders
mechanistically, yet future (prospective) studies are warranted to confirm the
hypothesized directionality of this effect.
Maintaining or improving quality of life (QoL) is a key outcome of clinical
interventions in older people. Fear of falling (FoF) is associated with activity
restriction as well as with poorer physical and cognitive functions and may be an
important contributor to a diminished QoL. The objectives of this systematic review
were to determine i) the effect of FoF on QoL in older people, ii) whether the
association between these two constructs depends on the use of specific
conceptualizations and measurement instruments, and iii) the role of fall events as
mediating factor in this relationship. Four electronic databases (PubMed, EMBASE,
CINAHL, and Cochrane Library) were searched from their inceptions to February 2018.
Thirty mostly cross-sectional studies in nearly 30.000 people (weighted mean age
75.6 years (SD =6.1); 73% women) were included. FoF was associated with QoL in most
studies, and this association appeared to be independent of the conceptualization
of FoF. Moreover, this relationship was independent of falls people experienced
which seemed to have a lower impact. FoF should be considered not only as by-
product of falls and targeted interventions in parts different from those to reduce
falls are likely required. Studies are needed showing that reducing FoF will lead
to increased QoL.
Background Cognitive-behavioural theories of panic disorder posit that panic
attacks arise from a positive feedback loop between arousal-related bodily
sensations and perceived threat. In a recently developed computational model
formalising these theories of panic attacks, it was observed that the response to a
simulated perturbation to arousal provided a strong indicator of vulnerability to
panic attacks and panic disorder. In this review, we evaluate whether this
observation is borne out in the empirical literature that has examined responses to
biological challenge (eg, CO2 inhalation) and their relation to subsequent panic
attacks and panic disorder. Method We searched PubMed, Web of Science and PsycINFO
using keywords denoting provocation agents (eg, sodium lactate) and procedures (eg,
infusion) combined with keywords relevant to panic disorder (eg, panic). Articles
were eligible if they used response to a biological challenge paradigm to
prospectively predict panic attacks or panic disorder. Results We identified four
eligible studies. Pooled effect sizes suggest that there is biological challenge
response has a moderate prospective association with subsequent panic attacks, but
no prospective relationship with panic disorder. Conclusions These findings provide
support for the prediction derived from cognitive-behavioural theories and some
preliminary evidence that response to a biological challenge may have clinical
utility as a marker of vulnerability to panic attacks pending further research and
development.
N-Methyl D-aspartate receptors (NMDAR) are central mediators of glutamate actions
underlying learning and memory processes including those required for extinction of
fear and fear-related behaviors. Consistent with this view, in animal models,
antagonists of NMDAR typically impair fear extinction, whereas partial agonists
have facilitating effects. Promoting NMDAR function has thus been recognized as a
promising strategy towards reduction of fear symptoms in patients suffering from
anxiety disorders and post-traumatic disorder (PTSD). Nevertheless, application of
these drugs in clinical trials has proved of limited utility. Here we summarize
recent advances in our knowledge of NMDAR pharmacology relevant for fear
extinction, focusing on molecular, cellular, and circuit aspects of NMDAR function
as they relate to fear extinction at the level of behavior and cognition. We also
discuss how these advances from animal models might help to understand and overcome
the limitations of existing approaches in human anxiety disorders and how novel,
more specific, and personalized approaches might help advance future therapeutic
strategies.
Fear is an emotion that serves as a driving factor in how organisms move through
the world. In this review, we discuss the current understandings of the subjective
experience of fear and the related biological processes involved in fear learning
and memory. We first provide an overview of fear learning and memory in humans and
animal models, encompassing the neurocircuitry and molecular mechanisms, the
influence of genetic and environmental factors, and how fear learning paradigms
have contributed to treatments for fear-related disorders, such as posttraumatic
stress disorder. Current treatments as well as novel strategies, such as targeting
the perisynaptic environment and use of virtual reality, are addressed. We review
research on the subjective experience of fear and the role of autobiographical
memory in fear-related disorders. We also discuss the gaps in our understanding of
fear learning and memory, and the degree of consensus in the field. Lastly, the
development of linguistic tools for assessments and treatment of fear learning and
memory disorders is discussed.
Background: Benzodiazepines (BZs) and selective serotonin reuptake inhibitors
(SSRIs) are effective in the pharmacologic treatment of panic disorder (PD).
However, treatment guidelines favor SSRIs over BZs based on the belief that BZs are
associated with more adverse effects than SSRIs. This belief, however, is currently
supported only by opinion and anecdotes. Aim: The aim of this review and meta-
analysis was to determine if there truly is evidence that BZs cause more adverse
effects than SSRIs in acute PD treatment. Methods: We systematically searched Web
of Science, PubMed, Cochrane Central Register of Controlled Trials, and clinical
trials register databases. Short randomized clinical trials of a minimum of four
weeks and a maximum of 12 weeks that studied SSRIs or BZs compared to placebo in
acute PD treatment were included in a meta-analysis. The primary outcome was all-
cause adverse event rate in participants who received SSRIs, BZs, or placebo.
Results: Overall, the meta-analysis showed that SSRIs cause more adverse events
than BZs in short-term PD treatment. Specifically, SSRI treatment was a risk factor
for diaphoresis, fatigue, nausea, diarrhea, and insomnia, whereas BZ treatment was
a risk factor for memory problems, constipation, and dry mouth. Both classes of
drugs were associated with somnolence. SSRIs were associated with abnormal
ejaculation, while BZs were associated with libido reduction. BZs were protective
against tachycardia, diaphoresis, fatigue, and insomnia. Conclusion: Randomized,
blinded studies comparing SSRIs and BZs for the short-term treatment of PD should
be performed. Clinical guidelines based on incontrovertible evidence are needed.
Objective To determine whether distraction techniques (DT) reduce
children's/adolescent's anxiety and fear during dental treatment. Methods
Randomized controlled trials (RCTs) in which any type of DT were used to manage
dental anxiety and dental fear in children/adolescents were included. A systematic
search of PubMed, Web of Science, Scopus, Cochrane Library, Lilacs, and Google
Scholar was conducted. Two independent reviewers selected studies, extracted data,
assessed methodological quality of studies using the Cochrane Collaboration's Risk
of Bias tool (CCRBT), and approached certainty of evidence using GRADE (Grading of
Recommendations, Assessment, Development and Evaluation). Data were analysed
descriptively. Results Twenty studies covering several types of DT (audio,
audiovisual, instruments camouflage, biofeedback, dental operating microscope,
toys) were included. Qualitative analysis showed with very low certainty of
evidence that DT effectively reduced dental anxiety and fear depending on the
distraction type, instrument used to measure dental anxiety and dental fear, and
dental procedure. CCRBT evaluation identified many methodological issues in
included studies. Conclusion There is a very low certainty of evidence that DT can
be effective in managing children's/adolescents' dental fear and anxiety during
dental treatment. The heterogeneity of methodologies and findings in the studies,
however, suggests more robust, and well-executed RCTs are needed.
Cognitive reappraisal and fear extinction learning represent two different
approaches to emotion regulation. While their respective neural correlates have
been widely studied with functional magnetic resonance imaging (fMRI), few direct
comparisons between these processes have been conducted. We conducted a meta-
analysis of fMRI studies of reappraisal and fear extinction, with the aim of
examining both commonalities and differences in their neural correlates. We also
conducted independent analyses that focused on specific reappraisal strategies
(reinterpretation, distancing). Overall, we observed that the dorsal anterior
cingulate cortex (dACC) and the bilateral anterior insular cortex (AIC) were
similarly consistently engaged by reappraisal and extinction. Extinction was more
consistently linked to activation of sensory and emotion processing regions,
whereas reappraisal was more consistently associated with activation of a dorsal
fronto-parietal network. Interestingly, the amygdala was preferentially deactivated
by distancing. These results suggest that the dACC and the AIC are involved in
domain-general regulatory networks. Differences between extinction and reappraisal
could be explained by their relative processing demands on visual perceptual versus
higher cognitive neural systems.
Objective: to verify if fear of falling is a risk factor in older people living in
the community. Methods: A systematic review was conducted with a meta-analysis
based on the Preferred Reporting Items for Systematic Reviews and MetaAnalyses. The
PECOS search strategy was used: Patient elderly person aged 60 years or above,
living in a community with a previous history of falls; Exposure Fear of falling.
Comparison group without fear of falling, "Outcome" fall outcome and "Studies"
included comparative observational studies. The searches e conducted in May 2018 in
the following electronic databases CINAHL, Medline, Cochrane, Embase, Lilacs,
PsycINFO and PEDro, through the following descriptors: "aged", "elderly", older
adults, fear, fear of falling, accidental falls, fall, falls. Cross-references and
gray literature were also searched. Two reviewers independently performed the
identification, selection, eligibility and incision of the studies. The
methodological quality of the studies was carried out by applying the STROBE tool.
For the meta analysis, the Review Mananger 5.3 Program was used (R). Results: 01
4.891 publications, five studies enabled a meta-analysis with 3,112 elderly. There
was a chance of a fall of 12.15 times higher for the group of elderly people with
fear of falling. Conclusion: fear of falling was identified as a risk factor for
falling in the elderly population that lives in the community and that has a
history of falling. it is necessary the investigation by health professionals in
order to establish preventive measures.
To conceptualize a novel bio-psychosocial-behavioral treatment model of panic
disorder (PD), it is necessary to completely integrate behavioral,
psychophysiological, neurobiological, and genetic data. Molecular genetic research
on PD is specifically focused on neurotransmitters, including serotonin,
neuropeptides, glucocorticoids, and neurotrophins. Although pharmacological
interventions for PD are currently available, the need for more effective, faster-
acting, and more tolerable pharmacological interventions is unmet. Thus,
glutamatergic receptor modulators, orexin receptor antagonists, corticotrophin-
releasing factor 1 receptor antagonists, and other novel mechanism-based anti-panic
therapeutics have been proposed. Research on the neural correlates of PD is focused
on the dysfunctional "cross-talk" between emotional drive (limbic structure) and
cognitive inhibition (prefrontal cortex) and the fear circuit, which includes the
amygdala-hippocampus-prefrontal axis. The neural perspective regarding PD supports
the idea that cognitive-behavioral therapy normalizes alterations in top-down
cognitive processing, including increased threat expectancy and attention to
threat. Consistent with the concept of "personalized medicine," it is speculated
that Research Domain Criteria can enlighten further treatments targeting
dysfunctions underlying PD more precisely and provide us with better definitions of
moderators used to identify subgroups according to different responses to
treatment. Structuring of the "negative valence systems" domain, which includes
fear/anxiety, is required to define PD. Therefore, targeting glutamate-and orexin-
related molecular mechanisms associated with the fear circuit, which includes the
amygdala-hippocampus-prefrontal cortex axis, is required to define a novel bio-
psychosocial-behavioral treatment model of PD.
The symptoms of post-traumatic stress disorder (PTSD) include cognitive impairment
related to medial prefrontal cortical dysfunction. Indeed, a deficit of cognitive
flexibility, i.e., an inability to modify previously learned thoughts and behaviors
based on changes in the environment, may underlie many of the other symptoms of
PTSD, such as changes in mood, hyper-arousal, intrusive thoughts, exaggerated and
over-generalized fear, and avoidance behavior. Cognitive-behavioral therapies
target the cognitive dysfunction observed in PTSD patients, training them to
recalibrate stress-related perceptions, interpretations and responses.
Preclinically, the extinction of conditioned fear bears resemblance to one form of
cognitive therapy, exposure therapy, whereby an individual learns, through repeated
exposure to a fear-provoking stimulus in a safe environment, that the stimulus no
longer signals imminent threat, and their fear response is suppressed. In this
review article, we highlight recent findings from our lab using fear extinction as
a preclinical model of exposure therapy in rodents exposed to chronic unpredictable
stress (CUS). We specifically focus on the therapeutic effects of extinction on
stress-compromised set-shifting as a measure of cognitive flexibility, and active
vs. passive coping behavior as a measure of avoidance. Finally, we discuss
mechanisms involving activity and plasticity in the medial prefrontal cortex (mPFC)
necessary for the therapeutic effects of extinction on cognitive flexibility and
active coping.
Emotions are complex reactions that allow individuals to cope with significant
positive and negative events. Research on emotion was pioneered by Darwin's work on
emotional expressions in humans and animals. But Darwin was concerned mainly with
facial and bodily expressions of significance for humans, citing mainly examples
from mammals (e.g., apes, dogs, and cats). In birds, emotional expressions are less
evident for a human observer, so a different approach is needed. Understanding
avian emotions will provide key evolutionary information on the evolution of
related behaviors and brain circuitry. Birds and mammals are thought to have
evolved from different groups of Mesozoic reptiles, theropod dinosaurs and
therapsids, respectively, and therefore, their common ancestor is likely to be a
basal reptile living about 300 million years ago, during the Carboniferous or
Permian period. Yet, birds and mammals exhibit extensive convergence in terms of
relative brain size, high levels of activity, sleep/wakefulness cycles, endothermy,
and social behavior, among others. This article focuses on two basic emotions with
negative valence: fear and frustration. Fear is related to the anticipation of
dangerous or threatening stimuli (e.g., predators or aggressive conspecifics).
Frustration is related to unexpected reward omissions or devaluations (e.g., loss
of food or sexual resources). These results have implications for an understanding
of the conditions that promote fear and frustration and for the evolution of
supporting brain circuitry.
Purpose of ReviewAnxiety- and trauma-related disorders are prevalent and
debilitating mental illnesses associated with a significant socioeconomic burden.
Current treatment approaches often have inadequate therapeutic responses, leading
to symptom relapse. Here we review recent preclinical and clinical findings on the
potential of cannabinoids as novel therapeutics for regulating fear and
anxiety.Recent FindingsEvidence from preclinical studies has shown that the non-
psychotropic phytocannabinoid cannabidiol and the endocannabinoid anandamide have
acute anxiolytic effects and also regulate learned fear by dampening its
expression, enhancing its extinction and disrupting its reconsolidation. The
findings from the relevant clinical literature are still very preliminary but are
nonetheless encouraging.SummaryBased on this preclinical evidence, larger-scale
placebo-controlled clinical studies are warranted to investigate the effects of
cannabidiol in particular as an adjunct to psychological therapy or medication to
determine its potential utility for treating anxiety-related disorders in the
future.
BackgroundIn the spring of 1918, the War to End All Wars, which would ultimately
claim more than 37 million lives, had entered into its final year and would change
the global political and economic landscape forever. At the same time, a new global
threat was emerging and would become one of the most devastating global health
crises in recorded history.Main textThe 1918 H1N1 pandemic virus spread across
Europe, North America, and Asia over a 12-month period resulting in an estimated
500 million infections and 50-100 million deaths worldwide, of which similar to 50%
of these occurred within the fall of 1918 (Emerg Infect Dis 12:15-22, 2006, Bull
Hist Med 76:105-115, 2002). However, the molecular factors that contributed to the
emergence of, and subsequent public health catastrophe associated with, the 1918
pandemic virus remained largely unknown until 2005, when the characterization of
the reconstructed pandemic virus was announced heralding a new era of advanced
molecular investigations (Science 310:77-80, 2005). In the century following the
emergence of the 1918 pandemic virus we have landed on the Moon, developed the
electronic computer (and a global internet), and have eradicated smallpox. In
contrast, we have a largely remedial knowledge and understanding of one of the
greatest scourges in recorded history.ConclusionHere, we reflect on the 1918
influenza pandemic, including its emergence and subsequent rapid global spread. In
addition, we discuss the pathophysiology associated with the 1918 virus and its
predilection for the young and healthy, the rise of influenza therapeutic research
following the pandemic, and, finally, our level of preparedness for future
pandemics.
Salinity is an ever-present major constraint and a major threat to legume crops,
particularly in areas with irrigated agriculture. Legumes demonstrate high
sensitivity, especially during vegetative and reproductive phases. This review
gives an overview of legumes sensitivity to salt stress (SS) and mechanisms to cope
with salinity stress under unfavorable conditions. It also focuses on the promising
management approaches, i.e., agronomic practices, breeding approaches, and genome
editing techniques to improve performance of legumes under SS. Now, the onus is on
researchers to comprehend the plants physiological and molecular mechanisms, in
addition to various responses as part of their stress tolerance strategy. Due to
their ability to fix biological nitrogen, high protein contents, dietary fiber, and
essential mineral contents, legumes have become a fascinating group of plants.
There is an immense need to develop SS tolerant legume varieties to meet growing
demand of protein worldwide. This review covering crucial areas ranging from
effects, mechanisms, and management strategies, may elucidate further the ways to
develop SS-tolerant varieties and to produce legume crops in unfavorable
environments.
Wildlife, as well as human beings, are prone to be affected by fear. Large
predators and mesopredators usually produce this fear in animals. This effect is
recognised in the form of various behavioural changes and adaptations, which, in
turn, affects the whole ecosystem. However, we often overlook the role of large
predators and mesopredators in the sustenance of our ecosystem by such non-lethal
effects, because fear is often seen as a psychological effect rather than something
that can be found through explicit scientific means. Indeed, the fear that
predators trigger inside their prey may play a significant role in the maintenance
of the natural environment. This paper aims to analyse this hypothesis by reviewing
the function of the ecology of fear based on the interaction among predators, prey,
and mesopredators. We consider the factors involved in the effective functionality
of the ecology of fear, including habitat landscape, season, weather, and predation
risk. We also assess the extent of influence of large predators on behaviour and
distribution of prey and mesopredators in terms of predation cues and prey grouping
as responses to predation risk. Finally, we discuss the implications of fear
ecology for wildlife conservation and management and new challenges.
Social behaviors largely constitute mutual exchanges of social cues and the
responses to them. The adaptive response also requires proper interpretation of the
current context. In fear behaviors, social signals have bidirectional effects-some
cues elicit or enhance fear whereas other suppress or buffer it. Studies on the
social facilitation and social buffering of fear provide evidence of competition
between social cues of opposing meanings. Co-expression of opposing cues by the
same animal may explain the contradicting outcomes from the interaction between
naive and frightened conspecifics, which reflect the fine balance between fear
facilitation and buffering. The neuronal mechanisms that determine that balance
provide an exciting target for future studies to probe the brain circuits
underlying social modulation of emotional behaviors.
Even though anyone can be exposed to traumatic events, only some people develop
posttraumatic stress disorder (PTSD). This disorder can affect in a variety of ways
and become a problem at physiological, personal, social and occupational levels,
among others. Although the causes that lead to the development, maintenance and/or
overcoming of PTSD are unknown, some biological hypotheses have been proposed that
could potentially explain an individual's predisposition to develop the disorder
(e.g.: neurogenesis). On the other hand, there are many studies that address the
importance of social support, the communication of emotional states and the use of
pharmacotherapy in PTSD treatment, in order to extinguish fear-related symptoms
with the main objective of eventually overcoming the trauma. The present article
exposes a review of the available evidence originated from research in animal
models, as well as clinical studies that approach this disorder from different
perspectives.
This review addresses recent developments in fear of movement-related pain and
avoidance research, adopting a contemporary learning approach focusing on
cognitive, emotional, and behavioral factors, and emphasizing the role of the
motivational context including pain-avoidance goals but also other valued life
goals. We particularly demonstrated the role of classical conditioning in the
acquisition, generalization, and extinction of fear of movement-related pain, and
how safety-seeking behavior during exposure-based treatment may hamper genuine
extinction causing relapse. We further highlighted the importance of newly
developed methods to study operant conditioning of behavioral avoidance itself, and
its relationship with individual vulnerability factors (e.g. catastrophizing) and
resiliencies (e.g. positive affect) to further our understanding of mechanisms
underlying the development and persistence of chronic pain disability.
Aims The aim of this study was to evaluate the prevalence of needle fear and
summarize the characteristics of individuals who exhibit this fear. Background
Injections are among the most common medical procedures, yet fear of needles can
result in avoidance of preventive measures and treatment. Design Systematic review
and meta-analysis. Data Sources MEDLINE (1966-2017), Embase (1947-2017), PsycINFO
(1967-2017), and CINAHL (1961-2017) were searched, with no restrictions by age,
gender, race, language, or country. Review Methods The prevalence of needle fear
was calculated and restricted maximum likelihood random effects models were used
for meta-analysis and meta-regression. Results The search yielded 119 original
research articles which are included in this review, of which 35 contained
sufficient information for meta-analysis. The majority of children exhibited needle
fear, while prevalence estimates for needle fear ranged from 20-50% in adolescents
and 20-30% in young adults. In general, needle fear decreased with increasing age.
Both needle fear and needle phobia were more prevalent in females than males.
Avoidance of influenza vaccination because of needle fear occurred in 16% of adult
patients, 27% of hospital employees, 18% of workers at long-term care facilities,
and 8% of healthcare workers at hospitals. Needle fear was common when undergoing
venipuncture, blood donation, and in those with chronic conditions requiring
injection. Conclusions Fear of needles is common in patients requiring preventive
care and in those undergoing treatment. Greater attention should be directed to
interventions which alleviate fear in high-risk groups.
Pain-related fear is considered a strong psychological predictor for both chronic
pain and disability. The aims of this study were to systematically review and
critically appraise the concurrent association and the predictive value of pain-
related fear affecting both pain intensity and disability in individuals with
chronic musculoskeletal pain (MSK). PubMed, AMED, CINAHL, PsycINFO, PubPsych, and
the grey literature were searched from inception to January 2019. Observational
studies reporting cross-sectional and longitudinal associations between pain-
related fear and pain intensity and/or disability were included. The GRADE criteria
judged whether the overall quality and strength of the evidence was high or low in
terms of risk of bias, inconsistency, indirectness, imprecision and publication
bias. Seventy observational studies (97% cross-sectional) were included with a
total sample of 15,623 individuals (63.56% females) with chronic MSK. Pain-related
fear is composed of fear of pain, pain related anxiety, and fear-avoidance beliefs.
Greater levels of fear of pain, pain-related anxiety, and fear-avoidance beliefs
were significantly associated with greater pain intensity and disability. However,
the quality and strength of the evidence was very low owing to the imprecision of
results, risk of bias, indirectness, and publication bias were common across the
included studies. Despite these limitations, these findings highlight the potential
role that pain-related fear may play in chronic MSK and disability. The field would
benefit from research using higher quality studies and longitudinal designs.
Perspective: This article presents promising results about the concurrent
association between pain related fear and both pain intensity and disability in
individuals with chronic MSK. Nevertheless, the overall quality and strength of the
evidence was very low in terms of risk of bias, indirectness, imprecision, and
publication bias. Thus, the findings should be taken with caution, and further
research is needed. PROSPERO: CRD42018082018 (C) 2019 by the American Pain Society
An understanding of how memory is acquired and how it can be modified in fear-
related anxiety disorders, with the enhancement of failing memories on one side and
a reduction or elimination of traumatic memories on the other, is a key unmet
challenge in the fields of neuroscience and neuropsychiatry. The latter process
depends on an important form of learning called fear extinction, where a previously
acquired fear-related memory is decoupled from its ability to control behaviour
through repeated non-reinforced exposure to the original fear-inducing cue.
Although simple in description, fear extinction relies on a complex pattern of
brain region and cell-type specific processes, some of which are unique to this
form of learning and, for better or worse, contribute to the inherent instability
of fear extinction memory. Here, we explore an emerging layer of biology that may
compliment and enrich the synapse-centric perspective of fear extinction. As
opposed to the more classically defined role of protein synthesis in the formation
of fear extinction memory, a neuroepigenetic view of the experience-dependent gene
expression involves an appreciation of dynamic changes in the state of the entire
cell: from a transient change in plasticity at the level of the synapse, to
potentially more persistent long-term effects within the nucleus. A deeper
understanding of neuroepigenetic mechanisms and how they influence the formation
and maintenance of fear extinction memory has the potential to enable the
development of more effective treatment approaches for fear-related
neuropsychiatric conditions.
Fear learning and extinction are controlled by the activity of three interconnected
regions: the amygdala, hippocampus, and prefrontal cortex. Of these, the medial
prefrontal cortex modulates specific aspects in fear and extinction via a top-down
regulation. In recent years, extensive progress has been made in our understanding
of the neural circuits that mediate fear-related behaviors and their modulation by
ascending systems. The development of new experimental techniques is now revealing
the details of the intrinsic circuits within these structures as well as the
connections between them. Here, we highlight recent advances in our understanding
of how the prefrontal cortex may mediate such a top-down regulation.
Threat processing is central to understanding debilitating fear- and trauma-related
disorders such as post-traumatic stress disorder (PTSD). Progress has been made in
understanding the neural circuits underlying the "engram'' of threat or fear memory
formation that complements a decades-old appreciation of the neurobiology of fear
and threat involving hub structures such as the amygdala. In this review, we
examine key recent findings, as well as integrate the importance of hormonal and
physiological approaches, to provide a broader perspective of how bodily systems
engaged in threat responses may interact with amygdala-based circuits in the
encoding and updating of threat-related memory. Understanding how trauma-related
memories are encoded and updated throughout the brain and the body will ultimately
lead to novel biologically-driven approaches for treatment and prevention.
Aim To conduct a meta-study of qualitative empirical research to explore the links
between patient safety and fear of childbirth in the maternity care context. The
review questions were: How are patient safety and fear of childbirth described? and
What are the links between patient safety and fear of childbirth in the maternity
care context? Design Data sources Meta-study. The CINAHL, Cochrane, PubMed, Webb of
Science, Proquest and Medline (Ovid) electronic databases were searched for
articles published between June 2000-June 2016. Review methods Results APPENDIX A
meta-study of qualitative research with a thematic analysis followed by a
synthesis. Four descriptive themes emerged: "Physical risks associated with giving
birth vaginally"; "Control and safety issues"; "Preventing psychological maternal
trauma and optimizing foetal well-being"; and "Fear of the transition to motherhood
due to lack of confidence". The two overarching analytical themes: "Opting for
safety" and "An insecure environment breeds fear of childbirth", represent a deeper
understanding and constitute the synthesis of the links between patient safety and
fear of childbirth. This meta-study indicates the need for increased commitment to
safe care and professional support to reduce risks and prevent unnecessary harm in
maternity care.
The amygdala and, more recently, also the bed nucleus of the stria terminalis, have
been widely implicated in fear and anxiety. Much of our current knowledge is
derived from animal studies and suggests an intricate convergence and divergence in
functions related to defensive responding. In a recent paper, Klumpers and
colleagues set out to examine these functions in a human fear learning procedure
using functional magnetic resonance imaging. Their main findings were a role for
the bed nucleus of the stria terminalis in threat anticipation, and for the
amygdala in threat confrontation. Here, we provide a critical summary of this
interesting study and point out some important issues that were not addressed by
its authors. In particular, we first take a closer look at the striking differences
between both samples that were combined for the study, and, secondly, we provide an
in-depth discussion of their findings in relation to existing neurobehavioral
models.
Rationale The ability to memorize threat-associated cues and subsequently react to
them, exhibiting escape or avoidance responses, is an essential, often life-saving
behavioral mechanism that can be experimentally studied using the fear (threat)
conditioning training paradigm. Presently, there is substantial evidence supporting
the Synaptic Plasticity-Memory (SPM) hypothesis in relation to the mechanisms
underlying the acquisition, retention, and extinction of conditioned fear memory.
Objectives The purpose of this review article is to summarize findings supporting
the SPM hypothesis in the context of conditioned fear control, applying the set of
criteria and tests which were proposed as necessary to causally link lasting
changes in synaptic transmission in corresponding neural circuits to fear memory
acquisition and extinction with an emphasis on their pharmacological diversity.
Results The mechanisms of synaptic plasticity in fear circuits exhibit complex
pharmacological profiles and satisfy all four SPM criteria-detectability,
anterograde alteration, retrograde alteration, and mimicry. Conclusion The reviewed
findings, accumulated over the last two decades, provide support for both necessity
and sufficiency of synaptic plasticity in fear circuits for fear memory acquisition
and retention, and, in part, for fear extinction, with the latter requiring
additional experimental work.
Purpose Fear of cancer recurrence (FCR) affects 50-70% of cancer survivors.
Evidence-based psychological interventions for FCR are effective but
resource-/time-consuming. This systematic review identified interventions by non-
mental health specialists addressing FCR, evidence of a relationship between
specialist communication and FCR and stakeholder perspectives on how specialist
communication can address FCR. Methods A systematic literature review was conducted
using nine databases (Medline Ovid, EMBASE, Cochrane, CINAHL, Scopus, PsychINFO,
Informit, Web of Science and Google Scholar). Included studies were English,
published 1997-2018, on adult cancer patients examining 'fear'/'worry' and 'cancer
recurrence'/'progression' and 'health communication'/'medical
encounter'/'interventions'. Data was extracted, summarised and rated for quality by
two authors. Results Of 6248 articles screened, 16 were included. No phase III
randomised controlled trials were found. Five studies piloted an intervention,
three were correlational studies, five were cross-sectional patient surveys and
three were specialist surveys. Four out of five interventional studies were nurse-
led: one trained patients in discussing FCR with their specialist while three
delivered supportive counselling and/or taught strategies to manage FCR. The last
intervention trained mixed health professionals to manage FCR through
normalisation, education and lifestyle strategies. Three intervention studies
measured FCR objectively, and two demonstrated a reduction in FCR in the short
term. Consultation duration, empathy and clear information delivery were associated
with FCR. Patients indicated desire to discuss FCR; however, specialists indicated
discomfort with managing FCR. Conclusions Research on non-mental health
practitioner-led interventions to address FCR is lacking. Further studies on
whether specialist interventions delivered during follow-up consultations are
useful in managing FCR are required.
Depression and panic disorder (PD) share the common pathophysiology from the
perspectives of neuro-transmitters. The relatively high comorbidity between
depression and PD contributes to the substantial obstacles to differentiate from
depression and PD, especially for the brain pathophysiology. There are significant
differences in the diagnostic criteria between depression and PD. However, the
paradox of similar pathophysiology and different diagnostic criteria in these two
disorders were still the issues needing to be addressed. Therefore the
clarification of potential difference in the field of neuroscience and
pathophysiology between depression and PD can help the clinicians and scientists to
understand more comprehensively about significant differences between depression
and PD. The researchers should be curious about the underlying difference of
pathophysiology beneath the significant distinction of clinical symptoms. In this
review article, I tried to find some evidences for the differences between
depression and PD, especially for neural markers revealed by magnetic resonance
imaging (MRI). The distinctions of structural and functional alterations in
depression and PD are reviewed. From the structural perspectives, PD seems to have
less severe gray matter alterations in frontal and temporal lobes than depression.
The study of white matter microintegrity reveals more widespread alterations in
fronto-limbic circuit of depression patients than PD patients, such as the uncinate
fasciculus and anterior thalamic radiation. PD might have a more restrictive
pattern of structural alterations when compared to depression. For the functional
perspectives, the core site of depression pathophysiology is the anterior
subnetwork of restingstate network, such as anterior cingulate cortex, which is not
significantly altered in PD. A possibly emerging pattern of fronto-limbic
distinction between depression and PD has been revealed by these explorative
reports. The future trend for machine learning and pattern recognition might
confirm the differentiation pattern between depression and PD based on the
explorative results.
The core concept for pathophysiology in panic disorder (PD) is the fear network
model (FNM). The alterations in FNM might be linked with disturbances in the
autonomic nervous system (ANS), which is a common phenomenon in PD. The traditional
FNM included the frontal and limbic regions, which were dysregulated in the
feedback mechanism for cognitive control of frontal lobe over the primitive
response of limbic system. The exaggerated responses of limbic system are also
associated with dysregulation in the neurotransmitter system. The neuroimaging
studies also corresponded to FNM concept. However, more extended areas of FNM have
been discovered in recent imaging studies, such as sensory regions of occipital,
parietal cortex and temporal cortex and insula. The insula might integrate the
filtered sensory information via thalamus from the visuospatial and other sensory
modalities related to occipital, parietal and temporal lobes. In this review
article, the traditional and advanced FNM would be discussed. I would also focus on
the current evidences of insula, temporal, parietal and occipital lobes in the
pathophysiology. In addition, the white matter and functional connectome studies
would be reviewed to support the concept of advanced FNM. An emerging dysregulation
model of fronto-limbic-insula and temporo-occipitoparietal areas might be revealed
according to the combined results of recent neuroimaging studies. The future
delineation of advanced FNM model can be beneficial from more extensive and
advanced studies focusing on the additional sensory regions of occipital, parietal
and temporal cortex to confirm the role of advanced FNM in the pathophysiology of
PD.
Neuroimaging studies in the area of mindfulness research have provided preliminary
support for the idea of fear extinction as a plausible underlying mechanism through
which mindfulness exerts its positive benefits. Whilst brain regions identified in
the fear extinction network are typically found at a subcortical level, studies
have also demonstrated the feasibility of cortical measures of the brain, such as
electroencephalogram (EEG), in implying subcortical activations of the fear
extinction network. Such EEG studies have also found evidence of a relationship
between brain reactivity to unpleasant stimuli (i.e., fear extinction) and severity
of posttraumatic stress symptoms (PTSS). Therefore, the present paper seeks to
briefly review the parallel findings between the neurophysiological literature of
mindfulness and fear extinction (particularly that yielded by EEG measures), and
discusses the implications of this for fear-based psychopathologies, such as
trauma, and finally presents suggestions for future studies. This paper also
discusses the clinical value in integrating EEG in psychological treatment for
trauma, as it holds the unique potential to detect neuromarkers, which may enable
earlier diagnoses, and can also provide neurofeedback over the course of treatment.
This meta-analysis examined the associations between the fears of compassion and
mental health. We extracted 19 studies reporting 154 effect sizes (Pearson's r)
from 22 independent samples published during the last seven years, with data from
4723 participants. All studies used the Fears of Compassion Scales (FCS), which
includes three subscales; fears of compassion for self, for others, and receiving
from others. Specific mental health outcomes included: depression; anxiety;
distress; and well-being, as well as the psychological vulnerability factors of
self-criticism and shame. The overall association between the three FCS subscales
and mental health difficulties was .49, .30 and .48 for fears of self-compassion,
fears of compassion for others, and fears of compassion from others, respectively.
Across mental health domains and vulnerability factors, pooled effect sizes ranged
between r = .13 and .55 (in absolute value), with the strongest associations found
between the mental health variables of shame, self-criticism, and depression, and
the FCS subscales of fears of self-compassion and fears of receiving compassion.
Moderator analyses were also conducted, including, age, gender, publication status,
and sample (clinical vs. non-clinical). Overall, clinical populations demonstrated
significantly stronger associations between mental health difficulties and fears of
self-compassion, relative to non-clinical populations.
Empathy enables social mammals to recognize and share emotion with others and is
well-documented in non-human primates. During the past few years, systematic
observations have showed that a primal form of empathy also exists in rodents,
indicating that empathy has an evolutionary continuity. Now, using rodents
exhibiting emotional empathy, the molecular and cellular study of empathy in
animals has begun in earnest. In this article, we will review recent reports that
indicate that rodents can share states of fear with others, and will try to
highlight new understandings of the neural circuitry, biochemistry and genetics of
empathic fear. We hope that the use of rodent models will enhance understanding of
the mechanisms of human empathy and provide insights into how to treat social
deficits in neuropsychiatric disorders characterized by empathy impairment.
Post-traumatic stress disorder (PTSD) is a psychiatric disorder associated with
memories of traumatic experiences. Conditioned fear memory, a representative model
of traumatic memories, is observed across species from lower to higher animals,
including humans. Numerous studies have investigated the mechanisms ofconditioned
fear memory and have led to the identification of the underlying processes involved
in fear memory regulation, including cellular and systems consolidation of fear
conditioning, destabilization/reconsolidation and extinction after fear memory
retrieval, and forgetting of fear memory. These studies suggested that mechanisms
for fear memory regulation are shared by humans and other higher animals.
Additionally, rodent studies have identified the mechanisms of fear memory at the
molecular, cellular, and circuit levels. Findings from these studies in rodents
have been applied to facilitate the development and improvement of PTSD
intervention. For instance, reconsolidation and extinction of fear memories have
been applied for PTSD treatment to improve prolonged exposure (PE) therapy, an
effective psychotherapy for PTSD. Combination of medications weakening retrieved
traumatic memory (e.g., by facilitating both destabilization and extinction) with
PE therapy may contribute to improvement of PTSD. Interestingly, a recent study in
mice identified forgetting of fear memory as another potential therapeutic target
for PTSD. A better understanding of the mechanisms involved in fear memory
processes is likely to facilitate the development of better treatments for PTSD.
This review describes fear memory processes and their mechanisms and discusses the
pros and cons of applying how this knowledge can be applied in the development of
interventions for PTSD.
Observational fear learning in rodent, is a type of context-dependent fear
conditioning in which an unconditioned stimulus (US) is provided vicariously by
observing conspecific others receiving foot shocks. This suggests the involvement
of affective empathy, with several recent studies showing many similarities between
this behavior and human empathy. Neurobiologicallv. it is important to understand
the neural mechanisms by which the vicarious US activates the fear circuit via the
affective pain system, obviating the sensory pain pathway and eventually leading to
fear memory formation. This paper reviews current studies on the neural mechanisms
underlying observational fear learning and provides a perspective on future
research on this subject.
The present paper aims to describe a case of a schizophrenia spectrum disorder
relapse leading to attempted murder, review literature, and investigate the
epidemiological data and expression of violent behavior among Capgras-related
incidents. 109 case reports deriving from various scientific areas dating from 1971
to 2017 were evaluated and juxtaposed with an equivalent comparison group of random
psychiatry inpatients, who were examined for the same variables. Quantitative and
qualitative differences were observed between samples. High level of interpersonal
violence was disclosed among Capgras-related incidents, especially towards the main
care-givers, with higher propensity among male patients. Homicidal behavior was
also expressed in higher levels among male patients experiencing the Capgras
delusion. A multidisciplinary approach is vital for the optimal management of these
incidents. Further research on the pathophysiology of Capgras delusion with the
utilization of functional imaging techniques is of exceptional significance for the
understanding of issues of neuroscience.
Despite its relatively well-understood role as a reproductive and pro-social
peptide, oxytocin (OT) tells a more convoluted story in terms of its modulation of
fear and anxiety. This nuanced story has been obscured by a great deal of research
into the therapeutic applications of exogenous OT, driving more than 400 ongoing
clinical trials. Drawing from animal models and human studies, we review the
complex evidence concerning OT's role in fear learning and anxiety, clarifying the
existing confusion about modulation of fear versus anxiety. We discuss animal
models and human studies demonstrating the prevailing role of OT in strengthening
fear memory to a discrete signal or cue, which allows accurate and rapid threat
detection that facilitates survival. We also review ostensibly contrasting
behavioral studies that nonetheless provide compelling evidence of OT attenuating
sustained contextual fear and anxiety-like behavior, arguing that these OT effects
on the modulation of fear vs. anxiety are not mutually exclusive. To disambiguate
how endogenous OT modulates fear and anxiety, an understudied area compared to
exogenous OT, we survey behavioral studies utilizing OT receptor (OTR) antagonists.
Based on emerging evidence about the role of OTR in rat dorsolateral bed nucleus of
stria terminalis (BNST) and elsewhere, we postulate that OT plays a critical role
in facilitating accurate discrimination between stimuli representing threat and
safety. Supported by human studies, we demonstrate that OT uniquely facilitates
adaptive fear but reduces maladaptive anxiety. Last, we explore the limited
literature on endogenous OT and its interaction with corticotropin-releasing factor
(CRF) with a special emphasis on the dorsolateral BNST, which may hold the key to
the neurobiology of phasic fear and sustained anxiety.
Purpose of ReviewThe purpose of this paper is to provide a current review of the
recent literature (2015-2018) on psychophysiological markers of fear and
anxiety.Recent FindingRelative to healthy controls, fear-based disorders are
characterised by heightened physiological reactivity to circumscribe threat salient
stimuli, whereas anxiety-related disorders are associated with a more blunted
pattern of physiological reactivity.SummaryFear and anxiety disorders are marked by
abnormal patterns of physiological reactivity, characterised by hyper- and hypo-
reactivity in response to stimuli varying in threat salience.
Fears of cancer recurrence (FCR) in patients with breast cancer may develop during
radiotherapy. Radiographer communication with their patients may influence early
survivorship FCR level.AimTo investigate the management of emotional talk in
patients with breast cancer attending their initial review appointments during
radiotherapy and predict FCR at 6-8weeks follow-up.MethodsA mixed-methods
observational study was conducted. Patients (consecutive sample, n=60) with breast
cancer, attending a major Scottish cancer centre, had their first two review
appointments with their therapeutic radiographer (TR) audio-recorded. In addition,
FCR was assessed (FCR7) at baseline and at 6-8weeks following their final
radiotherapy visit. Two TRs participated. Audio files were coded by the VR-CoDES
system to identify emotional cues and therapeutic radiographer (TR) responses.
Linear regression models were tested for fit and to identify factors associated
with follow-up FCR, i.e. patient cues, responses by TR.ResultsFollow-up FCR was
predicted negatively (robust estimator, p=.01) by level of patient emotional talk
at the second review session. The provision of space by the TR, at the second
session, to enable patients to expand their emotional utterances was also
associated, but negatively (p=.01), with follow-up FCR. These effects were
maintained after inclusion of covariates: age, treatment received and living
conditions.ConclusionsPatient's emotional expression and TR responses at the second
review meeting predicted follow-up FCR. The study shows the effect of communication
processes on this specific distress component of the patient's survivorship
experience.Trial registrationNCT02599506
Odors have proven to be the most resilient trigger for memories of high emotional
saliency. Fear associated olfactory memories pose a detrimental threat of
potentially transforming into severe mental illness such as fear and anxiety-
related disorders. Many studies have deliberated on auditory, visual and general
contextual fear memory (CFC) processes; however, fewer studies have investigated
mechanisms of olfactory fear memory. Evidence strongly suggests that the
neuroanatomical representation of olfactory fear memory differs from that of
auditory and visual fear memory. The aim of this review article is to revisit the
literature regarding the understanding of the neurobiological process of fear
conditioning and to illustrate the circuitry of olfactory fear memory.
Background. The three terms "panic", "irrationality", and "herding" are ubiquitous
in the crowd dynamics literature and have a strong influence on both modelling and
management practices. The terms are also commonly shared between the scientific and
nonscientific domains. The pervasiveness of the use of these terms is to the point
where their underlying assumptions have often been treated as common knowledge by
both experts and lay persons. Yet, at the same time, the literature on crowd
dynamics presents ample debate, contradiction, and inconsistency on these topics.
Method. This review is the first to systematically revisit these three terms in a
unified study to highlight the scope of this debate. We extracted from peer-
reviewed journal articles direct quotes that offer a definition, conceptualisation,
or supporting/contradicting evidence on these terms and/or their underlying
theories. To further examine the suitability of the term herding, a secondary and
more detailed analysis is also conducted on studies that have specifically
investigated this phenomenon in empirical settings. Results. The review shows that
(i) there is no consensus on the definition for the terms panic and irrationality
and that (ii) the literature is highly divided along discipline lines on how
accurate these theories/terminologies are for describing human escape behaviour.
The review reveals a complete division and disconnection between studies published
by social scientists and those from the physical science domain and also between
studies whose main focus is on numerical simulation versus those with empirical
focus. (iii) Despite the ambiguity of the definitions and the missing consensus in
the literature, these terms are still increasingly and persistently mentioned in
crowd evacuation studies. (iv) Different to panic and irrationality, there is
relative consistency in definitions of the term herding, with the term usually
being associated with "(blind) imitation'. However, based on the findings of
empirical studies, we argue why, despite the relative consistency in meaning, (v)
the term herding itself lacks adequate nuance and accuracy for describing the role
of "social influence' in escape behaviour. Our conclusions also emphasise the
importance of distinguishing between the social influence on various aspects of
evacuation behaviour and avoiding generalisation across various behavioural layers.
Conclusions. We argue that the use of these three terms in the scientific
literature does not contribute constructively to extending the knowledge or to
improving the modelling capabilities in the field of crowd dynamics. This is
largely due to the ambiguity of these terms, the overly simplistic nature of their
assumptions, or the fact that the theories they represent are not readily
verifiable. Recommendations. We suggest that it would be beneficial for advancing
this research field that the phenomena related to these three terms are clearly
defined by more tangible and quantifiable terms and be formulated as verifiable
hypotheses, so they can be operationalized for empirical testing.
Translational neuroscience bridges insights from specific mechanisms in rodents to
complex functions in humans and is key to advance our general understanding of
central nervous function. A prime example of translational research is the study of
cross-species mechanisms that underlie responding to learned threats, by employing
Pavlovian fear conditioning protocols in rodents and humans. Hitherto, evidence for
(and critique of) these cross-species comparisons in fear conditioning research was
based on theoretical viewpoints. Here, we provide a perspective to substantiate
these theoretical concepts with empirical considerations of cross-species
methodology. This meta-research perspective is expected to foster cross-species
comparability and reproducibility to ultimately facilitate successful transfer of
results from basic science into clinical applications.
Background Comorbidity of anxiety disorders, stressor- and trauma-related
disorders, and substance use disorders is extremely common. Moreover, therapies
that reduce pathological fear and anxiety on the one hand, and drug-seeking on the
other, often prove short-lived and are susceptible to relapse. Considerable
advances have been made in the study of the neurobiology of both aversive and
appetitive extinction, and this work reveals shared neural circuits that contribute
to both the suppression and relapse of conditioned responses associated with trauma
or drug use. Objectives The goal of this review is to identify common neural
circuits and mechanisms underlying relapse across domains of addiction biology and
aversive learning in preclinical animal models. We focus primarily on neural
circuits engaged during the expression of relapse. Key findings After extinction,
brain circuits involving the medial prefrontal cortex and hippocampus come to
regulate the expression of conditioned responses by the amygdala, bed nucleus of
the stria terminalis, and nucleus accumbens. During relapse, hippocampal
projections to the prefrontal cortex inhibit the retrieval of extinction memories
resulting in a loss of inhibitory control over fear- and drug-associated
conditional responding. Conclusions The overlapping brain systems for both fear and
drug memories may explain the co-occurrence of fear and drug-seeking behaviors.
Animals experience varying levels of predation risk as they navigate heterogeneous
landscapes, and behavioral responses to perceived risk can structure ecosystems.
The concept of the landscape of fear has recently become central to describing this
spatial variation in risk, perception, and response. We present a framework linking
the landscape of fear, defined as spatial variation in prey perception of risk, to
the underlying physical landscape and predation risk, and to resulting patterns of
prey distribution and antipredator behavior. By disambiguating the mechanisms
through which prey perceive risk and incorporate fear into decision making, we can
better quantify the nonlinear relationship between risk and response and evaluate
the relative importance of the landscape of fear across taxa and ecosystems.
Anxiety disorders impose a staggering burden on public health, underscoring the
need to develop a deeper understanding of the distributed neural circuits
underlying extreme fear and anxiety. Recent work highlights the importance of the
central extended amygdala, including the central nucleus of the amygdala (Ce) and
neighboring bed nucleus of the stria terminalis (BST). Anatomical data indicate
that the Ce and BST form a tightly interconnected unit, where different kinds of
threat-relevant information can be integrated to assemble states of fear and
anxiety. Neuroimaging studies show that the Ce and BST are engaged by a broad
spectrum of potentially threat-relevant cues. Mechanistic work demonstrates that
the Ce and BST are critically involved in organizing defensive responses to a wide
range of threats. Studies in rodents have begun to reveal the specific molecules,
cells, and microcircuits within the central extended amygdala that underlie signs
of fear and anxiety, but the relevance of these tantalizing discoveries to human
experience and disease remains unclear. Using a combination of focal perturbations
and whole-brain imaging, a new generation of nonhuman primate studies is beginning
to close this gap. This work opens the door to discovering the mechanisms
underlying neuroimaging measures linked to pathological fear and anxiety, to
understanding how the Ce and BST interact with one another and with distal brain
regions to govern defensive responses to threat, and to developing improved
intervention strategies.
Introduction: Historically, substance use prevention relied heavily on scare
tactics and fear-based messages. However, these messages were discouraged from use
due to research finding them ineffective or harmful. This review sought to
determine if recent research continues to support this finding. Methods: We
conducted a literature review of relevant peer-reviewed studies from 2005 to 2017,
categorising results as showing clear evidence of effectiveness, mixed evidence of
effectiveness or no evidence of effectiveness. Research on historical scare tactics
and fear-based messages was reviewed as a baseline and research on related
theoretical models was reviewed for context. Results: We identified 17 studies that
met our inclusion criteria: 10 targeting tobacco use, five targeting alcohol use,
one targeting marijuana use and one targeting methamphetamine use. Eight (8)
studies found that these messages were more effective at influencing substance use-
related measures than positive emotion prevention messages or control messages.
Five (5) studies found mixed evidence, and four (4) studies found no evidence of
effectiveness. Discussion: Though not conclusive, our results suggest that these
messages may be more effective than previously shown. However, many of the studied
messages differed in tone and content from similar, historical messages.
Organizations interested in implementing these messages should note these
differences.
Background: Fear of Public Speaking (FoPS) or public speaking anxiety is a type of
social anxiety and the single most commonly feared situation in the population.
FoPS is disabling with negative occupational, academic, and social consequences,
reported by up to one third of the population. FoPS in adolescence and adulthood is
associated with an increased risk of developing generalized social anxiety disorder
with further impairments. Since the last review on FoPS, a significant number of
randomized controlled trials (RCTs) have been conducted assessing the effects of
novel interventions with innovative modes of delivery. Objectives: The objectives
of the presentmeta-analysis are to (1) examine the short and long-term effects of
psychological interventions aimed at FoPS on FoPS and generalized social anxiety;
(2) assess whether differences exist between technology-assisted modes of delivery
(e.g., Internet-delivered therapies) and more traditional modes of delivering
treatment (e.g., face-to-face therapies); (3) investigate whether differences in
effect exist between theoretical frameworks; (4) inspect the differences in effect
size between self-report measures and other measures (i.e., physiological and
behavioral); (5) examine the effects of psychological interventions aimed at FoPS
on secondary outcome measures (e.g., depression); and (6) investigate whether a
"sleeper effect" is present for psychological interventions for FoPS and
generalized social anxiety. Methods: The study investigates the effects of
psychological interventions for FoPS through a quantitative meta-analysis of RCTs,
using a random-effects model. Results: A total of 30 RCTs with 1,355 participants
were included through systematic searches of PsycINFO, MEDLINE, Web of Science, and
Cochrane Library. The majority of the studies investigated the effects of cognitive
or behavioral interventions. Nearly half of the studies used active control groups
(e.g., attention placebo), whereas the other half used passive (e.g., waitlist)
controls. The overall effect of psychological interventions for FoPS across 62
interventions was 0.74 (Hedges g; 95% CI: 0.61-0.87) with low to moderate
heterogeneity. No difference in effect was found across theoretical frameworks. The
effects based on self-report measures were larger compared to physiological and
behavioral outcomes. Effects were robust against both active and passive control
groups. Furthermore, psychological interventions for FoPS had a small to moderate
effect on generalized social anxiety disorder (g = 0.35; 95% CI: 0.22-0.48). The
effect of psychological interventions aimed at FoPS at follow-up was large (g =
1.11, 95% CI: 0.90-1.31) and moderate to large for generalized social anxiety (g =
0.70, 95% CI: 0.59-0.80). A sleeper effect was found for cognitive and behavioral
interventions, indicating that patients continued to improve after treatment
termination. There were some indications of publication bias. Conclusions:
Psychological interventions are effective in reducing FoPS. Interventions using
technology-assisted modes of delivery are equally effective as traditional face-to-
face interventions in reducing FoPS. This finding highlights an opportunity to
increase access to evidence-based treatments through technology-delivered
interventions, which can be implemented at schools, in primary care and specialist
mental health care. Moreover, psychological interventions aimed at FoPS have an
effect on generalized social anxiety. Further implications are discussed.
Problem: Fear of childbirth negatively affects women during pregnancy and after
birth. Aim: To summarise the findings of published studies regarding possible
causes/predisposing factors and outcomes of fear of childbirth for childbearing
women. Design: A systematic review, searching five databases in March 2015 for
studies on causes/predisposing factors and outcomes of fear of childbirth, as
measured during pregnancy and postpartum. Quality of included studies was assessed
independently by pairs of authors. Data were extracted independently by reviewer
pairs and described in a narrative analysis. Findings: Cross-sectional, register-
based and case-control studies were included (n = 21). Causes were grouped into
population characteristics, mood-related aspects, and pregnancy and birth-related
aspects. Outcomes were defined as mood-related or pregnancy and birth-related
aspects. Differing definitions of fear of childbirth were found and meta-analysis
could only be performed on parity, in a few studies. Conclusions: Stress, anxiety,
depression and lack of social support are associated with fear during pregnancy.
Need for psychiatric care and presence of traumatic stress symptoms are reported
outcomes together with prolonged labour, longer labours, use of epidural and
obstetric complications. Nulliparous and parous women have similar levels of fear
but for different reasons. Since the strongest predictor for fear in parous women
is a previous negative birth experience or operative birth, we suggest it is
important to distinguish between fear of childbirth and fear after birth. Findings
demonstrate the need for creating woman-centred birthing environments where women
can feel free and secure with low risk of negative or traumatic birth experiences
and consequent fear. (c) 2018 Australian College of Midwives. Published by Elsevier
Ltd. All rights reserved.
Background: Culture is an important factor to determine fear of childbirth which is
shaped by social learning processes. The purpose of this study is to determine the
level of fear of childbirth among Turkish healthy pregnant women. Method: The
researchers reviewed the eight databases considering inclusion criteria and 14
studies were included. The data analysis was conducted using meta-analysis.
Results: Pregnant women experienced severe levels of fear, 67.26 +/- 4.08, 95%
confidence interval [59.26, 75.26], and 21 out of every 100 women experienced
clinical level of fear. Between study variance was significant for parity (Qb =
6.40, p = .04) and region (Qb = 19.14, p = .00) moderators. Conclusions: The high
level of FOC, particularly in the Eastern region, suggests that some of the
cultural factors in the Eastern region in Turkey negatively affect the birth
expectations. In a country like Turkey with a multicultural population, the health
care professional should provide culturally sensitive care.
INTRODUCTION: The management of anxiety and fear of patients experiencing medical
treatment is always a major issue. Dentistry is a branch of medicine that is daily
in managing these problems, especially in the case of pediatric patients.
Odontophobia can be managed in different ways, and the purpose of this study is to
eventually review which methods are currently accepted and which are the most
effective. EVIDENCE ACQUISITION: The literature analysis was conducted on a number
of articles, suitably skimmed, after a first research, obtained from the most
common scientific databases. The number of works included in the review is 28.
EVIDENCE SYNTHESIS: From the RCTs evaluated we could highlight that there are
different methods in the literature, equally effective and certainly conditioned by
the systemic condition of the patient. Another chapter instead turns out to be that
linked to the management of the syndromic patient. CONCLUSIONS: It is clear that
there are different methods and equally different ways to manage our patients in
the event of non-cooperation in the case of dental care. In addition to proper
management by the clinician, in the literature methods linked to audiovisual
distractions, hypnosis or pharmacological methods that produce conscious sedation
are effectively reported.
This is a comment on Minds Without Fear.
Objective Classifying mental disorders on the basis of objective makers might
clarify their aetiology, help in making the diagnosis, identify "at risk"
individuals, determine the severity of mental illness, and predict the course of
the disorder. This study aims to review biological and clinical markers of panic
disorder (PD). Methods A computerized search was carried out in PubMed and Science
Direct using the key words: "marker/biomarker/clinical marker/neurobiology/staging"
combined using Boolean AND operator with "panic." In addition, the reference lists
from existing reviews and from the articles retrieved were inspected. Only English
language papers published in peer-reviewed journals were included. Results
Structural changes in the amygdala, hippocampus, cerebral blood level in the left
occipital cortex, serotonin 5-TH and noradrenergic systems activation, aberrant
respiratory regulation, hearth rate variability, blood cells and peripheral blood
stem cells, hypothalamic-pituitary-adrenal axis dysregulation were identified as
potential candidate biomarkers of PD. Staging was identified as clinical marker of
PD. According to the staging model, PD is described as follows: prodromal phase
(stage 1); acute phase (stage 2); panic attacks (stage 3); chronic phase (stage 4).
Conclusion The clinical utility, sensitivity, specificity, and the predictive value
of biomarkers for PD is still questionable. The staging model of PD might be a
valid susceptibility, diagnostic, prognostic, and predictive marker of PD. A
possible longitudinal model of biological and clinical markers of PD is proposed.
Post-traumatic stress disorder (PTSD) is a debilitating disease with relatively
high lifetime prevalence. It is marked by a high diversity of symptoms and
comorbidity with other psychiatric disease. Furthermore, PTSD has a high level of
origin and symptom heterogeneity within the population. These characteristics taken
together make it one of the most challenging diseases to effectively model in
animals. However, with relatively little headway made in developing effective
disease interventions, PTSD remains as a high priority target for animal model
study. Learned Helplessness (LH) is a procedure classically used to model
depression, but has in recent years transitioned to use as a model of PTSD. Animals
in this procedure receive 100 inescapable and unpredictable tailshocks or simple
restraint without shock. The following day, the animals are tested in a shuttle
box, where inescapably-shocked subjects exhibit exaggerated fear and profound de fi
cit in escape performance. Stress-enhanced fear learning (SEFL) also uses an acute
(single session) stressor for modeling PTSD in rodents. The SEFL procedure begins
with exposure to 15 footshocks or simple context exposure without shock. Animals
that initially received the 15 footshocks exhibit future enhanced fear learning. In
this review, we will compare the behavior, physiology, and interventions of these
two animal models of PTSD. Despite considerable similarity (a single session
containing inescapable and uncontrollable shock) the two procedures produce a very
divergent set of behavioral consequences.
Survival in a natural environment forces an individual into constantly adapting
purposive behavior. Specified interoceptive neurons monitor metabolic and
physiological balance and activate dedicated brain circuits to satisfy essential
needs, such as hunger, thirst, thermoregulation, fear, or anxiety. Neuropeptides
are multifaceted, central components within such life-sustaining programs. For
instance, nutritional depletion results in a drop in glucose levels, release of
hormones, and activation of hypothalamic and brainstem neurons. These neurons, in
turn, release several neuropeptides that increase food-seeking behavior and promote
food intake. Similarly, internal and external threats activate neuronal pathways of
avoidance and defensive behavior. Interestingly, specific nuclei of the
hypothalamus and extended amygdala are activated by both hunger and fear. Here, we
introduce the relevant neuropeptides and describe their function in feeding and
emotional-affective behaviors. We further highlight specific pathways and
microcircuits, where neuropeptides may interact to identify prevailing homeostatic
needs and direct respective compensatory behaviors. A specific focus will be on
neuropeptide Y, since it is known for its pivotal role in metabolic and emotional
pathways. We hypothesize that the orexigenic and anorexigenic properties of
specific neuropeptides are related to their ability to inhibit fear and anxiety.
Aims To systematically review the evidence and determine the effectiveness of
cognitive behaviour therapy-based multicomponent interventions on fear of falling
and falls among community-dwelling older adults who are at risk of falling. Design
A systematic review and meta-analysis. Data Sources Six electronic databases,
including CENTRAL, CINAHL, EMBASE, PubMed, PsycInfo and Scopus, were searched.
Studies published in English from January 1998-July 2018 were included in this
review. Review Methods Only randomized controlled trials addressing fear of falling
and/or the occurrence of falls using cognitive behaviour therapy-based
multicomponent interventions were included. A standard procedure based on the
Cochrane Handbook for Systematic Reviews of Interventions was used to assess the
risk of bias of the selected studies. A meta-analysis was performed to determine
the effectiveness of cognitive behaviour therapy-based multicomponent interventions
on fear of falling immediately after the interventions, at <= 6 months and >6
months postinterventions. Results This review included 15 randomized controlled
trials involving 3,165 community-dwelling adults aged 60 years and older. The
pooled results showed that the intervention effects, including immediate, short-
term (i.e., <= 6 months postintervention) and long-term (i.e., >6 months
postintervention) effects, favoured the intervention group. Conclusion Cognitive
behaviour therapy-based multicomponent interventions are effective at reducing fear
of falling among community-dwelling older adults who are at risk of falling. Impact
Fear of falling has been implicated in activity restriction among older adults and
fall prevention interventions need to be multifaceted. Understanding and attending
to individual psychological needs are as important as exercise training.
Background Patients waiting or recovering from total joint arthroplasty (TJA) are
at risk for falls which can lead to restriction of activity and negatively impact
recovery. The objective of this scoping review is to critically appraise and
synthesize the evidence in the reported number of falls, fear of falling, and risk
factors associated with falls in older patients waiting for or recovering from TJA.
Methods Seven electronic databases were searched with no date limits and using
language restriction (English). The inclusion criteria were 1) cohorts that
included older adults 60+ years of age, 2) reported prevalence of falls, fear of
falling, and/or risk factors for falls in patients who were waiting or recovering
from TJA and 3) cross-sectional studies, cohort studies, and case control study
designs. The quality assessment of selected articles was assessed using the SIGN
Guidelines Checklist. Results Of the 866 citations identified, 12 studies met the
inclusion criteria and were reviewed. Prevalence of falls in pre-operative TJA
patients and post-operative TJA patients ranged from 23 to 63%, and 13 to 42%,
respectively. Of those five studies that examined fear of falling, pre-operative
TJA patients reported greater fear of falling than post-operative patients.
Modifiable risk factors for falls included fear of falling, joint range of motion,
and depression. Conclusions An increased risk of falls in patients with TJA was
reported both for patients waiting for and recovering from surgery. A number of
modifiable risk factors were identified including fear of falling that could be
targeted in fall prevention programs for TJA.
Introduction: The present systematic review aims to analyze articles between 2011
and 2017 that describe the involvement of epigenetic and molecular mechanisms
associated with extinction of fear memory. Methods: Inclusion and exclusion
criteria were considered to filter the final articles extracted from Science
Direct, Pubmed and Google Scholar. Results: From a total of 461 articles, 13
attended the criteria and were displayed in a table divided into: Objective, Brain
region, techniques and reference. These final articles were critically analyzed and
compared between each other. Discussion: Analysis of drug efficiency and molecular
mechanisms involved in extinction and/or consolidation of fear memory in mice and
rats may elucidate and thus contribute in the treatment of obsessive-compulsive
disorder, anxiety, phobia, panic and posttraumatic stress
The hippocampus plays a central role as a hub for episodic memory and as an
integrator of multimodal sensory information in time and space. Thereby, it
critically determines contextual setting and specificity of episodic memories. It
is also a key site for the control of innate anxiety states and involved in
psychiatric diseases with heightened anxiety and generalized fear memory such as
post-traumatic stress disorder (PTSD). Expression of both innate unlearned anxiety
and learned fear requires contextual processing and engagement of a brain-wide
network including the hippocampus together with the amygdala and medial prefrontal
cortex. Strikingly, the hippocampus is also the site of emergence of oscillatory
rhythms that coordinate information processing and filtering in this network. Here,
we review data on how the hippocampal network oscillations and their coordination
with amygdalar and prefrontal oscillations are engaged in innate threat evaluation.
We further explore how such innate oscillatory communication might have an impact
on contextualization and specificity of learned fear. We illustrate the partial
overlap of fear and anxiety networks that are built by the hippocampus in
conjunction with amygdala and prefrontal cortex. We further propose that (mal)-
adaptive interplay via (dis)-balanced oscillatory communication between the anxiety
network and the fear network may determine the strength of fear memories and their
resistance to extinction.
Although several treatment options for panic disorder (PD) are available, the best
intervention for each individual patient remains uncertain and the use of a more
personalized therapeutic approach in PD is required. In clinical practice,
clinicians combine general scientific information and personal experience in the
decision-making process to choose a tailored treatment for each patient. In this
sense, clinicians already use a somehow personalized medicine strategy. However,
the influence of their interpretative personal models may lead to bias related to
personal convictions, not sufficiently grounded on scientific evidence. Hence, an
effort to give some advice based on the science of personalized medicine could have
positive effects on clinicians' decisions. Based on a narrative review of meta-
analyses, systematic reviews, and experimental studies, we proposed a first-step
attempt of evidence-based personalized therapy for PD. We focused on some
phenomenological profiles, encompassing symptoms during/outside panic attacks,
related patterns of physiological functions, and some aspects of physical health,
which might be worth considering when developing treatment plans for patients with
PD. We considered respiratory, cardiac, vestibular, and
derealization/depersonalization profiles, with related implications for treatment.
Given the extensiveness of the topic, we considered only medications and some
somatic interventions. Our proposal should be considered neither exhaustive nor
conclusive, as it is meant as a very preliminary step toward a future, robust
evidence-based personalized therapy for PD. Clearly much more work is needed to
achieve this goal, and recent technological advances, such as wearable devices, big
data platforms, and the application of machine learning techniques, may help obtain
reliable findings. We believe that combining the efforts of different research
groups in this work in progress can lead to largely shared conclusions in the near
future.
In this review, we advocate a dimensional approach on the basis of candidate
endophenotypes to the development of animal models of post-traumatic stress
disorder (PTSD) capable of including genetic liability factors, variations in
symptoms profile and underlying neurobiological mechanisms, and specific
comorbidities. Results from the clinical literature pointed to two candidate
endophenotypes of PTSD: low sensory gating and high waiting impulsivity. Findings
of comparative studies in mice of two inbred strains characterized by different
expressions of the two candidate endophenotypes showed different strain-specific
neural and behavioral effects of stress experiences. Thus, mice of the standard
C57BL/6J strain show stress-induced helplessness, stress-learned helplessness, and
stress-extinction-resistant conditioned freezing. Instead, mice of the genetically
unrelated DBA/2J strain, expressing both candidate endophenotypes, show stress-
induced extinction-resistant avoidance and neural and behavioral phenotypes
promoted by prolonged exposure to addictive drugs. These strain differences are in
line with evidence of associations between genetic variants and specific stress-
promoted pathological profiles in PTSD, support a role of genotype in determining
different PTSD comorbidities, and offer the means to investigate specific
pathogenic processes.
Background Panic disorder is characterised by recurrent unexpected panic attacks
consisting of a wave of intense fear that reaches a peak within a few minutes.
Panic disorder is a common disorder, with an estimated lifetime prevalence of 1% to
5% in the general population and a 7% to 10% prevalence in primary care settings.
Its aetiology is not fully understood and is probably heterogeneous. Panic disorder
is treated with psychological and pharmacological interventions, often used in
combination. Although benzodiazepines are frequently used in the treatment of panic
disorder, guidelines recommend antidepressants, mainly selective serotonin reuptake
inhibitors (SSRIs), as first-line treatment for panic disorder, particularly due to
their lower incidence of dependence and withdrawal reaction when compared to
benzodiazepines. Despite these recommendations, benzodiazepines are widely used in
the treatment of panic disorder, probably because of their rapid onset of action.
Objectives To assess the efficacy and acceptability of benzodiazepines versus
placebo in the treatment of panic disorder with or without agoraphobia in adults.
Search methods We searched the Cochrane Common Mental Disorders Controlled Trials
Register (CCMDCTR Studies and References), the Cochrane Central Register of
Controlled Trials (CENTRAL), MEDLINE (1950-), Embase (1974-), and PsycINFO (1967-)
up to 29 May 2018. We handsearched reference lists of relevant papers and previous
systematic reviews. We contacted experts in the field for supplemental data.
Selection criteria All double-blind (blinding of patients and personnel) controlled
trials randomising adults with panic disorder with or without agoraphobia to
benzodiazepine or placebo. Data collection and analysis Two review authors
independently checked the eligibility of studies and extracted data using a
standardised form. Data were then entered data into Review Manager 5 using a
double-check procedure. Information extracted included study characteristics,
participant characteristics, intervention details, settings, and outcome measures
in terms of efficacy, acceptability, and tolerability. Main results We included 24
studies in the review with a total of 4233 participants, of which 2124 were
randomised to benzodiazepines and 1475 to placebo. The remaining 634 participants
were randomised to other active treatments in three-arm trials. We assessed the
overall methodological quality of the included studies as poor. We rated all
studies as at unclear risk of bias in at least three domains. In addition, we
judged 20 of the 24 included studies as having a high risk of bias in at least one
domain. Two primary outcomes of efficacy and acceptability showed a possible
advantage of benzodiazepines over placebo. The estimated risk ratio (RR) for a
response to treatment was 1.65 (95% confidence interval (CI) 1.39 to 1.96) in
favour of benzodiazepines, which corresponds to an estimated number needed to treat
for an additional beneficial outcome (NNTB) of 4 (95% CI 3 to 7). The dropout rate
was lower among participants treated with benzodiazepines (RR 0.50, 95% CI 0.39 to
0.64); the estimated NNTB was 6 (95% CI 5 to 9). We rated the quality of the
evidence as low for both primary outcomes. The possible advantage of benzodiazepine
was also seen for remission (RR 1.61, 95% CI 1.38 to 1.88) and the endpoint data
for social functioning (standardised mean difference (SMD) -0.53, 95% CI -0.65 to -
0.42), both with low-quality evidence. We assessed the evidence for the other
secondary outcomes as of very low quality. With the exception of the analyses of
the change score data for depression (SMD -0.22, 95% CI -0.48 to 0.04) and social
functioning (SMD -0.32, 95% CI -0.88 to 0.24), all secondary outcome analyses
showed an effect in favour of benzodiazepines compared to placebo. However, the
number of dropouts due to adverse effects was higher with benzodiazepines than with
placebo (RR 1.58, 95% CI 1.16 to 2.15; low-quality evidence). Furthermore, our
analyses of adverse events showed that a higher proportion of participants
experienced at least one adverse effect when treated with benzodiazepines (RR 1.18,
95% CI 1.02 to 1.37; low-quality evidence). Authors' conclusions Low-quality
evidence shows a possible superiority of benzodiazepine over placebo in the short-
term treatment of panic disorders. The validity of the included studies is
questionable due to possible unmasking of allocated treatments, high dropout rates,
and probable publication bias. Moreover, the included studies were only short-term
studies and did not examine the long-term efficacy nor the risks of dependency and
withdrawal symptoms. Due to these limitations, our results regarding the efficacy
of benzodiazepines versus placebo provide only limited guidance for clinical
practice. Furthermore, the clinician's choice is not between benzodiazepines and
placebo, but between benzodiazepines and other agents, notably SSRIs, both in terms
of efficacy and adverse effects. The choice of treatment should therefore be guided
by the patient's preference and should balance benefits and harms from treatment in
a long-term perspective.
The strong innate fear response shown by laboratory rodents to predator cues could
provide powerful and innovative tools for pest management. Predator cues are
routinely used to induce fear and anxiety in laboratory rodents for pharmacological
studies. However, research on the fear response induced by predator cues in
different species of rodents in the wild has been inconclusive with results often
contradictory to laboratory experiments. Potential explanations for this
inconsistency include the prey's: (i) physiological state; (ii) parasite load;
(iii) differential intensity of perceived threats; (iv) fear learning and
habituation; and (v) information gathering. In this review, we first explore
current knowledge on the sensory mechanisms and capabilities of rodents, followed
by the discussion of each of these explanations within the context of their
implications for the use of antipredator response as a pest rodent management tool.
Finally, we make recommendations on potential solutions and strategies to resolve
issues in rodent management related to these hypotheses.
Purpose of ReviewThis paper seeks to identify the risk factors of fear of
childbirth (FOC) and posttraumatic stress disorder (PTSD) related to birth and
reviews the efficacy of their respective screening tools and therapeutic
interventions.Recent FindingsBiofeedback, hypnosis, internet-based cognitive
behavioral therapy, and antenatal education are promising treatments for FOC.
Training midwives to address traumatic birth experiences could help in preventing
PTSD. A shorter more pragmatic screening tool for FOC than the Wijma Delivery
Expectancy/Experience Questionnaire (WDEQ) is needed. Women with PTSD attributed a
mismatch between the expected mode of delivery (MOD) and the actual MOD as the
cause of their trauma.SummaryA history of mental health disorders, lack of social
support, previous negative birth experiences, and MOD are correlated to FOC and
postpartum PTSD. Psycho-education and CBT-based treatments have been found to
reduce levels of FOC and PTSD.
Guillain-Barre syndrome (GBS) is an inflammatory disorder and an acute immune-
mediated demyelinating neuropathy that causes reduced signal transmissions,
progressive muscle weakness, and paralysis. The etiology of the syndrome still
remains controversial and uncertain. GBS can be initiated and triggered by
respiratory tract infections such as influenza, and intestinal infections such as
Campylobacter jejuni. In addition, there is considerable evidence suggesting links
between influenza vaccination and GBS. As reported previously, the incidence of GBS
in individuals receiving swine flu vaccine was about one to two cases per million.
Despite the influenza vaccine efficacy, its association with an immune-mediated
demyelinating process can be challenging as millions of people get vaccinated every
year. In this review we will discuss the association between influenza infection
and vaccination with GBS by focusing on the possible immunopathological mechanisms.
The generalization of fear memories is an adaptive neurobiological process that
promotes survival in complex and dynamic environments. When confronted with a
potential threat, an animal must select an appropriate defensive response based on
previous experiences that are not identical, weighing cues and contextual
information that may predict safety or danger. Like other aspects of fear memory,
generalization is mediated by the coordinated actions of prefrontal, hippocampal,
amygdalar, and thalamic brain areas. In this review article, we describe the
current understanding of the behavioral, neural, genetic, and biochemical
mechanisms involved in the generalization of fear. Fear generalization is a
hallmark of many anxiety and stress-related disorders, and its emergence, severity,
and manifestation are sex-dependent. Therefore, to improve the dialog between human
and animal studies as well as to accelerate the development of effective
therapeutics, we emphasize the need to examine both sex differences and remote
timescales in rodent models.
Background Internet-delivered psychological treatments have been suggested as a
chance to expand the access to professional help. However, little is known about
the usefulness of different support formats and approaches of digital treatments
for panic disorder among clinicians. Objective This narrative review aimed to
explore the recent evidence base on the efficacy and acceptability of different
internet-delivered treatments for adults with panic disorder. Methods A systematic
search in electronic databases (Pubmed/Medline, PSYNDEX) and a hand search were
performed to identify articles on randomized controlled trials published within the
past five years (2012/12/10-2017/12/12) in English peer-reviewed journals. Results
Eight studies (1,013 participants) involving 10 interventions met the inclusion
criteria. Nine interventions were primarly based on Cognitive Behavioral Therapy
principles. Most interventions were effective, when compared to a control condition
(6 of 8 comparisons). Minimal guidance was associated with improved outcomes in one
study and adherence in two studies (3 comparisons). Furthermore, no differences
were found based on treatment approach (2 comparisons). Regarding acceptability,
the attrition rates were moderate to high, ranging from 9.8% to 42.1% of randomized
participants. Adherence rates also varied largely (7.8-75%), whereas participant
satisfaction of program completers was assessed overall high (5 studies).
Conclusion Diverse effective internet-delivered treatments are available for the
self-management of panic symptoms. Especially self-guided and transdiagnostic
Cognitive Behavioral Therapy approaches appear being efficient options for the
dissemination in routine care. However, due to the limited evidence base, further
efforts are required to improve the actual uptake of internet-delivered treatments
and identify moderators of outcomes.
Military medical ethics has been challenged by the post-11 September 2001 'War on
Terror'. Two recurrent questions are whether military physicians are officers first
or physicians first, and whether military physicians need a separate code of
ethics. In this article, we focus on how the War on Terror has affected the way we
have addressed these questions since 2001. Two examples frame this discussion: the
use of military physicians to force-feed hunger strikers held in Guantanamo Bay
prison camp, and the uncertain fate of the Department of Defense's report on
'Ethical Guidelines and Practices for US Military Medical Professionals'.
Fear of cancer recurrence (FCR) is a significant issue for most cancer survivors,
with nearly half of cancer survivors reporting it at moderate to high levels of
intensity. We aimed to further explore the experience of having FCR from the point
of view of patients by systematically reviewing qualitative studies. Following
PRISMA guidelines, 87 qualitative studies were selected. All participants' quotes
about FRC were extracted, then analysed using a conceptual framework based on the
emotion-focused therapy theory of emotion schemes, which consist of
experienced/implicit emotions, along with perceptual-situational, bodily-
expressive, symbolic-conceptual and motivational-behavioral elements. According to
participant descriptions, FCR was found to be an intense, difficult, multi-
dimensional experience. Considering the diversity of experiences identified, it is
useful to look at FCR as an emotional experience that extends along a continuum of
adaptive and maladaptive responses. For some participants, FCR was described in
trauma-like terms, including forms of re-experiencing, avoidance, negative thoughts
and feelings, and arousal or reactivity related to cancer-related triggers or
memories. Vivid metaphors expressing vulnerability and conflict also reflect the
strong impact of FCR in patients' lives and can help therapists empathize with
their clients.
Cue-associated learning is vital to guiding behaviour for survival. Adolescence
represents a key developmental stage for perturbations in cue-related learning,
including a characteristic deficit in cue extinction learning. The present review
summarizes evidence from animal and human literature that cue extinction is
critically mediated by prefrontal dopamine, a system that undergoes dramatic
reorganization during adolescence. We propose that extinction learning and memory
is governed by a developmentally dynamic balance of dopamine receptors in the
prefrontal cortex, which changes across adolescence into adulthood. This is
contrary to the previous idea that extinction deficits during adolescence reflect
inefficiency in the same neural circuitry as adults. This leads to proposal of the
novel theory that cue extinction involves divergent prefrontal dopaminergic
mechanisms depending on the age of extinction. (C) 2017 Elsevier B.V. and ECNP. All
rights reserved.
Fear memory underlies anxiety-related disorders, including posttraumatic stress
disorder (PTSD). PTSD is a fear-based disorder, characterized by difficulties in
extinguishing the learned fear response and maintaining extinction. Currently, the
first-line treatment for PTSD is exposure therapy, which forms an extinction memory
to compete with the original fear memory. However, the extinguished fear often
returns under numerous circumstances, suggesting that novel methods are needed to
eliminate fear memory or facilitate extinction memory. This review discusses
research that targeted extinction and reconsolidation to manipulate fear memory.
Recent studies indicate that sleep is an active state that can regulate memory
processes. We also discuss the influence of sleep on fear memory. For each
manipulation, we briefly summarize the neural mechanisms that have been identified
in human studies. Finally, we highlight potential limitations and future directions
in the field to better translate existing interventions to clinical settings.
Fear of falling presents a significant problem for many older adults by reducing
physical function and increasing the risk of future falls. Several different types
of interventions have improved fear of falling and a summary of efficacious
interventions will help clinicians recommend treatment options. Using the Arksey
and O'Malley Framework for scoping reviews, the purpose of this review was to
identify efficacious interventions for treating fear of falling among community-
dwelling older adults in order to provide a list of potential treatment options for
care providers. A total of 45 publications were identified for inclusion in this
review. (C) 2018 Elsevier Inc. All rights reserved.
Memory reconsolidation has been demonstrated to offer a potential target period
during which the fear memories underlying fear disorders can be disrupted.
Reconsolidation is a labile stage that consolidated memories re-enter after
memories are reactivated. Reactivated memories, induced by cues related to
traumatic events, are susceptible to strengthening and weakening. Gene
transcription regulation and protein synthesis have been suggested to be required
for fear memory reconsolidation. Investigating the transcriptional regulation
mechanisms underlying reconsolidation may provide a therapeutic method for the
treatment of fear disorders such as post-traumatic stress disorder (PTSD). However,
the therapeutic effect of treating a fear disorder through interfering with
reconsolidation is still contradictory. In this review, we summarize several
transcription factors that have been linked to fear memory reconsolidation and
propose that transcription factors, as well as related signaling pathways can serve
as targets for fear memory interventions. Then, we discuss the application of
pharmacological and behavioral interventions during reconsolidation that may or not
efficiently treat fear disorders.
Introduction: Experiences of forced migration include traumas that are
interpersonal in nature, as well as ongoing emotional responses, stress, and
frustration in post-migration setti ngs. Open questions exist, regarding
anger/anger-like responses following experiences of persecution and ongoing stress.
The aim of this study was to explore the adaptive and maladaptive underlying
mechanisms of anger/anger-like responses, cultural, linguistic, and social
contingencies, and possible interventions for problematic anger behavior. Method:
We searched two databases (PsycINFO and PILOTS) with the following search terms:
(refugee OR "asylum seek*" OR IDP OR "internal* displac*" OR "forced migra*" OR
"involuntary migra*") AND anger. Findings: This search yielded 34 studies that were
included in the final review. Although, anger is a moral, adaptive, and prosocial
response, dysfunctional anger/anger-like responses arise from PTSD, "moral injury,"
complicated grief, and independent forms of anger behavior. Cultural, linguistic,
and social issues also emerged from the search. Finally, considerations for
treatment and intervention are discussed. Discussion: Anger responses following
experiences of forced migration may require assessment beyond PTSD models currently
framed by DSM and ICD. A very promising framework is the Adaptation and Development
after Persecution and Trauma (ADAPT) model.
The extinction of conditioned-fear represents a hallmark of current exposure
therapies as it has been found to be impaired in people suffering from post-
traumatic stress disorder (PTSD) and anxiety. A large body of knowledge focusing on
psychophysiological animal and human studies suggests the involvement of key brain
structures that interact via neural oscillations during the acquisition and
extinction of fear. Consequently, neural oscillatory correlates of such mechanisms
appear relevant regarding the development of novel therapeutic approaches to
counterbalance abnormal activity in fear-related brain circuits, which, in turn,
could alleviate fear and anxiety symptoms. Here, we provide an account of state-of-
the-art neural oscillatory correlates for the conditioning and extinction of fear,
and also deal with recent translational efforts aimed at fear extinction by neural
oscillatory modulation.
Extinction-based exposure therapy is the most common behavioral therapy for anxiety
and trauma-related disorders, but fear tends to resurface even after successful
extinction. Identification of novel strategies to enhance fear extinction and
reduce fear relapse is of paramount importance to mental health. Exercise can
enhance cognitive function, but it is not yet well understood whether exercise can
be an effective augmentation strategy for fear extinction. In the current review,
we present the current state of knowledge on the effects of exercise on fear
extinction. Effects of exercise duration, explanations for conflicting results, and
potential mechanisms, focusing on a hypothesized role for dopamine, are all
discussed. We also provide new data suggesting that the timing in which acute
exercise occurs relative to fear extinction, is a crucial variable in determining
whether exercise can enhance fear extinction. Clinical implications and ideas to
guide future research endeavors in this area are provided.
Background: providing appropriate care for pregnant women with high or severe fear
of childbirth (FOC) is a challenge in midwifery care today. FOC is associated with
predisposing anamnestic factors, various socio-demographic and psychosocial
characteristics, and may result in serious healthrelated consequences. It is
therefore important to establish which interventions may increase a woman's faith
in her own ability to cope with labour and birth. Aim: to systematically identify
and review studies examining interventions for relief of severe fear of childbirth
in pregnancy and their underlying conceptual foundation. Methods: a systematic
literature search was performed following Cochrane Collaboration and PRISMA
Statement recommendations. Inclusion criteria were: studies including pregnant
women diagnosed with high or severe FOC or who requested a caesarean section due to
severe FOC, studies (regardless of design) observing the effect of an intervention
addressing FOC, and studies published in English. Publications addressing anxiety
or stress were excluded. 377 references were screened by title and abstract. The
risk of bias was assessed. Findings: 19 articles referring to 15 research projects
were included in the analysis. The studies show heterogeneity regarding assessment
methods, type, conceptualisation and application of interventions. There is
evidence that both cognitive therapy sessions and a theory-based group
psychoeducation with relaxation are effective interventions. Key conclusions:
despite methodological limitations, single or group psychoeducation sessions for
nulliparous women or therapeutic conversation during pregnancy (in group or
individual sessions) have the potential to strengthen women's self-efficacy and
decrease the number of caesarean sections due to FOC. The theoretical validation of
an intervention deepens the understanding of psychological processes in women
coping with severe FOC.
BackgroundDespite a sharp increase in the number of publications that report on
treatment options for pregnancy-specific anxiety and fear of childbirth (PSA/FoB),
no systematic review of nonpharmacological prenatal interventions for PSA/FoB has
been published. Our team addressed this gap, as an important first step in
developing guidelines and recommendations for the treatment of women with PSA/FoB.
MethodsTwo databases (PubMed and Mendeley) were searched, using a combination of 42
search terms. After removing duplicates, two authors independently assessed 208
abstracts. Sixteen studies met eligibility criteria, ie, the article reported on an
intervention, educational component, or treatment regime for PSA/FoB during
pregnancy, and included a control group. Independent quality assessments resulted
in the retention of seven studies. ResultsSix of seven included studies were
randomized controlled trials (RCTs) and one a quasi-experimental study. Five
studies received moderate quality ratings and two strong ratings. Five of seven
studies reported significant changes in PSA/FoB, as a result of the intervention.
Short individual psychotherapeutic interventions (1.5-5hours) delivered by midwives
or obstetricians were effective for women with elevated childbirth fear.
Interventions that were effective for pregnant women with a range of different
fear/anxiety levels were childbirth education at the hospital (2hours), prenatal
Hatha yoga (8weeks), and an 8-week prenatal education course (16hours).
ConclusionsFindings from this review can inform the development of treatment
approaches to support pregnant women with PSA/FoB.
Aims and objectivesThis meta-synthesis aimed to identify key elements contributing
to FOC derived from women's own reports. BackgroundFear of childbirth (FOC)
encompasses fear or anxiety about giving birth, which can resemble a phobic
response. FOC holds implications for women's antenatal and postnatal well-being,
and decisions made about the birth but a clear definition of the construct does not
exist. MethodA meta-synthesis was conducted by searching databases (Web of
Knowledge, CINAHL, EBSCO, MEDLINE, PsychInfo and PsychArticles) for qualitative
studies describing women's perspectives with respect to fear, anxiety, concerns,
phobia or stress about birth. A total of 25 papers, reporting findings from 24
studies, fulfilled eligibility criteria and were included in the synthesis.
ResultsSix key elements of FOC were identified; fears of the unknown, potential for
injury, pain, capacity to give birth, losing control and adequacy of support from
care providers. A single overarching theme linking all elements was the
unpredictability of childbirth. Three moderators of FOC were also identified;
awareness of negative birthing experiences, information received about birth and
support received from care providers. ConclusionsFindings highlight the role of
uncertainty in the birthing process as an overarching theme underpinning women's
fears. Enhancing tolerance of uncertainty may be a way to reduce women's FOC.
Relevance to clinical practiceIdentification of the elements and moderators of FOC
provide an insight into the potential mechanisms that contribute to women's fears,
which can be used to inform methods of identifying women with FOC or a basis upon
which to base supportive strategies to reduce women's fears for giving birth.
In 2013, 3 systematic reviews of fear of cancer recurrence (FCR) and its predictors
were published. All 3 concurred that FCR is a highly prevalent problem and amongst
the largest unmet needs of cancer survivors, even 5 or more years after treatment.
However, between them they identified only 1 study that had investigated the
relationship between death anxiety and FCR. This is surprising because it is well
acknowledged that a diagnosis of cancer, a potentially life-threatening illness, is
associated with a number of existential issues that give rise to psychological
sequelae such as intrusive thoughts about death and other post-traumatic symptoms.
Outside the cancer literature, there has recently been a call to identify death
anxiety as a transdiagnostic construct that underlies many anxiety disorders even
in healthy people. And yet, the relevance of death anxiety to FCR has not been
studied. We explore the barriers to the study of death anxiety and FCR and the
reasons that a potential link between the 2 might have important theoretical and
clinical implications. We conclude that establishing the relationship between death
anxiety, FCR and other existential issues is essential in order to fully understand
FCR, particularly in the context of advanced disease. We further conclude that
whether death anxiety underlies FCR has important clinical implications which would
potentially allow us to optimise currently available evidence-based treatments.
We apply the models and tools of epidemiology and public health to propose a
unified field theory showing the role of ideologies, indoctrination, and
incitement, in genocide, genocidal terror, and terror by groups or individuals. We
examine the effects of indoctrination and incitement as exposures and risks in
relation to genocide and genocidal terror. Incitement has been recognized as a
trigger to these outcomes but indoctrination is upstream to incitement. Population-
wide exposure to indoctrination increases susceptibility to the effects of
incitement. These relationships have been seen in all major genocides and genocidal
terror in the late twentieth and twenty-first centuries. There is some insight into
the relationship between ideology, incitement, and genocidal acts of violence from
the so-called localized genocides in Bosnia, Rwanda, Darfur, Syria, and most
recently, among the Rohingya in Myanmar. There is a need to recognize the upstream
role of ideologies of hate in order to determine the degree to which indoctrination
posed, and continues to pose, a contributing factor. Epidemiologic models, such as
the iceberg model of exposure and disease and the concept of sick individuals and
sick populations, guide our understanding of the content and spread of
indoctrination and incitement and can provide essential insights for prevention.
The hateful indoctrination and ideologies behind genocidal violence must be
countered and replaced by positive ideologies and role models that emphasize
respect for life and human dignity for all.
To identify measurement tools which screen for the presence of fear of birth (FOB)
and to determine the most effective tool/s for use in clinical practice. Fear or
birth (FOB) is internationally recognised as a cause for increasing concern,
despite a lack of consensus on a definition or optimal measure of assessment. There
is a wide array of FOB measurement tools, however little clarity on which tool
should be used to screen for FOB in clinical practice. This review explores the use
of tools that are used to screen for FOB and discusses the perceived effectiveness
of such tools. A structured literature review was undertaken. Electronic databases
were searched in July 2017 and manuscripts reviewed for quality. The review
included 46 papers. The majority of studies were undertaken in Scandinavia (n = 29)
and a range of tools were used to measure FOB. The most widely used tool was the
Wilma Delivery Expectancy Experience Questionnaire' (W-DEQ). Inconsistencies were
found in the way this tool was used, including variations in assessment cut-off
points, implementation and use across a range of cultural settings and women of
varying gestations. Moreover, the tool may be too lengthy to use in clinical
practice. The Fear of Birth Scale (FOBS) has been shown to be as effective as W-DEQ
but has the advantage of being short and easy to administer. The inconsistencies in
tools reflect the difficulties in defining FOB. A clear consensus definition of FOB
would aid comparisons across practice and research. The W-DEQ is not used in
clinical practice; this may be due to its length and complexity. The FOBS is likely
to be a more versatile tool that can be used in clinical practice.
Social anxiety is characterized by a fear of being negatively evaluated by others
(i.e., Fear of Negative Evaluation [FNE]). In 2008, Weeks, Heimberg, and Rodebaugh
proposed Fear of Positive Evaluation (FPE) as a second cognitive component in
social anxiety. The article presents an overview of FPE, its psycho-evolutionary
theoretical foundation and assessment by the Fear of Positive Evaluation Scale as
well as relevant psychometric research on demographic characteristics. The
relationship of FPE with a wide range of established dimensions from clinical,
personality, and social psychology (i.e., self-esteem, perfectionism, or quality of
life) will be reviewed. The role of FPE for psychological comorbidities such as
other anxiety disorders, depression, eating, and substance use disorders as well as
for treatment of social anxiety will be discussed. Future research might address
questions of causality of FPE relative to related constructs, further data on
psychometric properties, as well as on its independence from FNE in longitudinal
studies. In sum, FPE seems to be a valid and reliable construct that explains
cognitions, emotions, and behavior related to social anxiety at subclinical and
clinical levels and therefore enriches the psychometric repertoire in the fields of
social psychology, personality, and clinical psychology.
Following sexual maturity, females disproportionately have higher rates of
posttraumatic stress disorder (PTSD) and experience greater symptom severity and
chronicity as compared with males. This observation has led many to examine sex
differences in PTSD risk factors. Though relatively few, these studies reveal that
the root causes of PTSD sex differences are complex, and partly represent
interactions between sex-specific nonbiological and biological risk factors, which
differentially shape PTSD vulnerability. Moreover, these studies suggest that sex-
specific PTSD vulnerability is partly regulated by sex differences in fear systems.
Fear, which represents a highly conserved adaptive response to threatening
environmental stimuli, becomes pathological in trauma-and stress-based psychiatric
syndromes, such as PTSD. Over the last 30 years, considerable progress has been
made in understanding normal and pathological molecular and behavioral fear
processes in humans and animal models. Thus, fear mechanisms represent a tractable
PTSD biomarker in the study of sex differences in fear. In this review, we discuss
studies that examine nonbiological and biological sex differences that contribute
to normal and pathological fear behaviors in humans and animal models. This, we
hope, will shed greater light on the potential mechanisms that contribute to
increased PTSD vulnerability in females.
Background: Panic disorder (PD) occurs in 3.4-4.7% of the general population.
Although accumulating evidence suggests that some inflammatory processes play a
role in the pathophysiology of mental disorders, very few studies have evaluated
cytokine levels in patients with PD. The aim of the present study was to
systematically review the characteristic cytokine profile of PD patients and
discuss some possibilities for future trials on this common and disabling disorder.
Methods: A comprehensive literature search was carried out in PubMed and Web of
Science databases (search terms: "panic disorder" or "panic attacks" and IL-1, IL-
2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, TNF-alpha and INF-gamma). Results: Eleven
studies involving measurements of cytokines in PD patients were included in this
review article. Increased serum levels of some inflammatory markers such as IL-6,
IL-1 ss and IL-5 were reported in PD patients compared with control subjects. There
are some conflicting results regarding IL-2, IL-12, and INF-gamma in association
with PD. Limitations: There are discrepant findings in the existing literature
regarding PD and cytokines. A significant portion of the recognized heterogeneity
may be attributable to variability in assay procedures. The discrepant findings may
also have been due to differences in the study populations. Conclusions: Cytokines
induce the production of acute-phase proteins and are linked to neurogenesis,
modification of the HPA axis, microglial activation, tryptophan metabolism and an
imbalance in excitatory and inhibitory neurotransmission. Investigation of
inflammatory biomarkers in PD could contribute to understanding the
pathophysiological mechanisms in this debilitating disorder.
Acid-sensitive ion channels, such as amiloride-sensitive cation channel (ACCN),
transient receptor potential vanilloid-1 (TRPV1), and T-cell death-associated gene
8 (TDAG8) are highly related to the expression of fear and are expressed in several
regions of the brain. These molecules can detect acidosis and maintain brain
homeostasis. An important role of pH homeostasis has been suggested in the
physiology of panic disorder (PD), with acidosis as an interoceptive trigger for
panic attacks. To examine the effect of acid-sensitive channels on PD symptoms, we
conducted a systematic review and meta-analysis of these chemosensors in rodents
and humans. Following PRISMA guidelines, we systematically searched the Web of
Science, Medline/Pubmed, Scopus, Science Direct, and SciELO databases. The review
included original research in PD patients and animal models of PD that investigated
acid-sensitive channels and PD symptoms. Studies without a control group, studies
involving patients with a comorbid psychiatric diagnosis, and in vitro studies were
excluded. Eleven articles met the inclusion criteria for the systematic review. The
majority of the studies showed an association between panic symptoms and acid-
sensitive channels. PD patients appear to display polymorphisms in the ACCN gene
and elevated levels of TDAG8 mRNA. The results showed a decrease in panic-like
symptoms after acid channel blockade in animal models. Despite the relatively
limited data on this topic in the literature, our review identified evidence
linking acid-sensitive channels to PD in humans and preclinical models. Future
research should explore possible underlying mechanisms of this association, attempt
to replicate the existing findings in larger populations, and develop new
therapeutic strategies based on these biological features.
Introduction: Panic disorder (PD) is a prevalent and disabling anxiety disorder
that can be treated effectively. Selective serotonin reuptake inhibitors (SSRIs)
and benzodiazepines are among the most frequently prescribed drugs for PD. In this
article, the authors review the current evidence on efficacy, adverse events, and
limitations of these two treatment options. Areas covered: MEDLINE/Pubmed and Web
of Science databases were searched for open or placebo-controlled trials on SSRIs
and/or benzodiazepines in PD treatment. Expert opinion: The literature search
yielded 4,957 articles related to the theme. Of these, 24 articles were included in
this review. Despite their usefulness in PD, SSRIs are associated with a delay of
several weeks in onset of therapeutic effect and have the potential to exacerbate
anxiety and panic early in the treatment course. Benzodiazepines present rapid
onset of action, but can cause tolerance and dependence. Despite strong evidence of
the effectiveness of SSRIs and benzodiazepines in the treatment of PD, few trials
have performed head-to-head comparisons of these two drug classes. Future studies
on the pharmacological treatment of PD should make direct comparisons of risks,
benefits, and limitations of each group. This could help improve the evidence-based
pharmacotherapy of PD.
Question Recent data suggest that anxiety disorders are as often comorbid with
bipolar disorder (BD) as with unipolar depression. The literature on panic disorder
(PD) comorbid with BD has been systematically reviewed and subject to meta-
analysis. Study selection and analysis The Preferred Reporting Items for Systematic
Reviews and Meta-Analyses guidelines were thoroughly followed for literature
search, selection and reporting of available evidence. The variance-stabilising
Freeman-Tukey double arcsine transformation was used in the meta-analysis of
prevalence estimates. Both fixed-effect and random-effects models with inverse
variance method were applied to estimate summary effects for all combined studies.
Heterogeneity was assessed and measured with Cochran's Q and I-2 statistics.
Findings Overall, 15 studies (n=3391) on cross-sectional prevalence and 25
independent lifetime studies (n=8226) were used to calculate pooled estimates. The
overall random-effects point prevalence of PD in patients with BD, after exclusion
of one potential outlier study, was 13.0% (95% CI 7.0% to 20.3%), and the overall
random-effects lifetime estimate, after exclusion of one potential outlier study,
was 15.5% (95% CI 11.6% to 19.9%). There were no differences in rates between BD-I
and BD-II. Significant heterogeneity (I-2 >95%) was found in both estimates.
Conclusions Estimates that can be drawn from published studies indicate that the
prevalence of PD in patients with BD is higher than the prevalence in the general
population. Comorbid PD is reportedly associated with increased risk of suicidal
acts and a more severe course. There is no clear indication on how to treat
comorbid PD in BD. Findings from the current meta-analysis confirm the highly
prevalent comorbidity of PD with BD, implicating that in patients with BD, PD might
run a more chronic course.
Cognitive-behaviour therapy (CBT) for panic disorder may consist of different
combinations of several therapeutic components such as relaxation, breathing
retraining, cognitive restructuring, interoceptive exposure and/or in vivo
exposure. It is therefore important both theoretically and clinically to examine
whether specific components of CBT or their combinations are superior to others in
the treatment of panic disorder. Component network meta-analysis (NMA) is an
extension of standard NMA that can be used to disentangle the treatment effects of
different components included in composite interventions. We searched MEDLINE,
EMBASE, PsycINFO and Cochrane Central, with supplementary searches of reference
lists and clinical trial registries, for all randomized controlled trials comparing
different CBT-based psychological therapies for panic disorder with each other or
with control interventions. We applied component NMA to disentangle the treatment
effects of different components included in these interventions. After reviewing
2526 references, we included 72 studies with 4064 participants. Interoceptive
exposure and face-to-face setting were associated with better treatment efficacy
and acceptability. Muscle relaxation and virtual-reality exposure were associated
with significantly lower efficacy. Components such as breathing retraining and in
vivo exposure appeared to improve treatment acceptability while having small
effects on efficacy. The comparison of the most v. the least efficacious
combination, both of which may be provided as evidence-based CBT,' yielded an odds
ratio for the remission of 7.69 (95% credible interval: 1.75 to 33.33). Effective
CBT packages for panic disorder would include face-to-face and interoceptive
exposure components, while excluding muscle relaxation and virtual-reality
exposure.
Terror management theory outlines how humans seek self-esteem and worldview
validation to manage death-related anxiety. Accumulating evidence reveals that
close relationships serve a similar role. However, to date, there has been no
synthesis of the literature that delineates when close relationships buffer
mortality concerns, under what conditions, on which specific outcomes, and for
whom. This systematic review presents over two decades of research to address these
questions. Findings from 73 reviewed studies revealed that close relationships
serve an important role in buffering death-related anxiety. A range of
dispositional and situational moderating factors influence either the activation or
inhibition of relational strivings to manage heightened death awareness, the most
influential being attachment, gender, and relationship-contingent self-esteem.
These findings were integrated into an overarching model that highlights some of
the conditions under which mortality salience (MS) influences relational outcomes.
We conclude by highlighting a range of theoretical and methodological concerns to
be addressed by future research.
Anxiety disorders are the most common mental disorders and are often chronic and
disabling. Although exposure-based treatments are effective, a substantial number
of individuals fail to fully remit or experience a return of symptoms after
treatment. Understanding the critical processes underlying the development and
treatment of anxiety disorders will help identify individuals at risk and optimize
treatments. Aversive associative learning offers explanatory pathways through which
fear and anxiety emerge, spread, persist, and resurge. This narrative review
examines the advances made in our understanding of associative fear and avoidance
learning In anxiety disorders. Overall, the extant literature supports a key role
of aversive associative learning in the development and treatment of anxiety
disorders. However, research targeting specific mechanisms such as extinction
generalization and avoidance, the fragility of extinction, and moderating
influences of individual differences pertinent to anxiety disorders (e.g., age,
sex, depression) is needed. We discuss the need for more ecological valid and
complex paradigms to model ambiguity and conflict as well as for clinical
translation studies to optimize treatment.
Background: In psychotherapy research numerous Randomized Controlled Trials (RCTs)
have used Waiting-List Control Groups (WLCGs). The focus was primarily on the
treatment effects, the results of the WLCGs were used for comparison only. However,
the changes occurring in WLCGs are of interest in themselves. They provide
information about the effects of waiting for a treatment, which may be, for
example, associated with disappointment or hope for improvement. Furthermore, these
results may be used as disorder-specific benchmarks for studies not including
WLCGs. For these reasons, a meta-analysis on the effects of WLCGs in panic disorder
was carried out. Method: A systematic literature search used the following
selection criteria: (1) randomized controlled trial, (2) testing an active
treatment against a waiting list condition, (3) primary diagnosis of panic
disorder, (4) use of reliable and valid outcome measures. Symptoms of panic were
used as the primary outcome. Results: The search led to the inclusion of 29 RCTs
(n=1899), covering 30 WLCGs and 48 treatment groups. Mean waiting time was 10.05
weeks. In the WLCGs, the pre-post effect size in measures of panic was g=0.10 (95%
CI: 0.024-0.180). Effects on other forms of anxiety, depression and psychosocial
functioning were g=0.15, g=0.100 and g=0.14. For the active treatments, large
within-group (g=1.09) and between-group effect sizes (g=0.99) in comparison to
WLCGs in measures of panic were found. Conclusion: Only small changes in terms of
effect sizes occur in patients with PD waiting for treatment in RCTs.
Objective: To assess the main fears and beliefs of people with rheumatoid arthritis
(RA) and their effect on treatment outcomes; Methods: A systematic literature
review was conducted in Pubmed/Medline; original articles published up to May 2017,
reporting fears and/or beliefs of adult patients with RA were analyzed. Fears and
beliefs were collected by two independent researchers and grouped into categories.
Results: Among 474 references identified, 84 were analyzed, corresponding to 24,336
RA patients. Fears were reported in 38.4% of the articles (N = 32/84): most studies
described fears related to pharmacological therapy (50.0%, N = 16/32) and fear of
disability (28.1%, N = 9/32). Beliefs were reported in 88.0% of articles (N =
74/84) and were found to moderate the patient-perceived impact of RA in 44.6% (N =
33/74), mainly the emotional impact (18.9%, N = 14/74); measures of function,
quality of life, fatigue and pain were also found to be affected by patients'
beliefs in 8.1% (N = 6/74), 6.8% (N = 5/74), 2.7% (N = 2/74) and 2.7% (N = 2/74) of
the articles, respectively. Beliefs about therapy were linked to adherence in 17.6%
of articles (N = 13/74) and beliefs about cause of RA predicted coping patterns in
12.2% of publications (N = 9/74). Only 9.5% (N = 8/84) of articles reported fears
and/or beliefs of patients living outside Europe and North America: there was only
one work which recruited patients in Latin America and no article included patients
from Africa. Conclusion: In RA, patients' beliefs are linked to impact of disease
and non-adherence. Further research is needed on fears/beliefs of patients living
outside Europe and North America.
Panic disorder with or without agoraphobia (PD/A) and obsessive-compulsive disorder
(OCD) are characterized by major behavioral dysruptions that may affect patients'
social and marital functioning. The disorders' impact on interpersonal
relationships may also affect the quality of support patients receive from their
social network. The main goal of this systematic review is to determine the
association between social or marital support and symptom severity among adults
with PD/A or OCD. A systematic search of databases was executed and provided 35
eligible articles. Results from OCD studies indicated a negative association
between marital adjustment and symptom severity, and a positive association between
accommodation from relatives and symptom severity. However, results were
inconclusive for negative forms of social support (e.g. criticism, hostility).
Results from PD/A studies indicated a negative association between perceived social
support and symptom severity. Also, results from studies using an observational
measure of marital adjustment indicated a negative association between quality of
support from the spouse and PD/A severity. However, results were inconclusive for
perceived marital adjustment and symptom severity. In conclusion, this systematic
review generally suggests a major role of social and marital support in PD/A and
OCD symptomatology. However, given diversity of results and methods used in
studies, more are needed to clarify the links between support and symptom severity
among patients with PD/A and OCD.
The catastrophic misinterpretation model of panic disorder (PD) predicts that the
catastrophic misinterpretation of bodily sensations is a distinctive characteristic
of PD. Existing research on this prediction has produced mixed findings. This paper
presents a systematic review and meta-analysis of studies comparing the strength of
catastrophic misinterpretation of bodily sensations and external events in patients
with PD, patients with other anxiety disorders, and healthy controls. Following a
systematic screening, seven studies were included in the meta-analysis. For the
catastrophic misinterpretation of bodily sensations, analyses showed medium to
large effects between patients with PD and healthy controls and between patients
with PD and patients with other anxiety disorders. For the catastrophic
misinterpretation of external events, analyses showed medium to large effects
between patients with PD and healthy controls and a small negative effect between
patients with PD and patients with other anxiety disorders. The findings support
the assumption that the catastrophic misinterpretation of bodily sensations is a
distinctive characteristic of panic disorder and thus lend support to the
catastrophic misinterpretation model of PD.
Background: Fear of Childbirth (FOC) is a common problem affecting women's health
and wellbeing, and a common reason for requesting caesarean section. The aims of
this review were to summarise published research on prevalence of FOC in
childbearing women and how it is defined and measured during pregnancy and
postpartum, and to search for useful measures of FOC, for research as well as for
clinical settings. Methods: Five bibliographic databases in March 2015 were
searched for published research on FOC, using a protocol agreed a priori. The
quality of selected studies was assessed independently by pairs of authors.
Prevalence data, definitions and methods of measurement were extracted
independently from each included study by pairs of authors. Finally, some of the
country rates were combined and compared. Results: In total, 12,188 citations were
identified and screened by title and abstract; 11,698 were excluded and full-text
of 490 assessed for analysis. Of these, 466 were excluded leaving 24 papers
included in the review, presenting prevalence of FOC from nine countries in Europe,
Australia, Canada and the United States. Various definitions and measurements of
FOC were used. The most frequently-used scale was the W-DEQ with various cut-off
points describing moderate, severe/intense and extreme/phobic fear. Different 3-,
4-, and 5/6 point scales and visual analogue scales were also used. Country rates
(as measured by seven studies using W-DEQ with >= 85 cut-off point) varied from 6.3
to 14.8%, a significant difference (chi-square = 104.44, d.f. = 6, rho < 0.0001).
Conclusions: Rates of severe FOC, measured in the same way, varied in different
countries. Reasons why FOC might differ are unknown, and further research is
necessary. Future studies on FOC should use the W-DEQ tool with a cut-off point of
>= 85, or a more thoroughly tested version of the FOBS scale, or a three-point
scale measurement of FOC using a single question as 'Are you afraid about the
birth?' In this way, valid comparisons in research can be made. Moreover,
validation of a clinical tool that is more focussed on FOC alone, and easier than
the longer W-DEQ, for women to fill in and clinicians to administer, is required.
Fear conditioning and extinction is a construct integral to understanding trauma-,
stress- and anxiety-related disorders. In the laboratory, associative learning
paradigms that pair aversive with neutral stimuli are used as analogues to real-
life fear learning. These studies use physiological indices, such as skin
conductance, to sensitively measure rates and intensity of learning and extinction.
In this review, we discuss some of the potential limitations in interpreting and
analysing physiological data during the acquisition or extinction of conditioned
fear. We argue that the utmost attention should be paid to the development of
modelling approaches of physiological data in associative learning paradigms, by
illustrating the lack of replicability and interpretability of results in current
methods. We also show that statistical significance may be easily achieved in this
paradigm without more stringent data and data analysis reporting requirements,
leaving this particular field vulnerable to misleading conclusions. This review is
written so that issues and potential solutions are accessible to researchers
without mathematical training. We conclude the review with some suggestions that
all laboratories should be able to implement, including visualising the full data
set in publications and adopting modelling, or at least regression-based,
approaches.
In this review article, genetic variation associated with brain responses related
to acute and chronic stress reactivity and fear learning in humans is presented as
an important mechanism underlying posttraumatic stress disorder. We report that
genes related to the regulation of the hypothalamic-pituitary-adrenal axis, as well
as genes that modulate serotonergic, dopaminergic, and neuropeptidergic functions
or plasticity, play a role in this context. The strong overlap of the genetic
targets involved in stress and fear learning suggests that a dimensional and
mechanistic model of the development of posttraumatic stress disorder based on
these constructs is promising. Genome-wide genetic analyses on fear and stress
mechanisms are scarce. So far, reliable replication is still lacking for most of
the molecular genetic findings, and the proportion of explained variance is rather
small. Further analysis of neurogenetic stress and fear learning needs to integrate
data from animal and human studies.
In the understanding of chronic pain, hypotheses derived from psychological
theories, together with insights from physiological assessments and brain imaging,
highlight the importance of mechanistically driven approaches. Physical system
changes, for example following injury, can result in alterations of psychological
processes and are accompanied by changes in corticolimbic circuits, which have been
shown to be essential in emotional learning and memory, as well as reward
processing and related behavior. In the present review, we thus highlight the
importance of motivational, reward/pain relief, and fear learning processes in the
context of chronic pain and discuss the potential of a mechanistic understanding of
chronic pain within a clinical perspective, for example for the development of
therapeutic strategies. We argue that changes in these mechanisms are not only
characteristic for chronic pain, reflecting consequences of the disorder, but are
also critically involved in the transition from acute to chronic pain states. (C)
2017 IBRO. Published by Elsevier Ltd. All rights reserved.
Anorexia nervosa (AN) is an often chronic and potentially lethal psychiatric
disorder, for which the precise etiology remains elusive. While current treatment
outcomes are modest at best, it is thought that the identification of translational
mechanisms driving the psychopathology of AN will assist in the development and
optimization of novel treatments. AN is a disorder characterized by fear and
avoidance, hypervigilant scrutiny of one's body, and an unnatural fear of weight
gain. Moreover, a suite of anxious traits and regimentation of behavior are
atypically common well in advance of the onset of restrictive eating in those with
AN. Here we consider the promise of shedding light on causal mechanisms of AN by
interrogating the role of fear-related learning, deficits in discriminating safety
cues, and extinction of acquired fear. We offer a translational rationale for this
line of inquiry, and discuss the clinical implications of considering fear as a
translational mechanism in the psychopathology of AN.
The current treatment of post-traumatic stress disorder (PTSD), phobias and other
anxiety disorders, remains insufficient particularly in producing long-lasting full
symptom control. Dysfunctional fear processing is common in these disorders,
including a deficiency in fear-inhibitory mechanisms and impairment in the ability
to discriminate between safety and danger cues. Research has aimed to elucidate
brain circuitries, neurotransmitters and downstream signaling pathways important in
the alleviation of aberrant fear, with a specific focus on mechanisms modulating
fear memory and its behavioral expression. MicroRNAs (miRNA) as fine tuners of gene
expression at the post-transcriptional level have emerged as critical regulators of
such mechanisms important in both, the generation and the inhibition of fear
memories. Along these lines, abnormal expression of miRNAs has been associated with
different fear-related disorders. After providing an updated overview on the
involvement of miRNAs in fear learning mechanisms, we summarize and discuss in
particular those studies in which the implication of miRNAs in successful
inhibition of fear has been explored. For a better overview, we dissociate the
different modes of fear alleviation investigated in this regard and present studies
in rodents demonstrating that specific miRNAs are involved in the destabilization
of fear by interfering with consolidation/reconsolidation mechanisms or that they
are associated with the generation of fear extinction or safety learning. Finally,
we discuss the potential of miRNAs as biomarkers and novel therapeutic targets, as
well as the challenges involved in applying the discovered mechanisms in the
development of improved treatments of fear- and trauma-related disorders.
Generating appropriate defensive behaviors in the face of threat is essential to
survival. Although many of these behaviors are 'hard-wired', they are also
flexible. For example, Pavlovian fear conditioning generates learned defensive
responses, such as conditioned freezing, that can be suppressed through extinction.
The expression of extinguished responses is highly context-dependent, allowing
animals to engage behavioral responses appropriate to the contexts in which threats
are encountered. Likewise, animals and humans will avoid noxious outcomes if given
the opportunity. In instrumental avoidance learning, for example, animals overcome
conditioned defensive responses, including freezing, in order to actively avoid
aversive stimuli. Recent work has greatly advanced understanding of the neural
basis of these phenomena and has revealed common circuits involved in the
regulation of fear. Specifically, the hippocampus and medial prefrontal cortex play
pivotal roles in gating fear reactions and instrumental actions, mediated by the
amygdala and nucleus accumbens, respectively. Because an inability to adaptively
regulate fear and defensive behavior is a central component of many anxiety
disorders, the brain circuits that promote flexible responses to threat are of
great clinical significance.
Fear and anxiety-related disorders are highly prevalent psychiatric conditions
characterized by avoidant and fearful reactions towards specific stimuli or
situations, which are disproportionate given the real threat such stimuli entail.
These conditions comprise the most common mental disorder group. There are a high
proportion of patients who fail to achieve remission and the presence of high
relapse rates indicate the therapeutic options available are far from being fully
efficient. Despite an increased understanding the neural circuits underlying fear
and anxiety-related behaviors in the last decades, a factor that could be partially
contributing to the lack of adequate therapies may be an insufficient understanding
of the core features of the disorders and their associated neurobiology.
Interestingly, the cerebellum shows connections with fear and anxiety-related brain
areas and functional involvement in such processes, but explanations for its role
in anxiety disorders are lacking. Therefore, the aims of this review are to provide
an overview of the neural circuitry of fear and anxiety and its connections to the
cerebellum, and of the animal studies that directly assess an involvement of the
cerebellum in these processes. Then, the studies performed in patients suffering
from anxiety disorders that explore the cerebellum will be discussed. Finally,
we'll propose a function for the cerebellum in these disorders, which could guide
future experimental approaches to the topic and lead to a better understanding of
the neurobiology of anxiety-related disorders, ultimately helping to develop more
effective treatments for these conditions.
The natural world presents a myriad of dangers that can threaten an organism's
survival. This diversity of threats is matched by a set of universal and species
specific defensive behaviors which are often subsumed under the emotions of fear
and anxiety. A major issue in the field of affective science, however, is that
these emotions are often conflated and scientists fail to reflect the ecological
conditions that gave rise to them. I attempt to clarify these semantic issues by
describing the link between ethologically defined defensive strategies and fear.
This in turn, provides a clearer differentiation between fears, the contexts that
evoke them and how they are organized within defensive survival circuits.
Fear conditioning represents an experimental paradigm ideally suited to investigate
aversive learning and memory mechanisms that are fundamental to the development,
maintenance and treatment of mental disorders. Men and women seem to differ in
their capability to learn and retrieve fear and extinction memories. This review
outlines how sex may influence human fear conditioning, with an emphasis on the sex
hormones and oral contraceptives. Available evidence suggests women with high
estrogen levels to acquire fear more readily, but also to extinguish fear more
easily, leading to an enhanced extinction memory trace. By contrast, women with low
estrogens (e.g. due to oral contraceptives) seem to show deficits in extinction
recall. These findings are highly relevant for future basic and applied studies
alike.
Fear learning reflects the adaptive ability to learn to anticipate aversive events
and to display preparatory fear reactions based on prior experiences. Usually,
these learning experiences are modeled in the lab with pairings between a neutral
conditioned stimulus (CS) and an aversive unconditioned stimulus (US) (i. e., fear
conditioning via CS-US pairings). Nevertheless, for humans, fear learning can also
be based on verbal instructions. In this review, we consider the role of verbal
instructions in laboratory fear learning. Specifically, we consider both the
effects of verbal instructions on fear responses in the absence of CS-US pairings
as well as the way in which verbal instructions moderate fear established via CS-US
pairings. We first focus on the available empirical findings about both types of
effects. More specifically, we consider how these effects are moderated by elements
of the fear conditioning procedure (i.e., the stimuli, the outcome measures, the
relationship between the stimuli, the participants, and the broader context).
Thereafter, we discuss how well different mental-process models of fear learning
account for these empirical findings. Finally, we conclude the review with a
discussion of open questions and opportunities for future research.
Purpose of review The volume of literature addressing fear of cancer recurrence
(FCR) is rapidly increasing. A summary of key developments in the research and
treatment of FCR was published by Sharpe et al. in 2017, and the current review
focuses on works published thereafter. Recent findings A comprehensive literature
review was conducted to provide an up-to-date summary of peer-reviewed publications
focusing on FCR. The search consisted of the most recent FCR reports published
between 2016 and 2017, which can be broadly categorized as: methods of assessment;
associations with FCR; FCR and caregivers; and FCR interventions. Summary FCR
assessments continue to undergo revisions, which may have positive implications for
clinicians and researchers seeking shorter measures to assess the FCR of their
patients and study participants. However, research is needed to determine if a
shorter FCR measure could be created using items that measure the construct alone,
yet still retaining optimal sensitivity and specificity, or also with its
determinants and consequences. Doing so would result in either unidimensional or
multidimensional measure of FCR. Notwithstanding these matters in FCR assessment,
the state of the literature continues to advance our understanding about
characteristics of survivors with highest FCR, which is useful to identify patients
in need of FCR interventions. These empirical results are useful to further
investigate the theoretical distinctions of FCR.
Understanding complex behavioral processes, both learned and innate, requires
detailed characterization of the principles governing signal flow in corresponding
neural circuits. Previous studies were hampered by the lack of appropriate tools
needed to address the complexities of behavior-driving micro- and macrocircuits.
The development and implementation of optogenetic methodologies revolutionized the
field of behavioral neuroscience, allowing precise spatiotemporal control of
specific, genetically defined neuronal populations and their functional
connectivity both in vivo and ex vivo, thus providing unprecedented insights into
the cellular and network-level mechanisms contributing to behavior. Here, we review
recent pioneering advances in behavioral studies with optogenetic tools, focusing
on mechanisms of fear-related behavioral processes with an emphasis on approaches
which could be used to suppress fear when it is pathologically expressed. We also
discuss limitations of these methodologies as well as review new technological
developments which could be used in future mechanistic studies of fear behavior.
Fear conditioning is a form of associative learning that is fundamental to survival
and involves potentiation of activity in excitatory projection neurons (PNs).
Current models stipulate that the mechanisms underlying this process involve
plasticity of PN synapses, which exhibit strengthening in response to fear
conditioning. However, excitatory PNs are extensively modulated by a diverse array
of GABAergic interneurons whose contributions to acquisition, storage, and
expression of fear memory remain poorly understood. Here we review emerging
evidence that genetically-defined interneurons play important subtype-specific
roles in processing of fear-related stimuli and that these dynamics shape PN firing
through both inhibition and disinhibition. Furthermore, intemeurons exhibit
structural, molecular, and electrophysiological evidence of fear learning-induced
synaptic plasticity. These studies warrant discarding the notion of intemeurons as
passive bystanders in long-term memory.
Background: fear of falling is prevalent among older people and associated with
various health outcomes. A growing number of studies have examined the effects of
interventions designed to reduce the fear of falling and improve balance among
older people, yet our current understanding is restricted to physiological
interventions. Psychological interventions such as cognitive behavioural therapy
(CBT) have not been reviewed and meta-analysed. Objective: to perform a systematic
review and meta-analysis evaluating the effects of CBT on reducing fear of falling
and enhancing balance in community-dwelling older people. Method: randomised
controlled trials (RCTs) addressing fear of falling and balance were identified
through searches of six electronic databases, concurrent registered clinical
trials, forward citation and reference lists of three previous systematic reviews.
Results: a total of six trials involving 1,626 participants were identified. Four
studies used group-based interventions and two adopted individual intervention.
Intervention period ranged from 4 to 20 weeks, and the number and duration of face-
to-face contact varied. Core components of the CBT intervention included cognitive
restructuring, personal goal setting and promotion of physical activities. The risk
of bias was low across the included studies. Our analysis suggests that CBT
interventions have significant immediate and retention effects up to 12 months on
reducing fear of falling, and 6 months post-intervention effect on enhancing
balance. Conclusions: CBT appears to be effective in reducing fear of falling and
improving balance among older people. Future researches to investigate the use of
CBT on reducing fear of falling and improving balance are warranted.
Despite being categorized as a procedure associated with a low risk of iatrogenic
hemorrhage, percutaneous pleural drainage in patients taking the ubiquitous
antiplatelet agent clopidogrel is still commonly perceived as a risky proposition.
There is mounting evidence, however, in support of the safety of percutaneous
needle procedures in persons receiving this medication. Establishing that these
pleural interventions can be performed safely without clopidogrel interruption
would be of great clinical significance, especially in those taking it for recent
cardiac stenting and therefore in danger of stent thrombosis should antiplatelet
therapy (APT) be withheld. The purpose of the present review is to summarize the
available data from published studies and series of thoracentesis and chest tube
insertion in patients exposed to clopidogrel. Also incorporated into this review
are relevant investigations from the thoracic surgery and interventional radiology
experience, which contribute indirect evidence and help shape the context for
interpreting the safety data reported in the pleural literature. At the end, an
attempt is made to synthesize the current knowledge on this topic into conclusions
for guiding practice.
Background: Fear of cancer recurrence (FCR) is reportedly common, persistent,
associated with significant morbidity and often higher in cancer caregivers than
cancer patients. This review will summarise empirical research on FCR to understand
its prevalence, severity, correlates, course and impact in families and caregivers
of adults diagnosed with cancer, and identify tested interventions that reduce its
effects. Methods: This review will include peer-reviewed, empirical, qualitative
and/or quantitative studies on fear, worry or concern of patients' cancer returning
or progressing among adult family members or caregivers of the cancer patient. It
will exclude records reporting no original empirical research on FCR. We will
search CINAHL, Embase, PubMed, PsycINFO, ProQuest Dissertations and Theses GLOBAL
from 1997 onwards. Pairs of reviewers will conduct independent screening, data
extraction and risk of bias assessment. Risk of bias will be assessed with the
Cochrane Risk of Bias tool for randomised studies, the Risk of Bias Assessment tool
for Nonrandomized Studies and the questions for qualitative studies in the mixed
methods appraisal tool. We will conduct a narrative synthesis of quantitative
studies and a thematic synthesis of qualitative studies. Discussion: This review
will provide further clarity on the prevalence and severity of FCR in families and
caregivers and differences by caregiver and care recipient demographic and medical
characteristics. Any intervention studies located may indicate therapies or
treatments that could reduce FCR in families and caregivers. Findings are expected
to provide guidance for individuals and organisations working to manage FCR in
families and caregivers of those with cancer.
Panic disorder (PD) is one of the most common psychiatric disorders. Recurrent,
unexpected panic attacks (PAs) are the primary symptom and strongly impact
patients' quality of life. Clinical manifestations are very heterogeneous between
patients, emphasizing the need for a dimensional classification integrating various
aspects of neurobiological and psychological circuits in line with the Research
Domain Criteria (RDoC) proposed by the US National Institute of Mental Health. To
go beyond data that can be collected in the daily clinical situation, experimental
panic provocation is widely used, which has led to important insights into involved
brain regions and systems. Genetic variants can determine the sensitivity to
experimental models such as carbon dioxide (CO2) exposure and can increase the risk
to develop PD. Recent developments now allow to better assess the dynamic course of
PAs outside the laboratory in patients' natural environment. This can provide novel
insights into the underlying mechanisms and the influence of environmental factors
that can alter gene regulation by changing DNA methylation. In this mini review, we
discuss assessment of PAs in the clinic, in the laboratory using CO2 exposure,
genetic associations, and the benefits of real-life assessment and epigenetic
research.
Objective: The WHO recently highlighted the need for research into potential
interventions that can be used to mitigate pain during mass vaccinations, in
addition to interventions specific for adolescents. The current review examines the
literature on potential interventions that can be used during mass vaccination
settings in healthy individuals between the ages of 4 and 15 years old. Methods:
Criteria for inclusion were: 1)participants between the ages of 4-15 years,
2)interventions that were patient-focused, 3)vaccinations in healthy individuals,
4)outcome measures to include self-reported pain, fear or distress. Results:
Twenty-seven articles were identified with a total of 31 interventions. Eleven
interventions used injection-site specific interventions, 17 used patient-led
interventions and three used a combination of both site-specific and patient-led
interventions. Conclusion: Interventions using coolant and vibration together, as
well as a combination of site-specific and patient-led interventions, showed the
most consistent effects in reducing self-reported pain, fear or distress.
Associative memory formation is essential for an animal's survival by ensuring
adaptive behavioral responses in an ever-changing environment. This is particularly
important under conditions of immediate threats such as in fear learning. One of
the key brain regions involved in associative fear learning is the amygdala. The
basolateral amygdala is the main entry site for sensory information to the amygdala
complex, and local plasticity in excitatory basolateral amygdala principal neurons
is considered to be crucial for learning of conditioned fear responses. However,
activity and plasticity of excitatory circuits are tightly controlled by local
inhibitory interneurons in a spatially and temporally defined manner. In this
review, we provide an updated view on how distinct interneuron subtypes in the
basolateral amygdala contribute to the acquisition and extinction of conditioned
fear memories.
CRISPR gene editing is poised to transform the therapeutic landscape for diseases
of genetic origin. The ease and agility by which CRISPR can make specific changes
to DNA holds great promise not only for the treatment of heritable diseases, but
also their prevention through germline editing. CRISPR-based therapeutic strategies
are currently under development for numerous monogenic diseases. These strategies
range from proof of concept studies demonstrating pre-fertilization gamete editing
to recently initiated clinical trials for postnatal ex vivo therapies. The promise
of CRISPR's human genome editing potential has captivated the public's attention.
It is of paramount importance that medical professionals who work with patients who
may have or carry a monogenic heritable disease understand CRISPR technology in
order to have informed and compassionate discussions with their patients.
Understanding CRISPR means understanding its evolving therapeutic applications'
nuances, limitations, and barriers to access as well as the regulatory landscape
they inhabit. In this piece we provide a review of the promises and pitfalls of
CRISPR germline gene editing and their implications for patient decision-making
throughout various stages of the reproductive process. (C) 2018 Elsevier Inc. All
rights reserved.
Use of fear appeals assumes that when people are emotionally confronted with the
negative effects of their behaviour they will change that behaviour. That reasoning
is simple and intuitive, but only true under specific, rare circumstances. Risk
perception theories predict that if people will experience a threat, they want to
counter that threat. However, how they do so is determined by their coping efficacy
level: if efficacy is high, they may change their behaviour in the suggested
direction; if efficacy is low, they react defensively. Research on fear appeals
should be methodologically sound, comparing a threatening to a non-threatening
intervention under high and low efficacy levels, random assignment and measuring
behaviour as outcome. We critically review extant empirical evidence and conclude
that it does not support positive effects of fear appeals. Nonetheless, their use
persists and is even promoted by health psychology researchers, causing scientific
insights to be ignored or misinterpreted.
Fear is considered an integral part of the brain's defensive mechanism that evolved
to protect animals and humans from predation and other ecological threats. Hence,
it is logical to study fear from the perspective of antipredator-survival behaviors
and circuits by sampling a range of threatening situations that organisms are
likely to encounter in the wild. In the past several decades, however, mainstream
fear research has focused on the importance of associative learning; that is, how
animals become frightened of innocuous cues as consequences of their contingent
pairing with aversive events. While significant discoveries have been made,
contemporary fear models derived from learning studies are likely to provide only a
partial picture of the brain's fear system because they cannot simulate the dynamic
range of risky situations in nature that require various adaptive actions and
decisions. This review considers two different approaches to study fear, grounded
on behaviorism and ethology and examines their contributions in revealing the
naturalistic workings of fear in guiding and shaping behavior as animals make real-
world choices.
Panic disorder is characterized by symptoms with abrupt surges of fear with
palpitations, sweating, trembling, heat sensations. Considering its disease burden
on each individual and on society, understanding its etiology is important. Though
no one specific etiology has been known, like other psychiatric disorders, multiple
factors such as genetic, environmental, neurobiological, psychopathological factors
have been suggested. In this article, we reviewed currently known etiologies and
related study results, regarding especially genetic and epigenetic aspects of the
panic disorder. Early studies, including twin studies, family studies, adoption
studies suggested highly familial trait of panic disorder. Linkage studies, either,
found panic disorder is not a single gene disorder but confirmed existence of
multiple related genes. Chromosome and candidate gene studies found few related
genes, NPY, ADORA2A, COMT, IKBKE. Newer method, genome-wide association studies
(GWAS) have been searching for newer genes. No genome-wide significant genes,
however, were detected, confirming previously known candidate genes, NPY5R on
4q31.3-32, BDKRB2 on 14q32, instead. Epigenetic modification has also been studied
on many different psychiatric disorders. Monoamine oxidase A (MAOA)
hypomethylation, taken together with negative life events, showed relation with
panic disorder. Glutamate decarbodylases 1 (GAD1) hypomethylation was also specific
on panic disorder patients. Relation with noradrenaline transporter (NET) gene
SLC6a2 promoter methylation has also been studied. In conclusion, no specific gene
or epigenetic pattern can fully explain etiology of panic disorder. Few genes and
epigenetic patterns, however, showed strong association with panic disorder
compared to healthy controls. Considering its multivariable background, further
studies with larger populations can confirm current results and clarify etiologies
of panic disorder.
The percutaneous coronary intervention (PCI) has undergone rapid evolution over the
last 40 years and has become one of the most widely performed medical procedures.
The introduction of intracoronary stents has improved the safety and efficacy of
PCI. However, with the advent of stenting, a new potentially fatal enemy has
emerged: stent thrombosis. Ever since, adjunct pharmacological therapy, stent
technique, and technology have been adjusted to reduce the risk of stent
thrombosis. The aim of the present article is to provide an overview of the past,
present, and future aspects of PCI in relation to stent thrombosis.
The purpose of the current paper was to review the empirical literature on the
cooccurrence of panic and epilepsy, in order to determine whether there is an
increased risk of panic attacks and panic disorder among adults with epilepsy and
an increased risk of epilepsy among adults with panic disorder. Given the overlap
between panic and ictal fear, a preliminary aim of the current review was to
critically evaluate the methodology used to differentiate between diagnoses of
panic disorder and epilepsy in existing research. A literature search was conducted
in relevant electronic databases, and articles that directly focused on panic and
epilepsy among adults were selected for the current review (n=17). Overall, results
suggest that rates of epilepsy are elevated among individuals with panic disorder
and that panic attacks are elevated among individuals with epilepsy, but rates of
panic disorder among people with epilepsy are inconsistent. However, most studies
did not use sufficiently rigorous methods to differentiate between panic disorder
and epilepsy. Therefore, a critical next step in this area of research is to
develop a standard procedure for differentiating ictal fear from panic attacks and
panic disorder. Published by Elsevier Inc.
Introduction: Psychogenic Non-Epileptic Seizures (PNES) are events that appear
epileptic but are instead thought to have a psychological origin. Increased rates
of several psychiatric disorders have been reported in PNES, including anxiety and
panic disorders. Some theories suggest panic and/or hyperventilation have
aetiological roles in PNES, though these remain unproven. Methods: We conducted a
systematic review of associations of panic and hyperventilation with PNES using
Ovid Medline and PubMed, and a meta-analysis where appropriate. Results: We found
eighteen studies reporting rates of panic in PNES and eight studies reporting
hyperventilation. The reported rate of panic attacks in PNES ranged from 17% to
83%, with physical symptoms more commonly reported, and affective symptoms less so.
'Dizziness or light-headedness' was found to be more prevalent than 'fear of dying'
by random-effects meta-analysis (68% vs. 23%). A proportion meta-analysis found a
weighted occurrence of 20% of panic disorder in PNES. A pooled meta analytic rate
of PNES events following voluntary hyperventilation induction was 30%, while the
clinically observed rates of peri-ictal hyperventilation in PNES without induction
varied from 15 to 46%. Conclusions: Previous studies have reported moderate rates
of association of panic in PNES, though the proportions varied considerably across
the literature, with physical symptoms more commonly reported than affective.
Hyperventilation is an effective inducer of PNES events in a minority, and can be
observed occurring in a minority of patients without induction. These results
support an important, albeit not essential, role for panic and hyperventilation in
the pathogenesis of PNES events. (C) 2018 British Epilepsy Association. Published
by Elsevier Ltd. All rights reserved.
Introduction: Fear of childbirth is a problematic mental health issue during
pregnancy. But, effective interventions to reduce this problem are not well
understood. Objectives: To examine effective interventions for reducing fear of
childbirth. Material and methods: The Cochrane Central Register of Controlled
Trials, PubMed, Embase and PsycINFO were searched since inception till September
2017 without any restriction. Randomised controlled trials and quasi-randomised
controlled trials comparing interventions for treatment of fear of childbirth were
included. The standardized mean differences were pooled using random and fixed
effect models. The heterogeneity was determined using the Cochran's test and I2
index and was further explored in meta-regression model and subgroup analyses.
Results: Ten studies inclusive of 3984 participants were included in the meta-
analysis (2 quasi-randomized and 8 randomized clinical trials). Eight studies
investigated education and two studies investigated hypnosis-based intervention.
The pooled standardized mean differences of fear for the education intervention and
hypnosis group in comparison with control group were -0.46 (95% CI -0.73 to -0.19)
and -0.22 (95% CI -0.34 to -0.10), respectively. Conclusions: Both types of
interventions were effective in reducing fear of childbirth; however our pooled
results revealed that educational interventions may reduce fear with double the
effect of hypnosis. Further large scale randomized clinical trials and individual
patient data meta-analysis are warranted for assessing the association. (c) 2017
Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.
Type 2 diabetes mellitus is highly prevalent in older adults (>= 65 years of age)
and increases fall risk. Fear of falling and low balance confidence are reported in
both fallers and nonfallers and can potentially be more debilitating than a fall
itself. Therefore, the objective of this scoping review was to examine and map the
current research evidence of balance confidence and fear of falling in older adults
with type 2 diabetes. A search of CINAHL, EMBASE and PubMed was conducted. The
search included MeSH terms and the key terms diabet* AND fear OR falls AND self-
efficacy OR balance confidence. Inclusion criteria were 1) population: older adults
(>= 65 years of age) with type 2 diabetes; and 2) outcome measure: balance
confidence or fear of falling. We included 21 studies: fear of falling (n=14);
balance confidence (n=7). We categorized them into 4 themes: prevalence, severity,
determinants and interventions. Determinants were further categorized into
physical, psychosocial and health-related domains. Fear of falling and low balance
confidence were highly prevalent and more severe in older adults with type 2
diabetes. Determinants of fear of falling and balance confidence occurred beyond
the physical domain and the presence of diabetic peripheral neuropathy. Targeted
group-based interventions (e.g. gait and balance training, tai chi, yoga) appear to
be beneficial in reducing fear of falling and improving balance confidence. Future
work is needed to generate best practices related to fear of falling and low
balance confidence in older adults with type 2 diabetes. (C) 2018 Canadian Diabetes
Association.
We will briefly examine the implication of a multi-dimensional and multi-level view
of evolution for addressing the role and function of survival circuits in the
context of human cognition, and the underlying emotional, memory, and behavioral
processes both impact. It is our contention that human cognition can partially
direct and channel these more ancient neurobiological regulatory systems. We argue
that while survival circuits can be helpful or hurtful to human functioning, they
are particularly likely to be problematic when they occur in the context of
cognitive processes that have become automatic and well-practiced, and thus beyond
normal conscious processes of cognitive control. Psychotherapy can be of help in
increasing access to such 'unconscious' process, reducing their automatic impact,
and allowing human goals and values to over-ride maladaptive processes engaged by
survival circuits.
Objective Fear of cancer recurrence (FCR) is a common existential concern and
source of distress among adults with a cancer history. Multiple randomized
controlled trials (RCTs) have examined mind-body approaches to mitigating FCR. We
summarized characteristics of these trials and calculated their pooled effects on
decreasing FCR. Methods Results Six electronic databases were systematically
searched from inception to May 2017, using a strategy that included multiple terms
for RCTs, cancer, mind-body medicine, and FCR. Data extraction and reporting
followed Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-
Analyses (PRISMA) guidelines. Pooled effect sizes on self-report measures of FCR
were computed by using random-effects models. Nineteen RCTs (pooled N = 2806) were
included. Most studies (53%) were published since 2015 and targeted a single cancer
type (84%; mostly breast). Intervention sessions (median = 6, mode = 4) tended to
last 120 minutes and occur across 1.5 months. Delivery was predominantly in-person
(63%) to either groups (42%) or individuals (42%). Most interventions incorporated
multiple mind-body components (53%), commonly cognitive-behavioral skills (58%), or
meditative practices (53%). Small-to-medium pooled effect sizes were observed
postintervention (Hedges' g = -0.36, 95% CI = -0.49, -0.23, P < .001) and at
follow-up assessments (median = 8 months, P < .001). Potential modifiers (control
group design, group/individual delivery, use of cognitive-behavioral or mindfulness
skills, number of mind-body components, cancer treatment status, and number of
sessions) did not reach statistical significance. Conclusions Mind-body
interventions are efficacious for reducing FCR, with small-to-medium effect sizes
that persist after intervention delivery ends. Recommendations include testing
effects among survivors of various cancers and exploring the optimal integration of
mind-body practices for managing fundamental uncertainties and fears during cancer
survivorship.
The locus coeruleus norepinephrine (LC-NE) system plays a broad role in learning
and memory. Here we begin with an overview of the LC-NE system. We then consider
how both direct and indirect manipulations of the LC-NE system affect cued and
contextual aversive learning and memory. We propose that NE dynamically modulates
Pavlovian conditioning and extinction, either promoting or impairing learning
aversive processes under different levels of behavioral arousal. We suggest that
under high levels of stress (e.g., during/soon after fear conditioning) the locus
coeruleus (LC) promotes cued fear learning by enhancing amygdala function while
simultaneously blunting prefrontal function. Under low levels of arousal, the LC
promotes PFC function to promote downstream inhibition of the amygdala and foster
the extinction of cued fear. Thus, LC-NE action on the medial prefrontal cortex
(mPFC) might be described by an inverted-U function such that it can either enhance
or hinder learning depending on arousal states. In addition, LC-NE seems to be
particularly important for the acquisition, consolidation and extinction of
contextual fear memories. This may be due to dense adrenoceptor expression in the
hippocampus (HPC) which encodes contextual information, and the ability of NE to
regulate long-term potentiation (LTP). Moreover, recent work reveals that the
diversity of LC-NE functions in aversive learning and memory are mediated by
functionally heterogeneous populations of LC neurons that are defined by their
projection targets. Hence, LC-NE function in learning and memory is determined by
projection-specific neuromodulation that accompanies various states of behavioral
arousal.
Women are disproportionately affected by posttraumatic stress disorder (PTSD), and
gonadal hormones are implicated in fear learning processes associated with PTSD. In
rodents, lower estradiol, particularly during metestrus when progesterone is also
low, is associated with impaired extinction. Based on theories that extinction
deficits underlie PTSD, individuals with lower estradiol and progesterone may
exhibit fear learning deficits and higher PTSD symptomatology. A systematic review
was conducted in Psycinfo, PubMed, and Medline databases for studies examining
estradiol, progesterone, or menstrual phase in relation to fear learning or PTSD
symptoms. Twenty-three studies are organized into fear learning (k = 17) and PTSD
symptom (k = 12) studies. Across fear learning studies, higher estradiol was
consistently associated with enhanced fear extinction recall and inconsistently and
weakly associated with better extinction learning and fear acquisition,
respectively. Extending to PTSD symptoms, the association with hormonal status was
reversed, such that luteal phase, associated with higher estradiol and
progesterone, was generally associated with higher re-experiencing symptoms.
Overall, human fear learning studies were consistent with rodent studies. Despite
strong experimental links between fear learning processes and PTSD, the clinical
translation was inconsistent and may reflect varying methods, imprecise
measurement, and greater complexity of hormonal effects on symptomatology.
The study of fear extinction represents an important example of translational
neuroscience in psychiatry and promises to improve the understanding and treatment
of anxiety and fear-related disorders. We present the results of a set of meta-
analyses of human fear extinction studies in healthy participants, conducted with
functional magnetic resonance imaging (fMRI) and reporting whole-brain results.
Meta-analyses of fear extinction learning primarily implicate consistent activation
of brain regions linked to threat appraisal and experience, including the dorsal
anterior cingulate and anterior insular cortices. An overlapping anatomical result
was obtained from the meta-analysis of extinction recall studies, except when
studies directly compared an extinguished threat stimulus to an unextinguished
threat stimulus (instead of a safety stimulus). In this latter instance, more
consistent activation was observed in dorsolateral and ventromedial prefrontal
cortex regions, together with other areas including the hippocampus. While our
results partially support the notion of a shared neuroanatomy between human and
rodent models of extinction processes, they also encourage an expanded account of
the neural basis of human fear extinction.
As companies connect with consumers on social media, privacy becomes a significant
area of concern. This research assesses consumers' understanding of social media
privacy policies (CUSPP) and fear related to those policies. Study one develops a
scale to measure CUSPP. Study two examines the influence of text, audio, and
pictorial cues used in social media privacy policies, on consumers' CUSPP and
physiologically-measured fear. Results suggest presentational cues affect CUSPP and
fear of social media privacy policies. This research is among the first to use
self-report and physiological measures to assess consumer understanding and
emotional reactions in a social media context.
Objective To conduct a systematic review of pain anxiety, pain catastrophizing, and
fear of pain measures psychometrically established in youth with chronic pain. The
review addresses three specific aims: (1) to identify measures used in youth with
chronic pain, summarizing their content, psychometric properties, and use; (2) to
use evidence-based assessment criteria to rate each measure according to the
Society of Pediatric Psychology (SPP) guidelines; (3) to pool data across studies
for meta-analysis of shared variance in psychometric performance in relation to the
primary outcomes of pain intensity, disability, generalized anxiety, and
depression. Methods We searched Medline, Embase, PsycINFO, and relevant literature
for possible studies to include. We identified measures studied in youth with
chronic pain that assessed pain anxiety, pain catastrophizing, or fear of pain and
extracted the item-level content. Study and participant characteristics, and
correlation data were extracted for summary and meta-analysis, and measures were
rated using the SPP evidence-based assessment criteria. Results Fifty-four studies
(84 papers) met the inclusion criteria, including seven relevant measures: one
assessed pain anxiety, three pain catastrophizing, and three fear of pain. Overall,
five measures were rated as "well established." We conducted meta-analyses on four
measures with available data. We found significant positive correlations with the
variables pain intensity, disability, generalized anxiety, and depression.
Conclusion Seven measures are available to assess pain anxiety, pain
catastrophizing, and fear of pain in young people with chronic pain, and most are
well established. We present implications for practice and directions for future
research.
MDMA-assisted psychotherapy for treatment of PTSD has recently progressed to Phase
3 clinical trials and received Breakthrough Therapy designation by the FDA. MDMA
used as an adjunct during psychotherapy sessions has demonstrated effectiveness and
acceptable safety in reducing PTSD symptoms in Phase 2 trials, with durable
remission of PTSD diagnosis in 68% of participants. The underlying psychological
and neurological mechanisms for the robust effects in mitigating PTSD are being
investigated in animal models and in studies of healthy volunteers. This review
explores the potential role of memory reconsolidation and fear extinction during
MDMA-assisted psychotherapy. MDMA enhances release of monoamines (serotonin,
norepinephrine, dopamine), hormones (oxytocin, cortisol), and other downstream
signaling molecules (BDNF) to dynamically modulate emotional memory circuits. By
reducing activation in brain regions implicated in the expression of fear-and
anxiety-related behaviors, namely the amygdala and insula, and increasing
connectivity between the amygdala and hippocampus, MDMA may allow for reprocessing
of traumatic memories and emotional engagement with therapeutic processes. Based on
the pharmacology of MDMA and the available translational literature of memory
reconsolidation, fear learning, and PTSD, this review suggests a neurobiological
rationale to explain, at least in part, the large effect sizes demonstrated for
MDMA in treating PTSD.
Pain is essential for avoidance of tissue damage and for promotion of healing.
Notwithstanding the survival value, pain brings about emotional suffering reflected
in fear and anxiety, which in turn augment pain thus giving rise to a self-
sustaining feedforward loop. Given such reciprocal relationships, the present
article uses neuro-scientific conceptualizations of fear and anxiety as a
theoretical framework for hitherto insufficiently understood pathophysiological
mechanisms underlying chronic pain. To that end, searches of PubMed-indexed
journals were performed using the following Medical Subject Headings' terms: pain
and nociception plus amygdala, anxiety, cognitive, fear, sensory, and unconscious.
Recursive sets of scientific and clinical evidence extracted from this literature
review were summarized within the following key areas: (1) parallelism between
acute pain and fear and between chronic pain and anxiety; (2) all are related to
the evasion of sensory-perceived threats and are subserved by subcortical circuits
mediating automatic threat-induced physiologic responses and defensive actions in
conjunction with higher order corticolimbic networks (e.g., thalamocortical,
thalamo-striato-cortical and amygdalo-cortical) generating conscious
representations and valuation-based adaptive behaviors; (3) some instances of
chronic pain and anxiety conditions are driven by the failure to diminish or block
respective nociceptive information or unconscious treats from reaching conscious
awareness; and (4) the neural correlates of pain-related conscious states and
cognitions may become autonomous (i.e., dissociated) from the subcortical
activity/function leading to the eventual chronicity. Identifying relative
contributions of the diverse neuroanatomical sources, thus, offers prospects for
the development of novel preventive, diagnostic, and therapeutic strategies in
chronic pain patients.
Great progress has been made in our understanding of how so-called memory engrams
in the brain enable the storage and retrieval of memories. This has led to the
realization that across the lifetime of an animal, the spatial and temporal
properties of a memory engram are not fixed, but instead are subjected to dynamic
modifications that can be both dependent and independent on additional experiences.
The dynamic nature of engrams is especially relevant in the case of fear memories,
whose contributions to an animal's evolutionary fitness depend on a delicate
balance of stability and flexibility. Though fear memories have the potential to
last a lifetime, their expression also needs to be properly tuned to prevent
maladaptive behavior, such as seen in patients with post traumatic stress disorder.
To achieve this balance, fear engrams are subjected to complex spatiotemporal
dynamics, making them informative examples of the "dynamic engram". In this review,
we discuss the current understanding of the dynamic nature of fear engrams in the
basolateral amygdala, a brain region that plays a central role in fear memory
encoding and expression. We propose that this understanding can be further advanced
by studying how fast dynamics, such as oscillatory circuit activity, support the
storage and retrieval of fear engrams that can be stable over long time intervals.
Through advances in both basic and clinical scientific research, Pavlovian fear
conditioning and extinction have become an exemplary translational model for
understanding and treating anxiety disorders. Discoveries in associative and
neurobiological mechanisms underlying extinction have informed techniques for
optimizing exposure therapy that enhance the formation of inhibitory associations
and their consolidation and retrieval over time and context. Strategies that
enhance formation include maximizing prediction-error correction by violating
expectancies, deepened extinction, occasional reinforced extinction, attentional
control and removal of safety signals/behaviours. Strategies that enhance
consolidation include pharmacological agonists of NMDA (i.e. D-cycloserine) and
mental rehearsal. Strategies that enhance retrieval include multiple contexts,
retrieval cues, and pharmacological blockade of contextual encoding. Stimulus
variability and positive affect are posited to influence the formation and the
retrieval of inhibitory associations. Inhibitory regulation through affect
labelling is considered a complement to extinction. The translational value of
extinction will be increased by more investigation of elements central to
extinction itself, such as extinction generalization, and interactions with other
learning processes, such as instrumental avoidance reward learning, and with other
clinically relevant cognitive-emotional processes, such as self-efficacy, threat
appraisal and emotion regulation, will add translational value. Moreover, framing
fear extinction and related processes within a developmental context will increase
their clinical relevance. This article is part of a discussion meeting issue 'Of
mice and mental health: facilitating dialogue between basic and clinical
neuroscientists'.
Advances in the care of infants and children with congenital heart disease (CHD)
have resulted in significantly improved survival of this population into adulthood.
Although the majority of patients with CHD have undergone surgical intervention or
transcatheter intervention, patients are not "cured" and almost all require
lifelong cardiac care. In many parts of the world, robust systems of care have been
developed for infants and children with CHD. Although there has been progress in
the development of programs for the care of adults with CHD, the time of transition
and transfer of care remains a time of high risk for lapses in care and becoming
lost to follow-up. Transition is a process of education and preparation for young
patients to assume their own care as they enter adulthood, while transfer is the
actual event of a patient moving their care from a pediatric to an adult
environment. The purpose of this review is to summarize what is known of best
practices related to the transition and transfer of patients with CHD to adult
services and to provide a practical approach to the sometimes daunting task of
preparing patients for the transfer of care. (C) 2018 Published by Elsevier Inc.
Objectives To evaluate the effectiveness and degree of acceptance by children and
adolescents of the use of oscillating tips compared with rotating drills. Design
Systematic review. Data sources PubMed, the Cochrane Central Register of Controlled
Trials (CENTRAL), the Cochrane Library and Web of Science (October 2017).
Eligibility criteria Controlled randomised or non-randomised trials that evaluated
sonic and ultrasonic oscillating devices versus rotating drill. Data extraction
Eligible studies were selected and data extracted independently by two reviewers.
Risk of bias was assessed using the Cochrane Method. Results Two controlled
clinical trials comprising 123 children aged 2-12 years old were identified. Both
trials were at high risk of selection bias and unclear risk of detection bias. In
one trial, pain due to the use of oscillating drill resulted lower than employing
rotating drill (Verbal Hochman Scale: RR 0.64 (95% CI 0.41 to 1.00); Visual Facial
Expression Scale: RR 0.64 (95% CI 0.44 to 0.94)). In another study, compared with
traditional drill ultrasonic tip was associated with a lower level of patient's
discomfort (RR 0.40 (95% CI 0.20 to 0.79)) but not with dental anxiety (RR 1.29
(95% CI 0.97 to 1.71)). The effectiveness of the removal of caries as well as
fillings durability were only considered in one study, but no statistically
significant differences were found between the two interventions. Conclusions The
evidence based on two low-quality studies was insufficient to conclude that the use
of oscillating tips for the management of pain and dental fear in children or
adolescents compared with rotating drills was more effective.
PROBLEM IDENTIFICATION: Fear of cancer recurrence (FCR) is prevalent among people
with cancer; therefore, it is important to determine whether interventions offered
to this population are effective in alleviating FCR. This review summarizes
randomized, controlled trials in the literature about the effect of psychosocial
interventions on FCR in people with cancer. LITERATURE SEARCH: A systematic review
of the literature was conducted using PubMed, Web of Science, EMBASE, and Cochrane
Library. DATA EVALUATION: Extracted data included cancer type, number of
participants, intervention type and duration, follow-ups, and primary and secondary
outcomes. SYNTHESIS: 10 studies met inclusion criteria. Types of interventions
included mindfulness-based therapy (n = 3), cognitive behavioral therapy (n = 4),
psychoeducational interventions (n = 1), gratitude interventions (n = 1), and
communication interventions (n = 1). IMPLICATIONS FOR PRACTICE: Psychosocial
interventions are beneficial for alleviating FCR and positively affect depression,
anxiety, and quality of life in people with cancer.
Dental fear/anxiety is a widely recognised problem affecting a large proportion of
the population. It can result in avoidance and/or difficulty accepting dental care.
We believe that psychological intrusion may play a role in the aetiology and
maintenance of dental fear for at least some individuals. In this narrative review
we will take a developmental perspective in order to understand its impact across
the lifespan. We will consider the nature of 'self,' parenting styles, the details
of intrusive parenting or parental psychological control, and briefly touch upon
child temperament and parental anxiety. Finally, we draw together the supporting
(largely unrecognised) evidence available in the dental literature. We illustrate
the paper with clinical examples and discuss possibly effective ways of addressing
the problem. We conclude that psychological intrusion appears to play an important
role in dental fear, for at least some individuals, and we call for detailed
research into the extent and exact nature of the problem. A simple means of
identifying individuals who are vulnerable to psychological intrusion would be
useful for dentists.
Context is an ever-present combination of discrete environmental elements capable
of influencing many psychological processes. When context is associated with an
aversive stimulus, a permanent contextual fear memory is formed. Context is
hypothesized to greatly influence the treatability of various fear-based
pathologies, in particular, post-traumatic stress disorder (PTSD). In order to
understand how contextual fear memories are encoded and impact underlying fear
pathology, delineation of the underlying neural circuitry of contextual fear memory
consolidation and maintenance is essential. Past understandings of contextual fear
suggest that the hippocampus only creates a unitary, or single, representation of
context. This representation is sent to the amygdala, which creates the associative
contextual fear memory. In contrast, here we review new evidence from the
literature showing contextual fear memories to be consolidated and maintained by
both amygdala and hippocampus. Based on this evidence, we revise the current model
of contextual fear memory consolidation, highlighting a larger role for
hippocampus. This new model may better explain the role of the hippocampus in PTSD.
Proposals to increase research reproducibility frequently call for focusing on
effect sizes instead of p values, as well as for increasing the statistical power
of experiments. However, it is unclear to what extent these two concepts are indeed
taken into account in basic biomedical science. To study this in a real-case
scenario, we performed a systematic review of effect sizes and statistical power in
studies on learning of rodent fear conditioning, a widely used behavioral task to
evaluate memory. Our search criteria yielded 410 experiments comparing control and
treated groups in 122 articles. Interventions had a mean effect size of 29.5%, and
amnesia caused by memory-impairing interventions was nearly always partial. Mean
statistical power to detect the average effect size observed in well-powered
experiments with significant differences (37.2%) was 65%, and was lower among
studies with non-significant results. Only one article reported a sample size
calculation, and our estimated sample size to achieve 80% power considering typical
effect sizes and variances (15 animals per group) was reached in only 12.2% of
experiments. Actual effect sizes correlated with effect size inferences made by
readers on the basis of textual descriptions of results only when findings were
non-significant, and neither effect size nor power correlated with study quality
indicators, number of citations or impact factor of the publishing journal. In
summary, effect sizes and statistical power have a wide distribution in the rodent
fear conditioning literature, but do not seem to have a large influence on how
results are described or cited. Failure to take these concepts into consideration
might limit attempts to improve reproducibility in this field of science.
Introduction: Several effective medications are available for treating panic
disorder (PD). However, outcomes are unsatisfactory in a number of patients,
suggesting the usefulness of expanding the array of antipanic drugs and improving
the quality of response to current recommended treatments. Areas covered: The
authors have performed an updated systematic review of pharmacological studies
(phase III onwards) to examine whether advances have been made in the last five
years. Only four studies were included. D-cycloserine no longer seemed promising as
a cognitive-behavioral therapy (CBT) enhancer. Some preliminary findings concerning
the optimization of recommended medications deserved consideration, including: the
possibility that SSRIs are more effective than CBT alone in treating panic attacks,
combined therapy is preferable when agoraphobia is present, and clonazepam is more
potent than paroxetine in decreasing panic relapse. Expert opinion: Given the lack
of novel treatments, expanding a personalized approach to the existing medications
seems to be the most feasible strategy to improve pharmacotherapy outcomes
regarding PD. Recent technological progress, including wearable devices collecting
real-time data, 'big data' platforms, and application of machine learning
techniques might help make outcome prediction more reliable. Further research on
previously promising novel treatments is also recommended.
The 9/11 terrorist attacks and heavy-handed state and popular response to them
stimulated increased scholarship on American Muslims. In the social sciences, this
work has focused mainly on Arabs and South Asians, and more recently on African
Americans. The majority of this scholarship has not engaged race theory in a
comprehensive or intersectional manner. The authors provide an overview of the work
on Muslims over the past 15 years and argue that the Muslim experience needs to be
situated within race scholarship. The authors further show that September 11 did
not create racialized Muslims, Arabs, or South Asians. Rather, the authors
highlight a preexisting, racializing war on terror and a more complex history of
these groups with race both globally and domestically. Islamophobia is a popular
term used to talk about Muslim encounters with discrimination, but the concept
lacks a clear understanding of race and structural racism. Newer frameworks have
emerged situating Muslim experiences within race scholarship. The authors conclude
with a call to scholars to embark on studies that fill major gaps in this emerging
field of study-such as intersectional approaches that incorporate gender,
communities of belonging, black Muslim experiences, class, and sexuality-and to
remain conscious of the global dimensions of this racial project.
Panic disorder is one of the most frequent psychiatric conditions and the incidence
is increasing. More worrying than the number of patients is the major negative
impact over personal, social and economic functioning. Due to the increasing risk
of death, whether by suicide or by cardiovascular disease, in patients suffering of
panic disorder a prompt, adequate intervention is essential. This condition has a
chronic evolution, with low rates of remission and a significant negative impact
over quality of life and over social and economic aspects. In this article we
presented different aspects related to the therapeutic management of panic
disorder, with special reference to pharmacotherapy and its specific classes and
psychotherapy, particularly Cognitive-Behavioral Therapy. These two therapeutic
categories proved to be the most efficient in both acute and long-term
symptomatology, with improvement of anxiogenic rumination, avoidance behavior or
agoraphobia. Pharmacotherapy, whether with antidepressants or benzodiazepines, is
recommended to be followed by psychotherapy. SSRIs and SSNRs are recommended as
first-line medication, while benzodiazepines are necessary only in acute phases or
until the therapeutic effect of the above-mentioned medicines is obtained. In
treatment-resistant patients at patients who do not respond sufficiently to any
first-line treatments it is necessary to use other classes of medicines, such as
atypical antipsychotics.
While much is known about fear of crime in the West, little is known about how
fearfulness of crime develops in non-Western societies, especially among university
students. Representing the first attempt to empirically compare levels of fear of
crime between Ghanaian and U.S. college students, this article examined students'
levels of fear of crime on campus, and tested the applicability of two evolving
models of fear of crimethe vulnerability and reassurance modelsusing comparative
data. The general finding is that Ghanaian and U.S. college students differ in
terms of their rates of fearfulness on campus. This significant difference adds to
the already existing differences between the two countries.
Background Panic disorder is characterised by repeated, unexpected panic attacks,
which represent a discrete period of fear or anxiety that has a rapid onset,
reaches a peak within 10 minutes, and in which at least four of 13 characteristic
symptoms are experienced, including racing heart, chest pain, sweating, shaking,
dizziness, flushing, stomach churning, faintness and breathlessness. It is common
in the general population with a lifetime prevalence of 1% to 4%. The treatment of
panic disorder includes psychological and pharmacological interventions. Amongst
pharmacological agents, the National Institute for Health and Care Excellence
(NICE) and the British Association for Psychopharmacology consider antidepressants,
mainly selective serotonin reuptake inhibitors (SSRIs), as the first-line treatment
for panic disorder, due to their more favourable adverse effect profile over
monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). Several
classes of antidepressants have been studied and compared, but it is still unclear
which antidepressants have a more or less favourable profile in terms of
effectiveness and acceptability in the treatment of this condition. Objectives To
assess the effects of antidepressants for panic disorder in adults, specifically:
1. to determine the efficacy of antidepressants in alleviating symptoms of panic
disorder, with or without agoraphobia, in comparison to placebo; 2. to review the
acceptability of antidepressants in panic disorder, with or without agoraphobia, in
comparison with placebo; and 3. to investigate the adverse effects of
antidepressants in panic disorder, with or without agoraphobia, including the
general prevalence of adverse effects, compared to placebo. Search methods We
searched the Cochrane Common Mental Disorders' (CCMD) Specialised Register, and
CENTRAL, MEDLINE, EMBASE and PsycINFO up to May 2017. We handsearched reference
lists of relevant papers and previous systematic reviews. Selection criteria All
double-blind, randomised, controlled trials (RCTs) allocating adults with panic
disorder to antidepressants or placebo. Data collection and analysis Two review
authors independently checked eligibility and extracted data using a standard form.
We entered data into Review Manager 5 using a double-check procedure. Information
extracted included study characteristics, participant characteristics, intervention
details and settings. Primary outcomes included failure to respond, measured by a
range of response scales, and treatment acceptability, measured by total number of
dropouts for any reason. Secondary outcomes included failure to remit, panic
symptom scales, frequency of panic attacks, agoraphobia, general anxiety,
depression, social functioning, quality of life and patient satisfaction, measured
by various scales as defined in individual studies. We used GRADE to assess the
quality of the evidence for each outcome Main results Forty-one unique RCTs
including 9377 participants overall, of whom we included 8252 in the 49 placebo-
controlled arms of interest (antidepressant as monotherapy and placebo alone) in
this review. The majority of studies were of moderate to low quality due to
inconsistency, imprecision and unclear risk of selection and performance bias. We
found low-quality evidence that revealed a benefit for antidepressants as a group
in comparison with placebo in terms of efficacy measured as failure to respond
(risk ratio (RR) 0.72, 95% confidence interval (CI) 0.66 to 0.79; participants =
6500; studies = 30). The magnitude of effect corresponds to a number needed to
treat for an additional beneficial outcome (NNTB) of 7 (95% CI 6 to 9): that means
seven people would need to be treated with antidepressants in order for one to
benefit. We observed the same finding when classes of antidepressants were compared
with placebo. Moderate-quality evidence suggested a benefit for antidepressants
compared to placebo when looking at number of dropouts due to any cause (RR 0.88,
95% CI 0.81 to 0.97; participants = 7850; studies = 30). The magnitude of effect
corresponds to a NNTB of 27 (95% CI 17 to 105); treating 27 people will result in
one person fewer dropping out. Considering antidepressant classes, TCAs showed a
benefit over placebo, while for SSRIs and serotonin-norepinephrine reuptake
inhibitor (SNRIs) we observed no difference. When looking at dropouts due to
adverse effects, which can be considered as a measure of tolerability, we found
moderate-quality evidence showing that antidepressants as a whole are less well
tolerated than placebo. In particular, TCAs and SSRIs produced more dropouts due to
adverse effects in comparison with placebo, while the confidence interval for SNRI,
noradrenergic reuptake inhibitors (NRI) and other antidepressants were wide and
included the possibility of no difference. Authors' conclusions The identified
studies comprehensively address the objectives of the present review. Based on
these results, antidepressants may be more effective than placebo in treating panic
disorder. Efficacy can be quantified as a NNTB of 7, implying that seven people
need to be treated with antidepressants in order for one to benefit.
Antidepressants may also have benefit in comparison with placebo in terms of number
of dropouts, but a less favourable profile in terms of dropout due to adverse
effects. However, the tolerability profile varied between different classes of
antidepressants. The choice of whether antidepressants should be prescribed in
clinical practice cannot be made on the basis of this review. Limitations in
results include funding of some studies by pharmaceutical companies, and only
assessing short-term outcomes. Data from the present review will be included in a
network meta-analysis of psychopharmacological treatment in panic disorder, which
will hopefully provide further useful information on this issue.
Objectives: To systematically locate, critically appraise, and synthesize the
available evidence regarding the effectiveness of cognitive behavioral therapies
(CBTs) and psychoeducation that can be implemented by rehabilitation specialists to
treat fear-avoidance beliefs in patients with acute, subacute, and chronic low back
pain (LBP). Data Sources: Electronic databases (CINAHL, PubMed, Psychology and
Behavior Sciences Collection, SPORTDiscus, PsycINFO) were searched from inception
to September 2017. Study Selection: Assessment of methodological quality was
completed using the Physiotherapy Evidence Database (PEDro) scale. The Strength of
Recommendation Taxonomy was used to evaluate the quality of evidence. Data
Extraction: Study sample, subject demographics, CBT and/or psychoeducation
intervention details, data collection time points, outcome assessments, statistical
analysis, results, and conclusions were extracted from each study. In addition,
effect sizes were calculated. Data Synthesis: Five high-quality studies (PEDro >=
6) were included. All included studies evaluated fear-avoidance beliefs. CBTs and
psychoeducation strategies designed to target patient-specific fears demonstrated
clinically meaningful results, while psychoeducation methodologies were not as
effective. Conclusions: There is inconsistent, patient-oriented evidence (grade B)
to support the use of CBTs and/or psychoeducation strategies by rehabilitation
specialists to treat fear-avoidance beliefs. Patient-centered and personalized CBTs
were most effective to treat these psychosocial factors in patients with LBP when
compared with a control treatment. (C) 2017 by the American Congress of
Rehabilitation Medicine
Guidance for medical staff reminds employees of the responsibility to deliver
spiritual care in its broadest sense, respecting the dignity, humanity,
individuality and diversity of the people whose cultures, faiths and beliefs
coexist in society. This is no small or simple task, and although GPs (family
practitioners) have been encouraged to deliver spiritual care, we suggest this is
proving to be challenging and needs further careful debate. This literature review
critiques and analyses existing studies and points to four categories of attitude
to spiritual care, and two related but distinct concepts of spirituality in use by
GPs. Our aims were to search for, summarise and critique the qualitative literature
regarding general practitioners' views on spirituality and their role in relation
to spiritual care. An integrative review was made by a multidisciplinary team using
a critical realism framework. We searched seven databases and completed thematic
and matrix analyses of the qualitative literature. A number of good-quality studies
exist and show that some but not all GPs are willing to offer spiritual care. Four
patterns of attitude towards delivering spiritual care emerge from the studies
which indicate different levels of engagement with spiritual care: embracing,
pragmatic, guarded and rejecting. Further research is needed to identify whether
these four views are fixed or fluid, whether training in spiritual care modifies
these and whether they relate to patterns of care in practice, or patient outcomes.
The authors suggest that some of the difference in viewpoint relate to the lack of
clear philosophical framework. The authors suggest critical realism as having
potential to facilitate interdisciplinary research and create clearer concepts of
spiritual care for GPs.
At its very first session, the United Nations General Assembly, adopted Resolution
59(I) which states that freedom of information is a fundamental human right and ...
the touchstone of all the freedoms to which the United Nations is consecrated". In
1948, it proclaimed the Universal Declaration of Human Rights in Paris. Article 19
of that Declaration states that everyone has the right to freedom of opinion and
expression; this right includes freedom to hold opinions without interference and
to seek, receive and impart information and ideas through any media and regardless
of frontiers. When we place these basic human rights against current global terror
threats, and consequent restrictive antiterror legislations to combat them, the
question becomes whether Article 19 is still relevant in the context of today's
changed security landscape. The aim of this paper is to explore ways that anti-
terror legislations can balance between national security, and the protection of
freedom of information.
We analyzed 12 studies from North America, South America, Europe, and Oceania (New
Zealand) on the association between fear of crime and subjective well-being. These
studies gather data from 39 countries and 407,474 subjects. Heterogeneity was found
between the studies. The random effect model showed an average effect of (r) over
bar = -.15 (rho = -.21). Two of the studies estimated fear of crime with a single
generic question and five studies assessed subjective well-being through one item
of satisfaction with life. Meta-regression showed that the effect was superior in
younger samples, with affective measurement of well-being in comparison with
cognitive ones, of mono-item (versus multi-items) and in the countries of Latin
America, suggesting that in contexts of greater frequency and seriousness of the
crime the fear of crime negatively affects subjective well-being. The diffuse or
concrete nature of the measure of fear did not show a significant moderator effect.
Limitations of the study and proposals for future research are discussed.
Preparedness theory is one of the most influential ideas in explaining the origin
of specific phobias. The theory proposes that fear conditioning is selective to
animals that have posed a threat to survival throughout human evolution, and that
acquired fear memories to such threats are resistant to extinction. We reviewed
fear conditioning studies testing whether autonomic responses conditioned to
pictures of snakes and spiders show greater resistance to extinction than neutral
cues. We identified 32 fear conditioning experiments published in 23 studies
including 1887 participants. Increased resistance to extinction of conditioned
responses to snake and spider pictures was found in 10 (31%) of the experiments,
whereas 22 (69%) experiments did not support the hypothesis. Thus, the body of
evidence suggests that preparedness theory does not explain the origin of specific
phobias.
Fear of falling (FoF) is as an important psychological problem among older people.
While it has been researched for around four decades, paradoxically there is no
agreed definition of FoF. Confusion over the definition of FoF inhibits current
understanding of empirical findings. The objective of this article is to critique
current definitions of FoF and to present a novel theoretical model that aims to
resolve theoretical misunderstanding. A narrative review was conducted to present
definitions of FoF and concepts often conflated with it including fall-related
self-efficacy and anxiety. Then, by drawing on posttraumatic stress disorder (PTSD)
theory and research, we present clear distinctions between the concepts. We argue
that the presence or absence of anxiety determines whether FoF becomes maladaptive
or adaptive, respectively, and that enhancing self-efficacy is key to optimizing
postfall psychological recovery. The theoretical clarity presented will aid future
research and application of evidence to the benefit older people.
Peptide therapeutics is currently one of the fastest growing markets worldwide and
consequently convenient ways of administration for these drugs are highly on
demand. In particular, oral dosage forms would be preferred. A relative large
molecular weight and high hydrophilicity, however, result in comparatively very low
oral bioavailability being in most cases below 1%. Lipid based formulations (LBF),
in particular self-emulsifying drug delivery systems (SEDDS) and solid lipid
nanoparticles (SLN) as well as liposomes are among the most promising tools for
oral peptide delivery. Key to success in orally delivering peptides via LBF seems
to be a sufficiently high lipophilic character of those therapeutic agents. Hence,
different non-covalent and covalent peptide lipidization methods from drug delivery
point of view are presented. On the one hand, among non-covalent lipidization
methods hydrophobic ion pairing seems to be a promising way to sufficiently
increase peptide lipophilicity providing high drug payloads in the lipid phase, a
protective effect against presystemic metabolism via thiol-disulphide exchange
reactions and proteolysis as well as an improved intestinal membrane permeability.
On the other hand, covalent methods like conjugating fatty acids via amidation,
esterification, reversible aqueous lipidization (REAL) and cyclization also show
potential. The present review therefore describes those lipidization methods in
detail and critically evaluates their contribution in successfully overcoming the
oral barriers.
Objective: The study aim was to provide an overview of the current evidence
available on the link between chemotherapy (CTX) and fear of cancer recurrence
(FoR). Methods: PubMED, Medline, Embase, PsycINFO and Web of Science databases were
searched to identify relevant studies. Two authors independently selected and
assessed the studies regarding eligibility criteria. Meta-analysis of suitable
studies was conducted, and quality rated. Results: Forty eligible studies were
included in the systematic review and twenty-nine of them were included in further
meta-analysis. Meta-analysis of the available data confirmed a weak relationship
between CTX and FoR (29 studies, 30,176 patients, overall r = 0.093, 95% CI: 0.062,
0.123, P (<) 0.001). Conclusions: The meta-analysis demonstrates a weak but
significant relationship between cancer patient's FoR and the receipt of
chemotherapy. However, these results should be interpreted with caution. Further
investigation is warranted to explore possible mechanisms of FoR increase in
patients who receive chemotherapy. Longitudinal studies assessing the trajectory of
FoR during chemotherapy are also warranted.
Objective This review aims to provide an overview of the current knowledge
available on the nature and extent of the relationship between external-beam
radiotherapy (RT) and fear of cancer recurrence (FoR). Methods PubMed, MEDLINE, and
EMBASE databases were searched to identify relevant studies. Systematic review
procedures were followed including a quality assessment. Meta-analysis of suitable
studies was conducted. Results Twenty-five eligible studies were included in the
systematic review, and 15 of them were included in further meta-analysis. Meta-
analysis of the available data confirmed a weak relationship between RT and FoR (15
studies, 9567 patients, overall r = 0.053, 95% confidence interval, 0.021-0.085, P
= .001). Subgroup analysis based on cancer site (breast cancer versus other types
of cancer) revealed that the correlation between RT and FoR was statistically
significant in "other cancer" group (P<.001) but was nonsignificant in "breast
cancer" group (P=.538). Conclusions While meta-analysis reports a statistically
significant association between cancer patient's FoR and the receipt of RT, these
results should be interpreted with caution owing to significant variability between
studies. Further longitudinal studies should be conducted to address the trajectory
of FoR over RT in greater detail.
Cholinergic activation regulates cognitive function, particularly long-term memory
consolidation. This Review presents an overview of the anatomical, neurochemical,
and pharmacological evidence supporting the cholinergic regulation of Pavlovian
contextual and cue-conditioned fear learning and extinction. Basal forebrain
cholinergic neurons provide inputs to neocortical regions and subcortical limbic
structures such as the hippocampus and amygdala. Pharmacological manipulations of
muscarinic and nicotinic receptors support the role of cholinergic processes in the
amygdala, hippocampus, and prefrontal cortex in modulating the learning and
extinction of contexts or cues associated with threat. Additional evidence from
lesion studies and analysis of in vivo acetylcholine release with microdialysis
similarly support a critical role of cholinergic neurotransmission in
corticoamygdalar or corticohippocampal circuits during acquisition of fear
extinction. Although a few studies have suggested a complex role of cholinergic
neurotransmission in the cellular plasticity essential for extinction learning,
more work is required to elucidate the exact cholinergic mechanisms and
physiological role of muscarinic and nicotinic receptors in these fear circuits.
Such studies are important for elucidating the role of cholinergic
neurotransmission in disorders such as posttraumatic stress disorder that involve
deficits in extinction learning as well as for developing novel therapeutic
approaches for such disorders. (c) 2016 Wiley Periodicals, Inc.
Background: Cancer has long inspired fear, but the effect of fear is not well
understood; it seems both to facilitate and to deter early diagnosis behaviours. To
elucidate fear's behavioural effects, we systematically reviewed and synthesised
qualitative literature to explore what people fear about cancer. Methods: We
searched Medline, Embase, PsycInfo, Web of Science, AnthroSource, and Anthrobase
for studies on cancer fear in breast, cervical, and colorectal cancer screening and
analysed 102 studies from 26 countries using thematic synthesis. Results: Fears of
cancer emanated from a core view of cancer as a vicious, unpredictable, and
indestructible enemy, evoking fears about its proximity, the (lack of) strategies
to keep it at bay, the personal and social implications of succumbing, and fear of
dying from cancer. Conclusions: This view of cancer as 'an enemy' reprises the
media's 'war on cancer' theme and may affect the acceptance of cancer early
detection and prevention messages, since cancer's characteristics influenced
whether 'fight' or 'flight' was considered appropriate.
AIM To provide an overview of the current research in the functional neuroanatomy
of panic disorder. METHODS Panic disorder (PD) is a frequent psychiatric disease.
Gorman et al (1989; 2000) proposed a comprehensive neuroanatomical model of PD,
which suggested that fear-and anxiety-related responses are mediated by a so-called
"fear network" which is centered in the amygdala and includes the hippocampus,
thalamus, hypothalamus, periaqueductal gray region, locus coeruleus and other
brainstem sites. We performed a systematic search by the electronic database
PubMed. Thereby, the main focus was laid on recent neurofunctional,
neurostructural, and neurochemical studies (from the period between January 2012
and April 2016). Within this frame, special attention was given to the emerging
field of imaging genetics. RESULTS We noted that many neuroimaging studies have
reinforced the role of the "fear network" regions in the patho-physiology of panic
disorder. However, recent functional studies suggest abnormal activation mainly in
an extended fear network comprising brainstem, anterior and midcingulate cortex
(ACC and MCC), insula, and lateral as well as medial parts of the prefrontal
cortex. Interestingly, differences in the amygdala activation were not as
consistently reported as one would predict from the hypothesis of Gorman et al
(2000). Indeed, amygdala hyperactivation seems to strongly depend on stimuli and
experimental paradigms, sample heterogeneity and size, as well as on limitations of
neuroimaging techniques. Advanced neurochemical studies have substantiated the
major role of serotonergic, noradrenergic and glutamatergic neurotransmission in
the pathophysiology of PD. However, alterations of GABAergic function in PD are
still a matter of debate and also their specificity remains questionable. A
promising new research approach is "imaging genetics". Imaging genetic studies are
designed to evaluate the impact of genetic variations (polymorphisms) on cerebral
function in regions critical for PD. Most recently, imaging genetic studies have
not only confirmed the importance of serotonergic and noradrenergic transmission in
the etiology of PD but also indicated the significance of neuropeptide S receptor,
CRH receptor, human TransMEMbrane protein (TMEM123D), and amiloride-sensitive
cation channel 2 (ACCN2) genes. CONCLUSION In light of these findings it is
conceivable that in the near future this research will lead to the development of
clinically useful tools like predictive biomarkers or novel treatment options.
Background: Panic disorder (PD) is a disabling psychiatry condition that affects
approximately 5% of the worldwide population. Currently, long-term selective
serotonin reuptake inhibitors (SSRIs) are the first-line treatment for PD; however,
the common side-effect profiles and drug interactions may provoke patients to
abandon the treatment, leading to PD symptoms relapse. Cannabidiol (CBD) is the
major non-psychotomimetic constituent of the Cannabis sativa plant with antianxiety
properties that has been suggested as an alternative for treating anxiety
disorders. The aim of the present review was to discuss the effects and mechanisms
involved in the putative anti-panic effects of CBD. Methods: electronic database
was used as source of the studies selected selected based on the studies found by
crossing the following keywords: cannabidiol and panic disorder; canabidiol and
anxiety, cannabidiol and 5-HT1A receptor). Results: In the present review, we
included both experimental laboratory animal and human studies that have
investigated the putative anti-panic properties of CBD. Taken together, the studies
assessed clearly suggest an anxiolytic-like effect of CBD in both animal models and
healthy volunteers. Conclusions: CBD seems to be a promising drug for the treatment
of PD. However, novel clinical trials involving patients with the PD diagnosis are
clearly needed to clarify the specific mechanism of action of CBD and the safe and
ideal therapeutic doses of this compound.
Posttraumatic stress disorder (PTSD) is associated with alterations in critical
brain regions such as the amygdala, hippocampus, and prefrontal cortex. This brief
review has two objectives: (1) to discuss research examining extinction and
reconsolidation processes as mechanisms in PTSD psychotherapy, and (2) present
possibilities for augmenting extinction and reconsolidation within treatment
through alterations to therapeutic interventions and novel approaches. A key
component of many effective PTSD therapies is exposure, which involves intentional
confrontation and processing of the traumatic memory. Our review suggests that
extinction and reconsolidation processes underlie effective exposure-based
treatment, but the neurobiological mechanisms of these processes in behavioral
treatments for PTSD remains unclear. We argue that enhancing extinction and/or
disrupting reconsolidation of a feared memory may improve the efficacy of existing
treatments (e.g., increased change for limited/non-responders, faster/greater
changes for responders), which can be done through multiple channels. Potential
avenues for augmentation of the processes of extinction and reconsolidation in PTSD
psychotherapies are reviewed, including behavioral modifications, pharmacotherapy
agents, and the use of devices during therapy. We further suggest that
investigations towards understanding the extent to which extinction and
reconsolidation processes are necessary in effective PTSD psychotherapy is an
important future direction for enhancing clinical care among PTSD populations.
Published by Elsevier Ireland Ltd.
Background: There is increasing recognition of the unique physical and psychosocial
concerns of the growing population of cancer survivors. An emerging literature
demonstrates that fear of cancer recurrence (FCR) is a problematic long-term and
late effect for cancer survivors. In fact, FCR is a top concern, and this article
provides a necessary synthesis of the extant research evidence and theory. Methods:
Literature searches were conducted using databases including MEDLINE and PsychINFO
using specified search terms including 'fear of recurrence' and 'worry about
recurrence'. A comprehensive narrative review summarizes early empirical findings
on FCR including current definitions, assessment tools, clinical presentations,
quality of life impact, prevalence, trajectory and risk factors. This paper also
critically reviews the relevant theoretical frameworks to best understand these
findings and considers multiple psychosocial treatment models that may have
relevance for addressing FCR in the clinical setting. Results: There is evidence of
substantial prevalence and quality of life impact of FCR. Several theories (e.g.
self-regulation model of illness, a family-based model, uncertainty in illness
theory, social-cognitive processing theory, terror management theory) directly or
indirectly help conceptualize FCR and inform potential treatment options for those
with clinically significant distress or impairment resulting fromFCR. Conclusions:
Further investigation into FCR is warranted to promote evidence-based care for this
significant cancer survivorship concern. Copyright (C) 2016 John Wiley & Sons, Ltd.
Purpose of review An expert meeting in Ottawa in 2015 galvanized efforts to answer
key questions relevant to the understanding and management of fear of cancer
recurrence (FCR). The aim of this review is to summarize key developments. Recent
findings A consensus on the definition of FCR has helped to further research in
this area. There have been a number of theories put forward to account for the
development of FCR, all of which share key components. Importantly, a number of
important trials have been published that confirm both brief and more intensive
interventions can successfully treat FCR. Summary The consensus definition of FCR
is an important development, as is the development of treatments for FCR. There are
now evidence-based options for the management of patients with clinical levels of
FCR. Future research priorities include determining the optimal cut-off points for
identifying clinically significant FCR, testing the major tenets of the recent
theoretical formulations of FCR; and determining the relative efficacy and cost-
effectiveness of different treatment approaches for managing FCR.
Fear of flying and flying phobia are very common in the general population and can
lead to serious restraints in daily life. The following article will give an
overview of the current state of research of these 2 subjects. First, the diagnosis
of flying phobia is discussed, including considerations regarding differential
diagnosis. After a review of the prevalence of fear of flying and flying phobia,
the etiology is discussed. In about half of the cases of flying phobia, the
disorder is triggered by a frightening event in a plane. Enhanced stress level,
anxiety sensitivity, and physiological factors can also contribute to the onset of
flying phobia. Media information has been proven to have a reinforcing influence on
fear of flying. Cognitive behavioral therapy with exposure in vivo has been shown
to be the most effective treatment of fear of flying and flying phobia. Specialized
group programs for fearful flyers and virtual-reality exposure therapy programs
against flying phobia have also proven to be very effective in several studies,
although there is a lack of studies about the effectiveness of fear-of-flying group
programs in German-speaking areas. In this article, we summarize the successful
therapeutic techniques and give recommendations for the treatment of fear of flying
and flying phobia in the clinical setting.
Lactate is considered an important metabolite in the human body, but there has been
considerable debate about its roles in brain function. Research in recent years has
suggested that lactate from astrocytes may be crucial for supporting axonal
function, especially during times of high metabolic demands or hypoglycemia. The
astrocyte-neuron lactate transfer shuttle system serves a protective function to
ensure a supply of substrates for brain metabolism, and oligodendrocytes appear to
also influence availability of lactate. There is increasing evidence for lactate
acting as a signaling molecule in the brain to link metabolism, substrate
availability, blood flow and neuronal activity. This review will attempt to connect
evidence to the relationship lactate has to panic disorder (PD), which suggests
that its transporters, receptors or metabolism warrant investigation as potential
therapeutic targets in PD.
Predicted increase in temperature variability can result in short duration of heat
stress episodes coinciding with vulnerable reproductive processes leading to
significant reduction in floret-fertility in crops. Recent knowledge on
alternations in the pollen and stigmatic morphology, pollen biochemical and lipid
composition, variable sensitivity of floral reproductive organs and differential
temperature thresholds across crops advances the knowledge on heat stress induced
reduction in seed-set and harvest index. Rapid increase in night-time temperature,
leading to narrowing diurnal temperature amplitude is a major emerging threat to
sustain crop productivity. Interestingly, wild wheat (Aegilops spp.) with higher
heat tolerance and wild rice (Oryza officinalis) escaping damage by completing
flowering during early morning hours, are examples of novel opportunities to breed
field crops resilient to heat stress. Information on mechanisms leading to heat
stress induced sterility is biased towards rice, wheat and sorghum, while the same
across other field crops is limited. Hence, increasing research efforts in this
direction is critical and timely. Published by Elsevier B.V.
Background: Obstetricians are often reluctant to grant requests for an elective
cesarean section (ECS) due to childbirth fear. To date, it is unknown if an ECS on
request improves mental well-being in the mother in the peripartum period and if
possible beneficial effects on anxiety and depression could outweigh the increased
risk of complications associated with a surgical delivery. A systematic review was
conducted to explore the effect of ECS on request on peripartum anxiety and
depression. Methods: We searched on PubMed, PsychoInfo and Embase. Studies were
included with primary data on anxiety and/or depression postpartum in women with
childbirth fear who had requested an ECS. After full-text evaluation of 65 papers
and quality analysis of four papers, three papers were included. Of one paper
additional and yet unpublished data were provided. Studies varied in outcome
measures, hence no meta-analysis was performed. Results: Women who requested an ECS
had higher antepartum depression and anxiety levels but no different postpartum
depression levels than women who delivered vaginally. One study of good quality
examined the effect of vaginal delivery in women preferring ECS: These women had
significantly higher symptom levels of post-traumatic stress disorder (PTSD) and
depression than women with normal vaginal delivery. Conclusions: The prospect of an
ECS does not lower antepartum anxiety and/or depression levels in women requesting
an ECS. If women resolutely persist in wishing an ECS despite adequate counselling
and/or psychiatric treatment, the risk of developing depressive and PTSD symptoms
in case of vaginal delivery should be taken into account, and an ECS may be
considered as a valid alternative.
Objectives:To assess the clinical validity and factor structure of the Fear-
Avoidance Components Scale (FACS), a new fear-avoidance measure.Materials and
Methods:In this study, 426 chronic musculoskeletal pain disorder patients were
admitted to a Functional Restoration Program (FRP). They were categorized into 5
FACS severity levels, from subclinical to extreme, at admission, and again at
discharge. Associations with objective lifting performance and other patient-
reported psychosocial measures were determined at admission and discharge, and
objective work outcomes for this predominantly disabled cohort, were assessed 1
year later.Results:Those patients in the severe and extreme FACS severity groups at
admission were more likely to drop out of treatment than those in the lower
severity groups (P=0.05). At both admission and discharge, the FACS severity groups
were highly and inversely correlated with objective lifting performance and
patient-reported fear-avoidance-related psychosocial variables, including
kinesiophobia, pain intensity, depressive symptoms, perceived disability, perceived
injustice, and insomnia (Ps<0.001). All variables showed improvement at FRP
discharge. Patients in the extreme FACS severity group at discharge were less
likely to return to, or retain, work 1 year later (P0.02). A factor analysis
identified a 2-factor solution.Discussion:Strong associations were found among FACS
scores and other patient-reported psychosocial and objective lifting performance
variables at both admission and discharge. High discharge-FACS scores were
associated with worse work outcomes 1 year after discharge. The FACS seems to be a
valid and clinically useful measure for predicting attendance, physical
performance, distress, and relevant work outcomes in FRP treatment of chronic
musculoskeletal pain disorder patients.
1. Predators affect prey by killing them directly (lethal effects) and by inducing
costly antipredator behaviours in living prey (risk effects). Risk effects can
strongly influence prey populations and cascade through trophic systems. A
prerequisite for assessing risk effects is characterizing the spatiotemporal
variation in predation risk. 2. Risk effects research has experienced rapid growth
in the last several decades. However, preliminary assessments of the resultant
literature suggest that researchers characterize predation risk using a variety of
techniques. The implications of this methodological variation for inference and
comparability among studies have not been well recognized or formally synthesized.
3. We couple a literature survey with a hierarchical framework, developed from
established theory, to quantify the methodological variation in characterizing risk
using carnivore-ungulate systems as a case study. Via this process, we documented
244 metrics of risk from 141 studies falling into at least 13 distinct
subcategories within three broader categories. 4. Both empirical and theoretical
work suggest risk and its effects on prey constitute a complex, multi-dimensional
process with expressions varying by spatiotemporal scale. Our survey suggests this
multi-scale complexity is reflected in the literature as a whole but often
underappreciated in any given study, which complicates comparability among studies
and leads to an overemphasis on documenting the presence of risk effects rather
than their mechanisms or scale of influence. 5. We suggest risk metrics be placed
in a more concrete conceptual framework to clarify inference surrounding risk
effects and their cascading effects throughout ecosystems. We recommend studies (i)
take a multi-scale approach to characterizing risk; (ii) explicitly consider 'true'
predation risk (probability of predation per unit time); and (iii) use risk metrics
that facilitate comparison among studies and the evaluation of multiple competing
hypotheses. Addressing the pressing questions in risk effects research, including
how, to what extent and on what scale they occur, requires leveraging the
advantages of the many methods available to characterize risk while minimizing the
confusion caused by variability in their application.
The study of inflammation in fear- and anxiety-based disorders has gained interest
as growing literature indicates that pro inflammatory markers can directly modulate
affective behavior. Indeed, heightened concentrations of inflammatory signals,
including cytokines and C-reactive protein, have been described in posttraumatic
stress disorder (PTSD), generalized anxiety disorder (GAD), panic disorder (PD),
and phobias (agoraphobia, social phobia, etc.). However, not all reports indicate a
positive association between inflammation and fear- and anxiety-based symptoms,
suggesting that other factors are important in future assessments of inflammation's
role in the maintenance of these disorders (ie, sex, co-morbid conditions, types of
trauma exposure, and behavioral sources of inflammation). The most parsimonious
explanation of increased inflammation in PTSD, GAD, PD, and phobias is via the
activation of the stress response and central and peripheral immune cells to
release cytokines. Dysregulation of the stress axis in the face of increased
sympathetic tone and decreased parasympathetic activity characteristic of anxiety
disorders could further augment inflammation and contribute to increased symptoms
by having direct effects on brain regions critical for the regulation of fear and
anxiety (such as the prefrontal cortex, insula, amygdala, and hippocampus). Taken
together, the available data suggest that targeting inflammation may serve as a
potential therapeutic target for treating these fear- and anxiety-based disorders
in the future. However, the field must continue to characterize the specific role
pro-inflammatory signaling in the maintenance of these unique psychiatric
conditions.
The association between panic disorder (PD) and cardiovascular diseases (CVD) has
been extensively studied in recent years and, although some studies have shown
anxiety disorders co-existing or increasing the risk of heart disease, no causal
hypothesis has been well established. Thus, a critical review was performed of the
studies that evaluated the association between PD and cardiovascular diseases;
synthesizing the evidence on the mechanisms mediators that theoretically would be
the responsible for the causal pathway between PD and CVD, specifically. This
overview shows epidemiological studies, and discusses biological mechanisms that
could link PD to CVD, such as pleiotropy, heart rate variability, unhealthy
lifestyle, atherosclerosis, mental stress, and myocardial perfusion defects. This
study tried to provide a comprehensive narrative synthesis of previously published
information regarding PD and CVD and open new possibilities of clinical management
and pathophysiological understanding. Some epidemiological studies have indicated
that PD could be a risk factor for CVD, raising morbidity and mortality in PD,
suggesting an association between them. These studies argue that PD pathophysiology
could cause or potentiate CVD. However, there is no evidence in favour of a causal
relationship between PD and CVD. Therefore, PD patients with suspicions of
cardiovascular symptoms need redoubled attention.
Why do only some individuals develop pathological anxiety following adverse events?
Fear acquisition, extinction and return of fear paradigms serve as experimental
learning models for the development, treatment and relapse of anxiety. Individual
differences in experimental performance were however mostly regarded as 'noise' by
researchers interested in basic associative learning principles. Our work for the
first time presents a comprehensive literature overview and methodological
discussion on inter-individual differences in fear acquisition, extinction and
return of fear. We tell a story from noise that steadily develops into a meaningful
tune and converges to a model of mechanisms contributing to individual
risk/resilience with respect to fear and anxiety related behavior. Furthermore, in
light of the present 'replicability crisis' we identify methodological pitfalls and
provide suggestions for study design and analyses tailored to individual difference
research in fear conditioning. Ultimately, synergistic transdisciplinary and
collaborative efforts hold promise to not only improve our mechanistic
understanding but can also be expected to contribute to the development of
specifically tailored ('individualized') intervention and targeted prevention
programs in the future.
The so-called 'replicability crisis' has sparked methodological discussions in many
areas of science in general, and in psychology in particular. This has led to
recent endeavours to promote the transparency, rigour, and ultimately,
replicability of research. Originating from this zeitgeist, the challenge to
discuss critical issues on terminology, design, methods, and analysis
considerations in fear conditioning research is taken up by this work, which
involved representatives from fourteen of the major human fear conditioning
laboratories in Europe. This compendium is intended to provide a basis for the
development of a common procedural and terminology framework for the field of human
fear conditioning. Whenever possible, we give general recommendations. When this is
not feasible, we provide evidence-based guidance for methodological decisions on
study design, outcome measures, and analyses. Importantly, this work is also
intended to raise awareness and initiate discussions on crucial questions with
respect to data collection, processing, statistical analyses, the impact of subtle
procedural changes, and data reporting specifically tailored to the research on
fear conditioning. (C) 2017 The Authors. Published by Elsevier Ltd.
In addition to modulating a number of cognitive functions including reward,
punishment, motivation, and salience, dopamine (DA) plays a pivotal role in
regulating threat-related emotional memory. Changes in neural circuits of the
amygdala nuclei are also critically involved in the acquisition and expression of
emotional memory. In this review, we summarize the regulation of amygdala circuits
by DA. Specifically, we describe DA signaling in the amygdala, and DA regulation of
synaptic transmission and synaptic plasticity of the amygdala neurons. Finally, we
discuss a potential contribution of DA-related mechanisms to the pathogenesis of
posttraumatic stress disorder.
Remembering and forgetting are fundamental features of an organism. Extinction is a
type of forgetting where there is a decrease in the significance and/or the meaning
of an associative memory when elements of that memory no longer predict one
another. The neural mechanisms underlying extinction of fear memories have been
extensively studied in the laboratory because extinction processes are clinically
relevant to exposure therapies that treat anxiety disorders. However, only in the
last decade have we begun to unveil the similarities and differences in plasticity
underlying extinction across development. So far it is clear that extinction is a
developmentally dissociated process in behavior and in pharmacology, however there
are many large gaps in the literature in understanding how the developmental
trajectory of different neurotransmitters contribute to changes in the nature of
extinction across development. We attempt to address these gaps in the present
review. Major neurotransmitter systems including the glutamatergic and GABAergic
systems, the monoamines, the endogenous opioid and cannabinoid systems,
acetylcholines, and neuropeptides such as oxytocin have all been identified to play
some role in extinction of fear memories and have been covered in this review. We
hope to facilitate more research into mechanisms of extinction at different stages
of life, especially noting that mental disorders are increasingly classified as
neurodevelopmental disorders. (C) 2016 Elsevier Inc. All rights reserved.
Although generalization to conditioned stimuli is not a new phenomenon, renewed
interest in understanding its biological underpinning has stemmed from its
association with a number of anxiety disorders. Generalization as it relates to
fear processing is a temporally dynamic process in which animals, including humans,
display fear in response to similar yet distinct cues or contexts as the time
between training and testing increases. This Review surveys the literature on
contextual fear generalization and its relation to several views of memory,
including systems consolidation, forgetting, and transformation hypothesis, which
differentially implicate roles of the hippocampus and neocortex in memory
consolidation and retrieval. We discuss recent evidence on the neurobiological
mechanisms contributing to the increase in fear generalization over time and how
generalized responding may be modulated by acquisition, consolidation, and
retrieval mechanisms. Whereas clinical perspectives of generalization emphasize a
lack of fear inhibition to CS- cues or fear toward intermediate CS cues, the time-
dependent nature of generalization and its relation to traditional views on memory
consolidation and retrieval are often overlooked. Understanding the time-dependent
increase in fear generalization has important implications not only for
understanding how generalization contributes to anxiety disorders but also for
understanding basic long-term memory function. (c) 2016 Wiley Periodicals, Inc.
The type 2 immune response is an adaptive immune program involved in defense
against parasites, detoxification, and wound healing, but is predominantly known
for its pathophysiological effects, manifesting as allergic disease. Engineered
nanoparticles (NPs) are non-self entities that, to our knowledge, do not stimulate
detrimental type 2 responses directly, but have the potential to modulate ongoing
reactions in various ways, including the delivery of substances aiming at providing
a therapeutic benefit. We review, here, the state of knowledge concerning the
interaction of NPs with type 2 immune responses and highlight their potential as a
multifunctional platform for therapeutic intervention.
This article breaks the silence on the politically progressive characteristics of a
moral panic. In contrast to the tacit scholarly consensus that moral panics entail
regressively conservative social reactions to putative harms, moral panics are
alternatively conceptualized as normatively ambivalent operations of power. The
article builds on continuing efforts to conceptualize moral panic as a form of
moral regulation by explaining how moral panics are capable of perpetuating as well
as disrupting and potentially even reversing the norms of intelligibility that
buttress hegemonic understandings of, and moral responsiveness to, violence,
injustice, suffering, and harm.
Fear, which can be expressed innately or after conditioning, is triggered when a
danger or a stimulus predicting immediate danger is perceived. Its role is to
prepare the body to face this danger. However, dysfunction in fear processing can
lead to psychiatric disorders in which fear outweighs the danger or possibility of
harm. Although recognized as highly debilitating, pathological fear remains
insufficiently treated, indicating the importance of research on fear processing.
The neurobiological basis of normal and pathological fear reactions is reviewed in
this article. Innate and learned fear mechanisms, particularly those involving the
amygdala, are considered. These fear mechanisms are also distinguished in specific
phobias, which can indeed be nonexperiential (implicating innate, learning-
independent mechanisms) or experiential (implicating learning-dependent
mechanisms). Poor habituation and poor extinction are presented as dysfunctional
mechanisms contributing to persistence of nonexperiential and experiential phobias,
respectively.
Animals are not distributed randomly in space and time because their movement
ecology is influenced by a variety of factors. Energy landscapes and the landscape
of fear have recently emerged as largely independent paradigms, both reshaping our
perspectives and thinking relating to the spatial ecology of animals across
heterogeneous landscapes. We argue that these paradigms are not distinct but rather
complementary, collectively providing a better mechanistic basis for understanding
the spatial ecology and decision-making of wild animals. We discuss the theoretical
underpinnings of each paradigm and illuminate their complementary nature through
case studies, then integrate these concepts quantitatively by constructing
quantitative pathways of movement modulated by energy and fear to elucidate the
mechanisms underlying the spatial ecology of wild animals.
The recent outbreak of Zika virus infection in Brazil has aroused considerable
media interest due to its association with neurological malformations in children
born from mothers infected by the virus and to its association with Guillain-Barre
syndrome in adults. This relationship has led to the World Health Organisation
declaring the current epidemic as a "Public Health Emergency of International
Concern". Controversy also emerged on the advisability of delaying or changing the
location of the Olympic and Paralympic Games, which were held in August at various
locations in Brazil. In this article, we review the available evidence on the risk
of Zika and dengue virus infection in individuals who travel to endemic countries,
especially for multitudinous events. (C) 2016 Elsevier Espana, S.L.U. and Sociedad
Espanola de Medicina Interna (SEMI). All rights reserved.
Learning about potential threats is critical for survival. Learned fear responses
are acquired either through direct experiences or indirectly through social
transmission. Social fear learning (SFL), also known as vicarious fear learning, is
a paradigm successfully used for studying the transmission of threat information
between individuals. Animal and human studies have begun to elucidate the
behavioral, neural and molecular mechanisms of SFL. Recent research suggests that
social learning mechanisms underlie a wide range of adaptive and maladaptive
phenomena, from supporting flexible avoidance in dynamic environments to
intergenerational transmission of trauma and anxiety disorders. This review
discusses recent advances in SFL studies and their implications for basic, social
and clinical sciences.
Glucocorticoid stress hormones are crucially involved in modulating mnemonic
processing of emotionally arousing experiences. They enhance the consolidation of
new memories, including those that extinguish older memories, but impair the
retrieval of information stored in long-term memory. As strong aversive memories
lie at the core of several fear-related disorders, including post-traumatic stress
disorder and phobias, the memory-modulating properties of glucocorticoids have
recently become of considerable translational interest. Clinical trials have
provided the first evidence that glucocorticoid-based pharmacotherapies aimed at
attenuating aversive memories might be helpful in the treatment of fear-related
disorders. Here, we review important advances in the understanding of how
glucocorticoids mediate stress effects on memory processes, and discuss the
translational potential of these new conceptual insights.
Objective: To compare prey and snake paradigms performed in complex environments to
the elevated plus-maze (EPM) and T-maze (ETM) tests for the study of panic attack-
and anticipatory anxiety-like behaviors in rodents. Methods: PubMed was reviewed in
search of articles focusing on the plus maze test, EPM, and ETM, as well as on
defensive behaviors displayed by threatened rodents. In addition, the authors'
research with polygonal arenas and complex labyrinth (designed by the first author
for confrontation between snakes and small rodents) was examined. Results: The EPM
and ETM tests evoke anxiety/fear-related defensive responses that are
pharmacologically validated, whereas the confrontation between rodents and snakes
in polygonal arenas with or without shelters or in the complex labyrinth offers
ethological conditions for studying more complex defensive behaviors and the
effects of anxiolytic and panicolytic drugs. Prey vs. predator paradigms also allow
discrimination between non-oriented and oriented escape behavior. Conclusions: Both
EPM and ETM simple labyrinths are excellent apparatuses for the study of anxietyand
instinctive fear-related responses, respectively. The confrontation between rodents
and snakes in polygonal arenas, however, offers a more ethological environment for
addressing both unconditioned and conditioned fear-induced behaviors and the
effects of anxiolytic and panicolytic drugs.
Introduction Several techniques have been proposed to manage dental fear/dental
anxiety (DFA) in children and adolescents undergoing dental procedures. To our
knowledge, no widely available compendium of therapies to manage DFA exists. We
propose a study protocol to assess the evidence regarding pharmacological and non-
pharmacological interventions to relieve dental anxiety in children and
adolescents. Methods and analysis In our systematic review, we will include
randomised trials, controlled clinical rials and systematic reviews (SRs) of trials
that investigated the effects of pharmacological and non-pharmacological
interventions to decrease dental anxiety in children and adolescents. We will
search the Cochrane Database of Systematic Reviews, the Cochrane Database of
Abstracts of Reviews of Effects=, the Cochrane Central Register of Controlled
Trials, PubMed, PsycINFO, Cumulative Index to Nursing and Allied Health Literature
and the Web of Science for relevant studies. Pairs of review authors will
independently review titles, abstracts and full texts identified by the specific
literature search and extract data using a standardised data extraction form. For
each study, information will be extracted on the study report (eg, author, year of
publication), the study design (eg, the methodology and, for SRs, the types and
number of studies included), the population characteristics, the intervention(s),
the outcome measures and the results. The quality of SRs will be assessed using the
A Measurement Tool to Assess Reviews instrument, while the quality of the retrieved
trials will be evaluated using the Cochrane Handbook for Systematic Reviews of
Interventions criteria. Ethics and dissemination Approval from an ethics committee
is not required, as no participants will be included. Results will be disseminated
through a peer-reviewed publications and conference presentations.
Aim The aim of this paper was to review the published scientific literature to
quantify the prevalence and mean score of dental fear/anxiety (DFA) in
children/adolescents and its variation according to several variables. Materials
and methods Cross-sectional and cohort studies published from 2000 to 2014, that
measured DFA in children /adolescents (aged 0-19 years), in the general population,
or visiting private or public dental services (general or pediatric) or attending
school and kindergarten, were searched, with specific terms, in 3 electronic
databases (Medline, Embase, Web Of Science). Primary data, collected with specific
questionnaires of demonstrated reliability and/or validity, were extracted. Results
After screening 743 abstracts and evaluating 164 full-text publications, 36
articles were selected. Dental fear/anxiety prevalence rates were 12.2%, 10.0%,
12.2%, 11.0% and 20.0% for the CFSS-DS, DAS, MDAS, DFS, and DFSS-SF scores,
respectively. In the studies that used MCDAS Dental fear/prevalence rates varied
from 13.3% to 29.3%. In the studies that used CFSS-DS ratings, the prevalence and
the mean score of dental fear/anxiety was lower in Northern Europe than the
remaining countries, the prevalence decreased with increasing age and the frequency
was higher in females than males. Conclusions Dental fear/anxiety is a common
problem in children/adolescents worldwide, therefore, new strategies to overcome
this relevant children/adolescent condition should be encouraged.
The last 10 years have witnessed a substantial progress in understanding the neural
mechanisms for the renewal of the extinguished fear memory. Based on the theory of
fear extinction, exposure therapy has been developed as a typical cognitive
behavioral therapy for posttraumatic stress disorder. Although the fear memory can
be extinguished by repeated presentation of conditioned stimulus without
unconditioned stimulus, the fear memory is not erased and tends to relapse outside
of extinction context, which is referred to as renewal. Therefore, the renewal is
regarded as a great obstruction interfering with the effect of exposure therapy. In
recent years, there has been a great deal of studies in understanding the
neurobiological underpinnings of fear renewal. These offer a foundation upon which
novel therapeutic interventions for the renewal may be built. This review focuses
on behavioral, anatomical and electrophysiological studies that interpret roles of
the hippocampus, prelimbic cortex and amygdala as well as the connections between
them for the renewal of the extinguished fear. Additionally, this review suggests
the possible pathways for the renewal: (1) the prelimbic cortex may integrate
contextual information from hippocampal inputs and project to the basolateral
amygdala to mediate the renewal of extinguished fear memory; the ventral
hippocampus may innervate the activities of the basolateral amygdala or the central
amygdala directly for the renewal. (C) 2017
Although emerging evidence has suggested an association between the Val66Met
(rs6265) polymorphisms in brain-derived neurotrophic factor (BDNF) gene and the
panic disorder, the conclusion is inclusive given the mixed results. This meta-
analysis reviewed and analyzed the recent studies addressing the potential
association between the Val66Met polymorphisms and panic disorder susceptibility.
Related case-control studies were retrieved by database searching and selected
according to established inclusion criteria. Six articles were identified, which
explored the association between the BDNF Val66Met polymorphism and panic disorder.
Statistical analyses revealed no association for the allele contrast and the
dominant model. However, the recessive model showed a significant association
between the BDNF Val66Met polymorphism and panic disorder (odds ratio=1.26, 95%
confidence interval=1.04-1.52, z=2.39, P=0.02). Despite of some limitations, this
meta-analysis suggests that the Val66Met polymorphism of BDNF gene is a
susceptibility factor for panic disorder.
Vasopressin (VP) and oxytocin (OT) are distinct molecules; these peptides and their
receptors [OT receptor (OTR) and V1a receptor (V1aR)] also are evolved components
of an integrated and adaptive system, here described as the OT-VP pathway. The more
ancient peptide, VP, and the V1aRs support individual survival and play a role in
defensive behaviors, including mobilization and aggression. OT and OTRs have been
associated with positive social behaviors and may function as a biological metaphor
for social attachment or "love." However, complex behavioral functions, including
selective sexual behaviors, social bonds, and parenting require combined activities
of OT and VP. The behavioral effects of OT and VP vary depending on perceived
emotional context and the history of the individual. Paradoxical or contextual
actions of OT also may reflect differential interactions with the OTR and V1aR.
Adding to the complexity of this pathway is the fact that OT and VP receptors are
variable, across species, individuals, and brain region, and these receptors are
capable of being epigenetically tuned. This variation may help to explain
experience-related individual and sex differences in behaviors that are regulated
by these peptides, including the capacity to form social attachments and the
emotional consequences of these attachments.
In the past years, the advent of the Internet and the democratisation of "smart"
phones the use of wearable digital tools linked to specific "apps" is becoming
increasingly common. Such use consists on the record of embodied and physiological
states and their transformation to biometric data via those tools. Data are
interpreted and even shared by individuals who intend to monitor or even control
their own health practices in everyday life. The aim of this article is to propose
a literature review in English and French within the field of digital health. Our
analysis reveals two main trends of recent work, regardless the discipline or the
origin of the articles. One trend is defined by its enthusiasm, often hand in hand
with hopes and promises regarding the development of digital health technologies.
The other trend is characterised by a critical attitude, focussing on socioeconomic
and political implications of such technologies in terms of surveillance and risk.
Our discussion consists on an in-depth reflection of the dimensions that define
each one of these trends. We identify a set of interrogations raised by existing
research, namely with regard to psychology. Finally, we conclude by highlighting
future research perspectives. (C) 2016 Societe Franyaise de Psychologie. Published
by Elsevier Masson SAS. All rights reserved.
Aim To present: the normative data on dental fear and caries status; the dental
fear cut-off points of young children in the city of Thessaloniki, Greece. Methods
Study Design: This is a cross-sectional study with two independent study groups. A
first representative sample consisted of 1484 children from 15 primary public
schools of Thessaloniki. A second sample consisted of 195 randomly selected age-
matched children, all patients of the Postgraduate Paediatric Dental Clinic of
Aristotle University of Thessaloniki. First sample: In order to select data on
dental fear and caries, dental examination took place in the classroom with
disposable mirrors and a penlight. All the children completed the Dental Subscale
of the Children's Fear Survey Schedule (CFSS-DS). Second sample: In order to define
the cut-off points of the CFSS-DS, dental treatment of the 195 children was
performed at the University Clinic. Children's dental fear was assessed using the
CFSS-DS and their behaviour during dental treatment was observed by one calibrated
examiner using the Venham scale. Statistics: Statistical analysis of the data was
performed with IBM SPSS Statistics 20 at a statistical significance level of
p<0.05. Results First sample: The mean CFSS-DS score was 27.1 +/- 10.8. Age was
significantly (p<0.05) related to dental fear. Mean differences between boys and
girls were not significant. Caries was not correlated with dental fear. Second
sample: CFSS-DS< 33 was defined as 'no dental fear', scores 33-37 as 'borderline'
and scores > 37 as 'dental fear'. In the first sample, 84.6% of the children did
not suffer from dental fear (CFSS-DS< 33). Conclusion Dental fear was correlated to
age and not to caries and gender. The dental fear cut-off point for the CFSS-DS was
estimated at 37 for 6-12 year old children (33-37 borderlines).
Landscapes of Fear (LOF), the spatially explicit distribution of perceived
predation risk as seen by a population, is increasingly cited in ecological
literature and has become a frequently used "buzz-word". With the increase in
popularity, it became necessary to clarify the definition for the term, suggest
boundaries and propose a common framework for its use. The LOF, as a progeny of the
"ecology of fear', conceptual framework, defines fear as the strategic
manifestation of the cost-benefit analysis of food and safety tradeoffs. In
addition to direct predation risk, the LOF is affected by individuals' energetic-
state, inter- and intra-specific competition and is constrained by the evolutionary
history of each species. Herein, based on current applications of the LOF
conceptual framework, I suggest the future research in this framework will be
directed towards: (1) finding applied management uses as a trait defining a
population's habitat-use and habitat-suitability; (2) studying multi-dimensional
distribution of risk-assessment through time and space; (3) studying variability
between individuals within a population; (4) measuring eco-neurological
implications of risk as a feature of environmental heterogeneity and (5) expanding
temporal and spatial scales of empirical studies.
The extinction of a conditioned fear response is of great interest in the search
for a means of ameliorating adverse neurobiological changes resulting from stress.
The discovery that endocannibinoid (EC) levels are inversely related to the extent
of such stress, and that the amygdala is a primary site mediating stress, suggests
that ECs in this brain region might play a major role in extinction. Supporting
this are the observations that the basolateral complex of the amygdala shows an
increase in ECs only during extinction and that early clinical trials indicate that
cannabinoid-like agents, when taken orally by patients suffering from post
traumatic stress disorder (PTSD), reduce insomnia and nightmares. In order to
optimize the potential of these agents to ameliorate symptoms of PTSD four
important questions need to be answered: first, what is the identity of the cells
that release ECs in the amygdala during extinction; second, what are their sites of
action; third, what roles do the ECs play in the alleviation of long-depression
(LTD), a process central to extinction; and finally, to what extent does brain
derived neurotrophic factor (BDNF) facilitate the release of ECs? A review of the
relevant literature is presented in an attempt to answer these questions. It is
suggested that the principal cell involved in EC synthesis and release during
extinction is the so-called excitatory extinction neuron in the basal nucleus of
the amygdala. Furthermore that the main site of action of the ECs is the adjacent
calcitonin gene-related peptide inhibitory interneurons, whose normal role of
blocking the excitatory neurons is greatly diminished. The molecular pathways
leading (during extinction trials) to the synthesis and release of ECs from
synaptic spines of extinction neurons, that is potentiated by BDNF, are also
delineated in this review. Finally, consideration is given to how the autocrine
action of BDNF, linked to the release of ECs, can lead to the sustained release of
these, so maintaining extinction over long times. (C) 2016 Elsevier B.V. All rights
reserved.
Nearly 15 years following the attacks on September 11, 2001, much learning has been
acquired regarding the psychological affects of mass violence. Less is known,
however, about the long-term impact of 9/11 on those with family members who died
in the attacks. A few quantitative studies were conducted specific to grief and
terrorism and these findings suggest that symptoms may be more severe and persist
over a longer period than for those facing death due to other violent
circumstances. While only a few studies examined the long-term experiences of
family members aggrieved by 9/11, several qualitative studies were conducted years
following the attacks but these investigations are found in the grey literature.
Therefore, this review included a sample of five qualitative studies, which met
inclusion criteria, and had not been published in the peer-review literature. The
purpose of this review was to understand if any common themes existed between
investigations that were conducted from 3 to 12 years after 9/11/01. Ten noteworthy
themes were found that were common across investigations. Several themes were
endorsed by participants in three to four studies, and included, sharing the
tragedy and personal grief publicly, taking action, and financial compensation. The
remaining themes were endorsed by family members across all five studies and
included discussions about bodily remains, persistent and comparative grief,
relationship changes, support groups and services, remembering their family member,
and healing and growth after loss. While the findings in this review cannot be
generalized to all families affected by 9/11, given the nature of the data, there
are a number of important implications from this review discussed that are relevant
for shaping future research and having clinical awareness about the long-term
affects of mass violence.
Anxiety disorders are the most prevalent mental disorders and are associated with
substantial healthcare costs and a high burden of disease. In this article, changes
in the new Diagnostic and Statistical Manual for Mental Disorders (the DSM-5) with
respect to panic disorder/agoraphobia, generalized anxiety disorder, social anxiety
disorder, specific phobias, and selective mutism are compared with the
International Classification of Diseases (ICD-10) system.
Objective: Dental anxiety, fear and phobia have different etiology, response
patterns, time courses, and intensities that justify a clear distinction between
these constructs. Differentiation of dental anxiety, fear or phobia in practice is
a critical prerequisite for developing and implementing effective treatment for
children. The aim of this study was to investigate whether current researches in
the pediatric dentistry appropriately discriminate the central construct of dental
anxiety, fear and phobia. We also highlighted the specific methodological issues in
the assessment of these issues in pediatric dentistry. Study design: A systematic
search was conducted in Pubmed/medline and Scopus for articles which assessed
dental anxiety, fear or phobia in children. Results: 104 research papers were
included in the review that had made a distinction between dental anxiety, fear and
phobia and had not used them interchangeably. Only five studies used different
clinical measures or cut-offs to discriminate between dental anxiety, fear and
phobia. Conclusion: The dental literature appears unable to capture and also
measure the multi-sided construct of dental anxiety, fear and phobia and,
therefore, there was a tendency to use them interchangeably.
The formation of fear memories is a powerful and highly evolutionary conserved
mechanism that serves the behavioral adaptation to environmental threats.
Accordingly, classical fear conditioning paradigms have been employed to
investigate fundamental molecular processes of memory formation. Evidence suggests
that a circadian regulation mechanism allows for a timestamping of such fear
memories and controlling memory salience during both their acquisition and their
modification after retrieval. These mechanisms include an expression of molecular
clocks in neurons of the amygdala, hippocampus, and medial prefrontal cortex and
their tight interaction with the intracellular signaling pathways that mediate
neural plasticity and information storage. The cellular activities are coordinated
across different brain regions and neural circuits through the release of
glucocorticoids and neuromodulators such as acetylcholine, which integrate
circadian and memory-related activation. Disturbance of this interplay by circadian
phase shifts or traumatic experience appears to be an important factor in the
development of stress-related psychopathology, considering these circadian
components are of critical importance for optimizing therapeutic approaches to
these disorders.
Recent prospective studies in emergency services have identified impaired fear
extinction learning and memory to be a significant predictor of Posttraumatic
Stress Disorder (PTSD), complementing a wealth of cross-sectional evidence of
extinction deficits associated with the disorder. Additional fields of research
show specific risk factors and biomarkers of the disorder, including candidate
genotypes, stress and sex hormones, cognitive factors, and sleep disturbances.
Studies in mostly nonclinicat populations also reveal that the aforementioned
factors are involved in fear extinction learning and memory. Here, we provide a
comprehensive narrative review of the literature linking PTSD to these risk
factors, and linking these risk factors to impaired fear extinction. On balance,
the evidence suggests that fear extinction may play a role in the relationship
between risk factors and PTSD. Should this notion hold true, this review carries
important implications for the improvement of exposure-based treatments, as well as
strategies for the implementation of treatment. (C) 2016 Elsevier Ltd. All rights
reserved.
Fear-relevant illusory correlations (ICs) are defined as the overestimation of the
relationship between a fear-relevant stimulus and aversive consequences. ICs
reflect biased cognitions affecting the learning and unlearning of fear in anxiety
disorders, and a deeper understanding might help to improve treatment. A model for
the maintenance of ICs is proposed that highlights the importance of amplified
aversiveness and salience of fear-relevant outcomes, impaired executive contingency
monitoring and an availability heuristic. The model explains why ICs are enhanced
in high fearful individuals and allows for some implications that might be applied
to augment the effectiveness of cognitive behavior therapy, such as emotion
regulation and the direction of attention to non-aversive experiences. Finally, we
suggest possible future research directions and an alternative measure of ICs. (C)
2016 Elsevier Ltd. All rights reserved.
Fearful individuals often overestimate the relationship between fear-relevant
stimuli and aversive consequences. Such fear-relevant illusory correlations (ICs)
might be involved in the maintenance of anxiety disorders. In this literature
review, we found clear evidence that ICs are present and enhanced in fear of
animals. We also revealed some evidence for ICs related to fear of flying, social
anxiety, contamination fear, panic disorder, and post-traumatic stress disorder,
but with considerably less clarity. Fear-relevant ICs seem to be best explained by
both a priori expectancies and biased encoding of the experienced associations.
Studies to date suggest that one important biased encoding process is the enhanced
aversiveness/salience of fear-relevant outcomes. Future studies may improve insight
by developing more reliable IC measures and testing the effect of encoding
processes on treatment outcomes. (C) 2016 Elsevier Ltd. All rights reserved.
Since the 1990s, developments in the field of genetics have led to many questions
on the use and possible misuse of genetic information. 'Genetic discrimination' has
been defined as the differential treatment of asymptomatic individuals or their
relatives on the basis of their real or assumed genetic characteristics. Despite
the public policy attention around genetic discrimination, there is currently still
much confusion surrounding this phenomenon. On the one hand, there is little
evidence of the occurrence of genetic discrimination. On the other hand, it appears
that people remain concerned about this theme, and this fear influences their
health and life choices. This article makes use of a systematic literature review
to investigate what is already known about the nature, extent and background of
these fears and concerns. The 42 included studies have found considerable levels of
concerns about genetic discrimination. Concerns dominate in insurance contexts and
within personal interactions. The extent of concerns appears to vary depending on
the type of genetic illness. Furthermore, installed laws prohibiting genetic
discrimination do not seem to alleviate existing fears. This raises important
questions as to the origins of these fears. Based on the findings, recommendations
for future research are made. First, research on the background of fears is needed.
Second, future research needs to assess more fully all different forms (for
example, direct and indirect) of genetic discrimination. Thirdly, it has to be
studied whether genetic discrimination is a form of discrimination that is
distinguishable from discrimination based on an illness or disability. Finally, a
last element that should be addressed in future research is the most recent
developments in research on genomics, such as next-generation sequencing or genome-
wide association studies.
Anxiety disorders and pregnancy may occur concurrently in some women. Although,
several epidemiological or clinical studies about anxiety disorders in pregnancy
exist, data on their treatment are very limited. Similar to other anxiety
disorders, specific pharmacological treatment approaches in pregnant women with
panic disorder (PD) have not been discussed in the literature. An important issue
in the treatment of pregnant women with any psychiatric diagnosis is the risk-
benefit profile of pharmacotherapy. Therefore, the treatment should be
individualized. Untreated PD seems to be associated with several negative outcomes
in the pregnancy. When the results of current study regarding the safety of
pharmacological agents on the fetus and their efficacy in PD were gathered,
sertraline, citalopram, imipramine and clomipramine at low doses for pure PD, and
venlafaxine appeared to be more favorable than the other potential drugs. However,
controlled studies examining optimum dosing, efficacy of antipanic medications and
risk-benefit profile of intrauterine exposure to treated or untreated PD are
urgently needed.
While anxiety disorders are the brain disorders with the highest prevalence and
constitute a major burden for society, a considerable number of affected people are
still treated insufficiently. Thus, in an attempt to identify potential new
anxiolytic drug targets, neuropeptides have gained considerable attention in recent
years. Compared to classical neurotransmitters they often have a regionally
restricted distribution and may bind to several distinct receptor subtypes.
Neuropeptide Y (NPY) is a highly conserved neuropeptide that is specifically
concentrated in limbic brain areas and signals via at least 5 different G-protein-
coupled receptors. It is involved in a variety of physiological processes including
the modulation of emotional-affective behaviors. An anxiolytic and stress-reducing
property of NPY is supported by many preclinical studies. Whether NPY may also
interact with processing of learned fear and fear extinction is comparatively
unknown. However, this has considerable relevance since pathological, inappropriate
and generalized fear expression and impaired fear extinction are hallmarks of human
post-traumatic stress disorder and a major reason for its treatment-resistance.
Recent evidence from different laboratories emphasizes a fear reducing role of NPY,
predominantly mediated by exogenous NPY acting on Y1 receptors. Since a reduction
of fear expression was also observed in Y1 receptor knockout mice, other Y
receptors may be equally important. By acting on Y2 receptors, NPY promotes fear
extinction and generates a long-term suppression of fear, two important
preconditions that could support cognitive behavioral therapies in human patients.
A similar effect has been demonstrated for the closely related pancreatic
polypeptide (PP) when acting on Y4 receptors. Preliminary evidence suggests that
NPY modulates fear in particular by activation of Y1 and Y2 receptors in the
basolateral and central amygdala, respectively. In the basolateral amygdala, NPY
signaling activates inhibitory G protein-coupled inwardly-rectifying potassium
channels or suppresses hyperpolarization-induced I(h) currents in a Y1 receptor
dependent fashion, favoring a general suppression of neuronal activity. A more
complex situation has been described for the central extended amygdala, where NPY
reduces the frequency of inhibitory and excitatory postsynaptic currents. In
particular the inhibition of long-range central amygdala output neurons may result
in a Y2 receptor-dependent suppression of fear. The role of NPY in processes of
learned fear and fear extinction is, however, only beginning to emerge, and
multiple questions regarding the relevance of endogenous NPY and different receptor
subtypes remain elusive. Y2 receptors may be of particular interest for future
studies, since they are the most prominent Y receptor subtype in the human brain
and thus among the most promising therapeutic drug targets when translating
preclinical evidence to potential new therapies for human anxiety disorders. (C)
2015 The Authors. Published by Elsevier Ltd. This is an open access article under
the CC BY-NC-ND license.
Pavlovian fear or threat conditioning, where a neutral stimulus takes on aversive
properties through pairing with an aversive stimulus, has been an important tool
for exploring the neurobiology of learning. In the past decades, this
neurobehavioral approach has been expanded to include the developing infant.
Indeed, protracted postnatal brain development permits the exploration of how
incorporating the amygdala, prefrontal cortex and hippocampus into this learning
system impacts the acquisition and expression of aversive conditioning. Here, we
review the developmental trajectory of these key brain areas involved in aversive
conditioning and relate it to pups' transition to independence through weaning.
Overall, the data suggests that adult-like features of threat learning emerge as
the relevant brain areas become incorporated into this learning. Specifically, the
developmental emergence of the amygdala permits cue learning and the emergence of
the hippocampus permits context learning. We also describe unique features of
learning in early life that block threat learning and enhance interaction with the
mother or exploration of the environment. Finally, we describe the development of a
sense of time within this learning and its involvement in creating associations.
Together these data suggest that the development of threat learning is a useful
tool for dissecting adult-like functioning of brain circuits, as well as providing
unique insights into ecologically relevant developmental changes.
Anxiety disorders are prevalent and associated with functional impairments. Outcome
research has focused on symptom reduction, rather than positive factors such as
life satisfaction and improved functioning. We review the impact of youth anxiety
disorders and elevated anxiety symptoms on academic, occupational, family, social,
and legal functioning. Emphasis is placed on the degree to which developmental
trajectories differ for youth with and without anxiety disorders. In some areas,
psychopathology generally, rather than anxiety specifically, is associated with
functional impairment. Other studies support youth anxiety as a unique predictor of
functional impairment. In particular, social anxiety is associated with impairments
in social functioning throughout development. The short- and long-term impacts of
anxiety treatment in youth are discussed. Last, research directions are suggested.
Fear acquisition and extinction are valid models for the etiology and treatment of
anxiety, trauma- and stressor-related disorders. These disorders are assumed to
involve aversive learning under acute and/or chronic stress. Importantly, fear
conditioning and stress share common neuronal circuits. The stress response
involves multiple changes interacting in a time-dependent manner (a) the fast
first-wave stress response [with central actions of noradrenaline, dopamine,
serotonin, corticotropin-releasing hormone (CRH), plus increased sympathetic tone
and peripheral catecholamine release] and (b) the second-wave stress response [with
peripheral release of glucocorticoids (GCs) after activation of the hypothalamus-
pituitary-adrenocortical (HPA) axis]. Control of fear during extinction is also
sensitive to these stress-response mediators. In the present review, we will thus
examine current animal and human data, addressing the role of stress and single
stress-response mediators for successful acquisition, consolidation and recall of
fear extinction. We report studies using pharmacological manipulations targeting a
number of stress-related neurotransmitters and neuromodulators [monoamines,
opioids, endocannabinoids (eCBs), neuropeptide Y, oxytocin, GCs] and behavioral
stress induction. As anxiety, trauma- and stressor-related disorders are more
common in women, recent research focuses on female sex hormones and identifies a
potential role for estradiol in fear extinction. We will thus summarize animal and
human data on the role of estradiol and explore possible interactions with stress
or stress-response mediators in extinction. This also aims at identifying time-
windows of enhanced (or reduced) sensitivity for fear extinction, and thus also for
successful exposure therapy.
How fear is represented in the brain has generated a lot of research attention, not
only because fear increases the chances for survival when appropriately expressed
but also because it can lead to anxiety and stress-related disorders when
inadequately processed. In this review, we summarize recent progress in the
understanding of the neural circuits processing innate fear in rodents. We propose
that these circuits are contained within three main functional units in the brain:
a detection unit, responsible for gathering sensory information signaling the
presence of a threat; an integration unit, responsible for incorporating the
various sensory information and recruiting downstream effectors; and an output
unit, in charge of initiating appropriate bodily and behavioral responses to the
threatful stimulus. In parallel, the experience of innate fear also instructs a
learning process leading to the memorization of the fearful event. Interestingly,
while the detection, integration, and output units processing acute fear responses
to different threats tend to be harbored in distinct brain circuits, memory
encoding of these threats seems to rely on a shared learning system.
The 2013-2016 West Africa Ebola virus disease pandemic was the largest, longest,
deadliest, and most geographically expansive outbreak in the 40-year interval since
Ebola was first identified. Fear-related behaviors played an important role in
shaping the outbreak. Fear-related behaviors are defined as "individual or
collective behaviors and actions initiated in response to fear reactions that are
triggered by a perceived threat or actual exposure to a potentially traumatizing
event. FRBs modify the future risk of harm." This review examines how fear-related
behaviors were implicated in (1) accelerating the spread of Ebola, (2) impeding the
utilization of life-saving Ebola treatment, (3) curtailing the availability of
medical services for treatable conditions, (4) increasing the risks for new-onset
psychological distress and psychiatric disorders, and (5) amplifying the downstream
cascades of social problems. Fear-related behaviors are identified for each of
these outcomes. Particularly notable are behaviors such as treating Ebola patients
in home or private clinic settings, the "laying of hands" on Ebola-infected
individuals to perform faith-based healing, observing hands-on funeral and burial
customs, foregoing available life-saving treatment, and stigmatizing Ebola
survivors and health professionals. Future directions include modeling the onset,
operation, and perpetuation of fear-related behaviors and devising strategies to
redirect behavioral responses to mass threats in a manner that reduces risks and
promotes resilience.
Fear and anxiety are adaptive responses but if left unregulated, or inappropriately
regulated, they become biologically and socially maladaptive. Dysregulated emotions
are manifest in a wide variety of psychiatric and neurological conditions but the
external expression gives little indication of the underlying causes, which are
inevitably multi determined. To go beyond the overt phenotype and begin to
understand the causal mechanisms leading to conditions characterized by anxiety and
disorders of mood, it is necessary to identify the base psychological processes
that have become dysregulated, and map them on to their associated neural
substrates. So far, attention has been focused primarily on the medial regions of
prefrontal cortex (PFC) and in particular their contribution to the expression and
extinction of conditioned fear. However, functional neuroimaging studies have shown
that the sphere of influence within the PFC is not restricted to its medial
regions, but extends into dorsal, ventrolateral (vIPFC) and orbitofrontal (OFC)
regions too; although the causal role of these other areas in the regulation of
fear and anxiety remains to be determined and in the case of the OFC, existing
findings are conflicting. Here, we review the evidence for the contribution of
these other regions in negative emotion regulation in rodents and old world and new
world monkeys. We consider a variety of different contexts, including conditioned
and innate fear, learned and unlearned anxiety and cost-benefit decision-making,
and a range of physiological and behavioral measures of emotion. It is proposed
that both the OFC and vIPFC contribute to emotion regulation via their involvement,
respectively, in the prediction of future outcomes and higher-order attentional
control. The fractionation of these neurocognitive and neurobehavioral systems that
regulate fear and anxiety opens up new opportunities for diagnostic stratification
and personalized treatment strategies.
The causes of fear and anxiety in working dogs are multifactorial and may include
inherited characteristics that differ between individuals (e.g. Goddard and
Beilharz, 1982; 1984a,b), influences of the environment (Lefebvre et al., 2007),
and learned experiences during particular sensitive periods (Appleby et al., 2002)
and throughout life. Fear-related behavior compromises performance, leads to
significant numbers of dogs failing to complete training (e.g., Murphy, 1995; Batt
et al., 2008), early withdrawals from working roles (Caron-Lormier et al., 2016),
and can jeopardize dog and handler safety. Hence, amelioration of fear and anxiety
is critical to maintain dogs in working roles and to ensure their well-being.
Although current methods of selection and training are seemingly effective at
producing many dogs which work in a remarkable array of environments, some dogs do
not make the grade, and longevity of service is not always maximized. Programs
should strive for optimal efficiency and they need to continually analyze the value
of each component of their program, seek evidence for its value and explore
potential evidence-based improvements. Here we discuss scientific evidence for
methods and strategies which may be of value in reducing the risk of fear behaviors
developing in the working dog population and suggest potentially valuable
techniques and future research to explore the benefit of these approaches. The
importance of environmental influences, learning opportunities, and effects of
underlying temperament on the outward expression of fear and anxiety should not be
underestimated. Identification of characteristics which predict resilience to
stress are valuable, both to enable careful breeding for these traits and to
develop predictive tests for puppies and procured animals. It is vitally important
to rear animals in optimal environments and introduce them to a range of stimuli in
a positive, controlled, and gradual way, as these can all help minimize the number
of dogs which develop work inhibiting fears. Future research should explore
innovative methods to best measure the relative resilience of dogs to stressful
events. This could include developing optimal exposure protocols to minimize the
development of fear and anxiety, and exploring the influence of social learning and
the most effective elements of stimulus presentation. (C) 2016 Elsevier Inc. All
rights reserved.
The objective of this narrative review was to examine the literature on fear of
childbirth from a psychological perspective, addressing the specificity of
childbirth fear, the pathways of fear acquisition, and the physiological, cognitive
and behavioral aspects of fear. Systematic procedures for literature search,
inclusion and exclusion left 86 original research papers for analysis. Findings
summarize the body of knowledge for each area of interest, as well as the number of
studies addressing each theme. Overall, few studies adopt a clear-cut psychological
perspective, leaving the psychological mechanisms of childbirth fear largely
unexplored. Although methodological limitations make conclusions difficult, results
give a hint of etiological diversity and possible psychological mechanisms commonly
described as transdiagnostic features in anxiety. Systematic investigations of
psychological mechanisms, longitudinal studies exploring possible vicious circles
of fear, and studies comparing psychological characteristics within the group of
women fearing childbirth are identified as research areas of high priority. (C)
2016 The Author(s). Published by Elsevier Ltd.
Infantile forgetting is a well-established, and ubiquitous, phenomenon that occurs
in nearly all species, including humans. Despite this, recent advances have shown
that apparently forgotten memories of early experiences can impact later behavior
as well as the neurobiology underlying later learning. In addition, there is
growing evidence that early-life adversity leads to faster maturation of the memory
system, resulting in early experiences being explicitly recalled for longer periods
of time. Understanding the neural mechanisms underpinning these effects may bring
us closer to identifying novel treatment approaches for reversing the effects of
early-life stress on memory and reducing subsequent risk for psychological
disorders.
Although medications and psychotherapy are often effective for the treatment of
posttraumatic stress disorder (PTSD), 20-30% of patients do not respond to these
conventional therapies. In psychiatry, DBS has been either approved or is currently
under investigation for different disorders. At present, whether DBS may be used to
treat PTSD remains unknown. Preclinical research may provide the scientific
rationale for helping conceive and further improve such trials. Some of the animal
models commonly used to date are more suitable for investigating mechanisms of
anxiety and fear than the long-lasting behavior that characterized PTSD. That said,
mechanisms and neurocircuits involved in paradigms such as fear conditioning and
extinction share several common features with those of PTSD. In this article, we
review preclinical studies in which electrical stimulation has been delivered to
animal models of PTSD-like behavior. In those studies, commonly targeted regions
were the basolateral amygdala, ventral striatum, hippocampus, and prefrontal
cortex. Overall, stimulation delivered at high frequencies to most of these targets
improved fear extinction and anxiety-like behavior. Though further research is
certainly needed, promising findings from DBS studies in animals are encouraging
and suggest a positive future perspective for the field.
The aim of the article is to review the evidence for the mediating role of pain-
related fear, and its immediate and long-term consequences in the initiation and
maintenance of chronic low back pain disability. Low back pain is one of the most
frequent reasons why patients ask for consultation and are on sick leave. In these
patients, pain-related fear can cause prolongation of chronic pain and create an
important barrier to successful treatment. In many cases, fear leads to compelling
functional damage. The "fear-avoidance" model described in the paper explains how
and why some individuals with acute pain develop the chronic pain syndrome.
Avoidance leads to reduction, continuation or exacerbation of fear and development
of a phobic state. The article describes available cognitive-behavioural as
sessment and psychotherapeutic methods of pain-related fear and avoidance.
Background Panic disorder is characterised by the presence of recurrent unexpected
panic attacks, discrete periods of fear or anxiety that have a rapid onset and
include symptoms such as racing heart, chest pain, sweating and shaking. Panic
disorder is common in the general population, with a lifetime prevalence of 1% to
4%. A previous Cochrane meta-analysis suggested that psychological therapy (either
alone or combined with pharmacotherapy) can be chosen as a first-line treatment for
panic disorder with or without agoraphobia. However, it is not yet clear whether
certain psychological therapies can be considered superior to others. In order to
answer this question, in this review we performed a network meta-analysis (NMA), in
which we compared eight different forms of psychological therapy and three forms of
a control condition. Objectives To assess the comparative efficacy and
acceptability of different psychological therapies and different control conditions
for panic disorder, with or without agoraphobia, in adults. Search methods We
conducted themain searches in the CCDANCTR electronic databases (studies and
references registers), all years to 16 March 2015. We conducted complementary
searches in PubMed and trials registries. Supplementary searches included reference
lists of included studies, citation indexes, personal communication to the authors
of all included studies and grey literature searches in OpenSIGLE. We applied no
restrictions on date, language or publication status. Selection criteria We
included all relevant randomised controlled trials (RCTs) focusing on adults with a
formal diagnosis of panic disorder with or without agoraphobia. We considered the
following psychological therapies: psychoeducation (PE), supportive psychotherapy
(SP), physiological therapies (PT), behaviour therapy (BT), cognitive therapy (CT),
cognitive behaviour therapy (CBT), third-wave CBT (3W) and psychodynamic therapies
(PD). We included both individual and group formats. Therapies had to be
administered face-to-face. The comparator interventions considered for this review
were: no treatment (NT), wait list (WL) and attention/psychological placebo (APP).
For this review we considered four short-term (ST) outcomes (ST-remission, ST-
response, ST-dropouts, ST-improvement on a continuous scale) and one long-term (LT)
outcome (LT-remission/response). Data collection and analysis As a first step, we
conducted a systematic search of all relevant papers according to the inclusion
criteria. For each outcome, we then constructed a treatment network in order to
clarify the extent to which each type of therapy and each comparison had been
investigated in the available literature. Then, for each available comparison, we
conducted a random-effects meta-analysis. Subsequently, we performed a network
meta-analysis in order to synthesise the available direct evidence with indirect
evidence, and to obtain an overall effect size estimate for each possible pair of
therapies in the network. Finally, we calculated a probabilistic ranking of the
different psychological therapies and control conditions for each outcome. Main
results We identified 1432 references; after screening, we included 60 studies in
the final qualitative analyses. Among these, 54 (including 3021 patients) were also
included in the quantitative analyses. With respect to the analyses for the first
of our primary outcomes, (short-term remission), the most studied of the included
psychological therapies was CBT (32 studies), followed by BT (12 studies), PT (10
studies), CT (three studies), SP (three studies) and PD (two studies). The quality
of the evidence for the entire network was found to be low for all outcomes. The
quality of the evidence for CBT vs NT, CBT vs SP and CBT vs PD was low to very low,
depending on the outcome. The majority of the included studies were at unclear risk
of bias with regard to the randomisation process. We found almost half of the
included studies to be at high risk of attrition bias and detection bias. We also
found selective outcome reporting bias to be present and we strongly suspected
publication bias. Finally, we found almost half of the included studies to be at
high risk of researcher allegiance bias. Overall the networks appeared to be well
connected, but were generally underpowered to detect any important disagreement
between direct and indirect evidence. The results showed the superiority of
psychological therapies over the WL condition, although this finding was amplified
by evident small study effects (SSE). The NMAs for ST-remission, ST-response and
ST-improvement on a continuous scale showed well-replicated evidence in favour of
CBT, as well as some sparse but relevant evidence in favour of PD and SP, over
other therapies. In terms of ST-dropouts, PD and 3W showed better tolerability over
other psychological therapies in the short term. In the long term, CBT and PD
showed the highest level of remission/response, suggesting that the effects of
these two treatments may be more stable with respect to other psychological
therapies. However, all the mentioned differences among active treatments must be
interpreted while taking into account that in most cases the effect sizes were
small and/or results were imprecise. Authors' conclusions There is no high-quality,
unequivocal evidence to support one psychological therapy over the others for the
treatment of panic disorder with or without agoraphobia in adults. However, the
results show that CBT -the most extensively studied among the included
psychological therapies - was often superior to other therapies, although the
effect size was small and the level of precision was often insufficient or
clinically irrelevant. In the only two studies available that explored PD, this
treatment showed promising results, although further research is needed in order to
better explore the relative efficacy of PD with respect to CBT. Furthermore, PD
appeared to be the best tolerated (in terms of ST-dropouts) among psychological
treatments. Unexpectedly, we found some evidence in support of the possible
viability of non-specific supportive psychotherapy for the treatment of panic
disorder; however, the results concerning SP should be interpreted cautiously
because of the sparsity of evidence regarding this treatment and, as in the case of
PD, further research is needed to explore this issue. Behaviour therapy did not
appear to be a valid alternative to CBT as a first-line treatment for patients with
panic disorder with or without agoraphobia.
Fear promotes adaptive responses to threats. However, when the level of fear is not
proportional to the level of threat, maladaptive fear-related behaviors
characteristic of anxiety disorders result. Post-traumatic stress disorder develops
in response to a traumatic event, and patients often show sensitized reactions to
mild stressors associated with the trauma. Stress-enhanced fear learning (SEFL) is
a rodent model of this sensitized responding, in which exposure to a 15-shock
stressor nonassociatively enhances subsequent fear conditioning training with only
a single trial. We examined the role of corticosterone (CORT) in SEFL.
Administration of the CORT synthesis blocker metyrapone prior to the stressor, but
not at time points after, attenuated SEFL. Moreover, CORT co-administered with
metyrapone rescued SEFL. However, CORT alone without the stressor was not
sufficient to produce SEFL. In these same animals, we then looked for correlates of
SEFL in terms of changes in excitatory receptor expression. Western blot analysis
of the basolateral amygdala (BLA) revealed an increase in the GluA1 AMPA receptor
subunit that correlated with SEFL. Thus, CORT is permissive to trauma-induced
changes in BLA function.
Foraging-associated predation risk is a natural problem all prey must face. Fear
evolved due to its protective functions, guiding and shaping behaviors that help
animals adapt to various ecological challenges. Despite the breadth of risky
situations in nature that demand diversity in fear behaviors, contemporary
neurobiological models of fear stem largely from Pavlovian fear conditioning
studies that focus on how a particular cue becomes capable of eliciting learned
fear responses, thus oversimplifying the brain's fear system. Here we review fear
from functional, mechanistic, and phylogenetic perspectives where environmental
threats cause animals to alter their foraging strategies in terms of spatial and
temporal navigation, and discuss whether the inferences we draw from fear
conditioning studies operate in the natural world.
Purpose of reviewTo review current data on HIV-1 resistance arising from the use of
fixed dose combination tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for
preexposure prophylaxis (PrEP) to prevent HIV-1 infection.Recent findingsResistance
to tenofovir (TNV) or FTC is infrequently selected by TDF/FTC PrEP if started
before HIV-1 infection has occurred, but is much more common when inadvertently
started during undiagnosed acute infection. Mathematical modeling predicts that the
number of HIV-1 infections averted by the use of PrEP far exceeds the increase in
drug-resistant infections that could occur from PrEP. Studies in macaques show that
TNV-resistant virus but not FTC-resistant virus can cause breakthrough infection
despite TDF/FTC PrEP. FTC resistance with M184V/I occurs more frequently than TFV
resistance with K65R in seroconverters from clinical trials of TDF/FTC
PrEP.SummaryThe benefit of preventing HIV-1 infections with TDF/FTC PrEP far
outweighs the risk of drug-resistant infection, provided PrEP is not started in
persons with undiagnosed HIV-1 infection. We should respect but not fear HIV-1
resistance from TDF/FTC PrEP and recognize that most TNV or FTC resistance will
arise from its use for antiretroviral therapy (ART). Preventing ART failure or
detecting it early is most important for preventing the spread of HIV-1 resistance
to TDF/FTC and preserving its effectiveness for both PrEP and ART.
This review article offers a critique of the social license concept, and of the
debate surrounding it. In order to best understand what is meant by "social
license", one must look beyond its constituent terminology and instead examine the
core drivers of contemporary mining practice. The working assumption inside the
industry is that if disapproval becomes too intense there is a chance that members
of the community will interrupt mining activities. This is what I refer to as 'the
fear of Mineras Interruptus'. If there is any meaning to attribute to the term
'social license to operate' - it is to be found in the fear of losing access -
because other factors relating to social performance or benefits are considered
peripheral. The author argues that the mining industry's adoption and application
of the concept should be viewed critically and not promoted on face value. (C) 2016
Elsevier Ltd. All rights reserved.
The neuropeptide oxytocin (OXT) has been revealed as a profound anxiolytic and
antistress factor of the brain, besides its many prosocial and reproductive
effects. Therefore, there is substantial scientific and medical interest in its
potential therapeutic use for the treatment of psychopathologies associated with
anxiety, fear, and social dysfunctions, such as generalized anxiety disorder,
posttraumatic stress disorder, and social anxiety disorder, as well as autism and
schizophrenia, among others. Focusing on preclinical studies, we review the
existing evidence for the regulatory capacity of OXT to fine-tune general and
social anxiety-related behaviors, as well as cued and social fear conditioning from
a translational perspective. The available evidence from animal and human studies
substantiates the hypothesis of an imbalance of the endogenous brain OXT system in
the etiology of anxiety disorders, particularly those with a social component such
as social anxiety disorder. In addition, such an imbalance of the OXT system is
also likely to be the consequence of chronic OXT treatment resulting in a dose-
dependent reduction in OXT receptor availability and increased anxiety.
There is a longstanding debate whether allowing safety-seeking behaviors (SSBs)
during cognitive-behavioral treatment hampers or facilitates the reduction of fear.
In this meta-analysis, we evaluate the impact of SSBs on exposure-based fear
reduction interventions. After filtering 409 journal articles, 23 studies were
included for systematic review of which 20 studies were coded for meta-analysis.
For each study, the Standardized Mean Difference (SMD or Hedges'g) of self-reported
fear was calculated at post-intervention. Two comparisons were distinguished: I)
exposure without safety-seeking behavior (SSB-) versus baseline behavior (BL), and
II) exposure with safety-seeking behavior (SSB+) versus BL. The results showed that
average effect sizes were in favor of SSB-, (I: SMD = 031, 95% CI [-0.04, 0.66]),
and in favor of BL, (II: SMD = 0.13, 95% CI [-037, 0.111). Neither of the effect
sizes were statistically significant (I: Z = 1.75, p = .08; II: Z = 1.07, p = .28).
The current meta-analysis could not provide compelling evidence supporting either
the removal or addition of SSB during exposure. More systematic and statistically
empowered replications, using comparable research methods, in (non-)clinical
settings are needed. Novel insights from fear conditioning research may also shed
light on the role of SSB in fear reduction. (C) 2016 Elsevier Ltd. All rights
reserved.
Fear and anxiety-related disorders are remarkably common and debilitating, and are
often characterized by dysregulated fear responses. Rodent models of fear learning
and memory have taken great strides towards elucidating the specific neuronal
circuitries underlying the learning of fear responses. The present review addresses
recent research utilizing optogenetic approaches to parse circuitries underlying
fear behaviors. It also highlights the powerful advances made when optogenetic
techniques are utilized in a genetically defined, cell-type specific, manner. The
application of next-generation genetic and sequencing approaches in a cell-type
specific context will be essential for a mechanistic understanding of the neural
circuitry underlying fear behavior and for the rational design of targeted, circuit
specific, pharmacologic interventions for the treatment and prevention of fear-
related disorders. (C) 2016 Elsevier Inc. All rights reserved.
Purpose: This review summarizes the current state of the science related to fear of
hypoglycemia (FOH) in adults with type 1 diabetes. Fear of hypoglycemia is a
critical deterrent to diabetes self-management, psychological well-being, and
quality of life. We examine the influence of contemporary treatment regimens,
technology, and interventions to identify gaps in knowledge and opportunities for
research and practice. Basic Procedures: A literature search was conducted of
MEDLINE, PsycINFO, and EMBASE. Fifty-three studies that examined fear of
hypoglycemia were included. Main Findings: Fear of hypoglycemia influences diabetes
management and quality of life. Gender and age differences exist in experiences and
responses. Responses vary from increased vigilance to potentially immobilizing
distress. Fear of hypoglycemia is greater at night and may contribute to poor sleep
quality. Strategies to reduce fear of hypoglycemia have had varying success. Newer
technologies hold promise but require further examination. Conclusions: Fear of
hypoglycemia remains a problem, despite advances in technology, insulin analogs,
and evidence-based diabetes management. Clinical care should consistently include
assessment for its influence on diabetes self-management and psychological health.
Further research is needed regarding the influence of newer technologies and
individualized strategies to reduce fear of hypoglycemia while maintaining optimal
glucose control. (C) 2016 Elsevier Inc. All rights reserved.
Pilot performance following unexpected critical events has been either ineffective
or inappropriate in some recent aircraft accidents. The deleterious effects of
startle have been identified as causal or contributory in these events. The startle
reflex, fight or flight reaction, and stress response are discussed. Threat has the
effect of potentiating startle effects and has significant deleterious effects on
cognition. This could contribute to poor performance following an unexpected
critical event in aviation. Training strategies for improved performance, which
would expose pilots to unexpected critical events more often, and develop greater
self-efficacy, are discussed.
Stress has a critical role in the development and expression of many psychiatric
disorders, and is a defining feature of posttraumatic stress disorder (PTSD).
Stress also limits the efficacy of behavioral therapies aimed at limiting
pathological fear, such as exposure therapy. Here we examine emerging evidence that
stress impairs recovery from trauma by impairing fear extinction, a form of
learning thought to underlie the suppression of trauma-related fear memories. We
describe the major structural and functional abnormalities in brain regions that
are particularly vulnerable to stress, including the amygdala, prefrontal cortex,
and hippocampus, which may underlie stress-induced impairments in extinction. We
also discuss some of the stress-induced neurochemical and molecular alterations in
these brain regions that are associated with extinction deficits, and the potential
for targeting these changes to prevent or reverse impaired extinction. A better
understanding of the neurobiological basis of stress effects on extinction promises
to yield novel approaches to improving therapeutic outcomes for PTSD and other
anxiety and trauma-related disorders.
Compelling evidence suggests that fear generalization (i.e. the transfer of fear
from a particular stimulus to another one sharing similarities with the original
stimulus) may contribute to the development of posttraumatic stress disorder
(PTSD), for which current treatments are ineffective. Deficits in hippocampus-
mediated pattern separation, the process by which memories are stored as unique
representations that are resistant to confusion, have been solely proposed as a
putative underlying marker of generalization. We delineate instead an enlarged
scenario, wherein conditioned and generalized fear memories share a common
neurocircuitry, with the hippocampus being the nub of contextual fear, and the
prefrontal cortex of both cued and contextual fear. The potential contribution of
the amygdala and insula will be highlighted as well. Finally, we will consider
vulnerability factors that may contribute to the development of PTSD, and suggest
avenues for novel therapeutics. A better understanding of the mechanisms behind
fear generalization is fundamental to provide further insight into treatment of
debilitating conditions such as PTSD. (C) 2015 Elsevier Ltd. All rights reserved.
The developing brain undergoes substantial maturation into adulthood and the
development of specific neural structures occurs on differing timelines. Transient
imbalances between developmental trajectories of corticolimbic structures, which
are known to contribute to regulation over fear learning and anxiety, can leave an
individual susceptible to mental illness, particularly anxiety disorders. There is
a substantial body of literature indicating that the endocannabinoid (eCB) system
critically regulates stress responsivity and emotional behavior throughout the life
span, making this system a novel therapeutic target for stress-and anxiety-related
disorders. During early life and adolescence, corticolimbic eCB signaling changes
dynamically and coincides with different sensitive periods of fear learning,
suggesting that eCB signaling underlies age-specific fear learning responses.
Moreover, perturbations to these normative fluctuations in corticolimbic eCB
signaling, such as stress or cannabinoid exposure, could serve as a neural
substrate contributing to alterations to the normative developmental trajectory of
neural structures governing emotional behavior and fear learning. In this review,
we first introduce the components of the eCB system and discuss clinical and rodent
models showing eCB regulation of fear learning and anxiety in adulthood. Next, we
highlight distinct fear learning and regulation profiles throughout development and
discuss the ontogeny of the eCB system in the central nervous system, and models of
pharmacological augmentation of eCB signaling during development in the context of
fear learning and anxiety.
Understanding the neural mechanism underlying the formation and extinction of fear
memory would guide the development of advanced strategies for treatment of post-
traumatic stress disorder (PTSD), a generalized anxiety disorder. The mediodorsal
thalamic nucleus (MD) is reciprocally connected with limbic circuitry including the
prefrontal cortex and amygdala, key structures for fear formation, and extinction.
In addition to the distinctive anatomical relationships, the MD participates in
learning and memory process in fear extinction through thalamic dual firing modes:
tonic and burst. This review will briefly describe neural mechanisms of fear
extinction and highlight the role of MD in modulation of fear extinction. We
suggest that excitability of the MD neurons may modulate fear circuits and can be a
novel target for treatment of anxiety disorders.
Tremendous progress has been made in basic neuroscience in recent decades. One area
that has been especially successful is research on how the brain detects and
responds to threats. Such studies have demonstrated comparable patterns of brain-
behavior relationships underlying threat processing across a range of mammalian
species, including humans. This would seem to be an ideal body of information for
advancing our understanding of disorders in which altered threat processing is a
key factor, namely, fear and anxiety disorders. But research on threat processing
has not led to significant improvements in clinical practice. The authors propose
that in order to take advantage of this progress for clinical gain, a conceptual
reframing is needed. Key to this conceptual change is recognition of a distinction
between circuits underlying two classes of responses elicited by threats: 1)
behavioral responses and accompanying physiological changes in the brain and body
and 2) conscious feeling states reflected in self-reports of fear and anxiety. This
distinction leads to a "two systems" view of fear and anxiety. The authors argue
that failure to recognize and consistently emphasize this distinction has impeded
progress in understanding fear and anxiety disorders and hindered attempts to
develop more effective pharmaceutical and psychological treatments. The two-system
view suggests a new way forward.
Objective: to determine the effect of exercise interventions on fear of falling in
community-living people aged = 65. Design: systematic review and meta-analysis.
Bibliographic databases, trial registers and other sources were searched for
randomised or quasi-randomised trials. Data were independently extracted by pairs
of reviewers using a standard form. Results: thirty trials (2,878 participants)
reported 36 interventions (Tai Chi and yoga (n = 9); balance training (n = 19);
strength and resistance training (n = 8)). The risk of bias was low in few trials.
Most studies were from high-income countries (Australia = 8, USA = 7). Intervention
periods (< 12 weeks = 22; 13-26 weeks = 7; > 26 weeks = 7) and exercise frequency
(1-3 times/week = 32; = 4 times/week = 4) varied between studies. Fear of falling
was measured by single-item questions (7) and scales measuring falls efficacy (14),
balance confidence (9) and concern or worry about falling (2). Meta-analyses showed
a small to moderate effect of exercise interventions on reducing fear of falling
immediately post-intervention (standardised mean difference (SMD) 0.37, 95% CI
0.18, 0.56; 24 studies; low-quality evidence). There was a small, but not
statistically significant effect in the longer term (< 6 months (SMD 0.17, 95% CI -
0.05, 0.38 (four studies) and = 6 months post-intervention SMD 0.20, 95% CI -0.01,
0.41 (three studies)). Conclusions: exercise interventions probably reduce fear of
falling to a small to moderate degree immediately post-intervention in community-
living older people. The high risk of bias in most included trials suggests
findings should be interpreted with caution. High-quality trials are needed to
strengthen the evidence base in this area.
Anxiety disorders are highly prevalent worldwide and engender substantial economic
costs and disability. The World Health Organization is currently developing the
Eleventh Revision of the International Classification of Diseases and Related
Health Problems (ICD-11), which represents the first opportunity to improve the
validity, clinical utility, and global applicability of the classification in more
than 25 years. This article describes changes in the organization and diagnostic
guidelines for anxiety and fear-related disorders proposed by the ICD-11 Working
Group on the Classification of Mood and Anxiety Disorders and the rationale and
evidence base for the proposals. In ICD-11, anxiety and fear-related disorders that
manifest across the lifespan are brought together under a new grouping, and are
partly distinguished by their focus of apprehension. The focus of apprehension is
the stimulus or situation that triggers the fear or anxiety and may be highly
specific as in specific phobia or relate to a broader class of situations as in
social anxiety disorder. The guidelines also clarify the relationship between panic
disorder and agoraphobia and a qualifier is provided for panic attacks in the
context of other disorders. A standardized format emphasizing essential features of
anxiety disorders is intended to improve clinical utility. Guidelines will be
further refined based on findings from two types of field studies: those using a
case-controlled vignette methodology disseminated via the Internet to practitioners
worldwide () and clinic-based field trials implemented globally at participating
field study centers.
Cholinergic input to the neocortex, dorsal hippocampus (dHipp), and basolateral
amygdala (BLA) is critical for neural function and synaptic plasticity in these
brain regions. Synaptic plasticity in the neocortex, dHipp, ventral Hipp (vHipp),
and BLA has also been implicated in fear and extinction memory. This finding raises
the possibility that basal forebrain (BF) cholinergic neurons, the predominant
source of acetylcholine in these brain regions, have an important role in mediating
fear and extinction memory. While empirical studies support this hypothesis, there
are interesting inconsistencies among these studies that raise questions about how
best to define the role of BF cholinergic neurons in fear and extinction memory.
Nucleus basalis magnocellularis (NBM) cholinergic neurons that project to the BLA
are critical for fear memory and contextual fear extinction memory. NBM cholinergic
neurons that project to the neocortex are critical for cued and contextual fear
conditioned suppression, but are not critical for fear memory in other behavioral
paradigms and in the inhibitory avoidance paradigm may even inhibit contextual fear
memory formation. Medial septum and diagonal band of Broca cholinergic neurons are
critical for contextual fear memory and acquisition of cued fear extinction. Thus,
even though the results of previous studies suggest BF cholinergic neurons modulate
fear and extinction memory, inconsistent findings among these studies necessitates
more research to better define the neural circuits and molecular processes through
which BF cholinergic neurons modulate fear and extinction memory. Furthermore,
studies determining if BF cholinergic neurons can be manipulated in such a manner
so as to treat excessive fear in anxiety disorders are needed. (C) 2016 Elsevier
Inc. All rights reserved.
This paper reviews the peer-reviewed scientific literature on interventions aimed
to reduce human fear of large carnivores in human-large carnivore conflicts. Based
on psychological theories, a wide definition of fear was adopted, including fear as
an emotion, as a perception and as an attitude. Four major categories of
interventions were identified: information and education, exposure to animal and
habitat, collaboration and participation, and financial incentives. Each of these
categories may have a potential to reduce fear responses. The scientific literature
on the effect of interventions addressing human fear of large carnivores is scarce
and partly contradictory, which makes it difficult for wildlife managers to rely on
current research when designing appropriate interventions. (C) 2016 Elsevier Ltd.
All rights reserved.
Fear memory is the best-studied form of memory. It was thoroughly investigated in
the past 60 years mostly using two classical conditioning procedures (contextual
fear conditioning and fear conditioning to a tone) and one instrumental procedure
(one-trial inhibitory avoidance). Fear memory is formed in the hippocampus
(contextual conditioning and inhibitory avoidance), in the basolateral amygdala
(inhibitory avoidance), and in the lateral amygdala (conditioning to a tone). The
circuitry involves, in addition, the pre- and infralimbic ventromedial prefrontal
cortex, the central amygdala subnuclei, and the dentate gyrus. Fear learning
models, notably inhibitory avoidance, have also been very useful for the analysis
of the biochemical mechanisms of memory consolidation as a whole. These studies
have capitalized on in vitro observations on long-term potentiation and other kinds
of plasticity. The effect of a very large number of drugs on fear learning has been
intensively studied, often as a prelude to the investigation of effects on anxiety.
The extinction of fear learning involves to an extent a reversal of the flow of
information in the mentioned structures and is used in the therapy of posttraumatic
stress disorder and fear memories in general.
In 1952, Bill Gaines, the entrepreneurial comic book publisher, embarked on a new
venture. He had already made a name for himself by introducing the horror comics
(Tales from the Crypt, The Vault of Terror) that had rapidly acquired an eager
readership. Those titles summoned up repressed aspects of postwar culture, reveling
in sadism, sexual infidelity, and grisly torture. But the id knows many pathways,
and in 1952 Gaines launched a humor magazine called Mad. The title was a
celebration of unreason. As its icon, Mad boasted Alfred E. Neuman, a grinning
half-wit who lived by the mantra, What, me worry?
Background Panic disorder is common and deleterious to mental well-being.
Psychological therapies and pharmacological interventions are both used as
treatments for panic disorder with and without agoraphobia. However, there are no
up-to-date reviews on the comparative efficacy and acceptability of the two
treatment modalities, and such a review is necessary for improved treatment
planning for this disorder. Objectives To assess the efficacy and acceptability of
psychological therapies versus pharmacological interventions for panic disorder,
with or without agoraphobia, in adults. Search methods We searched the Cochrane
Common Mental Disorders Group Specialised Register on 11 September 2015. This
register contains reports of relevant randomised controlled trials from the
Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1950 to
present), Embase (1974 to present), and PsycINFO (1967 to present). We cross-
checked reference lists of relevant papers and systematic reviews. We did not apply
any restrictions on date, language, or publication status. Selection criteria We
included all randomised controlled trials comparing psychological therapies with
pharmacological interventions for panic disorder with or without agoraphobia as
diagnosed by operationalised criteria in adults. Data collection and analysis Two
review authors independently extracted data and resolved any disagreements in
consultation with a third review author. For dichotomous data, we calculated risk
ratios (RR) with 95% confidence intervals (CI). We analysed continuous data using
standardised mean differences (with 95% CI). We used the random-effects model
throughout. Main results We included 16 studies with a total of 966 participants in
the present review. Eight of the studies were conducted in Europe, four in the USA,
two in the Middle East, and one in Southeast Asia. None of the studies reported
long-term remission/response (long term being six months or longer from treatment
commencement). There was no evidence of a difference between psychological
therapies and selective serotonin reuptake inhibitors (SSRIs) in terms of short-
term remission (RR 0.85, 95% CI 0.62 to 1.17; 6 studies; 334 participants) or
short-term response (RR 0.97, 95% CI 0.51 to 1.86; 5 studies; 277 participants)
(very low-quality evidence), and no evidence of a difference between psychological
therapies and SSRIs in treatment acceptability as measured using dropouts for any
reason (RR 1.33, 95% CI 0.80 to 2.22; 6 studies; 334 participants; low-quality
evidence). There was no evidence of a difference between psychological therapies
and tricyclic antidepressants in terms of short-term remission (RR 0.82, 95% CI
0.62 to 1.09; 3 studies; 229 participants), short-term response (RR 0.75, 95% CI
0.51 to 1.10; 4 studies; 270 participants), or dropouts for any reason (RR 0.83,
95% CI 0.53 to 1.30; 5 studies; 430 participants) (low-quality evidence). There was
no evidence of a difference between psychological therapies and other
antidepressants in terms of short-term remission (RR 0.90, 95% CI 0.48 to 1.67; 3
studies; 135 participants; very low-quality evidence) and evidence that
psychological therapies did not significantly increase or decrease the short-term
response over other antidepressants (RR 0.96, 95% CI 0.67 to 1.37; 3 studies; 128
participants) or dropouts for any reason (RR 1.55, 95% CI 0.91 to 2.65; 3 studies;
180 participants) (low-quality evidence). There was no evidence of a difference
between psychological therapies and benzodiazepines in terms of short-term
remission (RR 1.08, 95% CI 0.70 to 1.65; 3 studies; 95 participants), short-term
response (RR 1.58, 95% CI 0.70 to 3.58; 2 studies; 69 participants), or dropouts
for any reason (RR 1.12, 95% CI 0.54 to 2.36; 3 studies; 116 participants) (very
low-quality evidence). There was no evidence of a difference between psychological
therapies and either antidepressant alone or antidepressants plus benzodiazepines
in terms of short-term remission (RR 0.86, 95% CI 0.71 to 1.05; 11 studies; 663
participants) and short-term response (RR 0.95, 95% CI 0.76 to 1.18; 12 studies;
800 participants) (low-quality evidence), and there was no evidence of a difference
between psychological therapies and either antidepressants alone or antidepressants
plus benzodiazepines in terms of treatment acceptability as measured by dropouts
for any reason (RR 1.08, 95% CI 0.77 to 1.51; 13 studies; 909 participants; very
low-quality evidence). The risk of selection bias and reporting bias was largely
unclear. Preplanned subgroup and sensitivity analyses limited to trials with
longer-term, quality-controlled, or individual psychological therapies suggested
that antidepressants might be more effective than psychological therapies for some
outcomes. There were no data to contribute to a comparison between psychological
therapies and serotonin-norepinephrine reuptake inhibitors (SNRIs) and subsequent
adverse effects. Authors' conclusions The evidence in this review was often
imprecise. The superiority of either therapy over the other is uncertain due to the
low and very low quality of the evidence with regard to short-term efficacy and
treatment acceptability, and no data were available regarding adverse effects. The
sensitivity analysis and investigation of the sources of heterogeneity indicated
three possible influential factors: quality control of psychological therapies, the
length of intervention, and the individual modality of psychological therapies.
Future studies should examine the long-term effects after intervention or treatment
continuation and should provide information on risk of bias, especially with regard
to selection and reporting biases.
Adolescence is a time of critical brain changes that pave the way for adult
learning processes. However, the extent to which learning in adolescence is best
characterized as a transitional linear progression from childhood to adulthood, or
represents a period that differs from earlier and later developmental stages,
remains unclear. Here we examine behavioral literature on associative fear
conditioning and complex choice behavior with rodent models. Many aspects of fear
conditioning are intact by adolescence and do not differ from adult patterns.
Sufficient evidence, however, suggests that adolescent learning cannot be
characterized simply as an immature precursor to adulthood. Across different
paradigms assessing choice behavior, literature suggests that adolescent animals
typically display more impulsive patterns of responding compared to adults. The
extent to which the development of basic conditioning processes serves as a
scaffold for later adult decision making is an additional research area that is
important for theory, but also has widespread applications for numerous
psychological conditions. (C) 2016 Elsevier Ltd. All rights reserved.
Fear regulation is impaired in anxiety and trauma-related disorders. Patients
experience heightened fear expression and reduced ability to extinguish fear
memories. Because fear regulation is abnormal in these disorders and extinction
recapitulates current treatment strategies, understanding the underlying mechanisms
is vital for developing new treatments. This is critical because although
extinction-based exposure therapy is a mainstay of treatment, relapse is common. We
examine recent findings describing changes in network activity and functional
connectivity within limbic circuits during fear regulation, and explore how
activity-dependent signaling contributes to the neural activity patterns that
control fear and anxiety. We review the role of the prototypical activity dependent
molecule, brain-derived neurotrophic factor (BDNF), whose signaling has been
critically linked to regulation of fear behavior.
Fear conditioning has been commonly used as a model of emotional learning in
animals and, with the introduction of functional neuroimaging techniques, has
proven useful in establishing the neurocircuitry of emotional learning in humans.
Studies of fear acquisition suggest that regions such as amygdala, insula, anterior
cingulate cortex, and hippocampus play an important role in acquisition of fear,
whereas studies of fear extinction suggest that the amygdala is also crucial for
safety learning. Extinction retention testing points to the ventromedial prefrontal
cortex as an essential region in the recall of the safety trace, and explicit
learning of fear and safety associations recruits additional cortical and
subcortical regions. Importantly, many of these findings have implications in our
understanding of the pathophysiology of psychiatric disease. Recent studies using
clinical populations have lent insight into the changes in regional activity in
specific disorders, and treatment studies have shown how pharmaceutical and other
therapeutic interventions modulate brain activation during emotional learning.
Finally, research investigating individual differences in neurotransmitter receptor
genotypes has highlighted the contribution of these systems in fear-associated
learning.
A role for second-generation antipsychotics (SGAs) in the treatment of panic
disorders (PD) has been proposed, but the actual usefulness of SGAs in this
disorder is unclear. According to the PRISMA guidelines, we undertook an updated
systematic review of all of the studies that have examined, in randomized
controlled trials, the efficacy and tolerability of SGAs (as either monotherapy or
augmentation) in the treatment of PD, with or without other comorbid psychiatric
disorders. Studies until 31 December 2015 were identified through PubMed, PsycINFO,
Embase, Cochrane Library and Clinical trials. gov. Among 210 studies, five were
included (two involving patients with a principal diagnosis of PD and three
involving patients with bipolar disorder with comorbid PD or generalized anxiety
disorder). All were eight-week trials and involved treatments with quetiapine
extended release, risperidone and ziprasidone. Overall, a general lack of efficacy
of SGAs on panic symptoms was observed. Some preliminary indications of the
antipanic effectiveness of risperidone are insufficient to support its use in PD,
primarily due to major limitations of the study. However, several methodological
limitations may have negatively affected all of these studies, decreasing the
validity of the results and making it difficult to draw reliable conclusions.
Except for ziprasidone, SGAs were well tolerated in these short-term trials.
Mental processes depend upon a dynamic integration of brain and body. Emotions
encompass internal physiological changes which, through interoception (sensing
bodily states), underpin emotional feelings, for example, cardiovascular arousal
can intensify feelings of fear and anxiety. The brain is informed about how quickly
and strongly the heart is beating by signals from arterial baroreceptors. These
fire in bursts after each heartbeat, and are quiet between heartbeats. The
processing of fear stimuli is selectively enhanced by these phasic signals, and
these inhibit the processing of other types of stimuli including physical pain.
Behavioural and neuroimaging studies detail this differential impact of heart
signals on the processing of salient stimuli, and add to knowledge linking rhythmic
activity in brain and body to perceptual consciousness.
Fear conditioning is a model system used to study threat responses, fear memory and
their dysregulation in a variety of organisms. Newly developed tools such as
optogenetics, Cre recombinase and DREADD technologies have allowed researchers to
manipulate anatomically or molecularly defined cell subtypes with a high degree of
temporal control and determine the effect of this manipulation on behavior. These
targeted molecular techniques have opened up a new appreciation for the critical
contributions different subpopulations of cells make to fear behavior and
potentially to treatment of fear and anxiety disorders. Here we review progress to
date across a variety of techniques to understand fear-related behavior through the
manipulation of different cell subtypes within the amygdala. This article is part
of a Special Issue entitled: Neuropsychiatric Disease. (C) 2015 IBRO. Published by
Elsevier Ltd. All rights reserved.
Introduction: The prevalence of panic disorder (PD) in the population is high and
these patients have work impairment, high unemployment rates, seek medical
treatment more frequently and have more hospitalizations than people without panic
symptoms. Despite the availability of pharmacological, psychological and combined
treatments, approximately one-third of all PD patients have persistent panic
attacks and other PD symptoms after treatment.Areas covered: MEDLINE/Pubmed,
CENTRAL, PsycINFO and Web of Science databases were searched for clinical trials in
treatment-resistant PD. Only studies published between 1980 and 2015, in English,
with human subjects, considered journal articles and clinical trial were included.
We included trials recruiting only adult subjects with treatment-resistant PD,
consistent with criteria from DSM-III to DSM5. We included all prospective
experimental studies. Case, case series, retrospective studies or studies with <10
PD subjects were not included.Expert opinion: Only 11 articles were included in
this review. There were few quality studies, only two were randomized, controlled
and double blind. Augmentation of the pharmacological treatment with cognitive-
behavioral therapy demonstrated some short-term efficacy in treatment-resistant PD.
There were also preliminary evidences of efficacy for monotherapy with reboxetine
and olanzapine, and augmentation with pindolol, divalproex sodium, aripiprazole and
olanzapine in short-term treatment.
Fear of cancer recurrence (FCR) is prevalent among survivors. However, a
comprehensive and universally accepted theoretical framework of FCR to guide
intervention is lacking. This paper reviews theoretical frameworks previously used
to explain FCR and describes the formulation of a novel theoretical framework for
FCR. A systematic review of the literature was undertaken to identify conceptual
frameworks or theories applied to FCR. MEDLINE, PubMED, CINAHL, AMED, PsycINFO and
Web of Science were searched. Identified conceptual frameworks were reviewed for
strength of evidence supporting their validity. Of 558 papers initially identified,
16 made reference to six different conceptual frameworks relating to FCR. The most
comprehensive and evidence-based theoretical approach is the Common Sense Model
(CSM). Other approaches have limited evidence supporting their application to FCR.
Two theoretical approaches developed in the context of emotional disorders that
appear to be highly relevant to FCR: the Self-Regulatory Executive Function (S-REF)
model and Relational Frame Theory were combined with the CSM to produce a novel
cognitive processing account of FCR. Few conceptual frameworks have been used
consistently to guide FCR research, and not all frameworks are empirically well
supported, suggesting that further discussion regarding the conceptualisation of
FCR is needed. The novel theoretical framework for FCR presented highlights the
multidimensional nature of FCR and the importance of cognitive processing and
metacognitions in the development and maintenance of FCR. The novel theoretical
formulation of FCR outlined here provides a much-needed comprehensive framework to
further investigate and address FCR in cancer survivors.
Hypoglycemia is a frequent occurrence in children and adolescents with type 1
diabetes. A variety of efforts have been made to standardize the definition of
hypoglycemia and to define one of its most significant psychosocial consequences-
fear of hypoglycemia (FOH). In addition to documenting the experience of FOH in
children and adolescents type 1 diabetes and their parents, studies have
investigated the relations between FOH and glycemic control and diabetes technology
use. This review provides a summary of the recent FOH literature as it applies to
pediatric type 1 diabetes.
Research in fear conditioning has provided a comprehensive picture of the neuronal
circuit underlying the formation of fear memories. In contrast, our understanding
of the retrieval of fear memories is much more limited. This disparity may stem
from the fact that fear memories are not rigid, but reorganize over time. To bring
some clarity and raise awareness about the time-dependent dynamics of retrieval
circuits, we review current evidence on the neuronal circuitry participating in
fear memory retrieval at both early and late time points following auditory fear
conditioning. We focus on the temporal recruitment of the paraventricular nucleus
of the thalamus (PVT) for the retrieval and maintenance of fear memories. Finally,
we speculate as to why retrieval circuits change with time, and consider the
functional strategy of recruiting structures not previously considered as part of
the retrieval circuit.
BACKGROUND: To evaluate the influence of obstructive sleep apnea (OSA) on
postoperative cardiopulmonary complications in bariatric surgery patients. METHODS:
PubMed, Embase, and the Cochrane central register databases were searched. The
Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was
used for reviewing. RESULTS: Thirteen studies were included (n = 98,935). OSA was
documented in 36,368 (37%) patients. The cardiopulmonary complication rate varied
between .0% and 25.8%; no clear association with OSA was found (rate .0% to 18%),
possibly because of optimized situations such as continuous positive airway
pressure. OSA appeared to be no independent risk factor for intensive care unit
(ICU) admission, death, or longer length of stay in most studies. CONCLUSIONS:
Overall, presented data showed no clear association of OSA with cardiopulmonary
morbidity, ICU admissions, mortality, and length of stay after bariatric surgery.
Although this questions the justification of admitting OSA patients to the ICU,
future studies are required investigating the effect of monitoring strategies and
optimizing treatments including continuous positive airway pressure use. (C) 2016
Elsevier Inc. All rights reserved.
Fear-conditioning is one of the most widely used paradigms in attempts to unravel
the processes and mechanisms underlying learning and plasticity. In most Pavlovian
conditioning paradigms an auditory stimulus is used as the conditioned stimulus
(CS), but conditioning to a tactile CS can also be accomplished. The whisker-to-
barrel tactile system in mice offers a convenient way to investigate the brain
pathways and mechanisms of learning and plasticity of the cerebral cortex. To
support the claim that an animal learns during conditioning sessions and that the
resulting plastic changes are associative in nature, objective measures of behavior
are necessary. Multiple types of conditioned responses can develop depending on the
training situation, CS and unconditioned stimulus (UCS) characteristics. These
include physiological responses such as salivation, heart rate, and galvanic skin
reaction, and also behavioral responses such as startle reflex potentiation or
suppression of an ongoing behavior. When studying learning with the whisker system
in behaving mice, stimulation of individual whiskers in a well-controlled manner
may require animal restraint, which has the disadvantage of limiting the
observation of potential behavioral responses. Stimulation of whiskers in a neck-
restraining apparatus evokes head movements. When whisker stimulation (CS) is
paired with an aversive UCS during conditioning, the number of head movements
decrease in the course of the training. This reaction, called minifreezing,
resembles the frequently used behavioral measure known as the freezing response.
However, this is only applicable for freely moving animals. This article will
review experimental evidence confirming that minifreezing is a relevant index of
association formation between the neutral CS and aversive UCS.
Although cognitive and behavioral therapies are effective in the treatment of
anxiety disorders, it is not clear what the relative effects of these treatments
are. We conducted a meta-analysis of trials comparing cognitive and behavioral
therapies with a control condition, in patients with social anxiety disorder (SAD),
generalized anxiety disorder (GAD) and panic disorder. We included 42 studies in
which generic measures of anxiety were used (BAI, HAMA, STAI-State and Trait). Only
the effects of treatment for panic disorder as measured on the BAI (13.33 points;
95% Cl: 10.58-16.07) were significantly (p = 0.001) larger than the effect sizes on
GAD (6.06 points; 95% CI: 3.96-8.16) and SAD (5.92 points; 95% CI: 4.64-7.20). The
effects remained significant after adjusting for baseline severity and other major
characteristics of the trials. The results should be considered with caution
because of the small number of studies in many subgroups and the high risk of bias
in most studies. (C) 2016 Elsevier Ltd. All rights reserved.
Purpose: A great deal of research has been conducted on the fear of crime (FOC) to
date. Despite this attention, there are a wide range of equivocal results in
determining the segment of the population most likely to be afraid. Methods: A
meta-analysis was conducted using 114 studies in order to gauge a quantitative
relationship between FOC and several demographic variables at both the individual
(e.g., race, gender) and neighbourhood (i.e., the presence of incivilities,
collective efficacy) level. The current analysis resulted in 572 effect sizes.
Results: The results show that 8 of the 12 selected demographic characteristics
significantly predicted FOC. Conclusions: While data identifying the most fearful
segments of the population are generally robust, a moderator variable analysis
revealed several elements in the design of individual studies significantly impact
the trends they observe, particularly the way FOC is measured and the phrasing of
FOC questionnaires. (C) 2016 Published by Elsevier Ltd.
Careaga MBL, Girardi CEN, Suchecki D. Understanding posttraumatic stress disorder
through fear conditioning, extinction and reconsolidation. NEUROSCI BIOBEHAV REV -
Posttraumatic stress disorder (PTSD) is a psychopathology characterized by
exacerbation of fear response. A dysregulated fear response may be explained by
dysfunctional learning and memory, a hypothesis that was proposed decades ago. A
key component of PTSD is fear conditioning and the study of this phenomenon in
laboratory has expanded the understanding of the underlying neurobiological changes
in PTSD. Furthermore, traumatic memories are strongly present even years after the
trauma and maintenance of this memory is usually related to behavioral and
physiological maladaptive responses. Persistence of traumatic memory may be
explained by a dysregulation of two memory processes: extinction and
reconsolidation. The former may explain the over-expression of fear responses as an
imbalance between traumatic and extinction memory. The latter, in turn, explains
the maintenance of fear responses as a result of enhancing trauma-related memories.
Thus, this review will discuss the importance of fear conditioning for the
establishment of PTSD and how failure in extinction or abnormal reconsolidation may
contribute to the maintenance of fear response overtime. (C) 2016 Elsevier Ltd. All
rights reserved.
Background: The recognized relationship between panic disorder (PD) and cardiac
disorders (CDs) is not unequivocal. We reviewed the association between PD and
coronary artery disease (CAD), arrhythmias, cardiomyopathies, and sudden cardiac
death. Methods: We undertook an updated systematic review, according to PRISMA
guidelines. Relevant studies dating from January 1, 2000, to December 31, 2014,
were identified using the PubMed database and a review of bibliographies. The
psychiatric and cardiac diagnostic methodology used in each study was then to very
selective inclusion criteria. Results: Of 3044 studies, 14 on CAD, 2 on
cardiomyopathies, and 1 on arrhythmias were included. Overall, the studies
supported a panic-CAD association. Furthermore, in some of the studies finding no
association between current full-blown PD and CAD, a broader susceptibility to
panic, manifesting as past PD, current agoraphobia, or subthreshold panic symptoms,
appeared to be relevant to the development of CAD. Preliminary data indicated
associations between panic, arrhythmias, and cardiomyopathies. Limitations: The
studies were largely cross-sectional and conducted in cardiological settings. Only
a few included blind settings. The clinical conditions of patients with CDs and the
qualifications of raters of psychiatric diagnoses were highly heterogeneous. CDs
other than CAD had been insufficiently investigated. Conclusions: Our review
supported a relationship between PD and CDs. Given the available findings and the
involvement of the cardiorespiratory system in the pathophysiology of PD, an in-
depth investigation into the panic-CDs association is highly recommended. This
should contribute to improved treatment and prevention of cardiac events and/or
mortality, linked to PD. (C) 2016 Elsevier B.V. All rights reserved.
The fear circuitry orchestrates defense mechanisms in response to environmental
threats. This circuitry is evolutionarily crucial for survival, but its
dysregulation is thought to play a major role in the pathophysiology of psychiatric
conditions in humans. The amygdala is a key player in the processing of fear. This
brain area is prominently modulated by the neurotransmitter serotonin (5-
hydroxytryptamine, 5-HT). The 5-HT input to the amygdala has drawn particular
interest because genetic and pharmacological alterations of the 5-HT transporter
(5-HTT) affect amygdala activation in response to emotional stimuli. Nonetheless,
the impact of 5-HT on fear processing remains poorly understood. The aim of this
review is to elucidate the physiological role of 5-HT in fear learning via its
action on the neuronal circuits of the amygdala. Since 5-HT release increases in
the basolateral amygdala (BLA) during both fear memory acquisition and expression,
we examine whether and how 5-HT neurons encode aversive stimuli and aversive cues.
Next, we describe pharmacological and genetic alterations of 5-HT neurotransmission
that, in both rodents and humans, lead to altered fear learning. To explore the
mechanisms through which 5-HT could modulate conditioned fear, we focus on the
rodent BLA. We propose that a circuit-based approach taking into account the
localization of specific 5-HT receptors on neurochemically-defined neurons in the
BLA may be essential to decipher the role of 5-HT in emotional behavior. In keeping
with a 5-HT control of fear learning, we review electrophysiological data
suggesting that 5-HT regulates synaptic plasticity, spike synchrony and theta
oscillations in the BLA via actions on different subcellular compartments of
principal neurons and distinct GABAergic interneuron populations. Finally, we
discuss how recently developed optogenetic tools combined with electrophysiological
recordings and behavior could progress the knowledge of the mechanisms underlying
5-HT modulation of fear learning via action on amygdala circuits. Such advancement
could pave the way for a deeper understanding of 5-HT in emotional behavior in both
health and disease.
Prolonged distress and dysregulated memory processes are the core features of post-
traumatic stress disorder (PTSD) and represent the debilitating, persistent nature
of the illness. However, the neurobiological mechanisms underlying the expression
of these symptoms are challenging to study in human patients. Stress-enhanced fear
learning (SEFL) paradigms, which encompass both stress and memory components in
rodents, are emerging as valuable preclinical models of PTSD. Rodent models
designed to study the long-term mechanisms of either stress or fear memory alone
have identified a critical role for numerous epigenetic modifications to DNA and
histone proteins. However, the epigenetic modifications underlying SEFL remain
largely unknown. This review will provide a brief overview of the epigenetic
modifications implicated in stress and fear memory independently, followed by a
description of existing SEFL models and the few epigenetic mechanisms found to date
to underlie SEFL. The results of the animal studies discussed here highlight
neuroepigenetics as an essential area for future research in the context of PTSD
through SEFL studies, because of its potential to identify novel candidates for
neurotherapeutics targeting stress-induced pathogenic memories.
Many health professionals broadcast preventive messages designed to scare or shock.
The goal is to "appeal to fear" to warn people the dangers they could incur by
adopting certain behaviors and get them to perform more appropriate actions. Is
this an effective strategy and what are its effects? For over sixty years, research
on fear appeals has led many works and proposed various theoretical models
(Girandola, 2000). This paper presents these researches. We will first review main
models in this field of study, before presenting the most recent researches (1998-
2014) oriented towards cognitive processes related to information processing.
Research perspectives and proposal for a new model will be finally raised and
discussed.
Background A panic attack is a discrete period of fear or anxiety that has a rapid
onset, reaches a peak within 10 minutes and in which at least four of 13
characteristic symptoms are experienced, including racing heart, chest pain,
sweating, shaking, dizziness, flushing, stomach churning, faintness and
breathlessness. Panic disorder is common in the general population with a lifetime
prevalence of 1% to 4%. The treatment of panic disorder includes psychological and
pharmacological interventions. Amongst pharmacological agents, antidepressants and
benzodiazepines are the mainstay of treatment for panic disorder. Different classes
of antidepressants have been compared; and the British Association for
Psychopharmacology, and National Institute for Health and Care Excellence (NICE)
consider antidepressants (mainly selective serotonin reuptake inhibitors (SSRIs))
as the first-line treatment for panic disorder, due to their more favourable
adverse effect profile over monoamine oxidase inhibitors (MAOIs) and tricyclic
antidepressants (TCAs). In addition to antidepressants, benzodiazepines are widely
prescribed for the treatment of panic disorder. Objectives To assess the evidence
for the effects of antidepressants and benzodiazepines for panic disorder in
adults. Search methods The Specialised Register of the Cochrane Common Mental
Disorders Group (CCMDCTR) to 11 September 2015. This register includes relevant
randomised controlled trials from the Cochrane Central Register of Controlled
Trials (CENTRAL), MEDLINE (1950-), Embase (1974-) and PsycINFO (1967-). Reference
lists of relevant papers and previous systematic reviews were handsearched. We
contacted experts in this field for supplemental data. Selection criteria All
double-blind randomised controlled trials allocating adult patients with panic
disorder to antidepressants or benzodiazepines versus any other active treatment
with antidepressants or benzodiazepines. Data collection and analysis Two review
authors independently checked eligibility and extracted data using a standard form.
Data were entered in RevMan 5.3 using a double-check procedure. Information
extracted included study characteristics, participant characteristics, intervention
details, settings and outcome measures in terms of efficacy, acceptability and
tolerability. Main results Thirty-five studies, including 6785 participants overall
(of which 5365 in the arms of interest (antidepressant and benzodiazepines as
monotherapy)) were included in this review; however, since studies addressed many
different comparisons, only a few trials provided data for primary outcomes. We
found low-quality evidence suggesting no difference between antidepressants and
benzodiazepines in terms of response rate (risk ratio (RR) 0.99, 95% confidence
interval (CI) 0.67 to 1.47; participants = 215; studies = 2). Very low-quality
evidence suggested a benefit for benzodiazepines compared to antidepressants in
terms of dropouts due to any cause, even if confidence interval (CI) ranges from
almost no difference to benefit with benzodiazepines (RR 1.64, 95% CI 1.03 to 2.63;
participants = 1449; studies = 7). We found some evidence suggesting that serotonin
reuptake inhibitors (SSRIs) are better tolerated than TCAs (when looking at the
number of patients experiencing adverse effects). We failed to find clinically
significant differences between individual benzodiazepines. The majority of studies
did not report details on random sequence generation and allocation concealment;
similarly, no details were provided about strategies to ensure blinding. The study
protocol was not available for almost all studies so it is difficult to make a
judgment on the possibility of outcome reporting bias. Information on adverse
effects was very limited. Authors' conclusions The identified studies are not
sufficient to comprehensively address the objectives of the present review. The
majority of studies enrolled a small number of participants and did not provide
data for all the outcomes specified in the protocol. For these reasons most of the
analyses were underpowered and this limits the overall completeness of evidence. In
general, based on the results of the current review, the possible role of
antidepressants and benzodiazepines should be assessed by the clinician on an
individual basis. The choice of which antidepressant and/or benzodiazepine is
prescribed can not be made on the basis of this review only, and should be based on
evidence of antidepressants and benzodiazepines efficacy and tolerability,
including data from placebo-controlled studies, as a whole. Data on long-term
tolerability issues associated with antidepressants and benzodiazepines exposure
should also be carefully considered. The present review highlights the need for
further higher-quality studies comparing antidepressants with benzodiazepines,
which should be conducted with high-methodological standards and including
pragmatic outcome measures to provide clinicians with useful and practical data.
Data from the present review will be included in a network meta-analysis of
psychopharmacological treatment in panic disorder, which will hopefully provide
further useful information on this issue.
The generalization of fear is an adaptive, behavioral, and physiological response
to the likelihood of threat in the environment. In contrast, the overgeneralization
of fear, a cardinal feature of posttraumatic stress disorder (PTSD), manifests as
inappropriate, uncontrollable expression of fear in neutral and safe environments.
Overgeneralization of fear stems from impaired discrimination of safe from aversive
environments or discernment of unlikely threats from those that are highly
probable. In addition, the time-dependent erosion of episodic details of traumatic
memories might contribute to their generalization. Understanding the neural
mechanisms underlying the overgeneralization of fear will guide development of
novel therapeutic strategies to combat PTSD. Here, we conceptualize generalization
of fear in terms of resolution of interference between similar memories. We propose
a role for a fundamental encoding mechanism, pattern separation, in the dentate
gyrus (DG)-CA3 circuit in resolving interference between ambiguous or uncertain
threats and in preserving episodic content of remote aversive memories in
hippocampal-cortical networks. We invoke cellular-, circuit-, and systems-based
mechanisms by which adult-born dentate granule cells (DGCs) modulate pattern
separation to influence resolution of interference and maintain precision of remote
aversive memories. We discuss evidence for how these mechanisms are affected by
stress, a risk factor for PTSD, to increase memory interference and decrease
precision. Using this scaffold we ideate strategies to curb overgeneralization of
fear in PTSD.
Memories of threatening, fear-evoking events can persist even over a lifetime.
While fear memory is widely considered to be a highly persistent and durable form
of memory, its circuits are not. This article reviews the dynamic temporal
representation of remote fear memory in the brain, at the level of local circuits
and distributed networks. Data from the study of Pavlovian cued fear conditioning
suggests memory retrieval remains amygdala-dependent, even over protracted time
scales, all the while interconnected cortical and subcortical circuits are newly
recruited and progressively reorganized. A deeper understanding into how the
neurocircuitry of cued fear memory reorganizes with the passage of time will
advance our ongoing search for the elusive physical changes representing fear
memories in the brain. Considering that persistent, pathological fear memories are
a hallmark feature of post-traumatic stress disorder (PTSD), the behavioral and
circuit-level study of remote cued fear memory retrieval adds a key element towards
a systems understanding of PTSD. (C) 2016 Elsevier Ltd. All rights reserved.
Despite adolescence being a developmental window of vulnerability, up until very
recently there were surprisingly few studies on fear extinction during this period.
Here we summarise the recent work in this area, focusing on the unique behavioural
and neural characteristics of fear extinction in adolescent rodents, and humans
where relevant. A prominent hypothesis posits that anxiety disorders peak during
late childhood/adolescence due to the non-linear maturation of the fear inhibition
neural circuitry. We discuss evidence that impaired extinction retention in
adolescence is due to subregions of the medial prefrontal cortex and amygdala
mediating fear inhibition being underactive while other subregions that mediate
fear expression are overactive. We also review work on various interventions and
surprising circumstances which enhance fear extinction in adolescence. This latter
work revealed that the neural correlates of extinction in adolescence are different
to that in younger and older animals even when extinction retention is not
impaired. This growing body of work highlights that adolescence is a unique period
of development for fear inhibition. (C) 2016 Elsevier Ltd. All rights reserved.
The aim of this study was to review previous studies and to identify reliable
factors determining anxiety in adult patients undergoing tooth extraction
procedures. An electronic literature search was conducted of the MEDLINE,
ScienceDirect, SpringerLink, and Wiley Online Library databases covering the period
January 2005 to May 2015. Sequential screening was performed at the title/abstract
and full-text level. The review included all human prospective and retrospective
follow-up studies and clinical trials, cohort studies, case control studies, and
case series that demonstrated at least one factor determining tooth extraction
anxiety and/or fear and used specific scales for measurement. The search identified
16 articles meeting the inclusion criteria. Factors related to tooth extraction in
patients were assessed: propensity to anxiety (P < 0.05), pain experience or
expectations (P < 0.05), level of disturbance during the procedure (P < 0.001),
difficulty of the procedure (P = 0.034), marital status (P = 0.003), social class
(P = 0.012), and type of local anaesthesia (P = 0.008). Using a video as the method
of providing information (P < 0.05) and having had a previous negative dental
experience (P < 0.05) led to an increase in patient anxiety level. Due to
disagreements between studies, further investigations into the other factors are
required to clarify the results. However, the absence of a single and appropriate
scale that includes both the patient's evaluation and that of the doctor, hinders
the rating of patient anxiety.
Recent neuropsychological theories emphasize the influence of maladaptive learning
and memory processes on pain perception. However, the precise relationship between
these processes as well as the underlying mechanisms remain poorly understood;
especially the role of perceptual discrimination and its modulation by associative
fear learning has received little attention so far. Experimental work with
exteroceptive stimuli consistently points to effects of fear learning on perceptual
discrimination acuity. In addition, clinical observations have revealed that in
individuals with chronic pain perceptual discrimination is impaired, and that
tactile discrimination training reduces pain. Based on these findings, we present a
theoretical model of which the central tenet is that associative fear learning
contributes to the development of chronic pain through impaired interoceptive and
proprioceptive discrimination acuity. (C) 2015 Elsevier Ltd. All rights reserved.
It is widely reported that fear of falling (FOF) has a profound and largely
detrimental effect on balance performance in older adults. However, the mechanisms
by which FOF influence postural stability are poorly understood. In the current
article, we use psychological theory to explain FOF-related changes to postural
control. First, we review literature describing associations between FOF and the
'stiffening' strategies observed during control of posture, including observations
of eye and head movements. Second, we present a framework illustrating the
interactions between increased age, FOF, and altered attentional processes, which
in turn influence balance performance and fall-risk. Psychological theory predicts
that anxiety can cause attentional bias for threatening and task-irrelevant stimuli
and compromise the efficiency of working memory resources. We argue that while the
adoption of stiffening strategies is likely to be beneficial in avoiding a loss of
balance during simple postural tasks, it will ultimately compromise performance in
dynamic and highly demanding functional tasks. The adoption of stiffening
strategies leads to inadequate acquisition of the sensory information necessary to
plan and execute dynamic and interactive movements. We conclude with some
suggestions for future research. (C) 2014 The Authors. Published by Elsevier B.V.
Falls are the leading cause of injury-related morbidity and mortality among older
adults. In addition to the resulting physical injury and potential disability after
a fall, there are also important psychological consequences, including depression,
anxiety, activity restriction, and fear of falling. Fear of falling affects 20 to
43% of community-dwelling older adults and is not limited to those who have
previously experienced a fall. About half of older adults who experience fear of
falling subsequently restrict their physical and everyday activities, which can
lead to functional decline, depression, increased falls risk, and reduced quality
of life. Although there is clear evidence that older adults with visual impairment
have higher falls risk, only a limited number of studies have investigated fear of
falling in older adults with visual impairment and the findings have been mixed.
Recent studies suggest increased levels of fear of falling among older adults with
various eye conditions, including glaucoma and age-related macular degeneration,
whereas other studies have failed to find differences. Interventions, which are
still in their infancy in the general population, are also largely unexplored in
those with visual impairment. The major aims of this review were to provide an
overview of the literature on fear of falling, its measurement, and risk factors
among older populations, with specific focus on older adults with visual
impairment, and to identify directions for future research in this area.
Past literature reviews of gain-framed versus loss-based health messages have been
inconsistent and inconclusive. To resolve this and provide a clearer pattern, this
review focuses on the individual or person-specific characteristics of target
audiences. The results indicate that by answering the following four questions
about a target audience, one can predict whether a gain-framed or a loss-based
health message will be more effective. 1) Is there a low (versus high) level of
involvement in the issue? 2) Is there a high (versus low) certainty of the outcome?
3) Is there a low (versus high) preference for risk? 4) Is there a heuristic
(versus piecemeal) processing style? The profiling of audiences on these factors
has two distinct benefits; it resolves many of the seeming inconsistencies in past
positive-negative and gain-loss message research (such as fear appeals working
better with experts than nonexperts) and it helps predict which type of message
will be most effective with a given audience.
Panic disorder (PD), a complex anxiety disorder characterized by recurrent panic
attacks, represents a poorly understood psychiatric condition which is associated
with significant morbidity and an increased risk of suicide attempts and completed
suicide. Recently however, neuroimaging and panic provocation challenge studies
have provided insights into the pathoetiology of panic phenomena and have begun to
elucidate potential neural mechanisms that may underlie panic attacks. In this
regard, accumulating evidence suggests that acidosis may be a contributing factor
in induction of panic. Challenge studies in patients with PD reveal that panic
attacks may be reliably provoked by agents that lead to acid-base dysbalance such
as CO2 inhalation and sodium lactate infusion. Chemosensory mechanisms that
translate pH into panic-relevant fear, autonomic, and respiratory responses are
therefore of high relevance to the understanding of panic pathophysiology. Herein,
we provide a current update on clinical and preclinical studies supporting how
acid-base imbalance and diverse chemosensory mechanisms may be associated with PD
and discuss future implications of these findings.
Ebola virus disease (EVD-formerly known as Ebola hemorrhagic fever) is a severe
hemorrhagic fever caused by lipid-enveloped, nonsegmented, negative-stranded RNA
viruses belonging to the genus Ebolavirus. Case fatality rates may reach up to 76%
of infected individuals, making this infection a deadly health problem in the sub-
Saharan population. At the moment, there are still no indications on
ophthalmological clinical signs and security suggestions for healthcare
professionals (doctors and nurses or cooperative persons). This paper provides a
short but complete guide to reduce infection risks.
Background. Substantial healthcare resources are devoted to panic disorder (PD) and
coronary heart disease (CHD); however, the association between these conditions
remains controversial. Our objective was to conduct a systematic review of studies
assessing the association between PD, related syndromes, and incident CHD. Method.
Relevant studies were retrieved from Medline, EMBASE, SCOPUS and PsycINFO without
restrictions from inception to January 2015 supplemented with hand-searching. We
included studies that reported hazard ratios (HR) or sufficient data to calculate
the risk ratio and 95% confidence interval (CI) which were pooled using a random-
effects model. Studies utilizing self-reported CHD were ineligible. Twelve studies
were included comprising 1 131 612 persons and 58 111 incident CHD cases. Results.
PD was associated with the primary incident CHD endpoint [adjusted HR (aHR) 1.47,
95% CI 1.24-1.74, p < 0.00001] even after excluding angina (aHR 1.49, 95% CI 1.22-
1.81, p < 0.00001). High to moderate quality evidence suggested an association with
incident major adverse cardiac events (MACE; aHR 1.40, 95% CI 1.16-1.69, p =
0.0004) and myocardial infarction (aHR 1.36, 95% CI 1.12-1.66, p = 0.002). The risk
for CHD was significant after excluding depression (aHR 1.64, 95% CI 1.45-1.85) and
after depression adjustment (aHR 1.38, 95% CI 1.03-1.87). Age, sex, length of
follow-up, socioeconomic status and diabetes were sources of heterogeneity in the
primary endpoint. Conclusions. Meta-analysis showed that PD was independently
associated with incident CHD, myocardial infarction and MACE; however, reverse
causality cannot be ruled out and there was evidence of heterogeneity.
This review is devoted to neuroanatomical and neurophysiological mechanisms of
Pavlovian fear conditioning with a focus on the amydgalae, two subcortical nuclear
groups, as primary structures responsible for controlling conditioned fear
responses, and synaptic plasticity at their afferent and efferent projections as a
cellular mechanism to mediate the formation and retention of fear memory. We survey
current data on anatomical organization of the amygdaloid complex, as well as on
its afferent and efferent projections and their functional significance. A special
consideration is given to auditory inputs to the amygdala to analyze the mechanisms
of aversive conditioning to sensory (acoustic) stimuli.
Facial expression is one of the core issues in the ethological approach to the
study of human behaviour. This study discusses sex-specific aspects of the
recognition of the facial expression of fear using results from our previously
published experimental study. We conducted an experiment in which 201 participants
judged seven different facial expressions: anger, contempt, disgust, fear,
happiness, sadness and surprise (Trnka et al. 2007). Participants were able to
recognize the facial expression of fear significantly better on a male face than on
a female face. Females also recognized fear generally better than males. The
present study provides a new interpretation of this sex difference in the
recognition of fear. We interpret these results within the paradigm of human
ethology, taking into account the adaptive function of the facial expression of
fear. We argue that better detection of fear might be crucial for females under a
situation of serious danger in groups of early hominids. The crucial role of
females in nurturing and protecting offspring was fundamental for the reproductive
potential of the group. A clear decoding of this alarm signal might thus have
enabled the timely preparation of females for escape or defence to protect their
health for successful reproduction. Further, it is likely that males played the
role of guardians of social groups and that they were responsible for effective
warnings of the group under situations of serious danger. This may explain why the
facial expression of fear is better recognizable on the male face than on the
female face.
Decades of research has identified the brain areas that are involved in fear, fear
extinction, anxiety and related defensive behaviours. Newly developed genetic and
viral tools, optogenetics and advanced in vivo imaging techniques have now made it
possible to characterize the activity, connectivity and function of specific cell
types within complex neuronal circuits. Recent findings that have been made using
these tools and techniques have provided mechanistic insights into the exquisite
organization of the circuitry underlying internal defensive states. This Review
focuses on studies that have used circuit-based approaches to gain a more detailed,
and also more comprehensive and integrated, view on how the brain governs fear and
anxiety and how it orchestrates adaptive defensive behaviours.
Throughout the history of psychopathology, several meanings have been assigned to
the term melancholia. The main ones were related to affective disorders (fear and
sadness) and abnormal beliefs. At the time of Hippocrates melancholia was regarded
mainly in its affective component. Since that time, and until the eighteenth
century, authors and opinions have been divided, with both aspects (affective
disorders and abnormal beliefs), being valued. Finally, in the eighteenth to
nineteenth centuries, with Pinel at its peak, melancholia becomes exclusively a
synonym of abnormal beliefs. At the turn of the nineteenth to the twentieth
century, the affective component returns as the main aspect characterizing
melancholia.
For almost a century, Pavlovian conditioning is the imperative experimental
paradigm to investigate the development and generalization of fear. However,
despite the rich research tradition, the conceptualization of fear generalization
has remained somewhat ambiguous. In this selective review, we focus explicitly on
some challenges with the current operationalization of fear generalization and
their impact on the ability to make inferences on its clinical potential and
underlying processes. The main conclusion is that, despite the strong evidence that
learning influences perception, current research has largely neglected the role of
perceptual discriminability and its plasticity in fear generalization. We propose
an alternative operationalization of generalization, where the essence is that
Pavlovian conditioning itself influences the breadth of fear generalization via
learning-related changes in perceptual discriminability. Hence a conceptualization
of fear generalization is incomplete without an in-depth analysis of processes of
perceptual discriminability. Furthermore, this highlights perceptual learning and
discriminability as important future targets for pre-clinical and clinical
research. (C) 2015 Elsevier Ltd. All rights reserved.
Pathological fear and anxiety are highly debilitating and, despite considerable
advances in psychotherapy and pharmacotherapy they remain insufficiently treated in
many patients with PTSD, phobias, panic and other anxiety disorders. Increasing
preclinical and clinical evidence indicates that pharmacological treatments
including cognitive enhancers, when given as adjuncts to psychotherapeutic
approaches [cognitive behavioral therapy including extinction-based exposure
therapy] enhance treatment efficacy, while using anxiolytics such as
benzodiazepines as adjuncts can undermine long-term treatment success. The purpose
of this review is to outline the literature showing how pharmacological
interventions targeting neurotransmitter systems including serotonin, dopamine,
noradrenaline, histamine, glutamate, GABA, cannabinoids, neuropeptides (oxytocin,
neuropeptides Y and S, opioids) and other targets (neurotrophins BDNF and FGF2,
glucocorticoids, L-type-calcium channels, epigenetic modifications) as well as
their downstream signaling pathways, can augment fear extinction and strengthen
extinction memory persistently in preclinical models. Particularly promising
approaches are discussed in regard to their effects on specific aspects of fear
extinction namely, acquisition, consolidation and retrieval, including long-term
protection from return of fear (relapse) phenomena like spontaneous recovery,
reinstatement and renewal of fear. We also highlight the promising translational
value of the preclinial research and the clinical potential of targeting certain
neurochemical systems with, for example D-cycloserine, yohimbine, cortisol, and L-
DOPA. The current body of research reveals important new insights into the
neurobiology and neurochemistry of fear extinction and holds significant promise
for pharmacologically-augmented psychotherapy as an improved approach to treat
trauma and anxiety-related disorders in a more efficient and persistent way
promoting enhanced symptom remission and recovery. (C) 2014 The Authors. Published
by Elsevier Inc. This is an open access article under the CC BY-NC-ND license.
AimA systematic review of the literature was performed to establish evidence to
support the practice that in the presence of a colonoscopically diagnosed
colorectal cancer immediate endoscopic excision of synchronous polyps should not be
performed due to the risk of malignant cell implantation at the polypectomy site.
MethodA systematic literature search was performed using Medline, Embase and the
Cochrane Central Register of Controlled Trials to identify studies comparing the
rate of implantation of colorectal cancer cells in normal and damaged colonic
mucosa and reports of colorectal cancer cells seeding into sites of damaged mucosa
after polypectomy. ResultsNo randomized controlled trials were identified. Three
studies involving mammalian models of colonic mucosal damage were included. Pooling
relevant results revealed that out of 59 exposed mammals only one developed tumour
cell implantation at a site of colonic mucosal damage. This equates to a mammalian
invivo experimental risk of malignant cell implantation of 1.6%. ConclusionThe
topic of colorectal cancer seeding following endoscopic procedures has received
little attention. This review suggests that in the presence of a proximal colonic
carcinoma there is a negligible risk of malignant implantation if a more distal
polyp is endoscopically excised.
Interoceptive fear conditioning (IFC), fear generalization and a lack of safety
learning have all been hypothesized to play a role in the pathogenesis of panic
disorder, but have never been examined in a single paradigm. The present study aims
to investigate whether healthy participants (N = 43) can learn both fear and safety
to an interoceptive sensation, and whether such learning generalizes to other,
similar sensations. Two intensities of inspiratory breathing impairment (induced by
two pressure threshold loads of 6 and 25 cmH(2)O) served as interoceptive
conditional stimuli (CSs) in a differential conditioning paradigm. An inspiratory
occlusion was used as the unconditioned stimulus (US). Generalization was tested 24
h after conditioning, using four generalization stimuli with intensities in-between
CS+ and CS- (GSs: 8-10.5-14-18.5 cmH(2)O). Measures included US-expectancy, startle
blink EMG responses, electrodermal activity and respiration. Perceptual
discrimination of interoceptive CSs and GSs was explored with a discrimination task
prior to acquisition and after generalization. Results indicate that differential
fear learning was established for US-expectancy ratings. The group with a low
intensity CS+ and a high intensity CS-showed the typical pattern of differential
fear responding and a similarity-based generalization gradient. In contrast, the
high intensity CS+ and low intensity CS- group showed impaired differential
learning and complete generalization of fear. Our findings suggest that
interoceptive fear learning and generalization are modulated by stimulus intensity
and that the occurrence of discriminatory learning is closely related to fear
generalization.
A crucial element in the "the landscape of fear" concept is that prey animals are
aware of varying levels of predation risk at a spatial scale. This often leads to a
negative spatial relationship between prey and predator in which prey avoid the
most risky sites in the landscape. In this paper, we argue that our understanding
of large carnivore-ungulate interactions is biased by studies from highly
heterogeneous landscapes (e.g. the Yellowstone National Park). Due to a high
availability of refuges and foraging sites in such landscapes, prey are able to
reduce predation risk by showing habitat shifts. Besides the spatial heterogeneity
at the landscape scale, the ungulate response to predation risk can be affected by
the hunting mode (stalking vs. cursorial) of the predator. We propose that prey
cannot easily avoid predation risk by moving to less risky habitats in more
homogenous landscapes with concentrated food resources, especially where the large
carnivores' assemblage includes both stalking and cursorial species. No distinct
refuges for prey may occur in such landscapes due to equally high accessibility to
predators in all habitats, while concentrated resources make prey distribution more
predictable. We discuss a model of a densely forested landscape based on a case
study of the Bialowieza Primeval Forest, Poland. Within this landscape, ungulates
focus their foraging activity on small food-rich forest gaps, which turn out to be
"death traps" as the gaps are primarily targeted by predators (stalking lynx and
cursorial wolf) while hunting. No alternative of moving to low predation risk areas
exist for prey due to risk from wolves in surrounding closed-canopy forest. As a
result, the prey is exposed to constant high predation pressure in contrast to
heterogeneous landscapes with less concentrated resources and more refuge areas.
Future research should focus on explaining how ungulates are coping with predation
risk in these landscapes that offer little choice of escaping predation by
considering behavioural and physiological (e.g. metabolic, hormonal) responses.
Over the past years, numerous studies have provided a clear understanding of the
neuronal circuits and mechanisms involved in the formation, expression and
extinction phases of conditioned cued fear memories. Yet, despite a strong clinical
interest, a detailed understanding of these memory phases for contextual fear
memories is still missing. Besides the well-known role of the hippocampus in
encoding contextual fear behavior, growing evidence indicates that specific regions
of the medial prefrontal cortex differentially regulate contextual fear acquisition
and storage in both animals and humans that ultimately leads to expression of
contextual fear memories. In this review, we provide a detailed description of the
recent literature on the role of distinct prefrontal subregions in contextual fear
behavior and provide a working model of the neuronal circuits involved in the
acquisition, expression and generalization of contextual fear memories.
This mixed method systematic review appraises the individual, familial and systemic
effect of 9/11 and the war on terror for majority and minority children and youth
in North America. The results highlight the broad social consequences of the socio-
political transformations associated with the terror context, which cannot be
understood only through a trauma focus analysis. The social stereotypes transformed
youth experiences of belonging and exclusion. The difference between the
consequences for majority and minority youth suggests the need for a broader
appraisal of this societal context to support the development of prevention and
intervention intersectorial programs.
In the last several years, the importance of understanding what innate threat and
fear is, in addition to learning of threat and fear, has become evident. Odors from
predators are ecologically relevant stimuli used by prey animals as warnings for
the presence of danger. Of importance, these odors are not necessarily noxious or
painful, but they have innate threat-like properties. This review summarizes the
progress made on the behavioral and neuroanatomical fundamentals of innate fear of
the predator odor, 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), a component of fox
feces. TMT is one of several single molecule components of predator odors that have
been isolated in the last several years. Isolation of these single molecules has
allowed for rapid advances in delineating the behavioral constraints and selective
neuroanatomical pathways of predator odor induced fear. In naive mice and rats, TMT
induces a number of fear and defensive behaviors, including robust freezing,
indicating it is an innate threat stimulus. However, there are a number of
behavioral constraints that we do not yet understand. Similarly, while some of the
early olfactory sensory pathways for TMT-induced fear are being delineated, the
pathways from olfactory systems to emotional and motor output regions are less well
understood. This review will focus on what we know and what we still need to learn
about the behavior and neuroanatomy of TMT-induced fear.
Background: Despite the considerable efficacy of cognitive-behavioral therapy (CBT)
for panic disorder (PD) and agoraphobia, a substantial minority of patients fail to
improve for reasons that are poorly understood. Objective: The aim of this study
was to identify consistent predictors and moderators of improvement in CBT for PD
and agoraphobia. Data sources: A systematic review and meta-analysis of articles
was conducted using PsycInfo and PubMed. Search terms included panic, agoraphobi*,
cognitive behavio*, CBT, cognitive therapy, behavio* therapy, CT, BT, exposure, and
cognitive restructuring. Study selection: Studies were limited to those employing
semi-structured diagnostic interviews and examining change on panic- or
agoraphobia-specific measures. Data extraction: The first author extracted data on
study characteristics, prediction analyses, effect sizes, and indicators of study
quality. Interrater reliability was confirmed. Synthesis: 52 papers met inclusion
criteria. Agoraphobic avoidance was the most consistent predictor of decreased
improvement, followed by low expectancy for change, high levels of functional
impairment, and Cluster C personality pathology. Other variables were consistently
unrelated to improvement in CBT, understudied, or inconsistently related to
improvement. Limitations: Many studies were underpowered and failed to report
effect sizes. Tests of moderation were rare. Conclusions: Apart from agoraphobic
avoidance, few variables consistently predict improvement in CBT for PD and/or
agoraphobia across studies. (C) 2015 Elsevier Ltd. All rights reserved.
Memory formation associates with changes in strength and efficacy of existing
synapses and with the formation of new synapses. Dendritic spines, the membranous
protrusions from neuron dendrites that host the majority of excitatory synapses,
are the anatomical sites where neuronal activity reshapes brain networks in
response to stimuli. Mounting evidence indicates that structural changes in fear-
remodeled circuits undergo partially erasure following extinction, suggesting that
the changes that persist may serve to reactivate memory. Here we review data
showing how brain circuits are remodeled at the time fear memory is formed and
extinguished, with a special focus put on the post-extinction persistence of spine
enlargement in relation to memory reactivation.
In this review, we discuss the usefulness of the distinction between fear and
anxiety. The clinical use of the labels is ambiguous, often defining one in terms
of the other. We first consider what a useful, objective, and scientifically valid
definition would entail and then evaluate several fear/anxiety distinctions that
have been made in the neurobiological literature. A strong distinction should
specify the difference in conditions that lead to fear versus anxiety.
Additionally, fear and anxiety should generate distinct sets of behaviors. Ideally,
the two states should be supported by distinguishable neuroan-atomical circuits.
Such a conceptualization would be consistent with the National Institute of Mental
Health's Research Domain Criteria (RDoc). The majority of neurobiological
approaches to the fear versus anxiety distinction fail to differentiate the two
states in terms of behavior, often using the exact same behavioral measures as
indicators. Of the two that do, only Predatory Imminence Theory provides a
distinction both in terms of cause and effect. Indeed, that approach provides a
ready distinction of anxiety, fear, and panic in terms of both antecedent
conditions and response selection rules. Additionally, it appeals to distinct
neural circuits to generate these modes of action.
This article reviews two edited volumes on fear, important contributions to the
newly developing field of the history of emotions. The question at the center of
Jan Plamper and Benjamin Lazier's volume is how fear is constituted as an object;
this question is investigated in an interdisciplinary dialogue. Focusing on the
twentieth century, the editors bring together psychologists, historians of science
and of emotions, and specialists in literature studies, politics, and film. Taking
the dialogue beyond the social sciences is certainly an exciting and necessary
exercise, but it also raises the question whether both sides are really talking
about the same object. Michael Laffan and Max Weiss place fear in a global history
perspective. They cover a wide scope, from early modernity to the present, and
geographically including the Americas and Indonesia. Taken together, both volumes
not only give an impressive overview of the field of fear studies, and add to it
through a number of case studies, but also raise the question "what object is
fear?" in a new way. If this object is as fluid as appears from the two volumes-not
only with respect to the different events that trigger fear, the different uses it
was put to, and the politics it allowed, but as a felt emotion-this calls for
further investigation notably into the words and concepts used to make sense of the
experience.
Introduction: Panic disorder (PD) is a common disabling anxiety disorder associated
with relevant social costs. Effective anti-panic medications exist but have several
drawbacks. From a clinical perspective, there is still a strong unmet need for more
effective, faster acting and more tolerable therapeutic treatments. Areas covered:
The authors review the available results on novel mechanism-based anti-panic drugs
that are under investigation in animal studies up to Phase II studies. The
preclinical studies investigated include: the modulators of the
glutamate/orexin/cannabinoid systems, corticotrophin-releasing factor 1
(CRF1)/arginine vasopressine V-1B/angiotensin II receptor antagonists and
neuropeptide S. The Phase I/II studies investigated include: the modulators of the
glutamate system, isoxazoline derivative, translocator protein (18 kDa) ligands and
CRF1/neurokinin receptor antagonists. Expert opinion: There has been little
progress in recent times. However, glutamate-and orexin-related molecular targets
may represent very promising opportunities for treating panic attacks. Very
preliminary findings suggest that the antagonists of CRF1 and A-II receptors may
have anti-panic properties. However, new medications for PD are far from being
implemented in clinical use. The reasons are multiple, including: the heterogeneity
of the disorder, the translational validity of animal models and the insufficient
use of biomarkers in preclinical/clinical studies. Nevertheless, biomarker-based
strategies, pharmacogenomics, 'personalized psychiatry' and the NIH's Research
Domain Criteria approach could help to remove those obstacles limiting drug
development.
Objective: To assess demographic, medical, and psychological factors that are
associated with fear of recurrence (FCR) in ovarian cancer patients. Method: We
searched PubMed, EMBASE, Cochrane, CINAHL, and PsycINFO. For PubMed, a search using
Medical Subject Headings (MeSH) was run, as well as a text-word search from 1990 to
July of 2014. The search terms used consisted of ovarian terms, fear terms, and
recurrence/progression themes. Title and abstract reviews were conducted by two
independent reviewers to determine eligibility, and discrepancies were decided by a
third reviewer. Full-text reviews of potentially eligible articles were conducted
by the review team, which met regularly to ensure the reliability of eligibility
ratings across all articles. Results: A total of 15 articles met our inclusion
criteria. Nine were quantitative studies that utilized a cross-sectional design,
and the other six included three qualitative studies, two small intervention
studies, and one study that utilized content analysis to explore written
correspondence among ovarian cancer patients. FCR was reported as a significant
concern for both older and younger women at both early and advanced stages. Women
were distressed about recurrence at various times during their treatment and
posttreatment. FCR was noted to be prevalent around cancer follow-up examinations.
Many women reported not receiving adequate support for recurrence. FCR was also
shown to be linked in some way to hopelessness, faith/spirituality, and
posttraumatic stress disorder (PTSD). FCR was also linked to patients' anxiety
about death and dying and uncertainty about the future of their medical health.
Significance of Results: This review demonstrates that FCR is prevalent in the
ovarian cancer population. Moreover, cancer recurrence fears are not adequately
assessed or treated. More information is needed on the factors that may be related
to women's fears about recurrence of ovarian cancer. In addition, a validated
measure of FCR among ovarian cancer patients as well as a treatment intervention
are needed.
Emotional and traumatic experiences lead to the development of particularly strong
memories that can drive neuropsychiatric disorders, such as posttraumatic stress
disorder (PTSD) and drug addiction. Disruption of these memories would therefore
serve as a powerful treatment option, and targeting the pathologic emotional, but
not declarative, component of a memory would be ideal for clinical intervention.
Research reveals that after retrieval of a consolidated memory, the memory can be
destabilized, and must then be reconsolidated through synaptic plasticity to allow
subsequent retrieval. Disruption of reconsolidation-related plasticity would
therefore impair specific, reactivated memories. Noradrenergic signaling
strengthens synaptic plasticity and is essential for encoding the emotional
components of memory. Consistent with this, investigations have now revealed that
noradrenergic signaling is a critical mechanism for reconsolidation of emotional
memories in rodent and human models. Here, we discuss these investigations and
promising clinical trials indicating that disruption of noradrenergic signaling
during reconsolidation may abolish the pathologic emotional, but not declarative,
component of memories allowing alleviation of neuropsychiatric disorders including
PTSD and drug addiction.
PURPOSE: A case is presented and a systematic review of the literature is provided
to update our current knowledge of induction of fear by cortical stimulation.
METHODS: We present a case of refractory epilepsy associated with a lesion where
fear could be induced by intraoperative electrical stimulation of the posterior
inner part of the superior temporal gyrus. We performed a systematic review of the
literature using PubMed with the key words "epilepsy AND emotion", "cortical
stimulation AND emotion," and "human brain stimulation AND behavior'. RESULTS:
Intraoperative cortical stimulation of the inner part of the posterior superior
temporal gyms reliably induced fear and progressive screaming behavior. Stimulation
through subdural grid electrodes did not induce this phenomenon. A systematic
review of the literature identified fear induction by stimulation of different
widespread cortical areas including the temporal pole, the insula, and the anterior
cingulate cortex. The posterior part of the superior temporal gyrus has so far not
been associated with fear induction after electrical stimulation. CONCLUSION:
Although our observation suggests that this area of the brain could be part of a
network involved in the elicitation of fear, dysfunction of this network induced by
epilepsy could also explain the observed phenomenon. Electrophysiologic and imaging
studies must be conducted to improve our understanding of the cortical networks
forming the neuroanatomical substrate of higher brain functions and experiences
such as fear.
The -amino butyric acid (GABA) synthetic enzyme glutamic acid decarboxylase (GAD)65
is critically involved in the activity-dependent regulation of GABAergic inhibition
in the central nervous system. It is also required for the maturation of the
GABAergic system during adolescence, a phase that is critical for the development
of several neuropsychiatric diseases. Mice bearing a null mutation of the GAD65
gene develop hyperexcitability of the amygdala and hippocampus, and a phenotype of
increased anxiety and pathological fear memory reminiscent of posttraumatic stress
disorder. Although genetic association of GAD65 in human has not yet been reported,
these findings are in line with observations of reduced GABAergic function in these
brain regions of anxiety disorder patients. The particular value of GAD65(-/-) mice
thus lies in modeling the effects of reduced GABAergic function in the mature
nervous system. The expression of GAD65 and a second GAD isozyme, GAD67, are
differentially regulated in response to stress in limbic brain areas suggesting
that by controlling GABAergic inhibition these enzymes determine the vulnerability
for the development of pathological anxiety and other stress-induced phenotypes. In
fact, we could recently show that GAD65 haplodeficiency, which results in delayed
postnatal increase of GABA levels, provides resilience to juvenile-stress-induced
anxiety to GAD65(+/-) mice thus foiling the increased fear and anxiety in
homozygous GAD65(-/-) mice.
Research indicates that fears and phobias are significantly more prevalent and
emerge in response to a greater variety of stimuli, among children with autism
spectrum disorders (ASD) than among their developmentally disabled or typically
developing peers. Such findings are problematic given the difficulty of assessing
and identifying fears or phobias among the ASD population and the challenge of
identifying effective treatments for those with core diagnostic deficits in
comprehension, communication, and attentional skills. The current review aimed to
evaluate the literature describing interventions to treat fears, specific phobia,
or social phobia among children with ASD and to identify evidence-based practice in
this area. The review indicated that a variety of interventions, described as both
traditional and novel, were successful in treating fearful or phobic behavioral
responses to stimuli. The findings also suggest that behavioral intervention,
including reinforcement, modeling, and exposure, may be considered evidence-based
practice in the treatment of fears and phobias among children with ASD. However,
the current research base is limited by the predominant focus on the behavioral
element of the fear response, and the lack of research examining the cognitive or
physiological responses during assessment or treatment.
The endocannabinoid (eCB) system has emerged as a central integrator linking the
perception of external and internal stimuli to distinct neurophysiological and
behavioural outcomes (such as fear reaction, anxiety and stress-coping), thus
allowing an organism to adapt to its changing environment. eCB signalling seems to
determine the value of fear-evoking stimuli and to tune appropriate behavioural
responses, which are essential for the organism's long-term viability, homeostasis
and stress resilience; and dysregulation of eCB signalling can lead to psychiatric
disorders. An understanding of the underlying neural cell populations and cellular
processes enables the development of therapeutic strategies to mitigate behavioural
maladaptation.
Panic attacks (PAs), the core feature of panic disorder, represent a common
phenomenon in the general adult population and are associated with a considerable
decrease in quality of life and high health care costs. To date, the underlying
pathophysiology of PAs is not well understood. A unique feature of PAs is that they
represent a rare example of a psychopathological phenomenon that can be reliably
modeled in the laboratory in panic disorder patients and healthy volunteers. The
most effective techniques to experimentally trigger PAs are those that acutely
disturb the acid-base homeostasis in the brain: inhalation of carbon dioxide (CO2),
hyperventilation, and lactate infusion. This review particularly focuses on the use
of CO2 inhalation in humans and rodents as an experimental model of panic. Besides
highlighting the different methodological approaches, the cardio-respiratory and
the endocrine responses to CO2 inhalation are summarized. In addition, the
relationships between CO2 level, changes in brain pH, the serotonergic system, and
adaptive physiological and behavioral responses to CO2 exposure are presented. We
aim to present an integrated psychological and neurobiological perspective.
Remaining gaps in the literature and future perspectives are discussed. (C) 2015
Elsevier Ltd. All rights reserved.
Regulations for protecting humans against stochastic biological effects from
ionizing radiation are based on the linear no-threshold (LNT) risk assessment
model, which states that any amount of radiation exposure may lead to cancer in a
population. Based on the LNT model, risk from low-dose radiation increases linearly
with increasing doses of radiation. Imaging procedures in medicine and dentistry
are an important source of low-dose ionizing radiation. The increased use of
computerized tomography (CT) and cone beam computerized tomography (CBCT) has
raised health concerns regarding exposure to low-dose ionizing radiation. In oral
and maxillofacial surgery and implant dentistry, CBCT is now at the forefront of
this controversy. Although caution has been expressed, there have been no direct
studies linking radiation exposure from CT and CBCT used in dental imaging with
cancer induction. This article describes the concerns about radiation exposure in
dental imaging regarding the use of CT.
Recent neuro-imaging studies have implicated the cerebellum in several higher-order
functions. Its role in human fear conditioning has, however, received limited
attention. The current meta-analysis examines the loci of cerebellar contributions
to fear conditioning in healthy subjects, thus mapping, for the first time, the
neural response to conditioned aversive stimuli onto the cerebellum. By using the
activation likelihood estimation (ALE) technique for analyses, we identified
several distinct regions in the cerebellum that activate in response to the
presentation of the conditioned stimulus: the cerebellar tonsils, lobules HIV-VI,
and the culmen. These regions have separately been implicated in fear acquisition,
consolidation of fear memories and expression of conditioned fear responses. Their
specific role in these processes may be attributed to the general contribution of
cerebellar cortical networks to timing and prediction. Our meta-analysis highlights
the potential role of the cerebellum in human cognition and emotion in general, and
addresses the possibility how deficits in associative cerebellar learning may play
a role in the pathogenesis of anxiety disorders. Future studies are needed to
further clarify the mechanistic role of the cerebellum in higher order functions
and neuropsychiatric disorders. (C) 2015 Published by Elsevier Ltd.
Anxiety disorders are a group of crippling mental diseases affecting millions of
Americans with a 30% lifetime prevalence and costs associated with healthcare of
$42.3 billion. While anxiety disorders show high levels of co-morbidity with
smoking (45.3% vs. 22.5% in healthy individuals), they are also more common among
the smoking population (22% vs. 11.1% in the non-smoking population). Moreover,
there is clear evidence that smoking modulates symptom severity in patients with
anxiety disorders. In order to better understand this relationship, several animal
paradigms are used to model several key symptoms of anxiety disorders; these
include fear conditioning and measures of anxiety. Studies clearly demonstrate that
nicotine mediates acquisition and extinction of fear as well as anxiety through the
modulation of specific subtypes of nicotinic acetylcholine receptors (nAChRs) in
brain regions involved in emotion processing such as the hippocampus. However, the
direction of nicotine's effects on these behaviors is determined by several factors
that include the length of administration, hippocampus-dependency of the fear
learning task, and source of anxiety (novelty-driven vs. social anxiety). Overall,
the studies reviewed here suggest that nicotine alters behaviors related to fear
and anxiety and that nicotine contributes to the development, maintenance, and
reoccurrence of anxiety disorders. (C) 2015 Elsevier Inc. All rights reserved.
Injectable treatments, such as glucagon-like peptide-1 receptor agonists and
insulin, are options for the pharmacologic treatment of type 2 diabetes. Numerous
barriers lead to delay in initiating injectable treatment, which, in turn, may lead
to inadequate glycemic control and increased risk of diabetes-related
complications, underscoring the need to understand and address these barriers.
Barriers to the initiation of injectable therapy, strategies to mitigate barriers,
and information about needle attributes and their relation to needle pain are
reviewed on the basis of published literature retrieval and our clinical
experience. Barriers to the initiation of injectable therapy originate from both
patients and practitioners. Anxiety about and fear of injection-associated pain has
been estimated to affect approximately 30%-50% of patients before the initiation of
diabetes education interventions. Advances in needle design have minimized the pain
associated with injections, and recent data suggest that actual pain and bleeding
associated with various needle gauges (21-gauge to 31-gauge) are mild. Other
barriers include concerns about the ability to handle injectable therapy, concerns
about treatment side effects, and impacts on quality of life. Practitioners can
help to mitigate barriers to injectable treatment for type 2 diabetes by
understanding patient perceptions, improving education, and setting realistic
expectations about therapy. Strategies for minimizing injection-associated fear and
anxiety include a combination of assessment, appropriate needle selection, patient
education, behavioral interventions, and monitoring.
Impending fractures and spinal cord compression are frequent complications of bone
metastasis with debilitating consequences. The issue of impending fracture of the
femurs and risk of spinal cord compression was raised in an 83-year-old woman with
multiple myeloma. Some type of prophylactic treatment would appear suitable,
usually surgical, for this condition. While criteria for prophylactic treatment
exist in the orthopedic literature, most patients present to rheumatologists,
oncologists, or internists. This article reviews the various scoring systems
available to evaluate the risk of these very serious complications. We also discuss
the current limitations of such tools and the need for a research agenda to address
this common problem.
Introduction: Supporting individuals as they disclose their HIV serostatus may lead
to a variety of individual and public health benefits. However, many women living
with HIV are hesitant to disclose their HIV status due to fear of negative outcomes
such as violence, abandonment, relationship dissolution and stigma. Methods: We
conducted a systematic review of studies evaluating interventions to facilitate
safer disclosure of HIV status for women living with HIV who experience or fear
violence. Articles, conference abstracts and programme reports were included if
they reported post-intervention evaluation results and were published before 1
April 2015. Searching was conducted through electronic databases for peer-reviewed
articles and conference abstracts, reviewing websites of relevant organizations for
grey literature, hand searching reference lists of included studies and contacting
experts. Systematic methods were used for screening and data abstraction, which was
conducted in duplicate. Study quality (rigor) was assessed with the Cochrane risk
of bias tool. Results: Two interventions met the inclusion criteria: the Safe Homes
and Respect for Everyone cluster-randomized trial of combination HIV and intimate
partner violence (IPV) services in Rakai, Uganda, and the South Africa HIV/AIDS
Antenatal Post-Test Support study individual randomized trial of an enhanced
counselling intervention for pregnant women undergoing HIV testing and counselling.
Both programmes integrated screening for IPV into HIV testing services and trained
counsellors to facilitate discussions about disclosure based on a woman's risk of
violence. However, both were implemented as part of multiple-component
interventions, making it impossible to isolate the impact of the safer disclosure
components. Conclusions: The existing evidence base for interventions to facilitate
safe HIV serostatus disclosure for women who experience or fear violence is
limited. Development and implementation of new approaches and rigorous evaluation
of safe disclosure outcomes is needed to guide programme planners and policy
makers.
The historically understood role of the central amygdala (CeA) in fear learning is
to serve as a passive output station for processing and plasticity that occurs
elsewhere in the brain. However, recent research has suggested that the CeA may
play a more dynamic role in fear learning. In particular, there is growing evidence
that the CeA is a site of plasticity and memory formation, and that its activity is
subject to tight regulation. The following review examines the evidence for these
three main roles of the CeA as they relate to fear learning. The classical role of
the CeA as a routing station to fear effector brain structures like the
periaqueductal gray, the lateral hypothalamus, and paraventricular nucleus of the
hypothalamus will be briefly reviewed, but specific emphasis is placed on recent
literature suggesting that the CeA 1) has an important role in the plasticity
underlying fear learning, 2) is involved in regulation of other amygdala subnuclei,
and 3) is itself regulated by intra- and extra-amygdalar input. Finally, we discuss
the parallels of human and mouse CeA involvement in fear disorders and fear
conditioning, respectively.
The world has recently been witness to the emergence of a new contemporary
geopolitical phenomenon: the declaration of Islamic States by specific Islamic
organizations. This phenomenon has the potential to dramatically transform the
geopolitical setting of the Middle East and to have farreaching effects on a global
level. Of these most prominent, however, has undoubtedly been the June 2014
declaration by the "Islamic State" organization of a "caliphate" covering large
areas of the two war-torn states of Syria and Iraq. The aim of this article is to
interrogate the territorial aspects of the Islamic State and to discern what makes
it unique and exceptional in comparison to the many other Islamic political
organizations that have emerged in recent years. In order to facilitate a better
understanding of territoriality, I distinguish here between two major dimensions:
conceptions of territoriality and tactics of territoriality. My working assumption
is that by distinguishing between conceptions and tactics of territoriality, we can
compare the exercise of territoriality by states and, in the present case,
organizations. In this article, I argue that the Islamic State poses a challenge to
both the conceptual and tactical dimensions of the contemporary territory and
territoriality of modern states. Yet, while its conception of territoriality may be
widely shared by other political Islamic organizations, its uniqueness lies in its
tactics and strategies. Indeed, it is the brutal tactics of the Islamic State that
are less acceptable to many Muslims around the world, not its political conception,
which enjoys considerable support in the Muslim arena. Yet, when comparing it with
modern states, the Islamic State poses a challenge to the territory and
territoriality in both conception and tactics. (C) 2014 Elsevier Ltd. All rights
reserved.
At specific maturational stages neural circuits enter sensitive periods of
heightened plasticity during which the development of both brain and behavior are
highly receptive to particular experiential information. A relatively advanced
understanding of the regulatory mechanisms governing the initiation closure and
reinstatement of sensitive period plasticity has emerged from extensive research
examining the development of the visual system. In this article we discuss a large
body of work characterizing the pronounced nonlinear changes in fear learning and
extinction that occur from childhood through adulthood and their underlying neural
substrates. We draw upon the model of sensitive period regulation within the visual
system and present burgeoning evidence suggesting that parallel mechanisms may
regulate the qualitative changes in fear learning across development.
Fifty years ago, when the effect of antidepressants on panic disorder was
described, a significant progress in understanding this anxiety disorder has been
made. Theoretical mechanisms and models of fear and panic disorder were proposed
and tested in animal models and humans. With growing possibilities of non-invasive
neuroimaging techniques, there is an increasing amount of information on the panic
disorder. Unfortunately, a number of circumstances lead to inconsistent findings
and its interpretations. In our review, we focused on functional MRI in panic
disorder, limitations of current studies, possible interpretations and proposals
for future direction. In our opinion, the current findings support the
neuroanatomical model of panic disorder at the level of group data analysis. But at
the same time, the results suggest significant inter-individual differences across
the patients, which may be related to each patient's individual history, woven into
their neural network and affecting the individual symptoms and response to therapy.
Posttraumatic stress disorder (PTSD) is a psychiatric illness whose prevalence in
women is more than twice the rate as men. Despite a burgeoning literature
characterizing sex differences in PTSD incidence and its disproportionate burden on
society, there is a dearth of literature describing biological mechanisms
underlying these disparities. However, the recent identification of biomarkers of
PTSD by translational neuroscientists offers a promising opportunity to explore sex
interactions in PTSD phenotypes. A notable observation is that individuals with
PTSD show deficits in their ability to inhibit conditioned fear responding after
extinction training. Given that extinction procedures, via exposure-based cognitive
behavioral therapy, make up one of the predominant modes of treatment in PTSD,
there is a critical need for more research on sex interactions in this form of fear
regulation. An emerging hypothesis is that fluctuating gonadal hormones, especially
estrogen, in the menstrual cycle may play a critical role in fear extinction and,
hence, PTSD vulnerability and symptom severity in women. The current review
discusses how the study of putative activational effects of estrogen on fear
extinction may be harnessed to advance the search for better treatments for PTSD in
women. We conclude that estrogen treatment may be a putative pharmacologic adjunct
in extinction-based therapies and should be tracked in the menstrual cycle during
the course of PTSD treatment.
Once acquired, a fearful memory can persist for a lifetime. Although learned fear
can be extinguished, extinction memories are fragile. The resilience of fear
memories to extinction may contribute to the maintenance of disorders of fear and
anxiety, including post-traumatic stress disorder (PTSD). As such, considerable
effort has been placed on understanding the neural circuitry underlying the
acquisition, expression, and extinction of emotional memories in rodent models as
well as in humans. A triad of brain regions, including the prefrontal cortex,
hippocampus, and amygdala, form an essential brain circuit involved in fear
conditioning and extinction. Within this circuit, the prefrontal cortex is thought
to exert top-down control over subcortical structures to regulate appropriate
behavioral responses. Importantly, a division of labor has been proposed in which
the prelimbic (PL) and infralimbic (IL) subdivisions of the medial prefrontal
cortex (mPFC) regulate the expression and suppression of fear in rodents,
respectively. Here, we critically review the anatomical and physiological evidence
that has led to this proposed dichotomy of function within mPFC. We propose that
under some conditions, the PL and IL act in concert, exhibiting similar patterns of
neural activity in response to aversive conditioned stimuli and during the
expression or inhibition of conditioned fear. This may stem from common synaptic
inputs, parallel downstream outputs, or corticocortical interactions. Despite this
functional covariation, these mPFC subdivisions may still be coding for largely
opposing behavioral outcomes, with PL biased towards fear expression and IL towards
suppression.
This article is part of a Special Issue "SBN 2014". Beginning with Vale and
Colleagues in 1981, corticotropin releasing factor (CRF) also called corticotropin
releasing hormone (CRH) has repeatedly been identified as an important contributor
to fear and anxiety behavior. These findings have proven useful to further our
understanding of disorders that have significant fear-dysregulation, such as post-
traumatic stress, as well as other stress- and anxiety-related disorders.
Unfortunately, the data are not all in agreement. In particular the role of CRF in
fear learning is controversial, with studies pointing to contradictory effects from
CRF manipulation even within the same brain structure. Further, very few studies
address the potentially promising role of CRF manipulation in fear extinction
behavior. Here, we briefly review the role of CRF in anxiety, fear learning and
extinction, focusing on recent cell-type and neurotransmitter-specific studies in
the amygdala and bed nucleus of the stria terminalis (BNST) that may help to
synthesize the available data on the role of CRF in fear and anxiety-related
behaviors. (C) 2015 Published by Elsevier Inc.
An understanding of the neurobiological mechanisms involved in the regulation of
fear is essential for the development of new treatments for anxiety disorders, such
as phobias, panic, and post-traumatic stress disorders (PTSD). Orexins, also known
as hypocretins, are neuropeptides located exclusively in hypothalamic neurons that
have extensive projections throughout the central nervous system. Although this
system was initially believed to be primarily involved in the regulation of feeding
behavior, recent studies have shown that orexins also modulate neural circuits
implicated in the expression and extinction of fear memories. Here, we discuss
recent findings involving orexins in anxiety disorders and current clinical trials
using orexin ligands that could be applied to identify new therapies for diseases
characterized by pathological fear.
Comparatively little work on folk devils and moral panics has focused on mirror
image phenomena of collective joy, celebration, and hope. By introducing a theory
of "moral euphoria" and the concept of "folk heroes," and focusing on processes of
"deification," this article provides a fresh perspective within the moral panic
literature, showing how certain actors may go from "folk hero" fame to "folk devil"
infamy. Using the examples of Tony Blair and Barack Obama, the article shows how
politicians are particularly significant sociological actors in this regard. The
conclusion suggests wider implications for the role of academics in demonization
and deification processes.
Chemotherapy has made an essential contribution to cancer treatment in recent
decades despite its adverse effects. As cancer survivors have increased, concern
about ex-patient lifespan has become more important too. Doxorubicin is an
effective anti-neoplastic drug that produces a cardiotoxic effect. Cancer survivors
who received doxorubicin became more vulnerable to cardiac disease than the normal
population did. Many efforts have been made to prevent cardiac toxicity in patients
with cancer. However, current therapies cannot guarantee permanent cardiac
protection. One of their main limitations is that they do not promote myocardium
regeneration. In this review, we summarize and discuss the promising use of
mesenchymal stemcells for cardio-protection or cardio-regeneration therapies and
consider their regenerative potential without leaving aside their controversial
effects on tumor progression.
Fear generalization, in which conditioned fear responses generalize or spread to
related stimuli, is a defining feature of anxiety disorders. The behavioral
consequences of maladaptive fear generalization are that aversive experiences with
one stimulus or event may lead one to regard other cues or situations as potential
threats that should be avoided, despite variations in physical form. Theoretical
and empirical interest in the generalization of conditioned learning dates to the
earliest research on classical conditioning in nonhumans. Recently, there has been
renewed focus on fear generalization in humans due in part to its explanatory power
in characterizing disorders of fear and anxiety. Here, we review existing
behavioral and neuroimaging empirical research on the perceptual and non-perceptual
(conceptual and symbolic) generalization of fear and avoidance in healthy humans
and patients with anxiety disorders. The clinical implications of this research for
understanding the etiology and treatment of anxiety is considered and directions
for future research described.
Fear can be an adaptive emotion that helps defend against potential danger.
Classical conditioning models elegantly describe how animals learn which stimuli in
the environment signal danger, but understanding how this learning is generalized
to other stimuli that resemble aspects of a learned threat remains a challenge.
Critically, the overgeneralization of fear to harmless stimuli or situations is a
burden to daily life and characteristic of posttraumatic stress disorder and other
anxiety disorders. Here, we review emerging evidence on behavioral and neural
mechanisms of generalization of emotional learning with the goal of encouraging
further research on generalization in anxiety disorders. We begin by placing
research on fear generalization in a rich historical context of stimulus
generalization dating back to Pavlov, which lays the foundation for theoretical and
experimental approaches used today. We then transition to contemporary behavioral
and neurobiological research on generalization of emotional learning in humans and
nonhuman animals and discuss the factors that promote generalization on the one
hand from discrimination on the other hand.
During the past century, Pavlovian conditioning has served as the predominant
experimental paradigm and theoretical framework to understand how humans learn to
fear and avoid real or perceived dangers. Animal models for translational research
offer insight into basic behavioral and neurophysiological factors mediating the
acquisition, expression, inhibition, and generalization of fear. However, it is
important to consider the limits of traditional animal models when applied to
humans. Here, we focus on the question of how humans generalize fear. We propose
that to understand fear generalization in humans requires taking into account
research on higher-level cognition such as category-based induction, inferential
reasoning, and representation of conceptual knowledge. Doing so will open the door
for productive avenues of new research.
The aim of the current study was twofold: (1) to systematically examine differences
in fear conditioning between anxiety patients and healthy controls using meta-
analytic methods, and (2) to examine the extent to which study characteristics may
account for the variability in findings across studies. Forty-four studies
(published between 1920 and 2013) with data on 963 anxiety disordered patients and
1,222 control subjects were obtained through PubMed and PsycINFO, as well as from a
previous meta-analysis on fear conditioning (Lissek et al.). Results demonstrated
robustly increased fear responses to conditioned safety cues (CS-) in anxiety
patients compared to controls during acquisition. This effect may represent an
impaired ability to inhibit fear in the presence of safety cues (CS-) and/or may
signify an increased tendency in anxiety disordered patients to generalize fear
responses to safe stimuli resembling the conditioned danger cue (CS+). In contrast,
during extinction, patients show stronger fear responses to the CS+ and a trend
toward increased discrimination learning (differentiation between the CS+ and CS-)
compared to controls, indicating delayed and/or reduced extinction of fear in
anxiety patients. Finally, none of the included study characteristics, such as the
type of fear measure (subjective vs. psychophysiological index of fear), could
account significantly for the variance in effect sizes across studies. Further
research is needed to investigate the predictive value of fear extinction on
treatment outcome, as extinction processes are thought to underlie the beneficial
effects of exposure treatment in anxiety disorders.
For over a century, clinicians have consistently described the paradoxical co-
existence in posttraumatic stress disorder (PTSD) of sensory intrusive hypermnesia
and declarative amnesia for the same traumatic event. Although this amnesia is
considered as a critical etiological factor of the development and/or persistence
of PTSD, most current animal models in basic neuroscience have focused exclusively
on the hypermnesia, i.e., the persistence of a strong fear memory, neglecting the
qualitative alteration of fear memory. The latest is characterized by an
underrepresentation of the trauma in the context-based declarative memory system in
favor of its overrepresentation in a cue-based sensory/emotional memory system.
Combining psychological and neurobiological data as well as theoretical hypotheses,
this review supports the idea that contextual amnesia is at the core of PTSD and
its persistence and that altered hippocampal-amygdalar interaction may contribute
to such pathologic memory. In a first attempt to unveil the neurobiological
alterations underlying PTSD-related hypermnesia/amnesia, we describe a recent
animal model mimicking in mice some critical aspects of such abnormal fear memory.
Finally, this line of argument emphasizes the pressing need for a systematic
comparison between normal/adaptive versus abnormal/maladaptive fear memory to
identify biomarkers of PTSD while distinguishing them from general stress-related,
potentially adaptive, neurobiological alterations.
Objective: Fear of falling (FOF) is an important threat to autonomy. Current
interventions to reduce FOF have yielded conflicting results. A possible reason for
this discrepancy could be its multicausality. Some risk factors may not have been
identified and addressed in recent studies. The last systematic review included
studies until 2006. Methods: To identify additional risk factors for FOF and to
test those mentioned previously, we conducted a systematic literature review.
Studies examining FOF in community-dwelling older adults between 2006 and October
2013 were screened. Results: Outcomes are summarized with respect to different
constructs such as FOF, fall-related self-efficacy/balance confidence, and FOF-
related activity restriction. Odds ratios and p values are reported. There is no
clear pattern with regard to the different FOF-related constructs studied. The only
parameters robustly associated across all constructs were female gender,
performance-based and questionnaire-based physical function, the use of a walking
aid, and, less robust, a history of falls and poor self-rated health. Conflicting
results were identified for depression and anxiety, multiple drugs, and
psychotropic drugs. Other potentially modifiable risk factors were only mentioned
in one or two studies and warrant further investigation. Parameters with mainly
negative results are also presented. Conclusion: Only few risk factors identified
were robustly associated across all FOF-related constructs and should be included
in future studies on FOF. Some newer factors have to be tested again in different
cohorts. The comprehensive overview might assist in the conceptualization of future
studies.
Recent technological developments, such as single unit recordings coupled to
optogenetic approaches, have provided unprecedented knowledge about the precise
neuronal circuits contributing to the expression and recovery of conditioned fear
behavior. These data have provided an understanding of the contributions of
distinct brain regions such as the amygdala, prefrontal cortex, hippocampus, and
periaqueductal gray matter to the control of conditioned fear behavior. Notably,
the precise manipulation and identification of specific cell types by optogenetic
techniques have provided novel avenues to establish causal links between changes in
neuronal activity that develop in dedicated neuronal structures and the short and
long-lasting expression of conditioned fear memories. In this review, we provide an
update on the key neuronal circuits and cell types mediating conditioned fear
expression and recovery and how these new discoveries might refine therapeutic
approaches for psychiatric conditions such as anxiety disorders and posttraumatic
stress disorder.
The interactive roles of the visual and vestibular systems allow for postural
control within boundaries of perceived safety. In specific circumstances, visual
vestibular and postural interactions act as a cue that trigger fear, similarly to
what occurs in motion sickness. Unusual patterns of visuo-vestibular interaction
that emerge without warning can elicit fear, which can then become associated to a
certain stimuli or situation, creating a CS-US association, (i.e., phobia), or can
emerge without warning but also without becoming associated to a particular
concomitant event (i.e., panic). Depending on the individual sensitivity to visuo-
vestibular unusual patterns and its impact in postural control, individuals will be
more or less vulnerable to develop these disorders. As such, the mechanism we here
propose is also sufficient to explain the lack of certain fears albeit exposure.
Following this rationale, a new subcategory of anxiety disorders, named visuo-
vestibular fears can be considered. This model brings important implications for
developmental and evolutionary psychological science, and invites to place visuo-
vestibular fears in a particular subtype or specification within the DSM-5
diagnostic criteria. (C) 2014 Elsevier Ltd. All rights reserved.
Although there is general agreement that the central nucleus of the amygdala (CeA)
is critical for triggering the neuroendocrine response to visual threats, there is
uncertainty about the role of subcortical visual pathways in this process. Primates
in general appear to depend less on subcortical visual pathways than other mammals.
Yet, imaging studies continue to indicate a role for the superior colliculus and
pulvinar nucleus in fear activation, despite disconnects in how these brain
structures communicate not only with each other but with the amygdala. Studies in
fish and amphibians suggest that the neuroendocrine response to visual threats has
remained relatively unchanged for hundreds of millions of years, yet there are
still significant data gaps with respect to how visual information is relayed to
telencephalic areas homologous to the CeA, particularly in fish. In fact ray finned
fishes may have evolved an entirely different mechanism for relaying visual
information to the telencephalon. In part because they lack a pathway homologous to
the lateral geniculate-striate cortex pathway of mammals, amphibians continue to be
an excellent model for studying how stress hormones in turn modulate fear
activating visual pathways. Glucocorticoids, melanocortin peptides, and CRF all
appear to play some role in modulating sensorimotor processing in the optic tectum.
These observations, coupled with data showing control of the hypothalamus-
pituitary-adrenal axis by the superior colliculus, suggest a fear/stress/anxiety
neuroendocrine circuit that begins with first order synapses in subcortical visual
pathways. Thus, comparative studies shed light not only on how fear triggering
visual pathways came to be, but how hormones released as a result of this
activation modulate these pathways.
A systematic review of the entrepreneurship literature on fear published up to 2014
highlights several key characteristics. First, the predominant focus in research
examining the emotion of fear in entrepreneurship is on the specific concept of
fear of failure. However, this literature shows a lack of precision in the
conceptualization and operationalization of this construct. The impact of the
experience of fear on individual cognition and behaviour can be beneficial as well
as detrimental. Despite this dualistic nature, to date, fear is examined as only a
barrier to entrepreneurial behaviour. This review reveals a clear dichotomy in the
literature, with significantly more focus on fear as a trait that distinguishes
between people than as a temporary state that is commonly experienced by many
people. Defining fear of failure as a context-specific phenomenon, this paper
explains the importance of focusing on the temporary cognitive and emotional
experience of fear and use conceptual observations as a platform to develop an
agenda for future research.
Organisms generally have many defenses against predation, yet may lack effective
defenses if from populations without predators. Evolutionary theory predicts that
costly antipredator behaviors will be selected against when predation risk
diminishes. We examined antipredator behaviors in Aegean wall lizards, Podarcis
erhardii, across an archipelago of land-bridge islands that vary in predator
diversity and period of isolation. We examined two defenses, flight initiation
distance and tail autotomy. Flight initiation distance generally decreased with
declining predator diversity. All predator types had distinctive effects on flight
initiation distance with mammals and birds having the largest estimated effects.
Rates of autotomy observed in the field were highest on predator-free islands, yet
laboratory-induced autotomy increased linearly with overall predator diversity.
Against expectation from previous work, tail autotomy was not explained solely by
the presence of vipers. Analyses of populations directly isolated from rich
predator communities revealed that flight initiation distance decreased with
increased duration of isolation in addition to the effects of current predator
diversity, whereas tail autotomy could be explained simply by current predator
diversity. Although selection against costly defenses should depend on time with
reduced threats, different defenses may diminish along different trajectories even
within the same predator-prey system.
A reduction of dopamine release or D-2 receptor blockade in the terminal fields of
the mesolimbic system, particularly the amygdala, clearly reduces conditioned fear.
Similar D-2 receptor antagonism in the neural substrates of fear in the midbrain
tectum attenuates the processing of unconditioned aversive information. However,
the implications of the interplay between opposing actions of dopamine in the
rostral and caudal segments of the dopaminergic system are still unclear. Previous
studies from this laboratory have reported the effects of dopaminergic drugs on
behavior in rats in the elevated plus maze, auditory-evoked potentials (AEPs)
recorded from the midbrain tectum, fear-potentiated startle, and conditioned
freezing. These findings led to an interesting framework on the functional roles of
dopamine in both anxiety and fear states. Dopamine D-2 receptor inhibition in the
terminal fields of the mesolimbic dopamine system generally causes anxiolytic-like
effects, whereas the activity of midbrain substrates of unconditioned fear are
enhanced by D-2 receptor antagonists, suggesting that D-2 receptor-mediated
mechanisms play opposing roles in fear/anxiety processes, depending on the brain
region under study. Dopamine appears to mediate conditioned fear by acting at
rostral levels of the brain and regulate unconditioned fear at the midbrain level,
likely by reducing the sensorimotor gating of aversive events. (C) 2015 Federation
of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Posttraumatic stress disorder manifests after exposure to a traumatic event and is
characterized by avoidance/numbing, intrusive symptoms and flashbacks, mood and
cognitive disruptions, and hyperarousal/reactivity symptoms. These symptoms reflect
dysregulation of the fear system likely caused by poor fear inhibition/extinction,
increased generalization, and/or enhanced consolidation or acquisition of fear.
These phenotypes can be modeled in animal subjects using Pavlovian fear
conditioning, allowing investigation of the underlying neurobiology of normative
and pathological fear. Preclinical studies reveal a number of neurotransmitter
systems and circuits critical for aversive learning and memory that have informed
the development of therapies used in human clinical trials. In this review, we
discuss the evidence for a number of established and emerging pharmacotherapies and
device-based treatments for posttraumatic stress disorder that have been developed
via a bench to bedside translational model.
This review describes the latest developments in our understanding of how the
serotonergic system modulates Pavlovian fear conditioning, fear expression and fear
extinction. These different phases of classical fear conditioning involve
coordinated interactions between the extended amygdala, hippocampus and prefrontal
cortices. Here, I first define the different stages of learning involved in cued
and context fear conditioning and describe the neural circuits underlying these
processes. The serotonergic system can be manipulated by administering serotonin
receptor agonists and antagonists, as well as selective serotonin reuptake
inhibitors (SSRIs), and these can have significant effects on emotional learning
and memory. Moreover, variations in serotonergic genes can influence fear
conditioning and extinction processes, and can underlie differential responses to
pharmacological manipulations. This research has considerable translational
significance as imbalances in the serotonergic system have been linked to anxiety
and depression, while abnormalities in the mechanisms of conditioned fear
contribute to anxiety disorders. (C) 2014 Published by Elsevier B.V.
Fear memory is a motivational system essential for organisms survival having a
central role in organization of defensive behaviors to threat. In the last years
there has been a growing interest on conditioned fear memory reconsolidation and
extinction, two specific phases of memorization process, both induced by memory
retrieval. Understanding the mechanisms underlying these two mnemonic processes may
allow to work out therapeutic interventions for treatment of human fear and anxiety
disorders, such as specific phobias and post-traumatic stress disorder. Based on
the use of one-trial conditioning paradigms, which allow to follow the evolution of
a mnemonic trace in its various phases, the present paper has attempted to
reorganize the current literature relative to the rodents highlighting both the
role of several brain structures in conditioned fear memory reconsolidation and
extinction and the selective cellular processes involved. A crucial role seems to
be play by medial prefrontal cortex, in particular by prelimbic and infralimbic
cortices, and by distinct connections between them and the amygdala, hippocampus
and entorhinal cortex. (C) 2015 Elsevier Ltd. All rights reserved.
Background: Fear of falling (FOF) and increased gait variability are both
independent markers of gait instability. There is a complex interplay between both
entities. The purposes of this study were (1) to perform a qualitative analysis of
all published studies on FOF-related changes in gait variability through a
systematic review, and (2) to quantitatively synthesize FOF-related changes in gait
variability. Methods: A systematic Medline literature search was conducted in May
2014 using the Medical Subject Heading (MeSH) terms "Fear" OR "fear of falling"
combined with "Accidental Falls" AND "Gait" OR "Gait Apraxia" OR "Gait Ataxia" OR
"Gait disorders, Neurologic" OR "Gait assessment" OR "Functional gait assessment"
AND "Self efficacy" OR "Self confidence" AND "Aged" OR "Aged, 80 and over."
Systematic review and fixed-effects meta-analysis using an inverse-variance method
were performed. Results: Of the 2184 selected studies, 10 observational studies
(including 5 cross-sectional studies, 4 prospective cohort studies, and 1 case-
control study) met the selection criteria. All were of good quality. The number of
participants ranged from 52 to 1307 older community-dwellers (26.2%-85.0% women).
The meta-analysis was performed on 10 studies with a total of 999 cases and 4502
controls. In one study, the higher limits of the effect size's confidence interval
(CI) were lower than zero. In the remaining studies, the higher limits of the CI
were positive. The summary random effect size of 0.29 (95% CI 0.13 -0.45) was
significant albeit of small magnitude, and indicated that gait variability was
overall 0.29 SD higher in FOF cases compared with controls. Conclusions: Our
findings show that FOF is associated with a statistically significant, albeit of
small magnitude, increase in gait variability. (C) 2015 AMDA - The Society for
Post-Acute and Long-Term Care Medicine.
Enhanced fear responses to cues, which were not associated with the threat but
share perceptual characteristics with the threat signal, indicate generalization of
conditioned fear. Here, we investigated for the first time generalization processes
in contextual fear conditioning. Thirty-two participants were guided through two
virtual offices (acquisition phases). Mildly painful electric shocks (unconditioned
stimulus, US) were unpredictably delivered in one office (anxiety context, CTX+),
but never in the other office (safety context, CTX-). During the generalization
test, participants were guided through CTX+, CTX-, and the generalization context
(G-CTX), which contained features of both the CTX+ and the CTX-, but no US was
delivered. We found successful contextual fear conditioning (i.e., the CTX+
compared to the CTX- elicited potentiated startle responses and was rated with more
negative valence, higher arousal and higher anxiety). Importantly, implicit and
explicit responses dissociated in the generalization test. Thus, participants rated
the G-CTX as more arousing and anxiogenic than the CTX- indicating anxiety
generalization, but they showed enhanced startle responses to the CTX+ only, while
the G-CTX and the CTX- did not differ. In summary, healthy participants on an
explicit level responded to the generalization context like to the anxiety context,
but on an implicit level responded to the generalization context like to the safety
context. Possibly, this dissociation suggests distinct and specific generalization
processes underlying contextual fear.
Generalization of conditioned fear has been implicated in the maintenance and
proliferation of fear in anxiety disorders. The role of cognitive processes in
generalization of conditioning is an important yet understudied issue. Vervliet et
al. (2010) tested generalization of fear to a visual stimulus of a particular color
and shape paired with electric shock. Test stimuli shared either the color or shape
of the CS+. Prior to conditioning, participants were instructed that either color
or shape would be predictive of shock. Generalization was stronger to the stimulus
containing the instructed feature, suggesting that instructions impacted
generalization of fear. However, the result may also reflect the impact of
instructions on attention and learning during the conditioning phase. In the
present study, the instructional manipulation was given after the conditioning
phase to control for any impact of instructions on learning. A similar result to
that reported by Vervliet et al. was observed. On self-reported expectancy of
shock, generalization was greater to the test stimulus that included the instructed
stimulus feature. The same pattern was observed on skin conductance, although it
did not reach statistical significance. The findings indicate that explicitly
instructed information affected generalization of conditioned fear independently of
any impact on learning, pointing to the role of cognitive processes in human fear
generalization. They also support the utility of cognitive therapy approaches,
which are employed after fear has already developed, in addressing clinical
overgeneralization.
Fear, dysphoria, and distress are prominent components in the conceptualization of
posttraumatic stress disorder (PTSD). However, because our diagnostic categories
are open concepts, relying on observed patterns of symptoms for classification, it
is unclear whether these components represent core or auxiliary features of the
disorder. Convergence across multiple indices is critical for this understanding.
In this paper, we examine these components of PTSD across observed symptom
patterns, broader theoretical conceptualizations, underlying information processing
mechanisms of attention and memory, and underlying learning and neurobiological
mechanisms. For each, evidence for similarity or distinctiveness of PTSD with other
anxiety disorders and depression is examined. Throughout the review, key points of
similarity to the anxiety disorders and divergence with depression argue for a
distinction between core fear symptoms and auxiliary dysphoria and distress
symptoms. Implications are discussed, noting that, as heterogeneity increases, core
characteristics will become more diffused and ancillary constructs will gain an
inflated degree of importance. (C) 2013 Wiley Periodicals, Inc.
The elevated T-maze (ETM) was developed to test the hypothesis that serotonin (5-
HT) plays an opposing role in the regulation of defensive behaviors associated with
anxiety and panic. This test allows the measurement in the same rat of inhibitory
avoidance acquisition, related to generalized anxiety disorder, and of one-way
escape, associated with panic disorder. The evidence so far reported with the ETM
supports the above hypothesis and indicates that: (1) whereas 5-HT neurons located
at the dorsal raphe nucleus are involved in the regulation of both inhibitory
avoidance and escape, those of the median raphe nucleus are primarily implicated in
the former task; (2) facilitation of 5-HT1A-and 5-HT2A-mediated neuro-transmission
in the dorsal periaqueductal gray (dPAG) is likely to mediate the panicolytic drug
action; (3) stimulation of 5-HT2C receptors in the basolateral amygdala increases
anxiety and is implicated in the anxiogenesis caused by short-term administration
of antidepressant drugs, and (4) 5-HT1A and the p-opioid receptors work together in
the dPAG to modulate escape or panic attacks. These last results point to the
possible benefits of adjunctive opioid therapy for panic patients resistant to
antidepressants that act on 5-HT neurotransmission. (C) 2014 Elsevier Ltd. All
rights reserved.
BACKGROUND CONTEXT: Psychological factors including fear avoidance beliefs are
believed to influence the development of chronic low back pain (LBP). PURPOSE: The
purpose of this study was to determine the prognostic importance of fear avoidance
beliefs as assessed by the Fear Avoidance Beliefs Questionnaire (FABQ) and the
Tampa Scale of Kinesiophobia for clinically relevant outcomes in patients with
nonspecific LBP. DESIGN/SETTING: The design of this study was a systematic review.
METHODS: In October 2011, the following databases were searched: BIOSIS, CINAHL,
Cochrane Library, Embase, OTSeeker, PeDRO, PsycInfo, PubMed/Medline, Scopus, and
Web of Science. To ensure the completeness of the search, a hand search and a
search of bibliographies was conducted and all relevant references included. A
total of 2,031 references were retrieved, leaving 566 references after the removal
of duplicates. For 53 references, the full-text was assessed and, finally, 21
studies were included in the analysis. RESULTS: The most convincing evidence was
found supporting fear avoidance beliefs to be a prognostic factor for work-related
outcomes in patients with subacute LBP (ie, 4 weeks-3 months of LBP). Four cohort
studies, conducted by disability insurance companies in the United States, Canada,
and Belgium, included 258 to 1,068 patients mostly with nonspecific LBP. These
researchers found an increased risk for work-related outcomes (not returning to
work, sick days) with elevated FABQ scores. The odds ratio (OR) ranged from 1.05
(95% confidence interval [CI] 1.02-1.09) to 4.64 (95% CI, 1.57-13.71). The highest
OR was found when applying a high cutoff for FABQ Work subscale scores. This may
indicate that the use of cutoff values increases the likelihood of positive
findings. This issue requires further study. Fear avoidance beliefs in very acute
LBP (<2 weeks) and chronic LBP (>3 months) was mostly not predictive. CONCLUSIONS:
Evidence suggests that fear avoidance beliefs are prognostic for poor outcome in
subacute LBP, and thus early treatment, including interventions to reduce fear
avoidance beliefs, may avoid delayed recovery and chronicity. (C) 2014 Elsevier
Inc. All rights reserved.
BACKGROUND CONTEXT: Psychological factors are believed to influence the development
of chronic low back pain. To date, it is not known how fear-avoidance beliefs
(FABs) influence the treatment efficacy in low back pain. PURPOSE: To summarize the
evidence examining the influence of FABs measured with the Fear-Avoidance Belief
Questionnaire or the Tampa Scale of Kinesiophobia on treatment outcomes in patients
with low back pain. STUDY DESIGN/SETTING: This is a systematic review. PATIENT
SAMPLE: Patients with low back pain. OUTCOME MEASURES: Work-related outcomes and
perceived measures including return to work, pain, and disability. METHODS: In
January 2013, the following databases were searched: BIOSIS, CINAHL, Cochrane
Library, Embase, OTSeeker, PeDRO, PsycInfo, PubMed/Medline, Scopus, and Web of
Science. A hand search of the six most often retrieved journals and a bibliography
search completed the search. Study eligibility criteria, participants, and
interventions: research studies that included patients with low back pain who
participated in randomized controlled trials (RCTs) investigating nonoperative
treatment efficacy. Out of 646 records, 78 articles were assessed in full text and
17 RCTs were included. Study quality was high in five studies and moderate in 12
studies. RESULTS: In patients with low back pain of up to 6 months duration, high
FABs were associated with more pain and/or disability (4 RCTs) and less return to
work (3 RCTs) (GRADE high-quality evidence, 831 patients vs. 322 in nonpredictive
studies). A decrease in FAB values during treatment was associated with less pain
and disability at follow-up (GRADE moderate evidence, 2 RCTs with moderate quality,
242 patients). Interventions that addressed FABs were more effective than control
groups based on biomedical concepts (GRADE moderate evidence, 1,051 vs. 227
patients in studies without moderating effects). In chronic patients with LBP, the
findings were less consistent. Two studies found baseline FABs to be associated
with more pain and disability and less return to work (339 patients), whereas 3
others (832 patients) found none (GRADE low evidence). Heterogeneity of the studies
impeded a pooling of the results. CONCLUSIONS: Evidence suggests that FABs are
associated with poor treatment outcome in patients with LBP of less than 6 months,
and thus early treatment, including interventions to reduce FABs, may avoid delayed
recovery and chronicity. Patients with high FABs are more likely to improve when
FABs are addressed in treatments than when these beliefs are ignored, and treatment
strategies should be modified if FABs are present. (C) 2014 Elsevier Inc. All
rights reserved.
ObjectiveMany studies have investigated the efficacy and tolerability of
alternative pharmacotherapy for panic disorder. This study aims to provide a
comprehensive review of the existing literature regarding the efficacy and
tolerability of atypical antipsychotics for panic disorder. MethodsWe searched for
relevant published articles using Medline, the Cochrane database, and EMBASE on 19
June 2013. Prospective studies that examined the efficacy and tolerability of
atypical antipsychotics in the treatment of primary panic disorder or comorbid
panic disorder (or symptoms) in other psychiatric disorders were included in this
review. ResultsSeven prospective studies were included in this review. Among these,
four were open-label studies for refractory panic disorder. Two of the seven
included studies were randomized controlled trials among patients with panic
symptoms comorbid with bipolar disorder. The remaining study was a randomized
controlled trial for panic disorder or panic attack comorbid with major depression.
Except one negative risperidone study, the reviewed studies showed the favorable
efficacy results of atypical antipsychotics. ConclusionsAlthough the majority of
the evidence regarding the efficacy of atypical antipsychotics in the treatment of
panic disorder comes from small, open-label studies, this review suggests the
potential role of atypical antipsychotics in treating panic disorder. Copyright (c)
2014 John Wiley & Sons, Ltd.
Nearly 100 years ago, Ivan Pavlov demonstrated that dogs could learn to use a
neutral cue to predict a biologically relevant event: after repeated predictive
pairings, Pavlov's dogs were conditioned to anticipate food at the sound of a bell,
which caused them to salivate. Like sustenance, danger is biologically relevant,
and neutral cues can take on great salience when they predict a threat to survival.
In anxiety disorders such as posttraumatic stress disorder (PTSD), this type of
conditioned fear fails to extinguish, and reminders of traumatic events can cause
pathological conditioned fear responses for decades after danger has passed. In
this review, we use fear conditioning and extinction studies to draw a direct line
from Pavlov to PTSD and other anxiety disorders. We explain how rodent studies have
informed neuroimaging studies of healthy humans and humans with PTSD. We describe
several genes that have been linked to both PTSD and fear conditioning and
extinction and explain how abnormalities in fear conditioning or extinction may
reflect a general biomarker of anxiety disorders. Finally, we explore drug and
neuromodulation treatments that may enhance therapeutic extinction in anxiety
disorders. (C) 2013 Elsevier Inc. All rights reserved.
When prey animals detect the odor of a predator a constellation of fear-related
autonomic, endocrine, and behavioral responses rapidly occur to facilitate
survival. How olfactory sensory systems process predator odor and channel that
information to specific brain circuits is a fundamental issue that is not clearly
understood. However, research in the last 15 years has begun to identify some of
the essential features of the sensory detection systems and brain structures that
underlie predator odor fear. For instance, the main (MOS) and accessory olfactory
systems (AOS) detect predator odors and different types of predator odors are
sensed by specific receptors located in either the MOS or AOS. However, complex
predator chemosignals may be processed by both the MOS and AOS, which complicate
our understanding of the specific neural circuits connected directly and indirectly
from the MOS and AOS to activate the physiological and behavioral components of
unconditioned and conditioned fear. Studies indicate that brain structures
including the dorsal periaqueductal gray (DRAG), paraventricular nucleus (PVN) of
the hypothalamus, and the medial amygdala (MeA) appear to be broadly involved in
predator odor induced autonomic activity and hypothalamic-pituitary-adrenal (HPA)
stress hormone secretion. The MeA also plays a key role in predator odor
unconditioned fear behavior and retrieval of contextual fear memory associated with
prior predator odor experiences. Other neural structures including the bed nucleus
of the stria terminal's and the ventral hippocampus (VHC) appear prominently
involved in predator odor fear behavior. The basolateral amygdala (B LA), medial
hypothalamic nuclei, and medial prefrontal cortex (mPFC) are also activated by some
but not all predator odors. Future research that characterizes how distinct
predator odors are uniquely processed in olfactory systems and neural circuits will
provide significant insights into the differences of how diverse predator odors
activate fear.
Chest pain may be due benign diseases but often suggests an association with
coronary artery disease, which justifies a quick search for medical care. However,
some people have anxiety disorder with symptoms that resemble clearly an acute
coronary syndrome. More specifically, during a panic attack an abrupt feeling of
fear accompanied by symptoms such as breathlessness, palpitations and chest pain,
makes patients believe they have a heart attack and confuse physicians about the
diagnosis. The association between panic disorder and coronary artery disease has
been extensively studied in recent years and, although some studies have shown
anxiety disorders coexisting or increasing the risk of heart disease, one causal
hypothesis is still missing. The aim of this systematic review is to present the
various ways in which the scientific community has been investigating the relation
between chest pain, panic disorder and coronary artery disease.
Panic disorder is a mental disorder characterized by recurrent panic attacks
accompanied by significant somatic and psychological symptoms. Ethiopathogenesis of
panic disorder remains unclear although clinical manifestation and proven
algorithms of treatment are known. Due to paroxysmal nature of the disorder and its
symptoms, functional imaging techniques provide ambiguous results. Leading
neurotransmitter theories are based on the proven efficacy of antidepressants
treatment. This includes the role of the neurotransmitters involved in modulation
of fear circuit (serotonin, norepinephrine, gamma-aminobutyric acid, glutamate,
cortikoliberin etc.). From neuroanatomical point of view, the nucleus of amygdala,
with a large number of pathways involved in the panic reaction, plays the key role
in triggering panic attacks. In contrast, prolonged anxiety is associated with
activation of bed nucleus striae terminalis. The entire process is complex and
involves interaction of the brainstem and cortical centres, the role of which
consists of affective modulation of the limbic system and its regulation by
volitional processes.
The ability to differentiate danger and safety through associative processes
emerges early in life. Understanding the mechanisms underlying associative learning
of threat and safety can clarify the processes that shape development of normative
fears and pathological anxiety. Considerable research has used fear conditioning
and extinction paradigms to delineate underlying mechanisms in animals and human
adults; however, little is known about these mechanisms in children and
adolescents. The current paper summarizes the empirical data on the development of
fear conditioning and extinction. It reviews methodological considerations and
future directions for research on fear conditioning and extinction in pediatric
populations. (C) 2014 Elsevier B. V. All rights reserved.
Despite the availability of predictive tools and treatment guidelines,
anticoagulant therapies are underprescribed and many patients are undertreated for
conditions that predispose to thromboembolic complications, including stroke. This
review explores reasons for which physicians fear that the risks of anticoagulation
may be greater than the potential benefit. The results of numerous clinical trials
confirm that patients benefit from judiciously managed anticoagulation and that
physicians can take various approaches to minimize risk. Use of stratification
scores for patient selection and accurate estimation of stroke risk may improve
outcomes; bleeding risk is less important than stroke risk. Adoption of newer
anticoagulants with simpler regimens may help physicians allay their fears of
anticoagulant use in patients with atrial fibrillation. These fears, although not
groundless, should not overtake caution and hinder the delivery of appropriate
evidence-based care.
Luiz Carlos Schenberg, Fagna Giacomin Schimitel, Rubia de Souza Armini, Cristian
Setubal Bernabe, Caroline Azevedo Rosa, Sergio Tufik, Claudia Janaina Torres
Muller, Jeyce Willig Quintino-dos-Santos. Translational Approach to Studying Panic
Disorder in Rats: Hits and Misses. Neurosci. Biobehav. Rev. XX (X) XXX-XXX, 2014.
Panic disorder (PD) patients are specifically sensitive to 5-7% carbon dioxide.
Another startling feature of clinical panic is the counterintuitive lack of
increments in 'stress hormones'. PD is also more frequent in women and highly
comorbid with childhood separation anxiety (CSA). On the other hand, increasing
evidence suggests that panic is mediated at dorsal periaqueductal grey matter
(DPAG). In line with prior studies showing that DPAG-evoked panic-like behaviours
are attenuated by clinically-effective treatments with panicolytics, we show here
that (i) the DPAG harbors a hypoxia-sensitive alarm system, which is activated by
hypoxia and potentiated by hypercapnia, (ii) the DPAG suffocation alarm system is
inhibited by clinically-effective treatments with panicolytics, (iii) DPAG
stimulations do not increase stress hormones in the absence of physical exertion,
(iv) DPAG-evoked panic-like behaviours are facilitated in neonatally-isolated adult
rats, a model of CSA, and (v) DPAG-evoked responses are enhanced in the late
diestrus of female rats. Data are consistent with the DPAG mediation of both
respiratory and non-respiratory types of panic attacks. (C) 2014 Elsevier Ltd. All
rights reserved.
The present paper is the edited version of our presentations at the "First World
Symposium On Translational Models Of Panic Disorder", in Vitoria, E.S., Brazil, on
November 16-18, 2012. We also review relevant work that appeared after the
conference. Suffocation-False Alarm Theory (Klein, 1993) postulates the existence
of an evolved physiologic suffocation alarm system that monitors information about
potential suffocation. Panic attacks maladaptively occur when the alarm is
erroneously triggered. The expanded Suffocation-False Alarm Theory (Preter and
Klein, 2008) hypothesizes that endogenous opioidergic dysregulation may underlie
the respiratory pathophysiology and suffocation sensitivity in panic disorder.
Opioidergic dysregulation increases sensitivity to CO2, separation distress and
panic attacks. That sudden loss, bereavement and childhood separation anxiety are
also antecedents of "spontaneous" panic requires an integrative explanation. Our
work unveiling the lifelong endogenous opioid system impairing effects of childhood
parental loss (CPL) and parental separation in non-ill, normal adults opens a new
experimental, investigatory area. (C) 2014 Elsevier Ltd. All rights reserved.
Why are we scared by nonperceptual entities such as the bogeyman, and why does the
bogeyman only visit us during the night? Why does hearing a window squeaking in the
night suggest to us the unlikely idea of a thief or a killer? And why is this more
likely to happen after watching a horror movie? To answer these and similar
questions, we need to put mind and body together again and consider the embodied
nature of perceptual and cognitive inference. Predictive coding provides a general
framework for perceptual inference; I propose to extend it by including
interoceptive and bodily information. The resulting embodied predictive coding
inference permits one to compare alternative hypotheses (e.g., is the sound I hear
generated by a thief or the wind?) using the same inferential scheme as in
predictive coding, but using both sensory and interoceptive information as
evidence, rather than just considering sensory events. If you hear a window
squeaking in the night after watching a horror movie, you may consider plausible a
very unlikely hypothesis (e.g., a thief, or even the bogeyman) because it explains
both what you sense (e.g., the window squeaking in the night) and how you feel
(e.g., your high heart rate). The good news is that the inference that I propose is
fully rational and gives minds and bodies equal dignity. The bad news is that it
also gives an embodiment to the bogeyman, and a reason to fear it.
The Deakin/Graeff hypothesis proposes that different subpopulations of serotonergic
neurons through topographically organized projections to forebrain and brainstem
structures modulate the response to acute and chronic stressors, and that
dysfunction of these neurons increases vulnerability to affective and anxiety
disorders, including panic disorder. We outline evidence supporting the existence
of a serotonergic system originally discussed by Deakin/Graeff that is implicated
in the inhibition of panic-like behavioral and physiological responses. Evidence
supporting this panic inhibition system comes from the following observations: (1)
serotonergic neurons located in the 'ventrolateral dorsal raphe nucleus' (DRVL) as
well as the ventrolateral periaqueductal gray (VLPAG) inhibit dorsal periaqueductal
grayelicited panic-like responses; (2) chronic, but not acute, antidepressant
treatment potentiates serotonin's panicolytic effect; (3) contextual fear activates
a central nucleus of the amygdala-DRVL/VLPAG circuit implicated in mediating
freezing and inhibiting panic-like escape behaviors; (4) DRVL/VLPAG serotonergic
neurons are central chemoreceptors and modulate the behavioral and
cardiorespiratory response to panicogenic agents such as sodium lactate and CO2.
Implications of the panic inhibition system are discussed. (C) 2014 Elsevier Ltd.
All rights reserved.
Background: There is a growing body of literature investigating the
neuropsychological profile of panic disorder (PD), some of which suggests potential
cognitive dysfunction. This paper systematically reviews the existing literature on
neuropsychological performance in PD. Method: PsycINFO, EMBASE, MEDLINE and
PsycARTICLES databases were searched to identify articles reporting on
neuropsychological function in PD published in English during the time period 1980
to March 2012. 14 studies were identified. Results: There was limited support for
impairment in short term memory among individuals with PD, although this was not
found across all studies. Overall, the reviewed studies did not support the
presence of impairment in other areas of cognitive functioning, including executive
function, long term memory, visuospatial or perceptual abilities and working
memory. Limitations: Studies with samples of fewer than 15 participants per group
were excluded from this review. A limited amount of research has been published on
this topic and small sample sizes (under 25 per group) have been used by many
studies. Therefore, the current review is based on a small number of studies with
limited power. Conclusions: There is limited evidence of specific
neuropsychological impairments in participants with PD. Impairments in short term
memory warrant further investigation to establish their relevance to clinical
practice. Larger sample sizes and appropriate statistical adjustment for multiple
comparisons in future studies is highly recommended. (C) 2014 Elsevier B.V. All
rights reserved.
We review recent work on extinction learning with emphasis on its modulation.
Extinction is the learned inhibition of responding to previously acquired tasks.
Like other forms of learning, it can be modulated by a variety of neurotransmitter
systems and behavioral procedures. This bears on its use in the treatment of fear
memories, particularly in posttraumatic stress disorder (PTSD), for which it is the
treatment of choice, often under the name of exposure therapy. There have not been
many laboratories interested in the modulation of extinction, but the available
data, although not very abundant, are quite conclusive. Most studies on the nature
of extinction and on its modulation have been carried out on fear motivated
behaviors, possibly because of their applicability to the therapy of PTSD. A role
for D-serine and the glycine site of NMDA receptors has been ascertained in two
forms of extinction in the ventromedial prefrontal cortex, basolateral amygdala and
dorsal hippocampus. The serine analog, D-cycloserine, has received clinical trials
as an enhancer of extinction. The brain histaminergic system acting via H2
receptors, and the endocannabinoid system using CB1 receptors in the ventromedial
prefrontal cortex, hippocampus and basolateral amygdala enhance extinction.
Dopaminergic D1 and beta-noradrenergic receptors also modulate extinction by
actions on these three structures. Isolated findings suggest roles for on
serotonin-1A, dopaminergic-D2 and alpha- and beta-noradrenergic receptors in
extinction modulation. Importantly, behavioral tagging and capture mechanisms in
the hippocampus have been shown to play a major modulatory role in extinction. In
addition, extinction of at least one aversive task (inhibitory avoidance) can be
made state dependent on peripheral epinephrine. (C) 2014 Elsevier Inc. All rights
reserved.
Background: We aimed to assess available evidence on risk factors associated with
the onset of panic disorder (PD) and/or generalised anxiety disorder (GAD) in
cohort studies in the general adult population. Methods: Systematic review using
MEDUNE, PsyclINFO and Embase. Search terms included panic disorder, generalised
anxiety disorder, cohort studies and risk factors. Results: We finally selected 21
studies, involving 163,366 persons with a median follow-up of 5 years. 1)
Sociodemographic factors: PD was associated with age, female gender, and few
economic resources. GAD was associated with age, non-Hispanics and Blacks, being
divorced or widowed, and few economic resources. 2) Psychosocial factors: PD was
associated with smoking and alcohol problems. GAD was associated with stressful
life events in childhood and adulthood, and personality. 3) Physical and mental
health factors: PD was associated with the number of physical diseases suffered and
the joint hypermobility syndrome. PD was also associated with a parental history of
mental disorders, as well as with other anxiety disorders and other mental health
problems in the person affected. GAD was associated with a parental history of
mental disorders, as well as with other anxiety disorders and other mental health
problems in the person affected, plus already having received psychiatric care.
Limitations.: Few studies examined the same risk factors. Conclusions.:
Socioclemographic, psychosocial and mental physical health risk factors vvere
determinant for the onset of PD and GAD in the general adult population. These
findings could be useful for developing preventive interventions in PD and GAD. (C)
2014 Elsevier BM. All rights reserved.
In the context of the evidence presented in both the collected scholarship under
review and other select works, this article asks if and to what extent migration-
related issues have been securitized in Europe and the United States. In addressing
these questions it executes three tasks. First, it critically assesses the four
major dimensions across which contemporary immigration purportedly is securitized:
on one side, rhetorically addressing immigration-related issues through political
elite discourse, public opinion, and the mass media; and on the other, the policy
processes through which immigration is securitized. Second, this article identifies
the strengths and weaknesses of securitization theory as it has been applied to
immigration. Finally, it draws mostly negative conclusions about the veracity of
the central claims of the securitization of immigration literature and,
specifically, its causal story.
Studies have pointed at the negative side of urban green spaces in terms of evoking
fear of crime. However research on fear-provoking attributes suggests that there
usually is no single attribute that influences fear but that rather a combination
of attributes prevails. The aim of the paper is to systematically review those
attributes that evoke fear of crime in urban green spaces and to highlight their
complex interaction by adopting a social-ecological framework. Results include an
overview of the reviewed literature with regard to authorship, journal,
geographical distribution of the studies, types of urban green spaces studies,
types of landscape stimulus used, applied methods, types of respondents involved
and main study findings. Forty-eight studies met the authors' inclusion criteria.
The majority of the studies highlighted that individual-factors (such as gender and
past experience) were more influential than social and physical factors in evoking
fear of crime. A proposed socio-ecological framework highlights the attributes
which evoke fear of crime in urban green spaces and its interactions and can help
guide future research. (C) 2013 Elsevier GmbH. All rights reserved.
Panic disorder is twice a common in women than in men. In women, susceptibility to
panic increases during the late luteal (premenstrual) phase of the menstrual cycle,
when progesterone secretion is in rapid decline. This article considers the
evidence for the midbrain periaqueductal grey (PAG) as a locus for panic and for
the use of PAG stimulation as an animal model of panic in both sexes. We show in
females how a rapid fall in progesterone secretion, such as occurs during the late
dioestrus phase of the ovarian cycle in rats (similar to the late luteal phase in
women), triggers a neuronal withdrawal response during which the excitability of
the midbrain panic circuitry increases as a result of upregulation of extrasynaptic
GABA(A) receptors on inhibitory interneurones in the PAG. The withdrawal effect is
due not to the native hormone but to its neuroactive metabolite allopregnanolone.
Differences in the kinetics of allopregnanolone metabolism may contribute to
individual differences in susceptibility to panic in women. (C) 2014 Elsevier Ltd.
All rights reserved.
A key insight of associative learning theory is that learning depends on the
actions of prediction error: a discrepancy between the actual and expected outcomes
of a conditioning trial. When positive, such error causes increments in associative
strength and, when negative, such error causes decrements in associative strength.
Prediction error can act directly on fear learning by determining the effectiveness
of the aversive unconditioned stimulus or indirectly by determining the
effectiveness, or associability, of the conditioned stimulus. Evidence from a
variety of experimental preparations in human and non-human animals suggest that
discrete neural circuits code for these actions of prediction error during fear
learning. Here we review the circuits and brain regions contributing to the neural
coding of prediction error during fear learning and highlight areas of research
(safety learning, extinction, and reconsolidation) that may profit from this
approach to understanding learning. Crown Copyright (C) 2013 Published by Elsevier
Inc. All rights reserved.
Background Panic disorder (PD) is a common type of anxiety disorder, characterized
by unexpected and repeated panic attacks or fear of future panic attacks, or both.
Individuals with PD are often resistant to pharmacological or psychological
treatments and this can lead to the disorder becoming a chronic and disabling
illness. Repetitive transcranial magnetic stimulation (rTMS) can deliver sustained
and spatially selective current to suppress or induce cortical excitability, and
its therapeutic effect on pathological neuronal activity in people with PD has
already been examined in case studies and clinical trials. However, a systematic
review is necessary to assess the efficacy and safety of rTMS for PD. Objectives To
assess the effects of repetitive transcranial magnetic stimulation (rTMS) for panic
disorder (PD) in adults aged 18 to 65 years, either as a monotherapy or as an
augmentation strategy. Search methods An electronic search of the Cochrane
Depression, Anxiety and Neurosis Review Group Controlled Trials Register (CCDANCTR)
was conducted to 19 February 2014. The CCDANCTR includes reports of relevant
randomised controlled trials (RCTs) from MEDLINE (1950 to date), EMBASE (1974 to
date), PsycINFO(1967 to date) and the Cochrane Central Register of Controlled
Trials (CENTRAL) (all years). Additional searches were conducted in Psyndex and the
main Chinese medical databases. Selection criteria RCTs or quasi-randomised trials
evaluating rTMS for PD in people aged between 18 and 65 years, either as a
monotherapy or as an augmentation strategy. Data collection and analysis Two review
authors independently selected studies and extracted data and verified the data by
cross-checking. Disagreements were resolved by discussion. For binary data, we
calculated fixed-effect model risk ratio (RR) and its 95% confidence interval (CI).
For continuous data, we calculated fixed-effect model standardized mean difference
(SMD) and its 95% CI. Main results Two RCTs (n = 40) were included in this review.
The included trials compared rTMS with sham rTMS; no trials comparing rTMS with
active treatments (electroconvulsive therapy (ECT), pharmacotherapy, psychotherapy)
met our inclusion criteria. Both included studies used 1 Hz rTMS over the right
dorso-lateral prefrontal cortex (DLPFC) for two or four weeks as an augmentation
treatment for PD. However, in both studies the data for the primary outcome, panic
symptoms as measured by the Panic Disorder Severity Scale (PDSS), were skewed and
could not be pooled for a quantitative analysis. For this primary outcome one trial
with 25 participants reported a superior effect of rTMS in reducing panic symptoms
compared with sham rTMS (t = 3.04, df = 16.57, P = 0.007), but this trial had a 16%
dropout rate and so was deemed as having a high risk of attrition bias. The other
trial found that all 15 participants exhibited a reduction in panic symptoms but
there was no significant difference between rTMS and sham rTMS (Mann Whitney U
test, P > 0.05). Regarding the acceptability of rTMS, no significant difference was
found between rTMS and sham rTMS in dropout rates or in reports of side effects.
The quality of evidence contributing to this review was assessed as very low.
Assessments of the risk of bias for the two studies were hampered by the lack of
information provided in the reports, especially on methods of sequence generation
and whether allocation concealment had been applied. Of the remaining sources of
bias, we considered one of the studies to have been at risk of attrition bias.
Authors' conclusions Only two RCTs of rTMS were available and their sample sizes
were small. The available data were insufficient for us to draw any conclusions
about the efficacy of rTMS for PD. Further trials with large sample sizes and
adequate methodology are needed to confirm the effectiveness of rTMS for PD.
Incretin-based therapies appear to offer many advantages over other approaches for
treating type 2 diabetes. Some preclinical studies have suggested that chronic
activation of glucagon-like peptide 1 receptor (GLP1R) signalling in the pancreas
may result in the proliferation of islet beta-cells and an increase in beta-cell
mass. This provided hope that enhancing GLP1 action could potentially alter the
natural progression of type 2 diabetes. However, to date, there has been no
evidence from clinical trials suggesting that GLP1R agonists or dipeptidyl
peptidase-4 (DPP4) inhibitors can increase beta-cell mass. Nevertheless, while the
proliferative capacity of these agents remains controversial, some studies have
raised concerns that they could potentially contribute to the development of
pancreatitis and hence increase the risk of pancreatic cancer. Currently, there are
very limited clinical data to directly assess these potential benefits and risks of
incretin-based therapies. However, a review of the preclinical studies indicates
that incretin-based therapies probably have only a limited capacity to regenerate
pancreatic beta-cells, but may be useful for preserving any remaining beta-cells in
type 2 diabetes. In addition, the majority of preclinical evidence does not support
the notion that GLP1R agonists or DPP4 inhibitors cause pancreatitis. Journal of
Endocrinology
Post-traumatic stress disorder (PTSD) and other anxiety disorders stemming from
dysregulated fear memory are problematic and costly. Understanding the molecular
mechanisms that contribute to the formation and maintenance of these persistent
fear associations is crucial to developing treatments for PTSD. Epigenetic
mechanisms, which control gene expression to produce long-lasting changes in
cellular function, may support the formation of fear memory underlying PTSD. We
address here the role of epigenetic mechanisms in the formation, storage, updating,
and extinction of fear memories. We also discuss methods of targeting these
epigenetic mechanisms to reduce the initial formation of fear memory or to enhance
its extinction. Epigenetic mechanisms may provide a novel target for pharmaceutical
and other treatments to reduce aversive memory contributing to PTSD.
The ability to recognize and properly respond to instances of protection from
impending danger is critical for preventing chronic stress and anxiety-central
symptoms of anxiety and affective disorders afflicting large populations of people.
Learned safety encompasses learning processes, which lead to the identification of
episodes of security and regulation of fear responses. On the basis of insights
into the neural circuitry and molecular mechanisms involved in learned safety in
mice and humans, we describe learned safety as a tool for understanding neural
mechanisms involved in the pathomechanisms of specific affective disorders. This
review summarizes our current knowledge on the neurobiological underpinnings of
learned safety and discusses potential applications in basic and translational
neurosciences.
About ten percent of people experiencing a traumatic event will subsequently
develop post-traumatic stress disorder (PTSD). PTSD is characterized by an
exaggerated fear response which fails to extinguish over time and cannot be
inhibited in safe contexts. The neurobiological correlates of PTSD involve enhanced
salience processing (i.e. amygdala, dorsal anterior cingulate cortex (dACC) and
anterior insula (AI) hyperactivity), and reduced top-down inhibitory control over
this fear response (i.e. dorsal and ventromedial prefrontal cortex (vmPFC)
hypoactivity and diminished structural and functional connectivity between the
vmPFC, hippocampus and amygdala). Therefore, dampening the exaggerated fear
response (i.e. by reducing amygdala hyperactivity) and enhancing top-down
inhibitory control (i.e. by promoting prefrontal control over the amygdala) during
psychotherapy is an important target for medication-enhanced psychotherapy (MEP) in
PTSD patients. Since the neuropeptide oxytocin (OT) has been found to act on these
two processes, we propose that OT is a promising pharmacological agent to boost
treatment response in PTSD. Human fMRI studies indicate that intranasal OT
attenuates amygdala (hyper)activity and enhances connectivity of the amygdala with
the vmPFC and hippocampus, resulting in increased top-down control over the fear
response. In addition, intranasal OT was found to attenuate amygdala-brainstem
connectivity and to change activity and connectivity in nodes of the salience
network (i.e. AI and dACC). Furthermore, OT administration may modulate
hypothalamus-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS)
function and may enhance social behaviour, which could be beneficial in the
therapeutic alliance. We also discuss contextual and interindividual factors (e.g.
gender and social context) which may influence the effectiveness of OT in MEP. In
all, we propose that intranasal OT given prior to each psychotherapy session may be
an effective additive treatment to boost treatment response in PTSD. (C) 2013
Elsevier Ltd. All rights reserved.
Adolescence represents a uniquely sensitive developmental stage in the transition
from childhood to adulthood. During this transition, neuronal circuits are
particularly susceptible to modification by experience. In addition, adolescence is
a stage in which the incidence of anxiety disorders peaks in humans and over 75% of
adults with fear-related disorders met diagnostic criteria as children and
adolescents. While postnatal critical periods of plasticity for primary sensory
processes, such as in the visual system are well established, less is known about
potential critical or sensitive periods for fear learning and memory. Here, we
review the non-linear developmental aspects of fear learning and memory during a
transition period into and out of adolescence. We also review the literature on the
non-linear development of GABAergic neurotransmission, a key regulator of critical
period plasticity. We provide a model that may inform improved treatment strategies
for children and adolescents with fear-related disorders.
Pavlovian fear conditioning is a model of fear learning and memory. The mechanisms
regulating fear conditioning and memory have been investigated in humans and
rodents. In this paradigm, animals learn and memorize an association between a
conditioned stimulus (CS), such as context, and an unconditioned stimulus (US),
such as an electrical footshock that induces fear. Fear memory generated though
fear conditioning is stabilized via a memory consolidation process. Moreover,
recent studies have shown the existence of memory processes that control fear
memory following the retrieval of consolidated memory. Indeed, when fear memory is
retrieved by re-exposure to the CS, the retrieved memory is re-stabilized via the
reconsolidation process. On the other hand, the retrieval of fear memory by
prolonged re-exposure to the CS also leads to fear memory extinction, new
inhibitory learning against the fear memory, in which animals learn that they do
not need to respond to the CS. Importantly, the reinforcement of fear memory after
retrieval (i.e., re-experience such as flashbacks or nightmares) has been thought
to be associated with the development of emotional disorders such as post-traumatic
stress disorder (PTSD). In this review, I summarize recent progress in studies on
the mechanism of fear conditioning and memory consolidation, reconsolidation and
extinction, and furthermore, introduce our recent establishment of a mouse PTSD
model that shows enhancement of fear memory after retrieval.
It is proposed that targeting the environmental host that harbour 'superbugs' is an
effective strategy in our fight against infectious diseases.
Background Fear of falling is common in older people and associated with serious
physical and psychosocial consequences. Exercise (planned, structured, repetitive
and purposive physical activity aimed at improving physical fitness) may reduce
fear of falling by improving strength, gait, balance and mood, and reducing the
occurrence of falls. Objectives To assess the effects (benefits, harms and costs)
of exercise interventions for reducing fear of falling in older people living in
the community. Search methods We searched the Cochrane Bone, Joint and Muscle
Trauma Group Specialised Register (July 2013), the Central Register of Controlled
Trials (CENTRAL 2013, Issue 7), MEDLINE (1946 to July Week 3 2013), EMBASE (1980 to
2013 Week 30), CINAHL (1982 to July 2013), PsycINFO (1967 to August 2013), AMED
(1985 to August 2013), the World Health Organization International Clinical Trials
Registry Platform (accessed 7 August 2013) and Current Controlled Trials (accessed
7 August 2013). We applied no language restrictions. We handsearched reference
lists and consulted experts. Selection criteria We included randomised and quasi-
randomised trials that recruited community-dwelling people (where the majority were
aged 65 and over) and were not restricted to specific medical conditions (e.g.
stroke, hip fracture). We included trials that evaluated exercise interventions
compared with no intervention or a non-exercise intervention (e.g. social visits),
and that measured fear of falling. Exercise interventions were varied; for example,
they could be 'prescriptions' or recommendations, group-based or individual,
supervised or unsupervised. Data collection and analysis Pairs of review authors
independently assessed studies for inclusion, assessed the risk of bias in the
studies and extracted data. We combined effect sizes across studies using the
fixed-effect model, with the random-effect model used where significant statistical
heterogeneity was present. We estimated risk ratios (RR) for dichotomous outcomes
and incidence rate ratios (IRR) for rate outcomes. We estimated mean differences
(MD) where studies used the same continuous measures and standardised mean
differences (SMD) where different measures or different formats of the same measure
were used. Where possible, we performed various, usually prespecified, sensitivity
and subgroup analyses. Main results We included 30 studies, which evaluated 3D
exercise (Tai Chi and yoga), balance training or strength and resistance training.
Two of these were cluster-randomised trials, two were cross-over trials and one was
quasi-randomised. The studies included a total of 2878 participants with a mean age
ranging from 68 to 85 years. Most studies included more women than men, with four
studies recruiting women only. Twelve studies recruited participants at increased
risk of falls; three of these recruited participants who also had fear of falling.
Poor reporting of the allocation methods in the trials made it difficult to assess
the risk of selection bias in most studies. All of the studies were at high risk of
performance and detection biases as there was no blinding of participants and
outcome assessors and the outcomes were self reported. Twelve studies were at high
risk of attrition bias. Using GRADE criteria, we judged the quality of evidence to
be 'low' for fear of falling immediately post intervention and 'very low' for fear
of falling at short or long-term follow-up and all other outcomes. Exercise
interventions were associated with a small to moderate reduction in fear of falling
immediately post intervention (SMD 0.37 favouring exercise, 95% confidence interval
(CI) 0.18 to 0.56; 24 studies; 1692 participants, low quality evidence). Pooled
effect sizes did not differ significantly between the different scales used to
measure fear of falling. Although none of the sensitivity analyses changed the
direction of effect, the greatest reduction in the size of the effect was on
removal of an extreme outlier study with 73 participants (SMD 0.24 favouring
exercise, 95% CI 0.12 to 0.36). None of our subgroup analyses provided robust
evidence of differences in effect in terms of either the study primary aim
(reduction of fear of falling or other aim), the study population (recruitment on
the basis of increased falls risk or not), the characteristics of the study
exercise intervention or the study control intervention (no treatment or
alternative intervention). However, there was some weak evidence of a smaller
effect, which included no reduction, of exercise when compared with an alternative
control. There was very low quality evidence that exercise interventions may be
associated with a small reduction in fear of falling up to six months post
intervention (SMD 0.17, 95% CI -0.05 to 0.38; four studies, 356 participants) and
more than six months post intervention (SMD 0.20, 95% CI -0.01 to 0.41; three
studies, 386 participants). Very low quality evidence suggests exercise
interventions in these studies that also reported on fear of falling reduced the
risk of falling measured either as participants incurring at least one fall during
follow-up or the number of falls during follow-up. Very low quality evidence from
four studies indicated that exercise interventions did not appear to reduce
symptoms of depression or increase physical activity. The only study reporting the
effects of exercise interventions on anxiety found no difference between groups. No
studies reported the effects of exercise interventions on activity avoidance or
costs. It is important to remember that our included studies do not represent the
totality of the evidence of the effect of exercise interventions on falls,
depression, anxiety or physical activity as our review only includes studies that
reported fear of falling. Authors' conclusions Exercise interventions in community-
dwelling older people probably reduce fear of falling to a limited extent
immediately after the intervention, without increasing the risk or frequency of
falls. There is insufficient evidence to determine whether exercise interventions
reduce fear of falling beyond the end of the intervention or their effect on other
outcomes. Although further evidence from well-designed randomised trials is
required, priority should be given to establishing a core set of outcomes that
includes fear of falling for all trials examining the effects of exercise
interventions in older people living in the community.
Panic disorder (PD) is a severe anxiety disorder that is characterized by recurrent
panic attacks (PA), which can be unexpected (uPA, i.e., no clear identifiable
trigger) or expected (ePA). Panic typically involves an abrupt feeling of
catastrophic fear or distress accompanied by physiological symptoms such as
palpitations, racing heart, thermal sensations, and sweating. Recurrent uPA and ePA
can also lead to agoraphobia, where subjects with PD avoid situations that were
associated with PA. Here we will review recent developments in our understanding of
PD, which includes discussions on: symptoms and signs associated with uPA and ePAs;
Diagnosis of PD and the new DSM-V; biological etiology such as heritability and
gene x environment and gene x hormonal development interactions; comparisons
between laboratory and naturally occurring uPAs and ePAs; neurochemical systems
that are associated with clinical PAs (e.g. gene associations; targets for
triggering or treating PAs), adaptive fear and panic response concepts in the
context of new NIH RDoc approach; and finally strengths and weaknesses of
translational animal models of adaptive and pathological panic states. (C) 2014
Elsevier Ltd. All rights reserved.
Background Panic disorder is common in the general population. It is often
associated with other psychiatric disorders, such as drug dependence, major
depression, bipolar disorder, social phobia, specific phobia and generalised
anxiety disorder. Azapirones are a class of drugs used as anxiolytics. They are
associated with less drowsiness, psychomotor impairment, alcohol potentiation and
potential for addiction or abuse than benzodiazepines. However, azapirones are not
widely used in the treatment of panic disorder and evidence for their efficacy is
unclear. It is important to find out if azapirones are effective and acceptable in
the treatment of panic disorder. Objectives To assess the effects of azapirones on
panic disorder in adults, specifically: 1. to determine the efficacy of azapirones
in alleviating symptoms of panic disorder, with or without agoraphobia, in
comparison with placebo; 2. to review the acceptability of azapirones in panic
disorder, with or without agoraphobia, in comparison with placebo; and 3. to
investigate adverse effects of azapirones in panic disorder with or without
agoraphobia, including general prevalence of adverse effects, compared with
placebo. Search methods We searched the Cochrane Depression Anxiety and Neurosis
Group Trials Specialised Register (CCDANCTR, search date: 10th January 2014), which
includes relevant randomised controlled trials from The Cochrane Library (all
years), MEDLINE (1950-), EMBASE (1974-), and PsycINFO (1967-). Selection criteria
Randomised controlled trials that compared azapirones with placebo for panic
disorder in adults. Data collection and analysis Three review authors independently
identified studies, assessed trial quality and extracted data. We contacted study
authors for additional information. Main results Three studies involving 170
participants compared the azapirone buspirone with placebo. No study provided
enough usable information on our primary efficacy outcome (response). For our
primary acceptability outcome, moderate-quality evidence indicated that azapirones
had lower acceptability than placebo: risk ratio (RR) for dropouts for any reason
2.13 (95% confidence interval (CI) 1.11 to 4.07; 3 studies, 170 participants.
Evidence for secondary efficacy outcomes were of low quality. Results on efficacy
between azapirone and placebo in terms of agoraphobia (standardised mean difference
(SMD) -0.01, 95% CI -0.56 to 0.53; 1 study, 52 participants), general anxiety (mean
difference (MD) -2.20, 95% CI -5.45 to 1.06; 2 studies, 115 participants) and
depression (MD -1.80, 95% CI -5.60 to 2.00; 1 study, 52 participants) were
uncertain. None of the studies provided information for the assessment of
allocation concealment or sequence generation. Conflicts of interest were not
explicitly expressed. The risk of attrition bias was rated high for all three
studies. Information on adverse effects other than dropouts for any reason was
insufficient to include in the analyses. Authors' conclusions The efficacy of
azapirones is uncertain due to the lack of meta-analysable data for the primary
outcome and low-quality evidence for secondary efficacy outcomes. A small amount of
moderate-quality evidence suggested that the acceptability of azapirones for panic
disorder was lower than for placebo. However, only trials of one azapirone (namely
buspirone) were included in this review; this, combined with the small sample size,
limits our conclusions. If further research is to be conducted, studies with larger
sample sizes, with different azapirones and with less risk of bias are necessary to
draw firm conclusions regarding azapirones for panic disorder.
How sensory information is transformed by learning into adaptive behaviors is a
fundamental question in neuroscience. Studies of auditory fear conditioning have
revealed much about the formation and expression of emotional memories and have
provided important insights into this question. Classical work focused on the
amygdala as a central structure for fear conditioning. Recent advances, however,
have identified new circuits and neural coding strategies mediating fear learning
and the expression of fear behaviors. One area of research has identified key brain
regions and neuronal coding mechanisms that regulate the formation, specificity and
strength of fear memories. Other work has discovered critical circuits and neuronal
dynamics by which fear memories are expressed through a medial prefrontal cortex
pathway and coordinated activity across interconnected brain regions. Here we
review these recent advances alongside prior work to provide a working model of the
extended circuits and neuronal coding mechanisms mediating fear learning and
memory.
IMPORTANCE In primary care settings, generalized anxiety disorder (GAD) and panic
disorder are common but underrecognized illnesses. Identifying accurate and
feasible screening instruments for GAD and panic disorder has the potential to
improve detection and facilitate treatment. OBJECTIVE To systematically review the
accuracy of self-report screening instruments in diagnosing GAD and panic disorder
in adults. DATA SOURCES We searched MEDLINE, PsycINFO, and the Cochrane Library for
relevant articles published from 1980 through April 2014. STUDY SELECTION
Prospective studies of diagnostic accuracy that compared a self-report screening
instrument for GAD or panic disorder with the diagnosis made by a trained clinician
using Diagnostic and Statistical Manual of Mental Disorders or International
Classification of Diseases criteria. RESULTS We screened 3605 titles, excluded
3529, and performed a more detailed review of 76 articles. We identified 9
screening instruments based on 13 articles from 10 unique studies for the detection
of GAD and panic disorder in primary care patients Across all studies, diagnostic
interviews determined that 257 of 2785 patients assessed had a diagnosis of GAD
while 224 of 2637 patients assessed had a diagnosis of panic disorder. The best-
performing test for GAD was the Generalized Anxiety Disorder Scale 7 Item (GAD-7),
with a positive likelihood ratio of 5.1 (95% CI, 4.3-6.0) and a negative likelihood
ratio of 0.13 (95% CI, 0.07-0.25). The best-performing test for panic disorder was
the Patient Health Questionnaire, with a positive likelihood ratio of 78 (95% CI,
29-210) and a negative likelihood ratio of 0.20 (95% CI, 0.11-0.37). CONCLUSIONS
AND RELEVANCE Two screening instruments, the GAD-7 for GAD and the Patient Health
Questionnaire for panic disorder, have good performance characteristics and are
feasible for use in primary care. However, further validation of these instruments
is needed because neither instrument was replicated in more than 1 primary care
population.
Objectives:There is evidence of baseline respiratory abnormalities in panic
disorder (PD), but whether they are specific to PD remains unclear. To investigate
this issue, we meta-analyzed results from studies comparing baseline respiratory
and hematic variables between subjects with PD and subjects with other anxiety
disorders. Methods: A literature search in bibliographic databases was performed.
Fixed-effects models were applied. Several moderator analyses and publication bias
diagnostics were performed. Results: We found: (1) significantly lower mean end-
tidal partial pressure of CO2 (et-pCO(2)) in subjects with PD than in those with
social phobia (SP) or generalized anxiety disorder (GAD), and (2) higher mean
respiratory rate, lower venous et-pCO(2) and HCO3- concentration in subjects with
PD than in those with SP. No publication bias was found. Conclusions: Subjects with
PD show a condition of baseline hyperventilation when compared to subjects with SP
or GAD. Hematic variables suggest that the hyperventilation may be chronic. These
results support the idea that baseline respiratory abnormalities are specific to PD
pathophysiology. Further studies are needed to clarify whether these abnormalities
are related to a malfunction of the respiratory system or to specific
cognitive/emotional/behavioral factors in this population. (C) 2014 S. Karger AG,
Basel
The prefrontal cortex regulates the expression of fear based on previously learned
information. Recently, this brain area has emerged as being crucial in the initial
formation of fear memories, providing new avenues to study the neurobiology
underlying aberrant learning in anxiety disorders. Here we review the circumstances
under which the prefrontal cortex is recruited in the formation of memory,
highlighting relevant work in laboratory animals and human subjects. We propose
that the prefrontal cortex facilitates fear memory through the integration of
sensory and emotional signals and through the coordination of memory storage in an
amygdala-based network.
Public speaking is widely used as a model of experimental fear and anxiety. This
review aimed to evaluate the effects of pharmacological challenges on public
speaking responses and their implications for the understanding of the neurobiology
of normal and pathological anxiety, specifically panic disorder. We also describe
methodological features of experimental paradigms using public speaking as an
inducer of fear and stress. Public speaking is a potent stressor that can provoke
significant subjective and physiological responses. However, variations in the
manners in which public speaking is modelled can lead to different responses that
need to be considered when interpreting the results. Results from pharmacological
studies with healthy volunteers submitted to simulated public speaking tests have
similarities with the pharmacological responses of panic patients observed in
clinical practice and panic patients differ from controls in the response to the
public speaking test. These data are compatible with the Deakin and Graeff
hypothesis that serotonin inhibits fear, as accessed by public speaking tasks, and
that this inhibition is likely related to the actions of serotonin in the dorsal
periaqueductal grey matter. (C) 2014 Elsevier Ltd. All rights reserved.
Anxiety disorders pose one of the biggest threats to mental health in the world,
and they predominantly emerge early in life. However, research of anxiety disorders
and fear-related memories during development has been largely neglected, and
existing treatments have been developed based on adult models of anxiety. The
present review describes animal models of anxiety disorders across development and
what is currently known of their pharmacology. To summarize, the underlying
mechanisms of intrinsic 'unlearned' fear are poorly understood, especially beyond
the period of infancy. Models using 'learned' fear reveal that through development,
rats exhibit a stress hyporesponsive period before postnatal day 10, where they
paradoxically form odour-shock preferences, and then switch to more adult-like
conditioned fear responses. Juvenile rats appear to forget these aversive
associations more easily, as is observed with the phenomenon of infantile amnesia.
Juvenile rats also undergo more robust extinction, until adolescence where they
display increased resistance to extinction. Maturation of brain structures, such as
the amygdala, prefrontal cortex and hippocampus, along with the different temporal
recruitment and involvement of various neurotransmitter systems (including NMDA,
GABA, corticosterone and opioids) are responsible for these developmental changes.
Taken together, the studies described in this review highlight that there is a
period early in development where rats appear to be more robust in overcoming
adverse early life experience. We need to understand the fundamental
pharmacological processes underlying anxiety early in life in order to take
advantage of this period for the treatment of anxiety disorders.
Recent work on the extinction of fear-motivated learning places emphasis on its
putative circuitry and on its.modulation. Extinction is the learned inhibition of
retrieval of previously acquired responses. Fear extinction is used as a major
component of exposure therapy in the treatment of fear memories such as those of
the posttraumatic stress disorder (PTSD). It is initiated and maintained by
interactions between the hippocampus, basolateral amygdala and ventromedial
prefrontal cortex, which involve feedback regulation of the latter by the other two
areas. Fear extinction depends on NMDA receptor activation. It is positively
modulated by o-serine acting on the glycine site of NMDA receptors and blocked by
AP5 (2amino-5-phosphono propionate) in the three structures. In addition, histamine
acting on H2 receptors and endocannabinoids acting on CBI receptors in the three
brain areas mentioned, and muscarinic cholinergic fibers from the medial septum to
hippocampal CM positively modulate fear extinction. Importantly, fear extinction
can be made state-dependent on circulating epinephrine, which may play a role in
situations of stress. Exposure to a novel experience can strongly enhance the
consolidation of fear extinction through a synaptic tagging and capture mechanism;
this may be useful in the therapy of states caused by fear memory like PTSD. (C)
2014 Published by Elsevier Ltd.
There is considerable interest, from both a basic and clinical standpoint, in
gaining a greater understanding of how pharmaceutical or behavioral manipulations
alter fear extinction in animals. Not only does fear extinction in rodents model
exposure therapy in humans, where the latter is a cornerstone of behavioral
intervention for anxiety disorders such as post-traumatic stress disorder and
specific phobias, but also understanding more about extinction provides basic
information into learning and memory processes and their underlying circuitry. In
this paper, we briefly review three principal approaches that have been used to
modulate extinction processes in animals and humans: a purely pharmacological
approach, the more widespread approach of combining pharmacology with behavior, and
a purely behavioral approach. The pharmacological studies comprise modulation by:
brain derived neurotrophic factor (BDNF), D-cycloserine, serotonergic and
noradrenergic drugs, neuropeptides, endocannabinoids, glucocorticoids, histone
deacetylase (HDAC) inhibitors, and others. These studies strongly suggest that
extinction can be modulated by drugs, behavioral interventions, or their
combination, although not always in a lasting manner. We suggest that
pharmacotherapeutic manipulations provide considerable promise for promoting
effective and lasting fear reduction in individuals with anxiety disorders. This
article is part of a Special Issue entitled 'Memory enhancement'. (C) 2014 Elsevier
Inc. All rights reserved.
This study sought to contribute to a better understanding of children's attitudes
and opinions regarding health care, mainly in terms of medical procedures,
institutions and the efficacy of health professionals. The sample included 381
children, recruited from different schools in Lisbon. The more negative attitudes
were attributed to institutions, while positive attitudes were related to the
efficacy of health professionals. Medical procedures were considered less painful
compared to potential day-to-day accidents. Higher levels of pain were reported by
children of the female sex and by children during the primary education phase.
Medical fears mediated the relationship between the perception of pain and
children's attitudes with respect to health care. Higher levels of pain perception
were seen to be related to more negative attitudes regarding health care. However,
this relationship was diminished when children's fears about medical issues were
contemplated. In conclusion, a translated instrument to assess children's attitudes
regarding health care is needed, as it may even contribute to the development of
intervention programs within the scope of the promotion of attitudes towards health
care.
Cognitive models of panic disorder (PD) with or without agoraphobia have stressed
the role of catastrophic beliefs of bodily symptoms as a central mediating variable
of the efficacy of cognitive behavioral therapy (CBT). Perceived ability to cope
with or control panic attacks, panic self-efficacy, has also been proposed to play
a key role in therapeutic change; however, this cognitive factor has received much
less attention in research. The aim of the present review is to evaluate panic
self-efficacy as a mediator of therapeutic outcome in CBT for PD using descriptive
and meta-analytic procedures. We performed systematic literature searches, and
included and evaluated 33 studies according to four criteria for establishing
mediation. Twenty-eight studies, including nine randomized waitlist-controlled
studies, showed strong support for CBT improving panic self-efficacy (criterion 1);
ten showed an association between change in panic self-efficacy and change in
outcome during therapy (criterion 2); three tested, and one established formal
statistical mediation of panic self-efficacy (criterion 3); while four tested and
three found change in panic self-efficacy occurring before the reduction of panic
severity (criterion 4). Although none of the studies fulfilled all of the four
criteria, results provide some support for panic self-efficacy as a mediator of
outcome in CBT for PD, generally on par with catastrophic beliefs in the reviewed
studies. (C) 2014 Elsevier Ltd. All rights reserved.
We review recent work on the role of intrinsic amygdala networks in the regulation
of classically conditioned defensive behaviors, commonly known as conditioned fear.
These new developments highlight how conditioned fear depends on far more complex
networks than initially envisioned. Indeed, multiple parallel inhibitory and
excitatory circuits are differentially recruited during the expression versus
extinction of conditioned fear. Moreover, shifts between expression and extinction
circuits involve coordinated interactions with different regions of the medial
prefrontal cortex. However, key areas of uncertainty remain, particularly with
respect to the connectivity of the different cell types. Filling these gaps in our
knowledge is important because much evidence indicates that human anxiety disorders
results from an abnormal regulation of the networks supporting fear learning.
Over the past two decades, substantial knowledge has been attained about the
mechanisms underlying the acquisition and subsequent extinction of conditioned
fear. Knowledge gained on the biological basis of Pavlovian conditioning has led to
the general acceptance that fear extinction may be a useful model in understanding
the underlying mechanisms in the pathophysiology of anxiety disorders and may also
be a good model for current therapies treating these disorders. Lacking in the
current knowledge is how men and women may or may not differ in the biology of fear
and its extinction. It is also unclear how the neural correlates of fear extinction
may mediate sex differences in the etiology, maintenance, and prevalence of
psychiatric disorders. In this review, we begin by highlighting the epidemiological
differences in incidence rate. We then discuss how estradiol (E2), a primary
gonadal hormone, may modulate the mechanisms of fear extinction and mediate some of
the sex differences observed in psychiatric disorders.
The highly conserved mitogen-activated protein kinase/extracellular signal-
regulated kinase (MAPK/ERK) signaling cascade is involved in several intracellular
processes ranging from cell differentiation to proliferation, as well as in
synaptic plasticity. In the last two decades, the role of MAPK/ERK in long-term
memory formation in mammals, particularly in fear-related memories, has been
extensively investigated. In this review we describe knowledge advancement on the
role of MAPK/ERK in orchestrating the intracellular processes that lead to the
consolidation, reconsolidation and extinction of fear memories. In doing so, we
report studies in which the specific role of MAP/ERK in switching from memory
formation to memory erasure has been suggested. The possibility to target MAPK/ERK
in developing and/or refining pharmacological approaches to treat psychiatric
disorders in which fear regulation is defective has also been envisaged. (C) 2013
Elsevier Inc. All rights reserved.
The aim of this article was to analyze the theories underpinning dental fear,
anxiety and phobias. To be included, articles must have been published between the
years of 1949 and 2013 concerning fears and phobias within dentistry and/or
psychiatry. Of 200 articles originally under review, 140 were included and reviewed
by the authors.Five specific pathways relating to dental fear and anxiety were
identified; Cognitive Conditioning, Informative, Visual Vicarious, Verbal Threat,
and Parental. Eight currently accepted management techniques across all dental
disciplines for dental fear and anxiety were identified. Further research is
required to identify clinical diagnosis and treatment for fears originating from
different pathways. (c) 2014 Baishideng Publishing Group Inc. All rights reserved.
The present review covers two independent approaches, a neuroanatomical and a
pharmacological (focused on serotonergic transmission), which converge in
highlighting the critical role of the hypothalamus and midbrain periaqueductal gray
matter in the generation of panic attacks and in the mechanism of action of current
antipanic medication. Accordingly, innate and learned fear responses to different
threats (i.e., predator, aggressive members of the same species, interoceptive
threats and painful stimuli) are processed by independent circuits involving
corticolimbic regions (the amygdala, the hippocampus and the prefrontal and insular
cortices) and downstream hypothalamic and brainstem circuits. As for the drug
treatment, animal models of panic indicate that the drugs currently used for
treating panic disorder should work by enhancing 5-HT inhibition of neural systems
that command proximal defense in both the dorsal periaqueductal gray and in the
medial hypothalamus. For the anticipatory anxiety, the reviewed evidence points to
corticolimbic structures, such as the amygdala, the septo-hippocampus and the
prefrontal cortex, as its main neural substrate, modulated by stimulation of 5-HT2c
and 5-HT1A receptors. (C) 2014 Elsevier Ltd. All rights reserved.
The burden of anxiety disorders is growing, but the efficacy of available
anxiolytic treatments remains inadequate. Cognitive behavioural therapy for anxiety
disorders focuses on identifying and modifying maladaptive patterns of thinking and
behaving, and has a testable analogue in rodents in the form of fear extinction. A
large preclinical literature has amassed in recent years describing the neural and
molecular basis of fear extinction in rodents. In this review, we discuss how this
work is being harnessed to foster translational research on anxiety disorders and
facilitate the search for new anxiolytic treatments. We begin by summarizing the
anatomical and functional connectivity of a medial prefrontal cortex (mPFC)-
amygdala circuit that subserves fear extinction, including new insights from
optogenetics. We then cover some of the approaches that have been taken to model
impaired fear extinction and associated impairments with mPFC-amygdala dysfunction.
The principal goal of the review is to evaluate evidence that various
neurotransmitter and neuromodulator systems mediate fear extinction by modulating
the mPFC-amygdala circuitry. To that end, we describe studies that have tested how
fear extinction is impaired or facilitated by pharmacological manipulations of
dopamine, noradrenaline, 5-HT, GABA, glutamate, neuropeptides, endocannabinoids and
various other systems, which either directly target the mPFC-amygdala circuit, or
produce behavioural effects that are coincident with functional changes in the
circuit. We conclude that there are good grounds to be optimistic that the progress
in defining the molecular substrates of mPFC-amygdala circuit function can be
effectively leveraged to identify plausible candidates for extinction-promoting
therapies for anxiety disorders.
Purpose of reviewThe aim of this review is, first, to cover the different aspects
of visual height intolerance such as historical descriptions, definition of terms,
phenomenology of the condition, neurophysiological control of gaze, stance and
locomotion, and therapy, and, second, to identify warranted epidemiological and
experimental studies.Recent findingsVivid descriptions of fear of heights can be
found in ancient texts from the Greek, Roman, and Chinese classics. The life-time
prevalence of visual height intolerance is as high as 28% in the general
population, and about 50% of those who are susceptible report an impact on quality
of life. When exposed to heights, visual exploration by eye and head movements is
restricted, and the velocity of locomotion is reduced. Therapy for fear of heights
is dominated by the behavioral techniques applied during real or virtual reality
exposure. Their efficacy might be facilitated by the administration of d-
cycloserine or glucocorticoids.SummaryVisual height intolerance has a considerable
impact on daily life and interpersonal interactions. It is much more frequent than
fear of heights, which is defined as an environmental subtype of a specific phobia.
There is certainly a continuum stretching from acrophobia to a less-pronounced
visual height intolerance, to which the categorical distinction of a specific
phobia does not apply.
Objectives. Currently, there are no guidelines for when to use an antiepileptic
drug (AED) in nonepileptic panic disorder (PD) patients. We conducted this review
to ascertain what guidance available literature can provide as to when to consider
AEDs for PD patients. Methods. The primary data sources were PubMed and Google-
Scholars. Search was limited to "English" and "Humans". Only papers addressing use
of nonbenzodiazepine AEDs in PD were included. Data regarding study subjects, the
AED utilized, and clinical responses were collected. EEG data were used to classify
reports of patients with abnormal versus those with normal and/or no EEG work-up.
Results. Ten reports were identified for use of AEDs in PD patients with abnormal
EEGs with a total of 20 patients (17 responders). None of the 10 reports were
controlled studies. Eighteen reports were identified for use of AEDs in panic
patients with either normal EEGs or unselected groups (no EEG work-up). Out of the
18 reports, three were controlled studies. Included in the 18 studies were 253
patients (137 responders). Conclusions. We preliminary concluded that EEG work-up
could be useful in guiding the treatment in PD as an abnormal EEG may be indicative
of a higher likelihood of a positive response to an AED.
In recent years, the development and extensive use of optogenetics resulted in
impressive findings on the neurobiology of anxiety and depression in animals.
Indeed, it permitted to depict precisely the role of specific cell populations in
various brain areas, including the amygdala nuclei, the auditory cortex, the
anterior cingulate, the hypothalamus, the hippocampus and the bed nucleus of stria
terminalis in specific aspects of fear and anxiety behaviors. Moreover, these
findings emphasized the involvement of projections from the ventral tegmental area
to the nucleus accumbens and the medial prefrontal cortex in eliciting depressive-
like behaviors in stress-resilient mice or in inhibiting the expression of such
behaviors in stress-vulnerable mice. Here we describe the optogenetic toolbox,
including recent developments, and then review how the use of this technique
contributed to dissect further the circuit underlying anxiety- and depression-like
behaviors. We then point to some drawbacks of the current studies, particularly a)
the sharp contrast between the sophistication of the optogenetic tools and the
rudimentary aspect of the behavioral assays used, b) the fact that the studies were
generally undertaken using normal rodents, that is animals that have not been
subjected to experimental manipulations shifting them to a state relevant for
pathologies and c) that the opportunity to explore the potential of these
techniques to develop innovative therapeutics has been fully ignored yet. Finally,
we discuss the point that these findings frequently ignore the complexity of the
circuitry, as they focus only on a particular subpart of it. We conclude that users
of this cutting edge technology could benefit from dialog between behavioral
neuroscientists, psychiatrists and pharmacologists to further improve the impact of
the findings. (C) 2014 Elsevier Inc All rights reserved.
Genetically informative studies showed that genetic and environmental risk factors
act and interact to influence liability to (a) panic disorder, (b) its childhood
precursor separation anxiety disorder, and (c) heightened sensitivity to CO2, an
endophenotype common to both disorders. Childhood adversities including parental
loss influence both panic disorder and CO2 hypersensitivity. However, childhood
parental loss and separation anxiety disorder are weakly correlated in humans,
suggesting the presence of alternative pathways of risk. The transferability of
tests that assess CO2 sensitivity - an interspecific quantitative trait common to
all mammals to the animal laboratory setting allowed for environmentally controlled
studies of early parental separation. Animal findings paralleled those of human
studies, in that different forms of early maternal separation in mice and rats
evoked heightened CO2 sensitivity; in mice, this could be explained by gene-by-
environment interactional mechanisms. While several questions and issues (including
obvious divergences between humans and rodents) remain open, parallel
investigations by contemporary molecular genetic tools of (1) human longitudinal
cohorts and (2) animals in controlled laboratory settings, can help elucidate the
mechanisms beyond these phenomena. (C) 2014 Elsevier Ltd. All rights reserved.
Panic disorder commonly co-occurs in patients with chronic obstructive pulmonary
disease (COPD), and translational interventions are needed to address the fear of
physiological arousal in this population. This paper examines the utility of
interoceptive exposures (IE), a key component of cognitive behavioral therapy (CBT)
for panic disorder, in patients with comorbid panic and COPD. Our translational
review of the literature suggests that IE is supported by both cognitive- and
learning-theory perspectives of panic, and that the breathing exercises associated
with IE are safe and highly compatible with existing pulmonary rehabilitation
exercises for COPD. Unfortunately, few research studies have examined the use of
CBT to treat anxiety in COPD patients, and none have included IE. Given the strong
theoretical and empirical support for the use of IE, we suggest that mental health
providers should consider incorporating IE into CBT interventions for patients with
comorbid panic and COPD.
Analysis of multiple lung parenchymal abnormalities on HRCT is a real diagnostic
challenge. These abnormalities may be due to a disease of the pulmonary
interstitial tissue, the bronchial tree, the cardiovascular system or to abnormal
alveolar filling with fluid, blood, cells or tumor, several of these etiologies
possibly being concomitant. Systematic pathophysiological reasoning, in the form of
a logical checklist, guides reflection and covers many of the most frequent
diagnoses and potentially treatable emergencies that can be identified by the
nonspecialist radiologist. This approach also provides a basis for deepening
knowledge of each area. The use of the mnemonic FIBROVAKIM (fibrosis-bronchi-
vascular-cancer-infection-medication) is easy to apply and summarizes this
strategy. (C) 2013 Editions francaises de radiologie. Published by Elsevier Masson
SAS. All rights reserved.
There have been significant advances made towards understanding the processes
mediating extinction of learned fear. However, despite being of clear theoretical
and clinical significance, very few studies have examined fear extinction in
adolescence, which is often described as a developmental window of vulnerability to
psychological disorders. This paper reviews the relatively small body of research
examining fear extinction in adolescence. A prominent finding of this work is that
adolescents, both humans and rodents, exhibit a marked impairment in extinction
relative to both younger (e.g., juvenile) and older (e.g., adult) groups. We then
review some potential mechanisms that could produce the striking extinction deficit
observed in adolescence. For example, one neurobiological candidate mechanism for
impaired extinction in adolescence involves changes in the functional connectivity
within the fear extinction circuit, particularly between prefrontal cortical
regions and the amygdala. In addition, we review research on emotion regulation and
attention processes that suggests that developmental changes in attention bias to
threatening cues may be a cognitive mechanism that mediates age-related differences
in extinction learning. We also examine how a differential reaction to chronic
stress in adolescence impacts upon extinction retention during adolescence as well
as in later life. Finally, we consider the findings of several studies illustrating
promising approaches that overcome the typically-observed extinction impairments in
adolescent rodents and that could be translated to human adolescents. (C) 2013
Elsevier Inc. All rights reserved.
The recently published DSM-5 contains a number of changes pertinent to panic
disorder and agoraphobia. These changes include separation of panic disorder and
agoraphobia into separate diagnoses, the addition of criteria and guidelines for
distinguishing agoraphobia from specific phobia, the addition of a 6-month duration
requirement for agoraphobia, the addition of panic attacks as a specifier to any
DSM-5 diagnosis, changes to descriptors of panic attack types, as well as various
changes to the descriptive text. It is crucial that clinicians and researchers
working with individuals presenting with panic attacks and panic-like symptoms
understand these changes. The purpose of the current paper is to provide a summary
of the main changes, to critique the changes in the context of available empirical
evidence, and to highlight clinical implications and potential impact on mental
health service utilization. Several of the changes have the potential to improve
access to evidence-based treatment; yet, although certain changes appear justified
in that they were based on converging evidence from different empirical sources,
other changes appear questionable, at least based on the information presented in
the DSM-5 text and related publications. Ongoing research of DSM-5 panic disorder
and agoraphobia as well as application of the new diagnostic criteria in clinical
contexts is needed to further inform the strengths and limitations of DSM-5
conceptualizations of panic disorder and agoraphobia. Depression and Anxiety 31:
480-486, 2014. (C) 2014 Wiley Periodicals, Inc.
Extinction of fear memory is a particular form of cognitive function that is of
special interest because of its involvement in the treatment of anxiety and mood
disorders. Based on recent literature and our previous findings (EMBO J
30(19):4071-4083, 2011), we propose a new hypothesis that implies a tight
relationship among IGF signaling, adult hippocampal neurogenesis and fear
extinction. Our proposed model suggests that fear extinction-induced IGF2/IGFBP7
signaling promotes the survival of neurons at 2-4 weeks old that would participate
in the discrimination between the original fear memory trace and the new safety
memory generated during fear extinction. This is also called "pattern separation",
or the ability to distinguish similar but different cues (e.g., context). To
understand the molecular mechanisms underlying fear extinction is therefore of
great clinical importance.
Research on dopamine lies at the intersection of sophisticated theoretical and
neurobiological approaches to learning and memory. Dopamine has been shown to be
critical for many processes that drive learning and memory, including motivation,
prediction error, incentive salience, memory consolidation, and response output.
Theories of dopamine's function in these processes have, for the most part, been
developed from behavioral approaches that examine learning mechanisms in reward-
related tasks. A parallel and growing literature indicates that dopamine is
involved in fear conditioning and extinction. These studies are consistent with
long-standing ideas about appetitive-aversive interactions in learning theory and
they speak to the general nature of cellular and molecular processes that underlie
behavior. We review the behavioral and neurobiological literature showing a role
for dopamine in fear conditioning and extinction. At a cellular level, we review
dopamine signaling and receptor pharmacology, cellular and molecular events that
follow dopamine receptor activation, and brain systems in which dopamine functions.
At a behavioral level, we describe theories of learning and dopamine function that
could describe the fundamental rules underlying how dopamine modulates different
aspects of learning and memory processes. (C) 2013 Elsevier Inc. All rights
reserved.
One of the most exciting discoveries in the learning and memory field in the past
two decades is the observation that active regulation of gene expression is
necessary for experience to trigger lasting functional and behavioral change, in a
wide variety of species, including humans. Thus, as opposed to the traditional view
of 'nature' (genes) being separate from 'nurture' (environment and experience), it
is now clear that experience actively drives alterations in central nervous system
(CNS) gene expression in an ongoing fashion, and that the resulting transcriptional
changes are necessary for experience to trigger altered long-term behavior. In
parallel over the past decade, epigenetic mechanisms, including regulation of
chromatin structure and DNA methylation, have been shown to be potent regulators of
gene transcription in the CNS. In this review, we describe data supporting the
hypothesis that epigenetic molecular mechanisms, especially DNA methylation and
demethylation, drive long-term behavioral change through active regulation of gene
transcription in the CNS. Specifically, we propose that epigenetic molecular
mechanisms underlie the formation and stabilization of context-and cue-triggered
fear conditioning based in the hippocampus and amygdala, a conclusion reached in a
wide variety of studies using laboratory animals. Given the relevance of cued and
contextual fear conditioning to post-traumatic stress, by extension we propose that
these mechanisms may contribute to post-traumatic stress disorder (PTSD) in humans.
Moreover, we speculate that epigenetically based pharmacotherapy may provide a new
avenue of drug treatment for PTSD-related cognitive and behavioral function.
Neuropsychopharmacology Reviews (2013) 38, 77-93; doi:10.1038/npp.2012.79;
published online 13 June 2012
This book discussion demonstrates how the War on Terror-now spanning two American
administrations-has affected the role and authority of historical American
traditions on the justice of war. It highlights the continuing importance of four
principles rooted in American moral and ethical traditions: legitimate authority;
guidelines on preemption; the protection of civilians; and the importance of
democratic discourse in the deliberation of American conduct.
The study of fear memory is important for understanding various anxiety disorders
in which patients experience persistent recollections of traumatic events. These
memories often involve associations of contextual cues with aversive events;
consequently, Pavlovian classical conditioning is commonly used to study contextual
fear learning. The use of predator odor as a fearful stimulus in contextual fear
conditioning has become increasingly important as an animal model of anxiety
disorders. Innate fear responses to predator odors are well characterized and
reliable; however, attempts to use these odors as unconditioned stimuli in fear
conditioning paradigms have proven inconsistent. Here we characterize a contextual
fear conditioning paradigm using coyote urine as the unconditioned stimulus. We
found that contextual conditioning induced by exposure to coyote urine produces
long-term freezing, a stereotypic response to fear observed in mice. This paradigm
is context-specific and parallels shock-induced contextual conditioning in that it
is responsive to extinction training and manipulations of predator odor intensity.
Region-specific lesions of the dorsal and ventral hippocampus indicate that both
areas are independently required for the long-term expression of learned fear.
These results in conjunction with c-fos immunostaining data suggest that while both
the dorsal and ventral hippocampus are required for forming a contextual
representation, the ventral region also modulates defensive behaviors associated
with predators. This study provides information about the individual contributions
of the dorsal and ventral hippocampus to ethologically relevant fear learning. (c)
2013 Wiley Periodicals, Inc.
Typically, female rats demonstrate clear mate choice. Mate preference is driven by
the evolutionary need to choose males with heritable parasite resistance and to
prevent the transmission of contagious diseases during mating. Thus, females detect
and avoid parasitized males. Over evolutionary time scales, parasite-free males
plausibly evolve to advertise their status. This arrangement between males and
females is obviously detrimental to parasites, especially for sexually transmitted
parasites. Yet Toxoplasma gondii, a sexually transmitted parasite, gets around this
obstacle by manipulating mate choice of uninfected females. Males infected with
this parasite become more attractive to uninfected females. The ability of T.
gondii to not only advantageously alter the behavior and physiology of its host but
also secondarily alter the behavior of uninfected females presents a striking
example of the 'extended phenotype' of parasites. Toxoplasma gondii also abolishes
the innate fear response of rats to cat odor; this likely increases parasite
transmission through the trophic route. It is plausible that these two
manipulations are not two distinct phenotypes, but are rather part of a single
pattern built around testosterone-mediated interplay between mate choice,
parasitism and predation.
a Individuals with musculoskeletal pain exhibit abnormal movement patterns,
including antalgic gait, postural dysfunction, increased thoracolumbar stiffness,
decreased proprioception, and altered activation of abdominal and extensor muscles.
Additionally, aberrant or increased biomechanical forces over time produce joint or
structural damage that results in pain. A large body habitus resulting from
excessive weight can accelerate these musculoskeletal complaints. Irrespective of
age, obesity contributes to chronic musculoskeletal pain, impairment of mobility,
and eventual physical disability. Potential mechanisms that may mediate the
relationships between obesity-related pain and functional decline include skeletal
muscle strength deterioration, systemic inflammation, and psychosocial
characteristics (eg, pain catastrophizing, kinesiophobia, and depression).
Treatment considerations for obese patients with musculoskeletal pain include
assessment of kinesiophobia levels, biomechanical analysis, and pain medication
use. Ideally, a multidisciplinary team of physicians, psychologists, and physical
therapists should optimize the design of interventions specific to the patient. In
some cases, the use of appropriate pain medications or intra-articular injectable
agents may help control pain, fostering sustained activity, caloric expenditure,
and weight loss. Morbid obesity is a medical condition that alters biomechanical
forces on the tissues of the body. This condition provides the opportunity to
examine accelerated development of musculoskeletal pain syndromes and etiology. The
proposed therapeutic interventions can have multiple benefits in the obese
population including weight loss, improved psychological outlook and self-efficacy,
reduced kinesiophobia levels, reduced risk of functional dependence, and improved
quality of life.
Evidence from twin studies suggests that genetic factors contribute to the risk of
developing a fear or a phobia. The aim of the present study was to review the
current literature regarding twin studies describing the genetic basis of specific
phobias and their corresponding fears. The analysis included five twin studies on
fears and ten twin studies on specific phobias. Heritability estimates of fear
subtypes and specific phobia subtypes both varied widely, even within the subtypes.
A meta-analysis performed on the twin study results indicated that fears and
specific phobias are moderately heritable. The highest mean heritability (+/- SEM)
among fear subtypes was found for animal fear (45% +/- 0.004), and among specific
phobias for the blood-injury-injection phobia (33% +/- 0.06). For most phenotypes,
variance could be explained solely by additive genetic and unique environmental
effects. Given the dearth of independent data on the heritability of specific
phobias and fears, additional research is needed. (C) 2013 Elsevier Ltd. All rights
reserved.
Social fear and avoidance of social situations represent the main behavioral
symptoms of social anxiety disorder (SAD), a highly prevalent anxiety disorder that
is poorly elucidated and has rather unsatisfactory therapeutic options. Therefore,
animal models are needed to study the underlying etiology and pathophysiology of
SAD and to verify the efficacy of possible novel treatment approaches. In this
review, we describe and discuss the most important paradigms that have been shown
to induce social avoidance and fear in rodents, including foot shock exposure,
restraint stress, social isolation, social instability, social defeat, conditioned
defeat, social defeat/overcrowding, chronic subordinate colony housing, chronic
mild stress, maternal separation and social fear conditioning. We also describe
some of the behavioral paradigms used to assess social avoidance and fear in
rodents, including the social interaction test, the social preference-avoidance
test, the social approach-avoidance test, the three-chambered social approach test,
the partition test and the modified Y-maze test. We focus on the behavioral
alterations these paradigms induce, especially on social interaction, general
anxiety and depressive-like behavior given that SAD is strongly comorbid with
anxiety and affective disorders.
A systematic review of trauma treatment outcome literature was conducted to
determine the impact of treatment on comorbid panic symptoms. Major databases were
searched (from 1989 to 2013) and 64 randomized controlled trials using cognitive
behavioral approaches to treat acute stress disorder, subthreshold posttraumatic
stress disorder (PTSD), and full PTSD met inclusion criteria for this review.
Results showed that 41% of the studies reviewed did not assess for Axis I
psychiatric comorbidity at any point during the course of treatment. Only 5% of the
studies reviewed reported rates of comorbid panic disorder (PD) at more than one
time point during the study. Results indicate that approximately 56% of people no
longer meet PD criteria following PTSD treatment.
Aggression and fear are often thought to be distinct behavioral states, yet they
share several common output responses. In the mouse, both can be initiated by
specialized odor cues. How these cues signal through the olfactory system to
promote behavior is largely unknown. Recent experiments have started to uncover the
relevant signaling ligands, chemosensory receptors, and responsive sensory neurons
that together enable the precise manipulation of behaviorally relevant neural
circuits. Moreover, the use of molecular genetics and new experimental strategies
has begun to reveal how the central nervous system processes olfactory information
to initiate aggression and fear. A sensory-initiated comparative study of these two
fundamental threat reactions promises to offer new mechanistic insight.
A growing body of literature suggests that comorbid anxiety disorders are more
common and more prognostically relevant among migraine sufferers than comorbid
depression. Panic disorder (PD) appears to be more strongly associated with
migraine than most other anxiety disorders. PD and migraine are both chronic
diseases with episodic manifestations, involving significant functional impairment
and shared symptoms during attacks, interictal anxiety concerning future attacks,
and an absence of identifiable secondary pathology. A meta-analysis of high-quality
epidemiologic study data from 1990 to 2012 indicates that the odds of PD are 3.76
times greater among individuals with migraine than those without. This association
remains significant even after controlling for demographic variables and comorbid
depression. Other less-rigorous community and clinical studies confirm these
findings. The highest rates of PD are found among migraine with aura patients and
those presenting to specialty clinics. Presence of PD is associated with greater
negative impact of migraine, including more frequent attacks, increased disability,
and risk for chronification and medication overuse. The mechanisms underlying this
common comorbidity are poorly understood, but both pathophysiological (eg,
serotonergic dysfunction, hormonal influences, dysregulation of the
hypothalamicpituitaryadrenal axis) and psychological (eg, interoceptive
conditioning, fear of pain, anxiety sensitivity, avoidance behavior) factors are
implicated. Means of assessing comorbid PD among treatment-seeking migraineurs are
reviewed, including verbal screening for core PD symptoms, ruling out medical
conditions with panic-like features, and administering validated self-report
measures. Finally, evidence-based strategies for both pharmacologic and behavioral
management are outlined. The first-line migraine prophylactics are not indicated
for PD, and the selective serotonin re-uptake inhibitors used to treat PD are not
efficacious for migraine; thus, separate agents are often required to address each
condition. Core components of behavioral treatments for PD are reviewed, and their
integration into clinical headache practice is discussed.
Fear of cancer recurrence (FCR) is among the most commonly reported problems and
one of the most prevalent areas of unmet needs for cancer survivors and their
carers. This review aims to provide a comprehensive overview of current scientific
knowledge on FCR and to formulate recommendations for future research. A systematic
review was undertaken to identify quantitative studies associated with FCR.
Relevant studies were identified via Medline, CINAHL, PsycINFO and AMED databases
from 1996 through December 2011. Data from 130 eligible papers were extracted and
summarized following a systematic scheme. Multiple FCR assessment methods were
identified. Survivors reported low to moderate level of FCR but considered it as
one of the top greatest concerns and the most frequently endorsed unmet need. FCR
remains stable over the survivorship trajectory. Younger age, presence and severity
of physical symptoms, psychological distress and lower quality of life were
associated with higher FCR. Health behaviours, psychological reactions and
functional impairments were identified as FCR consequences. Carers reported higher
FCR than the patients. Limited data on interventions were available. FCR research
has expanded somewhat haphazardly over the last 20 years. Adopted consensual
definition and used well-validated measures will be necessary. Longitudinal
research examining the longer-term development and impact of FCR is clearly needed.
The proposal and evaluation of theoretical models of FCR is a priority. Identifying
the key features of FCR will stimulate the research and the development of targeted
interventions for cancer survivors and their carers.
As presently defined, post-traumatic stress disorder (PTSD) is an amalgam of
symptoms falling into: re-experiencing of the trauma, avoidance of reminders of it,
emotional numbing and hyperarousal. PTSD has a well-known proximate cause, commonly
occurring after a life-threatening event that induces a response of intense fear,
horror, and helplessness. Much of the advancement in understanding of the
neurobiology of PTSD has emerged from conceptualizing the disorder as one that
involves substantial dysfunction in fear processing. This article reviews recent
knowledge of fear processing markers in PTSD. A systematic search was performed of
reports within the specific three-year publication time period of January 2010 to
December 2012. We identified a total of 31 studies reporting fear processing
markers in PTSD. We further categorized them according to the following
classification: (1) neural-activation markers (n=10), (2) psychophysiological
markers (n=14), and (3) behavioral markers (n=7). Across most studies reviewed
here, significant differences between individuals with PTSD and healthy controls
were shown. Methodological, theoretical and clinical implications were discussed.
Understanding how crowds behave during collective displacement is at the heart of
both pedestrian traffic engineering and 'movement ecology'. Perhaps the most
critical reason for studying collective human dynamics under emergency/panic
conditions is the lack of complementary data to develop and validate an explanatory
model. A little used alternative is to study non-human model organisms. In this
paper, we review experiences in using non-human organisms to study crowd panic in
the literature. We then highlight the potential contribution that research with
biological entities could make to understand the complex pedestrian behaviour and
the enhancement of pedestrian safety during emergency/panic conditions. We also
emphasise that understanding of behavioural similarities and dissimilarities
between humans and animals is required for developing a good experimental design
aimed to study collective behaviour. A generic model that could describe the common
underlying mechanisms of crowd behaviour among organisms of different body sizes is
identified as future challenge. (c) 2012 Elsevier Ltd. All rights reserved.
Pain and fear are both aversive experiences that strongly impact on behaviour and
well being. They are considered protective when they lead to meaningful, adaptive
behaviour such as the avoidance of situations that are potentially dangerous to the
integrity of tissue (pain) or the individual (fear). Pain and fear may, however,
become maladaptive if expressed under inappropriate conditions or at excessive
intensities for extended durations. Currently emerging concepts of maladaptive pain
and fear suggest that basic neuronal mechanisms of memory formation are relevant
for the development of pathological forms of pain and fear. Thus, the processes of
erasing memory traces of pain and fear may constitute promising targets for future
therapies.
This article argues that much of the historical analysis of terror and terrorism in
history has been weak in understanding the limits on terrorist activity and how
terrorist campaigns eventually end. Reviewing three recent studies that examine
various aspects of terrorism and the language of terror, the article seeks to show
that states often play a major role in the way terrorist movements develop and
eventually end up either defeated or moving into mainstream political engagement.
The article points to a number of examples to illuminate this including the
Carbonara in nineteenth century Italy, the Paris Commune and the ending segregation
in the U.S. South in the 1960s.
This article is part of a Special Issue "Puberty and Adolescence". Throughout the
past several decades, studies have uncovered a wealth of information about the
neural circuitry underlying fear learning and extinction that has helped to inform
treatments for fear-related disorders such as post-traumatic stress and anxiety.
Yet, up to 40% of people do not respond to such treatments. Adolescence, in
particular, is a developmental stage during which anxiety disorders peak, yet
little is known about the development of fear-related neural circuitry during this
period. Moreover, pharmacological and behavioral therapies that have been developed
are based on mature circuitry and function. Here, we review neural circuitry
implicated in fear learning and data from adolescent mouse and human fear learning
studies. In addition, we propose a developmental model of fear neural circuitry
that may optimize current treatments and inform when, during development, specific
treatments for anxiety may be most effective. (C) 2013 Elsevier Inc. All rights
reserved.
Post-traumatic stress disorder, panic disorder and phobia manifest in ways that are
consistent with an uncontrollable state of fear. Their development involves
heredity, previous sensitizing experiences, association of aversive events with
previous neutral stimuli, and inability to inhibit or extinguish fear after it is
chronic and disabling. We highlight recent progress in fear learning and memory,
differential susceptibility to disorders of fear, and how these findings are being
applied to the understanding, treatment and possible prevention of fear disorders.
Promising advances are being translated from basic science to the clinic, including
approaches to distinguish risk versus resilience before trauma exposure, methods to
interfere with fear development during memory consolidation after a trauma, and
techniques to inhibit fear reconsolidation and to enhance extinction of chronic
fear. It is hoped that this new knowledge will translate to more successful,
neuroscientifically informed and rationally designed approaches to disorders of
fear regulation.
Mass panic situations usually occur at large public events although only rarely.
Nevertheless, (senior) emergency physicians need to be aware of, and prepare for,
such an eventuality with an eye to (emergency) crowd management, the local
situation, emergency escape routes and evacuation strategies. During such a large-
scale public event, an outbreak of panic is difficult to foresee and, therefore,
difficult to prevent. However, a number of measures exist to calm people facing a
rising mass panic. In the last resort, emergency physicians in charge need to be
familiar with measures and actions to be taken during and following a mass panic.
There is no doubt that, "panic prevention in the mind" is the most important
preventive measure in combatting mass panic and related phenomena. It is extremely
important to think through possible scenarios and strategies in advance, before
having to encounter such an event as mass panic. In the last resort, the worst
panic reaction is that experienced by the unprepared and clueless emergency
physician.
Objectives: To systematically review the instruments used to assess postural
control and fear of falling in people with chronic obstructive pulmonary disease
(COPD), and to synthesize and evaluate their breadth of content and measurement
properties. Data Sources: MEDLINE, EMBASE, Web of Science, CINAHL, CENTRAL,
PsycINFO, PEDro, and OTSeeker databases searched in September 2012. Study
Selection: Two independent reviewers performed the selection of articles, the ICF
linking process and quality assessment. Only quantitative studies were included,
irrespective of language or publication date. Data Extraction: This systematic
review comprised two phases. Phase 1 aimed to identify the commonly used
instruments to assess postural control and fear of falling in the COPD literature.
The breadth of content of each instrument was examined based on the International
Classification of Functioning, Disability and Health (ICF). In phase 2, a
measurement property search filter was adopted and used in four electronic
databases to retrieve properties reported in the COPD population. The COSMIN
checklist was used to assess the methodological quality of each measurement
property reported. Data Synthesis: Seventeen out of 401 publications were eligible
in phase 1. Seventeen instruments were identified including 15 for postural control
and 2 for fear of falling assessment. The Berg Balance Scale, the Short Physical
Performance Battery, and the Activities-specific Balance Confidence (ABC) scale
were the most frequently used instruments to assess postural control and fear of
falling respectively. The ICP categories covered varied considerably among
instruments. The Balance Evaluation Systems test and ABC presented the greatest
breadth of content. Measurement properties reported included criterion predictive
validity (4 instruments), construct validity (11 instruments) and responsiveness (1
instrument), with inconsistent findings based on 'fair' and 'poor' quality studies.
Conclusions: Different instruments with heterogeneous content have been used to
assess postural control and fear of falling outcomes. Standardized assessment
methods and best evidence on measurement properties is required in the COPD
literature. (C) 2013 by the American Congress of Rehabilitation Medicine
Severe exacerbation of symptoms following physical activity is characteristic for
chronic-fatigue syndrome (CFS) and fibromyalgia (FM). These exacerbations make it
understandable for people with CFS and FM to develop fear of performing body
movement or physical activity and consequently avoidance behaviour toward physical
activity. The aims of this article were to review what measures are available for
measuring fear of movement and avoidance behaviour, the prevalence fear of movement
and avoidance behaviour toward physical activity and the therapeutic options with
fear of movement and avoidance behaviour toward physical activity in patients with
CFS and FM. The review revealed that fear of movement and avoidance behaviour
toward physical activity is highly prevalent in both the CFS and FM population, and
it is related to various clinical characteristics of CFS and FM, including symptom
severity and self-reported quality of life and disability. It appears to be crucial
for treatment (success) to identify CFS and FM patients displaying fear of movement
and avoidance behaviour toward physical activity. Individually tailored cognitive
behavioural therapy plus exercise training, depending on the patient's
classification as avoiding or persisting, appears to be the most promising strategy
for treating fear of movement and avoidance behaviour toward physical activity in
patients with CFS and FM.
Panic disorder (PD) is a subtype of anxiety disorder in which the core phenomenon
is the spontaneous occurrence of panic attacks. Although studies with laboratory
animals have been instrumental for the understanding of its neurobiology and
treatment, few review articles have focused on the validity of the currently used
animal models for studying this psychopathology. Therefore, the aim of the present
paper is to discuss the strengths and limits of these models in terms of face,
construct and predictive validity. Based on the hypothesis that panic attacks are
related to defensive responses elicited by proximal threat, most animal models
measure the escape responses induced by specific stimuli. Some apply electrical or
chemical stimulation to brain regions proposed to modulate fear and panic
responses, such as the dorsal periaqueductal grey or the medial hypothalamus. Other
models focus on the behavioural consequences caused by the exposure of rodents to
ultrasound or natural predators. Finally, the elevated T-maze associates a one-way
escape response from an open arm with panic attacks. Despite some limitations,
animal models are essential for a better understanding of the neurobiology and
pharmacology of PD and for discovering more effective treatments.
Anxiety disorders are among the most common mental health problems; deficits in
extinction have been implicated as a possible risk factor for the development of
these disorders. Fear extinction refers to the ability to adapt as situations
change by learning to suppress a previously acquired fear. Attention is directed
toward the medial prefrontal cortex (mPFC) and the interaction it has with the
amygdala as this circuit has crucial roles in both the acquisition and the
extinction of fear associations. Here, we review converging evidence from different
laboratories pointing to multiple roles that the mPFC has in fear regulation.
Research on rodents indicates opposing roles that the different subregions of the
mPFC have in exciting and inhibiting fear. In addition, this review aims to survey
the findings addressing the mechanisms by which the mPFC regulates fear. Data from
our laboratory and others show that changes in plasticity in the mPFC could be one
of the mechanisms mediating extinction of fear. Recent findings on rodents and
nonhuman primates report that modifying plasticity in the mPFC alters fear and
affects extinction, suggesting that targeting plasticity in the mPFC could
constitute a therapeutic tool for the treatment of anxiety disorders.
Contexts surround and imbue meaning to events; they are essential for recollecting
the past, interpreting the present and anticipating the future. Indeed, the brain's
capacity to contextualize information permits enormous cognitive and behavioural
flexibility. Studies of Pavlovian fear conditioning and extinction in rodents and
humans suggest that a neural circuit including the hippocampus, amygdala and medial
prefrontal cortex is involved in the learning and memory processes that enable
context-dependent behaviour. Dysfunction in this network may be involved in several
forms of psychopathology, including post-traumatic stress disorder, schizophrenia
and substance abuse disorders.
Fear conditioning and fear extinction are Pavlovian conditioning paradigms
extensively used to study the mechanisms that underlie learning and memory
formation. The neural circuits that mediate this learning are evolutionarily
conserved, and seen in virtually all species from flies to humans. In mammals, the
amygdala and medial prefrontal cortex are two structures that play a key role in
the acquisition, consolidation and retrieval of fear memory, as well extinction of
fear. These two regions have extensive bidirectional connections, and in recent
years, the neural circuits that mediate fear learning and fear extinction are
beginning to be elucidated. In this review, we provide an overview of our current
understanding of the neural architecture within the amygdala and medial prefrontal
cortex. We describe how sensory information is processed in these two structures
and the neural circuits between them thought to mediate different aspects of fear
learning. Finally, we discuss how changes in circuits within these structures may
mediate fear responses following fear conditioning and extinction.
Background: The fear of crime may have negative consequences for health and
wellbeing. It is influenced by factors in the physical and social environment. This
study aimed to review and synthesize qualitative evidence from the UK on fear of
crime and the environment. Methods: Eighteen databases were searched, including
crime, health and social science databases. Qualitative studies conducted in the UK
which presented data on fear of crime and the environment were included. Quality
was assessed using Hawker et al.'s framework. Data were synthesized thematically.
Results: A total of 40 studies were included in the review. Several factors in the
physical environment are perceived to impact on fear of crime, including visibility
and signs of neglect. However, factors in the local social environment appear to be
more important as drivers of fear of crime, including social networks and
familiarity. Broader social factors appear to be of limited relevance. There is
considerable evidence for limitations on physical activity as a result of fear of
crime, but less for mental health impacts. Conclusions: Fear of crime represents a
complex set of responses to the environment. It may play a role in mediating
environmental impacts on health and wellbeing.
Objective: To present the most relevant findings regarding the Brazilian Medical
Association guidelines for the diagnosis and differential diagnosis of panic
disorder. Methods: We used the methodology proposed by the Brazilian Medical
Association for the Diretrizes Project. The MEDLINE (PubMed), Scopus, Web of
Science, and LILACS online databases were queried for articles published from 1980
to 2012. Searchable questions were structured using the PICO format (acronym for
"patient" [or population], "intervention" [or exposure], "comparison" [or control],
and "outcome"). Results: We present data on clinical manifestations and
implications of panic disorder and its association with depression, drug abuse,
dependence and anxiety disorders. In addition, discussions were held on the main
psychiatric and clinical differential diagnoses. Conclusions: The guidelines are
proposed to serve as a reference for the general practitioner and specialist to
assist in and facilitate the diagnosis of panic disorder.
The use of intravenous verapamil for tachyarrhythmia in infants is widely
considered contraindicated due to the perceived risk of hemodynamic collapse after
administration. This article reviews the relatively limited evidence that led to
this well-known contraindication and highlights the interesting process by which
medical practice may evolve in the absence of persuasive science.
Long term care elders with fear of falling may restrict their activity resulting in
declines in function and excess disability. To further explore this problem, a
review of the literature was conducted. The search yielded 26 studies on the
epidemiology of fear of falling in nursing homes and assisted living as well as
intervention studies in these settings. Fear of falling is common, affecting more
than 50% of long term care elders and is associated with negative outcomes,
including falls, functional impairments, depression, and poor quality of life.
Longitudinal studies are rare. There were few intervention studies, with most
testing exercise programs, including balance training, such as t'ai chi, and little
research testing other approaches. Few conclusions can be drawn about
interventions, as most sample sizes were small and the interventions and
measurement varied widely. Additional research is needed to identify long term care
residents most in need of intervention, and the best ways to reduce fear of falling
and its consequences. Copyright (C) 2013 - American Medical Directors Association,
Inc.
Background Increasing proportions of patients diagnosed with cancer will become
long-term survivors (=5?years post-diagnosis). However, survivors may continue to
experience negative effects of cancer and/or treatment, including fear of
recurrence (FoR). This review aims to provide an overview of current knowledge on
FoR, including determinants and consequences in long-term cancer survivors, and to
outline methodological and conceptual challenges that should be addressed in future
research. Methods Multiple databases including PUBMED, EMBASE, and PsycINFO were
searched to identify relevant articles. Seventeen articles were included. Data were
extracted by two reviewers and summarized following a systematic scheme. Results
Even years after initial diagnosis, cancer survivors suffer from FoR. Most studies
report low or moderate mean FoR scores, suggesting that FoR is experienced in
modest intensity by most survivors. Studies including long-term and short-term
survivors indicate no significant change of FoR over time. Lower level of
education, lower level of optimism, and being Hispanic or White/Caucasian were
found to be associated with higher levels of FoR. Significant negative associations
were reported between FoR and quality of life as well as psychosocial well-being.
All but three studies were conducted in the USA. General cut-offs for
severity/clinical significance have not been defined yet. Conclusions FoR at modest
intensity is experienced by most long-term cancer survivors. Future studies should
address determinants and consequences of FoR in more detail. Validated instruments
providing cut-offs for severity/clinical significance of FoR should be developed
and utilized. Efficient interventions should be implemented to reduce detrimental
effects of FoR. Copyright (c) 2012 John Wiley & Sons, Ltd.
Although exposure to major psychological trauma is unfortunately common, risk for
related neuropsychiatric conditions, such as post-traumatic stress disorder (PTSD),
varies greatly among individuals. Fear extinction offers a tractable and
translatable behavioral readout of individual differences in learned recovery from
trauma. Studies in rodent substrains and subpopulations are providing new insights
into neural system dysfunctions associated with impaired fear extinction. Rapid
progress is also being made in identifying key molecular circuits, epigenetic
mechanisms, and gene variants associated with differences in fear extinction. Here,
we discuss how this research is informing understanding of the etiology and
pathophysiology of individual differences in risk for trauma-related anxiety
disorders, and how future work can help identify novel diagnostic biomarkers and
pharmacotherapeutics for these disorders.
Fears and physical complaints are frequently attributed to the environment. In the
form of environmental illness or environmental syndromes they can often reach
clinical relevance, even if no causal relationship between subjective stimuli and
symptoms can even if be found. The role of psychotherapy is controversial,
especially because patients fear for the legitimacy of their complaints and
preferably seek somatic or alternative forms of treatment. In addition, there is
limited evidence for the effectiveness of psychotherapy. In view of the high degree
of suffering, especially as anticipatory anxiety, avoidance behavior, social
retreat and distrust, and comorbidity with mental illness, psychotherapy can
frequently enable patients to reach more self-efficacy, trust, a wider range of
activities and thus a better quality of life.
We aimed to investigate whether agoraphobia (A) in panic disorder (PD) has any
effects on oxidative and anti-oxidative parameters. We measured total antioxidant
capacity (TAG), paraoxonase (PUN), arylesterase (ARE) antioxidant and
malondialdehyde (MDA) oxidant levels using blood samples from a total of 31 PD
patients with A, 22 PD patients without A and 53 control group subjects. There was
a significant difference between the TAG, PUN, ARE and MDA levels of the three
groups consisting of PD with A, PD without A and the control group. The two-way
comparison to clarify the group creating the difference showed that the TAG, PUN,
and ARE antioxidants were significantly lower in the PD with A group compared to
the control group while the MDA oxidant was significantly higher. There was no
significant difference between the PD without A and control groups for TAG, PUN,
ARE and MDA levels. We clearly demonstrated that the oxidative stress and damage to
the anti-oxidative mechanism are significantly higher in the PD group with A. These
findings suggest that oxidative/anti-oxidative mechanisms may play a more important
role on the pathogenesis of PB with A.
Background: The presence of abnormalities in baseline respiratory function of
subjects with panic disorder (PD) is expected according to PD respiratory theories.
We aimed to meta-analyze results from studies comparing baseline respiratory and
hematic parameters related to respiration between subjects with PD and controls.
Methods: A literature research in bibliographic databases was performed. Fixed-
effects models were applied for all parameters while random-effects models only
when suitable (at least 10 independent studies). Several moderator analyses and
publication bias diagnostics were performed. Results: We found significantly higher
mean minute ventilation and lower et-pCO(2) in subjects with PD than controls.
Moreover we also found evidences of reduced HCO3- and PO4- hematic concentrations,
higher indexes of respiratory variability/irregularity and higher rate of sighs and
apneas. Evidence of heterogeneity was partly explained by moderator analyses. No
relevant publication bias was found. Limitations: Several shortcomings affected the
included studies, such as over-inclusive recruitment criteria, samples unbalanced
for socio-demographic characteristics, lack of statistical details and small number
of studies available for several parameters. Discussion: Our results support the
idea of abnormalities in respiratory function of subjects with PD. Compared to
controls, they showed baseline hyperventilation; the results from hematic
parameters suggest that hyperventilation may be chronic and not simply caused by
their high anxiety levels during respiratory assessment. Evidences of higher
variability and irregularity in respiratory patterns of subjects with PD were also
found. It is unclear to what extent the higher rate of sighs and apneas may explain
the other baseline respiratory abnormalities found in PD. (C) 2012 Elsevier B.V.
All rights reserved.
After several decades of intense clinical research, the great promise of Type I
interferons (IFN1) as the anticancer wonder drugs that could cure or, at the very
least, curb the progression of various oncological diseases has regrettably failed
to deliver. Severe side effects and low efficacy of IFN1-based pharmaceutics
greatly limited use of these drugs and further reduced the enthusiasm of clinical
oncologists for future optimization of IFN1-based therapeutic modalities.
Incredibly, extensive clinical studies to assess the efficacy of IFN1 alone or in
combination with other anticancer drugs have not been paralleled by an equal scope
in defining the determinants that confer cell sensitivity or refractoriness to
IFN1. Given that all effects of IFN1 on malignant and benign cells alike are
mediated by its receptor, the mechanisms regulating these receptor cell surface
levels should play a paramount role in shaping the magnitude and duration of IFN1-
elicited effects. These mechanisms and their role in controlling IFN1 responses, as
well as an ability of a growing tumor to commandeer these events, are the focus of
our review. We postulate that activation of numerous signaling pathways leading to
elimination of IFN1 receptor occurs in cancer cells and benign cells that
contribute to tumor tissue. We further hypothesize that activation of these
eliminative pathways enables the escape from IFN1-driven suppression of
tumorigenesis and elicits the primary refractoriness of tumor to the pharmaceutical
IFN1.
Do religious people fear death more or less than those who are nonreligious?
According to two theories, religiosity and fear of death should be inversely
correlated. A third theory suggests that moderately religious persons should be
more fearful than those who are extremely religious or nonreligious. Yet a fourth
theory predicts that religiosity and fear of death should be positively correlated.
Eighty-four studies were located in which pertinent findings have been presented,
several of which reached more than one conclusion based on different definitions of
religiosity. Overall, 40 studies provided findings supporting the conclusion that
religiosity and fear of death are inversely correlated, nine supported a
curvilinear relationship, 27 supported a positive correlation, and 32 indicated
that no significant relationship exists between religiosity and fear of death. Chi
square analyses of several features of these conflicting studies suggest that there
is probably a modest negative correlation between religiosity and fear of death
among persons who are at least modestly religious. However, when nonreligious
individuals are sampled alongside those who are both moderately and extremely
religious, the overall relationship shifts to being curvilinear, and possibly even
positive, depending on the aspect of religiosity being assessed. The implications
of these conclusions for the four theories are discussed.
In the period before the 20072008 elections, there was much talk from the regime
about the danger of a coloured revolution in Russia. The article considers whether
the fear of revolution was genuine or artificially created to discredit opposition
and strengthen support for the regime. It seems that tensions inside the regime and
the unexpected occurrence of the previous coloured revolutions led to real fears of
revolution in Russia, although this was in fact unlikely. Russian policy towards
the West and the rival election programmes are examined to investigate whether the
regime was creating an enemy image of the West.
In 2000, Gorman et al. published a widely acknowledged revised version of their
1989 neuroanatomical hypothesis of panic disorder (PD). Herein, a 'fear network'
was suggested to mediate fear- and anxiety-related responses: panic attacks result
from a dysfunctional coordination of 'upstream' (cortical) and 'downstream'
(brainstem) sensory information leading to heightened amygdala activity with
subsequent behavioral, autonomic and neuroendocrine activation. Given the emergence
of novel imaging methods such as fMRI and the publication of numerous neuroimaging
studies regarding PD since 2000, a comprehensive literature search was performed
regarding structural (CT, MRI), metabolic (PET, SPECT, MRS) and functional (fMRI,
NIRS, EEG) studies on PD, which will be reviewed and critically discussed in
relation to the neuroanatomical hypothesis of PD. Recent findings support
structural and functional alterations in limbic and cortical structures in PD.
Novel insights regarding structural volume increase or reduction, hyper- or
hypoactivity, laterality and task-specificity of neural activation patterns
emerged. The assumption of a generally hyperactive amygdala in PD seems to apply
more to state than trait characteristics of PD, and involvement of further areas in
the fear circuit, such as anterior cingulate and insula, is suggested. Furthermore,
genetic risk variants have been proposed to partly drive fear network activity.
Thus, the present state of knowledge generally supports limbic and cortical
prefrontal involvement as originally proposed in the neuroanatomical hypothesis.
Some modifications might be suggested regarding a potential extension of the fear
circuit, genetic factors shaping neural network activity and neuroanatomically
informed clinical subtypes of PD potentially guiding future treatment decisions.
This systematic review assesses the current state of clinical and preclinical
research on panic disorder (PD) in which the carbon dioxide (CO2) challenge was
used as a trigger for panic attacks (PAs). A total of 95 articles published from
1984 to 2012 were selected for inclusion. Some hypotheses for PD evolved greatly
due to the reproducibility of PAs in a controlled environment using the safe and
noninvasive CO2 test. The 35% CO2 protocol was the method chosen by the majority of
studies. Results of the test report specific sensitivity to hypercapnia in PD
patients of the respiratory PD subtype. The CO2 challenge helped assess the
antipanic effects of medication and non-pharmaceutical approaches such as physical
exercise and cognitive behavioral therapy. The test was also used in studies about
the genetic component of PD, in which twins and relatives of PD patients were
analyzed.
Fear and anxiety are debilitating conditions that affect a significant number of
individuals in their lifetimes. Understanding underlying mechanisms of these
disorders affords us the possibility of therapeutic intervention. Such clarity in
terms of mechanism and intervention can only come from an amalgamation of research
from human to animal studies that attempt to mimic the human condition, both of
which are discussed in this review. We begin by presenting an outline of our
current understanding of the neurobiological basis of fear and anxiety. This
outline spans various levels of organization that include the circuitry, molecular
pathways, genetic and epigenetic components of fear and anxiety. Using these
organizational levels as a scaffold, we then discuss strategies that are currently
used to ameliorate these disorders, and forecast future interventions that hold
therapeutic promise. Among these newer promising treatments, we include,
optogenetic, pharmacological, and extinction-based approaches, as well as lifestyle
modifications, with combinatorial treatment regimens of these holding the most
promise.
Background: Panic disorder, a relatively common anxiety disorder, is often
associated to agoraphobia and may be disabling. Its neurobiological underpinnings
are unknown, despite the proliferation of models and hypotheses concerning it;
investigating its correlates could provide the means for better understanding its
pathophysiology. Recent structural neuroimaging techniques may contribute to the
identification of possible brain morphological alterations that could be possibly
related to the clinical expression of panic disorder. Methods: Through careful
major database searches, using terms keen to panic, agoraphobia, structural
magnetic neuroimaging and the like, we identified papers published in peer-review
journals and reporting data on the brain structure of patients with panic disorder.
Included papers were used comparatively to speculate about the nature of reported
brain structural alterations. Results: Anxiety, which is the core feature of the
disorder, correlates with the function of the amygdala, which showed a smaller
volume in patients, as compared to healthy subjects. Data also showed a volumetric
decrease of the anterior cingulate along with increased fractional anisotropy, and
increase of some brainstem nuclei, particularly of the rostral pons. Other
structures with reported volumetric correlates of panic disorder are the
hippocampus and the parahippocampal cortices, the insula, the putamen, and the
pituitary gland. Volumetric changes in the anterior cingulate, frontal,
orbitofrontal, insular, and temporal cortices have also been described in
structural neuroimaging studies. Major methodological limitations are considered in
context. Conclusions: Several data point to the existence of structural
neuroanatomical alterations in panic disorder, consisting in significant volumetric
reductions or increases in different brain areas. White matter alterations were
shown also in the only diffusion tensor imaging study performed to date. Available
data do not allow us to conclude about the possible progression of these
alterations.
Objective Fear of cancer recurrence (FCR) is a significant psychological problem
for cancer survivors. Some survivors experience FCR, which is both persistent and
highly distressing. The aim of this systematic review was to identify the key
factors associated with fear of recurrence among cancer patients. Methods A
comprehensive literature search using keywords was performed with three databases,
followed by an organic search to identify additional relevant articles. Included
studies had a quantitative methodology presenting empirical findings focussed on
adult cancer patients. A methodological quality assessment was performed for each
study, and the strength of evidence was defined by the consistency of results.
Results Forty-three studies met the inclusion criteria and are presented in this
review. The most consistent predictor of elevated FCR was younger age. There was
strong evidence for an association between physical symptoms and fear of cancer
recurrence. Additional factors moderately associated with increased FCR included
treatment type, low optimism, family stressors and fewer significant others.
Inconsistent evidence was found for socio-demographic factors. Conclusions Fear of
cancer recurrence is a complex issue influenced by a multitude of factors,
including demographic, clinical and psychological factors. However, some studies
have reported contradictory evidence, and FCR has been measured using a range of
scales, which can hamper comparison across studies. Further research is needed to
clarify inconsistencies in the current published research. Copyright (c) 2012 John
Wiley & Sons, Ltd.
The medial prefrontal cortex (mPFC) has emerged as a key structure involved in the
modulation of fear behavior over the past few decades. Anatomical, functional and
electrophysiological studies have begun to shed light on the precise mechanisms by
which different prefrontal regions regulate the expression and inhibition of fear
behavior. These studies have established a canonical view of mPFC functions during
fear behavior with dorsal regions selectively involved in the expression of fear
behavior and ventral regions linked to the inhibition of fear behavior. Although
numerous reports support this view, recent data have refined this model and
suggested that dorsal prefrontal regions might also play an important role in the
encoding of fear behavior itself. The recent development of sophisticated
approaches such as large scale neuronal recordings, simultaneous multisite
recordings of spiking activity and local field potentials (LFPs) along with
optogenetic approaches will facilitate the testing of these new hypotheses in the
near future. Here we provide an extensive review of the literature on the role of
mPFC in fear behavior and propose further directions to dissect the contribution of
specific prefrontal neuronal elements and circuits in the regulation of fear
behavior. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
Selective serotonin reuptake inhibitors (SSRIs) are widely used for the treatment
of a spectrum of anxiety disorders, yet paradoxically they may increase symptoms of
anxiety when treatment is first initiated. Despite extensive research over the past
30 years focused on SSRI treatment, the precise mechanisms by which SSRIs exert
these opposing acute and chronic effects on anxiety remain unknown. By testing the
behavioral effects of SSRI treatment on Pavlovian fear conditioning, a well
characterized model of emotional learning, we have the opportunity to identify how
SSRIs affect the functioning of specific brain regions, including the amygdala, bed
nucleus of the stria terminalis (BNST) and hippocampus. In this review, we first
define different stages of learning involved in cued and context fear conditioning
and describe the neural circuits underlying these processes. We examine the results
of numerous rodent studies investigating how acute SSRI treatment modulates fear
learning and relate these effects to the known functions of serotonin in specific
brain regions. With these findings, we propose a model by which acute SSRI
administration, by altering neural activity in the extended amygdala and
hippocampus, enhances both acquisition and expression of cued fear conditioning,
but impairs the expression of contextual fear conditioning. Finally, we review the
literature examining the effects of chronic SSRI treatment on fear conditioning in
rodents and describe how downregulation of N-methyl-D-aspartate (NMDA) receptors in
the amygdala and hippocampus may mediate the impairments in fear learning and
memory that are reported. While long-term SSRI treatment effectively reduces
symptoms of anxiety, their disruptive effects on fear learning should be kept in
mind when combining chronic SSRI treatment and learning-based therapies, such as
cognitive behavioral therapy. (C) 2013 IBRO. Published by Elsevier Ltd. All rights
reserved.
Gene-environment interaction is a form of causal interplay, whereby genetic effects
on phenotypic variation change as a function of environmental exposure. While
conceptually appealing, there is still much debate on the veracity and the
relevance of this form of etiological interdependence for psychiatric disorders. By
focusing on panic disorder (PD) and posttraumatic stress disorder (PTSD), this
article outlines why gene-environment interaction is controversial, why it can be
important for both researchers and clinicians, and how it is investigated by
quantitative genetic, molecular genetic, and genomic strategies. It is suggested
that gene-environment interaction effects are more reliable and meaningful when
they can be harnessed to pinpoint specific biological pathways and mechanisms. In
psychiatry, this can be guided by phenotypic dissection and realized by adopting
intermediate phenotypes of a physiological nature, such as carbon dioxide
sensitivity for PD, or gene expression profiling after stress for PTSD. A
developmental framework of reference and the possibility of transferring the
investigation to animal models are additional key elements in this debate.
People who are highly anxious about undergoing dental treatment comprise
approximately one in seven of the population and require careful and considerate
management by dental practitioners. This paper presents a review of a number of
non-pharmacological (behavioural and cognitive) techniques that can be used in the
dental clinic or surgery in order to assist anxious individuals obtain needed
dental care. Practical advice for managing anxious patients is provided and the
evidence base for the various approaches is examined and summarized. The importance
of firstly identifying dental fear and then understanding its aetiology, nature and
associated components is stressed. Anxiety management techniques range from good
communication and establishing rapport to the use of systematic desensitization and
hypnosis. Some techniques require specialist training but many others could
usefully be adopted for all dental patients, regardless of their known level of
dental anxiety. It is concluded that successfully managing dentally fearful
individuals is achievable for clinicians but requires a greater level of
understanding, good communication and a phased treatment approach. There is an
acceptable evidence base for several non-pharmacological anxiety management
practices to help augment dental practitioners providing care to anxious or fearful
children and adults.
Selective serotonin reuptake inhibitors and venlafaxine are currently considered as
first-line agents for patients with panic disorder (PD). However, a systematic
comparison of newer antidepressants for the treatment of PD is lacking thus far.
Eligible studies focusing on PD patients treated with newer antidepressants were
entered in the Cochrane Collaboration Review Manager. Our primary outcome measure
was the mean change in panic symptoms from the baseline to the endpoint in patients
treated with antidepressants as compared with those treated with placebo. Secondary
outcome measures included the mean change in the overall anxiety scores and dropout
rates. Sensitivity analyses were also carried out. Fifty studies focusing on 5236
patients were included. The following antidepressants were significantly superior
to placebo for PD patients with the following increasing order of effectiveness:
citalopram, sertraline, paroxetine, fluoxetine, and venlafaxine for panic symptoms
and paroxetine, fluoxetine, fluvoxamine, citalopram, venlafaxine, and mirtazapine
for overall anxiety symptoms. Aside from reboxetine and fluvoxamine, all drugs were
associated with significantly lower dropout rates as compared with placebo. Several
clinical variables moderated clinical outcomes. However, because of some
inconsistencies across the studies and limited evidence for some drugs under
investigation, further head-to-head comparisons are required. Int Clin
Psychopharmacol 28:33-45 (C) 2012 Wolters Kluwer Health vertical bar Lippincott
Williams & Wilkins. International Clinical Psychopharmacology 2013, 28:33-45
Objective: To conduct a review of the literature on the possible neuropsychological
deficits present in patients with panic disorder. Methods: We performed a
systematic review and search of the PubMed, ISI and PsycInfo scientific databases,
with no time limits, using the following key words: cognitive, function, panic, and
disorder. Of the 971 articles found, 25 were selected and 17 were included in this
review. The inclusion criterion was at least one neuropsychological assessment task
in patients with panic disorder. Results: The number of publications has grown
gradually, especially those assessing executive functions, corresponding to the
neurobiological model most widely accepted. Of all the functions evaluated, these
patients had lower performance in memory tasks and higher performance in affective
processing tasks related to the disorder. However, these data require further
investigation due to the high rate of comorbidities, the small sample sizes of the
included studies and little standardization of instruments used. Conclusion: The
results showed a greater occurrence of deficits in memory and enhanced affective
processing related to panic disorder.
Each of us has felt afraid, and we can all recognize fear in many animal species.
Yet there is no consensus in the scientific study of fear. Some argue that 'fear'
is a psychological construct rather than something discoverable through scientific
investigation. Others argue that the term 'fear' cannot properly be applied to
animals because we cannot know whether they feel afraid. Studies in rodents show
that there are highly specific brain circuits for fear, whereas findings from human
neuroimaging seem to make the opposite claim. Here, I review the field and urge
three approaches that could reconcile the debates. For one, we need a broadly
comparative approach that would identify core components of fear conserved across
phylogeny. This also pushes us towards the second point of emphasis: an ecological
theory of fear that is essentially functional. Finally, we should aim even to
incorporate the conscious experience of being afraid, reinvigorating the study of
feelings across species.
Panic disorder (PD) is characterized by panic attacks, anticipatory anxiety and
avoidance behavior. Its pathogenesis is complex and includes both neurobiological
and psychological factors. With regard to neurobiological underpinnings, anxiety in
humans seems to be mediated through a neuronal network, which involves several
distinct brain regions, neuronal circuits and projections as well as
neurotransmitters. A large body of evidence suggests that the neuropeptide
cholecystokinin (CCK) might be an important modulator of this neuronal network. Key
regions of the fear network, such as amygdala, hypothalamus, peraqueductal grey, or
cortical regions seem to be connected by CCKergic pathways. CCK interacts with
several anxiety-relevant neurotransmitters such as the serotonergic, GABA-ergic and
noradrenergic system as well as with endocannabinoids, NPY and NPS. In humans,
administration of CCK-4 reliably provokes panic attacks, which can be blocked by
antipanic medication. Also, there is some support for a role of the CCK system in
the genetic pathomechanism of PD with particularly strong evidence for the CCK gene
itself and the CCK-2R (CCKBR) gene. Thus, it is hypothesized that genetic variants
in the CCK system might contribute to the biological basis for the postulated CCK
dysfunction in the fear network underlying PD. Taken together, a large body of
evidence suggests a possible role for the neuropeptide CCK in PD with regard to
neuroanatomical circuits, neurotransmitters and genetic factors. This review
article proposes an extended hypothetical model for human PD, which integrates
preclinical and clinical findings on CCK in addition to existing theories of the
pathogenesis of PD.
Background: Panic disorder (PD) has a strong genetic component showing high
heritability rates and familial aggregation. Moreover, there is evidence for
associations between parental PD and patterns of psychopathology. So far, little is
known about possible endophenotypes representing premorbid vulnerability markers in
high-risk subjects for PD. In the present study, we investigated saccadic eye
movement (SEM) as an index of CNS inhibitory function in subjects at high risk for
PD. Methods: 132 healthy children at high and low familial risk for PD were
included in the study. Basal SEM parameters were obtained using an electro-
oculography (EOG) based system measuring peak saccadic eye velocity (pSEV), latency
and accuracy. Moreover, with regard to self rating scales, state-trait-anxiety
(STAI-C), childhood behavioral inhibition (CSRI), and anxiety sensitivity (CASI)
were assessed. Results: There was a significant overall difference for basal SEM
parameters across groups as revealed by MANCOVA (F-7,F-118=2.184, p=.040). A
significant influence was found for the covariate age, while gender and puberty
status had no influence on SEM. High-risk (HR) subjects showed significantly lower
pSEV. Moreover, levels of state and trait anxiety were higher in HR children (F-
1=5.429, p=.021). Discussion: In our sample, measurement of pSEV allowed
discrimination between children at high and low risk for PD. Since these results
argue for possible alterations of saccadic function in high risk subjects,
differences in underlying neurobiological mechanisms might be discussed as a
possible endophenotype of PD.
Hypereosinophilia is asymptomatic but can induce organ damage, which may cause
neurological system abnormalities. We recently encountered a 29-year-old woman with
depressive episodes who had eosinophilia as well as hyperventilation attacks,
tremor, insomnia, and arthralgia of extremities after receiving paroxetine
treatment. In parallel with the decrease in paroxetine dose, eosinophil count
decreased and the related symptoms improved. Because it is sometimes difficult to
distinguish between psychiatric symptoms such as panic attack and eosinophilia-
related symptoms, frequent hematologic examination is required for patients treated
with paroxetine.
Previous terror management theory research has shown that mortality salience (MS; a
death reminder) leads to the derogation of those who are perceived to be threats to
or violators of one's cultural worldview. Immigrants may be viewed as such a
threat, but not necessarily to all majority group members of the culture. The
studies presented here tested the hypothesis that, depending upon the nature of the
participants' worldview, MS would either increase or decrease liking of an
immigrant. After being reminded of their mortality or a control topic, French and
American college students evaluated an immigrant. To assess differences in
worldview, participants completed a measure of right-wing authoritarianism (RWA).
Consistent across two studies, MS led to more negative evaluations of an immigrant
among those high in RWA, but more positive evaluations for those low in RWA.
Discussion focuses on the implications of these findings for understanding the
interplay of mortality concerns and RWA in determining attitudes toward immigrants.
Over the last decades there has been an increasing interest in a possible role of
curcumin on cancer. Although curcumin is considered safe for healthy people,
conclusive evidence on the safety and efficacy of curcumin for patients with
monoclonal gammopathies is, so far, lacking. The present paper reviews the
literature on molecular, cellular and clinical effects of curcumin in an attempt to
identify, reasons for optimism but also for concern. The results of this critical
evaluation can be useful for both patient- selection and monitoring in the context
of clinical trials. Curcumin might be helpful for some but certainly not for all
patients with monoclonal gammopathies. It is important to avoid unnecessary
detrimental side effects in some in order to safeguard curcumin for those that
could benefit. Parameters for patient monitoring, that can be used as early warning
signs and as indicators of a favorable development have therefore been suggested.
(c) 2012 Elsevier Ireland Ltd. All rights reserved.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a proven animal carcinogen.
Occupational cohorts with the highest exposures imply that there is a small risk of
all cancers combined, but it is difficult to pinpoint the confounding effect of the
main chemicals. Studies after major accidents do not unequivocally confirm this
risk. The risks to populations at the current dioxin levels seem trivial if present
at all. There is increasing evidence that the aryl hydrocarbon receptor (AhR), i.e.
the so called "dioxin receptor", is a physiological transcription factor exerting
important functions in the body. Consequently a certain level of AhR activation may
be beneficial rather than harmful. This challenges the wisdom of excessive
regulation of dioxin levels in certain foods and nutrients. This could pose
indirect nutritional risks, in fact being more harmful than even the worst case
predictions of the putative cancer risks attributable to dioxins. (C) 2012 Elsevier
Ireland Ltd. All rights reserved.
Conditioning and extinction of fear have traditionally been viewed as two
independent learning processes for encoding representations of contexts or cues
(conditioned stimuli, CS), aversive events (unconditioned stimuli, US), and their
relationship. Based on the analysis of protein kinase signaling patterns in neurons
of the fear circuit, we propose that fear and extinction are best conceptualized as
emotional states triggered by a single CS representation with two opposing values:
aversive and non-aversive. These values are conferred by the presence or absence of
the US and encoded by distinct sets of kinase signaling pathways and their
downstream targets. Modulating specific protein kinases thus has the potential to
modify emotional states, and hence, may emerge as a promising treatment for anxiety
disorders.
Published and informal assessments of the prospects for neuroimaging in political
science have tended to range from overexuberant to reflexively dismissive. We seek
to present a cautious but fair middle ground in considering this new methodology,
primarily from an epistemological perspective. Our examination centers on the
relationship between two levels of analysis, focusing on the potential for
connection between behavior-based theories of political psychology and cognition
and the neural processes and systems involved in generating behaviors and states of
mind. We explore the place of each level of analysis on its own, as well as the
potential for the fruitful interaction of the two. This analysis brings together
opinions and ideas presented by others in various forums and across multiple
disciplines, offers a discussion of the the promises and perils of neuroimaging in
its application to social science, as well as some practical thoughts regarding its
early-stage incorporation into political psychology. We argue in favor of
proceeding with more substantial incorporation of neuroimaging into political
psychology's methodological arsenal, but note that this will initially require both
(1) greater acceptance of work more focused on presenting empirical results than on
providing dispositive evidence in broader theoretical debates and (2) a commitment
on the part of those conducting this research to refrain from overstating the
definitiveness of its theoretical implications.
Introduction: Since fear of falling has been linked to self-restriction of activity
a further decline in physical functioning and a greater risk of falling,
interventions, such as use of telecare, to address a person's fear are essential to
reduce the risk of further falls. The aim of this critical review was to evaluate
the association between older people's fear of falling and the use of telecare, and
whether telecare could reduce this fear. Method: A search of major databases (1980-
2011) identified 424 results and, following screening, 10 articles were included in
the review. Findings: Perceptions of older people about using telecare were mixed:
some felt a greater sense of security and reassurance but, for others, confidence
levels were not increased. Studies suggest that an automatic fall detector was
useful for older people who were unable or reluctant to use a pendant alarm
following a fall. Conclusion: The use of telecare including the wearing of an
automatic fall detector, while improving confidence and reducing fear of falling in
some, does not suit everyone. A careful assessment of a person's views on his or
her falls risk and level of anxiety will determine how telecare can best meet the
person's needs to remain supported at home.
Evidence for the involvement of the endocannabinoid system (ECS) in anxiety and
fear has been accumulated, providing leads for novel therapeutic approaches. In
anxiety, a bidirectional influence of the ECS has been reported, whereby anxiolytic
and anxiogenic responses have been obtained after both increases and decreases of
the endocannabinoid tone. The recently developed genetic tools have revealed
different but complementary roles for the cannabinoid type 1 (CB1) receptor on
GABAergic and glutamatergic neuronal populations. This dual functionality, together
with the plasticity of CB1 receptor expression, particularly on GABAergic neurons,
as induced by stressful and rewarding experiences, gives the ECS a unique
regulatory capacity for maintaining emotional homeostasis. However, the promiscuity
of the endogenous ligands of the CB1 receptor complicates the interpretation of
experimental data concerning ECS and anxiety. In fear memory paradigms, the ECS is
mostly involved in the two opposing processes of reconsolidation and extinction of
the fear memory. Whereas ECS activation deteriorates reconsolidation, proper
extinction depends on intact CB1 receptor signalling. Thus, both for anxiety and
fear memory processing, endocannabinoid signalling may ensure an appropriate
reaction to stressful events. Therefore, the ECS can be considered as a regulatory
buffer system for emotional responses.
The endocannabinoid system seems to play very specific roles in fear extinction,
which can only be described within a well-defined model of the various fear relief
processes. We, therefore, seek to clarify the current conceptual framework of fear
relief within classical and operant fear conditioning paradigms as well as propose
new clarifications within this framework where necessary. Based on these revisions
as well as previous research involving the endocannabinoid system and fear relief,
we are able to pinpoint the processes in which endocannabinoids seem to play a
significant role. Following auditory-cued fear conditioning, this applies in
particular to habituation and its involvement in acute and long-lasting fear
relief. Following contextual conditioning, in contrast, endocannabinoids seem to
affect relearning processes as well. Furthermore, we describe how the involvement
of the endocannabinoid system develops over the course of the fear relief process
and what this may imply for the clinical use of pharmacotherapies targeting the
endocannabinoid system in treating fear and anxiety disorders. This article is part
of a Special Issue entitled: Stress, Emotional Behavior and the Endocannabinoid
System. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
Background: The validity of experimentally induced panic attacks as a model to
study the pathophysiology of panic disorder has been questioned. Unspecific,
unpleasant and aversive effects as well as specific patterns of psychovegetative
symptoms pointing to different subtypes of panic disorder patients have been
observed. These findings raise the question of challenge paradigms as a valuable
tool to identify different vulnerabilities in patients with panic disorder.
Methods: We compared the two most widely studied panicogenic drugs sodium lactate
and cholecystokinine tetrapeptide (CCK-4) with placebo in 25 patients with panic
disorder and matched healthy control subjects. Psychophysiological changes were
measured using the Acute Panic Inventory (API) and visual analogue scales for
anxiety and arousal. Results: In patients with panic disorder 18 out of 25
experienced a sodium lactate- or a CCK-4 induced panic attack. Lactate or CCK-4
induced symptoms and induced panic attacks were only correlated in healthy
controls, but not in patients with panic disorder. Conclusion: The mechanisms of
lactate and CCK-4 induced panic attacks are distinct in panic disorder patients but
not in healthy controls. Different neurobiological vulnerabilities may be uncovered
by different challenges.
This review summarizes the latest developments in our understanding of amygdala
networks that support classical fear conditioning, the experimental paradigm most
commonly used to study learned fear in the laboratory. These recent advances have
considerable translational significance as congruent findings from studies of fear
learning in animals and humans indicate that anxiety disorders result from
abnormalities in the mechanisms that normally regulate conditioned fear. Because of
the introduction of new techniques and the continued use of traditional approaches,
it is becoming clear that conditioned fear involves much more complex networks than
initially believed, including coordinated interactions between multiple excitatory
and inhibitory circuits within the amygdala.
Over the course of natural history, countless animal species have evolved adaptive
behavioral systems to cope with dangerous situations and promote survival.
Emotional memories are central to these defense systems because they are rapidly
acquired and prepare organisms for future threat. Unfortunately, the persistence
and intrusion of memories of fearful experiences are quite common and can lead to
pathogenic conditions, such as anxiety and phobias. Over the course of the last 30
years, neuroscientists and psychologists alike have attempted to understand the
mechanisms by which the brain encodes and maintains these aversive memories. Of
equal interest, though, is the neurobiology of extinction memory formation as this
may shape current therapeutic techniques. Here we review the extant literature on
the neurobiology of fear and extinction memory formation, with a strong focus on
the cellular and molecular mechanisms underlying these processes. (C) 2012 Elsevier
Ltd. All rights reserved.
The habenula is a part of an evolutionarily highly conserved conduction pathway
within the limbic system that connects telencephalic nuclei to the brain stem
nuclei such as interpeduncular nucleus (IPN), the ventral tegmental area (VTA), and
the raphe. In mammals, the medial habenula receives inputs from the
septohippocampal system, and relaying such information to the IPN. In contrast, the
lateral habenula receives inputs from the ventral pallidum, a part of the basal
ganglia. The physical adjunction of these two habenular nuclei suggests that the
habenula may act asan intersection of the neural circuits for controlling emotion
and behavior. We have recently elucidated that zebrafish has the equivalent
structure as the mammalian habenula. The transgenic zebrafish, in which the neural
signal transmission from the lateral subnucleus of the dorsal habenula to the
dorsal IPN was selectively impaired, showed extremely enhanced levels of freezing
response to presentation of the conditioned aversive stimulus. Our observation
supports that the habenula may act as the multimodal switching board for
controlling emotional behaviors and/or memory in experience dependent manners. (c)
2011 Wiley Periodicals, Inc. Develop Neurobiol 72: 386394, 2012
Pharmacological treatment of anxiety is an important part of drug treatment in
palliative care. In this review we searched for the current evidence of
pharmacological treatment of anxiety in palliative care. A systematic search of
PubMed, Embase, PsycLIT, PsycINFO, CINAHL for studies of anxiety in palliative care
was carried out in January 2012. Furthermore we searched the Cochrane Library,
references of literature and leading textbooks. Studies were identified and
information was filled in a standardized extraction sheet. Studies have been
categorized and anxiety as an endpoint determined. A total of four controlled
studies, three uncontrolled studies, two retrospective studies, one case report,
two surveys, one systematic Cochrane review and one unsystematic review were
analyzed and included in this review. This indicates an overall low number of
studies for the pharmacological treatment of anxiety in palliative care. According
to our results, benzodiazepines are the most commonly used drugs in palliative
care. However, based on our review, there is no evidence-based recommendation for
the therapeutic use in palliative care. With the existing evidence no general
recommendations for pharmacological treatment of anxiety in palliative care can be
given. Even for the commonly used benzodiazepines, neuroleptics, antidepressants,
antihistamines and beta blockers for the treatment of anxiety no evidence based
recommendations can be made. However, these medications are commonly used to treat
anxiety in other patient populations and can also be used in palliative care
patients. According to our review we cannot recommend a single drug or give
recommendations regarding the dosage of drugs. There is a strong need for
randomized controlled trials to evaluate the effect of drug treatment of anxiety in
palliative care patients. The English full text version of this article will be
available in SpringerLink as of November 2012 (under "Supplemental").
Objective: To investigate the potential impact of increasing prescription rates of
alprazolam for the treatment of panic disorder (PD) in Australia through a review
of efficacy, tolerability and adverse outcome literature. Methods: Data were
sourced by a literature search using MEDLINE, Embase, PsycINFO and a manual search
of scientific journals to identify relevant articles. Clinical practice guidelines
from the American Psychiatric Association, National Institute of Clinical
Excellence, Royal Australian and New Zealand College of Psychiatrists and World
Federation of Societies of Biological Psychiatry were sourced. Prescription data
were sourced from Australian governmental sources. Results: Alprazolam has shown
efficacy for control of PD symptoms, particularly in short-term controlled clinical
trials, but is no longer recommended as a first-line pharmacological treatment due
to concerns about the risks of developing tolerance, dependence and abuse
potential. Almost no evidence is available comparing alprazolam to current first-
line pharmacological treatment. Despite this, prescription rates are increasing. A
number of potential issues including use in overdose and impact on car accidents
are noted. Conclusion: Although effective for PD symptoms in clinical trials, a
number of potential issues may exist with use. Consideration of its future place in
PD treatment in Australia may be warranted.
The transient receptor potential vanilloid type 1 channel (TRPV1; originally
vanilloid receptor VR1) is activated in peripheral terminals of nociceptive fibers
by noxious heat, low pH, and natural products such as capsaicin, the pungent
ingredient of red-hot chilli peppers. Evidence has been accumulating that TRPV1 is
expressed also in the brain, where it seems to be involved in antinociception,
locomotor control, and regulation of affective behaviors. This ion channel might be
activated by arachidonoyl ethanolamide (anandamide), the endogenous agonist of the
cannabinoid type 1 (CBI) receptor. However, while CB., activation leads to a
decrease in intracellular calcium and attenuation of synaptic transmission,
anandamide binding to TRPV1 results in elevated calcium levels and potentiated
synaptic transmission. This suggests a tripartite regulatory system with
antagonistic effects of CB, and TRPV1, which are tied together by the same
endogenous ligand. Such a system may have important implication for the modulation
of behavioral responses. The present commentary elaborates on this interplay
between CB, receptors and TRPV1 channels in the context of fear- and anxiety-
related behaviors. This article is part of a Special Issue entitled: Stress,
Emotional Behavior and the Endocannabinoid System. (C) 2011 IBRO. Published by
Elsevier Ltd. All rights reserved.
The capacity to associate neutral stimuli with affective value is an important
survival strategy that can be accomplished by cell assemblies obeying Hebbian
learning principles. In the neuroscience laboratory, classical fear conditioning
has been extensively used as a model to study learning-related changes in neural
structure and function. Here, we review the effects of classical fear conditioning
on electromagnetic brain activity in humans, focusing on how sensory systems adapt
to changing fear-related contingencies. By considering spatiotemporal patterns of
mass neuronal activity, we illustrate a range of cortical changes related to a
retuning of neuronal sensitivity to amplify signals consistent with fear-associated
stimuli at the cost of other sensory information. Putative mechanisms that may
underlie fear-associated plasticity at the level of the sensory cortices are
briefly considered, and several avenues for future work are outlined.
Both the rates of cesarean section and the rates and payouts from obstetrical
malpractice suits have risen in past decades, albeit not always in tandem. A great
deal of evidence suggests that physicians practice defensive medicine, and many
obstetricians acknowledge that a more liberal recourse to cesarean section is one
such behavior in which they sometimes engage. However the degree to which fear of
litigation actually is a contributor to, or perhaps even a driver of, the rising
cesarean section rate is not as clearly known. In this article I will discuss the
research that has been performed that attempts to epidemiologically assess the link
between lawsuits, malpractice premiums and cesarean section rates. I will also
consider factors beyond dollars and cents (e.g., cognitive biases, changing risk
tolerance of doctors and patients) that may lie at the base of the relationship.
Finally I will offer a brief discussion of how professional ethics should inform
the actions that physicians take in these difficult circumstances. Semin Perinatol
36:390-394 (C) 2012 Elsevier Inc. All rights reserved.
In 1993, the National Institutes of Health issued a mandate that funded research
must include participation by racial and ethnic minority groups, and researchers
were required to include in their proposals strategies by which they would achieve
diversity in their samples. A methodological search for randomized clinical trials
of panic disorder was conducted to evaluate ethnoracial differences in panic
disorder symptoms, rates of minority inclusion in North American studies, and
effective methods of minority recruitment. Less than half of the studies identified
reported ethnic and racial data for their sample. Of the 21 studies that did report
this information (n = 2687), 82.7% were European American/non-Hispanic White, 4.9%
were African American/Black, 3.4% were Hispanic, 1.1% were Asian American, and 1.4%
were another ethnicity. The remaining 6.5% was simply classified as other/non-
White. The primary recruitment techniques utilized were clinical referral and
advertising, but neither of these methods were correlated with improved minority
participation, nor was the number of recruitment sites. As minorities are greatly
underrepresented in panic disorder studies, reported treatment outcomes may not
generalize to all ethnic and cultural groups. Researchers have not followed NIH
guidelines regarding inclusion of special populations. Inclusion of minorities in
future studies is needed to fully understand issues related to the treatment of
panic disorder in non-White populations. Suggestions for improved recruitment of
ethnoracial minorities are discussed. (C) 2012 Elsevier Ltd. All rights reserved.
Guided by the diagnostic nosology, anxiety patients are expected to show defensive
hyperarousal during affective challenge, irrespective of the principal phenotype.
In the current study, patients representing the whole spectrum of anxiety disorders
(i.e., specific phobia, social phobia, panic disorder with or without agoraphobia,
obsessive-compulsive disorder, generalized anxiety disorder (GAD), posttraumatic
stress disorder(PTSD)), and healthy community control participants, completed an
imagery-based fear elicitation paradigm paralleling conventional intervention
techniques. Participants imagined threatening and neutral narratives as
physiological responses were recorded. Clear evidence emerged for exaggerated
reactivity to clinically relevant imagerymost pronounced in startle reflex
responding. However, defensive propensity varied across principal anxiety
disorders. Disorders characterized by focal fear and impairment (e.g., specific
phobia) showed robust fear potentiation. Conversely, for disorders of long-
enduring, pervasive apprehension and avoidance with broad anxiety and depression
comorbidity (e.g., PTSDsecondary to cumulative trauma, GAD), startle responses were
paradoxically diminished to all aversive contents. Patients whose expressed symptom
profiles were intermediate between focal fearfulness and broad anxious-misery in
both severity and chronicity exhibited a still heightened but more generalized
physiological propensity to respond defensively. Importantly, this defensive
physiological gradientthe inverse of self-reported distresswas evident not only
between but also within disorders. These results highlight that fear circuitry
could be dysregulated in chronic, pervasive anxiety, and preliminary functional
neuroimaging findings suggest that deficient amygdala recruitment could underlie
attenuated reflex responding. In summary, adaptive defensive engagement during
imagery may be compromised by long-term dysphoria and stressa phenomenon with
implications for prognosis and treatment planning.
Anxiety disorders represent the most prevalent psychiatric disorders. In addition,
a considerable burden is associated with them, not only for individual sufferers,
but also for the health care system. However, many patients who might benefit from
treatment are not diagnosed or treated. This may partly be due to lack of awareness
of the anxiety disorders by primary care practitioners and by the sufferers
themselves. In addition, the stigma still associated with psychiatric disorders and
lack of confidence in psychiatric treatments are factors leading to no/under
recognition and treatment, or the use of unnecessary or inappropriate treatments.
This paper aims to provide a comprehensive review of recommendations for the
pharmacological treatment of two common anxiety disorders, in particular obsessive-
compulsive disorder (OCD) and panic disorder (PD). The first-line treatments of OCD
include medium-high doses of selective serotonin reuptake inhibitors (SSRIs) and
clomipramine, a tricyclic (TCA) antidepressant with prevalent serotonergic
activity. The recommended drugs for PD include SSRIs, TCAs and serotonin-
norepinephrine reuptake inhibitors (SNRIs); in treatment-resistant cases,
benzodiazepines like alprazolam may be used in patients with no history of
addiction and tolerance. Other treatment options include irreversible and
reversible monoamine-oxidase inhibitors, hydroxyzine, and others. Besides
pharmacological treatments, some psychological strategies have been shown to be
effective, in particular, cognitive behavior therapy (CBT) and other variants of
behavior therapy that have been sufficiently investigated in controlled studies,
and, therefore, will be reviewed herein.
Posttraumatic stress disorder (PTSD) is an anxiety disorder that can develop after
a traumatic experience such as domestic violence, natural disasters or combat-
related trauma. The cost of such disorders on society and the individual can be
tremendous. In this article, we review how the neural circuitry implicated in PTSD
in humans is related to the neural circuitry of fear. We then discuss how fear
conditioning is a suitable model for studying the molecular mechanisms of the fear
components that underlie PTSD, and the biology of fear conditioning with a
particular focus on the brain-derived neurotrophic factor (BDNF)-tyrosine kinase B
(TrkB), GABAergic and glutamatergic ligand-receptor systems. We then summarize how
such approaches might help to inform our understanding of PTSD and other stress-
related disorders and provide insight to new pharmacological avenues of treatment
of PTSD.
Musculoskeletal pain (MP) is common in the general population and has been
associated with anxiety in several ways: (a) muscle tension is included as a part
of the diagnostic criteria for generalized anxiety disorder, (b) pain can be a
common symptom and a good indicator of an anxiety disorder, (c) anxiety is an
independent predictor of quality of life in patients with chronic MP, (d) anxiety
leads to higher levels of pain chronification, and (e) fear, anxiety, and avoidance
are related to MP. The objective of this article is to explore the mechanisms
underlying the relation between anxiety disorders and musculoskeletal pain as well
as its management. We have also highlighted the role of spirituality and
religiosity in MP treatment. We found some similarities between proposed mechanisms
and explicative models for both conditions as well as an overlapping between the
treatments available. The recognition of this association is important for
professionals who deal with chronic pain.
This paper presents the findings from a review of the theoretical and empirical
literature on the links between crime and fear of crime, the social and built
environment, and health and wellbeing. A pragmatic approach was employed, with
iterative stages of searching and synthesis. This produced a holistic causal
framework of pathways to guide future research. The framework emphasises that crime
and fear of crime may have substantial impacts on wellbeing, but the pathways are
often highly indirect, mediated by environmental factors, difficult to disentangle
and not always in the expected direction. The built environment, for example, may
affect health via its impacts on health behaviours; via its effects on crime and
fear of crime; or via the social environment. The framework also helps to identify
unexpected factors which may affect intervention success, such as the risk of
adverse effects from crime prevention interventions as a result of raising
awareness of crime. (C) 2012 Elsevier Ltd. All rights reserved.
The past two decades have brought dramatic progress in the neuroscience of anxiety
due, in no small part, to animal findings specifying the neurobiology of Pavlovian
fear-conditioning. Fortuitously, this neurally mapped process of fear learning is
widely expressed in humans, and has been centrally implicated in the etiology of
clinical anxiety. Fear-conditioning experiments in anxiety patients thus represent
a unique opportunity to bring recent advances in animal neuroscience to bear on
working, brain-based models of clinical anxiety. The current presentation details
the neural basis and clinical relevance of fear conditioning, and highlights
generalization of conditioned fear to stimuli resembling the conditioned danger cue
as one of the more robust conditioning markers of clinical anxiety. Studies testing
such generalization across a variety of anxiety disorders (panic, generalized
anxiety disorder, and social anxiety disorder) with systematic methods developed in
animals will next be presented. Finally, neural accounts of overgeneralization
deriving from animal and human data will be described with emphasis given to
implications for the neurobiology and treatment of clinical anxiety.
The present review examines the role of perirhinal cortex (PRC) in Pavlovian fear
conditioning. The focus is on rats, partly because so much is known, behaviorally
and neurobiologically, about fear conditioning in these animals. In addition, the
neuroanatomy and neurophysiology of rat PRC have been described in considerable
detail at the cellular and systems levels. The evidence suggests that PRC can serve
at least two types of mnemonic functions in Pavlovian fear conditioning. The first
function, termed stimulus unitization, refers to the ability to treat two or more
separate items or stimulus elements as a single entity. Supporting evidence for
this perceptual function comes from studies of context conditioning as well as
delay conditioning to discontinuous auditory cues. In a delay paradigm, the
conditional stimulus (CS) and unconditional stimulus (US) overlap temporally and
co-terminate. The second PRC function entails a type of transient memory.
Supporting evidence comes from studies of trace cue conditioning, where there is a
temporal gap or trace interval between the CS offset and the US onset. For learning
to occur, there must be a transient CS representation during the trace interval. We
advance a novel neurophysiological mechanism for this transient representation.
These two hypothesized functions of PRC are consistent with inferences based on
non-aversive forms of learning. (C) 2012 Wiley Periodicals, Inc.
This article is part of a Special Issue "Neuroendocrine-Immune Axis in Health and
Disease." Behavioural and neurophysiological traits and responses associated with
anxiety and predation-related fear have been well documented in rodent models.
Certain parasites and pathogens which rely on predation for transmission appear
able to manipulate these, often innate, traits to increase the likelihood of their
life-cycle being completed. This can occur through a range of mechanisms, such as
alteration of hormonal and neurotransmitter communication and/or direct
interference with the neurons and brain regions that mediate behavioural
expression. Whilst some post-infection behavioural changes may reflect 'general
sickness' or a pathological by-product of infection, others may have a specific
adaptive advantage to the parasite and be indicative of active manipulation of host
behaviour. Here we review the key mechanisms by which anxiety and predation-related
fears are controlled in mammals, before exploring evidence for how some infectious
agents may manipulate these mechanisms. The protozoan Toxoplasma gondii, the
causative agent of toxoplasmosis, is focused on as a prime example. Selective
pressures appear to have allowed this parasite to evolve strategies to alter the
behaviour in its natural intermediate rodent host. Latent infection has also been
associated with a range of altered behavioural profiles, from subtle to severe, in
other secondary host species including humans. In addition to enhancing our
knowledge of the evolution of parasite manipulation in general, to further our
understanding of how and when these potential changes to human host behaviour
occur, and how we may prevent or manage them, it is imperative to elucidate the
associated mechanisms involved. (C) 2012 Elsevier Inc. All rights reserved.
Catechol-O-methyltransferase (COMT) and serotonin receptor 2A (5HTR2A)
polymorphisms have been investigated for their possible role in panic disorder
(PD). The aim of this study was to investigate the genotype distribution of the
COMT val158met and 5HTR2A 102T/C polymorphisms in PD. COMT val158met is a
polymorphism at codon 158 that results in variations in COMT enzymatic activity
with high-(H) and low-activity (L) alleles. The 5HTR2A 102T/C polymorphism
comprises a T-to-C mutation at position 102. The effects of symptom severity,
gender, and age of onset were also investigated. The participants were 105
outpatients with PD and 130 controls. The severity of the symptoms of PD was
assessed by the Panic and Agoraphobia Scale (PAS). Polymorphisms of the 5HTR2A and
COMT genes were identified using polymerase chain reaction and restriction fragment
length polymorphism analysis. A significant relationship was found between the COMT
Val158Met polymorphism and PD. No significant differences were found in genotype
distributions or allele frequencies of the 5HTR2A polymorphisms between the PD and
control groups. There were no significant relationships between the COMT and 5HTR2A
polymorphisms and age of onset, gender, presence of agoraphobia, or PAS scores in
the PD group (p > 0.05). (C) 2011 Elsevier Inc. All rights reserved.
Panic disorder (PD) is a severe anxiety disorder characterized by susceptibility to
induction of panic attacks by subthreshold interoceptive stimuli such as sodium
lactate infusions or hypercapnia induction. Here we review a model of panic
vulnerability in rats involving chronic inhibition of GABAergic tone in the
dorsomedial/perifornical hypothalamic (DMH/PeF) region that produces enhanced
anxiety and freezing responses in fearful situations, as well as a vulnerability to
displaying acute panic-like increases in cardioexcitation, respiration activity and
"flight" associated behavior following subthreshold interoceptive stimuli that do
not elicit panic responses in control rats. This model of panic vulnerability was
developed over 15 years ago and has provided an excellent preclinical model with
robust face, predictive and construct validity. The model recapitulates many of the
phenotypic features of panic attacks associated with human panic disorder (face
validity) including greater sensitivity to panicogenic stimuli demonstrated by
sudden onset of anxiety and autonomic activation following an administration of a
sub-threshold (i.e., do not usually induce panic in healthy subjects) stimulus such
as sodium lactate, CO2, or yohimbine. The construct validity is supported by
several key findings; DMH/PeF neurons regulate behavioral and autonomic components
of a normal adaptive panic response, as well as being implicated in eliciting
panic-like responses in humans. Additionally, patients with PD have deficits in
central GABA activity and pharmacological restoration of central GABA activity
prevents panic attacks, consistent with this model. The model's predictive validity
is demonstrated by not only showing panic responses to several panic-inducing
agents that elicit panic in patients with PD, but also by the positive therapeutic
responses to clinically used agents such as alprazolam and antidepressants that
attenuate panic attacks in patients. More importantly, this model has been utilized
to discover novel drugs such as group II metabotropic glutamate agonists and a new
class of translocator protein enhancers of GABA, both of which subsequently showed
anti-panic properties in clinical trials. All of these data suggest that this
preparation provides a strong preclinical model of some forms of human panic
disorders. (C) 2012 Elsevier Inc. All rights reserved.
Pavlovian fear conditioning, also known as classical fear conditioning is an
important model in the study of the neurobiology of normal and pathological fear.
Progress in the neurobiology of Pavlovian fear also enhances our understanding of
disorders such as posttraumatic stress disorder (PTSD) and with developing
effective treatment strategies. Here we describe how Pavlovian fear conditioning is
a key tool for understanding both the neurobiology of fear and the mechanisms
underlying variations in fear memory strength observed across different phenotypes.
First we discuss how Pavlovian fear models aspects of PTSD. Second, we describe the
neural circuits of Pavlovian fear and the molecular mechanisms within these
circuits that regulate fear memory. Finally, we show how fear memory strength is
heritable; and describe genes which are specifically linked to both changes in
Pavlovian fear behavior and to its underlying neural circuitry. These emerging data
begin to define the essential genes, cells and circuits that contribute to normal
and pathological fear. This article is part of a Special Issue entitled 'Post-
Traumatic Stress Disorder'. (C) 2011 Published by Elsevier Ltd.
Emotional responses are triggered by environmental signals and involve profound
changes at multiple levels, from molecular to behavior. Much has been learnt about
two emotions, fear and anxiety, by studying mammalian models. In particular, neural
circuits and the corresponding molecular mechanisms essential for the learning and
retention of fear, as well as the activation of anxiety, are well known. In
contrast, little is known about how these emotions are terminated. The zebrafish is
a newcomer to the world of emotion research. A number of assays for fear and
anxiety now exist, but the underlying neural circuitry is largely undefined. Recent
experiments, however, appear to provide a hint as to how anxiety is downregulated.
In particular, they point to an essential role for a circuit involving the
posterior septum, medial habenula, and interpeduncular nucleus. This evolutionarily
conserved circuit may fulfill a similar function in mammals. (c) 2011 Wiley
Periodicals, Inc. Develop Neurobiol 72: 395403, 2012
Panic disorder is a frequent and disabling mental disorder characterized by
recurrent periods or abrupt surges of intense fear or discomfort, the panic
attacks. The clinical phenomenology of panic attacks suggests a prominent role of a
disturbed stress response regulation in the aetiopathology of this disorder. We
summarize the results of challenge tests of the hypothalamus-pituitary-
adrenocortical (HPA) axis in panic disorder and give an overview of studies using
psychosocial challenge paradigms. The results of HPA axis challenge tests suggest
an increased expression of the hypothalamic neuropeptides, but an intact negative
feedback inhibition at the level of the pituitary. Psychosocial challenge tests
give evidence for dissociation between the subjective stress response and the HPA
axis response in panic disorder, which might be the result of an over-focussed
self-monitoring leading to an enhanced stress perception despite normal HPA axis
activation. We integrated these findings in a cognitive stress control model
suggesting that panic disorder patients develop efficient strategies to control the
somatic stress response despite a hypothalamic hyperdrive of the HPA axis. To
employ these strategies at the right time, patients acquired an enhanced perception
of stress symptoms, leading to the reported dissociation of the subjective and HPA
axis response. It can be inferred from these findings that cognitive behavioral
therapy addressing over-focussed self-monitoring and maladaptive control strategies
in combination with pharmacological treatment against over-expression of the
hypothalamic neuropeptides should be an effective treatment in severe forms of
panic disorder, which corresponds with recent treatment guidelines.
Fear is an emotion that has powerful effects on behaviour and physiology across
animal species. It is accepted that the amygdala has a central role in processing
fear. However, it is less widely appreciated that distinct amygdala outputs and
downstream circuits are involved in different types of fear. Data show that fear of
painful stimuli, predators and aggressive members of the same species are processed
in independent neural circuits that involve the amygdala and downstream
hypothalamic and brainstem circuits. Here, we discuss data supporting multiple fear
pathways and the implications of this distributed system for understanding and
treating fear.
Ionizing radiation during pregnancy can negatively impact a fetus. In light of the
Fukushima nuclear plant disaster in Japan, we discuss existing knowledge on the
health effects of radiation and preventive measures for pregnant women. Overall,
the risk of exposure to radiation is limited but severe defects can result from
fetal radiation exposure > 100 mGy equivalent to 10 rad ( > 1000 chest x-rays).
While such high-level exposure rarely occurs during single medical diagnostic
procedures, caution should be exercised for pregnant women. As a protective public
health measure in light of a disaster, evacuation, shielding, and elimination of
ingested radioactive isotopes should all be considered. Detailed radiation reports
with health effects and precautionary measures should be available for a population
exposed to more than background radiation.
Panic disorder patients are vulnerable to recurrent panic attacks. Two
neurochemical hypotheses have been proposed to explain this susceptibility. The
first assumes that panic patients have deficient serotonergic inhibition of neurons
localized in the dorsal periaqueductal gray matter of the midbrain that organize
defensive reactions to cope with proximal threats and of sympathomotor control
areas of the rostral ventrolateral medulla that generate most of the
neurovegetative symptoms of the panic attack. The second suggests that endogenous
opioids buffer normal subjects from the behavioral and physiological manifestations
of the panic attack, and their deficit brings about heightened suffocation
sensitivity and separation anxiety in panic patients, making them more vulnerable
to panic attacks. Experimental results obtained in rats performing one-way escape
in the elevated T-maze, an animal model of panic, indicate that the inhibitory
action of serotonin on defense is connected with activation of endogenous opioids
in the periaqueductal gray. This allows reconciliation of the serotonergic and
opioidergic hypotheses of panic pathophysiology, the periaqueductal gray being the
fulcrum of serotonin-opioid interaction.
Anxiety and fear are among the most frequently reported emotional responses to
hospitalization and are known to be contributing factors to pain and other negative
patient outcomes. The first step in confronting unnecessary anxiety and fear is to
identify valid and clinically feasible assessment instruments. The purpose of this
paper is to review and evaluate instruments that measure children's fear or anxiety
associated with hospitalization or painful procedures. A search was conducted of
published English-language literature from 1980 through 2010 with the use of Ovid
Health and Psychosocial Instruments, Medline, Nursing/Academic Edition, Cinahl, and
Google Scholar. Inclusion criteria specified that the self-report instrument: 1)
was developed in English; 2) was developed for and/or widely used with hospitalized
children or children undergoing medical procedures or treatment; and 3) had
research evidence of psychometric properties from at least five different studies.
A comprehensive review of the literature revealed only five fear or anxiety
instruments with adequate testing for evaluation of reliability and validity.
Although all instruments have beginning psychometric adequacy, no one tool stands
out as superior to the others. Therefore, we recommend that researchers and
clinicians exercise caution in choosing assessment instruments, balancing potential
strengths with reported limitations. Using more than one tool (triangulating) may
be one way to achieve more credible results. Knowledge of credible existing
instruments alerts us to what is possible today and to the imperative for research
that will improve communication with children tomorrow. (C) 2012 by the American
Society for Pain Management Nursing
Anxiety is an important component of the psychopathology of the obsessive-
compulsive disorder (OCD). So far, most interventions that have proven to be
effective for treating OCD are similar to those developed for other anxiety
disorders. However, neurobiological studies of OCD came to conclusions that are not
always compatible with those previously associated with other anxiety disorders.
Objectives: The aim of this study is to review the degree of overlap between OCD
and other anxiety disorders phenomenology and pathophysiology to support the
rationale that guides research in this field. Results: Clues about the
neurocircuits involved in the manifestation of anxiety disorders have been obtained
through the study of animal anxiety models, and structural and functional
neuroimaging in humans. These investigations suggest that in OCD, in addition to
dysfunction in cortico-striatal pathways, the functioning of an alternative
neurocircuitry, which involves amygdalo-cortical interactions and participates in
fear conditioning and extinction processes, may be impaired. Conclusion: It is
likely that anxiety is a relevant dimension of OCD that impacts on other features
of this disorder. Therefore, future studies may benefit from the investigation of
the expression of fear and anxiety by OCD patients according to their type of
obsessions and compulsions, age of OCD onset, comorbidities, and patterns of
treatment response.
The present meta-analysis aimed to clarify whether deficits in emotion recognition
in psychopathy are restricted to certain emotions and modalities or whether they
are more pervasive. We also attempted to assess the influence of other important
variables: age, and the affective factor of psychopathy. A systematic search of
electronic databases and a subsequent manual search identified 26 studies that
included 29 experiments (N=1376) involving six emotion categories (anger, disgust,
fear, happiness, sadness, surprise) across three modalities (facial, vocal,
postural). Meta-analyses found evidence of pervasive impairments across modalities
(facial and vocal) with significant deficits evident for several emotions (i.e.,
not only fear and sadness) in both adults and children/adolescents. These results
are consistent with recent theorizing that the amygdala, which is believed to be
dysfunctional in psychopathy, has a broad role in emotion processing. We discuss
limitations of the available data that restrict the ability of meta-analysis to
consider the influence of age and separate the sub-factors of psychopathy,
highlighting important directions for future research. (C) 2012 Elsevier Ltd. All
rights reserved.
Purpose Panic Disorder (PD) is a classic example of a disease where symptom
remission may be achieved, yet patient quality of life (QOL) remains low, providing
further support for the need to measure QOL as an additional outcome in patient
care. The objectives of this review are to examine the substantial QOL impairments
in PD and to determine whether modern treatments for PD, which have been proven to
achieve symptom remission, have been shown to restore QOL. Methods We identified
studies on QOL in PD from 1980 to 2010 by searching MEDLINE, PsycINFO, and PubMed
databases. Results The literature reveals substantial QOL impairments in PD, often
resulting in poor sense of health, frequent utilization of medical services,
occupational deficiency, financial dependency, and marital strife. Modern therapies
have been demonstrated to achieve symptom remission and improve QOL in PD; however,
post-treatment QOL is still significantly lower than community averages.
Conclusions QOL needs to be added as an essential outcome measure in patient care.
Further research should be conducted to better understand the nature of
comorbidities in PD as well as to determine whether additional interventions that
have been studied in other psychiatric disorders, such as exercise, meditation,
yoga, humor, massage, and nutritional supplements, can be utilized to improve QOL
in PD to normal community levels.
Both news media and entertainment fiction may lead to short-term and enduring
fright reactions. Even TV programs, movies and news made for children may trigger
fear. Preoperational children (3 to 7 years of age) are most afraid of fantasy
characters, transformations and interpersonal violence. Operational children (8 to
11 years) are more afraid of abstract ideas and imagined implications regarding
their own risk. Pediatricians must include media in their history taking and beware
of ensuing fear, phobias, sleep and behavior problems. Parents can play a vital
role in preventing exposure to or mediating the effects of frightening media.
Hospitals must have a pediatric media exposure policy. Conclusion: Media use can
have immediate and enduring fear effects that affect many children and that are far
from trivial.
Understanding the spatial. dimension of fear of crime in the urban environment is
important to understanding behaviors in response to this concern. Making this
connection between perception and action has long been a goal of scholars in the
social and health sciences, though this complex relationship has yet to be fully
elucidated. Specifically, in studies on fear of crime and its influence on
behavior, a variety of definitions and methods have been employed. This situation
has yielded insights, as well as inconsistencies. In the past decade, Geographic
Information Systems (GIS) has been added to this methodological mix, though it too
has contributed limited understanding of the environmental perception-behavior
nexus. During this time, sonic scholars have integrated a traditional technique for
accessing environmental perception, the sketch map, with this newer technology.
This article provides a review and critical assessment: of the way GIS has been
used to understand fear of crime, specifically through the integration of sketch
maps. This focus is framed by an overview of substantive and methodological
concerns and concludes with a discussion of continued research needs. As behavioral
responses to fear of crime are acknowledged to impact physical and mental health
and overall well-being, in addition to the viability of neighborhoods, research in
this area will continue apace. However, for integration of sketch maps in GIS to be
a valuable methodological contributor to this line of inquiry, users of the
approach must understand its complexities. This article outlines these issues so
that they may be considered in future research and may improve the ability for this
approach to yield new understanding of fear of crime.
Safety signals are learned cues that predict the nonoccurrence of an aversive
event. As such, safety signals are potent inhibitors of fear and stress responses.
Investigations of safety signal learning have increased over the last few years due
in part to the finding that traumatized persons are unable to use safety cues to
inhibit fear, making it a clinically relevant phenotype. The goal of this review is
to present recent advances relating to the neural and behavioral mechanisms of
safety learning, and expression in rodents, nonhuman primates, and humans.
Results from the first publication of the Women's Health Initiative trial were
announced by press release and press conference in July 2002. The announcement
explained that the combined hormone trial had been terminated early because of
'increased breast cancer risk'. The dramatic nature of the announcement set the
tone for the early news reporting from the study and introduced a note of confusion
into the media's perception of hormone replacement therapy (HRT). Such a tone
persisted until July 2007, when the trial revised its findings on cardiovascular
risk. Despite investigators 'protests to the contrary, the results were perceived
by the press as a U-turn, and reinforced the media's confused interpretation of the
safety and benefits of HRT. We argue that the WHI's melodramatic presentation of
its results explains the media response.
The evidence-based pharmacotherapy of panic disorder continues to evolve. This
paper reviews data on first-line pharmacotherapy, evidence for maintenance
treatment, and management options for treatment-refractory patients. A Medline
search of research on pharmacotherapy was undertaken, and a previous systematic
review on the evidence-based pharmacotherapy of panic disorder was updated.
Selective serotonin reuptake inhibitors remain a first-line pharmacotherapy of
panic disorder, with the serotonin noradrenaline reuptake inhibitor venlafaxine
also an acceptable early option. Temporary co-administration of benzodiazepines can
be considered. Maintenance treatment reduces relapse rates, but further research to
determine optimal duration is needed. For patients not responding to first-line
agents several pharmacotherapy options are available, but there is a notable
paucity of data on the optimal choice.
GJG Asmundson, M Noel, M Petter, HA Parkerson. Pediatric fear-avoidance model of
chronic pain: Foundation, application and future directions. Pain Res Manage
2012;17(6):397-405. The fear-avoidance model of chronic musculoskeletal pain has
become an increasingly popular conceptualization of the processes and mechanisms
through which acute pain can become chronic. Despite rapidly growing interest and
research regarding the influence of fear-avoidance constructs on pain-related
disability in children and adolescents, there have been no amendments to the model
to account for unique aspects of pediatric chronic pain. A comprehensive
understanding of the role of fear-avoidance in pediatric chronic pain necessitates
understanding of both child/adolescent and parent factors implicated in its
development and maintenance. The primary purpose of the present article is to
propose an empirically-based pediatric fear-avoidance model of chronic pain that
accounts for both child/adolescent and parent factors as well as their potential
interactive effects. To accomplish this goal, the present article will define
important fear-avoidance constructs, provide a summary of the general fear-
avoidance model and review the growing empirical literature regarding the role of
fear-avoidance constructs in pediatric chronic pain. Assessment and treatment
options for children with chronic pain will also be described in the context of the
proposed pediatric fear-avoidance model of chronic pain. Finally, avenues for
future investigation will be proposed.
Brain-derived neurotrophic factor (BDNF) is the most studied neurotrophin involved
in synaptic plasticity processes that are required for long-term learning and
memory. Specifically, BDNF gene expression and activation of its high-affinity
tropomyosin-related kinase B (TrkB) receptor are necessary in the amygdala,
hippocampus and prefrontal cortex for the formation of emotional memories,
including fear memories. Among the psychiatric disorders with altered fear
processing, there is post-traumatic stress disorder (PTSD) which is characterized
by an inability to extinguish fear memories. Since BDNF appears to enhance
extinction of fear, targeting impaired extinction in anxiety disorders such as PTSD
via BDNF signalling may be an important and novel way to enhance treatment
efficacy. The aim of this review is to provide a translational point of view that
stems from findings in the BDNF regulation of synaptic plasticity and fear
extinction. In addition, there are different systems that seem to alter fear
extinction through BDNF modulation like the endocannabinoid system and the
hypothalamicpituitary adrenal axis. Recent work also finds that the pituitary
adenylate cyclase-activating polypeptide and PAC1 receptor, which are upstream of
BDNF activation, may be implicated in PTSD. Especially interesting are data that
exogenous fear extinction enhancers such as antidepressants, histone deacetylases
inhibitors and d-cycloserine, a partial N-methyl d-aspartate agonist, may act
through or in concert with the BDNFTrkB system. Finally, we review studies where
recombinant BDNF and a putative TrkB agonist, 7,8-dihydroxyflavone, may enhance
extinction of fear. These approaches may lead to novel agents that improve
extinction in animal models and eventually humans.
Popular psychology as well as academic research share the concern about the risks
faced by children and adolescents with the use of Internet, such as addiction,
cyberbullying, sexual harassment, among others. The concept of 'risk' as analytical
category becomes essential in the information society, as well as in the research
oriented to find out answers to questions such as 'which are the risks', 'what
prevalence have', and 'how extended are in contemporary societies'. The concept of
'risk in this review' is related to the sociological concept of 'moral panic' as a
reaction to uncertainty and the loss of control generated by media, due to the fact
that they make possible to have access and to be exposed to violent and sexual
contents since early childhood. The main issues under study are identified, its
scope, recommendations and pedagogical implications for reflection on media
literacy.
This systematic review aimed to examine the results of studies that have
investigated the induction of panic attacks and/or the anxiogenic effect of the
caffeine challenge test in patients with panic disorder. The literature search was
performed in PubMed, Biblioteca Virtual em Saude and the ISI Web of Knowledge. The
words used for the search were caffeine, caffeine challenge test, panic disorder,
panic attacks and anxiety disorder. In total, we selected eight randomized, double-
blind studies where caffeine was administered orally, and none of them controlled
for confounding factors in the analysis. The percentage of loss during follow-up
ranged between 14.3% and 73.1%. The eight studies all showed a positive association
between caffeine and anxiogenic effects and/or panic disorder.
The amygdala is known to be a critical brain region for emotional fear. It is
believed that synaptic plasticity within the amygdala is the cellular basis of fear
memory. Recent studies demonstrate that cortical areas such as the prefrontal
cortex (PFC) and anterior cingulate cortex (ACC) may also contribute to the
formation of fear memory, including trace fear memory and remote fear memory. At
synaptic level, fear conditioning also triggers plastic changes within the cortical
areas immediately after the condition. These results raise the possibility that
certain forms of synaptic plasticity may occur within the cortex while synaptic
potentiation takes place within synapses in the hippocampus and amygdala. This
hypothesis is supported by electrophysiological evidence obtained from freely
moving animals that neurons in the hippocampus/amygdala fire synchronous activities
with cortical neurons during the learning. To study fear-related synaptic
plasticity in the cortex and its functional connectivity with neurons in the
amygdala and hippocampus will help us understand brain mechanisms of fear and
improve clinical treatment of emotional disorders in patients.
Fear and anxiety are poorly delineated in much of the clinical and research
literatures. Although some theorists and researchers have posited explanations for
how trait fear and trait anxiety differ, many others conceptualize the constructs
as largely or entirely interchangeable. The primary goals of this review are to
examine clinical conceptualizations and neurobiological studies of fear and
anxiety, examine the animal and human literatures on the correlates of fear and
anxiety, provide clearer definitions of these two constructs, and discuss their
implications for psychopathology. A secondary goal is to evaluate content of self-
report measures of trait fear and anxiety, and meta-analyze the relations between
self-reported trait fear and anxiety. We found that existing measures share
significant content overlap across constructs. Despite this overlap, our meta-
analysis revealed only a moderate (r=0.32) relationship between measures of trait
fear and anxiety, with an even lower relationship (r=0.14) when we examined trait
fear measures operationalized in terms of harm avoidance. These findings suggest
that fear and anxiety are largely distinct emotions, and that psychological
disorders of trait fear and trait anxiety warrant classification in separate
higher-order categories. Moreover, they suggest that future research should focus
on deriving more content valid measures of trait fear and trait anxiety from the
neurobiological and diagnostic literatures. (C) 2010 Elsevier Ltd. All rights
reserved.
Aim: The aim of the present review is to summarize available evidence about the
efficacy and side effects of novel antidepressants for the treatment of panic
disorder. Methods: A literature search was undertaken using MEDLINE, ISI web of
knowledge and references of retrieved articles. The search included articles
published in English up to September 2009. Both controlled and uncontrolled trials
were included. The quality of the reviewed articles was also assessed. Results:
Fourteen mainly poor-quality studies were included. Mirtazapine showed some
efficacy in reducing the number and the severity of panic symptoms in many
uncontrolled studies and was comparable to selective serotonin reputake inhibitors
(SSRIs) in direct-comparison studies. Reboxetine was significantly more efficacious
than placebo but less effective than SSRIs. Further uncontrolled studies suggested
preliminary evidence for the use of milnacipran and duloxetine as well. All drugs
were usually well tolerated. Discussion: Current studies do not yet provide
convincing evidence supporting the efficacy of mirtazapine, reboxetine, milnacipran
and duloxetine for the treatment of panic disorder patients. However, on account of
positive preliminary results, further research is warranted. Copyright (C) 2010 S.
Karger AG, Basel
Panic disorder (PD) is one of the most common anxiety disorders, with a prevalence
of 3.4-4.7%. Although PD seems to have no known cause, and its underlying aetiology
is not well understood, studies have consistently shown that genetic factors
explain about half of the variance. It is likely that most cases of PD have a
complex genetic basis. Existing data suggest, however, that the genetic
architecture underlying PD is heterogeneous and differs between cases. For example,
the degree of genetic complexity, and the pattern of genes involved might differ in
familial versus non-familial cases, in early-versus late-onset cases, or when
different comorbid conditions, gender and potential intermediate or sub-phenotypes
are considered. At the molecular genetic level, linkage and association studies-the
latter including traditional candidate gene and recent genome-wide studies-have
been used to study PD. Although no robust molecular genetic findings have emerged
so far, it is conceivable that the first PD susceptibility genes will be identified
in the coming years via the application of modern molecular genetic methods and
through multicentre collaborations to bring together combined, large datasets. Such
findings could have a major impact on our understanding of the pathophysiology of
this disorder, and would provide important opportunities to investigate genotype-
phenotype correlations, as well as the interaction between genetic and
environmental factors involved in the pathogenesis of PD. Here, the authors
summarise the latest genetics findings about PD, and give an overview of
anticipated future developments.
BACKGROUND CONTEXT: For patients with low back pain, fear-avoidance beliefs (FABs)
represent cognitions and emotions that underpin concerns and fears about the
potential for physical activities to produce pain and further harm to the spine.
Excessive FABs result in heightened disability and are an obstacle for recovery
from acute, subacute, and chronic low back pain. PURPOSE: This article summarizes
past research concerning the etiology, impact, and assessment of FABs; reviews the
results and relevance to clinical practice of trials that have addressed FAB as
part of low back pain treatment; and lists areas in need of further study. STUDY
DESIGN: This article reports on a plenary presentation and discussion of an expert
panel and workshop entitled "Addressing fear-avoidance beliefs in a fear-avoidant
world-translating research into clinical practice'' that was held at Forum X,
Primary Care Research on Low Back Pain, during June 2009, at the Harvard School of
Public Health in Boston, MA, USA. METHODS: Important issues including the
definition, etiology, impact, and treatment of FAB on low back pain outcomes were
reviewed by six panelists with extensive experience in FAB-related research. This
was followed by a group discussion among 40 attendees. Conclusion and
recommendations were extracted by the workshop panelist and summarized in this
article. RESULTS: Fear-avoidance beliefs are derived from both emotionally based
fears of pain and injury and information-based beliefs about the soundness of the
spine, causes of spine degeneration, and importance of pain. Excessively elevated
FABs, both in patients and treating health care providers, have a negative impact
on low back pain outcomes as they delay recovery and heighten disability. Fear-
avoidance beliefs may be best understood when patients are categorized into
subgroups of misinformed avoiders, learned pain avoiders, and affective avoiders as
these categories elucidate potential treatment strategies. These include FAB-
reducing information for misinformed avoiders, pain desensitizing treatments for
pain avoiders, and fear desensitization along with counseling to address the
negative cognition in affective avoiders. Although mixed results have been noted,
most clinical trials have documented improved outcomes when FAB is addressed as
part of treatment. Deficiencies in knowledge about brief methods for assessing FAB
during clinical encounters, the importance of medical explanations for back pain,
usefulness of subgroup FABs, core points for information-based treatments, and
efficient strategies for transferring FAB-reducing information to patients hamper
the translation of FAB research into clinical practice. CONCLUSIONS: By
incorporating an understanding of FAB, clinicians may enhance their ability to
assess the predicaments of their patients with low back pain and gain insight into
potential value of corrective information that lessen fears and concerns on well-
being of their patients. (C) 2011 Elsevier Inc. All rights reserved.
Introduction: Panic disorder (PD) is a common anxiety disorder impairing strongly
quality of life with high social costs. Effective anti-panic medications exist but
a substantial proportion of patients do not fully respond, the available drugs have
several side effects and most medications have a delayed onset of their therapeutic
effect. Thus, further advances are needed. Areas covered: We review available data
on emerging drugs for the treatment of PD including those in development, such as
metabotropic glutamate II receptor agonists, D-cycloserine and levetiracetam, and
new compounds with potential efficacy that may be relevant for future developments,
such as modulators of cholinergic and orexin systems. Expert opinion: To date, the
pharmacological research on PD appears to be relatively limited and probably still
needs more time before making available new advances beyond the currently used
medications. Many reasons may explain these difficulties, including the
heterogeneity of the disorder, the incomplete understanding of its underlying
pathophysiological mechanisms and difficulties in the selection of appropriate
animal models in preclinical studies. Defining biomarkers and endophenotypes in PD
may offer advantages in both understanding the pathophysiology of the disorder and
selecting appropriate targets and outcomes for planning future pharmacological
research.
Evidence from behavioral neuroscience strongly suggests that the unconditional
(innate) capacity to experience fear, along with fear-typical patterns of autonomic
and behavioral arousal, arise from specific systems of the brain the most prominent
being a FEAR circuit which courses between the central amygdala and the
periaqueductal gray of the midbrain. These circuits also mediate the raw affective
properties of FEAR since animals escape and avoid such brain stimulation and
develop conditioned place aversions to locations where they have had such negative
experiences. These ancient emotional-affective systems appear to be relatively
conserved among all mammalian species. Thus, the knowledge derived from common
laboratory animals such as rats and mice, probably has basic scientific and
therapeutic implications for all other mammals, including human beings. The
neurochemical controls of the FEAR system range from benzodiazepines to
neuropeptides that have implications in the search for new anti-anxiety treatments.
Minor tranquilizers work by dampening activity in this emotional system through
increased GABA-mediated neural inhibition. Drugs that can control clinical anxiety
are summarized, and future directions are plotted. (C) 2010 Published by Elsevier
B.V.
Background: Panic disorder (PD) is a severe and chronic psychiatric disorder with
genetic components underlying in its etiology. The Phosphodiesterase 4B (PDE4B)
gene has been reported to be associated with several psychiatric disorders. Several
studies indicated that PDE4B may be involved in the regulation of anxiety and
depression. Therefore, we investigate the association of PDE4B with PD in the
Japanese population. Methods: We genotyped 14 single nucleotide polymorphisms
(5NPs) of PDE4B in 231 PD cases (85 males and 146 females) and 407 controls (162
males and 245 females). Differences in the genotype, allele and haplotype
frequencies between the two groups were compared. Results: We found a significant
association between PDE4B and PD in the haplotype analysis (haplotype C-T-T-A,
permutation P=0.031, OR=1.81, 95% CI=1.30-2.51). Sex-specific analyses demonstrated
that PDE4B was associated with PD in females in the allele/genotype and haplotype
analyses (rs10454453, allele P=0.042, genotype P=0.0034; haplotype C-T-T-A,
permutation P=0.028). Conclusion: Our results suggest that PDE4B may play a role in
the pathophysiology of PD in the Japanese population. Replication studies using
larger samples will be needed for more reliable conclusions. (C) 2010 Elsevier Inc.
All rights reserved.
Fear is a universal response to a threat to one's body or social status. Disruption
in the detection and response of the brain's fear system is commonly observed in a
variety of neurodevelopmental disorders, including fragile X syndrome (FXS), a
brain disorder characterized by variable cognitive impairment and behavioral
disturbances such as social avoidance and anxiety. The amygdala is highly involved
in mediating fear processing, and increasing evidence supports the idea that
inhibitory circuits play a key role in regulating the flow of information
associated with fear conditioning in the amygdala. Here, we review the known and
potential importance of amygdala fear circuits in FXS, and how developmental
studies are critical to understand the formation and function of neuronal circuits
that modulate amygdala-based behaviors. Copyright (C) 2011 S. Karger AG, Basel
The 2:1 female-to-male sex difference in the prevalence of panic disorder (PD)
suggests that there is a sex-specific vulnerability involved in the etiology and/or
maintenance of this disorder. The purpose of this paper is to present a new
conceptual model, which emphasizes the interaction between a cognitive
vulnerability for PD, anxiety sensitivity, and the effects of progesterone and its
metabolite, allopregnanolone, on behavioral and physiological responses to stress
during the premenstrual phase. This interaction is proposed to be a potential sex-
specific pathway that may initiate and/or maintain panic and anxiety symptoms in
women. This review paper presents preliminary evidence from both the human and
animal literatures to support this new model. Specific topics reviewed include:
psychopathology related to the menstrual cycle, anxiety sensitivity and its
relationship to the menstrual cycle, PMS, and PMDD, anxiety-modulating effects of
progesterone and its neuroactive metabolite, allopregnanolone, and how results from
the neuroendocrine literature relate to psychopathology or symptoms associated with
the menstrual cycle. (C) 2011 Elsevier Ltd. All rights reserved.
Percutaneous treatment (PT) emerged in the mid-1980s as an alternative to surgery
for selected cases of abdominal cystic echinococcosis (CE). Despite its efficacy
and widespread use, the puncture of echinococcal cysts is still far from being
universally accepted. One of the main reasons for this reluctance is the perceived
risk of anaphylaxis linked to PTs. To quantify the risk of anaphylactic reactions
and lethal anaphylaxis with PT, we systematically searched MEDLINE for publications
on PT of CE and reviewed the PT-related complications. After including 124
publications published between 1980 and 2010, we collected a total number of 5943
PT procedures on 5517 hepatic and non-hepatic echinococcal cysts. Overall, two
cases of lethal anaphylaxis and 99 reversible anaphylactic reactions were reported.
Lethal anaphylaxis occurred in 0.03% of PT procedures, corresponding to 0.04% of
treated cysts, while reversible allergic reactions complicated 1.7% of PTs,
corresponding to 1.8% of treated echinococcal cysts. Analysis of the literature
shows that lethal anaphylaxis related to percutaneous treatment of CE is an
extremely rare event and is observed no more frequently than drug-related
anaphylactic side effects.
Panic disorder is one of the chronic and disabling anxiety disorders. There has
been evidence for either genetic heterogeneity or complex inheritance, with
environmental factor interactions and multiple single genes, in panic disorder's
etiology. Linkage studies have implicated several chromosomal regions, but no
research has replicated evidence for major genes involved in panic disorder.
Researchers have suggested several neurotransmitter systems are related to panic
disorder. However, to date no candidate gene association studies have established
specific loci. Recently, researchers have emphasized genome-wide association
studies. Results of two genome-wide association studies on panic disorder failed to
show significant associations. Evidence exists for differences regarding gender and
ethnicity in panic disorder. Increasing evidence suggests genes underlying panic
disorder overlap, transcending current diagnostic boundaries. In addition, an
anxious temperament and anxiety-related personality traits may represent
intermediate phenotypes that predispose to panic disorder. Future research should
focus on broad phenotypes, defined by comorbidity or intermediate phenotypes.
Genome-wide association studies in large samples, studies of gene-gene and gene-
environment interactions, and pharmacogenetic studies are needed.
Pavlovian fear conditioning depends on synaptic plasticity at amygdala neurons.
Here, we review recent electrophysiological, molecular and behavioral evidence
suggesting the existence of a distributed neural circuitry regulating amygdala
synaptic plasticity during fear learning. This circuitry, which involves
projections from the midbrain periaqueductal gray region, can be linked to
prediction error and expectation modulation of fear learning, as described by
associative and computational learning models. It controls whether, and how much,
fear learning occurs by signaling aversive events when they are unexpected.
Functional neuroimaging and clinical studies indicate that this prediction circuit
is recruited in humans during fear learning and contributes to exposure-based
treatments for clinical anxiety. This aversive prediction error circuit might
represent a conserved mechanism for regulating fear learning in mammals.
Genetically modified organisms are those whose genome has been changed using
genetic engineering techniques. As a result the organism has acquired a new,
desired feature which it did not previously display. Manipulation of genetic
material and construction of transgenic organisms raises many hopes and
controversies. This article presents the potential opportunities and fears related
to the use of genetically modified organisms, especially regarding to commercially
important crop species.
Learning to contend with threats in the environment is essential to survival, but
dysregulation of memories for traumatic events can lead to disabling
psychopathology. Recent years have witnessed an impressive growth in our
understanding of the neural systems and synaptic mechanisms underlying emotional
memory formation. As a consequence, interest has emerged in developing strategies
for suppressing, if not eliminating, fear memories. Here, I review recent work
employing sophisticated behavioral, pharmacological, and molecular tools to target
fear memories, placing these memories firmly behind the crosshairs of
neurobiologically informed interventions.
Fear conditioning and extinction represent basic forms of associative learning with
considerable clinical relevance and have been implicated in the pathogenesis of
anxiety disorders. There is considerable inter-individual variation in the ability
to acquire and extinguish conditioned fear reactions and the study of genetic
variants has recently become a focus of research. In this review, we give an
overview of the existing genetic association studies on human fear conditioning and
extinction in healthy individuals and of related studies on cognitive-behavioral
treatment (CBT) and exposure, as well as pathology development after trauma.
Variation in the serotonin transporter (5HTT) and the catechol-o-methyltransferase
(COMT) genes has consistently been associated with effects in pre-clinical and
clinical studies. Interesting new findings, which however require further
replication, have been reported for genetic variation in the dopamine transporter
(DAT1) and the pituitary adenylate cyclase 1 receptor (ADCYAP1R1) genes, whereas
the current picture is inconsistent for variation in the brain-derived neurotrophic
factor (BDNF) gene. We end with a discussion of the findings and their limitations,
as well as future directions that we hope will aid the field to develop further.
Translational Psychiatry (2011) 1, e41; doi:10.1038/tp.2011.36; published online 20
September 2011
The formation and storage of fear memory is needed to adapt behavior and avoid
danger during subsequent fearful events. However, fear memory may also play a
significant role in stress and anxiety disorders. When fear becomes
disproportionate to that necessary to cope with a given stimulus, or begins to
occur in inappropriate situations, a fear or anxiety disorder exists. Thus, the
study of cellular and molecular mechanisms underpinning fear memory may shed light
on the formation of memory and on anxiety and stress related disorders. Evidence
indicates that fear learning leads to changes in neuronal synaptic transmission and
morphology in brain areas underlying fear memory formation including the amygdala
and hippocampus. The actin cytoskeleton has been shown to participate in these key
neuronal processes. Recent findings show that the actin cytoskeleton is needed for
fear memory formation and extinction. Moreover, the actin cytoskeleton is involved
in synaptic plasticity and in neuronal morphogenesis in brain areas that mediate
fear memory. The actin cytoskeleton may therefore mediate between synaptic
transmission during fear learning and long-term cellular alterations mandatory for
fear memory formation.
Panic patients have many functional deficiencies in the hypothalamic-pituitary-
adrenal (HPA) axis. Previous studies have shown changed pituitary gland volume in
some psychiatric disorders that have functional deficiencies in the HPA axis:
However, to date no study has evaluated the pituitary gland volume in patients with
panic disorder (PD). We investigated the pituitary gland volume in patients with PD
(n = 27) and age- and sex-matched healthy controls (n = 27), using 1.5-T magnetic
resonance imaging in this study. Analysis showed that patients with PD had
significantly smaller pituitary volume compared to healthy subjects. Patients with
agoraphobia especially had a significantly smaller pituitary volume than patients
without agoraphobia. There was a significant relationship between the pituitary
volume and both the severity of symptoms and the illness duration in the patient
group. The results show that patients with PD have reduced pituitary volume, which
may reflect the functional abnormalities seen in this disorder. These findings may
help us better understand the pathology of PD. (C) 2010 Elsevier Inc. All rights
reserved.
In anxiety disorders, such as posttraumatic stress disorders and phobias, classical
conditioning pairs natural (unconditioned) fear-eliciting stimuli with contextual
or discrete cues resulting in enduring fear responses to multiple stimuli.
Extinction is an active learning process that results in a reduction of conditioned
fear responses after conditioned stimuli are no longer paired with unconditioned
stimuli. Fear extinction often produces incomplete effects and this highlights the
relative permanence of bonds between conditioned stimuli and conditioned fear
responses. The animal research literature is rich in its demonstration of cognitive
enhancing agents that alter fear extinction. This review specifically examines the
fear extinguishing effects of cognitive enhancers that act on gamma-aminobutyric
acid (GABA), glutamatergic, cholinergic, adrenergic, dopaminergic, and cannabinoid
signaling pathways. It also examines the effects of compounds that alter epigenetic
and neurotrophic mechanisms in fear extinction. Of these cognitive enhancers,
glutamatergic N-methyl D-aspartate (NMDA) receptor agonists, such as D-cycloserine,
have enhanced fear extinction in a context-, dose- and time-dependent manner.
Agents that function as glutamatergic alpha-amino-3-hydroxy-5-methyl-4-
isoxazolepropionic acid (AMPA) receptor agonists, alpha2-adrenergic receptor
antagonists (such as yohimbine), neurotrophic factors (brain derived neurotrophic
factor or BDNF) and histone deacetylase inhibitors (valproate and sodium butyrate)
also improve fear extinction in animals. However, some have anxiogenic effects and
their contextual and temporal effects need to be more reliably demonstrated.
Various cognitive enhancers produce changes in cortico-amygdala synaptic plasticity
through multiple mechanisms and these neural changes enhance fear extinction. We
need to better define the changes in neural plasticity produced by these agents in
order to develop more effective compounds. In the clinical setting, such use of
effective cognitive enhancers with cue exposure therapy, using compounds derived
from animal model studies, provides great hope for the future treatment of anxiety
disorders. Published by Elsevier Inc.
Pavlovian fear conditioning is a particularly useful behavioral paradigm for
exploring the molecular mechanisms of learning and memory because a well-defined
response to a specific environmental stimulus is produced through associative
learning processes. Synaptic plasticity in the lateral nucleus of the amygdala (LA)
underlies this form of associative learning. Here, we summarize the molecular
mechanisms that contribute to this synaptic plasticity in the context of auditory
fear conditioning, the form of fear conditioning best understood at the molecular
level. We discuss the neurotransmitter systems and signaling cascades that
contribute to three phases of auditory fear conditioning: acquisition,
consolidation, and reconsolidation. These studies suggest that multiple
intracellular signaling pathways, including those triggered by activation of
Hebbian processes and neuromodulatory receptors, interact to produce neural
plasticity in the LA and behavioral fear conditioning. Collectively, this body of
research illustrates the power of fear conditioning as a model system for
characterizing the mechanisms of learning and memory in mammals and potentially for
understanding fear-related disorders, such as PTSD and phobias.
Among drugs that act on serotonergic neurotransmission, selective serotonin (5-HT)
reuptake inhibitors (SSRIs) are now the gold standard for the treatment of anxiety
disorders. The precise mechanisms of the anxiolytic actions of SSRIs are unclear.
We reviewed the literature related to the effects of SSRIs and the neurochemical
changes of 5-HT in conditioned fear. Acute SSRIs and 5-HT1A receptor agonists
reduced the acquisition and expression of contextual conditioned fear. Chronic SSRI
administration enhanced anxiolytic-like effects. Microinjection studies revealed
the amygdala as the target brain region of both classes of serotonergic drugs, and
the hippocampus as the target of 5-HT1A receptor agonists. These findings highlight
the contribution of post-synaptic 5-HT receptors, especially 5-HT1A receptors, to
the anxiolytic-like effects of serotonergic drugs. These results support the new 5-
HT hypothesis of fear/anxiety: the facilitation of 5-HT neurotransmission
ameliorates fear/anxiety. Furthermore, these behavioral data provide a new
explanation of neurochemical adaptations to contextual conditioned fear: increased
5-HT transmission seems to decrease, not increase, fear. (C) 2011 Elsevier Inc. All
rights reserved.
How will people respond to the discovery of extra-terrestrial life? Potentially
useful resources for addressing this question include historical prototypes,
disaster studies and survey research. Reactions will depend on the interplay of the
characteristics of the newly found life, the unfolding of the discovery, the
context and content of the message and human information processing as shaped by
biology, culture and psychology. Pre-existing images of extra-terrestrials as god-
like, demonic, or artificial will influence first impressions that may prove highly
resistant to change. Most probably people will develop comprehensive images based
on minimal information and assess extra-terrestrials in the same ways that they
assess one another. Although it is easy to develop frightening scenarios, finding
microbial life in our Solar System or intercepting a microwave transmission from
many light years away are less likely to be met with adverse reactions such as fear
and pandemonium than with positive reactions such as equanimity and delight.
In this review, the authors propose that the fear extinction model can be used as
an experimental tool to cut across symptom dimensions of multiple anxiety disorders
to enhance our understanding of the psychopathology of these disorders and
potentially facilitate the detection of biomarkers for them. The authors evaluate
evidence for this proposition from studies examining the neurocircuitry underlying
fear extinction in rodents, healthy humans, and clinical populations. The authors
also assess the potential use of the fear extinction model to predict vulnerability
for anxiety and treatment response and to improve existing treatments or develop
novel ones. Finally, the authors suggest potential directions for future research
that will help to further validate extinction as a biomarker for anxiety across
diagnostic categories and to bridge the gap between basic neuroscience and clinical
practice.
Anxiety disorders have a high prevalence, and despite the substantial advances in
the psychological treatment of anxiety, relapse is still a common problem. One
approach to improving existing psychological treatments for anxiety has been to
develop pharmacological agents that can be used to enhance the processes underlying
exposure therapy, which is the most commonly used and empirically validated
psychological treatment for anxiety during which individuals are taught to
appropriately inhibit fear. Animal models of exposure therapy, particularly fear
extinction, have proved to be a very useful way of examining the neural and
molecular correlates of fear inhibition, which has in turn led to the
identification of numerous drugs that enhance these processes in rats. Several of
these drugs have subsequently been tested as novel pharmacological adjuncts to
exposure therapy in humans with a range of anxiety disorders. The purpose of this
review is to outline the key animal models of exposure therapy and to describe how
these have been used to develop potential pharmacological adjuncts for anxiety
disorders. Drugs that are currently in clinical use, as well as those currently in
the preclinical stages of investigation, are described.
Introduction: Panic disorder (PD) is a prevalent psychiatric disorder characterized
by unexpected and recurrent panic attacks. PD patients present significant
psychosocial impairment and a high risk of psychiatric comorbidities and suicide.
PD should be treated effectively as soon as the symptoms emerge because the longer
these patients remain without treatment, the worse the prognosis will be. Areas
covered: The authors carried out a systematic review of the literature regarding
the pharmacological treatment of PD in the last 10 years. Only open studies,
placebo-controlled studies or comparative clinical trials were selected. Expert
opinion: Compounds with reported effectiveness in the treatment of PD included
tricyclic antidepressants, benzodiazepines, serotonin selective reuptake inhibitors
(SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs) and other drugs.
SSRIs and SNRIs are the first-line compounds in the treatment of PD. These drugs
were better tolerated than tricyclics and benzodiazepines as they had a low risk of
dependence and overdosing complications. The serotonergic, noradrenergic and
GABAergic pathways play a major role in the fear network and in the physiopathology
of PD. A better understanding of the role of these neurotransmitter systems in PD
will allow the development of more effective drugs for this psychiatric condition.
Fear perception and subsequent appropriate behavioural response are crucial for the
adaptation of species. During the past few decades functional neuro-imaging studies
in humans exploring the neural basis of fear have contributed significantly to the
understanding of its mechanisms. Imaging studies help to clarify the role of the
amygdala-based neurocircuitry in fear activation. The aim of this paper is briefly
to review the most recent functional neuro-imaging studies on fear perception,
modulation and learning. Important knowledge has been acquired about the factors
that set fear in motion, including the role of non-conscious processes and how fear
drives attention. A subcortical network interacts with the prefrontal cortex to
modulate emotional responses that allow better coping with environmental and social
demands. Fear learning reduces the need to relearn about dangerous stimuli.
Flexible processes allow fear behaviour to be readjusted when circumstances change.
Future improvement of functional and other neuro-imaging techniques may better
clarify the role of the neurocircuitry involved in fear perception, learning and
modulation.
The current review deals with interoceptive conditioning as a viable mechanism
maintaining fear of pain: The available literature suggests that interoceptive -
i.e., internal bodily - sensations may become predictors of pain and will
subsequently elicit fear of pain. After a short overview of interoceptive (fear)
conditioning and its role in the maintenance of panic disorder, the existing
literature on conditioning in the field of pain and fear of pain is reviewed. Next,
the authors propose an interoceptive fear conditioning model of fear of pain,
suggesting that bodily sensations can function as predictors of pain and as
conditioned stimuli become endowed with the capacity to elicit an (anticipatory)
fear response. The review concludes with a number of theoretical and clinical
considerations, introducing interoceptive exposure as a potentially effective
treatment for fear of pain. (C) 2011 European Federation of International
Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights
reserved.
Pavlovian conditioning is commonly used to investigate the mechanisms of fear
learning. Because the Wistar-Kyoto (WKY) rat strain is particularly stress-
sensitive, we investigated the effects of a psychological stressor on sleep in WKY
compared to Wistar (WIS) rats. Male WKY and WIS rats were either fear-conditioned
to tone cues or received electric foot shocks alone. In the fear-conditioning
procedure, animals were exposed to 10 tones (800 Hz, 90 dB, 5 s), each co-
terminating with a foot shock (1.0 mA, 0.5 s), at 30-s intervals. In the shock
stress procedure, animals received 10 foot shocks at 30-s intervals, without tones.
All subjects underwent a tone-only test both 24h (Day 1) and again two weeks (Day
14) later. Rapid eye movement sleep (REMS) continuity was investigated by
partitioning REMS episodes into single (inter-REMS episode interval >3 min) and
sequential (interval min) episodes. In the fear-conditioned group, freezing
increased from baseline in both strains, but the increase was maintained on Day 14
in WKY rats only. In fear-conditioned WIN rats, total REMS amount increased on Day
1, sequential REMS amount increased on Day 1 and Day 14, and single REMS amount
decreased on Day 14. Alterations were due to changes in the number of sequential
and single REMS episodes. Shock stress had no significant effect on REMS
microarchitecture in either strain. The shift toward sequential REMS in fear-
conditioned WKY rats may represent REMS fragmentation, and may provide a model for
investigating the neurobiological mechanisms of sleep disturbances reported in
posttraumatic stress disorder. (C) 2010 Elsevier Inc. All rights reserved.
This review article explores the emotional attractions of war and military combat.
Using Sebastian Junger's recently published book War as a central point of
reference, it elucidates and supports the idea that, for combatants, war is often
experienced as a profoundly exciting and existentially rewarding human activity. By
bringing into focus and helping to conceptualize the raw appeal of combat, Junger's
account of war can be enlisted as a resource for understanding the positive
emotional drives behind acts of terrorism.
A 51-year-old woman had panic disorder with agoraphobia and major depressive
disorder sequentially. The aforementioned symptoms subsided significantly after
treatment with milnacipran, 125 mg, administered daily for 2 months. However, panic
attacks with agoraphobia were noted frequently when she tapered down milnacipran to
50 mg daily. She consequently experienced depression that gradually increased in
degree, with poor energy, poor sleep, thoughts of helplessness, and ideas of death.
After administration of a daily dose of 125 mg of milnacipran for 1 month, her
panic attacks with agoraphobia and depressed mood were again alleviated. The
present report shows significant effects of milnacipran on the comorbidity of panic
disorder with agoraphobia and major depressive disorder.
Objectives: We have recently reported that spontaneously hypertensive rats (SHR)
present a contextual fear conditioning (CFC) deficit. This deficit is improved by
antipsychotic drugs, potentiated by proschizophrenia manipulations and not altered
by acute administration of carbamazepine, lamotrigine and valproic acid.
Nevertheless, the effects of lithium a classical mood stabilizer or repeated
treatment with these drugs were not evaluated. The main aim of the present study
was to extend our previous work by investigating a possible beneficial effect of
acute and/or chronic treatments with lithium or lamotrigine on the acquisition
deficit of CFC presented by SHR. Methods: Rats were submitted to CFC task after an
acute treatment with lithium and/or a repeated treatment with lithium and
lamotrigine. Results: Our data revealed that the CFC deficit presented by SHR is
not improved by acute or repeated treatment with lithium. Repeated lamotrigine
treatment potentiated the deficit presented by SHR and impaired CFC in control
animals (Wistar Rats). Conclusions: These data reinforce the absence of beneficial
effects of mood stabilizers on the emotional context processing impairment modeled
by SHR. (C) 2011 Elsevier Inc. All rights reserved.
Anxious individuals exhibit threat biases at multiple levels of information
processing. From a developmental perspective, abnormal safety learning in childhood
may establish threat-related appraisal biases early, which may contribute to
chronic disorders in adulthood. This review illustrates how the interface among
attention, threat appraisal, and fear learning can generate novel insights for
outcome prediction. This review summarizes data on amygdala function, as it relates
to learning and attention, highlights the importance of examining threat appraisal,
and introduces a novel imaging paradigm to investigate the neural correlates of
threat appraisal and threat-sensitivity during extinction recall. This novel
paradigm can be used to investigate key questions relevant to prognosis and
treatment. Depression and Anxiety 28:5-17, 2011. (C) 2010 Wiley-Liss, Inc.
The objective of this review was to systematically describe and analyze fear of
falling (FoF) in patients after a hip fracture, focusing on measurement instruments
for FoF, the prevalence of FoF, factors associated with FoF, and interventions that
may reduce FoF. Fifteen relevant studies were found through a systematic literature
review, in which the PubMed, Embase, PsychINFO, and CINAHL databases were searched.
Some of these studies indicated that 50% or more of patients with a hip fracture
suffer from FoF, although adequate instruments still have to be validated for this
specific group. FoF was associated with several negative rehabilitation outcomes,
such as loss of mobility, institutionalization, and mortality. FoF was also related
to less time spent on exercise and an increase in falls, although knowledge about
risk factors, the prevalence over a longer time period, and the exact causal
relations with important health outcomes is limited. Most studies suffer from
selection bias by excluding patients with physical and cognitive disorders. Hence,
more research is required, including in patients who are frail and have
comorbidities. Only when knowledge such as this becomes available can interventions
be implemented to address FoF and improve rehabilitation outcomes after a hip
fracture.
Objective Schizophrenia patients had decreased levels of quality of life compared
to normal population The aim of this study was to investigate the impact of panic
attacks on quality of life in patients with schizophrenia Methods. Eighty-eight
patients with schizophrenia and 85 healthy subjects were included in the study.
World Health Organization Quality of Life Instrument-Short Form (WHOQOL-Bref) was
given to patients and healthy subjects to assess quality of life Panic module of
Structured Clinical Interview for DSM-IV (SCID) was administered to patients for
diagnosis of panic attacks and panic disorder Positive and Negative Syndrome Scale
(PANSS) for symptom severity and Calgary Depression Scale (CDS) for depressive
symptoms were administered to the patients Results Patients with schizophrenia
demonstrated significantly lower scores compared to healthy controls in all domains
of WHOQOL-Bref Twenty-five patients (28.4%) with schizophrenia had panic attacks
(PA) and 10 patients (11 4%) met criteria for panic disorder (PD) Schizophrenia
patients with PA had significantly lower scores on psychological domain of WHOQOL-
Bref compared to the patients without PA Schizophrenic patients with panic attacks
had higher CDS scores than patients without PA In the multivariate regression
analyses the variance in psychological domain of WHOQOL-Bref was explained by
depression rather than panic attack Conclusion In patients with schizophrenia
comorbid panic attacks may have a negative Impact on quality of life, which is
associated with depression significantly. Panic attacks and depressive
symptomatology must be examined comprehensively in order to improve quality of life
in patients with schizophrenia (C) 2010 Elsevier Inc All rights reserved.
Chronic pain is a pervasive health care issue affecting over 50 million Americans
and costing more than $100 billion dollars annually in lost productivity and health
care costs. As a financially and emotionally taxing condition, the families and
friends of people with chronic pain, as well as society at large, are affected.
Current theory supports the role of biological, psychological, and environmental
factors in the etiology, exacerbation, and maintenance of chronic pain. Recently,
the specific role of pain-related fear in pain experience has received increasing
attention. This article summarizes current understanding of the role of pain-
related fear in the onset of acute pain incidents, the transition of acute pain to
chronic, and the pain severity and disability of patients with ongoing chronic pain
conditions. Treatments demonstrated to reduce pain-related fear are presented,
evidence demonstrating their efficacy at reducing disability and pain severity are
summarized, and recent criticisms of the fear-avoidance model and future directions
are considered.
The irrelevance of habeas corpus and the abolition of "double jeopardy," secret and
protracted outsourcing of detention and torture, and increasing geographic
prevalence of surveillance technologies across Anglo-American "democracies" have
many citizens concerned about the rapidly convergent, authoritarian behavior of
political oligarchs and the actual destruction of sovereignty and democratic values
under the onslaught of antiterrorism hubris, propaganda, and fear. This article
examines synchronic legislative isomorphism in responses to 9/11 in the United
States, the United Kingdom and European Union, and Australia in terms of enacted
terrorism legislation and, also, diachronic, oligarchic isomorphism in the
manufacture of fear within a convergent world by comparing the "Politics of Fear"
being practiced today to Stalinist-Russian and McCarthyist-U.S. abuse of "fear."
The immediate future of Anglo-American democratic hubris, threats to civil society,
and oligarchic threats to democratic praxis are canvassed. This article also raises
the question as to whether The USA PATRIOT Acts of 2001/2006, sanctioned by the
U.S. Congress, are examples, themselves, of state crimes against democracy. In the
very least, any democratically inclined White House occupant in 2009 would need to
commit to repealing these repressive, and counterproductive, acts.
Background. The relationship between parental and child dental fear has been
studied for over a century. During this time, the concept of dental fear as well as
methodological approaches to studying dental fear in children have evolved
considerably. Aim. To provide an overview of the published empirical evidence on
the link between parental and child dental fear. Design. A structured literature
review and meta-analysis. Results. Forty-three experimental studies from across the
six continents were included in the review. The studies ranged widely with respect
to research design, methods used, age of children included, and the reported link
between parental and child dental fear. The majority of studies confirmed a
relationship between parental and child dental fear. This relationship is most
evident in children aged 8 and under. A meta-analysis of the available data also
confirmed an association between parental and child dental fear. Conclusion. The
narrative synthesis as well as the meta-analysis demonstrate a significant
relationship between parental and child dental fear, particularly in children 8
years and younger.
Although fear research has largely focused on the amygdala, recent findings
highlight cortical control of the amygdala in the service of fear regulation. In
rodent models, it is becoming well established that the infralimbic (IL) prefrontal
cortex plays a key role in extinction learning, and recent findings are uncovering
molecular mechanisms involved in extinction-related plasticity. Furthermore,
mounting evidence implicates the prelimbic (PL) prefrontal cortex in the production
of fear responses. Both IL and PL integrate inputs from the amygdala, as well as
other structures to gate the expression of fear via projections to inhibitory or
excitatory circuits within the amygdala. We suggest that dual control of the
amygdala by separate prefrontal modules increases the flexibility of an organism's
response to danger cues.
The panic attack is able to mimic the clinical presentation of an acute coronary
syndrome (ACS), to the point of being clinically indistinguishable without
appropriate investigations. However, the literature actually demonstrates that the
2 conditions are more related than just being differential diagnoses. Through a
review of the literature involving epidemiological studies, randomised controlled
trials, systematic reviews and meta-analyses found on a Medline search, the
relation between panic disorder and ACS is explored in greater depth. Panic
disorder, a psychiatric condition with recurrent panic attacks, has been found to
be an independent risk factor for subsequent coronary events. This has prognostic
bearing and higher mortality rates. Through activation of the sympathetic system by
differing upstream mechanisms, the 2 conditions have similar presentations. Another
psychiatric differential diagnosis would be that of akathisia, as an adverse effect
to antidepressant medications. An overview on the investigations, diagnostic
process, treatment modalities and prognoses of the two conditions is presented.
Panic disorders remain under-diagnosed, but various interviews are shown to allow
physicians without psychiatric training to accurately pick up the condition.
Comprehensive multidisciplinary approaches are needed to help patients with both
coronary heart disease and anxiety disorder.
Anxiety disorders are a significant problem in the community, and recent
neuroimaging research has focused on determining the brain circuits that underlie
them. Research on the neurocircuitry of anxiety disorders has its roots in the
study of fear circuits in animal models and the study of brain responses to
emotional stimuli in healthy humans. We review this research, as well as
neuroimaging studies of anxiety disorders. In general, these studies have reported
relatively heightened amygdala activation in response to disorder-relevant stimuli
in post-traumatic stress disorder, social phobia, and specific phobia. Activation
in the insular cortex appears to be heightened in many of the anxiety disorders.
Unlike other anxiety disorders, post-traumatic stress disorder is associated with
diminished responsivity in the rostral anterior cingulate cortex and adjacent
ventral medial prefrontal cortex. Additional research will be needed to (1) clarify
the exact role of each component of the fear circuitry in the anxiety disorders,
(2) determine whether functional abnormalities identified in the anxiety disorders
represent acquired signs of the disorders or vulnerability factors that increase
the risk of developing them, (3) link the findings of functional neuroimaging
studies with those of neurochemistry studies, and (4) use functional neuroimaging
to predict treatment response and assess treatment-related changes in brain
function. Neuropsychopharmacology Reviews (2010) 35, 169-191;
doi:10.1038/npp.2009.83; published online 22 July 2009
Suicide rates have been increasing in military personnel since the start of
Operation Enduring Freedom and Operation Iraqi Freedom, and it is vital that
efforts be made to advance suicide risk assessment techniques and treatment for
members of the military who may be experiencing suicidal symptoms. One potential
way to advance the understanding of suicide in the military is through the use of
the Interpersonal-Psychological Theory of Suicide. This theory proposes that three
necessary factors are needed to complete suicide: feelings that one does not belong
with other people, feelings that one is a burden on others or society, and an
acquired capability to overcome the fear and pain associated with suicide. This
review analyzes the various ways that military service may influence suicidal
behavior and integrates these findings into an overall framework with relevant
practical implications. Findings suggest that although there are many important
factors in military suicide, the acquired capability may be the most impacted by
military experience because combat exposure and training may cause habituation to
fear of painful experiences, including suicide. Future research directions, ways to
enhance risk assessment, and treatment implications are also discussed. (C) 2009
Elsevier Ltd. All rights reserved.
Panic disorder (PD) is the most common anxiety disorder. Although PD seems to occur
unprovoked and the underlying etiology is not well understood, studies have
consistently shown that genetic factors explain approximately 48% of the variance.
Moreover, family and twin studies support the view that the majority of PD cases
have a complex genetic basis. Promising findings have most recently implicated the
polymorphisms at the 3' end of the serotonin transporter gene SLC6A4 as PD risk
variants. If independent studies can replicate the observed association with the
SLC6A4 variants and their functional effects on gene expression, this would have a
great impact on our understanding of the disease pathophysiology and would provide
opportunities to investigate genotype-phenotype correlations.
Learned fear is a process allowing quick detection of associations between cues in
the environment and prediction of imminent threat. Adaptive function in a changing
environment, however, requires organisms to quickly update this learning and have
the ability to hinder fear responses when predictions are no longer correct. Here
we focus on three strategies that can modify conditioned fear, namely extinction,
reversal and regulation of fear, and review their underlying neural mechanisms. By
directly comparing neuroimaging data from three separate studies that employ each
strategy, we highlight overlapping brain structures that comprise a general
circuitry in the human brain. This circuitry potentially enables the flexible
control of fear, regardless of the particular task demands.
Although the efficacy of psychological treatment for panic disorder (PD) with or
without agoraphobia has been the subject of a great deal of research, the specific
contribution of techniques such as exposure, cognitive therapy, relaxation training
and breathing retraining has not yet been clearly established. This paper presents
a meta-analysis applying random- and mixed-effects models to a total of 65
comparisons between a treated and a control group, obtained from 42 studies
published between 1980 and 2006. The results showed that, after controlling for the
methodological quality of the studies and the type of control group, the
combination of exposure. relaxation training, and breathing retraining gives the
most consistent evidence for treating PD. Other factors that improve the
effectiveness of treatments are the inclusion of homework during the intervention
and a follow-up program after it has finished. Furthermore, the treatment is more
effective when the patients have no comorbid disorders and the shorter the time
they have been suffering from the illness. Publication bias and several
methodological factors were discarded as a threat against the validity of our
results. Finally the implications of the results for clinical practice and for
future research are discussed. (C) 2009 Elsevier Ltd. All rights reserved
By comparing efficacious psychological therapies of different kinds, inferences
about common effective treatment mechanisms can be made. We selected six therapies
for review on the basis of the diversity of their theoretical rationales and
evidence for superior efficacy: psychoanalytic psychotherapy, hypercapnic breathing
training, hypocapnic breathing training, reprocessing with and without eye-movement
desensitization, muscle relaxation, and cognitive behavior therapy. The likely
common element of all these therapies is that they reduce the immediate expectancy
of a panic attack, disrupting the vicious circle of fearing fear. Modifying
expectation is usually regarded as a placebo mechanism in psychotherapy, but may be
a specific treatment mechanism for panic. The fact that this is seldom the
rationale communicated to the patient creates a moral dilemma: Is it ethical for
therapists to mislead patients to help them? Pragmatic justification of a
successful practice is a way out of this dilemma. Therapies should be evaluated
that deal with expectations directly by promoting positive thinking or by fostering
non-expectancy. Depression and Anxiety 27:5-11, 2010. Published 2009 Wiley-Liss,
Inc.(dagger)
Pape H-C, Pare D. Plastic Synaptic Networks of the Amygdala for the A cquisition,
Expression, and Extinction of Conditioned Fear. Physiol Rev 90: 419-463, 2010;
doi:10.1152/physrev.00037.2009.-The last 10 years have witnessed a surge of
interest for the mechanisms underlying the acquisition and extinction of
classically conditioned fear responses. In part, this results from the realization
that abnormalities in fear learning mechanisms likely participate in the
development and/or maintenance of human anxiety disorders. The simplicity and
robustness of this learning paradigm, coupled with the fact that the underlying
circuitry is evolutionarily well conserved, make it an ideal model to study the
basic biology of memory and identify genetic factors and neuronal systems that
regulate the normal and pathological expressions of learned fear. Critical advances
have been made in determining how modified neuronal functions upon fear acquisition
become stabilized during fear memory consolidation and how these processes are
controlled in the course of fear memory extinction. With these advances came the
realization that activity in remote neuronal networks must be coordinated for these
events to take place. In this paper, we review these mechanisms of coordinated
network activity and the molecular cascades leading to enduring fear memory, and
allowing for their extinction. We will focus on Pavlovian fear conditioning as a
model and the amygdala as a key component for the acquisition and extinction of
fear responses.
This is the second of a two part review which critically evaluates research
published in disparate sources into the psychological treatment of fear of flying.
Part I established fear of flying as a complex heterogeneous clinical phenomenon.
This paper discusses the way in which evidence from clinical trials translates to
best practice in treating fear of flying. Published research on psychological
interventions uses terminology which bears a close resemblance to cognitive
behavioural therapy. It is, however, questionable whether some treatment approaches
reflect the implementation of the cognitive behavioural model as it is described in
the wider literature on the treatment of anxiety disorders. This review evaluates a
synthesis of published research which considers fear of flying and related anxiety
disorders with the aim of deriving best practice. It concludes that the most
effective psychological interventions will be those based on an accurate functional
assessment of an individual and their social context relevant to fear of flying and
not merely a set of standard and invariant protocols. Most published research has
been carried out on participants who self refer or volunteer for treatment and it
is probable that this is a biased clinical group which may distort reported
efficacy and treatment outcomes. It concludes by highlighting directions for future
research and the development of psychological treatments for fear of flying. (C)
2010 Elsevier Ltd. All rights reserved.
Fear of flying, its nature, prevalence, etiology and treatment, has been the
subject of a substantial quantity of research over the past 30 years. With the
exception of a dated review of treatment methods however, there has been no
evaluation of this expanding body of evidence, its contribution to theory and
influence on clinical practice. Published research has also generally failed to
apply developments in the understanding and treatment of anxiety disorders
generally to fear of flying. This review provides a critical evaluation of the
existing literature and what it reveals about theory and practice. It does this
from the perspective of Cognitive Behavioural Therapy. The evidence reviewed
demonstrates that fear of flying is a heterogeneous phenomenon which is acquired
under the influence of complex psychological, social and physiological factors
unique to each affected individual. Effective psychological interventions must
therefore be founded on a comprehensive functional assessment of each individual, a
finding which is considered in detail in the second part of this review. (C) 2010
Elsevier Ltd. All rights reserved.
Glucocorticoids play a role in memory formation, and they may contribute to memory
changes in stress-related mental disorders, such as posttraumatic stress disorder
Cortisol may act through mineralocorticoid (MR) or glucocorticoid (GR) receptors,
and the objective of the present study was to evaluate the effects of the MR
antagonist spironolactone, the GR antagonist mifepristone, the MR agonist
fludrocortisone, and the GR agonist dexamethasone on the extinction of contextually
conditioned fear in rats Propranolol was used as a positive control As expected,
propranolol administered before the test session increased memory extinction Pre-
test administration of spironolactone and low-dose dexamethasone also increased the
extinction of an aversive memory, whereas fludrocortisone impaired extinction High-
close dexamethasone and mifepristone were found to have no effect in this model
Post-test spironolactone treatment impaired aversive memory extinction. These
results indicate that MR and GR ate related to extinction of aversive memories, and
MR blockade may be a promising candidate for the treatment of stress-related memory
disorders (C) 2010 Elsevier Inc All rights reserved.
The processes of fear conditioning and extinction are thought to be related to the
pathophysiology of anxiety disorders including obsessive-compulsive disorder (OCD).
We have reported alterations of auditory P50 suppression in human fear conditioning
and extinction in healthy control subjects (Kurayama et al., 2009). In the study,
P50 suppression was impaired transiently in the course of fear acquisition and
extinction. In this study, we investigated the changes of P50 suppression with OCD
patients in the course of the same experimental paradigm. 39 patients with OCD and
21 healthy control subjects were recruited. In the acquisition phase of classical
fear conditioning, 10 pairings of the conditioned stimulus (CS; the visual stimulus
from a light-emitting diode) and the unconditioned stimulus (US; the electrical
stimulus to the wrist) were administered, and in the extinction phase, 10 CS
without US were administered. P50 auditory evoked potentials were measured as the
first stimulus sound (SI) and the second stimulus sound (S2) in double-click
paradigm with a 500 ms interval. P50 S2/S1 ratio was used to evaluate P50
suppression. The mean P50 S2/S1 ratio in patients with OCD significantly elevated
from baseline level during the fear acquisition as that in healthy controls, but
the elevated S2/S1 ratio did not recover to baseline level. The S2/S1 ratio in the
extinction phase was significantly higher in the OCD patient group than in the
healthy control group. In conclusion, our data suggested that P50 sensory gating in
fear extinction was impaired in patients with OCD. (C) 2009 Elsevier Inc. All
rights reserved.
The selective serotonin-reuptake inhibitors are widely used in clinical practice in
the treatment of panic disorder (PD). This article undertakes an up-to-date,
systematic review of the published double-blind, placebo-controlled, randomized,
short-term studies with currently available selective serotonin-reuptake inhibitors
in the treatment of PD. Sertraline, paroxetine, citalopram, escitalopram,
fluoxetine and fluvoxamine have all been proven to be superior to pill-placebo,
although the placebo effect has been shown to be extremely important in patients
with PD. The authors also explore the anxiolytic mechanism of action of this
antidepressant drug class and the preclinical studies that are being developed to
clarify the etiopathogenic mechanisms of PD and, more precisely, the role of the
serotoninergic system in this pathogenesis. These steps are considered fundamental
for the improvement of pharmacological treatment of PD.
Importance of the field: Successful treatment of fear and anxiety disorders is
presently a difficult task. A major limitation is the fact that underlying
physiological mechanisms of fear and anxiety are only now beginning to be
understood. As we obtain more information about mechanisms and brain circuits
involved, treatment of these conditions will become increasingly realistic. Areas
covered in this review: Gene therapy is a promising treatment strategy that has
several advantages over the more widely used pharmacological approaches. In this
review we discuss the potential and limitation of gene therapy in the amygdala.
This review concerns itself with papers published within the last 20 years in the
field of gene therapy for fear and anxiety, and has been primarily conducted in
rodent models. What the reader will gain: We present the current state of research
into gene therapy for anxiety disorders, using a few case studies. The review will
delineate challenges, limitations and opportunities for successful gene therapy.
Take home message: There are sizeable gains in knowledge about functioning of the
fear system. This will inform future improvements in gene therapy approaches. An
ideal gene therapy strategy will involve improvements in both delivery vectors and
in design of therapeutic cargo.
Fear conditioning is influenced by stress but opposing effects in mates and females
have often been reported. In a previous human functional magnetic resonance imaging
(fMRI) study, we observed acute effects of the stress hormone cortisol on
prefrontal structures. Men showed evidence for impaired fear conditioning after
cortisol treatment, while the opposite pattern was found for women. In the current
experiment, we tested whether similar sex-dependent effects would occur on the
neural level if contingency awareness was prevented experimentally to investigate
implicit learning processes. A differential fear conditioning experiment with
transcutaneous electrical stimulation as unconditioned stimulus and geometric
figures as conditioned stimuli (CS) was conducted. One figure was always paired
(CS+), whereas the other (CS-) was never paired with the UCS. Thirty-nine (19
female) subjects participated in this fMRI study, receiving either placebo or 30 mg
cortisol (hydrocortisone) before conditioning. Dependent variables were skin
conductance responses (SCRs) and neural activity (BOLD signal). In tine with prior
findings in unaware participants, no differential learning could be observed for
the SCRs. However, a sex x cortisol interaction was detected with a reduced mean
response to the CS after cortisol treatment in men, while the opposite pattern was
observed in women (enhanced mean SCR under cortisol). In the contrast CS+ minus
CS-, neural activity showed a sex x cortisol interaction in the insula and further
trends in the hippocampus and the thalamus. In these regions, cortisol. reduced the
CS+/CS- differentiation in men but enhanced it in women. In contrast to these sex
specific effects, differential amygdala activation was found in the placebo group
but not in the cortisol group, irrespective of sex. Further, differential neural
activity in the amygdala and thalamus were positively correlated with the SCRs in
the placebo group only. The present study in contingency unaware participants
illustrates that cortisol has in some brain regions sex specific effects on neural
correlates of emotional learning. These effects might translate into a different
vulnerability of the two sexes for anxiety disorders. (c) 2009 Elsevier Ltd. All
rights reserved.
Several lines of evidence suggest that the N-methyl-D-aspartate (NMDA) receptor
plays a significant role in fear conditioning and extinction. However, our
knowledge of the role of D-serine, an endogenous ligand for the glycine site of the
NMDA receptor, in fear extinction is quite limited compared to that of D-
cycloserine, an exogenous partial agonist for the same site. In the current study,
we examined the effects of D-serine on fear extinction and phosphorylation of
extracellular signal-regulated kinase (ERR) in the hippocampus, basolateral
amygdala (BLA), and medial prefrontal cortex (mPFC) during the process of fear
extinction. Systemic administrations of D-serine (2.7 g/kg, i.p.) with or without
the ERR inhibitor SL327 (30 mg/kg, i.p.) to C57BL/6 J mice were performed before
fear extinction in a cued fear conditioning and extinction paradigm. Cytosolic and
nuclear ERR 1/2 phosphorylation in the hippocampus, BLA, and mPFC were measured 1 h
after extinction (El h), 24 h after extinction (E24h), and 1 h after recall (R1h)
by Western blotting. We found that D-serine enhanced the extinction of fear memory,
and the effects of D-serine were reduced by the ERR phosphorylation inhibitor
SL327. The Western blot analyses showed that D-serine significantly increased
cytosolic ERR 2 phosphorylation at El h in the hippocampus and cytosolic ERR 1/2
phosphorylation at R1h in the BLA. The present study suggested that D-serine might
enhance fear extinction through NMDA receptor-induced ERK signaling in mice, and
that D-serine has potential clinical importance for the treatment of anxiety
disorders. (C) 2010 Elsevier Inc. All rights reserved.
Several anticonvulsants, although as yet not lamotrigine (LTG), have been found
useful in the treatment of panic disorder with (PDA) or without agoraphobia. We
administered LTG (200 mg/d) to 4 outpatients with PDA, as an augmentation therapy
(3 patients with chronic and severe agoraphobia) or monotherapy (1 drug-naive
patient with first-onset PDA) in a 14-week trial. The patient under LTG monotherapy
improved significantly, whereas PDA symptoms in 2 of the other patients improved to
some extent.
The molecular genetic research on panic disorder (PD) has grown tremendously in the
past decade. Although the data from twin and family studies suggest an involvement
of genetic factors in the familial transmission of PD with the heritability
estimate near 40%, the genetic substrate underlying panicogenesis is not yet
understood. The linkage studies so far have suggested that chromosomal regions 13q,
14q, 22q, 4q31-q34, and probably 9q31 are associated with the transmission of PD
phenotypes. To date, more than 350 candidate genes have been examined in
association studies of PD, but most of these results remain inconsistent, negative,
or not clearly replicated. Only Val158Met polymorphism of the catechol-O-
methyltransferase gene has been implicated in susceptibility to PD by several
studies in independent samples and confirmed in a recent meta-analysis. However,
the specific role of this genetic variation in PD requires additional analysis
considering its gender- and ethnicity-dependent effect and putative impact on
cognitive functions. The recent advantages in bioinformatics and genotyping
technologies, including genome-wide association and gene expression methods,
provide the means for far more comprehensive discovery in PD. The progress in
clinical and neurobiological concepts of PD may further guide genetic research
through the current controversies to more definitive findings. Molecular Psychiatry
(2010) 15, 681-701; doi:10.1038/mp.2009.145; published online 5 January 2010
The current review systematically documents the role of gamma-amino-butyric acid
(GABA) in different aspects of fear memory-acquisition and consolidation,
reconsolidation, and extinction, and attempts to resolve apparent contradictions in
the data in order to identify the function of GABA(A) receptors in fear memory.
First, numerous studies have shown that pre- and post-training administration of
drugs that facilitate GABAergic transmission disrupt the initial formation of fear
memories, indicating a role for GABA(A) receptors, possibly within the amygdala and
hippocampus, in the acquisition and consolidation of fear memories. Similarly,
recent evidence indicates that these drugs are also detrimental to the restorage of
fear memories after their reactivation. This suggests a role for GABA(A) receptors
in the reconsolidation of fear memories, although the precise neural circuits are
yet to be identified. Finally, research regarding the role of GABA in extinction
has shown that GABAergic transmission is also disruptive to the formation of newly
acquired extinction memories. We argue that contradictions to these patterns are
the result of variations in (a) the location of drug infusion, (b) the dosage of
the drug and/or (c) the time point of drug administration. The question of whether
these GABA-induced memory deficits reflect deficits in retrieval is discussed.
Overall, the evidence implies that the processes mediating memory stability
consequent to initial fear learning, memory reactivation, and extinction training
are dependent on a common mechanism of reduced GABAergic neurotransmission.
Neuropsychopharmacology (2010) 35, 1625-1652; doi:10.1038/npp.2010.53; published
online 21 April 2010
Objective. Tai Chi (TC) is an exercise training that is becoming increasingly
popular as an intervention for single fall prevention. This meta-analysis was
performed to evaluate the efficacy of TC on fall rate, fear of falling and balance
in older people. Methods. Randomized controlled trials published between 1988 and
January 2009 were included. In the Netherlands (2009) we used random effects models
for the analyses, with data reported as incidence rate ratios (IRR) for falls and
standardized mean differences (SMD) for fear of falling and balance. Results. Nine
trials (representing 2203 participants) were included in the analyses. Compared
with exercise controls, TC participants showed significant improvements in fall
rates (2 trials included, IRR: 0.51, 95% CI 0.38-0.68) and static balance (2 trials
included. SMD: 0.47, 95% CI 0.23-0.72). Compared with non-exercise controls, no
improvement was found for TC participants in fall rates (5 trials, IRR: 0.79, 95%
CI 0.60-1.03) or static balance (2 trials, SMD: 0.30, 95% CI -0.50-1.10), but a
significant improvement was found for fear of falling (SMD: 0.37, 95% CI = 0.03-
0.70). Conclusions. Currently there is insufficient evidence to conclude whether TC
is effective in fall prevention, decreasing fear of falling and improving balance
in people over age 50 years. (C) 2010 Elsevier Inc. All rights reserved.
The prevalence of panic disorder in patients with chronic obstructive pulmonary
disease (COPD) is up to 10 times greater than the overall population prevalence of
1.5-3.5%, and panic attacks are commonly experienced. When present, clinically
significant anxiety decreases quality of life for COPD patients, and also increases
health care costs. Therefore, understanding why COPD patients have such high rates
of panic attacks and panic disorder is important for optimal management of COPD.
The cognitive model of panic anxiety is the most widely accepted theory of panic
attacks and panic disorder in physically healthy adults. According to this model,
panic attacks occur when catastrophic misinterpretations of ambiguous physical
sensations (such as shortness of breath or increased heart rate) increase arousal,
creating a positive feedback loop that results in panic. As the major symptom of a
terminal illness that threatens our most basic physical requirement, dyspnea in
COPD is open to catastrophic misinterpretation. There is some experimental and
clinical evidence for the applicability of the cognitive model of panic anxiety in
COPD, and of the utility of cognitive behavior therapy (CBT), based on this model,
for treating anxiety symptoms and panic attacks in COPD patients. However, there is
much need for further studies. Evidence is increasing that mental health
professionals, in collaboration with multidisciplinary pulmonary teams, potentially
have key roles to play in preventing and treating panic attacks and panic disorder
in COPD patients. This review addresses diagnosis, epidemiology, theoretical
conceptualizations, treatment, and recommendations for future research. (C) 2010
Elsevier Ltd. All rights reserved.
The newly proposed criteria for posttraumatic stress disorder (PTSD) in the
Diagnostic and Statistical Manual (DSM-V) include dysregulation of a variety of
emotional states including fear, anger, guilt, and shame, in addition to
dissociation and numbing. Consistent with these revisions, we postulate two models
of emotion dysregulation in PTSD in which fear is not the prevailing emotion but is
only one of several components implicated in a dysregulated emotional system that
also mediates problems regulating anger, guilt, shame, dissociation, and numbing.
We discuss whether there is a relationship between fear and other emotion
regulation systems that may help further our understanding of PTSD and its
underlying neurocircuitry. Two pathways describing the relationship between fear
and other emotion regulation systems in PTSD are proposed. The first pathway
describes emotion dysregulation as an outcome of fear conditioning through stress
sensitization and kindling. The second pathway views emotion dysregulation as a
distal vulnerability factor and hypothesizes a further exacerbation of fear and
other emotion regulatory problems, including the development of PTSD after exposure
to one or several traumatic event(s) later in life. Future research and treatment
implications are discussed.
Studies on gene environment interactions in mental disorders are characterized by
powerful genetic techniques and well defined "candidate genes," whereas a
definition of "candidate stressors," in most cases assessed in the form of life
events (LEs), is inconsistent or not even provided. This review addresses this
problem, with particular attention to the clinical phenotype of panic disorder
(PD), by providing an overview and critical discussion for which life events are
known to contribute to the etiology of the disease and how they may be
conceptualized. There is converging evidence for a significant impact of cumulative
as well as specific life events, such as threat, interpersonal and health-related
events in adulthood, and abuse or loss/separation experiences in childhood,
respectively, on the pathogenesis of panic disorder with some overlapping effect
across the anxiety disorder spectrum as well as on comorbid major depression.
Besides genetic vulnerability factors, personality and behavioral characteristics,
such as anxiety sensitivity, neuroticism, and cognitive appraisal might moderate
the influence of LEs on the development of panic disorder. The present state of
knowledge regarding the specification and conceptualization of LEs in PD within a
more complex multifactorial model, involving mediating and moderating factors in
between genes and the clinical phenotype, is hoped to aid in informing future gene
environment interaction studies in panic disorder. Depression and Anxiety 27:716-
730, 2010. (C) 2010 Wiley-Liss, Inc.
Research with adult animals suggests that extinction depends, at least partly, on
new inhibitory learning that is specific to the context in which it is learned.
However, several recent studies show that extinction processes are dissociated
across development. The present article reviews research on the behavioral and
neurobiological mechanisms underlying extinction in developing rats. To summarize,
postweanling aged rats (i.e., 24-day-olds) display adult-like extinction in that
they show renewal, reinstatement, spontaneous recovery, and compound summation of
extinguished stimuli. However, preweanling aged rats (i.e., 17-day-olds) do not
show any of those behavioral phenomena. Pharmacological studies also show that
reducing N-methyl-D-aspartate, gamma-aminobutryic acid, and opioid
neurotransmission impairs extinction in 24-day-old rats, but extinction in P17 rats
is only affected by the blocking of opioid neurotransmission. Lastly, extinction in
24-day-old rats involves the amygdala and the ventromedial prefrontal cortex
(vmPFC), which are critical brain areas in the neural circuitry of extinction in
adult rats. Interestingly, extinction in 17-day-old rats involves the amygdala but
not the vmPFC. The existing models of extinction cannot account for these
developmental differences. These findings showing that distinct processes mediate
extinction at different stages of development may have significant clinical
implications, which are discussed in this review.
Exposure to traumatic events that produce extreme fear and horror is all too common
in both military and civilian populations, but not all individuals develop
posttraumatic stress disorder (PTSD) as a result of the exposure. What mediates
risk and resilience in the development of PTSD and other stress-related
psychopathology is of paramount importance to our further understanding of trauma-
related psychopathology as well as the development of new treatment approaches.
Biological factors, such as genotype and neurobiology, interact with environmental
factors, such as childhood background and trauma load, to affect vulnerability and
resilience in the aftermath of trauma exposure. One of the core symptoms of PTSD is
the inability to control fear, which has led some investigators and clinicians to
conceptualize PTSD as a disorder of fear or, more importantly, its inhibition. This
review focuses on translational methods that have been used to examine fear
conditioning and inhibition of fear in PTSD and summarizes genetic and
neurobiological factors related to fear inhibition. The authors also discuss
different pharmacological approaches that enhance fear inhibition and may improve
treatment outcomes for patients with PTSD. (Am J Psychiatry 2010; 167:648-662)
The goal of my research is to gain insight using rodent models into the fundamental
molecular, cellular and systems that make up the base of memory formation. My work
focuses on fear memories. Aberrant fear and/or anxiety may be at the heart of many
psychiatric disorders. In this article, I review the results of my research group;
these results show that particular neurons in the lateral amygdala, a brain region
important for fear, are specifically involved in particular fear memories. We
started by showing that the transcription factor CREB (cAMP/Ca(2+) response element
binding protein) plays a key role in the formation of fear memories. Next, we used
viral vectors to overexpress CREB in a subset of lateral amygdala neurons. This not
only facilitated fear memory formation but also "drove" the memory into the neurons
with relatively increased CREB function. Finally we showed that selective ablation
of the neurons overexpressing CREB in the lateral amygdala selectively erased the
fear memory. These findings are the first to show disruption of a specific memory
by disrupting select neurons within a distributed network.
There is evidence for either genetic heterogeneity or complex inheritance with an
interaction of environmental factors and multiple single genes in the etiology of
panic disorder. Although linkage analyses of panic disorder have implicated several
chromosomal regions including 1q, 2q, 4q, 7p, 9q, 12q, 13q, 15q and 22q, they so
far have not been able to identify a major gene responsible for panic disorder.
Several genes of classical candidate neurotransmitter systems have been reported to
be associated with panic disorder. Genetic variation in genes of monoamine oxidase
A, catechol-O-methyltransferase, adenosine receptor (ADORA2A) and cholecystokinin B
receptor have been inconsistently replicated. There are multiple lines of evidence
for highly relevant effects of gender and ethnicity. Future research strategies
might focus on broad phenotypes defined by comorbidity or intermediate phenotypes
and include the use of animal models for identifying candidate genes, such as the
regulator of G-protein signaling (RGS2) gene, genome-wide association studies in
large samples, studies of gene gene and gene environment interactions and
pharmacogenetic studies. The identification of novel pathophysiological pathways
may provide the basis for the development of novel therapeutic interventions.
Prepulse inhibition (PPI) of the acoustic startle response is one of the few and
major paradigms for investigating sensorimotor gating systems in humans and rodents
in a similar fashion. PPI deficits are observed not only in patients with
schizophrenia, but also in patients with anxiety disorders. Previous studies have
shown that PPI in rats can be enhanced by auditory fear conditioning. In this
study, we evaluated the effects of contextual fear conditioning (FC) for six times
a day and fear extinction (FE) for seven days on PPI in mice. C57BL/6J mice (male,
8-12 weeks) were divided into three groups; no-FC (control), FC and FC + FE. We
measured PPI at the following three time points, (I) baseline before FC, (2) after
FC, and (3) after FE. The results showed that PPI was increased after FC. Moreover,
the enhanced PPI following FC was observed even after FE with decreased freezing
behaviors. These results suggested contextual fear conditioning could enhance
acoustic PPI, and that contextual fear extinction could decrease freezing
behaviors, but not acoustic PPI. (C) 2009 Elsevier Inc. All rights reserved.
There is current interest in identifying drugs that facilitate fear extinction, as
this form of learning is the basis of certain cognitive therapies for anxiety
disorders. Following an initial report several years ago that the alpha 2-
adrenoreceptor antagonist yohimbine facilitated extinction in mice, more recent
studies have shown mixed effects or even impairment. It has become clear that the
effect of yohimbine on extinction depends on a number of factors, including genetic
background, contextual variables and the presence of competing behaviors. To what
extent theses effects of yohimbine are mediated through the alpha 2-adrenoreceptor,
as opposed to other sites of action, is also uncertain. More work is needed before
this drug can be approved as a pharmacological adjunct for extinction-based
therapies. More generally, the case of yohimbine may serve as a model for the
development of other extinction facilitators.
Fear extinction is a form of inhibitory learning that allows for the adaptive
control of conditioned fear responses. Although fear extinction is an active
learning process that eventually leads to the formation of a consolidated
extinction memory, it is a fragile behavioural state. Fear responses can recover
spontaneously or subsequent to environmental influences, such as context changes or
stress. Understanding the neuronal substrates of fear extinction is of tremendous
clinical relevance, as extinction is the cornerstone of psychological therapy of
several anxiety disorders and because the relapse of maladaptative fear and anxiety
is a major clinical problem. Recent research has begun to shed light on the
molecular and cellular processes underlying fear extinction. In particular, the
acquisition, consolidation and expression of extinction memories are thought to be
mediated by highly specific neuronal circuits embedded in a large-scale brain
network including the amygdala, prefrontal cortex, hippocampus and brain stem.
Moreover, recent findings indicate that the neuronal circuitry of extinction is
developmentally regulated. Here, we review emerging concepts of the neuronal
circuitry of fear extinction, and highlight novel findings suggesting that the
fragile phenomenon of extinction can be converted into a permanent erasure of fear
memories. Finally, we discuss how research on genetic animal models of impaired
extinction can further our understanding of the molecular and genetic bases of
human anxiety disorders.
The ability to alter emotional responses as circumstances change is a critical
component of normal adaptive behavior and is often impaired in psychological
disorders. In this review, we discuss four emotional regulation techniques that
have been investigated as means to control fear: extinction, cognitive regulation,
active coping, and reconsolidation. For each technique, we review what is known
about the underlying neural systems, combining findings from animal models and
human neuroscience. The current evidence suggests that these different means of
regulating fear depend on both overlapping and distinct components of a fear
circuitry. Neuropsychopharmacology Reviews (2010) 35, 136-146;
doi:10.1038/npp.2009.121; published online 26 August 2009
International studies report marked increases in the prevalence of food allergy,
along with increases in hospital admissions and emergency presentations for severe
allergic reactions due to foods. The prevalence of self-reported food allergy is
common, but generally exceeds that which can be verified from challenge studies,
although nut allergies appear to be an important exception to this rule. Studies
examining food allergy deaths suggest that those who die of food allergy usually
have co-existent asthma. Adolescents and young adults are at most risk, and
adrenaline auto-injectors are sub-optimally used. Food chemical sensitivity is very
commonly reported but not usually verified by challenge testing. However, the
exception to this is sulphite sensitivity, which can elicit reproducible reactions
in some. The increasing prevalence of severe food allergies and awareness of its
risk in those with asthma demands an especially rigorous approach to the diagnosis
and management of co-existent food allergy and asthma, especially in young people
who appear to be at most risk from death from severe food allergy.
Objective: Our objective is to summarize the new findings concerning the
respiratory subtype (RS) of panic disorder (PD) since its first description.
Methods: Two searches were made in the Institute for Scientific Information Web of
Science: with the keywords "panic disorder" and "respiratory symptoms," and all
articles that cited Briggs and colleagues' 1993 article "Subtyping of Panic
Disorder by Symptom Profile" (Br J Psychiatry 1993;163:201-9). Altogether, 133
articles were reviewed. Results: We describe and discuss RS epidemiology, genetics,
psychopathology, demographic features, clinical features, correlations with the
respiratory system, traumatic suffocation history, provocative tests, and nocturnal
panic. Compared to patients with the nonrespiratory subtype (non-RS), the RS
patients had higher familial history of PD, lower comorbidity with depression,
longer duration of illness, lower neuroticism scores, and higher scores in severity
scales, such as the Panic and Agoraphobia Scale, Panic-Agoraphobia Spectrum scale
and the Clinical Global Impression scale. Tests to induce panic attacks, such as
those with CO2, hyperventilation, and caffeine, produce panic attacks in a higher
proportion of RS patients than non-RS patients. Differences in the subtypes'
improvement with the pharmacologic treatment were found. There are also some
controversial findings regarding the RS, including the age of onset of PD, and
alcohol and tobacco use in RS patients. Conclusions: Some characteristics, such as
the increased sensitivity to CO2 and the higher familial history of PD, clearly
distinguish the RS from the non-RS. Nevertheless, there are also controversial
findings. More studies are needed to determine the validity of the RS subtype.
(HARV REV PSYCHIATRY 2010;18:220-229.)
The brain does not learn and remember in a unitary fashion. Rather, different
circuits specialize in certain classes of problems and encode different types of
information. Damage to one of these systems typically results in amnesia only for
the form of memory that is the specialty of the affected region. However, the
question of how the brain allocates a specific category of memory to a particular
circuit has received little attention. The currently dominant view (multiple memory
systems theory) assumes that such abilities are hard wired. Using fear conditioning
as a paradigmatic case, I propose an alternative model in which mnemonic processing
is allocated to specific circuits through a dynamic process. Potential circuits
compete to form memories, with the most efficient circuits emerging as winners.
However, alternate circuits compensate when these 'primary' circuits are
compromised.
Exercise is associated with improved cognitive function in humans as well as
improved learning across a range of tasks in rodents. Although these studies
provide a strong link between exercise and learning, to date studies have largely
focused on tasks that principally involve the hippocampus. However, exercise has
been shown to produce alterations in other brain areas suggesting that the
cognitive enhancing effects of exercise may be more general. Therefore we set out
to examine the effects of voluntary exercise on cued Pavlovian fear conditioning, a
form of learning that is critically dependent on the amygdala. In Experiment 1 we
showed that mice given 2 weeks of access to a running wheel prior to tone and foot
shock fear conditioning showed enhanced conditioned fear as measured by fear-
potentiated startle. This effect was not the result of altered shock reactivity nor
was it to due to reduced baseline startle amplitude in exercising mice. In
subsequent experiments we sought to examine whether the enhanced cued conditioned
fear was the result of an improvement in learning, consolidation or retrieval of
conditioned fear. In separate groups of mice, two weeks of access to a running
wheel was begun either prior to fear conditioning, immediately after fear
conditioning (consolidation period) or 2 weeks after fear conditioning. Compared to
sedentary mice, mice that exercised either prior to fear conditioning, or
immediately after fear conditioning, showed enhanced cued conditioned fear. Fear
conditioning was not enhanced in mice that began exercising 2 weeks after fear
conditioning. Taken together these results suggest that voluntary exercise improves
the learning and consolidation of cued conditioned fear but does not improve the
retrieval or performance of conditioned fear. Because a great deal is known about
the neural circuit for cued conditioned fear, it is now possible to examine the
cellular, molecular and pharmacological changes associated with exercise in this
well-understood neural circuit. (C) 2009 Elsevier B.V. All rights reserved.
Several methods to experimentally induce panic cause profound acid-base
disturbances. Evidence suggests that CO2 inhalations, lactate infusions and, to a
certain extent, voluntary hyperventilation can conceivably lead to a common
scenario of brain acidosis in the face of disparate intravascular pH alterations.
The importance of this event is reflected in data that support a model in which
experimental panic attacks, as proxy to those occurring spontaneously, constitute a
response to acute brain acidosis. Given that central CO2/H+ chemoreception is an
important drive for ventilation, and many chemosensitive neurons are related to
respiration and arousal, this model can explain much of the connection between
panic and respiration. We propose that the shared characteristics of CO2/H+ sensing
neurons overlap to a point where threatening disturbances in brain pH homeostasis,
such as those produced by CO2 inhalations, elicit a primal emotion that can range
from breathlessness to panic.
This systematic review focuses on the role of the intensity of fear in patient's
delay in cancer and in myocardial infarction. In a search of literature published
between 1990 and June 2009, 161 articles were found. After the use of inclusion and
exclusion criteria, 11 articles in cancer and 4 articles in myocardial infarction
remained. High levels of fear are associated with earlier help-seeking in both
diseases; for low levels of fear, the picture is unclear. The level of fear is an
important factor, which should be taken into account when facilitating help-seeking
by patients.
Acute pain informs the individual that there is an imminent threat of body damage,
and is associated with the urge to escape and avoid. Fear learning takes place when
neutral stimuli receive the propensity to predict the occurrence of pain, and when
defensive responses are initiated in anticipation of potential threats to the
integrity of the body. Fear-avoidance models have been put forward featuring the
role of individual differences in catastrophic interpretations of pain in the
modulation of learning and avoidance. Based on extensive literature on fear
reduction in anxiety disorders; cognitive-behavioral treatments have been developed
and applied to patients with chronic pain reporting substantial pain-related fear.
In this article, we discuss mechanisms underlying the acquisition, the assessment
and extinction of pain-related fear through the cognitive-behavioral treatment of
pain-related fear. Finally, we provide a number of critical notes and directions
for future research in the field of chronic pain and pain-related fear.
Panic disorder (PD) is a multidimensional anxiety disorder that involves the
activation of a complex brain fear-network. The goals of this systematic review are
to pinpoint some working functions of the most important neuroanatomical structures
of fear and panic neurocircuitry and to raise hypotheses about how cognitive-
behaviour therapy (CBT) may work on modulating the neurocircuitry of fear. The
bibliographical search was carried out using mainly the PubMed database. Fifty-six
articles were selected. A number of studies regarding several brain sites that
participate in fear and anxiety circuitry were found and each region was described
with its functionalities within the circuitry. Among the structures chosen were:
the amygdala, the hippocampus and the prefrontal cortex, which play a special role.
Study hypotheses showed that CBT may operate upstream from the amygdala and exert
inhibitory effects on a variety of learned responses. It may work by strengthening
the medial prefrontal cortex ability to inhibit firing of amygdala neurons, under
the modulation of the hippocampus. Only two studies examined the modulation of fear
neurocircuitry with CBT in PD. The results indicate that CBT has the potential to
modify the dysfunctional neural circuitry associated with PD, but there is
insufficient evidence to support the preliminary hypothesis.
Thanks to brain imaging great advances have been made concerning the comprehension
of neural substrates related to panic disorder (PD). This article aims to: review
the recent functional MRI (fMRI) studies concerning PD; correlate the PD fMRI
neurobiological findings with the fear neurocircuitry hypothesis; discuss the fear
neurocircuitry hypothesis and link it to cognitive-behavior therapy findings; and
comment on fMRI study limitations and suggest methodological changes for future
research. As a whole, there is increasing evidence that brain structures such as
the prefrontal cortex, the anterior cingulate cortex and limbic areas (hippocampus
and amygdala) might play a major role in the panic response.
Data will be reviewed using the acoustic startle reflex in rats and humans based on
our attempts to operationally define fear vs anxiety. Although the symptoms of fear
and anxiety are very similar, they also differ. Fear is a generally adaptive state
of apprehension that begins rapidly and dissipates quickly once the threat is
removed (phasic fear). Anxiety is elicited by less specific and less predictable
threats, or by those that are physically or psychologically more distant. Thus,
anxiety is a more long-lasting state of apprehension (sustained fear). Rodent
studies suggest that phasic fear is mediated by the amygdala, which sends outputs
to the hypothalamus and brainstem to produce symptoms of fear. Sustained fear is
also mediated by the amygdala, which releases corticotropin-releasing factor, a
stress hormone that acts on receptors in the bed nucleus of the stria terminalis
(BNST), a part of the so-called 'extended amygdala.' The amygdala and BNST send
outputs to the same hypothalamic and brainstem targets to produce phasic and
sustained fear, respectively. In rats, sustained fear is more sensitive to
anxiolytic drugs. In humans, symptoms of clinical anxiety are better detected in
sustained rather than phasic fear paradigms. Neuropsychopharmacology Reviews (2010)
35, 105-135; doi:10.1038/npp.2009.109; published online 19 August 2009
This review covers the literature since the publication of DSM-IV on the diagnostic
criteria for panic attacks (PAs) and panic disorder (PD). Specific recommendations
are made based. on the evidence available. In particular, slight changes are
proposed for the wording of the diagnostic criteria, for PAs to ease the
differentiation between panic and surrounding anxiety; simplification and
clarification of the operationalization of types of PAs (expected vs. unexpected)
is proposed; and consideration is given to the value of PAs as a specifier for am
DSM diagnoses and to the cultural validity of certain symptom profiles. In.
addition, slight changes are proposed for the wording of the diagnostic criteria to
increase clarity and parsimony of the criteria. Finally, based on the available
evidence, no changes are proposed with regard to the developmental expression of
PAs or PD. This review prevents a number of options and preliminary recommendations
to be considered for DSM-V. Depression and Anxiety 27:93-112, 2010. (C) 2010 Wiley-
Liss, Inc.
Objective: Cigarette smoking increases the risk of panic disorder with or without
agoraphobia's emerging. Although the cause of this comorbidity remains
controversial, the main explanations are that (1) cigarette smoking promotes panic
by inducing respiratory abnormalities/lung disease or by increasing potentially
fear-producing bodily sensations, (2) nicotine produces physiologic effects
characteristic of panic by releasing norepinephrine, (3) panic disorder promotes
cigarette smoking as self-medication, and (4) a shared vulnerability promotes both
conditions. The aim of this review was to survey the literature in order to
determine the validity of these explanatory models. Data sources: Studies were
identified by searching English language articles published from 1960 to November
27, 2008, in MEDLINE using the key words: nicotine AND panic, tobacco AND panic,
and smoking AND panic. Study selection: Twenty-four studies were reviewed and
selected according to the following criteria: panic disorder with or without
agoraphobia and nicotine dependence, when used, diagnosed according to the
Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised,
Fourth Edition, or Fourth Edition, Text Revision; no additional comorbidity or, if
present, adjustment for it in the statistical analyses; use of adult or adolescent
samples; comparison with a nonclinical control group or application of a crossover
design. Data extraction: Non-significant results or trends only were reported as no
difference. Data on anxiety disorders or substance abuse in general were not
included. Data synthesis: Panic and cigarette smoking each appear to have the
capacity to serve as a causal factor/facilitator in the development of the other.
Although the temporal pattern and the pathogenetic explanations of such a co-
occurrence are still being discussed, cigarette smoking tends to precede the onset
of panic and to promote panic itself. Conclusions: Additional studies are strongly
recommended. Clin Psychiatry 20161;70(5):606-615 (C) Copyright 2009 Physicians
Postgraduate Press, Inc.
Posttraumatic stress disorder (PTSD) and social anxiety disorder (SAD) are
frequently camorbid among veteran and community samples. Several studies have
demonstrated significant camorbidity between trauma, PTSD, and social anxiety (SA),
and a growing number of studies have explored the nature of this association.
Although a diagnosis of either PTSD or SAD alone can result in significant
impairment in social and occupational functioning, these difficulties are often
magnified in persons suffering from both disorders. This review describes the
current state-of-the-art regarding the co-occurrence of trauma, PTSD, and SA.
First, we provide an overview of empirical data on the prevalence of co-occurring
trauma, PTSD, and SAD. Second, we describe possible explanatory models of the co-
occurrence, with a specific focus on the shared vulnerability model. Third, we
review the available empirical data addressing the postulates of this model,
including both genetic and psychological vulnerabilities. Fourth, we describe
additional factors guilt, shame, and depressive symptoms that may help to explain
the co-occurrence of PTSD and SA. A better understanding of this complex
relationship will improve the efficacy of treatment for individuals suffering from
both disorders. We conclude with key areas for future research. Depression and
Anxiety 27:1017-1026, 2010. (C) 2010 Wiley-Liss, Inc.
Panic disorder (PD) represents an insidious, often chronic, recurrent and relapsing
illness. Although studying PD is a topical subject because it affects both
treatment costs and patients' quality of life, the literature demonstrates that
long-term studies are rare and not very systematic. Even if many short-term studies
(within 6 months) show that the present treatment strategies have very good
results, the outcome data in the long term suggest that a significant rate of
patients with PD, in remission at the end of a treatment, relapses during the
follow-up, so that there is the need to find treatment strategies to maintain the
remission achieved in the short-term as long as possible. This study offers an
overview of 35 studies on the long-term outcomes of PD, reviewing the recent
follow-up studies with at least 6 months of follow-up and that investigate the role
of comorbidity in the follow-up of PD, the outcome predictors and the present
treatment strategies.
Early childhood fears are common and transient. Some may give rise to specific
phobias persisting into adulthood. The origins and nature of early fears and
phobias and their relationship with later phobias remain contentious. This paper
examines and aims to resolve some of the associated theoretical and clinical issues
using a reinterpretation derived from the neural model introduced here. The
foundation of the model is evidence that neonates and infants react to the hedonic
(pleasant/unpleasant) properties of visual stimuli, suggesting that such reactivity
is inherent in visual systems. A model of the reactivity and the associated
learning, based on the work of LeDoux (2000) and others, is used to argue that
certain stimuli, such as the sight of snakes, produce intrinsic aversive effects.
These become associated with stimulus identity (a snake). External consequences (a
bite) are not required for the learning. Such associations can form the basis of
developmental and some later fears and phobias. The contributions of the model and
its limitations are discussed. It is then applied to reinterpreting 'developmental
fears' and specific phobias, proposing that reactivity to certain stimulus
properties begins early and remains over the life-span, leading to the potential
for phobias to arise at any time, even without earlier precursors, and for treated
phobias to re-emerge. Some of the research and clinical and implications of this
reinterpretation are highlighted. (C) 2010 Elsevier Ltd. All rights reserved.
Estradiol affects the structure and function of the hippocampus. We have found that
repeated estradiol affects neurogenesis and cell death in the hippocampus of adult
female, but not male rats. In the present study we sought to determine whether
using the same regimen of estradiol would influence hippocampus-dependent
behaviour. Adult male and female rats were given estradiol or sesame oil for 15
days, and then tested using a contextual pre-exposure paradigm in which performance
depends on the hippocampus. The time spent freezing displayed by rats was scored on
subsequent days in (1) the training context, (2) a novel context in which rats had
never been shocked, and (3) the training context a second time. Irrespective of
treatment, males showed stronger memory for the context by exhibiting greater
freezing in both the training context exposures and the novel context. Previous
estradiol treatment, in either sex, did not affect the ability to learn and retain
information about the training context. However, female rats treated with estradiol
and exposed to a novel context after fear conditioning exhibited less freezing
behaviour than controls. Taken together, our results demonstrate that
gonadectomized male rats outperform females, regardless of previous treatment with
estradiol, on a hippocampus-contextual fear conditioning test, and that previous
estradiol treatment has a subtle effect on performance in female but not male rats.
(C) 2009 Elsevier Inc. All rights reserved.
Purpose of review Vaccines remain an effective yet controversial method for
preventing infectious diseases like those caused by human papillomavirus (HPV) and
pandemic influenza (H1N1). However, reports of postvaccination serious adverse
events such as autoimmunity, although rare, have caused great concerns among the
general public. We aimed to summarize the recent knowledge regarding such
interactions, mainly focusing on these new vaccines. Recent findings Autoimmune
phenomena have been associated with specific vaccines, and mechanisms for how this
occurs have been elucidated for different vaccine components like the infectious
antigen and adjuvant. New vaccines that include infrequently used or new adjuvants
have been introduced for both HPV and the H1N1-pandemic influenza. Additionally,
two formulations have been approved for use against HPV, and various formulations
for the H1N1 influenza vaccine. Whereas preliminary studies are successful, early
and late postimmunization events and differences between reagents must be followed
closely, especially during mass immunization programs. Summary As more diseases are
found to be preventable through vaccination, it is of great importance to design
better, more effective and better tolerated vaccines. This goal may be achieved
utilizing improved vaccine components and a postmarketing system that may allow
detection of rare postvaccination phenomena.
5-HT1A receptors are implicated in the modulation of cognitive processes including
encoding of fear learning. However, their exact role has remained unclear due to
contrasting contributions of pre- vs. postsynaptic 5-HT1A receptors. Therefore,
their role in fear conditioning was studied in mice using the selective ligand
S15535, which fully activates 5-HT1A autoreceptors, yet only weakly stimulates
their postsynaptic counterparts. The effects of S15535 were compared to those of
the full agonist 8-OH-DPAT and the selective antagonist NAD-299. 8-OH-DPAT dose-
dependently (0.01-0.5 mg/kg) and markedly impaired both context- and tone-dependent
fear conditioning, as determined by complementary measures of inactivity and
freezing. 8-OH-DPAT-mediated impairments were blocked by pre-injection of the
selective 5-HT1A antagonist WAY100635. S15535 (0.01-5.0 mg/kg) mimicked 8-OH-DPAT
in predominantly impairing conditioned contextual fear, though with smaller effect
size than 8-OH-DPAT. consistent with lower efficacy at postsynaptic 5-HT1A
receptors. Furthermore, S15535 (1.0 mg/kg) tended to attenuate the impairment of
fear conditioning by 8-OH-DPAT (0.3 mg/kg). In contrast, NAD-299 (0.3 and I mg/kg)
facilitated contextual freezing. WAY100635 (0.3 mg/kg) prevented the impairment of
contextual fear by S15535 (I and 5 mg/kg), underpinning the role of 5-HT1A
receptors in the actions of S15535. Collectively, these data indicate that 5-HT1A
receptor ligands modulate fear conditioning in a bidirectional manner: activation
of postsynaptic 5-HT1A sites exerts an inhibitory influence, whereas their blockade
promote facilitation of fear conditioning. The results with S15535 underscore the
importance of ligand efficacy in determining the actions of 5-HT1A receptor ligands
in fear conditioning and other models of cognitive function. (C) 2009 Elsevier Ltd.
All rights reserved.
BACKGROUND: Panic disorder is a common and severe psychiatric disorder. The
estimated current prevalence rate for panic disorder is 1% to 2% of the adult
population. Panic disorder is commonly accompanied by major depression, substance
use disorders, and other anxiety disorders. Female gender, low socioeconomic
status, and anxious childhood temperament are common risk factors for panic
disorder. Panic disorder can produce marked distress and impairment and is
associated with significant suicide risk. Panic disorder appears to increase risk
for all-cause mortality because it may increase risk for cardiovascular disease.
Various empirical data suggest that individuals with Panic Disorder (PD) fail to
appropriately assign significance to sensory stimuli within the internal and
external milieu, including those stimuli which are patently threat-neutral. The
failure to appropriately discriminate 'signal' stimuli from among 'noise' signals
[Gordon, E., Liddell, B.J., Brown, K.J., Bryant, R., Clark, C.R, Das, P., et al.
2007. Integrating objective gene-brain-behavior markers of psychiatric disorders.
J. Integr. Neurosci. 6, 1-34.] results in disturbances of information processing
and attentional deployment which manifests across multiple levels of functioning
(e.g., brain, behaviour, autonomic). The present event-related potential (ERP)
study, therefore, investigated attentive information processing in PD, using a
standard two-tone auditory oddball paradigm, to assess patients' response to
infrequent 'target' tones (i.e., signals) and frequent 'non-target' tones (i.e.,
noise). Simultaneously-recorded autonomic data provided converging measures of the
concomitants of disordered information processing. PD patients (n = 50) showed
increased N1 amplitude to frequent non-target tones and reduced P3 amplitude to
infrequent targets, compared to matched controls (n = 98). There were no between-
group differences for N1 targets, N2 or P2. Patients additionally showed increased
heart rate, fewer spontaneous skin conductance responses (trend) to significant
stimuli, and reduced P3 latency compared to controls, although the latter result
was accounted for by patients who frequently experienced depersonalization and/or
derealisation during panic. Patients showed several disturbances of attentive
information processing in a simple auditory discrimination task: Increased N1 to
repeated stimuli suggests impaired stimulus filtering, whereas reduced P3 amplitude
and latency represent the under-allocation of neural resources for infrequent,
goal-relevant stimuli, and their increased speed of processing, respectively. These
disturbances likely contribute to patients' aversive outcomes in stimulus-rich
environments. (c) 2009 Elsevier B.V. All rights reserved.
Animals have the ability to respond to threatening situations with sets of
defensive behaviors. This review demonstrates that defensive behaviors change
during early life in mammals. First, unlearned responses are reorganized during
early ontogeny and expressed in an age-specific way. Second, the expression of
defensive responses is influenced by early experience prior to the first encounter
with a threat. Third, once animals have been exposed to a threatening stimulus they
subsequently modify their behavior. The neural bases of defensive behavior and the
processes that alter them during development are discussed. Maturation of
components and connections of the fear circuit seem to contribute to changes in
unlearned fear responses. Early experience and learning modify these developmental
processes and shape the expression of defensive behavior. Continuous reorganization
of the neural substrate and defensive behavior during ontogeny seems to allow the
animal to adjust to the conditions it encounters at a given age in a given
environment. It is proposed that the developmental changes in defensive behavior
can be conceptualized as phenotypic plasticity. (c) 2008 Elsevier Ltd. All rights
reserved.
Questionable tactics in America's war on terror continue to undergo scrutiny due to
their threats to human rights, chief among them 'enhanced' interrogation and
torture. Indeed, a growing chorus of criticism has been leveled at the political,
legal, and ethical considerations of those policies and practices. Scholars,
nonetheless, have neglected other important aspects of the controversy, for
instance, the extent to which modern torture has been influenced by 'scientific'
claims involving the effectiveness and appropriateness of certain procedures.
Filling the void, this analysis explores the invention of modern torture as it
draws on behavioral and psychological research in developing a new paradigm for
pain. Delving into the assertions of 'enhanced' techniques, the critique focuses on
a science studies perspective aimed at deciphering the allure of science in
policing as well as in the war on terror. Such 'scientification', as discussed
herein, reinforces the illusion that the state's capacity to unveil the truth is
infallible.
Background The efficacy of combining psychotherapy and benzodiazepines for panic
disorder is unclear, despite widespread use. Objectives To examine the efficacy of
the combination compared with either treatment alone. Search strategy Randomised
trials comparing the combination of psychotherapy and benzodiazepine with either
therapy alone for panic disorder were identified. The Cochrane Depression, Anxiety
and Neurosis Group Studies and References Registers were searched. References of
relevant trials and other reviews were checked. Experts in the field were
contacted. Additional unpublished data were sought from authors of the original
trials. Selection criteria Two authors independently checked the records retrieved
by the searches to identify randomised trials comparing the combined therapy versus
either of the monotherapies, among adults with panic disorder. Data collection and
analysis Two authors independently checked eligibility, assessed quality and
extracted data from the eligible trials using a standardised data extraction form.
The primary outcome was "response" based on global judgement. Random-effects meta-
analyses were conducted, combining data from included trials. Main results Three
trials met eligibility criteria. A 16-week behaviour therapy intervention was used
in two trials, and a 12-week cognitive-behaviour therapy intervention in the third.
Duration of follow-up varied, ranging from 0 to 12 months. Two trials (total 166
participants) provided data comparing combination with psychotherapy alone (both
using behaviour therapy). No statistically significant differences were observed in
response during the intervention (relative risk (RR) for combination 1.25, 95% CI
0.78 to 2.03, P = 0.35), at the end of the intervention (RR 0.78, 0.45 to 1.35, P =
0.37), or at the last follow-up time point, although the follow-up data suggested
that the combination might be inferior to behaviour therapy alone (RR 0.62, 0.36 to
1.07, P = 0.08). One trial (77 participants) compared combination with a
benzodiazepine alone. No differences were found in response during the intervention
(RR 1.57, 0.83 to 2.98, P = 0.17). Although the combination appeared to be superior
to the benzodiazepine alone at the end of treatment (RR 3.39, 1.03 to 11.21, P =
0.05) the finding was only borderline statistically significant, and no significant
differences were observed at the 7-month follow-up (RR 2.31, 0.79 to 6.74, P =
0.12). Authors' conclusions The review established the paucity of high quality
evidence investigating the efficacy of psychotherapy combined with benzodiazepines
for panic disorder. Currently, there is inadequate evidence to assess the clinical
effects of psychotherapy combined with benzodiazepines for patients who are
diagnosed with panic disorder.
The medial division of the central nucleus of the amygdala (CeA(M)) and the lateral
division of the bed nucleus of the stria terminalis (BNSTL) are closely related.
Both receive projections from the basolateral amygdala (BLA) and both project to
brain areas that mediate fear-influenced behaviors. In contrast to CeA(M) however,
initial attempts to implicate the BNST in conditioned fear responses were largely
unsuccessful. More recent studies have shown that the BNST does participate in some
types of anxiety and stress responses. Here, we review evidence suggesting that the
CeA(M) and BNSTL are functionally complementary, with CeA(M) mediating short- but
not long-duration threat responses (i.e., phasic fear) and BNSTL mediating long-
but not short-duration responses (sustained fear or 'anxiety'). We also review
findings implicating the stress-related peptide corticotropin-releasing factor
(CRF) in sustained but not phasic threat responses, and attempt to integrate these
findings into a neural circuit model which accounts for these and related
observations. (C) 2009 Elsevier Inc. All rights reserved.
It has been suggested that different brain areas are involved in the modulation and
expression of fear and anxiety. In the present study we investigated these
potential differences by using the fear-potentiated-startle (FPS) and light-
enhanced-startle (LES) paradigms to differentiate between fear and anxiety,
respectively. Male Wistar rats were tested in the FPS and LES paradigm and perfused
I h after the test session. Fos immunoreactivity (IR) was quantified in 21 brain
areas and compared between FPS, LES and four control conditions. Both FPS and LES
procedures significantly enhanced the acoustic startle response. A principal
component analysis of Fos-IR-data showed that 70% of the changes in Fos-IR could be
explained by three independent components: an arousal-component, identifying brain
areas known to be activated under conditions of vigilance, arousal and stress, a
LES- and an FPS-component. The LES component comprised the septohippocampal system
and functionally interrelated areas including nucleus accumbens, anterior cingulate
cortex, lateral habenula and supramammillary areas, but not the dorsolateral part
of the bed nucleus of the stria terminalis. The central amygdaloid nucleus and the
dorsolateral part of the bed nucleus of the stria terminalis loaded exclusively on
the FPS component. Analysis of the separate brain areas revealed significantly
higher Fos-IR in LES relative to FPS in the anterior cingulate cortex, nucleus
accumbens shell, lateral septum, lateral habenula and area postrema. We conclude
that the neural circuitry activated during FPS and LES shows clear differences. In
anxiety as induced by LES, activation of the septohippocampal system and related
areas seems to play a major role. In fear as induced by FPS, the central amygdaloid
nucleus and the dorsolateral part of the bed nucleus of the stria terminalis loaded
on the same component, but Fos-IR observed in these brain regions did not
differentiate between anxiety and fear. Furthermore, principal-component analysis
appears a useful tool in detecting and describing correlated changes in patterns of
neuronal activity. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.
Integrative hierarchical models have sought to account for the extensive
comorbidity between various Internalizing disorders in terms of broad individual
difference factors these disorders share However. such models have been developed
largely oil the basis of self-report and diagnostic symptom data Toward the goal of
linking such models to neurobiological systems. we reviewed studies that have
employed variants of the affect-modulated startle paradigm to investigate emotional
processing in internalizing, disorders its well as personality constructs known to
be associated with these disorders Specifically. we focused oil four parameters of
startle reactivity fear-potentiated startle. inhibition of startle in the context
of pleasant stimuli. context-potentiated startle, and general startle reactivity.
On the basis of available data, we argue that these varying effects index differing
neurobiological processes related to mood and anxiety disorders that are
interpretable from the standpoint of dimensional models of the Internalizing
spec(rum Further, we contend that these empirical findings can feed back into and
help reshape conceptualizations of Internalizing disorders in ways that make them
more amenable to neurobiological analysis.
SINCE the wars in Afghanistan and Iraq, military strategists, historians, soldiers,
and policymakers have made counterinsurgency's principles and paradoxes second
nature, and they now expect that counterinsurgency operations will be the likely
wars of the future. Yet despite counterinsurgency's ubiquity in military and policy
circles, legal scholars have almost completely ignored it. This Article evaluates
the laws of war in light of modern counterinsurgency strategy. It shows that the
laws of war are premised on a kill-capture strategic foundation that does not apply
in counterinsurgency, which follows a win-the-population strategy. The result is
that the laws of war are disconnected from military realities in multiple areas-
from the use of non-lethal weapons to occupation law. This Article also argues that
the war on terror legal debate has been somewhat myopic. The shift from a kill-
capture to a win-the-population strategy not only expands the set of topics legal
scholars interested in contemporary conflict must address, but also requires
incorporating the strategic foundations of counterinsurgency when considering
familiar topics in the war on terror legal debates.
Fear conditioning and extinction are basic forms of associative learning that have
gained considerable clinical relevance in enhancing our understanding of anxiety
disorders and facilitating their treatment. Modern neuroimaging techniques have
significantly aided the identification of anatomical structures and networks
involved in fear conditioning. On closer inspection, there is considerable
variation in methodology and results between studies. This systematic review
provides an overview of the current neuroimaging literature on fear conditioning
and extinction on healthy subjects, taking into account methodological issues such
as the conditioning paradigm. A Pubmed search, as of December 2008, was performed
and supplemented by manual searches of bibliographies of key articles. Two
independent reviewers made the final study selection and data extraction. A total
of 46 studies on cued fear conditioning and/or extinction on healthy volunteers
using positron emission tomography or functional magnetic resonance imaging were
reviewed. The influence of specific experimental factors, such as contingency and
timing parameters, assessment of conditioned responses, and characteristics of
conditioned and unconditioned stimuli, on cerebral activation patterns was
examined. Results were summarized descriptively. A network consisting of fear-
related brain areas, such as amygdala, insula, and anterior cingulate cortex, is
activated independently of design parameters. However, some neuroimaging studies do
not report these findings in the presence of methodological heterogeneities.
Furthermore, other brain areas are differentially activated, depending on specific
design parameters. These include stronger hippocampal activation in trace
conditioning and tactile stimulation. Furthermore, tactile unconditioned stimuli
enhance activation of pain related, motor, and somatosensory areas. Differences
concerning experimental factors may partly explain the variance between
neuroimaging investigations on human fear conditioning and extinction and should,
therefore, be taken into serious consideration in the planning and the
interpretation of research projects.
In recent years there has been an increased concern regarding the potential use of
chemical and biological weapons for mass urban terror. In particular, there are
concerns that ricin could be employed as such an agent. This has been reinforced by
recent high profile cases involving ricin, and its use during the cold war to
assassinate a high profile communist dissident. Nevertheless, despite these events,
does it deserve such a reputation? Ricin is clearly toxic, though its level of risk
depends on the route of entry. By ingestion, the pathology of ricin is largely
restricted to the gastrointestinal tract where it may cause mucosal injuries; with
appropriate treatment, most patients will make a full recovery. As an agent of
terror, it could be used to contaminate an urban water supply, with the intent of
causing lethality in a large urban population. However, a substantial mass of pure
ricin powder would be required. Such an exercise would be impossible to achieve
covertly and would not guarantee success due to variables such as reticulation
management, chlorination, mixing, bacterial degradation and ultra-violet light. By
injection, ricin is lethal; however, while parenteral delivery is an ideal route
for assassination, it is not realistic for an urban population. Dermal absorption
of ricin has not been demonstrated. Ricin is also lethal by inhalation. Low doses
can lead to progressive and diffuse pulmonary oedema with associated inflammation
and necrosis of the alveolar pneumocytes. However, the risk of toxicity is
dependent on the aerodynamic equivalent diameter (AED) of the ricin particles. The
AED, which is an indicator of the aerodynamic behaviour of a particle, must be of
sufficiently low micron size as to target the human alveoli and thereby cause major
toxic effects. To target a large population would also necessitate a quantity of
powder in excess of several metric tons. The technical and logistical skills
required to formulate such a mass of powder to the required size is beyond the
ability of terrorists who typically operate out of a kitchen in a small urban
dwelling or in a small ill-equipped laboratory. Ricin as a toxin is deadly but as
an agent of bioterror it is unsuitable and therefore does not deserve the press
attention and subsequent public alarm that has been created. (C) 2009 Elsevier Ltd.
All rights reserved.
Individual psychological responses to heights vary on a continuum from acrophobia
to height intolerance, height tolerance, and height enjoyment. This paper reviews
the English literature and summarizes the physiologic and psychological factors
that generate different responses to heights while standing still in a static or
motionless environment. Perceptual cues to height arise from vision. Normal
postural sway of 2 cm for peripheral objects within 3 in increases as eye-object
distance increases. Postural sway > 10 cm can result in a fall. A minimum of 20
minutes of peripheral retinal arc is required to detect motion. Trigonometry
dictates that a 20-minute peripheral retinal arch can no longer be achieved in a
standing position at an eye-object distance of >20 m. At this distance, visual cues
conflict with somatosensory and vestibular inputs, resulting in variable degrees of
imbalance. Co-occurring deficits in the Visual, vestibular, and somatosensory
systems can significantly increase height imbalance. An individual's psychological
makeup, influenced by learned and genetic factors, can influence reactions to
height imbalance. Enhancing peripheral vision and vestibular, proprioceptive, and
haptic functions may improve height imbalance. Psychotherapy may improve the
troubling subjective sensations to heights.
Fear arousal, initiated by an environmental threat, leads to activation of the
stress response, a state of alarm that promotes an array of autonomic and endocrine
changes designed to aid self-preservation. The stress response includes the release
of glucocorticoids from the adrenal cortex and catecholamines from the adrenal
medulla and sympathetic nerves. These stress hormones, in turn, provide feedback to
the brain and influence neural structures that control emotion and cognition. To
illustrate this influence, we focus on how it impacts fear conditioning, a
behavioral paradigm widely used to study the neural mechanisms underlying the
acquisition, expression, consolidation, reconsolidation, and extinction of
emotional memories. We also discuss how stress and the endocrine mediators of the
stress response influence the morphological and electrophysiological properties of
neurons in brain areas that are crucial for fear-conditioning processes, including
the amygdala, hippocampus, and prefrontal cortex. The information in this review
illuminates the behavioral and cellular events that underlie the feedforward and
feedback networks that mediate states of fear and stress and their interaction in
the brain.
Nicotine alters cognitive processes that include working memory and long-term
memory. Trace fear conditioning may involve working memory during acquisition while
also allowing the assessment of long-term memory. The present study used trace fear
conditioning in C57BL/6 mice to investigate the effects of acute nicotine, chronic
nicotine and withdrawal of chronic nicotine on processes active during acquisition
and recall 24 h later and to examine the nicotinic acetylcholine receptor subtypes
(nAChRs) involved in withdrawal deficits in trace fear conditioning. During
training, acute nicotine (0.09 mg/kg) enhanced, but chronic nicotine (6.3
mg/kg/day, 13 days) and withdrawal of chronic nicotine (6.3 mg/kg/day, 12 days) had
no significant effect on, acquisition of trace conditioning. At recall, acute
treatment enhanced conditioning while chronic nicotine had no effect and withdrawal
of chronic nicotine resulted in deficits. Antagonist-precipitated withdrawal was
used to characterize the nAChRs involved in the withdrawal deficits. The low-
affinity nAChR antagonist MLA (1.5, 3 or 9 mg/kg) had no effect on trace fear
conditioning, but the high-affinity nAChR antagonist DH beta E (3 mg/kg)
precipitated deficits in trace fear conditioning if administered at training or
training and testing, but not if administered at testing alone. The beta 2 nAChR
subunit is involved in the withdrawal effects as withdrawal of chronic nicotine
produced deficits in trace fear conditioning in wildtype but not in beta 2-knockout
mice. Thus, nicotine alters processes involved in both acquisition and long-term
memory of trace fear conditioning, and high-affinity beta 2 subunit-containing
nAChRs are critically involved in the effects of nicotine withdrawal on trace fear
conditioning.
In recent years, much has been learned about the strategic and organizational
contexts of suicide attacks. However, motivations of the agents who commit them
remain difficult to explain. In part this is because standard models of social
learning as well as Durkheimian notions of sacrificial behavior are inadequate in
the face of the actions of human bombers. In addition, the importance of
organizational structures and practices in reinforcing commitment on the part of
suicide recruits is an under-explored factor in many analyses. This essay examines
the potential applicability of evolutionary models of altruism to the understanding
of commitment to suicide on the part of terrorist organizational recruits. Three
evolutionary models of sacrificial behavior in nonhuman species and many categories
of human behavior are explored cross-organizationally: reciprocity, inclusive
fitness theory, and induced altruism. Reciprocal altruism is unlikely to be a major
motivator in suicide attacks because the costs exhibited by attackers are too high
to be adequately compensated. However, the role of evolved self-deception in
perceptions of personal death, and thus of rewards in the afterlife, is potentially
illuminating. Inclusive fitness theory can help explain the motivations of
attackers because rewards to kin often are offered by organizations to suicide
recruits. However, suicide bombers also often act out of revenge for the loss of or
injury to relatives, and inclusive fitness theory generally, as well as more
specific theoretical models of retaliatory aggression, may not adequately account
for the bombers' actions. Predictions from induced altruism theory appear to be
well supported because suicide terror organizations tend to be tightly structured
around practices intended to maintain and reinforce commitment though the
manipulation of kinship-recognition cues.
Extinction is a form of inhibitory learning that suppresses a previously
conditioned response. Both fear and drug seeking are conditioned responses that can
lead to maladaptive behavior when expressed inappropriately, manifesting as anxiety
disorders and addiction, respectively. Recent evidence indicates that the medial
prefrontal cortex (mPFC) is critical for the extinction of both fear and drug-
seeking behaviors. Moreover, a dorsal-ventral distinction is apparent within the
mPFC, such that the prelimbic (PL-mPFC) cortex drives the expression of fear and
drug seeking, whereas the infralimbic (IL-mPFC) cortex suppresses these behaviors
after extinction. For conditioned fear, the dorsal-ventral dichotomy is
accomplished via divergent projections to different subregions of the amygdala,
whereas for drug seeking, it is accomplished via divergent projections to the
subregions of the nucleus accumbens. Given that the mPFC represents a common node
in the extinction circuit for these behaviors, treatments that target this region
may help alleviate symptoms of both anxiety and addictive disorders by enhancing
extinction memory.
This Article develops both a framework for a theory of desistance from crime and an
analytical strategy with which to examine desistance. With respect to the former,
an identity theory of the desistance from crime that is more cognitive and
individualistic than some and more forward-looking than others is sketched out.
This framework contributes to and complements existing theoretical arguments by
building upon the work of others through integrating several diverse bodies of work
that range from social psychology to collective movements in sociology. In this
framework, offenders have "working selves" as criminal offenders with a set of
preferences and social networks consistent with that self In addition to the
working self, or the self in the present, there is a future, or possible, self that
consists both of desires as to what the person wishes or hopes to become (the
positive possible self) and anxiety over what they fear they may become (the feared
self). Persons are committed to their working self until they determine that the
cost of this commitment is greater than the benefits. A perception that one may in
fact turn out to become the,feared self, a perception assisted by the linking of
life failures, or what has been called the "crystallization of discontent,
"provides the initial motivation to change the self. This initial motivation brings
with it a change in preferences and social networks that stabilize the newly
emerging self. This identity theory of desistance can be empirically developed by
thinking about it in terms of a structural break in an individual-level time series
of offending. This theory and the process of desistance itself can be profitably
examined by examining such time series of offending over a long time period at the
individual level.
Background: in a prior concordance study of affected sibling pairs with a community
diagnosis of pediatric bipolar disorder (PBD) a behavioral phenotype termed Fear of
Harm (FOH) was found to have one of the strongest concordance coefficients (rho)
between probands and siblings, and the widest contrasts between the rho-estimates
for the proband/sibling vs. proband/comparison pairs [Papolos, D., Hennen, J.,
Cockerham, M.S, Lachman, H., 2007]. A strategy for identifying phenotypic subtypes:
concordance of symptom dimensions between sibling pairs who met screening criteria
for a genetic linkage study of childhood-onset bipolar disorder using the Child
Bipolar Questionnaire (CBQ) was employed. J. Affect. Disord. 99, 27-36.]. We used
the Child Bipolar Questionnaire (OUT) (CBQ) to further elucidate this behavioral
phenotype of PBD. We hypothesized that selectve factors including parent reported
symptoms of mania and depression, would be distinguishing features of impairment
between groups defined by I) the magnitude of their score on a continuous measure
of FOH, and 2) the high FOH group Would have significantly greater levels of
severity on course of illness variables. These measures included earlier age of
onset of first psychiatric symptoms, first hospitalization, and frequency of
psychiatric hospitalizations, as well as, degree of social impairment as determined
by exposure to the juvenile justice system and school performance problems.
Methods: The sample was comprised of children with community diagnoses of bipolar
disorder or at risk for the illness based on enriched family history with multiple
first degree relatives diagnosed with BPD (N = 5335). Included were all subjects
who had >40 positively endorsed CBQ symptom items at frequencies of very often,
almost always, and always. This group was divided randomly into two groups, the
exploratory group (N = 2668) and the hypothesis testing (study) group (N 2666). The
exploratory group was used for the development of hypotheses and the study group
was used to test these hypotheses on a new set of data. All results reported here
derive from the latter group. In subsequent analyses, we classified each child as
having a high degree of FOH, low FOH, or no FOH. We examined a Subset of the sample
for differences in age of onset of first psychiatric symptoms, course of illness
and measures of symptom severity. These groups were compared using the chi-square
procedure for categorical data and the Analysis of Variance (ANOVA) with Scheffe
pair wise tests for continuous variables. The Child Bipolar Questionnaire V.2.0,
the Yale-Brown Obsessive Compulsive Scale (YBOCS) and the Overt Aggression Scale
(OAS) were the principal instruments used to obtain diagnostic information for this
study. Results: We found that children representative of the FOH phenotype when
compared to children with PBD who lack this trait had higher indices of severity of
mania and depression, as well as other indices that reflect severity and course of
illness. Trait factors we re derived from a factor analysis of CBQ in a large
population of children diagnosed with or at risk for PBD, and used to further
elucidate trait features of children with FOH. Children with the FOH traits were
also more likely to be defined by six CBQ factors; Sleep/Arousal, Harm to Self and
Others, Territorial Aggression, Anxiety, Self-esteem, Psychosis/Parasomnias/Sweet
Cravings/Obsessions (PPSO). Limitations: This data is derived from samples enriched
with bipolar disorder cases. Further validation is needed with samples in which
childhood-onset 131) is rarer and diagnoses more diverse. Clinician diagnosis was
not validated via research interview. Conclusions: The FOH phenotype, as defined by
a metric derived from combining items from the YBOCS/OAS, is a clinically
homogeneous behavioral phenotype of PBD with early age of onset. severe manic and
depressive symptoms, and significant social impairment that is strongly associated
with 6 CBQ factors and can be easily identified using the CBQ. Through the
examination of dimensional features of PBD in an enriched sample of large size, we
were able to further refine a phenotype and identify clinical dimensions
potentially linked to endophenotypic markers that may prove fruitful in
differential diagnosis, treatment and etiological studies of PBD. The nature of the
sets of specific symptoms that comprise the FOH factors enabled us to propose a
biological model for the phenotype (OUT) that involves a complex orexigenic circuit
which links hypothalamic, limbic, and other brain nuclei primarily responsible for
the regulation of behavioral and proposed physiological features of the FOH
phenotype. (C) 2009 Elsevier B.V. All rights reserved.
This paper questions the recent recasting of fear within critical geopolitics. It
identifies a widespread metanarrative, 'globalized fear', analysis of which lacks
grounding and is remote, disembodied and curiously unemotional. A hierarchical
scaling of emotions, politics and place overlooks agency, resistance and action.
Drawing on feminist scholarship, I call for an emotional geopolitics of fear which
connects political processes and everyday emotional topographies in a less
hierarchical, more enabling relationship. I employ conscientization as a tool to
inform the reconceptualization of global fears within critical geopolitics, and to
move forward epistemological practice and our relationship as scholars with social
change.
Corticotropin releasing factor (CRF) is a neuropeptide that is a major regulator of
the hypothalamic-pituitary-adrenal system. Recent findings have shown that CRF
exists in extrahypothalamic areas in the brain as well as in the hypothalamus, and
extrahypothalamic CRF is also deeply involved in stress responses. Therefore, CRF
has been a major target of drug development for treatment of stress-related
disorders. However, whether CRF is a cause or a result of fear/anxiety has not been
investigated extensively, even though this issue is extremely important to the
development of treatments for stress-related disorders. This article aims to 1)
introduce readers to several functional aspects of CRF, focusing on aspects that
have been missed or ignored when determining the roles of CRF in responses to
emotional stress; 2) critically review previous studies regarding the roles of CRF
in responses to emotional stress, considering functional aspects of CRF described
in 1); and 3) put forward a hypothesis about the roles of CRF in stress responses.
Considering different functional aspects of CRF, it is suggested that CRF is a
result of fear/anxiety, rather than a cause. In other words, CRF could be
responsible for stress responses to cope with dangerous situations but not for
fear/anxiety itself. CRF as a potential target of drug development for treatment of
stress-related disorders is also discussed.
Objective: To provide a systematic review of studies investigating respiration in
PD and comments on relative inconsistencies. Method: A Medline search of controlled
studies focusing on pCO(2), respiratory rate, tidal volume, and minute volume in PD
patients was conducted for baseline/resting condition, challenge, and recovery
phase. Respiratory variability and comparisons between panickers and non-panickers
were also examined. Results: Lower pCO(2) levels in PD subjects are a consistent
finding during the baseline/resting condition, the challenge, and recovery phases.
Tidal volume and minute volume are increased in PD subjects relative to controls
during the baseline/resting condition. However, the most robust finding is a higher
than normal respiratory variability, which appears to be a promising factor for the
identification of respiratory etiopathological pathways in PD. Conclusion:
Respiratory variability might be a candidate for a biological marker of PD: an
abnormal breathing pattern as found in panic disorder (PD) patients compared with
controls might indicate instability of the respiratory homeostasis.
Anxiety disorders, particularly panic disorder (PD), are associated with
respiratory abnormalities. PD consists of unexpected panic attacks (PA) with
anxiety, fear and many autonomic and respiratory symptoms. There is a substantial
body of literature demonstrating that stimulation of respiration is a common event
in panic disorder patients during PA. A number of abnormalities in respiration,
such as enhanced CO2 sensitivity, have been detected in PD patients. As a result,
some investigators advanced that there is a fundamental abnormality in the
physiological mechanisms that control breathing in PD. Studies indicate that PD
patients with dominant respiratory symptoms are particularly sensitive to
respiratory tests compared with those who do not manifest dominant respiratory
symptoms, possibly representing a distinct subtype. Accumulated evidence suggests
that respiratory physiology remains normal in PD patients and that their tendency
to hyperventilate and to react with panic to respiratory stimulants like CO2
represents the triggering of a hypersensitive fear network. However, some recent
evidences support the presence of subclinical abnormalities in respiration and
other functions related to body homeostasis. The fear network, composed by the
hippocampus, the medial prefrontal cortex, the amygdala and its brainstem
projections, may be abnormally sensitive in PD patients. This theory might explain
why both medication and psychosocial therapies are clearly effective. The evidence
of abnormalities in several neurochemical systems might be just the expression of
the complex interactions among brain circuits. Our aim was to review the
relationship between respiration and panic disorder, addressing the respiratory
subtype of panic disorder, the hyperventilation syndrome, the respiratory challenge
tests, the current mechanistic concepts and the pharmacological implications. (C)
2008 Elsevier B.V. All rights reserved.
This article compares the place of fear in French, German, and Russian medical
theories of military "trauma". It focuses on pathogenesis (the importance military
psychiatrists accorded to fear in their descriptions of the origins of mental
illness), masculinity (the relationship between fear and concepts of manhood), and
spatiality (how soldierly fear correlates with specific spaces, such as the
trenches or the home front). One of its conclusions is that the professional
identity of the military psychiatric profession and its relationship to the state
were critical factors in determining a national military psychiatry's conception of
soldierly fear.
Substantial evidence indicates that women report greater fear and are more likely
to develop anxiety disorders than men. Women's greater vulnerability for anxiety
disorders can be partly understood by examining gender differences in the
etiological factors known to contribute to anxiety. This review examines evidence
for gender differences across a broad range of relevant factors, including
biological influences, temperamental factors, stress and trauma, cognitive factors,
and environmental factors. Gender differences are observed with increasing
consistency as the scope of analysis broadens to molar levels of functioning.
Socialization processes cultivate and promote processes related to anxiety. and
moderate gender differences across levels of analysis. (C) 2009 Elsevier Ltd. All
rights reserved.
This article provides an empirical review of the elements and efficacy of both
pharmacologic and psychosocial treatments for panic disorder. Both monotherapies
and combination treatment strategies are considered. The available evidence
suggests that both cognitive behavioral therapy (CBT) and pharmacotherapy
(prominently, selective serotonin reuptake inhibitors or serotonin-norepinephrine
reuptake inhibitors) are effective first-line agents and that CBT offers particular
cost efficacy relative to both pharmacotherapy alone and combined pharmacotherapy
and CBT. Predictors of non-response and mechanisms of action are considered, as are
novel treatment strategies, including the use of memory enhancers to improve CBT
outcome.
Objective: Breath-holding (BH) has been used as a simple probe to increase
endogenous carbon dioxide (CO2). In patients with Panic Disorder (PD), lower
baseline BH duration is associated with caffeine-induced panic attacks. In this
paper, we assessed BH duration in PD patients in relation to panic attacks induced
by caffeine intake. Methods: BH duration and state anxiety were assessed in 40 PD
patients (12 males), both at baseline and after a 400-mg caffeine challenge test.
Results: Patients panicking after caffeine administration (14 patients, 4 males)
exhibited a significant reduction of their post-challenge BH duration, while no
change of the BH duration was observed in non-panicking patients (26 patients, 8
males), Reduction in post-challenge BH duration was not related to higher anxiety
levels - as reflected in the State-Trait Anxiety Inventory-State Form scores -
independently of the occurrence of a panic attack. Panickers exhibited
significantly lower baseline BH duration, compared to non-panickers. Conclusions:
Our findings indicate that in PD patients, caffeine-induced panic attacks are
strongly associated with a significant reduction of BH duration at both pre- and
post-challenge. jointly, these findings suggest that in a Subgroup of PD patients,
sensitivity to endogenous CO2 accumulation may underlie both the lower BH durations
and the caffeine-induced panic attacks. In this subgroup of PD patients, caffeine
might exert its panicogenic properties through the exacerbation of patients'
already pathological hypersensitivity to CO2 accumulation, as indicated by both the
significant decrease of their BH duration at post-challenge and by their
significantly lower baseline BH duration respectively. (c) 2008 Elsevier Inc. All
rights reserved.
The peroxisome proliferator-activated receptor superfamily (PPARs) comprises a
class of nuclear receptors with significant effects in regulating multiple cellular
pathways. Much research and clinical interest has surrounded the PPAR-gamma isoform
because of its key role in the transcriptional regulation of metabolic pathways and
the efficacy of thiazolidinediones, the most clinically used PPAR-gamma agonist, in
the management of type 2 diabetes mellitus. In this review, we discuss the
pathogenic role of PPAR-gamma in experimental models of kidney disease, clinical
trials of thiazolidinediones in diabetic and non-diabetic kidney disease, recent
safety concerns surrounding PPAR-gamma agonists and reflect on their potential use
in 'orphan' kidney diseases. Copyright (C) 2009 S. Karger AG, Basel
The short allele of a functional polymorphism (5-HTTLPR) in the serotonin
transporter (5-HTT) promoter is associated with reduced serotonin transporter
expression, lower in vivo 5-HTT binding, higher neuroticism and amygdala reactivity
as well as facilitated fear conditioning and is a candidate variant for panic
disorder. However, case-control studies have consistently failed to show an
association between 5-HTTLPR and panic disorder. As psychiatric disorders are
broadly defined phenotypes merging different symptoms to syndromes, they may not be
very well suited for genetic association studies. An alternative approach is to
measure symptoms along continuous symptom dimensions which may more appropriately
reflect their biological underpinnings and may reveal subpopulations within
clinical diagnostic groups. We recorded the symptomatic profile in 73 in panic
disorder patients using observer-rated instruments (Panic Disorder Severity Scale,
PDSS; Montgomery-Asberg Depression Rating Scale, MADRS) and hypothesized more
severe symptoms in patients carrying the 5-HTTLPR s-allele. We observed a strong
association between bi- and triallelic 5-HTTLPR polymorphisms and the symptomatic
profile. Carriers of the 5-HTTLPR s-allele suffered from most severe panic and
depressive symptoms. Our data highlight the importance of defining appropriate
phenotypes for psychiatric genetic studies and demonstrate that the 5-HTTLPR
genotype may be related to the symptomatic profiles rather than to the
vulnerability to develop panic disorder. (C) 2009 Elsevier Inc. All rights
reserved.
The authors tested whether coping styles and fear of pain mediate the relationship
between positive affect and negative affect on one hand and pain-related distress
(PD) on the other. Among African American and Caucasian female college students,
negative affect, fear of pain, and emotion-oriented coping together accounted for
34% of the variance in PD among African American women and 40% the variance in PD
among Caucasian women. Emotion-oriented coping and fear of pain fully mediated the
relationship between negative affect and PD among Caucasian women and partly
mediated the relationship between negative affect and PD among African American
women. Results suggest that reducing college women's reliance on emotion-oriented
coping and their fears of pain may help reduce PD.
Li G, Nair SS, Quirk GJ. A biologically realistic network model of acquisition and
extinction of conditioned fear associations in lateral amygdala neurons. J
Neurophysiol 101: 1629-1646, 2009. First published November 26, 2008;
doi:10.1152/jn.90765.2008. The basolateral amygdala plays an important role in the
acquisition and expression of both fear conditioning and fear extinction. To
understand how a single structure could encode these "opposite" memories, we
developed a biophysical network model of the lateral amygdala (LA) neurons during
auditory fear conditioning and extinction. Membrane channel properties were
selected to match waveforms and firing properties of pyramidal cells and
interneurons in LA, from published in vitro studies. Hebbian plasticity was
implemented in excitatory AMPA and inhibitory GABA(A) receptor-mediated synapses to
model learning. The occurrence of synaptic potentiation versus depression was
determined by intracellular calcium levels, according to the calcium control
hypothesis. The model was able to replicate conditioning-and extinction-induced
changes in tone responses of LA neurons in behaving rats. Our main finding is that
LA activity during both acquisition and extinction can be controlled by a balance
between pyramidal cell and interneuron activations. Extinction training depressed
conditioned synapses and also potentiated local interneurons, thereby inhibiting
the responses of pyramidal cells to auditory input. Both long-term depression and
potentiation of inhibition were required to initiate and maintain extinction. The
model provides insights into the sites of plasticity in conditioning and
extinction, the mechanism of spontaneous recovery, and the role of amygdala NMDA
receptors in extinction learning.
The clinical and therapeutic aspects of nocturnal panic attacks (NPAs) remain
poorly understood. Some authors present NPAs as a more severe and less cognitive
form of panic disorder (PD), whereas others treat it as a different manifestation
of conventional panic attack. Overall, few articles address NPA relative to the
large amount of literature regarding PD. Important aspects regarding the management
of NPAs, such as the appropriate pharmacological and psychological treatment, rely
on relatively few studies. This review provides an update and review of the most
relevant articles regarding conceptualization of NPA, differential diagnosis,
comorbidities, treatments, etiological theories and new investigations developed by
various research centers. We also discuss the etiological hypotheses of NPAs,
focusing on the suffocation false alarm theory and conditioned fear. NPA patients
may represent a subtype of PD with specific agoraphobic features, respiratory
connections and unique therapeutic aspects.
Cognitive-behavioral therapy can be regarded as gold standard in treating panic
disorder and agoraphobia. Frequently endorsed intervention techniques are a)
psychoeducation about anxiety and panic, b) cognitive restructuring regarding the
tendency to catastrophize perceived bodily symptoms, c) exposure to internal as
well as external cues, and d) training of coping strategies for dealing with bodily
symptoms, e. g., relaxation techniques and breathing retraining. Empirical findings
on these interventions are reviewed and discussed regarding their importance within
the frame of evidence-based CBT treatment for panic disorder and agoraphobia.
Background: Panic disorder is a heterogeneous disorder, comprising a variety of
somatic, pbysiological, and cognitive symptoms during repeated panic attacks As a
result, considerable data have examined whether panic attacks may be classified
into distinct diagnostic or functional subtypes. The aim of this study is to
evaluate the existing literature regarding the validity of panic attack subtypes.
Methods: This review focuses on data published since 2000, with the publication of
DSM-IV-TR, augmented by replicated data published since 1980, with the publication
of DSM-III and subsequently DSM-IV Published reports evaluating empirical evidence
for the validity of panic attack subtypes are reviewed. Results: Five sets of panic
symptoms (respiratory, nocturnal, nonfearful, cognitive, and vestibular) have been
shown to cluster together at varying degrees of consistency. However, none of these
potential subtypes have been associated with sufficient and reliable external
validation criteria indicative of functional differences This apparent lack of
findings may be related to methodological inconsistencies or limitations across the
reviewed studies. Conclusions: Although at present the data do not warrant the
utility of subtyping, further research aimed at patent gaps in the literature,
including clearer operationalization of symptom subtypes, greater use of biological
challenge paradigms and pbysiological and other more objective measures of fear and
anxiety, and exploration of subtyping based on biological factors such as genetics,
may support the future designation of panic attack subtypes and their ultimate
clinical utility. Depression and Anxiety 26:878-887, 2009. (C) 2009 Wiley-Liss,
Inc.
Introduction: Bipolar mood disorder carries a serious suicide risk. Panic disorder,
which also confers an independent risk of suicide and psychiatric comorbidity, in
general has been found to amplify suicidality in mood-disordered patients. This
article assesses the available literature on how panic and suicide relate to each
other in bipolar mood-disordered patients. Methods: We conducted a search on
Medline and PsyclNFO using the keywords "anxiety", "attempted suicide", "completed
suicide", "mortality", "self-harm" in combination with "bipolar", "manic
depression" and "panic". Twenty-four articles were included in the evaluation.
Results: 14 papers support increased risk, 9 papers do not support increased risk,
and 3 papers are inconclusive. Conclusions: The presence of comorbid panic disorder
in individuals with bipolar disorder may confer an increased risk of suicide risk.
Some papers' reviewed have conflicting conclusions but the majority of papers
support ail increased risk. This is consistent with a recent (2008) literature
review supporting increased risk Of Suicide in bipolar patients with comorbid
anxiety disorders. Future research should study specific bipolar Subgroups, focus
on anxiety and panic symptoms rather than diagnosis, and look at the role of
specific pharmacological treatment in patients with comorbid mood and anxiety
disorders. (C) 2009 Elsevier B.V. All rights reserved.
Power spectral analysis of electrocardiogram (ECG) R-R intervals is useful for the
detection of autonomic dysfunction in various clinical disorders. Although both
panic disorder (PD) and major depressive disorder (MDD) are known to have effects
on the cardiac autonomic nervous system, no previous study has tested this among
drug-naive (i.e. no history of treatment) patients with MDD and PD in the same
study. The purpose of this study was to compare cardiac autonomic functions among
drug-naive patients with MDD and PD and those of healthy controls. Subjects were 17
drug-naive PD patients, 15 drug-naive MDD patients and 15 normal controls. ECGs
were recorded under both supine resting and supine deep-breathing conditions (10-12
breaths/min: 0.17-0.20 Hz). We measured the low-frequency power (LF; 0.05-0.15 Hz),
which may reflect baroreflex function, the high-frequency power (HF; 0.15-0.40 Hz),
which reflects cardiac parasympathetic activity, as well as the LF/HF ratio. As
expected, deep breathing induced an increase in HF power and a decrease in the
LF/HF ratio in healthy controls. Compared to these controls, however, the MDD group
had a lower response to regular deep breathing in LF power and in LF/HF ratio. PD
patients showed intermediate results between normal controls and MDD patients. The
results indicate that the reactivity to deep breathing revealed diminished cardiac
autonomic reactivity in drug-naive MDD patients. (C) 2009 Elsevier Inc. All rights
reserved.
Wireless capsule endoscopy is a simple, non-invasive technique for the
visualization of the entire small bowel. It was introduced in clinical praxis in
2001 and has already become the method of choice for the investigation of small-
bowel pathology. Capsule retention is a major complication, with an overall
incidence of 1-2%, although reported rates vary widely from 0% to 21%, depending on
the indication for the examination. This complication can occur at any level of the
gastrointestinal tract and in most cases runs asymptomatically. However,
symptomatic bowel obstruction requiring surgical or endoscopic removal of the
impacted capsule can occur. Rarely, capsule retention can lead to intestinal
perforation. Despite several years of experience with wireless capsule endoscopy,
there is up to the present no safe means of predicting capsule retention.
Radiological studies have a low diagnostic yield and tend to underestimate or
overestimate small-bowel strictures. The role of the new generation patency capsule
(Agile patency capsule) needs to be further documented. The experts agree that
obtaining a careful history is perhaps the best single method to detect the
possibility of retention.
The goals of this article are to discuss the potential risk of children whose
parents were traumatized by terror, to present literature on parenting in the
context of terror, and to consider factors that may mediate the transmission Of
trauma-effects from parents to children. Mediators considered are parents'
traumatic distress. disturbed parent-child interactions. trauma-related
disturbances in parents' thinking. and effects of stress on children's neural
functioning. Also discussed are genetic and environmental factors that may moderate
the transmission of intergenerational effects and promote children's risk and
resilience. Points raised during the discussion are illustrated with segments front
interviews of women who were pregnant or gave birth some time after direct exposure
to a terror attack. The authors conclude that empirical studies are needed to learn
more about the intergenerational transmission Of trauma-effects and processes that
underlie it. The authors join others in the call to improve evaluation. treatment,
and Support of trauma victims and their children to stymie the transmission of
problems from one generation to the next.
This paper examines vulnerability and risk perception in the fear of crime. Past
studies have often treated gender and age as proxies for vulnerability, and on the
few occasions that vulnerability has been operationalized, there has been little
agreement on the mechanisms that underpin perceived susceptibility. To develop a
more theoretically-driven approach, the current study examines whether markers of
vulnerability are associated with higher levels of fear through mediating
assessments of likelihood, control and consequence. Females are found to worry more
frequently than males partly because (a) they feel less able to physically defend
themselves, (b) they have lower perceived self-efficacy, (c) they have higher
perceived negative impact, and (d) they see the likelihood of victimization as
higher for themselves and for their social group. Younger people are also found to
worry more frequently than older people, but differential vulnerability does not
explain this association. Finally, structural equation modelling shows that the
effects on worry of physical defence capabilities, self-efficacy and perceived
consequence are mostly mediated through judgements of absolute and relative risk.
Conclusions focus on the implications of this finding for debates about the
rationality of the fear of crime.
Aims: Anxiety a core feature of panic disorder, is linked to function of the
amygdala. Volume alterations in the brain of patients with panic disorder have
previously been reported, but there has been no report of amygdala volume
association with anxiety. Methods: Volumes of hippocampus and amygdala were
manually measured using magnetic resonance imaging obtained from 27 patients with
panic disorder and 30 healthy comparison subjects. In addition the amygdala was
focused on, applying small volume correction to optimized voxel-based morphometry
(VBM). State-Trait Anxiety Inventory and the NEO Personality Inventory Revised were
also used to evaluate anxiety. Results: Amygdala volumes in both hemispheres were
significantly smaller in patients with panic disorder compared with control
subjects (left: t = -2.248, d.f. = 55, P = 0.029; right: t = -2.892, d.f. = 55, P =
0.005). VBM showed that structural alteration in the panic disorder group occurred
on the corticomedial nuclear group within the right amygdala (coordinates [x, y, z
(mm)]: [26,-6,-16], Z score = 3.92, family-wise error-corrected P = 0.002). The
state anxiety was negatively correlated with the left amygdala volume in patients
with panic disorder (r = -0.545, P = 0.016). Conclusions: These findings suggested
that the smaller volume of the amygdala may be associated with anxiety in panic
disorder. Of note, the smaller subregion in the amygdala estimated on VBM could
correspond to the corticomedial nuclear group including the central nucleus, which
may play a crucial role in panic attack.
Exposure-based therapy, a leading technique in the treatment of a range of anxiety
disorders, is facilitated by D-cycloserine (DCS), a partial N-methyl-D-aspartate
receptor agonist. This review discusses the potential mechanisms involved in this
facilitation and its implications for developing theories of fear conditioning in
humans. Basic research in rodents suggests that DCS acts by speeding up extinction.
However, several laboratory-based investigations found that DCS had no effect on
extinction in humans. This report proposes that these observations can be accounted
for by a dual-model theory of fear conditioning in humans that engages two
complementary defensive systems: a reflexive lower-order system independent of
conscious awareness and a higher-order cognitive system associated with conscious
awareness of danger and expectation. The DCS studies in animals seem to have
explored lower-order conditioning mechanisms, whereas human studies have explored
higher-order cognitive processes. These observations suggest that DCS might act
preferentially on lower-rather than higher-order learning. This report presents
evidence suggesting that, in humans, DCS might similarly affect lower-order
learning during exposure-based therapy and, consequently, might be less effective
during cognitive therapy (e.g., cognitive restructuring). Finally, it is
recommended that extinction studies using DCS in humans be conducted with fear-
relevant stimuli (e.g., snakes), short conditional stimulus-unconditioned stimulus
intervals and intense unconditioned stimulus to promote lower-order conditioning
processes.
Brain imaging studies performed over the past 20 years have generated new knowledge
about the specific brain regions involved in the brain diseases that have been
classically labeled as psychiatric. These include the mood and anxiety disorders,
and the schizophrenias. As a natural next step, clinical researchers have
investigated whether the minimally invasive brain stimulation technologies
(transcranial magnetic Stimulation [TMS] or transcranial direct current stimulation
[tDCS]) might potentially treat these disorders. In this review, we critically
review the research studies that have examined TMS or tDCS as putative treatments
for depression, mania, obsessive-complusive disorder, posttraumatic stress
disorder, panic disorder, or schizophrenia. (Separate controversy articles deal
with using TMS or tDCS to treat pain or tinnitus. We will not review here the large
number of studies using TMS or tDCS as research probes to understand disease
mechanisms of psychiatric disorders.) Although there is an extensive body of
randomized controlled trials showing antidepressant effects of daily prefrontal
repetitive TMS, the magnitude or durability of this effect remains controversial.
US Food and Drug Administration approval of TMS for depression was recently
granted. There is much less data in kill other diseases, and therapeutic effects in
other psychiatric conditions, if any, are still controversial. Several issues and
problems extend across all psychiatric TMS studies, including the optimal method
for a sham control, appropriate coil location, best device parameters (intensity,
frequency, dosage, and dosing schedule) and relining what subjects should he doing
during treatment (activating pathologic circuits or not). In general, TMS or tDCS
as it treatment for most psychiatric disorders remains exciting but controversial,
other than prefrontal TMS for depression. (C) 2009 Elsevier Inc. All rights
reserved.
Falling is a serious problem for the elderly which consequences - fractures, other
lesions and the fear of falling - may result in auto-restrictions in daily living
activities, producing immobility and accelerating the physical decline associated
with aging. The ptophobia (phobic fear of falling) is characterized by an out-of-
control fear of walking, even without locomotion alteration, loss of self-esteem
and social isolation. Interventions for the prevention and treatment of the falling
fear in the elderly are very important to assure a good quality of life.
Psychotherapy and physical rehabilitation have been related as ways of treatment of
ptophobia in the elderly.
Objective: The adequate attainment and maintenance of good hemoglobin A1c control
in diabetes are major challenges. Although insulin use as the mainstay of diabetes
treatment has resulted in favorable treatment outcomes, poor adherence/compliance
occurs due to factors such as fear of insulin or fear of injection. This study was
undertaken to conduct a systematic review of the impact of fear of
insulin/injection on the treatment outcomes of diabetes patients. Methods: A
structured search of EMBASE, Ovid MEDLINE, PubMed, and PsycINFO for the years 1990-
2008 was conducted to identify published English-language articles addressing fear
of insulin or fear of injection in diabetes. The following key words and their
combinations were used in the search: diabetes, insulin, injection, fear, phobia,
and psychological insulin resistance. Google Scholar website was used to search for
any additional references. Manual searches on the references of retrieved articles
were also performed to find additional studies. Results: Six studies were selected
for in depth assessment. The treatment outcomes included hemoglobin A1c in two
studies, complications of diabetes in two studies, general health and psychological
comorbidities in two studies, and mortality in one study. Although the number of
studies was limited, all identified adverse treatment outcomes in diabetes patients
with fear of insulin or fear of injection. No studies with outcomes of resource
utilizations or costs were identified. Limitations: Most of the studies we reviewed
had a cross-sectional design, where the findings primarily presented associations
without firm determinations of the impact of fear of insulin/injection on the
treatment outcomes of diabetes. Conclusions: Fear of insulin or fear of injection
is associated with poor glycemic control, clinical complications, psychological
comorbidities, poor general well-being and health status, and increased risk of
mortality for diabetes patients.
We compare a variety of theories of panic disorder using a neutral framework:
causal modeling. The framework requires identification of key constructs and
specification of their interaction. Biological, cognitive, and behavioral elements
of the theory have to be clearly distinguished, as do critical past events and
current trigger conditions. The theories compared were drawn from the psycho-
dynamic, cognitive, and neurobiological literature. We conclude that there are
substantive differences among the cognitive theories and between the biological
theories reviewed. However, cognitive and biological theories appear to be
compatible in principle. It is not clear whether substantive differences among
theories are due to the existence of subtypes of PD or due to the predominance of
multifactorial cause. It is argued that current treatment methods imply particular
theories, and that particular patterns of success and failure can be understood in
relation to theory through the methods we have employed. (C) 2009 Elsevier Ltd. All
rights reserved.
Classical fear conditioning is a powerful behavioral paradigm that is widely used
to study the neuronal substrates of learning and memory. Previous studies have
clearly identified the amygdala as a key brain structure for acquisition and
storage of fear memory traces. Whereas the majority of this work has focused on
principal cells and glutamatergic transmission and its plasticity, recent studies
have started to shed light on the intricate roles of local inhibitory circuits.
Here, we review current understanding and emerging concepts of how local inhibitory
circuits in the amygdala control the acquisition, expression, and extinction of
conditioned fear at different levels.
A 34-year-old woman with a 9-year history Of unprovoked attacks of anxiety and
dyspnea associated with symptoms of depersonalization and derealization is
presented. The attacks increased in frequency and were associated with internal
derogatory voices, vivid frightening imagery, and suicidal ideation, leading to 3
emergency psychiatric hospitalizations in a period of less than 3 months. She had
been treated unsuccessfully for a presumptive diagnosis of panic disorder without
agoraphobia, prompting a reconsideration of this diagnosis. Although
electroencephalography and magnetic resonance imaging findings were normal,
temporal lobe epilepsy was considered and the patient responded rapidly and
dramatically to carbamazepine. Panic disorder and temporal lobe epilepsy can be
confused with each other; proper diagnosis is necessary for selection of effective
pharmacotherapy. Although uncertain, the contribution of sustained exposure to
carbon monoxide as an adult may have contributed to the emergence of panic
symptoms, which would be an Unusual clinical presentation.
Data from studies with humans have suggested that abnormalities of midbrain
structures, including the periaqueductal gray matter (PAG), could be involved in
the neurobiology of panic disorder (PD). The electrical stimulation of the PAG in
neurosurgical patients induces panic-like symptoms and the effect of drugs that are
effective in the treatment of PD in the simulation of public speaking model of
anxiety is in agreement with data from animal models of PD. Structural neuroimaging
studies have shown increases in gray matter volume of midbrain and pons of PD
patients. There is also evidence of lower serotonin transporter and receptor
binding, and increases of metabolism in the midbrain of PD patients. Nevertheless,
these midbrain abnormalities can not be considered as specific findings, since
neuroimaging data indicate that PD patients have abnormalities in other brain
structures that process fear and anxiety.
Public opinion about sentencing and correctional issues has emerged in recent
decades as a salient topic in criminology. Empirical studies have suggested that
the public has dynamic perceptions about these criminal justice issues. Sentencing
and correctional policy have become key issues confronting legislators and
policymakers, as correctional budgets and public interest in these areas have
increased. Despite the focus on public opinion about sentencing and corrections,
previous research has largely ignored how the public feels about the role of
policymakers regarding these issues, and what influences opinions about whether
public fear should be an important consideration in policy decisions. The current
study partly replicated the work of Cullen and colleagues by examining perceptions
of crime salience, crime causation. goals of the criminal justice system. and
attitudes towards imprisonment and rehabilitation. It uniquely examined perceptions
about the importance of legislator consideration of a specific determinant, namely,
public fear, in decision making about sentencing and correctional policy. (C) 2009
Elsevier Ltd. All rights reserved.
Anxiety disorders have traditionally been conceptualized as reflecting the emotions
of fear and anxiety. A developing program of research demonstrates a relation
between disgust and three specific anxiety disorders: blood-injection-injury (BII)
phobia, spider phobia, and contamination-related obsessive-compulsive disorder
(OCD). This review serves three purposes. First, the authors review the response
patterns predicted to be observed if the emotional response in these disorders
involved disgust versus fear. The review suggests specific response patterns that
characterize disgust and fear in the domains of heart rate, facial expression,
neural activity, and cognitive processes. Second, the authors review extant
research employing measures of these domains in spider phobia, BII phobia, and
contamination-related OCD. The evidence suggests that both fear and disgust
Characterize each of these disorders, but the magnitude at which the emotions
characterize the disorders may depend on the response domain measured. For example,
disgust may be more involved in spider phobia in appraisals and facial expression,
but less involved in neural correlates or heart rate domains. Third. the authors
suggest guidelines for future research, including concurrent use of specific
measures as well as examining whether the different emotions in different response
domains respond to similar interventions (e.g., exposure). (C) 2008 Elsevier Ltd.
All rights reserved.
Despite the existence of effective interventions for anxiety disorders, relapse -
or the return of fear - presents a significant problem for patients and clinicians
in the longer term. The present paper draws on the experimental and clinical
behavioural literature, reviewing the mechanisms by which the return of fear can
occur. The aim of the paper was to generate a list of treatment recommendations for
clinicians aimed at reducing relapse in successfully treated anxiety disorders.
Clinical and experimental literature on the mechanisms of renewal, reinstatement,
spontaneous recovery and reacquisition are reviewed. These are linked with the
clinical and experimental literature on the return of fear in successfully treated
anxiety. A list of recommendations to assist in reducing the probability of relapse
in successfully treated anxiety is presented. This list includes methods for use in
behavioural (exposure) treatment of anxiety disorders that aim to enhance clinical
outcomes. Despite the significant problem of relapse in successfully treated
anxiety, there are methods available to reduce the probability of relapse through
return of fear. Clinicians engaging in treatment of anxiety disorders should be
mindful of these methods to ensure optimal patient outcome.
This paper examines the nature and extent of news reports using the sociological
concept, 'moral panic' (MP). Qualitative content analysis reveals that moral panic
is commonly used in news reports in the USA, UK, Australia, and other countries,
but it is more likely to be compatible with print (e. g. newspaper) formats than
television reports. It is also widely used in literary and art reviews, editorials
and op-ed pieces, often by social scientists. Use of the concept has increased over
the last decade, particularly in news reports as part of an 'opposing' voice or the
'other side' of articles about deviant behavior, sexual behavior, and drug use. It
is suggested that moral panic as 'opposition' fits the entertainment news format,
and while this sustains its use by writers and familiarity to audience members, it
also appears to be associated with certain topics (e. g. sex and drugs), but not
others, such as terrorism in the mainstream media. Questions are raised for
additional research.
Noting that the social and emotional experiences of American children today often
heavily involve electronic media, Barbara Wilson takes a close look at how exposure
to screen media affects children's well-being and development. She concludes that
media influence on children depends more on the type of content that children find
attractive than on the sheer amount of time they spend in front of the screen.
Wilson begins by reviewing evidence on the link between media and children's
emotions. She points out that children can learn about the nature and causes of
different emotions from watching the emotional experiences of media characters and
that they often experience empathy with those characters. Although research on the
long-term effects of media exposure on children's emotional skill development is
limited, a good deal of evidence shows that media exposure can contribute to
children's fears and anxieties. Both fictional and news programming can cause
lasting emotional upset, though the themes that upset children differ according to
a child's age. Wilson also explores how media exposure affects children's social
development. Strong evidence shows that violent television programming contributes
to children's aggressive behavior. And a growing body of work indicates that
playing violent video games can have the same harmful effect. Yet if children spend
time with educational programs and situation comedies targeted to youth, media
exposure can have more prosocial effects by increasing children's altruism,
cooperation, and even tolerance for others. Wilson also shows that children's
susceptibility to media influence can vary according to their gender, their age,
how realistic they perceive the media to be, and how much they identify with
characters and people on the screen. She concludes with guidelines to help parents
enhance the positive effects of the media while minimizing the risks associated
with certain types of content.
Introduction: Data on basal hypothalamo-pituitary-adrenomedullary (HPA) function
over controlled treatment trials with serotonergic drugs in anxiety disorders are
still rare. Methods: 29 patients with panic disorder participating in a 10 week
randomized, controlled trial (paroxetine vs. placebo with exercise or relaxation;
N=60) collected urine for cortisol excretion over 3 consecutive nights before start
and before termination of the treatment episode. Urinary cortisol was measured by
radioimmunoassay. Efficacy measures were the Clinical Global Impression Scale (CGI)
and the Panic and Agoraphobia Scale (P&A). 83% were female (p<.05 vs. males). 55%
received additional aerobic exercise, and 45% relaxation. 55% received paroxetine
treatment, and 45% placebo. Significantly fewer males received placebo treatment
(p<.05). Results: All subjects improved significantly. Cortisol excretion did not
differ between treatment groups or at pre-/post measurements. Females showed a
significantly higher variability of cortisol excretion compared to males, at pre-
(p<.005) and post (p=.015) assessments. Males displayed a trend to lower basal HPA
function at end of treatment (p=.08). HPA variability after treatment showed a
trend to be higher in the paroxetine (p=.052) -who clinically improved
significantly better-compared to the placebo group. No relationship between HPA
activity and treatment response or with exercise was detected. Discussion: HPA
function shows significant gender differences, with females having a higher HPA
function variability. Future studies on HPA function in treatment trials should
address gender and medication effects.
The concept of the "extended amygdala", developed and explored by Lennart Heimer,
Jose de Olmos, George Alheid, and their collaborators, has had an enormous impact
on the field of neuroscience and on our own work. Measuring fear-potentiated
startle test using conditioned stimuli that vary in length we suggest that the
central nucleus of the amygdala (CeA) and the lateral division of the bed nucleus
of the stria terminalis (BNSTL) are involved in short-term versus long-term fear
responses we call phasic versus sustained fear, respectively. Outputs from the
basolateral amygdala (BLA) activate the medial division of the CeA (CeA(M)) to very
rapidly elicit phasic fear responses via CeA(M) projections to the hypothalamus and
brainstem. The BLA also projects to the BNSTL, which together with other BNSTL
inputs from the lateral CeA (CeA(L)) initiate a slower developing, but sustained
fear response, akin to anxiety. We hypothesize this occurs because the CeA(L)
releases the peptide corticotropin releasing hormone (CRF) into the BNSTL which
facilitates the release of glutamate from BLA terminals. This activates the BNSTL
which projects to hypothalamic and brainstem areas similar to those innervated by
the CeA(M) that mediate the specific signs of fear and anxiety. The generality of
this idea is illustrated by selective studies looking at context conditioning,
social defeat, drug withdrawal and stress induced reinstatement.
Some major leftist thinkers, including Alain Badiou, Slavoj Zizek and Terry
Eagleton, have lately offered readings that claim the relevance of alternative
interpretations of the Christian tradition in the face both of the conservative
turn in the Catholic Church and of the contemporary secular oblivion of anything
that has to do with religion. Furthermore, post-colonial studies have tended to
blame the West en bloc for the disasters of past and present colonization, and have
attacked the western endeavour to extend universal truths as an ethnocentric device
to facilitate and justify exploitation. In Holy Terror, Terry Eagleton both
condemns western politics and questions its appeal to universals; but he also hears
in this tradition a demand for a relationship with the other which offers an
alternative to that established by current politics and capitalist exploitation.
The other is the excluded, the oppressed, the exploited; the true material, rather
than ideal, universal produced by global capitalist exploitation. As a consequence,
anything that happens in any part of the planet belongs in our world and indicts
us, though we tend to build barriers around an ideally safe and stable identity
that ignores part of its own reality and that is therefore haunted by it. Texts
like the Bacchae or the New Testament open the gates of the city and of the heart
to the excluded. Terrorists - saints for their own communities and satanic for the
rest - offer an example of the other that is impossible to comprehend within our
conventional ways of life. Nevertheless, only if we hear in their violence a demand
for justice can an exit be found from the vicious circle of violence and revenge.
Since 1972, there has been an association between terrorism, violence, and the
Olympic Games. The events of September 11, 2001, however, clearly reescalated
concerns about the Games being a terrorist target. This conceptual article
discusses the theories of the risk society and the precautionary principle to
understand and interpret how visitors to the most recent Summer Games, Athens 2004,
trained their decision to attend. Consistent with risk theory, a strong public and
financial commitment to safety at the Games was evident, with the organizers
undertaking wide-ranging large-scale risk management initiatives. Athens attendees,
while displaying tenets of risk aversion and engagement with a discourse of fear,
also showed resilience, resistance, and indifference to potential terrorism
threats. Implications for both theory and practice are noted.
The aim of this article is to explore the U.S.-led anti-terror war in Somalia and
evaluate its impact on the status and role of Somali women. With the al-Qaeda
attacks on U.S. embassies in Nairobi (Kenya) and Dar es Salam (Tanzania) in August
1998, Islamic fundamentalism and terrorism became a major threat to the region. In
response to this threat, the United States initiated an anti-terror war in East
Africa, in particular in Somalia. In both the anti-terror war and the Somali civil
war, Somali women's participation has been significant. So far, however, no serious
research has been conducted into women's role in these conflicts or into the
impacts of these conflicts on women in Somalia, a country already plagued by
famine, political instability, ethnic war, and gender-based violence. Armed
conflicts offer new opportunities and responsibilities in both domestic and public
spheres that assist in redefining social relations between women and men. After
conflicts, however, the changes in gender roles often do not persist and pre-war
patriarchal gender roles re-appear in many societies. By investigating the case of
Somalia, this paper examines the reasons behind the re-emergence of pre-war gender
roles after conflicts.
Individuals with psychosis are often feared. In fact, they are themselves likely to
be victims of violence; however, the main aim of this review is to provide an
overview of the evidence on relations between psychosis and violence to others. The
terms psychosis and violence were used in a literature search limited to the
Cochrane Library and PubMed, a manual search of 8 journals, and a follow-up of
additional references in the articles found. The overview draws on new empirical
data and major reviews. Almost all Sound epidemiologic data on psychosis and
violence dates from 1990. There is consistency on a small but significant relation
between schizophrenia and violent acts. Since then there has also been movement
toward understanding the nature of associations and progress on strategies for
managing individuals who have psychosis and are violent. Public fears about
individuals with psychotic illnesses are largely unfounded, although there Would be
benefit in greater attention to the safety of those in their close social circle.
The task for the next 10 years must be the development and application of knowledge
to improve specific treatments-that is, interventions that go beyond holding and
caring to bring about substantial change.
Background: The Illness Attitude Scales (IAS) were developed by Robert Kellner as a
clinimetric index for measuring hypochondriacal fears and beliefs (worry about
illness, concerns about pain, health habits, hypochondriacal beliefs,
thanatophobia, disease phobia, bodily preoccupations, treatment experience and
effects of symptoms). The IAS have been extensively used in the past two decades,
but there has been no comprehensive review of their properties and applications.
Methods: A review of the literature using both computerized (Medline, PsycINFO) and
manual searches was performed. Results: The IAS were found to successfully
discriminate between hypochondriacal patients and control subjects, and between
patients with various manifestations of illness behaviour. They showed a high test-
retest reliability in normal subjects, and changed in the expected direction after
treatment of hypochondriasis. The IAS were also positively related to other
hypochondriasis-related measures, and yielded important information in a variety of
medical and surgical settings. Their content has paved the way for the development
of some of the Diagnostic Criteria for Psychosomatic Research. Conclusions: The
clinimetric properties and high sensitivity of the IAS make them the gold standard
for the self-rated assessment of hypochondriacal fears and beliefs. Copyright (c)
2008 S. Karger AG, Basel.
Vascular endothelial growth factor (VEGF) plays a key role in the development of
both proliferative diabetic retinopathy (PDR) and diabetic macular oedema (DMO). In
recent years, anti-VEGF agents have emerged as new approaches to the treatment of
these devastating diabetic complications. Although Phase III studies in the
diabetic population are needed, intravitreal anti-VEGF therapy is currently being
used in clinical practice. Intravitreal injection is an effective means of
delivering anti-VEGF drugs to the retina. However, this is an invasive procedure
associated with potentially serious complications, such as endophthalmitis or
retinal detachment, which may be significant for patients requiring serial
treatment over many years. In addition, although delivered within the vitreous,
anti-VEGF drugs could pass into the systemic circulation, which could potentially
result in hypertension, proteinuria, increased cardiovascular events and impaired
wound healing. Pegaptanib, ranibizumab and bevacizumab are the currently available
anti-VEGF agents. Ranibizumab and bevacizumab block all VEGF isoforms, thus
impairing both physiological and pathological neovascularisation. Pegaptanib only
blocks the VEGF(165) isoform, and would therefore seem the best option for avoiding
systemic adverse effects in diabetic patients, although this remains to be
demonstrated in clinical trials. In this regard, head-to-head studies designed to
evaluate not only the efficacy, but also the systemic adverse effects of these
drugs in a high-risk population such as diabetic patients are warranted.
Background fear of falling (FOF) is a major health problem among the elderly living
in communities, present in older people who have fallen but also in older people
who have never experienced a fall. The aims of this study were 4-fold: first, to
study methods to measure FOF; second, to study the prevalence of FOF among fallers
and non-fallers; third, to identify factors related to FOF; and last, to
investigate the relationship between FOF and possible consequences among community-
dwelling older persons. Methods several databases were systematically searched, and
selected articles were cross-checked for other relevant publications. Results a
systematic review identified 28 relevant studies among the community-dwelling
elderly. Due to the many different kinds of measurements used, the reported
prevalence of FOF varied between 3 and 85%. The main risk factors for developing
FOF are at least one fall, being female and being older. The main consequences were
identified as a decline in physical and mental performance, an increased risk of
falling and progressive loss of health-related quality of life. Conclusion this
review shows that there is great variation in the reported prevalence of FOF in
older people and that there are multiple associated factors. Knowledge of risk
factors of FOF may be useful in developing multidimensional strategies to decrease
FOF and improve quality of life. However, the only identified modifiable risk
factor of FOF is a previous fall. In order to measure the impact of interventions,
a uniform measurement strategy for FOF should be adopted, and follow-up studies
should be conducted.
Although it has been long thought that it could not be possible for a child to
experience panic, the existence of Panic Disorder in children and adolescents is
nowadays unquestionable. This disorder presents a chronic course, high interference
and high comorbidity with other psychiatric and medical conditions. Due to these
factors, there has been an increasing interest among clinicians and researchers in
order to develop more effective assessment and treatment strategies for children
and adolescents with this disorder. The present paper aims to contribute to a
better understanding and sharing of the most recent information on Panic Disorder
in children and adolescents by reviewing aspects such as classification,
differential diagnosis, epidemiological data, assessment and treatment strategies.
Furthermore, we also discuss what we consider to be current challenges that may
point to future developments, both in clinical and research settings.
Claims of regulatory expropriation have been raised in diverse venues adjudicating
international investment disputes. Although a basic consensus position has emerged
on a state's power to affect private property rights without compensation to
investors, the legality of such actions will and should depend on the specific
regime and institutional context in which they are appraised. A uniform doctrinal
answer is thus impossible and undesirable, and many worries about fragmentation of
international law are misplaced.
This review paper presents an amplification of the suffocation false alarm theory
(SFA) of spontaneous panic [Klein DF (1993). False suffocation alarms, spontaneous
panics, and related conditions. An integrative hypothesis. Arch Gen Psychiatry;
50:306-17.]. SFA postulates the existence of an evolved physiologic suffocation
alarm system that monitors information about potential suffocation. Panic attacks
maladaptively occur when the alarm is erroneously triggered. That panic is distinct
from Cannon's emergency fear response and Selye's General Alarm Syndrome is shown
by the prominence of intense air hunger during these attacks. Further, panic
sufferers have chronic sighing abnormalities outside of the acute attack. Another
basic physiologic distinction between fear and panic is the counter-intuitive lack
of hypothalamic-pituitary-adrenal (HPA) activation in panic. Understanding panic as
provoked by indicators of potential suffocation, such as fluctuations in pCO(2) and
brain lactate, as well as environmental circumstances fits the observed respiratory
abnormalities. However, that sudden loss, bereavement and childhood separation
anxiety are also antecedents of "spontaneous" panic requires an integrative
explanation. Because of the opioid system's central regulatory role in both
disordered breathing and separation distress, we detail the role of opioidergic
dysfunction in decreasing the suffocation alarm threshold. We present results from
our laboratory where the naloxone-lactate challenge in normals produces supportive
evidence for the endorphinergic defect hypothesis in the form of a distress episode
of specific tidal volume hyperventilation paralleling challenge-produced and
clinical panic. (C) 2007 Elsevier Inc. All rights reserved.
The neurosteroid allopregnanolone is a potent positive allosteric modulator of GABA
action at GABA(A) receptors. Allopregnanolone is synthesized in the brain from
progesterone by the sequential action of 5 alpha-reductase type I (5 alpha-RI) and
3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD). 5 alpha-RI and 3 alpha-HSD are
co-expressed in cortical, hippocampal, and olfactory bulb glutamatergic neurons and
in output neurons of the amygdala, thalamus, cerebellum, and striatum. Neither 5
alpha-RI nor 3 alpha-HSD mRNAs is expressed in glial cells or in cortical or
hippocampal GABAergic interneurons. It is likely that allopregnanolone synthesized
in principal output neurons locally modulates GABA(A) receptor function by reaching
GABA(A) receptor intracellular sites through lateral membrane diffusion. This
review will focus on the behavioral effects of allopregnanolone on mouse models
that are related to a sexually dimorphic regulation of brain allopregnanolone
biosynthesis. Animal models of psychiatric disorders, including socially isolated
male mice or mice that receive a long-term treatment with anabolic androgenic
steroids (AAS), show abnormal behaviors such as altered fear responses and
aggression. In these animal models, the cortico-limbic mRNA expression of 5 alpha-
RI is regulated in a sexually dimorphic manner. Hence, in selected glutamatergic
pyramidal neurons of the cortex, CA3, and basolateral amygdala and in granular
cells of the dentate gyrus, mRNA expression of 5 alpha-RI is decreased, which
results in a downregulation of allopregnanolone content. In contrast, 5 alpha-RI
mRNA expression fails to change in the striatum medium spiny neurons and in the
reticular thalamic nucleus neurons, which are GABAergic. By manipulating
allopregnanolone levels in glutamatergic cortico-limbic neurons in opposite
directions to improve [using the potent selective brain steroidogenic stimulant
(SBSS) S-norfluoxetine] or induce (using the potent 5 alpha-RI inhibitor SKF
105,111) behavioral deficits, respectively, we have established the fundamental
role of cortico-limbic allopregnanolone levels in the sexually dimorphic regulation
of aggression and fear. By selectively targeting allopregnanolone downregulation in
glutamatergic cortico-limbic neurons, i.e., by improving the response of GABA(A)
receptors to GABA, new therapeutics would offer appropriate and safe management of
psychiatric conditions, including impulsive aggression, irritability, irrational
fear, anxiety, posttraumatic stress disorders, and depression.
Neurochemical studies have shown that mesocortical dopamine projections are
particularly responsive in aversive situations such as fear conditioning. The
present study assessed behavioural and medial prefrontal cortex (mPFC) dopamine
responses utilizing in vivo microdialysis during acquisition and expression of a
conditioned fear response. In two independent experiments, rats were presented with
either two or nine tone-shock pairings during formation of a conditioned fear
response. In the second experiment, rats were pre-treated with repeated injections
of either amphetamine or saline over a 6-day period and tested during withdrawal.
Amphetamine pre-treatment as well as the conditioning procedure itself potentiated
an increase in dopamine levels during formation, but not expression of a
conditioned fear response. Locomotor activity induced by an amphetamine challenge
(1 mg/ka) was also enhanced in pre-treated amphetamine compared to saline pre-
treated animals (experiment two). However, mPFC dopamine response to amphetamine
challenge did not differ between treatment groups. We conclude that while the exact
role of mPFC dopamine in behavioural sensitization is yet to be determined, mPFC
dopamine release may underlie the increased fear response during acquisition but
not expression of fear response. (c) 2007 Elsevier B.V. All rights reserved.
Background: Translational research suggests that D-cycloserine (DCS), a partial N-
methyl-D-aspartate (NMDA) receptor agonist, might facilitate fear extinction and
exposure therapy by either enhancing NMDA receptor function during extinction or by
reducing NMDA receptor function during fear memory consolidation. This article
provides a quantitative review of DCS-augmented fear extinction and exposure
therapy literature. Methods: English-language journal articles that examined DCS
augmented with fear extinction or exposure therapy were identified through public
databases from June 1998 through September 2007, through references of originally
identified articles and contact with DCS investigators. Data were extracted for
study author, title, and year; trial design; type of subject (animal vs. human;
clinical vs. nonclinical); sample size, DCS dose, and timing in relation to
extinction/exposure procedures; dependent variable; group means and SIDs at post-
extinction/exposure; and follow-up outcome. Results: D-cycloserine enhances fear
extinction/exposure therapy in both animals and anxiety-disordered humans. Gains
generally were maintained at follow-up, although some lessening of efficacy was
noted. D-cycloserine was more effective when administered a limited number of times
and when given immediately before or after extinction training/exposure therapy.
Conclusions: This meta-analysis suggests that DCS is a useful target for
translational research on augmenting exposure-based treatment via compounds that
impact neuroplasticity. D-cycloserine's major contribution to exposure-based
therapy might be to increase its speed or efficiency, because the effects of DCS
seem to decrease over repeated sessions. This information might guide translational
researchers in discovering more selective and/or effective agents that effectively
enhance (or reduce) NMDA receptor function.
Legal theorists have long debated the relationship between substantive and
procedural law. This Article examines this relationship in the context of the "war
on terror." The most controversial programs in the "war on terror" involve profound
infringements of individual rights-torture and other forms of cruel treatment,
imprisonment, deportation, scrutiny of private phone calls and personal records.
And yet six years after the attacks of September 11, 2001, most of the court
decisions in cases challenging these policies have not directly addressed
substantive rights claims. Instead, the court decisions have almost all been about
process: whether particular courts have jurisdiction to hear the cases; whether the
proper branch of government has made the determination of policy; whether
particular Plaintiffs have standing to challenge the policy; whether evidence is
protected from discovery by the state secrets privilege; and so forth. These
process focused decisions have significant implications for substantive rights, but
the relation between substance and procedure in these cases has received little
attention. To fill this gap in our understanding of some of the most important
cases of our time, the Article provides a descriptive and normative framework for
examining the interconnection between substance and process. While this framework
is developed in the context of the "war on terror" cases, it is relevant to and
engages with broader debates about the relationship between substantive and
procedural law.
Prepulse inhibition (PPI) is the reduction of the startle reflex when the startling
stimulus is shortly preceded by a non-startling stimulus. Previous studies have
shown that PPI in rats can be enhanced by auditory fear conditioning (AFC) but
weakened by isolation rearing. This study investigated whether isolation rearing
affects the effect of AFC on PPI. The results show that PPI was lower in isolation-
reared rats than that in socially reared rats, and it was markedly enhanced by AFC
in socially reared rats. However, the AFC-induced PPI enhancement in isolation-
reared rats was much lower than that in socially reared rats. Moreover, the AFC-
induced PPI enhancement was blocked by intraperitoneal injection (1 mg/kg) of the
selective antagonist of metabotropic glutamate receptor subtype 5 (mGluR5), 2-
methyl-6-(phenylethynyl)-pyridine (MPEP), 30 minutes before AFC, The baseline
startle was also enhanced by isolation rearing. Thus, isolation rearing impairs not
only PPI but also the AFC-induced PPI enhancement, which depends on mGluR5
activity. This study advances the animal model for investigating both neural bases
and cognitive features of schizophrenia.
Fear extinction is an important form of emotional learning, and affects neural
plasticity. Cue fear extinction is a classical form of inhibitory learning that can
be used as an exposure-based treatment for phobia, because the long-term extinction
memory produced during cue fear extinction can limit the over-expression of fear.
The expression of this inhibitory memory partly depends on the context in which the
extinction learning occurs. Studies such as transient inhibition, electrophysiology
and brain imaging have proved that the hippocampus - an important structure in the
limbic system - facilitates memory retrieval by contextual cues. Mediation of the
hippocampus-medial prefrontal lobe circuit may be the neurobiological basis of this
process. This article has reviewed the role of the hippocampus in the learning and
retrieval of fear extinction. Contextual modulation of fear extinction may rely on
a neural network consisting of the hippocampus, the medial prefrontal cortex and
the amygdala.
Fear of falling has been reported in a high percentage of community-dwelling
elderly who both do and don't have a history of falling. The aims of this review
are to: (a) elucidate the definition of fear of falling; (b) clarify measurements
of fear of falling based on its definition; and (c) describe the risk factors for
fear of falling. Despite the importance of the percentage and the consequences of
fear of falling, its definition is still vague and warrants clarification. Based on
a literature review, major fear of falling measurements involve the evaluation of
fear of falling and use of a fall efficacy scale. Using a correct definition of
fear of falling, nurses working close with older adults need to identify the
different definitions of fear of falling and fall efficacy scale. In addition,
nurses who work closely with older adults should encourage them to increase or
maintain modifiable factors by maximizing their basic health status and enhancing
their physical activity to decrease fear of falling. [Asian Nursing Research
2008;2(4):214-222]
Anxiety disorders are highly prevalent. Fear conditioning and extinction learning
in animals often serve as simple models of fear acquisition and exposure therapy of
anxiety disorders in humans. This article reviews the empirical and theoretical
literature on cognitive processes in fear acquisition, extinction, and exposure
therapy. It is concluded that exposure therapy is a form of cognitive intervention
that specifically changes the expectancy of harm. Implications for therapy research
are discussed. (c) 2007 Elsevier Ltd. All rights reserved.
This article examines the relationship between German Catholicism and the so-called
'crisis' of masculinity of the early twentieth century. Focusing on the masculinist
rhetoric of reform-oriented Catholics, particularly within the context of an
energetic and colourful campaign against the institution of mandatory clerical
celibacy, the article sheds new light both on the intersection of religion and
culture in Wilhelmine Germany and, more specifically, on a rather striking
convergence of Catholic masculinism and volkisch-oriented thought in Munich on the
eve of the First World War.
Despite decades of research, the causal mechanisms of hot flashes are not
adequately understood, and a biopsychosocial perspective on hot flashes remains
underdeveloped. This article explores overlooked parallels between hot flashes and
panic attacks within 5 areas: course and symptomatology, physiological indicators,
neurocircuitry and biochemical mechanisms, pharmacotherapy, and psychological
treatment, noting both similarities and important differences between the 2 events.
An integrative conceptual model is presented that identifies key ways in which
psychological factors may influence the experience of hot flashes, with clinical
implications and areas of future research. This model yields readily testable
hypotheses and may provide a template for exploring the role of cognition in the
frequency and severity of hot flashes and, in turn, a basis for the development of
nonpharmacological treatments.
Glascher and Adolph (2003) proposed that both amydalae are specialized for fear,
but that the right one is a fast, short, and relatively automatic fear processor,
whereas the left one is more detail-oriented and perceptual-cognitive. According to
this model, early ictal fear should occur more often in cases with a right temporal
lobe epileptic focus. Several authors have tried to find a hemispheric
specialization for ictal fear, but have not reached the power to attain a
statistically significant effect of focus side. In this study, using previously
published cases of unilateral epileptic focus causing early ictal symptoms of fear,
we found 144 cases, of which 98 had a right hemisphere focus (68%) and 46 having
left hemisphere focus (32%, p < 0.0005). Several control variables were assembled
to verify possible alternative explanations of the main effect.
The amygdala has been implicated in the recognition of facial emotions, especially
fearful expressions, in adults with early-onset right temporal lobe epilepsy (TLE).
The present study investigates the recognition of facial emotions in children and
adolescents, 8-16 years old, with epilepsy. Twenty-nine subjects had TLE (13 right,
16 left) and eight had fronto-central epilepsy (FCE). Each was matched on age and
gender with a control subject. Subjects were asked to label the emotions expressed
in pictures of children's faces miming five basic emotions (happiness, sadness,
fear, disgust and anger) or neutrality (no emotion). All groups of children with
epilepsy performed less well than controls. Patterns of impairment differed
according to the topography of the epilepsy: the left-TLE (LTLE) group was impaired
in recognizing fear and neutrality, the right-TLE (RTLE) group was impaired in
recognizing disgust and, the FCE group was impaired in recognizing happiness. We
clearly demonstrated that early seizure onset is associated with poor recognition
of facial expression of emotion in TLE group, particularly for fear. Although
right-TLE and left-TLE subjects were both impaired in the recognition of facial
emotion, their psychosocial adjustment, as measured by the CBCL questionnaire
[Achenbach, T. M. (1991). Manual for the Child Behavior Checklist and Youth Self
report. Burlington, VT: University of Vermont Department of Psychiatry], showed
that poor recognition of fearful expressions was related to behavioral disorders
only in children with right-TLE. Our study demonstrates for the first time that
early-onset TLE can compromise the development of recognizing facial expressions of
emotion in children and adolescents and suggests a link between impaired fear
recognition and behavioral disorders. (C) 2008 Elsevier Ltd. All rights reserved.
This article introduces a terror management health model (TMHM). The model
integrates disparate health and social psychology literatures to elucidate how the
conscious and nonconscious awareness of death can influence the motivational
orientation that is most operative in the context of health decisions. Three formal
propositions are presented. Proposition I suggests that conscious thoughts about
death can instigate health-oriented responses aimed at removing death-related
thoughts from current focal attention. Proposition 2 suggests that the unconscious
resonance of death-related cognition promotes self-oriented defenses directed
toward maintaining, not one's health, but a sense of meaning and self-esteem. The
last proposition suggests that confrontations with the physical body may undermine
symbolic defenses and thus present a previously unrecognized barrier to health
promotion activities. In the context of each proposition, moderators are proposed,
research is reviewed, and implications for health promotion are discussed.
The review article systematizes the Current academic debate on U. S. foreign policy
after 9/11. The main focus lies on different explanations of the causes and
consequences of the "war on terror". Such a problem-oriented approach mirrors the
heterogeneity of the debate which cannot adequately be captured by the conventional
categories of IR research and foreign policy analysis. It is fair to say that the
analysis of U. S. foreign policy as a case of empirical investigation profits from
this disciplinary emancipation.
Intra-cerebral (i.c.) microinfusion of selective receptor agonists and antagonists
into behaving animals can provide both neuroanatomical and neurochemical insights
into the neural mechanisms of anxiety. However, there have been no systematic
reviews of the results of this experimental approach that include both a range of
unconditioned anxiety reactions and a sufficiently broad theoretical context. Here
we focus on amino acid, monoamine, cholinergic and peptidergic receptor ligands
microinfused into neural structures previously implicated in anxiety, and
subsequent behavioral effects in animal models of unconditioned anxiety or fear.
GABA(A) receptor agonists and glutamate receptor antagonists produced the most
robust anxiolytic-like behavioral effects, in the majority of neural substrates and
animal models. In contrast, ligands of the other receptor systems had more
selective, site-specific anti-anxiety effects. For example. 5-HT1A receptor
agonists produced anxiolytic-like effects in the raphe nuclei, but inconsistent
effects in the amygdala, septum, and hippocampus. Conversely, 5-HT3 receptor
antagonists produced anxiolytic-like effects in the amygdala but not in the raphe
nuclei. Nicotinic receptor agonists produced anxiolytic-like effects in the raphe
and anxiogenic effects in the septum and hippocampus. Unexpectedly, physostigmine,
a general cholinergic agonist, produced anxiolytic-like effects in the hippocampus.
Neuropeptide receptors, although they are popular targets for the development of
selective anxiolytic agents, had the least reliable effects across different animal
models and brain structures, perhaps due in part to the fact that selective
receptor ligands are relatively scarce. While some inconsistencies in the
microinfusion data can easily be attributed to pharmacological variables such as
dose or ligand selectivity, in other instances pharmacological explanations are
more difficult to invoke: e.g., even the same dose of a known anxiolytic compound
(midazolam) with a known mechanism of action (the benzodiazepine-GABA(A) receptor
complex), can selectively affect different fear reactions depending upon the
different subregions of the nucleus into which it is infused (CeA versus BLA).
These particular functional dissociations are important and may depend on the
ability of a GABA(A) receptor agonist to interact with distinct isoforms and
combinations of GABA(A) receptor subunits (e.g., alpha 1-6, beta 1-3, gamma 1-2,
delta), many of which are unevenly distributed throughout the brain. Although this
molecular hypothesis awaits thorough evaluation, the microinfusion data overall
give some support for a model of "anxiety" that is functionally segregated along
different levels of a neural hierarchy, analogous in some ways to the organization
of sensorimotor systems. (C) 2008 Elsevier Inc. All rights reserved.
The Terror is often described as having a "military logic," but this assessment is
doubly misguided: the laws of war in prerevolutionary Europe were codified in the
liberal droit des gens, and the harshest laws during the Terror were in fact
authorized by a legal exception in natural-right theory. This exception concerned
the individual who violated the laws of nature: denounced as an "enemy of the human
race" (hostis humani generis), he could be executed without legal proceedings. The
first civilian to be targeted as an ennemi du genre humain was the king; while the
Montagnards were unsuccessful in blocking his trial, this model of an exceptional
enemy soon reappeared as the hors la loi, another civil category. Only toward the
end of the Terror was this model extended to enemy soldiers, thus reversing two
hundred years of military jurisprudence and contributing to the rise of "total
war.".
A generation ago, Hall et al.'s ( 1978) work Policing the Crisis gave a
sophisticated analysis of the British media's mundane ability to 'encode' events so
as to help produce a moral panic about mugging. Although this work remains
relatively neglected in its home country, it has begun to be utilized for empirical
analysis in North America. This article suggests, however, that Hall et al.' s
analysis remains a poor import. This is not, however because of its age or cultural
specificity. Instead Policing the Crisis fails, quite simply because it repeats in
its own analysis the same 'ideological practices' ( albeit at a higher logical
level), which it discovered in its empirical investigation of the British media.
Pharmacological magnetic resonance imaging (phMRI) is a method to study effects of
psychopharmacological agents on neural activation. Changes of the blood oxygen
level dependent (BOLD), the basis of functional MRI (fMRI), are typically obtained
at relatively high sampling frequencies. This has more recently been exploited in
the field of fMRI by applying independent component analysis (ICA), an explorative
data analysis method decomposing activation into distinct neural networks. While
already successfully used to investigate resting network and task-induced activity,
its use in phMRI is new. Further extension of this method to tensorial
probabilistic ICA (tensor PICA) allows to group similar brain activation across the
anatomical, temporal, subject or session domain. This approach is useful for
pharmacological experiments when no pharmacokinetic model exists. We exemplify this
method using data from a placebo-controlled cholecystokinine-4 (CCK-4) injection
experiment performed on 16 neuropsychiatrically and medically healthy males (age
25.6 +/- 4.2 years). Tensor PICA identified strong increases in activity in 12
networks. Comparison with results gained from the standard approach (voxelwise
regression analysis) revealed good reproduction of areas previously associated with
CCK-4 action, such as the anterior cingulate, orbitofrontal cortex, cerebellum,
temporolateral, left parietal and insular areas, striatum, and precuneus. Several
other components such as the dorsal anterior cingulate and medial prefrontal cortex
were identified, suggesting higher sensitivity of the method. Exploration of the
time courses of each activated network revealed differences, that might be lost
when a fixed time course is modeled, e. g. neuronal responses to an acoustic
warning signal prior to injection. Comparison of placebo and CCK-4 runs further
showed that a proportion of networks are newly elicited by CCK-4 whereas other
components are significantly active in the placebo conditions but further enhanced
by CCK-4. In conclusion, group ICA is a promising tool for phMRI studies that
allows quantifying and visualizing the modulation of neural networks by
pharmacological interventions.
Background: Recently, a growing body of research has appeared on different aspects
of virtual reality exposure (VRE) therapy applied to the treatment of anxiety
disorders. The purpose of this article was to review with a systematic methodology
the evidences that support the potential effectiveness of this therapy in the
treatment of fear of flying (FOF), a problem that significantly affects patients'
social functioning and personal welfare. Methods: Potential studies were identified
via computerized search using the PubMed/Medline and Web of Science databases, and
additional review of their references. Articles ranged from 1969 to 2007 and the
keywords used in the search were: "virtual reality" and "fear of flying"; "virtual
reality" and "flying phobia"; or "virtual reality" and "flight phobia." Results:
There were 40 studies using VRE in the treatment of FOF identified, mostly on the
effectiveness of VRE therapy in group and case studies. Several components of the
treatment protocols differed among the studies, which made the results comparison a
challenging task. Nevertheless, controlled studies demonstrate that VRE treatment
is effective with or without cognitive behavior therapy (CBT) and/or
psychoeducation and that it is considered to be an effective component of the
treatment of FOF. Conclusions: All studies that used cognitive and relaxation
techniques in addition to VRE treatment were effective. More randomized clinical
trials are required in which VRE therapy could be compared with standard exposure
therapy. Thus, we suggest that CBT, psychoeducation, and VRE could be combined to
treat FOF.
Six studies examined the role of young adults' parental attachment in terror
management. Studies 1-3 revealed that activating thoughts of one's parent in
response to mortality salience (MS) reduced death-thought accessibility and
worldview defense and increased feelings of self-worth. Studies 4-5 demonstrated
that MS led to greater ease of recalling positive maternal interactions and greater
difficulty recalling negative interactions, and increased attraction to a stranger
who was described as being similar to one's parent. If reliance on parents for
terror management purposes reflects the operation of attachment mechanisms, then
such effects should vary on the basis of an individual's attachment style. Study 6
demonstrated that, after MS, insecure individuals were more likely to rely on
relationships with their parents, whereas secure individuals were more likely to
rely on relationships with romantic partners.
Conditioned fear to context, a pure form of psychological stress, is associated
with sympathetically mediated changes including a marked hypertension. To identify
the possible premotor sympathetic neurons mediating these changes, we conducted
double-immunolabelling experiments combining fear-induced Fos with retrograde
tracing from the thoracic cord (T2-L1). Presympathetic groups showing the greatest
increase in the proportion of spinally projecting cells double-labelled with Fos
compared with resting controls were the perifornical area (PeF; 22.7% vs. 0.4%) and
paraventricular nucleus (Pa; 10.5% vs. 0.2%) in the hypothalamus, and the A5
noradrenergic group (33.6% vs. 0.2%) in the pons. In contrast, there was only a
small increase in the presympathetic groups of the rostral ventral medulla,
including the lateral paragigantocellular group (LPGi; 4.3% vs. 0.5%), raphe magnus
and pallidus (1.1% vs. 0.6% and 1.8% vs. 0.5%), and the vasopressor group of the
rostral ventrolateral medulla (RVLM; 1.9% vs. 0.8%). PeF, Pa, A5 and LPGi accounted
for 21, 15, 16 and 6% of all the double-labelled cells, respectively, and RVLM for
only 1%. Double-immunolabelling of Fos and tyrosine hydroxylase confirmed that many
A5 neurons were activated (19%) and that practically no C1 neurons in RVLM were
(1.3%). The results suggest that the main premotor sympathetic drive of the fear
response comes from hypothalamic (PeF and Pa) and A5 neurons that project directly
to the thoracic cord and bypass medullary presympathetic groups, and that the
vasopressor premotor sympathetic neurons of the RVLM are unlikely to mediate the
hypertensive pressure response of contextual fear.
EDITORS' PREFACE: The management of chronic low back pain (CLBP) has proven very
challenging in North America, as evidenced by its mounting socioeconomic burden.
Choosing among available nonsurgical therapies can be overwhelming for many
stakeholders, including patients, health providers, policy makers, and third-party
payers. Although all parties share a common goal and wish to use limited health-
care resources to support interventions most likely to result in clinically
meaningful improvements, there is often uncertainty about the most appropriate
intervention for a particular patient. To help understand and evaluate the various
commonly used nonsurgical approaches to CLBP, the North American Spine Society has
sponsored this special focus issue of The Spine Journal, titled Evidence-Informed
Management of Chronic Low Back Pain Without Surgery. Articles in this special focus
issue were contributed by leading spine practitioners and researchers, who were
invited to summarize the best available evidence for a particular intervention and
encouraged to make this information accessible to nonexperts. Each of the articles
contains five sections (description, theory, evidence of efficacy, harms, and
summary) with common subheadings to facilitate comparison across the 24 different
interventions profiled in this special focus issue, blending narrative and
systematic review methodology as deemed appropriate by the authors. It is hoped
that articles in this special focus issue will be informative and aid in decision
making for the many stakeholders evaluating nonsurgical interventions for CLBP. (C)
2008 Elsevier Inc. All rights reserved.
BACKGROUND: Seven previous systematic reviews (SRs) have evaluated back schools,
and one has evaluated brief education, with the latest SR including studies until
November 2004. The effectiveness of fear-avoidance training has not been assessed.
PURPOSE: To assess the effectiveness of back schools, brief education, and fear-
avoidance training for chronic low back pain (CLBP). STUDY DESIGN: A SR. METHODS:
We searched the MEDLINE database of randomized controlled trials (RCT) until August
2006 for relevant trials reported in English. Assessment of effectiveness was based
on pain, disability, and sick leave. RCTs that reported back schools, or brief
education as the main intervention, were included. For fear-avoidance training,
evaluation of domain-specific outcome was required. Two reviewers independently
reviewed the studies. RESULTS: Eight RCTs including 1,002 patients evaluated back
schools, three studies were of high quality. We found conflicting evidence for back
schools compared with waiting list, placebo, usual care, and exercises, and a
cognitive behavioral back school. Twelve trials including 3,583 patients evaluated
brief education. Seven trials, six of high quality, evaluated brief education in
the clinical setting. We found strong evidence of effectiveness on sick leave and
short-term disability compared with usual care. We found conflicting or limited
evidence for back book or Internet discussion (five trials, two of high quality)
compared with waiting list, no intervention, massage, yoga, or exercises. Three
RCTs of high quality, including 364 patients, evaluated fear-avoidance training. We
found moderate evidence that there is no difference between rehabilitation
including fear-avoidance training and spinal fusion. CONCLUSIONS: Consistent
recommendations are given for brief education in the clinical setting, and fear-
avoidance training should be considered as an alternative to spinal fusion, and
back schools may be considered in the occupational setting. The discordance between
reviews can be attributed differences in inclusion criteria and application of
evidence rules. (C) 2008 Elsevier Inc. All rights reserved.
Forty years on from the initial idea that fears could be learnt vicariously through
observing other people's responses to a situation or stimulus, this review looks at
the evidence for this theory as an explanatory model of clinical fear. First, we
review early experimental evidence that fears can be learnt vicariously before
turning to the evidence from both primate and human research that clinical fears
can be acquired in this way. Finally, we review recent evidence from research on
non-anxious children. Throughout the review we highlight problems and areas for
future research. We conclude by exploring the likely underlying mechanisms in the
vicarious learning of fear and the resulting clinical implications. Crown Copyright
(c) 2008 Published by Elsevier Ltd. All rights reserved.
The amygdala's historical role in processing stimuli related to threat and fear is
being modified to suggest a role that is broader and more abstract. Amygdala
lesions impair the ability to seek out and make use of the eye region of faces,
resulting in impaired fear perception. Other studies in rats and humans revive
earlier proposals that the amygdala is important not only for fear perception as
such, but also for detecting saliency and biological relevance. Debates about some
features of this processing now suggest that while the amygdala can process fearful
facial expressions in the absence of conscious perception, and while there is some
degree of preattentive processing, this depends on the context and is not
necessarily more rapid than cortical processing routes. A large current research
effort extends the amygdala's putative role to a number of psychiatric illnesses.
Objective: In many individuals with diabetes, the unpleasant symptoms and negative
consequences associated with hypoglycemia may result in significant anxiety or even
a fear of hypoglycemia (FoH). This fear may have significant clinical implications
for diabetes management. The aim of this review is to integrate existing research
on FoH (its measurement, predictors, correlates, impact and treatment) and discuss
its implications for diabetes management and patient education. Methods: A
literature search was conducted using Medline and Embase. The search was limited to
journal articles published in English from 1985 to 2007 inclusive. Three hundred
and one abstracts were reviewed and 273 were rejected on the basis of non-
relevance. In addition to the 28 papers included, six additional papers were
identified by further searches and were added to this review. Results: FoH appears
to be a widespread phenomenon. It is measured primarily through the use of a
specific scale, the Hypoglycemic Fear Survey (HFS). There are a number of factors
that relate to whether an individual is likely to develop FoH including whether
there is a history of hypoglycemia in an individual, length of time since first
insulin treatment, and a higher level of variability in blood glucose level. FoH
has been linked to both state and trait anxiety although the relationship is
complex. Conclusions: There is evidence that FoH may have a significant negative
impact on diabetes management, metabolic control and subsequent health outcomes.
There is evidence that blood glucose (BG) awareness training and CBT can reduce
levels of fear and improve disease management. More research is needed on how FoH
arises and the individual variables which predict its development. In addition,
well designed research is required to better understand the behavioral and medical
impact of FoH, and interventions to reduce it. Practice implications: There is some
evidence to suggest that interventions including BG awareness training and
cognitive behavioral therapy can reduce levels of fear and improve disease
management. While many aspects of FoH require further well-designed research, it is
evident that this phenomenon can have a major impact on diabetes management and
needs to be specifically addressed in patient education programs. (c) 2007 Elsevier
Ireland Ltd. All rights reserved.
Significant socio-legal transformations since September 11th have attracted
scholarly investigations in pursuit of identifying the precise nature of a newly
configured form of power. In the course of suspending law, the US government has
instituted controversial tactics in the war on terror, many of which are deemed
illegal under international law (i.e., the unlawful enemy combatant designation,
torture, and the war in Iraq). This work attends to recent analyses on sovereignty,
governmentality, counter-law, and states of exception in an effort to elaborate on
state impunity since it is regarded as an important phenomenon warranting greater
exploration. Due to an absence of accountability that would otherwise hold specific
government actors responsible, key counter-terrorism strategies perpetuate serious
state crimes. The article situates those transgressions within a conceptual context
that deepens our understanding of power in a post-9/11 world while inviting further
critique on the war on terror as it undermines the rule of law and established
human rights protections.
This paper analyses how different institutional frameworks condition the influence
of selected social traits: the social stigma to entrepreneurial failure and the
presence of entrepreneurial role models. over enterpreneurial activity levels in a
rural area with strong industrial and entrepreneurial history versus those that are
not necessarily characterized by such a tradition. To attain this objective We
undertake a rare events logit model using a robust Spanish dataset from 2003. The
main Contribution of the study indicates that there is a significant difference
between entrepreneurial activity levels in rural Catalonia as compared to rural
areas in the rest of Spain. This difference is in large part explained by the
distinct impact of the observed social traits, where the presence of
entrepreneurial role models is a prominent explanatory factor favouring
entrepreneurial activity in rural (Catalonia) areas with strong industrial
tradition. The findings of the paper back the growing call for territorial
specificity in the formulation and application of entrepreneurship support
measures, distinguishing between rural and urban areas. Hence, and in accordance
with the new rural paradigm, entrepreneurship promotion Should take a more holistic
character and become all integral part of any rural development plan. The paper's
results imply that fostering business creation in rural areas is more often than
not a generational process, where the search for short-term benefits call result in
the mistaken impression that in rural areas entrepreneurship support policy does
not work.
Between 1876 and 1881 Massachusetts experienced an outbreak of human rabies
(hydrophobia). The entire state-the Governor, the legislature, the State Board of
Health, newspapers, and the citizenry and elected officials of every town and city-
reacted to the disease. Central to the response was the Commonwealth's legislature
called the General Court. Through public hearings, their own debates, and the
passage of legislation, it resolved widespread fear and anger, mediated conflicting
concepts of disease, and promoted social solidarity in the face of an epidemic.
This article first narrates the General Court's legislative actions; it then
examines the conflicting understandings of disease causality; finally, it explores
the social and political rituals the legislature drew upon to deal with this public
health crisis. Arguing that public health legislation is simultaneously
instrumental and symbolic, this article demonstrates that attention to both
enriches the study of epidemics, historical and yet to come.
Many patients suffering from panic disorder do not receive adequate care. Advances
in the conceptualization and treatment of panic disorder encourage innovative
strategies for targeting core fears (fears of anxiety sensations) that underlie
this disorder. In this article, we discuss the use of exercise as a potential
strategy for therapeutic exposure to these feared sensations, and the role that
exercise may play as an acceptable intervention to aid the dissemination of
exposure-based approaches to the treatment of panic disorder Evidence for the
efficacy of exercise for the treatment of anxiety and panic is presented; along
with strategies to enhance the role exercise can play as an interoceptive (internal
sensation) exposure procedure. Finally, issues of comorbidity and exercise
acceptability are discussed. Our conclusion is that exercise-based interventions
are promising strategies for improving the utilization of exposure-based
interventions for panic disorder. Clinical guidelines and future research
directions are discussed.
The ongoing moral panic surrounding adolescent boys continues to cause concern,
proving pivotal in popular discourses centring on the 'problem of youth'. Drawing
on ethnographic data from a large co-educational secondary school, this paper
illustrates how school outcomes are adversely affected by working class boys'
investments in peer regulated 'hegemonic' masculinity. Echoing traditional working
class masculine identities formed in relation to the physical requirements of
industrial labour, these performances reject associations with activities
constructed as 'feminine', leading to disaffection with schoolwork. The paper
argues that, in a school culture of pervasive homophobia, some teachers
paradoxically acted as 'cultural accomplices', naturalizing compulsory
heterosexuality in engaging alienated and disruptive young men. Moreover, evidence
suggests that this is an emerging response to managerialist pressures to
'continuously improve' grades by adopting 'boy friendly' approaches. This renders
questionable strategies predicated on naturalizing assumptions about boys and makes
problematic calls for more 'role models' without investigating how gendered
pedagogies affect schooling for girls and boys.
Much of the research on long-term potentiation (LTP) is motivated by the question
of whether changes in synaptic strength similar to LTP underlie learning and
memory. Here we discuss findings from studies on fear conditioning, a form of
associative learning whose neural circuitry is relatively well understood, that may
be particularly suited for addressing this question. We first review the evidence
suggesting that fear conditioning is mediated by changes in synaptic strength at
sensory inputs to the lateral nucleus of the amygdala. We then discuss several
outstanding questions that will be important for future research on the role of
synaptic plasticity in fear learning. The results gained from these studies may
shed light not only on fear conditioning, but may also help unravel more general
cellular mechanisms of learning and memory. (c) 2006 Elsevier Ltd. All rights
reserved.
Background: Early life adverse experience alters adult emotional and cognitive
development. Here we assess early life learning about adverse experience and its
consequences on adult fear conditioning and amygdala activity. Methods: Neonatal
rats were conditioned daily from 8-12 days-old with paired odor (conditioned
stimulus, CS) .5mA shock, unpaired, odor-only, or naive (no infant conditioning).
In adulthood, each infant training group was divided into three adult training
groups: paired, unpaired or odor-only, using either the same infant CS odor, or a
novel adult CS odor without or with the infant CS present as context. Adults were
cue tested for freezing (odor in novel environment), with amygdala C-14 2-DG
autoradiography and electrophysiology assessment. Results: Infant paired odor-shock
conditioning attenuated adult fear conditioning, but only if the same infant CS
odor was used. The C-14 2-DG activity correlated with infant paired odor-shock
conditioning produced attenuated amygdala but heightened olfactory bulb activity.
Electrophysiological amygdala assessment further suggests early experience causes
changes in amygdala processing as revealed by increased paired-pulse facilitation
in adulthood. Conclusions: This suggests some enduring effects of early life
adversity (shock) are under CS control and dependent upon learning for their impact
on later adult fear learning.
Abnormalities in social functioning are a significant feature of schizophrenia. One
critical aspect of these abnormalities is the difficulty these individuals have
with the recognition of facial emotions, particularly negative expressions such as
fear. The present work focuses on fear perception and its relationship to the
paranoid symptoms of schizophrenia, specifically, how underlying limbic system
structures (i.e. the amygdala) react when probed with dynamic fearful facial
expressions. Seven paranoid and eight non-paranoid subjects (all males) with a
diagnosis of schizophrenia took part in functional magnetic resonance imaging study
(1.5 T) examining neural responses to emerging fearful expressions contrasted with
dissipating fearful expressions. Subjects viewed emerging and dissipating
expressions while completing a gender discrimination task. Their brain activation
was compared to that of 10 healthy male subjects. Increased hippocampal activation
was seen in the non-paranoid group, while abnormalities in the bilateral amygdalae
were observed only in the paranoid individuals. These patterns may represent trait-
related hippocampal dysfunction, coupled with state (specifically paranoia) related
amygdala abnormalities. The findings are discussed in light of models of paranoia
in schizophrenia. (c) 2006 Elsevier Ltd. All rights reserved.
British Muslims have substantial claims of social ostracism, discrimination, and
denials of a right to identity. There is increasing anger and frustration at the
United Kingdom's pursuit of the global "war on terror." The draconian legislation
and administrative policies of the recent Labour Governments overtly target Muslim
minorities. This article critically analyzes the issues confronted by British
Muslim communities in the context of a socially and politically strained
environment since the 7 July 2005 London bombings.
Agoraphobia with panic disorder is a phobic-anxious syndrome where patients avoid
situations or places in which they fear being embarrassed, or being unable to
escape or get help if a panic attack occurs. During the last half-century,
agoraphobia has been thought of as being closely linked to the recurring panic
attack syndrome, so much so that in most cases it appears to be the typical
development or complication of panic disorder. Despite the high prevalence of
agoraphobia with panic disorder in patients in primary-care settings, the condition
is frequently under-recognised and undertreated by medical providers.
Antidepressants have been demonstrated to be effective in preventing panic attacks,
and in improving anticipatory anxiety and avoidance behaviour. These drugs are also
effective in the treatment of the frequently coexisting depressive symptomatology.
Among antidepressant agents, SSRIs are generally well tolerated and effective for
both anxious and depressive symptomatology, and these compounds should be
considered the first choice for short-, medium- and long-term pharmacological
treatment of agoraphobia with panic disorder. The few comparative studies conducted
to date with various SSRIs reported no significant differences in terms of
efficacy; however, the SSRIs that are less liable to produce withdrawal symptoms
after abrupt discontinuation should be considered the treatments of first choice
for long-term prophylaxis. Venlafaxine is not sufficiently studied in the long-term
treatment of panic disorder, while TCAs may be considered as a second choice of
treatment when patients do not seem to respond to or tolerate SSRIs. High-potency
benzodiazepines have been shown to display a rapid onset of anti-anxiety effect,
having beneficial effects during the first few days of treatment, and are therefore
useful options for short-term treatment; however, these drugs are not first-choice
medications in the medium and long term because of the frequent development of
tolerance and dependence phenomena. Cognitive-behavioural therapy is the best
studied nonpharmacological approach and can be applied to many patients, depending
on its availability.
Research across species highlights the critical role of the amygdala in fear
conditioning. However, fear conditioning, involving direct aversive experience, is
only one means by which fears can be acquired. Exploiting aversive experiences of
other individuals through social fear learning is less risky. Behavioral research
provides important insights into the workings of social fear learning, and the
neural mechanisms are beginning to be understood. We review research suggesting
that an amygdala-centered model of fear conditioning can help to explain social
learning of fear through observation and instruction. We also describe how
observational and instructed fear is distinguished by involvement of additional
neural systems implicated in social-emotional behavior, language and explicit
memory, and propose a modified conditioning model to account for social fear
learning. A better understanding of social fear learning promotes integration of
biological principles of learning with cultural evolution.
Panic disorder is a common anxiety disorder characterized by sudden and recurrent
panic attacks. Previous studies have indicated significant genetic contributions
and a susceptibility locus for panic disorder has been mapped to human chromosome
7p15. The receptor for Neuropeptide S (NPS) is located in the same genomic region
while NPS is known to produce arousal and anxiolytic-like effects in rodents. Here
we report that a coding polymorphism in the Neuropeptide S receptor (NPSR) is
associated with panic disorder in male patients of Japanese ancestry. The
polymorphism (Asn(107)Ile) results in a gain-of-function of the receptor protein by
increasing the agonist sensitivity about tenfold. The allele representing the less
active isoform (NPSR Asn(107)) was found under-represented in male panic disorder
patients, indicating a potential protective function of the protein. Two unrelated
groups of patients diagnosed with schizophrenia or attention-deficit/hyperactivity
disorder (ADHD) showed no association of particular NPSR alleles with the
disorders. These results provide evidence for a gender-specific effect of NPSR in
the pathogenesis of panic disorder. (c) 2007 Elsevier Inc. All rights reserved.
The azapirone derivatives, including tandospirone and buspirone, are anxiolytics
with 5-HT1A receptor agonistic action. Previous in vitro studies have suggested
these azapirone derivatives are mainly metabolized by the cytochrome P450 (CYP) 3A4
isoform. The purpose of this study was to clarify the effects CYP3A4 inhibitors
have on the anxiolytic action of tandospirone in a conditioned fear stress rat
model. One day after fear conditioning, the orally administered tandospirone (30-
100 mg/kg) significantly inhibited conditioned freezing in a dose-dependent manner.
Co-administration of oral tandospirone and CYP3A4 inhibitors [ketoconazole (10
mg/kg, i.p.) and cimetidine (200 mg/kg, p.o.)] markedly inhibited conditioned
freezing. Ketoconazole significantly increased the anxiolytic effect of buspirone
similar to tandospirone. As with freezing behavior, the plasma concentrations of
tandospirone and buspirone were increased by CYP3A4 inhibitors. This suggests the
CYP3A4 isoform is involved in the metabolism of tandospirone, in vivo. Therefore,
drugs with CYP3A4 inhibitory property may facilitate the anxiolytic effect of
tandospirone when treating human anxiety disorders. (c) 2007 Elsevier Inc. All
rights reserved.
Excessive fear and anxiety are hallmarks of a variety of disabling anxiety
disorders that affect millions of people throughout the world. Hence, a greater
understanding of the brain mechanisms involved in the inhibition of fear and
anxiety is attracting increasing interest in the research community. In the
laboratory, fear inhibition most often is studied through a procedure in which a
previously fear conditioned organism is exposed to a fear-eliciting cue in the
absence of any aversive event. This procedure results in a decline in conditioned
fear responses that is attributed to a process called fear extinction. Extensive
empirical work by behavioral psychologists has revealed basic behavioral
characteristics of extinction, and theoretical accounts have emphasized extinction
as a form of inhibitory learning as opposed to an erasure of acquired fear. Guided
by this work, neuroscientists have begun to dissect the neural mechanisms involved,
including the regions in which extinction-related plasticity occurs and the
cellular and molecular processes that are engaged. The present paper will cover
behavioral, theoretical and neurobiological work, and will conclude with a
discussion of clinical implications.
Technology is a social practice that embodies the capacity of societies to
transform themselves by creating and manipulating not only physical objects, but
also symbols and cultural forms. It is an illusion that scientific and
socioeconomic drivers are the sole elements determining the destiny of a
technology. Although they are important, what is really crucial is the way in which
a human community 'metabolizes' a new technology, that is the way in which a new
technology becomes part of the mental landscape of people living in that society.
In this paper I argue that today, fear of technology mainly emerges from a lack of
meaning surrounding the technology revolution. Present technology is developing
without a sound cultural framework that could give technology a sense beyond mere
utilitarian considerations. Frightening stories then end up being a privileged way
to incorporate technology into a meaningful context. However, fear is not the sole
emotion that can enable integration of new concepts into mental schemes, two other
powerful emotional forces should be considered: wonder and curiosity.
The cognitive and emotional effects of amygdala or frontal cortex lesions were
compared in rats trained to time both a 50-s visual signal paired with food and an
embedded 10- or 20-s auditory signal that was paired with either appetitive (food)
or aversive (footshock) outcomes. When both auditory and visual signals were paired
with food, control and amygdalar-lesioned rats were able to divide attention and to
time both signals simultaneously, whereas when the embedded auditory signal was
paired with footshock, control rats were impaired in their ability to divide
attention and were able to time only one signal at a time. In contrast, amygdalar
inactivation blocked this fear-related impairment and allowed rats to time both
signals simultaneously, whereas rats with frontal cortex lesions demonstrated
sequential processing under all conditions. These results support the proposal that
the frontal cortex exerts executive control over the allocation of attentional
resources, but that under stressful conditions the amygdala is crucial for the
emergence of fear-evoked increments in selective attention leading to deficits in
the ability to time 2 or more signals simultaneously.
Research studies focusing on the fear-avoidance model have expanded considerably
since the review by Vlaeyen and Linton (Vlaeyen J. W. S. & Linton, S. J. (2000).
Fear-avoidance and its consequences in chronic musculoskeletal pain: a state of the
art. Pain, 85(3), 317-332). The fear-avoidance model is a cognitive-behavioral
account that explains why a minority of acute low back pain sufferers develop a
chronic pain problem. This paper reviews the current state of scientific evidence
for the individual components of the model: pain severity, pain catastrophizing,
attention to pain, escape/avoidance behavior, disability, disuse, and
vulnerabilities. Furthermore, support for the contribution of pain-related fear in
the inception of low back pain, the development of chronic low back pain from an
acute episode, and the maintenance of enduring pain, will be highlighted. Finally,
available evidence on recent clinical applications is provided, and unresolved
issues that need further exploration are discussed.
The endocannabinoid system recently emerged as an important modulator of many
neuronal functions. Among them, the control of anxiety and acquired fear represents
nowadays one of the most interesting fields of research. Despite contrasting
results obtained by the use of cannabinoid receptor agonists in experimental
animals, there is growing evidence that the physiological activation of the
endocannabinoid system plays a central role in the control of basal anxiety levels
and in the modulation of fear responses. This review will summarise recent data on
the role of the endocannabinoid system in most commonly used tests of anxiety and
in the processing of acquired fear, with particular attention to its involvement in
fear extinction. Finally, a neurobiological model possibly able to implement the
role of the endocannabinoid system in these processes will be proposed. (c) 2007
Elsevier Ltd. All rights reserved.
Objectives: The objectives of this article were to examine the literature published
from 1982 to 2006 and to evaluate prevalence of dental fear and anxiety (DFA) and
dental behaviour management problems (DBMP) in children and adolescents, and their
relationships to age, sex, general anxiety, temperament, and general behavioural
problems. Methods: A broad search of the PubMed database was performed using three
combinations of search terms. Results: A large proportion of the identified
articles could not be used for the review owing to inadequate endpoints, measures
or poor study design. Thirty-two papers of acceptable quality were identified and
reviewed. The prevalence of both DFA and DBMP were estimated to 9%, with a decrease
in prevalence with age. DFA/DBMP were more frequent in girls. DFA/DBMP were related
to general fear and both internalizing and externalizing behavioural problems,
although these relationships were not clear-cut. Temperament was related to both
DFA and DBMP but with different temperamental characteristics, while general
behavioural problems mainly correlated with DBMP. Conclusions: DFA/DBMP are common,
and several psychological factors are associated with the development of these
problems. In order to better understand these relationships, a number of issues
concerning design of research and measurement of DFA/DBMP have to be dealt with.
Previous work suggests the gamma-aminobutyric acid (GABA)ergic system may be
dynamically regulated during emotional learning. In the current study we examined
training-induced changes in the expression of GABA(A)-related genes and the binding
of GABA receptor radioligands in the amygdala after the acquisition and extinction
of Pavlovian fear. Using in situ hybridization, we examined the expression pattern
changes of mRNAs for GABAergic markers in the lateral, basolateral and central
subdivisions of the amygdala in C57Bl/6J mice. These markers included GABA-
synthesizing enzymes (GAD67 and GAD65), major GABA(A) receptor subunits (alpha 1,
alpha 2, alpha 3, alpha 5, beta 2 and gamma 2) and the expression of mRNAs that are
involved in a variety of GABA-related intracellular processes, including GABA
transporter-1 (GAT1), GABA(A) receptor-associated protein and the GABA(A)
clustering protein, gephyrin. With fear conditioning, we found decreased mRNA
levels of alpha 1, alpha 5 and GAD67, as well as deceased benzodiazepine binding in
the amygdala. Fear extinction induced an increase in mRNA levels of alpha 2, beta
2, GAD67 and gephyrin, as well as a decrease in GAT1. Together, these findings
indicate that the acquisition of fear induced a downregulation of mRNA markers
related to a decrease in amygdala GABAergic function, whereas the acquisition of
fear extinction produced an upregulation of GABAergic markers related to enhanced
GABAergic transmission.
The purpose of this study was to investigate the brain gamma-aminobutyric acid
(GABA) concentration and its relationship with clinical variables in patients with
panic disorder (PD). Single voxel proton magnetic resonance spectroscopy (H-MRS)
scan was performed on 22 medicated subjects with PD and 25 age and sex-matched
healthy comparison subjects. GABA and other metabolite levels were measured in the
anterior cingulate cortex (ACC) and basal ganglia. GABA levels were significantly
lower in the ACC and basal ganglia of PD patients relative to comparison subjects.
Lactate and choline concentrations in the ACC in PD patients were also higher than
in the comparison subjects. Our data suggested in part that alterations of the GABA
function and the energy metabolism in ACC and basal ganglia may play an important
role in the pathophysiology of panic disorder. (c) 2006 Elsevier Inc. All rights
reserved.
Panic disorder is a major cause of medical attention with substantial social and
health service cost. Based on pharmacological studies, research on its
etiopathogenesis has been focused on the possible dysfunction of specific
neurotransmitter systems. However, recent work has related the genes involved in
development, synaptic plasticity and synaptic remodeling to anxiety disorders. This
implies that learning processes and changes in perception, interpretation and
behavioral responses to environmental stimuli are essential for development of
complex anxiety responses secondary to the building of specific brain neural
circuits and to adult plasticity. The focus of this review is on progress achieved
in identifying genes that confer increased risk for panic disorder through genetic
epidemiology and the use of genetically modified mouse models. The integration of
human and animal studies targeting behavioral, systems-level, cellular and
molecular levels will most probably help identify new molecules with potential
impact on the pathogenetic aspects of the disease.
Background Panic disorder can be treated with pharmacotherapy, psychotherapy or in
combination, but the relative merits of combined therapy have not been well
established. Objectives To review evidence concerning short- and long-term
advantages and disadvantages of combined psychotherapy plus antidepressant
treatment for panic disorder with or without agoraphobia, in comparison with either
therapy alone. Search strategy The Cochrane Collaboration Depression, Anxiety and
Neurosis Controlled Trials Registers (CCDANCTR-Studies and CCDANCTR-References)
were searched on 11/10/2005, together with a complementary search of the Cochrane
Central Register of Controlled Trials and MEDLINE, using the keywords
antidepressant and panic. A reference search, SciSearch and personal contact with
experts were carried out. Selection criteria Two independent review authors
identified randomised controlled trials comparing the combined therapy against
either of the monotherapies among adult patients with panic disorder with or
without agoraphobia. Data collection and analysis Two independent review authors
extracted data using predefined data formats, including study quality indicators.
The primary outcome was relative risk (RR) of "response" i.e. substantial overall
improvement from baseline as defined by the original investigators. Secondary
outcomes included standardised weighted mean differences in global severity, panic
attack frequency, phobic avoidance, general anxiety, depression and social
functioning and relative risks of overall dropouts and dropouts due to side
effects. Main results We identified 23 randomised comparisons (representing 21
trials, 1709 patients), 21 of which involved behaviour or cognitive behaviour
therapies. In the acute phase treatment, the combined therapy was superior to
antidepressant pharmacotherapy (RR 1.24, 95% confidence interval (CI) 1.02 to 1.52)
or psychotherapy (RR 1.17, 95% CI 1.05 to 1.31). The combined therapy produced more
dropouts due to side effects than psychotherapy (number needed to harm (NNH) around
26). After the acute phase treatment, as long as the drug was continued, the
superiority of the combination over either monotherapy appeared to persist. After
termination of the acute phase and continuation treatment, the combined therapy was
more effective than pharmacotherapy alone (RR 1.61, 95% CI 1.23 to 2.11) and was as
effective as psychotherapy (RR 0.96, 95% CI 0.79 to 1.16). Authors' conclusions
Either combined therapy or psychotherapy alone may be chosen as first line
treatment for panic disorder with or without agoraphobia, depending on patient
preference.
Pretraining lesions of rat perirhinal cortex (PR) severely impair pavlovian fear
conditioning to a 22 kHz ultrasonic vocalization (USV) cue. However, PR lesions are
without significant effect when the cue is a continuous tone at the same or a lower
frequency. Here we examined fear-conditioning-produced changes in single-unit
firing elicited in rat PR by a 22 kHz tone cue or a 22 kHz USV cue. Chronic
recording electrodes were introduced from the lateral surface of the skull.
Altogether, 200 well isolated units were studied in 28 rats. Overall, 73% of the
recorded single units (145 of 200 units) evidenced statistically significant firing
changes in response to the tone or USV conditional stimulus (CS) after it had been
paired several times with an aversive unconditional stimulus (US). Interestingly,
33% of units (66 of 200 units) that were initially CS-unresponsive became CS-
responsive after conditioning. After conditioning, there were two notable
differences between single-unit responses elicited by the USV cue and those
elicited by the tone cue. First, 11% of the units (14 of 123 units) recorded from
the USV-conditioned group displayed a precisely timed increase in firing rate
during the 260 ms interval in which the US had previously occurred. This US-timed
response was unique to the USV-conditioned group. Second, the mean latency of cue-
elicited firing was similar to 30 ms longer in the USV-conditioned group than in
the tone-conditioned group. These cue-specific differences in acquired firing
latencies and acquired firing patterns suggest that spectrotemporal properties of a
CS can control the essential circuitry or neurophysiological mechanisms underlying
fear conditioning.
Fear is arguably the most commonly investigated emotion in domestic animals. In the
current review we attempt to establish the level of repeatability and validity
found for fear tests used on cattle, pigs, sheep and goats, poultry and horses. We
focus the review on the three most common types of fear tests: the arena test (open
field), the novel object test, and the restraint test. For some tests, e.g. tonic
immobility in poultry, there is a good and broad literature on factors that affect
the outcome of the test, the validity of the test and its age dependency. However,
there are comparatively few of these well defined and validated tests and what is
especially missing for most tests is information on the robustness, i.e., what
aspects can be changed without affecting the validity of the tests. The relative
absence of standardized tests hampers the development of applied ethology as a
science. (c) 2007 Elsevier Inc. All rights reserved.
OBJECTIVE To describe for family physicians screening, diagnosis, and treatment of
panic disorder with or without agoraphobia (PD/A). QUALITY OF EVIDENCE Articles
were identified through PsycLIT, PsyINFO, and MEDLINE (1985 to 2006) using the
terms panic disorder, psychotherapy, psychosocial treatment, treatment, and
pharmacotherapy. Recommendations on treatment choices and guidelines are based on
data from high-quality studies only. information about assessment and diagnosis of
PD/A is supported by the most recent epidemiologic studies, as well as expert
consensus and opinion. MAIN MESSAGE Panic disorder with or without agoraphobia is a
psychiatric disease frequently encountered in primary care. It appears to be
underdiagnosed and undertreated in this medical setting. Early successful screening
requires a focus on unexplained symptoms and specific questions aimed at
identifying panic attacks and their meaning for patients. The treatment of choice
for PD/A is cognitive-behavioral therapy administered by a specialized psychologist
or psychiatrist. When such therapy is hard to come by or unavailable, family
physicians can prescribe drug therapy. CONCLUSION Family physicians can contribute
greatly to early detection and treatment of PD/A.
A review of previous research suggests increased probability of the prevalence of
anxiety disorders, and particularly panic disorder and panic attacks in patients
with asthma, as compared to a normal population. Research also indicates
significant levels of co-morbidity between asthma and anxiety as measured on
dimensional scales of anxiety and panic. Clinical anxiety and panic manifestations
affect symptom perception and asthma management through the effects of anxiety
symptoms such as hyperventilation, and indirectly through self-management behavior
and physician response. However, there is limited data on the impact of anxiety co-
morbidity on asthma quality of life. Some studies indicate that individuals with
co-morbid asthma and anxiety or panic report worse asthma quality of life both in
general and in relation to their symptomatotogy, being limited in their daily
activities, in response to environmental stimuli and in regard to feelings of
emotional distress. Cognitive-behavioral therapy (CBT) is an effective and
empirically supported treatment of choice for anxiety disorders and panic attacks.
However, standard CBT protocols for anxiety and panic may need to be specifically
targeted at improving asthma outcomes. Also, asthma research literature is tacking
in randomized controlled trials applying CBT to patients with co-morbid asthma and
clinical anxiety manifestations. Trials evaluating CBT interventions in individuals
with clinical anxiety manifestations and asthma may provide evidence of these
interventions as an effective adjunct to improve asthma management and control. (c)
2006 Elsevier Ltd. All rights reserved.
This meta-analysis of studies of the persuasive impact of fear appeals evaluated
the contribution of our stage model of the processing of fear-arousing
communications relative to other fear appeal theories. In contrast to other
theories, our stage model (a) specifies the cognitive processes underlying
persuasion through fear-arousing communications, (b) proposes that threat-induced
defensive processing does not interfere with the effectiveness of fear-arousing
communications but actually contributes to it, and (c) predicts that vulnerability
and severity manipulations have differential effects on measures of attitude as
compared with intention and behavior. To evaluate these predictions, the authors
expanded on previous meta-analyses by assessing the independent as well as joint
effects of vulnerability to and severity of a risk, both on information processing
and on measures of persuasion (attitude, intention, behavior). Overall, findings
were consistent with the stage model. The theoretical and practical implications of
these findings are discussed.
Objectives: Selective serotonin reuptake inhibitors (SSRIs) are currently
considered as the first drug of choice in the treatment of panic disorder (PD). The
aim of this long-term, naturalistic comparison study was to compare 4 SSRIs with
respect to tolerability and treatment outcome of PD. Outcome measures included
relapse rates and adverse effects. Methods: Two hundred patients with PD were
enrolled in our study. All subjects met DSM-IV criteria for PD or PD with
agoraphobia (PDA). All patients were assigned to receive SSRI monotherapy for 12
months with either citalopram (n = 50), fluoxetine (n = 50), fluvoxamine (n = 50),
or paroxetine (n = 50) in a randomized, nonblinded fashion. Both the treating
psychiatrist and the patients were not blind to the assigned treatment, but the
clinician raters were blind to the study medication. The study design allowed for
assignment of a particular SSRI as indicated according to the clinical judgment of
the study psychiatrists. The Panic Self-Questionnaire, which is a self-report
scale, was administered at baseline and then once per month during the duration of
the 12-month study. The visual analog scale and the Clinical Global Impression
Scale were administered at baseline and then once per month during the period of
the study. Reports of sexual dysfunction were assessed using a nonstructured
clinical interview at monthly visits. The body weight of study subjects was
measured at baseline, and then at the 12th month visit end point. Results: Of 200
patients who entered the study, 127 patients (63.5%) completed the full 12-month
protocol. Retention rates were highest for paroxetine (76% [38/50]), intermediate
for citalopram (68% [34/50]) and fluvoxamine (60% [30/50]), and lowest for
fluoxetine (50% [25/50]). Patients who completed the 12-month protocol responded
favorably to the study treatment. The paroxetine and the citalopram groups had
significantly lower rates of panic symptoms as measured at visits on weeks 4 and 8.
At visits on months 3, 6, 9, and 12, however, there were no statistically
significant differences between the 4 groups in relapse rates (defined as the
occurrence of I or more panic attacks during the previous week of treatment) (F-
1,F-127 = 0.17; P = 0.13 [not statistically significant]). At the 12th month end
point, patients in all 4 treatment groups had a statistically significant increase
in body weight. Body weight among the study population increased by 6.1 + 4.9 kg
from a mean weight of 72.4 + 7.3 kg at the onset of treatment. Reports of sexual
adverse effects at the 12th month visit were similar in the citalopram, fluoxetine,
and paroxetine groups, but the fluvoxamine patient group reported fewer sexual
adverse effects at the 12th month visit. Conclusions: Most of our PD patients
responded well to 12month treatment with either citalopram, fluoxetine,
fluvoxamine, or paroxetine, and the overall response rate was equal after the first
4 weeks of treatment. Although patients treated with paroxetine had the lowest
dropout rates during the initiation phase, they had the highest rate of adverse
effects as measured at the 12th month visit. Conversely, patients in the
fluvoxamine group had the highest dropout rate (which was primarily caused by
adverse effects in the initiation phase of treatment.); however, patients who were
able to tolerate fluvoxamine throughout the full course of the study were observed
to have lower rates of sexual dysfunction and weight gain compared with patients
treated with the other agents. Overall, when measured-at the 12th month visit,
monotherapy with paroxetine and citalopram was associated with a higher rate of
sexual adverse effects than was treatment with fluoxetine or fluvoxamine. in
addition, monotherapy with paroxetine, citalopram, and fluoxetine seemed to cause
more weight gain than did treatment with fluvoxamine.
The last decade has witnessed remarkable progress in the understanding of the
mammalian cannabinoid system, from the cloning of the endogenous cannabinoid
receptor to the discovery of new pharmacologic compounds acting on this receptor.
Current and planned studies in humans include compounds with effects ranging from
direct antagonists to inhibitors of reuptake and breakdown. This progress has been
accompanied by a much greater understanding of the role of the cannabinoid system
in modulating the neural circuitry that mediates anxiety and fear responses. This
review focuses on the neural circuitry and pharmacology of the cannabinoid system
as it relates to the acquisition, expression, and extinction of conditioned fear as
a model of human anxiety. Preclinical studies suggest that these may provide
important emerging targets for new treatments of anxiety disorders.
Erythrophobia is the pathological form of fear of blushing. This review is based
upon an extensive literature research and supplemented by clinical observations
from a pilot study of a cognitive-behavioural group therapy for fear of blushing.
Current knowledge about fear of blushing is reported regarding diagnostic
considerations, aetiologic and pathogenetic mechanisms, and cognitive-behavioural
therapy. In conclusion, this review indicates that fear of blushing should be
classified as a sub-syndrome of social phobia. Patients suffering from fear of
blushing as predominant complaint differ from other patients with social phobia in
health-care utilisation, treatment expectation and treatment goals. However, the
most prominent difference lies in the exaggerated and inflexible self-focused
attention these patients direct to their arousal and bodily symptoms. Therefore,
attention training as a specific treatment unit is promising and should be
integrated in standard treatment approaches for social phobia. Finally, options for
further research are outlined.
A significant portion of the war on terror detainees who have been charged at
Guantanamo have announced their intentions to dismiss their attorneys, to waive
their right to be present at their trials, or to take both actions simultaneously
so that their interests will not be represented. This Note demonstrates that strong
justifications, rooted in international and domestic legal rules and precedent,
support honoring the detainees' requests. Yet the military tribunal proceedings are
designed to follow the adversarial model to achieve just outcomes; granting the
detainees' procedural requests can, in certain situations, undermine the ability of
the military commissions to reach just outcomes in favor of the personal whims of
the detainees. When a detainee's procedural request threatens to undermine the
adversarial model, I propose that military adjudicators appoint an amicus curiae
counsel to provide sufficient process on behalf of the tribunal.
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis may play a role in
panic disorder. HPA studies in patients with panic disorder, however, have produced
inconsistent results. Seeking to understand the inconsistencies, we reexamined
endocrine data from four studies of patients with panic disorder, in light of
animal data highlighting the salience of novelty, control, and social support to
HPA axis activity. Patients with panic disorder were studied (1) at rest over a
full circadian cycle, (2) before and after activation by a panicogenic respiratory
stimulant (doxapram) that does not directly stimulate the HPA axis, and (3) before
and after a cholecystokinin B (CCK-B) agonist that is panicogenic and does directly
stimulate the HPA axis. Patients with I panic disorder had elevated overnight
cortisol levels, which correlated with sleep disruption. ACTH and cortisol levels
were higher in a challenge paradigm (doxapram) than in a resting state study, and
paradigm-related ACTH secretion was exaggerated in patients with panic disorder.
Panic itself could be elicited without HPA axis activation. Patients with panic
disorder showed an exaggerated ACTH response to pentagastrin stimulation, but this
response was normalized by prior exposure to the experimental context or
psychological preparation to reduce novelty and enhance sense of control. Novelty
is one of a number of contextual cues known from animal work to activate the HPA
axis. The HPA axis abnormalities seen in patients with panic disorder in the four
experiments reviewed here might all be due to exaggerated HPA axis reactivity to
novelty cues. Most of the published panic/HPA literature is consistent with the
hypothesis that HPA axis dysregulation in panic is due to hypersensitivity to
contextual cues. This hypothesis requires experimental testing.
As a way of tracking Popular framing of CMC, this article critically reviews an
international corpus of 101 print-media accounts (from 2001 to 2005) of language-
use in technologies Such as instant messaging and text-messaging. From the combined
perspective of folk linguistics and critical discourse analysis, this type of
metadiscourse (i.e., discourse about discourse) reveals the conceptual and
ideological assumptions by which particular communication practices come to be
institutionalized and understood. The article is illustrated with multiple examples
from across the corpus in order to demonstrate the most recurrent metadiscursive
themes in mediatized depictions of technologically- or computer-mediated discourse
(CMD). Rooted in extravagant characterizations of the prevalence and impact of CMD,
together with highly caricatured exemplifications of actual practice, these Popular
but influential (mis) representations typically exaggerate the difference between
CMD and non-mediated discourse, misconstrue the 'evolutionary' trajectory of
language change, and belie the cultural embeddedness of CMD.
Experimental animal models provide an important tool for the identification of
inheritable components of fear and anxiety. 'Pavlovian' fear conditioning has been
tremendously successful to characterize the neuronal circuitry and cellular
mechanisms of the formation, consolidation and extinction of fear memories. Here we
summarize recent progress that has led to the identification of gene products
contributing to such experience-dependent changes in fear and anxiety and may guide
the search for genetic factors involved in the development and treatment of human
anxiety disorders.
Fear has become the emotion du jour, among scholars and, most of them argue, among
wider publics as well. This essay reviews several important works, in several
disciplines, that have appeared over the past seven years. The essay discusses
their relationship to earlier historical findings and their implications for recent
emotional history and its ramifications in culture and politics.
Application of repetitive transcranial magnetic stimulation was effective and safe
in treating a 55-year-old man with comorbid depression and panic disorder, which
occurred 6 months after a myocardial infarction. (c) 2006 Elsevier Inc. All rights
reserved.
Panic disorder is a common mental disorder that affects up to 5% of the population
at some point in life. It is often disabling, especially when complicated by
agoraphobia, and is associated with substantial functional morbidity and reduced
quality of life. The disorder is also costly for individuals and society, as shown
by increased use of health care, absenteeism, and reduced workplace productivity.
Some physical illnesses leg, asthma) commonly occur with panic disorder, and
certain lifestyle factors (eg, smoking) increase the risk for the disorder, but
causal pathways are still unclear. Genetic and early experiential susceptibility
factors also exist, but their exact nature and pathophysiological mechanisms remain
unknown. Despite an imprecise, although increased, understanding of cause, strong
evidence supports the use of several effective treatments (eg, pharmacological,
cognitive-behavioural). The adaptation and dissemination of these treatments to the
frontlines of medical-care delivery should be urgent goals for the public-health
community.
This article reviews research in both animals and humans on the considerable
progress made in elucidating a brain circuitry of fear, particularly the importance
of the amygdala in fear conditioning. While there is considerable agreement about
the participation of the amygdala in fear in both animals and humans, there are
several issues about the function of the amygdala raised by the human research that
have not been addressed by or may be answered by animal research. Three of these
are addressed in this article: (1) is the amygdala involved in or necessary for
both fear learning and unconditioned fear? (2) Does the amygdala code for intensity
of fear? (3) Is the amygdala preferentially involved in fear, or is it also
activated when there are no overt fear or aversive stimuli, but where the situation
can be described as uncertain? We present evidence indicating that the rodent
amygdala is involved in some types of fear (conditioned fear), but not all types
(unconditioned fear), and may therefore have significance for a differential
neurobiology of certain anxiety disorders in humans. Further, similar to the human
amygdala, the rodent amygdala responds to varying intensities of aversive
stimulation. Finally, it is suggested that, similar to humans, the rodent amygdala
is involved in the evaluation of uncertainty. We conclude that progress on
elucidating the role of the amygdala in fear is facilitated by corroboration of
findings from both animal and human research. (c) 2006 Elsevier B.V. All rights
reserved.
The neurotransmitter glutamate and its associated receptors perform an important
role in the brain circuitry underlying normal fear processing. The glutamate NMDA
receptor, in particular, is necessary for the acquisition and recollection of
conditioned-fear responses. Here the authors examine how acute blockage of the NMDA
receptor with sub-anaesthetic doses of ketamine affects behavioural assays of fear-
conditioned stress (e.g. freezing) and cFos expression in a network of brain areas
that have previously been implicated in fear processing. Fear-conditioned rats
displayed significantly more freezing behaviour than non-conditioned controls. In
fear-conditioned rats that also received ketamine, this conditioning effect was
largely neutralised. Fear conditioning also led to increased cFos expression in
various areas central to fear processing, including the basolateral nucleus of the
amygdala, the paraventricular nucleus of the hypothalamus and the anterior
cingulate. Ketamine abolished such increases in cFos expression in most brain areas
investigated. The present study therefore demonstrates that systemic ketamine
administration in rats interferes with fear conditioning on a behavioural level and
in a network of brain regions associated with fear and anxiety. The combination of
ketamine and fear conditioning may therefore provide a useful model of abnormal
fear processing, as observed in certain psychiatric conditions. (c) 2006 Elsevier
Inc. All rights reserved.
Kamin blocking in fear conditioning is thought to reflect diminished processing of
the unconditional stimulus (US) in the presence of a conditional stimulus (CS')
that was previously paired with this US. According to Fanselow's (1998) hypothesis,
the CS' drives output from the amygdala that ultimately produces analgesia by
causing opiate release onto afferent pain circuits. This hypothesis was explored
quantitatively through neurophysiological simulations. The results suggest that
opiate-mediated, negative-feedback control of US processing is too slow for
efficient blocking of cue conditioning. The reason is that conditioning-produced
synaptic modifications can be induced before the opiate-mediated inhibition has any
substantial effect on US processing. The results suggest the existence of an
additional, faster-acting, inhibitory neurotransmitter in the blocking circuit.
Rat pups must learn maternal odor to support attachment behaviors, including
nursing and orientation toward the mother. Neonates have a sensitive period for
rapid, robust odor learning characterized by increased ability to learn odor
preferences and decreased ability to learn odor aversions. Specifically, odor-0.5
mA shock association paradoxically causes an odor preference and coincident failure
of amygdala activation in pups until postnatal day 10 (P10). Because sensitive-
period termination coincides with a declining "stress hyporesponsive period" when
corticosterone release is attenuated, we explored the role of corticosterone in
sensitive-period termination. Odor was paired with 0.5 mA shock in either
sensitive-period (P8) or postsensitive-period (P12) pups while manipulating
corticosterone. We then assessed preference/aversion learning and the olfactory
neural circuitry underlying its acquisition. Although sensitive-period control
paired odor-shock pups learned an odor preference without amygdala participation,
systemic (3 mg/ kg, i.p.; 24 h and 30 min before training) or intra-amygdala
corticosterone (50 or 100 ng; during training) permitted precocious odor-aversion
learning and evoked amygdala neural activity similar to that expressed by older
pups. In postsensitive-period (P12) pups, control paired odor-shock pups showed an
odor aversion and amygdala activation, whereas corticosterone- depleted
(adrenalectomized) paired odor-shock pups showed odor-preference learning and
activation of an odor learning circuit characteristic of the sensitive period.
Intra-amygdala corticosterone receptor antagonist (0.3 ng; during training) infused
into postsensitive-period (P12) paired odor-shock pups also showed odor-preference
learning. These results suggest corticosterone is important in sensitive-period
termination and developmental emergence of olfactory fear conditioning, acting via
the amygdala as a switch between fear and attraction. Because maternal stimulation
of pups modulates the pups' endogenous corticosterone, this suggests maternal care
quality may alter sensitive-period duration.
Fear extinction is the decrease in conditioned fear responses that normally occurs
when a conditioned stimulus (CS) is repeatedly presented in the absence of the
aversive unconditioned stimulus (US). Extinction does not erase the initial CS-US
association, but is thought to form a new memory. After extinction training,
extinction memory competes with conditioning memory for control of fear expression.
Deficits in fear extinction are thought to contribute to post-traumatic stress
disorder (PTSD). Herein, we review studies performed in rats showing that the
medial prefrontal cortex plays a critical role in the retention and expression of
extinction memory. We also review human studies indicating that prefrontal areas
homologous to those critical for extinction in rats are structurally and
functionally deficient in patients with PTSD. We then discuss how findings from rat
studies may allow us to: (1) develop new fear extinction paradigms in humans, (2)
make specific predictions as to the location of extinction-related areas in humans,
and (3) improve current extinction-based behavioral therapies for anxiety
disorders. (c) 2006 Elsevier B.V. All rights reserved.
The ability to detect and learn about the predictive relations existing between
events in the world is essential for adaptive behavior. It allows US to Use past
events to predict the future and to adjust our behavior accordingly. Pavlovian fear
conditioning allows anticipation of sources of danger in the environment. It guides
attention away from poorer predictors toward better predictors of danger and
elicits defensive behavior appropriate to these threats. This article reviews the
differences between learning about predictive relations and learning about
contiguous relations in Pavlovian fear conditioning. It then describes behavioral
approaches to the Study of these differences and to the examination of subtle
variations in the nature and consequences of predictive learning. Finally, it
reviews recent data from rodent and human studies that have begun to identify the
neural mechanisms for direct and indirect predictive fear learning.
The survey examines writings in three areas: (1) the causes and cures of the rise
of religious violence and terrorism, with particular attention to how Christian
theology and the Bible contribute to or challenge this violence; (2) the ethical
challenges of terrorism and the need to find a moral response to this threat; and
(3) the strengths and limits of just war thinking in responding to contemporary
forms of violence.
Although panic disorder usually emerges in early to middle adulthood, adults with
panic disorder often retrospectively report that their panic symptoms began in
childhood or early adolescence. The majority of these juvenile cases are being
misdiagnosed, and/or do not come to clinical attention. Awareness of early-onset
panic disorder, as well as a more precise definition of early signs and possible
clinical subtypes, can favour timely diagnosis and treatment, reduce clinical
impairment and improve the prognosis of these patients. In the context of a
multimodal approach, pharmacological treatment can be helpful. This review focuses
on the empirical evidence of pharmacotherapy in early-onset panic disorder,
including selective serotonin re-uptake inhibitors, benzodiazepines and tricyclics.
The data supporting efficacy are still limited, and no controlled studies are
available. Practical guidelines for the management of these patients are provided,
including treatment of the most frequent psychiatric comorbidities.
The essential role of serotonin (5-hydroxytryptamine (5-HT)) system in the
neurobiology and pharmacotherapy of panic disorder (PD) continues to be a topic of
intensive interdisciplinary research. Interest in the involvement of 5-HT in PD has
been fuelled by clinical studies demonstrating that medications increasing the
synaptic availability of 5-HT, such as selective 5-HT re-uptake inhibitors, are
effective in the treatment of PD. Rival theories of 5-HT deficiency vs excess have
attempted to explain the impact of 5-HT function in PD. In the past decade,
knowledge of the role of 5-HT in the neurobiology of PD has expanded dramatically
due to much new research including experimental, treatment, brain-imaging, and
genetic studies. The current review attempts to summarize the new data and their
implications. The challenge and treatment studies generally confirm the specific
inhibitory influence of 5-HT on panicogenesis. The brain-imaging studies in PD
patients demonstrate functional and clinically relevant alterations in various
elements of 5-HT system affecting the neurocircuitry of panic. The findings of
genetic association studies suggest that certain 5-HT-related genes may contribute
to the susceptibility to PD; however, these data are rather limited and
inconsistent. It appears that, even if not the primary etiological factor in PD,
the 5-HT function conveys important vulnerability, as well as adaptive factors. A
better understanding of these processes may be critical in achieving progress in
the treatment of patients suffering from PD.
Objective: In this naturalistic and prospective study, personality was assessed in
patients with panic disorder (PD), in order to evaluate whether personality
features negatively influence the outcome of pharmacological treatment. Method:
Before drug treatment, PD was diagnosed with the Structured Clinical Interview for
DSM-IV disorders and personality was assessed with the Structured Interview for
DSM-IV Personality Disorders. Moreover, all patients were evaluated with the SCL-
90, the Ham-A and Ham-D. Then, patients were randomly treated with paroxetine (33.5
+/- 13.3 mg/day) or citalopram (34.7 +/- 15.2 mg/day) and were followed at monthly
intervals for 1 year. Absence of full and limited-symptom attacks, anticipatory
anxiety, phobic avoidance and depression for 3 months was used to establish
remission. The effect of personality traits on each symptom domain was evaluated.
Results: Seventy-one patients completed the study. Remission rate was 76% for panic
attacks and 46% for complete remission. When the effects of age, gender, age of
onset and duration of PD, baseline SCL-90 phobic anxiety, Ham-A and Ham-D scores,
Axis I comorbidity and the SIDP traits on remission were analyzed in a logistic
regression, only borderline traits negatively influenced remission of panic attacks
(OR=0.69; 95% CI=0.49-0.96;p=0.03), where as the number of traits of each
personality Cluster and the total number of SIDP traits did not affect the outcome
of treatment. Conclusions: This study suggests that in PD patients, borderline
features may negatively influence the response to monotherapy with SSRI drugs;
therefore, other treatment strategies (i.e., combination of SSRI with
psychotherapy) are needed to obtain remission in these patients. (c) 2006 Elsevier
Inc. All rights reserved.
Perhaps the quintessential role of government is to protect its citizens from
threats of all types: war, global warming, terrorism, disease, toxic substances.
This essay provides a review and critique of Sunstein's innovative contribution to
the lively debate over how government should perform this role, a debate that often
pits cost-benefit analysis against the precautionary principle. The authors contend
that Sunstein's critique of the precautionary principle has merit, but that his
much-discussed Laws of Fear proposals are deficient in several significant
respects. Sunstein's proposals fail to solve problems related to cost-benefit
analysis, implementation of deliberative democracy, and incorporation of social
values into responses to threats. The essay concludes with a recommendation for
reconceptualizing the precautionary principle in a manner that saves it from
Sunstein's critiques.
Developmental plasticity of HPA and fear responses in rats has been proposed to be
mediated by environment-dependent variation in active maternal care. Here, we
review this maternal mediation hypothesis based on the postnatal manipulation
literature and on our own recent research in rats. We show that developmental
plasticity of HPA and fear responses in rats cannot be explained by a linear
single-factor model based on environment-dependent variation in active maternal
care. However, by adding environmental stress as a second factor to the model, we
were able to explain the variation in HPA and fear responses induced by postnatal
manipulations. In this two-factor model, active maternal care and environmental
stress (as induced, e.g., by long maternal separations or maternal food
restriction) exert independent, yet opposing, effects on HPA reactivity and
fearfulness in the offspring. This accounts well for the finding that completely
safe and stable, as well as, highly stressful maternal environments result in high
HPA reactivity and fearfulness compared to moderately challenging maternal
environments. Furthermore, it suggests that the downregulation of the HPA system in
response to stressful maternal environments could reflect adaptive developmental
plasticity based on the increasing costs of high stress reactivity with
increasingly stressful conditions. By contrast, high levels of environmental stress
induced by environmental adversity might constrain such adaptive plasticity,
resulting in non-adaptive or even pathological outcomes. Alternatively, however,
developmental plasticity of HPA and fear responses in rats might be a function of
maternal HPA activation (e.g., levels of circulating maternal glucocorticoid
hormones). Thus, implying a U-shaped relationship between maternal HPA activation
and HPA reactivity and fearfulness in the offspring, increasing maternal HPA
activation with increasing environmental adversity would explain the effects of
postnatal manipulations equally well. This raises the possibility that variation in
active maternal care is an epiphenomenon, rather than a causal factor in
developmental plasticity of HPA and fear responses in rats. Developmental
plasticity of HPA and fear responses in rats and other animals has important
implications for the design of animal experiments and for the well-being of
experimental animals, both of which depend on the exact underlying mechanism(s).
Importantly, however, more naturalistic approaches are needed to elucidate the
adaptive significance of environment-dependent variation of HPA reactivity and
fearfulness in view of discriminating between effects reflecting adaptive
plasticity, phenotypic mismatch and pathological outcomes, respectively. (c) 2006
Elsevier Inc. All rights reserved.
Context: Bipolar/panic comorbidity has been observed in clinical, community and
familial samples. As both are episodic disorders of affect regulation, the common
pathophysiological mechanism is likely to involve deficits in amygdala-mediated,
plasticity-dependent emotional conditioning. Evidence: Neuronal genesis and
synaptic remodeling occur in the amygdala; bipolar and panic disorders have both
been associated with abnormality in the amygdala and related structures, as well as
in molecules that modulate plasticity, such as serotonin, norepinephrine, brain-
derived neurotrophic factor ( BDNF) and corticotrophin releasing factor (CRF).
These biological elements are involved in behavioral conditioning to threat and
reward. Model: Panic attacks resemble the normal acute fear response, but are
abnormally dissociated from any relevant threat. Abnormal reward-seeking behavior
is central to both manic and depressive syndromes. Appetites can be elevated or
depressed; satisfaction of a drive may fail to condition future behavior. These
dissociations may be the result of deficits in plasticity-dependent processes of
conditioning within different amygdala subregions. Conclusions: This speculative
model may be a useful framework with which to connect molecular, cellular, anatomic
and behavioral processes in panic and bipolar disorders. The primary clinical
implication is that behavioral treatment may be critical to restore function in
some bipolar patients who respond only partially to medications.
The bulk of fear-of-crime research has concentrated on three basic models
explaining fear of crime among neighborhood residents: a victimization model, a
disorder model and a model pertaining to the social integration of residents.
Hierarchical linear models are tested with survey data (N = 3612) from 49 districts
of the city of Hamburg. Multilevel analyses indicate that indicators of fear of
crime vary significantly across neighborhoods. The results of two-level
hierarchical linear analyses show that micro-level variables (perceived physical
and social incivilities, personal and indirect victimization, trust to neighbors,
perceptions of police patrol, age, gender) and macro-level variables (concentrated
disadvantage, population density) are good predictors of different dimensions of
fear of crime (affective, cognitive, behavioral) among neighborhood residents.
Current formal psychiatric approaches to nosology are plagued by an unwieldy degree
of heterogeneity with insufficient appreciation of the commonalities of emotional,
personality, behavioral, and addictive disorders. We address this challenge by
building a spectrum model that integrates the advantages of Cloninger's and
Akiskatian approaches to personality and temperament while avoiding some of their
limitations. We specifically propose that "fear" and "anger" traits - used in a
broader connotation than in the conventional literature - provide an optimum basis
for understanding how the spectra of anxiety, depressive, bipolar, ADHD, alcohol,
substance use and other impulse-control, as well as cluster B and C personality
disorders arise and relate to one another. By erecting a bidimensional approach, we
attempt to resolve the paradox that apparently polar conditions (e.g. depression
and mania, compulsivity and impulsivity, internalizing and externalizing disorders)
can coexist without canceling one another. The combination of excessive or
deficient fear and anger traits produces 4 main quadrants corresponding to the main
temperament types of hyperthymic, depressive, cyclothymic and labile individuals,
which roughly correspond to bipolar 1, unipolar depression, bipolar 11 and ADHD,
respectively. Other affective temperaments resulting from excess or deficiency of
only fear or anger include irritable, anxious, apathetic and hyperactive. Our model
does not consider schizophrenia. We propose that "healthy" or euthymic individuals
would have average or moderate fear and anger traits. We further propose that
family history, course and comorbidity patterns can also be understood based on
fear and anger traits. We finally discuss the implications of the new derived model
for clinical diagnosis of the common psychiatric disorders, and for subtyping
depression and anxiety as well as cognitive and behavioral styles. We submit this
proposed schema represented herein as a heuristic attempt to build bridges between
basic and clinical science. (c) 2006 Elsevier B.V. All rights reserved.
Current psychiatry relies on a purely categorical paradigm for diagnosis of mental
disorders that profoundly impacts research and clinical practice. However, high
comorbidity rates and relative non-specificity of family history for psychiatric
disorders suggests that this categorical approach fails to identify the underlying
diathesis. As an attempt to overcome such limitations, we developed a bidimensional
model based on fear and anger traits or temperaments which does not preclude the
use of a categorical approach. As a result, it is hypothesized that mood,
behavioral and personality disorders share a neurobiological substrate according to
combinations of fear and anger traits. Both fear and anger, when excessive or
deficient, lead to increased risk for mental disorders and should be considered in
genetic, neurobiological and neuroimaging studies. Fear traits are much influenced
by the amygdala and the serotonergic, noradrenergic and GABAergic systems, whereas
anger seems to be mostly regulated by the nucleus accumbens and the dopaminergic
and glutamatergic systems. Pharmacological treatments with antidepressants and
anxiolytics can be considered as essentially restraint on fear, whereas lithium and
alpha 2 noradrenergic agonists would attenuate fear deficiency. Dopaminergic
antidepressants and psychostimulants are anger enhancers and antipsychotics and
mood stabilizers, such as divalproate and carbamazepine, may share antianger
effects. Drugs effective for manic and depressive phases probably have both
antianger and antifear effects. This framework may lead to a better understanding
of the neurobiological basis of mental health and disease, providing an integrative
approach for future research. (c) 2006 Elsevier B.V. All rights reserved.
Panic disorder may be associated with defective scrotonin (5-HT) neurotransmission.
This study was to investigate the association between the tryptophan hydroxylase
(TPH) gene and a serotonin transporter gene promoter polymorphism (5-HTTLPR), with
panic disorder in a Korean population. 244 Korean patients with panic disorder and
the 227 controls were genotyped by a polymerase chain reaction-based method. The
severity of panic disorders was assessed by number of panic attacks during the
previous. I month, as well as scores for anticipatory anxiety, panic distress, and
agoraphobic distress, as determined by a visual analogue scale (VAS). All the
subjects completed the assessment measures including Spielberger State-Trait
Anxiety Inventory-State (STAI-S), Spielberger State-Trait Anxiety Inventory-Trait
(STAI-T), Beck Depression Inventory (BDI), Symptom Checklist-90-Revised (SCL-90-R),
Revised Anxiety Sensitivity Index (ASI-R), Clinical Global Impression Scale -
Severity of Illness (CGI-S), Panic Disorder Severity Scale (PDSS), and the Hamilton
Depression Rating Scale (HAMD). Responder analyses were conducted based on changes
in CGI-I scores after 10 weeks of treatment. We found no significant differences in
the genotype and allele frequencies in TPH A218C and 5-HTTLPR polymorphisms between
the panic patients and the control group. Subgroup analyses in terms of
comorbidities, response, and other primary clinical variables, indicated no
differences in these polymorphisms. Our findings suggest that the TPH A218C
polymorphism and 5-HTTLPR play no significant roles in the pathogenesis and
clinical symptomatologies, at least in a Korean population. (c) 2006 Elsevier Inc.
All rights reserved.
Pavlovian or classical fear conditioning is recognized as a model system to
investigate the neurobiological mechanisms of learning and memory in the mammalian
brain and to understand the root of fear-related disorders in humans. In recent
decades, important progress has been made in delineating the essential neural
circuitry and cellular-molecular mechanisms of fear conditioning. Converging lines
of evidence indicate that the amygdala is necessarily involved in the acquisition,
storage and expression of conditioned fear memory, and long-term potentiation (LTP)
in the lateral nucleus of the amygdala is often proposed as the underlying synaptic
mechanism of associative fear memory. Recent studies further implicate the
prefrontal cortex-amygdala interaction in the extinction (or inhibition) of
conditioned fear. Despite these advances, there are unresolved issues and findings
that challenge the validity and sufficiency of the Current amygdalar LTP hypothesis
of fear conditioning. The purpose of this review is to critically evaluate the
strengths and weaknesses of evidence indicating that fear conditioning depend
crucially upon the amygdalar circuit and plasticity. (c) 2005 Elsevier Ltd. All
rights reserved.
This article examines the claim by Natan Sharansky that the establishment of
democracy in countries that are currently under an autocratic or tyrannical regime
will result in an end terror. Sharansky sees a direct link between the promotion of
human rights and democracy on the one hand and peace and security on the other. The
review article argues that the establishment of democracy alone will not be
sufficient to end terror. The pursuit of justice, including tackling poverty and
solving the Israel-Palestine problem, and the promotion of religious tolerance are
necessary additional components.
Against the background of the broad intellectual response to the events of 9/11,
the paper examines the complicity of the media in the West's so-called War on
Terror. Rejecting erroneous conceptions of a conspiratorial state control of the
media (and consequent distortion of the picture of a given reality), the paper
focuses primarily on the form of the media: its role in distorting the nature of
reality itself. By elucidating problems with the kind of media analysis that
portrays the media as a propaganda machine, the significance of the mediasphere
itself is highlighted. The paper considers the media's role in promulgating the
myth of antagonistic collective identities ('Us' vs. 'Them'); in promoting a desire
that subjugates the individual to the social formations that feed off it; in
sustaining a range of fundamentalisms; and in characterizing terrorism as Evil
incarnate. The paper thus offers a sympathetic reassessment of Baudrillard's
consistent attempt to engage with the geopolitics of the real, measured against a
contrasting range of responses from Badiou, Latour, Zizek, and others. (c) 2006
Elsevier Ltd. All rights reserved.
Terror management theory suggests that people cope with awareness of death by
investing in some kind of literal or symbolic immortality. Given the centrality of
death transcendence beliefs in most religions, the authors hypothesized that
religious beliefs play a protective role in managing terror of death. The authors
report three studies suggesting that affirming intrinsic religiousness reduces both
death-thought accessibility following mortality salience and the use of terror
management defenses with regard to a secular belief system. Study 1 showed that
after a naturally occurring reminder of mortality, people who scored high on
intrinsic religiousness did not react with worldview defense, whereas people low on
intrinsic religiousness did. Study 2 specified that intrinsic religious belief
mitigated worldview defense only if participants had the opportunity to affirm
their religious beliefs. Study 3 illustrated that affirmation of religious belief
decreased death-thought accessibility following mortality salience only for those
participants who scored high on the intrinsic religiousness scale. Taken as a
whole, these results suggest that only those people who are intrinsically vested in
their religion derive terror management benefits from religious beliefs.
We address the question why fear dominates hope in the life of individuals and
collectives on the basis of the accumulated knowledge in the psychology, neurology
and sociology of emotions. This knowledge suggests that fear, as primary emotion,
is grounded in the experienced present and based on the memorized past, processed
both consciously and unconsciously, causes freezing and conservatism, and sometimes
leads to pre-emptive aggression. Hope, in contrast, as a secondary emotion,
involves cognitive activity, which requires anticipation and the search for new
ideas and thus is based on complex processes of creativity and flexibility.
Therefore, hope is often preceded and inhibited by spontaneous, automatically
activated and faster fear Fear and hope can each become a collective emotional
orientation, and as such organize society's views and direct its actions. Societies
involved in intractable conflict are dominated by a collective fear orientation.
This orientation is functional for society's coping with the stressful and
demanding situation-but it may serve as a psychological obstacle to any peace
process, once it starts. The case of the collective fear orientation in the Jewish
Israeli society is presented as an example. The article ends with a presentation of
a particular approach, suggesting that individuals and collectives can overcome
their fear with much determination, and establish an orientation of hope which
allows change in situations dominated by fear Copyright (c) 2006 John Wiley & Sons,
Ltd.
Conditioned fear (CF) is one of the most frequently used behavioral paradigms;
however, little work has mapped changes in cerebral perfusion during CF in the rat-
the species which has dominated CF research. Adult rats carrying an implanted
minipump were exposed to a tone (controls, n = 8) or a tone conditioned in
association with footshocks (CS group, n = 9). During reexposure to the tone 24 h
later, animals were injected intravenously by remote activation with [C-14]-
iodoantipyrine using the pump. Significant group differences in regional CBF-
related tissue radioactivity (CBF-TR) were determined by region-of-interest
analysis of brain autoradiographs, as well as in the reconstructed, three-
dimensional brain by statistical parametric mapping (SPM). CS animals demonstrated
significantly greater, fear-enhanced increases in CBF-TR in auditory cortex than
controls. The lateral amygdala was activated, whereas the basolateral/basomedial
and central amygdala were deactivated. In the hippocampus and medial prefrontal
cortex, CBF-TR increased significantly ventrally but not dorsally. Significant
activations were noted in medial striatum and the thalamic midline and intralaminar
nuclei. However, the ventrolateral/dorsolateral striatum and its afferents from
motor and somatosensory cortex were deactivated, consistent with the behavioral
immobility seen during CF. Significant activations were also noted in the lateral
septum, periaqueductal gray, and deep mesencephalic nucleus/tegmental tract. Our
results show that auditory stimuli endowed with aversive properties through
conditioning result in significant redistribution of cerebral perfusion. SPM is a
useful tool in the brain mapping of complex rodent behaviors, in particular the
changes in activation patterns in limbic, thalamic, motor, and cortical circuits
during CF. (c) 2005 Elsevier Inc. All rights reserved.
Objective: To determine which factors impact on the efficacy of cognitive
behavioural therapy (CBT) for depression and anxiety. Factors considered include
those related to clinical practice: disorder, treatment type, duration and
intensity of treatment, mode of therapy, type and training of therapist and
severity of patients. Factors related to the conduct of the trial were also
considered, including: year of study, country of study, type of control group,
language, number of patients and percentage of dropouts from the trial. Method: We
used the technique of meta-analysis to determine an overall effect size
(standardized mean difference calculated using Hedges' g) and meta-regression to
determine the factors that impact on this effect size. We included randomized
controlled trials with a wait list, pill placebo or attention/psychological placebo
control group. Study participants had to be 18 years or older and all have
diagnosed depression, panic disorder ( with or without agoraphobia) or generalized
anxiety disorder ( GAD). Outcomes of interest included symptom, functioning and
health-related quality of life measures, reported as continuous variables at post-
treatment. Results: Cognitive behavioural therapy for depression, panic disorder
and GAD had an effect size of 0.68 (95% CI= 0.51 - 0.84, n= 33 studies, 52
comparisons). The heterogeneity in the effect sizes was fully explained by
treatment, duration of therapy, inclusion of severe patients in the trial, year of
study, country of study, control group, language and number of dropouts from the
control group. Disorder was not a significant predictor of the effect size.
Conclusions: Cognitive behavioural therapy is significantly less effective for
severe patients and trials that compared CBT to a wait-list control group found
significantly larger effect sizes than those comparing CBT to an attention placebo,
but not to a pill placebo. Further research is needed to determine whether CBT is
effective when provided by others than psychologists and whether it is effective
for non-English-speaking patient groups.
Background: Panic disorder (PD) is a common illness with a definite but "complex"
genetic contribution and estimated heritability of 30-46%. Methods: We report a
genome scan in 120 multiplex PD pedigrees consisting of 1591 individuals of whom
992 were genotyped with 371 markers at an average spacing of 9cM. Parametric two-
point, multipoint, and nouparametric analyses were performed using three PD models
(Broad, Intermediate, Narrow) and allowing for homogeneity or heterogeneity, The
two-point analyses were also performed allowing for independent male and female
recombination fractions (theta). Genome-wide significance was empirically evaluated
using simulations of this dataset. Results: Evidence for linkage reached genome-
wide significance in one region on chromosome 15q (near GABA-A receptor subunit
genes) and was suggestive at loci on 2p, 2q and 9p using an averaged theta.
Analyses allowing for sex-specific theta's were consistent except that support at
one locus on 2q increased to genome-wide significance and an additional region of
suggestive linkage on 12q was identified. However, differences in male and female
recombination fractions predicted by the sex-specific approach were not consistent
with current physical maps. Conclusions: These data provide evidence for
chromosomal regions on 15q and 2q that may be important in genetic susceptibility
to panic disorder. Although we are encouraged by the findings of analyses using
sex-specific recombination fractions, we also note that further understanding of
this analytic strategy will be important.
Background Panic disorder can be treated with psychotherapy, pharmacotherapy or a
combination of both. Aims To summarise the evidence concerning the short- and long-
term benefits and adverse effects of a combination of psychotherapy and
antidepressant treatment. Method Meta-analyses and meta-regressions were undertaken
using data from all relevant randomised controlled trials identified by a
comprehensive literature search. The primary outcome was relative risk (RR) of
response. Results We identified 23 randomised comparisons (21 trials involving a
total of 1709 patients). In the acute-phase treatment, the combined therapy was
superior to antidepressant pharmacotherapy (RR=1.24,95% Cl 1.02-1.52) or
psychotherapy (RR=1.16,95% Cl 1.03-1.30). After termination of the acute-phase
treatment, the combined therapy was more effective than pharmacotherapy alone
(RR=1.61,95% Cl 1.23-2.11) and was as effective as psychotherapy (RR=0.96, 95% Cl
0.79-1.16). Conclusions Either combined therapy or psychotherapy alone may be
chosen as first-line treatment for panic disorder with or without agoraphobia,
depending on the patient's preferences. Declaration of interest T.A.F. has received
research grants and fees for speaking from several pharmaceutical companies. These
companies did not provide funding for the current study (see Acknowledgements).
A goal of fear and anxiety research is to understand how to treat the potentially
devastating effects of anxiety disorders in humans. Much of this research utilizes
classical fear conditioning, a simple paradigm that has been extensively
investigated in animals, helping outline a brain circuitry thought to be
responsible for the acquisition, expression and extinction of fear. The findings
from non-human animal research have more recently been substantiated and extended
in humans, using neuropsychological and neuroimaging methodologies. Research across
species concur that the neural correlates of fear conditioning include involvement
of the amygdala during all stages of fear learning, and prefrontal areas during the
extinction phase. This manuscript reviews how animal models of fear are translated
to human behavior, and how some fears are more easily acquired in humans (i.e.,
social-cultural). Finally, using the knowledge provided by a rich animal
literature, we attempt to extend these findings to human models targeted to helping
facilitate extinction or abolishment of fears, a trademark of anxiety disorders, by
discussing efficacy in modulating the brain circuitry involved in fear conditioning
via pharmacological treatments or emotion regulation cognitive strategies. (c) 2006
Elsevier B.V. All rights reserved.
Objectives: The aim of this naturalistic follow-up study was to examine the effect
of pregnancy as a predicting factor of relapse in patients with panic disorder
(PD). Methods: Eighty-five female patients with PD (between the ages of 20 and 35
years) were included in this study. They were divided into 2 groups based on
whether the onset of PD had been during pregnancy (PD-pregnancy [PD-P]) or whether
the onset of PD had been while not pregnant (PD-nonpregnant [PD-NP]). Patients were
treated with paroxetine up to 40 mg/day for 12 months, and the full responders were
tapered off their medication and were monitored for an additional 6 years.
Treatment response was assessed using the Panic Self-Questionnaire (PSQ) with full
response being defined as '' 0 '' panic attacks. Assessments using the PSQ were
made at baseline and every 4 weeks for the first twelve months. During the 6-year
drug-free follow-up period, patients were assessed using the PSQ every 3 months.
Relapse was defined as the occurrence of a panic attack in any phase of the study.
The effect of group membership (PD-P vs. PD-NP) and new pregnancies as risk factors
for relapse were explored. Results: Sixty-eight patients completed the 6-year
follow-up, and each of the study groups (PD-P and PD-NP) was composed of 34
patients. Twenty-six of 34 (76.6%) patients in the PD-P group had another
pregnancy, and 15/26 (57%) in this group experienced a relapse during the
subsequent pregnancy. Three of 8 (37%) PD-P patients experienced a relapse without
pregnancy. Among the second group (PD-NP), 18/34 (52.9%) became pregnant and 8/18
(44.4%) experienced a relapse at the time of pregnancy, whereas 4/16 (25%)
experienced a relapse while not pregnant. Patients who relapsed during pregnancy
had a more severe relapse (as defined by the severity of the PSQ score) compared
with nonpregnant relapsers. Conclusions: Our naturalistic follow-up study
demonstrated that pregnancy might confer an increased risk of relapse in PD.
Moreover, when compared with patients who develop PD while not pregnant (PD-NP),
patients who develop PD during pregnancy (PD-P) appear to have a higher risk of
relapse at the time of a subsequent pregnancy (P < 0.001).
Cancer is increasing, in incidence and prevalence in North America and around the
world. The mass print media play an important role in information provision about
prevention, diagnosis and treatment of this disease, as well as informing health
policy and personal experience. This paper reports on a content analysis of the
portrayal of cancer in the highest circulating magazines available in Canada and
published in Canada or the USA in 1991, 1996, 2001. It includes both manifest and
latent analysis of the framing and content of cancer stories. Manifest analysis
documented the dominance of the medical as compared to the lifestyle and political
economy frames and the predominance of articles on breast as compared to other
cancers. Latent themes included: an emphasis on fear of cancer in that: (1) cancer
and fear are frequently conflated; cancer is said to grow outside of awareness
cancer is portrayed as (almost) inevitable; cancer is associated with normal
experiences; early detection is associated with diagnosis; and scary statistics are
emphasized; (2) contradictions and confusion exist within and between articles; and
(3) metaphors of war and battle are used frequently. The paper concludes with a
discussion of the implications of the linking of fear with cancer in the context of
medicine as the solution. (c) 2005 Elsevier Ltd. All rights reserved.
Considering the influence of the substantia nigra on mesencephalic neurons involved
with fear-induced reactions organized in rostral aspects of the dorsal midbrain,
the present work investigated the topographical and functional neuroanatomy of
similar influence on caudal division of the corpora quadrigemina, addressing: (a)
the neural hodology connecting the neostriamm, the substantia nigra, periaqueductal
gray matter and inferior colliculus (IC) neural networks; (b) the influence of the
inhibitory neostriatonigral-nigrocollicular GABAergic links on the control ofthe
defensive behavior organized in the IC. The effects of the increase or decrease of
activity of nigrocollicular inputs on defensive responses elicited by either
electrical or chemical stimulation of the IC were also determined. Electrolytic or
chemical lesions of the substantia nigra, pars reticulata (SNpr), decreased the
freezing and escape behaviors thresholds elicited by electrical stimulation of the
IC, and increased the behavioral responses evoked by the GABA(A) blockade in the
same sites of the mesencephalic tectum (MT) electrically stimulated. These findings
were corroborated by similar effects caused by microinjections of the GABA(A)-
receptor agonist muscimol in the SNpr, followed by electrical and chemical
stimulations of the IC. The GABA(A) blockade in the SNpr caused a significant
increase in the defensive behavior thresholds elicited by electrical stimulation of
the IC and a decrease in the mean incidence of panic-like responses induced by
microinjections of bicuculline in the mesencephalic tectum (inferior colliculus).
These findings suggest that the substantia nigra receives GABAergic inputs that
modulate local and also inhibitory GABAergic outputs toward the IC. In fact,
neurotracing experiments with fast blue and iontophoretic microinjections of
biotinylated dextran amine either into the inferior colliculus or in the reticular
division of the substantia nigra demonstrated a neural link between these
structures, as well as between the neostriatum and SNpr. (c) 2006 Elsevier B.V. All
rights reserved.
Unlike past American wars, the current war on terror has not been associated with a
centrally proffered narrative providing some guidance and orientation for those
administering government services under state-of-war conditions. War is as much a
cultural endeavor as it is a military undertaking, and the absence of a clear
sensemaking narrative was detected in this study of public administrators from
three agencies with varying proximity to the conflict. Q-methodology was used to
explore the way individuals processed the war narratives put forth by the Bush
administration and reported in the media immediately following the September 11
attacks. Though no distinct state-of-war narratives were found among the public
administrators in this study, there are clear indications that latent narratives
reflecting local political and organizational task environments have emerged.
The DSM-III, DSM-IV, DSM-IV-TR and ICD-10 have judiciously minimized discussion of
etiologies to distance clinical psychiatry from Freudian psychoanalysis. With this
goal mostly achieved, discussion of etiological factors should be reintroduced into
the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). A
research agenda for the DSM-V advocated the "development of a pathophysiologically
based classification system". The author critically reviews the neuroevolutionary
literature on stress-induced and fear circuitry disorders and related amygdala-
driven, species-atypical fear behaviors of clinical severity in adult humans. Over
30 empirically testable/falsifiable predictions are presented. It is noted that in
DSM-IV-TR and ICD-10, the classification of stress and fear circuitry disorders is
neither mode-of-acquisition-based nor brain-evolution-based. For example, snake
phobia (innate) and dog phobia (overconsolidational) are clustered together.
Similarly, research on blood-injection-injury-type-specific phobia clusters two
fears different in their innateness: 1) an arguably ontogenetic memory-trace-
overconsolidation-based fear (hospital phobia) and 2) a hardwired (innate) fear of
the sight of one's blood or a sharp object penetrating one's skin. Genetic
architecture-charting of fear-circuitry-related traits has been challenging.
Various, non-phenotype-based architectures can serve as targets for research. In
this article, the author will propose one such alternative genetic architecture.
This article was inspired by the following: A) Nesse's "Smoke-Detector Principle",
B) the increasing suspicion that the "smooth" rather than "lumpy" distribution of
complex psychiatric phenotypes (including fear-circuitry disorders) may in some
cases be accounted for by oligogenic (and not necessarily polygenic) transmission,
and Q insights from the initial sequence of the chimpanzee genome and comparison
with the human genome by the Chimpanzee Sequencing and Analysis Consortium
published in late 2005. Neuroevolutionary insights relevant to fear circuitry
symptoms that primarily emerge overconsolidationally (especially Combat related
Posttraumatic Stress Disorder) are presented. Also introduced is a human-evolution-
based principle for clustering innate fear traits. The "Neuroevolutionary Time-
depth Principle" of innate fears proposed in this article may be useful in the
development of a neuroevolution-based taxonomic re-clustering of stress-triggered
and fear-circuitry disorders in DSM-V. Four broad clusters of evolved fear circuits
are proposed based on their time-depths: 1) Mesozoic (mammalian-wide) circuits
hardwired by wildtype alleles driven to fixation by Mesozoic selective sweeps; 2)
Cenozoic (simian-wide) circuits relevant to many specific phobias; 3) mid
Paleolithic and upper Paleolithic (Homo sapiens-specific) circuits (arguably
resulting mostly from mate-choice-driven stabilizing selection); 4) Neolithic
circuits (arguably mostly related to stabilizing selection driven by gene-culture
co-evolution). More importantly, the author presents evolutionary perspectives on
warzone-related PTSD, Combat-Stress Reaction, Combat-related Stress, Operational-
Stress, and other deployment-stress-induced symptoms. The Neuroevolutionary Time-
depth Principle presented in this article may help explain the dissimilar stress-
resilience levels following different types of acute threat to survival of oneself
or one's progency (aka DSM-III and DSM-V PTSD Criterion-A events). PTSD rates
following exposure to lethal inter-group violence (combt, warzone exposure or
intentionally caused disasters such as terrorism) are usually 5-10times higher than
rates following large-scale natural disasters such as forest fires, floods,
hurricanes, volcanic eruptions, and earthquakes. The author predicts that both
intentionally-caused large-scale bioevent-disasters, as well as natural bioevents
such as SARS and avian flu pandemics will be an exception and are likely to be
followed by PTSD rates approaching those that follow warzone exposure. During
bioevents, Amygdala-driven and locus-coeruleus-driven epidemic pseudosomatic
symptoms may be an order of magnitude more common than infection-caused cytokine-
driven symptoms. Implications for the red cross and FEMA are discussed. It is also
argued that hospital phobia as well as dog phobia, bird phobia and bat phobia
require re-taxonomization in DSM-V in a new "overconsolidational disorders"
category anchored around PTSD. The overconsolidational spectrum category may be
conceptualized as straddling the fear circuitry spectrum disorders and the
affective spectrum disorders categories, and may be a category for which Pitman's
secondary prevention propranolol regimen may be specifically indicated as a
"morning after pill" intervention. Predictions are presented regarding obsessive-
compulsive disorder (OCD) (e.g., female-pattem hoarding vs. male-pattern hoarding)
and "culture-bound" acute anxiety symptoms (taijin-kyofusho, koro, shuk yang, shook
yong, suo yang, rokjoo, jinjinia-bernar, karoshi, gwarosa, Voodoo death). Also
discussed are insights relevant to pseudoneurological. symptoms and to the
forthcoming Dissociative-Conversive disorders category in DSM-V, including what the
author terms fright-triggered acute pseudo-localized symptoms (i.e.,
pseudoparalysis, pseudocerebellar imbalance, psychogenic blindness, pseudoseizures,
and epidemic sociogenic illness). Speculations based on studies of the human
abnormal-spindle-like, microcephaly-associated (ASPM gene, the microcephaly primary
autosomal recessive (MCPR) gene, and the forkhead box p2 (FOXP2) gene are made and
incorporated into what is termed "The pre-FOXP2 Hypothesis of Blood-Injection-
Injury Phobia." Finally, the author argues for a non-reductionistic fusion of
"distal (evolutionary) neurobiology" with clinical "proximal neurobiology,"
utilizing neurological heuristics. It is noted that the value of re-clustering fear
traits based on behavioral ethology, human-phylogenomics-derived endophenotypes and
on ontogenomics (gene-enviromnent interactions) can be confirmed or disconfirmed
using epidemiological or twin studies and psychiatric genomics. Published by
Elsevier Inc.
The legal commentary surrounding terrorism, concerned with pressing constitutional
questions, has to date largely ignored the role that regulatory agencies can play
in reducing terrorism risks. This gap in the literature is peculiar because
regulatory agencies have long assumed primary responsibility within the government
for assessing and managing abstract risks and are therefore remarkably well-
positioned to shore up our vulnerabilities against terrorist strikes. In an effort
to turn the academic discussion to the regulatory aspects of the war on terror this
Article assesses the federal government's incipient regulatory effort to reduce
terrorism risks to the nation's critical infrastructure. After concluding that the
cornerstone of this administration's risk-reduction approach, the Critical
Infrastructure Information Act of 2002, will fail to ensure that the government has
adequate information to serve as a foundation for a coherent regulatory response,
the Article proposes an alternative strategy based on a practice known as
benchmarking. Under this approach, independent auditors would inspect high-risk
firms within an industry and publicly rank those firms against each other according
to their relative security vulnerabilities. Armed with this information, both the
public and government regulators could bring continuous pressure to bear on private
firms to reduce their vulnerabilities where most appropriate. Although a
benchmarking approach would be plagued with some predictable weaknesses, the
Article concludes that it nevertheless could prove to be an important feature of a
comprehensive regulatory strategy to secure our critical infrastructure.
This paper attempts to fill the partial theoretical vacuum surrounding the
understanding of fear acquisition. A review of recent and contemporary theories of
the etiology of fear is presented, serving as a justification for further
theorizing and allowing for greater understanding of those aspects of fear that
remain to be adequately explained. A new model of the etiology of specific fears is
subsequently put forward and the various aspects and implications of this model are
discussed. How an individual perceives a stimulus is proposed as being critical in
determining fear in relation to the stimulus. In particular, perceptions of the
stimulus as uncontrollable, unpredictable, dangerous and disgusting create a schema
of vulnerability. The Cognitive Vulnerability Model integrates much of the
extensive body of research on fears and specific phobias into a unifying theory of
the etiology of fear. The model offers parsimonious explanations for the various
characteristics of specific fears and phobias. (c) 2006 Elsevier Ltd. All rights
reserved.
This article seeks to explain the basic impulses behind coloured exclusivity in
white supremacist South Africa and to elaborate on continuity and change in the
processes of coloured self-definition by identifying the core attributes of
coloured identity and outlining the ways in which they operated to reinforce and
reproduce that identity. The central argument is that coloured identity is better
understood not as having evolved through a series of transformations, as
conventional historical thinking would have it and as the existing literature
assumes, but as having remained remarkably stable throughout the era of white rule.
It is argued that this stability derived from a core of enduring characteristics
that informed the manner in which colouredness functioned as an identity during
this period. This is not to contend that coloured identity was static or that it
lacked fluidity, but that there were both important constraints on the ways in
which it was able to find expression and sufficiently strong continuities in its
day-to-day functioning for coloured identity to have remained recognisably uniform
despite radical changes in the social and political landscape during this time. The
principal constituents of this stable core are the assimilationism of the coloured
people, which spurred hopes of future acceptance into the dominant society; their
intermediate status in the racial hierarchy, which generated fears that they might
lose their position of relative privilege and be relegated to the status of
Africans; the negative connotations, especially the shame attached to racial
hybridity, with which colouredness was imbued; and finally, the marginality of the
coloured community, which severely limited their options for social and political
action, giving rise to a great deal of frustration.
gamma-Aminobutyric acid (GABA) is the most important inhibitory neurotransmitter in
the central nervous system (CNS). It exerts its rapid inhibitory action mostly
through GABA(A) receptors, which are targets for benzodiazepines, barbiturates,
neuroactive steroids and distinct anticonvulsive agents. There is considerable
evidence that dysfunction of GABA, receptors or dysregulation of GABA
concentrations in the CNS (or both) plays an important role in the pathophysiology
of panic disorder. Currently, benzodiazepines are the only drugs directly targeting
the GABA, receptors that are approved for the treatment of anxiety disorders.
Because of their well-known anxiolytic effects, they are widely used in this
setting, but side effects limit their use in long-term treatment. The question of
whether drugs that selectively increase GABA concentrations in the CNS could
improve symptoms of anxiety has been discussed. Recent investigations by our group
have demonstrated that enhancement of endogenous GABA (through blockade of GABA
transaminase by vigabatrin or through inhibition of GABA transporters by tiagabine)
exerts anxiolytic effects on experimentally induced panic. Our studies in healthy
volunteers have shown that both compounds lead to a significant reduction in panic
symptoms elicited by cholecystokinin-tetrapeptide. Moreover, benzodiazepine-like
effects on the activity of the hypothalamic-pituitary-adrenal axis have been
observed in association with vigabatrin treatment. Small open studies in patients
with panic disorder also showed an improvement in panic and anxiety with both
compounds. This review summarizes our recent research on the effects of selective
GABAergic treatment in experimentally induced panic and outlines the possible role
of compounds targeting the GABA binding site of the GABA(A)-benzodiazepine receptor
for the treatment of panic and anxiety.
The empirical literature regarding panic-spectrum problems (i.e., panic attacks,
panic disorder, and agoraphobia) and cigarette smoking is reviewed. In the first
section of the paper, empirical studies that document the prevalence of smoking and
panic-related problems are presented and discussed. In the second section of the
paper, studies pertaining to the role cigarette smoking may play in the onset and
maintenance of panic-related problems are critically reviewed. In the third section
of the paper, studies related to the association between panic vulnerability
factors and the nature of smoking behavior are presented. In the fourth section of
the paper, specific areas not otherwise covered in the review are presented to
stimulate further development in these areas (e.g., specialized treatment
development). (c) 2005 Elsevier Ltd. All rights reserved.
It has long been recognized that humans vary in their conditionability, yet the
factors that contribute to individual variation in emotional learning remain to be
delineated. The goal of the present study was to investigate the relationship among
sex, stress hormones, and fear conditioning in humans. Forty-five healthy adults
(22 females) underwent differential delay conditioning, using fear-relevant
conditioned stimuli and a shock unconditioned stimulus. Salivary cortisol samples
were taken at baseline and after acquisition training and a 24-h-delayed retention
test. The results showed that acquisition of conditioning significantly correlated
with postacquisition cortisol levels in males, but not in females. This sex-
specific relationship was found despite similar overall levels of conditioning,
unconditioned responding, and cortisol. There was no effect of postacquisition
cortisol on consolidation of fear learning in either sex. These findings have
implications for the understanding of individual differences in fear acquisition
and risk factors for the development of affective disorders.
Tetramethylenedisulfotetramine has accounted for numerous intentional an
unintentional posionings in China. In may 2002, thefirst known case of human
illness in the united states caused by tetramethylenedisulotetramine, a banned
neurotoxic rodenticide from China, occured in New York City. The clinical
presentation after tetramethylenedisulfotetramine exposure is dose dependent, and
the most recognized complication is status epilepticus. Posionings may be fatal
within hours. No known antidote exists, and treatment mainly is supportive.
Anecdotal reports, case reports, and 2 animal studies suggest possible success with
certain pharmacological interventions, including pyridoxine and chelation therapy.
Pesticide and rodenticide posonings, whether intentional or unintentional, pose a
serious threat to populations, and the availability of a banned rodenticide such as
tetramethylenedisulfotramine, with its associated morbidity and lethality, is a
serious public health concern. Given the recent case report that confirms the
presence of tetramethylenedisulfotramine in the United States, the toxicity of the
compound, its unique physical properties, the absence of an antidote, and the
history of its use as an agent of intentional mass poisoning, public health
entities have undertaken educational efforts to inform the public, health care
providers, and emergency personnel of this potentially lethal rodentricide.
Context: Attentional bias to disease-relevant emotional cues is considered to be
pathogenetically relevant in anxiety disorders. Objective: To investigate
functional neural correlates and disease specificity of attentional bias across
different anxiety disorders. Design: A cognitive and emotional Stroop task,
consisting of congruent and incongruent color words, obsessive-compulsive disorder
(OCD)-related and panic-related negative words, and neutral words, was used in 3
patient groups and a control group during functional magnetic resonance imaging.
Setting: Academic outpatient department for anxiety disorders. Patients and
Participants: Medication-free patients with OCD (n=16), panic disorder (PD) (n=15),
and hypochondriasis (n = 13) and 19 controls. Main Outcome Measure: Voxel-wise
analyses of cerebral blood flow changes for contrasts of interest (incongruent vs
congruent color words, OCD-related vs neutral words, and panic-related vs neutral
words) within and between groups. Results: During incongruent vs congruent color
naming, all patient groups recruited additional posterior brain regions relative to
controls, but performance was impaired only in OCD. In OCD, color naming OCD-
related, but not PD-related, words correlated with increased activation of frontal-
striatal and temporal regions, although performance was unimpaired. In contrast, in
PD, increased frontal-striatal involvement was found during color naming both OCD-
related and panic-related words. In PD, color naming panic-related words was slowed
and correlated with increased activation of the right amygdala and hippocampus.
Patients with hypochondriasis showed a similar activation pattern to patients with
PD. Conclusions: Our results support the hypothesis of increased distractibility
for irrelevant information in patients with OCD, PD, and hypochondriasis associated
with frontal-striatal and limbic involvement compared with controls. Although
patients with OCD did not display an attentional bias in behavior relative to
controls, there was a clear, specific neural response during color naming OCD-
related words, involving mainly ventral brain regions. In contrast, generalized
emotional interference effects were found in PD and hypochondriasis, involving
ventral and widespread dorsal brain regions, reflecting not only unconscious
emotional stimulus processing but also increased cognitive elaboration.
Studies attest to the chronic nature of anxiety in youth. Consequently, there is a
growing literature examining causative pathways to these disorders and efficacious
treatments for them. This review examines separation anxiety disorder, a commonly
occurring childhood anxiety disorder, and panic disorder, a more rare anxiety
disorder in youth. Finally, school refusal, which may be tied to an internalizing
or externalizing disorder or no disorder at all, is examined.
Cleavage of the ring-like cohesin complex by separase triggers segregation of
sister chromatids in anaphase. This simplistic model has recently been extended by
exciting discoveries on three levels: regulation of anaphase by posttranslational
modifications and the cohesin protector shugoshin; non-proteolytic roles of
separase; and cohesin-independent linkage of sister chromatids.
Panic disorder (PD) is a complex, multidimensional psychiatric disorder
characterized by the Presence of Panic attacks as well as anticipatory anxiety and
panic-related phobias (eg, agoraphobia). Although the etiology of this disabling
disorder remains unclear, advances in basic neuroscience and in imaging studies
have led to a greater understanding of the neurocircuitry and neurochemistry that
are involved in modulating fear and anxiety and that are relevant to understanding
PD. A preliminary integrated model can be outlined, but there is a need for
additional research that cuts across genetic investigation, provocation studies,
neuroimaging techniques, and treatment trials. As research continues and greater
insight into the mechanisms underlying PD is achieved, additional treatment
strategies may emerge. CNS Spectr. 2005.
Several lines of evidence suggest that genetic factors might contribute to
susceptibility to panic disorder. Our previous studies show that the brain-derived
neurotrophic factor (BDNF) may play a role in the pathophysiology of major
depressive disorders and eating disorders. Assuming that BDNF may be implicated in
the putative common pathophisiology of depression and anxiety, we analyzed the
association of two BDNF gene single nucleotide polymorphisms (SNPs), 132C>T
(formerly named C270T) in the noncoding region of exon V and 196G>A (va166met) in
the coding region of exon XIIIA, with panic disorder. In this study, 109 patients
with panic disorder diagnosed according to the DSM-IV criteria, and 178 control
subjects were recruited. There were no significant differences in the frequency of
the genotype or allele in these two SNPs between patients and controls [132C>T in
exon V: genotype, p=1.0, allele, p=0.59; 196G>A (val66met) in exon XIIIA: genotype,
p=0.77, allele,p=0.78]. Furthermore, no significant associations of agoraphobia
with the two SNPs were detected. This study suggests that the BDNF gene
polymorphisms are not associated with panic disorder in our Japanese population.
(C) 2005 Elsevier Inc. All rights reserved.
Inbred mouse strains have different genetic backgrounds that likely influence
memory and long-term potentiation (LTP). LTP, a form of synaptic plasticity, is a
candidate cellular mechanism for some forms of learning and memory. Strains with
impaired fear memory may have selective LTP deficits in different hippocampal
subregions or in the amygdala. The authors assessed fear memory in 4 inbred
strains: C57BL/6NCr1BR (136), 129S1/SvImJ (129), C3H/HeJ (C3H), and DBA/2J (D2).
The authors also measured LTP in the hippocampal Schaeffer collateral (SC) and
medial perforant pathways (MPP) and in the basolateral amygdala. Contextual and
cued fear memory, and SC and amygdalar LTP, were intact in B6 and 129, but all were
impaired in C3H and D2. MPP LTP was similar in all 4 strains. Thus, SC, but not
MPP, LTP correlates with hippocampus-dependent contextual memory expression, and
amygdalar LTP correlates with amygdala-dependent cued memory expression, in these
inbred strains.
Inbred mouse strains have different genetic backgrounds that can result in
impairments of synaptic plasticity and memory. They are valuable models for probing
the mechanisms of memory impairments. We examined fear memory in several inbred
strains, along with synaptic plasticity that may underlie fear memory. Long-term
potentiation (LTP) is a form of activity-dependent synaptic plasticity that is a
candidate cellular mechanism for some forms of learning and memory. Strains with
impaired contextual or cued fear memory may have selective LTP deficits in
different hippocampal subregions, or in the amygdala. We measured fear memory and
its extinction in five inbred strains: C57BL/6NCrlBR (B6), A/J, BALB/cByJ (BALB),
C57BL/10J (B10), and SM/J (SM). We also measured LTP in the basolateral amygdala
and in the hippocampal Schaeffer collateral-commissural (SC) and medial perforant
pathways (MPP). All strains exhibited intact contextual fear memory 24 h post-
training, but cued fear memory was impaired in strains A/J, BALB, and SM. At 1 h
post-training, both contextual and cued fear memory deficits were more widespread:
all strains except for B6 and B10 showed impairments of both types of memory.
Contextual fear extinction was impaired in BALB and SM. We found that amygdalar LTP
was reduced in strains A/J and BALB, but SC LTP was intact in all strains (except
for a selective multi-train LTP impairment in BALB). MPP LTP was similar in all
five strains. Thus, reduced amygdalar LTP is correlated with impaired cued fear
memory in strains A/J and BALB. Also, hippocampal SC LTP is more strongly
correlated with 24-h (long-term) than with 1-h (short-term) contextual fear memory.
in this first conjoint study of amygdala-dependent memory and amygdalar LTP in
inbred mice, we identified specific hippocampal and amygdalar LTP deficits that
correlate with fear memory impairments. These deficits should be considered when
selecting inbred strains for genetic modification. (c) 2005 Wiley-Liss, Inc.
In addition to coordinating movement, the cerebellum participates in motor
learning, emotional behavior, and fear memory. Fear learning is reflected in a
change of autonomic and somatic responses, such as heart rate and freezing,
elicited by a neutral stimulus that has been previously paired with a painful one.
Manipulation of the vermis affects these responses, and its reversible inactivation
during the consolidation period impairs fear memory. The neural correlate of
cerebellar involvement in fear consolidation is provided by a behaviorally induced
long-term increase of synaptic efficacy between parallel fibers and a Purkinje
cell. Similar synaptic changes after fear conditioning are well documented in the
amygdala and hippocampus, providing a link between emotional experiences and
changes in neural activity. In addition, in hotfoot mice, with a primary deficiency
of parallel fiber to Purkinje cell synapse, short- and long-term fear memories are
affected. All these data support the idea that the cerebellum participates in fear
learning. The functional interconnection of the vermis with hypothalamus, amygdala,
and hippocampus suggests a more complex role of the cerebellum as part of an
integrated network regulating emotional behavior.
The authors examine 6 theories of panic attacks as to whether empirical approaches
are capable of falsifying them and their heuristic value. The authors conclude that
the catastrophic cognitions theory is least falsifiable because of the elusive
nature of thoughts but that it has greatly stimulated research and therapy. The
vicious circle theory is falsifiable only if the frightening internal sensations
are specified. The 3-alarms theory postulates an indeterminate classification of
attacks. Hyperventilation theory has been falsified. The suffocation false alarm
theory lacks biological parameters that unambiguously index dyspnea or its
distinction between anticipatory and panic anxiety. Some correspondences postulated
between clinical phenomena and brain areas by the neuroanatomical hypothesis may be
falsifiable if panic does not depend on specific thoughts. All these theories have
heuristic value, and their unfalsifiable aspects are capable of modification.
During the 1650s and 1660s, the Dutch Republic witnessed a wave of moral panic
created by moralists. Every natural disaster economic setback, and war that the
Republic was involved in was considered to be a sign of God's wrath on Holland's
newly acquired freedom, wealth, and secular society. Much of the finger-pointing
was directed toward Holland's young people, who were accused of being vain, defying
the Sabbath, visiting the theater gambling, drinking, and fornicating. These
accusations were, however misplaced. This article examines the moral crusade of the
1650s and 1660s, and discovers that moralists were more upset that the Dutch
Republic became a secular society and did not evolve into a theocratic state or
"Dutch Israel," as they had hoped. Holland's youth were used as a scapegoat to
create moral panic among political leaders, so they would reform Holland's secular
society.
The efficacy of (cognitive) behavioural ((C)BT) and pharmacological therapy was
investigated using meta-analytic techniques. After a comprehensive review of the
literature, the results of 124 studies were included. (C)BT was more effective than
a no-treatment control and a placebo control. No difference of efficacy was found
when using cognitive elements compared to not using them for anxiety; for
associated depressive symptoms, additional cognitive elements seems superior.
Pharmacotherapy was more effective than a placebo control; there was no superiority
of any drug class. Sample size was related to effect size in pharmacotherapy and
publication bias was found. (C)BT was at least as effective as pharmacotherapy and
depending on type of analysis even significantly more effective. There were no
significant differences between (C)BT alone and a combination approach but
characteristics of studies have to be considered. (c) 2005 Elsevier B.V. All rights
reserved.
The terrorist attacks of September 11, 2001, had a profound effect on the Bush
administration's foreign policy. This review essay examines a set of books and
documents that illuminate the dominant U.S. threat perceptions in the post-
September 11 environment and analyze both the strategies and the new directions
that have emerged in U.S. policy in response to the new threat perceptions. Several
of the books under review explore the deep socioeconomic and ideological origins of
the wide support found in the U.S. public for the Bush administration's bold and
often controversial policy choices. Taken together, these works convey the
impression that Bush's strategic impulses will have considerable staying power in
the U.S. body politic.
Narratives of the Tibetan resistance army are not a part Of national history in the
Tibetan exile community. Drawing on stories by veterans of the resistance to the
Chinese invasion and the explanations they give of its absence in Tibetan national
history, I argue that this history has been "arrested" because of the challenges it
poses to normative versions of history and community and, in turn, to internal and
external representations of Tibet. This practice signifies the postponing of
narrating certain histories until a time in the future when the dangers they pose
to sustaining a unified Tibetan community in exile has receded. This Practice of
historical (un)production offers insight into temporality and subjectivity, plural
identities in the face of national hegemony, and why history might be considered a
combination of truth, fear, and lies.
While mass panic (and/or violence) and self-preservation are often assumed to be
the natural response to physical danger and perceived entrapment, the literature
indicates that expressions of mutual aid are common and often predominate, and
collective flight may be so delayed that survival is threatened. In fact, the
typical response to a variety of threats and disasters is not to flee but to seek
the proximity of familiar persons and places; moreover, separation from attachment
figures is a greater stressor than physical danger. Such observations can be
explained by an alternative "social attachment" model that recognizes the
fundamentally gregarious nature of human beings and the primacy of attachments. In
the relatively rare instances where flight occurs, the latter can be understood as
one aspect of a more general affiliative response that involves escaping from
certain situations and moving toward other situations that are perceived as
familiar but which may not necessarily be objectively safe. The occurrence of
flight-and-affiliation depends mainly on the social context and especially the
whereabouts of familiar persons (i.e., attachment figures); their physical presence
has a calming effect and reduces the probability of flight-and-affiliation, while
their absence has the opposite effect. Combining the factors of perceived physical
danger and the location of attachment figures results in a four-fold typology that
encompasses a wide spectrum of collective responses to threat and disaster.
Implications of the model for predicting community responses to terrorist attacks
and/or use of weapons of mass destruction are briefly discussed.
The world is a dangerous place. Whether this danger takes the form of an automobile
careening toward you or a verbal threat from a stranger, your brain is highly
adapted to perceive such threats. organize appropriate defensive behaviors, and
record the circumstances surrounding the experience. Indeed. memories of fearful
events serve a critical biological function by allowing humans and other animals to
anticipate future dangers. But these memories can also feed pathological fear,
yielding crippling clinical conditions such as panic disorder. In this review, the
author will examine how the brain builds fear memories and how these memories come
to be suppressed when they no longer predict danger. The review will focus on the
fundamental role for synapses in the amygdala in acquiring fear memories and the
function of neural circuits interconnecting the amygdala, hippocampus, and
prefrontal cortex in modulating the expression of such memories once learned. The
discovery of the neural architecture for fear memory highlights the powerful
interplay between animal and human research and the promise for understanding the
neurobiological mechanisms of other complex cognitive phenomena.
Fear conditioning represents the process by which a neutral stimulus comes to evoke
fear following its repeated pairing with an aversive stimulus. Although fear
conditioning has long been considered a central pathogenic mechanism in anxiety
disorders, studies employing lab-based conditioning paradigms provide inconsistent
support for this idea. A quantitative review of 20 such studies, representing fear-
learning scores for 453 anxiety patients and 455 healthy controls, was conducted to
verify the aggregated result of this literature and to assess the moderating
influences of study characteristics. Results point to modest increases in both
acquisition of fear learning and conditioned responding during extinction among
anxiety patients. Importantly, these patient-control differences are not apparent
when looking at discrimination studies alone and primarily emerge from studies
employing simple, single-cue paradigms where only danger cues are presented and no
inhibition of fear to safety cues is required. Published by Elsevier Ltd.
Little is known about biological predictors of treatment response in panic
disorder. Our previous studies show that the brain-derived neurotrophic factor
(BDNF) may play a role in the pathophysiology of major depressive disorders and
eating disorders. Assuming that BDNF may be implicated in the putative common
etiologies of depression and anxiety, the authors examined serum BDNF levels of the
patients with panic disorder, and its correlation with therapeutic response to
group cognitive behavioral therapy (CBT). Group CBT (10 consecutive 1 It weekly
sessions) was administered to the patients with panic disorder after consulting the
panic outpatient special service. Before treatment, serum concentrations of BDNF
and total cholesterol were measured. After treatment, we defined response to
therapy as a 40% reduction from baseline on Panic Disorder Severity Scale (PDSS)
score as described by Barlow et al. (2000) [Barlow, D.H., Gorman, J.M., Shear,
M.K., Woods, S.W., 2000. Cognitive-behavioral therapy, imipramine, or their
combination for panic disorder: A randomized controlled trial. JAMA. 283, 2529-
2536]. There were 26 good responders and 16 poor responders. 31 age- and sex-
matched healthy normal control subjects were also recruited in this study. The
serum BDNF levels of the patients with poor response (25.9 ng/ml [S.D. 8.7]) were
significantly lower than those of the patients with good response (33.7 ng/ml [S.D.
7.5]). However, there were no significant differences in both groups of the
patients, compared to the normal controls (29.1 ng/ml [S.D. 7.1]). No significant
differences of other variables including total cholesterol levels before treatment
were detected between good responders and poor responders. These results suggested
that BDNF might contribute to therapeutic response of panic disorder. A potential
link between an increased risk of secondary depression and BDNF remains to be
investigated in the future. (C) 2005 Elsevier Inc. All rights reserved.
The aim of this study was to investigate correlations between thyroid function and
severity of anxiety or panic attacks in patients with panic disorder. The authors
examined 66 out-patients with panic disorder (medicated, n=41; non-medicated,
n=25). and measured their free thriiodothyronine (T3), free thyroxine (T4) and
thyroid-stimulating hormone (TSH) levels. Significant correlations between the
thyroid hormone levels and clinical features were observed in the non-medicated
patients. The more severe current panic attacks were. the higher the TSH levels
were. In addition, severity of anxiety correlated negatively with free T4 levels.
In this study, we discuss relationship between thyroid function and the clinical
severity or features of panic disorder. (C) 2004 Elsevier Inc. All rights reserved.
Does the existential anxiety of man have a particular religious dimension, as a
famous tradition of philosophical criticism of religion asserts? Does it even have
a specific Christian quality? In trying to answer these questions, this essay
starts with a phenomenological reconstruction of Gen 3, the story of the Fall of
Man. In the ensuing sections, three existential phenomenologists are consulted:
Kierkegaard, Heidegger and Schleiermacher. Kierkegaard describes anxiety as a
fundamental phenomenon of human freedom. In this sense, anxiety is an indication of
man's alienation on the ethical level. Paradoxically, at the same time anxiety is
the crucial impetus for man's transition to the religious level. Anxiety also plays
a central role in Heidegger's existential analysis of being. It is the fundamental
mode which reveals the particular possibilities of existence: the possibility of
essentiality and, paradoxically, the possibility of non-essentiality. Applying
Schleiermacher's theory of Christian self-consciousness, a decidedly Christian
interpretation of the phenomenon of anxiety is undertaken. From this point of view
neither anxiety itself nor an act of freedom founded in anxiety proves to be
redeeming for human existence. Anxiety as such has neither a genuinely religious
dimension, nor indeed a decidedly Christian quality. Like Christ himself, the
faithful, too, remains vulnerable to anxiety all his life, but he is confident that
anxiety will finally be overcome.
The present Study investigated the hypothesis that both nicotinic acetylcholinergic
receptors (nAChRs) and glutamate receptors (alpha-amino-3-hydroxy-5-methyl-4-
isoxazole propionate receptors (AMPARs) and N-methyl-D-aspartate glutamate
receptors (NMDARs)) are involved in fear conditioning, and may modulate similar
processes. The effects of the nAChR antagonist mecamylamine administered alone, the
AMPAR antagonist NBQX administered alone, and the NMDAR antagonist MK-801
administered alone oil Cued fear conditioning, contextual fear conditioning, and
latent inhibition Of Cued fear conditioning were examined. In addition, the effects
of coadministration of either mecamylamine and NBQX or mecamylamine and MK-801 oil
these behaviors were examined. Consistent with previous Studies, neither
mecamylamine nor NBQX administered alone disrupted any of the tasks. However,
coadministration of mecamylamine and NBQX disrupted both contextual fear
conditioning and latent inhibition of cued fear conditioning. In addition,
coadministration of mecamylamine with a dose of MK-801 Subthreshold for disrupting
either task disrupted both contextual fear conditioning and latent inhibition of
cued fear conditioning. Coadministration of mecamylamine and NBQX, and
coadministration of mecamylamine with a dose of MK-801 Subthreshold for disrupting
fear conditioning had little effect oil Cued fear conditioning. These results
suggest that nAChRs and glutamate receptors may Support similar processes mediating
acquisition of contextual fear conditioning and latent inhibition of fear
conditioning.
Aging has diverse effects on different behaviors and underlying neural systems.
This study utilized fear conditioning to determine if aged mice have deficits in
the acquisition and/or retention of memories for contextual or cued fear
conditioning, and to determine if galantamine, an acetylcholinesterase (AChE)
inhibitor and allosteric modulator of nicotinic acetylcholinergic receptors, would
alter acquisition and/or retention of fear conditioning memories in young (2-3
months) and aged (19-20 months) C57BL/6 mice. Mice were trained with two white-
noise CS (85 dB, 30 s)-footshock US (0.57 mA, 2 s) presentations. In the initial
study, separate groups were tested 24,48, or 96 h post-training. All mice were
retested 1 week after the initial test. Aged mice were impaired in freezing to the
CS for the 48 and 96 h train-test intervals, but not the 24-h interval. When
retested 1 week after the initial test, freezing to the CS was significantly lower
for all train-test intervals. No age-related deficits were found in contextual fear
conditioning. In the second study, 2 mg/kg galantamine was administered to young
and aged mice before fear conditioning and conditioned fear was assessed 48 h
later. No age-related deficits in cued fear conditioning were seen in galantamine-
treated aged mice. Thus, aged C57BL/6 mice are impaired in the long-term retention
of auditory cued fear conditioning,. but not the acquisition of auditory cued or
contextual fear conditioning. This retention deficit for cued fear conditioning is
ameliorated by treatment with the AChE inhibitor galantamine. (c) 2005 Elsevier
B.V. All rights reserved.
Terrorist attacks and their aftermath have had a powerful impact on children and
their families. Media and television exposure of terrorist events throughout the
world has increased during the past few years. There is increasing concern about
the effects of this exposure on children who witness these violent images. To
develop a proactive and strategic response to reactions of fear, clinicians,
educators, and policy makers must understand the psychologic effects of media
coverage of terrorism on children. Previous research has focused on media coverage
of criminal violence and war. Recent studies have examined the effect of remote
exposure of terrorist attacks and have shown a significant clinical impact on
children and families.
This paper examines the use of the term 'territorial integrity', a term with two
interlinked and usually compatible meanings. The first is that states should not
seek to promote border changes or secessionist movements within other states, or
attempt to seize territory by force. The second meaning is the standard idea that
within its own borders, within its territory, a state is sovereign. The second of
these two meanings has come under increased pressure in recent years, in part in
relation to international intervention for 'humanitarian' reasons, and even more so
since September 11 2001. And yet the other meaning is being stressed even more
explicitly, often at the same time and in the same places that the second meaning
is being challenged. This paper considers various historical and contemporary
examples, and suggests that the two meanings of territorial integrity are
increasingly in tension.
Fear conditioning, during which emotional significance is attached to an initially
biologically insignificant conditioned stimulus, when such neutral stimulus is
paired with an aversive unconditioned stimulus. provides an experimental paradigm
that is most commonly used to study fear learning. The amygdala. a subcortical
nuclear group, is a brain structure critically important for fear conditioning.
Recent studies indicate that both fear conditioning-induced neuronal plasticity and
LTP at the amygdala synapses share common mechanisms of induction and expression.
These findings provide the most direct evidence yet available that the mechanisms
of LTP are recruited in the experimental animals during behavioral training and
that such mechanisms might be utilized for memory storage.
This chapter provides a review of recent empirical developments, current
controversies, and areas in need of further research in relation to factors that
are common as well as specific to the etiology and maintenance of panic disorder,
phobias, and generalized anxiety disorder. The relative contribution of broad risk
factors to these disorders is discussed, including temperament, genetics,
biological influences, cognition, and familial variables. In addition, the role
that specific learning experiences play in relation to each disorder is reviewed.
In an overarching hierarchical model, it is proposed that generalized anxiety
disorder, and to some extent panic disorder, loads most heavily on broad underlying
factors, whereas specific life history contributes most strongly to circumscribed
phobias.
Nocturnal panic (NP), waking from steep in a state of panic, is a common occurrence
among patients with panic disorder, with 44-71% reporting at least one such attack.
NP is a non-REM event that is distinct from steep terrors, steep apnea, nightmares
or dream-induced arousals. This review outlines recent advances in the
characterization of NP, as well as current approaches to the assessment and
treatment of NP. In contrast to earlier work, more recent studies suggest that
patients with NP do not differ from patients without NP on steep architecture,
steep physiology, self-reported steep quality and severity of panic disorder.
However, more precise measurement of physiological precipitants and features is
warranted. Assessment of NP focuses on ruling out other explanations for NP, with
differential diagnosis based on interviews, steep polysomnography and ambulatory
recording of steep. Psychological treatment (cognitive-behavioral therapy) targets
misappraisals of anxiety sensations, hyperventilatory response, and conditioned
reactions to internal, physical cues. Recent evidence supports the efficacy of this
approach, however, controlled studies on pharmacological agents in the treatment of
NP are tacking. Research is needed to examine the effects of combined cognitive-
behavioral therapy and medications, compared to medication alone in the treatment
of NP. &COPY; 2004 Elsevier Ltd. All rights reserved.
In light of the increasing threat of large-scale massacres such as terrorism
against non-combatants (civilians), more attention is warranted not only to
posttraumatic stress disorder (PTSD) but also to acute sociogenic
pseudoneurological ("conversion") symptoms, especially epidemic sociogenic
symptoms. We posit that conversion disorders are etiologically related to specific
evolutionary pressures (inescapable threats to life) in the late stage of the human
environment of evolutionary adaptedness (EEA). Bracha et al. have recently argued
that from the neuroevolutionary perspective, medically unexplained efferent
vasovagal syncope and medically unexplained craniofacial musculoskeletal pain in
young otherwise healthy individuals, may be taxonomized as stress and fear-
circuitry disorders. In the present article, we extend neuroevolutionary
perspectives to acute pseudoneurological sociogenic ("conversive") symptoms:
psychogenic non-epileptic attacks ("pseudoseizures"), epidemic sociogenic disorders
(DSM-IV-TR Epidemic "Hysteria"), conversive motor deficits (pseudo-paralysis and
pseudo-cerebellar symptoms), and psychogenic blindness. We hypothesize that these
perplexing pseudoneurological stress-triggered symptoms, which constitute
psychopathology in extant humans, are traceable to allele-variant polymorphisms
which spread during the Neolithic EEA. During Neolithic warfare, conversive
symptoms may have increased the survival odds for some noncombatants by visually
(i.e., "non-verbally") signaling to predatory conspecifics that one does not
present a danger. This is consistent with the age and sex pattern of conversive
disorders. Testable and falsifiable predictions are presented; e.g., at the genome-
transcriptome interface, one of the major oligogenic loci involved in conversive
spectrum disorders may carry a developmentally sensitive allele in a stable
polymorphism (balanced polymorphism) in which the gene expression mechanism is
gradually suppressed by pleiotropic androgens especially dehydroxyepiandrosterone
sulfate (DHEA-S). Taxonomic implications for the much-needed rapprochement between
the forthcoming Diagnostic and Statistical Manual tor Mental Disorders, Fifth
Edition (DSM-V) and the International Classification of Diseases (ICD) are
discussed, Published by Elsevier B.V.
The concept of panic disorder was derived from neurobiological models which were
quickly assimilated and differentiated by behavioural approaches. Psychoanalytic
reception, however, has been reserved. This review presents recent neurobiological,
behavioural and psychodynamic models. Neurobiological approaches describe the
central and peripheral dysregulation of stress hormone systems. Behavioural
approaches explain the maintenance of panic disorders based on interoceptive
conditioning, cognitive interpretative biases and dispositional anxiety
sensitivity. Recent psychodynamic concepts have identified a reduced tolerance for
intensive affects and for separation based on a lack of stable object
representations as underlying factors. They provide links to experimental and
neurobiological studies which have demonstrated the impact of premature separation
for a lifelong vulnerability to stress and for fearfulness. Neurobiological,
behavioural and psychodynamic models represent complementary aspects useful for the
conceptualization of this heterogeneous disorder.
Video-excerpts from routine oncology interviews are examined to reveal how patients
demonstrate and doctors respond to "fears" about cancer. Vocally and visually,
embodied impacts of dealing with dreaded consequences of cancer are apparent when
addressing both good and potentially bad cancer news. Even a "brush" with cancer
can promote negative and ongoing impacts provoking unresolved illness dilemmas. We
reveal how. in the midst of extending answers and initiating concerns, patients
exhibit trepidations when volunteering narrative information about their medical
history and experience of symptoms. In response, doctors are shown to acknowledge
yet exhibit minimal receptiveness to patients' lifeworld disclosures and
demonstrations (e.g., redirecting attention away from patients' concerns by
offering "textbook" symptoms and related pursuits of biomedical agendas).
Discussion focuses, on interactional criteria for identifying "fears", patients'
lay orientations to medical visits, and implications for relining educational
workshops for oncologists. (C) 2004 Published by Elsevier Ltd.
Two important paradigm shifts have occurred in the war on terror. First, the United
States has treated terrorism as a military issue, not a law enforcement problem.
Second, the United States has centralized its intelligence apparatus under the
direction of the newly-created Director of National Intelligence and lowered the
wall that separated external security or foreign intelligence activity from
internal security or domestic law enforcement. In tandem, these changes are of
historic dimension. They also occur against a backdrop in modern times in which the
executive branch has steadily accumulated power. In pursuit of the war on terror,
we have begun to blur traditional lines meant to protect civil liberty from the
danger of excessive executive power: the line between the military and domestic law
enforcement on the one hand, and between domestic law enforcement and foreign
intelligence on the other. This blurring of lines already has led to difficult
questions regarding the limits of executive prerogative and will undoubtedly lead
to more. The cumulative effect of both paradigm shifts is to enlarge executive
authority and to increase the risk of civil liberty abuses.
To review current evidence for the clinical and cost-effectiveness of self-
management interventions for panic disorder, phobias and obsessive-compulsive
disorder (OCD). Papers were identified through computerized searches of databases
for the years between 1995 and 2003, manual searches and personal contacts. Only
randomized-controlled trials were reviewed. Ten studies were identified (one OCD,
five panic disorder, four phobias). Effective self-management interventions
included cognitive-behavioural therapy (CBT) and exposure to the trigger stimuli
for phobias and panic disorders. All involved homework. There was evidence of
effectiveness in terms of improved symptoms and psychological wellbeing when
compared with standard care, waiting list or relaxation. Brief interventions and
computer-based interventions were effective for most participants. In terms of
quality, studies were mainly based on small samples, lacked long-term follow-up,
and failed to address cost-effectiveness. Despite the limitations of reviewed
studies, there appears to be sufficient evidence to warrant greater exploration of
self-management in these disorders.
Fear extinction, the reduction of fear by repeated exposure to the object of fear,
is a crucial paradigm of inhibitory learning and the acknowledged preclinical model
for behavior therapy of human anxiety. Recent insights have clarified roles for
infralimbic prefrontal cortex, hippocampus and periaqueductal gray in extinction
learning, while maintaining a central role for the basolateral amygdaloid nucleus
in the acquisition and storage of this learning. Simultaneously, molecular insights
have implicated several neurotransmitter and second messenger systems in extinction
learning, and revealed that extinction is surprisingly easy to improve, yielding
the promise of a novel approach to improved psychiatric treatments for a variety of
human anxiety disorders.
This article examines the workings of the sexual closet within the enormously
popular genre of the Russian detektiv, or detective story. Informed by the work of
Eve Kosofsky Sedgwick and D. A. Miller, the article focuses on the dramatization of
homosexual panic among various male characters in Aleksandra Marinina's Stilist
(1996) and Boris Akunin's Koronatsiia (2001) in order to explore the experience of
masculine subjectivity in post-Soviet culture. In both novels, a perceived crisis
in patriarchal authority unleashes suspicions and anxieties regarding the
experience of being and becoming a man, which is defined against the feminine and
the homosexual. Figured both as an effect of and as a threat to male-male bonds,
homosexual panic testifies to the interiorization of sexual and gender norms, which
makes being male a highly self-conscious enterprise and fuels nostalgia for a
mythic time before the appearance of homosexuality.
A growing body of research derived from terror management theory [e.g., Solomon,
S., Greenberg, J., & Pyszczynski, T. (1991). A terror management theory of social
behavior: The psychological functions of self-esteem and cultural worldviews. In M.
P. Zanna (Ed.), Advances in experimental social psychology: vol. 24 (pp. 93-159).
New York: Academic Press] suggests that the human struggle with the awareness of
inevitable death can greatly impact people's physical and psychological well-being.
The current article reviews converging lines of research that investigate the role
of terror management processes in physical and mental health. Specifically, we
present research that elucidates the role of death concerns in (1) conscious
threat-focused defenses, (2) self-esteem striving, (3) depression, (4) anxiety
disorders, (5) discomfort with the physicality of the body and (6) neuroticism. We
conclude that terror management theory builds upon the work of other existential
scholars and mental health perspectives to provide a broad conceptual and
empirically based account of how deeply rooted existential fears manifest in ways
that prove both psychologically and physically problematic. We also suggest how
future research and social interventions can be employed to help individuals manage
basic fears in ways that do not compromise their psychological and physical health.
(c) 2005 Elsevier Ltd. All rights reserved.
During the last two centuries, the world has seen a substantial increase in the
number and availability of vaccines for the prevention of infectious disease.
Smallpox vaccine remains the most celebrated vaccine-related achievement in human
history, but worldwide reductions in many other diseases including measles, mumps,
rubella, polio, diphtheria, and whooping cough (Bordetella pertussis) also
illustrate the power of vaccination in controlling outbreaks of contagious
diseases. Ironically, as advances in vaccination successfully limit disease
outbreaks, the impact that these infectious agents once had on society becomes
marginalized. Public confidence in vaccination may erode because of real or
perceived risks associated with immunization, and this in turn may lead to lower
vaccination coverage and loss of herd immunity. Here, we will discuss some of the
elements associated with public perceptions and fear of vaccination and place these
into the context of how deadly several vaccine-preventable childhood diseases can
be if vaccination coverage is insufficient.
The phenomenon known as one-trial tolerance (OTT) to the anxiolytic effects of
benzodiazepines observed in rats submitted to the elevated plus-maze test (EPM) is
considered to be due to the emergence of phobic states across the test/retest
sessions. Antinociception is a usual component of the defense reaction. Until now,
no study has examined antinociception and OTT together in freely behaving rats in
the EPM. This work is a new approach looking at the sensorimotor gatings underlying
OTT through the examination of the changes in reactivity to noxious stimuli during
OTT development. We used the tail-flick test to assess the reactivity of rats to
noxious stimulus during the effects of midazolam in test/retest sessions using two
types of EPM, one with opaque (standard EPM) and another one with transparent walls
(modified EPM). The authors had previously shown that this modified test caused an
overall stressful situation more related to anxiety while the standard test coursed
with a mixture of anxiety and high fear levels. In both plus mazes, the study was
conducted in two experiments: (i) midazolam before the first trial, and (ii)
midazolam before the second trial. In each experimental condition the effects of
midazolam were tested under two doses (0.5 and 1.0 mg/kg) against a control group
that received injections of saline. The anxiolytic effects of midazolam were more
pronounced in animals tested in the modified EPM than in the standard EPM.
Stressful stimuli present in both types of maze were able to elicit one-trial
tolerance to midazolam on re-exposure. However, anxiolytic-insensitive behaviors in
the first and the reduction in exploratory activity in the second trial are more
pronounced in the standard EPM indicating that this test is more prone to transfer
fear-related states across trials than the modified maze test. Antinociception is
not present upon the re-exposure of rats to the EPM. These findings show that
animals tested in the modified EPM showed higher sensitivity to the anxiolytic
effects of midazolam than the standard EPM. Antinociception was not a concomitant
of the shift in the emotional state present in the retest sessions of the EPM.
These results are in agreement with the premises that repeated stressful experience
leads to anxiolytic-insensitive fear state different from anxiety. (c) 2005
Elsevier Inc. All rights reserved.
Among primates in general, pheromones are of variable importance to social
communication. Data on humans have generated the greatest controversy regarding the
existence of pheromonal communication. In this review, the likelihood of pheromonal
communication in humans is assessed with a discussion of chemical compounds
produced by the axilla that may function as pheromones; the likelihood that the
vomeronasal organ (VNO), a putative pheromone receptor organ in many other mammals,
is functional in humans; and the possible ways pheromones operate in humans. In the
human axilla, the interactions between the cutaneous microflora and axillary
secretions render this region analogous to scent glands found in other primates.
Both the chemistry of axillary secretions and their effects on conspecifics in
humans appear to be analogous to other mammalian pheromone systems. Whichever
chemical compounds serve a pheromonal function in humans, another unknown is the
receptor. Although the VNO has been implicated in the reception of pheromones in
many vertebrates, it is not the only pathway through which such information has
access to the central nervous system; there is ample evidence to support the view
that the olfactory epithelium can respond to pheromones. Furthermore, if a chemical
activates receptors within the VNO, this does not necessarily mean that the
compound is a pheromone. An important caveat for humans is that critical components
typically found within the functioning VNO of other, nonprimate, mammals are
lacking, suggesting that the human VNO does not function in the way that has been
described for other mammals. In a broader perspective, pheromones can be classified
as primers, signalers, modulators, and releasers. There is good evidence to support
the presence of the former three in humans. Examples include affects on the
menstrual cycle (primer effects); olfactory recognition of newborn by its mother
(signaler); individuals may exude different odors based on mood (suggestive of
modulator effects). However, there is no good evidence for releaser effects in
adult humans. It is emphasized that no bioassay-guided study has led to the
isolation of true human pheromones, a step that will elucidate specific functions
to human chemical signals. (C) 2004 Wiley-Liss, Inc.
The authors review research on police effectiveness in reducing crime, disorder,
and fear in the context of a typology of innovation in police practices. That
typology emphasizes two dimensions: one concerning the diversity of approaches, and
the other, the level of focus. The authors find that little evidence supports the
standard Model of policing-low on both of these dimensions. In contrast, research
evidence does support continued investment in police innovations that call for
greater focus and tailoring of police efforts, combined with an expansion of the
tool box of policing beyond simple law enforcement. The strongest evidence of
police effectiveness in reducing crime and disorder is found in the case of
geographically focused police practices, such as bot-spots policing. Community
policing practices are found to reduce fear of crime, but the authors do not find
consistent evidence that community policing (when it is implemented without models
of problem-oriented policing) affects either crime or disorder. A developing body
of evidence points to the effectiveness of problem oriented policing in reducing
crime, disorder, and fear. More generally, the authors find that many policing
practices applied broadly throughout the United States either have not been the
subject of systematic research or have been examined in the context of research
designs that do not allow practitioners or policy makers to draw very strong
conclusions.
Patients with premenstrual dysphoric disorder (PMDD) and patients with panic
disorder (PD) both experience high rates of panic attacks in laboratory panic
provocation studies. Recently, this shared elevated rate of challenge-induced panic
has received increasing attention. Researchers have suggested that PMDD and panic
disorder may share a pathophysiological or psychobiological link. The purpose of
this paper is to review the findings from PMDD challenge studies and the theories
advanced to connect PMDD to panic disorder. Taken together, the results of the PMDD
challenge studies confirm that agents that incite panic in PD patients do so as
well in PMDD women. This shared elevated challenge-induced panic cannot be
accounted for by explanations such as a history of PD in PMDD women. None of the
physiological theories as currently expressed-suffocation false alarm, gamma-
aminobutyric acid (GABA), noradrenergic, serotonergic, and cholecystokinin-yet
provides a compelling candidate to account for shared elevated challenge-induced
panic in PD and PMDD patients. Psychological perspectives on panic emphasize that
bodily sensations themselves can cause fear. Researchers have yet to apply several
influential psychological approaches-conditioning, catastrophic misinterpretation,
and anxiety sensitivity-to PMDD patients. Because psychological factors influence
anxious responding in challenge studies, the search for the biological abnormality
best accounting for PMDD panic might benefit from a refraining of the question to
one that considers the psychological perspective as well. (C) 2004 Elsevier Ltd.
All rights reserved.
Panic disorder (PD) is a highly prevalent, debilitating disorder. The heritability
of the disease has been estimated by twin studies to be between 30 and 60%. The
vulnerability for PD overlaps with an increased risk of bipolar disorder in some
families. Classical genetic methods such as linkage analysis and association
studies have not yet identified genetic risk factors beyond doubt. However, two
independent studies confirm linkage of a specific syndrome characterized by PD,
bladder problems, severe headaches, mitral valve prolapse and thyroid dysfunction
to genetic markers on chromosome 13q. Association studies, although showing
divergent results, give some support to a causative role for the genes encoding for
monoamine oxidase A (MAO-A), cholecystokinin (CCK) and catechol-O-methyltransferase
(COMT). Finally, a somatic duplication of a 19-Mb region on chromosome 15 has been
associated with PD, but this intriguing finding awaits confirmation.
Background: The interaction between immune cells; neurotransmitters and the
neuroendocrinological systems plays a role in affective disorders, especially
depression. Although panic disorder (PD) shares a lot of features with depression,
it is clearly a distinct disorder. Reports on immunological parameters in PD don't
provide a clear picture of the immunological status of PD patients. This can partly
be attributed to methodological differences between studies and small patient
groups. Objective: The present study alms to assemble all studies on immunological
parameters in PD in order to combine all available data to gain a broader
perspective on this matter. Method: PubMed was searched for studies describing
immunological parameters in PD patients without comorbid disorders or medication
use. All studies had to include a healthy control group and the outcome measures
had to be shared by at least one other study. Results: Fourteen articles were
found. Although the T-lymphocytic branch and the innate immune system were normal,
the B-lymphocytic branch showed some differences between PD patients and healthy
controls. B-cell counts were increased in PD patients, which was underlined by
increased human leucocyte antigen (HLA)-DR counts and increased immunoglobulin A
levels. However, B-cell activity following mitogen stimulation was normal.
Conclusions: PD patients show increased B-cell numbers. The finding that B-cell
activity is not increased can possibly be attributed to functional exhaustion of
these cells. The meaning of this finding remains unclear, although it may be
potentially important in affective disorders as the same has been found in
depression.
Fear extinction refers to the ability to adapt as Situations change by learning to
suppress a previously learned fear. This process involves a gradual reduction in
the capacity of a fear-conditioned stimulus to elicit fear by presenting the
conditioned stimulus repeatedly on its own. Fear extinction is context-dependent
and is generally considered to involve the establishment of inhibitory control of
the prefrontal cortex over amygdala-based fear processes. In this paper, we review
research progress on the neural basis of fear extinction with a focus Oil the role
of the amygdala and the prefrontal cortex. We evaluate two competing hypotheses for
how the medial prefrontal cortex inhibits amygdala Output. In addition, we present
new findings showing that lesions of the basal amygdala do not affect fear
extinction. Based on this result, we propose an updated model for integrating
hippocampal-based Contextual information with prefrontal-amygdala circuitry.
Contextual fear conditioning is an important behavioral paradigm for studying the
neurobiology of learning and memory and the mnemonic function of the hippocampus.
We suggest that research in this domain can profit by a better theoretical
understanding of the processes that contribute to this phenomenon. To facilitate
this understanding, we describe a theory which assumes that physical elements of a
conditioning context represented in the brain as either (a) a set of independent
features or (b) features bound into a conjunctive representation by the hippocampus
which supports pattern completion. Conditioning produced by shocking a rat in a
particular context, in principle, can be produced by strengthening connections
between the feature representations and/or the conjunctive representation and
basolateral region of the amygdala. We illustrate how this theory clarifies some of
the complexities associated with the existing literature and how it can be used to
guide future empirical work. We also argue that the mechanisms (conjunctive
representations and pattern completion) that mediate the contribution the
hippocampus makes to contextual fear conditioning are the same ones that enable the
hippocampus to support declarative memory in humans. (C) 2004 Elsevier Ltd. All
rights reserved.
Alprazolam-XR is an extencled-release formulation of alprazolam designed to deliver
sustained therapeutic concentrations for 24 h after once-daily dosing. Plasma
concentrations gradually decline as the time for the next dose approaches, but
still remain above therapeutic minimum levels. The anti-panic efficacy of
alprazolam-XR appears to be comparable to the original formulation of alprazolam.
The main advantage of the new extended-release formulation appears to be its
greater tolerability and safety. The speed with which high-potency benzodiazepines
are absorbed, and rise to peak concentrations is correlated with both abuse
potential and with the incidence and severity of common adverse events, such as
sedation and cognitive and psychomotor impairment. Alprazolam-XR does not exhibit
the sudden increases in plasma concentration characteristic of the original
formulation of alprazolam. This pharmacokinetic difference appears to translate
into a reduced liability of abuse and a reduced incidence of sedation and cognitive
and psychomotor impairment during acute therapy. This would appear to give
alprazolam-XR a more favourable benefit:risk profile than the original formulation
of alprazolam. In addition, the once-daily dosing (as opposed to three or four
times per day) reduces clock-watching, increases compliance and it eliminates the
penalty of breakthrough anxiety and panic that many patients experience if they
inadvertently miss a dose. It should be noted that long-term therapy with
alprazolam-XR carries the same risk of dependence and withdrawal during
discontinuation as the original formulation of alprazolam.
Anxiety disorders are among the most common psychological disturbances in the
industrialized world. Current behavioral therapy procedures for these disorders are
somewhat effective, but their efficacy could be Substantially improved. Because
these procedures are largely based on the process of extinction, manipulations that
enhance extinction may lead to improvements in treatment effectiveness. We review
the evidence that D-cycloserine (DCS), a partial NMDA agonist, facilitates
extinction of learned fear in rats. Although only a few studies have examined the
effects of DCS on extinction of learned fear, this work suggests that this drug may
have a number of potential clinical benefits. In addition, attempts at interpreting
this research illustrate our limited understanding of the processes involved in
extinction.
There has been growing interest in the role of serotonin (5-hydroxytryptamine, 5-
HT) in anxiety, including pathological states such as panic disorder. The technique
of tryptophan depletion (TD), which causes an acute, temporary and reversible
reduction in brain 5-HT levels, is a useful minimally invasive paradigm to aid the
research of the role of 5-HT in various disorders. This review discusses the
evidence supporting the hypothesis that 5-HT function is of importance in the
neurobiology of panic disorder and considers in more detail how our understanding
has been influenced by work using the technique of TD. Possible avenues for future
research are also discussed.
One of the most common paradigms used to study the biological basis of emotion, as
well as of learning and memory, is Pavlovian fear conditioning. In the acquisition
phase of a fear conditioning experiment, an emotionally neutral conditioned
stimulus (CS)-which can either be a discrete stimulus, such as a tone, or a
contextual stimulus, such as a specific environment-is paired with an aversive
unconditioned stimulus (US), for example a foot shock. As a result, the CS elicits
conditioned fear responses when subsequently presented alone during the expression
phase of the experiment. While considerable work has been done in relating specific
circuits of the brain to fear conditioning, less is known about its regulation by
neuromodulators; the understanding of which would be of therapeutic relevance for
fear related diseases such as phobia, panic attacks, post traumatic stress
disorder, obsessive compulsive disorder, or generalized anxiety disorder. Dopamine
is one of the neuromodulators most potently acting on the mechanisms underlying
states of fear and anxiety. Recently, a growing body of evidence has suggested that
dopaminergic mechanisms are significant for different aspects of affective memory,
namely its formation, expression, retrieval, and extinction. The aim of this review
is to clarify the complex actions of dopamine in fear conditioning with respect to
the wide-spread distribution of dopaminergic innervation over structures
constituting the fear related circuitry. A particular effort is made to understand
how dopamine in the amygdala, medial prefrontal cortex and nucleus accumbens-target
structures of the mesolimbic dopamine system originating from the ventral tegmental
area-could relate to different aspects of fear conditioning. (C) 2004 Elsevier Ltd.
All rights reserved.
There is some experimental evidence to support the existence of a connection
between panic and respiration. However, only recent studies investigating the
complexity of respiratory physiology have revealed consistent irregularities in
respiratory pattern, suggesting that these abnormalities might be a vulnerability
factor to panic attacks. The source of the high irregularity observed, together
with unpleasant respiratory sensations in patients with panic disorder (PD), is
still unclear and different underlying mechanisms might be hypothesized. It could
be the result of compensatory responses to abnormal respiratory inputs or an
intrinsic deranged activity in the brainstem network shaping the respiratory
rhythm. Moreover, since basic physiological functions in the organism are strictly
interrelated, with reciprocal modulations and abnormalities in cardiac and balance
system function having been described in PD, the respiratory findings might arise
from perturbations of these other basic systems or a more general dysfunction of
the homeostatic brain. Phylogenetically ancient brain circuits process
physiological perceptions/sensations linked to homeostatic functions, such as
respiration, and the parabrachial nucleus might filter and integrate interoceptive
information from the basic homeostatic functions. These physiological processes
take place continuously and subconsciously and only occasionally do they pervade
the conscious awareness as 'primal emotions'. Panic attacks could be the expression
of primal emotion arising from an abnormal modulation of the
respiratory/homeostatic functions.
It is currently believed that the acquisition of classically conditioned fear
involves potentiation of conditioned thalamic inputs in the lateral amygdala ( LA).
In turn, LA cells would excite more neurons in the central nucleus ( CE) that, via
their projections to the brain stem and hypothalamus, evoke fear responses.
However, LA neurons do not directly contact brain stem-projecting CE neurons. This
is problematic because CE projections to the periaqueductal gray and pontine
reticular formation are believed to generate conditioned freezing and fear-
potentiated startle, respectively. Moreover, like LA, CE may receive direct
thalamic inputs communicating information about the conditioned and unconditioned
stimuli. Finally, recent evidence suggests that the CE itself may be a critical
site of plasticity. This review attempts to reconcile the current model with these
observations. We suggest that potentiated LA outputs disinhibit CE projection
neurons via GABAergic intercalated neurons, thereby permitting associative
plasticity in CE. Thus plasticity in both LA and CE would be necessary for
acquisition of conditioned fear. This revised model also accounts for inhibition of
conditioned fear after extinction.
This article reflects on the importance of Mitchell's work in the United Kingdom,
where notions of intimacy sit uneasily with psychoanalytic practice. The author
argues that a reluctance to take up intimacy in the consulting room has a
deleterious effect on intimate relations outside it. Drawing on her work with
women, in particular, she posits that the erotic is still an undertheorized area of
relational analysis. Although most orthodox theory has been jettisoned, new theory
is necessary for an understanding of what the author observes to be a "false"
erotic in many of her patients in whom the erotic. is temporarily available but is
unreliable as a desire and as a source of identity.
Catatonia, long viewed as a motor disorder, may be better understood as a fear
response, akin to the animal defense strategy tonic immobility (after G. G. Gallup
& J. D. Maser, 1977). This proposal, consistent with K. L. Kahlbauln's (1874/1973)
original conception, is based on similarities between catatonia and tonic
immobility ("death feint") as well as evidence that catatonia is associated with
anxiety and agitated depression and responds dramatically to benzodiazepines. It is
argued that catatonia originally derived from ancestral encounters with carnivores
whose predatory instincts were triggered by movement but is now inappropriately
expressed in very different modern threat situations. Found in a wide range of
psychiatric and serious medical conditions, catatonia may represent a common "end
state" response to feelings of imminent doom and can serve as a template to
understand other psychiatric disorders.
In many altricial species, fear responses such as freezing do not emerge until
sometime later in development. In infant rats, fear to natural predator odors
emerges around postnatal day (PN) 10 when infant rats begin walking. The behavioral
emergence of fear is correlated with two physiological events: functional emergence
of the amygdala and increasing corticosterone (CORT) levels. Here, we hypothesize
that increasing corticosterone levels influence amygdala activity to permit the
emergence of fear expression. We assessed the relationship between fear expression
(immobility similar to freezing), amygdala function (c-fos) and the level of
corticosterone in pups in response to presentation of novel male odor (predator),
littermate odor and no odor. CORT levels were increased in PN8 pups (no fear,
normally low CORT) by exogenous CORT Q mg/kg) and decreased in PN 12 pups (express
fear, CORT levels higher) through adrenalectomy and CORT replacement. Results
showed that PN8 expression of fear to a predator odor and basolateral/lateral
amygdala activity could be prematurely evoked with exogenous CORT, while
adrenalectomy in PN12 pups prevented both fear expression and amygdala activation.
These results suggest that low neonatal CORT level serves to protect pups from
responding to fear inducing stimuli and attenuate amygdala activation. This
suggests that alteration of the neonatal CORT system by environmental insults such
as alcohol, stress and illegal drugs, may also alter the neonatal fear system and
its underlying neural control. (C) 2004 ISDN. Published by Elsevier Ltd. All rights
reserved.
Estrogens affect a variety of behaviors in addition to sexual responses, some of
them related to motor activity and emotional reactivity. This is true in
experimental animals and in humans. The literatures on these subjects are confusing
because not all of the experimental results point in the same direction. Here we
propose the following theoretical suggestion, hoping to account for the variety of
reports extant: following the generally arousing effects of estrogens, their
hormonal actions on motor activity and fear depend on context. In a safe
environment. estrogen treatment causes increased activity. But in a novel
environment or in contexts otherwise perceived as threatening, activity is reduced
by estrogen, due to the hormone's arousing action, which heightens fear. Many
hormone-dependent neural circuits involving several neuropeptides could provide
mechanisms for this dynamic. We suggest a causal route could involve the activation
of corticotropin releasing hormone gene expression in the brain. In sum, estrogenic
effects on arousal states, as manifest differently according to details of the
environmental context during behavioral test, could account for some of the
discrepancies in the literature. (C) 2003 Elsevier Ltd. All rights reserved.
We present in this paper a picture of the neural systems controlling defense that
updates and simplifies Gray's "Neuropsychology of Anxiety". It is based on two
behavioural dimensions: 'defensive distance' as defined by the Blanchards and
'defensive direction'. Defensive direction is a categorical dimension with
avoidance of threat corresponding to fear and approach to threat corresponding to
anxiety. These two psychological dimensions are mapped to underlying neural
dimensions. Defensive distance is mapped to neural level, with the shortest
defensive distances involving the lowest neural level (periaqueductal grey) and the
largest defensive distances the highest neural level (prefrontal cortex). Defensive
direction is mapped to separate parallel streams that run across these levels. A
significant departure from prior models is the proposal that both fear and anxiety
are represented at all levels. The theory is presented in a simplified form that
does not incorporate the interactions that must occur between non-adjacent levels
of the system. It also requires expansion to include the dimension of escapability
of threat. Our current development and these proposed future extensions do not
change the core concepts originally proposed by Gray and, we argue, demonstrate
their enduring value. (C) 2004 Elsevier Ltd. All rights reserved.
The learning and remembering of fearful events depends on the integrity of the
amygdala, but how are fear memories represented in the activity of amygdala
neurons? Here, we review recent electrophysiological studies indicating that
neurons in the lateral amygdala encode aversive memories during the acquisition and
extinction of Pavlovian fear conditioning. Studies that combine unit recording with
brain lesions and pharmacological inactivation provide evidence that the lateral
amygdala is a crucial locus of fear memory. Extinction of fear memory reduces
associative plasticity in the lateral amygdala and involves the hippocampus and
prefrontal cortex. Understanding the signalling of aversive memory by amygdala
neurons opens new avenues for research into the neural systems that support fear
behaviour.
Drawing on lay epistemology theory (A. W. Kruglanski, 1980, 1989), the authors
assessed a terror management analysis (J. Greenberg, S. Solomon, & T. Pyszczynski,
1997) of the psychological function of structuring social information. Seven
studies tested variations of the hypothesis that simple, benign interpretations of
social information function, in part, to manage death-related anxiety. In Studies
1-4, mortality salience (MS) exaggerated primacy effects and reliance on
representative information, decreased preference for a behaviorally inconsistent
target among those high in personal need for structure (PNS), and increased high-
PNS participants' preference for interpersonal balance. In Studies 5-7, MS
increased high-PNS participants' preference for interpretations that suggest a just
world and a benevolent causal order of events in the social world.
Objectives: The aim of this meta-analytic and systematic quantitative approach is
to examine the effects of behavioral interventions for dental anxiety and dental
phobia. Methods: Eighty studies were identified where dental fear treatment with
behavioral methods was evaluated. Thirty-eight of 80 met entry criteria and were
included in a meta-analysis. Results: The calculated effect sizes (ESs) for self-
reported anxiety after intervention indicate positive changes in 36 of the 38
studies and no changes in two. The overall ES = 1.8 (95% CI: 1.6, 1.8). The percent
of subjects with post-treatment dental visits in the first 6 months post-treatment
varied between 50 and 100%. The overall ES for attendance at dental visits,
weighted by sample size, is 1.4 (95% CI: 1.3, 1.6). The homogeneity analysis
indicates that the studies cannot be adequately described in one ES. The reported
percentage of subjects with a dental visit between 6 months and 4 years post-
treatment varied from 48 to 100%. The overall weighted ES for visiting the dentist,
adjusted for drop-outs in the studies, is 1.2 (95% CI: 0.99, 1.4). Conclusions:
Despite extensive heterogeneity, changes in self-reported anxiety represent medium
to large ESs. Patients signing up for a behavioral intervention for dental fear can
be expected to report a significant reduction in their fear, and this effect
generally seems to be lasting. Mean long-term attendance (>4 years after treatment)
is 77%.
The number of herds with group housed non-lactating sows is increasing rapidly in
Europe as a consequence of changed legislation initiated by elevated public concern
for animal welfare. However, lower litter size and pregnancy rate in group housed
compared to individually housed nonlactating sows has been observed in several on-
farm studies. Based upon existing knowledge, it is considered whether stress and
fear caused by social interactions are possible mediators of impaired reproduction
in group housed sows. A review of 15 experiments with group housed sows showed that
although the results are few and inconsistent, there are indications that stress
and fear may be contributory reasons for the impaired reproduction seen in group
housed sows and that possible initiators of stress and fear might be the mixing of
unfamiliar sows and high stocking rate levels. A suggestion for indicators of
stress and fear related reproduction problems suitable for use in practice are put
forward.
Background: The purpose of this systematic review was to identify characteristics
of the chest pain associated with the presence of panic disorder, to determine the
strength of the association between panic disorder and coronary artery disease
( CAD), and to determine the association between panic disorder and known
cardiovascular risk factors. Methods: Potential studies were identified via
computerized search using MEDLINE and PSYCINFO databases, and review of
bibliographies. MeSH headings used included "panic disorder" with "chest pain,"
"panic disorder" with "coronary disease or cardiovascular disorders or heart
disorders," and " panic disorder" with " cholesterol or essential hypertension or
tobacco smoking." Studies had to base their diagnosis of panic disorder on criteria
from the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, and
objective criteria of CAD and risk factors had to be used. Only case-control and
cohort studies were included. Results: The relative risk of panic disorder in
patients with nonanginal chest pain is 2.03 [ confidence interval ( CI), 1.41 to
2.92]. Concerning the relationship between panic disorder and CAD, studies
conducted in emergency departments found a relative risk of 1.25 ( CI, 0.87 to
1.80). However, there is an inverse relationship between the prevalence of CAD in
the study and the prevalence of panic disorder among the patients with CAD (r = -.
469, P = .086). Panic disorder has also been linked to cardiac risk factors.
Conclusions: Panic disorder and CAD are correlated in noncardiology settings, and
recurrent panic attacks may actually cause CAD. Recognition of either condition
should lead the family physician to consider the other, resulting in increased
vigilance and possible screening.
The management of chronic illness is becoming increasingly patient-centred.
Although patients with inflammatory bowel disease have a normal life expectancy,
most individuals experience an impact of inflammatory bowel disease on their daily
lives as well as on their attitudes, fears and beliefs. Although currently
available therapies for ulcerative colitis and Crohn's disease are becoming
increasingly effective, there are still many unmet needs to address in this patient
population. Physicians and patients' spouses or significant others underestimate
the type and severity of problems reported by inflammatory bowel disease patients.
Physical problems are frequently measured using disease activity indices. Emotional
and social problems are reported using quality of life questionnaires and other
specific measurement tools pertinent to the question of interest. Studies have
indicated a poorer physical and emotional function in inflammatory bowel disease
patients than in the general population. Effective therapies, both medical and
surgical, produce significant improvements in the general and disease-specific
quality of life. The quality of life is worse when the disease is more severe.
Concomitant anxiety or depression appears to impair the quality of life even
further. Common fears include the possibility of unanticipated flares, the need for
surgery, poor energy levels and the side-effects of medication. Recent studies have
suggested that more prominent patient participation in management has the potential
for greater patient satisfaction, better outcomes and more efficient health
resource utilization. Thus, future studies should focus not only on ensuring the
wider availability of effective therapies, but on increasing access to health care
that is tailored to individuals - more structure for some and more independence and
self-management for others, with health provider supervision.
This paper focuses on the option of dollarization or euroization for emerging-
market economies. There are no "one-size-fits-all" exchange-rate policies for
emerging-market economies; however, there are macroeconomic disadvantages
associated with flexible exchange-rate regimes in such economies. Similarly, the
timing of euro adoption in EU accession countries is a complex matter as well. The
paper compares the costs and benefits of euro adoption, in particular to unilateral
euroization.
This article criticizes the predominant use of fear appeals in social marketing.
Laboratory studies, which have been the basis for most of the research on fear
appeals and which generally suggest that high fear works, have limitations that
include forced exposure, short-term measurement, and an overdependence on student
samples. Although, unfortunately, field research evaluations of fear appeals are
few, they usually reveal that fear has both weaker effects and unintended
deleterious effects in real-world social marketing campaigns. Ethical concerns
about fear appeals include maladaptive responses such as chronic heightened anxiety
among those most at risk and, paradoxically, complacency among those not directly
targeted, and increased social inequity between those who respond to fear
campaigns, who tend to be better off, and those who do not, who tend to be the less
educated and poorer members of society. Alternatives to fear appeals are the use of
positive reinforcement appeals aimed at the good behavior, the use of humor, and,
for younger audiences, the use of postmodern irony. (C) 2004 Wiley Periodicals,
Inc.
Panic disorder (PD) is associated with the rapid onset of fear-related
symptomatology, often somatic in nature. As a result, individuals with the disorder
often fear that they are experiencing a life-threatening emergency and present in
hospital emergency departments (EDs). As the operating heuristics of EDs are geared
toward identifying organic causes and allow only brief physician-patient contact,
the diagnosis of PD is more often than not overlooked. Those with the disorder go
on to incur enormous costs as they seek out an explanation for their symptoms.
Efforts to alleviate this problem, including increased physician education and the
development of screening instruments, have been largely unsuccessful. The continued
misidentification and mismanagement of this disorder argues for greater
incorporation of mental health professionals into the ED, allowing collaborative
efforts that recognize the relationship between physiological and psychological
aspects of panic.
Objective: The purpose of this study is to test the association between joint
hypermobility syndrome (JHS) and panic disorder (PD) and to determine whether
mitral valve prolapse (MVP) modifies or accounts in part for the association.
Method: A total of 115 subjects are included in this study in three groups. Group I
(n = 42): panic disorder patients with MVP. Group II (n = 35): panic disorder
patients without mitral valve prolapse. Group III (n = 38): control subjects who
had mitral valve prolapse without any psychiatric illness. Beighton criteria were
used to assess joint hypermobility syndrome. Two-dimensional and M-mode
echocardiography was performed on each subject to detect mitral valve prolapse.
Results: Joint hypermobility syndrome was found in 59.5% of panic disorder patients
with mitral valve prolapse, in 42.9% of patients without mitral valve prolapse and
in 52.6% of control subjects. Beighton scores was 4.93 +/- 2.97 in group I, 4.09
+/- 2.33 in group II, and 4.08 +/- 2.34 in group III. There was no significant
difference between groups according to Beighton scores. Conclusion: We did not
detect a statistically significant relationship between panic disorder and joint
hypermobility syndrome. Mitral valve prolapse and joint hypermobility syndrome are
known to be etiologically related and we suggest that mitral valve prolapse affects
the prevalence of joint hypermobility syndrome in the panic disorder patients. (C)
2004 Published by Elsevier Inc.
This article reviews experimental evidence and theoretical constructs that
implicate serotonin (5-HT) modulation of defensive behavior within the midbrain
periaqueductal gray in panic disorder (PD). Evidence with conflict tests in
experimental animals indicates that 5-HT enhances anxiety, whereas results with
aversive stimulation of the dorsal periaqueductal gray point to an anxiolytic role
of 5-HT. To solve this contradiction, it has been suggested that the emotional
states determined by the two types of animal model are different. Conflict tests
would generate conditioned anxiety, whereas periaqueductal gray stimulation would
produce unconditioned fear, as evoked by proximal threat. Clinically, the former
would be related to generalized anxiety while the latter to PD. Thus, 5-HT is
supposed to facilitate anxiety, but to inhibit panic. This hypothesis has been
tested in the animal model of anxiety and panic named the elevated T-maze, in two
procedures of human experimental anxiety applied to healthy volunteers or panic
patients, and in CO2-induced panic attacks. Overall, the obtained results have
shown that drugs that enhance 5-HT function increase different indexes of anxiety,
but decrease indexes of panic. Drugs that impair 5-HT function have the opposite
effects. Thus, so far the predictions derived from the above hypothesis have been
fulfilled. (C) 2004 Elsevier Ltd. All rights reserved.
The early detection of prostate cancer and the aggressive treatment is the only
chance for a cure. The use of PSA-related screening techniques brings forward the
diagnosis of the disease by 5-10 years [1-3] While such early detection regimens
shift the stage at the time of detection towards locally confined disease, and
while there is no doubt that. early treatment is the only way of curing prostate
cancer, the application of screening in practice and healthcare policy remains
controversial. This is because there are uncertainties about the degree of ,,over-
diagnosis" which most probably results from screening, and from uncertainties about
the risk-benefit balance. Randomized studies will show whether early detection of
prostate cancer can reduce cancer-specific mortality. Conclusive data will not be
available before 2005 respectively 2008. At that time, only the validated complied
information about the risks and benefits of screening and about the possible
therapeutic consequences may provide a way out of this current dilemma [4]. A
synopsis of the "European Randomized Study of Screening for Prostate Cancer" was
given by F. H. Schroder in the British journal of Urology International, December
2003.
The present review critically examines the available empirical literature on coping
and panic disorder (PD). As a basis for the review, key terms are defined and
conceptual models are presented. The empirical literature on coping processes in
relation to PD is then critically reviewed with a specific focus on methodology.
For each section, primary conclusions are presented. In the final section,
directions for future research are provided both in terms of methodological and
conceptual issues. (C) 2004 Elsevier Ltd. All rights reserved.
To use behaviours as indicators of stress it is important to understand their
underlying causation. For a prey animal in the wild, such as a sheep, behavioural
responses have evolved to evade detection and capture by predators. The behavioural
responses of the wild ancestors of domestic sheep to the threat of predation are
characterised predominantly by vigilance, flocking, flight to cover and behavioural
inhibition once refuge has been reached Some limited defensive behaviours are seen,
mainly in females with young against small predators. Vigilance and flight distance
are affected by the animal's assessment of risk and are influenced by the
environment social group size, age, sex and reproductive condition, as well as by
previous experience with potential predators. Under conditions of stress, domestic
sheep show similar behavioural reactions to wild sheep, although the threshold at
which they are elicited may be elevated. This is particularly evident when
comparing less selected hill breeds with more highly selected lowland breeds, and
suggests that a continuum of responsiveness exists between wild and feral sheep,
through hill breeds to the lowland sheep breeds. However, this may be confounded by
the previous experience of the breeds, particularly their familiarity with humans.
Behavioural and neurobiological evidence suggests that although the behavioural
response to predators (vigilance, flight) is innate, the stimuli that elicit this
behavioural pattern may have a learned component. Since vigilance and flight
distances are affected by the animal's perception of threat, they may be useful
indices of stress in sheep and, as graded responses, give some indication of the
level of threat experienced by the sheep. Thus they may indicate the amount of fear
or distress experienced by the sheep and hence have the potential to be used in the
assessment of welfare states.
Anaphase is the stage of the cell cycle when the duplicated genome is separated to
opposite poles of the cell. The irreversible nature of this event confers a unique
burden on the cell and it is therefore not surprising that the regulation of this
cell cycle stage is complex. In budding yeast, a signaling network known as the Cdc
fourteen early anaphase release (FEAR) network and its effector, the protein
phosphatase Cdc14, play a key role in the coordination of the multiple events that
occur during anaphase, such as partitioning of the DNA, regulation of spindle
stability, activation of microtubule forces, and initiation of mitotic exit. These
functions of the FEAR network contribute to genomic stability by coordinating the
completion of anaphase and the execution of mitotic exit.
Anxiety, fear, and worry are variously described as facilitators and barriers of
breast cancer screening. However, several contradictions are evident in this
research. A review article described the literature regarding the relations among
fear, anxiety, and worry, along with emotion regulatory styles, and breast cancer
screening behaviors before critiquing it in an attempt to uncover preliminary
explanations for these discrepancies. Three main conclusions are drawn. First, it
is suggested that researchers need to clearly define the components of cancer and
the screening process that women are afraid of as each may bear a different
relation to screening behavior. Second, greater care needs to be taken to employ
psychometrically valid and reliable measures of fear and anxiety. Third, studies
need to more systematically test findings across the minority and ethnic groups at
greatest risk. A framework is presented and suggestions regarding the continued
development of this promising area of research are made.
One reason for the neglect of the role of positive factors in cognitive-behavioural
therapy (CBT) may relate to a failure to develop cognitive models that integrate
positive and negative cognitions. Bandura [Psychol. Rev. 84 (1977) 191; Anxiety
Res. 1 (1988) 77] proposed that self-efficacy beliefs mediate a range of emotional
and behavioural outcomes. However, in panic disorder, cognitively based research to
date has largely focused on catastrophic misinterpretation of bodily sensations.
Although a number of studies support each of the predictions associated with the
account of panic disorder that is based on the role of negative cognitions, a
review of the literature indicated that a cognitively based explanation of the
disorder may be considerably strengthened by inclusion of positive cognitions that
emphasize control or coping. Evidence to support an Integrated Cognitive Model
(ICM) of panic disorder was examined and the theoretical implications of this model
were discussed in terms of both schema change and compensatory skills accounts of
change processes in CBT. (C) 2004 Elsevier Ltd. All rights reserved.
An investigation was conducted into human fear of dogs and experiences of canine
aggression in an adult community sample (<(n)underbar >= 292). Consistent with
expectations, it was found that, while fear of dogs was relatively common (present
in almost half the respondents), fear of dog attacks was less so, and extreme fear
of dog attacks was very rare. Women, middle-aged and older adults were more likely
to fear dogs than men and younger adults, while older people were more likely than
younger ones to fear dog attacks. Reported encounters with canine aggression,
particularly threatening behavior, were relatively common, but having been attacked
by a dog was less strongly related to fear of dogs than having been threatened by a
dog. Logistic regression analyses revealed that being female, having been
threatened by a dog, and being older were strong predictors of dog-related fear
while being older and obtaining higher scores on a measure of trait anxiety
predicted fear of dog attacks. (c) 2004 International Society for Anthrozoology
Evidence for implication of cholecystokinin (CCK) in the neurobiology of panic
disorder is reviewed through animal and human pharmacological studies. The results
of these investigations raise two issues: (i) selectivity of action of CCK-2
agonists in anxiety disorders; and (ii) aberrations of the CCK system in anxiety
disorders, both of which are discussed.
A substantial number of patients with panic disorder and agoraphobia may remain
symptomatic after standard treatment (including selective serotonin reuptake
inhibitors, tricyclic antidepressants, benzodiazepines, or irreversible monamine
oxidase inhibitors). In this review, recommendations for the treatment of patients
with panic disorder and agoraphobia who do not respond to these drugs are provided.
Nonresponse to drug treatment could be defined as a failure to achieve a 50%
reduction on a standard rating scale after a minimum of 6 weeks of treatment in
adequate dose. When initial treatments have failed, the medication should be
changed to other standard treatments. In further attempts at treatment, drugs
should be used that have shown promising results in preliminary studies, such as
venlafaxine. Combination treatments may be used, such as the combination of an
selective serotonin reuptake inhibitor and a benzodiazepine. Psychological
treatments such as cognitive-behavioral therapy have to be considered in all
patients, regardless whether they are nonresponders or not. According to existing
studies, a combination of pharmacologic treatment with cognitive-behavioral therapy
can be recommended.
An integrated theoretical conceptualization of the co-occurrence of panic disorder
and smoking (PDSM) is presented. First, the nature and prevalence of this
apparently costly, yet largely unrecognized, co-occurrence of health care problems
is described. Second, a theoretical analysis regarding how smoking may negatively
impact panic disorder is described. Third, the negative impact of panic disorder on
smoking outcomes is discussed. Finally, primary implications of this
conceptualization for the research and treatment of individuals with PDSM are
elaborated, including the need to assess for smoking among persons with panic
disorder and the potential need for specialized treatment approaches.
We have shown previously that psychological stress (predator exposure) impairs
spatial memory in rats. We have extended that finding here to show that predator
stress selectively impaired recently acquired (hippocampal-dependent) spatial
working memory without affecting long-term (hippocampal-independent) spatial
reference memory. We also investigated why predator exposure impairs memory. Was
spatial memory impaired because of the fear-provoking aspects of predator exposure
or only because the cat was a novel and arousing stimulus? If the latter
possibility was correct, then any novel and arousing stimulus, independent of its
emotional valence (i.e., aversive or appetitive), would impair memory. We found
that spatial working memory was not impaired when the male rats were exposed to a
sexually receptive female rat, a stimulus that was novel and arousing to them, but
not aversive. We also found that there was an equivalent increase in serum
corticosterone levels in male rats exposed to either a cat or a female rat, but
only the cat-exposed rats exhibited a significant correlation between
corticosterone levels and impaired memory. Overall, this series of experiments
demonstrates that (1) predator stress selectively impaired working (hippocampal-
dependent), but not reference (hippocampal-independent), memory; (2) a fear-
provoking stimulus, and not merely novelty and increased arousal, impaired spatial
memory; and (3) increased corticosterone levels correlated with impaired spatial
working memory only under predator exposure, that is, fear-provoking conditions.
Cognitive impairment in patients with panic disorder (PD) has been studied using
event-related potentials (ERPs). However, previous studies obtained ERP data only
at a few scalp sites, and seldom investigated N200 measurements from the difference
waveforms. In the present study, auditory ERPs were recorded at 16 scalp sites
during an active discrimination task of oddball paradigm. Fourteen PD patients (8
with agoraphobia; 6 without agoraphobia) were compared with 14 sex- and age-matched
control subjects. For the nontarget waveforms, P2 amplitude was reduced in PD
patients. For the target waveforms, a topographical difference between female PD
patients and female controls was found for N200 amplitude, which attenuated in
female PD patients over the parietal area. Two subcomponents of N200, N2a and N2b,
were measured from the difference waveforms. A significant group difference was
found for N2b amplitude, which reduced in PD patients compared with unaffected
control subjects. It is suggested that N2b reduction reflects an abnormally
controlled processing of stimulus information in PD. (C) 2003 Elsevier Inc. All
rights reserved.
The bed nucleus of the stria terminalis is a limbic forebrain structure that
receives heavy projections from, among other areas, the basolateral amygdala, and
projects in turn to hypothalamic and brainstem target areas that mediate many of
the autonomic and behavioral responses to aversive or threatening stimuli. Despite
its strategic anatomical position, initial attempts to implicate the bed nucleus of
the stria tenninalis in conditioned fear were largely unsuccessful. Recent studies
have shown, however, that the bed nucleus of the stria tenninalis does participate
in certain types of anxiety and stress responses. In this work, we review these
findings and suggest from the emerging pattern of evidence that, although the bed
nucleus of the stria terminalis may not be necessary for rapid-onset, short-
duration behaviors which occur in response to specific threats, the bed nucleus of
the stria terminalis may mediate slower-onset, longer-lasting responses that
frequently accompany sustained threats, and that may persist even after threat
termination. (C) 2003 Elsevier Science B.V. All rights reserved.
As is the case for normal individual variation in anxiety levels, the conditions
panic disorder, agoraphobia and other phobias have a significant genetic basis.
Recent reports have started to untangle the genetic relationships between
predispositions to anxiety and anxiety disorders.
The periaqueductal gray (PAG) has been traditionally considered to be an exit relay
for defensive responses. Functional mapping of its subdivisions has advanced our
knowledge of this structure, but synthesis remains difficult mainly because results
from lesion and stimulation studies have not correlated perfectly. After using a
strategy that combined both techniques and a reevaluation of the available
literature on PAG function and connections, we propose here that freezing could be
mediated by different PAG subdivisions depending on the. presence of immediate
danger or exposure to related signaling cues. These subdivisions are separate
functional entities with distinct descending and ascending connections that are
likely to play a role in different defensive responses. The existence of ascending
connections also suggests that the PAG is not simply a final common path for
defensive responses. For example, the possibility that indirect ascending
connections to the cingulate cortex could play a role in the expression of freezing
evoked by activation of the neural substrate of fear in the dorsal PAG has been
considered.
Diagnostic symptom provocation has a long tradition in medicine. In psychiatry,
symptom provocation studies are used to study the pathophysiology and treatment of
disorders. Sudden and unexpected panic attacks have a characteristic course and a
typical pattern of somatic, cognitive, emotional, and behavioral symptoms.
Beginning with the study of Pitts and McClure, who described the panicogenic
activity of sodium lactate,the experimental induction of panic attacks with
different challenges has been used to characterize the neurobiology of anxiety.
Furthermore, experimentally induced panic attacks can be used to study possible new
treatment approaches. The anxiolytic activity of atrial natriuretic peptide
suggests that modulation of natriuretic peptide receptors with nonpeptidergic
ligands may be a new treatment approach. Experimentally induced panic attacks are a
tool to characterize the neurobiology of anxiety and panic and may be used to
develop new treatment approaches.
We propose that fear and power-dominance drive motivation are generated by the
presence of elevated plasma and cerebrospinal fluid (CSF) levels of certain peptide
hormones. For the fear drive, the controlling hormone is corticotropin releasing
factor, and we argue that elevated CSF and plasma levels of this peptide which
occur as a result of fear-evoking and other stressful experiences in the recent
past are detected and transduced into neuronal activities by neurons in the
vicinity of the third ventricle, primarily in the periventricular and arcuate
hypothalamic nuclei. For the power-dominance drive, we propose that the primary
signal is the CSF concentration of vasopressin, which is detected in two
circumventricular organs, the subfornical organ and organum vasculosum of the
lamina terminalis. We suggest that the peptide-generated signals detected in
periventricular structures are transmitted to four areas in which neuronal
activities represent fear and power-dominance: one in the medial hypothalamus, one
in the dorsolateral quadrant of the periaqueductal gray matter, a third in the
midline thalamic nuclei, and the fourth within medial prefrontal cortex. The
probable purpose of this system is to maintain a state of fear or anger and
consequent vigilant or aggressive behavior after the initial fear- or anger-
inducing stimulus is no longer perceptible. We further propose that all the
motivational drives, including thirst, hunger and sexual desire are generated in
part by non-steroidal hormonal signals, and that the unstimulated motivational
status of an individual is determined by the relative CSF and plasma levels of
several peptide hormones. (C) 2003 Elsevier Science Ltd. All rights reserved.
Severe fear of childbirth complicates 6% to 10% of parturients and is manifested as
nightmares, physical complaints and difficulties in concentrating on work or on
family activities. Very often fear of childbirth leads to request for an elective
cesarean section (CS). In Finland, Sweden, and the United Kingdom, fear of
childbirth or maternal request is the reason for about 7-22% of CS births. Fear of
childbirth is as common in nulliparous as in parous women. Fear of labor pain is
strongly associated with the fear of pain in general, and a previous complicated
childbirth or inadequate pain relief are the most common reasons for requesting a
CS among parous women. Previous psychological morbidity and a great number of daily
stressors expose a woman to a great risk of fear of childbirth. Fear of childbirth
is not an isolated problem but associated with the woman's personal
characteristics, mainly general anxiety, low self-esteem, and depression, and
dissatisfaction with their partnership, and lack of support. Also the partners of
women with fear have a certain pattern of low psychological well-being, resulting
in low life-satisfaction, dissatisfaction with partnerships, and depression. A
vivid debate about the woman's right to choose the mode of delivery is going on in
obstetric literature, but discussion on the reasons for women to request a CS, or
on the possibilities to help them overcome the fear of vaginal childbirth is
scanty. Preliminary Swedish and Finnish reports demonstrated the results of
treatment during pregnancy, when more than half of the women withdrew their request
after being able to discuss their anxiety and fear, and vaginal deliveries after
treatment were successful.
Gamma aminobutyric acid (GABA) is the most important inhibitory neurotransmitter in
the central nervous system. Its action is exerted in the brain through GABA(A)
receptors which belong to the family of ligand-gated ion channels. These GABA(A)
receptors consist of various subunits and are targets for benzodiazepines,
barbiturates, neuroactive steroids, and distinct anticonvulsive agents. Meanwhile,
there is considerable evidence that a dysfunction of GABA(A) receptors plays an
important role in the pathophysiology of panic disorder. The anxiolytic effects of
benzodiazepines are widely used in the treatment of panic disorder. Nevertheless,
side effects of benzodiazepines, e.g., dependency and withdrawal symptoms, limit
their use as a long-term treatment. In the meantime, antidepressants, especially
selective serotonin reuptake inhibitors, comprise first-line treatment in the
pharmacotherapy of panic disorder. They interfere with the synthesis of endogenous
neuroactive steroids that allosterically modulate GABA(A) receptor function. With
regard to experimentally evoked panic attacks in patients with panic disorder and
healthy controls, recent investigations demonstrated that enhancing endogenous GABA
through the blockade of the GABA transaminase by vigabatrin or inhibition of GABA
transporters by tiagabine may exert anxiolytic effects. This novel strategy
targeting the GABA binding site of the GABA(A)/benzodiazepine receptor complex and
specific agonists for the benzodiazepine binding site present interesting
perspectives for the future pharmacotherapy of panic disorder.
This study demonstrates that microinjection of an AMPA/kainate glutamate antagonist
elicits motivated fear and feeding behaviour mapped along rostrocaudal gradients of
positive-to-negative valence in nucleus accumbens shell (similar to rostrocaudal
shell gradients recently reported for GABA agonist microinjections). Rats received
rostral or caudal microinjections of the glutamate AMPA/kainate receptor antagonist
DNQX (0, 50,450 or 850 ng in 0.5 muL) or the NMDA receptor antagonist MK-801 (0,
0.5, 1 or 2 mug in 0.5 muL), into medial accumbens shell prior to behavioural tests
for fear, feeding or conditioning of place preference or avoidance. Another group
received rostral or caudal microinjections of DNQX in nucleus accumbens core.
Rostral shell DNQX microinjections potently increased appetitive food intake and
established only weak conditioned place avoidance. Caudal shell DNQX
microinjections elicited defensive treading behaviour, caused rats to defensively
bite the experimenter and emit fearful distress vocalizations when handled, and
established strong conditioned place avoidance. By contrast, no rostrocaudal
gradients of motivational bivalence were produced by microinjections of the
glutamate AMPA/kainate receptor antagonist DNQX into the core, or by
microinjections of the NMDA antagonist MK-801 into the shell. Our results indicate
that appetitive and aversive motivation is carried in anatomically differentiated
channels by mesocorticolimbic glutamate signals to microcircuits in the medial
shell. Hyperpolarization of local shell ensembles by AMPA/kainate glutamate
receptor blockade elicits fear and feeding behaviours mapped along distinct
positive-to-negative rostrocaudal gradients.
This article provides an overview of cognitive-behavioral therapy (CBT) for panic
disorder. CBT is currently considered a first-line treatment for panic disorder. It
offers benefit after short-term intervention, typically consisting of 12-15
sessions conducted in either an individual or a group format. The treatment focuses
on the elimination of the patterns that underlie and perpetuate the disorder.
Through CBT, patients learn about the nature of the disorder and acquire a set of
strategies that counter the fears of panic attacks themselves, and break the
recurring cycle of anticipatory anxiety, panic, and agoraphobic avoidance. The
collaborative format of treatment, and a focus on elimination of core fears may be
factors in enhancing longer-term outcome. In this article, we review the efficacy
of CBT as a first-line treatment, a strategy for medication nonresponders, a
replacement strategy for patients who wish to discontinue pharmacotherapy, and a
potential preventive strategy for at-risk individuals. We also discuss some of the
complex issues involved with combination-treatment strategies.
Fear can be conceived as a functional defense behavior system representing a part
of the innate species-specific behavioral repertoire (ethogram). basic to the
survival of individuals and species. Its function is to protect living beings
against dangerous, threatening and aversive situations. A distinction is made
between anticipatory defense behaviors released by potential dangers and those
elicited by effective dangers, especially predators. The neural mechanisms serving
the defense system constitute a hierarchical network with the amygdala as point of
convergence of the various threatening stimuli. The central nucleus of the amygdala
projects to the midbrain periaqueductal gray (PAG), the hypothalamus and the
brainstem which coordinate various defensive responses such as flight, defensive
fight, freezing, avoidance reactions, submissive postures. tonic immobilization,
hypoalgesia and autonomic arousal. These circuits may be activated either by
unconditioned or conditioned stimuli. (C) 2003 Editions scientifiques et medicales
Elsevier SAS. All rights reserved.
The latest studies on psychopathology and biology of attacks and other findings
related to sleep in panic disorder are reviewed. While some of the newer articles
doubt that nocturnal panics present a more severe variation of panic disorder,
older studies and some newer articles support this notion. Some studies suggest
that nocturnal panic maybe also be associated with other, more severe pathology.
This interesting syndrome, or variant of disorder, may have its own etiology,
psychopathology, and underlying biology. (C) 2003 Wiley-Liss, Inc.
The purpose of this paper is (1) to specify, among studies on the links between
marital relationship and cognitive-behavioral treatment of panic disorder with
agoraphobia (PDA), the conceptual and methodological limitations that may have
produced inconsistent results in this field so far; and (2) to propose avenues of
research that will help in remedying current weaknesses and answering important
questions in this area. Following definition of PDA and a survey of its
socioeconomic consequences, the authors examine results of the various ways
research has tried to specify the links between marital relationship and the
development, maintenance, and treatment of this disorder: the study of major life
events before and after the onset of PDA, interpersonal problems and quality of
marital relationship, in the presence of PDA, the links between marital
relationship and PDA treatment outcome, variability of experimental outcomes
according to types of measure used to study these links, the effect of the spouse
as co-therapist in PDA treatment, and the impact of a PDA treatment based on
marital communication and problem-solving. Research hypotheses and methodological
procedures are proposed to improve understanding of PDA and its treatment outcome.
(C) 2003 Elsevier Science Ltd. All rights reserved.
Objective: This paper examines the relation between coronary artery disease (CAD)
and panic disorder (PD), discusses the implications of this relation to the general
medical system, and suggests future assessment and intervention strategies for
emergency departments. Method: We reviewed the literature on CAD and PD using
Medline and PsycINFO. Results: PD is more expensive to our nonpsychiatric, general
medical system than any other psychiatric condition. The main reason for PD
patients' continued use of general medicine for their psychological symptoms is
that their PD remains undiagnosed. In the emergency room (ER), PD patients with
chest pain have their PD go undiagnosed about 98% of the time. By having ERs
implement specific assessment and intervention strategies for patients presenting
with chest pain, the savings to the general medical system could be substantial.
Conclusions: By improving recognition of PD in the ER, there is the potential to
generate large savings in general medical care. With the availability of
empirically supported or effective psychological and pharmacologic treatments for
PD, appropriately diagnosing and subsequently treating patients with PD may prevent
them from experiencing many years of disability and higher rates of fatal coronary
events.
1. Considerable progress has been made over the past 20 years in relating specific
circuits of the brain to emotional functions. Much of this work has involved
studies of Pavlovian or classical fear conditioning, a behavioral procedure that is
used to couple meaningless environmental stimuli to emotional (defense) response
networks. 2. The major conclusion from studies of fear conditioning is that the
amygdala plays critical role in linking external stimuli to defense responses. 3.
Before describing research on the role of the amygdala in fear conditioning,
though, it will be helpful to briefly examine the historical events that preceded
modern research on conditioned fear.
Fear (i.e., decreased percentage time spent on open-arm exploration) in the
elevated plus-maze can be potentiated by prior inescapable stressor exposure, but
not by escapable stress. The use of fear-potentiated plus-maze behaviour has
several advantages as compared to more traditional animal models of anxiety. (a) In
contrast to the traditional (spontaneous) elevated plus-maze, which measures innate
fear of open spaces, fear-potentiated plus-maze behaviour reflects an enhanced
anxiety state (allostatic state). This "state anxiety" can be defined as an
unpleasant emotional arousal in face of threatening demands or dangers. A cognitive
appraisal of threat is a prerequisite for the experience of this type of emotion.
(b) Depending on the stressor used (e.g., fear of shock, predator odour, swim
stress, restraint, social defeat, predator stress (cat)), this enhanced anxiety
state can last from 90 min to 3 weeks. Stress effects are more severe when rats are
isolated in comparison to group housing. (c) Drugs can be administered in the
absence of the original stressor and after stressor exposure. As a consequence,
retrieval mechanisms are not affected by drug treatment. (d) Fear-potentiated plus-
maze behaviour is sensitive to proven/putative anxiolytics and anxiogenics which
act via mechanisms related to the benzodiazepine-gamma-aminobutyric acid receptor,
but it is also sensitive to corticotropin-releasing receptor antagonists and
glucocorticoid receptor antagonists and serotonin receptor agonists/antagonists
complex (high predictive validity). (e) Fear-potentiated plus-maze behaviour is
very robust, and experiments can easily be replicated in other labs. (f) Fear-
potentiated plus-maze behaviour can be measured both in males and females. (g)
Neural mechanisms involved in contextual fear conditioning, fear potentiation and
state anxiety can be studied Thus, fear-potentiated plus-maze behaviour may be a
valuable measure in the understanding of neural mechanisms involved in the
development of anxiety disorders and in the search for novel anxiolytics. Finally,
the involvement of corticotropin-releasing factor and corticosteroid-corticotropin-
releasing factor interactions in the production of fear-potentiated plus-maze
behaviour are discussed. (C) 2003 Elsevier Science B.V. All rights reserved.
Pregnancy is a major life event for all women. However, when a psychiatric disorder
is added to or exacerbated by the pregnancy then the problem requires expert
knowledge from more than one area of medicine. This paper looks at pregnancy and
the relationship with depression, eating disorders, and pathological fear of
childbirth or tokophobia. It also examines the outcome for these women and their
babies. Mental illness is a serious concern. It is now recognised that death from
suicide is the leading cause of maternal death overall. Research in these areas is
relatively sparse but an attempt is made to collate what is known.
Risk issues become complicated when scientific evidence concerning a potential
environmental exposure is equivocal; particularly when many argue,that the public
health benefits of a policy action outweigh any potential negative health effects.
Chlorinated drinking water, and chlorinated disinfection byproducts (CDBPs) that
are formed during the disinfection process, represent a useful case-study for
examining these complications. We conduct a media analysis of chlorinated drinking
water stories in the Canadian print media from 1977 to 2000. We examine media
presentations of science compared to framings by scientists, regulators, the
chlorine industry, water utility representatives, and non-governmental
organizations of the CDBP issue based on key informant interviews. We argue that
there are two main framings of the debate, each of which are powerful in
constructing risk perceptions. On the one hand, many frame the debate as a
'voluntary' risk: we choose chlorine disinfection to protect against microbial
risks with a possible adverse consequence of that protection. On the other hand,
others frame the issue as an 'involuntary' risk: chlorine disinfection was a
'choice' imposed by public health and water utility officials; a choice that
carries a potential cancer risk, and alternative disinfection technologies are
advocated. We demonstrate these different frames by examining metaphorical
constructs of water, chlorine and cancer contained within them. (C) 2002 Elsevier
Science Ltd. All rights reserved.
Panic disorder (PD) in children and adolescents is a disabling and chronic
condition, which is accompanied by psychosocial and academic difficulties, both
during adolescence and into adulthood. In this article, the prevalence, clinical
characteristics, risk factors, comorbid states, differential diagnosis, and
treatment of PD are reviewed. Although PD was thought to be rare in children and
adolescents, the prevalence of PD in community samples ranges between 0.5% and 5.0,
and in pediatric psychiatric clinics from 0.2% to 10%. Panic attacks are reported
to be equally prevalent in males and females. Clinical studies have shown that the
majority of the PD pediatric patients receiving consultation in clinics are older
adolescents, Caucasian, female, and middle class. Up to 90% of children and
adolescents with PD have other anxiety disorders (generalized anxiety
disorder/overanxious disorder, separation anxiety disorder, social phobia or
agoraphobia), or mood disorders (major depressive disorder or bipolar disorder). PD
patients can be misdiagnosed or having neurologic, cardiovascular, pulmonary, or
gastrointestinal illness. Psycho-education and psychosocial treatments are
recommended, and it appears that selective serotonin reuptake inhibitors (SSRIs)
are a safe and promising treatment for children and adolescents with PD. The
clinical characteristics, long-term course, and treatment of PD in children and
adolescents needs to be further assessed by well-designed studies.
The Mouse Defense Test Battery was developed from tests of defensive behaviors in
rats, reflecting earlier studies of both acute and chronic responses of laboratory
and wild rodents to threatening stimuli and situations. It measures flight,
freezing, defensive threat and attack, and risk assessment in response to an
unconditioned predator stimulus, as well as pretest activity and postthreat
(conditioned) defensiveness to the test context. Factor analyses of these indicate
four factors relating to cognitive and emotional aspects of defense, flight, and
defensiveness to the test context. In the Mouse Defense Test Battery, GABA(A)-
benzodiazepine anxiolytics produce consistent reductions in defensive threat/attack
and risk assessment, while panicolytic and panicogenic drugs selectively reduce and
enhance, respectively, flight. Effects of GABA(A)-benzodiazepine, serotonin, and
neuropeptide ligands in the Mouse Defense Test Battery are reviewed. This review
suggests that the Mouse Defense Test Battery is a sensitive and appropriate tool
for preclinical evaluation of drugs potentially effective against defense-related
disorders such as anxiety and panic. (C) 2003 Elsevier Science B.V. All rights
reserved.
While the 'trafficking in persons' is a problem that has long plagued the
international community, sensationalized media coverage and governmental anti-
organized crime initiatives have produced a new set of discursive practices that
conflate violent crime against women with complex forms of post-communist gendered
migration. These discourses refer to many different forms of exploitation and
migration as 'trafficking in women for purposes of sexual exploitation'. In other
words, they portray all international, often illegal, migration and labour as acts
of violated gender and raced innocence and of international organized crime. In
this frame, criminalization of all activities related to trafficking appears to be
the most logical and effective means of redressing this problem. It simultaneously,
however, subjects all East European migrant sex workers to categorizations that
defuse what may function as the challenges presented by their sovereign and
symbolic boundary transgressions. A focus on crime and violated borders (rather
than on the conditions under which women migrate or are forced to work) extends
barriers to migration and renders it more dangerous for women while not necessarily
hindering movement or assisting the actual victims. Because it emphasizes the role
of state-based institutions in fighting international organized crime,
criminalization also serves as a means through which practices of 'statecraft' work
to reiterate the privileged place of the state in IR. As such, discourses of sex-
trafficking provide a particularly incisive site at which to examine European
integration, immigration, 'globalization' and their effects on IR in a gendered and
race-cognizant frame.
Background: The Royal Australian and New Zealand College of Psychiatrists is co-
ordinating the development of clinical practice guidelines (CPGs) in psychiatry,
funded under the National Mental Health Strategy (Australia) and the New Zealand
Health Funding Authority. Method: For these guidelines, the CPG team reviewed the
treatment outcome literature, consulted with practitioners and patients and
conducted a meta-analysis of recent outcome research. Treatment recommendations:
Education for the patient and significant others covering: (i) the nature and
course of panic disorder and agoraphobia; (ii) an explanation of the
psychopathology of anxiety, panic and agoraphobia; (iii) rationale for the
treatment, likelihood of a positive response, and expected time frame. Cognitive
behaviour therapy (CBT) is more effective and more cost-effective than medication.
Tricyclic antidepressants (TCAs) and serotonin selective reuptake inhibitors are
equal in efficacy and both are to be preferred to benzodiazepines. Treatment choice
depends on the skill of the clinician and the patient's circumstances. Drug
treatment should be complemented by behaviour therapy. If the response to an
adequate trial of a first-line treatment is poor, another evidence-based treatment
should be used. A second opinion can be useful. The presence of severe agoraphobia
is a negative prognostic indicator, whereas comorbid depression, if properly
treated, has no consistent effect on outcome.
In 1989, while reporting the well-publicized attack on a female jogger in New York
City, the media discovered wilding, a newly stylized word used to describe sexual
violence committed by a group of urban teens. Sociologically, the term wilding
became particularly significant due to its racial connotation, perpetuating a
stereotype of young Black (and Latino) males belonging to a dangerous class. This
work explores the contours of moral panic over wilding by attending to elements of
race, class, and fear of crime, especially as they manifest in the media. The
findings contribute to a critical understanding of youth in society by offering an
interpretation of wilding, a distinctive form of moral panic that symbolizes not
only a threat to society at large but also to a political economy that reproduces
racial and social disparities.
In this study, we aimed to investigate event-related potential (ERP) changes in
panic disorder (PD) and generalised anxiety disorder (GAD) and to determine whether
two disorders are different from each other in terms of endogenous potentials. A
total of 35 outpatients who fully met DSM-III-R criteria for PD (8 males and 27
females) were included in this study as the PD group. The GAD group consisted of 30
subjects (5 males and 25 females) who met DSM-III-R GAD criteria, The control group
consisted of 29 healthy age and sex-matched volunteers (5 males and 24 females)
having no history of psychiatric or neurological illness. ERPs were recorded by
using auditory "odd-ball two-tone discrimination task" method. It was found that
there was significant prolongation in P3 latency in the PD group compared to the
GAD and control groups, Our study suggests that there are some disturbances in
early information processing in patients with PD but not with GAD. (C) 2001
Elsevier Science Inc. All rights reserved.
Smallpox is a disease that followed humanity for thousands of years up until 30
years ago. It was possible to eradicate, because an effective live vaccine from
crossreacting vaccinia could be developed. Twenty years have passed since
vaccinations stopped and very few people are protected against the disease today.
Variola today has become an object of discussion due to the possibility that it can
be used as a bioweapon. Due to the number of complications that can be expected a
general vaccination is probably not possible. Research is ongoing to develop new
vaccines. Many countries are improving their capabilities to respond to a renewed
threat of a smallpox epidemic.
This article reviews the research on driving-related fear (DRF). Until recently,
research has concentrated almost exclusively on the effect of motor vehicle
accidents (MVAs) on subsequent levels of DRF. However, recent findings have
suggested that MVAs are not solely responsible for this fear reaction, and that
non-MVA driving fear can be just as strong. Studies of the broader driving-fearful
population have encountered difficulty with diagnostic conceptualisation of DRF,
although some have investigated a possible typology of DRT. Driving skill has been
a neglected issue in the DRF research, and may prove to be a useful part of
assessment and remediation of this potentially debilitating problem. Issues of
definitional inconsistency are highlighted, and suggestions are made for several
directions that future research might profitably take. (C) 2002 Elsevier Science
Inc. All rights reserved.
The amygdala modulates memory consolidation and the storage of emotionally relevant
information in other brain areas, and itself comprises a site of neural plasticity
during aversive learning. These processes have been intensively studied in
Pavlovian fear conditioning, a leading aversive learning paradigm that is dependent
on the structural and functional integrity of the amygdala. The rapidness and
persistence, and the relative ease, with which this conditioning paradigm can be
applied to a great variety of species have made it an attractive model for
neurochemical and electrophysiological investigations on memory formation. In this
review we summarise recent studies which have begun to unravel cellular processes
in the amygdala that are critical for the formation of long-term fear memory and
have identified molecular factors and mechanisms of neural plasticity in this brain
area.
The Antiterrorism and Effective Death Penalty Act (AEDPA), enacted by Congress in
1996 in the wake of the Oklahoma City bombing, curtailed habeas corpus review in
numerous respects, including establishing severe restrictions on prisoners' ability
to file successive federal habeas corpus petitions. In this Article, Professor
Bryan Stevenson examines the origins, nature, and effects of these expanded
restrictions on successive filings. In reviewing the history of the legal system's
treatment of successive petitions, Stevenson demonstrates that the Supreme Court's
and Congress's choices in this area were shaped not only by doctrinal
considerations but also political variables and unexamined assumptions about
prisoners and their lawyers. Stevenson uses actual examples to illustrate the
apparently unintended consequences of AEDPA's successive petition provisions,
including the foreclosure of certain types of constitutional claims and the
injection of numerous procedural complexities that undermine reliability and
fairness. The Article identifies a variety of potential remedies, including
congressional reform, liberal judicial interpretation of the statute's provisions,
expanded use of the Supreme Court's original habeas corpus jurisdiction, and
alternative procedural devices like Federal Rule of Civil Procedure 60(b) and
expanded successive state postconviction review. Stevenson concludes that these
devices are a necessary part of a much larger process of rethinking America's
flawed capital punishment system.
Based on the available literature on activation of brain structures by fear- and
anger-inducing stimuli, on the effects of electrical and chemical stimulation and
lesions of candidate structures, and on connectional data, we propose that both the
fear and power-dominance drives are represented in four distinct locations: the
medial hypothalamus, lateral/dorsolateral periaqueductal gray, midline thalamic
nuclei, and medial prefrontal cortex. The hypothalamic fear representation is
located in the dorsomedial and posterior hypothalamic nuclei, the midbrain
representation in the caudal part of the lateral/dorsolateral periaqueductal gray,
the thalamic representation primarily in parts of the paraventricular and reuniens
thalamic nuclei, and the cortical representation in prelimbic cortex. The
hypothalamic power-dominance representation is located in the anterior hypothalamic
nucleus, dorsomedial aspect of the ventromedial nucleus, and in adjacent parts of
the medial preoptic area. The corresponding midbrain representation occurs in
rostral part of the lateral/dorsolateral periaqueductal gray, and the thalamic
representation in parts of the paraventricular, parataenial, and reuniens thalamic
nuclei. We discuss sensory/mnemonic inputs to these representations, and outputs to
premotor structures in the medulla, caudate-putamen, and cortex, and their
differential contributions to involuntary, learned sequential, and voluntary motor
acts. We examine potential contributions of neuronal activities in these
representations to the subjective awareness of fear and anger. (C) 2002 Elsevier
Science Ltd. All rights reserved.
Male Fischer 344 rats received either tap water or water containing 250 ppm lead
for 90 days prior to training in either Pavlovian fear conditioning or consummatory
contrast, an aversive reward reduction paradigm. In Experiment 1, lead-exposed and
-unexposed rats were trained in operant chambers over a 6-min session. After 3 min
elapsed, three tone-shock pairings were presented over the remainder of the
session. Rats then received 7 days of extinction training in an identical procedure
with only tones presented, no shocks. Lead-exposed rats exhibited greater
behavioral suppression to both the contextual and auditory cues that predicted
shock. In Experiment 2, rats were placed in operant chambers daily and allowed to
consume either a 15% or a 5% fructose solution for 7 days. On Day 8, the rats
consuming the 15% fructose solution were shifted to the 5% solution for 3 days.
Lead-exposed rats did not differ from their controls in either initial consumption
of either solution. or in the suppression of their consumption after shifting to
the 5% solution. Taken together, these findings suggest that lead impairs the
extinction of fear conditioning and this finding is not due to a nonspecific
increase in aversive emotionality. (C) 2002 Elsevier Science Inc. All rights
reserved.
People exposed to high altitudes often experience somatic symptoms triggered by
hypoxia, such as breathlessness, palpitations, dizziness, headache, and insomnia.
Most of the symptoms are identical to those reported in panic attacks or severe
anxiety. Potential causal links between adaptation to altitude and anxiety are
apparent in all three leading models of panic, namely, hyperventilation (hypoxia
leads to hypocapnia), suffocation false alarms (hypoxia counteracted to some extent
by hypocapnia), and cognitive misinterpretations (symptoms from hypoxia and
hypocapnia interpreted as dangerous). Furthermore, exposure to high altitudes
produces respiratory disturbances during sleep in normals similar to those in panic
disorder at low altitudes. In spite of these connections and their clinical
importance, evidence for precipitation of panic attacks or more gradual increases
in anxiety during altitude exposure is meager. We suggest some improvements that
could be made in the design of future studies, possible tests of some of the
theoretical causal links, and possible treatment applications, such as systematic
exposure of panic patients to high altitude. (C) 2002 Wiley-Liss, Inc.
It is axiomatic that the capacity to experience fear is adaptive, enabling rapid
and energetic response to imminent threat or danger. Despite the generally accepted
utility of functional fear, the nature of maladaptive fear remains controversial.
There is still no consensus about how specific fears and phobias are acquired and
modulated. Two major schools of thought are apparent: those suggesting
dysfunctional fear arises largely as the result of associative-conditioning
processes versus those who favour more biologically based etiological explanations.
In this regard, the non-associative model of fear acquisition postulates the
existence of a limited number of innate, evolutionary-relevant fears, while
emphasising conditioning modes of onset for evolutionary-neutral fears. Recent
retrospective and longitudinal studies have tested predictions from the non-
associative model. In general, findings support non-associative hypotheses and are
difficult to reconcile with neo-conditioning explanations of fear acquisition.
These data suggest that four pathways to fear may provide the most parsimonious
theory of fear etiology. The theoretical and practical implications of adding a
fourth, non-associative path to Rachman's (Behav. Res. Ther. (1977) 15, 375-387)
three 'associative' pathways are discussed. Unresolved issues requiring further
investigation are considered. (C) 2002 Elsevier Science Ltd. All rights reserved.
In this paper, panic disorder is described and the possible causes are reviewed. A
hierarchical organization is presented in which causes extend from general causes
of neurotic disorders to specific causes of particular symptoms. One particular
cause of relevance to panic disorder is anxiety sensitivity. The pharmacological
and psychological treatments for panic disorder are then reviewed and discussed in
the context of anxiety sensitivity. (C) 2002 Lippincott Williams Wilkins.
There is consistent support for the efficacy of cognitive-behavior therapy (CBT) to
aid the successful discontinuation of benzodiazepine (BZ) medication in patients
with panic disorder, and help these individuals maintain treatment gains while off
medication. In this article, we provide a conceptual model for BZ discontinuation
difficulties in patients with panic disorder. Outcome studies are reviewed, and are
placed in the context of other evidence for the efficacy of CBT in patients with
this disorder.
This report focuses on a case of major depression and panic disorder after heart
transplantation. Due to these disorders, the male patient's compliance with
cardiological treatment became increasingly insufficient. There are no controlled
studies on psychopharmacological opportunities in cases such as this one. The
patient was treated with sertraline and the outcome was healthy, without
cardiovascular adverse effects or drug-drug interactions.
Variations in the normal regulation of the mitotic cell cycle can lead to such
global cellular changes as differential development or malignant transformation.
Studies on the control of mitosis are particularly important to discover the
details of the basic mechanisms responsible for normal cell division, as well as to
learn about strategies employed by cancerous cells to indefinitely proliferate. The
past years have brought noteworthy progress in elucidating the molecular pathways
that regulate crucial events during mitosis such as: chromosome condensation,
formation of the mitotic spindle, chromosome segregation, cytokinesis, and
disassembly of the mitotic spindle.
It is proposed that alcoholism and panic disorder/agoraphobia demonstrate in part
common genetic and environmental origins. Shared subthreshold symptom patterns in
the parents' generation could confirm the proposed genetic role in alcoholism and
panic disorder/ agoraphobia, even if the parents do not fulfil the diagnostic
criteria for a primary psychiatric diagnosis. This is the first family study of
exploratively analyzing subthreshold symptoms in both disorders. The authors
investigated families with panic disorder agoraphobia and/or alcoholism with the
Munich-Composite International Diagnostic Interview (M-CIDI). We documented the
diagnoses according to Diagnostic and Statistical Manual of Mental Disorders,
Fourth Edition (DSM-IV) criteria and subdivided the answers of the probands into 16
subthreshold diagnostic groups comprising 259 single items. We found statistically
significant correlations of subthreshold syndrome profiles in the parents of
patients with panic disorder/agoraphobia and alcoholism, The presented method of
analyzing syndrome profiles in a family study seems to be a possibility to
demonstrate references to genetic links between patients and parents in anxiety-
and alcohol-related disorders, (C) 2002 Elsevier Science Inc. All rights reserved.
The operation No. 00447 of July 30th 1937 against former kulaks, criminals,
religious groups and communities, former members of political parties, former
members of the Tsarist machinery of state, Cossacks and Whites, constituted the
most important single campaign of mass-arrests carried out by the secret police.
During the 15 months of the campaign approximately half of all "political"
verdicts, including executions, can be attributed to this order. Part Tow of our
publication deals with the victims of Order No. 00447. This is in contrast to
exiting research which is restricted to the history of the perpetrators. For
example, we devote our interest to the "criminals and marginal elements" who up
until now have not been rehabilitated, although they were mostly executed on the
basis of petty offences. In conclusion, we attempt to place the two parts of our
publication on Order No. 00447 into the context of the discussion about the "Great
Terror". In our opinion, the "anti-kulak" terror offensive can be seen in the wider
context of Bolshevik "problem-solving": terror as an instrument of "social
engineering" against perceived hooligans, criminals and other "outcasts"; terror
against the ideological enemy, closely associated with terror as a means of
creating a communist Utopia (i.e. extermination of religious communities and
groups, Socialist-revolutionaries and former Tsarist state officials); terror as a
preventative measure or as an attempt to consolidate Bolshevik rule (in the pre-war
period).
Background Episodes of mass sociogenic illness are becoming Increasingly recognised
as a significant health and social problem that is more common than is presently
reported. Aims To provide historical continuity with contemporary episodes of mass
sociogenic illness in order to gain a broader transcultural and transhistorical
understanding of this complex, protean phenomenon. Method Literature survey to
identify historical trends. Results Mass sociogenic illness mirrors prominent
social concerns, changing in relation to context and circumstance. Prior to 1900,
reports are dominated by episodes of motor symptoms typified by dissociation,
histrionics and psychomotor agitation incubated in an environment of preexisting
tension, Twentieth-century reports feature anxiety symptoms that are triggered by
sudden exposure to an anxiety-generating agent, most commonly an innocuous odour or
food poisoning rumours. From the early 1980s to the present there has been an
increasing presence of chemical and biological terrorism themes, climaxing in a
sudden shift since the 11 September 2001 terrorist attacks in the USA. Conclusions
A broad understanding of the history of mass sociogenic illness and a knowledge of
episode characteristics are useful in the more rapid recognition and treatment of
outbreaks. Declaration of interest None.
Non-human primates exhibit similar physiological and behavioral responses to
anxiety-inducing situations as humans and have, in fact, been successfully employed
in both conditioned (i.e. conflict paradigms) and ethologically based tests of
fear/anxiety (i.e. involuntary isolation, social interaction, human threat,
predator confrontation). In the last decade, a renewed and growing interest in non-
human primate models has resulted from the use of the small callitrichid species in
behavioral pharmacology and neuroscience. This review focuses on the available non-
human primate models for investigating fear/anxiety, addressing their advantages,
shortcomings, and conceptual framework on which they are based. Lastly, a new
ethologically based model to study anxiety and fear-induced avoidance in
callitrichids-the marmoset predator confrontation test-is discussed. (C) 2002
Elsevier Science Ltd. All rights reserved.
Objective: To compare the short-term efficacy of selective serotonin reuptake
inhibitors (SSRIs) vs. tricyclic antidepressants (TCAs) in the treatment of panic
disorder (PD) a meta-analysis was conducted. Method: Included were 43 studies (34
randomized, nine open), pertaining to 53 treatment conditions, 2367 patients at
pretest and 1804 at post-test. Outcome was measured with the proportion of patients
becoming panic-free, and with pre/post Cohen's d effect sizes, calculated for four
clinical variables: panic, agoraphobia, depression, and general anxiety. Results:
There were no differences between SSRIs and TCAs on any of the effect sizes,
indicating that both groups of antidepressants are equally effective in reducing
panic symptoms, agoraphobic avoidance, depressive symptomatology and general
anxiety. Also the percentage of patients free of panic attacks at post-test did not
differ. The number of drop-outs, however, was significantly lower in the group of
patients treated with SSRIs (18%) vs. TCAs (31%). Conclusion: SSRIs and TCAs are
equal in efficacy in the treatment of panic disorder, but SSRIs are tolerated
better.
The authors report a meta-analysis of high-quality studies published from 1990-1998
on the efficacy of manualized psychotherapies for depression, panic disorder, and
generalized anxiety disorder (GAD) that bear on the clinical utility and external
validity of empirically supported therapies. The results suggest that a substantial
proportion of patients with panic improve and remain improved; that treatments for
depression and GAD produce impressive short-term effects; that most patients in
treatment for depression and GAD do not improve and remain improved at clinically
meaningful follow-up intervals; and that screening procedures used in many studies
raise questions about generalizability, particularly in Tight of a systematic
relation across studies between exclusion rates and outcome. The data suggest the
importance of reporting, in both clinical trials and meta-analyses, a range of
outcome indices that provide a more comprehensive, multidimensional portrait of
treatment effects and their generalizability. These include exclusion rates,
percent improved, percent recovered, percent who remained improved or recovered at
follow-up, percent seeking additional treatment at follow-up, and data on both
completes and intent-to-treat samples.
We investigated the effects of one-trial fear conditioning on phospholipase C-beta
1a catalytic activity and protein level in hippocampal formation and medial frontal
cortex of untreated control rats and rats prenatally exposed to ethanol. One hour
following fear conditioning of untreated control rats, phospholipase C-beta 1a
protein level was increased in the hippocampal cytosolic fraction and decreased in
the hippocampal membrane and cortical cytosolic and cortical membrane fractions.
Twenty-four hours after fear conditioning, phospholipase C-beta 1a protein level
was reduced in the hippocampal cytosolic fraction and elevated in the cortical
nuclear fraction; in addition, 24 h after conditioning, phospholipase C-beta 1a
activity in the cortical cytosolic fraction was increased. Rats that were exposed
prenatally to ethanol displayed attenuated contextual fear conditioning, whereas
conditioning to the acoustic-conditioned stimulus was not different from controls.
In behavioral control (unconditioned) rats, fetal ethanol exposure was associated
with reduced phospholipase C-beta1 a enzyme activity in the hippocampal nuclear,
cortical cytosolic, and cortical membrane fractions and increased phospholipase C-
beta 1a protein level in the hippocampal membrane and cortical cytosolic fractions.
In certain cases, prenatal ethanol exposure modified the relationship between fear
conditioning and changes in phospholipase C-beta 1a protein level and/or activity.
The majority of these effects occurred 1h, rather than 24 h, after fear
conditioning. Multivariate analysis of variance revealed interactions between fear
conditioning, subcellular fraction, and prenatal ethanol exposure for measures of
phospholipase C-beta 1a protein level in hippocampal formation and phospholipase C-
beta 1a enzyme activity in medial frontal cortex. In the majority of cases, fear
conditioning-induced changes in hippocampal phospholipase C-beta 1a protein level
were augmented in rats prenatally exposed to ethanol. In contrast, fear
conditioning-induced changes in cortical phospholipase C-beta 1a activity were,
often, in opposite directions in prenatal ethanol-exposed compared to diet control
rats. We speculate that alterations in subcellular phospholipase C-beta 1a
catalytic activity and protein level contribute to contextual fear conditioning and
that learning deficits observed in rats exposed prenatally to ethanol result, in
part, from dysfunctions in phospholipase C-beta 1a signal transduction. (C) 2001
Academic Press.
The extent and reasons for nonparticipation in preventive drug intervention
programs were reviewed. Special attention was payed to the magnitude of "steroid-
phobia" in cases of early treatment of asthma patients, with inhaled steroids. A
Medicine search yielded 11 studies. One study addressed the topic of treatment with
inhaled steroids, in early asthma patients Nonparticipation rates to "early" drug
treatment ranged from 0.3% to 4.8%. Fear of adverse effects and lack of knowledge
about the treatment were given as the most important reasons for nonparticipation.
Educational measures to increase knowledge about the drug were advised by most of
the authors. In the asthma study a specific "steroid-phobia" was not indicated,
possibly due to the continuous education about the steroid treatment throughout the
study. Proper and repeating information about the safety and the minimal adverse
effects of preventive drug treatment, especially inhaled steroids, seems essential
to improve the treatment rate.
Several effective pharmacotherapeutic treatments exist for panic disorder; however,
not all patients respond to treatment. between 20 % to 40 % are nonresponders.
Recent studies have reported several predictors of nonresponse to pharmacotherapy.
In this review two questions are addressed: is there consensus with respect to
predictors of nonresponse and are there any differences between short-term and
long-term predictors? In this review both short-term and long-term outcome studies
are discussed. Studies were included if at least DSM-III criteria were used and
baseline variables were investigated as possible predictor of response, or
nonresponse, to pharmacotherapy. Of each clinical predictor, tallies were made of
the particular predictors employed and of those predictors that predicted
nonresponse. It appears that a long duration of illness and severe agoraphobic
avoidance are robust predictors of nonresponse, particularly in long-term studies.
Personality disorders, or even personality traits, are possibly the most robust
predictors of nonresponse. Several factors appear to be robust predictors of
nonresponse: factors that are present before treatment and exert their influence on
short-term and long-term treatment outcome. Prospective studies are needed to
further investigate these factors and to test whether it is viable to intervene in
an attempt to increase treatment response. (C) 2001 Wiley-Liss, Inc.
Pavlovian fear conditioning has emerged as a leading behavioral paradigm for
studying the neurobiological basis of learning and memory. Although considerable
progress has been made in understanding the neural substrates of fear conditioning
at the systems level, until recently little has been learned about the underlying
cellular and molecular mechanisms. The success of systems-level work aimed at
defining the neuroanatomical pathways underlying fear conditioning, combined with
the knowledge accumulated by studies of long-term potentiation (LTP), has recently
given way to new insights into the cellular and molecular mechanisms that underlie
acquisition and consolidation of fear memories. Collectively, these findings
suggest that fear memory consolidation in the amygdala shares essential biochemical
features with LTP, and hold promise for understanding the relationship between
memory consolidation and synaptic plasticity in the mammalian brain.
Research into the effects of fear-arousal on precautionary motivation and action is
reviewed. Current models do not adequately distinguish between emotional (i.e.,
fear arousal) and cognitive (i.e., threat perception) responses to fear appeals
and, in general, are not well supported. Evidence suggesting that (i) coping
appraisals are more powerful predictors of precautionary action than threat
perception and that (ii) fear control processes may interfere with precautionary
motivation, recommends cautious and limited use of fear appeals in health
promotion. It seems likely that fear arousal is less important in motivating
precautionary action than perceptions of action effectiveness and self-efficacy.
Moreover, perceived personal relevance may be critical to the emotional and
cognitive impact of threat information. Available findings are summarised in the
form of a process model that highlights the potential complexity of fear arousal
effects. Sequential measurement of fear arousal, other than by self-report, is
recommended in studies seeking to clarify these effects.
This article details a moral panic in 1998-2000 about "ethnic gangs" in I Sydney's
south-western suburbs and analyses its ideological construction of the links
between ethnicity, youth and crime. It documents the racisms of labelling and
targeting of immigrant young people which misread, oversimplify and misrepresent
complex and class-related social realities as racial, and the common-sense(1)
sharing of these understandings, representations and practices by "mainstream"
media, police and vocal representatives in state, local and "ethnic" politics. The
data used in this analysis are largely comprised of English-language media
extracts, press, radio, television - both commercial and government-funded; and
national, state and local in circulation, supplemented by interview material, from
an ethnographic pilot study, with Lebanese-Australian youth, Lebanese immigrant
parents, ethnic community workers, community leaders and police.
In everyday clinical practice, the simultaneous treatment of patients with anxiety
disorders with behavioral and drug therapy is frequently applied. As both of these
treatments have been shown to be highly effective, such a practice appears to be
plausible. Yet, from published studies it is surprisingly difficult to support this
practice. Can meta-analyses of these studies improve the evidence? For agoraphobia
and panic disorder, four of eight published meta-analyses did investigate the
effects of combined behavioral and drug treatment. In two of these studies, the
shortterm effects of exposure treatment and imipramine appeared to be better than
those of their single application; in the two other studies no differences were
found. The controversial results of these studies seem to be dependent on the meta-
analytic methodology applied: Effect Sizes (ES) derived from pre- to posttreatment
comparison of treatments showed a superiority of their simultaneous application. ES
derived from treatment - vs. control group comparisons at posttreatment - did not
show any significant differences in outcome. Unfortunately, there are no meta-
analytic studies on the long-term outcome of simultaneous behavioral and drug
treatment in these disorders. Basically, the generalizability of the results of
meta-analyses is limited, as diagnostic and treatment variations between the
reviewed studies have not been adequately taken into account. There is increasing
evidence that subgroups of agoraphobia and panic disorder receive different modes
of behavioral treatment. Furthermore, even within one symptom-directed technique
like exposure, huge variations in application have been used: classical systematic
desensitization or the flooding type of exposure in vivo and in fantasy; treatment
sessions may last from 20 min to more than 5 h continuously; the degree of
therapist-aided versus self-applied exposure varies greatly. Therefore,
recommendations as to whether and in what conditions (simultaneously or
sequentially) combined behavioral and drug treatment is to be recommended, can
reliably be drawn only from studies that have considered these variables. In spite
of the huge amount of publications on these disorders, studies with this type of
approach have only just begun.
An evolved module for fear elicitation and fear learning with 4 characteristics is
proposed. (a) The fear module is preferentially activated in aversive contexts by
stimuli that are fear relevant in an evolutionary perspective. (b) Its activation
to such stimuli is automatic. (c) It is relatively impenetrable to cognitive
control. (d) It originates in a dedicated neural circuitry, centered on the
amygdala. Evidence supporting these propositions is reviewed from conditioning
studies, both in humans and in monkeys; illusory correlation studies; studies using
unreportable stimuli; and studies from animal neuroscience. The fear module is
assumed to mediate an emotional level of fear learning that is relatively
independent and dissociable from cognitive learning of stimulus relationships.
1. Isolation-reared rats display fear-like behavior and depressive-like behavior in
several behavioral tasks, suggesting that isolation rearing may model certain
aspects of human psychopathologies. 2. After weaning (20 days old), male and female
Wistar rats were isolation-reared during 20, 50 or 70 days. After that, they were
tested in the elevated plus maze test, and in the open field test. Another group of
isolation-reared rats (70 days of isolation) were tested in an auto-shaping task.
3. Isolation-reared rats displayed high levels of fear-like behavior in the
elevated plus-maze test, and hyperlocomotion in the open field test. But,
isolation-reared rats learned an auto-shaping task. 4. In conclusion, isolation
rearing induced fear-like behavior, without affect learning abilities of rats.
Learning the relationships between aversive events and the environmental stimuli
that predict such events is essential to the survival of organisms throughout the
animal kingdom. Pavlovian fear conditioning is an exemplar of this form of learning
that is exhibited by both rats and humans. Recent years have seen an incredible
surge in interest in the neurobiology of fear conditioning. Neural circuits
underlying fear conditioning have been mapped, synaptic plasticity in these
circuits has been identified, and biochemical and genetic manipulations are
beginning to unravel the molecular machinery responsible for the storage of fear
memories. These advances represent an important step in understanding the neural
substrates of a rapidly acquired and adaptive form of associative learning and
memory in mammals.
Corticosteroids play extremely important roles in fear and anxiety. The mechanisms
by which corticosteroids exert their effects on behavior are often indirect,
because, although corticosteroids do not regulate behavior, they induce chemical
changes in particular sets of neurons making certain behavioral outcomes more
likely in certain contexts as a result of the strengthening or weakening of
particular neural pathways. The timing of corticosteroid increase (before, during
or after exposure to a stressor) determines whether and how behavior is affected.
The present review shows that different aspects of fear and anxiety are affected
differentially by the occupation of the mineralocorticoid receptor (MR) or
glucocorticoid receptor (GR) at different phases of the stress response.
Corticosteroids, at low circulating levels, exert a permissive action via brain MRs
on the mediation of acute freezing behavior and acute fear-related plus-maze
behavior. Corticosteroids, at high circulating levels, enhance acquisition,
conditioning and consolidation of an inescapable stressful experience via GR-
mechanisms. Brain GR-occupation also promotes processes underlying fear
potentiation. Fear potentiation can be seen as an adjustment in anticipation of
changing demands. However, such feed-forward regulation may be particularly
vulnerable to dysfunction. MR and/or GR mechansisms are involved in fear
extinction. Brain MRs may be involved in the extinction of passive avoidance, and
GRs may be involved in mediating the extinction of active avoidance. In the
developing brain, corticosteroids play a facilitatory role in the ontogeny of
freezing behavior, probably via GRs in the dorsal hippocampus, and their influence
on the development of the septo-hippocampal cholinergic system. Corticosteroids can
exert maladaptive rather than adaptive effects when their actions via MRs and GRs
are chronically unbalanced due to chronic stress. Both mental health of humans and
animal welfare is likely to be seriously threatened after psychosocial stress,
prolonged stress, prenatal stress or postnatal stress, especially when maternal
care or social support is absent, because these can chronically dysregulate the
central MR/GR balance. In such circumstances the normally adaptive corticosteroid
responses can become maladaptive. (C) 2001 Elsevier Science Ltd. All rights
reserved.
This article reviews the efficacy of the benzodiazepines and the selective
serotonin reuptake inhibitor class of antidepressant in the treatment of panic
disorder. The benzodiazepine alprazolam has been used successfully in the treatment
of panic disorder, but its long-term use presents problems with dependence. Since
panic may be mediated by a dysfunction of serotonin neuronal pathways, there is a
rationale for treatment with antidepressants that modulate serotonergic systems. In
clinical trials, members of the SSRI class of antidepressant reduced panic attack
frequency to zero in 36-86% of patients and were well tolerated over long-term
administration, all important factors in ensuring patient compliance. In addition,
antidepressants are preferable to benzodiazepines in the treatment of panic and
comorbid depression, of which there is a high prevalence among panic disorder
patients. This review emphasises the need for long-term treatment of this chronic
and disabling condition with a therapy that is well tolerated and provides complete
and sustained recovery from panic attacks, and resolution of anticipatory anxiety.
(C) 2001 Elsevier Science B.V. All rights reserved.
The lecture develops a civil perspective on states engaged in systematic but
arbitrary armed violence against their home populations. what the Nurnberg Tribunal
called 'government by terror'. Civilians, or most of them, appear uniquely
vulnerable to such violence and the gross violations of human rights accompanying
it Moreover, this, rather than wars as usually understood, involved the largest
uses of armed force in the twentieth century. It was the main cause of violent
death of civilians. Two geographical concerns are addressed. the 'geographic'
nature of such violence, and its implications for the thought and practice of
geographers. They are explored especially through the work of two geographers whose
lives bracket the past 'century of violence', Peter Kropotkin and Augusto Pinochet.
Pinochet's dictatorship in Chile fully illustrates the scope of state terror
Geographies of coercion are seen in the system of political prisons and torture,
the making of a society and landscapes of fear, and the unmaking of civil life. The
atrocities also violated Chile's former commitment to human rights initiatives.
Pinochet's geographical work, especially the geopolitics, is in accord with, or
offers no counter to, the repressive, authoritarian regime he headed. Kropotkin's
descriptions of imperial Russia show many parallels to the Chilean case, and the
kind of repressive state power that he rejected to dedicate his life to its
vulnerable and innocent victims Almost alone among geographers he developed a
coherent, influential vision of violence, social justice and interpersonal ethics,
based on geographical investigations as well as an anarchist perspective. These two
may also seem to represent conceptual and lived extremes - respectively, an extreme
deployment of state violence, and a total rejection of the state because of the
facts and potential of violent repression. Unfortunately, enquiries into violence
and the state, let alone terrorist states, are virtually absent from contemporary
geographical scholarship. Its emergence as an essentially 'civil field has
reinforced this - when it should have had the opposite effect. In part this
involves a failure to temper our long, and less-than-critical, service to the state
in all areas, and a continuing governmental mind-set. It is suggested that the
absence of critical reflection on the contested relations of civil society and the
state, especially as they involve state violence, undermines the intellectual value
and ethical standards of our work.
Public mistrust in the medical profession is not new. We describe a series of
street riots that took place in the city of Liverpool in north-west England in 1832
during a cholera epidemic. The disturbances were directed primarily against the
local medical fraternity. The episode is of interest, since the same city recently
experienced a similar crisis of confidence between doctors and public. On this
occasion the cause was not cholera, but rather the reports from Alder Hey
Children's Hospital that organ parts from deceased infants undergoing necropsy had
been kept for several years without parental consent.
This article examines some of the major concepts used to model the Thai AIDS
epidemic and to direct interventions, in particular, the concepts of discrete risk
groups and of the sequential spread of HIV from group to group in a wave-like
fashion which, although they have been largely discredited in the international
AIDS literature, retain a high degree of currency in Thailand. I argue that
Thailand's HIV/AIDS epidemic had the effect of bringing sexual practices from the
private sphere into the public arena, where the concept of risk group rendered
visible the social body of modern Thailand as a hierarchy of risk, with specific
groups attributed behaviours necessitating control. This notion found enduring
favour in Thailand because it reinforced existing social prejudices about members
of groups such as the male underclass, prostitutes and injecting drug users, and
legitimated the claims of government and nongovernment organizations for the
monitoring and control of these groups. There has been a high level of consensus
over this strategy, and a lack of competing discourses. Thus Thai AIDS discourse
has not only failed to transcend state and middle-class notions of morality and
normativity, but it has also failed to come to terms with Thailand's changing
sexual cultures.
The need to disseminate information about empirically supported treatments is
becoming paramount in the current cost-minimizing health care climate. Cognitive-
behavioral treatments are clearly effective for panic disorder, and yet the
majority of persons suffering from panic disorder do not receive this treatment.
Publications like the American Psychiatric Association's "Practice Guideline for
the Treatment of Patients With Panic Disorder" (1998) potentially have a widespread
influence on mental health-care practitioners, and therefore it is essential that
the guideline be accurate and up-to-date. In this paper, we critique the
guideline's presentation of cognitive-behavioral therapy (CBT) in terms of
scientific basis, clinical practice, training of behavior therapists, and diversity
issues. Although the guideline appropriately highlights CBT as a primary treatment
for panic disorder, the discussions of its breadth, techniques, and utility are
understated.
Motivational and cognitive factors have been used to explain negative attitudes
toward out-group members. According to the integrated threat theory of prejudice,
negative intergroup attitudes are predicted by proximal factors consisting of
perceived threats from out-group members; these threats, in turn, are predicted by
distal factors such as perceived differences in group status or negative out-group
contact. In the present study, White and First Nation people completed measures
assessing distal and proximal variables and attitudes toward members of the other
ethnic group. Path analyses indicated that realistic and symbolic threats,
intergroup anxiety, and negative stereotypes predicted negative out-group
attitudes. Many of these threats, and in some cases ethnic attitudes, were
associated with negative intergroup contact, strength of in-group identity,
perceptions of intergroup conflict, and perceived status inequality. Theoretical
and applied implications of these findings were discussed.
This article features a selective review of attachment theory and research that
have contributed knowledge about dynamics underlying early trauma, mechanisms by
which maladaptive responses to trauma may be transmitted between generations, and
trauma-related risk factors for psychopathology in children, adolescents, and
adults. First, we focus on the foundations of attachment theory and discuss ways in
which the attachment, exploratory, and fear behavioral systems Interact to promote
infants' survival. The second section of the paper examines the connection. between
frightening experiences and disorganized attachment. Infants who are regularly and
seriously frightened by aspects of their caregiving environment are believed to be
at risk for "unsolvable fear" in which organized attachment responses to fear are
impossible. We describe the behaviors and representations characteristic of
disorganized children and their parents. Next, we review recent research about
relations among attachment, trauma, and psychopathology across the lifespan.
Finally, we discuss implications of these findings for clinical practice.
For over 60 years, ideas about emotion in neuroscience and psychology have been
dominated by a debate on whether emotion can be encompassed within a single.
unifying model. In neuroscience, this approach is epitomized by the limbic system
theory and, in psychology, by dimensional models of emotion. Comparative research
has gradually eroded the limbic model, and some scientists have proposed that
certain individual emotions are represented separately in the brain. Evidence from
humans consistent with this approach has recently been obtained by studies
indicating that signals of fear and disgust are processed by distinct neural
substrates. We review this research and its implications for theories of emotion.
Several theories of the development of panic disorder (PD) with or without
agoraphobia have emerged in the last 2 decades. Early theories that proposed a role
for classical conditioning were criticized on several grounds. However, each
criticism can be met and rejected when one considers current perspectives on
conditioning and associative learning. The authors propose that PD develops because
exposure to panic attacks causes the conditioning of anxiety land sometimes panic)
to exteroceptive and interoceptive cues. This process is reflected in a variety of
cognitive and behavioral phenomena but fundamentally involves emotional learning
that is best accounted for by conditioning principles. Anxiety, an anticipatory
emotional state that functions to prepare the individual for the next panic, is
different from panic, an emotional state designed to deal with a traumatic event
that is already in progress. However, the presence of conditioned anxiety
potentiates the next panic, which begins the individual's spiral into PD. Several
biological and psychological factors create vulnerabilities by influencing the
individual's susceptibility to conditioning. The relationship between the present
view and other views, particularly those that emphasize the role of catastrophic
misinterpretation of somatic sensations, is discussed.
Efficacious psychological treatments for panic disorder. This work presents a
revision of empirically validated psychological treatments for Panic Disorder. It
has been carried out according to the criteria established by the American
Psychological Association (Task Force on Promotion and Dissemination of
Psychological Procedures, 1995) and having into account the subsequent revisions
and recommendations (Chambles et al., 1996; 1998; Chambles & Hollon, 1998: Nathan &
Gorman, 1998) on the methodological requirements that research studies have to
fulfill. Attention is paid both to the results obtained on Axis I (internal
validity or efficacy) and Axis II (clinical utility, external validity or
effectiveness) of the guidelines developed by the APA (Template for Developing
Guidelines: Interventions for Mental Disorders and Psychological Aspects of
Physical Disorders). Such guidelines intend to provide practical instructions for
conducting psychological interventions. Therefore, the available empirical evidence
on this issue is analyzed with the aim of examining the efficacy of any given
intervention. The applicability and possibility of the psychological intervention
in the specific context that is to be offered is analyzed, as well.
Fear conditioning is a form of associative learning in which subjects come to
express defense responses to a neutral conditioned stimulus (CS) that is paired
with an aversive unconditioned stimulus (US). Considerable evidence suggests that
critical neural changes mediating the CS-US association occur in the lateral
nucleus of the amygdala (LA). Further, recent studies show that associative long-
term potentiation (LTP) occurs in pathways that transmit the CS to LA, and that
drugs that interfere with this LTP also disrupt behavioral fear conditioning when
infused into the LA, suggesting that associative LTP in LA might be a mechanism for
storing memories of the CS-US association. Here, we develop a detailed cellular
hypothesis to explain how neural responses to the CS and US in LA could induce LTP-
like changes that store memories during fear conditioning. Specifically, we propose
that the CS evokes EPSPs at sensory input synapses onto LA pyramidal neurons, and
that the US strongly depolarizes these same LA neurons. This depolarization, in
turn, causes calcium influx through NMDA receptors (NMDARs) and also causes the LA
neuron to fire action potentials. The action potentials then back-propagate into
the dendrites, where they collide with CS-evoked EPSPs, resulting in calcium entry
through voltage-gated calcium channels (VGCCs). Although calcium entry through
NMDARs is sufficient to induce synaptic changes that support short-term fear
memory, calcium entry through both NMDARs and VGCCs is required to initiate the
molecular processes that consolidate synaptic changes into a long-term memory.
The related emotions of disgust and fear are examined in their full range from
normal to pathological. We propose that disgust plays a functional role in some
anxiety disorders, specific phobias in particular. Basic research in disgust and
fear is reviewed, and these emotions are contrasted in terms of their functional
value, behavioral intentions,physiological acquisition mechanisms. Cognitive
appraisals of danger and contamination are discussed as a mechanism for the role of
disgust in some anxiety disorders. Finally, we evaluate competing explanations
regarding the relationship between disgust and fear in these contexts, finding
value in the concepts of imprecise emotional labeling and a synergistic model of a
bidirectional association between disgust and fear. implications for treatment are
discussed.
In an attempt to explain how and why some individuals with musculoskeletal pain
develop a chronic pain syndrome, Lethem et al. (Lethem J, Slade PD, Troup JDG,
Bentley G. Outline of a fear-avoidance model of exaggerated pain perceptions. Behav
Res Ther 1983;21:401-408) introduced a so-called 'fear-avoidance' model. The
central concept of their model is fear of pain. 'Confrontation' and 'avoidance' are
postulated as the two extreme responses to this fear, of which the former leads to
the reduction of fear over time. The latter, however, leads to the maintenance or
exacerbation of fear, possibly generating a phobic state. In the last decade, an
increasing number of investigations have corroborated and refined the fear-
avoidance model. The aim of this paper is to review the existing evidence for the
mediating role of pain-related fear, and its immediate and long-term consequences
in the initiation and maintenance of chronic pain disability. We first highlight
possible precursors of pain-related fear including the role negative appraisal of
internal and external stimuli, negative affectivity and anxiety sensitivity may
play. Subsequently, a number of fear-related processes will be discussed including
escape and avoidance behaviors resulting in poor behavioral performance,
hypervigilance to internal and external illness information, muscular reactivity,
and physical disuse in terms of deconditioning and guarded movement. We also review
the available assessment methods for the quantification of pain-related fear and
avoidance. Finally, we discuss the implications of the recent findings for the
prevention and treatment of chronic musculoskeletal pain. Although there are still
a number of unresolved issues which merit future research attention, pain-related
fear and avoidance appear to be an essential feature of the development of a
chronic problem for a substantial number of patients with musculoskeletal pain. (C)
2000 International Association for the Study of Pain. Published by Elsevier Science
B.V. All rights reserved.
Alprazolam (a benzodiazepine in the group of the triazolobenzodiazepines) is a
potent drug for the treatment of panic disorder. This is possible due to four
different interactions with neurotransmittor systems. First, it facilitates, as all
diazepines, the inhibitory acitivity of gamma-amino-butyric-acid (GABA). The
chemical structure differs from the benzodiazepines by incorporation of the
triazoloring. Due to this triazoloring, the drug has three additional modes of
action. These modes of action inhibit the locus coeruleus which plays a role in the
origin of panic disorder. A first specific action is a stimulation of the
serotonergic system. Triazolobenzodiazepines are also alpha(2)-adrenoreceptor
agonists. Both mechanisms are responsible for inhibition of the locus coeruleus.
Triazolobenzodiazepines inhibit the platelet-activating-factor (PAF). PAF
stimulates the corticotropin-releasing-hormone (CRH). This hormone stimulates the
locus coeruleus. CRH in patients with panic attacks is elevated. This could be a
result of hyperactive metabolism of the right parahippocampal area, which is
observed in patients with panic attacks. Triazolobenzodiazepines decrease the
activity of the locus coeruleus because of a low CRH-level due to inhibited PAF.
Background: There are facilities established around the world for treating
passenger flight anxiety, often as a joint activity of airlines and private
entrepreneurs or mental health professionals. in the scientific and professional
literature, there is little information about how these facilities operate and what
the components of their treatment programs are. This paper is the first review to
date to provide this information. Method: There were 212 airlines and treatment
facilities approached for information on treatment programs for flying phobia, 43
of which were active in this field. Extensive information could be obtained from
15, which were the best known and well-developed. information was collected both
with a questionnaire and by meeting representatives from 15 international rear of
flying treatment facilities that participated in the First International Conference
on Fear of Flying (Feb. 1996). Results: Fear of flying among passengers is a
phenomenon with epidemic proportions, effecting roughly 10-40% of the adult
population. All treatment programs share two basic elements, an information
component and a test flight. The programs vary considerably in terms of treatment
components. However, there is little available information on efficacy.
Conclusions: To date there is a wide variety between facilities for the treatment
for fear of flying in terms of methods and protocols used. Experts agree on the
clear-cut need for standardization of a "best" minimum protocol for fear of flying
treatment programs for which the main components where identified.
Background: A review of the studies examining the genetic etiology of panic
disorder shows the familial nature of the disorder and demonstrates that the
etiology is greatly influenced by genetic factors. Strong evidence for vertical
transmission in family studies led to molecular genetic studies, of which
association designs appear promising, particularly when based on trait markers.
Data Sources: The MEDLINE and PsycLIT databases were searched for all reports
published between 1966 and 2000 containing the keywords panic, genetic, twin,
adoption, linkage, association, and QTL. Conclusion: We conclude that the
multifactorial nature of panic disorder requires a multidisciplinary approach to
gain insight into the determinants of the phenotype and the interaction of
environmental and genetic factors.
This article reviews the literature with regard to firearms accidents among low-
income, urban children younger than 13. The tendency of low-income families to keep
unsecured protection guns may contribute to the higher rare of firearms accidents
among low-income children. The evidence suggests that the decision to keep a gun
for protection is largely a practical response to the conditions a person perceives
in his or her neighborhood. Reducing the consequences of risky gun behavior among
low-income families requires policies and programs that eliminate experiences
associated with such behavior and that train children to recognize and avoid risky
gun situations.
Chest pain is a common presentation to both primary and secondary care physicians
but is often non-cardiac in origin. Patients presenting with chest: pain may be
experiencing a panic attack. Panic disorder is a disabling psychiatric condition
with serious consequences, such as impaired social functioning and increased risk
of suicide. Comorbidity of panic disorder with other psychiatric conditions is
common and often leads to increased severity of anxiety symptoms and a poorer
prognosis. The cost of misdiagnosing non-cardiac chest pain is high. it is
important for physicians to be able to recognise panic attacks and to distinguish
them from cardiac disease, thus avoiding unnecessary use of healthcare resources.
This review discusses the prevalence and diagnosis of panic attack and panic
disorder in patients presenting with chest pain to primary care physicians and
cardiologists. Treatment options for panic disorder are considered, particularly
the selective serotonin reuptake inhibitors, which are emerging as the first-line
choice for the treatment of panic disorder.
This article reviews the literature on fear of crime of interest to the
geographical and environmental disciplines. After discussing definitional and
methodological issues, the article focuses on accounts which link fear with the
physical environment, and then on fear, social identity and exclusion. It considers
the significance of one area of recent research that attempts to link place and
social relations through developing local ethnographies of fear. The review
concludes with some suggestions for building upon this work, and highlights the
relevance of the geographical themes discussed to current policy debates.
The clinical and psychopharmacological profile of panic disorder in human patients
shows a remarkable similarity to the defensive behavioral response evoked in
experimental animals by activation of neurons in the dorsal part of the midbrain
periaqueductal gray matter (PAG). Studies of the neural circuitry within the PAG
indicate that a subpopulation of GABAergic neurons in the dorsolateral sector may
act as an amplifying stage that potentiates inhibitory serotonergic input to the
"defense area" within the PAG. These neurons may function as a gain-control system
that sets the level of excitability of efferent output neurons, which mediate the
autonomic and somatomotor components of panic behavior. Dysfunctional activity
within the dorsolateral PAG leading to a destabilization of this control system may
be a factor underlying panic behavior and predisposes to the development of panic
disorder in susceptible persons.
The aim of this paper is to explicate what is special about emotional information
processing, emphasizing the neural foundations that underlie the experience and
expression of fear. A functional, anatomical model of defense behavior in animals
is presented and applications are described in cognitive and physiological studies
of human affect. It is proposed that unpleasant emotions depend on the activation
of an evolutionarily primitive subcortical circuit, including the amygdala and the
neural structures to which it projects. This motivational system mediates specific
autonomic (e.g., heart rate change) and somatic reflexes (e.g., startle change)
that originally promoted survival in dangerous conditions. These same response
patterns are illustrated in humans, as they process objective, memorial, and media
stimuli. Furthermore, it is shown how variations in the neural circuit and its
outputs may separately characterize cue-specific fear las in specific phobia) and
more generalized anxiety. Finally, again emphasizing links between the animal and
human data, we focus on special, attentional features of emotional processing: The
automaticity of fear reactions, hyper-reactivity to minimal threat-cues, and
evidence that the physiological responses in fear may be independent of slower,
language-based appraisal processes. (C) 2000 Elsevier Science B.V. All rights
reserved.
Panic disorder is a common condition that includes symptoms that may masquerade as
a primary cardiovascular disorder. In addition, many patients with cardiovascular
disease may also have panic disorder. To date, no definitive pathophysiological
mechanism for panic disorder has been found; however, there are several hypotheses
in the literature. Patients with syndrome X, coronary artery disease and/or
palpitations, in addition to panic disorder all present to cardiologists. How ever,
many patients go undiagnosed and ultimately place large costs on the health care
system as a result. Panic disorder is a treatable condition, and cardiologists
could easily identify patients with panic disorder and initiate appropriate therapy
and/or referral. (C) 2000 Elsevier Science Inc. All rights reserved.
This paper reviews over a century's research into the developmental patterns of
normal fear Normal fear has been defined as a normal reaction to a real or imagined
threat and is considered to be an integral and adaptive affect of development with
the primary function of promoting survival. Across a wide range of methodologies
and assessment instruments researchers have been particularly focussed on
investigating whether fear content, prevalence and intensity differ depending upon
age, gender, socio-economic status, and culture. The structure and continuity of
normal fears have also received much attention. The most consistently documented
findings include that fear. decreases in prevalence and intensity with age and that
specific fears are transitory in nature. there are, also predictable changes in the
content of normal fear over the course of development. Such changes are
characterized by a transition from infant fears which are related to immediate
concrete and prepotent stimuli, and which are largely non-cognitive, to fears of
late childhood and adolescence which are related to anticipatory, abstract, and
more global stimuli and events. Recent research into normal feal has more closely
examined the validity of the more frequently used current assessment technique
(i.e., the fear survey schedule). This research has provided some Encouraging
results as well as directions for future investigation. (C) 2000 Elsevier Science
Ltd.
Objective: In a 1989 article, the authors provided a hypothesis for the
neuroanatomical basis of panic disorder that attempted to explain why both
medication and cognitive behavioral psychotherapy are effective treatments. Here
they revise that hypothesis to consider developments in the preclinical
understanding of the neurobiology of fear and avoidance. Method: The authors review
recent literature on the phenomenology, neurobiology, and treatment of panic
disorder and impressive developments in documenting the neuroanatomy of conditioned
fear in animals. Results: There appears to be a remarkable similarity between the
physiological and behavioral consequences of response to a conditioned fear
stimulus and a panic attack. In animals, these responses are mediated by a "fear
network" in the brain that is centered in the amygdala and involves its interaction
with the hippocampus and medial prefrontal cortex. Projections from the amygdala to
hypothalamic and brainstem sites explain many of the observed signs of conditioned
fear responses. It is speculated that a similar network is involved in panic
disorder. A convergence of evidence suggests that both heritable factors and
stressful life events, particularly in early childhood, are responsible for the
onset of panic disorder. Conclusions: Medications, particularly those that
influence the serotonin system, are hypothesized to desensitize the fear network
from the level of the amygdala through its projects to the hypothalamus and the
brainstem. Effective psychosocial treatments may also reduce contextual fear and
cognitive misattributions at the level of the prefrontal cortex and hippocampus.
Neuroimaging studies should help clarify whether these hypotheses are correct.
From the perspective of terror management theory, the human body is problematic
because it serves as a perpetual reminder of the inevitability of death. Human
beings confront this problem through the development of cultural worldviews that
imbue reality-and the body as part of that reality-with abstract symbolic meaning.
This fanciful flight from death is in turn the psychological impetus for distancing
from other animals and the need to regulate behaviors that remind us of our
physical nature. This analysis is applied to questions concerning why people are
embarrassed and disgusted by their bodies' functions; why sex is such a common
source of problems, difficulties, regulations, and ritualizations; why sex tends to
be associated with romantic love; and why cultures value physical attractiveness
and objectify women. This article then briefly considers implications of this
analysis for understanding psychological problems related to the physical body and
cultural variations in the need to separate oneself from the natural world.
Evidence from psychological research has shown the importance of fear on attitude
and/or behavior change. First, this article reviews theoretical explanations and
recent experimental research regarding persuasive and resistance effects. A four-
step model is then proposed concerning fear-based appeals in health communications.
Several variables are particularly important : description of the threat,
prevention or detection behaviors as responses, self-efficacy or individual's
belief in his or her ability to perform the recommended response to the threat,
danger and fear control processes and their impact on subsequent attitude and
behavior, and past behaviors. These variables must be simultaneously taken into
account if one wants to set up an effective fear-persuasive communication campaign.
Objective: To critically review existing literature examining the relationship
between panic disorder (PD) and coronary artery disease (CAD). We specifically
sought answers to the following questions: (1) What is the prevalence of PD in CAD
patients? (2) What is the directionality of the relationship between PD and CAD?
(3) What mechanisms may mediate the link between PD and CAD? Methods: Medline and
Psych-lit searches were conducted using the following search titles: "panic
disorder and coronary artery disease", "panic disorder and coronary heart disease",
and "panic disorder and cardiovascular disease" for the years 1980-1998. The above
search was also repeated replacing "panic disorder" with "panic attacks" for the
same period. Results: The prevalence of PD in both cardiology out-patients and
patients with documented CAD ranges from 10% to 50%. The association between PD and
CAD appeared strongest in patients with atypical chest pain or symptoms that could
not be fully explained by coronary status. There is some evidence linking phobic
anxiety but not PD per sc to CAD risk, but little evidence linking CAD to PD risk.
Studies of the mechanisms linking PD to CAD are still in their infancy, but there
is preliminary evidence linking PD to reduced heart rate variability (HRV) and
myocardial ischemia, two pathophysiological mechanisms related to CAD. Conclusion:
PD is prevalent in CAD patients, but it is unclear the extent to which PD confers
risk for and/or exacerbates CAD. Prospective research is needed to more firmly
establish PD as a distinct risk factor for the development and progression of CAD.
However, because many of the symptoms of PD mimic those of CAD, differentiating
these disorders and learning how they may influence each other is imperative for
clinical practice. (C) 2000 Elsevier Science Inc. All rights reserved.
1. Studies on the pathogenesis of panic disorder (PD) have concentrated on panic
attacks. However, PD runs a chronic or episodic course and panic patients remain
clinically unwell between attacks. Panic patients chronically hyperventilate, but
the implications of this are unclear. 2. Provocation of panic experimentally has
indicated that several biological mechanisms may be involved in the onset of panic
symptoms. Evidence from provocation studies using lactate, but particularly carbon
dioxide (CO2) mixtures, suggests that panic patients may have hypersensitive CO2
chemoreceptors. Klein proposed that PD may be due to a dysfunctional brain's
suffocation alarm and that panic patients hyperventilate to keep pCO(2) low. 3.
Studies of panic patients in the non-panic state have shown EEG abnormalities in
this patient group, as well as abnormalities in cerebral blood flow and cerebral
glucose metabolism. These abnormalities can be interpreted as signs of cerebral
hypoxia that may have resulted from hyperventilation. 4. Cerebral hypoxia is
probably involved in the causation of symptoms of anxiety in sufferers of chronic
obstructive pulmonary diseases. By chronically hyperventilating, panic patients may
likewise be at risk of exposure to prolonged periods of cerebral hypoxia which, in
turn, may contribute to the chronicity of their panic and anxiety symptoms. 5.
Chronic hyperventilation may engender a self-perpetuating mechanism within the
pathophysiology of PD, a hypothesis which warrants further studies of panic
patients in the non-panic state.
Regulation S provides U.S. issuers with an exemption from the registration
requirements of the Securities Act of 1933 to the extent that securities are
offered and sold solely outside the United States. Through resales buck into the
United States, however, U.S. investors may become exposed to unregistered
securities initially distributed abroad through Regulation S. This Article
identifies two distinct risks from an offshore securities offering First, issuers
may conduct an offering under Regulation S as a means to sell securities indirectly
into the United States through resales in situations where the U.S. secondary
market overvalues the issuer's securities. Second even where the U.S. secondary
market does not overvalue an issuer's securities, the managers of the issuer may
utilize Regulation S to engage in self-dealing and other opportunistic behavior for
their own private benefit at the expense of U.S. investors. Employing a dataset of
701 offerings conducted pursuant to Regulation S from 1993 to 1997, this Article
presents evidence that insider self-dealing may result in a greater offering
discount for certain overseas offerings. Given the specific risks facing U.S.
investors, the Article then argues that the SEC's 1998 reforms to Regulation S
represent only an untailored response. Instead the Article recommends specific
reforms that both reduce the risk facing U.S. investors and lessen the regulatory
burden on offshore securities offerings that pose little risk of investor abuse.
Sertraline is a selective serotonin reuptake inhibitor that is approved by the U.S.
Food and Drug Administration for the treatment of major depression, obsessive-
compulsive disorder (in adults and children), and panic disorder. Although numerous
studies have found sertraline to be very effective in the treatment of anxiety,
there have been few case reports of panic attacks actually being induced by
treatment with sertraline. In this article, we present the cases of two patients
without any personal or family history of anxiety disorders who developed panic
attacks shortly after the initiation of sertraline therapy. We will also review the
literature in regard to the development of anxiety symptoms during treatment with
the newer antidepressants and discuss the neurochemical basis of these
antidepressant-induced panic attacks.
Classical conditioning, the simplest form of associative learning, is one of the
most studied paradigms in behavioural psychology. Since the formal description of
classical conditioning by Pavlov, lesion studies in animals have identified a
number of anatomical structures involved in, and necessary for, classical
conditioning, In the 1980s, with the advent of functional brain imaging techniques,
particularly positron emission tomography (PET), it has been possible to study the
functional anatomy of classical conditioning in humans. The development of
functional magnetic resonance imaging (fMRI) - in particular single-trial or event-
related fMRI - has now considerably advanced the potential of neuroimaging for the
study of this form of learning. Recent event-related fMRI and PET studies are
adding crucial data to the current discussion about the putative role of the
amygdala in classical fear conditioning in humans.
Alteplase for acute ischemic stroke may be the first stroke intervention to have a
significant public health impact. In February 1999, this therapy was conditionally
licensed in Canada for acute ischemic stroke within three hours of symptom onset.
However, considerable controversy exists regarding its safety, its wider
applicability outside clinical trials, and its ultimate availability. In this
article we review the thrombolytic literature, attempt to answer many of the
concerns, provide new guidelines for its use, and cite the need for more
information about whom we should and should not be treating with this therapy.
This essay considers the changes in standards for children's fear and for ways of
handling it in Dutch parental guidance literature between 1850 and 1950. Steams and
Haggerty's hypothesis about a Western transformation of fear from an avoidable and
relatively unimportant emotion to fear as a normal aspect of a child's mental life,
inspired by the American case, is put to the test of comparison. First, an outline
of Dutch social history is given, focusing on those processes that are supposed to
have acted as determinants of the transition: urbanization, secularization, and a
smaller family size. Next, the essay discusses fear as subject of the Dutch
parental guidance literature. As in the United States since the 1920s fear changed
from a relatively unimportant to a major topic in child-rearing literature. It
turned into a fully normal and accepted childhood emotion, which deserved parental
respect and compassion. However, unlike in the United States, the same social
processes cannot have caused this transition, as they did not occur or did not
occur nationwide in the Netherlands at the time. The author draws the conclusion
that the cultural shock brought about by World War 1 and its intellectual aftermath
has caused the transition.
The relation between fear and anxiety remains unclear, though psychometric data
strongly suggest they are independent emotional systems. Because central
norepinephrine (NE) projection systems are at the core of models of both fear and
anxiety, the present experiment explored whether this independence extends to NE
functioning. Two different aspects of NE functioning were assessed in a healthy
young adult sample (N = 18): pupillary reactivity to (a) a specific NE alpha-1
agonist challenge to assess receptor reactivity and (b) a darkness challenge to
assess contributions of central NE. Pupillary reactivity to the former was strongly
and specifically related to A. Tellegen's (1982) Multidimensional Personality
Questionnaire (MPQ) Harm Avoidance scale (i.e., trait fear), whereas the latter was
strongly and specifically related to MPQ Negative Emotionality (i.e., trait
anxiety). Implications for conceptualizing fear and anxiety as emotional systems
are discussed.
Based on findings that stress and anxiety may modulate immune function, we compared
the production of interleukin-2 (IL-2) and interleukin-3 (IL-3) by peripheral blood
mononuclear cells between 24 patients with nonmajor depressed panic disorders, 9
with agoraphobia and 15 without, and 19 healthy volunteers. No differences in the
production of these cytokines was noted between the patients with panic disorders
and the volunteers or between the patients with and without agoraphobia. However,
in the patients, a negative correlation was found for interleukin-3 production with
severity of state anxiety, but not with trait anxiety or depression. This finding
indicates that interleukin-3 levels may be sensitive to the presence of anxiety and
stress.
Here we present a real-time model of fear conditioning in which the functional
anatomy and neurophysiology of the lateral amygdala and perirhinal cortex provide a
mechanism for temporal learning during Pavlovian conditioning. The model uses
realistic neuronal and circuit dynamics to map time onto space and relies on a
conventional Hebbian Yearning rule that requires strict temporal contiguity for
synaptic modification. The input-output relationships of the model neurons simulate
our physiological recordings with respect to latency to fire, firing frequency, and
accommodation tendency. Chains of these neurons form a spectrum of activity windows
delayed by various amounts from the conditioned stimulus onset. Simulations reveal
that learning occurs only when the conditioned and unconditioned stimuli are
explicitly paired, tat the interstimulus interval (ISI) is accurately learned over
a time range from 0.5 to 16 sec, and that low-frequency noise causes the accuracy
of temporal learning to decrease as the ISI increases, in accordance with a Weber-
type law.
This article examines the literature regarding the health care provider/AIDS
patient relationship for a 14 year period from 1984 through 1998. For each of the
four time periods (1984-1989, 1990-1992, 1993-1995, 1996-1998), we present the
general themes and concerns of the literature at that time. We begin the review of
each time period with a depiction of what was happening in biomedical circles and
in the broader society around HIV/AIDS. To provide a closer look at the setting for
the work completed within each time period, we draw on research interviews
conducted by the first author with nurses involved in AIDS care since the early
days of the epidemic. Nurses' retrospective comments on what it was like to do the
work at various times reveal the local reality and provide an important rationale
for the work that we review. Each time period closes with a discussion of the
lessons learned and suggestions of new possibilities fur future efforts to enhance
the well-being of both health care providers and patients with HIV/AIDS.
Individuals that may be especially susceptible to panic attacks in the
rehabilitation setting are patients who have suffered traumatic brain injuries,
post-concussion syndrome, lesions, or encephalopathy. An individual is described
who suffered a traumatic brain injury and was determined to have suffered a panic
attack during his rehabilitation stay. The manifestations of panic attacks are
described, using the case report as an example. The psychological aetiology of
panic disorders is also reviewed, and treatment options using four major classes of
neuropharmacologic agents: benzodiazepines, tricyclic antidepressants, monoamide
oxidase inhibitors, and serotonin reuptake inhibitors, are discussed. Given the
increasing incidence and survival of patients with traumatic brain injuries, the
complications of panic attacks and disorders will become more important; they are a
serious condition that can affect an individual's lifestyle, employment, and
relationships, and increase the risk of suicide. Rehabilitation specialists should
be aware of the manifestations and management of panic attacks and come to
appreciate that recognition of this treatable condition is important during all
stages of rehabilitation.
Panic disorder (PD) is a well-known and frequently described psychiatric disorder
in adults, that can cause clinically significant distress and impairment of social
and occupational functioning, It is characterized by a discrete period of intense
fear and discomfort, that develops abruptly and reaches a peak in 10 minutes or
less, with other somatic and cognitive symptoms. PD in prepubertal children and
early adolescents in rarely reported, but 18% of adult patients with PD indicate
onset of PA before 10 years of age. Probably many of the prepubertal cases are
being misdiagnosed, and/or they can have a different clinical expression from
adults. The lack of identification of these affected subjects can have serious
consequences on social and academic development. The aim of this paper is to review
clinical literature describing PD in children and adolescents. Prevalence,
specificity of clinical features, comorbidity, instruments for diagnosis are
described. Directions in pharmacological, psychotherapeutic and educational
management of PD in children and adolescents are suggested.
We extend a neurodevelopmental model of specific phobias to the etiology of an
initial panic attack and its elaboration into panic disorder. An important
difference between the initial panic attack and specific phobia is the
developmental timing of critical emotional experience: Those occurring early in
development lead to panic; those occurring later in development: lead to specific
phobia. By this account, sensory and emotional experiences that occur early in
development are stored in a set of modules, each with a unique developmental
trajectory. Reinstatement, which occurs during hormonal stress, produces an
aggregate of sensory and emotional memories and the first experience of an
unexplained panic attack. Panic disorder, which evolves from unexplained panic
attacks, involves retrieval of a disaggregate set of sensory and emotional memory
fragments supplemented by an inferential fitting of an explanatory context to this
incomplete aggregate.
1. The authors investigated the effect of the benzodiazepine receptor antagonist
flumazenil on freezing behavior induced by conditioned fear stress and used a time-
sampling procedure. 2. Rats were individually subjected to 5 min of inescapable
electric footshock in a shock chamber. Twenty-four hours after the footshock, the
rats were again placed in the shock chamber and observed for 5 min without shocks:
this procedure is termed conditioned fear stress. 3. Subcutaneous administration of
flumazenil (10 mg/kg) 30 min before conditioned fear stress reduced conditioned
freezing, while flumazenil (1-10 mg/kg) 30 min before footshock did not. This
indicates that flumazenil reduced the expression of conditioned fear, suggesting an
anxiolytic effect of flumazenil. 4. This effect may be attributable to antagonism
by flumazenil to endogenous inverse agonist-like ligands for benzodiazepine
receptors. It is suggested that endogenous inverse agonist-like ligands for
benzodiazepine receptors are involved in the expression of conditioned fear stress.
There is little known about the effect of pregnancy and the puerperium on the risk
for; and course of anxiety disorders. Initial case reports concerning the
relationship between panic disorder (PD) and pregnancy/puerperium suggested that
pregnancy protected against PD, while the postpartum period seemed to increase the
risk for onset or exacerbation dPD Later studies have offered a more mixed picture.
A computerized search identified eight relevant studies in this area. All were non-
controlled and all but one retrospective. Out of the total 215 pregnancies that
were described in these studies, 89 (41%) were associated with improvement of PD
symptom; during the pregnancy, while 38% of the described pregnancies exhibited
onset or exacerbation of PD in the postpartum period. No definite conclusions
regarding the effect of pregnancy and puerperium on PD can be drawn from these
revalued studies.
Various studies suggest alpha(2)-adrenergic receptor (alpha(2)AR) dysregulation in
panic disorder (PD). Platelet alpha(2)-AR exist in high- and low-conformational
states as a function of their coupling to G(i) protein, alpha(2)-AR coupling is
important in signal transduction and is modulated by antidepressants. alpha(2)AR
density in the high- and low-conformational states, agonist affinity, and coupling
efficiency were investigated in 21 healthy controls, 21 drug-free PD patients, and
eight imipiramine-treated patients using norepinephrine displacement of H-3-
yohimbine binding. Percentage of receptors in the high-conformational state (%R-H)
and the ratio of the agonist dissociation constant to the receptor in the
low-/high-conformational state (K-L/K-H), calculated from displacement experiments,
were used as coupling indices. Patients had high alpha(2)AR density in both
conformational states. %R-H and K-L/K-H ratio were significantly different,
particularly in patients with Hamilton scale for depression (HAMD) scores greater
than or equal to 15, Imipramine treatment (29 weeks) had no effect on alpha(2)AR
density or coupling, despite improvement in anxiety ratings. High pretreatment
alpha(2)AR density and coupling predicted low severity of anxiety after treatment.
Increased alpha(2)AR density and abnormal coupling may represent an adaptive
mechanism or trait marker in PD. [Neuropsychopharmacology 20:162-276, 1999] (C)
1998 American College of Neuropsychopharmacology.
Every public offering of securities is necessarily made some time during a fiscal
quarter. Companies are obliged to disclose fall quarter operating results, but
their obligations regarding the as-yet-incomplete quarter remain unclear. In this
Article, Professor Mitu Gulati tackles both the normative question of whether
companies doing offerings should be required to disclose their unripe information
concerning the current quarter and the doctrinal question of whether such an
obligation already exists within the framework of disclosure duties. The Article
concludes that, while market forces and regulatory requirements operate to solve
the interim nondisclosure problem in the majority of cases, there exists a small
subset of cases-paradoxically, the subset of cases involving the largest, most
well-established companies-that calls for regulation. The doctrinal approach taken
by the courts thus far, which has been to impose no more than a narrow disclosure
obligation under Item 303 and reject any general obligations under Rule 10b-5,
dovetails with the type of circumscribed disclosure obligation that the Article's
normative analysis suggests.
After a few pairings of a threatening stimulus with a formerly neutral cue, animals
and humans will experience a state of conditioned fear when only the cue is
present. Conditioned fear provides a critical survival-related function in the face
of threat by activating a range of protective behaviors. The present review
summarizes and compares the results of different laboratories investigating the
neuroanatomical and neurochemical basis of conditioned fear, focusing primarily on
the behavioral models of freezing and fear-potentiated startle in rats. On the
basis of these studies, we describe the pathways mediating and modulating fear. We
identify several key unanswered questions and discuss possible implications for the
understanding of human anxiety disorders. (C) 1999 Elsevier Science Ltd. All rights
reserved.
The aim of this review was to survey the available literature on prodromal and
residual symptoms of panic disorder. Both a computerized (Medline) and a manual
search of the literature were performed. In a substantial proportion of patients
with panic disorder with agoraphobia a prodromal phase can be identified. Most
patients report residua I symptoms despite successful treatment. Residual symptoms
upon remission have a prognostic value. There appears to be a relationship between
residual and prodromal symptomatology (the rollback phenomenon). Appraisal of
subclinical symptomatology in panic disorder has important implications as to the
pathophysiological model of disease, its conceptualization and treatment.
Self-monitoring has become a popular assessment tool in treatment outcome research
and descriptive psychopathology for panic and anxiety disorders. Commonly used
formats of self-monitoring for each anxiety disorder are described. Self-monitoring
is compared with self-report estimation. On the one hand, self-monitoring may be
influenced by reactivity, as well as by attentional and judgmental biases that
underlie fear and anxiety. On the other hand, self-monitoring may minimize certain
influences that tarnish estimation, such as response demand biases, memory
deficits, inflation of aversive experiences, and availability heuristics. Issues
for statistical analysis of self-monitored data for panic and the anxiety disorders
are outlined. Finally, directions for future research and clinical use of self-
monitoring are discussed.
The presence of asthma is a risk factor for the development of panic disorder. The
co-occurrence of panic disorder and asthma is greater than would be expected based
on their individual prevalence rates. This may be due in part to the important role
of respiratory factors in panic disorder. Panic and anxiety can directly exacerbate
asthma symptoms through hyperventilation, and are associated with patients' overuse
of as-needed asthma medications, with more frequent hospital admissions and longer
hospital stays, and with more frequent steroid treatment, ail of which are
independent of degree of objective pulmonary impairment. This paper reviews the
literature on the relationship between panic and anxiety on the one hand, and the
experience and management of asthma on the other.
Based on the observation of low to moderate correlations among multiple measures of
anxiety or panic, Lang (1968, 1978, 1979) and Rachman (1978a, 1978b, 1990)
developed the three-systems model that rejects the notion of anxiety or panic as
unitary latent constructs. This model is critically reviewed with an emphasis on
discussing its implications for intervention, methodology, and theory An
alternative conceptualization, the hierarchical model of anxiety and panic, is
offered in which anxiety and panic are seen as unitary latent constructs at a
higher level of a hierarchical structure that coexist with several separable
response systems at a lower level of the hierarchy. The hierarchical model retains
many of the strengths of the three-systems model while overcoming many of the
limitations of the three-systems model.
There is a high prevalence of panic disorder in medical patients, as well as an
association between panic disorder and high rates of utilization of medical
services and excessive medical costs incurred from extensive medical workups. The
association between panic disorder and specific cardiac, gastrointestinal,
respiratory, and neurologic symptoms and disorders are described, and
psychophysiological models attempting to account for the medical comorbidity
associated with panic disorder are addressed. Finally, clinical trials
investigating pharmacological and psychological interventions to treat the somatic
symptoms with which patients with panic disorder often present are reviewed and
critiqued, and productive avenues for further research on panic disorder in medical
patients are recommended. (C) 1998 Elsevier Science Inc.
While there has been burgeoning interest in the psychiatric literature about the
phenomenology and biology of panic disorder, there is little new information about
the psychodynamics of this condition. The reintroduction of a psychodynamic
perspective could be useful in guiding research strategies to identify traits which
predispose to panic and in designing treatments to address such traits. A
psychodynamic model hypothesizes a relationship between current psychological
functioning, early experiences, and ongoing psychological traits. Recent published
reports about the nature of underlying psychodynamics and psychological
characteristics of panic disorder ate discussed.
The objective of the article is to develop a theory of the causes and transmission
of moral panics. The theory is designed to explain forms of collective behavior,
previously labeled panics, scares and persecutions. Part one of this article
presents criteria for the identification of moral panics. Part two of the article
offers models for analyzing the social conditions, which cause moral panics and
lead to the social construction of definitions of deviance. Finally, part three
examines the social processes by which moral panics are transmitted between
different societies. In order to illustrate the theoretical analysis, the article
presents information about the current moral panic involving criminal accusations
of ritual child abuse by secret, satanic cults.
Treatment of chronic airflow obstruction with inhaled corticosteroids at an early
stage has been shown to preserve the lung function. We tested the hypothesis that
"fear of corticosteroids" may be an important reason for nonparticipation in the
Detection, early Intervention and Monitoring programme on Chronic obstruction
pulmonary disease (COPD) and Asthma ("DIMCA") project. One thousand seven hundred
and forty nine adult subjects from 10 general practices were invited to participate
in the several parts of the "DIMCA" programme. Refusers were questioned about the
reason(s) for nonparticipation. Together the screening, monitoring and three drug
interventions of the study showed on average 25-35% refusers. The most frequent
reasons for nonparticipation were absence of pulmonary symptoms and lack of time.
For those invited to take part in one of the three drug interventions, "dislike of
medication" was the most important reason for nonparticipation (33, 45 and 67% of
the refusers), "Fear of corticosteroids" specifically was the reason for
nonparticipation in 8% of the refusers on the basis of "dislike of medication". We
concluded that a specific fear of corticosteroids was not a major obstacle for
early intervention with inhaled corticosteroids.
Objective: With recent advances in molecular genetics, the rate-limiting step in
identifying susceptibility genes for psychiatric disorders has become phenotype
definition. The success of psychiatric genetics may require the development of a
"genetic nosology" that can classify individuals in terms of the heritable aspects
of psychopathology. The authors' aim is to begin to apply this analysis to the
anxiety disorders, focusing on panic and phobic disorders. Method: Two parallel
traditions of defining anxiety phenotypes are reviewed: the first, more closely
identified with clinical psychiatry has identified categorical diagnoses (e.g.,
panic disorder and social phobia). The other, more closely identified with
psychological studies of personality development, has examined dimensional traits
(e.g., neuroticism) and anxious temperament (e.g., behavioral inhibition). Results:
The authors suggest that a genetic nosology of panic and phobic disorders may
incorporate features of both traditions and discuss strategies for optimizing
genetic approaches to anxiety including I) studying phenotypic extremes, 2)
identifying biological trait markers, and 3) using animal models to identify
candidate loci. Conclusions: An important dividend from the effort to define the
boundaries of heritable phenotypes for genetic studies of anxiety may be a
refinement of the nosology of anxiety disorders.
Evidence supports the idea of two distinct corticotropin-releasing hormone (CRH)
systems in the brain: one which is constrained by glucocorticoids and the other
which is not. It is this latter system that includes two primary sites (central
nucleus of the amygdala and the lateral bed nucleus of the stria terminalis) in
which the regulation of CRH gene expression can be disassociated from that of the
paraventricular nucleus of the hypothalamus. It is this other system that we think
is linked to fear and anxiety and to clinical syndromes (excessively shy fearful
children, melancholic depression, post-traumatic stress disorder and self-
administration of psychotropic drugs). The excess glucocorticoids and CRH, and the
state of anticipatory anxiety, contribute to allostatic load, a new term that
refers to the wear and tear on the body and brain arising from attempts to adapt to
adversity. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.
Panic disorder, an intense exacerbation of anxiety accompanied by a variety of
physical symptoms, is twice as common among women as among men. Onset is bimodal
(teens/20s and mid-30s/40s), 50% of cases are accompanied by agoraphobia, and the
etiology is probably multifactorial. Treatment in the primary care setting includes
pharmacologic (selective serotonin reuptake inhibitors) and cognitive-behavioral
intervention. Medication is initiated at low doses, and the drug-evaluation trial
is of 6 weeks duration. Psychiatric referral is helpful in nonresponders and in
those with comorbid psychiatric conditions. Outcome varies, with most patients
experiencing relief with treatment. For some people, however, the disorder is
chronic, with ongoing exacerbations and remissions.
In this article the authors address how pathological anxiety may develop from
adaptive fear states. Fear responses (e.g., freezing, startle, heart rate and blood
pressure changes, and increased vigilance) are functionally adaptive behavioral and
perceptual responses elicited during danger to facilitate appropriate defensive
responses that can reduce danger or injury (e.g., escape and avoidance). Fear is a
central motive state of action tendencies subserved by fear circuits, with the
amygdala playing a central role. Pathological anxiety is conceptualized as an
exaggerated fear state in which hyperexcitability of fear circuits that include the
amygdala and extended amygdala (i.e., bed nucleus of the stria terminalis) is
expressed as hypervigilance and increased behavioral responsivity to fearful
stimuli. Reduced thresholds for activation and hyperexcitability in fear circuits
develop through sensitization-or kindling-like processes that involve
neuropeptides, hormones, and other proteins. Hyperexcitability in fear circuits is
expressed as pathological anxiety that is manifested in the various anxiety
disorders.
Panic disorder is a common and disabling condition which frequently leads to
excessive reliance upon medical facilities. It is also closely associated with the
development of agoraphobia. Medical approaches implicate disturbances of ascending
brain noradrenergic and serotonergic systems, and support related
pharmacotherapies. Contemporary psychological approaches focus upon
misinterpretations of bodily sensations and an undue appreciation of the risk of
life-threatening illness, and support cognitive/behavioral psychotherapies. A
synthesis is possible by developing the view that the implicated ascending
aminergic systems normally play a part in "effortful" or context-sensitive
behavior. A relative failure of this under conditions of heightened arousal might
be responsible for the rigid patterns of fear, belief, and behavior that
characterize these patients. Clinical and research implications are discussed. (C)
1998 Elsevier Science Inc.
The relationship between traumatic experiences and dissociation with pretreatment
psychopathology and rates of recovery, relapse and maintenance for patients
receiving cognitive-behavioral treatments for panic disorder with agoraphobia (PDA)
were investigated. One-hundred and forty-seven subjects who met DSM-III criteria
for agoraphobia with panic attacks and who completed participation in one of two
previously conducted treatment outcome studies were mailed packets containing
measures to assess history of trauma, victimization and dissociation. Eighty-nine
of these were returned and completed sufficiently to be included in the present
study. It was hypothesized that a variety of trauma-related variables (e.g. history
of traumatic experience, type of trauma, age at which the trauma first occurred,
perceived responsibility, social supports available, self-perceived severity, level
of violence, and whether or not the traumatic event was followed by self-injurious
or suicidal thoughts and/or behaviors) and dissociative symptomatology would be
predictive of (1) greater psychopathology at pretreatment, (2) poorer treatment
response and (3) higher relapse rates and poorer maintenance over a 1 year
longitudinal follow-up. These hypotheses were supported by the findings and the
theoretical, empirical and clinical implications are discussed. (C) 1998 Elsevier
Science Ltd. All rights reserved.
Public awareness and misunderstandings of lactose intolerance are at an all-time
high. Many people erroneously believe they are lactose intolerant or develop
gastrointestinal symptoms after intake of lactose. Consequently, lactose-containing
foods such as milk and other dairy foods may be eliminated unnecessarily from the
diet. Because these foods are a major source of calcium, low intake of them can
compromise calcium nutriture. This, in turn, can increase the risk of major chronic
diseases such as osteoporosis (porous bones) and hypertension. This review is
intended to help dietetics professionals alleviate clients' fears about lactose
intolerance and recommend dietary strategies to improve tolerance to lactose.
Scientific findings indicate that the prevalence of lactose intolerance is grossly
overestimated. Other physiologic and psychologic factors can contribute to
gastrointestinal symptoms that mimic lactose intolerance. Scientific findings also
indicate that people with laboratory-confirmed low levels of the enzyme lactase can
consume 1 serving of milk with a meal or 2 servings of milk per day in divided
doses at breakfast and dinner without experiencing symptoms. Several dietary
strategies are available to help lactose maldigesters include milli and other dairy
foods in their diet without experiencing symptoms.
Chest pain and palpitations are commonly described in the general population and
are frequent presenting symptoms in all medical settings, Although often transient,
they can be persistent and are associated with considerable disability; distress,
and concern about heart disease and use of medical resources. Both symptoms are
associated with panic but also with other psychiatric disorders. II is most useful
to consider etiology as multicausal and interactive; psychological factors affect
interpretation of bodily perceptions and have deleterious effects on quality of
life and use of medical resources. There is evidence that general measures and
specific drug and psychological treatments can be effective. There is still
uncertainty about the most appropriate ways of providing effective care to large
numbers of patients. (C) 1998 Elsevier Science Inc.
An association between panic disorder and functional gastrointestinal disease has
emerged since the introduction of reliable diagnostic criteria, first for
psychiatric disorders and more recently for functional gastrointestinal disorders,
At the same time, a more rigorous review of methodology of older reports linking
structural gastrointestinal diseases such as peptic ulcer and inflammatory bowel
disease to psychiatric illness has cast doubt on the validity of their association.
In this review original articles reporting an association between panic disorder
and globus, functional chest pain of presumed esophageal origin, functional
dyspepsia, and irritable bowel syndrome are critically reviewed and it is concluded
that panic disorder is overrepresented in noncardiac chest pain and irritable bowel
syndrome. Original reports of the prevalence of panic disorder in structural
gastrointestinal disease are reviewed and it is concluded that they do not support
an association with panic. Hypotheses explaining the statistical link of panic
disorder and functional gastrointestinal disease are discussed. (C) 1998 Elsevier
Science Inc.
The lateral amygdala (LA) and its afferent connections from the medial geniculate
(MG) play a pivotal role in auditory fear conditioning. The authors evaluated
whether those neurons could express in paradoxical sleep (PS) physiological
plasticity acquired in waking. After a habituation session, rats received tone-
footshock pairings in 3 sessions. After each session, the tone alone was presented
during PS episodes. Multiunit activity was simultaneously recorded in the LA and
the medial part of the MG. Both in LA and MG, conditioned responses emerged rapidly
(within 5 trials), were expressed with short latency (<20 ms), and were maintained
in PS after training. Such changes were not observed in pseudoconditioned rats.
These results are discussed regarding the question of the primary sites of
plasticity in auditory fear conditioning and regarding the functional significance
of preserved expression in PS of learning-induced neuronal plasticity.
In this article, we review how the knowledge of the pathophysiology of panic
disorder has expanded, with special emphasis on laboratory models using lactate and
carbon dioxide challenges. Experiments in the late 1960s revealed that lactate
infusion can induce panic attacks. A prominent feature of these attacks is
hyperventilation. Because lactate infusion induces a metabolic alkalosis, one would
rather expect a compensatory hypoventilation. For years hyperventilation was
thought to be causally linked to panic, but it has since been proven to be a
symptom rather than a cause of panic attacks. Similarly, it is not hypocapnia but
hypercapnia that has proven to be capable of provoking panic attacks. Carbon
dioxide challenges are comparable to lactate infusion in the degree to which they
meet the criteria for an ideal model of panic disorder. Experiments with carbon
dioxide in first-degree relatives of panic disorder patients and in monozygotic
twins support the idea of a constitutional predisposition to panic disorder. Of the
various other agents that have been used to trigger panic attacks, cholecystokinin
seems particularly promising as a valid laboratory model of panic disorder and may
provide valuable data regarding the mechanism of panic attacks. The false
suffocation alarm theory, proposed by Klein, is an integrative hypothesis that may
account for a large number of the laboratory as well as clinical observations. (C)
1998 Elsevier Science Inc.
1. The effects of lesions of the bed nucleus of the stria terminalis (BST) on the
acquisition of conditioned fear were examined. In Experiment 1, BST lesions did not
block acquisition of fear-potentiated startle to an explicit visual conditioned
stimulus (CS) over 20 days of training. However, BST lesions blocked a gradual
elevation in baseline startle also seen over the course of training. 2. The gradual
increase in baseline startle was replicated in Experiment 2 without the presence of
an explicit CS, using unoperated subjects. Experiment 2 showed that the elevation
was due to repetitive exposure to shock, because unshocked control subjects did not
show any elevation over sessions. 3. In Experiment 3, lesions of the BST did not
disrupt rapid sensitization of the startle reflex by footshock, showing that
different neural substrates underlie sensitization of startle by acute and chronic
exposure to footshock. 4. These data indicate that the BST, despite its anatomical
continuity with the amygdala, is not critically involved in the acquisition of
conditioned fear to an explicit CS. Nevertheless, the BST is involved in mediating
a stress-induced elevation in the startle reflex. This suggests that the BST and
the CeA, which constitute part of the "extended amygdala" have complementary roles
in responses to stress.
In Pavlovian first-order conditioning, a conditioned response is acquired by
pairing a neutral stimulus (S1) with a stimulus that has innate motivational value.
In higher-order conditioning, a neutral stimulus (S2) is paired with S1 either
after (second-order conditioning) or before (sensory preconditioning) first-order
conditioning has been acquired. Thus, in higher-order conditioning the motivational
value of the reinforcer is acquired rather than innate. This review describes some
of the potential uses of higher-order conditioning in investigating the neural
substrates of fearful memories. First, because in second-order fear conditioning S2
is not paired directly with a painful stimulus, any effect of a treatment on the
acquisition of fear cannot be attributed to the treatment's possible effects on
transmission of nociceptive information. Second, higher-order conditioning provides
opportunities for analyzing where and how different types of events, or different
aspects of the same events, are represented in the brain. (C) 1998 Elsevier Science
Ltd. All rights reserved.
Panic disorder is a psychiatric illness in which etiology and underlying
neurobiological mechanisms remain unclear. In this article, avalaible data which
support the existence of an organic pathology responsible for this disorder are
reviewed, including the especifity of certain pharmacological therapies, the
possible genetical basis, neuroanatomy and neuroimage data and chemical models of
panic induction. Abnormalities in Locus Coeruleus (LC) and noradrenergic
neurotransmission are consistent candidates to explain panic attacks, although
another dysfunctions (in amygdala, hippocampus, GABA, CCK, 5-HT) can also play an
important role. We conclude that is neccesary the development of models-functional
neural netscapables of integrating the data obtained until this moment in a
coherent manner. In addition, a recent model (Charney), which fulfill the features
mentioned above and can serve as hypothesis for future research, is presented.
1. Changes in the plasma cortisol level were reported in a male patient with panic
disorder during the period of low-dose alprazolam treatment (mean 0.62+/-0.15
mg/day) compared with during the period of high-dose period (mean 1.08+/-0.28
mg/day). 2. The plasma cortisol level was significantly higher in the low-dose
period (mean 13.90+/-3.35 ug/ml) than in the high-dose period (mean 9.06+/-2.75
ug/ml) although, paradoxically, the panic attack frequency was significantly lower
in the low-dose period (mean 1.35+/-0.29/day) than in the high-dose period (mean
2.09+/-0.66/day). 3. Thus, the decreased plasma cortisol level during alprazolam
treatment of panic disorder was suggested to be caused not by symptom alleviation
due to alprazolam but by alprazolam administration itself.
The analysis of heart rate variability (HRV) is becoming widely used in clinical
research to provide a window into autonomic control of HR. This technique has been
valuable in elucidating the autonomic underpinnings of panic disorder (PD), a
condition that is marked by reports of heart palpitations. A body of research has
emerged that implicates a relative reduction in HRV and cardiac vagal tone in PD,
as indicated by various HRV measures. These data are consistent with the cardiac
symptoms of panic attacks, as well as with developmental evidence that links high
vagal tone with enhanced attention, effective emotion regulation, and organismic
responsivity. Implications of these findings for nosology and pathophysiology are
discussed. Reports of reduced HRV in PD contrast with portrayals of excess
autonomic lability in anxiety. This contradiction is addressed in the context of
traditional homeostatic models versus a systems perspective that views physiologic
variability as essential to overall stability. (C) 1998 Elsevier Science Inc.
Several symptoms of panic disorder mimic those of cardiovascular diseases and
patients with this disorder frequently consult physicians with the fear of dying
from a heart attack. The salient question is: Can the patient with panic disorder
die from the cardiovascular consequences of his/her panic attacks? We critically
review the six studies that have examined the association between panic disorder
(or panic-like anxiety) and cardiovascular mortality or complications associated
with the cardiovascular system. We then briefly review the evidence by which
mechanisms panic may be Linked to cardiovascular mortality and conclude with
proposed guidelines for patient management. (C) 1998 Elsevier Science Inc.
Psychoanalysis as a profession is in difficulty because changes in the mental
health field have exposed vulnerabilities inherent in psychoanalytic traditions. In
this setting, scientific outcome studies of psychoanalytic treatment are a
necessity. To enable such studies, certain preliminary research is required. In
particular, a set of reliable diagnoses that recognize psychodynamic factors, in
addition to "descriptive" criteria, must be developed. This paper outlines the
rationale, significance, and design of a pilot study in the area of anxiety
disorders, agoraphobia in particular, intended to provide a basis for
recategorization of the currently predominant DSM system.
Recent studies of lynching have focused on structural theories that have been
tested with demographic, economic and electoral data without much explanatory
success. This article suggests that lynching was largely a reflection of a
facilitating subculture of violence within which these atrocities were
situationally determined by cultural factors not reported in census and economic
tabulations, or election returns. Lynching declined in the twentieth century, in
part, as a result of segregation and disfranchisement policies, but mainly because
state executioners replaced lynch mobs in carrying out the will of the white
majority.
This article is Part II of a review of the neuronal circuits, neural mechanisms,
and neuromodulators that seem to be involved in anxiety and fear states. Part I
focused on the specific brain structures, including the roles of the amygdala,
locus coeruleus, hippocampus, and various cortical regions and the neural
mechanisms of fear conditioning, extinction, and behavioral sensitization in
mediating the signs and symptoms of anxiety and fear. Part II attempts to develop a
better understanding of neurochemical mediation of traumatic remembrance and the
neurobiological consequences of stress, particularly when experienced early in
life. Finally, the data is synthesized to provide a basis for understanding the
pathophysiology of anxiety disorders, such as Panic disorder and Posttraumatic
Stress Disorder.
There have been tremendous advances in our knowledge of the neurobiological basis
of human anxiety and fear. This review seeks to highlight how specific neuronal
circuits, neural mechanisms, and neuromodulators may play a critical role in
anxiety and fear states. It focuses on several brain structures, including the
amygdala, locus coeruleus, hippocampus, and various cortical regions and the
functional interactions among brain noradrenergic (NE), corticotropin releasing
hormone (CRH), and the hypothalamic pituitary adrenal axis (HPA). Particular
attention is directed toward results that can lead to a better understanding of the
constellation of the symptoms associated with two of the more severe anxiety
disorders, panic disorder and posttraumatic stress disorder (PTSD), the persistence
of traumatic memories, and the effects of stress, particularly early life adverse
experiences, on brain function and clinical outcome.
The presence of asthma is a risk factor for the development of panic disorder. The
co-occurrence of panic disorder and asthma is greater than would be expected based
on their individual prevalence rates. This may be due in part to the important role
of respiratory factors in panic disorder. Panic and anxiety can directly exacerbate
asthma symptoms through hyperventilation, and are associated with patients' overuse
of as-needed asthma medications, with more frequent hospital admission and longer
hospital stays, and with more frequent steroid treatment, all of which are
independent of degree of objective pulmonary impairment. The study of panic
disorder among asthmatics can contribute to improved medical outcome for this
subgroup, while also improving our understanding of the biological and
psychological etiology of panic. This article will review the literature on this
relationship by examining how panic disorder and panic symptoms affect the course
of asthma, how asthma affects the symptoms and physiology of panic disorder, and
the consequent research implications of this relationship. (C) 1998 Elsevier
Science Inc.
Various provocative agents, including sodium lactate, carbon dioxide (CO2),
caffeine, yohimbine, serotoninergic agents, and cholecystokinin (CCK), have been
utilized as panicogenics in studies on healthy volunteers as well as in panic
disorder patients. An overview of the utilization of these agents to study the
neurobiology of panic disorder is presented. The possible roles of several
neurotransmitters and neuromodulators in the etiology of panic disorder and in the
actions of drugs used in its treatment are also discussed. (C) 1998 Elsevier
Science Inc.
Using Pavlovian conditioned increases in the amplitude of the acoustic startle
reflex as a behavioral indicator of fear motivation, the authors previously showed
a resistance to extinction after repeated associations of cocaine with the fear-
evoking conditioned stimulus (CS). In Experiment 1, acute administration of
cocaine, amphetamine, and the dopamine (DA) D-1 receptor agonist SKF 38393 produced
a similar fear enhancement. In Experiment 2, a noncontingent injection of cocaine
and SKF 38393 provoked a CS potentiation of acoustic startle in fear-extinguished
laboratory rats. Potential behavioral, neurochemical, and neuroendocrine
explanations for the effects of psychomotor stimulants on conditional fear were
discussed. It was suggested that DA agonist drugs increase fear expression possibly
by activating mesoamygdaloid associative neurocircuitry involved in excitatory
conditioned fear reactions.
Panic disorder, a psychiatric disorder characterised by frequent panic attacks, is
the most common anxiety disorder, affecting 2 to 6% of the general population. No
one line of treatment has been found to be superior, making a risk-benefit
assessment of the treatments available useful for treating patients. Choice of
treatment depends on a number of issues, including the adverse effect profile,
efficacy and the presence of concomitant syndromes. Tricyclic antidepressants
(TCAs) are beneficial in the treatment of panic disorder. They have a proven
efficacy, are affordable and are conveniently administered. Adverse effects,
including jitteriness syndrome, bodyweight gain, anticholinergic effects and
orthostatic hypotension are commonly associated with TCAs, but can be managed
successfully. Selective serotonin (5-hydroxytryptamine; 5HT) reuptake inhibitors
are also potential first line agents and are well tolerated and effective, with a
favourable adverse effects profile. There is little risk in overdose or of
anticholinergic effects. Adverse effects include sedation, dyspepsia and headache
early in treatment, and sexual dysfunction and increased anxiety, but these can be
effectively managed with proper dosage escalation and management. Benzodiazepines
are an effective treatment, providing short-term relief of panic-related symptoms.
Patients respond to treatment quickly, providing rapid relief of symptoms. Adverse
effects include ataxia and drowsiness, and cognitive and psyche-motor impairment.
There are reservations over their first-line use because of concerns regarding
abuse and dependence. Monoamine oxidase inhibitors, because of their adverse
effects profile, potential drug interactions, dietary restrictions, gradual onset
of effect and overdose risk, are not considered to be first-line agents. They are
effective however, and should be considered for patients with refractory disease.
Valproic acid (valproate sodium), while not intensively studied, shows potential
for use in panic disorder. More studies are needed in this area before the
available data can be confirmed. As a supplement to drug therapy, cognitive
behavioural therapy is effective. It is well tolerated, and may be beneficial in
certain clinical situations. Its main drawback is the time commitment and effort
needed to be made by the patient.
Background Tricyclic(TCA)and monoamine oxidase inhibitor (MAOI) antidepressants are
effective in the treatment of panic disorder. Two selective serotonin reuptake
inhibitors (SSRls) have also been licensed in the UK for this indication and
studies with three other SSRls have recently been completed. These provide further
evidence for the role of serotonin in panic. Method Review of clinical, animal and
laboratory studies, Results SSRls have been shown to be effective in the treatment
of panic disorder. The reported rates of improvement of 60-70% of patients taking
SSRls are similar to those seen with TCAs and greater than placebo. Other
serotonergic agents do not appear to be effective. Animal work and human studies
including measures of 5-HT in plasma. cerebrospinal fluid and platelets, challenge
paradigms and tryptophan depletion show that the relationship between 5-HT and
anxiety is complex. Conclusion Clinical trials have shown that of all the
serotonergic agents only the SSRls are effective in panic disorder. They are as
beneficial as the TCAs and seem to be better tolerated which may be particularly
significant in view of the chronic nature of the condition. Serotonin plays a role
in panic disorder and serotonergic dysfunction, however the results and evidence do
not fit one theory alone. It is also likely that different brain regions and 5-HT
receptors are involved in specific ways.
The pressures on the scientific community, both in industry and in academia, to
succeed in an environment of competition, short time-lines and high expectation has
taken its toll on the altruistic ideals of 'science'. The author describes how the
motivation for scientists has changed in the light of increasing pressures and what
effect this may have if it continues.
The purpose of this article is to provide a general overview of the growing
literature on the relationship between panic disorder and vestibular disturbance.
This relationship has been examined from two distinct perspectives, including: (a)
the assessment of vestibular dysfunction in patients with panic disorder; and (b)
the evaluation of panic symptomatology in patients with vestibular disturbance.
Consequently, this review focuses primarily on the literature pertaining to
vestibular symptoms in patients with panic disorder and panic symptomatology in
patients with vestibular complaints. Subsequent to this review we discuss clinical
implications suggested by the data, outline recommendations for treatment, and
highlight some directions for future investigation. (C) 1998 Elsevier Science Inc.
After a general description of the Panic Disorder and of the most important
pathogenetic biological theories, the Authors analyze the data of the literature
about the psychotropic drugs used in the short and long term treatment of this
disorder, with particular attention to the most recent drugs (RIMA, SSRI, SNRI), As
there is a 20-80 percentage of relapse when the therapeutic path is not completed
or is interrupted, with an high risk of cronicization and a compromission of the
life quality of the patient, it can be easily understood how important is to define
and go on with a low side effect profile pharmachotherapeutical programme. At the
end the Authors highlight the importance of an integrated psychopharmaco-
psychological treatment, programmed for each patient on the basis of his
transversal and longitudinal comorbidity.
1. Considerable experimental attention has been directed at understanding the role
of opioid peptides in mediating stress effects. Fewer studies have utilized non-
physical or 'psychological' methods to investigate the role of the opioid system in
stress. 2. Recent studies have shown that conditioned fear, a psychological
stressor, can augment morphine induced analgesia and acute dependence. Two
experiments were conducted to assess withdrawal-like behavioral changes induced by
the general opioid antagonist naloxone, in the absence of morphine, following
exposure to a context conditioned fear stimulus. 3. Experiment 1 demonstrated that
a high dose of naloxone (10 mg/kg) produced a specific increase in one behavioral
index of negative affect, forepaw tremor behavior, in rats exposed to a context
fear stimulus. 4. Experiment 2 assessed the relative effects of several naloxone
(0, 1, 5, 10 mg/kg) doses in inducing withdrawal-like behavioral changes in animals
exposed to a conditioned fear context. This experiment revealed that low doses of
naloxone produced an overall increase in all behaviors. High naloxone doses tended
to increase only forepaw tremor behavior. 5. The results are discussed ih terms of
opioid systems and stress.
The whole-body acoustic startle response is a short-latency reflex mediated by a
relatively simple neural circuit in the lower brainstem and spinal cord. The
amplitude of this reflex is markedly enhanced by moderate fear levels, and less
effectively increased by higher fear levels. Extensive evidence indicates that the
amygdala plays a key role in the potentiation of startle by moderate fear. More
recent evidence suggests that the periaqueductal gray is involved in the loss of
potentiated startle at higher levels of fear. The influence of both structures may
be mediated by anatomical connections with the acoustic startle circuit, perhaps at
the level of the nucleus reticularis pontis caudalis. The present chapter reviews
these data. (C) 1997 Elsevier Science Ltd.
This paper reports application of a theoretical persuasive health message framework
grounded in literature on fear appeals, message design logic, and health persuasion
theory to assess the effectiveness of the materials used most frequently by
national immunization organizations in the United States. The severity of the
problem of inadequate preschool immunization with its associated target audience
and barriers is identified. Analysis revealed that national immunization message
designers are creating materials most likely to match what health communication
research would recommend along the dimension of response efficacy (i.e., showing
parents that attaining immunizations is realistic, available, affordable, safe, and
effectively prevents specific diseases). However the materials were least likely to
match along the dimension of self-efficacy (i.e., building parents' beliefs that
they have the ability and motivation to perform preventive immunization behavior
for their children). Implications for practitioners in developing more effective
immunization fear appeals, and suggestions for future research in the area, are
addressed in the Conclusion.
Panic disorder with or without agoraphobia has been the subject of sustained
treatment-outcome research. Studies have been conducted by both pharmacologically-
and psychologically-oriented researchers each employing their own methodologies.
Problems arise in attempting to reconcile the demands of these two treatment-
outcome methodologies, whilst at the same time ensuring that research designs
reflect the reality of wider clinical practice. In the following discussion a
series of studies comparing pharmacological and psychological treatments for panic
disorder and agoraphobia are reviewed. The review highlights areas where the
competing demands of research design and clinical applicability lead to dilemmas
for the researcher. Attempts to overcome such dilemmas are described and
alternative solutions discussed.
Patients with panic disorder often believe they are suffering a myocardial
infarction or another life-threatening illness. The history and physical
examination and a few tests usually suffice to diagnose this disorder, which is
treatable with behavioral therapy, antidepressants, and benzodiazepines.
Objective: The blood platelet has been proposed as a model of central neurons and
may therefore be used as a peripheral marker of psychiatric illness. One method of
investigating serotonin function in panic disorder has relied on the use of the
platelet as a model of serotonergic neurons. This article reviews the studies of
platelet function in panic disorder. Method: A literature search and review of
relevant papers was undertaken. Result: Studies examining platelet serotonin uptake
and concentration in panic disorder patients have to date yielded conflicting
results, with some investigators reporting increased serotonin uptake, others
reduced uptake. Similarly studies of platelet H-3-imipramine binding have also
yielded conflicting results. Two studies of platelet H-3-paroxetine binding have
shown a reduction in the density of binding sites (max) in patients with panic
disorder. platelet monoamine oxidase activity in anxiety disorders has been
reported to be increased by some investigators but decreased by others.
Methodological considerations may have been responsible for these differences.
Finally, studies of alpha(2) adrenoceptor density have also produced contrasting
findings. Conclusion: The findings of these studies indicate that platelet function
is altered in panic disorder. Such changes may allow an insight into the
biochemical aetiology of the illness. Further studies are required to delineate the
role of serotonin and non-adrenaline in panic disorder.
Premature ejaculation is a common sexual disturbance among men. Both open-label and
double-blind studies have demonstrated the effectiveness of serotonergic
medications for this disorder, These studies support the hypothesis that the
serotonergic system has an important role in the modulation of sexual response,
especially attainment of orgasm. Serotonergic dysfunction also has been linked to
the pathogenesis of panic disorder. Several studies have demonstrated the efficacy
of serotonergic drugs in this disorder, The purpose of the present study was to
examine the efficacy of fluoxetine, a serotonin selective reuptake inhibitor for
the treatment of comorbid premature ejaculation and panic disorder, in IO men in an
open-label design. The patients were given 20 mg of fluoxetine for 8 weeks of the
study. Parameters pertaining to sexual function and measures of anxiety were
examined. Improvement of premature ejaculation was noted as of week 2 of the study,
whereas measures of panic and sexual satisfaction became statistically significant
only as of week 4. Further studies with larger samples and longer periods of
follow-up are needed in order to determine the usefulness of fluoxetine for the
treatment of comorbid premature ejaculation and panic disorder.
Physiological (heart rate, blood pressure, electrodermal activity), biochemical
(epinephrine, norepinephrine, cortisol) and subjective parameters (self-rating
score) of 33 patients with panic disorder (diagnoses according to DSM-III-R)
before, during and after stress exposure were compared with those of healthy
controls. As stressors a video containing frightening scenes (FS), mental
arithmetic (MA), a video documenting a patient suffering from a panic attack (PA)
and an improvised speech (IS) were applied. We found significantly higher baseline
levels of electrodermal activity (EDA) and norepinephrine (NE) secretion and a
subsequent further increase during stress exposure in panic disorder patients as
compared with normal controls. The most potent stressors during the trial proved to
be mental arithmetics and improvised speech, which was evident in both groups. The
situation panic attack video appeared to be a ''panic disorder patient-specific''
stressor; here we noticed the most pronounced reactions in the patient group. Panic
disorder patients had significantly higher self-rating scores of the parameters
panicky feelings, anxiety and nervousness at the beginning and throughout the
investigation. We conclude that panic disorder patients have a higher degree of
activation compared with normal controls, which is evident regarding levels of
electrodermal activity and norepinephrine secretion. Furthermore, the panic attack
video appears to be a panic disorder patient-specific stressor.
Paroxetine is the first selective serotonin (5-hydroxytrypamine; 5-HT) reuptake
inhibitor (SSRI) to be approved for the treatment of patients with panic disorder
with or without agoraphobia. It is a highly selective inhibitor-of presynaptic
serotonin reuptake and does not interact with adrenergic, dopaminergic,
histaminergic or serotonergic receptors to any significant extent. Oral paroxetine
10 to 60 mg/day is significantly more effective than placebo in reducing the
frequency of panic attacks and improving associated symptoms, as shown in short
term trials In patients with panic disorder. with of without agoraphobia. The
efficacy of the drug was maintained during Icp to 6 months' treatment, and
continued therapy reduced the risk of relapse. Oral paroxetine 10 to 60 mg/day was
at least as effective as clomipramine 10 to 150 mg/day, but appeared to have a more
rapid onset of effect, in a placebo-controlled trial. The tolerability profile of
paroxetine is similar to that established for other SSRls and is characterised by
adverse events such as nausea, headache, somnolence, dry mouth, tremor insomnia,
asthenia, sweating, constipation, dizziness and sexual dysfunction. Paroxetine was
better tolerated overall than clomipramine and was associated with a lower
incidence of certain anticholinergic events (such as dry mouth and constipation) in
a comparative trial. It is not associated with the type of dependence seen with
benzodiazepines, and it appears to be safer in overdose than the tricyclic
antidepressants. Paroxetine 20 or 30mg does not significantly impair psychomotor
function or interact with alcohol (ethanol). In conclusion, the good tolerability
profile of paroxetine, including lack of dependence potential and relative safety
in overdose, makes it attractive for the treatment of patients with panic disorder:
It appears to be at least as effective as clomipramine in reducing panic attacks
and associated symptoms. Although further trials to compare the efficacy and
tolerability of paroxetine with that of other tricyclic agents (especially
imipramine), high-potency benzodiazepines and monoamine oxidase inhibitors are
needed the drug appears to have the potential to become a first-line treatment for
panic disorder .
Noncardiac chest pain is a common costly phenomenon in the cardiology setting.
Recent research suggests that panic disorder, a highly distressful yet treatable
anxiety disorder, occurs in a significant proportion of noncardiac chest pain
patients. This article reviews research on the prevalence of panic disorder in
patients seen in cardiology settings for unexplained chest pain. Financial,
psychosocial, and historical aspects of noncardiac chest pain are described. Panic
disorder and the potential consequences of its nonrecognition by physicians are
examined. Current psychological and pharmacologic treatments are reviewed.
Recommendations on the management of panic patients in the cardiology setting are
provided.
Panic disorder is a frequently chronic condition with extensive patterns of
psychiatric comorbidity. Optimum pharmacotherapy with traditional agents is limited
by side effects, long-term tolerability, and other problems. Recent research
findings support the characterization of panic disorder as an illness involving
derangements of central serotonergic function. Selective serotonin reuptake
inhibitors could become first-line treatment of the disorder, as they seem to have
fewer side effects than tricyclic antidepressants and benzodiazepines.
Evidence from many different laboratories using a variety of experimental
techniques and animal species indicates that the amygdala plays a crucial role in
conditioned fear and anxiety, as well as attention. Many amygdaloid projection
areas are critically involved in specific signs used to measure fear and anxiety.
Electrical stimulation of the amygdala elicits a pattern of behaviors that mimic
natural or conditioned fear. Lesions of the amygdala block innate or conditioned
fear, as well as various measures of attention, and local infusions of drugs into
the amygdala have anxiolytic effects in several behavioral tests. N-methyl-D-
aspartate (NMDA) receptors in the amygdala may be important in the acquisition of
conditioned fear, whereas non-NMDA receptors are important for the expression of
conditioned fear. The peptide corticotropin-releasing hormone appears to be
especially important in fear or anxiety and may act within the amygdala to
orchestrate parts of the fear reaction.
This article reviews the phenomenon of nocturnal panic, or waking from sleep in a
state of panic. The review covers the presenting features of nocturnal panic and
the evidence for cognitive and physiological mediating variables. A
psychobiological conceptualization that parallels conceptualizations for daytime
panic attacks is offered. Obstacles for future research in this area include
ambiguities in the definition of nocturnal panic, and its distinctiveness from
other sleep disorders, as well as measurement issues. Implications from a
psychobiological conceptualization include the appropriateness of cognitive-
behavioral treatment for nocturnal panic.
Objective: Psychiatric classification is still a topic of considerable discussion
and debate in spite of major advances in the past two decades. The debate involves
categorical versus dimensional approaches, cutoff numbers of symptoms to define a
case, degree of impairment, objective diagnostic criteria versus more theoretically
based criteria, episodic versus trait-like symptoms, and the role of atypical and
subclinical symptoms. All of these issues have been raised for the anxiety
disorders and depression. This article presents the conceptualization of a
relatively novel and testable approach to the diagnosis and classification of panic
and agoraphobia, the panic-agoraphobic spectrum, and pilot data on a new
questionnaire to assess it. Method: Pilot testing of the Panic-Agoraphobic Spectrum
Questionnaire was undertaken with 100 inpatients who had lifetime diagnoses of
panic disorder, unipolar depression, comorbid panic and unipolar depressive
disorders, or an eating disorder. The instrument emphasizes impairment related to
144 behaviors and experiences in seven panic-agoraphobic symptom domains. Results:
Patients with panic disorder scored highest on the questionnaire, and those with
comorbid depression showed even greater severity of illness. The scores of the
patients with eating disorders and of the depressed patients differed from those of
the other groups but also differed from 0. Conclusions: The spectrum model of panic
and agoraphobia is a flexible and comprehensive means of describing this clinical
complex. The proposed model, complementary to the categorical approach, presumably
expresses a unitary pathophysiology. Its usefulness is discussed in terms of its
value for patient-therapist communication, outcome measures, identification of
subtle personality traits, and subtyping of patients for research and treatment.
1. Previous studies have shown that morphine analgesia is enhanced when analgesia
testing is conducted in an environment that has been previously paired with shock,
but not in a novel or neutral environment. 2. Two experiments were conducted to
assess if enhanced morphine analgesia could be demonstrated in a neutral context if
rats were first exposed to conditioned fear cues. This was done by pre-exposing
rats to a context previously paired with shock and testing for enhanced morphine
analgesia in a neutral context immediately following removal from the conditioned
fear context. To determined if conditioned analgesia contributed to the enhanced
morphine analgesia, rats were tested for analgesic responsiveness immediately
following removal from conditioned fear cues, prior to morphine administration. 3.
In Experiment 1, although conditioned analgesia was not observed, a small
enhancement of morphine analgesia was demonstrated in an neutral context in rats
pre-exposed to conditioned fear cues, compared to non-conditioned controls. 4. In
Experiment 2, which employed more sensitive test procedures, a strong enhancement
of morphine analgesia was observed in a neutral context only in those rats that
demonstrated conditioned analgesia. (C) 1997 Elsevier Science Inc.
A repertoire of reliable and valid self-report instruments to assess panic and
panic disorder would help both researchers and clinicians. This review presents a
description and an analysis of the available instruments. Following a comprehensive
search of the literature, 14 instruments with published information on reliability
and validity were reviewed. The following information is reported for each
instrument: brief description of the instrument and its development, mean and
standard deviation for clinical and nonclinical samples, and psychometric
properties. Four types of instruments are presented: general assessment and
information (n = 2), severity of panic disorder (n = 2), body sensations (n = 2)
and cognitive dimensions of panic (n = 8). Overall, it would seem that panic
measures have moderate to excellent psychometric qualities. However, the comparison
between the instruments is difficult because the amount of empirical support
available varies widely from one instrument to the other. (C) 1997 Elsevier Science
Ltd.
Practicing psychiatrists frequently encounter elderly patients with generalized
anxiety disorder or panic disorder. Unfortunately, the empirical literature
regarding the assessment, diagnosis, and treatment of these illnesses in older
individuals is sparse, despite the attention directed to them in younger patients.
In this paper studies of generalized anxiety and panic disorders among the elderly
are reviewed and compared to similar investigations among younger adults to assess
our current understanding of the epidemiology, etiology, diagnosis, and treatment
of these conditions. Articles were selected from those retrieved by Index Medicus
(papers in English, published in 1992 or later; search terms ''anxiety,'' ''anxiety
disorders,'' ''panic disorder,'' and ''elderly'').
Charles Darwin (1809-1882) suffered from a chronic illness that, throughout much of
his adult life, impaired his functioning and severely limited his activities. The
writings of this famous scientist as well as biographical materials indicate that
he probably suffered from an anxiety disorder. His symptoms, when considered
individually, suggest a variety of conditions, but taken together they point toward
panic disorder with agoraphobia. This diagnosis brings coherence to Darwin's
activities and explains his secluded lifestyle, including difficulty in speaking
before groups and meeting with colleagues.
Recent discoveries about the neural system and cellular mechanisms in pathways
mediating classical fear conditioning have provided a foundation for pursuing
concurrent connectionist models of this form of emotional learning. The models
described are constrained by the known anatomy underlying the behavior being
simulated. To date, implementations capture salient features of fear learning, both
at the level of behavior and at the level of single cells, and additionally make
use of generic biophysical constraints to mimic fundamental excitatory and
inhibitory transmission properties. Owing to the modular nature of the systems
model, biophysical modeling can be carried out in a single region, in this case the
amygdala. Future directions include application of the biophysical model to
questions about temporal summation in the two sensory input paths to amygdala, and
modeling of an attentional interrupt signal that will extend the emotional
processing model to interactions with cognitive systems.
A brief review of biological and psychological classification systems reveals that
existing taxonomies have focused on discrete, static classifications of panic. Our
paper introduces a dynamic, idiographic phenomenological system to characterize
panic as it occurs across the anxiety disorders. The model consists of four grids,
each with four quadrants, that focus on the degree and specificity of physiological
change, catastrophic cognitions, and somatic sensations, as well as the extent and
type of affect experienced. Preliminary data from an ambulatory home monitoring
study are presented to demonstrate the utility of the model. A primary contribution
of the model is that it increases precision and emphasizes assessment across
measurement domains. The proposed system may provide the basis for future research
in a number of areas, which are delineated.
Despite the preeminence of English in international discourse and census data
indicating that ninety-nine percent of Americans speak English either very well or
well, the Official English movement has garnered significant political support over
the last ten years. Divorced from its political polemic, the objective of the
Official English movement is the adoption of an ''English Language Amendment''
(ELA) to the Constitution that would require the use of English in public discourse
as a matter of law. This Article approaches the question of what legal difference
an ELA would make by studying the French experience under a recently adopted
constitutional amendment to officialize its national language and comparing the
French linguistic regime to its American counterpart. The Article demonstrates that
the French approach to language regulation has not been particularly successful.
Moreover, the degree to which France has gone to protect its language requires a
level of government intrusion into speech that would not be tolerable under the
U.S. Constitution. The Article concludes that the French approach is both futile
and unnecessarily repressive and suggests that the proposed ELA is similarly ill-
conceived and unwarranted.
Fear is an emotion or a motivational state induced by a perception of danger and
producing behavioural and physiological reactions in order to be prepared to escape
from or to face such danger. Fearfulness, or the susceptibility to be afraid,
appears to be a characteristic of an individual which varies according to a wide
range of genetic (breed, strain, sex) or environmental (social or non social)
factors. Knowledge of factors which affect fear reactions of farm animals allows to
consider improvement of rearing conditions and selection criteria in order to
enhance adaptation of animals to their environment (welfare), while maintaining
optimal productivity.
1. The authors investigated the psychological and biochemical factors associated
with challenge by 5% CO2-95% O-2 inhalation for 20 min. While fifteen healthy
people were used as control, thirteen cases who were diagnosed by DSM-III-R as
suffering from panic disorder were used as subjects. CO2 inhalation induced panic
in 38% of the panic disorder patients, but did not cause panic in any of the
control cases (0%). 2. Acute panic inventory (API), heart rate, and breathing rate
of the panic group increased significantly after CO2 inhalation compared with the
values in the control and non-panic groups. 3. Heart rates and systolic blood
pressure were significantly higher those in the panic disorder and non-panic groups
than in the control group prior to CO2 inhalation. The cortisol values in the panic
and non-panic groups also were significantly higher than those in the control group
before and after CO2 inhalation. 4. These results suggest elevated activity of the
sympathetic nervous system during panic. The significantly higher heart rate,
systolic blood pressure and cortisol values of the panic disorder subjects relative
to the control before CO2 inhalation may have been due to circumstantial factors.
The present findings of convincing evidence for behavioral, physiological, and
biochemical hypersensitivity to CO2 in patients with panic disorders are consistent
with a model of interoceptive conditioning in these patients.
The prevalence of panic disorder in the general population is 2,3% over a person's
whole life, and 0,5-1% per year. international studies have yielded more widely
varying estimates of the prevalence of panic attacks (4-12%). The proportion of
patients consulting their doctors for panic disorder is also highly variable; the
frequency is a function of the medical specialty (being highly represented in
cardiology and the emergency services). In psychiatry, panic disorder represents
the main diagnosis in one patient out of 10 or 20. Panic disorder is more common in
women than men, and in young or middle-aged subjects and those living alone
(separated, widowed or divorced). In socio-economic terms, it is the socio-
educational level rather than income or profession that appears to be the
determining factor. Lastly, residence (urban/rural) and the fact of belonging to a
particular sociocultural group seem to play little part. As with many mental
disorders, two predisposing factors have been found to operate: a genetic element,
as shown by family and twin studies, and an element relating to psychoaffective
development (traumatic events in childhood, separation anguish, etc.). Panic
disorder is commonly associated as a comorbid trait with other neurotic and anxiety
disorders, depression, alcoholism and drug abuse. These associations represent poor
prognostic factors associated with chronicity attempted suicide and social
handicap. Prospective studies of overall outcome have shown complete remission
rates of 10-20% at 3 or 5 years. However, if the occasional occurrence of a few
panic attacks is regarded as acceptable, the prognosis can be regarded as good for
two-thirds of affected subjects.
This review was designed to provide a detailed analysis of long-term outcome data
from treatment studies for panic disorder, with the goal of ascertaining
differential efficacy of the available treatments. Studies were included if they
were published after 1980 and if follow-up took place at least 6 months after
treatment termination. Thirty-one studies were located. A variety of methodological
problems were found in these studies, including lack of clarity of diagnosis, lack
of clarity in the treatment administered, and inadequately tracked nonstudy
treatments during the study and follow-up periods, which Limited the information
that could be obtained about long-term outcome. Long-term outcome studies that
closely track the additional treatments that patients receive are necessary to draw
more definitive conclusions about differential treatment efficacy for panic
disorder. Available data suggest that there is limited evidence for long-term
maintenance of short-term treatment gains in panic disorder patients in the absence
of continued treatment.
Over the past decade, panic disorder has become a major research focus in
psychopathology and treatment. Initial interest in the causes of the disorder was
triggered by biological theories and investigators. More recently, however,
research on newly developed psychological approaches has advanced our understanding
of panic disorder and has led to the development of specific treatment programs.
This review describes symptomatology and course, the psychophysiological model of
panic and a psychological treatment that directly targets panic attacks and the
fears and behaviors associated with them.
Numerous studies in both rats and humans indicate the importance of the amygdala in
the acquisition and expression of learned fear. The identification of the amygdala
as an essential neural substrate for fear conditioning has permitted
neurophysiological examinations of synaptic processes in the amygdala that may
mediate fear conditioning. One candidate cellular mechanism for fear conditioning
is long-term potentiation (LTP), an enduring increase in synaptic transmission
induced by high-frequency stimulation of excitatory afferents. At present, the
mechanisms underlying the induction and expression of amygdaloid LTP are only
beginning to be understood, and probably involve both the N-methyl-D-aspartate
(NMDA) and alpha-amino3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) subclasses of
glutamate receptors. This article will examine recent studies of synaptic
transmission and plasticity in the amygdala in an effort to understand the
relationships of these processes to aversive learning and memory.
Major depression is a common mental disorder with a lifetime prevalence of
approximately 15% of the general population, affecting almost twice as many females
as males. Panic disorder is a severe anxiety disorder with a lifetime prevalence of
2-3% or more. Like major depression, panic disorder affects nearly twice as many
females as males. Both panic disorder and major depression are often chronic
conditions, resulting in significant morbidity and mortality. Among patients who
seek treatment for either panic disorder or major depression, both conditions are
present in approximately one-third of the patient population. Substantial
information suggests that individuals who suffer from both panic disorder and major
depression respond poorly to acute treatment, are more likely to remain ill over
the long term, require more psychiatric treatment, and are at approximately twice
the risk of suicide attempts than individuals who suffer from either condition
alone. There has been very little systematic study of individuals with coexisting
panic disorder and major depression. This has left significant gaps in our
knowledge about optimal treatment for the substantial subgroup of individuals
suffering from both disorders simultaneously. Social phobia is a common disorder
which affects 2-8% (females more than males) of the population. Recent advances in
the pharmacological treatment of social phobia are reviewed. Patterns of
comorbidity, effects of coexisting psychiatric disorders on disability, health care
utilization and suicidality are discussed, together with treatment implications for
coexisting social phobia and major depression.
Panic disorder is a devastating condition with a higher prevalence in female
patients and young adults. Panic disorder is frequently associated with major
depression, agoraphobia, substance abuse, suicide attempts, and impaired quality of
life. Only one half of the subjects with panic disorder seek care for their
attacks, and those who do seek care tend to present to primary care and emergency
department settings. If treated appropriately, panic disorder has a favorable
prognosis.
Pear is now widely regarded as an undesirable state of suffering by many members of
the public, the scientific community, welfare and policy groups, as well as by a
growing number of farmers. At first glance this view appears to be inconsistent
with one based on biological significance, in which fear is regarded as an adaptive
state with fear behaviour functioning to protect the animal from injury. Fear is
often adaptive in ideal circumstances but neither we nor the animals in our care
live in an ideal world. In reality, many farming systems prevent the animals from
responding in an adaptive fashion to potentially threatening stimuli. In these
circumstances, fear can be a powerful and potentially damaging stressor,
particularly if it is intense or persistent. Both acute and chronic fear can
seriously harm the welfare and performance of poultry. Certain fear responses, such
as violent escape or panic, are inappropriate in intensive systems and can cause
injury, pain or even the death of birds. High levels of underlying fearfulness have
also been negatively associated with plumage condition, egg production, egg shell
quality, growth, and food conversion efficiency. Furthermore, because fear inhibits
all other motivational systems, its elicitation is likely to impair the ability of
birds to adapt to environmental change, to interact successfully with each other or
with the stock person, and to utilize new resources. Therefore, high fear is
clearly undesirable from the bird's and the farmer's viewpoint and its reduction is
of major importance. This objective had been hampered because of the complexity of
the concept of fear and the controversy over its measurement. However, operational
definitions of fear and its components are given in this review and a number of
tests which have been used to measure fear in poultry are described. Strong intra-
individual correlations found between the fear scores afforded in many of these
tests suggested that they are measuring the same intervening variable, presumably
underlying fearfulness, rather than purely stimulus-specific responses. Two of the
commonest and potentially most frightening events encountered by poultry are sudden
changes in their physical or social environment and exposure to humans. Other more
specific types of alarming stimuli are also listed. Hitherto, the most promising
ways of reducing underlying fearfulness and increasing adaptability, at least in
the laboratory, involve one or more of the following approaches: environmental
enrichment, regular handling or related treatments, vitamin C supplementation of
the diet or drinking water, and genetic selection. The potential benefits and
shortcomings of these remedial measures are discussed, with attention to their
practical relevance as well as to their more fundamental implications. Other
measures to mask and/or minimize the incidence of frightening events are also
briefly mentioned. Our objective should be not only to achieve a balance between
maintaining an emotional state that facilitates the avoidance of danger while
reducing the likelihood of overreaction and the expression of inappropriate
responses, but also to provide a stimulating, safe but economically viable
environment. Continued investigation should enable recommendations to be made
concerning the most effective programme, in terms of environmental modification,
human-animal interaction, nutritive manipulation, and selective breeding, in order
to achieve the optimal levels of fear in poultry, whatever the future trends in the
industry.
In order to verify the accuracy of the commonly used statement, ''I sweat blood,''
a survey of the literature in the subject of hematidrosis was made. Seventy-six
cases were studied and classified into categories according to the causative
factor. These were, component of systemic disease, vicarious menstruation,
excessive exertion, psychogenic, and unknown. The psychogenic were further
subdivided into those that occurred only one time, those that recurred and the
stigmatics. Acute fear and intense mental contemplation were found to be the most
frequent inciting causes. Hematidrosis is an extremely rare clinical phenomenon
with only few instances reported to have occurred within the twentieth century.
1. The nosological status of panic disorder is still a matter of debate.
Nevertheless, evidence is emerging that panic attacks have a different pattern of
drug responsiveness from other forms of anxiety. 2. Several experimental animal
models of panic attacks have been developed. These vary in the extend to which they
meet criteria for face validity, predictive validity and construct validity,
normally applied to such models. 3. In the present review, the authors examine the
possibility that predator-elicited flight responses in Swiss-Webster mice might
serve as an experimental model for the screening of panic-modulating drugs. 4. Drug
effects on flight responses clearly indicate that this model has good predictive
validity as panic-promoting agents increase flight reactions, while panicolytic
drug challenge induces opposite effects. In addition, drugs devoid of any effect on
panic attack, also do not alter flight behavior. 5. These findings strongly suggest
that the model of predator-elicited flight responses in Swiss-Webster mice is
useful for the investigation of panic-modulating drugs.
Epidemiological studies have found that few cases of panic disorder arise for the
first time after the age of 40 years, and there is a steady decline in the
prevalence of existing cases in the latter half of life. The authors review these
epidemiological findings and explore various hypotheses that might explain the
decreased frequency of panic disorder in old age. There is no available evidence to
suggest that methodological factors have led to an underestimation of the
prevalence of this disorder in older rather than younger age groups. However, there
is evidence that disorder-associated mortality and age-related changes in brain
neurochemistry may contribute to the decreased frequency of this illness in later
life. A cohort effect also should be considered, although currently there are no
data available to support or refute this idea.
A third of a million adults in the UK sleepwalk while a million suffer from night
terrors. In both conditions the individual is unaware of the fullness of their
surroundings and is totally focussed in their concern or activity. Doctors are only
likely to become involved if the individual comes to harm or seeks help or if other
people are inconvenienced or threatened. The constitutional basis of the disorder
is beyond doubt, although the actual expression may be related to stressful life-
events resulting from an individual's personality, relationships and circumstances.
Treatment may include the provision of a secure environment, counselling, and the
use of benzodiazepines and serotonin re-uptake inhibitors.
This paper reviews the evidence that provides the basis for a functional
neuroanatomy of anxiety and fear. The afferent arm of the anxiety circuit includes
the exteroceptive sensory systems of the brain, which convey the sensory
information contained in a fear- or anxiety-inducing stimulus to the dorsal
thalamus. Visceral afferent pathways alter the function of the locus coeruleus and
the amygdala The thalamus relays sensory information to the primary sensory
receptive areas of the cortex, which project to adjacent unimodal and polymodal
cortical association areas. The cortical association areas send projections to the
amygdala, entorhinal cortex, orbitofrontal cortex, and cingulate gyrus. A pivotal
role for the amygdala in the transmission and interpretation of fear and anxiety is
suggested by extensive afferents to the amygdala from thalamic and cortical
exteroceptive systems, as well as by subcortical visceral afferent pathways. The
neuronal interactions between the amygdala enable the individual to initiate
adaptive behaviors to threat based upon the nature of the threat and prior
experience. The efferent pathways involving the amygdala, locus coeruleus,
hypothalamus, periaqueductal gray, and striatum mediate autonomic, neuroendocrine,
and skeletal-motor responses associated with fear and anxiety. The proposed brain
structures, neural mechanisms, and neural circuits related to anxiety provide a
basis for increased understanding of the pathophysiology of anxiety disorders.
The authors review outcome studies in the treatment of panic disorder without
agoraphobia for on adult population. Empirical evidence is presented to support the
efficacy of psychopharmacological and cognitive-behavioural interventions. In
addition, this article can serve as the basis for the development of emerging
standards of care for the diagnosis and treatment of panic disorder.
Neurochemical accounts of panic disorder focus on peripheral indices of central
transmitter activity, hormonal correlates and therapeutic efficacy. Anxiogenic
agents augment norepinephrine activity, some anxiolytics increase serotonin
neurotransmission while benzodiazepines and antidepressants influence
catecholamine, indoleamine and gamma-aminobutyric acid turnover in infrahuman
subjects. Reliable correlates of central transmitter activity in panic disorder are
not in evidence. While animal models of anxiety may not mirror the symptom profile
of panic, neurobiological accounts of panic disorder fail to consider extensive
central colocalization of neurotransmitter and putative neurotransmitters. In
effect, transmitter release in major ascending and descending transmitter systems
is modulated by variable neuropeptide interfacing. The behavioral concomitants of
psychological disturbance likely follow from variable neurochemical release induced
by stimuli as well as conditioning and sensitization. The functional role of
receptor sites associated with multiple neurochemical systems may vary and the
sensitivity and/or density of receptor sites may be modified. Accordingly, the
behavioral and neurochemical concomitants of acute and chronic pathology may be
fundamentally different from one another. The present review argues that the
symptoms of panic disorder and the etiology of the illness must be evaluated
against a background of genetic, organismic and experiential factors. Such
variables presumably underlie the diverse behavioral symptoms associated with panic
disorder and variations in the therapeutic efficacy of pharmacological treatment.
Etiological models and treatment protocols for panic have been derived from
biological, psychological, and integrative formulations, and it is increasingly
apparent that a biopsychosocial approach will be necessary to accommodate the
clinical and empirical phenomena associated with this disorder. Recently developed
cognitive-behavioral interventions for panic disorder include techniques such as
cognitive restructuring, breathing retraining, and exposure to internal physical
sensations of panic. Exposure to fearful situations has been implemented
successfully in the reduction of agoraphobic avoidance. The combination of
cognitive-behavioral techniques with pharmacotherapy is still being investigated.
This article will review the research concerned with psychological and
pharmacological interventions for panic disorder. (C) 1995 John Wiley & Sons, Inc.
For many years, researchers have noted that certain individuals report an
exaggerated response to so-called biological challenge procedures (such as sodium
lactate infusions, hyperventilation, carbon dioxide inhalations). To date, much
interest has focused on the role of various biochemical variables in the response
to such procedures. However, there is growing evidence that the affective response
to biological challenge procedures can also be markedly influenced by certain
psychological constructs. There is currently evidence to suggest that greater
distress will be reported in response to these procedures by patients who associate
particular physical symptoms with danger and have low perceptions of control over
symptoms.
Scuba diving is a high-risk sport: it is estimated that 3 to 9 deaths per 100 000
divers occur annually in the US alone, in addition to increasing numbers of cases
of decompression illness each year. However, there has been a tendency within the
diving community to de-emphasise the risks associated with scuba diving. While
there are numerous factors responsible for the injuries and fatalities occurring in
this sport, there is general consensus that many of these cases are caused by
panic. There is also evidence that individuals who are characterised by elevated
levels of trait anxiety are more likely to have greater state anxiety responses
when exposed to a stressor, and hence, this sub-group of the diving population is
at an increased level of risk. Efforts to demonstrate that selected interventions
such as hypnosis, imagery, meditation and relaxation can reduce stress responses in
anxious divers has not yielded consistent findings, and there is a need for
systematic research dealing with the efficacy of selected intervention strategies.
Advances over the past 2 decades in our understanding of the biology of panic
disorder have paralleled a remarkable increase in the development of new
pharmacological agents with antipanic effects. Although we can not presently use
biological tests to help with our choice of therapeutic agent for individual
patients, we can use this biological understanding in the development of overall
pharmacotherapeutic strategies. Current evidence does not support the hypothesis
that panic disorder is associated with a primary disorder in one neurotransmitter
system. Rather, the data suggest that the biological aetiology of panic disorder is
related to abnormalities in the function of a variety of neurotransmitters
including serotonin (5-hydroxytryptamine; 5-HT), noradrenaline (norepinephrine),
gamma-aminobutyric acid (GABA), dopamine, and cholecystokinin. It is likely,
however, that panic disorder is a biologically heterogeneous condition and that
biological subtypes may exist in which the primary abnormality may involve one or a
few neurotransmitter systems. Currently, the data best support the hypothesis that
pharmacotherapeutic agents with primary action at sites within the GABA and
serotonin systems are the most effective in the treatment of panic disorder.
Nevertheless, some patients will respond well to drugs with predominant activity in
other systems, or may require pharmacotherapy designed to affect the function of
more than 1 neurotransmitter. As our understanding of the biological aetiology of
panic disorder evolves, the pharmacotherapeutic agents and strategies used in the
treatment of this disorder will continue to evolve as well.
During the last two decades substantial progress has been achieved in the
development and evaluation of effective treatment approaches to panic disorder and
agoraphobia. Many clinical research studies in this area were begun after the
definition of operationalized diagnostic criteria for panic disorder and
agoraphobia in the DSM-III in 1980. Different concepts concerning the etiology,
pathogenesis and maintaining factors of these disorders are still controversial. At
the beginning of this controversy, psychopharmacological treatment was believed to
suppress spontaneous panic attacks while behavioral treatment mainly focused on
anticipatory fears and avoidance behavior. Meanwhile both treatment approaches have
proved their effectiveness in reducing panic attacks and agoraphobia. Therefore, it
was hypothesized that a combination of both individual treatments could enhance
therapeutic efficacy. The few studies examining this question did not allow clear
conclusions because of methodological shortcomings. In the short run, there seems
to be a trend for better results with combined treatment. In the long run, however,
combined therapy has not been observed to be superior to cognitive-behavioral
therapy without any psychopharmacological support. In practice, adverse side
effects restrict the application of psychopharmacological approaches. On the other
hand, qualified cognitive-behavioral therapists are not always available, or
patients are referred to them by general practitioners and psychiatrists after a
delay. Criteria for the application of behavioral therapy, psychopharmacological
therapy and their combination are proposed and discussed.
Persistence of individual differences in animal behavior in reactions to various
environmental challenges could reflect basic divergences in temperament, which
might be used to predict details of adaptive response. Although studies have been
carried out on fear and anxiety in various species, including laboratory, domestic
and wild animals, no consistent definition of fearfulness as a basic trait of
temperament has emerged. After a classification of the events that may produce a
state of fear, this article describes the great variability in behavior and in
physiological patterns generally associated with emotional reactivity. The
difficulties of proposing fearfulness - the general capacity to react to a variety
of potentially threatening situations - as a valid basic internal variable are then
discussed. Although there are many studies showing covariation among the
psychobiological responses to different environmental challenges, other studies
find no such correlations and raise doubts about the interpretation of fearfulness
as a basic personality trait. After a critical assessment of methodologies used in
fear and anxiety studies, it is suggested that discrepancies among results are
mainly due to the modulation of emotional responses in animals, which depend on
numerous genetic and epigenetic factors. It is difficult to compare results
obtained by different methods from animals reared under various conditions and with
different genetic origins. The concept of fearfulness as an inner trait is best
supported by two kinds of investigations. First, an experimental approach combining
ethology and experimental psychology produces undeniable indicators of emotional
reactivity. Second, genetic lines selected for psychobiological traits prove useful
in establishing relationships between behavioral and neuroendocrine aspects of
emotional reactivity. It is suggested that fearfulness could be considered a basic
feature of the temperament of each individual, one that predisposes it to respond
similarly to a variety of potentially alarming challenges, but is nevertheless
continually modulated during development by the interaction of genetic traits of
reactivity with environmental factors, particularly in the juvenile period. Such
interaction may explain much of the interindividual variability observed in
adaptive responses.
The present survey of controlled studies on the treatment of panic disorder and
agoraphobia (PDA) reveals that treatment with tricyclic antidepressants (e.g.,
imipramine and clomipramine), benzodiazepines (e.g., alprazolam), serotonin
reuptake inhibitors (e.g., fluvoxamine) and the monoamine oxidase inhibitor
phenelzine has been proven effective. Among psychological therapies, cognitive
therapy and exposure therapy in agoraphobia have been shown to be effective. There
is an insufficient number of comparisons between pharmacological and psychological
treatments. From the existing studies it can be assumed that none of these
treatment modalities is superior to the other. The few existing follow-up studies
do not suffice to prove a longer lasting effect for the psychological therapies,
compared with drug therapies. Because of the low number of investigations, it
cannot be clearly stated whether it is useful or harmful do treat patients with
psychopharmacological drugs during psychological therapy. It is more likely that
this combination is advantageous.
This review presents data on HIV epidemiology and suicide mortality, and summarizes
studies on fear of AIDS in completed suicides in Finland. Finland has a low
prevalence of HIV and a high suicide mortality. A 12-month nationwide suicide
population, 1987-88 (n = 1397, all HIV negative) at the time of a sensational media
campaign against HIV included 28 (2%) cases with fear of AIDS as a contributing
factor. Triggers of fear could be classified in 20 cases: persistent symptoms in
10, casual sex contacts in eight, and a TV programme in two. The AIDS fear cases
were younger, had more major depression and more health care contacts than the
others. Suicidal fear and underlying depression were not being properly identified
and treated. Despite recent improvement in media reporting, health education and
identification of depression, clinical experience, help line calls and population
surveys indicate that AIDS fear still persists in the population, but seems to be
less often a contributing factor in committed suicides.
1. Interest in the biological aspects of panic disorder has been focussed mainly on
the noradrenergic and serotonergic systems in the brain. 2. Recently evidence has
been found that Cholecystokinin (CCK) receptors in the Central Nervous System (CNS)
may be involved in panic disorders. This hypothesis is based on the results of
animal electrophysiological studies, animal models of anxiety and on challenge test
using CCK fragments in humans. 3. In this review, the studies evaluating the
putative involvement of CCK, and especially CCK-B receptors, in panic disorder will
be discussed.
1. Some reports have suggested that there: may be a link between the experience of
traumatic life events in childhood and adolescence and the development of panic
disorder in adults. In addition early loss event also seems increase depressive
risk by a factor about two to three. 2. The authors wondered whether panic patients
who experienced a traumatic life event would have a higher prevalence of subsequent
major depressive episode than panic patients without history of depression. 3. One
hundred fifty seven patients with panic disorder according DSM III - R criteria are
included in this study. Fifty three (33.7%) had experienced a major loss or
separation before the age of 15 years. 4. The panic group with early life events
showed a significantly higher life time prevalence of major depression than the
panic group who did not exprience early life events.
This paper reviews the methodologic considerations that are important in evaluating
and interpreting panic disorder outcome studies and the results of the most well-
designed of these studies. Sixteen studies that used modern diagnostic criteria and
interviewed at least 25 patients on at least two occasions over a minimum follow-up
period of one year are reviewed. Results show that, despite the availability of
effective anti-panic treatments, panic disorder remains a chronic illness. While
most patients improve, few are ''cured.'' The presence of agoraphobia, major
depression and personality disorder seems to predict poorer outcome. The important
of measuring multiple clinical dimensions of panic is emphasized, along with the
need to reach a consensus about the definition of ''outcome'' and the particular
instruments to use to measure it. (C) 1995 Wiley-Liss, Inc.
Several placebo-controlled drug trials have shown that a substantial placebo
response occurs in panic disorder patients. A short review is presented with focus
on recent studies on this topic. Methodological problems encountered when studying
placebo phenomena are presented. Severity of the disorder at entrance into the
trial, including the specific subtype of the panic disorder, is suggested to be a
significant predictor of placebo response. In addition, some responders tend to
improve early after start of placebo treatment. Although panic disorder often has a
chronic course, most studies on placebo response have so far been carried out as
short-term clinical trials. The implications for treatment in an ordinary clinical
setting can therefore only be indicated with caution.
Insulin-induced hypoglycaemia, the most frequent side-effect of insulin-therapy, is
a potential source of considerable morbidity and has a recognised mortality. Acute
hypoglycaemia produces an intense physiological stress with profound
sympathoadrenal stimulation and widespread activation of hormonal counterregulatory
systems, leading to secondary haemodynamic and haemorheological changes. The
clinical effects of acute and recurrent severe hypoglycaemia are associated with
significant morbidity including reversible, and permanent, abnormalities of
cardiovascular, neurological and cognitive function, in addition to trauma and road
traffic accidents. Comprehension of the morbidity of hypoglycaemia is important
when designing insulin regimens and determining therapeutic goals for individual
patients if the frequency and adverse effects of this dangerous side-effect of
insulin therapy are to be limited.
The influence of water deprivation on hippocampal long-term potentiation (LTP),
theta rhythm, and contextual fear conditioning in rats was examined. In Experiment
1, hippocampal EEG activity and perforant path LTP were assessed in pentobarbital-
anesthetized rats. Water deprivation did not affect baseline cell excitability or
low-frequency synaptic transmission in the dentate gyrus, but it increased the
magnitude of perforant path LTP and elevated the proportion of theta rhythm in the
EEG. In Experiment 2, rats were classically conditioned to fear a novel context
through the use of aversive footshocks. Water deprivation facilitated the rate of
contextual fear conditioning but did not alter the asymptote of learning.
Experiment 3 demonstrated that the facilitation of contextual fear conditioning was
not due to a change in unconditional shock sensitivity. These results suggest that
water deprivation exerts an influence on contextual fear conditioning by modulating
hippocampal LTP and theta rhythm and that these processes serve to encode
contextual information during learning.
Research over the last three decades has demonstrated that a substantial minority
of both professional and lay people have negative and rejecting attitudes towards
the mentally ill. We argue that these attitudes may, in part, be a function of a
tendency to perceive the mentally ill as somehow inherently dangerous and liable to
violence. The evidence for the association between schizophrenia and violence
suggests that although people with schizophrenia may be somewhat more likely to act
violently than members of the general public, the magnitude of the differential is
not sufficient to explain the perceived association. Alternative explanations for
the correlation are therefore considered. Specifically, the influences of the
media, errors in information processing and the process of stereotyping in
accounting for the development of a perceived association between schizophrenia and
violence are examined. Finally, the implications for enhancing the acceptance of
people with schizophrenia into the community are discussed.
The need for hypotheses concerning the nature of those functions that have been
impaired in stereotyped psychiatric syndromes is emphasized. With regard to panic
disorder, the key role of the spontaneous panic attack became apparent from several
viewpoints. However, panics seem to be a type of misreleased fear, which guided the
thinking concerning the nature of possible psychological or physiological
malfunctions. We indicate that spontaneous panic cannot be fear, but must represent
some other malfunction and suggest that the spontaneous panic is a suffocation
false alarm. The development of this idea is outlined, and attempts to develop
tests of this hypothesis are indicated. In particular, studies of children with
congenital hypoventilation syndrome, patients with Chronic Obstructive Pulmonary
Disease, dyspnea, field measures of panic, pregnancy, childbirth and the postpartum
period, as well as the premenstrual syndrome afford pointed opportunities, new
information and potential tests of the theory. A recent challenge to the theory
from acetazolamide infusion is discussed. Developing a possible antecedent for the
pathologically depressed threshold for the suffocation alarm, in the form of a
phasic endorphinergic deficiency, is presented. (C) 1994 Wiley-Liss, Inc.
This article reviews the literature examining family variables associated with
anorexia nervosa and bulimia nervosa and family systems treatments for these eating
disorders. Definitions of and diagnostic criteria for anorexia and bulimia are
presented, and the prevalence of these disorders is discussed. The role
psychopathological, sociological, and interpersonal factors play in the etiology of
eating disorders is reviewed. Family therapy approaches to treating anorexia and
bulimia are discussed, and recommendations for future research are presented.
A number of recent reports have indicated a higher risk of sudden infant death
syndrome (SIDS) in the prone sleeping position, compared with the supine position.
However, the biological mechanisms for this increased risk have not been
established. For this report, two biological explanations are proposed, each of
which may be influenced by altered sleeping position in such a way that they may
create conditions for increased triggering of SIDS.
1. Prolactin and cortisol responses to d-fenfluramine were measured in 16 patients
with DSM-III-R panic disorder and 14 normal controls. 2. Patients showed a greater
mean prolactin response than controls but the difference between groups was not
statistically significant(P > 0.05, MANOVA). 3. No consistent differences were
observed between patients and controls with respect to cortisol responses (P >
0.05, MANOVA). 4. The results do not support the hypothesis of hypersensitive post-
synaptic serotonin receptors in patients with panic disorder. 5. Studies in larger
groups are necessary to confirm the trend and to explore receptor subtype
sensitivity.
Social problems may fruitfully be looked at as constructed phenomena, that is, what
constitutes a problem is the concern that segments of the public feel about a given
condition. From the constructionist perspective, that concern need not bear a close
relationship with the concrete harm or damage that the condition poses or causes.
At times, substantial numbers of the members of societies are subject to intense
feelings of concern about a given threat which a sober assessment of the evidence
suggests is either nonexistent or considerably less than would be expected from the
concrete harm posed by the threat. Such over-heated periods of intense concern are
typically short-lived. In such periods, which sociologists refer to as ''moral
panics,'' the agents responsible for the threat-''folk devils''-are stereotyped and
classified as deviants. What accounts for these outbreaks or episodes of moral
panics? Three theories have been proposed: grassroots, elite-engineered, and
interest group theories. Moral panics are unlike fads; though both tend to be
relatively short-lived, moral panics always leave an informal, and often an
institutional, legacy.
Objective: To examine the association among panic disorder, atypical chest pain and
coronary artery disease (CAD). This article's purpose is to inform cardiologists of
the prevalence of psychiatric disorders, primarily panic disorder, among patients
consulting for chest pain. Panic disorder is described. Treatment modalities are
summarized, and social, financial and medical consequences of nondetection are
underlined. Data Sources: PSYCHLIT and MEDLINE searches under panic disorder and
chest pain-related headings were conducted. Data Extraction: The search covered
January 1973 to June 1993. Thirty-eight articles were studied. Data Synthesis:
Panic disorder is present in 30% or more of chest pain patients with no or minimal
CAD and may coexist with CAD. Panic disorder may often be unrecognized by
physicians. Left untreated, risk for disease progression may be augmented, and
social vocational disability as well as medical costs may increase. Conclusion:
Physicians should attend to the panic symptomatology and, when in doubt, refer
possible panic patients with or without CAD to a mental health professional for
assessment and treatment. Future panic prevalence studies in cardiology patients
should be prospective, attempt to increase sample size and use randomized protocols
where experimenters are blind to chest pain and medical diagnoses. Studies should
also focus on CAD patients with atypical chest pain refractory to optimal cardiac
therapy.
1. Benzodiazepines were discontinued in 16 patients who had recovered from panic
disorder with agoraphobia after exposure treatment. 2. Drug discontinuation yielded
a significant decrease in anxiety sensitivity and state anxiety in these long-term
users. 3. Several likely explanations for the findings are discussed. 4. In the
short term, treatment of panic disorder with benzodiazepines may lower anxiety
symptoms. However, in the long run, it may decrease the individual tolerance to
anxiety and discomfort.
A selective review of theories of fear appeals is carried out which concludes that
these theories have gradually become divorced from the notion of fear. The forces
that motivated that separation are examined and a set of arguments are advanced
favoring a reunion of fear with a theory of fear appeals. As a means of achieving
that union, emotion theory is reviewed and a set of axioms extracted. The axiomatic
framework is then used to demonstrate how an emotional perspective on fear appeals
might shed new light on this area of persuasion. Recommendations are offered for
future studies of fear appeals.
Sexual assault is increasingly recognized as an urgent and pervasive problem on
university campuses. Women's fear of sexual assault is similarly significant and
widespread. Growing university assault prevention efforts on campuses have often
overlooked the negative implications of women's fear. Depending on their onus of
responsibility, university sexual assault prevention strategies may implicitly
reinforce gendered social norms for public behavior by increasing women's fear in
public spaces, with consequent detrimental effects for women's positive experience
on campus. Based on a conceptualization of fear of sexual assault as a form of
social control, this review discusses societal, individual, and university/campus
factors (organizational, social, and especially physical) associated with women's
fear of assault on campus. In conclusion, it suggests university assault prevention
strategies that may also reduce women's fear.
An impressive amount of evidence from many different laboratories using a variety
of experimental techniques indicates that the amygdala plays a crucial role in the
acquisition, consolidation and retention or expression of conditioned fear.
Electrophysiological data are beginning to detail the transmitters and inter-
amygdala connections that transmit information to, within, and out of the amygdala.
In general, treatments that increase the excitability of amygdala output neurons in
the basolateral nucleus (for example, by decreasing opiate and GABA transmission,
and increasing noradrenergic transmission) improve aversive conditioning, whereas
treatments that decrease excitability of these neurons (by increasing opiate and
GABA transmission, and decreasing NMDA and noradrenergic transmission) retard
aversive conditioning as well as producing anxiolytic effects in appropriate animal
tests. A better understanding of brain systems that inhibit the amygdala, as well
as the role of its very high levels of peptides, might eventually lead to the
development of more effective pharmacological strategies for treating clinical
anxiety and memory disorders.
The purpose of this article is to review, in a succinct and critical manner, the
evaluation methods of panic disorder accompanied or not by agrophobia. The first
part deals with definitions and diagnostic criteria contained in the DSM-III-R. The
following sections describe the evaluation methods (interviews, scales and
questionnaires, behavioural, cognitive and physiological measures and self-study)
and points to their respective strengths and weaknesses. The authors then deal with
phenomena of concordance and synchrony and discuss the concept of clinical meaning.
Finally, they suggest avenues for research in order to evaluate panic disorder more
adequately, with or without agrophobia.
This article reviews the current status of behavioral approaches to the assessment
and treatment of Panic Disorder (PD). One goal in writing this article is to
facilitate exchange between the science and the practice of behavior therapy for
PD. Although current behavioral and cognitive-behavioral treatment interventions
for PD show favorable results, this disorder remains fairly common. Prior to
reviewing the data from controlled trials of these types of intervention
approaches, the presentation and diagnosis of PD is discussed. Additionally, an
overview of conceptual accounts of PD is included, as these provide the rationale
for current approaches to assessment and treatment. Specific recommendations
regarding assessment, treatment planning, progress monitoring, and outcome
evaluation are included throughout. As noted, behavioral approaches to PD represent
a vital, active area of the field, where many innovations and answers have been
forthcoming. This review highlights these recent developments and suggests future
directions which would further enhance our knowledge about PD.
1. Forty patients who had had syndromally-defined episodes of post-psychotic
depression at least 6 months previously were interviewed in detail for life-time
histories of substance abuse, panic attacks, and suicidal ideation. 2. No
relationship was found between life-time history of suicidal ideation and substance
abuse. 3. Statistically significant associations were found between lifetime
history of suicidal ideation and both a life-time history of panic attacks and the
panic disorder syndrome.
1. The charts of 78 panic disorder outpatients treated with alprazolam (mean dose
4.30 mg/day, mean duration 31.9 months) were reviewed for demographics, past
history (including substance abuse and major depression), and evidence of
alprazolam abuse. In addition, the patients were evaluated by Clinical Global Index
for improvement at last contact. 2. Moderate to significant recovery was found in
77% of patients. Major depression was seen in 41%. Depressed patients were more
likely to have coexisting agoraphobia and a past history of alcohol abuse than non-
depressives. 3. There was no DSM-III-R anxiolytic abuse, but 12% showed
unauthorized use of the alprazolam. These subjects were three times more likely to
have a history of drug abuse than non-misusers. 4. These results indicate that
alprazolam is effective in the long-term treatment of panic disorder, but that
prolonged management may be required. Further, the data raise concerns about use in
panic patients with substance abuse histories.
This article reviews and assesses six dental anxiety and fear questionnaires. The
construct aimed at by the questionnaires, the data collected, their reliability,
validity and normative scores are considered. Some attention is given to the
correlations between the questionnaires, their ambiguity, the presence of manuals,
and whether the questionnaires tap the three segments distinguishable on
theoretical ground in dental anxiety/fear. All questionnaires are open to
criticism. In the final assessment Kleinknecht's Dental Fear Survey is preferred to
Corah's Dental Anxiety Scale. The latter, however, appears useful in getting a
quick impression of anxiety and in evaluative studies. Three recently developed
questionnaires, Stouthard's Dental Anxiety Inventory, Weiner's Fear Questionnaire
and Morin's Adolescents' Fear of Dental Treatment Cognitive Inventory are
considered promising, but for the last two instruments more data, in particular
with regard to their validity, are needed. It is concluded that in dental anxiety
research more than one questionnaire should be used and that it may be worthwhile
to include other, non-anxiety questionnaires as well.
Drug treatment of panic disorder is reviewed with focus on recent controlled
studies. The efficacy of alprazolam, a triazolobenzodiazepine, and imipramine, a
tricyclic antidepressant, has consistently been demonstrated, but there is
reasonable evidence that other benzodiazepines or antidepressants might also be
effective if equipotent doses are used. Most controlled studies demonstrate drug
efficacy on several psychopathological symptoms, including the core symptom panic
attacks. Limited evidence indicates that alprazolam may be more efficacious in
treating panic attacks than avoidance behaviour, and the reverse when imipramine is
concerned. Drug efficacy appears to be most consistently documented in moderately
to severely ill panic patients. The benzodiazepines are better tolerated than
antidepressants in terms of patient acceptance, and the improvement sets in faster
with benzodiazepines. In the presence of depressive symptoms considered secondary
to panic attacks and/or agoraphobia, both types of drugs appear efficacious.
Difficulty discontinuing high-dose benzodiazepine treatment remains the most
important side effect of the treatment but sedation can, like anticholinergic side
effects of the tricyclic antidepressants, be troublesome, thereby diminishing
patient compliance. The role of newly developed antidepressants with a more
specific mode of action and milder side effects awaits evaluation in controlled
trials.
Objective of this article is to offer a comprehensive, data-based explanation of
the relationship between hyperventilation and panic disorder linking CO2
hypersensitivity, cognitive/behavioral factors, and the respiratory effects of
antipanic pharmacologic and psychological treatments. Methods: The authors
conducted a computerized search of MEDLINE for relevant articles. Results: Some
panic patients have a chronic, subtle respiratory disturbance. Acute
hyperventilation is neither necessary nor sufficient for panic to occur.
Respiratory abnormalities in panic patients may adaptively aim at coping with a
hypersensitive CO2 chemoreceptor system. Pharmacologic panicogens also stimulate
the respiratory system, causing hyperventilation. Triggering this hypersensitive
respiratory control mechanism may in panic. Antipanic medications may reset the
receptor threshold. Misattribution and catastrophic interpretation of somatic
symptoms or the sense of loss of control may contribute to panic symptoms.
Behavioral interventions such as desensitization or breathing retraining may block
the full-blown attack. Cognitive strategies through cognitive control of
respiration may supplement and accentuate these interventions. Conclusions: Panic
disorder may be due to an inherently unstable autonomic nervous system, coupled
with cognitive distress.
Hyperventilation is probably the most frequently discussed correlate of panic
attacks. Although some authors see it as the main or even unique cause of panic
attacks, there have been numerous reviews with contradictory conclusions. Recent
research, however, provides some more clarity. After a short overview of the
characteristics of hyperventilation, the present article discusses (1) indirect
measures of the overlap between panic and hyperventilation, (2) direct measures of
hyperventilation at rest and during naturally occurring panic, (3) the influence of
cognitive variables, and (4) the major theories attempting, to explain the
relationship between hyperventilation and panic. The results indicate a substantial
overlap between panic and hyperventilation, but by far no one-to-one relationship
and no chronic hyperventilation in panic patients if anticipatory anxiety is ruled
out. In addition, cognitive studies firmly support the relevance of perceptive and
associative processes. Theories that consider hyperventilation as a necessary or
sufficient condition for panic attacks are clearly discarded by the imperfect
relationship between the two phenomena. The central chemoreceptor sensitivity
theory of panic is consistent with the physiologic effects of both hyperventilation
and CO2 inhalation but has to face inconsistent results on ventilatory
characteristics of panic patients. Furthermore, it can neither explain the weak
responses to hyperventilation or CO2 in some panic patients nor the influence of
cognitive variables. Only a psychophysiological theory that takes cognitive,
conditioning and physiologic factors into account is consistent with the total body
of research accumulated to date. According to this approach, hyperventilation is
related to panic in two ways: First, it is one of many processes that can lead to
the perception of bodily sensations which may trigger positive feedback loops
between sensations and anxiety responses. Second, because of the circular nature of
such feedback processes, hyperventilation can also be a response to anxiety. In
conclusion, hyperventilation is not uniquely relevant for panic, but the degree of
overlap between the two phenomena gives it a prominent role as a trigger for panic
and a vehicle for successful psychological treatment.
Ancient anxieties that the growth of cities would be accompanied by an assortment
of social ills took on a special intensity in the nineteenth century. Because the
incidence and distribution of suicide were used as evidence to demonstrate the
dangers of modernity, suicide itself could never be viewed outside that framework.
Nostalgic views of the family and of community were put forward as ideological
alternatives to the alleged social and cultural disintegration caused by modem
urban life. Because they were more subsumed in the family, women were assumed to be
more immune than men to the social disintegration that led to self-destructive
behaviors. Given this context, it was impossible to come to any conclusion other
than that suicide was a male behavior. Yet, assertions that women were less
suicidal than men rested upon contested data, whose privileging reveals a set of
gendered assumptions that conflated women's biology with their behavior. A gender
analysis exposes the extent to which that conclusion was informed by unspoken
assumptions about the ''nature'' of men and women; assumptions which flowed from
the confusion between a biological category (sex) and grammatical description
(gender).
A carbon dioxide hypersensitivity theory of panic has been posited. We hypothesize
more broadly that a physiologic misinterpretation by a suffocation monitor misfires
an evolved suffocation alarm system. This produces sudden respiratory distress
followed swiftly by a brief hyperventilation, panic, and the urge to flee. Carbon
dioxide hypersensitivity is seen as due to the deranged suffocation alarm monitor.
If other indicators of potential suffocation provoke panic, this theoretical
extension is supported. We broadly pursue this theory by examining Ondine's curse
as the physiologic and pharmacologic converse of panic disorder, splitting panic in
terms of symptomatology and challenge studies, reevaluating the role of
hyperventilation, and reinterpreting the contagiousness of sighing and yawning, as
well as mass hysteria. Further, the phenomena of panic during relaxation and sleep,
late luteal phase dysphoric disorder, pregnancy, childbirth, pulmonary disease,
separation anxiety, and treatment are used to test and illuminate the suffocation
false alarm theory.
1 .Panic disorder (PD) is an illness that can be acute or chronic and is often
complicated by depression, phobias and obsessions. This illness affects at least
10% of the population. 2. Panic disorder has been recognized as a psychopathologic
condition for at least 100 years. Over the last several decades, health
professionals have changed their view of PD, and in 1987 the DSM-III included PD as
a distinctive syndrome. 3. Several studies have shown PD to be a chronic illness
with only little to no improvement in 36 - 40% of the subjects after 1 to 20 years
of treatment. Studies also suggest that duration of illness affects the degree of
impairment: subjects who had PD for more than 6 months showed more impairment that
subjects who had PD for less than 6 months. 4. Several studies show that 50-75% of
patients with PD have had at least one episode of major depression. Findings also
indicate that subjects with both PD and secondary depression are a more severely
ill group. 5. The HARP study is an ongoing 12-site naturalistic, longitudinal
examination of patients with current or past PD. One of the major goals of this
study is to describe the patterns of the clinical course of PD related disorders.
6. Clinical experience indicates that an estimated 40% of PD patients may need
treatment for one year and between 20-40% will require continued maintenance
treatment. Long-term treatment may include behavioral therapy and/or medication. 7.
Anxiety disorders are common and familial and are consistently higher among women.
Panic Disorder is a chronic condition frequently complicated by Axis I and II
disorders. Continued long-term maintenance studies of medications and psychotherapy
for anxiety disorders is critical in the treatment of this chronic illness.
The use of cognitive and behavioural procedures in the treatment of panic disorder
is relatively a recent phenomenon. The aim of the present paper was to find out
about the current state of knowledge in this area of clinical research. A critical
examination of the literature revealed that there were quite a few studies
confirming the efficacy of cognitive-behavioural methods in the treatment of panic
disorder. Furthermore, it was found that some of those studies were well controlled
enough for their conclusions to be considered as valid. During our examination, we
also observed that the limitations and the therapeutic mechanisms of these methods
had been submitted to almost no scientific scrutiny. Because we believe that time
has come to study new questions, proposals were made at the end of the paper as to
the direction of future research in the area.
First, after a short introduction, the author goes into the threatened identity in
adoptive families and the role sexuality hereby plays. This is demonstrated with a
case example. Then the unconscious phantasies and dealing with the incest
prohibition are described, followed by thoughts about therapy and the problem of
the right time to tell the child about his adoption.
Panic attacks and panic disorder often first present in the emergency room or to
the family practitioner. The presentation and differential diagnosis of this
disabling disorder are described in this review, together with the etiology and
health effects of the syndrome. Both medication and psychological treatments are
described, as are the indications, side effects, and expected outcome for each
therapy alone and in combination.
Initial etiological theories of panic were largely grounded in a biological
framework due to the seemingly spontaneous nature of most attacks. More recently,
however, cognitive, hyperventilatory, and conditioning theories of panic have been
proposed. Cognitive theorists emphasize the causal role of catastrophic
missattributions of benign somatic cues in panic; therefore, treatment involves
providing the client with corrective information. Proponents of the
hyperventilatory theory of panic implicate inappropriately increased ventilation;
consequently, interventions emphasize breathing retraining. Finally, conditioning
theorists hold that initial attacks are caused by hyperventilation or some other
discrete event and that contiguous interoceptive stimuli become conditioned
elicitors of future panics; as a result, treatment consists of exposure to the
interoceptive cues which trigger panic. Combinations of treatments address possible
multiple causal pathways and have been found to be relatively more effective than
interventions based on only one etiological perspective.
The present behavioral medical paper is a contribution to basic research in
neuroimmunology. The relationship of panic/agoraphobia and allergy/anaphylaxis
(IgE-mediated immediate reaction) is demonstrated and discussed with specific
consideration of vasomotor reactions, tachycardia and hyperventilation in panic
patients and allergics with anaphylactic reactions. The vegetative symptoms of
panic reactions and anaphylaxis showed a high correlative correspondence. 74% of 23
panic and/or agoraphobia patients in a pretest to an epidemiologic study turned out
to have an allergic illness that needed treatment; but there were no more anxiety
disorders disclosed in 50 allergic patients than in the general population
according to expectancies found in epidemiologic publications. If these data are
confirmed then panic and agoraphobia cannot be seen as merely a cognitive-emotional
event, but also as a further kind of allergic disease with genetic, ecological,
psychological and social determinants; they would then have to be diagnosed as
psychoimmunological disturbances and treated with behavior medicine (preferably
with exposition and immunotherapy or hyposensitization). Anxiety therapies would
improve qualitatively and could be cut down in duration.
The delineation of panic disorder as a distinct diagnostic entity has provided
renewed impetus for research into panic. This review describes and examines the
range of neurobiological theories of panic attacks. It illustrates the diversity of
mechanisms that have been invoked to explain the production of panic attacks, and
which have influenced much of the current thinking about the neurochemistry of
anxiety.
Objective: Panic disorder bas been considered an adulthood disorder that does not
occur in children or adolescents. The authors' goals were to critically review the
available evidence for panic attacks and/or panic disorder in children and
adolescents, to review the limited data on the biological basis of panic disorder
as it bas been studied in children and adolescents, to discuss the possible
treatment approaches for panic disorder in children, and to suggest potential
opportunities for further research on panic disorder in children. Data Collection:
Sixty-three articles pertaining to panic disorder in children and adolescents were
critically reviewed. These articles included retrospective histories of adults with
panic disorder, clinical case reports of children and adolescents with panic
disorder, studies of psychiatrically referred children and adolescents, reports
from epidemiologic community and school samples of children and adolescents,
studies of children and adolescents at risk for psychiatric disorder, reports of
panic-like symptoms in pediatric patients, family studies of panic, studies of the
biological basis of panic in adults, and studies of treatment for panic. Findings:
There is strong evidence that panic disorder occurs in children and adolescents and
that its clinical presentation in this population is similar to that found in
adults. Conclusions: Extending the many adult studies of panic disorder to children
and adolescents would be extremely fruitful. Like adults with panic disorder, many
children and adolescents are brought to emergency and medical clinics for the
physical symptoms of unrecognized panic disorder.
The antipanic utility of imipramine and monoamine oxidase inhibitors has led to
hypotheses of noradrenergic and/or serotonin (5-HT)-related abnormalities
underlying panic disorder (PD) and its agoraphobic complications. Further data
support significant antipanic effects for agents with acute 5-HT reuptake blockade
effects. It is unlikely that ameliorative effects observed following chronic
administration of 5-HT drugs remain 5-HT specific. Despite a range of recently
discovered 5-HT receptor subtypes, evidence for a specific receptor abnormality in
PD is lacking. Preclinical studies suggest an important role for 5-HT effects in
several animal models of anxiety, including separation-induced infant protest
responses and respiratory modulation. Induction of anxiety with putative 5-HT
agents such as meth-chloro-phenylpiperazine and fenfluramine lend further support
to 5-HT involvement in anxiety states. Critical behavioral, physiologic, and
neuroendocrine differences between putative 5-HT anxiogens and "classic"
panicogens, such as lactate and carbon dioxide are discussed. We propose that 5-HT
agents mediate antipanic effects through amelioration of a deranged internal
evaluative mechanism along cybernetic lines, rather than simple augmentation or
reduction of 5-HT function.
A review of the literature indicates that fear of future illness shares many
characteristics with a wide variety of conditions. Concepts such as
hypochondriasis, adjustment disorders, generalized anxiety, and mass hysteria must
be considered. Also, factors such as reporting bias, influential others, collective
behavior, political groups, and litigation appear to induce symptom reporting from
patients complaining of fear of illness and cancerphobia. Cancerphobia may result
in impairment ranging from avoidance behaviors to cognitive dysfunctions. Various
treatment modalities have been used successfully in treating cancerphobia, and the
prognosis is typically good. Complaints of chemical AIDS, universal allergy, or
twentieth century disease have little medical or empirical support and require
further investigation. Researchers and clinicians must recognize multiple factors
contribute to fear of future illness or cancerphobic complaints, and additional
research must be undertaken if a thorough understanding of fear of future illness,
cancerphobia, and perceptions of chemical AIDS is to be obtained.
Immunological, neuroendocrine and psychological parameters were examined in 14
psychophysically healthy subjects and in 17 panic disorder patients before and
after a 30-day course of alprazolam therapy. T lymphocyte proliferation in response
to the mitogen phytohemoagglutinin, lymphocyte beta-endorphin (beta-EP)
concentrations, plasma ACTH, cortisol and beta-EP levels were examined in basal
conditions and after corticotropin-releasing hormone (CRH) stimulation. Cortisol
inhibition by dexamethasone (DST) and basal growth hormone (GH) and prolactin
levels were also examined. Depression, state or trait anxiety, anticipatory
anxiety, agoraphobia, simple and social phobias, severity and frequency of panic
attacks were monitored by rating scales. The immune study did not reveal any
significant difference between patients and controls, or any effect of alprazolam
therapy. The hormonal data for the two groups were similar, except for higher than
normal basal ACTH and GH plasma levels, lower than normal ratios between the ACTH
and cortisol responses to CRH, and blunted DST in some patients. All the
impairments improved after alprazolam therapy, in parallel with decreases in
anxiety and in severity and frequency of panic attacks.
Panic disorder (DSM-III, DSM-III-R) has been thoroughly studied in recent years.
The main evidence for panic disorder as a nosological entity is reviewed, to
delineate some important questions for future research. Validation criteria include
epidemiological, phenomenological, genetic, neurobiological, pharmacological and
behavioral findings. Biological, behavioral and psychodynamic considerations on
etiology, pathogenesis and treatment are presented.
This article reviews the risk of suicide in panic disorder beginning with early
studies showing increased mortality, including suicide, among patients belonging to
the broad category of neuroses. More recent follow-up studies of patients with
anxiety disorders have found about 20% of deaths due to suicide, a proportion
similar to that found in depressive disorders. Also, suicide attempts have been
reported by similar proportions of subjects with panic disorder and major
depression from the general population. Preliminary data indicate that more
severely ill patients with coexisting depression and substance abuse are more
likely to attempt or complete suicide. Thus, although limited, the data indicate
that the risk of suicide in panic disorder is substantial. As a consequence,
clinicians should alert themselves to this preventable outcome and approach
treatment with added caution.
A review was conducted of the psychoanalytic and psychodynamic literature in order
to identify patients with panic disorder who received dynamic treatment. Thirty-
five cases were located that fit the description of panic disorder. Their
characteristics are compared with those of a current anxiety disorder clinic panic
disorder population. Features of the successful dynamic treatment of panic disorder
are summarized.
The research evidence strongly suggests that the most effective form of treatment
for panic disorder is cognitive therapy. It is more practical, however, to initiate
treatment with alprazolam or with imipramine. Either drug will suppress symptoms
and even a half of the patients will stay well.
1. Because imipramine has lowered T4 in uncontrolled studies we examined the effect
of imipramine on serum thyroid levels in panic disorder patients in a double-blind
placebo and diazepam treatment controlled study. 2. Treatment with imipramine (10
subjects) was associated with a significant decrease of T4 and FTI and treatment
with diazepam (8 subject) was associated with a significant decrease of T4.
However, there was no significant difference across treatment groups. 3. This
finding suggests that previously reported decreases in thyroid hormones during
antidepressant therapy may be due to nonspecific effects of treatment rather than
to the drug itself.
Captive rearing is commonly used to support efforts to restore extirpated or
diminished wild populations. Many rearing programs include antipredator training in
an effort to reduce post-release mortality due to predation, but the value such
training adds to restoration efforts is not fully understood. Analyses of
antipredator training impacts often focus on changes in prey following training and
not the actual effects when prey are exposed to predators. Studies also commonly
assess prey traits instead of fitness. However, changes in prey following training
may not translate to desired increase in fitness upon release for a self-sustaining
population. To consider these relationships, we identified studies that analyzed
changes in organisms following both training and lethal exposure to predators.
Notably, we identified only 12 studies that analyzed outcomes in both training and
lethal exposure settings and found the majority of measurements focused on traits.
Although meta-analysis indicated that antipredator training changed prey traits and
increased prey survival, relationships between changes in traits and fitness could
not be assessed given the rarity of studies that included both outcomes. While
these results support the general use of antipredator training, they also suggest
that trait changes cannot be reliably used as proxies for fitness impacts. Future
work should seek to more clearly measure impacts on fitness and determine when
changes in traits can truly be used as a surrogate for training efficacy. These
issues reflect recent concerns regarding research on non-consumptive effects and
highlight potential avenues for future collaborative research on fear.
Background Adverse childhood experiences (ACEs) increase the risk of mental health
difficulties in general, but the link to panic disorder (PD) has received
comparatively little attention. There are no data for the magnitudes between ACEs
and PD. This systematic review and meta-analysis estimated the overall, as well as
the subgroups, odds ratio of having PD in adults who report ACEs, compared to
adults who do not. Methods The study was pre-registered on PROSPERO
[CRD42018111506] and the database was searched in June 2021. In order to overcome
the violation of independent assumptions due to multiple estimations from the same
samples, we utilized a robust variance estimation model that supports meta-analysis
for clustered estimations. Accordingly, an advanced method relaxing the
distributional and asymptotic assumptions was used to assess publication bias and
sensitivity. Results The literature search and screening returned 34 final studies,
comprising 192,182 participants. Ninety-six estimations of 20 types of ACEs were
extracted. Pooled ORs are: overall 2.2, CI (1.82-2.58), sexual abuse 1.92, CI
(1.37-2.46), physical abuse 1.71, CI (1.37-2.05), emotional abuse 1.61, CI (0.868-
2.35), emotional neglect 1.53, CI (0.756-2.31), parental alcoholism 1.83, CI (1.24-
2.43), and parental separation/loss 1.82, CI (1.14-2.50). No between-group
difference was identified by either sociolegal classification (abuse, neglect,
household dysfunction) or threat-deprivation dimensions (high on threat, high on
deprivation and mixed). Conclusions There are links of mild to medium strength
between overall ACEs and PD as well as individual ACEs. The homogeneous effect
sizes across ACEs either suggest the effects of ACEs on PD are comparable, or
raised the question whether the categorical or dimensional approaches to
classifying ACEs are the definitive ways to conceptualize the impact of ACEs on
later mental health.
Posttraumatic stress disorder (PTSD) is a psychiatric disorder that is associated
with long-lasting memories of traumatic experiences. Extinction and discrimination
of fear memory have become therapeutic targets for PTSD. Newly developed
optogenetics and advanced in vivo imaging techniques have provided unprecedented
spatiotemporal tools to characterize the activity, connectivity, and functionality
of specific cell types in complicated neuronal circuits. The use of such tools has
offered mechanistic insights into the exquisite organization of the circuitry
underlying the extinction and discrimination of fear memory. This review focuses on
the acquisition of more detailed, comprehensive, and integrated neural circuits to
understand how the brain regulates the extinction and discrimination of fear
memory. A future challenge is to translate these researches into effective
therapeutic treatment for PTSD from the perspective of precise regulation of the
neural circuits associated with the extinction and discrimination of fear memories.
Background The COVID-19 pandemic has negatively affected the mental health of
people globally. Despite substantial research on the short-term psychological
impact of COVID-19, its long-term consequences on mental health remain relatively
unexplored. Aims We aimed to examine mental health literature on prior outbreaks to
provide recommendations for developing effective strategies to mitigate the short-
and long-term psychological impact of the current pandemic. Methods We conducted a
narrative review of 41 studies to analyze the adverse impact of the following
epidemics and pandemics on the mental health of individuals, groups, and
communities: Middle East Respiratory Syndrome, Severe Acute Respiratory Syndrome,
Influenza A/H1N1, and Ebola Virus Disease. Results We noted that these past
epidemics and pandemics escalated stress, distress, anxiety, fear, and stigma that
persisted in countries and communities. We also identified the role of
misinformation in propagating discrimination and prejudice towards certain groups.
Conclusions We discuss how the mental health outcomes of previous pandemics
differed from the COVID-19 outbreak. We believe that strategies that reduce
misinformation, educational initiatives, and mental health programs when introduced
at the individual and community level have the potential to effectively diminish
the negative psychological impact of COVID-19. PRISMA This study followed the
PRISMA guidance and was not registered in PROSPERO. This is a narrative review that
used qualitative thematic analysis. Publishing a protocol on a protocol repository
for such reviews is not the standard of practice.
Fear of failure is a popular catchphrase used by performers in a variety of domains
to reference motivating and/or inhibiting forces. In 2001, Conroy produced a review
of research on the development of fear of failure and associated problems across a
variety of different domains that also offered ideas on future research directions
in relation to treatment. His review provided researchers with an understanding of
the fear of failure at a time when little research had been conducted in the sport
and exercise domain. The present scoping review is focused upon research in sport,
exercise, and physical activity on fear of failure emerging subsequent to Conroy's
review to provide readers with an up-to-date understanding of how fear of failure
is manifested among participants in sport and exercise. A total of 48 articles are
included in this scoping review, which are divided into a total of four groups; (1)
measurement of fear of failure, (2) antecedents of fear of failure, (3) outcomes of
fear of failure, and (4) fear of failure and gender/sex differences. Future
recommendations for research are discussed.
Fear of cancer recurrence (FCR) is the most common psychosocial issue amongst
cancer survivors. However, fear of progression (FoP) has rarely been studied
outside of the cancer context. This review aimed to: (1) meta-synthesise
qualitative studies of FoP in illnesses other than cancer; and (2) quantify the
relationship between FoP and anxiety, depression, and quality of life (QoL) in non-
cancer chronic illnesses. We identified 25 qualitative and 11 quantitative studies
in a range of chronic illnesses. Participants described fears of progression and
recurrence of their illness, including fears of dying, and fears of becoming a
burden to family. Fears were often triggered by downward comparison (i.e., seeing
people worse off than themselves). Participants coped in different ways, including
by accepting the illness or seeking knowledge. Those for whom these fears caused
distress reported hypervigilance to physical symptoms and avoidance. Distress, and
seeking information, were associated with adherence. In quantitative analyses, FoP
was moderately associated with QoL, and strongly associated with anxiety and
depression. These results suggest that FoP in illnesses other than cancer is
similar to FCR. FoP appears to be an important transdiagnostic construct associated
with distress. Evidence-based FCR interventions could be adapted to better manage
FoP in other illnesses.
Terror management theory postulates that mortality salience (MS) increases the
motivation to defend one's cultural worldviews. How that motivation is expressed
may depend on the social norm that is momentarily salient. Meta-analyses were
conducted on studies that manipulated MS and social norm salience. Results based on
64 effect sizes for the hypothesized interaction between MS and norm salience
revealed a small-to-medium effect of g = 0.34, 95% confidence interval [0.26,
0.41]. Bias-adjustment techniques suggested the presence of publication bias and/or
the exploitation of researcher degrees of freedom and arrived at smaller effect
size estimates for the hypothesized interaction, in several cases reducing the
effect to nonsignificance (range g(corrected) = -0.36 to 0.15). To increase
confidence in the idea that MS and norm salience interact to influence behavior,
preregistered, high-powered experiments using validated norm salience manipulations
are necessary. Concomitantly, more specific theorizing is needed to identify
reliable boundary conditions of the effect.
People in Croatia have recently experienced two major earthquakes in the midst of
COVID-19 pandemic, which are possible sources of increased fear. In order to
capture and understand the effects of the simultaneously occurring threatening
events, the aims of this study were threefold. First, we aimed to examine the
psychometric properties and factor structure of the Croatian version of the Fear of
COVID-19 scale (FCV-19S). Second, bearing in mind that there is a lack of
instruments for measuring fear of earthquakes, the study aimed to develop and
examine the psychometric properties the Fear of Earthquake Scale (FES), as a
version of FCV-19S, modified for the earthquake experience. Finally, the study
aimed to examine differences in well-being indicators (life satisfaction, positive
and negative affect) between four groups of participants who either had/did not
have COVID-19 disease or had experienced/did not have experienced earthquake. The
study was conducted among 1136 participants adults who took part in the fourth year
of the Croatian longitudinal study on well-being. Among them, N = 665 participants
experienced earthquake and responded to additional questions regarding that
experience. The analyses demonstrated valid psychometric properties and one-
factorial structure of FCV-19S and FES scales. The findings showed that people who
went through earthquake experience (vs. those without earthquake experience and
COVID-19 infection) reported higher negative affect and lower positive affect,
indicating that people in Croatia seem to have been more fearful of earthquakes
than COVID-19 pandemic. Findings suggest the long-term negative effects of
earthquake on fear and well-being in comparison to COVID-19 pandemic.
This review is an attempt to establish concepts of splicing and alternative
splicing giving proper relevance to introns, the key actors in this mechanism. It
might also work as a guide for those who found their favorite gene undergoes
alternative splicing and could benefit from gaining a theoretical framework to
understand the possible impacts of this process. This is not a thorough review of
all the work in the field, but rather a critical review of some of the most
relevant work done to understand the underlying mechanisms of splicing and the key
questions that remain unanswered such as: What is the physiological relevance of
alternative splicing? What are the functions of the different outcomes? To what
extent do different alternative splicing types contribute to the proteome? Intron
retention is the most frequent alternative splicing event in plants and, although
scientifically neglected, it is also common in animals. This is a heterogeneous
type of alternative splicing that includes different sub-types with features that
have distinctive consequences in the resulting transcripts. Remarkably, intron
retention can be a dead end for a transcript, but it could also be a stable
intermediate whose processing is resumed upon a particular signal or change in the
cell status. New sequencing technologies combined with the study of intron lariats
in different conditions might help to answer key questions and could help us to
understand the actual relevance of introns in gene expression regulation.
Patients with serious illnesses often do not engage in discussions about end-of-
life care decision-making, or do so reluctantly. These discussions can be useful in
facilitating advance care planning and connecting patients to services such as
palliative care that improve quality of life. Terror Management Theory, a social
psychology theory stating that humans are motivated to resolve the discomfort
surrounding their inevitable death, has been discussed in the psychology literature
as an underlying basis of human decision-making and behavior. This paper explores
how Terror Management Theory could be extended to seriously ill populations and
applied to their healthcare decision-making processes and quality of care received.
Background There is impairment in maintaining balance while doing activities of
daily living in aging individuals due to deterioration in the sensory, cognitive,
and musculoskeletal systems. The positive effects of aerobic and resistance
exercise in older people have already been established. Nowadays, researchers are
stressing over the importance of multicomponent exercise programs where a
combination of exercises like aerobic, resistance, and balance and coordination
exercises, etc., was used. Purpose The present review summarizes the effects of
concurrent exercise training (aerobic + resistance) and multicomponent exercise
programs on balance, fear of falling, and muscle strength in older adults. Methods
MEDLINE (accessed by PubMed) and Web of Science (Web of Science Core Collection)
were searched using a combination of keywords. Results The result in a majority of
the included studies showed positive improvement in balance, fear of fall, and
strength of muscles. Improvement in muscle strength is more evident when subjected
to resistance exercise training alone than concurrent training. Conclusions
Multicomponent exercise training program when compared with concurrent training is
more effective in improving balance, fear of fall, and muscle strength in older
adults.
Several in-person and remote delivery formats of cognitive-behavioural therapy
(CBT) for panic disorder are available, but up-to-date and comprehensive evidence
on their comparative efficacy and acceptability is lacking. Our aim was to evaluate
the comparative efficacy and acceptability of all CBT delivery formats to treat
panic disorder. To answer our question we performed a systematic review and network
meta-analysis of randomised controlled trials. We searched MEDLINE, Embase,
PsycINFO, and CENTRAL, from inception to 1st January 2022. Pairwise and network
meta-analyses were conducted using a random-effects model. Confidence in the
evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). The
protocol was published in a peer-reviewed journal and in PROSPERO. We found a total
of 74 trials with 6699 participants. Evidence suggests that face-to-face group
[standardised mean differences (s.m.d.) -0.47, 95% confidence interval (CI) -0.87
to -0.07; CINeMA = moderate], face-to-face individual (s.m.d. -0.43, 95% CI -0.70
to -0.15; CINeMA = Moderate), and guided self-help (SMD -0.42, 95% CI -0.77 to -
0.07; CINeMA = low), are superior to treatment as usual in terms of efficacy,
whilst unguided self-help is not (SMD -0.21, 95% CI -0.58 to -0.16; CINeMA = low).
In terms of acceptability (i.e. all-cause discontinuation from the trial) CBT
delivery formats did not differ significantly from each other. Our findings are
clear in that there are no efficacy differences between CBT delivered as guided
self-help, or in the face-to-face individual or group format in the treatment of
panic disorder. No CBT delivery format provided high confidence in the evidence at
the CINeMA evaluation.
Purpose The study aims to provide an updated overview of studies that show the
impact of psychotherapeutic interventions on fear of cancer recurrence (FCR), to
explore the relationship between FCR and related factors (psychological distress,
well-being, anxiety, depression, fear, coping strategies, quality of life), and to
identify the most effective therapeutic approaches in managing FCR. Methods Three
databases were searched between January 2021 and April 2021 using the key words
"fear of cancer recurrence - psychotherapy - intervention" following the a priori
established PRISMA protocol. Results Thirteen studies were included in the final
review. The database search identified 239 potential papers. After removing
duplicates and irrelevant articles by title and language, population, and type of
study, 13 articles were assessed for eligibility of the abstract, and 13 full-text
articles were reviewed and included in this systematic review. The studies were
mainly from the Netherlands (4 out of 13). Positive benefits of therapeutic
interventions on FCR were reported. Conclusions This research highlights challenges
in using therapeutic approaches in dealing with FCR and its management. Therapeutic
intervention is an effective means of managing not only FCR but also related
factors (distress, well-being, quality of life). However, individual needs and
preferences must be taken into consideration whilst choosing a therapeutic
approach. Cognitive behavioural therapy (CBT), acceptance and commitment therapy
(ACT), and mindfulness-based interventions are the most used approaches with CBT
being the most effective, especially in a blended form (i.e. standard CBT combined
with other self-help activities). Implications for Cancer Survivors The aim was to
provide information about the most effective therapeutic approaches for coping with
FCR.
Unraveling the neuronal mechanisms of fear learning might allow neuroscientists to
make links between a learned behavior and the underlying plasticity at specific
synaptic connections. In fear learning, an innocuous sensory event such as a tone
(called the conditioned stimulus, CS) acquires an emotional value when paired with
an aversive outcome (unconditioned stimulus, US). Here, we review earlier studies
that have shown that synaptic plasticity at thalamic and cortical afferents to the
lateral amygdala (LA) is critical for the formation of auditory-cued fear memories.
Despite the early progress, it has remained unclear whether there are separate
synaptic inputs that carry US information to the LA to act as a teaching signal for
plasticity at CS-coding synapses. Recent findings have begun to fill this gap by
showing, first, that thalamic and cortical auditory afferents can also carry US
information; second, that the release of neuromodulators contributes to US-driven
teaching signals; and third, that synaptic plasticity additionally happens at
connections up- and downstream of the LA. Together, a picture emerges in which
coordinated synaptic plasticity in serial and parallel circuits enables the
formation of a finely regulated fear memory.
Parents have a critical role to play in the sexual education of their children. We
conducted a systematic review of studies assessing the experiences of parents
regarding the role they play in the sexual education of their children. We included
qualitative, quantitative, and mixed methods studies conducted among parents in
Europe. We searched PubMed, Web of Science and Scopus, and screened 20,244 unique
records. Forty-nine studies enrolling 18,083 unique parents met inclusion criteria.
The studies show that parents have ideals regarding the sexual education of their
children that center around the importance of trust, open conversations, and
honesty. However, challenges and concerns, related to parents' and children's
gender, children's age, children's specific situations, and limited parental
knowledge and communication skills prevented them from living up to these ideals.
Parents pointed to the role of other institutions as ways to support and strengthen
parents' contributions to the sexual development of their children. We conclude
that parents may require guidance and support to identify what is appropriate
sexual education for their children, based on age, gender, and other
characteristics, how to provide appropriate sexual education, and to strengthen
their sexual communication skills and knowledge of contemporary sexual health
issues.
Purpose This review aims to elucidate the most commonly reported method to quantify
fear of reinjury or kinesiophobia and to identify key variables that influence the
degree of kinesiophobia following primary anterior cruciate ligament reconstruction
(ACLR). Methods A systematic search across three databases (Pubmed, Ovid (MEDLINE),
and EMBASE) was conducted from database inception to August 7th, 2022. The authors
adhered to the PRISMA guidelines and the Cochrane Handbook for Systematic Reviews
of Interventions. Quality assessment of the included studies was conducted
according to the Methodological Index for Non-Randomized Studies (MINORS) criteria.
Results Twenty-six studies satisfied the inclusion criteria and resulted in 2,213
total patients with a mean age of 27.6 years and a mean follow-up time of 36.7
months post-surgery. The mean MINORS score of the included studies was 11 out of 16
for non-comparative studies and 18 out of 24 for comparative studies. Eighty-eight
percent of included studies used variations of the Tampa Scale of Kinesiophobia
(TSK) to quantify kinesiophobia and 27.0% used Anterior Cruciate Ligament Return to
Sport After Injury (ACL-RSI). The results of this study shows a common association
between higher kinesiophobia and poor patient-reported functional status measured
using International Knee Documentation Committee (IKDC) Scores, Activity of Daily
Living (ADL), Quality of Life (QOL), and Sports/Recreation (S/R) subscales of Knee
Osteoarthritis and Outcome Score (KOOS) and Lysholm scores. Postoperative symptoms
and pain catastrophizing measured using the KOOS pain and symptom subscales and
Pain Catastrophizing Score (PCS) also influenced the degree of kinesiophobia
following ACLR. Patients with an increased injury to surgery time and being closer
to the date of surgery postoperatively demonstrated higher levels of kinesiophobia.
Less common variables included being a female patient, low preoperative and
postoperative activity status and low self-efficacy. Conclusion The most common
methods used to report kinesiophobia following primary ACLR were variations of the
TSK scale followed by ACL-RSI. The most commonly reported factors influencing
higher kinesiophobia in this patient population include lower patient-reported
functional status, more severe postoperative symptoms such as pain, increased
injury to surgery time, and being closer to the date of surgery postoperatively.
Kinesiophobia following primary ACLR is a critical element affecting post-surgical
outcomes, and screening should be implemented postoperatively to potentially treat
in rehabilitation and recovery.
Objective To evaluate the effectiveness of different interventions in reducing
pain-related fear outcomes in people with knee osteoarthritis who have or have not
had previous knee surgery, and to analyze whether included trials reported their
interventions in full detail. Methods Systematic searches were carried out in the
Cochrane CENTRAL, CINAHL, EMBASE, PEDro, PsycINFO, PubMed, and SPORTDiscus from the
inception of the database up to November 2019. Searches were manually updated to
July 2021. We included randomized clinical trials that evaluated pain-related fear
outcomes as a primary or secondary outcome in adults with knee osteoarthritis. The
Cochrane Risk of Bias Tool 2 and the GRADE approach evaluated the risk of bias and
the certainty of the evidence, respectively. Results Eighteen trials were included.
Four trials evaluated pain-related fear as a primary outcome and all evaluated
kinesiophobia in samples that had previously undergone a knee surgical procedure.
These trials found that interventions based primarily on cognitive aspects (e.g.
cognitive-behavioral principles) can be effective in reducing kinesiophobia. Trials
evaluating pain-related fear as the secondary outcome also found that interventions
that included cognitive aspects (e.g. pain neuroscience education) decreased the
levels of pain-related fear (e.g. fear of falling or kinesiophobia) in patients
with or without a previous knee surgery. However, serious to very serious risk of
bias and imprecisions were found in included trials. Thus, the certainty of the
evidence was judged as low and very low using the GRADE approach. All trials
reported insufficient details to allow a complete replication of their
interventions. Conclusions Interventions that include cognitive aspects may be the
best option to reduce pain-related fear in people with knee osteoarthritis.
However, we found a general low and very low certainty of the evidence and the
findings should be considered with caution.
Persistent fear is a cardinal feature of posttraumatic stress disorder (PTSD), and
deficient fear extinction retention is a proposed illness mechanism and target of
exposure-based therapy. However, evidence for deficient fear extinction in PTSD has
been mixed using laboratory paradigms, which may relate to underidentified
methodological variation across studies. We reviewed the literature to identify
parameters that differ across studies of fear extinction retention in PTSD. We then
performed Multiverse Analysis in a new sample, to quantify the impact of those
methodological parameters on statistical findings. In 25 PTSD patients (15 female)
and 36 trauma-exposed non-PTSD controls (TENC) (20 female), we recorded skin
conductance response (SCR) during fear acquisition and extinction learning (day 1)
and extinction recall (day 2). A first Multiverse Analysis examined the effects of
methodological parameters identified by the literature review on comparisons of
SCR-based fear extinction retention in PTSD versus TENC. A second Multiverse
Analysis examined the effects of those methodological parameters on comparisons of
SCR to a danger cue (CS+) versus safety cue (CS-) during fear acquisition. Both the
literature review and the Multiverse Analysis yielded inconsistent findings for
fear extinction retention in PTSD versus TENC, and most analyses found no
statistically significant group difference. By contrast, significantly elevated SCR
to CS+ versus CS- was consistently found across all analyses in the literature
review and the Multiverse Analysis of new data. We discuss methodological
parameters that may most contribute to inconsistent findings of fear extinction
retention deficit in PTSD and implications for future clinical research.
Introduction Operations Iraqi Freedom and Enduring Freedom saw higher rates of
combat ocular trauma (COT) than any past U.S. conflict. The improvised explosive
device, the signature weapon of the conflicts, as well as improved personal
protective equipment and combat medical care all attributed to COT being the fourth
most common injury sustained by wounded U.S. service members. This review describes
the epidemiology, mechanisms, and treatment patterns and discusses the relationship
of traumatic brain injuries (TBIs) to ocular injuries sustained by U.S. service
members during the War on Terror. Materials and Methods A mixed-methods review of
the literature was conducted by extracting data from PubMed, Embase, and Cochrane
research databases between December 15, 2020, and January 25, 2021, using the
COVIDENCE review management software. Results Of 827 articles for review, 50 were
deemed relevant. Articles were separated using the Birmingham Eye Trauma
Terminology into open globe, closed globe, mixed/injury management only, and TBI.
Seventeen articles were found to discuss data pertaining to particular databases.
Overall, six articles discussed open-globe injuries in the setting of overall COT
with a reported rate of 38-64%. Three articles discussed closed-globe injuries in
the context of overall COT with a rate of 39-47%. Numerous articles discussed the
relationship between COT and TBI. Within the Walter Reed Ocular Trauma Database,
40% of patients with ocular trauma had concomitant TBI. Additionally, the visual
sequelae of ocular trauma ranged from 9% to 50% among reporting studies. Other
ocular injury patterns receiving attention include neuro-ophthalmic and
oculoplastic injuries. By far the most common mechanism of COT was blast injury
(64-84%), with improvised explosive devices (IEDs) accounting for 51-69% of ocular
injuries. Among the large reporting databases, 41-45% of COT required surgical
treatment with an overall enucleation rate of 12-17%. Conclusions The Global War on
Terrorism saw an evolution in the types of ocular injuries sustained by U.S.
service members compared to previous conflicts. The widespread use of IEDs led to
injury patterns not encountered in previous conflicts. Weapons of today utilize
blast and shrapnel as the mechanism for destruction. Sequelae such as TBIs and
complicated head and neck trauma have pushed innovation in the field of
ophthalmology. Improvements in medical technology and personal protective equipment
have resulted in not only survival of previously life-threatening injuries, but
also a greater chance of severe loss of vision. By analyzing ocular injury data
from the trauma literature, improvements in education and training can lead to
improvements in point-of-injury care and eye protection for the next generation of
warfighters.
The global COVID-19 pandemic has disrupted the lives of workers and taken its toll
on health and well-being. In line with recent calls for more inductive and
abductive occupational health science research, we exploratorily meta-analyzed
workers' COVID-19 distress, defined as psychological and psychosomatic strain
contextualized to experiencing the virus and pandemic broadly. We identified many
existing COVID-19 distress measures (e.g., Fear of COVID-19 Scale by Ahorsu et al.,
International Journal of Mental Health and Addiction, 2020; Coronavirus Anxiety
Scale by Lee, Death Studies, 44(7), 393-401, 2020a) and correlates, including
demographic variables (viz., gender, marital status, whether worker has children),
positive well-being (e.g., quality of life, perceived social support, resilience),
negative well-being (e.g., anxiety, depression, sleep problems), and work-related
variables (e.g., job satisfaction, burnout, task performance). Additionally, we
found preliminary evidence of subgroup differences by COVID-19 distress measure and
country level moderation moderators (viz., cultural values, pandemic-related
government response) as well as COVID-19 distress's incremental validity over and
above anxiety and depression. The findings-based on k= 135 independent samples
totaling N=61,470 workers-were abductively contextualized with existing theories
and previous research. We also call for future research to address the grand
challenge of working during the COVID-19 pandemic and ultimately develop a
cumulative occupational health psychology of pandemics.
Introduction After over 20 years of war in the Middle East, orthopedic injuries
have been among the most prevalent combat-related injuries, accounting for 14% of
all surgical procedures at Role 2/3 (R2/R3) facilities according to the DoD Trauma
Registry. To further delineate the role of the deployed orthopedic surgeon on the
modern battlefield, a retrospective review was performed highlighting both
quantitative and qualitative analysis factors associated with orthopedic surgical
care during the war in the Middle East. Methods A retrospective review was
conducted of orthopedic surgeons in the Middle East from 2001 to 2021. A
comprehensive literature search was conducted using the PubMed and Embase databases
using a two-reviewer strategy. Articles were compiled and reviewed using Covidence.
Inclusion criteria included journal articles focusing on orthopedic injuries
sustained during the Global War on Terror (GWoT) in an adult U.S. Military
population. In the event of a conflict, a third author would determine the
relevance of the article. For the remaining articles, a full-text review was
conducted to extract relevant predetermined quantitative data, and the Delphi
consensus method was then utilized to highlight relevant qualitative themes.
Results The initial search yielded 1,226 potentially relevant articles. In all, 40
studies ultimately met the eligibility criteria. With the consultation of
previously deployed orthopedic surgeons at the Walter Reed National Military
Medical Center, a retrospective thematic analysis of the 40 studies revealed five
themes encompassing the orthopedic surgeons experience throughout GWoT. These
themes include unique mechanisms of orthopedic injury compared to previous war
injuries due to novel weaponry, differences in interventions depending on R2 versus
R3 locations, differences in injuries from those seen in civilian settings, the
maintained emphasis on humanitarian aspect of an orthopedic surgeon's mission, and
lastly relation of pre-deployment training to perceived deployed success of the
orthopedic surgeons. From this extensive review, we found that explosive mechanisms
of injury were greatly increased when compared to previous conflicts and were the
etiology for the majority of orthopedic injuries sustained. With the increase of
complex explosive injuries in the setting of improved body armor and overall
survival, R2/3 facilities showed an increased demand for orthopedic intervention
including debridement, amputations, and external fixation. Combat injuries
sustained during the GWoT differ in the complications, management, and complexity
when compared to civilian trauma. "Humanitarian" cases made up a significant number
of operative cases for the deployed orthopedic surgeon. Lastly, heterogeneous
training opportunities were available prior to deployment (fellowship, combat
extremity surgical courses, and dedicated pre-deployment training), and the most
commonly identified useful training was learning additional soft-tissue coverage
techniques. Conclusion These major themes indicate an emphasis on pre-deployment
training and the strategic positioning of orthopedic surgeons to reflect the
changing landscape of musculoskeletal trauma care. Moving forward, these authors
recommend analyzing the comfort and perceived capability of orthopedic surgeons in
these unique military environments to best prepare for a changing operational
format and the possibility of future peer-peer conflicts that will likely lead to a
lack of medical evacuation and prolonged field care.
RationaleSelective serotonin reuptake inhibitors (SSRIs) are considered first-line
medication for anxiety-like disorders such as panic disorder, generalized anxiety
disorder, and post-traumatic stress disorder. Fear learning plays an important role
in the development and treatment of these disorders. Yet, the effect of SSRIs on
fear learning are not well known.ObjectiveWe aimed to systematically review the
effect of six clinically effective SSRIs on acquisition, expression, and extinction
of cued and contextual conditioned fear.MethodsWe searched the Medline and Embase
databases, which yielded 128 articles that met the inclusion criteria and reported
on 9 human and 275 animal experiments.ResultsMeta-analysis showed that SSRIs
significantly reduced contextual fear expression and facilitated extinction
learning to cue. Bayesian-regularized meta-regression further suggested that
chronic treatment exerts a stronger anxiolytic effect on cued fear expression than
acute treatment. Type of SSRI, species, disease-induction model, and type of
anxiety test used did not seem to moderate the effect of SSRIs. The number of
studies was relatively small, the level of heterogeneity was high, and publication
bias has likely occurred which may have resulted in an overestimation of the
overall effect sizes.ConclusionsThis review suggests that the efficacy of SSRIs may
be related to their effects on contextual fear expression and extinction to cue,
rather than fear acquisition. However, these effects of SSRIs may be due to a more
general inhibition of fear-related emotions. Therefore, additional meta-analyses on
the effects of SSRIs on unconditioned fear responses may provide further insight
into the actions of SSRIs.
After reviewing two complementary analyses of the plight of the Uyghur people in
contemporary North-West China, one by the American cultural anthropologist Darren
Byler and the other by the imprisoned Uyghur public intellectual Ilham Tohti, this
essay concludes with reflections on the appropriateness of the concept of
"capitalism" to describe the hybrid economic forms promoted by the authoritarian
regime of Xi Jinping.
Rationale and objectives Fear conditioning is an important aspect in the
pathophysiology of anxiety disorders. The fear-potentiated startle test is based on
classical fear conditioning and over the years, a broad range of drugs have been
tested in this test. Synthesis of the available data may further our understanding
of the neurotransmitter systems that are involved in the expression of conditioned
fear. Methods Following a comprehensive search in Medline and Embase, we included
68 research articles that reported on 103 drugs, covering 56 different drug
classes. The systematic review was limited to studies using acute, systemic drug
administration in naive animals. Results Qualitative data synthesis showed that
most clinically active anxiolytics, but not serotonin-reuptake inhibitors, reduced
cued fear. Anxiogenic drugs increased fear potentiation in 35% of the experiments,
reduced fear potentiation in 29% of the experiments, and were without effect in 29%
of the experiments. Meta-analyses could be performed for five drug classes and
showed that benzodiazepines, buspirone, 5-HT1A agonists, 5-HT1A antagonists, and
mGluR2,3 agonists reduced cued conditioned fear. The non-cued baseline startle
response, which may reflect contextual anxiety, was only significantly reduced by
benzodiazepines and 5-HT1A antagonists. No associations were found between drug
effects and methodological characteristics, except for strain. Conclusions The
fear-potentiated startle test appears to have moderate to high predictive validity
and may serve as a valuable tool for the development of novel anxiolytics. Given
the limited available data, the generally low study quality and high heterogeneity
additional studies are warranted to corroborate the findings of this review.
AimsTo summarize and critically appraise evidence regarding the effectiveness of
educational and/or behavioural interventions in reducing fear of hypoglycaemia
among adults with type 1 diabetes. MethodsSystematic searches of medical and
psychology databases were conducted. Risk-of-bias was assessed using the Joanna
Briggs Institute Critical Appraisal Tools. Data were synthesized using random-
effects meta-analyses for randomized controlled trials (RCTs) and narrative
synthesis for observational studies. ResultsFive RCTs (N = 682) and seven
observational studies (N = 1519) met the inclusion criteria, reporting on
behavioural, structured education and cognitive-behavioural therapy (CBT)
interventions. Most studies assessed fear of hypoglycaemia using the Hypoglycaemia
Fear Survey Worry (HFS-W) and Behaviour (HFS-B) subscales. Mean fear of
hypoglycaemia at baseline was relatively low across studies. Meta-analyses showed a
significant effect of interventions on HFS-W (SMD = -0.17, p = 0.032) but not on
HFS-B scores (SMD = -0.34, p = 0.113). Across RCTs, Blood Glucose Awareness
Training (BGAT) had the largest effect on HFS-W and HFS-B scores, and one CBT-based
program was as effective as BGAT in reducing HFS-B scores. Observational studies
showed that Dose Adjustment for Normal Eating (DAFNE) was associated with
significant fear of hypoglycaemia reductions. ConclusionsCurrent evidence suggests
that educational and behavioural interventions can reduce fear of hypoglycaemia.
However, no study to date has examined these interventions among people with high
fear of hypoglycaemia.
Background The Fear of Childbirth (FOC) is regarded as a general problem, which
affects women's health and well-being, justifying demanding caesarean section.
Several primary studies have been performed in relation to the interventions
performed to reduce the fear of childbirth, which show contradictions between the
results of these studies. Objective This review aims to provide a comprehensive
review of the different types of interventions used to reduce the fear of
childbirth in pregnant mothers. Methods In this study, systematic review of study
information related to the effect of different therapies on reducing the fear of
childbirth using subject-related keywords and validated with MeSH in SID, MagIran,
IranMedex, IranDoc, Embase, ProQuest, Scopus, PubMed, Web of Science (ISI)
databases and Google Scholar Search Engine were extracted without any time limit
until February 2021. Results After removing duplicates and irrelevant works from
among the 5396 articles found, 63 articles remained in the study. The participants
in these 63 articles were 5415 cases and 5770 controls. In addition, three studies
were on epidural anesthesia, 33 on the effects of psychotherapy, 19 on the effects
of education, and eight on the influence of other interventions on alleviating FOC.
As shown by the results, psychotherapy intervention and education decreased FOC
significantly. Conclusion According to the results of this study, to prevent the
fear of childbirth, pregnancy training and prenatal preparation courses are
recommended to empower pregnant women. It also seems beneficial to use
psychotherapy approaches for women who are afraid of childbirth.