Tal Harmelech, PhD

This looks good, by an excellent researcher .. Developing the neurobiology of emotion regulation https://lnkd.in/dUDy-3wX

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It doesn’t end here 2nd generation atypical antipsychotics also have similar problems again to be followed up in a Newsletter Here are studies that support the potential for newer, atypical antipsychotics to induce oxidative stress: 1. Kramar, B., Pirc Marolt, T., Yilmaz Goler, A. M. (2024) • Title: “Aripiprazole, but Not Olanzapine, Alters the Response to Oxidative Stress in Fao Cells by Reducing the Activation of Mitogen-Activated Protein Kinases” • This study explores how prolonged exposure to atypical antipsychotics like olanzapine and aripiprazole affects oxidative stress responses in liver cells. While aripiprazole may reduce oxidative stress pathways, olanzapine is shown to have a less favorable impact, potentially leading to increased oxidative stress. 2. Al-Juhaishi, A. M., Ismael, A. H., Jasim, A. H. (2024) • Title: “Hepatoprotective Activity of Ezetimibe Against Risperidone-Induced Liver Injury in Rats” • This research highlights risperidone’s potential to induce oxidative stress in liver tissue, which contributes to hepatic injury. The study examines how antioxidants might mitigate these effects, suggesting that managing oxidative stress is essential in atypical antipsychotic treatment. 3. Stojkovic, M., Jovanovic, M., Jakovljevic, V., Zivkovic, V. (2024) • Title: “Protective Effect of Hyperprolactinemia on Oxidative Stress in Patients with Psychotic Disorder on Atypical Antipsychotics Risperidone and Paliperidone” • The study investigates how atypical antipsychotics like risperidone and paliperidone contribute to oxidative stress, especially in patients with hyperprolactinemia. Findings suggest that oxidative stress may be a significant side effect, necessitating antioxidant support. 4. Mani, V., Alshammeri, B. S. (2023) • Title: “Aripiprazole Attenuates Cognitive Impairments Induced by Lipopolysaccharide in Rats through the Regulation of Neuronal Inflammation, Oxidative Stress” • This study explores aripiprazole’s influence on oxidative stress and inflammation in the brain, indicating its impact on cognitive function and neural health through oxidative pathways. 5. El-Borm, H. T., Badawy, G. M., Sherifa, F. A. (2024) • Title: “Therapeutic Action of Ashwagandha Extract on Apoptosis and Cell Proliferation in the Heart of Rat Fetuses Prenatally Treated with Clozapine” • This study discusses clozapine’s impact on oxidative stress in developing tissues, highlighting its potential oxidative and apoptotic effects on the heart in prenatal exposure. Ashwagandha extract is explored as a therapeutic antioxidant. 6. Pérez-Neri, I., Lamas-Aguilar, R., Ríos, C. (2024) • Title: “Evaluation of the Antioxidant Effect of Olanzapine in Combination with N-acetylcysteine in a Mouse Model of Schizophrenia” • This study examines olanzapine’s oxidative stress effects and evaluates the use of N-acetylcysteine as an adjunct to mitigate oxidative damage in schizophrenia models.

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New in #JNeurosci: Researchers from the Cajal Institute in Madrid discover transgenerational memory improvements from moderate physical exercise in mice that may be driven by a set of microRNAs. Learn more ▶️ https://bit.ly/3WozfHK

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This disturbing paper came to my attention: Take away points: 1) informed consent must make sure patients understand that withdrawal symptoms can last years 2) sometimes withdrawal symptoms onset can be delayed and not manifest for weeks or months, making distinction between relapse and withdrawal symptoms very difficult 3) we must listen to our patients and maintain a high index of suspicion of the occurrence of withdrawal symptoms 4) after all, both the pharma industry and clinicians initially insisted that there are no withdrawal symptoms , then maintained through flawed studies that they are “mild” then we learned the opposite from our patients. 5) the malignant term of “antidepressant discontinuation symptoms” was a pharma coined term which in theory is more palatable to doctors and patients alike. Don’t use this term please.

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Mild Traumatic Brain Injuries (mTBIs) were traditionally considered to be relatively innocuous compared to more severe forms of brain injuries. However, it is now recognized that even mild TBIs can have significant and long-lasting effects, leading to conditions such as Persistent Post Concussion Syndrome (PPCS) in a substantial number of patients. PPCS refers to the persistence of post-concussion symptoms beyond the expected recovery period, which can include issues such as headaches, dizziness, cognitive difficulties, and emotional disturbances. These symptoms can have a profound impact on an individual's quality of life and daily functioning. Studies have shown that even mild TBIs can result in permanent symptoms for some individuals, challenging the notion that these injuries are minor or inconsequential. Research has highlighted the importance of recognizing and addressing the potential long-term effects of mTBIs, including the need for appropriate treatment and support for individuals experiencing PPCS. In the context of HBOT treatment, studies have demonstrated promising results in improving symptoms and cognitive function in patients with mTBI and PPCS. HBOT has shown potential in providing therapeutic benefits and enhancing recovery for individuals with these conditions, further emphasizing the significance of addressing even mild TBIs with appropriate care and interventions. Overall, while mild TBIs may have been previously viewed as innocuous, it is now understood that they can have lasting consequences and require proper attention, treatment, and support to address the associated symptoms and challenges. Hyperbaric Oxygen Therapy (HBOT) shows promise in treating Persistent Post Concussion Syndrome (PPCS) caused by traumatic brain injuries, including mild Traumatic Brain Injuries (mTBIs). Studies have indicated that HBOT, particularly at 1.5 ATA oxygen, has demonstrated statistically significant improvements in symptoms and cognitive function in patients with mild traumatic brain injury PPCS. This suggests that HBOT may be effective in alleviating symptoms and enhancing cognitive outcomes for individuals with PPCS. While the research landscape highlights the potential benefits of HBOT for treating PPCS, further comprehensive and conclusive studies are needed to solidify these findings. BreatheHope research efforts aim to provide concrete evidence regarding the effectiveness of HBOT in addressing the symptoms and challenges associated with PPCS.

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Researchers have uncovered a pivotal connection, affecting infants as young as six months old. This correlation links the physical stature of infants to their cognitive abilities, intricately tied to brain function, based on the concept of ‘visual working memory.’ https://lnkd.in/e92ECKwg FuturistSpeaker.com #foresight #predictions #futuretrends #futureofwork #futurejobs #keynotespeaker #futuriststrategy #mostquoted

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Good news! The fourth edition of the Encyclopedia of Toxicology has been published. In it, I have contributed a chapter on nicotine. This is the third academic book to which I have contributed. #nicotine #neurotoxin https://lnkd.in/g2T6rTt6

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💥 New Article Alert 🎯 "Vitactions: vitamins for the brain" from Professor Rafael Franco at Universitat de Barcelona 💬 Insightful comments on a recent article that put forward a novel concept in the mind/body interface. ⭕ Read to learn more at https://lnkd.in/gUVsUcEt #Vitactions #behaviour #neuropsychology #neuroprotection #neurodegenerative diseases #Alzheimer’s disease #vitactin #vitamin Related original article: https://lnkd.in/gCkpeJ5a

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Dr. Stephen Porges' newest paper has been published in the Journal of Neurogastroenterology and Motility: "Disorders of gut–brain interaction through the lens of Polyvagal Theory." This paper introduces a metric capable of tracking a hypothetical brainstem “switching” mechanism involved in regulating the afferent influence of blood pressure on the vagal efferent control of heart rate. In theory, this metric could be applied to evaluate the “efficiency” of brainstem pathways involved in common mechanisms of autonomic function involving the vagal influences on the gut as well as the heart. Thus, by exploring the dynamic “efficiency” of the brainstem feedback circuit linking heart rate to posture, a clinically relevant index of vagal flexibility might be extracted that would provide a generalizable window into the vagal regulation of both the heart and gut. Recent research supports this contention and has documented that this metric, VE, appears to covary with disorders of the gut. Clinical application of this metric might identify individual vulnerabilities that frequently reflect symptoms assumed to have features of a dysregulated autonomic nervous system (i.e., dysautonomia). If this is confirmed by additional research, then this objective measure of neural regulation of autonomic function might provide insight into the pathogenesis of disorders of gut–brain interaction. Available on open access here: https://loom.ly/ZIdnYO8

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The most comprehensive evidence for microdosing has just been published for #LSD. These results, backed by EEG and less subjective measures, help to differentiate from the placebo effect. A total of 54 healthy volunteers were given either placebo or low dose (15 ug) LSD, 4x over a two-week period. #EEG was collected 3-4 hours after dose administration and audio and visual data was collected to determine long-term potentiation (LTP), a core phenomenon underlying neuroplasticity learning and memory. Low dose LSD reduced resting state EEG signals of delta, theta, and alpha power. This is congruence with other low dose studies of LSD and #psilocybin along with higher doses of psychedelics. The corresponding level of stimulatory effect is similar to that of caffeine or dopaminergic amphetamines. LTP was inhibited on the 4th dosing day with LSD and effects were more pronounced in subjects with higher baselines. This is similar to effects seen with higher doses but the effects are transient and resolved after PK effects have worn off. Lastly, neural effects (reduced delta in resting EEG) were persistent one week after the last dose of LSD. It’s known that psychedelics have durable effects but this appears to be the first evidence to support these effects with a lower, non-psychedelic dose. I think this is a really important finding which has been demonstrated in rodents and now in humans. To me, it does not appear that psychedelic effects (as a PK/PD measure) are a hurdle that must be overcome to have beneficial effects on psyche and underlying biology. As with most drugs there is a linear dose-response, so I hope this spurs more studies in between a microdose and a 10x psychedelic dose. This may help reduce side effects (hallucinations, anxiety, nausea, headaches, etc) while also providing therapeutic effects. The authors suggest this dosing regimen could be suitable for ADHD or obsessive-compulsive disorders given the elevated EEG signals which could be attenuated by low-dose LSD. There’s also a large body of evidence in subjective reports from ADHD users showing benefits. In regards to the important psychedelic blinding question, there was no significant trends for participants guessing whether they had received placebo or low-dose LSD. This is much easier to achieve with low doses rather than the psyche-altering high doses. This is a really well-designed study to quantitatively measure the effects of #microdosing. There has been quite a bit published on this topic but too many studies are not blinded, measured for expectancy, and results have not been shown to be statistically significant over placebo. This is a step in the right direction but now let’s replicate to see if therapeutic effects can be found! #sciencesunday https://lnkd.in/eTwNqj3e

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Vortioxetine (Trintellix) has a linear dose-response, with 50% of the effects at 5 mg and 95% at 18mg/day, from new analysis of 16 trials in #depression: https://lnkd.in/eba-Urqt Most antidepressants do not have a linear dose-response curve. More updates in Carlat #Psychiatry News: https://lnkd.in/eQzQrUCs

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e-Cigs equaled varenicline (#Chantix) in this large randomized trial of #smoking cessation: https://lnkd.in/eC4bE_Fv Nice design with placebo vapes, real vapes, and placebo pills Last week I posted that varenicline can help people stop #vaping, which has its own risks More updates in Carlat #Psychiatry News: https://lnkd.in/egtvqhnM #vapelife #StopSmoking

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Silexan is a branded lavender extract approved for #anxiety in Europe (and available over the counter in US). Although many think of natural therapies for milder conditions, it has double the effect size of SSRIs and - in this analysis of 5 trials - worked better for those with more severe anxiety: https://lnkd.in/etmRXzqi Learn how to use it in the Carlat Podcast: https://lnkd.in/eD_p_uDw And where to get it (under vitamins): https://lnkd.in/geYcDYnt #mentalhealth #psychiatry

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