Mechanisms through which exercise reduces symptom severity and/or functional impairment in posttraumatic stress disorder (PTSD): Protocol for a living systematic review of human and non-human studies

Wellcome Open Research, Год журнала: 2025, Номер 8, С. 494 - 494

Опубликована: Янв. 13, 2025

Background Exercise can play an important role in reducing symptom severity and improving functional impairment patients with posttraumatic stress disorder (PTSD). However, the precise mechanisms underpinning effect of exercise PTSD management are not fully understood. This living systematic review aims to synthesize triangulate evidence from non-human human studies gain insight into biopsychosocial through which reduces impairment. Methods Independent searches will be conducted electronic databases identify eligible studies. Two reviewers independently conduct study selection, data extraction, risk bias assessment. We extract outcome variables that act as modifiers or mediators exercise. For studies, include equivalents clusters. primary severity. The secondary outcomes avoidance severity, reexperiencing hyperarousal negative cognitions mood impairment, loss diagnosis, dropout rates. To explain affects interest, we effects relate impact on potential mediating later outcomes. Comparison within-study direct indirect obtained mediation analysis, when reported, provide importance examined mediator. If appropriate, results using meta-analyses. examine total understand better symptoms function (when possible). about association between PTSD-related considered a consensus meeting sufficient is available. Protocol registration PROSPERO-ID: 453615

Язык: Английский

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Endocannabinoids and Stress-Related Neurospsychiatric Disorders: A Systematic Review and Meta-Analysis of Basal Concentrations and Response to Acute Psychosocial Stress

Cannabis and Cannabinoid Research, Год журнала: 2024, Номер 9(5), С. 1217 - 1234

Опубликована: Апрель 29, 2024

Dysregulation of the endocannabinoid (eCB) system is implicated in various stress-related neuropsychiatric disorders (SRDs), including anxiety, depression, and post-traumatic stress disorder (PTSD). In this systematic review meta-analysis, our objectives were to characterize circulating anandamide (AEA) 2-arachidonoylglycerol (2-AG) concentrations at rest response acute laboratory-based psychosocial individuals with SRDs without (controls). Our primary aims assess effects on eCB controls (Aim 1), compare baseline (prestress) between 2), explore differential responses compared 3).

Язык: Английский

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Sex Differences in Endocannabinoid and Inflammatory Markers Associated with Posttraumatic Stress Disorder

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 14, 2025

Abstract Background Posttraumatic stress disorder (PTSD) is one of the most sex-polarized psychiatric disorders, with women exhibiting twice prevalence men. The biological mechanisms underlying this sex disparity are not fully understood. Growing evidence suggests that alterations stress-buffering endocannabinoid (eCB) system and heightened inflammation central to PTSD pathophysiology may contribute sex-biases in risk severity. Here, we examined sex-differences levels circulating eCBs peripheral pro-inflammatory markers a cohort men non-psychiatric controls. Methods 88 individuals 85 sex- age-matched controls (HC) were retrospectively selected from Mass General Brigham Biobank. Serum was assayed measure [anandamide (AEA), 2-arachidonyl glycerol (2-AG), oleoylethanolamide (OEA), arachidonic acid (AA] inflammatory [interleukin-1β (IL-1β), IL-6, IL-8, IL-18, tumor necrosis factor-alpha (TNFα), C-reactive Protein (CRP)]. Linear regression used predict differential abundance each analyte by disease state (PTSD/HC) within male female subgroups. Two-sided t-tests Benjamini-Hochberg correction examine differences across Analyses repeated those comorbid major depressive disorder. Results Male patients showed significant decrease AEA, AA OEA compared ( p ’s < .001) subgroups (PTSD HCs) p< .001 ). In contrast, among females, elevated IL-6 p<.05 ) IL-8 Both exhibited an increase TNFα concentrations ), HCs. Similar results obtained subgroup MDD after controlling for FAAH 385A genotype. Conclusions Our findings show first time eCB absent PTSD, who turn exhibit broader markers, thus suggesting perturbations vary sex.

Язык: Английский

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Mechanisms through which exercise reduces symptom severity and/or functional impairment in posttraumatic stress disorder (PTSD): Protocol for a living systematic review of human and non-human studies

Wellcome Open Research, Год журнала: 2025, Номер 8, С. 494 - 494

Опубликована: Апрель 14, 2025

Background Exercise can play an important role in reducing symptom severity and improving functional impairment patients with posttraumatic stress disorder (PTSD). However, the precise mechanisms underpinning effect of exercise PTSD management are not fully understood. This living systematic review aims to synthesize triangulate evidence from non-human human studies gain insight into biopsychosocial through which reduces impairment. Methods Independent searches will be conducted electronic databases identify eligible studies. Two reviewers independently conduct study selection, data extraction, risk bias assessment. We extract outcome variables that act as modifiers or mediators exercise. For studies, include equivalents clusters. primary severity. The secondary outcomes avoidance severity, reexperiencing hyperarousal negative cognitions mood impairment, loss diagnosis, dropout rates. To explain affects interest, we effects relate impact on potential mediating later outcomes. Comparison within-study direct indirect obtained mediation analysis, when reported, provide importance examined mediator. If appropriate, results using meta-analyses. examine total understand better symptoms function (when possible). about association between PTSD-related considered a consensus meeting sufficient is available. Protocol registration PROSPERO-ID: 453615

Язык: Английский

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Cannabinoid Receptor 2 Blockade Prevents Anti-Depressive-like Effect of Cannabidiol Acid Methyl Ester in Female WKY Rats

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(4), С. 3828 - 3828

Опубликована: Фев. 14, 2023

The pathophysiology of major depressive disorder (MDD) is diverse and multi-factorial, yet treatment strategies remain limited. While women are twice as likely to develop the men, many animal model studies antidepressant response rely solely on male subjects. endocannabinoid system has been linked depression in clinical pre-clinical studies. Cannabidiolic Acid-Methyl Ester (CBDA-ME, EPM-301) demonstrated anti-depressive-like effects rats. Here, we explored acute CBDA-ME some possible mediating mechanisms, using a depressive-like genetic model, Wistar-Kyoto (WKY) rat. In Experiment 1, Female WKY rats underwent Forced swim test (FST) following oral ingestion (1/5/10 mg/kg). 2, Male female FST after injection CB1 (AM-251) CB2 (AM-630) receptor antagonists 30 min before (1 mg/kg, males; 5 females). Serum levels Brain-Derived Neurotrophic Factor (BDNF), numerous endocannabinoids hippocampal Fatty Acid Amide Hydrolase (FAAH) were assessed. Results indicate that females required higher doses (5 10 mg/kg) induce an effect FST. AM-630 blocked antidepressant-like females, but not males. was accompanied by elevated serum BDNF low expression FAAH. This study shows sexually behavioral anti-depressive underlying mechanisms supporting its potential use for treating MDD related disorders.

Язык: Английский

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PREFRONTAL CORRELATES OF FEAR GENERALIZATION DURING ENDOCANNABINOID DEPLETION

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 30, 2024

Abstract Maladaptive fear generalization is one of the hallmarks trauma-related disorders. The endocannabinoid 2-arachidonoylglycerol (2-AG) crucial for modulating anxiety, fear, and stress adaptation but its role in balancing discrimination versus not known. To address this, we used a combination plasma measurement neuroimaging from childhood maltreatment exposed non-exposed mixed population combined with human rodent conditioning models. Here show that 2-AG levels are inversely associated at behavioral level both mice humans. In mice, depletion increases proportion neurons, similarity between neuronal representations, threat-predictive neutral stimuli within prelimbic prefrontal cortex ensembles. humans, increased dorsolateral cortical-amygdala resting state connectivity correlated generalization. These data provide convergent cross-species evidence key regulator suggest deficiency could represent disorder susceptibility endophenotype.

Язык: Английский

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Endocannabinoid Hydrolase Inhibitors: Potential Novel Anxiolytic Drugs

Drug Design Development and Therapy, Год журнала: 2024, Номер Volume 18, С. 2143 - 2167

Опубликована: Июнь 1, 2024

Abstract: Over the past decade, idea of targeting endocannabinoid system to treat anxiety disorders has received increasing attention. Previous studies focused more on developing cannabinoid receptor agonists or supplementing exogenous cannabinoids, which are prone various adverse effects due their strong pharmacological activity and poor selectivity, limiting application in clinical research. Endocannabinoid hydrolase inhibitors considered be most promising development strategies for treatment disorders. More recent efforts have emphasized that inhibition two major endogenous hydrolases, monoacylglycerol lipase (MAGL) fatty acid amide (FAAH), indirectly activates receptors by levels synaptic gap, circumventing desensitization resulting from direct enhancement signaling. In this review, we comprehensively summarize anxiolytic MAGL FAAH potential mechanisms, highlight reported novel natural products, provide an outlook future directions field. Keywords: inhibitors, system, disorders, anxiolytic, MAGL,

Язык: Английский

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Investigating endocannabinoid system and subjective responses to exercise in cancer patients: Rationale and future research directions

JSAMS Plus, Год журнала: 2024, Номер 4, С. 100073 - 100073

Опубликована: Июль 16, 2024

Язык: Английский

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Mechanisms through which exercise reduces symptom severity and/or functional impairment in posttraumatic stress disorder (PTSD): Protocol for a living systematic review of human and non-human studies

Wellcome Open Research, Год журнала: 2023, Номер 8, С. 494 - 494

Опубликована: Окт. 25, 2023

Background Exercise can play an important role in reducing symptom severity and improving functional impairment patients with posttraumatic stress disorder (PTSD). However, the precise mechanisms underpinning effect of exercise PTSD management are not fully understood. This living systematic review aims to synthesize triangulate evidence from non-human human studies gain insight into biopsychosocial through which reduces impairment. Methods Independent searches will be conducted electronic databases identify eligible studies. Two reviewers independently conduct study selection, data extraction, risk bias assessment. We extract outcome variables that act as modifiers or mediators exercise. For studies, include equivalents clusters. primary severity. The secondary outcomes avoidance severity, reexperiencing hyperarousal negative cognitions mood impairment, loss diagnosis, dropout rates. To explain affects interest, we effects relate impact on potential mediating later outcomes. Comparison within-study direct indirect obtained mediation analysis, when reported, provide importance examined mediator. If appropriate, results using meta-analyses. examine total understand better symptoms function (when possible). about association between PTSD-related considered a consensus meeting sufficient is available. Protocol registration PROSPERO-ID: 453615

Язык: Английский

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The influence of aerobic exercise on model-based decision making in women with posttraumatic stress disorder

Journal of Mood and Anxiety Disorders, Год журнала: 2023, Номер 2, С. 100015 - 100015

Опубликована: Июль 27, 2023

Individuals with PTSD often exhibit deficits in executive functioning. An unexplored aspect of neurocognitive functions associated is the type learning system engaged during decision-making. A model-free (MF) habitual nature and involves trial-and-error that updated based on most recent experience (e.g., repeat action if rewarded). model-based (MB) goal-directed development an abstract representation environment to facilitate decisions choose sequence actions according current contextual state predicted outcomes). The existing literature suggests hypothesis greater reliance MF vs MB strategies when navigating their environment. While systems may be more cognitively efficient, they do not afford flexibility making prospective predictions about likely outcomes different decision-tree branches. Emerging research acute bout aerobic exercise improves certain aspects neurocognition, thereby could promote utilization over decision making, although prior has yet tested this hypothesis. Accordingly, study administered a lab-based two-stage Markov decision-making task capable discriminating order determine moderate-intensity (either shortly after or 30-minutes ended) promotes engagement behavioral compared light-intensity adult women without (N=61). Results revealed control generally displayed higher levels behavior was further increased following immediate exercise, particularly exercise. By contrast, group lower behavior, exhibited completing regardless whether there short long delay between task. Additionally, demonstrated less impairment controls These results suggest boosts PTSD, play important role enhancing cognitive for PTSD.

Язык: Английский

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