The Relationship between Body Mass Index and Level of Response to Alcohol Across the Spectrum of Alcohol Use: Total Body Water and Beyond.

Background: A low level of response (LR) to alcohol is a known risk factor for alcohol use disorder (AUD). Although higher total body water (TBW) is associated with lower blood alcohol concentrations and reduced responses following alcohol consumption, the relationship between morphometric measures such as body mass index (BMI) and LR is less clear. This study aimed to examine the relationship between BMI and LR to alcohol, and the contribution of TBW to this relationship.

Global Epidemiology of Alcohol-Related Liver Disease, Liver Cancer, and Alcohol Use Disorder, 2000-2021.

Background/aims: Alcohol represents a leading burden of disease worldwide, including alcohol use disorder (AUD) and alcohol-related liver disease (ALD). We aim to assess the global burden of AUD, ALD, and alcohol-attributable primary liver cancer between 2000-2021.

Methods: We registered the global and regional trends of AUD, ALD, and alcohol-related liver cancer using data from the Global Burden of Disease 2021 Study, the largest and most up-to-date global epidemiology database.

Explanatory models of common mental disorders among South Asians in high-income countries: A systematic review.

Mental health service use by individuals of South Asian origin living outside of South Asia is influenced by cultural factors such as endorsing psycho-social-spiritual over biological explanations, somatisation, and stigma. The aim of this review is to synthesise the evidence about (a) explanatory models of common mental disorders (CMDs) among people of South Asian origin residing in high-income countries, and (b) their help-seeking for CMDs, including formal and informal care. The systematic review protocol was registered a priori on Prospero (registration number CRD42021287583).

Hospital and physician-based mental healthcare during 12 months of opioid agonist treatment for opioid use disorder: Exploring costs and factors associated with acute care.

Background: Individuals with opioid use disorder (OUD) have a high prevalence of co-occurring mental health disorders; however, there exists little information on mental health service use for this population. We aimed to determine the prevalence of non-substance use-related mental health emergency department (ED) visits, hospitalizations, and outpatient physician visits for individuals receiving treatment for OUD over one year. We also explored individual-level characteristics associated with mental health care service use and estimated the costs of this care.

Sex and Age Differences in Glucocorticoid Signaling After an Aversive Experience in Mice.

Background: glucocorticoids may play an important role in the formation of fear memory, which is relevant to the neurobiology of post-traumatic stress disorder (PTSD). In our previous study, we showed the glucocorticoid receptor (GR) forms a protein complex with FKBP51, which prevents translocation of GR into the nucleus to affect gene expression; this complex is elevated in PTSD patients and by fear-conditioned learning in mice, and disrupting this complex blocks the storage and retrieval of fear-conditioned memories. The timing of release of glucocorticoid relative to the formation of a traumatic memory could be important in this process, and remains poorly understood.

High Intensity Physician-Based Service Use for Mental Health Concerns in a General-Population Sample of Children and Youth: Utilisation des services de haute intensité dispensés par des médecins pour les problèmes de santé mentale dans un échantillon d'enfants et de jeunes de la population générale.

Objective: To examine factors associated with high intensity physician-based mental health care services in a population-based sample of children and youth in Ontario, Canada.

Methods: Data from the 2014 Ontario Child Health Study (OCHS) were linked at the person-level to longitudinal health administrative databases containing physician contacts in outpatient settings, emergency departments and hospitals. Our analytical sample (15.

Multifaceted Roles of MeCP2 in Cellular Regulation and Phase Separation: Implications for Neurodevelopmental Disorders, Depression, and Oxidative Stress.

Methyl CpG binding protein 2 (MeCP2) is a chromatin-associated protein that remains enigmatic despite more than 30 years of research, primarily due to the ever-growing list of its molecular functions, and, consequently, its related pathologies. Loss of function MECP2 mutations cause the neurodevelopmental disorder Rett syndrome (RTT); in addition, dysregulation of MeCP2 expression and/or function are involved in numerous other pathologies, but the mechanisms of MeCP2 regulation are unclear. Advancing technologies and burgeoning mechanistic theories assist our understanding of the complexity of MeCP2 but may inadvertently cloud it if not rigorously tested.

Identifying causal neural oscillations underlying working memory.

Electroencephalography is instrumental in understanding neurophysiological mechanisms underlying working memory. While numerous studies have associated electroencephalography features to working memory, understanding causal relationships leads to better characterization of the neurophysiological mechanisms that are directly linked to working memory. Personalized causal modeling is a tool to discover these direct links between brain features and working memory performance.

Addition of long-acting injectable antipsychotics during manic episodes in bipolar disorder: A retrospective analysis of rehospitalizations.

Introduction: Bipolar disorder (BD) often necessitates hospitalization, especially during manic episodes. Long-acting injectable antipsychotics (LAIs) are theorized to enhance treatment adherence and decrease rehospitalization rates compared to oral medications. This study aimed to evaluate the real-world effectiveness of LAIs in reducing rehospitalizations among BD patients admitted for bipolar mania.

Mapping global evidence of caregiver experiences in bipolar disorder in low and middle-income countries: A scoping review.

Background: Bipolar disorder (BD) imposes significant social, psychological, and economic burdens on individuals and their caregivers. While developing treatments for BD patients is crucial, supportive interventions for caregivers in low- and middle-income countries (LMICs) are equally important, given the limited resources and healthcare infrastructure. Understanding caregiver experiences in these settings is essential for creating effective interventions.

Cigarette smoking is associated with reduced neuroinflammation and better cognitive control in people living with HIV.

People living with HIV (HIV+) are roughly twice as likely to smoke cigarettes (Smok+) as the general population. With the advent of effective antiretroviral therapies, it is increasingly important to understand the effects of chronic HIV infection and cigarette smoking on brain function and cognition since HIV+ individuals have heightened neuroinflammation and cognitive deficits even with such therapies. Based on prior studies demonstrating that smoking reduces a marker for neuroinflammation in HIV- individuals, we hypothesized that HIV+/Smok+ individuals would have less neuroinflammation and better cognitive control than HIV+/Smok- individuals.

Beliefs and attitudes about men's alcohol-related sexual harassment and aggression (BAMASHA): Development and initial validation of a new scale.

Background: Men's perpetration of sexual violence (SV) toward women in drinking venues is a pervasive yet understudied phenomenon with significant downstream consequences for women. Although men's negative attitudes and beliefs toward women play an important role in SV, current attitude measures are limited in that they do not focus on SV specific to drinking contexts, thereby precluding understandings of SV in this context. As such, we developed and evaluated a measure of beliefs and attitudes about men's alcohol-related sexual harassment and aggression (BAMASHA) toward women in drinking venues to better understand this ubiquitous problem.

Therapeutic dose prediction of α5-GABA receptor modulation from simulated EEG of depression severity.

Treatment for major depressive disorder (depression) often has partial efficacy and a large portion of patients are treatment resistant. Recent studies implicate reduced somatostatin (SST) interneuron inhibition in depression, and new pharmacology boosting this inhibition via positive allosteric modulators of α5-GABAA receptors (α5-PAM) offers a promising effective treatment. However, testing the effect of α5-PAM on human brain activity is limited, meriting the use of detailed simulations.

Preferences, Perceptions, and Environmental Considerations of Natural and Synthetic Psychedelic Substances: Findings from the Global Psychedelic Survey.

Although several studies have well described the characteristics of people who use psychedelics alongside their motivations and beliefs, little research has examined the preferences surrounding the source of psychedelic substances. In an anonymous online survey, we collected data from 6,379 consumers of 11 different psychedelic substances from 85 different countries, exploring their preferences and perceptions on natural and synthetic psychedelics. There was a strong preference of natural sources over synthetic alternatives for psilocybin (75%), DMT (56%), and mescaline (56%).

Trends, characteristics, and circumstances surrounding stimulant toxicity deaths in Ontario, Canada from 2018 to 2021.

Introduction: As the drug toxicity crisis continues to evolve globally, harms related to non-opioid substances, including stimulants, have risen in parallel. Our study aims were to describe trends in accidental stimulant toxicity deaths and to characterize demographic characteristics of decedents and the circumstances surrounding death.

Methods: We conducted a population-based repeated cross-sectional study, of all accidental stimulant toxicity deaths between January 1, 2018, and December 31, 2021, in Ontario, Canada.

Associations between mental health conditions in pregnancy and maternal socioeconomic status: a population-based retrospective cohort study in Ontario, Canada.

Background: The World Health Organization has recognized maternal mental illness as an emerging issue. Previous studies have indicated that maternal mental illness is associated with socioeconomic status (SES). However, there is a lack of research concerning the mental health of pregnant people with low SES in Ontario, Canada.

The role of the psychedelic experience in psilocybin treatment for treatment-resistant depression.

Objective: To determine the relationships between psilocybin dose, psychedelic experiences, and therapeutic outcome in treatment-resistant depression.

Methods: For treatment-resistant depression, 233 participants received a single dose of 25, 10, or 1 mg of COMP360 psilocybin (a proprietary, pharmaceutical-grade synthesized psilocybin formulation, developed by the sponsor, Compass Pathfinder Ltd.) with psychological support.

Chromosome X-wide common variant association study in autism spectrum disorder.

Autism spectrum disorder (ASD) displays a notable male bias in prevalence. Research into rare (<0.1) genetic variants on the X chromosome has implicated over 20 genes in ASD pathogenesis, such as MECP2, DDX3X, and DMD.

Medical chart-reported alcohol consumption, substance use, and mental health issues in association with HIV pre-exposure prophylaxis (PrEP) nonadherence among gay, bisexual, and other men-who-have-sex-with-men.

Background: Although some evidence suggests that alcohol, substance use, and mental health issues diminish adherence to HIV Pre-Exposure Prophylaxis (PrEP) among gay, bisexual, and other men-who-have-sex-with-men (gbMSM), findings are somewhat inconsistent and have primarily derived from studies involving non-random samples. Medical chart extraction can provide unique insight by in part surmounting sampling-related limitations, as data for entire PrEP clinic populations can be examined. Our investigation entailed comprehensive chart extraction to assess the extent to which chart-reported alcohol, substance use, and mental health issues were associated with chart-reported PrEP nonadherence.

Procognitive and neurotrophic benefits of α5-GABA-A receptor positive allosteric modulation in a β-amyloid deposition mouse model of Alzheimer's disease pathology.

Reduced somatostatin (SST) and SST-expressing GABAergic neurons are well-replicated findings in Alzheimer's disease (AD) and are associated with cognitive deficits. SST cells inhibit pyramidal cell dendrites through α5-GABA-A receptors (α5-GABAA-R). α5-GABAAR positive allosteric modulation (α5-PAM) has procognitive and neurotrophic effects in stress and aging models.

PET in neurotherapeutic discovery and development.

Positron emission tomography (PET) is a highly sensitive, quantitative imaging technique that can track sub-nanomolar quantities of positron-emitting radionuclides throughout the body. By incorporating such radionuclides into molecules of interest, we can directly assess their pharmacokinetic and pharmacodynamic (PK/PD) characteristics in vivo without changing their physicochemical characteristics or eliciting a pharmacological response. As such, PET imaging has long been used as a tool to aid drug discovery programs from preclinical biomarker validation all the way through to clinical trials.