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.

Correlates of Using Medically-Authorized Cannabis in a Large Cohort of People Living with HIV Who Use Cannabis.

Many people living with HIV (PLWH) use cannabis to manage symptoms, but a large proportion do so without medical cannabis authorization and use cannabis obtained outside the medical stream. In jurisdictions where non-medical cannabis use is legal, PLWH who hold medical cannabis authorization may represent a unique subgroup; yet, research on the correlates of using medical cannabis (authorized by a healthcare provider) in the context of non-medical cannabis legalization is lacking. Thus, this study examined the cannabis- and health-related correlates of medical cannabis use among PLWH in Ontario, Canada, where non-medical cannabis is legal.

The Implementation of Integrated Youth Services in Canada: Planning and Costing of a Pan-Canadian Model: La mise en œuvre des services intégrés pour les jeunes au Canada : planification et établissement des coûts d'un modèle pancanadien.

Objective: The implementation of Integrated Youth Services (IYS) can help ensure that youth are adequately supported. The objective of this analysis was to provide a model for the planning and costing of IYS throughout Canada over a 15-year period.

Methods: To estimate resource allocation for IYS, we determined the number of hubs and hub staffing requirements by service level and jurisdiction, backbone support and infrastructure requirements by jurisdiction.

Real-World Treatment of Schizophrenia in Adults With a 22q11.2 Microdeletion: Traitement dans le monde réel de la schizophrénie chez des adultes atteints du syndrome de microdélétion 22q11.2.

Objective: One in every 4 individuals born with a 22q11.2 microdeletion will develop schizophrenia. Thirty years of clinical genetic testing capability have enabled detection of this major molecular susceptibility for psychotic illness.

Burnout, motivation and job satisfaction among community health workers recruited for a depression training in Madhya Pradesh, India: a cross-sectional study.

Introduction: Burnout, low motivation, and poor job satisfaction among community health workers (CHWs) have negative impacts on health workers and on patients. This study aimed to characterize levels of burnout, motivation, and job satisfaction in CHWs in Madhya Pradesh, India and to determine the relation between these levels and participant characteristics. This study can inform efforts to promote wellbeing and address stress in this population.

Cognitive flexibility in autism: How task predictability and sex influence performances.

While cognitive flexibility challenges are frequently reported in autistic individuals, inconsistencies in the findings prompt further investigation into the factors influencing this flexibility. We suggest that unique aspects of the predictive brain in autistic individuals might contribute to these challenges, potentially varying by sex. Our study aimed to test these hypotheses by examining cognitive flexibility under different predictability conditions in a sample including a similar number of males and females.

Metabolic Dysfunction and Alcohol-related Liver Disease (MetALD): Position statement by an expert panel on alcohol-related liver disease.

This position statement explores the intricate relationship between alcohol intake and metabolic dysfunction in the context of the 2023 nomenclature for steatotic liver disease (SLD). Recent and lifetime alcohol use should be accurately assessed in all patients with SLD to facilitate classification of alcohol use in grams of alcohol per week. Alcohol biomarkers (i.

Adult Phenotype of -Associated Disorders.

Background And Objectives: Pathogenic variants are associated with neurodevelopmental disorders and developmental and epileptic encephalopathy. While pediatric phenotypes have been readily explored, adult phenotypes are not well understood. We aimed to investigate the phenotypic spectrum of adult patients with variants.

Willingness of population health survey participants to provide personal health information and biological samples.

Background: Biological sample collection and data linkage can expand the utility of population health surveys. The present study investigates factors associated with population health survey respondents' willingness to provide biological samples and personal health information.

Methods: Using data from the 2019 Centre for Addiction and Mental Health (CAMH) Monitor survey (n = 2,827), we examined participants' willingness to provide blood samples, saliva samples, probabilistic linkage, and direct linkage with personal health information.

Psychometric properties of the Taiwan version of Emotion Dysregulation Inventory in Autism Spectrum Disorder.

Background: While the Emotion Dysregulation Inventory (EDI) for autistic people has been validated in many Western countries, its psychometric properties have remained unclear in East Asia.

Methods: We translated the EDI into traditional Chinese and evaluated its psychometric properties among autistic children and youth in Taiwan. We enrolled 200 participants (182 male/18 female) aged 7-30 years from five clinical trials and conducted secondary analyses, assessing internal consistency reliability, confirmatory factor analysis, and convergent validity.

Assessing plasticity in the primary sensory cortex and its relation with atypical tactile reactivity in autism: A TMS-EEG protocol.

Background: Atypical sensory reactivity is a cardinal presentation in autism. Within the tactile domain, atypical tactile reactivity (TR) is common, it emerges early, persists into adulthood, and impedes social interaction and daily functioning. Hence, atypical TR is a key target for biological intervention to improve outcomes.

Neuronal viability/astrocyte activity ratio in the dorsolateral prefrontal cortex as a biomarker of Alzheimer's dementia: a proton magnetic resonance spectroscopy study.

N-acetyl-aspartate (NAA) and myo-inositol (mI) are neurometabolites reflecting neuronal viability and astrocyte activity, respectively. These are quantified using proton magnetic resonance spectroscopy (1H-MRS) and may be biomarkers for Alzheimer's disease dementia (AD). Our objectives were: 1) Compare dorsolateral prefrontal cortex (DLPFC) NAA and mI levels between AD and cognitively healthy control participants (HC) 2) assess if NAA/mI ratio can distinguish groups, and 3) explore the relationship between metabolites and cognition.