Transcriptomic pathology of neocortical microcircuit cell types across psychiatric disorders.

Psychiatric disorders such as major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are characterized by altered cognition and mood, brain functions that depend on information processing by cortical microcircuits. We hypothesized that psychiatric disorders would display cell type-specific transcriptional alterations in neuronal subpopulations that make up cortical microcircuits: excitatory pyramidal (PYR) neurons and vasoactive intestinal peptide- (VIP), somatostatin- (SST), and parvalbumin- (PVALB) expressing inhibitory interneurons. Using laser capture microdissection followed by RNA sequencing (LCM-seq), we performed cell type-specific molecular profiling of subgenual anterior cingulate cortex, a region implicated in mood and cognitive control.

Beneficial adjunctive effects of the 5HT3 receptor antagonist ondansetron on symptoms, function and cognition in early phase schizophrenia in a double-blind, 2 × 2 factorial design, randomised controlled comparison with simvastatin.

Background: Variable benefits have been reported from the adjunctive use of simvastatin and the 5HT3 receptor antagonist, ondansetron, in patients with schizophrenia. We investigated their independent efficacy and possible synergy to improve negative symptoms of schizophrenia within a single trial.

Methods: A 6-month, randomised, double-blind, placebo-controlled trial with a 4-arm, 2 × 2 factorial design, in three centres in Pakistan.

Surveillance of alcohol use through population surveys in the Americas from 2010 to 2019.

Aims: The aims of this study were to identify alcohol-related population surveys administered in the Americas, determine which alcohol-related measures are examined and identify coverage gaps regarding alcohol-related measures.

Methods: As part of the Global Information System on Alcohol and Health study, a systematic search was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria to identify regionally or nationally representative survey reports of the general population from 1 January 2010 to 6 August 2019. Alcohol-related measures extracted from surveys were categorized into 10 domains: alcohol consumption status; alcohol consumption; unrecorded alcohol consumption; drinking patterns; symptoms of dependence and/or harmful use; drinking during pregnancy; treatment coverage; second-hand harms; economic; and other.

Trend of alcohol use disorder as a percentage of all-cause mortality in North America.

Objective: To evaluate the trend of alcohol use disorder (AUD) mortality as a percentage of all-cause mortality in Canada and the United States (US) between 2000 and 2019, by age group.

Results: Joinpoint regression showed that AUD mortality as a percentage of all-cause mortality significantly increased between 2000 and 2019 in both countries, and across all age groups (i.e.

Alcohol Rehabilitation Within 3 Months After Alcohol Hepatitis and Survival - A National Analysis.

Background & Aims: There is limited understanding of the benefits of alcohol rehabilitation after alcohol hepatitis (AH).

Methods: We conducted a 2012 to 2021 national longitudinal study involving adult inpatients diagnosed with AH in France. We assessed the primary outcome of liver transplantation or death within 1 year after AH, including in its complicated form (CAH) defined as ≥2 hepatic or extrahepatic complications within 4 weeks after AH.

Social and Emotional Functioning of Pediatric Brain Tumor Survivors and Typically Developing Youth Following the Onset of the Pandemic.

: Social competence is a domain in which pediatric brain tumour survivors (PBTS) are at risk of challenges. To follow-up on our earlier work, in this study we assessed specific social interaction behaviors and emotional functioning in PBTS relative to typically developing youth (TD). The study coincided with the onset of the global pandemic.

Neurophysiological markers of motor compensatory mechanisms in early Parkinson's disease.

Compensatory mechanisms in Parkinson's disease are defined as the changes that the brain uses to adapt to neurodegeneration and progressive dopamine reduction. Motor compensation in early Parkinson's disease could, in part, be responsible for a unilateral onset of clinical motor signs despite the presence of bilateral nigrostriatal degeneration. Although several mechanisms have been proposed for compensatory adaptations in Parkinson's disease, the underlying pathophysiology is unclear.

Mapping Epigenetic Gene Variant Dynamics: Comparative Analysis of Frequency, Functional Impact and Trait Associations in African and European Populations.

Epigenetic modifications influence gene expression levels, impact organismal traits, and play a role in the development of diseases. Therefore, variants in genes involved in epigenetic processes are likely to be important in disease susceptibility, and the frequency of variants may vary between populations with African and European ancestries. Here, we analyse an integrated dataset to define the frequencies, associated traits, and functional impact of epigenetic gene variants among individuals of African and European ancestry represented in the UK Biobank.

Emerging targets for positron emission tomography imaging in proteinopathies.

Positron emission tomography (PET) imaging of neurodegenerative disease has historically focused on a small number of established targets. The development of selective PET radiotracers for novel biological targets enables new ways to interrogate the neuropathology of proteinopathies and will advance our understanding of neurodegeneration. This perspective aims to highlight recent PET radiotracers developed for five emerging targets in proteinopathies (i.

Changes in Alcohol-Specific Mortality During the COVID-19 Pandemic in 14 European Countries.

Aim: Exploring trends in 1) alcohol-specific mortality and 2) alcohol sales in European countries in the years before and during the COVID-19 pandemic.

Method: Complete data on alcohol-specific mortality and alcohol sales were obtained for 14 European countries (13 EU countries and UK) for the years 2010 to 2020, with six countries having mortality data available up to 2021. Age-standardised mortality rates were calculated and descriptive statistics used.

The impact of COVID-19-related national lockdowns on alcohol-related traffic collisions, injuries, and fatalities in Lithuania.

Background: The national lockdowns that occurred all over the world in response to the Coronavirus Disease 2019 (COVID-19) pandemic have been found to have impacted alcohol use. The aim was to evaluate the impact of COVID-19-related national lockdowns on alcohol-related traffic collisions, injuries, and fatalities in Lithuania.

Methods: Using monthly data from the Lithuanian Road Police Service for January 2004 to December 2022, we performed interrupted time-series analyses using a generalized additive model to evaluate the impact of COVID-19-related national lockdowns on alcohol-related traffic collisions, injuries, and fatalities.

"A whole ball of all-togetherness": The interwoven experiences of intimate partner violence, brain injury, and mental health.

Background: Intimate partner violence (IPV) is a global public health crisis, with physical violence leaving IPV survivors at high risk of brain injury (BI). Both BI and IPV have significant physical, psychological, cognitive, and social impacts, including a high risk of mental health concerns, yet there is limited exploration of IPV survivors' experiences with BI and mental health. This study aimed to explore the BI- and mental health-related needs and experiences of IPV survivors from the perspectives of survivors and service providers with the objective of developing knowledge translation materials to raise awareness and support survivors and service providers in addressing these concerns.

Factors associated with presentation to the emergency department during an intensive post-discharge intervention in patients with substance use disorders.

Background: Early identification of patients with substance use disorders (SUDs) with a higher risk of emergency department (ED) presentations after being discharged can be useful. We performed a chart review of patients from the Intensive Recovery Discharge Team (IRDT) program, which provides two weeks of outpatient support for patients with SUDs discharged from a mental health hospital.

Method: Demographic, service utilization, and clinical data from 716 patients enrolled in IRDT from February 2021-February 2023 were extracted from electronic health records.

Estrogens dynamically regulate neurogenesis in the dentate gyrus of adult female rats.

Estrone and estradiol differentially modulate neuroplasticity and cognition. How they influence the maturation of new neurons in the adult hippocampus, however, is not known. The present study assessed the effects of estrone and estradiol on the maturation timeline of neurogenesis in the dentate gyrus (DG) of ovariectomized (a model of surgical menopause) young adult Sprague-Dawley rats using daily subcutaneous injections of 17β-estradiol, estrone or vehicle.

"Like the Wild West": Health care provider perspectives on impacts of recreational cannabis legalization on patients and providers at a tertiary psychiatric hospital in Ontario, Canada.

Introduction: Legalization has increased cannabis availability in Canada. Research shows complex relationships between cannabis use and mental health, and a need for health care providers to engage with patients about cannabis use. Providers have noted gaps in knowledge and research on the medical effects of cannabis as barriers to service delivery.

Feasibility and Tolerability of Daily Theta Burst Stimulation in Autistic Youth with Intellectual Disabilities and Minimally Speaking Status: A Pilot Double-Blind Randomized Sham-Controlled Trial.

Scarce clinical trials involving autistic people with intellectual disability (ID) and minimally speaking (MS) status have been a substantial unmet research need in the field. Although earlier studies have demonstrated the feasibility and beneficial potentials of repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) in intellectually able autistic people, the feasibility and tolerability of applying rTMS in autistic people with ID/MS has never been studied. We conducted the world-first 4-week randomized, double-blind, sham-controlled pilot trial to investigate the feasibility, tolerability, and safety of intermittent theta burst stimulation (iTBS, a variant of excitatory rTMS) over the left DLPFC in autistic youth with ID/MS.

Add-on Sodium Benzoate and -Acetylcysteine in Patients With Early Schizophrenia Spectrum Disorder: A Multicenter, Double-Blind, Randomized Placebo-Controlled Feasibility Trial.

Background And Hypothesis: Oxidative stress pathways may play a role in schizophrenia through direct neuropathic actions, microglial activation, inflammation, and by interfering with NMDA neurotransmission. -acetylcysteine (NAC) has been shown to improve negative symptoms of schizophrenia, however, results from trials of other compounds targeting NMDA neurotransmission have been mixed. This may reflect poor target engagement but also that risk mechanisms act in parallel.

Testing the PEST hypothesis using relevant Rett mutations in MeCP2 E1 and E2 isoforms.

Mutations in methyl-CpG binding protein 2 (MeCP2), such as the T158M, P152R, R294X, and R306C mutations, are responsible for most Rett syndrome (RTT) cases. These mutations often result in altered protein expression that appears to correlate with changes in the nuclear size; however, the molecular details of these observations are poorly understood. Using a C2C12 cellular system expressing human MeCP2-E1 isoform as well as mouse models expressing these mutations, we show that T158M and P152R result in a decrease in MeCP2 protein, whereas R306C has a milder variation, and R294X resulted in an overall 2.

Interrupted Time Series Design and Analyses in Health Policy Assessment.

Interrupted time series design is a quasi-experimental study design commonly used to evaluate the impact of a particular intervention (e.g., a health policy implementation) on a specific outcome.