A randomized, double-blind, placebo-controlled study of a GHSR blocker in people with alcohol use disorder.

BACKGROUNDStudies have demonstrated the role of ghrelin in alcohol-related behaviors and consumption. Blockade of the growth hormone secretagogue receptor (GHSR), which is the ghrelin receptor, has been shown to decrease alcohol drinking and reward-related behaviors across several animal models. We previously conducted a human study testing a GHSR inverse agonist/competitive antagonist, PF-5190457, in individuals who are heavy drinkers and showed its safety when coadministered with alcohol.

Adjusting for principal components can induce collider bias in genome-wide association studies.

Principal component analysis (PCA) is widely used to control for population structure in genome-wide association studies (GWAS). Top principal components (PCs) typically reflect population structure, but challenges arise in deciding how many PCs are needed and ensuring that PCs do not capture other artifacts such as regions with atypical linkage disequilibrium (LD). In response to the latter, many groups suggest performing LD pruning or excluding known high LD regions prior to PCA.

Considerations in the search for epistasis.

Epistasis refers to changes in the effect on phenotype of a unit of genetic information, such as a single nucleotide polymorphism or a gene, dependent on the context of other genetic units. Such interactions are both biologically plausible and good candidates to explain observations which are not fully explained by an additive heritability model. However, the search for epistasis has so far largely failed to recover this missing heritability.

Effects of acceptance and commitment therapy on trauma-related symptoms: A systematic review and meta-analysis.

Objective: Acceptance and commitment therapy (ACT) is a third-wave cognitive behavioral therapy that has shown promise as an effective treatment for reducing trauma-related symptoms. Although there have been systematic reviews on the clinical effectiveness of ACT for posttraumatic stress disorder, there are no known meta-analyses published on the impact of ACT in adult populations with trauma-related symptoms. Hence, the purpose of this meta-analysis and systematic review was to update the literature and assess the effectiveness of ACT interventions for decreasing trauma-related distress in adults who have developed trauma symptoms following exposure to one or more traumatic events.

Evaluation of Smartphone Technology on Spatiotemporal Gait in Older and Diseased Adult Populations.

Advancements in smartphone technology provide availability to evaluate movement in a more practical and feasible manner, improving clinicians' ability to diagnose and treat adults at risk for mobility loss. The purpose of this study was to evaluate the validity and reliability of a smartphone application to measure spatiotemporal outcomes during level (primary) and uphill/downhill (secondary) walking with and without an assistive device for older adults (OAs), Parkinson's Disease (PD) and cerebrovascular accident (CVA) populations. A total of 50 adults (OA = 20; PD = 15; CVA = 15) underwent gait analysis at self-selected gait speeds under 0-degree, 5-degree uphill and 5-degree downhill environments.

Effect of N-acetylcysteine on neural alcohol cue reactivity and craving in adolescents who drink heavily: A preliminary randomized clinical trial.

Background: Alcohol craving is related to problematic alcohol use; therefore, pharmacotherapies that modulate alcohol craving are of interest. N-acetylcysteine, an over-the-counter antioxidant, is a candidate pharmacotherapy for adolescent alcohol use with the potential to impact craving. Cue-reactivity paradigms using functional magnetic resonance imaging (fMRI) can identify neural regions implicated in craving and serve as a screening tool for novel pharmacotherapy options.

Simultaneous estimation of genotype error and uncalled deletion rates in whole genome sequence data.

Genotype data include errors that may influence conclusions reached by downstream statistical analyses. Previous studies have estimated genotype error rates from discrepancies in human pedigree data, such as Mendelian inconsistent genotypes or apparent phase violations. However, uncalled deletions, which generally have not been accounted for in these studies, can lead to biased error rate estimates.

Predictors of Substance Use Initiation by Early Adolescence.

Objective: Substance use initiation during early adolescence is associated with later development of substance use and mental health disorders. This study used various domains to predict substance use initiation, defined as trying any nonprescribed substance (e.g.

Adjusting for principal components can induce spurious associations in genome-wide association studies in admixed populations.

Principal component analysis (PCA) is widely used to control for population structure in genome-wide association studies (GWAS). Top principal components (PCs) typically reflect population structure, but challenges arise in deciding how many PCs are needed and ensuring that PCs do not capture other artifacts such as regions with atypical linkage disequilibrium (LD). In response to the latter, many groups suggest performing LD pruning or excluding known high LD regions prior to PCA.

Biobank-scale inference of multi-individual identity by descent and gene conversion.

We present a method for efficiently identifying clusters of identical-by-descent haplotypes in biobank-scale sequence data. Our multi-individual approach enables much more computationally efficient inference of identity by descent (IBD) than approaches that infer pairwise IBD segments and provides locus-specific IBD clusters rather than IBD segments. Our method's computation time, memory requirements, and output size scale linearly with the number of individuals in the dataset.

Multi-modal neuroimaging reveals differences in alcohol-cue reactivity but not neurometabolite concentrations in adolescents who drink alcohol.

Background: The objective of this multi-modal neuroimaging study was to identify neuroscience-informed treatment targets for adolescent alcohol use disorder (AUD) by examining potential neural alterations associated with adolescent alcohol use.

Methods: Adolescents (ages 17-19) who heavily used (n=49) or did not use alcohol (n=22) were recruited for a multi-modal neuroimaging protocol, including proton magnetic resonance spectroscopy within the dorsal anterior cingulate cortex (dACC) and an fMRI alcohol cue-reactivity task. The alcohol cue-reactivity task was analyzed across 11 a priori regions-of-interest (ROI), including the dACC, and in an exploratory whole-brain approach.

Pairwise comparisons of three medication adherence outcomes in adolescents who use alcohol.

Background: Accurate assessment of medication adherence is important for understanding pharmacotherapy outcomes across all phases of adolescent substance use disorder (SUD) clinical trials. The objective of this study was to describe and assess the pairwise concordance between three commonly used non-biological medication adherence assessment methods in adolescents who use alcohol to inform the selection of medication adherence measures for use in future youth SUD trials.

Methods: Participants (N = 32, 17-19-years-old) took N-acetylcysteine and placebo, in a randomized cross-over design, for 10 days each.

Biobank-scale inference of multi-individual identity by descent and gene conversion.

We present a method for efficiently identifying clusters of identical-by-descent haplotypes in biobank-scale sequence data. Our multi-individual approach enables much more efficient collection and storage of identity by descent (IBD) information than approaches that detect and store pairwise IBD segments. Our method's computation time, memory requirements, and output size scale linearly with the number of individuals in the dataset.

The adolescent and young adult microbiome and its association with substance use: a scoping review.

Aims: The microbiome is a critical factor in health throughout human development. The aims of this scoping review are to (i) elucidate the differences between the youth (post-natal day 21-65 for rodents, 2-7 years for non-human primates, and 10-25 years for humans) microbiome with other life stages and (ii) identify youth-specific microbial changes associated with substance use.

Methods: Peer-reviewed studies published up to May 2023 were identified in PubMed and SCOPUS and included gut and oral microbiome studies from rodents, non-human primates, and humans (N = 1733).

Identity-by-descent-based estimation of the X chromosome effective population size with application to sex-specific demographic history.

The effective size of a population (Ne) in the recent past can be estimated through analysis of identity-by-descent (IBD) segments. Several methods have been developed for estimating Ne from autosomal IBD segments, but no such effort has been made with X chromosome IBD segments. In this work, we propose a method to estimate the X chromosome effective population size from X chromosome IBD segments.

N-acetylcysteine does not alter neurometabolite levels in non-treatment seeking adolescents who use alcohol heavily: A preliminary randomized clinical trial.

Current treatments for adolescent alcohol use disorder (AUD) are mainly psychosocial and limited in their efficacy. As such, pharmacotherapies are being investigated as potential adjunctive treatments to bolster treatment outcomes. N-acetylcysteine is a promising candidate pharmacotherapy for adolescent AUD because of its tolerability and demonstrated ability to modulate glutamatergic, GABAergic, and glutathione systems.

Fast, accurate local ancestry inference with FLARE.

Local ancestry is the source ancestry at each point in the genome of an admixed individual. Inferred local ancestry is used for admixture mapping and population genetic analyses. We present FLARE (fast local ancestry estimation), a method for local ancestry inference.

Statistical phasing of 150,119 sequenced genomes in the UK Biobank.

The first release of UK Biobank whole-genome sequence data contains 150,119 genomes. We present an open-source pipeline for filtering, phasing, and indexing these genomes on the cloud-based UK Biobank Research Analysis Platform. This pipeline makes it possible to apply haplotype-based methods to UK Biobank whole-genome sequence data.

Patient-reported outcomes measurement information system physical function and knee injury and osteoarthritis outcome score relationship on performance measures in people undergoing total knee arthroplasty.

Purpose: Primary purpose was to identify relationships between performance-based measures onto both computerized adaptive testing [Physical Function-Computer Adaptive Testing (PF-CAT)] and joint-specific legacy [Knee injury and Osteoarthritis Outcome Score-Activities of Daily Living (KOOS-ADL)] instruments pre- and 12-month post-TKA.

Methods: The PF-CAT and KOOS-ADL were identified as outcomes and performance on the 40-m fast-paced walking test, stair climb test and chair stand test were identified as predictors. Linear regression was used for all comparisons after adjusting for confounders.

The lateral habenula is not required for ethanol dependence-induced escalation of drinking.

The lateral habenula (LHb) is an epithalamic nuclei that has been shown to signal the aversive properties of ethanol. The present study tested the hypothesis that activity of the LHb is required for the acquisition and/or expression of dependence-induced escalation of ethanol drinking and somatic withdrawal symptoms. Male Sprague-Dawley rats completed 4 weeks of baseline drinking under a standard intermittent access two-bottle choice (2BC) paradigm before undergoing 2 weeks of daily chronic intermittent ethanol (CIE) via vapor inhalation.