Utility of Candidate Genes From an Algorithm Designed to Predict Genetic Risk for Opioid Use Disorder.

Importance: Recently, the US Food and Drug Administration gave premarketing approval to an algorithm based on its purported ability to identify individuals at genetic risk for opioid use disorder (OUD). However, the clinical utility of the candidate genetic variants included in the algorithm has not been independently demonstrated.

Objective: To assess the utility of 15 genetic variants from an algorithm intended to predict OUD risk.

A core beliefs model of disordered eating: processes and pathways to eating disorder symptomatology.

Objective: At present there is no clear, cohesive, and comprehensive theoretical understanding of the role of core beliefs in the development of disordered eating. The present study aimed to develop and test a theoretical model outlining important processes and pathways from core beliefs to eating disorder (ED) behaviours. It also aimed to explore potential differences (or similarities) in contributions of four core belief dimensions to the development and maintenance of ED symptomatology.

Advancing Gene Discovery for Substance Use Disorders Using Additional Traits Related to Behavioral Disinhibition.

Importance: Substance use disorders (SUDs) frequently co-occur with each other and with other traits related to behavioral disinhibition, a spectrum of outcomes referred to as externalizing. Nevertheless, genome-wide association studies (GWAS) typically study individual SUDs separately. This single-disorder approach ignores genetic covariance between SUDs and other traits and may contribute to the relatively limited genetic discoveries to date.

Family income and polygenic scores are independently but not interactively associated with cognitive performance among youth genetically similar to European reference populations.

Cognitive abilities are heritable and influenced by socioeconomic status (SES). It is critical to understand the association between SES and cognition beyond genetic propensity to inform potential benefits of SES-based interventions and to determine if such associations vary across (i) cognitive domains, (ii) facets of SES, and/or (iii) genetic propensity for different aspects of cognition. We examined the contributions of neighborhood socioeconomic advantage, family income, and polygenic scores (PGS) for domains of cognition (i.

Leveraging normative personality data and machine learning to examine the brain structure correlates of obsessive-compulsive personality disorder traits.

Brain structure correlates of obsessive-compulsive personality disorder (OCPD) remain poorly understood as limited OCPD assessment has precluded well-powered studies. Here, we tested whether machine learning (ML; elastic net regression, gradient boosting machines, support vector regression with linear and radial kernels) could estimate OCPD scores from personality data and whether ML-predicted scores are associated with indices of brain structure (cortical thickness and surface area and subcortical volumes). Among older adults (ns = 898-1,606) who completed multiple OCPD assessments, ML elastic net regression with Revised NEO Personality Inventory personality items as features best predicted Five-Factor Obsessive-Compulsive Inventory-Short Form (FFOCI-SF) scores, root-mean-squared error (RMSE)/SD = 0.

Associations between polygenic scores for cognitive and non-cognitive factors of educational attainment and measures of behavior, psychopathology, and neuroimaging in the adolescent brain cognitive development study.

Background: Educational attainment (EduA) is correlated with life outcomes, and EduA itself is influenced by both cognitive and non-cognitive factors. A recent study performed a 'genome-wide association study (GWAS) by subtraction,' subtracting genetic effects for cognitive performance from an educational attainment GWAS to create orthogonal 'cognitive' and 'non-cognitive' factors. These cognitive and non-cognitive factors showed associations with behavioral health outcomes in adults; however, whether these correlations are present during childhood is unclear.

A Phenome-Wide Association Study (PheWAS) of Genetic Risk for C-Reactive Protein in Children of European Ancestry: Results From the ABCD Study.

Background: C-reactive protein (CRP) is a moderately heritable marker of systemic inflammation that is associated with adverse physical and mental health outcomes. Identifying factors associated with genetic liability to elevated CRP in childhood may inform our understanding of variability in CRP that could be targeted to prevent and/or delay the onset of related health outcomes.

Methods: We conducted a phenome-wide association study (PheWAS) of genetic risk for elevated CRP (i.

Multivariate, Multi-omic Analysis in 799,429 Individuals Identifies 134 Loci Associated with Somatoform Traits.

Somatoform traits, which manifest as persistent physical symptoms without a clear medical cause, are prevalent and pose challenges to clinical practice. Understanding the genetic basis of these disorders could improve diagnostic and therapeutic approaches. With publicly available summary statistics, we conducted a multivariate genome-wide association study (GWAS) and multi-omic analysis of four somatoform traits-fatigue, irritable bowel syndrome, pain intensity, and health satisfaction-in 799,429 individuals genetically similar to Europeans.

Applications and efficacy of radically open dialectical behavior therapy (RO DBT): A systematic review of the literature.

Radically open dialectical behaviour therapy (RO DBT) is a transdiagnostic treatment, originally developed as a variant of dialectical behaviour therapy (DBT), that emerged as a novel treatment approach for those presenting with excessive or maladaptive overcontrol. Despite RO DBT's growing popularity among clinicians as a treatment for chronic depression, personality disorders and eating disorders, to date, no systematic review has been conducted to summarise the evidence on this therapy. Therefore, the aim of this study was to systematically review the literature to provide a current and comprehensive summary of the available evidence on the clinical applications and efficacy of RO DBT.

Generalized genetic liability to substance use disorders.

Lifetime and temporal co-occurrence of substance use disorders (SUDs) is common and compared with individual SUDs is characterized by greater severity, additional psychiatric comorbidities, and worse outcomes. Here, we review evidence for the role of generalized genetic liability to various SUDs. Coaggregation of SUDs has familial contributions, with twin studies suggesting a strong contribution of additive genetic influences undergirding use disorders for a variety of substances (including alcohol, nicotine, cannabis, and others).

Candidate Genes from an FDA-Approved Algorithm Fail to Predict Opioid Use Disorder Risk in Over 450,000 Veterans.

Importance: Recently, the Food and Drug Administration gave pre-marketing approval to algorithm based on its purported ability to identify genetic risk for opioid use disorder. However, the clinical utility of the candidate genes comprising the algorithm has not been independently demonstrated.

Objective: To assess the utility of 15 variants in candidate genes from an algorithm intended to predict opioid use disorder risk.

Alcohol milestones and internalizing, externalizing, and executive function: longitudinal and polygenic score associations.

Background: Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear.

Two common and distinct forms of variation in human functional brain networks.

The cortex has a characteristic layout with specialized functional areas forming distributed large-scale networks. However, substantial work shows striking variation in this organization across people, which relates to differences in behavior. While most previous work treats individual differences as linked to boundary shifts between the borders of regions, here we show that cortical 'variants' also occur at a distance from their typical position, forming ectopic intrusions.

Multi-ancestry meta-analysis of tobacco use disorder identifies 461 potential risk genes and reveals associations with multiple health outcomes.

Tobacco use disorder (TUD) is the most prevalent substance use disorder in the world. Genetic factors influence smoking behaviours and although strides have been made using genome-wide association studies to identify risk variants, most variants identified have been for nicotine consumption, rather than TUD. Here we leveraged four US biobanks to perform a multi-ancestral meta-analysis of TUD (derived via electronic health records) in 653,790 individuals (495,005 European, 114,420 African American and 44,365 Latin American) and data from UK Biobank (n = 898,680).

A phenome-wide association and Mendelian randomisation study of alcohol use variants in a diverse cohort comprising over 3 million individuals.

Background: Alcohol consumption is associated with numerous negative social and health outcomes. These associations may be direct consequences of drinking, or they may reflect common genetic factors that influence both alcohol consumption and other outcomes.

Methods: We performed exploratory phenome-wide association studies (PheWAS) of three of the best studied protective single nucleotide polymorphisms (SNPs) in genes encoding ethanol metabolising enzymes (ADH1B: rs1229984-T, rs2066702-A; ADH1C: rs698-T) using up to 1109 health outcomes across 28 phenotypic categories (e.

Implementation of the Symptom Based Risk Calculator for Head and Neck Cancer HaNC-RC v.2 Post COVID-19 Pandemic. A Single Centre Audit.

Background: As the incidence of head and neck cancer continues to rise, the volume of referrals to our urgent suspected cancer clinics continues to rise with it. Cancer referral and review time targets are not being met within the UK, and our centre has experienced an increase in volume of referrals which cannot be met by available clinic slots. We proposed a pathway to the North East London Cancer Alliance to safely triage these patients using the Head and Neck Cancer Risk Calculator version 2 (HaNC-RCv2).

Pleiotropy and genetically inferred causality linking multisite chronic pain to substance use disorders.

Individuals suffering from chronic pain develop substance use disorders (SUDs) more often than others. Understanding the shared genetic influences underlying the comorbidity between chronic pain and SUDs will lead to a greater understanding of their biology. Genome-wide association statistics were obtained from the UK Biobank for multisite chronic pain (MCP, N = 387,649) and from the Million Veteran Program and the Psychiatric Genomics Consortium meta-analyses for alcohol use disorder (AUD, N = 296,974), cannabis use disorder (CanUD, N = 161,053), opioid use disorder (OUD, N = 57,120), and problematic tobacco use (PTU, N = 270,120).

Imaging of Anterior Segment Tumours: A Comparison of Ultrasound Biomicroscopy Versus Anterior Segment Optical Coherence Tomography.

Anterior segment tumours of the eye are relatively rare but can pose significant morbidity and mortality. We conducted a literature review to compare the performance of ultrasound biomicroscopy to anterior segment optical coherence tomography in the imaging of these tumours. A total of seven studies were included accounting for a cumulative 1,114 eyes.

Psychometric properties of self-report measures of eating disorder cognitions: a systematic review.

Background: Although eating disorder (ED) models display some differences in theory and treatment approach, cognitive-behavioural, schema-focused, and disorder-specific models all highlight the fundamental nature of cognitions as key factors in ED development and maintenance processes. As such, it is vital that ED cognitions continue to be assessed and monitored as therapeutic targets and treatment outcomes as well as being examined as constructs in empirical research. This review aimed to systematically identify and evaluate the psychometric properties of existing self-report measures of ED cognitions.

Multi-ancestry study of the genetics of problematic alcohol use in over 1 million individuals.

Problematic alcohol use (PAU), a trait that combines alcohol use disorder and alcohol-related problems assessed with a questionnaire, is a leading cause of death and morbidity worldwide. Here we conducted a large cross-ancestry meta-analysis of PAU in 1,079,947 individuals (European, N = 903,147; African, N = 122,571; Latin American, N = 38,962; East Asian, N = 13,551; and South Asian, N = 1,716 ancestries). We observed a high degree of cross-ancestral similarity in the genetic architecture of PAU and identified 110 independent risk variants in within- and cross-ancestry analyses.

Associations Between Polygenic Scores for Cognitive and Non-cognitive Factors of Educational Attainment and Measures of Behavior, Psychopathology, and Neuroimaging in the Adolescent Brain Cognitive Development Study.

Background: Both cognitive and non-cognitive (e.g., traits like curiosity) factors are critical for social and emotional functioning and independently predict educational attainment.