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.

Evaluating alternative models of youth externalizing using quantitative genetic analyses.

Interest has increased in the recent literature on characterizing psychopathology dimensionally in hierarchical models. One dimension of psychopathology that has received considerable attention is externalizing. Although extensively studied and well-characterized in late adolescents and adults, delineation of the externalizing spectrum in youth has lagged behind.

A multivariate approach to understanding the genetic overlap between externalizing phenotypes and substance use disorders.

Substance use disorders (SUDs) are phenotypically and genetically correlated with each other and with other psychological traits characterized by behavioural under-control, termed externalizing phenotypes. In this study, we used genomic structural equation modelling to explore the shared genetic architecture among six externalizing phenotypes and four SUDs used in two previous multivariate genome-wide association studies of an externalizing and an addiction risk factor, respectively. We first evaluated five confirmatory factor analytic models, including a common factor model, alternative parameterizations of two-factor structures and a bifactor model.

A broad internalizing dimension accounts for the genetic associations between personality and individual internalizing disorders.

Much research has demonstrated that psychopathology can be described in terms of broad dimensions, representing liability for multiple psychiatric disorders. Broad spectra of psychopathology (e.g.

The role of parental genotype in the intergenerational transmission of externalizing behavior: Evidence for genetic nurturance.

The purpose of this study was to examine possible pathways by which genetic risk associated with externalizing is transmitted in families. We used molecular data to disentangle the genetic and environmental pathways contributing to adolescent externalizing behavior in a sample of 1,111 adolescents (50% female; 719 European and 392 African ancestry) and their parents from the Collaborative Study on the Genetics of Alcoholism. We found evidence for genetic nurture such that parental externalizing polygenic scores were associated with adolescent externalizing behavior, over and above the effect of adolescents' own externalizing polygenic scores.

Parsing genetically influenced risk pathways: genetic loci impact problematic alcohol use via externalizing and specific risk.

Genome-wide association studies (GWAS) identify genetic variants associated with a trait, regardless of how those variants are associated with the outcome. Characterizing whether variants for psychiatric outcomes operate via specific versus general pathways provides more informative measures of genetic risk. In the current analysis, we used multivariate GWAS to tease apart variants associated with problematic alcohol use (ALCP-total) through either a shared risk for externalizing (EXT) or a problematic alcohol use-specific risk (ALCP-specific).

Multivariate analysis of 1.5 million people identifies genetic associations with traits related to self-regulation and addiction.

Behaviors and disorders related to self-regulation, such as substance use, antisocial behavior and attention-deficit/hyperactivity disorder, are collectively referred to as externalizing and have shared genetic liability. We applied a multivariate approach that leverages genetic correlations among externalizing traits for genome-wide association analyses. By pooling data from ~1.

Testing structural models of psychopathology at the genomic level.

Genome-wide association studies (GWAS) have revealed hundreds of genetic loci associated with the vulnerability to major psychiatric disorders, and post-GWAS analyses have shown substantial genetic correlations among these disorders. This evidence supports the existence of a higher-order structure of psychopathology at both the genetic and phenotypic levels. Despite recent efforts by collaborative consortia such as the Hierarchical Taxonomy of Psychopathology (HiTOP), this structure remains unclear.

Construct validity of youth psychopathic traits as assessed by the Antisocial Process Screening Device.

The study of psychopathic traits in youth is in its nascent stages and the nature and the structure of these traits is still poorly understood. In one of the most comprehensive analyses to date of the construct validity of the widely used Antisocial Processing Screening Device (APSD), we used two independent samples of youth, one community ( = 2203) and one clinic-referred ( = 534), ages 4 to 19 (51% female), to investigate the external correlates of the Callous-unemotionality (CU), Narcissism, and Impulsivity dimensions of youth psychopathy. We used parent reports of externalizing and internalizing psychopathology, personality, and aggressive behavior to examine the pattern of associations between psychopathic trait dimensions and relevant external correlates.

Correction to: The Association of Oxytocin Receptor Gene (OXTR) Polymorphisms with Antisocial Behavior: A Meta-analysis.

The original version of this article inadvertently omitted the word "with" between "Polymorphisms" and "Antisocial" from the title. The title "The Association of Oxytocin Receptor Gene (OXTR) Polymorphisms Antisocial Behavior: A Meta-Analysis" should be "The Association of Oxytocin Receptor Gene (OXTR) Polymorphisms with Antisocial Behavior: A Meta-Analysis." as presented above.

The Association of Oxytocin Receptor Gene (OXTR) Polymorphisms with Antisocial Behavior: A Meta-analysis.

Evidence suggests that the Oxytocin Receptor Gene (OXTR) influences human social cognition and behavior. OXTR has been investigated in relation to antisocial behavior, but studies examining this association have produced varying results in terms of the magnitude and significance of the association as well as which SNPs are implicated. This meta-analysis, based on 15 samples in 12 studies with a total sample of 12,236 individuals, examined the overall effects and consistency of associations between eight SNPs in OXTR and antisocial behavior.

The nature and correlates of the dark triad: The answers depend on the questions.

The past several decades have witnessed a proliferation of research on the dark triad (DT), a set of traits comprising Machiavellianism, narcissism, and psychopathy. The bulk of DT research has been marked by several core assumptions, most notably that each DT construct is a monolithic entity that is clearly separable from its counterpart DT constructs. To examine the tenability of these assumptions, we pooled data from 2 samples of North American community members (ns = 312 and 351) to explore (a) the external validity and profile similarities of DT indicators and (b) the factor structure of the DT.

Measuring the hierarchical general factor model of psychopathology in young adults.

There is evidence that models of psychopathology specifying a general factor and specific second-order factors fit better than competing structural models. Nonetheless, additional tests are needed to examine the generality and boundaries of the general factor model. In a selected second wave of a cohort study, first-order dimensions of psychopathology symptoms in 499 23- to 31-year-old twins were analyzed.

External validity of a hierarchical dimensional model of child and adolescent psychopathology: Tests using confirmatory factor analyses and multivariate behavior genetic analyses.

Several recent studies of the hierarchical phenotypic structure of psychopathology have identified a General psychopathology factor in addition to the more expected specific Externalizing and Internalizing dimensions in both youth and adult samples and some have found relevant unique external correlates of this General factor. We used data from 1,568 twin pairs (599 MZ & 969 DZ) age 9 to 17 to test hypotheses for the underlying structure of youth psychopathology and the external validity of the higher-order factors. Psychopathology symptoms were assessed via structured interviews of caretakers and youth.