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 ~1.5 million people, our approach is statistically more powerful than single-trait analyses and identifies more than 500 genetic loci. The loci were enriched for genes expressed in the brain and related to nervous system development. A polygenic score constructed from our results predicts a range of behavioral and medical outcomes that were not part of genome-wide analyses, including traits that until now lacked well-performing polygenic scores, such as opioid use disorder, suicide, HIV infections, criminal convictions and unemployment. Our findings are consistent with the idea that persistent difficulties in self-regulation can be conceptualized as a neurodevelopmental trait with complex and far-reaching social and health correlates

Emotional Understanding as a Mediator of ADHD and Negative Social Outcomes

Children with Attention Deficit/Hyperactivity Disorder are more likely than peers without the disorder to be disliked or rejected by peers. In turn, social rejection of children with ADHD may be tied to more aggression or other negative behaviors shown by these children. The present study investigated to what extent children with ADHD symptoms exhibit negative behaviors during a playgroup with previously unacquainted children and whether children’s understanding of others’ emotions explained the relationship between ADHD symptoms and negative social outcomes. Sixty-one children aged 8-10 years old watched an episode of a televised family comedy. Then, participants were asked cued recall questions concerning the story characters’ emotions and internal states. Children later participated in playgroups of 6-10 unfamiliar children. The children completed six tasks, including creating a group name, cooperating to solve a problem, and completing a puzzle. The number of ADHD symptoms was measured by parent and teacher reports. Emotional understanding was measured by the number of correctly answered cued recall questions about TV characters’ emotions and internal states. Behavior measurements included the number of positive and negative behaviors displayed, as well as global ratings of each child’ positive and negative behaviors, acceptance and rejection, and emotion dysregulation. Preliminary analyses indicated that children rated higher in ADHD symptoms by parents and teachers were rated by independent coders as higher in negative behaviors and emotion dysregulation than children rated lower in ADHD symptoms. Further analyses will evaluate the role of emotional understanding in the relation between ADHD symptoms and social behaviors

Evaluating the Validity of Alternative Models of Youth Externalizing using Behavior 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. As a complement to structural analyses of Externalizing, in this study we use quantitative genetic analyses of twin data to adjudicate among alternative models of youth Externalizing that differ in granularity. Specifically, we compared model fit, estimates of genetic and environmental influences on the Externalizing dimension, and the average, variability, and precision of genetic and environmental influences on individual symptoms due to the Externalizing dimension, specific symptom dimensions, and unique etiological influences. Given that none of these criteria are definitive on their own, we looked to the confluence of these criteria to exclude particular models while highlighting others as leading contenders. We analyzed parent-report data on 38 externalizing symptoms from a population-representative, ethnically-diverse sample of 883 youth twin pairs (51% female), who were on average 8.5 years old. Although models including an Externalizing composite and ADHD, ODD, and CD diagnoses and symptom dimensions showed similar heritability to latent variable models of Externalizing, models that included latent dimensions of Externalizing and more fine-grained symptom dimensions fit better and were more balanced in the magnitude of genetic and environmental influences on individual symptoms due to the Externalizing dimension and specific symptom dimensions. Pending replication, these more elaborated model(s) can be useful for advancing research on causes and outcomes of youth Externalizing and its fine-grained specific components

Testing models for the underlying structure of psychopathology using genetic correlations

In this project, we will test alternative structural models of psychopathology using genetic correlations among relevant disorders and traits derived from GWAS summary statistics

Riskier Tests of the Validity of Bifactor Models of Psychopathology

We advanced several “riskier tests” of the validity of bifactor models of psychopathology, which included that the general and specific factors should be reliable and well-represented by their indicators, and that including a general factor should improve the correlated factor model’s external validity. We compared bifactor and correlated factors models using data from a community sample of youth (N=2498) whose parents provided ratings on psychopathology and external criteria (i.e., temperament, aggression, antisociality). Bifactor models tended to yield either general or specific factors that were unstable and difficult to interpret. The general factor appeared to reflect a differentially-weighted amalgam of psychopathology rather than a liability for psychopathology broadly construed. With rare exceptions, bifactor models did not explain additional variance in psychopathology symptom dimensions or external criteria compared with correlated factors models. Together, our findings call into question the validity of bifactor models of psychopathology, and the p-factor more broadly

Riskier Tests of the Validity of the Bifactor Model of Psychopathology

We advanced several “riskier tests” of the validity of bifactor models of psychopathology, which included that the p-factor and specific psychopathology factors should be reliable and well-represented by their respective indicators, and that modeling the p-factor should increase the model’s external validity. We compared bifactor and correlated factors models of psychopathology using data from a community sample of youth (N=2498) whose parents provided ratings on psychopathology and theoretically-relevant external criteria (i.e., personality, aggression, antisociality). Bifactor models tended to yield either general or specific factors that were unstable and difficult to interpret. The p-factor appeared to reflect a differentially-weighted amalgam of psychopathology rather than a liability for psychopathology broadly construed. Compared with correlated factors models, bifactor models tended not to explain additional variance in first-order psychopathology symptom dimensions or external criteria. Together, our findings call into question the validity of bifactor models of psychopathology, and the p-factor more broadly