Evidence for two genetically distinct pathways to co-occurring internalizing and externalizing problems in adolescence characterized by negative affectivity or behavioral inhibition

Abstract

Unique pathways to adolescents' co-occurring internalizing/externalizing problems, a severe and common form of psychopathology, remain poorly delineated; this paucity of knowledge impedes the development of personalized interventions. We examined established measures of genetic risk and early childhood temperamental dimensions to clarify potentially distinct pathways to adolescents' co-occurring internalizing/externalizing problems. Participants were drawn from a longitudinal randomized controlled trial of a family-based intervention. The study employed multiple informants and methods, including observer ratings of toddlers' negative affectivity and behavioral inhibition, and primary caregiver ratings of toddlers' inhibitory control; internalizing and aggression polygenic risk scores (PRS) based on prior meta-genome-wide association studies (GWAS); and parents' and teachers' reports of adolescents' internalizing and externalizing problems. Higher levels of the aggression PRS indirectly predicted primary caregiver- and teacher-reported co-occurring problems relative to all other groups through greater early childhood negative affectivity. Lower levels of the aggression PRS and higher levels of the internalizing PRS indirectly predicted co-occurring problems relative to the externalizing "only" and low problem groups (primary caregivers only) through greater early childhood behavioral inhibition. Findings suggest two different genetic pathways to co-occurring problems that could lead to distinct prevention and intervention efforts. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Figure 1.

Final model results. Covariates, correlations among mediators within-age, non-significant paths, and direct effects from PRSs to age 14 outcomes are not shown to enhance interpretability. CO: co-occurring. INT: Internalizing ‘only’. EXT: Externalizing ‘only’. Low: Low problems. “Co > Low” denotes that co-occurring group was higher on that variable than low problems group. Standardized coefficients depicted (*p<0.05). Akaike Information Criteria=28190.511, Bayesian Information Criteria=29451.029, Sample-Size Adjusted Bayesian Information Criteria=28508.298.