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Poster #66 - Toddler Behavioral Inhibition Mediates, and Positive Behavior Support Moderates Genetic Influence on Adolescents’ Psychopathology

Sat, March 23, 9:45 to 11:00am, Baltimore Convention Center, Floor: Level 1, Exhibit Hall B

Integrative Statement

Understanding the risk pathways that unfold between genetic risk and adolescents’ psychopathology is important for clarifying etiological processes and guiding targets for intervention. Behavioral inhibition (BI), which describes the tendency towards withdrawal in the face of novelty (Kochanska et al., 1991), may mediate the relation between genetic risk factors and internalizing/externalizing problems. Indeed, BI is genetically correlated with both internalizing (positively) and externalizing (negatively) problems (Rhee et al., 2015) and appears early in life, often prior to the onset of psychopathology (Kagan et al., 1986). However, few studies have examined whether BI is an intermediate phenotype underlying the particularly troubling and common outcome of co-occurring internalizing/externalizing problems. In this study, we extend the literature by investigating whether 2 year-olds’ observed BI mediated the effect of polygenic scores for internalizing problems and aggression on co-occurring problems relative to “internalizing only,” “externalizing only,” and low problem groups. Because parenting has been shown to modify genetic risk (Krueger et al., 2008), we also tested whether these paths were moderated by observations of parents’ positive behavior support (PBS).

Thus, we hypothesized that internalizing polygenic risk would positively predict, and aggression polygenic risk would negatively predict BI, which in turn, would be elevated in the co-occurring group relative to all groups but “internalizing only.” We also expected that genetic risk would be exacerbated in the context of low PBS.

Participants were a subsample of the Early Steps Multisite study who had genetic data and were followed from ages 2 to 14 as part of an RCT testing the Family Check-Up (n=514; Dishion et al., 2008). BI and PBS were observed during age 2 laboratory tasks (Dishion et al., 2008). Primary caregivers reported on six subscales of adolescents’ (age 14) internalizing and externalizing problems using the Achenbach Child Behavior Checklist. Genome-wide polygenic scores were created by weighting and summing SNPs exceeding p< 0.05 in meta-GWAS results of children’s internalizing problems (Benke et al., 2014) and aggression (Pappa et al., 2015).

Latent profile analysis identified the hypothesized co-occurring, “externalizing only,” “internalizing only,” and low problem groups (age 14), which were compared using multinomial logistic regression. See Table and Figure 1 for final model results. Although polygenic scores had no main effects on BI, PBS interacted with internalizing polygenic risk; higher internalizing polygenic risk predicted higher BI for those whose parents’ PBS was low (β=0.17, p<0.05), but not average (β=0.06, ns) or high (β=-0.05, ns). BI was elevated among youth with co-occurring problems relative to “externalizing only” and low problems, but not “internalizing only.” According to the joint significance test, BI mediated the relation between internalizing polygenic risk and co-occurring problems (relative to low and “externalizing only”), but only at low PBS.

Genetic factors specific to internalizing, but not aggression, may influence toddlers’ tendency to withdraw from unfamiliar social and nonsocial contexts (i.e., BI), but only with low PBS. Because BI subsequently increased risk for adolescents’ co-occurring problems, PBS may be a salient intervention target for this problematic outcome, particularly for genetically-vulnerable youth.

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