Genetic Factors Interact with Maternal Depression to Predict Adolescents’ Co-occurring Internalizing/Externalizing Problems

• In Event: 3-233 - Parental Depression and Youths’ Outcomes: Integrating Advanced Methods to Gain Novel Insights

Integrative Statement

Maternal depression is associated with multiple forms of psychopathology in adolescence, with some youth more vulnerable than others (Goodman et al., 2011). Identifying the characteristics that drive these differences in vulnerability may help elucidate etiological processes and provide targets for interventions. Similarly, genetic characteristics influence how individuals respond to the environment (Rutter et al., 2006), yet few studies have examined whether associations between maternal depression and youth problem behavior are moderated by genetic factors. Even fewer studies have examined genetic moderation of maternal depression in relation to co-occurring internalizing and externalizing problems, an outcome associated with particularly severe problems in adulthood. This gap is considerable as prior research has only examined direct relations between maternal depression and co-occurring versus more “pure” problem and low problem groups (Basten et al., 2013; Fanti & Heinrich, 2010), and done so only up until pre-adolescence when many forms of psychopathology have yet to onset.

Thus, the current study sought to extend prior research by examining direct associations between maternal depressive symptoms in early childhood and co-occurring problem behavior during adolescence and whether these relations were moderated by polygenic risk composites. We hypothesized that maternal depression would be elevated among adolescents with co-occurring problems, but only in the context of genetic risk.

Participants were drawn from a subsample of the Early Steps Multisite study, who were followed from ages 2 to 14 as part of an RCT testing the Family Check-Up (n=485; Dishion et al., 2008). Mothers’ depression was assessed using the Center for Epidemiological Studies on Depression Scale (age 2). Primary caregivers reported on adolescents’ internalizing and externalizing problems using six subscales from the Achenbach Child Behavior Checklist. Genotyping was performed using the Affymetrix Axiom Biobank1 Array. Polygenic scores were created by weighting and summing SNPs exceeding p< 0.05 in a meta-GWAS of children’s internalizing (Benke et al., 2014) and aggression (Pappa et al., 2015). Covariates were gender, intervention group, genetic ancestry, and age 2 internalizing and externalizing. Latent profile analysis identified co-occurring, “externalizing only,” “internalizing only,” and low problem groups. Multinomial logistic regression compared groups.

Four latent classes representing the hypothesized groups fit the data best. See Table 1 for final results. Significant interactions showed that maternal depression was elevated for the co-occurring group relative to the others only for those whose internalizing polygenic risk was high (B=-0.10 to -0.12, p<0.001) or average (B=-0.06 to -0.07, p<0.05), but not low (B=0.00 to -0.02, ns). Similarly, maternal depression was only elevated for the co-occurring group relative to the “internalizing only” (marginal interaction) and low problems group (significant interaction) for those whose aggression polygenic scores were high (B=-0.09 to -0.10, p<0.05) or average (B=-0.06 to -0.07, p<0.05), but not low (B=-0.03 to -0.05, ns). Subsequent analyses will test two- and three-way interactions with intervention status.

Findings suggest that adolescents with high and average levels of internalizing and aggression polygenic scores are susceptible to exposure to maternal depression. Treating maternal depression could help reduce co-occurring internalizing and externalizing problems for youth at genetic risk.

Authors

• Frances Lynn Wang, University of Pittsburgh
  Presenting Author

• Kathryn Lemery-Chalfant, Arizona State University
  Non-Presenting Author

• Melvin N. Wilson, University of Virginia
  Non-Presenting Author

• Daniel S. Shaw, University of Pittsburgh
  Non-Presenting Author