Interactions among catechol-O-methyltransferase genotype, parenting, and sex predict children's internalizing symptoms and inhibitory control: Evidence for differential susceptibility

abstract: We used sex, observed parenting quality at 18 months, and three variants of the catechol-O-methyltransferase gene (Val[superscript 158]Met [rs4680], intron1 [rs737865], and 3′-untranslated region [rs165599]) to predict mothers' reports of inhibitory and attentional control (assessed at 42, 54, 72, and 84 months) and internalizing symptoms (assessed at 24, 30, 42, 48, and 54 months) in a sample of 146 children (79 male). Although the pattern for all three variants was very similar, Val[superscript 158]Met explained more variance in both outcomes than did intron1, the 3′-untranslated region, or a haplotype that combined all three catechol-O-methyltransferase variants. In separate models, there were significant three-way interactions among each of the variants, parenting, and sex, predicting the intercepts of inhibitory control and internalizing symptoms. Results suggested that Val[superscript 158]Met indexes plasticity, although this effect was moderated by sex. Parenting was positively associated with inhibitory control for methionine–methionine boys and for valine–valine/valine–methionine girls, and was negatively associated with internalizing symptoms for methionine–methionine boys. Using the “regions of significance” technique, genetic differences in inhibitory control were found for children exposed to high-quality parenting, whereas genetic differences in internalizing were found for children exposed to low-quality parenting. These findings provide evidence in support of testing for differential susceptibility across multiple outcomes.This is the authors' final manuscript as accepted. The final published version can be viewed at DEVELOPMENT AND PSYCHOPATHOLOGY / Volume 27 / Issue 3 / 2015-08-01, pp 709-723 Copyright Cambridge University Press 2015 DOI: 10.1017/S095457941400080