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

We used sex, observed parenting quality at 18 months, and three variants of the catechol-O-methyltransferase gene (Val¹⁵⁸Met [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, Val¹⁵⁸Met 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 Val¹⁵⁸Met 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.