Interaction between hypothalamic-pituitary-adrenal axis genetic variation and maternal behavior in the prediction of amygdala connectivity in children

Abstract

High levels of negative, and low levels of positive parenting behaviors can increase the risk of internalizing symptoms in children, but the mechanisms underlying this association are still unclear. One possibility is that parenting behaviors affect the neural correlates of emotion processing in children. Further, genetic variants relevant to the function of the hypothalamic-pituitary-adrenal (HPA) axis are thought to moderate the effect of early experiences on the brain circuits underlying emotion processing, particularly those involving the amygdala. However, no studies have investigated the interactive effect of parenting behaviors and HPA axis-related genes on amygdala activity and connectivity during emotion processing, and in turn internalizing symptoms in children. Participants comprised 80 children (46 females, mean age\u202f=\u202f10.0 years) from the community. Observational measures of maternal behavior were collected during mother-child interactions. Children underwent functional magnetic resonance imaging while performing an implicit emotion-processing task, and mothers and children completed measures of child internalizing symptoms. Genetic risk was calculated using an HPA genetic risk score. HPA genetic risk score was indirectly associated with greater child self-reported depressive symptoms via increased amygdala-precuneus connectivity during the emotion-processing task, and interacted with negative maternal parenting behavior to predict increased connectivity between amygdala and superior frontal gyrus, anterior cingulate cortex and parietal cortex. HPA-related genetic variation appears to moderate the effect of negative maternal parenting behavior on the neural underpinnings of emotion processing in children, and may confer risk for depressive symptoms via modulation of amygdala connectivity.