HPA Axis Multilocus Genetic Profile Score Moderates the Impact of Interpersonal Stress on Prospective Increases in Depressive Symptoms for Offspring of Depressed Mothers

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Although offspring of depressed mothers are at an increased risk for depression themselves, not all of these children develop depression, highlighting the need to identify specific environmental and genetic moderators of risk. The goal of this study was to examine the aggregate influence of genetic polymorphisms associated with the regulation of the hypothalamic–pituitary–adrenal (HPA) axis as a potential moderator of the relation between environmental stress and prospective changes in depressive symptoms for offspring of depressed mothers. Participants were 238 mother–offspring dyads recruited from the community based on the mother’s lifetime history of major depression during the youth’s lifetime (present vs. absent). Mothers and youth completed assessments every 6 months for 2 years (5 total). Results indicated that offspring of depressed mothers showing the greatest increases in depressive symptoms during the follow up were those who had higher HPA multilocus genetic profile scores and who experienced the highest levels of interpersonal stress. These relations were significant for interpersonal stress and were not observed for noninterpersonal stress. These findings suggest that HPA multilocus genetic profile scores may be important genetic markers of stress reactivity and depression risk for offspring of depressed mothers. They also highlight interpersonal stress as a potentially modifiable risk factor for these high-risk youth.

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