Examining the influence of an additive genetic risk score of HPA axis polymorphisms with recent stress on depression onset in emerging adults

Abstract

Prior research suggests that HPA-axis genetic variation moderates the association between stress and depression, but has historically focused on individual variants with small effects. Recent studies, however, have tested an additive genetic score of biologically-plausible variants (multilocus genetic profile score; MGPS) in the HPA-axis (e.g., Pagliaccio et al., 2014). Among adolescents, an HPA-MGPS moderated the effects of stress on depressive symptoms; higher HPA-MGPS predicted heightened depressive symptoms when stress was high, but reduced symptoms when stress was low (Starr & Huang, 2019), consistent with differential susceptibility theory (Belsky & Pluess, 2009). Whether this same effect extends to emerging adults, however, is untested. Thus, the current study will test whether an HPA-MGPS interacts with chronic and episodic stress to predict depression onset in emerging adults. We hypothesize that an HPA-MGPS will interact with episodic (total, interpersonal), and chronic (interpersonal, non-interpersonal) stress, to predict depression onset, such that a higher HPA-MGPS will predict depression when stress is high, but reduced risk when stress is low. Participants (n=387) from the Youth Emotion Project, a longitudinal study of risk for emotional disorders that oversampled high school juniors for high levels of neuroticism, gave DNA and completed annual diagnostic and life stress interviews. Five years of data will be used. DNA was genotyped for 14 HPA-axis variants for inclusion in an HPA-MGPS. Hypotheses will be tested using Cox regression; results will be available by the time of the conference. Results will be discussed considering implications for future MGPS research and differential susceptibility theory.