Few findings in psychological science are as well replicated as evidence that stress precipitates depression. A wealth of evidence supports dysregulation of two major stress response systems—the hypothalamic-pituitary-adrenal (HPA) axis and its cortisol biomarker, and the sympathetic nervous system (SNS) with its salivary alpha-amylase (sAA) biomarker—as complicit in the etiology of depression risk. Prior research points to genetic variation as one source of individual differences within these systems. Although recent work emphasizes additive approaches to genetics, almost no research has examined if additive genetic risk in the HPA axis (HPA multilocus genetic profile score; MGPS) influences responding to lab-based stress exposure. Similarly, despite neurobiological connections between the HPA and SNS, no work has tested whether additive HPA-related genetic risk influences SNS reactivity to stress, or whether vulnerability in both systems, indicated by HPA-related genetic risk and SNS hyperreactivity, might work together to predict cortisol reactivity to stress. Using a diathesis stress framework to test responding to negative evaluative psychosocial stress, I examined whether an additive HPA MGPS: 1) predicts blunted cortisol reactivity, 2) predicts heightened sAA reactivity, and 3) interacts with heightened sAA reactivity to predict blunted cortisol reactivity. Findings indicated that an HPA MGPS did not significantly moderate the relationship between stress condition and cortisol or sAA reactivity respectively. However, sAA reactivity and HPA MGPS moderated the relationship between stress condition and cortisol reactivity. Findings help explicate how individual differences across two stress responsive systems influence cortisol reactivity
