Examining hypothalamic‐pituitary‐adrenal axis genetic variation on cortisol and alpha‐amylase reactivity during an explicit negative‐evaluative stress induction

Abstract Prior work consistently links additive genetic variation in the hypothalamic‐pituitary‐adrenal (HPA) axis—a multilocus genetic profile score (MGPS)—to depression risk in the context of stress exposure. However, despite that HPA MGPS variants were selected based on evidence that they elevate cortisol reactivity, there are surprisingly few tests of whether an HPA MGPS elevates cortisol reactivity to lab‐based stress. Similarly, despite neurobiological connections and coordination between the HPA axis and the sympathetic nervous system (e.g., in the paraventricular nucleus and locus coeruleus), no work has tested whether an HPA MGPS influences sympathetic nervous system reactivity to stress. We investigated whether an HPA MGPS moderates the relation between lab‐based stress and: (1) HPA activity indexed by cortisol, and/or (2) sympathetic activity indexed by salivary alpha‐amylase, sAA. Emerging adults ( N = 152; mean age = 19.5, largest subsample 44.4% Black/African American) were randomly assigned to one of two Trier Social Stress Test variations, a non‐evaluative control, or an explicitly negative‐evaluative condition. Participants provided DNA and repeated saliva samples for sAA and cortisol. The HPA MGPS did not significantly moderate the relationship between stress condition and cortisol or sAA reactivity, respectively; moreover, post‐hoc tests highlight that individual polymorphisms showed non‐significant effects in opposite directions from each other, cancelling out in aggregate. Findings suggest that the HPA MGPS's associations with cortisol reactivity are not as straightforward as initially believed. We speculate that the relationships of some HPA variants to biomarker reactivity may vary between modest lab‐based stressors and the explicit negative‐evaluative induction used here.