Given the regulatory role of the amygdala in the biological stress response system (17), as well as the associations between stress and amygdala function reviewed above, stress-related genetic variation may independently, and interactively with stress exposure, contribute to individual differences in amygdala reactivity. Alongside numerous regulatory mechanisms, the high-affinity mineralocorticoid receptor and low-affinity glucocorticoid receptor regulate the onset and termination, respectively, of the hypothalamic-pituitary-adrenal (HPA) axis stress response (18). One of the primary functions of the glucocorticoid receptor is to normalize brain activity to prestress levels through negative feedback inhibition of the HPA axis. In contrast, the mineralocorticoid receptor, because of its relatively high affinity and nearly constant occupancy by cortisol, mediates tonic inhibition of the HPA axis under basal and stressful conditions (18). The mineralocorticoid receptor also has a role in behavioral stress response functions, including the appraisal of novel situations and the selection of appropriate responses to deal with challenges (18). Research on these functions, combined with rodent data indicating that mineralocorticoid receptor overexpression in the amygdala reduces corticosterone release and anxiety-like behavior (19), highlights the potentially powerful
