The objective of the proposed Mentored Clinical Scientist Development Award (K08) is to promote the candidate's development as an independent behavioral science researcher, with a focus on neuroendocrine responses to stress, and their effects on mental and physical health. During the five-year career development period, the candidate will engage in formal and informal training in psychoneuroendocrinology and stress and coping, complete three research projects, build collaborations, and address basic questions about relationships between stress, hormones, and risk for depression and cardiovascular disease. Chronic psychological stress contributes strongly to depression and cardiovascular disease, but the mechanisms are unclear. Most research in this area has focused on the deleterious effects of catabolic stress hormones like cortisol. Although hypercortisolemia turned out to be a weak biological marker of depression, it may be more revealing when examined in combination with anabolic hormones, such as dehydroepiandrosterone (DHEA) and growth hormone (GH), which can buffer the damaging effects of cortisol. The long-term goal of the current research program is to examine whether anabolic and catabolic hormones, as well as their levels relative to each other (anabolic balance) serve as a mediating pathway from stress to depression and to risk factors for cardiovascular disease (insulin resistance, visceral fat, and atherosclerosis). Studies 1 and 2 will examine whether history of chronic stress predicts low anabolic balance, depression, and risk for disease in longitudinal cohorts of younger adults (N = 1000) and older adults (N = 1000). Study 3 will assess whether chronic stress alone and with major depression is related to basal and reactive measures of anabolic balance and disease risk in caregivers, who serve as a unique model of chronic stress. If warranted, future research will compare effects of stress reduction and hormonal supplementation on mood and disease risk.