Depression, Stress & Health: Role of Anabolic Hormones

描述(由申请人提供)：建议的导师临床科学家发展奖(K08)的目标是促进候选人作为一名独立的行为科学研究人员的发展，重点是神经内分泌对压力的反应及其对身心健康的影响。在五年的职业发展期间，应聘者将接受心理神经内分泌学以及压力和应对方面的正式和非正式培训，完成三个研究项目，建立合作关系，并解决压力、激素与抑郁和心血管疾病风险之间的基本问题。 慢性心理压力会导致抑郁症和心血管疾病，但其机制尚不清楚。这一领域的大多数研究都集中在皮质醇等分解代谢应激激素的有害影响上。尽管高皮质醇血症被证明是抑郁症的一个微弱的生物标志，但如果与合成激素(如脱氢表雄酮(DHEA)和生长激素(GH))结合检查，它可能会更能揭示出来，这些激素可以缓冲皮质醇的损害作用。当前研究计划的长期目标是检查合成代谢激素和分解代谢激素以及它们之间的相对水平(合成代谢平衡)是否充当从应激到抑郁以及心血管疾病(胰岛素抵抗、内脏脂肪和动脉粥样硬化)风险因素的中介途径。 研究1和2将检验在年轻人(N=1000)和老年人(N=1000)的纵向队列中，慢性应激史是否预示合成代谢平衡低下、抑郁和疾病风险。研究3将评估慢性压力本身和伴有严重抑郁的情况是否与照顾者的合成代谢平衡和疾病风险的基础和反应性测量有关，后者是慢性压力的独特模型。如果有必要，未来的研究将比较减压和激素补充对情绪和疾病风险的影响。

DESCRIPTION (provided by applicant): 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.