Depression, Stress & Health: Role of Anabolic Hormones

建议指导临床科学家发展奖（K08）的目的是促进候选人作为独立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，候选人将参加心理神经内分泌学和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，并解决有关压力，激素和抑郁症和心血管疾病风险之间关系的基本问题。 慢性心理应激与抑郁症和心血管疾病密切相关，但其机制尚不清楚。这一领域的大多数研究都集中在分解代谢应激激素（如皮质醇）的有害影响上。虽然高皮质醇血症被证明是抑郁症的一个弱生物标志物，但当与合成代谢激素（如脱氢表雄酮（DHEA）和生长激素（GH））结合使用时，它可能会更有启发性，这些激素可以缓冲皮质醇的破坏作用。目前研究计划的长期目标是检查合成代谢和分解代谢激素，以及它们相对于彼此的水平（合成代谢平衡）是否作为从压力到抑郁症和心血管疾病风险因素（胰岛素抵抗，内脏脂肪和动脉粥样硬化）的中介途径。 研究1和2将检查慢性应激史是否预测年轻人（N = 1000）和老年人（N = 1000）纵向队列的低合成代谢平衡，抑郁症和疾病风险。研究3将评估慢性压力单独和重度抑郁症是否与护理人员的合成代谢平衡和疾病风险的基础和反应性措施有关，他们作为慢性压力的独特模型。如果有必要，未来的研究将比较减轻压力和补充激素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.