Cognitive Modulation of Human Neuroendocrine Stress Axis

下丘脑-垂体肾上腺(HPA)轴是一个中枢控制的应激反应神经内分泌系统。它通过将心理社会应激源与认知/情绪和生理反应联系起来，破坏体内平衡调节，在抑郁症、乳腺癌和艾滋病等不同疾病中发挥病理生理学作用。更好地了解心理社会因素如何调节HPA轴的活动将促进我们对它们如何加速和缓和这些疾病的进程的理解。对特定的认知和情绪调节因子进行实验室研究，有助于完善和更广泛地应用能够减轻这些疾病的进展和负担的心理社会干预措施。它还可以帮助确定心理社会因素调节HPA轴的生物学机制。这项建议的目的是(1)证明认知/情绪因素实际上是人类HPA轴对药物和心理挑战的反应的有力调节器，以及(2)开始识别对HPA轴最显著的特定心理因素。长期目标是(1)更准确地识别这些因素，以开发改进的应激接种干预措施，以及(2)促进对应激敏感性和复原力的心理生物学的一般和机械理解。具体地说，该项目将建立在以前资助的工作的基础上，证明对预期、新颖性和感知控制的短暂认知操纵显著减缓了人类HPA轴对强大的药理激活剂的反应。这项研究将试图复制这种认知干预对HPA轴的影响，检查其与轴的其他药物和心理激活剂的效力，并解构干预以更准确地确定哪些认知/情绪成分最有影响。利用实验室挑战范式和随机分配实验设计，该项目将检验短暂的认知干预对促肾上腺皮质激素(ACTH)和皮质醇对CCK-B受体激动剂(五肽胃泌素)、促肾上腺皮质激素释放激素和Trier社会应激测试的影响。现有的动物数据将被用来确定认知干预中可能解释其有效性的因素，并将进行拆解研究，以检查这些因素的可分离影响。

The hypothalamic-pituitary adrenal (HPA) axis is a centrally controlled, stress-responsive neuroendocrine system. It plays a pathophysiological role in diseases as divergent as depression, breast cancer and AIDS, by linking psychosocial stressors to cognitive/emotional and physiological responses that can disrupt homeostatic regulation. Better understanding of how psychosocial factors modulate activity of the HPA axis will advance our understanding of how they accelerate and moderate the course of these diseases. Laboratory study of specific cognitive and emotional modulators could facilitate refinement and wider application of psychosocial interventions capable of ameliorating progression and burden of these diseases. It can also help identify the biological mechanism through which psychosocial factors modulate the HPA axis. The goals of this proposal are (1) to demonstrate that cognitive/emotional factors are in fact potent modulators of human HPA axis reactivity to pharmacological and psychological challenges and (2) to begin to identify the specific psychological factors that are most salient to the axis. The long-term objectives are (1) to use more precise identification of these factors to develop improved stress inoculation interventions and (2) to advance general and mechanistic understanding of the psychobiology of stress sensitivity and resilience. Specifically, the project will build on previously funded work demonstrating that a brief cognitive manipulation of expectancies, novelty, and perceived control significantly moderates the human HPA axis response to a robust pharmacological activator. This study will seek to replicate the impact of this cognitive intervention on the HPA axis, examine its potency with other pharmacological and psychological activators of the axis, and deconstruct the intervention to determine more precisely those cognitive/emotional components that are most impactful. Using a laboratory challenge paradigm and a random-assignment experimental design, the project will examine the effects of a brief cognitive intervention on adrenocorticotropin (ACTH) and cortisol response to a cholecystokinin-B receptor agonist (pentagastrin), to corticotropin-releasing hormone, and to the Trier Social Stress Test. Existing animal data will be used to identify factors within the cognitive intervention which likely account for its potency and dismantling studies will be done to examine the separable effects of these factors.