Cognitive Modulation of Human Neuroendocrine Stress Axis

下丘脑-垂体-肾上腺（HPA）轴是一个集中控制的应激反应神经内分泌系统。它通过将社会心理压力源与认知/情绪和生理反应联系起来，从而破坏体内平衡调节，在抑郁症、乳腺癌和艾滋病等多种疾病中发挥病理生理作用。更好地了解社会心理因素如何调节下丘脑轴的活动将促进我们对它们如何加速和缓和这些疾病进程的理解。对特定认知和情绪调节剂的实验室研究可以促进改进和更广泛地应用能够改善这些疾病进展和负担的社会心理干预措施。它还可以帮助确定通过社会心理因素调节HPA轴的生物学机制。本提案的目标是：(1)证明认知/情感因素实际上是人类HPA轴对药理和心理挑战反应的有效调节剂；(2)开始确定对HPA轴最显著的特定心理因素。长期目标是：(1)使用更精确的识别这些因素来开发改进的应激接种干预措施；(2)推进对应激敏感性和恢复力的心理生物学的一般和机制理解。具体来说，该项目将建立在先前资助的工作基础上，证明预期、新奇和感知控制的短暂认知操纵显著地调节了人类HPA轴对强效药物激活剂的反应。本研究将试图复制这种认知干预对下丘脑轴的影响，与其他药理和心理激活剂一起检验其效力，并解构干预，以更准确地确定那些最具影响力的认知/情感成分。采用实验室挑战范式和随机分配实验设计，该项目将检查短暂认知干预对促肾上腺皮质激素（ACTH）和皮质醇对胆囊收缩素- b受体激动剂（pentagastrin）、促肾上腺皮质激素释放激素和特里尔社会压力测试的反应的影响。现有的动物数据将用于识别认知干预中可能解释其效力的因素，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.