DEX/CRH Response: Mood/Anxiety Disorder Endophenotype?

描述(由申请人提供)：这项拟议的研究是一项前瞻性横断面调查的修订版，研究对象是没有表现出任何精神障碍但对地塞米松/促肾上腺皮质激素释放激素(DEX/CRH)刺激试验有夸大皮质醇反应的个人。DEX/CRH是目前对人类下丘脑-垂体-肾上腺(HPA)轴功能最敏感的检测方法。这种标准化的实验室测试检测到的HPA功能障碍的模式，可能预示着情绪和焦虑症的稳定的内表型。越来越多的临床前文献描述了在发育早期暴露于应激的持续神经内分泌和行为后果，提供了一种概念性机制，通过这种机制，在早期暴露于逆境的成年人中可能存在这种HPA过度活动。我们的初步数据表明，在没有当前精神病理学的健康成年人中，自我报告的童年时期压力严重程度的评级可以预测皮质醇对DEX/CRH测试的反应。DEX/CRH皮质醇高反应性的存在，与某些已知的风险因素，如早期暴露于重大应激源，积极的情绪障碍家族史，以及具有某种认知方式，最终可能被用来识别情绪和焦虑障碍或其他不良健康后果的高危个体，并帮助他们预防。这项拟议的研究将产生有关非抑郁、健康的人的临床特征的关键数据，这些人具有HPA过度活动的内表型，通过对DEX/CRH测试的“高”皮质醇反应(HCR)来衡量。一组HCR患者将与一组DEX/CRH“低”皮质醇应答者(LCR)在一些相关评估上进行比较。我们将回答关于被提议的HCR内表型的关键问题，包括：它与感知的童年逆境和最近的压力源的本质关系是什么？它能预测对标准化心理压力测试的自主神经、行为和神经内分泌反应吗？它与某些气质或个性特征有关吗？它是否与医学发病率或生活质量有关？随着时间的推移，它是否稳定？这些信息为评估潜在的情感性疾病生物标记物的预测效用的纵向研究提供了基础。

DESCRIPTION (provided by applicant): The proposed study is a revised version of a prospective, cross-sectional investigation of individuals who do not manifest any psychiatric disorder but demonstrate an exaggerated cortisol response to the dexamethasone/corticotropin releasing hormone (DEX/CRH) stimulation test. The DEX/CRH is the most sensitive test of human hypothalamus-pituitary-adrenal (HPA) axis function available. A pattern of HPA dysfunction, as detected by this standardized laboratory test, may signal a stable endophenotype of mood and anxiety disorders. A growing body of preclinical literature, describing persistent neuroendocrine and behavioral consequences of exposure to stress during early development, provides a conceptual mechanism by which such HPA hyperactivity may be present in adult humans who were exposed to adversity during early life. Our preliminary data suggest that self-reported ratings of severity of stress during childhood predict cortisol response to the DEX/CRH test in healthy adults without current psychopathology. The presence of DEX/CRH cortisol hyperresponsivity, taken together with certain known risk factors, such as exposure to significant stressors during early life, positive family history of mood disorder, and having a certain cognitive style, may eventually be used to identify individuals at high risk for development of mood and anxiety disorders or other adverse health outcomes, and aid in their prevention. The proposed investigation will generate critical data about the clinical characteristics of nondepressed, healthy individuals who have the HPA hyperactivity endophenotype as measured by "high" cortisol response (HCR) to the DEX/CRH test. A group of HCR individuals will be compared with a group of DEX/CRH "low" cortisol responders (LCR) on a number of relevant assessments. We will answer key questions about the proposed HCR endophenotype, including: What is the nature of its relationship to perceived childhood adversity and recent stressors? Does it predict autonomic, behavioral and neuroendocrine response to a standardized psychological stress test? Is it associated with certain temperament or personality features? Is it associated with medical morbidity or quality of life? Is it stable over time? Such information provides the groundwork for a longitudinal study to assess the predictive utility of a potential biomarker for affective illness.