DEX/CRH Response: Mood/Anxiety Disorder Endophenotype?

描述（由申请人提供）：拟议的研究是一项前瞻性横断面调查的修订版本，研究对象为未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）刺激试验表现出夸大的皮质醇反应的个体。DEX/CRH是目前最灵敏的人类下丘脑-垂体-肾上腺（HPA）轴功能检测方法。这种标准化的实验室测试检测到的下丘脑功能障碍模式，可能预示着情绪和焦虑障碍的稳定内表型。越来越多的临床前文献描述了在早期发育期间暴露于压力下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，HPA过度活跃可能存在于早期生活中暴露于逆境的成年人中。我们的初步数据表明，在没有当前精神病理的健康成年人中，童年时期自我报告的压力严重程度评分可以预测对DEX/CRH测试的皮质醇反应。DEX/CRH皮质醇高反应性的存在，加上某些已知的风险因素，如早期生活中暴露于重大压力源，积极的情绪障碍家族史，以及具有某种认知风格，可能最终用于识别情绪和焦虑障碍发展或其他不良健康结果的高风险个体，并有助于预防这些风险。通过对DEX/CRH测试的“高”皮质醇反应（HCR）来测量具有HPA多动性内表型的非抑郁健康个体的临床特征，提出的研究将产生关键数据。将一组HCR个体与一组DEX/CRH“低”皮质醇应答者（LCR）进行多项相关评估比较。我们将回答关于提出的HCR内表型的关键问题，包括：它与感知到的童年逆境和最近的压力源的关系的本质是什么？它能预测对标准化心理压力测试的自主、行为和神经内分泌反应吗？它是否与某种气质或性格特征有关？它是否与医疗发病率或生活质量有关？随着时间的推移是否稳定？这些信息为纵向研究提供了基础，以评估潜在生物标志物对情感性疾病的预测效用。

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.