DEX/CRH Response: Mood/Anxiety Disorder Endophenotype?

DEX/CRH 反应：情绪/焦虑症内表型？

• 批准号: 6773425
• 负责人: LINDA L CARPENTER
• 金额: $ 29.23万
• 依托单位: BUTLER HOSPITAL (PROVIDENCE, RI)
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-23 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6773425
• 关键词: anxiety disorders; behavioral /social science research tag; biomarker; body physical characteristic; child abuse; clinical research; corticotropin releasing factor; cortisol; dexamethasone; disease /disorder proneness /risk; early experience; functional ability; human middle age (35-64); human morbidity; human subject; hypothalamic pituitary adrenal axis; interview; mental disorder diagnosis; parent offspring interaction; personality; phenotype; psychological stressor; quality of life; steroid hormone metabolism; young adult human (21-34)

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.

描述（由申请方提供）：拟定研究是一项前瞻性横断面研究的修订版，研究对象为未表现出任何精神疾病但对地塞米松/促肾上腺皮质激素释放激素（DEX/CRH）刺激试验表现出过度皮质醇反应的个体。DEX/CRH是人类下丘脑-垂体-肾上腺（HPA）轴功能最敏感的测试。HPA功能障碍的模式，如通过这种标准化的实验室检测，可能是一个稳定的情绪和焦虑症的内在表型信号。越来越多的临床前文献，描述了持续的神经内分泌和行为后果暴露于压力在早期发展，提供了一个概念性的机制，这种HPA活动过度可能存在于成年人谁暴露于逆境中的早期生活。我们的初步数据表明，自我报告的评级的压力在儿童时期预测皮质醇反应的DEX/CRH测试在健康成人没有目前的精神病理学。DEX/CRH皮质醇高反应性的存在，以及某些已知的风险因素，如在早期生活中暴露于显著的压力源，积极的心境障碍家族史，并具有一定的认知风格，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风险个体，并有助于预防。拟议的调查将产生关键数据的临床特征的非抑郁症，健康的个人谁有HPA活动过度的内表型，测量“高”皮质醇反应（HCR）的DEX/CRH测试。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。我们将回答有关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关系的性质是什么？它能预测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？它与医学发病率或生活质量有关吗？随着时间的推移，它是否稳定？这些信息为纵向研究提供了基础，以评估情感疾病潜在生物标志物的预测效用。