Dex/CRH Response: Mood/Anxiety Disorder Endophenotype?

描述（由申请人提供）：本研究是正在进行的项目“Dex/CRH反应：情绪和焦虑障碍的内表型？”的第二阶段工作。（5 r01 mh068767）。第一阶段是对健康成人标准实验室测试中激素（皮质醇）反应模式的横断面前瞻性研究。第一阶段的初步数据表征了不同类型的皮质醇反应（“内表型”），并证实了这种生物标志物在检测情绪障碍发展风险方面具有相当大的潜力。第二阶段是一项对200名成年人的前瞻性纵向研究，以批判性地评估Dex/CRH测试反应在前瞻性预测5-10年情绪健康结果中的作用。在5年的资助期内，200名没有诊断出精神疾病的成年人将在我们的实验室完成基线Dex/CRH测试和广泛的访谈和自我报告评估。受试者的历史信息（早期生活逆境史、精神健康障碍家族史）、生物数据（Dex/CRH皮质醇反应、候选遗传多态性）、心理数据（人格特征、弹性特征）以及对持续和新环境压力源的纵向评估将汇集在一个丰富的数据库中，该数据库允许检查这些变量之间复杂的相互作用，因为它们与阈值(即，可诊断障碍的发作)和阈下情绪健康结果随时间的变化。这项研究计划的首要目标是开发一种有用的生物标志物，可以在标准门诊实验室环境中测量。我们相信，Dex/CRH测试在预测个体经历常见和致残性精神健康障碍或亚综合征症状的风险水平方面具有实用价值，这些症状会对个体的生活质量和功能产生重大影响。本研究的目的是检验提出的内表型独立预测结果的能力，并作为多维模型的一部分，确定Dex/CRH反应是否反映了个体对当代生活压力源的敏感性，评估候选基因在内表型中的作用，并阐明一个内表型组中出现的症状/障碍是否与另一组中观察到的症状/障碍在质量上不同。

DESCRIPTION (provided by applicant): This study represents the second phase of work on an ongoing project entitled "Dex/CRH Response: Mood and Anxiety Disorder Endophenotype?" (5 R01 MH068767). The first phase is a cross-sectional, prospective study of patterns of hormone (cortisol) response to a standard laboratory test in healthy adults. The preliminary data from the first phase characterized distinct classes of cortisol response ("endophenotypes"), and confirmed considerable potential for this biomarker to be valuable in detecting risk for development of mood disorders. The second phase is a prospective, longitudinal study of 200 adults to critically evaluate the role of Dex/CRH test response in prospectively predicting emotional health outcomes over 5-10 years. A cohort of 200 adults without diagnosable psychiatric disorders who have completed a baseline Dex/CRH test and an extensive battery of interview and self-report assessments in our laboratory will be followed during 5 years of funding. Subjects' historical information (history of early life adversity, family history of mental health disorders), biological data (Dex/CRH cortisol response, candidate genetic polymorphisms), psychological data (personality characteristics, resiliency features) and longitudinal assessment of ongoing and new environmental stressors will come together in a rich database which allows for examination of the intricate interactions between these variables as they relate to threshold (i.e., onset of diagnosable disorder) and subthreshold emotional health outcomes over time. The overarching goal of this research program is development of a useful biomarker that can be measured in a standard outpatient laboratory setting. We believe the Dex/CRH test could have practical value in forecasting an individual's level of risk for experiencing common and disabling mental health disorders or subsyndromal symptoms that meaningfully impact an individual's quality of life and functioning. The aims of the study are to examine the ability of the proposed endophenotype to predict outcomes independently and as part of a multidimensional model, to determine whether Dex/CRH response reflects individual sensitivity to contemporary life stressors, to evaluate the role of candidate genes in relation to the endophenotype, and to elucidate whether the symptoms/disorders which emerge in one endophenotype group are qualitatively different than those which are observed in the other group.