Dex/CRH Response: Mood/Anxiety Disorder Endophenotype?

描述(申请人提供)：这项研究是正在进行的项目“Dex/CRH反应：情绪和焦虑障碍内表型？”的第二阶段工作(5 R01 MH068767)。第一阶段是对健康成年人的激素(皮质醇)对标准实验室测试的反应模式的横断面前瞻性研究。来自第一阶段的初步数据表征了不同类别的皮质醇反应(“内表型”)，并证实了这种生物标记物在检测情绪障碍发展风险方面的巨大潜力。第二阶段是一项对200名成年人进行的前瞻性纵向研究，旨在批判性地评估Dex/CRH测试反应在预测5-10年情绪健康结果中的作用。在5年的资助期间，将对200名没有可诊断的精神障碍的成年人进行队列调查，他们已经在我们的实验室完成了基线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、候选基因多态)、心理数据(人格特征、弹性特征)以及对持续和新的环境应激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的复杂交互作用，因为它们与阈值(即可诊断疾病的发病)和阈值以下的情绪健康结果有关。这项研究计划的首要目标是开发一种有用的生物标记物，可以在标准的门诊实验室中进行测量。我们相信，Dex/CRH测试在预测个人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可能具有实用价值，这些症状对个人的生活质量和功能产生有意义的影响。本研究的目的是检验所提出的内表型作为多维模型的一部分独立预测结果的能力，确定Dex/CRH反应是否反映了个体对当代生活应激源的敏感性，评估候选基因与内表型相关的作用，并阐明在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/障碍有本质上的不同。公共卫生相关性：情绪和焦虑症是常见的、使人丧失能力的公共卫生问题。通过标准的实验室测试可以获得的有效生物标记物可以预测发生这些疾病的风险，可以广泛用于评估健康成年人的风险，并针对可能预防疾病发病或以其他方式改善随后的心理健康和福祉过程的干预措施。

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. PUBLIC HEALTH RELEVANCE: Mood and anxiety disorders are common and disabling public health problems. A valid biomarker obtainable with a standard laboratory test, that could predict risk for developing these conditions, could be widely used to assess risk in healthy adults and target interventions that might prevent the disorder onset or otherwise improve the ensuing course of mental health and wellbeing.