Dex/CRH Response: Mood/Anxiety Disorder Endophenotype?

Dex/CRH 反应：情绪/焦虑症内表型？

• 批准号: 7730258
• 负责人: LINDA L CARPENTER
• 金额: $ 58.9万
• 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 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7730258
• 关键词: Accounting; Adult; Age; Alleles; Anxiety; Anxiety Disorders; Biological; Biological Markers; Brain-Derived Neurotrophic Factor; CRH gene; Candidate Disease Gene; Characteristics; Child Abuse and Neglect; Clinical; Data; Databases; Detection; Development; Diagnostic; Disease; Emotional; Enrollment; Event; Family history of; Female; Funding; Future; Gender; Genes; Genetic Polymorphism; Genotype; Goals; Health; Hormones; Hydrocortisone; Individual; Intervention; Interview; Laboratories; Life; Longitudinal Studies; Major Depressive Disorder; Measures; Mental Health; Mental disorders; Modeling; Mood Disorders; Moods; Neurosecretory Systems; Onset of illness; Outcome; Outpatients; Patient Self-Report; Pattern; Personality; Phase; Pilot Projects; Prospective Studies; Public Health; Quality of life; Recording of previous events; Recruitment Activity; Relative (related person); Research; Risk; Risk Factors; Role; Severities; Signal Transduction; Stress; Symptoms; Syndrome; Testing; Time; Work; clinical phenotype; cohort; cost; depression; endophenotype; environmental stressor; experience; follow-up; gene environment interaction; improved; indexing; prevent; programs; prospective; psychologic; public health relevance; response; stressor

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.

描述（由申请人提供）：本研究代表了正在进行的题为“Dex/CRH反应：情绪和焦虑障碍内表型？“（5 R01 MH068767）。第一阶段是一个横断面的，前瞻性的研究模式的激素（皮质醇）的反应，以标准的实验室测试在健康成人。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。第二阶段是对200名成年人进行的前瞻性纵向研究，以批判性地评估Dex/CRH测试反应在前瞻性预测5-10年的情绪健康结果中的作用。在5年的资助期间，将对200名没有可诊断精神疾病的成年人进行随访，这些人已经完成了基线Dex/CRH测试，并在我们的实验室进行了广泛的访谈和自我报告评估。受试者历史信息（早期生活逆境史，精神健康障碍家族史），生物学数据（Dex/CRH皮质醇反应，候选基因多态性），心理数据（个性特征，弹性特征）对正在进行的和新的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的复杂相互作用，因为它们涉及到阈值（即，可诊断障碍的发作）和随时间推移的阈下情绪健康结果。这项研究计划的首要目标是开发一种有用的生物标志物，可以在标准的门诊实验室环境中进行测量。我们认为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可能具有实用价值，这些症状会对个体的生活质量和功能产生有意义的影响。该研究的目的是检查拟议的内在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，评估候选基因的作用与内在表型相关，并阐明在一个内表型组中出现的症状/病症是否与在另一组中观察到的症状/病症在性质上不同。公共卫生相关性：情绪和焦虑症是常见的和致残的公共卫生问题。通过标准实验室测试获得的有效生物标志物可以预测发展这些疾病的风险，可以广泛用于评估健康成人的风险，并针对可能预防疾病发作或以其他方式改善随后的心理健康和福祉的干预措施。