Dex/CRH Response: Mood/Anxiety Disorder Endophenotype?

Dex/CRH 反应：情绪/焦虑症内表型？

• 批准号: 7893657
• 负责人: LINDA L CARPENTER
• 金额: $ 56.42万
• 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/7893657
• 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 Depression; 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; 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项目的第二阶段，标题为“ DEX/CRH响应：情绪和焦虑症的内型？”？ （5 R01 MH068767）。第一阶段是对健康成年人对标准实验室测试的激素（皮质醇）反应的横断面的前瞻性研究。第一阶段的初步数据表征了不同类别的皮质醇反应（“内型型”），并确认了该生物标志物在检测情绪障碍发展风险方面具有价值的巨大潜力。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5 - 10年以来预测情绪健康结果中的作用。在5年的资助期间，将遵循200名没有可诊断的精神病患者的200名成年人，这些成年人没有可诊断的精神疾病，他们在我们的实验室中进行了大量的访谈和自我报告评估。受试者的历史信息（早期生命逆境的历史，心理健康疾病的家族史），生物学数据（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）和持续的环境压力和新的环境压力的纵向评估，可以在富裕的数据库中进行研究，从而可以进行这些相互作用，从而使这些相互作用的相互作用（这些相互作用）是相互作用的（这些相互作用）（这些相互作用的互动）（这些相互作用）（这些相互作用）（这些相互作用）（这些相互作用）的变量（既可以进行）。随着时间的流逝，可诊断障碍的发作）和亚阈值情绪健康结果。该研究计划的总体目标是开发有用的生物标志物，可以在标准的门诊实验室环境中进行衡量。我们认为，DEX/CRH测试可能具有实践价值，可以预测个人经历常见和致残的心理健康障碍或副症状的风险水平，这些症状有意义地影响个人的生活质量和功能。 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在另一组中观察到。公共卫生相关性：情绪和焦虑症是普遍的，并且使公共卫生问题禁用。可以通过标准实验室测试获得的有效生物标志物可以预测开发这些疾病的风险，可以广泛用于评估健康的成年人的风险和目标干预措施，从而可以防止疾病发作或以其他方式改善随后的心理健康和福祉的过程。