HPA axis dysregulation and phenomenology of depression

HPA 轴失调与抑郁症的现象学

• 批准号: 6915197
• 负责人: ERIK Bertil NELSON
• 金额: $ 18.23万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6915197
• 关键词: adrenocorticotropic hormone; anorexia; anxiety; arousal; behavioral /social science research tag; blood chemistry; clinical research; corticotropin releasing factor; cortisol; dexamethasone; fatigue; hormone regulation /control mechanism; human middle age (35-64); human subject; hypothalamic pituitary adrenal axis; major depression; overeating; patient oriented research; psychological stressor; psychological tests; psychophysiology; sign /symptom; sleep disorders; urinalysis; young adult human (21-34)

DESCRIPTION (provided by applicant): The aim of this NIMH Mentored Patient-Oriented Research Career Development Award application is to support my career objective to become an independent investigator specializing in the relationship between neurobiological mechanisms and clinical features of depression. My previous training focuses on phenomenological and treatment studies in mood disorders. Studies suggest that HPA dysregulation influences the presentation of depression related to melancholic and atypical symptom dimensions. A better understanding of the mechanisms underlying these differences could lead to novel targets for the treatment of depression, and help to explain variability among neuroendocrine studies that typically included heterogeneous samples with regard to depressive subtypes. Toward this end, I have proposed a training plan that includes obtaining expertise in the neurobiology of HPA dysregnlation in depression, statistical design and analysis of studies integrating biological and clinical data, and human research ethics. The research plan includes assessing HPA activity and measures of acute stress responses in healthy volunteers and depressed patients as they relate to melancholic and atypical symptom dimensions. The hypothesis is that elevated HPA axis activity in depression is associated with hyperarousal and anorexia in melancholia, whereas low HPA activity is linked with fatigue and hyperphagia in atypical depression. Moreover, increased HPA activity and melancholic symptoms are hypothesized to correlate with greater response to the Trier Social Stress Test (TSST), whereas low HPA activity and atypical symptoms are hypothesized to correlate with a decreased stress response to the TSST. These hypotheses will be tested by collection of 24-hour urinary free cortisol, and plasma cortisol and ACTH levels in depressed patients in three separate conditions: one-hour serial collections in the morning and evening; after a neuroendocrine challenge used to assess central HPA drive (DEX/CRH test); and in response to the TSST. This study will be conducted in two highly productive research settings, the Biological Psychiatry and Bipolar and Psychotic Disorder Research Programs of the University of Cincinnati Dept. of Psychiatry. The proposed training and research plans will foster my development as an independent researcher in the areas described above, and increase our understanding of the neurobiology related to the symptom profiles associated with depressive subtypes.

描述（由申请人提供）：这种NIMH指导的以患者为导向的研究职业发展奖的目的是支持我的职业目标，成为一名独立研究者，专门研究神经生物学机制和抑郁症的临床特征之间的关系。我以前的培训重点是情绪障碍的现象学和治疗研究。研究表明，HPA失调会影响与忧郁和非典型症状维度有关的抑郁症的介绍。对这些差异的基础机制有更好的了解可能导致抑郁症治疗的新靶标，并有助于解释神经内分泌研究的变异性，这些研究通常包括抑郁症亚型的异质样本。为此，我提出了一项培训计划，其中包括获得抑郁症，统计设计和整合生物学和临床数据的研究的HPA临床诊断，统计设计和分析的专业知识，以及人类研究伦理。该研究计划包括评估健康志愿者和抑郁症患者急性应激反应的度量，因为它们与忧郁症和非典型症状维度有关。假设是，抑郁症的HPA轴活动升高与忧郁症中的高阳极和厌食症有关，而低HPA活性与非典型抑郁症的疲劳和倍率有关。此外，假设HPA活性增加和忧郁症症状与对Trier社会压力测试（TSST）的反应更大相关，而HPA活性低和非典型症状则被认为与对TSST的压力降低相关。这些假设将通过在抑郁症患者的三个不同条件下收集24小时的无尿皮质醇以及血浆皮质醇和ACTH水平来测试：早晨和晚上的一小时连续收集；在用于评估中央HPA驱动器（DEX/CRH测试）的神经内分泌挑战之后；并回应TSST。这项研究将在辛辛那提大学精神病学系的两个高生产性研究环境中进行，即生物精神病学和躁郁症和精神病研究计划。拟议的培训和研究计划将促进我作为上述领域的独立研究人员的发展，并增强我们对与抑郁症相关的症状特征相关的神经生物学的理解。