HPA axis dysregulation and phenomenology of depression

HPA 轴失调与抑郁症的现象学

• 批准号: 7092544
• 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/7092544
• 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）：NIMH 指导的以患者为导向的研究职业发展奖申请的目的是支持我的职业目标，成为一名专门研究神经生物学机制与抑郁症临床特征之间关系的独立研究者。我之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相关的抑郁症的表现。更好地理解这些差异背后的机制可能会产生治疗抑郁症的新靶点，并有助于解释神经内分泌研究中的变异性，这些研究通常包括抑郁亚型的异质样本。为此，我提出了一项培训计划，其中包括获得抑郁症 HPA 失调的神经生物学专业知识、整合生物和临床数据的研究的统计设计和分析以及人类研究伦理。该研究计划包括评估健康志愿者和抑郁症患者的 HPA 活动和急性应激反应测量，因为它们与忧郁和非典型症状维度相关。该假设认为，抑郁症患者的 HPA 轴活性升高与忧郁症的过度警觉和厌食有关，而 HPA 轴活性低则与非典型抑郁症的疲劳和食欲亢进有关。此外，HPA 活性增加和忧郁症状被假设与特里尔社会压力测试 (TSST) 的更大反应相关，而 HPA 活性低和非典型症状被假设与 TSST 压力反应降低相关。这些假设将通过在三种不同条件下收集抑郁症患者 24 小时尿游离皮质醇、血浆皮质醇和 ACTH 水平来检验：早上和晚上一小时连续收集；用于评估中枢 HPA 驱动力的神经内分泌挑战后（DEX/CRH 测试）；并响应 TSST。这项研究将在两个高效的研究环境中进行，即辛辛那提大学精神病学系的生物精神病学和双相情感障碍研究项目。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，并增加我们对与抑郁亚型相关的症状特征相关的神经生物学的理解。