HPA axis dysregulation and phenomenology of depression

HPA 轴失调与抑郁症的现象学

• 批准号: 7243449
• 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/7243449
• 关键词: Acute; Agitation; Anorexia; Anxiety; Area; Atypical depressive disorder; Biological; Biological Psychiatry; Biology; Body Weight decreased; Characteristics; Clinical; Clinical Data; Collection; Condition; Corticotropin; DSM-IV; Depressed mood; Desire for food; Development; Dexamethasone; Dimensions; Disease; Esthesia; Exhibits; Fatigue; Fostering; Functional disorder; Future; Goals; Guilt; HPSE gene; Hormones; Hour; Human; Hydrocortisone; Hyperactive behavior; Hyperphagia; Investigation; Laboratories; Lead; Learning; Limb structure; Link; Major Depressive Disorder; Measures; Mental Depression; Mentored Patient-Oriented Research Career Development Award; Monoamine Oxidase Inhibitors; Mood Disorders; Moods; National Institute of Mental Health; Neurobiology; Neurosecretory Systems; Patients; Peripheral; Phenotype; Plasma; Protocols documentation; Psychiatry; Psychotic Disorders; Reporting; Research; Research Design; Research Ethics; Research Personnel; Research Training; Sampling; Score; Sleeplessness; Stress; Symptoms; Testing; Training; Tricyclic Antidepressive Agents; Trier Social Stress Test; United States Environmental Protection Agency; Universities; Weight Gain; acute stress; biological adaptation to stress; biological research; career; depressive symptoms; design; driving force; healthy volunteer; hypothalamic-pituitary-adrenal axis; increased appetite; neurobiological mechanism; neurophysiology; novel; programs; response; social; stressor; tool; urinary

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）：这个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，成为一名独立的研究者，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。我以前的训练集中在情绪障碍的现象学和治疗研究。研究表明，HPA失调影响抑郁症的表现与抑郁症和非典型症状的维度。更好地理解这些差异的机制可能会导致抑郁症治疗的新靶点，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性样本。为此，我提出了一个培训计划，包括获得抑郁症HPA失调的神经生物学专业知识，整合生物学和临床数据的研究的统计设计和分析，以及人类研究伦理。研究计划包括评估健康志愿者和抑郁症患者的HPA活性和急性应激反应的措施，因为它们与抑郁症和非典型症状维度有关。该假说认为，抑郁症中HPA轴活性升高与抑郁症中的过度觉醒和厌食有关，而HPA轴活性降低与非典型抑郁症中的疲劳和暴食有关。此外，假设HPA活性增加和抑郁症状与对特里尔社会应激测试（TSST）的更大反应相关，而假设低HPA活性和非典型症状与对TSST的应激反应降低相关。这些假设将通过在三种不同条件下收集抑郁症患者的24小时尿游离皮质醇、血浆皮质醇和ACTH水平进行检验：在早晨和晚上连续收集1小时;用于评估中枢HPA驱动的神经内分泌激发后（DEX/CRH试验）;以及对TSST的反应。本研究将在两个高生产力的研究环境中进行，即辛辛那提大学系的生物精神病学和双相情感障碍研究项目。精神病学。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。