HPA Axis in Depression and Anxiety

HPA 轴在抑郁和焦虑中的作用

• 批准号: 6882703
• 负责人: ELIZABETH ANN YOUNG
• 金额: $ 12.83万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6882703
• 关键词: anxiety disorders; clinical depression; clonidine; comorbidity; cortisol; hormone regulation /control mechanism; human subject; hypothalamic pituitary adrenal axis; norepinephrine; panic disorder; patient oriented research; physiologic stressor; posttraumatic stress disorder; psychological stressor; psychological tests; somatotropin; urinalysis

DESCRIPTION: (Applicant's abstract) This is a Research Scientist Award Application. I have received 15 years of salary support through the RSDA program and have become a leader in the area of HPA axis regulation in depression. Future studies proposed in this application will continue to explore hormonal abnormalities in depression and also in related anxiety disorders, panic disorder and PTSD. Current research indicates that depression is accompanied by abnormalities of the HPA axis, while anxiety disorders, particularly Panic Disorder, is accompanied by abnormalities of the central noradrenergic system, as reflected by a blunted growth hormone response to clonidine. Specific research aims in this proposal are I) to determine if abnormalities of central noradrenergic system are present in both pure depression, pure panic disorder and depression plus panic disorder. We will study a group of well characterized pure depressed, pure panic and mixed panic and depressed patients with the clonidine/growth hormone challenge to determine if all depressed patients manifest abnormalities in clonidine stimulated growth hormone release or if only those with co-morbid panic symptoms manifest this abnormality. 2) To determine if abnormal activation of HPA axis secretion occurs in Panic Disorder patients. We will examine 24 hr urinary cortisol excretion, collected in 8 hrs segments in pure depressed, pure panic and and mixed panic and depressed patients. 3) To evaluate noradrenergic and HPA axis 'reactivity' to two simple challenges in pure depression, depression plus anxiety, panic disorder patients and normal controls. These challenges include orthostatic challenge and the Trier Social Stress Test (TSST). We hypothesize that panic disorder patients and depressed patients with co-morbid anxiety will demonstrate exaggerated catecholamine response to orthostatic challenge i.e increased reactivity. We hypothesize that depressed patients will have altered HPA axis responses to stress response while Panic Disorder patients will have normal HPA axis response to the TSST. 4 ) To determine if the abnormalities in basal HPA axis dysregulation, exaggerated responses to stress and blunted response to clonidine-growth hormone challenge studies occur in the same individuals and if the results of these biological studies support the nosological distinction between Panic Disorder, pure Major Depression and Major Depression with co-morbid Panic Disorder. Finally we will examine whether HPA axis and noradrenergic dysfunction reflect a common factor, degree of impairment, more than a specific mood and anxiety disorder. With regards to PTSD, we will explore whether decreases in urinary free cortisol and increases in urinary catecholamines are present in epidemiological sample of subjects exposed to trauma both with and without PTSD and normal subjects not exposed to trauma who are free of Psychiatric disorders.

描述：（申请人的摘要）这是研究科学家奖 应用。我通过RSDA获得了15年的薪水支持 计划并已成为HPA轴法规领域的领导者 沮丧。该应用程序中提出的未来研究将继续 探索抑郁症和相关焦虑的激素异常 疾病，恐慌症和PTSD。当前的研究表明抑郁症 伴随着HPA轴的异常，而焦虑症， 特别是恐慌症，伴随着中央的异常 去甲肾上腺素能系统，由生长激素对 可乐定。该提案中的具体研究目的是i）确定是否是否 中央去甲肾上腺素能系统的异常存在于纯净 抑郁症，纯粹的恐慌和抑郁症以及恐慌症。我们将 研究一组表征纯净的抑郁，纯恐慌和混合恐慌 以及抑郁患者患有可乐定/生长激素挑战的患者以确定 如果所有抑郁症患者表现出异常，可乐定刺激生长 激素释放，或者只有合并恐慌症状的激素表现出来 紊乱 etc。 2）确定HPA轴分泌异常激活是否异常 发生在恐慌症患者中。我们将检查24小时的尿皮质醇 排泄物，在纯凹陷，纯粹的恐慌和 混合恐慌和抑郁的患者。 3）评估去甲肾上腺素和HPA轴 纯抑郁症，抑郁症加上两个简单挑战的“反应性” 焦虑，恐慌症患者和正常对照。这些挑战包括 体位挑战和Trier社会压力测试（TSST）。我们假设 恐慌症患者和抑郁症患者合并焦虑症将 证明对体位挑战的夸大儿茶酚胺反应，即 反应性提高。我们假设抑郁的患者将改变 HPA轴对压力反应的反应，而恐慌症患者将具有 正常的HPA轴对TSST的响应。 4）确定是否异常 基底HPA轴失调，对压力的夸张反应和钝性 对可乐定生长激素挑战研究的反应发生在同一 个人以及这些生物学研究的结果支持 恐慌症，纯粹的严重抑郁症和重大疾病之间的病态学区别 抑郁症患有恐慌症。最后，我们将检查HPA是否 轴和去甲肾上腺功能障碍反映了一个共同的因素，程度 损害，不仅仅是特定的情绪和焦虑症。关于 PTSD，我们将探索是否减少无尿皮质醇并增加 在尿中的儿茶酚胺中存在于受试者的流行病学样本中 在有或没有PTSD和正常受试者的情况下暴露于创伤 没有精神疾病的创伤。