HPA Axis in Depression and Anxiety

描述：(申请者摘要)这是研究科学家奖 申请。我通过RSDA获得了15年的工资支持 计划，并已成为HPA轴调节领域的领导者 抑郁症。本申请中提出的未来研究将继续 探讨抑郁症和相关焦虑的激素异常 精神障碍、惊恐障碍和创伤后应激障碍。目前的研究表明，抑郁症 伴随着HPA轴的异常，而焦虑症， 尤其是恐慌性障碍，是伴随着中枢的异常 去甲肾上腺素能系统，反映在生长激素对 可乐定。该提案中的具体研究目的是：i)确定 中枢去甲肾上腺素能系统异常在两者中都存在 抑郁、单纯惊恐障碍和抑郁加惊恐障碍。我们会 研究一组特征良好的纯抑郁、纯恐慌和混合恐慌 和抑郁症患者用可乐定/生长激素的挑战来确定 如果所有抑郁症患者都表现出可乐定刺激生长的异常 荷尔蒙释放，或者只有那些有共同恐慌症状的人才会表现出这一点 反常现象。2)确定HPA轴分泌是否异常激活 发生在恐慌症患者身上。我们将检测24小时尿皮质醇 排泄物，在纯粹的沮丧、纯粹的恐慌和和 混杂着恐慌和抑郁的病人。3)评估去甲肾上腺素能轴和HPA轴 对单纯抑郁症的两个简单挑战--抑郁症+ 焦虑、惊恐障碍患者和正常对照组。这些挑战包括 立位挑战和特里尔社会压力测试(TSST)。我们假设 恐慌症患者和患有共病焦虑的抑郁症患者会 展示对立位挑战的夸大儿茶酚胺反应，即 增加了反应性。我们假设抑郁症患者会改变 HPA轴对应激反应的反应而恐慌症患者将有 正常HPA轴对TSST的反应。4)以确定是否存在异常 基础HPA轴失调，对应激反应夸大和迟钝 对可乐定-生长激素挑战的反应研究也在同一 如果这些生物学研究的结果支持 惊恐障碍、单纯抑郁症和重度抑郁症的病因学区别 抑郁症伴发恐慌症。最后，我们将检查HPA是否 轴和去甲肾上腺素能功能障碍反映了一个共同的因素，程度 精神障碍，不仅仅是一种特定的情绪和焦虑障碍。关于…… ，我们将探讨尿中游离皮质醇是否减少和增加 尿中儿茶酚胺存在于受试者的流行病学样本中 暴露于创伤后应激障碍和非创伤后应激障碍以及正常受试者 没有精神障碍的精神创伤患者。

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.