HPA Axis in Depression and Anxiety

描述：（申请人摘要）这是一个研究科学家奖 应用程序.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， 萧条本申请中提出的未来研究将继续进行， 探索抑郁症和相关焦虑症的激素异常 恐慌症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， 特别是恐慌症，伴随着中枢神经系统的异常， 去甲肾上腺素能系统，反映了迟钝的生长激素反应， 可乐定本提案的具体研究目标是：（I）确定 中枢去甲肾上腺素能系统的异常存在于两个纯 抑郁症、单纯恐慌症和抑郁症加恐慌症。我们将 研究了一组特征明确的纯抑郁、纯恐慌和混合恐慌患者 和抑郁症患者的可乐定/生长激素挑战，以确定 如果所有的抑郁症患者都表现出可乐定刺激生长的异常， 激素释放或如果只有那些与共病恐慌症状表现出这一点 异常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查24小时尿皮质醇 排泄，在纯抑郁、纯恐慌和 混合着恐慌和抑郁的病人3)评价去甲肾上腺素能和HPA轴 “反应性"两个简单的挑战，在纯粹的抑郁症，抑郁症加上 焦虑、惊恐障碍患者和正常对照。这些挑战包括 直立挑战和特里尔社会压力测试（TSST）。我们假设 恐慌症患者和抑郁症患者的共病焦虑， 证明对直立性挑战的过度的儿茶酚胺反应，即 增加反应性。我们假设抑郁症患者会发生改变 HPA轴对应激反应的反应，而惊恐障碍患者将有 正常HPA轴对TSST的反应。4）确定是否存在异常 基础HPA轴失调，对应激反应过度， 对可乐定-生长激素激发的反应研究发生在相同的 如果这些生物学研究的结果支持 惊恐障碍、单纯重度抑郁症和重度抑郁症之间的疾病分类学区别 抑郁症伴惊恐障碍。最后，我们将研究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 障碍，多为特定的情绪和焦虑障碍。关于 PTSD，我们将探讨尿游离皮质醇的减少和尿游离皮质醇的增加 尿中儿茶酚胺存在于受试者流行病学样本中 暴露于有或没有创伤后应激障碍的创伤和未暴露于 没有精神障碍的创伤患者。

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.