BIOLOGY OF COMORBID DEPRESSION AND ANXIETY

描述（改编自申请人的摘要）：本补助金申请 专注于情绪和焦虑症的压力生物学， 提供关键的神经内分泌数据来测试焦虑和抑郁模型， 具体目标中提出的共病状态。 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， 中央NA系统异常，如钝性生长所反映的 激素（GH）反应可乐定。 具体研究目的在此 应用是：1）确定是否异常的中央NA系统， 存在于单纯的抑郁症，单纯的恐慌症和抑郁症加 恐慌症 研究者将研究一组充分表征的 单纯性抑郁症、单纯性恐慌症和混合性恐慌症与抑郁症患者 可乐定/GH激发，以确定是否所有抑郁症患者都表现出 可乐定刺激GH释放的异常，或者如果只有那些 共病的惊恐症状表现出这种异常。 2)以确定是否 惊恐障碍患者HPA轴分泌异常激活 以及抑郁症患者。 调查员将24小时检查 尿游离皮质醇（UFC）排泄，在纯 抑郁症、单纯性恐慌症、混合性恐慌症和抑郁症患者。 3)到 评估NA和HPA轴的“反应性”，以两个简单的挑战，在纯 抑郁症、抑郁症加焦虑症、惊恐障碍患者和正常人 对照 这些挑战是直立挑战和特里尔社会 应力测试（TSST）。 研究者假设恐慌症 患者和抑郁症患者的共病焦虑将证明， 对直立性挑战的过度的儿茶酚胺反应，即，增加 反应性 研究人员假设抑郁症患者会有 改变HPA轴对压力的反应，而惊恐障碍患者将有 正常HPA轴对TSST的反应。 4)为了确定基础HPA轴是否 调节、应激反应和对可乐定-GH激发的反应， 如果这两者之间的关系 系统（HPA和儿茶酚胺）被疾病状态改变。 最后 研究者将评估HPA轴和NA功能障碍 反映了一个共同的因素，损害程度，比一个特定的情绪和 焦虑症 这些研究的结果将提供数据， 这些疾病的生物学支持疾病分类学上的区别， 惊恐障碍、单纯重性抑郁症和重性抑郁症伴共病 恐慌症

DESCRIPTION (Adapted from applicant's abstract): This grant application focuses upon the stress biology of mood and anxiety disorders and will provide key neuroendocrine data to test models of anxiety and depression and the co-morbid state proposed in the Specific Aims. 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 NA system, as reflected by a blunted growth hormone (GH) response to clonidine. Specific research aims in this application are: 1) to determine if abnormalities of central NA system are present in both pure depression, pure panic disorder and depression plus panic disorder. The investigator will study a group of well characterized pure depressed, pure panic and mixed panic and depressed patients with the clonidine/GH challenge to determine if all depressed patients manifest abnormalities in clonidine stimulated GH 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 as well as in depressed patients. The investigator will examine 24 hour urinary-free cortisol (UFC) excretion, collected in 8 hour segments in pure depressed, pure panic and mixed panic and depressed patients. 3) To evaluate NA and HPA axis "reactivity" to two simple challenges in pure depression, depression plus anxiety, panic disorder patients and normal controls. These challenges are orthostatic challenge and the Trier Social Stress Test (TSST). The investigator hypothesizes that panic disorder patients and depressed patients with co-morbid anxiety will demonstrate exaggerated catecholamine response to orthostatic challenge, i.e., increased reactivity. The investigator hypothesizes that depressed patients will have altered HPA axis responses to stress while panic disorder patients will have normal HPA axis response to the TSST. 4) To determine if basal HPA axis regulation, responses to stressor and response to clonidine-GH challenge are correlated within individuals and if the relationship between these two systems (HPA and catecholamine) is altered by disease state. Finally, the investigator will evaluate the hypothesis that HPA axis and NA dysfunction reflect a common factor, degree of impairment, more than a specific mood and anxiety disorder. The results of these studies will provide data on whether the biology of these disorders support the nosological distinction between panic disorder, pure major depression and major depression with co-morbid panic disorder.