BIOLOGY OF COMORBID DEPRESSION AND ANXIETY

描述(改编自申请者摘要)：本次资助申请 重点关注情绪、焦虑症和意志障碍的压力生物学 为测试焦虑和抑郁模型提供关键的神经内分泌数据 在具体目标中提出的共病状态。当前的研究 说明抑郁症伴有下丘脑轴的异常， 而焦虑症，特别是恐慌症，会伴随着 中央NA系统异常，表现为生长迟钝 激素(GH)对可乐定的反应。这方面的具体研究目标是 应用范围为：1)确定中枢NA系统异常是否 出现在单纯抑郁症、单纯惊恐障碍和抑郁症加 恐慌症。调查员将研究一组很有特色的 单纯抑郁、纯粹恐慌和混合恐慌与抑郁的患者 可乐定/生长激素试验确定是否所有抑郁症患者都表现出来 可乐定的异常刺激了GH的释放，或者仅仅是那些 共病的恐慌症状体现了这种异常。2)确定是否 惊恐障碍患者HPA轴分泌异常激活 在抑郁症患者中也是如此。调查员将24小时进行检查 无尿皮质醇(UFC)排泄量，按8小时分段收集，纯 抑郁、纯粹的恐慌和混合的恐慌和抑郁的患者。3)至 评估NA和HPA轴对两个简单挑战的反应性 抑郁、抑郁加焦虑、惊恐障碍患者和正常 控制。这些挑战是直立挑战和Trier Social 压力测试(TSST)。调查员假设恐慌症 患有共病焦虑的患者和抑郁症患者将展示 对立位挑战的夸大儿茶酚胺反应，即增加 反应性。研究人员假设抑郁症患者将会有 HPA轴对压力的反应改变，而恐慌症患者将 正常HPA轴对TSST的反应。4)确定基础HPA轴是否 调节、对应激源的反应和对可乐定-生长激素挑战的反应是 在个体内部相互关联，如果这两者之间的关系 系统(HPA和儿茶酚胺)会因疾病状态而改变。最后， 研究人员将评估HPA轴和NA功能障碍的假设 反映一个共同的因素，损害的程度，而不是一个特定的情绪和 焦虑症。这些研究的结果将提供数据，说明 这些疾病的生物学特征支持病因学上的区别 惊恐障碍、单纯重度抑郁和重度抑郁伴共病 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.