Effects of comorbid anxiety disorders on the HPA axis profile of depression

共病情绪和焦虑障碍是一种常见的发生在精神病人群。临床 抑郁症的病程和对抑郁症治疗的反应在存在共病焦虑的情况下更差 disorder.我们以前的数据使用应激激活HPA轴，证明ACTH应激 抑郁症和社交焦虑障碍（SAD）共病者的反应性增加 与正常受试者相比，以及纯重性抑郁症（MDD）。儿童受虐待妇女研究 而MDD发现对相同的应激源TSST也有类似的夸大反应。这些数据表明 早发性焦虑症和创伤可显示类似的增加的应激反应。其他人的研究 提示早期创伤和MDD导致对地塞米松敏感性增加， 在传统的抑郁症患者中观察到的。在本建议中，我们将评估是否增加反应性的 在共病情绪和焦虑障碍中，HPA轴对TSST的作用也伴随着基础水平的增加， 活性，如通过ACTH对甲吡酮的反应所评估的，这是一种纯粹的“内分泌”挑战。此外我们 将评价相同受试者对地塞米松负反馈的反应，以确定是否 增加的应激反应性与抑制系统的失败有关，或者这两种现象是否 独立的我们将检查创伤的时间（成人与儿童），以确定不同的模式是否 创伤后应激障碍和抑郁症患者HPA轴的失调与创伤时间有关 exposure.我们还将通过比较合并MDD+的结果来检查创伤的特异性。 PTSD组与MDD合并早发SAD组比较。我们假设所有的共病焦虑 疾病将导致对TSST的过度应激反应，但早期创伤或早期发作的MDD SAD将显示正常的PM驱动（如通过甲吡酮评估的）和对地塞米松的夸大反馈。 我们进一步假设，只有成人创伤继发的伴有PTSD的MDD患者基础驱动力增加 减少了对地塞米松的负反馈，这是典型的MDD模式。最后，我们假设 单纯MDD将显示甲吡酮反应增加，对地塞米松不敏感和正常反应 到TTST。这些数据将进一步加深我们对创伤对HPA轴的影响和时间的理解 强调反应性和反馈。暴露于一种类型的压力源，创伤，可以导致创伤后应激障碍，但仍然存在争议， 创伤后应激障碍有任何特征性的应激激素变化本提案将探讨是否首次 创伤，即儿童与成人，导致不同的后果基础分泌的应激激素 在晚上和反馈敏感性的变化，地塞米松，一种合成化合物类似于 皮质醇我们还将探讨创伤的时间是否会改变公众演讲时的应激激素反应 挑战.

Comorbid mood and anxiety disorders are a frequent occurence in psychiatric populations. The clinical course of depression and response to treatment of depression is worse in the presence of a comorbid anxiety disorder. Our previous data using a stressor to activate the HPA axis, demonstrated that ACTH stress reactivity was increased in subjects with comorbid major depression and social anxiety disorder (SAD) compared to normal subjects, and pure major depression (MDD). Studies of women with childhood abuse and MDD found a similar exaggerated response to the same stressor, the TSST. These data suggest that early onset anxiety disorders and trauma may show similar increased stress reactivity. Studies by others suggest that early trauma and MDD leads to increased sensitivity to dexamethasone, the opposite of what is observed in traditional depressed patients. In this proposal we will evaluate whether increased reactivity of the HPA axis to the TSST in comorbid mood and anxiety disorders is also accompanied by increased basal activity, as assesed by the ACTH response to metyrapone, a purely "endocrine" challenge. In addition we will evaluate the response to dexamethasone negative feedback in the same subjects to determine if increased stress reactivity is linked to failure of the inhibitory systems or whether these two phenomenon are independent. We will examine if timing of trauma (adult vs childhood) to determine if different patterns of HPA axis dysregulation are observed in patients with PTSD and MDD dependent upon the time of trauma exposure. We will also examine the specificity of trauma by comparint the results in the comorbid MDD plus PTSD groups to a comorbid MDD plus early onset SAD group. We hypothesize that all comorbid anxiety disorders will lead to exaggerated stress response to the TSST but that MDD with early trauma or early onset SAD will show normal PM drive (as assessed by metyrapone) and exaggerated feedback to dexamethasone. We further hypothesize that MDD with PTSD secondary to adult trauma only will show increased basal drive and decreased negative feedback to dexamethasone, the classic MDD pattern. Finally, we hypothesize that pure MDD will show increased metyrapone response, insensitivity to dexamethasone and a normal response to the TTST. These data will further our understanding of the effects and timing of trauma on the HPA axis stress reactivity and feedback. Exposure to one type of stressor, a trauma, can lead to PTSD but controversy still exists as to whether there are any characteristic stress hormone changes with PTSD. This proposal will explore if timing of first trauma, i.e. childhood versus adult, leads to different consequences on basal secretion of stress hormones in the evening and to changes in feedback sensitivity to dexamethasone, a synthetic compound similar to cortisol. We will also explore if timing of trauma changes the stress hormone response to a public speaking challenge.