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

共病焦虑症对抑郁症 HPA 轴特征的影响

• 批准号: 7754453
• 负责人: James L Abelson
• 金额: $ 34.2万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7754453
• 关键词: Acoustics; Adrenal Glands; Adult; Affect; Anxiety; Anxiety Disorders; Behavior; Biological; Biological Phenomena; Biology; CRH gene; Characteristics; Child Abuse; Childhood; Circadian Rhythms; Citalopram; Clinical; Clonidine; Communities; Comorbidity; Corticotropin; Data; Depressed mood; Development; Dexamethasone; Diagnosis; Disease; Disease remission; Early-life trauma; Employee Strikes; Endocrine; Epidemiology; Evaluation; Exposure to; Failure; Feedback; Female; Functional disorder; Genetic; Glucocorticoids; Hormones; Hydrocortisone; Hypothalamic structure; Lead; Life Stress; Link; Macaca mulatta; Major Depressive Disorder; Mediating; Mental Depression; Mental disorders; Metyrapone; Modeling; Mood Disorders; Moods; Neurobiology; Neurosecretory Systems; Odds Ratio; Patients; Pattern; Pituitary Gland; Population; Post-Traumatic Stress Disorders; Public Speaking; Recording of previous events; Reporting; Resistance; Risk; Risk Factors; Sampling; Secondary to; Somatotropin; Sorting - Cell Movement; Specificity; Stress; Study Subject; Substance abuse problem; Surveys; Symptoms; Syndrome; System; Testing; Time; Trauma; Trier Social Stress Test; Veterans; Woman; Work; animal data; base; biological adaptation to stress; burden of illness; central sensitization; combat; depressive symptoms; disease classification; early onset; high risk; hypothalamic-pituitary-adrenal axis; lifetime risk; male; maternal separation; nonhuman primate; noradrenergic; pediatric trauma; psychosocial; public health relevance; response; single episode major depressive disorder; social; stressor; treatment response

DESCRIPTION (provided by applicant): Comorbid mood and anxiety disorders are a frequent occurrence 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 assessed 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 phenomena 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 comparing 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. PUBLIC HEALTH RELEVANCE: 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.

描述（由申请人提供）：共病情绪和焦虑障碍在精神病人群中经常发生。如果存在共病焦虑症，抑郁症的临床病程和对抑郁症治疗的反应会更差。我们之前使用压力源激活 HPA 轴的数据表明，与正常受试者和纯粹的重度抑郁症 (MDD) 相比，患有重度抑郁症和社交焦虑症 (SAD) 共病的受试者的 ACTH 应激反应性增加。对遭受童年虐待和抑郁症的女性进行的研究发现，对同一压力源 TSST 也有类似的过度反应。这些数据表明，早发性焦虑症和创伤可能表现出类似的应激反应性增加。其他研究表明，早期创伤和抑郁症会导致对地塞米松的敏感性增加，这与传统抑郁症患者观察到的情况相反。在本提案中，我们将评估在共病情绪和焦虑症中 HPA 轴对 TSST 的反应性增加是否也伴随着基础活性的增加，如通过 ACTH 对甲吡酮（纯粹的“内分泌”挑战）的反应来评估。此外，我们将评估同一受试者对地塞米松负反馈的反应，以确定应激反应性增加是否与抑制系统的故障有关，或者这两种现象是否独立。我们将检查创伤发生的时间（成人与儿童），以确定是否根据创伤暴露时间在 PTSD 和 MDD 患者中观察到不同的 HPA 轴失调模式。我们还将通过比较共病 MDD 加 PTSD 组与共病 MDD 加早发 SAD 组的结果来检查创伤的特异性。我们假设所有合并的焦虑症都会导致对 TSST 的过度应激反应，但早期创伤或早发 SAD 的 MDD 将表现出正常的 PM 驱动力（通过美替拉酮评估）和对地塞米松的过度反馈。我们进一步假设，MDD 伴继发于成人创伤的 PTSD 只会表现出基础驱动力增加和对地塞米松的负反馈减少，这是典型的 MDD 模式。最后，我们假设纯 MDD 将表现出美替拉酮反应增加、对地塞米松不敏感以及对 TTST 的正常反应。这些数据将进一步我们了解创伤对 HPA 轴应激反应和反馈的影响和时间。暴露于一种压力源（创伤）可能导致 PTSD，但关于 PTSD 是否存在任何特征性应激激素变化仍存在争议。公共健康相关性：该提案将探讨首次创伤的时间（即儿童与成人）是否会对晚上应激激素的基础分泌产生不同的影响，以及对地塞米松（一种类似于皮质醇的合成化合物）的反馈敏感性的变化。我们还将探讨创伤发生的时间是否会改变应激激素对公开演讲挑战的反应。