HYPOTHALAMIC-PITUITARY ADRENAL AXIS REGULATION IN DEPRESSION

抑郁症下丘脑-垂体肾上腺轴的调节

• 批准号: 7376484
• 负责人: ELIZABETH ANN YOUNG
• 金额: $ 2.55万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-05 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7376484
• 关键词: blood; brain; cortisol; depression; secretion; stress

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Previous studies in depression have shown that there are abnormalities in the hypothalamic-pituitary-adrenal axis (HPA axis), specifically the hypothesis in the overdrive of CRH. It is our attempt to explain this by one of two hypotheses: 1. In depression, the secretion of the master stress hormone of the brain, CRH, is increased throughout the day and night. We can evaluate this possibility by administering a drug known as metyrapone, for an entire day (24 hours) and then look at its effects on a hormone in the blood known as ACTH.2. 2. In depression, the normal daily rhythm of the CRH hormone that is secreted from the brain is not regulated properly. This accompanies changes in the daily pattern of the ACTH and cortisol that is secreted, as well. Specifically, there is a failure in limiting the HPA axis hormonal secretions in the evening portion of the circadian pattern. In this study, we will examine the stress hormones (ACTH and cortisol) in the presence of metyrapone (a medication that is used to block an enzyme needed to produce cortisol). Blood samples will be taken from an intravenous catheter every 10min. for 28hrs. Metyrapone 750mg, will be given orally every 4 hrs. (except for 12 midnight and 4 am doses) for a total of 7 doses. A 24 hr. urine collection will also be measured for cortisol. As well, an activity monitor will be worn for 7 days prior to the blood collection and during. A sleep EEG will occur during the times of 8am- 8pm. Additionally, depression is increasingly seen as a risk factor for coronary artery disease. It is thought that depression may alter the inner lining of the blood vessel, called the endothelium. To better understand this association, study subjects will also be evaluated for endothelial function in the absence and presence of metryapone by having an ultrasound of the brachial arteries of the arm every four hours while awake.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。先前在抑郁症的研究表明，下丘脑 - 垂体 - 肾上腺轴（HPA轴）有异常，特别是CRH越过的假设。我们试图通过两个假设之一来解释这一点：1。在抑郁症中，大脑的主要压力激素CRH的分泌在整个白天和黑夜中都增加了。我们可以通过施用称为Metyrapone的药物（24小时）来评估这种可能性，然后查看其对Acth.2的血液中激素的影响。 2。在抑郁症中，从大脑分泌的CRH激素的正常每日节奏不能适当调节。这也伴随着分泌的ACTH和皮质醇的日常模式的变化。具体而言，在昼夜散发器模式的晚期部分限制HPA轴激素分泌的失败。在这项研究中，我们将在存在Metyrapone的情况下检查应激激素（ACTH和皮质醇）（一种用于阻断产生皮质醇所需的酶的药物）。血液样本将每10分钟从静脉内导管取。为28小时。 Metyrapone 750mg，每4小时口服一次。 （除了12个午夜和凌晨4剂）总共7剂。 24小时。尿液收集也将用于皮质醇。同样，在收集血液之前和期间将佩戴活动监测器7天。睡眠脑电图将在上午8点至晚上8点发生。另外，抑郁症越来越被视为冠状动脉疾病的危险因素。人们认为抑郁症可能会改变血管内皮的内壁，称为内皮。为了更好地理解这种关联，还将通过在醒着时每四个小时的臂动脉进行超声进行超声检查，从而在不存在和存在metryapone的情况下评估研究对象的内皮功能。