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。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。以往的研究表明，抑郁症有异常的下丘脑-垂体-肾上腺轴（HPA轴），特别是在CRH的发病假说。这是我们试图解释这两个假设之一：1。在抑郁症中，大脑中主要的应激激素CRH的分泌在白天和晚上都会增加。我们可以评估这种可能性，通过管理一种药物称为甲吡酮，一整天（24小时），然后看看它对血液中的激素称为ACTH的影响。2. 2.在抑郁症中，大脑分泌的CRH激素的正常每日节律没有得到适当的调节。这伴随着ACTH和皮质醇分泌的日常模式的变化。具体地，在昼夜节律模式的晚上部分中限制HPA轴激素分泌失败。在这项研究中，我们将检查压力激素（ACTH和皮质醇）在甲吡酮（一种用于阻断产生皮质醇所需的酶的药物）的存在下。每10分钟从静脉导管中采集一次血样。28小时。甲吡酮750 mg，每4小时口服一次。（除了午夜12点和凌晨4点给药），共7次给药。还将测量24小时尿液采集的皮质醇。此外，在采血前7天和采血期间将佩戴活动监测器。睡眠EEG将在上午8点至下午8点期间发生。此外，抑郁症越来越被视为冠状动脉疾病的危险因素。据认为，抑郁症可能会改变血管的内层，称为内皮。为了更好地理解这种关联，还将通过在清醒时每四小时对臂动脉进行一次超声检查来评估研究受试者在不存在和存在甲硝苯酮的情况下的内皮功能。