HYPOTHALAMIC-PITUITARY ADRENAL AXIS REGULATION IN DEPRESSION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。以往对抑郁症的研究表明，下丘脑-垂体-肾上腺轴（HPA轴）存在异常，特别是CRH过度驱动的假说。我们试图用两个假设中的一个来解释这一点：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在增加。我们可以通过服用一种叫做metyrapone的药物来评估这种可能性，持续一天（24小时），然后观察它对血液中一种叫做acth的激素的影响。2. 在抑郁症中，大脑分泌的CRH激素的正常日常节律没有得到适当的调节。这也伴随着ACTH和皮质醇分泌的日常模式的变化。具体来说，在昼夜节律模式的夜间部分，HPA轴激素分泌受到限制。在这项研究中，我们将检查在美替拉酮（一种用于阻断产生皮质醇所需酶的药物）存在下的应激激素（ACTH和皮质醇）。每10分钟从静脉导管中抽取血样，持续28小时。甲替拉酮750mg，每4小时口服一次。（午夜12时及凌晨4时除外），共7剂。24小时。尿液收集也将测量皮质醇。此外，在采血前和采血过程中，需要佩戴活动监测器7天。睡眠脑电图将在早上8点至晚上8点进行。此外，抑郁症越来越被视为冠状动脉疾病的一个危险因素。据认为，抑郁可能会改变血管的内层，即内皮。为了更好地了解这种关联，研究对象还将在清醒时每4小时对手臂肱动脉进行超声检查，以评估在没有和存在metryapone的情况下的内皮功能。

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.