HYPOTHALAMIC-PITUITARY ADRENAL AXIS REGULATION IN DEPRESSION

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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.