To evaluate the CRH overdrive hypothesis in depression, we will evaluate two alternative hypotheses explaining the HPA axis abnormalities in depression. Only one of these two hypotheses can be valid. These hypotheses are:1. In depression there is increased central CRH secretion, including increased PVN CRH secretion, that is dampened by glucocorticoid negative feedback. When ACTH is examined in the absence of negative feedback (open loop system), produced by metyrapone blockade of cortisol production, there will be increased ACTH secretion throughout the day. OR 2. In depression there is dysregulation of circadian driven CRH secretion accompanied by alterations in the circadian rhythm of ACTH and cortisol secretion. A failure of the inhibitory circuits to restrain HPA axis secretion occurs at a specific circadian phase, the evening.

Project Start
1998-12-01
Project End
1999-11-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
39
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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