PATHOPHYSIOLOGY OF CORTICOSTEROID DYSREGULATION IN DEPRESSION

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Stress activates a number of systems but particularly the hypothalamic-pituitary adrenal axis, resulting in cortisol secretion. Cortisol feeds back to turn off its own secretion by acting at two types of receptors, MR and GR. MR and GR function cooperatively in many instances, although at times they can be antagonistic, so the proper balance of MR and GR is important for regulation of a number of neurotransmitter systems. Chronic stress affects the balance of MR and GR and generally decreases MR. Individuals suffering from depression have increased cortisol and no longer turn off secretion of cortisol properly. Thus this project seeks to understand if individuals with depression have abnormal MR function. We accomplish this by administering spironolactone, an MR antagonist, and measuring ACTH and cortisol secretion.