Lack of effect of a single dose of hydrocortisone on serotonin(1A) receptors in recovered depressed patients measured by positron emission tomography with [C-11]WAY-100635

Background: Elevated cortisol levels might account for the reduction in central serotonin 1A (5-hydroxytryptamine [5-HT](1A)) receptor binding and function observed in patients with major depression. We tested this hypothesis by studying the effect of acute administration of hydrocortisone on 5-HT1A receptor binding potential (BP) in subjects recovered from depression. Methods: We studied 14 subjects (8 male, 6 female) who had recovered from at least two episodes of major depression and had been euthymic and drug free for at least 6 months. Serotonin 1A receptor BP was measured by [C-11]WAY-100635 in conjunction with positron emission tomography. Subjects were tested on two occasions in a double-blind, random-order, crossover design after administration of either hydrocortisone (100 mg orally) or placebo 12 hours previously. Positron emission tomography scans were analyzed with a region of interest analysis. Results: Hydrocortisone treatment did not decrease 5-HT1A receptor BP either in the hippocampus, which was our a priori hypothesis, or in other cortical 5-HT1A regions; however, female subjects had a higher 5-HT1A receptor BP in certain brain areas compared with male subjects. Conclusions: These data are consistent with an earlier study in healthy volunteers and do not support the proposal that decreased 5-HT1A receptor BP in patients with acute major depression is a consequence of cortisol hypersecretion. (C) 2003 Society of Biological Psychiatry.