Lack of effect of a single dose of hydrocortisone on serotonin1A receptors in recovered depressed patients measured by positron emission tomography with [11C]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 [11C]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.