Lack of effect of a single dose of hydrocortisone on serotonin(1A) 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-HT(1A) 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 [(11)C]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-HT(1A) receptor BP either in the hippocampus, which was our a priori hypothesis, or in other cortical 5-HT(1A) regions; however, female subjects had a higher 5-HT(1A) 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-HT(1A) receptor BP in patients with acute major depression is a consequence of cortisol hypersecretion.
Clinical Sciences Centre Medical Research Council, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom.
Zubin
Z
Bhagwagar
Andrew J
AJ
Montgomery
Paul M
PM
Grasby
Philip J
PJ
Cowen
D000328:Adult; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002250:Carbon Radioisotopes; D003865:Major Depressive Disorder / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010879:Piperazines; D011725:Pyridines; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects* / Q000378:metabolism; D012702:Serotonin Antagonists; D014055:Tomography, Emission-Computed / Q000379:methods
D002250:Carbon Radioisotopes; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D006854:Hydrocortisone