title: Central glucocorticoid receptor-mediated effects of the antidepressant, citalopram, in humans: a study using EEG and cognitive testing.
abstract: Our previous work in cellular and animal models has shown that antidepressants activate glucocorticoid receptor (GR) translocation, induce GR down-regulation, and decrease GR-mediated effects in the presence of GR agonists. However, whether these effects can be extrapolated to the human brain is still unclear. In this study, the effects of four days of treatment with the antidepressant, citalopram (20 mg/day), or placebo, were assessed in a double-blind, placebo-controlled, cross-over study. Central GR-mediated effects were examined by the effects of a single dose of cortisol (30 mg, orally) on two measures known to be sensitive to glucocorticoid administration: EEG alpha power and working memory function. Twenty healthy male subjects aged between 18 and 33 years participated to the study. The results suggest that GR activation by antidepressants, and the subsequent decrease in GR-mediated effects in the presence of GR agonists, indeed occurs in the human brain. Specifically, pre-treatment with citalopram decreased the well-known ability of cortisol to increase EEG alpha power and to impair working memory: cortisol-induced increase in EEG alpha power was (anteriorly) +15 to +20% (p=0.01) after placebo and +5 to +8% (p>0.5) after citalopram; and cortisol-induced increase in working memory errors was (at level 12, on average) 2.50 vs. 4.55 (p<0.05) after placebo and 4.10 vs. 3.35 (p>0.05) after citalopram. No effects were detected on alerting. These results are consistent with the notion that citalopram treatment activates GR translocation and inhibits the functional consequences of the subsequent cortisol administration. Our study further emphasizes the importance of the GR as a target for antidepressant action in humans.
authors.affiliation: Department of Psychological Medicine, Section of Perinatal Psychiatry and Stress, Psychiatry and Immunology Laboratory (SPI-Lab), Institute of Psychiatry, King's College London, London, UK. carmine.pariante@kcl.ac.uk
authors.forename: Carmine M
authors.initials: CM
authors.lastname: Pariante
authors.forename: Hamid A
authors.initials: HA
authors.lastname: Alhaj
authors.forename: Vijay Edmund
authors.initials: VE
authors.lastname: Arulnathan
authors.forename: Peter
authors.initials: P
authors.lastname: Gallagher
authors.forename: Andy
authors.initials: A
authors.lastname: Hanson
authors.forename: E
authors.initials: E
authors.lastname: Massey
authors.forename: R Hamish
authors.initials: RH
authors.lastname: McAllister-Williams
mesh_terms: D000293:Adolescent; D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage*; D015283:Citalopram / Q000008:administration & dosage*; D003071:Cognition / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004569:Electroencephalography; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D011965:Receptors, Glucocorticoid / Q000819:agonists*; D055815:Young Adult
chemical_list: D018687:Antidepressive Agents, Second-Generation; D011965:Receptors, Glucocorticoid; D015283:Citalopram; D006854:Hydrocortisone