Central glucocorticoid receptor-mediated effects of the antidepressant, citalopram, in humans: a study using EEG and cognitive testing
Open accessAbstract
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.
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In healthy volunteers, antidepressants reverse GR resistance, increasing GR function as measured by HPA axis negative feedback and the effects of cortisol on the EEG.
“In two studies in healthy volunteers, we were also able to confirm that antidepressants reverse GR resistance, that is, increase GR function as measured by the HPA axis negative feedback (Pariante et al., 2004a) and the effects of cortisol on the EEG (Pariante et al., 2012).”
From Why are depressed patients inflamed? A reflection on 20 years of research on depression, glucocorticoid resistance and inflammation (2017) · cites this paper as Pariante et al., 2012
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- Authors
- Pariante, C. M., Alhaj, H. A., Arulnathan, V. E., Gallagher, P., Hanson, A., Massey, E., & McAllister-Williams, R. H.
- Affiliations
- King's College London (GB)
- Newcastle University (GB)
- Corresponding author
- Pariante, Carmine M.
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 37
- Issue
- 5
- Pages
- 618-628
- ISSN
- 0306-4530 (ISSN-L)
- OpenAlex
- W2130161396
- Cited by
- 33
- References
- 58
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2021: 4 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 5 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 4 · 2012: 3
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- National Institute for Health and Care Research (ACF-2008-01-010)
- Medical Research Council (MR/J002739/1)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- citalopram, glucocorticoid receptor, antidepressants, cortisol, EEG alpha power, working memory, alerting, human brain
- MeSH terms
- Adolescent, Adult, Cognition, Double-Blind Method, Electroencephalography, Humans, Hydrocortisone, Male, Memory, Short-Term, Receptors, Glucocorticoid, Citalopram, Cross-Over Studies, Antidepressive Agents, Second-Generation, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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