Clomipramine in vitro reduces glucocorticoid receptor function in healthy subjects but not in patients with major depression
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Previously, we have shown that in vitro antidepressants modulate glucocorticoid receptor (GR) function and expression, and have suggested that these effects could be relevant for the mechanism of action of antidepressants. To further clarify the interaction between antidepressants and glucocorticoids, we evaluated the in vitro effect of the tricyclic antidepressant, clomipramine (CMI), on the GR function in 15 treatment-resistant depressed inpatients and 28 healthy controls. Diluted whole-blood cells were incubated for 24 h in the presence or absence of CMI (10 muM). Glucocorticoid function was measured by glucocorticoid inhibition of lypopolysaccharide (LPS)-stimulated interleukin-6 (IL-6) levels. The results show that glucocorticoids (dexamethasone, prednisolone, cortisol and corticosterone) caused a concentration-dependent inhibition of LPS-stimulated IL-6 levels. In healthy controls, CMI decreased glucocorticoid inhibition of LPS-stimulated IL-6 levels, while this effect was not present in depressed patients. Therefore, depressed patients, who were clinically treatment resistant, also showed a lack of effect of the antidepressant in vitro. Upcoming studies shall test whether assessing the effects of antidepressants in vitro on GR function could predict future treatment response in a clinical setting.
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In 2008, increased plasma cortisol levels and increased inflammation (plasma IL-6) were described in the same depressed individuals, a group of severely depressed inpatients with treatment-resistant depression.
“In 2008 we described increased plasma cortisol levels and increased inflammation (plasma IL-6) in the same depressed individuals, a group of severely depressed inpatients with treatment-resistant depression (Carvalho et al., 2008)”
From Why are depressed patients inflamed? A reflection on 20 years of research on depression, glucocorticoid resistance and inflammation (2017) · cites this paper as Carvalho et al., 2008
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- Authors
- Carvalho, L. A., Juruena, M. F., Papadopoulos, A. S., Poon, L., Kerwin, R., Cleare, A. J., & Pariante, C. M.
- Affiliations
- King's College London (GB)
- Corresponding author
- Carvalho, Livia A
- Venue
- Neuropsychopharmacology
- Published
- 2008-03-26
- Volume
- 33
- Issue
- 13
- Pages
- 3182-3189
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3513411
- OpenAlex
- W2048418520
- Cited by
- 75
- References
- 42
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 8 · 2018: 7 · 2017: 7 · 2016: 2 · 2015: 5 · 2014: 5 · 2013: 2 · 2012: 2
- FWCI
- 3.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- South London and Maudsley NHS Foundation Trust
- National Alliance for Research on Schizophrenia and Depression
- National Institute for Health and Care Research
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- clomipramine, glucocorticoid receptor, major depressive disorder, treatment-resistant depression, tricyclic antidepressants, antidepressant mechanism, interleukin-6, lipopolysaccharide, glucocorticoid inhibition, dexamethasone, prednisolone, cortisol, corticosterone, whole blood cells, treatment response prediction
- MeSH terms
- Adult, Brain, Brain Chemistry, Cells, Cultured, Clomipramine, Major Depressive Disorder, Dose-Response Relationship, Drug, Female, Glucocorticoids, Humans, Hypothalamo-Hypophyseal System, Inflammation, Lipopolysaccharides, Male, Middle Aged, Pituitary-Adrenal System, Receptors, Glucocorticoid, Stress, Psychological, Down-Regulation, Interleukin-6, Selective Serotonin Reuptake Inhibitors, Inflammation Mediators
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