title: Clomipramine in vitro reduces glucocorticoid receptor function in healthy subjects but not in patients with major depression.
abstract: 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.
authors: King's College London, Section for Laboratory of Stress, Psychiatry and Immunology, Institute of Psychiatry, London, UK. l.carvalho@iop.kcl.ac.uk
authors: Livia A
authors: LA
authors: Carvalho
authors: Mario F
authors: MF
authors: Juruena
authors: Andrew S
authors: AS
authors: Papadopoulos
authors: Lucia
authors: L
authors: Poon
authors: Rob
authors: R
authors: Kerwin
authors: Anthony J
authors: AJ
authors: Cleare
authors: Carmine M
authors: CM
authors: Pariante
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D002997:Clomipramine / Q000494:pharmacology*; D003865:Major Depressive Disorder / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005260:Female; D005938:Glucocorticoids / Q000097:blood* / Q000494:pharmacology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology; D018836:Inflammation Mediators / Q000494:pharmacology; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013315:Stress, Psychological / Q000150:complications / Q000276:immunology / Q000503:physiopathology
chemical_list: D002997:Clomipramine; D005938:Glucocorticoids; D018836:Inflammation Mediators; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011965:Receptors, Glucocorticoid; D017367:Selective Serotonin Reuptake Inhibitors