Cutaneous glucocorticoid receptor sensitivity and proinflammatory cytokine levels in antidepressant-resistant depression

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dc.contributor.authorFitzgerald, Peter
dc.contributor.authorO'Brien, Sinead M.
dc.contributor.authorScully, Paul
dc.contributor.authorRijkers, Kim
dc.contributor.authorScott, Lucinda V.
dc.contributor.authorDinan, Timothy G.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderHealth Research Boarden
dc.contributor.funderWellcome Trust, United Kingdomen
dc.date.accessioned2013-02-14T13:33:29Z
dc.date.available2013-02-14T13:33:29Z
dc.date.copyright2005
dc.date.issued2006-01
dc.description.abstractABSTRACT Background. There is evidence to indicate that peripheral glucocorticoid receptor (GR) function is reduced in major depression, and a possible molecular explanation for this is the impact of raised pro-inflammatory cytokines. The topical steroid vasoconstriction assay provides a convenient probe of peripheral GR function. The present study sought to assess the sensitivity of peripheral GRs in antidepressant-resistant major depressives and investigate the association between GR sensitivity and circulating plasma cytokines. Method. Nineteen antidepressant-resistant depressives together with age- and sex-matched healthy controls underwent the steroid vasoconstriction assay using three commercial preparations of corticosteroids containing clobetasol propionate 0.05%, betamethasone valerate 0.1%, and clobetasone butyrate 0.05%, corresponding to very potent, potent, and moderately potent steroid creams respectively. The pro-inflammatory cytokines, tumour necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6) were measured using enzyme-linked immunosorbent assays. The severity of the depressive episode was assessed using the Hamilton Depression Scale (HAMD). Results. Depressed subjects had a significantly reduced vasoconstriction response across all three strengths of steroid. They also had significantly higher concentrations of TNF-a and IL-6. There was a significant inverse correlation between TNF-a concentration and vasoconstriction response and also between the HAMD score and vasoconstriction response. Conclusions. These findings suggest that cutaneous GR function is abnormal in antidepressantresistant depression, that circulating TNF-a may play a significant role in this abnormality and that the efficacy of topical steroids in antidepressant-resistant depressives is reduced.en
dc.description.sponsorshipScience Foundation Ireland (SFI-CSET)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationPETER FITZGERALD, SINEAD M. O'BRIEN, PAUL SCULLY, KIM RIJKERS, LUCINDA V. SCOTT and TIMOTHY G. DINAN (2006). Cutaneous glucocorticoid receptor sensitivity and proinflammatory cytokine levels in antidepressantresistant depression. Psychological Medicine, 36,pp 3743 doi:10.1017/S003329170500632Xen
dc.identifier.doi10.1017/S003329170500632X
dc.identifier.endpage43en
dc.identifier.issued1en
dc.identifier.journaltitlePsychological Medicineen
dc.identifier.startpage37en
dc.identifier.urihttps://hdl.handle.net/10468/961
dc.identifier.volume36en
dc.language.isoenen
dc.publisherCambridge University Pressen
dc.relation.urihttp://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=361866&fulltextType=RA&fileId=S003329170500632X
dc.rights©2006, Cambridge University Pressen
dc.subjectCutaneous glucocorticoid Receptoren
dc.subjectAntidepressant-resistanten
dc.subjectPro-inflammatory cytokine levelsen
dc.subjectGR functionen
dc.subjectHamilton depression scaleen
dc.subjectDepressionen
dc.titleCutaneous glucocorticoid receptor sensitivity and proinflammatory cytokine levels in antidepressant-resistant depressionen
dc.typeArticle (peer-reviewed)en
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