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

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Fitzgerald, Peter
O'Brien, Sinead M.
Scully, Paul
Rijkers, Kim
Scott, Lucinda V.
Dinan, Timothy G.
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Cambridge University Press
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ABSTRACT 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.
Cutaneous glucocorticoid Receptor , Antidepressant-resistant , Pro-inflammatory cytokine levels , GR function , Hamilton depression scale , Depression
PETER 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/S003329170500632X
©2006, Cambridge University Press