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

Published online by Cambridge University Press:  28 October 2005

PETER FITZGERALD
Affiliation:
Department of Psychiatry & Alimentary Pharmabiotic Centre, University College Cork, Ireland
SINEAD M. O'BRIEN
Affiliation:
Department of Psychiatry & Alimentary Pharmabiotic Centre, University College Cork, Ireland
PAUL SCULLY
Affiliation:
Department of Psychiatry & Alimentary Pharmabiotic Centre, University College Cork, Ireland
KIM RIJKERS
Affiliation:
Department of Psychiatry & Alimentary Pharmabiotic Centre, University College Cork, Ireland
LUCINDA V. SCOTT
Affiliation:
Department of Psychiatry & Alimentary Pharmabiotic Centre, University College Cork, Ireland
TIMOTHY G. DINAN
Affiliation:
Department of Psychiatry & Alimentary Pharmabiotic Centre, University College Cork, Ireland

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-α) 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-α and IL-6. There was a significant inverse correlation between TNF-α concentration and vasoconstriction response and also between the HAMD score and vasoconstriction response.

Conclusions. These findings suggest that cutaneous GR function is abnormal in antidepressant-resistant depression, that circulating TNF-α may play a significant role in this abnormality and that the efficacy of topical steroids in antidepressant-resistant depressives is reduced.

Type
Original Article
Copyright
2005 Cambridge University Press

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