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


METHODS
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-alpha) 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-alpha and IL-6. There was a significant inverse correlation between TNF-alpha 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-alpha may play a significant role in this abnormality and that the efficacy of topical steroids in antidepressant-resistant depressives is reduced.
Fitzgerald
Peter
P
Department of Psychiatry & Alimentary Pharmabiotic Centre, University College Cork, Ireland.
O'Brien
Sinead M
SM
Scully
Paul
P
Rijkers
Kim
K
Scott
Lucinda V
LV
Dinan
Timothy G
TG
D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D004351:Drug Resistance; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000453:epidemiology* / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011965:Receptors, Glucocorticoid / Q000276:immunology* / Q000378:metabolism*; D012720:Severity of Illness Index; D012867:Skin / Q000276:immunology* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D014661:Vasoconstriction / Q000502:physiology
D000928:Antidepressive Agents; D015850:Interleukin-6; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha