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

Psychol Med. 2006 Jan;36(1):37-43. doi: 10.1017/S003329170500632X. Epub 2005 Oct 28.

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-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antidepressive Agents / therapeutic use*
  • Depressive Disorder, Major* / drug therapy
  • Depressive Disorder, Major* / immunology
  • Depressive Disorder, Major* / metabolism
  • Drug Resistance*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Hypersensitivity / epidemiology*
  • Hypersensitivity / immunology*
  • Interleukin-6 / immunology*
  • Male
  • Middle Aged
  • Receptors, Glucocorticoid / immunology*
  • Receptors, Glucocorticoid / metabolism*
  • Severity of Illness Index
  • Skin / immunology*
  • Skin / metabolism*
  • Tumor Necrosis Factor-alpha / immunology*
  • Vasoconstriction / physiology

Substances

  • Antidepressive Agents
  • Interleukin-6
  • Receptors, Glucocorticoid
  • Tumor Necrosis Factor-alpha