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Cited by 66Stress Responses and CortisolTryptophan and brain disordersTreatment of Major Depression

Cutaneous glucocorticoid receptor sensitivity and pro-inflammatory 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.·2006·Psychological Medicine
DOI 10.1017/s003329170500632x
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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-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.

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Crossref · 10.1017/s003329170500632x

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  • Decreased glucocorticoid responsiveness in depressed patients is not solely a function of altered in vivo pharmacokinetic properties of glucocorticoids (including DEX) in depressed patients.

    “These latter findings indicate that decreased glucocorticoid responsiveness in depressed patients is not solely a function of altered in vivo pharmacokinetic properties of glucocorticoids (including DEX) in depressed patients.”

    From Cytokines and Glucocorticoid Receptor Signaling (2009) · cites this paper as [40]

    The Results (SIV) report reduced skin blanching after topical steroids in antidepressant-resistant depressed patients, supporting reduced responsiveness in a setting that does not depend on systemic delivery. But the paper does not test glucocorticoid pharmacokinetics or dexamethasone specifically, and the Discussion limits its conclusion to cutaneous responsiveness rather than depressed patients generally. (LLM, conf=0.84)

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  • Reduced sensitivity to glucocorticoids in depressed patients is evident in immune cells stimulated in vitro and in the skin following topical application of glucocorticoids.

    “Reduced sensitivity to glucocorticoids in depressed patients is also evident in immune cells stimulated in vitro and in the skin following topical application of glucocorticoids.7,11,40”

    From Cytokines and Glucocorticoid Receptor Signaling (2009) · cites this paper as [40]

    The Discussion reports reduced skin-blanching after topical steroid application in antidepressant-resistant depressed patients compared with healthy controls. The paper does not report reduced glucocorticoid sensitivity in immune cells stimulated in vitro; its blood assays measured circulating cytokines. That part of the claim is not supported by this source. (LLM, conf=0.86)

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  • Reduced glucocorticoid signaling is apparent in a number of cell types and tissues, including neuroendocrine, immune and dermal elements.

    “taken together, these data indicate that reduced glucocorticoid signaling is apparent in a number of cell types and tissues, including neuroendocrine, immune and dermal elements.”

    From Cytokines and Glucocorticoid Receptor Signaling (2009) · cites this paper as [40]

    The Introduction (page not provided) discusses possible reduced glucocorticoid-receptor sensitivity in the HPA axis and abnormalities in peripheral blood cells; the Discussion reports reduced cutaneous sensitivity in antidepressant-resistant depression. But the Discussion cautions that cutaneous subsensitivity does not necessarily extend to other tissues, so the claim presents reduced signaling across cell types more definitively than the paper does. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Reduced skin sensitivity to topical glucocorticoid administration in depressed patients was found to significantly correlate with increased blood concentrations of TNF-α.

    “reduced skin sensitivity to topical glucocorticoid administration in depressed patients was found to significantly correlate with increased blood concentrations of TNF-α.40”

    From Cytokines and Glucocorticoid Receptor Signaling (2009) · cites this paper as [40]

  • Medically healthy depressed patients resistant to antidepressant therapy have higher circulating inflammatory cytokines and CRP than responders.

    “Medically healthy depressed patients who are resistant to antidepressant therapy demonstrate higher concentrations of circulating inflammatory cytokines and CRP than patients who respond to antidepressants”

    From Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications (2013) · cites this paper as Fitzgerald et al., 2006

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Research works printed but not linked: 2

  1. Dinan, T. G., O'Brien, S. & Scott, L. V. (2005). Biological factors sustaining hypothalamic-pituitary-adrenal axis overactivation in affective disorders : focus on vasopressin. In Bipolar Disorder : The Upswing in Research and Treatment (ed. C. McDonald, K. Schulze, R. M. Murray and M. Tohen), pp. 135-145. Taylor & Francis : London.
  2. Szigethy, E., Levy-Warren, A., Whitton, S., Bousvaros, A., Gauvreau, K. & Beardslee, W. (2004). Depressive symptoms and inflamma- tory bowel disease in children and adolescents. Journal of Pediatric Gastroenterology & Nutrition 39, 395-403.

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Authors
FITZGERALD, P., O'BRIEN, S. M., SCULLY, P., RIJKERS, K., SCOTT, L. V., & DINAN, T. G.
Affiliations
University College Cork (IE)
ORCID
Venue
Psychological Medicine
Publisher
Cambridge University Press (CUP)
Published
2005-10-28
Volume
36
Issue
1
Pages
37-43
ISSN
  • 0033-2917 (ISSN-L)
  • 1469-8978
DOI
10.1017/s003329170500632x
OpenAlex
W2117615657
Cited by
66
References
31
Citations by year
2026: 2 · 2025: 1 · 2021: 3 · 2019: 4 · 2018: 6 · 2017: 6 · 2016: 3 · 2015: 9 · 2014: 5 · 2013: 6 · 2012: 4
FWCI
0.83
Type
journal article
Language
en
Open access
Licence
www.cambridge.org/core/terms (unspecified)
Locations
  • Psychological Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Arrow@dit (Dublin Institute of Technology) (submittedVersion)
  • Cork Open Research Archive (University College Cork, Ireland) (submittedVersion)
Funders
  • Wellcome Trust
  • Health Research Board
  • Science Foundation Ireland
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
antidepressant-resistant depression, major depressive disorder, glucocorticoid receptor sensitivity, topical corticosteroids, inflammatory cytokines, TNF-α, interleukin-6
MeSH terms
Adult, Aged, Antidepressive Agents, Depressive Disorder, Major, Major Depressive Disorder, Drug Resistance, Enzyme-Linked Immunosorbent Assay, Female, Humans, Hypersensitivity, Male, Middle Aged, Receptors, Glucocorticoid, Severity of Illness Index, Skin, Tumor Necrosis Factor-alpha, Vasoconstriction, Interleukin-6

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