Peripheral Alterations in Cytokine and Chemokine Levels After Antidepressant Drug Treatment for Major Depressive Disorder: Systematic Review and Meta-Analysis

Cristiano A. Köhler, Thiago H. Freitas, Brendon Stubbs, Michael Maes, Marco Solmi, Nicola Veronese, Nayanna Q. de Andrade, Gerwyn Morris, Brisa S. Fernandes, André R. Brunoni, Nathan Herrmann, Charles L. Raison, Brian J Miller, Krista L. Lanctôt, André F. Carvalho

Research output: Contribution to journalReview article

101 Scopus citations

Abstract

Mounting evidence suggests that aberrations in immune-inflammatory pathways contribute to the pathophysiology of major depressive disorder (MDD), and individuals with MDD may have elevated levels of predominantly pro-inflammatory cytokines and C-reactive protein. In addition, previous meta-analyses suggest that antidepressant drug treatment may decrease peripheral levels of interleukin-1 beta (IL-1β) and IL-6. Recently, several new studies examining the effect of antidepressants on these cytokines have been published, and so we performed an updated meta-analysis of studies that measured peripheral levels of cytokines and chemokines during antidepressant treatment in patients with MDD. The PubMed/MEDLINE, EMBASE, and PsycInfo databases were searched from inception through March 9, 2017. Forty-five studies met inclusion criteria (N = 1517). Peripheral levels of IL-6, tumor necrosis factor-alpha (TNF-α), IL-1β, IL-10, IL-2, IL-4, interferon-γ, IL-8, the C-C motif ligand 2 chemokine (CCL-2), CCL-3, IL-1 receptor antagonist, IL-13, IL-17, IL-5, IL-7, and the soluble IL-2 receptor were measured in at least three datasets and thus were meta-analyzed. Antidepressant treatment significantly decreased peripheral levels of IL-6 (Hedges g = −0.454, P <0.001), TNF-α (g = −0.202, P = 0.015), IL-10 (g = −0.566, P = 0.012), and CCL-2 (g = −1.502, P = 0.006). These findings indicate that antidepressants decrease several markers of peripheral inflammation. However, this meta-analysis did not provide evidence that reductions in peripheral inflammation are associated with antidepressant treatment response although few studies provided separate data for treatment responders and non-responders.

Original languageEnglish (US)
Pages (from-to)4195-4206
Number of pages12
JournalMolecular Neurobiology
Volume55
Issue number5
DOIs
StatePublished - May 1 2018

Keywords

  • Antidepressant
  • Chemokines
  • Cytokines
  • Depression
  • Inflammation
  • Meta-analysis

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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    Köhler, C. A., Freitas, T. H., Stubbs, B., Maes, M., Solmi, M., Veronese, N., de Andrade, N. Q., Morris, G., Fernandes, B. S., Brunoni, A. R., Herrmann, N., Raison, C. L., Miller, B. J., Lanctôt, K. L., & Carvalho, A. F. (2018). Peripheral Alterations in Cytokine and Chemokine Levels After Antidepressant Drug Treatment for Major Depressive Disorder: Systematic Review and Meta-Analysis. Molecular Neurobiology, 55(5), 4195-4206. https://doi.org/10.1007/s12035-017-0632-1