title: A meta-analysis of cytokines in major depression.
abstract: BACKGROUND
  Major depression occurs in 4.4% to 20% of the general population. Studies suggest that major depression is accompanied by immune dysregulation and activation of the inflammatory response system (IRS). Our objective was to quantitatively summarize the data on concentrations of specific cytokines in patients diagnosed with a major depressive episode and controls.
  
  
  METHODS
  We performed a meta-analysis of studies measuring cytokine concentration in patients with major depression, with a database search of the English literature (to August 2009) and a manual search of references.
  
  
  RESULTS
  Twenty-four studies involving unstimulated measurements of cytokines in patients meeting DSM criteria for major depression were included in the meta-analysis; 13 for tumor necrosis factor (TNF)-alpha, 9 for interleukin (IL)-1beta, 16 for IL-6, 5 for IL-4, 5 for IL-2, 4 for IL-8, 6 for IL-10, and 4 for interferon (IFN)-gamma. There were significantly higher concentrations of TNF-alpha (p < .00001), weighted mean difference (WMD) (95% confidence interval) 3.97 pg/mL (2.24 to 5.71), in depressed subjects compared with control subjects (438 depressed/350 nondepressed). Also, IL-6 concentrations were significantly higher (p < .00001) in depressed subjects compared with control subjects (492 depressed/400 nondepressed) with an overall WMD of 1.78 pg/mL (1.23 to 2.33). There were no significant differences among depressed and nondepressed subjects for the other cytokines studied.
  
  
  CONCLUSIONS
  This meta-analysis reports significantly higher concentrations of the proinflammatory cytokines TNF-alpha and IL-6 in depressed subjects compared with control subjects. While both positive and negative results have been reported in individual studies, this meta-analytic result strengthens evidence that depression is accompanied by activation of the IRS.
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Yekta
authors.initials: Y
authors.lastname: Dowlati
authors.forename: Nathan
authors.initials: N
authors.lastname: Herrmann
authors.forename: Walter
authors.initials: W
authors.lastname: Swardfager
authors.forename: Helena
authors.initials: H
authors.lastname: Liu
authors.forename: Lauren
authors.initials: L
authors.lastname: Sham
authors.forename: Elyse K
authors.initials: EK
authors.lastname: Reim
authors.forename: Krista L
authors.initials: KL
authors.lastname: Lanctôt
mesh_terms: D003865:Major Depressive Disorder / Q000276:immunology*; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology*; D016209:Interleukin-8 / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D053583:Interleukin-1beta; D007376:Interleukin-2; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha