Elsevier

Biological Psychiatry

Volume 67, Issue 5, 1 March 2010, Pages 446-457
Biological Psychiatry

Archival Report
A Meta-Analysis of Cytokines in Major Depression

https://doi.org/10.1016/j.biopsych.2009.09.033Get rights and content

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)-α, 9 for interleukin (IL)-1β, 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)-γ. There were significantly higher concentrations of TNF-α (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-α 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.

Section snippets

Methods and Materials

Only original studies that measured cytokine concentrations in depressed and nondepressed subjects were included in the meta-analysis. Studies were included if subjects met DSM-III-R or DSM-IV (3) criteria for major depression. Studies were included if they were published in English, if cytokine concentrations were measured in subjects free of major medical comorbidities (cancer, heart disease, etc.), if subjects were free of antidepressant medications for at least 1 week before the initiation

Results

A total of 136 studies were identified for review. One hundred twelve studies did not meet inclusion criteria. Studies were excluded based on the presence of comorbid medical diseases (23, 25, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86) (n = 52), use of concomitant medications (87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102

Discussion

This study reports significantly higher concentrations of the proinflammatory cytokines TNF-α 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 the evidence that depression is accompanied by activation of the IRS.

Both TNF-α and IL-6 are acute-phase proteins secreted into the bloodstream in response to immunologic challenge and elevations of these cytokines in the

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