Meta-Analysis of Cytokine Alterations in Schizophrenia: Clinical Status and Antipsychotic Effects

doi:10.1016/j.biopsych.2011.04.013

Biological Psychiatry

Volume 70, Issue 7, 1 October 2011, Pages 663-671

https://doi.org/10.1016/j.biopsych.2011.04.013 Get rights and content

Background

Schizophrenia is associated with immune system dysfunction, including aberrant cytokine levels. We performed a meta-analysis of these associations, considering effects of clinical status and antipsychotic treatment following an acute illness exacerbation.

Methods

We identified articles by searching PubMed, PsychInfo, and Institute for Scientific Information and the reference lists of identified studies.

Results

Forty studies met the inclusion criteria. Effect sizes were similar for studies of acutely relapsed inpatients (AR) and first-episode psychosis (FEP). Interleukin (IL)-1β, IL-6, and transforming growth factor-β (TGF-β) appeared to be state markers, as they were increased in AR and FEP (p < .001 for each) and normalized with antipsychotic treatment (p < .001, p = .008, and p = .005, respectively). In contrast, IL-12, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and soluble IL-2 receptor (sIL-2R) appeared to be trait markers, as levels remained elevated in acute exacerbations and following antipsychotic treatment. There was no difference in IL-6 levels between stable medicated outpatients and control subjects (p = .69). In the cerebrospinal fluid, IL-1β was significantly decreased in schizophrenia versus controls (p = .01).

Conclusions

Similar effect sizes in AR and FEP suggest that the association between cytokine abnormalities and acute exacerbations of schizophrenia is independent of antipsychotic medications. While some cytokines (IL-1β, IL-6, and TGF-β) may be state markers for acute exacerbations, others (IL-12, IFN-γ, TNF-α, and sIL-2R) may be trait markers. Although these results could provide the basis for future hypothesis testing, most studies did not control for potential confounding factors such as body mass index and smoking.

Section snippets

Study Selection

Studies of blood and CSF cytokine (and cytokine receptor or antagonist) levels in schizophrenia were identified from two sources. First, supplementary material from Potvin et al. (5), which describes a systematic search of studies through the end of 2005, was accessed. Second, studies on cytokine (and cytokine receptor or antagonist) levels in schizophrenia published after 2005 were systematically searched using MEDLINE (National Center for Biotechnology Information, US National Library of

Results

Figure 1 and Table 1 present effect size estimates with 95% confidence intervals by clinical status.

Discussion

Taken together, our findings suggest that cytokine alterations in schizophrenia may vary with clinical status. IL-1β, IL-6, and TGF-β appeared to be state-related markers, as they were increased during acute exacerbations (AR and/or FEP; p < .001 for each) and normalized with antipsychotic treatment (p < .001, p = .008, and p = .005, respectively). Furthermore, there was a significant positive correlation between the change in IL-6 levels and change in total psychopathology scores in two

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Archival ReportMeta-Analysis of Cytokine Alterations in Schizophrenia: Clinical Status and Antipsychotic Effects

Background

Methods

Results

Conclusions

Section snippets

Study Selection

Results

Discussion

Biol Psychiatry

Biol Psychiatry

Psychiatry Res

Schizophr Res

Schizophr Res

Schizophr Res

Med Hypotheses

Med Hypotheses

Brain Behav Immun

Schizophr Res

Schizophr Res

Schizophr Res

J Psychiatr Res

Prog Neuropsychopharmacol Biol Psychiatry

Psychiatry Res

Schizophr Res

Prog Neuropsychopharmacol Biol Psychiatry

Psychiatry Res

Schizophr Res

J Psychiatr Res

Schizophr Res

Prog Neuropsychopharmacol Biol Psychiatry

Schizophr Res

J Psychiatr Res

Schizophr Res

Schizophr Res

Eur Neuropsychopharmacol

Schizophr Res

Psychiatry Res

Eur Psychiatry

Schizophr Res

Psychiatry Res

Int Immunopharmacol

Biol Psychiatry

Prog Neuropsychopharmacol Biol Psychiatry

Schizophr Res

J Autoimmun

Life Sci

Cytokine

Psychiatry Res

Biol Psychiatry

Schizophr Res

Exp Neurol

Neuropsychopharmacology

Schizophr Res

Prostaglandins Leukot Essent Fatty Acids

Schizophr Res

Schizophrenia as an immunologic disorder. I. Demonstration of antibrain globulins by fluorescent antibody techniques

Arch Gen Psychiatry

Schizophrenia as an immunologic disorder. II. Effects of serum protein fractions on brain function

Arch Gen Psychiatry

Schizophrenia as an immunologic disorder. 3. Effects of antimonkey and antihuman brain antibody on brain function

Arch Gen Psychiatry

Archival Report
Meta-Analysis of Cytokine Alterations in Schizophrenia: Clinical Status and Antipsychotic Effects