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.
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.
Authors: Roosmarijn C Drexhage; Roos C Padmos; Harm de Wit; Marjan A Versnel; Herbert Hooijkaas; Aart-Jan van der Lely; Nico van Beveren; Roel H deRijk; Dan Cohen Journal: Schizophr Res Date: 2008-05-16 Impact factor: 4.939
Authors: Peter S Bloomfield; Sudhakar Selvaraj; Vincenzo de Paola; Oliver D Howes; Mattia Veronese; Gaia Rizzo; Alessandra Bertoldo; David R Owen; Michael Ap Bloomfield; Ilaria Bonoldi; Nicola Kalk; Federico Turkheimer; Philip McGuire Journal: Am J Psychiatry Date: 2015-10-16 Impact factor: 18.112
Authors: Paulo L Lizano; Matcheri S Keshavan; Neeraj Tandon; Ian T Mathew; Suraj Sarvode Mothi; Debra M Montrose; Jeffrey K Yao Journal: Schizophr Res Date: 2015-12-11 Impact factor: 4.939
Authors: Daisuke Fukudome; Lindsay N Hayes; Travis E Faust; Catherine A Foss; Mari A Kondo; Brian J Lee; Atsushi Saito; Shin-Ichi Kano; Jennifer M Coughlin; Atsushi Kamiya; Martin G Pomper; Akira Sawa; Minae Niwa Journal: Schizophr Res Date: 2018-02-03 Impact factor: 4.939