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Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects.

Abstract

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.

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  • Authors+Show Affiliations

    ,

    Department of Psychiatry and Health Behavior, Georgia Health Sciences University, Augusta, Georgia 30912, USA. brmiller@georgiahealth.edu

    , , ,

    Source

    Biological psychiatry 70:7 2011 Oct 01 pg 663-71

    MeSH

    Antipsychotic Agents
    Biomarkers
    Cytokines
    Humans
    Interleukin 1 Receptor Antagonist Protein
    Receptors, Cytokine
    Recurrence
    Schizophrenia

    Pub Type(s)

    Journal Article
    Meta-Analysis
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    21641581

    Citation

    Miller, Brian J., et al. "Meta-analysis of Cytokine Alterations in Schizophrenia: Clinical Status and Antipsychotic Effects." Biological Psychiatry, vol. 70, no. 7, 2011, pp. 663-71.
    Miller BJ, Buckley P, Seabolt W, et al. Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry. 2011;70(7):663-71.
    Miller, B. J., Buckley, P., Seabolt, W., Mellor, A., & Kirkpatrick, B. (2011). Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biological Psychiatry, 70(7), pp. 663-71. doi:10.1016/j.biopsych.2011.04.013.
    Miller BJ, et al. Meta-analysis of Cytokine Alterations in Schizophrenia: Clinical Status and Antipsychotic Effects. Biol Psychiatry. 2011 Oct 1;70(7):663-71. PubMed PMID: 21641581.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. AU - Miller,Brian J, AU - Buckley,Peter, AU - Seabolt,Wesley, AU - Mellor,Andrew, AU - Kirkpatrick,Brian, Y1 - 2011/06/08/ PY - 2010/09/29/received PY - 2011/03/21/revised PY - 2011/04/01/accepted PY - 2011/6/7/entrez PY - 2011/6/7/pubmed PY - 2012/1/24/medline SP - 663 EP - 71 JF - Biological psychiatry JO - Biol. Psychiatry VL - 70 IS - 7 N2 - 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. SN - 1873-2402 UR - https://www.unboundmedicine.com/medline/citation/21641581/full_citation L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-3223(11)00404-5 DB - PRIME DP - Unbound Medicine ER -