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

Brian J. Miller, Peter Buckley, Wesley Seabolt, Andrew Mellor, Brian Kirkpatrick

Research output: Contribution to journalArticle

833 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)663-671
Number of pages9
JournalBiological Psychiatry
Volume70
Issue number7
DOIs
StatePublished - Oct 1 2011

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Antipsychotic Agents
Meta-Analysis
Schizophrenia
Interleukin-1
Psychotic Disorders
Cytokines
Inpatients
Interleukin-6
Interleukin-2 Receptors
Transforming Growth Factors
Interleukin-12
Interferons
Tumor Necrosis Factor-alpha
PubMed
Cerebrospinal Fluid
Immune System
Body Mass Index
Outpatients
Therapeutics
Smoking

Keywords

  • Cytokines
  • first-episode psychosis
  • meta-analysis
  • relapse
  • schizophrenia

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Meta-analysis of cytokine alterations in schizophrenia : Clinical status and antipsychotic effects. / Miller, Brian J.; Buckley, Peter; Seabolt, Wesley; Mellor, Andrew; Kirkpatrick, Brian.

In: Biological Psychiatry, Vol. 70, No. 7, 01.10.2011, p. 663-671.

Research output: Contribution to journalArticle

Miller, Brian J. ; Buckley, Peter ; Seabolt, Wesley ; Mellor, Andrew ; Kirkpatrick, Brian. / Meta-analysis of cytokine alterations in schizophrenia : Clinical status and antipsychotic effects. In: Biological Psychiatry. 2011 ; Vol. 70, No. 7. pp. 663-671.
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