title: 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.
authors.affiliation: Department of Psychiatry and Health Behavior, Georgia Health Sciences University, Augusta, Georgia 30912, USA. brmiller@georgiahealth.edu
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Miller
authors.forename: Peter
authors.initials: P
authors.lastname: Buckley
authors.forename: Wesley
authors.initials: W
authors.lastname: Seabolt
authors.forename: Andrew
authors.initials: A
authors.lastname: Mellor
authors.forename: Brian
authors.initials: B
authors.lastname: Kirkpatrick
mesh_terms: D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D016207:Cytokines / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000187:drug effects; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood / Q000134:cerebrospinal fluid / Q000187:drug effects; D018121:Receptors, Cytokine / Q000097:blood / Q000187:drug effects; D012008:Recurrence; D012559:Schizophrenia / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000188:drug therapy
chemical_list: D014150:Antipsychotic Agents; D015415:Biomarkers; D016207:Cytokines; D053590:Interleukin 1 Receptor Antagonist Protein; D018121:Receptors, Cytokine