title: Role of T helper lymphokines in the immune-inflammatory pathophysiology of schizophrenia: Systematic review and meta-analysis.
abstract: BACKGROUND
  Schizophrenia is highly complex multifactorial psychiatric disorder with poorly defined etiopathophysiology, which also has manifestations in the immune system.
  
  
  OBJECTIVE
  The aim of this review is to meta-analyze the available evidence regarding the role of immune activation indicated by the T helper cells in order to evaluate etiopathophysiological links between the immune system and schizophrenia.
  
  
  METHODS
  A literature search was performed in multiple electronic databases for relevant research papers published between 1990 and May 2014. Meta-analyses were conducted under both random- (REM) and fixed-effect models (FEM) by calculating weighted mean differences with 95% confidence intervals. Heterogeneity was assessed with the I(2) index.
  
  
  RESULTS
  Twenty-one studies were selected after observing inclusion and exclusion criteria. In vitro interferon-gamma (INF-γ) and interleukin (IL)-2 production was significantly lower in the schizophrenic patients compared with non-schizophrenic control individuals under both FEM and REM. Serum levels of IL-2 and serum/in vitro IL-4 were not significantly different in both groups under both FEM and REM. Overall Th1:Th2 ratio (INF-γ:IL-4 and IL-2:IL-4) in the serum samples was significantly deflected towards Th2 under both models in the serum samples (- 0.33 [- 0.59 to - 0.06]; P < 0.03, FEM and - 2.44 [- 4.27 to - 0.60]; P < 0.009, REM) but in vitro production Th1:Th2 ratio (INF-γ:IL-4 and IL-2:IL-4) was deflected towards Th1 under both the models (1.11 [0.45-1.78]; P < 0.002, FEM and 6.68 [0.72-12.64]; P < 0.03, REM).
  
  
  CONCLUSIONS
  Whereas the Th1:Th2 ratio in the serum samples deflected towards T2, in vitro Th1:Th2 ratio favored Th1 when the individual study data were meta-analyzed.
authors.affiliation: Jing Guo, M.D., Clinical Laboratory, The 261st Hospital of The People's Liberation Army , Beijing , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.forename: Chaojun
authors.initials: C
authors.lastname: Liu
authors.forename: Yaxi
authors.initials: Y
authors.lastname: Wang
authors.forename: Baie
authors.initials: B
authors.lastname: Feng
authors.forename: Xueyan
authors.initials: X
authors.lastname: Zhang
mesh_terms: D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008222:Lymphokines / Q000097:blood / Q000378:metabolism*; D012559:Schizophrenia / Q000097:blood / Q000276:immunology*; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
chemical_list: D016207:Cytokines; D008222:Lymphokines
keywords: Immune activation; Interleukin; Schizophrenia; T helper cells; Th1:Th2 ratio