Role of T helper lymphokines in the immune-inflammatory pathophysiology of schizophrenia: Systematic review and meta-analysis.

BACKGROUND: Schizophrenia is highly complex multifactorial psychiatric disorder with poorly defined etiopathophysiology, which also has manifestations in the immune system. AIMS: 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.