Article

Inflammatory cytokine alterations in schizophrenia a systematic review.

Department of Psychiatry, Faculty of Medicine, University of Montreal, Fernand-Seguin Research Center, Louis-H Lafontaine Hospital, Montreal, Quebec, Canada.
Biological psychiatry (Impact Factor: 9.47). 05/2008; 63(8):801-8. DOI: 10.1016/j.biopsych.2007.09.024
Source: PubMed

ABSTRACT Cytokines play an important role in infection and inflammation and are crucial mediators of the cross-talk between the brain and the immune system. Schizophrenia would be associated with an imbalance in inflammatory cytokines, leading to a decrease in Th1 and an increase in Th2 cytokine secretion. However, data published so far have been inconsistent. The primary objective of the present meta-analysis was to verify whether the cytokine imbalance hypothesis of schizophrenia is substantiated by evidence.
Cross-sectional studies were included if they assessed in vivo plasma or serum cytokine concentrations and/or in vitro secretion of cytokines by peripheral blood leukocytes from schizophrenia patients and healthy volunteers.
Data from 62 studies involving a total sample size of 2298 schizophrenia patients and 1858 healthy volunteers remained for analysis. Ten cytokines were assessed, including the prototypic Th1 and Th2 cytokines gamma interferon (IFN-gamma) and interleukin 4 (IL-4) as well as IL-2, soluble IL-2 receptor (sIL-2R), IL-1beta, IL-1 receptor antagonist (IL-1RA), tumor necrosis factor-alpha (TNF-alpha), IL-6, soluble IL-6 receptor (sIL-6R), and IL-10. The results show that an increase occurs in in vivo IL-1RA, sIL-2R, and IL-6 and a decrease occurs in in vitro IL-2 in schizophrenia. No significant effect sizes were obtained for the other cytokines.
These findings provide the first evidence of establishment of an inflammatory syndrome in schizophrenia, which refutes the current hypothesis of a Th2 slant. Caveats are presented to data interpretation, including the role of stress and the effect of weight gain that develops in schizophrenia.

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    • "The neural activities of pro-inflammatory cytokines are mainly mediated by microglia. There have been consistent reports that increased levels of pro-inflammatory cytokines and microglial activation are associated with schizophrenia (Miller et al., 2011; Potvin et al., 2008; van Berckel et al., 2008). Microglia are found in the CNS and account for approximately up to 20% of the glial cell population in the CNS (Lawson et al., 1992), with particularly high concentrations in the hippocampus, basal ganglia, and substantia nigra (Badoer, 2010). "
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    • "These mechanisms may lead to changes in feeding behaviors and exercise activity [3] [4]. Alterations in these biological systems, also as the consequence of childhood trauma, have been widely reported in firstepisode psychosis subjects [25] [26] [27] [28] [29] [30]. "
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