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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Available from: Amir Sepehry, Jul 28, 2015
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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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    ABSTRACT: Cytokines are pleiotropic molecules with important roles in inflammatory responses. Pro-inflammatory cytokines and neuroinflammation are important not only in inflammatory responses but also in neurogenesis and neuroprotection. Sustained stress and the subsequent release of pro-inflammatory cytokines lead to chronic neuroinflammation, which contributes to depression. Hippocampal glucocorticoid receptors (GR) and the associated hypothalamus-pituitary-adrenal (HPA) axis have close interactions with pro-inflammatory cytokines and neuroinflammation. Elevated pro-inflammatory cytokine levels and GR functional resistance are among the most widely investigated factors in the pathophysiology of depression. These two major components create a vicious cycle. In brief, chronic neuroinflammation inhibits GR function, which in turn exacerbates pro-inflammatory cytokine activity and aggravates chronic neuroinflammation. On the other hand, neuroinflammation causes an imbalance between oxidative stress and the antioxidant system, which is also associated with depression. Although current evidence strongly suggests that cytokines and GR have important roles in depression, they are essential components of a whole system of inflammatory and endocrine interactions, rather than playing independent parts. Despite the evidence that a dysfunctional immune and endocrine system contributes to the pathophysiology of depression, much research remains to be undertaken to clarify the cause and effect relationship between depression and neuroinflammation. Copyright © 2015. Published by Elsevier Inc.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 06/2015; DOI:10.1016/j.pnpbp.2015.06.008 · 4.03 Impact Factor
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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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    General Hospital Psychiatry 03/2015; DOI:10.1016/j.genhosppsych.2015.03.017 · 2.90 Impact Factor
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    • "Moreover, serum concentrations of several pro-inflammatory cytokines are found raised in patients with schizophrenia [2] [8], where these cytokines may alter neurotransmitter, neurodevelopmental and neural network activity [3]. Such altered cytokine levels have also been linked to the disease state, metabolic factors and antipsychotic medication [9]. Notably, while altered levels of and/or polymorphisms in IL12, IL17 and IL6 in patients with schizophrenia have been reported [10], aberrant IL23 levels have, to our knowledge, not been demonstrated. "
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    ABSTRACT: Schizophrenia is a mental disorder, where genetic and environmental factors contribute to disease onset and progression. The immune system appears to play a role in schizophrenia, where altered cytokines levels and autoantibodies have been described. Notably however, to our knowledge, IL23 levels have not before been measured in schizophrenia patients treated with depot medication. We examined IL23 levels in serum samples obtained from patients with schizophrenia, treated with depot medication (n=35) compared with healthy controls (n=38) and correlated these levels with treatment time, patient age and illness severity. IL23 levels were raised in depot treated groups compared with healthy controls. No correlation was observed, however, between IL23 levels and treatment time, patient age or illness severity. IL23 levels are raised in schizophrenia patients prescribed with depot medication, supporting the role of aberrant cytokine signalling in schizophrenia. Copyright © 2014. Published by Elsevier Ltd.
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