The inflammatory response system in treatment-resistant schizophrenia: increased serum interleukin-6. Schizophr Res

Clinical Research Center for Mental Health (CRC-MH), University Department of Psychiatry, Antwerp, Belgium.
Schizophrenia Research (Impact Factor: 3.92). 07/1998; 32(1):9-15. DOI: 10.1016/S0920-9964(98)00034-6
Source: PubMed


There is some evidence that the pathophysiology of schizophrenia is related to activation of the inflammatory response system (IRS), as indicated by increased serum concentrations of interleukin-6 (IL-6), IL-6 receptor (IL-6R), IL-1R antagonist (IL-1RA) and IL-2R and lower serum concentrations of CC16, an endogenous anti-inflammatory protein with immunosuppressive and anti-inflammatory effects. The aims of the present study were to examine serum CC16 in relation to IL-6, IL-6R and gp130, the IL-6 transducing signal protein, in schizophrenia and in treatment-resistant schizophrenia (TRS). Serum IL-6 and sIL-6R were significantly higher in medicated schizophrenic patients than in normal controls. Serum IL-6 was significantly higher in TRS than in normal volunteers, whereas schizophrenic patients without TRS showed intermediate values. Serum CC16 was significantly lower in schizophrenic patients with a positive family history for psychoses than in normal volunteers and patients without a positive family history. There was a significant inverse relationship between serum CC16 and serum IL-6 or sIL-6R in schizophrenic patients, but not in normal volunteers. The results suggest that the inflammatory response in schizophrenia, as indicated by increased serum IL-6 and sIL-6R, may be causally related to lower serum CC16 and that the latter might be a trait marker for schizophrenia.

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Available from: Michael Maes, Aug 20, 2015
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    • "Historically thought of as a culmination of 'a number of conditions which may lead to a severe disturbance of the ego',4) SCZ is now understood to arise from a complex interplay of genetic and environmental risk factors acting across many stages of brain development.5-11) Several neurochemical and neuropathological theories have been proposed to explain the pathological processes intrinsic to SCZ, including impairments in dopaminergic,12) glutamatergic13,14) and GABAergic signalling,15,16) impaired prefrontal cortex function,17-19) aberrant neurodevelopment, 11,20) stress vulnerability21) and variations in the inflammatory response.22,23) "
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    ABSTRACT: Schizophrenia (SCZ) is a polygenic, multi-factorial disorder and a definitive understanding of its pathophysiology has been lacking since it was first described more than a century ago. The predominant pharmacological approach used to treat SCZ is the use of dopamine receptor antagonists. The fact that many patients remain symptomatic, despite complying with medication regimens, emphasises the need for a more encompassing explanation for both the causes and treatment of SCZ. Recent neuroanatomical, neurobiological, environmental and genetic studies have revived the idea that inflammatory pathways are involved in the pathogenesis of SCZ. These new insights have emerged from multiple lines of evidence, including the levels of inflammatory proteins in the central nervous system of patients with SCZ and animal models. This review focuses on aberrant inflammatory mechanisms present both before and during the onset of the psychotic symptoms that characterise SCZ and discusses recent research into adjunctive immune system modulating therapies for its more effective treatment.
    Clinical Psychopharmacology and Neuroscience 12/2013; 11(3):107-117. DOI:10.9758/cpn.2013.11.3.107
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    • "Most interestingly, it stimulates the synthesis of catecholamines [7, 8]. In addition, overproduction of IL-6 has been found to correlate with clinical indices of schizophrenia [9, 10] and antipsychotic treatment decreases the plasma level of IL-6 [6]. The next cytokine, IFN-γ which is a Th1 cytokine plays a key role in antiviral defense, stimulates macrophage activity and induces expression of major histocompatibility complex (MHC) antigens [11, 12]. "
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    ABSTRACT: Immense body of evidence indicates that dysfunction of immune system is implicated in the etiology of schizophrenia. The immune theory of schizophrenia is supported by alterations in cytokine profile in the brain and peripheral blood. Given the strong genetic background of schizophrenia, it might be assumed that aberrant production of cytokines might be the consequence of genetic factors. This study aimed at investigating the association between schizophrenia susceptibility and selected functional polymorphisms in genes encoding cytokines including: interleukin-2 (IL2 -330T>G, rs2069756), interleukin-6 (IL-6 -174G>C, rs1800795), interferon-γ (IFNG +874T>A, rs2430561) as well as for the first time transforming growth factor-β1 (TGFB1 +869T>C, rs1800470 and +916G>C, rs1800471). We recruited 151 subjects with schizophrenia and 279 controls. There was a significant difference in the genotype distribution and allelic frequency of the TGFB1 +869T>C between patients with schizophrenia and healthy controls (p < 0.05). The risk of schizophrenia was more than two-fold higher in carriers of T allele (CT+TT genotypes) than individuals with CC genotype. Given documented gender differences in incidence of schizophrenia, we conducted separate analyses of male and female participants. We have shown that the association was significant in females, while in males it reached a trend toward statistical significance. To the best of our knowledge, it is the first report showing the association between TGFB1 +869T>C polymorphism and schizophrenia.
    Molecular Biology Reports 09/2013; 40(10). DOI:10.1007/s11033-013-2662-8 · 2.02 Impact Factor
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    • "A significant positive correlation was observed between the IL-6 levels and total psychopathology scores at the baseline; there was also a significant positive correlation between the change in the IL-6 levels and in the total psychopathology scores after antipsychotic treatment (Miller et al., 2011). Patients with schizophrenia that are resistant to antipsychotics display persistently high IL-6 levels (Lin et al., 1998). Patients included in our study protocol were not resistant to antipsychotic therapy and this lack of resistance was consistent with decreased concentrations of Fig. 1. "
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    ABSTRACT: Objective: We recently reported that the type-2 cytokine response is increased in schizophrenia. The aim of this study was to analyse the effects of antipsychotic drugs on the serum levels of type-1 (TNF-α, IFN-γ), type-2 (IL-4, IL-10), type-17 (IL-17) and regulatory cytokines (TGF-β, IL-27 and IL-6). Methods: Cytokine measurements in the patients were performed on day 0 and day 30 of the treatment using standard ELISA assays. Three groups of subjects were studied: patients that were unmedicated with First Episode Psychosis (FEP; n=88), patients that were treated with antipsychotics with Schizophrenia in relapse (SC in relapse; n=45) and healthy controls (n=36). Results: TGF-β levels were increased in both patient groups and were further enhanced after treatment in the FEP group (p=0.014) but not in the SC relapse group. Antipsychotic treatment was correlated with lower levels of IL-4, IL-6 and IL-27 (p<0.005) in the FEP group. Finally, the serum levels of IL-17 were not significantly altered between the two measurements but were significantly lower in the FEP group (p<0.001) when compared with healthy controls. After therapy, patients with SC who were in relapse had decreased serum levels of IL-4 (p=0.006) and IL-6 (p=0.007). We also observed a weak negative correlation between the IFN-γ/TGF-β ratio and the total PANSS score and between the IL-17/TGF-β ratio and the negative and general psychopathology subscales. Conclusion: The increased type-2 cytokine serum levels in schizophrenia appear to be downregulated by antipsychotic treatment.
    Schizophrenia Research 04/2013; DOI:10.1016/j.schres.2013.03.027 · 3.92 Impact Factor
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