The Interaction of Nuclear Factor-Kappa B and Cytokines Is Associated with Schizophrenia

Song, Xueqin; Lv, Luxian; Li, Wenqiang; Hao, Yihui; Zhao, Jingping

doi:10.1016/j.biopsych.2008.10.018

Cited by 168 publications

(109 citation statements)

References 59 publications

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“…A combination of genetic and environmental factors resulting in some immune dysregulation in general and the lack of the CMV IgG antibodies in particular could be the most plausible speculations. While there are no specific research results supporting this finding in existing literature, the activation of the immune system and prolonged neuroinflammation are well established phenomena implicated in the etiopathogenesis and symptomatology of schizophrenia (Lin et al, 1998;Nikkila et al, 1999;Kim et al, 2000;Theodoropoulou et al, 2001;Ebrinc et al, 2002;Patterson, 2002;Zhang et al, 2002;Garver et al, 2003;Zhang et al, 2004;Coelho et al, 2008;Potvin et al, 2008;Doorduin et al, 2009;Kim et al, 2009;Song et al, 2009;Drexhage et al, 2010;Romero et al, 2010;Drexhage et al, 2011;Weigelt et al, 2011;Beumer et al, 2012;Brito-Melo et al, 2012). Other mechanisms could also be considered.…”

Section: Discussionmentioning

confidence: 83%

Association between antibodies to multiple infectious and food antigens and new onset schizophrenia among US military personnel

Li¹,

Weber²,

Fisher³

et al. 2013

Schizophrenia Research

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a b s t r a c t a r t i c l e i n f oIntroduction: Multiple studies have documented immune activation in many individuals with schizophrenia suggesting that antigens capable of generating a prolonged immune response may be important environmental factors in many cases of this disorder. While existing studies have found single-agent associations of antibodies to food and neurotropic infectious agents with schizophrenia, a simultaneous examination of multiple agents may shed light on agent interactions or possible etiopathogenic pathways. Methods: We used traditional regression and novel statistical techniques to examine associations of single and combined infectious and food antigens with schizophrenia. We tested 6106 serum samples from 855 cases and 1165 matched controls. Results: Higher antibody levels to casein were borderline significant in the prediction of schizophrenia (HR = 1.08, p = 0.06). Study participants with higher cytomegalovirus (CMV) IgG antibody levels had a reduced risk of developing schizophrenia (HR = 0.90; p = 0.02). While IgG antibodies to gliadin, Toxoplasma gondii, vaccinia, measles, and human herpesvirus-6 (HHV-6) showed no significant independent associations with schizophrenia, the increase in antibody levels to several combinations of agents, to include casein, measles, CMV, T. gondii and vaccinia, was predictive of an 18-34% increase in the risk of developing schizophrenia. Conclusion: Certain patterns of antibodies, involving some agents, were predictive of developing schizophrenia, with the magnitude of association rising when the level of antibodies increased to two or more agents. A heightened antibody response to a combination of several infectious/food antigens might be an indicator of an altered immune response to antigenic stimuli.Published by Elsevier B.V.

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Section: Discussionmentioning

confidence: 83%

Association between antibodies to multiple infectious and food antigens and new onset schizophrenia among US military personnel

Li¹,

Weber²,

Fisher³

et al. 2013

Schizophrenia Research

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“…The presence of increased levels of IL-6, TNF-α and IL-1β in individuals with first-episode psychosis is consistently reported across several different studies [18,19,20,21,22]. Indeed, abnormal levels of other inflammatory markers have also been reported in first-episode psychosis, including increased levels of IL-12, IL-1α and TGF-β, and decreased levels of IL-5 [18,23,24,25].…”

Section: Markers Of Inflammation In First-episode Psychosismentioning

confidence: 83%

First-Episode Psychosis: An Inflammatory State?

Zajkowska

Mondelli²

2014

Neuroimmunomodulation

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In the last decade an increasing body of research has focussed on the potential role of inflammation in the onset of psychiatric disorders. Although the association between inflammation and depression appears now widely acknowledged, mixed findings have been reported in psychosis leaving the pathophysiological role of inflammation in psychosis still unclear. This paper aims to review studies focussing on inflammation in first-episode psychosis, in order to avoid the possible confounding effects of the long duration of illness and chronic treatment with psychotropic medications. Increased levels of IL-6, TNF-α and IL-1β are the most consistent findings from the studies conducted in first-episode psychosis patients. Mixed findings on other cytokines could be partly due to the different methodologies of the studies reviewed. The findings on the association between inflammatory markers and clinical symptoms and physical health, as well as on the effect of antipsychotic medications on inflammation at the onset of psychosis are also reviewed and discussed. The increased inflammation at onset of psychosis as well as in other psychiatric conditions, such as depression, suggests the presence of biological abnormalities which play a pathophysiological role across different diagnostic categories. Future research should test if increased inflammation could be used for the development of biomarkers, as well as as a potential therapeutic target for different subsamples of patients independently of their diagnostic category.

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“…In contrast, a more recent longitudinal study demonstrated lack of changes in IL-6 over 12 weeks of antipsychotic treatment in FEP, indicating that it could be a more trait-like marker [33]. As IL-12, IFN-γ, TNF-α and sIL-2R increased levels did not normalise with treatment, these were suggested to be disease trait markers [21,25,34]. However, a later study did not find any cytokine to fuction as a trait marker, as all the studied cytokines-IL-6, IL-10, TNF-α and IL-4-initially increased in FEP and normalised after risperidone treatment [35].…”

Section: Immunoinflammatory Biomarkersmentioning

confidence: 89%

Biomarkers and schizophrenia: a qualitative review

Silva¹,

Pinto²

2017

IJCNMH

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Schizophrenia (SCZ) is a psychiatric disorder with a broad spectrum of biological and clinical manifestations of yet not completely clear pathophysiological mechanisms. Several lines of evidence have been supporting the idea that immunoinflammatory, oxidative, hormonal and cellular dysfunctions are implicated on the biomolecular basis of SCZ. However, accurate diagnosis and selection of appropriate treatments remains challenging as a result of the scarcity of objective tests. Furthermore, there is a compelling need to find biomarkers that could predict drug response and tailor pharmacological treatment, particularly in drug-naïve first episode psychosis (FEP). Hence, numerous technologies have been employed in order to search for SCZ biological markers, but evidence relating them to treatment efficacy is lacking. In this regard, some preliminary data suggest promising results. The current review provides information on: (1) potential biomarkers associated with biological disturbances and (2) biological markers associated with treatment response.

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The Interaction of Nuclear Factor-Kappa B and Cytokines Is Associated with Schizophrenia

Cited by 168 publications

References 59 publications

Association between antibodies to multiple infectious and food antigens and new onset schizophrenia among US military personnel

Association between antibodies to multiple infectious and food antigens and new onset schizophrenia among US military personnel

First-Episode Psychosis: An Inflammatory State?

Biomarkers and schizophrenia: a qualitative review

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