Autoimmune diseases and infections as risk factors for schizophrenia

National Center for Register-based Research, Aarhus University, Aarhus, Denmark.
Annals of the New York Academy of Sciences (Impact Factor: 4.38). 07/2012; 1262(1):56-66. DOI: 10.1111/j.1749-6632.2012.06638.x
Source: PubMed


Immunological hypotheses have become increasingly prominent when studying the etiology of schizophrenia. Autoimmune diseases, and especially the number of infections requiring hospitalization, have been identified as significant risk factors for schizophrenia in a dose-response relationship, which seem compatible with an immunological hypothesis for subgroups of patients with schizophrenia. Inflammation and infections may affect the brain through many different pathways that are not necessarily mutually exclusive and can possibly increase the risk of schizophrenia in vulnerable individuals. However, the findings could also be an epiphenomenon and not causal, due to, for instance, common genetic vulnerability, which could be supported by the observations of an increased prevalence of autoimmune diseases and infections in parents of patients with schizophrenia. Nevertheless, autoimmune diseases and infections should be considered in the treatment of individuals with schizophrenia symptoms, and further research is needed of the immune system's possible contributing pathogenic factors in the etiology of schizophrenia.

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    • "Several lines of evidence suggest that infection, inflammation and autoimmunity may contribute to the aetiology of schizophrenia (Benros et al., 2011, 2012; Fillman et al., 2013), and in a recent study, we associated schizophrenia with MBL and mannan-binding lectinassociated serine protease-2 (MASP-2), two key components of the lectin pathway of complement activation (Foldager et al., 2012). The aetiology of both bipolar (Leboyer et al., 2012) and panic respectively anxiety disorder (Salazar et al., 2012; Chen et al., 2013) is suspected to be associated with an inflammatory state, and autoimmune processes and infections may precede bipolar Contents lists available at ScienceDirect journal homepage: "
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    ABSTRACT: Background Mannan-binding lectin (MBL) and mannan-binding lectin-associated serine protease-2 (MASP-2) represent important arms of the innate immune system, and different deficiencies may result in infections or autoimmune diseases. Both bipolar and panic disorders are associated with increased inflammatory response, infections and mutual comorbidity. However, associations with MBL, MASP-2 or the gene, MBL2, coding for MBL, have not been investigated thoroughly. Methods One hundred patients with bipolar disorder, 100 with panic disorder and 349 controls were included. Serum concentrations of MBL and MASP-2 were measured and seven single nucleotide polymorphisms (SNPs) influencing these concentrations were genotyped. Disease association with genetic markers and serum levels were investigated. Results In panic disorder, we observed a large proportion (30%) of MBL deficient (<100 ng/ml) individuals and significantly lower levels of MBL and MASP-2 plus association with the MBL2 YA two-marker haplotype. Bipolar disorder was associated with the MBL2 LXPA haplotype and lower MASP-2 levels. Limitations No information on course or severity of disorders was included, and only MBL and MASP-2 were measured, excluding other components from the complement pathway. Restrictions defined by ethnical committees preclude information of control's ethnic origin. Conclusions Significant differences in MBL and MASP-2 concentrations were observed between cohorts, especially an intriguing finding associating panic disorder with MBL deficiency. These differences could not be fully explained by allele or haplotype frequency variations. Since MBL deficiency is highly heterogeneous and associated with both infectious and autoimmune states, more research is needed to identify which complement pathway components could be associated with bipolar respectively panic disorder.
    Journal of Affective Disorders 08/2014; 164C:148-154. DOI:10.1016/j.jad.2014.04.017 · 3.38 Impact Factor
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    • "Schizophrenia is a highly heterogeneous disorder, and some investigators have proposed that immune abnormalities may be involved in the etiology and pathophysiology of schizophrenia (Muller and Schwarz 2006; Benros et al. 2012; Mansur et al. 2012; Na et al. 2014; Richard and Brahm 2012; Altamura et al. 2014). Cytokines function as chemical messengers between immune cells and have numerous important functions in immune regulation. "
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    ABSTRACT: Objective A substantial body of evidence implicates TNF-alpha (TNFα) and TNFα-related signaling pathways in the pathophysiology of schizophrenia. The current study examined the relationship between TNFα serum levels and both psychopathological as well as cognitive symptoms in schizophrenia. Materials and methods Serum TNFα levels were assessed in 89 patients diagnosed with schizophrenia and compared to 43 healthy control subjects matched for age and gender. Schizophrenic symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS), and serum TNFα levels were measured by sandwich enzyme-linked immunosorbent assay (ELISA). Results TNFα levels were significantly lower in patients with chronic schizophrenia relative to healthy control subjects (p
    Psychopharmacology 06/2014; 232(1). DOI:10.1007/s00213-014-3650-y · 3.88 Impact Factor
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    • "Conversely, a national case-registry based study of SZ patients from Taiwan indicated increased prevalence of auto-immune diseases including Graves' disease, psoriasis, celiac disease, pernicious anemia, and hypersensitivity vasculitis [Chen et al., 2012]. An increased prevalence of auto-immune disorders has also been observed among non-psychotic relatives of patients with SZ [Eaton et al., 2010; Benros et al., 2012]. On the other hand, patients with SZ have reduced prevalence of rheumatoid arthritis, another auto-immune disease [Chen et al., 2012]. "
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    ABSTRACT: Associations between human leukocyte antigen (HLA) polymorphisms on chromosome 6p and schizophrenia (SZ) risk have been evaluated for over five decades. Numerous case-control studies from the candidate gene era analyzed moderately sized samples and reported nominally significant associations with several loci in the HLA region (sample sizes, n = 100-400). The risk conferred by individual alleles was modest (odds ratios < 2.0). The basis for the associations could not be determined, though connections with known immune and auto-immune abnormalities in SZ were postulated. Interest in the HLA associations has re-emerged following several recent genome-wide association studies (GWAS); which utilized 10- to 100-fold larger samples and also identified associations on the short arm of chromosome 6. Unlike the earlier candidate gene studies, the associations are statistically significant following correction for multiple comparisons. Like the earlier studies; they have modest effect sizes, raising questions about their utility in risk prediction or pathogenesis research. In this review, we summarize the GWAS and reflect on possible bases for the associations. Suggestions for future research are discussed. We favor, in particular; efforts to evaluate local population sub-structure as well as further evaluation of immune-related variables in future studies. © 2013 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 01/2014; 165(1). DOI:10.1002/ajmg.b.32195 · 3.42 Impact Factor
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