Prevalence of autoimmune diseases in in-patients with schizophrenia: Nationwide population-based study

Yuli Mental Research Center, Department of Psychiatry, Yuli Veteran Hospital, Hualien, and Institute of Medical Science, Tzu Chi University, Hualien, Taiwan.
The British journal of psychiatry: the journal of mental science (Impact Factor: 7.99). 03/2012; 200(5):374-80. DOI: 10.1192/bjp.bp.111.092098
Source: PubMed


The association between autoimmune diseases and schizophrenia has rarely been systematically investigated.
To investigate the association between schizophrenia and a variety of autoimmune diseases and to explore possible gender variation in any such association.
Taiwan's National Health Insurance Research Database was used to identify 10 811 hospital in-patients with schizophrenia and 108 110 age-matched controls. Univariate and multiple logistic regression analyses were performed, separately, to evaluate the association between autoimmune diseases and schizophrenia. We applied the false discovery rate to correct for multiple testing.
When compared with the control group, the in-patients with schizophrenia had an increased risk of Graves' disease (odds ratio (OR) = 1.32, 95% CI 1.04-1.67), psoriasis (OR = 1.48, 95% CI 1.07-2.04), pernicious anaemia (OR = 1.71, 95% CI 1.04-2.80), celiac disease (OR = 2.43, 95% CI 1.12-5.27) and hypersensitivity vasculitis (OR = 5.00, 95% CI 1.64-15.26), whereas a reverse association with rheumatoid arthritis (OR = 0.52, 95% CI 0.35-0.76) was also observed. Gender-specific variation was found for Sjögren syndrome, hereditary haemolytic anaemia, myasthenia gravis, polymyalgia rheumatica and dermatomyositis.
Schizophrenia was associated with a greater variety of autoimmune diseases than was anticipated. Further investigation is needed to gain a better understanding of the aetiology of schizophrenia and autoimmune diseases.

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    • "The increased incidence of immune disorders in schizophrenia patients and their parents is generally consistent with other epidemiological findings (Leucht et al., 2007; Eaton et al., 2010; Chen et al., 2012). A notable exception is the risk of rheumatoid arthritis, which has been found to be increased in parents of schizophrenia patients compared to parents of controls (Gilvarry et al., 1996; Eaton et al., 2006), whereas other epidemiological studies comparing patients with controls have reported schizophrenia to be a protective factor for rheumatoid arthritis (Leucht et al., 2007; Chen et al., 2012). This discrepancy suggests that although environmental and diseaserelated factors may protect schizophrenia patients from rheumatoid arthritis, genetic or other family-related factors may increase the risk of rheumatoid arthritis. "
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    ABSTRACT: Background: Schizophrenia patients and their parents have an increased risk of immune disorders compared to population controls and their parents. This may be explained by genetic overlap in the pathogenesis of both types of disorders. The purpose of this study was to investigate the genetic overlap between schizophrenia and three immune disorders and to compare with the overlap between schizophrenia and two disorders not primarily characterized by immune dysregulation: bipolar disorder and type 2 diabetes. Methods: We performed a polygenic risk score analysis using results from the schizophrenia Psychiatric GWAS consortium (PGC) (8922 cases and 9528 controls) and five Wellcome Trust Case Control Consortium (WTCCC) case samples as target cases: bipolar disorder (n=1998), type 1 diabetes (n=2000), Crohn's diseases (n=2005), rheumatoid arthritis (n=1999), and type 2 diabetes (n=1999). The WTCCC British Birth Cohort and National Blood Service samples (n=3004) were used as target controls. Additionally, we tested whether schizophrenia polygenic risk scores significantly differed between patients with immune disorder, bipolar disorder, and type 2 diabetes respectively. Results: Polygenic risk scores for schizophrenia significantly predicted disease status in all three immune disorder samples (Nagelkerke-R(2) 1.1%-1.3%; p<0.05). The polygenic risk of schizophrenia in patients with immune disorders was significantly lower than in patients with bipolar disorder (Nagelkerke-R(2) 6.0%; p<0.05), but higher than in type 2 diabetes patients (Nagelkerke-R(2) 0.5%; p<0.05). Conclusions: Our results suggest that genetic factors are shared between schizophrenia and immune disorders. This contributes to an accumulating body of evidence that immune processes may play a role in the etiology of schizophrenia.
    Full-text · Article · Sep 2014 · Schizophrenia Research
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    • "Major risk factors for schizophrenia include a history of maternal and prenatal infections, prior hospitalization for severe infection, and autoimmune comorbidity (Yolken and Torrey, 1995; Gilvarry et al., 1996; Torrey et al., 1997; Buka et al., 2001; Brown et al., 2005; Eaton et al., 2006; Mortensen et al., 2007; Torrey et al., 2007; Buka et al., 2008; Brown and Derkits, 2010; Benros et al., 2011; Chen et al., 2012; Benros et al., 2014a,b)—all of which link elevated pro-inflammatory cytokines to the pathogenesis schizophrenia (as reviewed by Miller et al. (2013a) and Meyer (2013)). Prenatal exposure to inflammation or infection can injure developing oligodendroglia, resulting in prominent white matter pathology and motor, cognitive, and behavioral impairments (recently reviewed by Deng (2010))—all of which are associated with pre-psychosis and schizophrenia (Chew et al., 2013). "
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    ABSTRACT: Background: Neuroinflammation and white matter pathology have each been independently associated with schizophrenia, and experimental studies have revealed mechanisms by which the two can interact in vitro, but whether these abnormalities simultaneously co-occur in people with schizophrenia remains unclear. Method: We searched MEDLINE, EMBASE, PsycINFO and Web of Science from inception through 12 January 2014 for studies reporting human data on the relationship between microglial or astroglial activation, or cytokines and white matter pathology in schizophrenia. Results: Fifteen studies totaling 792 subjects (350 with schizophrenia, 346 controls, 49 with bipolar disorder, 37 with major depressive disorder and 10 with Alzheimer's disease) met all eligibility criteria. Five neuropathological and two neuroimaging studies collectively yielded consistent evidence of an association between schizophrenia and microglial activation, particularly in white rather than gray matter regions. Ultrastructural analysis revealed activated microglia near dystrophic and apoptotic oligodendroglia, demyelinating and dysmyelinating axons and swollen and vacuolated astroglia in subjects with schizophrenia but not controls. Two neuroimaging studies found an association between carrier status for a functional single nucleotide polymorphism in the interleukin-1β gene and abnormal white as well as gray matter volumes in schizophrenia but not controls. A neuropathological study found that orbitofrontal white matter neuronal density was increased in schizophrenia cases exhibiting high transcription levels of pro-inflammatory cytokines relative to those exhibiting low transcription levels and to controls. Schizophrenia was associated with decreased astroglial density specifically in subgenual cingulate white matter and anterior corpus callosum, but not other gray or white matter areas. Astrogliosis was consistently absent. Data on astroglial gene expression, mRNA expression and protein concentration were inconsistent. Conclusion: Neuroinflammation is associated with white matter pathology in people with schizophrenia, and may contribute to structural and functional disconnectivity, even at the first episode of psychosis.
    Full-text · Article · Jun 2014 · Schizophrenia Research
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    • "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]. Others have also reported a reduced prevalence of type 1 diabetes mellitus among patients with SZ in a Finnish national registry [Juvonen et al., 2007] in contrast to the Danish studies [Benros et al., 2011]. "
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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.
    Preview · Article · Jan 2014 · American Journal of Medical Genetics Part B Neuropsychiatric Genetics
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