A systematic, quantitative review of blood autoantibodies in schizophrenia.
ABSTRACT Schizophrenia is associated with immune system dysfunction, including an increased prevalence of autoimmune disorders and autoantibodies. We performed a systematic, quantitative review of self-reacting blood antibodies in patients with schizophrenia.
We identified articles by searching PubMed, PsychInfo, and ISI, and the reference lists of identified studies.
Eighty-one of 111 studies identified met the inclusion criteria. There was a significant increased prevalence of positive titers for 20 different autoantibodies in patients with schizophrenia compared to controls. The prevalence of positive anti-cardiolipin IgG and NMDA receptor titers was also significantly increased in subjects with first-episode psychosis versus controls (p<0.01). Absolute titers for anti-cardiolipin IgG and IgM, and nerve growth factor were significantly increased in patients with schizophrenia compared to controls (p<0.02 for each).
Schizophrenia is associated with an increased prevalence of multiple autoantibodies, although there is marked study heterogeneity, and correlations between autoantibodies and clinical features are inconsistent. This area merits more research evaluation, especially controlling for potential confounding factors such as clinical status, age, genetic background, psychotropic medications, BMI, and smoking.
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ABSTRACT: Epidemiological studies are inconsistent on the relationship between schizophrenia (SCZ) and rheumatoid arthritis (RA). Several studies have shown that SCZ has a protective effect on RA, with RA occurring less frequently in SCZ cases than would be expected by chance, whilst other studies have failed to replicate this. We sought to test the hypothesis that this effect is due to a protective effect of SCZ risk alleles on RA onset. We first reviewed the literature on the comorbidity of RA and SCZ and performed a meta-analysis. We then used polygenic risk scoring in an RA case control study in order to investigate the contribution of SCZ risk alleles to RA risk. Meta-analysis across studies over the past half-century showed that prevalence of RA in SCZ cases was significantly reduced (OR = 0.48, 95% CI: 0.34-0.67, p < 0.0001). The relationship between SCZ genetic risk and RA status was weak. Polygenic risk of SCZ explained a small (0.1%) and non-significant (p = 0.085) proportion of variance in RA case control status. This relationship was nominally positive, with RA cases carrying more SCZ risk alleles than controls. The current findings do not support the assertion that the relationship between RA and SCZ is explained by genetic factors, which appear to have little or no effect. The protective effect of SCZ on RA may be due to environmental factors, such as an anti-inflammatory effect of anti-psychotic medication or merely due to confounding limitations in study designs. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.American Journal of Medical Genetics Part B Neuropsychiatric Genetics 02/2015; 168(2). DOI:10.1002/ajmg.b.32282 · 3.27 Impact Factor
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ABSTRACT: Encephalitis with antibodies against N-methyl-D-aspartate receptor (NMDA-R) is classified as an autoimmune disorder with psychotic symptoms, which are frequently dominant. However, it remains unclear how frequently NMDA-R antibodies lead to a condition that mimics psychosis and first-episode schizophrenia. In our work, we investigated the presence of antibodies against NMDA-R in patients with first-episode psychosis (FEP) in comparison with healthy volunteers. This study included 50 antipsychotic-naïve patients with FEP (including 21 women) and 50 healthy volunteers (including 21 women). The mean age of the patients was 27.4 (±7.4) years and that of the healthy controls was 27.0 (±7.3) years. Antibodies against NMDA-R in the serum were detected by immunofluorescence. None of the investigated patients with an FEP and none of the healthy controls showed positive antibodies against NMDA-Rs. According to results of studies, a small proportion of patients with an FEP possess antibodies against NMDA-R. However, the extent to which this finding contributes to the etiopathogenesis of the response to antipsychotic medication and whether immunomodulatory therapy is indicated in these cases remains uncertain.Neuropsychiatric Disease and Treatment 01/2015; 11:619-23. DOI:10.2147/NDT.S80746 · 2.15 Impact Factor
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ABSTRACT: When Eugen Bleuler coined the term 'schizophrenia' he believed that various causes of illness may underlie this disease. Currently, neurodevelopmental abnormalities and consecutive impairments in dopaminergic and glutamatergic neurotransmission are considered as major causes of schizophrenia. However, there are various indications for involvement of immune processes, at least in subgroups of patients. Circulating antineuronal antibodies provide a promising link between the well-described disturbances in neurotransmission and the immune hypothesis of schizophrenia. This review summarizes important studies that have examined the role of glutamate, dopamine, acetylcholine and serotonin receptor autoantibodies, and other antineuronal antibodies against synaptic proteins in the serum of patients diagnosed with schizophrenia. Currently, it is not known whether the presence of antineuronal antibodies in blood should be considered as a causal or disease-modulating factor in schizophrenia. Due to emerging evidence regarding the important role of the blood-brain barrier, combined testing of serum and cerebrospinal fluid is likely to be more appropriate to answer this question than pure serum analyses. We suggest implementation of such testing in first-onset and treatment-resistant patients as part of the diagnostic process. In addition, future clinical trials should evaluate if immunotherapy (e.g. cortisone pulse therapy, intravenous immunoglobulins, plasmapheresis, rituximab, or cyclophosphamide) is helpful in cases with a neuroinflammatory component.CNS Drugs 02/2015; DOI:10.1007/s40263-015-0233-3 · 4.38 Impact Factor