Submitted to: Schizophrenia Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/11/2009
Publication Date: N/A
Citation: Interpretive Summary: It has long been speculated that there is a link between celiac disease and schizophrenia with some studies showing a linkage and others finding none. In this study of 17 schizophrenic patients, rigorous analysis for the presence or absence of DQ2 and DQ8 genes (necessary for celiac disease) and levels of transglutaminase-2 (an enzyme that is diagnostic for celiac disease) showed that most of the patients do not have celiac disease. The pattern of antibodies to gluten proteins in the patients was different from that of celiac patients and pointed towards increased intestinal permeability and immunologic abnormalities in the schizophrenia patients. The results are important in defining biomarkers for schizophrenia, helpful in analyzing for the disease, and provide supporting evidence for the possibility of an immune mechanism in schizophrenia.
Technical Abstract: Background: A link between celiac disease and schizophrenia, has been speculated for several years. The reported association is based primarily on reports of elevated levels of antibodies to gliadin (a component of gluten). However, the significance of such antibodies in schizophrenia and whether they are associated with celiac disease remain unknown. The aim of this study was to characterize the anti-gluten antibody response in patients with schizophrenia at the molecular level and to determine its relevance in the context of celiac disease-associated biomarkers. Methods: Serum specimens from 17 patients with established schizophrenia and elevated anti-gluten antibodies, 25 patients with celiac disease, and 25 healthy subjects were studied. Levels of antibodies to deamidated gluten peptides and transglutaminase 2 (TG2) enzyme, which have high specificities for celiac disease, were examined. Selected patients were tested for DQ2 and DQ8 HLA genes. The anti-gluten antibody response was further characterized through examination of reactivity towards chromatographically separated gluten proteins. Target proteins of interest were identified by peptide mass mapping. Results: The anti-gluten immune response in schizophrenia was not associated with anti-TG2 antibodies or HLA-DQ2/DQ8 markers. Unlike the celiac disease subjects, gluten-sensitive schizophrenic patients did not exhibit significant antibody reactivity to selectively deamidated gluten peptides. Detailed characertization of the antibody specificity indicated preferential reactivity towards different gluten proteins in schizophrenia and celiac disease groups. A protein specifically targeted by antibodies in a subset of schizophrenic patients was identified as a 33 kDa '-gliadin. Conclustion: The specificity of the antibody response in gluten-sensitive schizophrenic patients is different from that in individuals with celiac disease. Unlike celiac disease, the anti-gluten immune mechanism in psychiatric subjects does not appear to involve the transglutaminase enzyme or the HLA-DQ2 and -DQ8 MHC molecules. The presence of elevated levels of antibodies to specific gluten proteins points to increased intestinal permeability and shared immunologic abnormalities in a subset of patients with schizophrenia. Further characterization and understanding of the immune response to gluten in schizophrenic patients may provide novel insights into the etiopathogenesis of particular disease phenotypes and yield novel biomarkers for the diagnosis and follow-up of specific patient subsets.