Coeliac disease and schizophrenia: population based case control study with linkage of Danish national registers
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《英国医生杂志》
1 Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, 624 North Broadway, Baltimore, MD 21205, USA, 2 National Centre for Register-Based Research, Aarhus University, Taasingegade 1, 8000 Aarhus C, Denmark, 3 Institute of Basic Psychiatric Research, Psychiatric Hospital in Aarhus, Skovagervej 2, 8240 Risskov, Denmark
Correspondence to: W W Eaton weaton@jhsph.edu
Introduction
A history of coeliac disease is a risk factor for schizophrenia, as shown in this epidemiological study. The risk relation is strong but reflects a small proportion of cases of either disorder, since both disorders are rare.
Coeliac disease is presumably underascertained in this study. Only coeliac disease occurring before onset of schizophrenia in the case was considered, and only cases in hospitals or specialty clinics are included. Clinical symptoms of coeliac disease occur in only a fraction (about one in seven) of people with the pathognomic antibody.
Ascertainment bias does not explain the results because it would exist with equal strength for Crohn's disease and ulcerative colitis, and the relative risk for them is weak. Ascertainment bias would not affect the relation of schizophrenia and coeliac disease in parents, which had similar strength to that in cases.
Removal of gluten from the diet is not dangerous or expensive and is an effective treatment for coeliac disease. Failure of replication in earlier clinical trials of gluten withdrawal may have been the result of sampling fluctuation since coeliac disease is rare. New screening tests for coeliac disease are inexpensive and carry minimal risk and discomfort. An important question is the degree to which removal of gluten from the diet will alleviate symptoms in the small proportion of people with schizophrenia who screen positively for coeliac disease but do not show its classical symptoms.
Contributors: WWE and PBM designed the study. WWE, EA, and MB conducted the analyses of data. WWE drafted the manuscript. All authors contributed to the design of the analysis, interpretation of data and reporting of results. Noel Rose, Peter Zandi, and Alessio Fasano provided helpful advice. WWE had full access to (anonymous) data and assumes responsibility for the decision to submit the paper for publication.
Funding: Danish National Research Foundation, Stanley Medical Research Institute, and NIMH grant #53188.
Competing interests: None declared.
Ethical approval: Danish Data Protection Agency, Committee on Human Research of the Bloomberg School of Public Health, and Single Project Assurance Committee in Aarhus, Denmark, established according to regulations from the US National Institutes of Health.
References
Dohan F. Cereals and Schizophrenia Data and Hypothesis. Acta Psychiatrica Scand 1966;42: 125-52.
Singh MM, Kay S. Wheat gluten as a pathogenic factor in schizophrenia. Science 1976;191: 191-2.
Zhong F, McCombs CC, Olson JM, Elston RC, Stevens FM, McCarthy CF, et al. An autosomal screen for genes that predispose to celiac disease in the western counties of Ireland. Nature Genetics 1996;14: 329-33.
Straub RE, MacLean CJ, O'Neill FA, Burke J, Murphy B, Duke F, et al. A potential vulnerability locus for schizophrenia on chromosome 6p24-22: evidence for genetic heterogeneity. Nature Genetics 1995;11: 287-93.
Mortensen PB, Pedersen CB, Westergaard T, Wohlfahrt J, Ewald H, Mors O, et al. Familial and non-familial risk factors for schizophrenia: a population-based study. N Engl J Med 1999;340: 603-8.(William Eaton, professor1)
Correspondence to: W W Eaton weaton@jhsph.edu
Introduction
A history of coeliac disease is a risk factor for schizophrenia, as shown in this epidemiological study. The risk relation is strong but reflects a small proportion of cases of either disorder, since both disorders are rare.
Coeliac disease is presumably underascertained in this study. Only coeliac disease occurring before onset of schizophrenia in the case was considered, and only cases in hospitals or specialty clinics are included. Clinical symptoms of coeliac disease occur in only a fraction (about one in seven) of people with the pathognomic antibody.
Ascertainment bias does not explain the results because it would exist with equal strength for Crohn's disease and ulcerative colitis, and the relative risk for them is weak. Ascertainment bias would not affect the relation of schizophrenia and coeliac disease in parents, which had similar strength to that in cases.
Removal of gluten from the diet is not dangerous or expensive and is an effective treatment for coeliac disease. Failure of replication in earlier clinical trials of gluten withdrawal may have been the result of sampling fluctuation since coeliac disease is rare. New screening tests for coeliac disease are inexpensive and carry minimal risk and discomfort. An important question is the degree to which removal of gluten from the diet will alleviate symptoms in the small proportion of people with schizophrenia who screen positively for coeliac disease but do not show its classical symptoms.
Contributors: WWE and PBM designed the study. WWE, EA, and MB conducted the analyses of data. WWE drafted the manuscript. All authors contributed to the design of the analysis, interpretation of data and reporting of results. Noel Rose, Peter Zandi, and Alessio Fasano provided helpful advice. WWE had full access to (anonymous) data and assumes responsibility for the decision to submit the paper for publication.
Funding: Danish National Research Foundation, Stanley Medical Research Institute, and NIMH grant #53188.
Competing interests: None declared.
Ethical approval: Danish Data Protection Agency, Committee on Human Research of the Bloomberg School of Public Health, and Single Project Assurance Committee in Aarhus, Denmark, established according to regulations from the US National Institutes of Health.
References
Dohan F. Cereals and Schizophrenia Data and Hypothesis. Acta Psychiatrica Scand 1966;42: 125-52.
Singh MM, Kay S. Wheat gluten as a pathogenic factor in schizophrenia. Science 1976;191: 191-2.
Zhong F, McCombs CC, Olson JM, Elston RC, Stevens FM, McCarthy CF, et al. An autosomal screen for genes that predispose to celiac disease in the western counties of Ireland. Nature Genetics 1996;14: 329-33.
Straub RE, MacLean CJ, O'Neill FA, Burke J, Murphy B, Duke F, et al. A potential vulnerability locus for schizophrenia on chromosome 6p24-22: evidence for genetic heterogeneity. Nature Genetics 1995;11: 287-93.
Mortensen PB, Pedersen CB, Westergaard T, Wohlfahrt J, Ewald H, Mors O, et al. Familial and non-familial risk factors for schizophrenia: a population-based study. N Engl J Med 1999;340: 603-8.(William Eaton, professor1)