16 March 2006. A large epidemiological study from Denmark shows an association between schizophrenia and a wide variety of autoimmune diseases. In an analysis of patient data from national registers, researchers found that the prevalence of several autoimmune diseases was significantly higher among people with schizophrenia and their parents than in an unaffected control sample population.
The new study, the largest of its kind ever reported, supports the idea that immune dysfunction plays a role in schizophrenia, a controversial hypothesis that has been studied for decades. The work, from William Eaton of The Johns Hopkins University, along with Preben Bo Mortensen and colleagues at the National Centre for Register-Based Research and the University Hospital in Aarhus, Denmark, appears in the March Issue of the American Journal of Psychiatry.
To look for a link between autoimmunity and schizophrenia, the researchers took advantage of country-wide national patient registers that cover all 7,704 Danes treated for schizophrenia between 1981 and 1998. Matching those records to a national patient register for general medical care allowed the researchers to determine how many of the subjects, or their parents, had also been diagnosed with any autoimmune disease. The incidence of different autoimmune conditions was compared with a sample of 192,590 matched non-affected subjects and their parents.
Overall, in people with schizophrenia, and their parents, the incidence of any autoimmune disease was nearly 50 percent higher than normal. Of 29 autoimmune diseases identified in the population, nine were significantly more prevalent among schizophrenia patients compared to the control group, and 12 had higher rates among parents of schizophrenia patients than parents of the unaffected group. Five diseases (thyrotoxicosis, celiac disease, acquired hemolytic anemia, interstitial cystitis, and Sjogren’s syndrome) showed higher prevalence among both patients and parents versus control subjects.
Despite the large population studied, the actual case numbers for rare autoimmune conditions were low, so that the analysis of individual diseases must be taken with a grain of salt. Nonetheless, among the five diseases found to be more prevalent in both patients and parents, three (celiac disease, thyrotoxicosis, and acquired hemolytic anemia) have previously been associated with schizophrenia. This is the strongest data to date for celiac disease and autoimmune thyroid disease, with incidence ratios that are comparable to past studies. The association with interstitial cystitis (which itself has been genetically linked to panic disorder) and Sjogren’s syndrome are novel.
Eaton et al. did not replicate a common finding of a negative relationship between the incidence of rheumatoid arthritis and schizophrenia, but they point out that their study design required the onset of the autoimmune disease to precede the diagnosis of schizophrenia. Because of this, association with late-onset conditions, such as arthritis, may also have been missed or underestimated.
The range of autoimmune diseases associated with schizophrenia is larger than previously suspected, the authors conclude. The nature of the connection is not known, and could be due to common genetic causes, perhaps related to the HLA or other genes. It has been suggested that some cases of schizophrenia result from production of autoantibodies that disrupt brain function (reviewed in Jones et al., 2005). The authors suggest that keeping an eye on the immune system in future studies of schizophrenia may yield more information on the causes of both types of diseases.—Pat McCaffrey.
Eaton WW, Byrne M, Ewald H, Mors O, Chen CY, Agerbo E, Mortensen PB. Association of schizophrenia and autoimmune diseases: linkage of Danish national registers. Am J Psychiatry. 2006 Mar;163(3):521-8. Abstract