Association of Schizophrenia and Autoimmune Diseases: Linkage of Danish National Registers
Eaton WW, Byrne M, Ewald H, Mors O, Chen CY, Agerbo E and Mortensen PB;
Commented by , 22 Mar 2006
Aim of the study
The finding that the new atypical antipsychotics are associated with a number of metabolic problems such as weight gain or prolactin increase has increased the interest in the association between schizophrenia and physical illnesses. While the relationship between schizophrenia and some physical illnesses has been extensively investigated (e.g. cancer, rheumatoid arthritis, pregnancy complications) others are underresearched.
One of these domains are autoimmune disorders of which only rheumatoid arthritis has been well studied while for other diseases such as celiac disease or thyroid diseases only inconclusive evidence exists. The aim of the current study therefore was to analyse the association between schizophrenia and a number of autoimmune diseases in a population based epidemiological study.
Methods
The authors linked the Danish Psychiatric Register which included all 7,704 persons in Denmark diagnosed with schizophrenia from 1981 to 1998 with the National Patient Register and a register with socioeconomic information. They hereby formed a database allowing to compare the incidence of autoimmune diseases in people with schizophrenia with a sample of matched comparison subjects and with their parents. A condition of the data linkage was that the autoimmune disease occured before the diagnosis of schizophrenia was established.
Results
The following autoimmune disorders had higher prevalence among patients with schizophrenia than among controls: thyreotoxicosis, intestinal malabsorption, acquired haemolytic anemia, chronic active hepatitis, interstitial cystitis, alopecia areata, myositis, polymyalgia rheumatica and Sjögren’s syndrome. 12 autoimmune diseases had higher prevalence rates among parents of schizophrenia patients than among parents of comparison subjects (incidence rate ratios ranging from 1.3 to 3.8).
Finally, the increase in risk for schizophrenia associated with a history of any autoimmune disease was 45%. Five autoimmune diseases - thyrotoxicosis, celiac disease, acquired hemolytic anemia, interstitial cystitis, and Sjögren’s syndrome – were more prevalent among people with schizophrenia compared to normal controls and among family members of patients with schizophrenia compared to family members of controls.
Dr Leucht's comments
Schizophrenia may be associated with a number of autoimmune diseases. For some of the diseases identified the current study replicated previously found associations. For example, the relationship between schizophrenia and celiac disease has been investigated since the 1960s and there are numerous reports on thyroid dysfunction in schizophrenia.
In contrast to most previous studies the authors did not find a reduced prevalence of rheumatoid arthritits in schizophrenia. As one explanation of this discrepancy they discuss that in the current study all autonomic diseases had to be prevalent before the onset of schizophrenia, but the onset of rheumatoid arthritis is often later than that of schizophrenia.
Important limitations are the low prevalence of autoimmune disorders limiting the robustness of the results (e.g. although the difference between schizophrenics and controls was statistically significant there was only one case of Sjögren syndrome among the patients with schizophrenia) and that the register approach may not have been able to detect all cases, for example because some patients were treated by general practicioners rather than specialists and did thus not enter the registers.
Since in both schizophrenia and at least some of the autoimmune diseases genetic factors play a role, there is a speculation that common genes may account for both diseases. Further investigations on these associations may therefore be important for the understanding of the pathogenesis of both schizophrenia and autoimmune disorders.