People with a history of schizophrenia appear to have a lower risk of developing rheumatoid arthritis (RA) than the general population, but the association may be due to underreporting, say researchers.
Carl Sellgren (Karolinska Institutet, Stockholm, Sweden) and co-authors report in Schizophrenia Bulletin that individuals with schizophrenia have a 31% lower risk of developing RA than the general population, but they also have a 38% lower risk of developing ankylosing spondylitis and a 51% lower risk of osteoarthritis.
This suggests “that a substantial part of the observed inverse association between RA and schizophrenia may be due to other factors than disease-specific biology”, says the team.
They analysed Swedish National Patient Register data from 31,193 people, born between 1932 and 1989, with a diagnosis of schizophrenia. They also looked at rates of RA among 74,260 first-degree relatives of the schizophrenia probands, as well as people with schizoaffective disorder (n=10,676) and bipolar disorder (n=34,744) and their first-degree relatives (n=27,112 and 97,528, respectively).
Individuals with schizoaffective disorder had similar reductions in risks of RA, ankylosing spondylitis and osteoarthritis to those with schizophrenia, but no such associations were observed for bipolar disorder.
“In light of the more severe loss of function in schizophrenia and schizoaffective disorder patients in comparison to [bipolar disorder] patients, this is compatible with differential misclassification bias in the observed inverse association between schizophrenia and RA”, say the researchers.
They add that the finding emphasizes “the need of assessing and being aware of nonpsychiatric symptoms in schizophrenia patients.”
The researchers found no association between RA overall and schizophrenia among the first-degree relatives of the people with schizophrenia. However, when they analysed the data by RA subtype, they found that children and siblings of individuals with schizophrenia had an “unexpected” significantly decreased risk of seronegative RA, at hazard ratios of 0.13 and 0.67, respectively.
No such associations were observed for relatives of those with schizoaffective or bipolar disorder.
Sellgren and co-authors conclude: “[F]urther molecular genetic studies of the association between RA and schizophrenia should include stratification by RA subtype and focus on the unique genetic cause of schizophrenia rather than the common genetic cause of schizophrenia and [bipolar disorder].”
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