The association between schizophrenia and rheumatoid arthritis: a nationwide population-based Swedish study on intraindividual and familial risks.
Numerous studies have reported a reduced risk of rheumatoid arthritis (RA) in schizophrenia. The mechanisms are unknown, but recent genome-wide association studies of schizophrenia have shown strong associations with markers spanning the major histocompatibility complex region, indicating a possible role for adaptive immunity also in schizophrenia. In this population-based cohort study, we assess the associations between RA and schizophrenia and the extent to which any observed associations are specific to RA/schizophrenia. We then extend the assessments per RA subtype and to risks in first-degree relatives. The study population included every individual identified in the Swedish Population Register born in Sweden between 1932 and 1989. The risk for RA in schizophrenia was significantly decreased (hazard ratio [HR] = 0.69, 95% CI = 0.59-0.80), but similar reductions were noted for osteoarthritis (a noninflammatory joint disorder) and ankylosing spondylitis (a non-RA inflammatory disorder). Comparable associations were seen in schizoaffective subjects while no significant associations were observed in bipolar disorder. Overall, first-degree relatives of schizophrenia patients were not at reduced risk of RA, but the risk for seronegative RA was significantly decreased in children and siblings of schizophrenia probands (HR = 0.13, 95% CI = 0.02-0.95 and HR = 0.67, 95% CI = 049-0.92, respectively). In conclusion, our intraindividual analyses suggest that differential misclassification bias is an important factor for the observed inverse association and emphasize the need of optimized care-provision for nonpsychiatric symptoms in schizophrenia patients. Our familial analyses indicted the possibility of an inverse coinheritance of schizophrenia and seronegative RA.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; carl.sellgren@ki.se.
Carl
C
Sellgren
Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden;
Thomas
T
Frisell
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden;
Paul
P
Lichtenstein
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden;
Mikael
M
Landèn
Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
Johan
J
Askling
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D015331:Cohort Studies; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012042:Registries / Q000706:statistics & numerical data*; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics; D013548:Sweden / Q000453:epidemiology
epidemiology; major histocompatibility complex; population register; rheumatoid arthritis; schizophrenia