Objective: Previous research has found an increased risk of schizophrenia in individuals with autoimmune diseases and smaller but significant associations with a family history of autoimmune diseases. This study investigates, for the first time, the association between schizophrenia and subsequent autoimmune diseases (the reverse temporality) and also considers the effect of infections, a possible risk factor for both schizophrenia and autoimmune diseases.
Method: Danish nationwide registers were linked to establish a cohort of 3.83 million people, identifying 39,364 individuals with schizophrenia-like psychosis and 142,328 individuals with autoimmune disease. Data were analyzed using survival analysis and adjusted for calendar year, age, and sex.
Results: Individuals with schizophrenia had an elevated risk of subsequent autoimmune diseases, with an incidence rate ratio of 1.53 (95% CI=1.46-1.62). Among persons without hospital contacts for infections, the effect of having schizophrenia was smaller, with an increased incidence rate ratio of 1.32 (95% CI=1.22-1.43) for autoimmune diseases. For individuals with schizophrenia as well as hospital contacts for infections, the combined risk of autoimmune diseases was 2.70 (95% CI=2.51-2.89). A family history of schizophrenia slightly increased the overall risk of developing autoimmune diseases (incidence rate ratio=1.06, 95% CI=1.02-1.09). Autoimmune diseases developed subsequently in 3.6% of people with schizophrenia, and 3.1% of people with autoimmune diseases had a family history of schizophrenia.
Conclusions: The increased risk of subsequent autoimmune diseases in individuals with schizophrenia may involve neuropsychiatric manifestations from the undiagnosed autoimmune disease, medical treatment or lifestyle associated with schizophrenia, or common etiological mechanisms, such as infections and shared genetic factors.