Autoimmune diseases and severe infections as risk factors for schizophrenia: a 30-year population-based register study.
Level 3 - non-randomized controlled study
Nationwide prospective register-based cohort study
PubMed 22193673 · doi:10.1176/appi.ajp.2011.11030516
What was done
Researchers linked Danish nationwide population-based registers across a 30-year period to evaluate whether a history of autoimmune disease, severe infection requiring hospitalization, or both increased the risk of developing schizophrenia. Data were evaluated using survival analysis, calculating incidence rate ratios (IRRs) with 95% confidence intervals adjusted for calendar year, age, sex, substance use disorders, and family history of psychiatric disorders.
What was found
A history of autoimmune disease was associated with a 29% increased risk of schizophrenia (IRR = 1.29, 95% CI = 1.18–1.41). A prior hospitalization for infection was associated with a 60% increased risk (IRR = 1.60, 95% CI = 1.56–1.64). Combining both risk factors yielded an IRR of 2.25 (95% CI = 2.04–2.46). Risk increased in a dose-response pattern with repeated infections; individuals with an autoimmune disease and three or more hospital contacts for infection had an IRR of 3.40 (95% CI = 2.91–3.94). Nearly 24% of individuals diagnosed with schizophrenia had a hospital contact for an infection prior to their diagnosis.
Why it matters
These findings support an immunological contribution to the etiology of schizophrenia, suggesting that peripheral inflammation, autoantibodies, and severe infectious exposures may interact to alter neurodevelopmental risk.
Limits
The abstract does not state the exact sample size or total person-years. Severe infections were identified solely via hospital admissions, missing milder or community-treated infections. Inherent observational limitations preclude establishing direct biological causality.
Cited by
- supports Severe infections requiring hospitalization or autoimmune conditions earlier in life significantly increase the risk of subsequently developing major depression and schizophrenia.