Autoimmune diseases and severe infections as risk factors for mood disorders: a nationwide study.
Level 3 - non-randomized controlled study
Nationwide non-randomized prospective cohort study
PubMed 23760347 · doi:10.1001/jamapsychiatry.2013.1111
What was done
A nationwide population-based prospective cohort study followed 3.56 million individuals born between 1945 and 1996 using Danish longitudinal health registers from 1977 through 2010 (78 million person-years). The study evaluated whether prior hospital contact for autoimmune diseases or infections was associated with a first lifetime mood disorder diagnosis made by a psychiatrist in hospital, outpatient clinic, or emergency settings. Incidence rate ratios (IRRs) were estimated using survival analysis adjusted for calendar year, age, and sex.
What was found
A prior hospital contact for autoimmune disease increased the risk of a subsequent mood disorder by 45% (IRR, 1.45; 95% CI, 1.39-1.52). Prior hospitalization for infection increased mood disorder risk by 62% (IRR, 1.62; 95% CI, 1.60-1.64). Co-occurrence of both risk factors produced a synergistic increase in risk (IRR, 2.35; 95% CI, 2.25-2.46). Risk increased in a dose-response relationship with the number of infections and autoimmune diseases. Among individuals diagnosed with a mood disorder, 32% had previous hospital contact for infection and 5% for autoimmune disease.
Why it matters
This nationwide study provides large-scale longitudinal evidence supporting an immunological contribution to mood disorder etiology, demonstrating that severe infections and autoimmune diseases substantially precede psychiatric diagnoses.
Limits
The study captured only severe autoimmune diseases, infections, and mood disorders requiring hospital, clinic, or emergency contacts, omitting milder cases treated solely in primary care. As an observational register study, residual confounding from unmeasured socioeconomic, genetic, or environmental factors cannot be excluded.
Cited by
- supports Severe infections requiring hospitalization or autoimmune conditions earlier in life significantly increase the risk of subsequently developing major depression and schizophrenia.