Somatic Diseases and Conditions before the First Diagnosis of Schizophrenia: A Nationwide Population-based Cohort Study in More Than 900 000 Individuals

Objective: Schizophrenia is associated with excess physical comorbidity. Yet, to our knowledge, large studies are lacking on the associations with somatic diseases before the onset of schizophrenia. The authors conducted a nationwide study of the full spectrum of treated somatic diseases before the first diagnosis of schizophrenia. Method: Nationwide sample of the Danish population consisting of singletons (n = 954351) born 1977-1993 and followed from birth to 2009, during which period 4371 developed schizophrenia. Somatic diagnoses at all general hospital contacts (admitted or outpatient care at a somatic hospital) from 1977 to 2009 were used as exposures. The incidence rate ratio (IRR) of schizophrenia was calculated using Poisson regression adjusted for confounders. Results: Among the 4371 persons who developed schizophrenia from 1992 to 2009, a total of 4180 (95.6%) persons had a previous somatic hospital contact. A history of any somatic hospital contact was associated with an elevated risk of schizophrenia (IRR = 2.04, 95% CI = 1.77-2.37). A wide range of somatic diseases and conditions were associated with an increased risk of schizophrenia, including epilepsy (IRR = 2.26, 95% CI = 1.93-2.62), nutritional or metabolic disorders (IRR = 1.57, 95% CI = 1.39-1.77), circulatory system diseases (IRR = 1.63, 95% CI= 1.38-1.92), and brain injury (IRR = 1.58, 95% CI = 1.45-1.72). Conclusions: A wide range of potential etiological factors could have contributed to the observed associations, including genetic or physiological overlaps between conditions, and interacting immunological, behavioral, and neurodevelopmental factors.