Risk factors for unnatural mortality in persons with serious mental illness

Rates of unnatural death in persons with serious mental illness greatly exceed those in the general population. These deaths largely result from suicides and accidents and are potentially preventable. There have been few prospective studies which have characterized clinical and biological risk factors for unnatural mortality in this population. A cohort of 1517 individuals with schizophrenia, bipolar disorder, or major depressive disorder was assessed at baseline. Unnatural cause mortality was determined from the US National Death Index with up to 23.9 years of follow-up and encompassing 18,952 person years of observation. Clinical, demographic, and serological variables were related to unnatural mortality using least absolute shrinkage and selection operators (LASSO) and Cox proportional hazard models. Sensitivity analyses were employed to determine risk factors in individuals who died due to definite or possible suicide. A total of 53 (3.5%) individuals died of unnatural causes, 29 as a result of suicide or possible suicide and 24 from accidental causes. Poisoning was the most common cause of death. Independent baseline factors that were associated with unnatural death were male sex, a diagnosis of major depressive disorder, low maternal education, more severe negative symptoms, younger age, and elevated levels of IgG antibodies to cytomegalovirus. Limitations of the study include the relatively small number of deaths due to suicide and accidents and also the exclusion of persons with primary substance use disorders. The factors associated with unnatural mortality in this study warrant further investigation in larger cohorts.