Schizophrenia susceptibility and age of diagnosis--a frailty approach

Using a frailty model approach, we aim to evaluate the effect of early-life risk factors on susceptibility and age at diagnosis of schizophrenia. We assume paternal age and familial schizophrenia influence the susceptibility, while these and several early risk factors influence the age of diagnosis.

Schizophrenia incidence data were derived from the population-based Swedish Patient Registry; including individuals aged 18 to 45 years, diagnosed between 1974 and 2008. Data were analyzed by a frailty model, a random effects model in survival analysis, using a compound Poisson model.

15,340 incident schizophrenia cases were included. For individuals without familial schizophrenia, a protective effect was seen across most ages of diagnosis for females, low paternal age, born in rural areas, and being born in later cohorts. For individuals with familial schizophrenia, a protective effect is found for females diagnosed between ages 18 and 30 years, corresponding values were 18-25 years for low paternal age. Being born in rural areas and in the last birth cohort was protective for all. The estimated proportion of susceptible was 5% for those without familial schizophrenia and 18% for individuals with familial schizophrenia. There was no statistically significant effect of paternal age on the proportion of susceptible.

To our knowledge, this is the first regression modeling of time to schizophrenia diagnosis allowing for a non-susceptible fraction of the population, including age dependent modeling of covariate effects and an interaction. Applying frailty model to schizophrenia provide etiological clues, elucidating patterns of susceptibility and age-at-diagnosis for which early-life factors are of importance.