Family structure and risk factors for schizophrenia: case-sibling study

BACKGROUND Several family structure-related factors, such as birth order, family size, parental age, and age differences to siblings, have been suggested as risk factors for schizophrenia. We examined how family-structure-related variables modified the risk of schizophrenia in Finnish families with at least one child with schizophrenia born from 1950 to 1976. METHODS We used case-sibling design, a variant of the matched case-control design in the analysis. Patients hospitalized for schizophrenia between 1969 and 1996 were identified from the Finnish Hospital Discharge Register, and their families from the Population Register Center. Only families with at least two children (7914 sibships and 21059 individuals) were included in the analysis. Conditional logistic regression with sex, birth cohort, maternal schizophrenia status, and several family-related variables as explanatory variables was used in the case-sibling design. The effect of variables with the same value in each sibship was analyzed using ordinary logistic regression. RESULTS Having a sibling who was less than five years older (OR 1.46, 95% CI 1.29-1.66), or being the firstborn (first born vs. second born 1.62, 1.87-1.4) predicted an elevated risk, but having siblings who were more than ten years older predicted a lower risk (0.66, 0.56-0.79). CONCLUSIONS Several family-structure-related variables were identified as risk factors for schizophrenia. The underlying causative mechanisms are likely to be variable.