Family load estimates of schizophrenia and associated risk factors in a nation-wide population study of former child and adolescent patients up to forty years of age.

Objectives: This nation-wide register-based study investigates the family load of schizophrenia (SZ) across three generations in affected families compared to control families. Furthermore the study compares the family load in case vs. control families considering the age of onset of the disorder in the cases. In addition, the study addresses the impact of certain socio-demographic risk factors, i.e. sex, region of residence, year of birth, month of birth, and maternal and paternal age at birth.

Method: A total of N=2020 child and adolescent psychiatric cases born between 1969 and 1985 registered in the Danish Central Psychiatric Register (DCPR) before the age of 18 developed SZ before the age of 40. N=5982 controls without any psychiatric diagnosis before age 18 were matched for age, sex, and residential region. Psychiatric diagnoses were also obtained on the first-degree relatives, i.e. parents, siblings, and offspring as a part of the Danish Three Generation Study (3GS). A family load was obtained by using various mixed regression models.

Results: SZ did occur more often in case than in control families. Having a mother, father or a sibling with the disorder was proven to be a risk factor. The year of birth, the region of residence, and paternal age at birth (≥ 35) were associated with SZ. However, the family load was not dependent on age of onset of the case-proband. Furthermore, case relatives did not develop SZ earlier than control relatives.

Conclusions: These findings based on a very large and representative dataset provide further and solid evidence for the high family aggregation of SZ. The year of birth, the region of residence, and paternal age at birth play an additional role in the development of the disorder.