The risk of schizophrenia has been linked with a family history of schizophrenia and less strongly with other psychiatric disorders in family members. Using data from the Copenhagen Perinatal Cohort and from the Danish Psychiatric Case Register, we studied the relationship between offspring risk of schizophrenia and a range of psychotic and non-psychotic psychiatric diagnoses in parents. Psychiatric admission data after 1969 were available for 7047 cohort members born between 1959 and 1961, and for 7006 mothers and 6993 fathers. Univariate analysis showed that neurosis, alcohol and substance dependence in both parents were associated with elevated risk of offspring schizophrenia; in addition, maternal schizophrenia, affective disorder and personality disorder were associated with elevated risk. Controlling for parental age, parental social status, and parental psychiatric co-diagnosis, offspring risk of schizophrenia was associated with maternal schizophrenia (OR = 15.41 with 95% CI 5.96-39.81) and, independently, with paternal hospitalisation with neurosis (OR = 5.90 with 95% CI 2.23-15.62). The risk of schizophrenia associated with paternal neurosis remained significant after excluding offspring of parents with non-affective psychosis from the sample. These findings suggest that genetic and family studies should not only focus on parental history of schizophrenia since the simple distinction between positive and negative family history could not accurately describe offspring risk in this sample.
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