Our aim was to investigate the association between parental psychosis and potential risk factors for schizophrenia and their interaction. We evaluated whether the factors during pregnancy and birth have a different effect among subjects with and without a history of parental psychosis and whether parental psychosis may even explain their effects on the risk of schizophrenia. The sample comprised 10,526 individuals from the Northern Finland 1966 Birth Cohort. A total of 150 (1.4%) cohort members had schizophrenia by the age of 44 years, of them 18 (12.0%) had a parent with a history of psychosis. In non-psychotic cohort members, this figure was 495 (4.8%). In the parental psychosis group, significant early biological risk factors for schizophrenia included high birth weight (hazard ratio, HR 11.4; 95% confidence interval 3.3-39.7) and length (HR 4.1; 1.3-12.5), high birth weight in relation to gestational age (HR 3.2; 1.1-9.0), and high maternal age (HR 2.6.; 1.0-6.7). High birth weight and length and high maternal education had a significant interaction with parental psychosis. The presence of any biological risk factor increased the risk of schizophrenia significantly only among the parental psychosis group (HR 4.0; 1.5-10.5), whereas the presence of any psychosocial risk factor had no interaction with parental psychosis. Parental psychosis can act as an effect modifier on early risk factors for schizophrenia. Evaluation of the mechanisms behind the risk factors should, therefore, include consideration of the parental history of psychosis.

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