DESCRIPTION (provided by applicant): This study will investigate the role of prenatal determinants of schizophrenia and schizophrenia spectrum disorder (SSD) by following-up a cohort of 19,000 individuals born in 1959-1967 in Alameda County, CA. The study builds upon and extends two prior investigations: The Child Health and Development Study, which collected extensive data on over 20,000 pregnancies in a representative cohort of women belonging to Kaiser Foundation Health Plan (KFHP) in Oakland, CA; and the Prenatal Determinants of Schizophrenia (PDS) Study, which used KFHP membership records and psychiatric treatment registries to ascertain and diagnose 71 cases of SSD among the adolescent/adult offspring from the CHDS. The membership and treatment registries of KFHP, as well as electronic records of state residence and county mental health services, will be used to ascertain and diagnose additional SSD cases from the same cohort, resulting in a sample of over 180 SSD cases for study. Using a nested case-control design, matched controls will be selected from the population at risk for each case. The study will also obtain family history of SSD for cases and a matched sample of controls, and obtain blood from cases and controls for later genetic studies. Stored maternal serum samples from the index pregnancies will be assayed for infectious and immunologic exposures. Using statistical methods appropriate to the nested case-control design, the study will then proceed to replicate findings from the prior PDS study (e.g., maternal influenza infection in early pregnancy significantly increases risk of SSD in offspring); examine other potential determinants of SSD (e.g., prenatal exposure to maternal amphetamine use); and investigate the potential causal pathways between prenatal factors and risk of SSD. The study will hypothesize relationships among factors associated with SSD, including family history of schizophrenia, maternal and paternal factors, and prenatal exposures, then systematically analyze and describe the pathways among factors that predict SSD.