Prenatal Determinants of Schizophrenia, II

描述（由申请人提供）：本研究将通过随访1959-1967年出生于加利福尼亚州阿拉米达县的19，000人队列，调查精神分裂症和精神分裂症谱系障碍（SSD）的产前决定因素的作用。 这项研究建立在并扩展了两项先前的调查：儿童健康和发展研究，该研究收集了属于加利福尼亚州奥克兰凯撒基金会健康计划（KFHP）的代表性妇女队列中超过20，000例怀孕的广泛数据;和精神分裂症产前决定因素（PDS）研究，使用KFHP成员记录和精神病治疗登记处来确定和诊断CHDS青少年/成年后代中的71例SSD。KFHP的成员和治疗登记处，以及州居民和县精神卫生服务的电子记录，将用于确定和诊断来自同一队列的其他SSD病例，从而产生超过180个SSD病例的样本用于研究。使用巢式病例对照设计，将从每个病例的风险人群中选择匹配的对照。该研究还将获得病例的SSD家族史和对照组的匹配样本，并从病例和对照组中获得血液用于以后的遗传研究。将对储存的首次妊娠母体血清样本进行感染和免疫暴露分析。使用适用于巢式病例对照设计的统计方法，研究将继续重复先前PDS研究的结果（例如，怀孕早期的母亲流感感染显著增加了后代患SSD的风险）;检查SSD的其他潜在决定因素（例如，产前暴露于母体苯丙胺使用）;并调查产前因素和SSD风险之间的潜在因果关系。本研究将假设精神分裂症家族史、父母因素、产前暴露等与SSD相关的因素之间的关系，系统分析和描述SSD的预测因素之间的通路。

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.