Prenatal Determinants of Schizophrenia, II

描述(申请人提供)：这项研究将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，跟踪调查1959-1967年出生于加利福尼亚州阿拉米达县的19,000人。这项研究是在先前两项调查的基础上进行和扩展的：一项是儿童健康和发展研究，它收集了加利福尼亚州奥克兰凯撒基金会健康计划(KFHP)一组有代表性的妇女中2万多名孕妇的广泛数据；另一项是精神分裂症的产前决定因素(PDS)研究，它使用KFHP成员记录和精神治疗登记，在CHDS的青少年/成人后代中确定和诊断了71例SSD病例。KFHP的成员和治疗登记以及州居住地和县精神卫生服务的电子记录将被用来确定和诊断同一队列中的其他SSD病例，从而产生180多个SSD病例的样本供研究。采用嵌套式病例对照设计，将从每个病例的危险人群中选择匹配的对照。这项研究还将获得病例和匹配的对照样本的SSD家族史，并从病例和对照中获取血液，用于以后的遗传学研究。储存的孕妇血清样本将用于检测感染和免疫暴露情况。使用适用于嵌套病例对照设计的统计方法，该研究将继续复制先前PDS研究的结果(例如，怀孕早期母亲感染流感显著增加后代患SSD的风险)；检查SSD的其他潜在决定因素(例如，产前接触母亲使用苯丙胺)；并调查产前因素与SSD风险之间的潜在因果路径。本研究将假设与SSD相关的因素之间的关系，包括精神分裂症的家族史、母亲和父亲的因素以及产前暴露，然后系统地分析和描述预测SSD的因素之间的路径。

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.