CORE--NEURODEVELOPMENTAL AND GENETIC EPIDEMIOLOGY RESEARCH CORE

NGERC寻求推进对神经发育性精神分裂症的前因的研究，即，这种疾病的神经发育障碍的起源和早期表现。我们将使用来自生命历程队列的数据，这些队列从生命早期开始跟踪，现在处于精神分裂症的风险年龄。利用MHCRC的资源和基础设施，我们建议将数据的使用扩展到三种类型的生命历程队列中的每一种：基于人口的出生队列、遗传高风险队列和表观遗传高风险队列。基于群体的出生队列针对任何特定病因学被富集，而遗传高风险队列被选择以便针对遗传病因学被富集，并且表观遗传高风险队列被选择以便针对可以影响遗传程序化神经发育的环境因素（例如，产前脑损伤）。具体目的是调查神经发育性精神分裂症的前因：1。一项结合了四个出生队列数据的合作研究。这项研究包括大型奥克兰儿童健康和发展研究出生队列以及来自多地点国家围产期合作项目的三个队列。每个队列均基于1959-1966年期间的出生，从产前期到儿童期或更晚，并且目前正在由本提案中的共同研究者对精神分裂症进行随访。单独来看，每个队列的统计功效有限，特别是对于罕见暴露。相比之下，约30 000例活产婴儿的合并样本为全面调查提供了足够的力量。使用MHCRC的基础设施，我们将能够创建一个组合数据库，进行合作研究，并使该数据库成为其他精神分裂症研究人员的资源。2.一个富含遗传病因学的队列。在纽约高风险项目中，L. NGERC的Erlenhmeyer-Kimling博士对324名精神分裂症患者、情感疾病患者和正常父母的后代进行了成年中期的跟踪研究。本研究致力于扩展数据分析，集中在精神分裂症神经发育障碍的早期表现。3.一个富含表观遗传病因学的队列。在风疹出生缺陷评估项目中，对70名在妊娠期接触风疹的人进行了跟踪调查，直到成年，结果显示，他们患精神分裂症的风险大大增加。本研究将扩展家族史和脑成像数据的收集和使用。虽然MCHRC的其他核心对所有三个目标都是必不可少的，但该核心反过来又旨在为其他核心做出贡献，不仅提供独特的数据，而且还通过促进共同构思和进行的跨学科研究。

The NGERC seeks to advance research on the antecedents of neurodevelopmental schizophrenia, i.e., on the origins and early manifestations of neurodevelopmental disturbance in this disorder. We will use data from life course cohorts that have been followed from early life and are now either in the age of risk for schizophrenia. Drawing on the resources and infrastructure of the MHCRC, we propose to extend the uses of the data for each of three types of life course cohorts: population- based birth cohorts, genetic high-risk cohorts, and epigenetic high-risk cohorts. Population-based birth cohorts are unselected for any specific etiology, whereas a genetic high-risk cohort is selected so as to be enriched for genetic etiology, and an epigenetic high-risk cohort is selected so as to be enriched for an environmental factor which can impact on genetically programmed neurodevelopment (e.g., prenatal brain insult). The specific aims are to investigate antecedents of neurodevelopmental schizophrenia in: 1. a collaborative study that combines data across four birth cohorts. This study includes the large Oakland Child Health and Development Study birth cohort together with three cohorts derived from the multi-site National Collaborative Perinatal Project. Each cohort was based on births during 1959-1966, was followed from the prenatal period into childhood or later, and is currently being followed up for schizophrenia by Co- investigators in this proposal. Taken alone each cohort has limited statistical power, especially for rare exposures. By contrast, the combined sample of approximately 30,000 live births provide adequate power for a comprehensive investigation. Using the infrastructure of the MHCRC, we will be able to create a combined database, conduct collaborative research, and make this database a resource for other schizophrenia researchers. 2. a cohort enriched for genetic etiology. In the New York High-Risk Project, of L. Erlenhmeyer-Kimling of the NGERC, 324 offspring of schizophrenic, affectively ill, and normal parents have been followed into mid-adulthood. The present study undertakes to extend the data analysis to focus on early manifestations of neurodevelopmental disturbance in schizophrenia. 3. a cohort enriched for epigenetic etiology. in the Rubella Birth Defects Evaluation Project, 70 individuals exposed to rubella during gestation have been followed into adulthood and have been shown to have a greatly increased risk of schizophrenia. The present study will extend the collection and uses of family history and brain imaging data. While the other Cores of the MCHRC are essential to all three aims, this Core in turn is designed to contribute to each of the other Cores, not only by providing unique data, but also by fostering interdisciplinary research that is jointly conceived and conducted.