CORE--NEURODEVELOPMENTAL AND GENETIC EPIDEMIOLOGY RESEARCH CORE

NGERC旨在推进神经发育性精神分裂症的前驱因素的研究，即这种疾病的神经发育障碍的起源和早期表现。我们将使用生命周期队列的数据，这些队列从小就被跟踪，现在要么处于精神分裂症的风险年龄。根据母婴健康研究中心的资源和基础设施，我们建议扩大数据在三种类型的生命过程队列中的使用：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。基于人口的出生队列不是针对任何特定的病因选择的，而是选择遗传高风险队列以丰富遗传病因学，并选择表观遗传高风险队列以丰富可能影响遗传编程神经发育的环境因素(例如，产前脑损伤)。具体目的是在以下方面调查神经发育性精神分裂症的前驱因素：1.一项合作研究，结合了四个出生队列的数据。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合作围产期项目的三个队列。每个队列是基于1959-1966年间的出生，从产前到儿童或更晚的时期进行跟踪，目前正在由这项提案中的联合调查人员跟踪调查精神分裂症。单独来看，每个队列的统计能力有限，特别是对于罕见的暴露。相比之下，大约30,000名活产婴儿的联合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，进行协作研究，并使该数据库成为其他精神分裂症研究人员的资源。2.丰富了遗传病因学的队列。在纽约高危项目中，NGERC的L.Erlenhmeyer-Kimling对324名患有精神分裂症、情感疾病和正常父母的子女进行了跟踪调查，直到成年。本研究致力于将数据分析扩展到精神分裂症神经发育障碍的早期表现。3.丰富表观遗传病因学的队列。在风疹出生缺陷评估项目中，70名在怀孕期间接触风疹的人被跟踪到成年，并被证明患精神分裂症的风险大大增加。本研究将扩大家族史和脑成像数据的收集和使用范围。虽然MCHRC的其他核心对所有三个目标都是必不可少的，但这一核心反过来又被设计为促进其他核心的每一个，不仅通过提供独特的数据，而且通过促进共同构思和实施的跨学科研究。

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.