Project 1: Environmental Epidemiology of Autism

项目一：自闭症环境流行病学

• 批准号: 7158279
• 负责人: Irva Hertz-Picciotto
• 金额: $ 18.4万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7158279
• 关键词: autism; biomarker; children; developmental disease /disorder; developmental immunology; developmental neurobiology; embryo /fetus toxicology; environmental health; family genetics; gene environment interaction; genetic susceptibility; genetic transcription; human pregnant subject; human subject; immunogenetics; immunoglobulins; immunotoxicity; infant human (0-1 year); influenza; longitudinal human study; mental health epidemiology; metals; neurotoxicology; pesticides; preschool child (1-5)

The Epidemiology Project of the UC Davis Center for Children's Environmental Health (CCEH), will, in the second funding period, build upon our discovery of immunologicand molecular biomarkers specific to children with autism found in 2-5 year olds enrolled in the CHARGE (Childhood Autism Risks from Genetics and Environment) Study. First, newborn blood spots from children in each of three groups (i.e., autism, developmental delay, and general population controls) will be analyzed in Project 2 for a variety of immune biomarkers and in Core 3 (Analytical Chemistry) for metal concentrations. The data obtained from newborn bloodspots, when compared to data we have already collected from the same individuals in early childhood, will provide important information for the period shortly before birth about immune dysfunction and metal exposures or metabolism in children who are later diagnosed with autism. In other words, we will extend our investigation of post-diagnosis differences to the pre-diagnostic period. The hypothesis we will test is that children with autism can be distinguished from those without autism by markers of immune dysregulation (at birth, as well as post-diagnosis) and by prenatal, immunologically relevant events and exposures. Second, in collaboration with Core 3, we will determine if children with and without autism differ with regard to exposures, body burdens, and excretion of xenobiotics, including metals, pesticides and PBOE's. Exposures are based on questionnaire information and environmental databases covering toxic emissions, hazardous air pollutants and pesticide applications. Body burdens are measured in blood or plasma, and excretion is evaluated in hair or urine; these measurements are performed in the Core 3 laboratories. Third, we will test the hypothesis that transcriptional genomic profiles of children with autism differ from those of children without autism. Particular attention will be placed on genes related to biotic and xenobiotic metabolism. Fourth, Projects 1 and 2 in collaboration with the COTC (Core 2) will collect a second set of blood samples from 375 children who enrolled in the CHARGE study in the first project period. This study (CHARGE-BACK) will examine stability overtime in the immune cell markers that were determined when these children were 2- 5 years old. CHARGE-BACK blood samples will provide peripheral immune cells to study how autism alters properties of cell activation, and susceptibility to known immunotoxicants (Project 2 and Core 4). Fifth, Project 1 will launch a new cohort study that tracks 200 women at high risk of giving birth to a child who develops autism, starting from early pregnancy and following the pregnancies and the babies to the age of three years. This new cohort study is called Markers of Autism Risk in Babies - Learning Early Signs (MARBLES). Fieldwork for the MARBLES study will be tightly integrated with the COTC (Core 2) efforts, and the specimens will be evaluated in Cores 3 and 4, and in Project 2. The goal is to determine early predictors of autism, whether they be immunologic, genomic, or environmental.

加州大学戴维斯分校儿童环境健康中心 (CCEH) 的流行病学项目将在 第二个资助期，建立在我们对特定于免疫学和分子生物标志物的发现之上 参加 CHARGE（遗传因素造成的儿童自闭症风险）的 2-5 岁儿童中发现患有自闭症的儿童 和环境）研究。首先，来自三组儿童（即自闭症、 发育迟缓和一般群体控制）将在项目 2 中分析各种免疫 生物标记物和核心 3（分析化学）中的金属浓度。从新生儿获得的数据 与我们在幼儿时期从同一个人身上收集到的数据相比，血斑 将提供出生前不久有关免疫功能障碍和金属的重要信息 后来被诊断患有自闭症的儿童的暴露或新陈代谢。换句话说，我们将延长我们的 调查诊断后与诊断前的差异。我们要检验的假设是 患有自闭症的儿童可以通过免疫失调的标志物（在 出生以及诊断后）以及产前、免疫相关事件和暴露。第二， 与 Core 3 合作，我们将确定自闭症儿童和非自闭症儿童在以下方面是否存在差异： 异生物质（包括金属、农药和 PBOE）的暴露、身体负担和排泄。曝光 基于调查问卷信息和环境数据库，涵盖有毒物质排放、有害物质排放 空气污染物和农药的应用。身体负荷通过血液或血浆测量，排泄是 通过头发或尿液进行评估；这些测量在 Core 3 实验室中进行。第三，我们要测试 自闭症儿童的转录基因组谱与正常儿童不同的假设 没有自闭症。将特别关注与生物和外源代谢相关的基因。 第四，与COTC（核心2）合作的项目1和2将采集第二组血液样本 来自在第一个项目期间参加 CHARGE 研究的 375 名儿童。本研究（退款） 将检查这些儿童 2 岁时确定的免疫细胞标记物的稳定性。 5岁。 CHARGE-BACK 血液样本将提供外周免疫细胞来研究自闭症如何改变 细胞活化的特性以及对已知免疫毒物的敏感性（项目 2 和核心 4）。第五， 项目 1 将启动一项新的队列研究，追踪 200 名生育高风险的女性 患有自闭症，从怀孕早期开始，并在怀孕和婴儿出生后一直到 20 岁 三年。这项新的队列研究称为婴儿自闭症风险标记 - 学习早期迹象 （弹珠）。 MARBLES 研究的实地工作将与 COTC（核心 2）工作紧密结合，并且 这些样本将在核心 3 和 4 以及项目 2 中进行评估。目标是确定早期预测变量 自闭症，无论是免疫学、基因组还是环境学。