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 第二资金期间，基于我们发现特定的免疫和分子生物标志物 在2-5岁的孩子中发现自闭症的儿童参加了这项费用（遗传学的儿童自闭症风险 和环境）研究。首先，三组中每一个儿童的新生儿斑点（即自闭症， 将在项目2中分析发育延迟和一般人口控制）各种免疫 金属浓度的生物标志物和核心3（分析化学）。从新生儿获得的数据 与数据相比，我们已经在童年时期已经从同一个人收集的血点了， 将在出生前不久就提供有关免疫功能障碍和金属的重要信息 后来被诊断出自闭症的儿童的暴露或代谢。换句话说，我们将扩展我们的 诊断后诊断后诊断后期的研究。我们要检验的假设是 自闭症儿童可以通过免疫失调的标记与没有自闭症的患者区分开（在 出生，以及诊断后）以及产前，免疫学相关的事件和暴露。第二， 与Core 3合作，我们将确定患有和没有自闭症的孩子在 异种生物的暴露，身体负担和排泄，包括金属，农药和PBOE。暴露 基于问卷的信息和环境数据库，涉及有毒排放，危险 空气污染物和农药应用。身体负担以血液或血浆测量，排泄物为 在头发或尿液中评估；这些测量值在Core 3实验室中进行。第三，我们将测试 自闭症儿童的转录基因组特征与儿童的转录基因组谱的假设 没有自闭症。特别关注与生物和异种代谢有关的基因。 第四，项目1和2与COTC（核心2）合作将收集第二组血样 在第一个项目期间参加指控研究的375名儿童。这项研究（收费） 将检查这些儿童在2-时确定的免疫细胞标记中的稳定加班 5岁。抵押血液样本将提供外周免疫细胞，以研究自闭症如何改变 细胞活化的特性以及对已知免疫毒性剂的敏感性（项目2和CORE 4）。第五， 项目1将启动一项新的队列研究，该研究追踪200名妇女，有生育孩子的高风险 从怀孕早期开始，妊娠和婴儿到年龄 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 （大理石）。大理石研究的现场工作将与COTC（核心2）的努力紧密整合，并且 标本将在核心3和4中进行评估，在项目2中。目标是确定早期预测因子 自闭症，无论是免疫，基因组还是环境。