Environment, Imprinting, and Neurodevelopment

环境、印记和神经发育

• 批准号: 8838798
• 负责人: Jia Chen
• 金额: $ 77.21万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8838798
• 关键词: Arousal; Autistic Disorder; Behavior Disorders; Biological Markers; Bipolar Disorder; Birth; Brain; Child; Child health care; Clinical; Cohort Studies; Complex; DNA Methylation; Data; Data Collection; Defect; Development; Diagnostic; Disease; Early Intervention; Early identification; Elderly; Environment; Environmental Exposure; Environmental Risk Factor; Epidemiologic Studies; Epigenetic Process; Exposure to; Fetal Development; Fetus; Future; Gene Expression; Genes; Genomic Imprinting; Gilles de la Tourette syndrome; Goals; Growth and Development function; Health; Impaired cognition; Infant; Intervention; Laboratories; Life Style; Link; Measures; Mediating; Mental Health; Mental disorders; Metal exposure; Methylation; Modeling; Movement; Neurodevelopmental Deficit; Neurologic; Neurotoxins; New Hampshire; Newborn Infant; Organ; Outcome; Pathway interactions; Pattern; Perinatal Exposure; Placenta; Play; Prevention; Procedures; Psyche structure; Public Health; Research; Resources; Rhode Island; Risk; Role; Schizophrenia; Shapes; Socioeconomic Status; Staging; Tissues; Trace metal; Work; Xenobiotics; alertness; base; behavioral health; biobank; cohort; epigenetic marker; experience; fetal programming; imprint; improved; in utero; mRNA Expression; molecular marker; neurobehavior; neurobehavioral; neurodevelopment; neuromuscular function; novel; novel strategies; psychological distress; psychosocial; sample collection; socioeconomics; tool

DESCRIPTION (provided by applicant): There is growing evidence that lifelong health, including mental health, is particularly shaped by the environment experienced during the in-utero developmental period. The intrauterine environment is influenced by a complex variety of factors, including maternal lifestyle, environmental exposures, socioeconomic status, and psychosocial aspects, making risk determination based on identification of these factors difficult and inaccurate. Yet, defining children at-risk early is utterly critical to improving future mental health outcomes. Due to the unique regulatory features of imprinted genes and their sensitivity to environmental exposures, genomic imprinting has been proposed as an ideal integrated measure of the intrauterine environment for use in epidemiologic studies of the developmental origins of health and disease. As imprinted genes in the placenta can impact the function of this critical organ in directing fetal development and programming, there is also strong evidence to support establishing and validating the link between alterations in imprinting and newborn neurodevelopmental outcomes. Compelled by strong rationale and by emerging evidence, including work from our laboratories linking placenta imprinted gene expression to infant neurodevelopment, this project aims to develop an imprinting-based biomarker that can prospectively predict neurobehavioral outcomes, which ultimately can be used for immediate identification of infants at-risk in order for early intervention to be initiated/implemented. We have developed a multi-stage research plan to first utilize the comprehensive resources of the ongoing Rhode Island Child Health Study (RICHS), which employs the validated and prospectively predictive NICU Network Neurobehavioral Scales (NNNS) as a phenotypic measure of newborn neurobehavior in a birth cohort of 900 newborn infants, to define a biomarker panel associated with key neurobehavioral measures. We will then demonstrate the validity and generalizability of this biomarker using an established but independent resource, the New Hampshire Birth Cohort Study (NHBCS), which uses similar data collection procedures as RICHS. In addition, although the environment is extraordinarily complex, we have decided to focus on fetal exposure to metals, specifically those which are widely considered neurotoxins or those considered protective, as a paradigm to build a comprehensive model to examine the inter-relationships among in utero trace metals exposure, genomic imprinting, and newborn neurobehavioral outcomes. Identification of an imprinting signature associated with abnormal neurodevelopment or environmental exposure would have significant clinical and public health implications by pinpointing certain environmental risk factors for neurobehavioral defects or serve as a basis for early diagnostic tools thus providing an opportunity for early intervention.

描述（由申请人提供）：越来越多的证据表明，包括心理健康在内的终身健康受到尤其是在局内发育时期所经历的环境的影响。宫内环境受到各种因素的影响，包括孕产妇的生活方式，环境暴露，社会经济地位和社会心理方面，这是基于对这些因素的识别而难以确定的风险确定。然而，定义儿童早日定义对于改善未来的精神至关重要 健康结果。由于印迹基因的独特调节特征及其对环境暴露的敏感性，因此已经提出了基因组印记，作为对健康和疾病发展起源的流行病学研究的理想综合度量。由于胎盘中的印迹基因会影响这种关键器官在指导胎儿发育和编程中的功能，因此也有强有力的证据支持建立和验证印迹和新生儿神经发育结果的变化之间的联系。该项目旨在开发一种基于烙印的生物标志物，可以预测神经性的生物标志物，从而可以在早期的互助中启动，从而可以预测神经性的生物标志物，否则可以预测神经脱落的结果，最终可以在早期介入/实施启动时，该项目最终可以直接识别，从而可以预测神经性疾病的成果。 We have developed a multi-stage research plan to first utilize the comprehensive resources of the ongoing Rhode Island Child Health Study (RICHS), which employs the validated and prospectively predictive NICU Network Neurobehavioral Scales (NNNS) as a phenotypic measure of newborn neurobehavior in a birth cohort of 900 newborn infants, to define a biomarker panel associated with key neurobehavioral措施。然后，我们将使用已建立但独立的资源，即新罕布什尔州出生队列研究（NHBC）来证明该生物标志物的有效性和概括性，该研究使用与富人相似的数据收集程序。此外，尽管环境非常复杂，但我们还是决定专注于胎儿接触金属，特别是那些被广泛认为是神经毒素或被认为是保护性的金属的物质，作为一种范式，是建立一个全面的模型，以检查子宫痕量金属的相互关系，痕量金属暴露，基因组印迹，新生儿神经bobeaverave and newborn neurobeavioralalave and newborn neurobeavioralalalalalavioralalalalavioralalavioralalavioravioralalavioralalavioralalavioralalavioravioralalavioralalalalavioravioralalavioralalavioralalavioralalavioralalavioralal ulobeasessemes。通过查明对神经行为缺陷的某些环境风险因素，鉴定与异常神经发育或环境暴露相关的烙印签名将对临床和公共卫生产生重大影响，或者作为早期诊断工具的基础，从而为早期干预提供了机会。