Longitudinal Antecedents of Attention Problems in Very Preterm Children: Role of Epigenetics, Executive Function, and Caregiver Psychological Distress

项目总结/摘要 该K 01提案将为候选人提供独立的研究职业生涯， 在典型发育和高风险人群中对儿童神经发育轨迹的生物学贡献者， 具有人类发育行为表观遗传学和临床相关认知方面的专业知识， 表型（例如，注意力不集中）。发展性精神病理学的研究已经成功地确定了 多个领域的注意力问题的风险因素，包括生物学，认知和认知因素。 然而，一个错过的机会是研究与健康相关的风险因素的多个纵向轨迹， 不注意的轨迹。具体而言，需要了解是否存在异构 幼儿期注意力不集中的轨迹，特别是在向正规学校教育过渡期间（5-7岁）， 注意力不集中的增加是常见的。此外，了解儿童早期风险因素的变化 与过渡到正规学校的注意力不集中的变化有关， 关于筛查和干预高危儿童的可修改目标和最佳时机。的 拟议的研究将利用来自两项母赠款的现有数据（R 01 HD 072267; R 01 HD 084515;诺维研究） 专注于早产儿的神经发育结果。目前的研究旨在测试 生物轨迹之间的关联（即，DNA甲基化），认知（即，执行功能）和 压缩（即，心理困扰）的因素和轨迹的儿童注意力不集中的样本出生的儿童 极早产儿，这是一个已知的注意力问题风险较高的群体。具体目标如下：（1） 描述极早产儿注意力不集中的轨迹;（2）测试生物学，认知， 以及不注意轨迹的影响因素;以及（3）测试生物，认知和 注意力不集中的轨迹与注意力不集中的轨迹有关。申请人的导师团队将搭建完成 的研究目的，并提供所需的培训（1）处理和（2）分析高维，纵向 表观遗传数据，（3）用于纵向数据分析的先进统计技术，和（4）框架（例如， RDOC）研究儿童精神病理学。布朗中心的资源和智力环境， 《危险儿童研究》、妇女和婴儿医院、布朗大学沃伦·阿尔珀特医学院 大学是开展独立研究事业的理想场所。本项目将提供 未来R 01研究DNA甲基化轨迹如何建立和改变的初步数据 跨越发展（例如，根据环境风险因素）以及诺维儿童的赠款 到后来的童年该项目与NIMH战略优先事项保持一致，因为其重点是绘制 儿童时期注意力不集中的发展，确定可能有助于注意力不集中的风险因素和生物标志物 作为新的干预目标，并为旨在减轻长期 功能障碍

PROJECT SUMMARY/ABSTRACT This K01 proposal will prepare the candidate for an independent research career studying environmental and biological contributors to child neurodevelopmental trajectories in typically-developing and high-risk populations, with specific expertise in human developmental behavioral epigenetics and clinically-relevant cognitive phenotypes (e.g., inattention). Research in developmental psychopathology has been successful in identifying risk factors for attention problems across multiple domains, including biological, cognitive, and caregiving factors. However, a missed opportunity is the study of multiple, longitudinal trajectories of risk factors in relation to trajectories of inattention. Specifically, there is a need to understand whether there are heterogeneous trajectories of inattention in early childhood, particularly during the transition to formal schooling (age 5-7) when increases in inattention are common. Further, understanding how changes in risk factors across early childhood relate to changes in inattention across the transition to formal schooling could provide critical information regarding modifiable targets and optimal timing for screening and intervening with high-risk children. The proposed study will leverage existing data from two parent grants (R01HD072267; R01HD084515; NOVI study) focused on neurodevelopmental outcomes in children born very preterm. The current study proposes to test associations between trajectories of biological (i.e., DNA methylation), cognitive (i.e., executive function) and caregiving (i.e., psychological distress) factors and trajectories of child inattention in a sample of children born very preterm, a group known to be at elevated risk for attention problems. Specific aims are as follows: (1) to characterize trajectories of inattention in very preterm children; (2) to test the contributions of biological, cognitive, and caregiving factors to trajectories of inattention; and (3) to test how changes in biological, cognitive, and caregiving factors relate to trajectories of inattention. The applicant’s mentorship team will scaffold completion of the study aims and provide needed training in (1) processing and (2) analysis of high-dimensional, longitudinal epigenetic data, (3) advanced statistical techniques for longitudinal data analysis, and (4) frameworks (e.g., RDOC) for studying child psychopathology. The resources and intellectual environment at the Brown Center for the Study of Children at Risk, Women and Infant’s Hospital, and Warren Alpert Medical School of Brown University constitute an ideal setting to launch an independent research career. This project will provide preliminary data for a future R01 investigating how trajectories of DNA methylation are established and altered across development (e.g., as a function of environmental risk factors) as well as grants that follow NOVI children into later childhood. This project is aligned with NIMH strategic priorities given its focus on charting the development of inattention in childhood, identifying risk factors and biomarkers for inattention that could serve as novel intervention targets, and isolating sensitive periods for interventions aimed at mitigating long-term functional impairment.