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

项目摘要/摘要 这份K01提案将为候选人的独立研究生涯做准备，学习环境和 在典型发育和高危人群中，儿童神经发育轨迹的生物学因素， 具有人类发育行为表观遗传学和临床相关认知方面的专门知识 表型(如注意力不集中)。发展精神病理学的研究已经成功地确定了 多个领域注意力问题的风险因素，包括生物学、认知和照顾因素。 然而，错失的机会是研究与以下因素相关的多个纵向风险因素的轨迹 注意力不集中的轨迹。具体地说，需要了解是否存在异构性 儿童早期注意力不集中的轨迹，特别是在向正规学校(5-7岁)过渡期间 注意力不集中的增加是很常见的。此外，了解儿童早期风险因素的变化 与过渡到正规学校期间注意力不集中的变化有关的信息可以提供关键信息 关于筛查和干预高危儿童的可修改目标和最佳时机。这个 拟议的研究将利用来自两个家长赠款的现有数据(R01HD072267；R01HD084515；Novi Study) 重点关注早产儿的神经发育结果。目前的研究建议测试 生物学轨迹(即DNA甲基化)、认知轨迹(即执行功能)和 出生儿童样本中的照管(即心理困扰)因素和儿童注意力不集中轨迹 非常早产，这是一个已知的注意力问题风险增加的群体。具体目标如下：(一) 描述早产儿注意力不集中的轨迹；(2)测试生物学的、认知的、 和护理因素对注意力不集中轨迹的影响；以及(3)测试生理、认知和心理方面的变化 照顾因素与注意力不集中的轨迹有关。申请者的指导团队将完成脚手架 研究目标，并提供(1)加工和(2)高维、纵向分析所需的培训 表观遗传数据，(3)用于纵向数据分析的高级统计技术，以及(4)框架(例如， RDoC)，用于研究儿童精神病理学。布朗中心的资源和智力环境 布朗大学危险儿童、妇幼医院和沃伦·阿尔伯特医学院的研究 大学构成了开始独立研究事业的理想环境。该项目将提供 研究DNA甲基化轨迹如何建立和改变的未来R01的初步数据 跨发展(例如，作为环境风险因素的函数)以及跟随Novi儿童的赠款 一直延续到童年后期。该项目与NIMH的战略优先事项保持一致，因为它的重点是绘制 儿童注意力不集中的发展，识别可能有助于注意力不集中的危险因素和生物标记物 作为新的干预目标，并隔离旨在缓解长期 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.