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

极早产儿注意力问题的纵向前因：表观遗传学、执行功能和照顾者心理困扰的作用

• 批准号: 10426765
• 负责人: Marie Camerota
• 金额: $ 19.11万
• 依托单位: WOMEN AND INFANTS HOSPITAL-RHODE ISLAND
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10426765
• 关键词: Age; Attention; Attention deficit hyperactivity disorder; Behavioral; Biological; Biological Markers; Birth; Caregivers; Child; Childhood; Cognitive; DNA Methylation; DNA Sequence; Data; Data Analyses; Development; Early Intervention; Early identification; Environment; Environmental Risk Factor; Epigenetic Process; Future; Gene Expression; Genes; Grant; Heterogeneity; Hospitals; Human; Individual; Individual Differences; Infant; Intervention; Joints; K-Series Research Career Programs; Lead; Life; Location; Longevity; Longitudinal Studies; Measures; Mediating; Mental disorders; Mentors; Mentorship; Mission; National Institute of Mental Health; Neonatal; Neurocognitive Deficit; Outcome; Pattern; Phenotype; Population; Pregnancy; Psychopathology; Research; Research Activity; Resources; Risk; Risk Factors; Role; Sampling; School-Age Population; Schools; Statistical Models; Strategic Planning; Structure; Symptoms; Techniques; Testing; Training; Training Activity; Universities; Woman; Work; adverse outcome; career; caregiving; clinically relevant; clinically significant; early childhood; endophenotype; executive function; experience; functional disability; functional outcomes; high dimensionality; high risk; high risk population; improved; inattention; medical schools; neurobehavior; novel; parent grant; performance based measurement; preterm newborn; programs; psychological distress; rate of change; relating to nervous system; resilience; response; scaffold; screening; skills; synergism

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.

项目摘要/摘要 该K01提案将为候选人做好准备的独立研究职业研究环境和 儿童神经发育轨迹的生物学贡献者在典型和高危人群中， 具有人类发育行为表观遗传学和临床上的认知方面的特定专业知识 表型（例如，注意力不集中）。发育心理病理学的研究已成功识别 跨多个领域的注意力问题的风险因素，包括生物学，认知和护理因素。 但是，错过的机会是研究多种风险因素的多个纵向轨迹 注意力不集中的轨迹。具体来说，有必要了解是否存在异质 童年时期的注意力不集中的轨迹，尤其是在过渡到正规教育的过程（5-7岁） 注意力不集中是普遍的。此外，了解幼儿期风险因素的变化如何 与在过渡到正规教育的过程中的注意力变化有关，可以提供关键信息 关于可修改的目标以及与高危儿童进行筛查和干预的最佳时机。 拟议的研究将利用来自两个家长赠款的现有数据（R01HD072267; R01HD084515; NOVI研究） 专注于出生的孩子的神经发育结果。当前的研究建议 生物学轨迹（即DNA甲基化），认知（即执行功能）和 护理（即心理困扰）因素和儿童的轨迹在出生的孩子样本中 非常早产，一个众所周知，注意力问题的风险较高。具体目的如下：（1）到 表征了非常早产儿童的注意力不集中的轨迹； （2）测试生物学，认知， 以及注意力不集中的轨迹； （3）测试生物学，认知和 护理因素与注意力不集中有关。申请人的Mentalship团队将脚手架完成 该研究的目的并提供了（1）处理和（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和（4）框架（例如， RDOC）用于研究儿童心理病理学。布朗中心的资源和知识环境 研究处于危险的儿童，妇女和婴儿医院以及沃伦·阿尔珀特医学院的研究 大学构成了启动独立研究职业的理想环境。这个项目将提供 未来R01的初步数据，研究如何建立DNA甲基化轨迹并改变 在整个发展（例如，作为环境风险因素的函数）以及跟随诺维儿童的赠款 进入后来的童年。该项目与NIMH战略优先级保持一致，鉴于其专注于绘制 童年时期不关心的发展，确定可能服务的危险因素和生物标志物 作为新的干预目标，并隔离旨在减轻长期的干预措施的敏感周期 功能障碍。