The Infants of Superstorm Sandy:The Epigenetic and Developmental Impact of Natural Disaster

超级风暴桑迪的婴儿：自然灾害的表观遗传和发育影响

• 批准号: 9086428
• 负责人: Yoko Nomura
• 金额: $ 68.59万
• 依托单位: QUEENS COLLEGE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-25 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9086428
• 关键词: Acute; Address; Age-Months; Animal Model; Animals; Archives; Area; Arousal; Autonomic nervous system; Biological Process; Birth; Brain; Candidate Disease Gene; Child; Childhood; Control Groups; DNA; DNA Methylation; Data; Development; Disasters; Disease; Divorce; Early Intervention; Emotional; Epidemiologic Studies; Epigenetic Process; Equation; Event; Exposure to; Fetal Development; Funding; Future; Gene Cluster; Gene Expression; Gene Expression Regulation; Genes; Genetic; Goals; Growth; Health; Human; Impairment; Impulsivity; Infant; Intervention; Language Development; Lead; Length; Life; Life Stress; Linear Models; Link; Long Island; Measures; Mental Health; Mental disorders; Metabolism; Methylation; Modeling; Molecular; Mothers; Motor Skills; Natural Disasters; Natural experiment; Neuraxis; Neurocognitive; Neurodevelopmental Impairment; Occupations; Outcome; Participant; Pathway interactions; Peripheral; Physiological; Placenta; Play; Predisposition; Pregnancy; Psychopathology; Psychophysiology; Psychosocial Stress; Randomized; Reaction; Regulation; Research; Research Infrastructure; Risk Factors; Rodent; Role; Saliva; Sampling; Serotonin; Severities; Socioeconomic Status; Specificity; Staging; Stress; Stressful Event; Temperament; Time; Tissues; Translating; Trauma; Umbilical Cord Blood; United States National Institutes of Health; Woman; biobank; cognitive function; critical period; design; early childhood; emotion dysregulation; emotion regulation; epigenetic regulation; executive function; experience; functional decline; gene function; hypothalamic-pituitary-adrenal axis; improved; in utero; infancy; maternal stress; multilevel analysis; nervous system development; neurobehavioral; neurodevelopment; neuropsychological; offspring; outcome forecast; postnatal; preempt; prenatal; prenatal exposure; prenatal stress; programs; psychologic

DESCRIPTION (provided by applicant): The intrauterine period is critically important for brain development and may influence mental health throughout life. Animal studies have shown that psychosocial stress during pregnancy, especially in early and mid-stages of gestation, lead to neurobehavioral problems associated with suboptimal Central Nervous System (CNS) development involving motor skills, arousal, impulsivity, and emotional dysregulation. Yet, these studies cannot be directly applied to humans. The overall goal of the proposed study is driven by the hypothesis that exposure to psychosocial stress in utero can program changes in the functioning of the offspring's CNS during sensitive windows of fetal development, leading to neurodevelopmental impairment. This study builds upon our on-going NIH-funded study which assesses prenatal stress as a critical neurodevelopmental risk factor. The participants (N=408) reside in Queens/Long Island, where "Superstorm Sandy" caused devastation, allowing us to conduct a natural experiment of stress during pregnancy. Capitalizing on existing infrastructure, an established biorepository, and prospectively collected data on Sandy-related trauma after the disaster (severity, timing of exposure, duration of adversity, and psychological reactions), and normative (from everyday life) psychosocial stress experienced during pregnancy, we propose to 1) follow offspring through 42 months of age to evaluate key areas of neurodevelopment as a function of their exposure to prenatal stress; 2) evaluate whether timing of exposure to Sandy trauma is associated with different neurodevelopmental trajectories; 3) examine the inter- relations of prenatal stress, child neurodevelopment, and epi/genetic (methylation and gene expression) regulation of candidate genes, encompassing 5 key stress modulation and neuro-development pathways in paired samples of placenta and cord blood, and further explore if epigenetic regulation in those genes induce different trajectories of neurodevelopment; 4) explore stability of epigenetic marks during early development in childhood. Given the distinct biological functions and tissue- and developmental stage-specificity of gene regulation, assessment of epi/genetic marks in paired samples of placenta and cord blood at birth and saliva in childhood could help clarify disease mechanism. By demonstrating the utility of less invasive ways to collect peripheral tissues at different times in life, the study will advance the design for future epidemiologic studies, and potentially improve prognosis and interventions for developmental psychopathology. Using structural equation modeling, multilevel growth curve modeling, and hierarchical linear models, we will elucidate the underlying mechanisms of suboptimal neurodevelopment in early childhood, in association with maternal psychosocial stress exposure (types, intensity, and timing) during the course of pregnancy. The study will ultimately help us chart the course of mental disorders from in utero to birth and early childhood, further our understanding of the critical periods of pregnancy and their effect on a molecular level in humans, and set the stage for research into early interventions that could preempt mental disorders that might emerge later in life.

描述（由申请人提供）：宫内时期对于大脑发育至关重要，可能影响一生的心理健康。动物研究表明，怀孕期间的社会心理压力，尤其是妊娠早期和中期，会导致与中枢神经系统 (CNS) 发育欠佳相关的神经行为问题，包括运动技能、觉醒、冲动和情绪失调。然而，这些研究不能直接应用于人类。拟议研究的总体目标是基于这样的假设：子宫内暴露于社会心理压力可以在胎儿发育的敏感窗口期间改变后代中枢神经系统的功能，从而导致神经发育障碍。这项研究建立在我们正在进行的美国国立卫生研究院资助的研究的基础上，该研究评估产前压力作为一个关键的神经发育危险因素。参与者（N = 408）居住在皇后区/长岛，“超级风暴桑迪”在那里造成了破坏，使我们能够在怀孕期间进行自然压力实验。利用现有基础设施、已建立的生物储存库以及前瞻性收集的灾难后桑迪相关创伤的数据（严重程度、暴露时间、逆境持续时间和心理反应）以及怀孕期间经历的规范（来自日常生活）心理社会压力，我们建议 1) 跟踪后代至 42 个月大，以评估神经发育的关键领域，作为其暴露于产前压力的函数； 2）评估桑迪创伤暴露时间是否与不同的神经发育轨迹相关； 3）检查产前应激、儿童神经发育和候选基因的表观/遗传（甲基化和基因表达）调节之间的相互关系，包括胎盘和脐带血配对样本中的5个关键应激调节和神经发育途径，并进一步探索这些基因的表观遗传调控是否会诱导不同的神经发育轨迹； 4）探索儿童早期发育过程中表观遗传标记的稳定性。鉴于基因调控的独特生物学功能以及组织和发育阶段特异性，对出生时胎盘和脐带血以及儿童期唾液配对样本中的表观/遗传标记进行评估有助于阐明疾病机制。通过展示在生命中不同时期收集外周组织的侵入性较小的方法的实用性，该研究将推进未来流行病学研究的设计，并有可能改善发育精神病理学的预后和干预措施。使用结构方程模型、多级生长曲线模型和分层线性模型，我们将阐明儿童早期神经发育欠佳的潜在机制，与怀孕期间母亲心理社会压力暴露（类型、强度和时间）相关。这项研究最终将帮助我们绘制从子宫内到出生和幼儿期的精神障碍的过程， 进一步加深我们对怀孕关键时期及其对人类分子水平影响的理解，并为研究早期干预措施奠定基础，以预防晚年可能出现的精神障碍。