Early Life Adversity, Biological Embedding, and Risk for Developmental Precursors of Mental Disorders

生命早期的逆境、生物嵌入和精神障碍发育先兆的风险

• 批准号: 10158509
• 负责人: JOAN L. LUBY
• 金额: $ 215.26万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-22 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10158509
• 关键词: 3 year old; Affect; Age; Amygdaloid structure; Area; Attention; Behavioral; Biological; Biological Markers; Birth; Brain; Caregiver support; Characteristics; Child; Childhood; Cognitive; Computing Methodologies; Data; Data Set; Development; Emotional; Environmental Risk Factor; Epigenetic Process; Exposure to; Face; First Pregnancy Trimester; Funding; Hippocampus (Brain); Immunologic Markers; Impairment; Incidence; Infant; Inflammation; Inflammatory; Inflammatory Response; Informal Social Control; Instruction; Life; Link; Measures; Mediating; Mediator of activation protein; Mental Health; Mental disorders; Mothers; Neurons; Outcome; Pathway interactions; Pattern; Perinatal; Poverty; Prefrontal Cortex; Pregnancy; Pregnancy Trimesters; Pregnant Women; Premature Birth; Premature Infant; Process; Prospective Studies; Psychopathology; Research; Research Domain Criteria; Risk; Risk Factors; Role; Sampling; Specimen; Stress; Structure; Testing; Third Pregnancy Trimester; Time; Toddler; Trauma; Universities; Washington; antenatal; base; cervicovaginal; cognitive control; cognitive development; cohort; critical period; deep learning; early childhood; early life adversity; emotion regulation; experience; fetal programming; gray matter; gut colonization; gut microbiome; high risk; in utero; infancy; infant gut microbiome; inflammatory marker; innovation; insight; maternal microbiome; microbial; microbial colonization; microbiome; neurodevelopment; neuroimaging; novel; offspring; perinatal period; postnatal; premature; prenatal; preventive intervention; prospective; psychosocial; recruit; relating to nervous system; systemic inflammatory response; white matter

Project Summary: Early life psychosocial adversity and stress are well-established as the most powerful environmental risk factors for poor neurodevelopmental and mental health outcomes in children. Impairments in developing emotion regulation and cognitive control and associated alterations in brain development have been shown to mediate the effects of adversity on risk for the development of psychopathology. Early psychosocial adversity impacts the epigenetic and inflammation-mediated processes that contribute to these negative outcomes, a process known as “biological embedding of stress.” While this risk trajectory has been clearly linked to increased rates of psychopathology, the mechanisms of this process, its targetable mediators and how early in development they operate are yet to be determined. Here we focus on the effects of early life adversity on brain, emotion regulation and cognitive control outcomes relevant to risk for mental disorders, beginning antenatally and extending to age 3. We will examine the role of pre- and postnatal adversity/stress, the maternal and child perinatal gut microbiome and early caregiver support on these key neurodevelopmental outcomes utilizing state-of-the-art neuroimaging. Our unifying hypothesis is that these factors modulate systemic inflammatory responses, induce neuronal effects through this and other processes that adversely impact brain development in limbic and cortical regions, and mediate the effects of early adversity on child emotion regulation, cognitive control and mental health outcomes. These factors will be studied in a unique, prospectively ascertained cohort of 370 mothers and their offspring at high psychosocial risk being recruited as part of an already funded March of Dimes project at Washington University. The cohort will include both term- and prematurely-born infants and toddlers given the increased risk of psychosocial adversity and aberrant gut microbiome in preterm children. The offspring will be intensively prospectively studied from the 1st trimester to age 3, providing a unique dataset in which to examine the interrelationships among pre- and postnatal adversity, biomarkers of inflammation, the gut microbiome and developmental and mental health outcomes. The perinatal and early childhood periods are critical times to study these exposures as adverse neurodevelopment associated with adversity begins in utero through fetal programming. Likewise, the perinatal period is a critical developmental window for microbial influences, when gut microbial colonization has its most enduring effects. The proposed study merges established research groups in these areas in a center with advanced infant and childhood neuroimaging and extensive microbiome expertise, and offers an unprecedented opportunity to understand the mechanisms of the biological embedding of adversity on brain, cognitive and emotional trajectories in a high-risk cohort. We will also apply innovative computational methods, using Deep Learning, to extend understanding of these data. Findings will provide critical and novel insights to inform early preventive interventions relevant to emotional, cognitive and mental health outcomes for children at greatest risk.

项目摘要：早年心理社会逆境和压力被认为是最强大的 儿童神经发育和心理健康结果不佳的环境风险因素。减值 发展情绪调节和认知控制以及大脑发育的相关改变 显示可以调节逆境对精神病理学发展风险的影响。早期社会心理 逆境会影响表观遗传和炎症介导的过程，从而导致这些负面影响 结果，这个过程被称为“压力的生物嵌入”。尽管这一风险轨迹已明确关联 精神病理学发病率的增加、这一过程的机制、其目标调节因素以及多久 在开发过程中，它们的运作方式尚未确定。在这里，我们重点关注早年逆境对人的影响。 与精神障碍风险相关的大脑、情绪调节和认知控制结果，开始 产前一直延续到 3 岁。我们将研究产前和产后逆境/压力、产妇 以及儿童围产期肠道微生物组和早期护理人员对这些关键神经发育结果的支持 利用最先进的神经影像学。我们的统一假设是这些因素调节系统性 炎症反应，通过这个过程和其他对大脑产生不利影响的过程诱导神经元效应 边缘系统和皮质区域的发育，并介导早期逆境对儿童情绪调节的影响， 认知控制和心理健康结果。这些因素将以独特的、前瞻性的方式进行研究 确定的 370 名母亲及其后代处于高心理社会风险的队列被招募为一项研究的一部分 已经资助了华盛顿大学的March of Dimes项目。该队列将包括学期和 早产婴儿和幼儿面临社会心理逆境和肠道异常的风险增加 早产儿的微生物组。后代将从妊娠第一个月到 3岁，提供了一个独特的数据集来检查产前和产后逆境之间的相互关系， 炎症、肠道微生物组以及发育和心理健康结果的生物标志物。围产期 儿童早期是研究这些暴露与不良神经发育相关的关键时期 逆境是在子宫内通过胎儿编程开始的。同样，围产期也是一个关键时期 微生物影响的发育窗口，此时肠道微生物定植具有最持久的影响。 拟议的研究将这些领域的既定研究小组合并到一个拥有高级婴儿和婴儿的中心。 儿童神经影像学和广泛的微生物组专业知识，并提供了前所未有的机会 了解逆境对大脑、认知和情感的生物嵌入机制 高风险人群的轨迹。我们还将利用深度学习应用创新的计算方法 加深对这些数据的理解。研究结果将为早期预防提供重要和新颖的见解 与风险最大的儿童的情绪、认知和心理健康结果相关的干预措施。