Psychosocial unpredictability during pregnancy and offspring neurodevelopment: Uncovering mechanisms and sensitive windows in utero

怀孕期间的心理社会不可预测性和后代神经发育：揭示子宫内的机制和敏感窗口

• 批准号: 10723733
• 负责人: Cassandra Lei Hendrix
• 金额: $ 12.37万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10723733
• 关键词: Affect; Autonomic nervous system; Award; Biogenesis; Biological Markers; Biology; Birth; Blood flow; Brain; Buffers; Child; Cognition; Conceptions; Coupled; Data; Development; Development Plans; Diagnostic; Discrimination; Ecological momentary assessment; Electrocardiogram; Exposure to; Faculty; Family; Fetal Development; Fetal Heart Rate; Fetal autonomic nervous system; Functional Magnetic Resonance Imaging; Future; Goals; Hydrocortisone; Image; Infant; Informal Social Control; Intervention; Knowledge; Life; Link; Longevity; Measures; Mental Depression; Mental disorders; Minority; Modeling; Nervous System; Nervous System Physiology; Neurosciences; Newborn Infant; Parents; Perinatal; Play; Positioning Attribute; Predisposition; Pregnancy; Process; Recording of previous events; Research; Research Project Grants; Resources; Rest; Risk; Risk Factors; Role; Shapes; Stress; System; Techniques; Temperament; Third Pregnancy Trimester; Time; Training; Trauma; Variant; Work; biobehavior; biological adaptation to stress; career; career development; cohort; depressive symptoms; experience; fetal; fetal blood; fetal programming; health disparity; heart rate variability; high risk; hypothalamic-pituitary-adrenal axis; immune activation; in utero; indexing; individual variation; infancy; insight; interest; intergenerational; knowledge base; longitudinal design; maternal stress; multimodality; nervous system development; neural; neural circuit; neurodevelopment; novel; offspring; perinatal mental health; postnatal period; prenatal; prenatal stress; programs; psychologic; psychosocial; recruit; resilience; statistics; symptomatology; translational research program; translational study; transmission process

PROJECT SUMMARY/ABSTRACT My career goal is to build a translational program of research that investigates the developmental origins of psychiatric disease, with a focus on perinatal mechanisms by which adversity can be transmitted from parents to their children. To date, I have obtained extensive training in the assessment of adversity and psychiatric symptomatology in historically minoritized families, maternal-infant cortisol functioning, infant fMRI, and perinatal mental health. My career development plan builds on this knowledge base by providing crucial, intensive training in the imaging and analysis of fetal brain networks, ecological momentary assessment, advanced longitudinal statistics, and fetal ECG. Completion of the proposed research and training is essential to prepare me to lead a lab that leverages multimodal developmental neuroscience techniques to discover risk and resilience processes during the earliest stages of life, which may help to disrupt the intergenerational transmission of health disparities. Research Project: Exposure to maternal stress during pregnancy is one of the most robust transdiagnostic risk factors for psychiatric illness across the lifespan. Yet we lack critical information about the features of stress that are most salient for fetal biology, the intrauterine mechanisms that link maternal stress to child psychiatric risk, and whether there are sensitive windows when fetal biology is most strongly impacted by maternal stress. Using a multimodal approach, the goal of this K99/R00 is to examine intraindividual variation in maternal prenatal stress as a unique predictor of two candidate mechanisms underlying psychiatric risk in children: fetal autonomic nervous system (ANS) development and fetal functional neurocircuitry. In the K99 portion of this award, we will leverage a repeated measures longitudinal design to examine associations between real-world variation in maternal stress and fetal ANS development across 14 weeks of pregnancy, including examination of sensitive windows (Aim 1). We will also examine how intraindividual variation in maternal stress relates to long-term trajectory of fetal ANS development and fetal neurocircuitry, predicting that stress unpredictability will uniquely impact fetal neurodevelopment (Aim 2). The R00 project will provide necessary context to this neuromaturational model by evaluating how interactions across stress-responsive systems (HPA axis and ANS) and maternal history of lifetime adversity modulate stress-related programming of the fetal brain in a high-risk cohort. In the R00, we will additionally assess whether adversity-related signatures in the fetal brain persist into infancy (Aim 3). This line of research has potential to isolate the beginning of developmental cascades that underscore emergence of depression and other psychiatric disorders, thus informing interventions that can leverage the unparalleled plasticity of the developing brain.

项目概要/摘要 我的职业目标是建立一个转化研究计划，调查人类的发展起源 精神疾病，重点关注父母传播逆境的围产期机制 给他们的孩子。迄今为止，我已经获得了逆境评估和精神科方面的广泛培训 历史上少数家庭的症状学、母婴皮质醇功能、婴儿功能磁共振成像和 围产期心理健康。我的职业发展计划建立在这个知识库的基础上，提供关键的、 胎儿大脑网络成像和分析、生态瞬时评估的强化训练， 高级纵向统计和胎儿心电图。完成拟议的研究和培训至关重要 让我做好准备领导一个利用多模式发育神经科学技术来发现风险的实验室 生命早期阶段的恢复力过程，这可能有助于破坏代际关系 健康差异的传播。 研究项目：怀孕期间母亲承受的压力是最有力的跨诊断之一 整个生命周期中精神疾病的危险因素。然而我们缺乏有关其特征的关键信息 对胎儿生物学最重要的压力，将母亲压力与孩子联系起来的宫内机制 精神风险，以及当胎儿生物学受到最强烈影响时是否存在敏感窗口 母亲的压力。使用多模式方法，K99/R00 的目标是检查个体内变异 母亲产前应激作为潜在精神风险的两种候选机制的独特预测因子 儿童：胎儿自主神经系统（ANS）发育和胎儿功能神经回路。在K99中 作为该奖项的一部分，我们将利用重复测量纵向设计来检查关联 怀孕 14 周期间母亲压力与胎儿 ANS 发育的现实变化之间， 包括检查敏感窗户（目标 1）。我们还将研究个体内差异如何 母亲的压力与胎儿 ANS 发育和胎儿神经回路的长期轨迹有关，预测 压力的不可预测性将对胎儿神经发育产生独特的影响（目标 2）。 R00项目将提供 通过评估压力反应之间的相互作用，了解该神经成熟模型的必要背景 系统（HPA 轴和 ANS）和母亲一生的逆境史调节与压力相关的编程 高危人群中胎儿大脑的变化。在 R00 中，我们将另外评估是否与逆境相关 胎儿大脑中的特征持续到婴儿期（目标 3）。这条研究线有可能分离出 发展级联的开始，强调抑郁症和其他精神疾病的出现 疾病，从而为可以利用发育中的大脑无与伦比的可塑性的干预措施提供信息。