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.

项目摘要/摘要 我的职业目标是建立一个研究的研究计划，该计划调查 精神病疾病，重点是可以从父母传播逆境的围产期机制 给他们的孩子。迄今为止，我已经获得了对逆境和精神病评估的广泛培训 历史上少数家庭的症状学，孕产妇皮质醇功能，婴儿fMRI和 围产期心理健康。我的职业发展计划是通过提供关键的知识基础建立的 在胎儿大脑网络的成像和分析中进行的深入培训，生态瞬时评估， 晚期纵向统计和胎儿心电图。拟议的研究和培训的完成至关重要 为了使我准备领导一个利用多模式发育神经科学技术的实验室发现风险 以及生活最早阶段的弹性过程，这可能有助于破坏代际 健康差异的传播。 研究项目：怀孕期间孕产妇压力是最强大的转诊之一 整个生命周期的精神病风险因素。但是我们缺乏有关特征的关键信息 对胎儿生物学最明显的压力，胎儿内机制将母性与儿童联系起来 精神病风险，以及当胎儿生物学受到最强烈影响时是否有敏感窗户 孕产妇压力。使用多模式的方法，该K99/R00的目标是检查个体内变化 在母亲产前压力中，作为两种候选机制的独特预测指标 儿童：胎儿自主神经系统（ANS）发育和胎儿功能性神经记录。在K99中 该奖项的一部分，我们将利用重复的措施纵向设计来检查关联 在孕产妇应力的现实世界变异与胎儿和胎儿的发展之间，整个怀孕14周之间 包括检查敏感窗户（AIM 1）。我们还将研究内部内部变化 孕产妇应力与胎儿ANS发育和胎儿神经记录的长期轨迹有关，预测 压力不可预测性将唯一影响胎儿神经发育（AIM 2）。 R00项目将提供 通过评估如何跨压力响应性的相互作用，对这种神经育模型的必要背景 系统（HPA轴和ANS）以及终生逆境的产妇历史调节与压力相关的编程 高危队列中的胎儿大脑。在R00中，我们还将评估是否与逆境有关 胎儿大脑中的签名一直持续到婴儿期（AIM 3）。这一研究有可能隔离 突显抑郁症和其他精神病的发展的发展级联 疾病，从而告知干预措施，这些干预措施可以利用发育中的大脑的无与伦比的可塑性。