Maternal Exposure to Childhood Abuse and Disparities in Offspring Neurodevelopment: Identifying Mechanisms

母亲童年遭受虐待和后代神经发育差异：识别机制

基本信息

批准号：
10380833
负责人：
Andrea Roberts
金额：
$ 66.17万
依托单位：
HARVARD SCHOOL OF PUBLIC HEALTH
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10380833
关键词：
Address Adrenal Glands Adult Affect Animals Anxiety Attention Attention deficit hyperactivity disorder Biological Biological Assay Caring Child Child Abuse Child Development Childhood Data Diagnosis Disease Disparity Documentation Early Intervention Endocrine Environmental Risk Factor Exhibits Exposure to Functional disorder Generations Genetic Genetic Load Genetic Risk Genetic Variation Genotype Goals Health Homeostasis Hormonal Human Hypothalamic structure Inflammation Inflammatory Intervention Life Cycle Stages Longevity Maternal Exposure Maternal-Fetal Transmission Measures Mediating Mental Depression Mental Health Mental disorders Morbidity - disease rate Mothers Neurodevelopmental Deficit Neurodevelopmental Disorder Nurses&apos Health Study Outcome Pathway interactions Pituitary Gland Population Pregnancy Pregnant Women Prenatal care Prevention Prospective cohort Recording of previous events Research Risk Sampling Sexual abuse Shapes Social Behavior Social Problems Stressful Event System Testing Thyroid Gland Time Unemployment Woman autism spectrum disorder biological systems cost depressive symptoms design disability disparity reduction emotional abuse experience genetic risk factor genome-wide high risk hypothalamic-pituitary-adrenal axis immune function improved neurodevelopment neuropsychiatric disorder neuropsychiatry offspring perinatal intervention physical abuse physical conditioning pituitary thyroid axis polygenic risk score prenatal prevent public health intervention public health priorities public health relevance screening stressor systemic inflammatory response

项目摘要

Project Summary Children of women exposed to childhood abuse exhibit increased risk for a wide array of neurodevelopmental deficits, including elevated risk of anxiety, depression, and social problems. Our studies have found that these children had a more than three-fold higher risk of autism and 70% higher risk of attention-deficit hyperactivity disorder (ADHD). Animal studies similarly find that maternal exposure to stressors is associated with offspring anxiety, depressive symptoms, and attention problems and decreased social behavior. Neurodevelopmental disorders are common and carry lifelong, costly burdens. Yet, extant research has failed to identify pathways by which children of women abused are at risk of harm. Identification of such pathways is a critical step in preventing neurodevelopmental deficits in these children. The present research focuses on three likely pathways that have largely been unexamined. We will identify biological dysregulation during pregnancy in women exposed versus unexposed to abuse in two systems: hormonal function and immune function. Dysregulation in these biological systems is known to harm offspring neurodevelopment and is present in adults who have experienced childhood abuse, yet it is largely unknown whether dysregulation in these systems occurs during the pregnancies of women exposure to abuse. We will collect biological samples to measure the functioning of these systems in a large, prospective cohort of pregnant women. Second, we will examine whether women who experienced abuse carry higher genetic loading for neuropsychiatric disorders by calculating genetic risk scores for 5 disorders including autism and ADHD in more than 8000 women. Genetically informed studies indicate that genetic variation plays a role in increased risk of negative neurodevelopmental outcomes in children of women abused. However, to date no studies have used genome- wide data to address this question. Our proposed study is uniquely suited to greatly expand our understanding of how childhood abuse affects health across generations and to inform interventions to protect the healthy development of children. This information is critical to establish public health priorities and to determine the optimal type and timing of interventions to prevent neurodevelopmental harm to children.

项目概要童年时期遭受虐待的妇女所生的孩子表现出多种神经发育的风险增加缺陷，包括焦虑、抑郁和社会问题的风险升高。我们的研究发现，这些儿童患自闭症的风险高出三倍多，患注意力缺陷多动症的风险高出 70% 障碍（多动症）。动物研究同样发现，母亲暴露于压力源与后代有关焦虑、抑郁症状、注意力问题和社交行为下降。神经发育疾病很常见，并且会带来终生的、代价高昂的负担。然而，现有研究未能确定途径受虐待妇女的子女面临受到伤害的风险。识别此类途径是关键一步预防这些儿童的神经发育缺陷。目前的研究重点关注三种可能的基本上未经检验的途径。我们将识别怀孕期间的生物失调与未遭受虐待的女性相比，她们的两个系统受到虐待：荷尔蒙功能和免疫功能。众所周知，这些生物系统的失调会损害后代的神经发育，并且存在于经历过童年虐待的成年人，但目前尚不清楚这些人是否存在调节失调系统发生在妇女怀孕期间遭受虐待的情况。我们将收集生物样本在一大群前瞻性孕妇中测量这些系统的功能。其次，我们将检查遭受虐待的女性是否携带更高的神经精神疾病遗传负荷通过计算 8000 多名女性的 5 种疾病（包括自闭症和多动症）的遗传风险评分。遗传研究表明，遗传变异在增加负面风险方面发挥着作用受虐待妇女的孩子的神经发育结果。然而，迄今为止，还没有研究使用基因组广泛的数据来解决这个问题。我们提出的研究非常适合极大地扩展我们的理解儿童虐待如何影响几代人的健康，并为保护健康的干预措施提供信息儿童的发展。这些信息对于确定公共卫生优先事项和确定预防儿童神经发育损害的最佳干预类型和时机。