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

项目摘要 遭受儿童期虐待的妇女的孩子患上一系列神经发育障碍的风险增加 缺陷，包括焦虑、抑郁和社会问题的风险增加。我们的研究发现，这些 儿童患自闭症的风险高三倍以上，患注意力缺陷多动症的风险高70% 精神障碍(ADHD)。动物研究同样发现，母亲暴露在压力源下与后代有关 焦虑、抑郁症状、注意力问题和社交行为减少。神经发育 疾病很常见，会带来终身的、代价高昂的负担。然而，现有的研究未能确定路径 受虐待妇女的子女有受到伤害的风险。识别这样的途径是在 预防这些儿童的神经发育缺陷。目前的研究集中在三个可能的 在很大程度上还没有被研究过的路径。我们将确定在怀孕期间的生物失调 在两个系统中，暴露于虐待和未暴露于虐待中的女性：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，并出现在 经历过童年虐待的成年人，但在很大程度上尚不清楚这些疾病是否存在调节失调 该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以 在一大群预期的孕妇中测量这些系统的功能。第二，我们将 检查经历过虐待的女性是否携带较高的神经精神障碍的基因负荷 通过计算8000多名女性中包括自闭症和ADHD在内的5种疾病的遗传风险得分。 遗传信息研究表明，遗传变异在增加阴性风险中起作用。 受虐待妇女子女的神经发育结果。然而，到目前为止，还没有研究使用基因组- 广泛的数据来解决这个问题。我们提议的研究非常适合极大地扩展我们的理解 了解儿童期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的优先事项和确定 预防儿童神经发育损害的最佳干预类型和时机。

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.