Mothers' childhood experiences, maternal sensitivity, and immune regulation in young children

不良童年经历(ACE)，如童年忽视、虐待和接触暴力， 物质使用，或精神健康问题，估计是10个主要原因中的9个的根本原因 美国的死亡事件。高水平的ACE可导致免疫功能和遗传功能的长期中断 监管机制。敏感的父母教育对于保护婴儿和儿童免受 王牌。然而，当父母自己也有A级的历史时，养育孩子可能特别具有挑战性，这 会削弱他们提供敏感护理的能力。然而，许多暴露于ACE的人不会发病。 健康状况不佳或变得不那么敏感的父母。积极的童年经历(PCE)通常是同时发生的 具有ACEs，并且可以是缓冲ACEs有害影响的重要弹性来源。然而， PCE的积极作用及其父母的ACEs和PCEs的生物行为机制 共同塑造儿童健康仍然知之甚少。拟议的K99/R00研究旨在澄清 母亲的ACE和PCE、母亲的敏感性和婴儿的免疫调节之间的关系(3 患有阿片类药物依赖的母亲的幼儿(12-36个月)，这是一个高危群体， 经常遇到一大堆逆境。这项研究将建立在NICHD资助的随机临床试验的基础上 (R01HD098525)，测试依恋和生物行为追赶(ABC)干预的有效性 在有阿片依赖的母亲和围产期有阿片类药物暴露的婴儿中。对儿童的评估 免疫调节目前不包括在父母的研究中。利用家长研究的预先干预 数据，K99阶段将调查100名母亲的A和PCE之间的关系，母亲 敏感性及其3个月大婴儿的免疫调节，以唾液C-反应蛋白(CRP)和 分泌型免疫球蛋白A(SIgA)。我的长期职业目标是成为一名独立调查员， 整合生物和行为概念和方法，促进家庭的健康和福祉 以及暴露在高度逆境中的年幼儿童。我之前的工作集中在行为途径上，通过 ACEs和PCEs可能会代代相传。到目前为止，我只接受了有限的研究培训 生物学的途径和方法。我有动力扩展我在评估免疫力方面的知识和技能 在K99阶段通过拟议的培训和研究进行生物标志物和干预研究。这 将为R00阶段奠定坚实的基础，并促进我向独立的过渡。在指导下 建立了保守的逆境转录反应基因组框架，R00阶段旨在 确定母亲的ACE和PCE如何与幼儿的免疫调节有关，这两项都表明 细胞(唾液CRP和SIgA)和转录(免疫细胞基因表达谱)生物标记物；这将 通过前瞻性地跟踪至少80名参加父母研究的12岁、24岁和 36个月。

Adverse childhood experiences (ACEs) such as childhood neglect, abuse, and exposure to violence, substance use, or mental health problems are estimated to be the root cause of 9 of the 10 leading causes of death in the US. High levels of ACEs can lead to long-term disruptions in immune function and genetic regulatory mechanisms. Sensitive parenting is essential for protecting infants and children from the impact of ACEs. Yet parenting can be particularly challenging when parents themselves have a history of ACEs, which can undermine their capacity to provide sensitive care. Nevertheless, many exposed to ACEs do not develop poor health outcomes or become less sensitive parents. Positive childhood experiences (PCEs) often co-occur with ACEs and can be an important source of resilience that buffers the deleterious effects of ACEs. However, the positive effects of PCEs and the biobehavioral mechanisms through which parents' ACEs and PCEs together shape child health remain poorly understood. The proposed K99/R00 study aims to elucidate the relationships among mothers' ACEs and PCEs, maternal sensitivity, and immune regulation in infants (3 months) and toddlers (12-36 months) of mothers who are living with opioid dependence, a high-risk group that often encounters a host of adversities. This study will build on an NICHD-funded randomized clinical trial (R01HD098525) that tests the efficacy of the Attachment and Biobehavioral Catch-up (ABC) intervention among mothers with opioid dependence and infants with perinatal opioid exposure. Assessment of child immune regulation is not currently included in the parent study. Leveraging the parent study's pre-intervention data, the K99 phase will investigate the associations between 100 mothers' ACEs and PCEs, maternal sensitivity, and their 3-month-old infants' immune regulation, indicated by salivary C-reactive protein (CRP) and secretory Immunoglobulin A (sIgA). My long-term career goal is to become an independent investigator who integrates biological and behavioral concepts and methods to promote the health and well-being of families and young children exposed to high levels of adversity. My prior work has focused on behavioral pathways by which ACEs and PCEs may transmit across generations. To date, I have had limited training in research using biological approaches and methods. I am motivated to expand my knowledge and skills in assessing immune biomarkers and intervention research through the proposed training and research during the K99 phase. This will build a strong foundation for the R00 phase and facilitate my transition to independence. Guided by the established Conserved Transcriptional Response to Adversity genomic framework, the R00 phase aims to determine how mothers' ACEs and PCEs are associated with toddlers' immune regulation as indicated by both cellular (salivary CRP and sIgA) and transcriptomic (immune cell gene expression profile) biomarkers; this will be accomplished by prospectively following at least 80 toddlers enrolled in the parent study at ages 12, 24, and 36 months.