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

不良童年经历（ACE），如童年忽视，虐待和暴露于暴力， 物质使用或心理健康问题估计是10个主要原因中的9个的根本原因。 死在美国。高水平的ACE可导致免疫功能和遗传功能的长期破坏。 监管机制。敏感的养育对于保护婴儿和儿童免受 ACE。然而，当父母自己有ACE病史时，养育子女可能特别具有挑战性， 可能会削弱他们提供敏感护理的能力。然而，许多接触ACE的人并没有发展 健康状况不佳或父母变得不那么敏感。积极的童年经历（PCE）通常同时发生 与ACE的，可以是一个重要的来源的弹性，缓冲有害影响的ACE。然而，在这方面， PCE的积极作用以及父母的ACE和PCE的生物行为机制 对儿童健康的共同影响仍然知之甚少。建议的K99/R 00研究旨在阐明 母亲ACE和PCE、母亲敏感性和婴儿免疫调节之间的关系（3 月）和幼儿（12-36个月）的母亲谁是生活与阿片类药物依赖，一个高风险群体， 经常会遇到很多逆境。这项研究将建立在NICHD资助的随机临床试验的基础上 （R 01 HD 098525），测试依恋和生物行为追赶（ABC）干预的有效性 阿片类药物依赖的母亲和围产期阿片类药物暴露的婴儿。儿童评估 免疫调节目前未包括在母研究中。利用母研究的干预前 数据，K99阶段将调查100名母亲的ACE和PCE之间的关联， 敏感性以及3个月大婴儿的免疫调节，由唾液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， 结合生物和行为的概念和方法，以促进家庭的健康和福祉 以及暴露在高水平逆境中的幼儿。我之前的工作主要集中在行为途径上， ACE和PCE可以跨代传输哪些。到目前为止，我只接受过有限的研究培训， 生物学方法和手段。我有动力扩展我在评估免疫方面的知识和技能， 在K99阶段通过拟议的培训和研究开展生物标志物和干预研究。这 将为R 00阶段奠定坚实的基础，并促进我向独立过渡。为指导 建立了逆境保守转录反应基因组框架，R 00阶段的目标是 确定母亲的ACE和PCE如何与幼儿的免疫调节相关， 细胞（唾液CRP和sIgA）和转录组（免疫细胞基因表达谱）生物标志物;这将 通过前瞻性随访至少80名12岁、24岁和24岁时参加父母研究的幼儿来实现。 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.