Mothers' childhoods and the intergenerational transmission of mental health risk in the context of adversity

童年的逆境和精神障碍往往会在几代人之间重演，导致 精神障碍和劣势的根深蒂固的循环。然而，这一传播时间框架-父母的童年 影响下一代心理健康风险的经历--才刚刚开始在 以人口为基础的人类队列和传播机制尚未得到很好的了解。早期生活压力 可能会让个人对后来的应激生活事件做出次优反应。母亲们自己的 因此，儿童时期的逆境可能与怀孕前后对应激源的高度反应有关 养育孩子。更多的担忧和相关的注意力控制缺陷可能会损害母亲的 提供敏感照料的能力，这是子女早期心理健康指标的关键预测指标。表观遗传 标记也可以发出代际效应的信号，并可能对理解生物学上的 精神健康风险传递的各个方面，并告知干预目标/措施。本K01大奖 将通过生物-心理健康指导培训来扩展我在基于人口的心理健康研究方面的专业知识 行为心理健康风险传递过程，包括分析母婴相互作用和 表观基因组DNA甲基化。与围产期心理生物学(Monk)的专家指导团队合作， 弱势群体心理健康(Duarte)、表观遗传学(Baccarelli)和儿童早期发展 (Hane)，这项建议包括一个课程作业、密集指导和研究的协同计划。 利用2491名波多黎各人的独特队列，纵向上紧随圣胡安和南布朗克斯 由于参与者是2000年的儿童，NIH ECHO Boricua青年研究(5UG3OD023328-02)，以及 添加母亲照料行为观察的原始数据收集，拟议的研究旨在 确定孕妇童年逆境史(前瞻性测量)与 她们在怀孕期间担心自己的后代，以及她们早期对母亲的照顾敏感。利用一种 英国雅芳地区1000对母婴的全基因组DNA甲基化数据集 父母和孩子的纵向研究，拟议的研究还旨在确定特定的基因座在 甲基化与她们童年的逆境有关的母亲，并确定甲基化是否在 在它们新生的后代中也存在已识别的基因位点。未来的R01将建议进行测试和分析 来自ECHO-BY的生物库DNA样本，比较更弱势群体的表观遗传学发现 人口，并跟踪儿童心理健康结果。完成这些研究目标并伴随着 培训将使我为基于群体的研究做好准备，在这些研究中，行为和表观遗传机制是 同时接受检查。这一研究职业轨迹使我作为一名研究员脱颖而出，为 在美国和世界各地以人口为基础的精神卫生工作与低资源社区的方法 促进了NIMH在弱势人群中进行心理健康预防研究的目标。

Both childhood adversities and mental disorders tend to be reproduced across generations, resulting in entrenched cycles of mental disorders and disadvantage. Yet this transmission timeframe— parental childhood experiences influencing mental health risk in the next generation— is only beginning to be studied in population-based human cohorts, and transmission mechanisms are not yet well understood. Early-life stress may set individuals on trajectories of suboptimal responses to later stressful life events. Mothers' own childhood adversity may therefore be associated with heightened reactions to stressors around pregnancy and childrearing. Increased worry and associated deficiency in attentional control could compromise mothers' ability to provide sensitive caregiving, a key predictor of early mental health indicators in offspring. Epigenetic markers could also signal intergenerational effects and may be important for understanding the biological aspects of mental health risk transmission and for informing intervention targets/measures. This K01 Award would extend my expertise in population-based mental health research through mentored training on bio- behavioral mental health risk transmission processes, including analysis of maternal-child interaction and epigenome-wide DNA methylation. Working with an expert mentorship team in perinatal psychobiology (Monk), vulnerable population mental health (Duarte), epigenetics (Baccarelli), and early childhood development (Hane), this proposal includes a synergistic program of coursework, intensive mentoring, and research. Leveraging a unique cohort of 2,491 Puerto Ricans followed longitudinally in San Juan and the South Bronx since the participants were children in 2000, the NIH ECHO Boricua Youth Study (5UG3OD023328-02), and adding original data collection of maternal caregiving behavior observations, the proposed research aims to determine the association between pregnant women's history of childhood adversity (measured prospectively), their worry during pregnancy about their offspring, and their early maternal caregiving sensitivity. Utilizing a dataset of genome-wide DNA methylation from 1,000 mother-infant dyads in the United Kingdom's Avon Longitudinal Study of Parents and Children, the proposed research also aims to identify specific gene loci in mothers with methylation associated with their childhood adversity, and to determine whether methylation in identified gene loci is also present in their newborn offspring. A future R01 will propose to assay and analyze biobanked DNA samples from ECHO-BYS, comparing the epigenetic findings in a more disadvantaged population, and tracking child mental health outcomes. Completion of these research aims and accompanying training will prepare me for population-based studies in which behavioral and epigenetic mechanisms are examined in tandem. This research career trajectory sets me apart as a researcher bringing translational approaches to population-based mental health work with low-resourced communities in the US and around the world, contributing to the NIMH's goal of mental health prevention research in vulnerable populations.