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

儿童时期的逆境和精神障碍往往会在几代人之间重现， 精神障碍和不利处境的根深蒂固的循环。然而，这种传播时间段-父母的童年 影响下一代心理健康风险的经验-才刚刚开始研究， 基于人口的人类队列和传播机制尚未得到很好的理解。生命早期应激 可能会使个体对后来的压力生活事件做出次优反应。母亲自己的 因此，童年的逆境可能与怀孕前后对压力源的反应增强有关， 抚养孩子增加的担忧和相关的注意力控制不足可能会损害母亲的健康。 提供敏感的自我评估的能力，这是后代早期心理健康指标的关键预测因素。后生 标记物也可能是代际效应的信号，对于理解生物学意义可能很重要。 心理健康风险传播的各个方面，并为干预目标/措施提供信息。K 01奖 我将通过生物学方面的指导培训， 行为心理健康风险传递过程，包括母婴互动分析， 表观基因组DNA甲基化与围产期心理生物学（Monk）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），该提案包括课程，密集辅导和研究的协同计划。 利用2,491名波多黎各人的独特队列，在圣胡安和南布朗克斯纵向跟踪 由于参与者是2000年的儿童，NIH ECHO Boricua青年研究（5 UG 3 OD 023328 -02），以及 本研究的目的是，增加对产妇分娩行为观察的原始数据收集， 确定孕妇的童年逆境史（前瞻性测量）， 她们在怀孕期间对后代的担心，以及她们早期的母性敏感。利用 来自英国雅芳1,000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位点， 母亲与甲基化与他们的童年逆境，并确定甲基化是否在 已鉴定的基因位点也存在于它们的新生后代中。未来的R 01将建议进行测定和分析 来自ECHO-BYS的生物库DNA样本，比较了在更弱势群体中的表观遗传学发现， 人口和跟踪儿童心理健康结果。完成这些研究目标和伴随 培训将使我为基于人群的研究做好准备，在这些研究中，行为和表观遗传机制被 在Tandem中检查。这一研究职业轨迹使我成为一名研究人员， 方法，以人口为基础的心理健康工作与低资源社区在美国和周围的 这是NIMH在世界范围内开展的一项研究，为NIMH在弱势群体中开展心理健康预防研究的目标做出了贡献。

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.