Doctoral Dissertation Research: Biosocial dynamics of intergenerational transmission of stress

博士论文研究：压力代际传递的生物社会动力学

• 批准号: 1918769
• 负责人: Marcia Inhorn
• 金额: $ 2.31万
• 依托单位: Yale University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1918769&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Research; Biosocial; dynamics

This doctoral research project examines how trauma experienced by women may be transmitted across generations, affecting their well-being and the well-being of their children. Working with populations who have endured high-stress environments, the investigators will conduct in-depth interviews with women when they are pregnant and subsequently measure markers of stress in those women and their infants, to understand how trauma affects women and children socially, emotionally, and biologically. Through these bio-ethnographic methods, the project will advance our understanding of epigenetic responses to the environment in humans. The project will also contribute to graduate training and mentoring and may inform public health research and behavioral health interventions. This project considers how biosocial inheritance, or the means by which social adversity or advantage is transmitted across generations, may play a role in intergenerational trauma. Specifically, this project considers (1) how women enduring adverse environments subjectively construct their traumatic experience; (2) whether maternal trauma may be "molecularized" at the level of the epigenome; (3) whether maternal traumatic experience is associated with neuroendocrine stress during pregnancy; and (4) whether maternal epigenetic or neuroendocrine signals correspond to those seen in offspring in early life. In this study of 112 mother-infant dyads, mothers' subjective appraisals of trauma will be elicited through semi-structured and life history interviews, which will be used to contextualize their responses to a survey of traumatic exposure and a trauma symptoms checklist. Their biological incorporation of trauma will be assessed with measures of DNA methylation and hair cortisol concentration. Methylation will be measured at five genes that are involved in the neuroendocrine stress response: NR3C1, FKBP5, BDNF, SLC6A4, and MAOA. To evaluate for broader patterns of epigenetic modification, epigenome-wide methylation analyses will also be conducted. To investigate the potential for intergenerational programming, this project will measure chronic cortisol secretion in mothers, cortisol reactivity following a modest stressor in infants at eight weeks of age, and DNA methylation at these five stress-related loci in both mothers and infants.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该博士研究项目研究了妇女经历的创伤如何在几代人之间传播，从而影响了她们的幸福和子女的幸福。调查人员与经历了高压力环境的人群合作，将在怀孕时对妇女进行深入的访谈，并随后衡量这些妇女及其婴儿的压力标记，以了解创伤如何在社交，情感和生物学上对妇女和儿童产生影响。通过这些生物以上的方法，该项目将提高我们对人类对环境的表观遗传反应的理解。该项目还将有助于研究生培训和指导，并可能为公共卫生研究和行为健康干预提供信息。该项目考虑了生物社会的继承或在各个一代传播社会逆境或优势的手段，可能在代际创伤中发挥作用。具体而言，该项目考虑（1）妇女如何忍受不利的环境主观建立创伤经验； （2）在表观基因组水平上，母体创伤是否可能被“分子化”； （3）孕产妇创伤经历是否与怀孕期间的神经内分泌压力有关； （4）孕产妇表观遗传学或神经内分泌信号是否与早期后代所见的信号相对应。在这项对112个母亲二元组的研究中，将通过半结构化和生活史访谈来引起母亲对创伤的主观评估，这将被用来将其对对创伤性暴露和创伤症状检查的调查的反应进行情境化。他们的创伤的生物掺入将通过DNA甲基化和毛皮质醇浓度的量度进行评估。甲基化将以涉及神经内分泌应激反应的五个基因进行测量：NR3C1，FKBP5，BDNF，SLC6A4和MAOA。为了评估表观遗传修饰的更广泛的模式，还将进行全依代组甲基化分析。为了调查代际编程的潜力，该项目将测量母亲的慢性皮质醇分泌，八周龄的婴儿中适度的压力源后皮质醇反应性，以及在这五个压力相关的母亲和婴儿中的DNA甲基化，这是NSF的法定任务和审查的范围。