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.

这个博士研究项目探讨了妇女所经历的创伤如何跨代传播，影响她们的福祉和子女的福祉。研究人员将与经历过高压力环境的人群一起工作，对怀孕的妇女进行深入访谈，随后测量这些妇女及其婴儿的压力标志物，以了解创伤如何影响妇女和儿童的社会，情感和生物学。通过这些生物人种学方法，该项目将促进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。这个项目考虑了生物社会遗传，或社会逆境或优势跨代传递的方式，可能在代际创伤中发挥作用。具体而言，该项目考虑（1）女性如何忍受不利环境主观地构建其创伤经历;（2）母体创伤是否可能在表观基因组水平上“分子化”;（3）母体创伤经历是否与妊娠期间的神经内分泌应激相关;以及（4）母体表观遗传或神经内分泌信号是否与早期生活中在后代中看到的信号相对应。在这项研究中，112个母婴二人组，母亲的主观评价的创伤将引起通过半结构化和生活史访谈，这将被用来情境化的创伤暴露和创伤症状检查表的调查，他们的反应。他们的创伤的生物整合将通过DNA甲基化和头发皮质醇浓度的测量来评估。将在参与神经内分泌应激反应的五个基因处测量甲基化：NR 3C 1、FKBP 5、BDNF、SLC 6A 4和MAOA。为了评估表观遗传修饰的更广泛模式，还将进行表观基因组范围的甲基化分析。为了调查代际规划的潜力，该项目将测量母亲的慢性皮质醇分泌，8周龄婴儿在适度压力刺激后的皮质醇反应，和DNA甲基化的影响该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查进行评估，被认为值得支持的搜索.