Doctoral Dissertation Research: Biosocial dynamics of intergenerational transmission of stress

这一博士研究项目考察了女性经历的创伤如何代代相传，影响她们的福祉及其子女的福祉。与忍受高压力环境的人群合作，调查人员将对怀孕期间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，以了解创伤如何在社会、情感和生物上影响妇女和儿童。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，或社会逆境或优势代代相传的方式，如何在代际创伤中发挥作用。具体地说，这个项目考虑了(1)承受不利环境的妇女如何主观地构建她们的创伤经历；(2)母亲创伤是否可以在表观基因组水平上被“分子化”；(3)母亲的创伤经历是否与怀孕期间的神经内分泌应激有关；以及(4)母亲的表观遗传或神经内分泌信号是否与早期生命中的后代的信号相对应。在这项对112名母婴的研究中，母亲对创伤的主观评价将通过半结构访谈和生活史访谈来获得，这些访谈将被用来结合她们对创伤暴露调查和创伤症状清单的反应。他们对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上进行甲基化检测：NR3C1、FKBP5、BDNF、SLC6A4和MAOA。为了评估更广泛的表观遗传修饰模式，还将进行表观基因组范围的甲基化分析。为了调查代际编程的可能性，该项目将测量母亲的慢性皮质醇分泌，8周大的婴儿在适度应激源下的皮质醇反应性，以及母亲和婴儿这五个与应激相关的基因座的DNA甲基化。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.