A BIOCULTURAL APPROACH TO UNDERSTANDING HOW PSYCHOSOCIAL STRESS BECOMES BIOLOGICALLY EMBEDDED IN HEALTH

Chu J. Hsiao
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Abstract

Stressful psychosocial experiences can substantially affect health and well -being, a process of biological embedding in which bodies literally incorporate the world we inhabit. This dissertation explored how disruptive social forces, such as racism and war, may leave detectable marks in measurable health metrics, such as blood pressure and newborn birthweight, through molecular mechanisms such as genetic variation and gene expression. Genetic variation plays a role in the human response to stressful situations, such as unfair treatment. In Chapter 2, I explored how lifetime experiences of unfair treatment interacted with specific genetic markers to impact blood pressure. Utilizing participants from the Jackson Heart Study (n = 2,393), a cohort study of African Americans in the southeastern United States, I observed a significant gene by unfair treatment interaction effect on systolic blood pressure. I then investigated the intergenerational effects of four stressful maternal exposures (chronic stress, war trauma, sexual violence, and general trauma) on the transcriptome and newborn birthweight. Utilizing samples from participants in the eastern Democratic Republic of Congo (n = 93), I found that maternal stress does not impact gene expression at the level of individual genes, but may impact global gene expression. Specifically, global placental gene expression may mediate part of the negative impact of war trauma on newborn birthweight (Chapter 3). To better understand mothers’ experiences, I used an unsupervised machine learning clustering method to identify clusters of maternal stress experiences. Birthweights were significantly different in the clusters, suggesting the impact of social experiences cannot be captured by just one measure of maternal stress but by a more holistic understanding of mothers’ lived experiences. I then used a supervised classification method to test how well maternal stress and global gene expression predicted newborns’ birthweight quartile and percentile (Chapter 4). My dissertation highlights the complexities associated with the human experience and demonstrates the utility of taking a biocultural approach to study the process of biological embedding. Future studies should strive to contextualize participants’ lives when studying the pathogenesis of complex diseases, particularly diseases with health inequities.
用生物文化的方法来理解心理社会压力如何在生物学上嵌入健康
压力的社会心理体验会严重影响健康和幸福,这是一个生物嵌入的过程,在这个过程中,身体实际上融入了我们所居住的世界。本论文探讨了破坏性的社会力量,如种族主义和战争,如何通过遗传变异和基因表达等分子机制,在可测量的健康指标(如血压和新生儿出生体重)中留下可检测的痕迹。基因变异在人类对压力情况(如不公平待遇)的反应中起着重要作用。在第二章中,我探讨了不公平待遇的一生经历如何与特定的遗传标记相互作用,从而影响血压。利用Jackson心脏研究的参与者(n = 2393),一项针对美国东南部非裔美国人的队列研究,我观察到不公平治疗对收缩压的显著基因相互作用。然后,我调查了四种压力母亲暴露(慢性压力,战争创伤,性暴力和一般创伤)对转录组和新生儿出生体重的代际影响。利用来自刚果民主共和国东部参与者的样本(n = 93),我发现母亲压力不会影响个体基因水平的基因表达,但可能会影响整体基因表达。具体而言,全球胎盘基因表达可能介导战争创伤对新生儿出生体重的部分负面影响(第3章)。为了更好地理解母亲的经历,我使用了一种无监督机器学习聚类方法来识别母亲压力经历的聚类。这表明,社会经历的影响不能仅仅通过对母亲压力的一种衡量来衡量,而是要通过对母亲生活经历的更全面的理解来衡量。然后,我使用了一种监督分类方法来测试母亲压力和全球基因表达对新生儿出生体重四分位数和百分位数的预测效果(第4章)。我的论文强调了与人类经验相关的复杂性,并展示了采用生物培养方法研究生物嵌入过程的实用性。在研究复杂疾病的发病机制时,未来的研究应努力将参与者的生活置于背景中,特别是具有卫生不平等的疾病。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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