Department of Sociology, University of Illinois, Urbana-Champaign, 702 South Wright St, Champaign, IL 61820, USA.
Department of Entomology, University of Kentucky, S-225 Agricultural Science Center North, Lexington, KY 40546, USA.
Psychoneuroendocrinology. 2021 May;127:105174. doi: 10.1016/j.psyneuen.2021.105174. Epub 2021 Feb 16.
Chronic stress threatens an individual's capacity to maintain psychological and physiological homeostasis, but the molecular processes underlying the biological embedding of these experiences are not well understood. This is particularly true for marginalized groups, presenting a fundamental challenge to decreasing racial, economic, and gender-based health disparities. Physical and social environments influence genome function, including the transcriptional activity of core stress responsive genes. We studied the relationship between social experiences that are associated with systemic inequality (e.g., racial segregation, poverty, and neighborhood violence) and blood cell (leukocytes) gene expression, focusing on the activation of transcription factors (TF) critical to stress response pathways. The study used data from 68 women collected from a convenience sample in 2013 from the Southside of Chicago. Comparing single, low-income Black mothers living in neighborhoods with high levels of violence (self-reported and assessed using administrative police records) to those with low levels of violence we found no significant differences in expression of 51 genes associated with the Conserved Transcriptional Response to Adversity (CTRA). Using TELiS analysis of promoter TF-binding motif prevalence we found that mothers who self-reported higher levels of neighborhood stress showed greater expression of genes regulated by the glucocorticoid receptor (GR). These findings may reflect increased cortisol output from the hypothalamic-pituitary-adrenal (HPA) axis, or increased GR transcriptional sensitivity. Transcript origin analyses identified monocytes and dendritic cells as the primary cellular sources of gene transcripts up-regulated in association with neighborhood stress. The prominence of GR-related transcripts and the absence of sympathetic nervous system-related CTRA transcripts suggest that a subjective perception of elevated chronic neighborhood stress may be associated with an HPA-related defeat-withdrawal phenotype rather than a fight-or-flight phenotype. The defeat-withdrawal phenotype has been previously observed in animal models of severe, overwhelming threat. These results demonstrate the importance of studying biological embedding in diverse environments and communities, specifically marginalized populations such as low-income Black women.
慢性压力威胁着个体维持心理和生理平衡的能力，但这些经历的生物学基础的分子过程还不是很清楚。对于边缘化群体来说尤其如此，这对减少种族、经济和性别健康差距构成了根本性挑战。物理和社会环境会影响基因组功能，包括核心应激反应基因的转录活性。我们研究了与系统性不平等相关的社会经历（例如，种族隔离、贫困和邻里暴力）与血细胞（白细胞）基因表达之间的关系，重点关注对应激反应途径至关重要的转录因子（TF）的激活。该研究使用了 2013 年从芝加哥南部随机抽样的 68 名女性的数据。我们比较了居住在暴力程度较高（通过行政警察记录自我报告和评估）和较低社区的单身、低收入黑人母亲，发现与逆境保守转录反应（CTRA）相关的 51 个基因的表达没有显著差异。使用启动子 TF 结合基序出现频率的 TELiS 分析，我们发现自我报告社区压力水平较高的母亲表现出受糖皮质激素受体（GR）调节的基因表达增加。这些发现可能反映了下丘脑-垂体-肾上腺（HPA）轴的皮质醇输出增加，或者 GR 转录敏感性增加。转录本起源分析确定单核细胞和树突状细胞是与邻里压力相关的基因转录上调的主要细胞来源。GR 相关转录本的突出性和交感神经系统相关 CTRA 转录本的缺失表明，对慢性邻里压力升高的主观感知可能与 HPA 相关的失败-撤退表型相关，而不是战斗或逃跑表型相关。在严重、压倒性威胁的动物模型中已经观察到了失败-撤退表型。这些结果表明，在不同的环境和社区中，特别是在低收入黑人妇女等边缘化群体中，研究生物嵌入的重要性。
