Summary: Chronic neighborhood stress alters gene activity in immune cells among low-income Black mothers living in areas with high violence and poverty.
Source: University of Chicago
New research shows that the prolonged stress of living in neighborhoods marked by high violence and concentrated poverty changes gene activity in immune cells of low-income, single Black mothers on Chicago’s South Side.
The study found that long-term exposure to threatening environments is linked to a pattern of gene expression consistent with a “hunker-down” physiological response. Rather than activating a classic immediate fight-or-flight reaction, the body appears to shift toward conserving resources and withdrawing—a strategy that may help short-term survival but can carry long-term health costs.
Researchers from the University of Illinois Urbana-Champaign, in collaboration with colleagues at the University of Kentucky and UCLA, report these findings in the journal Psychoneuroendocrinology. Their work highlights how chronic social stressors such as neighborhood violence, economic hardship, and racism can become biologically embedded and influence immune system function.
“We wanted to understand how stress gets under the skin and affects health,” said study leader Ruby Mendenhall, professor of African American studies and sociology at the University of Illinois and assistant dean for diversity and democratization of health innovation at the Carle Illinois College of Medicine. “Listening to the experiences of low-income single Black mothers on the South Side of Chicago helped us connect lived neighborhood stress with measurable changes in gene activity.”
The research team enrolled 68 women from neighborhoods with high reported violence. Participants shared personal stories, completed standardized stress assessments, and provided blood samples. The investigators combined self-reported experiences with administrative police records to measure neighborhood violence and other stressors tied to structural inequality.
Scientists analyzed gene expression in leukocytes (white blood cells) drawn from participants’ blood. Leukocytes are central to immune defense and respond to stress hormones, so patterns of gene activity in these cells can reveal how chronic stress affects health at a molecular level.
When the team examined genes linked to the sympathetic nervous system’s fight-or-flight response, they found no significant differences between women who perceived their neighborhoods as dangerous and those who did not. Instead, greater perceived neighborhood danger correlated with higher activity of genes regulated by the glucocorticoid receptor (GR), a key component of the hypothalamic-pituitary-adrenal (HPA) axis stress response.
“The glucocorticoid-regulated gene signature is consistent with a defeat-withdrawal or hunker-down phenotype observed in severe, chronic threat situations,” said co-author Steve Cole, a professor at UCLA. “This response conserves energy and avoids immediate confrontation, but over time it may reduce the body’s capacity to perform routine maintenance tasks that support long-term health.”
Co-author Clare Rittschof, formerly a postdoctoral researcher with the study team and now a professor at the University of Kentucky, emphasized the health implications: “Increased glucocorticoid activity is often associated with aging processes. The patterns we observed resemble accelerated aging, which may help explain why chronic stress contributes to poorer health outcomes in marginalized communities.”
Transcript origin analyses pointed to monocytes and dendritic cells as the primary sources of the up-regulated transcripts linked to neighborhood stress. The observed pattern—prominent GR-related activity with an absence of sympathetic nervous system-related transcripts—suggests a sustained HPA-axis response rather than an acute fight-or-flight reaction.
The researchers plan to continue this work by studying cultural coping strategies used by Black women in high-stress neighborhoods and by developing training for health care providers, social service professionals, and policymakers. Their goal is to identify practical approaches that reduce stress, improve health outcomes, and narrow disparities—while advocating for broad policies to address structural racism as a fundamental source of stress.
“Addressing these biological effects requires both community-level interventions and systemic policy changes aimed at eliminating structural racism,” the authors said in a joint statement. The findings align with a growing recognition across medical schools and health institutions that racism is a public health crisis.
Other contributors to the paper include Illinois graduate student Meggan Lee; Illinois professors Andrew Greenlee and Sandra Rodriguez-Zas; and Vanderbilt University professor Kedir Turi. Funding came from the University of Illinois Urbana-Champaign, the Richard and Margaret Romano Professorial Scholarship, and the USC/UCLA Center on Biodemography and Population Health.
About this genetics research news
Source: University of Illinois
Contact: Liz Ahlberg Touchstone – University of Illinois
Image: The image is in the public domain
Original Research: Closed access. “Transcriptomic analyses of black women in neighborhoods with high levels of violence” by Ruby Mendenhall et al., published in Psychoneuroendocrinology. DOI: 10.1016/j.psyneuen.2021.105174
Abstract
Transcriptomic analyses of Black women in neighborhoods with high levels of violence
Chronic stress undermines an individual’s ability to maintain psychological and physiological balance, but the molecular mechanisms that embed these social experiences in the body remain incompletely understood. This gap is especially important for marginalized groups and complicates efforts to reduce racial, economic, and gender health disparities. Physical and social environments influence genome function, including the transcriptional activity of genes that respond to stress.
This study examined relationships between social experiences associated with systemic inequality—such as racial segregation, poverty, and neighborhood violence—and gene expression in blood leukocytes. Focusing on transcription factors central to stress response pathways, the analysis used data collected in 2013 from a convenience sample of 68 single, low-income Black mothers living on the South Side of Chicago.
Comparing women in high-violence neighborhoods (measured by self-report and police records) with those in lower-violence areas, the researchers found no significant differences in expression of 51 genes linked to the Conserved Transcriptional Response to Adversity (CTRA). However, promoter analysis revealed that women reporting higher neighborhood stress exhibited greater expression of genes regulated by the glucocorticoid receptor (GR).
These GR-related patterns could reflect higher cortisol output from the HPA axis or increased GR transcriptional sensitivity. Monocytes and dendritic cells emerged as primary sources of the up-regulated transcripts associated with neighborhood stress. The prominence of GR-related transcripts, together with the absence of sympathetic nervous system-related CTRA transcripts, suggests a defeat-withdrawal phenotype—previously documented in animal models of overwhelming threat—rather than a fight-or-flight phenotype.
The findings underscore the importance of studying biological embedding in diverse communities, particularly marginalized populations such as low-income Black women, to better understand and address health inequities.