Two facts have emerged from research over the last two decades about racial discrimination in the United States.  A plethora of research papers across disciplines have documented the fact that Black people in the U.S. experience race-related stressors, “including systemic injustices and racial discrimination, on a regular basis,” in the words of a research team that has just published a study about the impacts of such discrimination on the brain.

“Repeated exposure to racial discrimination,” continues the team, which includes 6 recipients of BBRF grants, “has been associated with a greater incidence of brain health disorders,” including major depressive disorder, anxiety disorders, and PTSD. Associations with various kinds of cognitive impairment and neurodegenerative processes have also been suggested.

But how, exactly, does the experience of repeated discrimination alter human biology, including the biology of the brain? Studies to date have suggested that discrimination exerts its effects at least in part “via activation of stress-sensitive regulatory systems” which mediate stress in the brain and body.

Between 2012 and 2015, the team, led by Negar Fani, Ph.D., of the Emory University School of Medicine, studied a cohort of Black women between ages 18 and 62, who were recruited from the greater Atlanta community as part of the Grady Trauma Project, which investigates risk and resilience for trauma-related disorders in a largely Black population. Senior members of the team included Tanja Jovanovic, Ph.D., a 2015 BBRF Independent Investigator and 2010 Young Investigator; and Adriana Lori, Ph.D., a 2013 BBRF Young Investigator.

The team’s first report of results has now appeared in the online journal JAMA Network Open, and includes analysis of 90 Black women who were, on average, in their late 30s. The women were asked to complete a questionnaire (“Experiences of Discrimination”) about the type and frequency of exposures to discrimination over their lifetimes, and received functional MRI brain scans. Blood samples collected from the women were also analyzed. 72% of the women were high school graduates or had some college or technical school education; 83% had annual incomes less than $24,000.

The study provides evidence about how racial discrimination alters connectivity in the brain, which may, in turn, be linked with cells of the brain aging more rapidly than they otherwise would. These impacts, in turn, may increase the likelihood that those discriminated against will develop brain health problems.

Observing and analyzing structures and function in the deep brain and midbrain were at the focus of the team’s study. They looked in particular at several areas near the top of the brainstem: the locus coeruleus (LC), which plays a central role in orchestrating adaptive responses to threat; the periaqueductal grey (PAG), which facilitates coordination of cardiovascular, respiratory, and motor responses associated with emotional arousal; and the superior colliculus (SC), implicated in visual detection of threatening stimuli and coordination of defensive behaviors, including “fight or flight,” freezing, and emotional shut-down responses.

The working hypothesis was that racial discrimination can lead to greater regulation of emotional responses to racism-related threats and greater vigilance for future threats. “Over time, effort expended from these processes may contribute to the deterioration of body regulatory systems,” although in ways yet to be determined.

Results indicated that greater frequency of racial discrimination in one’s lifetime was associated with higher levels of resting-state functional connectivity between the locus coeruleus and a brain area called the precuneus. Resting-state connectivity registers brain activity when the mind is not focused on any particular task—a kind of default mode. Above-average activity in this circuit between the LC and the precuneus is significant because it is directly associated with rumination and internalization of emotion. A tendency of victims of frequent racial discrimination to mull over or relive past painful, traumatic, or angering events is a plausible contributory factor to increased vulnerability in the same individuals to stress-related disorders.

But there was also evidence of possible linkage with cognitive dysfunction and neurodegenerative disease. The team’s analysis of participants’ blood samples enabled them to perform empirical estimates of the rate of cellular aging in each individual. (This was possible via analysis of epigenetic patterns in the cells—chemical “tags” on DNA that affect gene expression and can be modified by adverse experience.) Regarding the elevated connectivity in the LC-precuneus network that they found in brain scans, the researchers said that “these connectivity patterns [in turn] are linked to greater cellular aging, possibly including brain aging, in Black individuals, amplifying the risk of brain health disparities.” These results are preliminary and only suggestive, as the cells sampled were not specifically brain cells.

The study begins to provide an empirical basis for determining exactly how an adverse experience such as repeated racial discrimination can harm people over time and affect their brain and stress-response systems. But the design of the study, the team stresses, makes it impossible to assume causal relationships among the various elements discussed—changes in brain functional connectivity and accelerated cellular aging. Rather, it indicates associations between these elements.

The team suggested that future research needs to go beyond self-reported discriminatory experiences to look at how people respond to such experiences, and to examine psychological responses directly, not after the fact. “Future studies with real-time assessment of racial discrimination are warranted” in part to control for imperfections in recalled memoires. Direct analysis of brain cells is needed in cellular aging analyses. Also, the fact that epigenetic changes are brought about by a wide range of potential environmental experiences must be factored into the analysis, they say. Finally, larger cohorts of participants need to be recruited for future studies, the team noted.

The team also included: Alicia K. Smith, Ph.D., 2012 BBRF Young Investigator; Sanne J. H. van Rooij, Ph.D., 2021 and 2018 BBRF Young Investigator; Charles F. Gillespie, M.D., Ph.D., 2007 BBRF Young Investigator; and Nathaniel G. Harnett, Ph.D., 2021 BBRF Young Investigator.