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. 2024 Jun 3;7(6):e2416588.
doi: 10.1001/jamanetworkopen.2024.16588.

Racial Discrimination, Neural Connectivity, and Epigenetic Aging Among Black Women

Aziz Elbasheir  1 , Seyma Katrinli  1 , Breanne E Kearney  2   3 , Ruth A Lanius  2 , Nathaniel G Harnett  4   5 , Sierra E Carter  6 , Timothy D Ely  1 , Bekh Bradley  1   7 , Charles F Gillespie  1 , Jennifer S Stevens  1 , Adriana Lori  1 , Sanne J H van Rooij  1 , Abigail Powers  1 , Tanja Jovanovic  8 , Alicia K Smith  1   9 , Negar Fani  1
Affiliations

Racial Discrimination, Neural Connectivity, and Epigenetic Aging Among Black Women

Aziz Elbasheir et al. JAMA Netw Open. .

Abstract

Importance: Racial discrimination increases the risk of adverse brain health outcomes, potentially via neuroplastic changes in emotion processing networks. The involvement of deep brain regions (brainstem and midbrain) in these responses is unknown. Potential associations of racial discrimination with alterations in deep brain functional connectivity and accelerated epigenetic aging, a process that substantially increases vulnerability to health problems, are also unknown.

Objective: To examine associations of racial discrimination with brainstem and midbrain resting-state functional connectivity (RSFC) and DNA methylation age acceleration (DMAA) among Black women in the US.

Design, setting, and participants: This cohort study was conducted between January 1, 2012, and February 28, 2015, and included a community-based sample of Black women (aged ≥18 years) recruited as part of the Grady Trauma Project. Self-reported racial discrimination was examined in association with seed-to-voxel brain connectivity, including the locus coeruleus (LC), periaqueductal gray (PAG), and superior colliculus (SC); an index of DMAA (Horvath clock) was also evaluated. Posttraumatic stress disorder (PTSD), trauma exposure, and age were used as covariates in statistical models to isolate racial discrimination-related variance. Data analysis was conducted between January 10 and October 30, 2023.

Exposure: Varying levels of racial discrimination exposure, other trauma exposure, and posttraumatic stress disorder (PTSD).

Main outcomes and measures: Racial discrimination frequency was assessed with the Experiences of Discrimination Scale, other trauma exposure was evaluated with the Traumatic Events Inventory, and current PTSD was evaluated with the PTSD Symptom Scale. Seed-to-voxel functional connectivity analyses were conducted with LC, PAG, and SC seeds. To assess DMAA, the Methylation EPIC BeadChip assay (Illumina) was conducted with whole-blood samples from a subset of 49 participants.

Results: This study included 90 Black women, with a mean (SD) age of 38.5 (11.3) years. Greater racial discrimination was associated with greater left LC RSFC to the bilateral precuneus (a region within the default mode network implicated in rumination and reliving of past events; cluster size k = 228; t85 = 4.78; P < .001, false discovery rate-corrected). Significant indirect effects were observed for the left LC-precuneus RSFC on the association between racial discrimination and DMAA (β [SE] = 0.45 [0.16]; 95% CI, 0.12-0.77).

Conclusions and relevance: In this study, more frequent racial discrimination was associated with proportionately greater RSFC of the LC to the precuneus, and these connectivity alterations were associated with DMAA. These findings suggest that racial discrimination contributes to accelerated biological aging via altered connectivity between the LC and default mode network, increasing vulnerability for brain health problems.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Harnett reported receiving grants from the National Institute of Mental Health (NIMH) and the Brain and Behavior Research Foundation outside the submitted work. Dr Jovanovic reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study and outside the submitted work. Dr Fani reported receiving grants from the NIH during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Association of Racial Discrimination With Brainstem Resting-State Functional Connectivity (RSFC) and Horvath DNA Methylation Age Acceleration (DMAA)
A, Brainstem and midbrain seed regions for connectivity analyses: locus coeruleus (LC; blue), periaqueductal gray (orange), and superior colliculus (green). B, Frequency of racial discrimination is associated with greater RSFC between the LC (blue) and bilateral precuneus (red; Montreal Neurological Institute coordinates: x = −4, y = −60, and z = 24). C, Greater RSFC between the LC and bilateral precuneus is positively associated with Horvath DMAA (r = .30; P = .04). Each dot represents data from 1 participant. The shaded area represents the 95% CI, and the diagonal line represents the regression line.
Figure 2.
Figure 2.. Association of Racial Discrimination With Horvath DNA Methylation Age Acceleration (DMAA) Through Left Locus Coeruleus (LC)-Precuneus Resting-State Functional Connectivity (RSFC)
Significant indirect effects were observed (β [SE] = 0.45 [0.16]; 95% CI, 0.12-0.77). aP < .05. bP = .007.
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