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

Key Points

Question

Is racial discrimination associated with brain connectivity, and are alterations in deep brain functional connectivity associated with accelerated epigenetic aging?

Findings

In this cohort study of 90 Black women in the US, higher self-reported racial discrimination was associated with greater resting-state functional connectivity (RSFC) between the locus coeruleus (LC) and precuneus. Significant indirect effects were observed for the association between racial discrimination frequency and DNA methylation age acceleration.

Meaning

These findings suggest that racial discrimination is associated with greater connectivity in pathways involved with rumination, which may increase vulnerability to stress-related disorders and neurodegenerative disease via epigenetic age acceleration.

Abstract

This cohort study uses neuroimaging to examine the association of racial discrimination with alterations in resting-state functional connectivity and accelerated epigenetic aging among Black women in the US.

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; t ₈₅ = 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.