Associations Between Racial Discrimination, Neural Network Alterations, and Health Open Access
Elbasheir, Aziz (Spring 2026)
Abstract
Racial discrimination (RD) is a chronic stressor linked to health disparities in Black individuals. Prior research has linked RD to dysregulation in physiological stress response systems and health disparities. However, less is known about the links between RD and brain network alterations, particularly networks involved with emotion regulation, and health biomarkers. I used a multimodal, translational neuroscience approach to examine these relationships in a population of trauma-exposed Black women. The first study investigated links between RD and a marker of systemic inflammation, C-reactive protein (CRP), and the potential moderating role of inflammation between RD and threat network reactivity. Findings revealed that CRP moderated the relationship between RD and activation in the ventromedial prefrontal cortex. The second study examined associations between RD and resting-state connectivity of brainstem regions that orchestrate threat response: the locus coeruleus, periaqueductal gray and superior colliculus, and associations of RD-related connectivity with a marker of accelerated biological aging, DNA-methylation age acceleration. Greater RD exposure was associated with increased connectivity between the locus coeruleus, the main noradrenergic input across the neuroaxis, and the precuneus, a region of the default mode network, and this pattern of connectivity mediated the relationship between RD and accelerated epigenetic aging. These findings provide evidence that through changes in the threat circuitry, RD may induce whole-body cellular changes associated with elevated risk for health vulnerabilities. The next two studies investigated whether RD-related neuroplastic changes in threat and emotion regulation circuits are related to clinical outcomes. One study showed that RD was associated with lesser insula-medial prefrontal cortex connectivity during processing of threat cues, and this, in turn associated with greater symptoms of derealization, a manifestation of dissociation. The second study demonstrated that structural deterioration of white matter tracts connecting emotion regulation areas (genu of corpus callosum and anterior cingulum) mediated the relationship between RD and poorer physical health outcomes. Together, this thesis provides further evidence that RD exerts its effects on health not only through peripheral stress response dysregulation but through neuroplastic alterations in brain networks that regulate those systems. These neuroplastic changes in turn contribute to accelerated biological aging and poor health outcomes.
Table of Contents
Chapter 1: Introduction 1
1.1 Racism is a Multifaceted and Chronic Stressor for Black Americans 1
1.2 Racial Discrimination and Health 3
1.3 Effects of Chronic Stress on Stress Response Systems 6
1.4 Racial Discrimination is Associated with Dysregulation of Stress Response Systems 23
1.5 Exposure to Race-Related Stressors and Neural Network Alterations 27
1.6 Gaps in Literature, Current Studies and Aims 34
Chapter 2: An Inflammatory Pathway Linking Racial Discrimination and Threat Network Activation: Racial Discrimination, CRP and vmPFC Activation 35
2.1 Abstract 35
2.2 Introduction 36
2.3 Methods 39
2.4 Results 44
2.5 Discussion 46
Chapter 3: Emotion Regulation Circuits and Epigenetics: Neural Pathways Linking Racial Discrimination to Epigenetic Accelerated Aging 49
3.1 Abstract 49
3.2 Introduction 50
3.3 Methods 53
3.4 Results 56
3.5 Discussion 57
Chapter 4: Racial Discrimination, Interoception Network Connectivity and Dissociation 61
4.1 Abstract 61
4.2 Introduction 62
4.3 Methods 64
4.4 Results 68
4.5 Discussion 70
Chapter 5: Structural Pathways of Health Risk: Associations between Racial Discrimination, White Matter Microstructure, and Medical Conditions 75
5.1 Abstract 75
5.2 Introduction 76
5.3 Methods 77
5.4 Results 80
5.5 Discussion 83
Chapter 6: Summary, Limitations and Future Directions 87
6.1 Summary 87
6.2 Inflammation as a mechanism for shaping threat network reactivity 89
6.3 RD is Linked to Accelerated Epigenetic Aging Through Altered Resting-State Functional Connectivity 92
6.3 RD is Associated with Derealization Symptoms Through Disrupted Interoceptive Circuitry During Attention to Threat 95
6.4 RD, White Matter Integrity and Health 97
6.5 Implications, Limitations and Future Directions 100
Figures and Tables 111
Table 2.1 Demographic and Clinical Characteristics (N= 40) 111
Figure 2.1 Schematic of Affective Number Stroop Task 112
Figure 2.2 C-Reactive Protein as a Moderator of the Relationship Between Racial Discrimination and Emotion Regulatory Network Activation During Attention to Threat 113
Table 2.2 Main effects and Interaction of Racial Discrimination and CRP on vmPFC Response to Threat vs Neutral Images After Controlling for Latency Between Blood Draw and Age 114
Table 2.3 Conditional (+/- 1 SD from the mean) Effects of CRP levels on Associations Between Racial Discrimination and vmPFC Response to Threat vs Neutral Images 114
Table 3.1. Demographic and Clinical Characteristics (N= 90) 115
Figure 3.1. Associations of racial discrimination with brainstem resting-state functional connectivity and Horvath’s DNAm age acceleration 116
Figure 3.2. Brainstem Resting-State Functional Connectivity Mediates the Relationship Between Racial Discrimination and Horvath’s DNAm age acceleration 117
Table 4.1. Demographics and Clinical Characteristics (N= 72) 118
Figure 4.1. Racial discrimination, Insula Seed-to-Voxel Connectivity and Dissociation 119
Table 4.2 Anatomical Locations of Insula functional Connectivity During Affective Stroop Task Performance 120
Table 4.3. Correlations between connectivity of significant insula-mPFC clusters, depersonalization, and derealization and harmonized PTSD scores 120
Table 4.4 Descriptives for Affective Number Stroop Task Performance 121
Table 4.5 Correlations Between Insula Functional Connectivity and Affective Stroop Performance 122
Figure 5.1 Significant Indirect Effects of Racial Discrimination on Medical Disorders Through Left Anterior Cingulum Bundle Fractional Anisotropy 124
Figure 5.2 Significant Indirect Effects of Racial Discrimination on Medical Disorders Through Genu of Corpus Callosum Fractional Anisotropy 124
Table 5.1. Demographic and Clinical Characteristics (N=79) 125
Table 5.2. Frequency of Medical Disorders. 126
Table 5.3. Correlations between racial discrimination, trauma exposure, income, total medical disorders, and FA in white matter pathways 127
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