Discrimination and Inflammation Help Explain Racial Differences In Depression

Background and Purpose

Experiences of discrimination are known predictors of depressive symptoms and inflammation, particularly for Black Americans. The Conserved Transcriptional Response to Adversity (CTRA) framework suggests that repeated activation of the stress response system through experiences like discrimination result in chronic inflammation, helping explain stress and inflammation-linked health problems. Interleukin-6 (IL-6), a pro-inflammatory cytokine, has been identified as a key mediator between psychosocial stress and depression. However, few studies have examined IL-6 as a biological mechanism linking discrimination to depression longitudinally, while examining race as the predictor. This study examined whether lifetime discrimination and IL-6 sequentially mediated the relationship between race and depression among adults.

Methods

Secondary data analyses were performed using the Midlife in the United States study, a national, longitudinal dataset (Wave 2: 2004-2006; Wave 3: 2017-2022). The analytic sample included White (83.4%), Black (16.6%), and other racial minority (3.4%) adults (N = 668; 57.3% female; mean age = 65.65, SD = 9.46). All analyses were conducted using SPSS v31.0. Serial mediation analyses were conducted using PROCESS Macro v5.0 Model 6 with 5,000 bootstrap samples, controlling for age, sex, other race, income, education, and substance use history. Race was dummy coded with White as the reference group and all coefficients are unstandardized. Lifetime discrimination was measured using the Lifetime Discrimination Scale (range 0-11), with higher scores indicating greater exposure to discriminatory experiences. IL-6 was assessed through blood samples and log-transformed prior to analysis (M = 1.39, SD = .53). Depression was measured using the CES-D, rescaled to range from 0-60, with higher scores indicating greater depressive symptomatology.

Results

Black participants reported significantly higher lifetime discrimination than White participants (b = 7.49, SE = .25, p < .001). Greater lifetime discrimination predicted higher IL-6 (b = .02, SE = .01, p < .05), and higher IL-6 predicted greater depression (b = 2.22, SE = .58, p < .001). The direct effect of race on depression was negative (b = -4.23, SE = 1.31, p < .01), suggesting protective factors among Black participants when discrimination and inflammation are controlled. The full serial indirect path from race through discrimination through IL-6 to depression was significant (indirect effect = .36, SE = .20, 95% CI [.04, .83]). Race alone did not significantly predict IL-6 (b = .05, SE = .09, p = .57), suggesting discrimination helps explain greater inflammation among Black Americans.

Conclusions and Implications

Findings suggest Black Americans who experience discrimination may have greater depressive symptoms through greater inflammation. Race was directly associated with IL-6 in the absence of discrimination; however, this association was attenuated when lifetime discrimination was included as a mediator, consistent with CTRA. These results highlight the need for psychosocial interventions tailored for Black Americans who have experienced discrimination, potentially reducing depressive symptoms and related inflammatory morbidities such as heart disease. At the policy level, dismantling structural racism is essential to disrupting biological pathways through which discrimination harms mental health. Future research should examine these pathways using explicit racial discrimination measures in larger, more racially diverse samples.