Perceived Racial Stress Effects on Neuropsychological Functioning in African Americans are Mediated by the Brain's...

The neurobiological mechanisms through which racism-related stress becomes biologically embedded in African Americans remain incompletely understood. This study examined whether perceived lifetime racial stress produces diminished executive functioning through coordinated neuroimmune and neuroendocrine pathways, e.g., a brain-body interaction along the stress neuroaxis. Employing community sampled adult African Americans (N = 212; mean age = 46 years), Hayes' PROCESS' moderated serial mediation statistic (Model 85) was used to test a comprehensive conceptual model hypothesizing perceived racial stress' (PRS total lifetime exposure; PRST) and its impact on cognitive flexibility and inhibitory control through hypothesized mediating stress-related neuromodulators, including dopamine, norepinephrine, epinephrine, cortisol, tumor necrosis factor-α, interleukin-1α, interleukin-6, and C-reactive protein. Gender was examined additionally as a moderator of these pathways. Results demonstrated significant total and indirect lifetime effects of chronic racial stress on executive functioning. Neuroimmune and neuroendocrine biomarkers served as key mediators of these relationships, with distinct gender-specific patterns. Among women, racial stress effects were more strongly mediated through inflammatory and catecholaminergic pathways, whereas among men, effects were more pronounced along neuroendocrine pathways involving cortisol and downstream inflammatory markers. Future research contrasting racism to general stressors may help further identify racism specific biological mechanisms impacting cognition. These findings advance understanding of how racism-related stress becomes biologically embedded through interacting neuroimmune and neuroendocrine systems, with measurable consequences for executive functioning. By identifying sex-specific neurobiological pathways linking racial stress to cognition, this study underscores the importance of targeted, neuroscience-informed interventions to mitigate cognitive and health disparities in racially marginalized populations.