Prefrontal Cortex Volume Mediates the Relationship Between Lifetime Chronic Stressor Exposure and Cognition in People Living With and Without HIV

Objective: Despite considerable research documenting how stress affects brain and neurobehavioral outcomes, few studies have assessed stressor exposure occurring over the entire life span, and no studies have investigated these associations in people living with HIV (PLWH), despite the high stress and disease burden experienced by this population. To address this issue, we examined how cumulative lifetime chronic stressor exposure related to cognition and brain integrity (i.e., gray matter volume) in White and African American PLWH and HIV-uninfected (HIV-) adults.

Method: Participants were 91 community-dwelling adults (47.3% PLWH) who completed a comprehensive interview assessing lifetime stressor exposure using the Stress and Adversity Inventory and underwent neuropsychological testing and structural magnetic resonance imaging. Regional brain volumes were derived from T1-weighted images processed through Freesurfer.

Results: As hypothesized, greater lifetime chronic stressor exposure was related to worse global cognition ( b = -0.06, standard error [SE] = 0.03, p = .032), processing speed ( b = -0.04, SE = 0.14, p = .041), and executive functioning ( b = -0.06, SE = 0.02, p = .02), and smaller prefrontal cortex (PFC) volume ( b = -16.20, SE = 5.78, p = .007). HIV status did not moderate any of these associations. Moreover, results from mediation analyses demonstrated that the relationship between lifetime chronic stressor exposure and processing speed was fully mediated by PFC volume.

Conclusions: These results highlight the critical role of the PFC in the maintenance of processing speed abilities and its vulnerability to cumulative stressor exposure. Specifically, the negative impact of lifetime chronic stressor exposure on cognition-particularly functions reliant on frontal lobe integrity-may be partly driven by smaller volumes in the PFC.