Abstract
The prevalence of depression is two to four times greater among people living with HIV (PLWH) compared to people living without HIV. Chronically elevated peripheral inflammation, primarily mediated by monocytes such as the CD16+ subset, is implicated in depression among PLWH. Glucocorticoid (GC) receptor signaling modulates monocyte-derived inflammation, yet its relationship with depression symptom severity in PLWH remains unclear. This study examined the relationship between pro-inflammatory cytokine production by CD16+ monocytes and depression symptom severity as a function of GC sensitivity, measured via dexamethasone-induced suppression (IC50 values) of TNF-alpha and IL-6 production.
In aim 1, we validated the invitro GC sensitivity assay by comparing IC50 values from depressed PLWH. Against published reference values. IC50 distributions for both TNF-alpha and IL-6, did not significantly differ from values observed in clinically depressed non-HIV samples (p>.05), supporting the assay’s construct validity.
Aim2a assessed the association between basal cytokine expression and depression severity measured by the Hamilton Depression Rating Scale-17 (HAM-D). Neither basal TNF-alpha nor IL-6 significantly predicted HAM-D total scores, although polysubstance use emerged as significant predictor of depression severity in covariate adjusted models (p=.030).
Aim 2b Tested whether GC sensitivity moderated this cytokine-depression relationship. In the TNF-alpha moderation model, the interaction approached significance (p=.053). The IL-6 moderation model showed a significant main effect for IL-6 (p=.023).
Overall, these findings suggest immune mechanisms underlying depression in PLWH are complex, potentially moderated by individual differences in GC sensitivity and substance use. Future research should consider depressive symptom-specific inflammatory profiles, and the impact of substance use on psychoneuroimmunological pathways in depression in PLWH.