Demographic statistics.

Physical activity appears associated with lower depression in treatment and epidemiological studies but specific biological mechanisms remain unclear. Research supports inflammation being positively associated with depression and negatively associated with physical activity, suggesting it could mediate physical activity’s effect on depression. This study examined longitudinal associations between physical activity, inflammation, and depression symptoms in 13,461 older adults (59% women, mean age = 68) using the Health and Retirement Study dataset. Depression, physical activity, and inflammation (high sensitivity C-reactive protein (hsCRP)) were measured three times, four years apart. We used random intercept cross-lagged panel models (RI-CLPM) to test for stable between-person and within-person associations over time. Between-person results found higher physical activity was associated with lower hsCRP (β = −0.40, SE = 0.087, p < 0.001) and depression scores (β = −0.48, SE = 0.137, p < 0.001), suggesting physical activity is associated with lower inflammation and depressive symptoms. Conversely, higher hsCRP was correlated with higher depression scores (β = 0.19, SE = 0.20, p < 0.001). Within-person results revealed no support for change in inflammation as a longitudinal mediator of the relation between physical activity and change in depressive symptoms. Findings suggest robust relations among trait levels of physical activity, inflammation, and depression, but little support for change in inflammation as a longitudinal mediator of the physical activity and depression association. Future studies with additional assessments and shorter intervals may clarify the temporal associations among physical activity, inflammation, and depression.