Systemic low-grade inflammation and subsequent depressive symptoms: Is there a mediating role of physical activity?

•Systemic inflammation is associated with lower levels of physical activity.•Regular physical activity reduces the risk of developing depressive symptoms.•Low physical activity mediates the inflammation-depressive symptoms pathway. Systemic low-grade inflammation has been associated with the onset of depression, but the exact mechanisms underlying this relationship remain elusive. This study examined whether physical activity (PA) explained the association between elevated serum levels of inflammatory markers and subsequent depressive symptoms. Prospective cohort design. The sample consisted of 3809 non-depressed men and women (aged 50+) recruited from the English Longitudinal Study of Ageing (ELSA). Serum levels of inflammatory markers (C-reactive protein (CRP), fibrinogen) and covariates (age, sex, education, wealth, body mass index, smoking, cholesterol, triglycerides) were measured at baseline (wave 4, 2008/09). Self-reported weekly moderate/vigorous (high) PA versus no weekly moderate/vigorous (low) PA was examined at a four-year follow-up (wave 6, 2012/13), using a single-item question. Depressive symptoms were assessed at baseline, four years (wave 6, 2012/13) and six years post baseline (wave 7, 2014/15), using the 8-item version of the Centre for Epidemiological Studies Depression Scale (CES-D). Participants with higher baseline concentrations of inflammatory markers were significantly more likely to report low PA levels four years later (CRP: OR: 1.25; 95% CI, 1.05–1.48; fibrinogen: OR: 1.18; 95% CI, 1.05–1.39). Moreover, low PA was associated with higher odds of elevated depressive symptoms at follow-up (OR: 1.59; 95% CI, 1.15–2.19). Mediation analyses revealed that low PA explained a total of 36.71% of the relationship between high CRP and elevated depressive symptoms, and 33.26% between higher levels of fibrinogen and elevated depressive symptoms six years later. No direct association was found between systemic low-grade inflammation and future depressive symptoms. These results suggest that low PA is a significant partial mediator of the relationship between systemic low-grade inflammation and subsequent elevated depressive symptoms in a nationally representative cohort of older adults.