The mediating role of CRP in the relationship between physical activity and depression: A nonlinear analysis

Physical activity can alleviate depressive symptoms and has anti-inflammatory effects. However, the extent to which inflammation mediates this relationship is unclear. This study explores the non-linear relationship between the metabolic equivalent of recreational physical activity (MET-RPA), high-sensitivity C-reactive protein (hs-CRP), and depressive symptoms, assessing hs-CRP's mediating role.

Data from the National Health and Nutrition Examination Survey from 2013 to 2020 were used, including the Patient Health Questionnaire-9 (PHQ-9) scores, hs-CRP, and PA data. Restricted cubic spline models analyzed non-linear relationships, and mediation analysis assessed the mediating role of hs-CRP.

MET-RPA exhibited a non-linear "U" shaped relationship with depressive symptoms, where increased MET-RPA initially reduced depressive symptoms risk until a lowest point (3072.96 MET-min/week; i.e., 375 min of vigorous exercise or 750 min of moderate-intensity exercise per week), beyond which the risk increased. A non-linear "L" shaped relationship was observed between MET-RPA and CRP, with a lowest point of 3888.24 MET-min/week. Furthermore, a significant inflexion point was identified at a CRP level of 9.85 mg/L, where depressive symptoms risk increased with rising CRP levels but at a slower rate beyond this point. Mediation analysis revealed that CRP significantly mediated the relationship between MET-RPA and depressive symptoms, accounting for 8.14 % of the total effect.

Moderate levels of RPA significantly reduce depressive symptoms, while excessive RPA slightly increases the risk of depression. The anti-inflammatory effect of exercise, represented by decreased hs-CRP levels, plays a partial but significant mediating role in the relationship between RPA and depression.