Effects of neutrophils on the relationship between physical activity and depression: Evidence from cross-sectional study and mendelian randomization analysis

Abstract

Objective

Physical activity (PA) is suggested to reduce the risk of depression, and inflammation is believed to play an important role in this antidepressant effect. The current study aims to investigate the effect of neutrophils, one of the most important markers of inflammation, on the relationship between PA and depression.

Methods

We cross-sectionally analyzed 34,317 adults who participated in the National Health and Nutrition Examination Survey. The moderation and mediation effects of neutrophils on the relationship between PA and depression were assessed using a four-way decomposition approach. Additional Mendelian Randomization (MR) analysis was conducted to validate the potential causal mediation effect.

Results

PA was associated with lower odds of depression [Odds Ratio (OR): 0.67; 95 % Confidence Interval (CI): 0.56–0.79] and a lower level of neutrophils (OR: 0.83; 95 % CI: 0.77–0.90). Neutrophils were associated with higher odds of depression in a non-linear manner. While neutrophils did not modify the association between PA and depression, a significant mediating effect was observed. The influence of PA and neutrophils on depression was attributed to the controlled direct effect (96 % proportion) and the pure indirect effect (2 % proportion). MR analysis did not confirm a potential causal effect.

Conclusion

There is a close relationship between PA, neutrophils, and depression. The effect of PA on depression did not differ among participants with different levels of neutrophils. Although neutrophils mediated the association between PA and depression, this mediating effect was not causal. Other unknown factors closely related to neutrophils may be involved in this mediating process.