Investigating the Role of Inflammatory Biomarkers in Mediating the Relationship Between Smoking and Depression:...

Smoking is associated with both systemic inflammation and depression, but few studies have examined inflammatory biomarkers as mediators of this relationship.

Using 2021-2023 National Health and Nutrition Examination Survey (NHANES) data, we investigated whether White Blood Cell (WBC) count, Platelet Count (PLT), High-Sensitivity C-Reactive Protein (hs-CRP), Mean Platelet Volume (MPV), and Red Cell Distribution Width (RDW) mediate associations between smoking status and depressive symptoms. Data from 6029 adults (14.3% current smokers, 25.5% former smokers, 60.2% never smokers) were analyzed with survey-weighted structural equation models and multiple imputation, adjusting for age, sex, and race/ethnicity.

Current smokers had higher depressive symptoms (M = 5.81, SD = 5.79) than former smokers (M = 4.08, SD = 4.71) and never smokers (M = 3.91, SD = 4.70). WBC, PLT, hs-CRP, and RDW were elevated in smokers and significantly predicted higher PHQ-9 scores. Mediation analyses showed that WBC explained 10.9% of the smoking-depression association in current smokers (β = 0.01, SE = 0.004, p < .001) and 7.6% in former smokers (β = 0.005, SE = 0.002, p = .008). PLT mediated 3.7% (current smokers: β = 0.005, SE = 0.002, p = .006) and 4.1% (former smokers: β = 0.003, SE = 0.001, p = .003). hs-CRP mediated 3.7% (current smokers: β = 0.005, SE = 0.002, p = .03) and 5.0% (former smokers β = 0.003, SE = 0.002, p = .05). RDW mediated 3.0% of the effect for current smokers (β = 0.004, SE = 0.002, p = .02). MPV showed no mediation.

These findings indicate that systemic inflammation partly explains the link between smoking and depression, highlighting biological pathways that may inform integrated cessation and mental health strategies.