Abstract Introduction Smoking is associated with both systemic inflammation and depression, but few studies have examined inflammatory biomarkers as mediators of this relationship. Methods 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. Results 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. Conclusions 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.
Cihan et al. (Tue,) studied this question.
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