Smoking and the Association Between Depressive Symptoms and Absolute Neutrophil Count in the Investigations Préventives et Cliniques Cohort Study.

Objectives: Depressive symptoms have been associated with chronic low-grade inflammation, including elevated neutrophil count. Smokers often have both high neutrophil count and depressive symptoms. Thus, smoking could explain the cross-sectional association between depressive symptoms and neutrophil count.

Methods: Total white blood cell count and subtypes, including absolute neutrophil, lymphocyte, monocyte, basophil, and eosinophil counts, were measured in 44,806 participants (28,534 men; mean [standard deviation] age = 38.9 [11.4] years), without a history of chronic disease or current medication. Depressive symptoms were assessed with the Questionnaire of Depression, Second Version, Abridged. Smoking status was self-reported and categorized in five classes. Sex, age, alcohol intake, self-rated health, body mass index, glycemia, physical activity, household composition, occupational status, and education were included as covariates. Associations were examined with general linear models and causal mediation analyses.

Results: After adjustment for all covariates except smoking, depressive symptoms were positively associated with neutrophil count only (β = 5.83, standard error [SE] = 2.41, p = .014). After further adjustment for a semiquantitative measure of smoking, this association was no longer significant (β = 2.40, SE = 2.36, p = .30). Causal mediation analyses revealed that smoking mediated the association (p < .001), accounting for 57% of its total variance. In contrast, depressive symptoms were negatively associated with lymphocyte count in fully adjusted model only (β = -3.21, SE = 1.11, p = .004).

Conclusions: Smoking may confound or mediate the association between depressive symptoms and neutrophil count. These results advocate for including an accurate measure of smoking in future studies addressing this association. When considering the link between depression and inflammation, one should not overlook the noxious effects of smoking.