Investigating the Role of Inflammatory Biomarkers in Mediating the Relationship Between Smoking and Depression: A Cross-Sectional Analysis Using NHANES Data

This project investigates whether systemic inflammation mediates the association between smoking and depressive symptoms. Smoking remains disproportionately common among individuals with mental illness and is linked to poorer mental health, yet the biological mechanisms underlying this association are not fully understood. Previous evidence suggests that inflammation may play a central role: prior studies have shown that smoking is associated with elevated inflammatory markers, and that these markers are also linked to depression, but most studies have examined these associations in isolation.

Using data from the 2021–2023 National Health and Nutrition Examination Survey (NHANES), we will test an integrated model of smoking, inflammation, and depression. Specifically, we will examine whether smoking status (current, former, never) is associated with depressive symptom severity, and whether inflammatory biomarkers including high-sensitivity C-reactive protein (hs-CRP), white blood cell count (WBC), platelet count (PLT), mean platelet volume (MPV), and red cell distribution width (RDW), mediate this relationship.

The purpose of this study is to extend prior research by simultaneously testing multiple inflammatory markers as mediators, under the hypothesis that all of these biomarkers contribute to the smoking–depression association. This research will help clarify potential biological pathways and inform future longitudinal studies and public health interventions.