Association Between Serum Cotinine Concentrations and Depression Among U.S. Adults: NHANES 2005–2018

Background: Evidence on the association between objective measures of tobacco exposure and depression remains limited. This study examined the relationship between serum cotinine and depression in a nationally representative U.S. population. Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2005–2018. Serum cotinine was analyzed as a biomarker of nicotine exposure. Depression was defined as a Patient Health Questionnaire-9 (PHQ-9) score ≥10. Weighted logistic regression and restricted cubic spline models were used to assess linear and nonlinear associations. Subgroup and sensitivity analyses were also performed. Results: A total of 29,514 participants were included. Serum cotinine concentrations were positively associated with depression. Each one-unit increase in log-transformed cotinine was associated with higher odds of depression (OR = 1.07, 95% CI: 1.06–1.09). Compared with the lowest tertile, participants in the highest tertile had increased odds of depression (OR = 1.72, 95% CI: 1.45–2.04). Restricted cubic spline analysis indicated a linear association between log-transformed serum cotinine concentrations and depression after excluding participants with serum cotinine concentrations at the lower limit of detection. The association remained robust after additional adjustment for smoking status (OR = 1.05, 95% CI: 1.03–1.07) and subgroup analyses. Conclusions: Serum cotinine concentrations were positively associated with depression in a nationally representative U.S. population. These findings suggest a potential link between nicotine exposure and depression and underscore the importance of further investigating the relationship between tobacco exposure and mental health.