Trends in Depression and Its Association With Gallstones: Evidence From NHANES With Exploration of Mediating Pathways

Abstract

Objective This study aimed to analyze long‐term trends (2005–2023) in the prevalence of depression among US adults and to specifically investigate the association between depression and gallstone disease. Methods Data from multiple cycles of the National Health and Nutrition Examination Survey (NHANES) were utilized. Depression was assessed using the patient health questionnaire‐9 (PHQ‐9), and gallstone status was determined by self‐reported physician diagnosis. Weighted logistic regression models were employed to evaluate the association between depression and gallstones, with multivariable‐adjusted models controlling for potential confounders. Furthermore, dose–response relationship analysis and mediation analysis were conducted. Results Between 2005 and 2023, the prevalence of depression among US adults demonstrated a significant increasing trend. In the 2017–2023 data, depression was significantly associated with higher odds of gallstones (odds ratio [OR] = 1.61, 95% confidence interval [CI]: 1.13–2.29). Dose–response analysis revealed a positive association between increasing PHQ‐9 scores and gallstone presence (p for trend <0.001). Mediation analyses suggested that smoking and obesity explained ~6.3% and 6%, respectively, of the total observed association between depression and gallstones. Conclusion This study highlights a rising trend in the prevalence of depression and provides evidence for an association between depression and gallstone disease. The association appears to be partially mediated by smoking and body mass index (BMI). These findings underscore the clinical importance of considering gallstone screening and implementing integrated health management strategies for individuals with depression, while further longitudinal studies are warranted to clarify the temporal direction of this relationship.