Association Between Gallstones and Depressive Symptoms: Results from NHANES and Mendelian Randomization Study

Ruidong Ma,* Wei Li,* Qiufeng Peng,* Ao Ren, Ling Zhao, Jiawei Li, Shiqiao Luo Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shiqiao Luo, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1st, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86-15002355050, Email [email protected]: Prior research has suggested a correlation between gallstones and depressive symptoms, yet the specifics of this relationship remain unclear. This study aims to explore the association between gallstones and depressive symptoms among adults.Patients and Methods: Initially, we conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2017 – March 2020. After propensity score matching (PSM) for participants with gallstones and those without gallstones, multivariate logistic regression analysis was used to explore the potential association between gallstones and depressive symptoms. This was followed by Mendelian randomization (MR) analysis to further elucidate the causal relationship between them. Using the genome-wide association study database, we extracted instrumental variables and performed bidirectional univariate and multivariate MR analyses.Results: In the cross-sectional study of NHANES 2017 – March 2020, 835 pairs of participants with comparable characteristics, both with and without gallstones, were identified after PSM. The multivariate adjusted logistic regression analyses revealed a significant association between gallstones and depressive symptoms [fully adjusted model: OR=1.821 (95% CI, 1.181– 2.808), P=0.007]. Subsequent MR analyses further clarified the causal relationship, indicating that genetically determined gallstones significantly increase the risk of developing depressive symptoms [forward univariate MR analysis: OR=1.04 (95% CI, 1.01– 1.06), P=0.002; multivariate MR analysis: OR=1.03 (95% CI, 1.01– 1.05), P=0.009], with no evidence of reverse causation [inverse univariate MR analysis: OR=1.28 (95% CI, 0.90– 1.83), P=0.17].Conclusion: Gallstones are a risk factor for depressive symptoms among adults. Hence, we recommend timely depression screening for patients diagnosed with gallstones, facilitating early detection and effective treatment of depressive symptoms, thus alleviating its impact on both individuals and society.Keywords: depressive symptoms, gallstones, risk factor, causality, genetic analysis, cross-sectional study