AccScience Publishing / JCBP / Online First / DOI: 10.36922/jcbp.5892
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ORIGINAL RESEARCH ARTICLE

The causal relationship between depression and chronic pancreatitis: A Mendelian randomization study

Dishuang Hu1 ,  Ruxin Yu2 ,  Jiacheng Rong3 ,  Yue Zhang4* ,  Shuliang Zhao2*
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1 Department of Gastroenterology, Ningbo Hangzhou Bay Hospital (Ningbo Branch of Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai), Ningbo, China
2 Division of Gastroenterology and Hepatology ; Shanghai Institute of Digestive Disease ; NHC Key Laboratory of Digestive Diseases ; State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
3 Department of Cardiology, Ningbo Hangzhou Bay Hospital (Ningbo Branch of Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai), Ningbo, China
4 Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China
JCBP, 5892 https://doi.org/10.36922/jcbp.5892
Submitted: 12 November 2024 | Revised: 18 February 2025 | Accepted: 19 February 2025 | Published: 13 March 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Observational studies have suggested a high prevalence of depression among patients with chronic pancreatitis (CP). However, the effects of depression on CP and the causal relationship between the two conditions remain unclear. We performed two-sample and multivariable Mendelian randomization (MR) analyses, as well as a two-step MR analysis, to investigate their causal associations. Data on depression and CP were obtained from summary statistics of non-overlapping samples in a genome-wide association study. Two-sample and multivariable MR analyses were conducted to explore the association between depression and CP. A subsequent two-step MR analysis explored the causal pathways between the two conditions and the role of mediators in this process. Genetically, predicted depression (per 1 standard deviation) showed a positive association with CP (odds ratio [OR]: 1.39; 95% confidence interval [CI]: 1.03 – 1.86; P = 0.03). The causal relationship was confirmed after adjusting for smoking, drinking, type 2 diabetes, body mass index, and triglycerides. We found that triglycerides (OR: 1.02; 95% CI: 1.01 – 1.04; P = 0.004), type 2 diabetes (OR: 1.03; 95% CI: 1.01 – 1.06; P = 0.030), and smoking initiation (OR: 1.06; 95% CI: 1.01 – 1.13; P = 0.046) may mediate the causal relationship between depression and CP, with the mediating effect accounting for 6.14%, 7.84%, and 17.06% of the total effect, respectively. Our study provides evidence for an independent causal effect of depression on CP, offering new insights into the correlation between depression and inflammation. Further research is necessary to clarify the pathophysiological mechanisms underlying this causal association.

Keywords
Depression
Chronic pancreatitis
Mendelian randomization
Genome-wide association study
Funding
This work was supported by the National Natural Science Foundation of China (Grant No. 81972655), the Shanghai Industry-university Research Practice Project (2023; Grant No. 81972655), and the Shanghai Jiao Tong University “Jiaotong Star” Plan Medical Engineering Cross Research Project (Grant No. 20230103 and YG2021QN07).
Conflict of interest
The authors declare no competing interests.
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Journal of Clinical and Basic Psychosomatics, Electronic ISSN: 2972-4414 Print ISSN: 3060-8562, Published by AccScience Publishing
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