Page 67 - JCBP-3-3

Journal of Clinical and
Basic Psychosomatics Depression and chronic pancreatitis: MR study

of pancreatic enzymes, which can damage the intestinal factors but also offers new insights into the link between
mucosa and lead to dysbiosis of the microbiota. Studies depression and CP. More importantly, it provides a novel
have shown that depression contributes to disturbances in approach for identifying new risk factors for predicting the
the gut microbiota and metabolic dysregulation through onset of CP.
modulation of the psycho-neuro-endocrine-immune
However, there are some limitations to this study. First,
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system in the brain-gut axis. Disruption of the gut multivariable MR models involving multiple exposures
microbiota and intestinal barrier function may lead to the may weaken the efficacy of exposure IVs, such as the causal
migration of lipopolysaccharides to the pancreas, possibly
activating the nuclear factor kappa-light-chain-enhancer of effect of depression when adjusted for triglycerides or BMI.
activated B-cells and Toll-like receptor signaling pathways, This should be interpreted with caution due to the risk of
promoting the expression of inflammatory mediators such weak instrument bias (F-statistics <10). Second, the lack of
as IL-6 and IL-10, and inducing macrophage polarization, a significant association between CP and depression should
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all of which contribute to pancreatic fibrosis. Moreover, be approached carefully, as it may be due to insufficient
metabolic products from the gut microbiota, such as validity or unaccounted confounding factors. In this study,
bile acids and phenylacetic acid, are closely linked to the limited number of IVs significantly associated with
lipid metabolism. The very-low-density lipoprotein CP may not fully explain the relationship between CP and
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receptor can accelerate pancreatic fibrosis by enhancing depression. By relaxing the p-threshold for SNP screening,
lipoprotein metabolism in pancreatic stellate cells. we increased the flexibility of the IVs, which also raised the
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Furthermore, Chen et al. pointed out that patients with likelihood of horizontal pleiotropy and heterogeneity. To
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depression often exhibit a heightened inflammatory address this, we conducted a rigorous sensitivity analysis
immune response. Consequently, some CP patients who to further validate and explain the relationship between
are genetically predisposed to depression may be more CP and depression. Finally, given that the population
susceptible to inflammatory changes and experience more in this study is primarily of European ancestry, caution
severe pain. Depressed patients also tend to have poorer should be taken when extrapolating our research findings
disease coping skills, higher frequencies of abdominal pain to other populations. Future research on non-European
attacks, and more intense pain. These changes brought populations is needed to confirm the generalizability of
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about by depression can exacerbate inflammation, cause these results.
immune disorders, and ultimately lead to CP. Research
on the effect of depression on CP is still in its early stages. 6. Conclusion
Further large-scale clinical studies are needed to analyze CP is currently considered a significant risk factor for
the specific impact of depression on the pathogenesis of CP. depression. Conversely, our study supports the independent
Future research should explore how depressive emotions causal effect of depression on CP. HLA-DQA1 may play
alter the composition of the gut microbiota and how a role in the potential pathogenesis of this relationship.
these disruptions in microbiota composition contribute Individuals with elevated triglyceride levels, type 2 diabetes,
to pancreatic diseases. Clarifying the effects of fecal and smoking behaviors, combined with depression, may
microbiota transplantation, probiotic supplementation, be at an increased risk of developing CP. Further research
and psychological intervention in individuals with CP and is needed to elucidate the pathophysiological mechanisms
depression will be the focus of our future work.
underlying the causal link between depression and CP.
5. Strength and limitations
Acknowledgments
This study has several strengths. First, we conducted the
first comprehensive MR analysis to establish a positive We would like to express our gratitude to the FinnGen
association between depression and CP, an issue that study, PGC, GSCAN, IIBDGC, and GIANT for sharing
has not been explored separately or thoroughly until their valuable data.
now. Compared to traditional observational studies, our Funding
approach minimizes bias caused by reverse causality.
Second, we used multivariable MR analysis to reveal a This work was supported by the National Natural Science
direct causal relationship between depression and CP Foundation of China (Grant No. 81972655), the Shanghai
while adjusting for confounding factors. Furthermore, we Industry-university Research Practice Project (2023),
conducted a sensitivity analysis to ensure the consistency and the Shanghai Jiao Tong University “Jiaotong Star”
of causal estimates and the robustness of our results. Our Plan Medical Engineering Cross Research Project (Grant
study not only minimizes the influence of confounding No. 20230103 and YG2021QN07).

Volume 3 Issue 3 (2025) 61 doi: 10.36922/jcbp.5892