Page 66 - JCBP-3-3

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

Table 1. The mediation effect of depression on chronic pancreatitis through smoking initiation, triglycerides, and type 2 diabetes
Mediator Total effect Effect α Effect β Mediation effect P Mediated proportion (%)
OR (95% CI) OR (95% CI) OR (95% CI) OR (95% CI)
Smoking initiation 1.39 (1.03 – 1.86) 1.24 (1.15 – 1.35) 1.30 (1.03 – 1.65) 1.06 (1.01 – 1.13) 0.046 17.60
Triglycerides 1.11 (1.06 – 1.15) 1.22 (1.08 – 1.38) 1.02 (1.01 – 1.04) <0.01 6.14
Type 2 diabetes 1.24 (1.08 – 1.42) 1.13 (1.04 – 1.22) 1.03 (1.01 – 1.06) 0.03 7.84
Notes: “Total effect” represents the effect of depression on CP. “Effect α” represents the effect of depression on smoking initiation/triglycerides/type 2
diabetes. “Effect β” represents the effect of smoking initiation/triglycerides/type 2 diabetes (adjusted for major depression disorder) on CP. “Mediation
effect” represents the effect of major depressive disorder on chronic pancreatitis through smoking initiation/triglycerides/type 2 diabetes. All effects
were calculated using inverse variance weighted, and the “mediation effect” was derived using the delta method. P<0.05 was considered statistically
significant.
Abbreviations: CI: Confidence interval; OR: Odds ratio.

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pancreatitis. It is well established that recurrent acute sample, multivariable, and two-step MR analyses focused
pancreatitis can progress to CP, and patients with CP often on the relationship between depression and CP.
suffer from impaired endocrine function, which results in Research has indicated a significant correlation between
type 2 diabetes. Our findings suggest that prevention of HLA-DQA1 and rhodopsin-like G-protein-coupled
CP should be prioritized in depressed patients who have receptors, which are implicated in various psychiatric
type 2 diabetes, engage in smoking, and have elevated disorders, including depression. We searched this gene
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triglyceride levels. in the GeneCards database (https://www.genecards.org)
Previous observational studies have suggested a strong and found that HLA-DQA1 plays a key role in the immune
association between depression and CP, with significant system by presenting peptides derived from extracellular
effects on QOL. 38-40 For instance, Chen et al. noted that proteins. Immune regulation and the inflammatory
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patients with CP often experience abdominal pain, weight response interact during both physiological and
loss, and complications such as pancreatic duct stones, pathological processes. Immune regulation can prevent the
diabetes, and an increased risk of pancreatic cancer. These excessive expansion and damage caused by inflammation.
psychological and physiological stressors may contribute Long-term emotional abnormalities, such as depression,
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to the development of depression. Similarly, Dunbar et al. may lead to immune disorders, resulting in inflammation
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found correlations between continuous and intense pain or autoimmune diseases. In this study, we utilized the
phenotypes and depression in patients with CP in the MR method to explore the causal relationship between
North American Pancreatitis Study II cohort. Yadav et al. depression and CP. Future research could incorporate
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suggested that continuous and intense pain is the main t-distributed stochastic neighbor embedding for nonlinear
factor responsible for poor physical and mental health dimensionality reduction and visualization techniques. 49,50
in CP patients. Sarkar et al. proposed that depression This approach may help identify SNP combinations
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in CP patients is linked to poor QOL, associated with potentially associated with the disease, providing valuable
choline and N-acetylaspartate in the brain. At present, insights for further investigation.
antidepressants are empirically used to manage pain in Several potential mechanisms could explain the
patients with CP. Furthermore, Shah et al. showed impact of depression on CP. The stress-responsive
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that depression is a predictive factor for readmissions hypothalamic-pituitary-adrenal axis has been implicated
within 30 days in patients with CP. Nevertheless, the in the pathophysiology of depression. Studies have
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direct causal effect of depression on CP has not yet been demonstrated that depressed patients exhibit higher
conclusively proven. To date, only one MR study has adrenocorticotropic hormone levels and cortisol
shown a link between genetic susceptibility to depression responses, which accelerate chronic inflammation and
and a higher risk of 12 gastrointestinal disease outcomes, stimulate the immune response. In parallel, excessive
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including CP. However, the study did not explore the activation of the hypothalamic-pituitary-adrenal axis
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mechanisms or pathways through which depression inhibits the nerve (VN). However, the VN is sensitive
affects CP. While the causality between depression and to peripheral pro-inflammatory cytokines, such as
CP remains incompletely evaluated, and the pathogenesis interleukin (IL)-1, IL-6, and tumor necrosis factor, which
of CP is still unclear, the pathophysiological mechanisms play an important role in defending against infection and
underlying the associations between these two conditions inflammation. 53,54 As is well known, patients with CP often
remain undefined. Therefore, we conducted separate two- experience long-term diarrhea due to insufficient secretion

Volume 3 Issue 3 (2025) 60 doi: 10.36922/jcbp.5892