Depression，Physical Activity，and Peptic Ulcer Disease: An Association Analysis Using a Prospective Cohort and Mendelian Randomization Study

Xiaocui CHEN; Chunyan LI; Keliang LIU; Jiamei RONG; Yichuan ZHANG

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Xiaocui CHEN, Chunyan LI, Keliang LIU, Jiamei RONG, Yichuan ZHANG. Depression，Physical Activity，and Peptic Ulcer Disease: An Association Analysis Using a Prospective Cohort and Mendelian Randomization Study[J]. Journal of Kunming Medical University.

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Depression，Physical Activity，and Peptic Ulcer Disease: An Association Analysis Using a Prospective Cohort and Mendelian Randomization Study

1.
Department of Gastroenterology，The First People’s Hospital of Yunnan Province，Kunming Yunnan 650032
2.
Department of Gastroenterology
3.
Minimally Invasive Endoscopy Center，Affiliated Hospital of Panzhihua University，Panzhihua Sichuan 617000
4.
Department of Gastroenterology，Yan’an Hospital Affiliated to Kunming Medical University，Kunming Yunnan 650051，China

Received Date: 2026-06-09
Available Online: 2026-11-03

Abstract

Abstract

Objective To investigate the causal relationships among depression, physical activity （PA）, and peptic ulcer （PU） in middle-aged and older adults in Europe. Methods A prospective cohort study and a Mendelian randomization （MR） study were conducted. Causal associations among depression, PA, and PU were examined through Cox regression analysis, mediation analysis, subgroup analyses, and sensitivity analyses. Results The mean baseline age of participants was （65.02 ± 9.02） years, and the incidence of PU was 3.38% （848/25, 053）. Compared with the group with depression and low-level vigorous-intensity PA （VPA） or moderate-intensity PA （MPA）, participants with depression and moderate-to-high levels of VPA （HR = 0.68, 95%CI: 0.56～0.84, P < 0.001） or MPA （HR = 0.77, 95%CI: 0.61～0.97, P = 0.029 ） had a reduced risk of PU. The greatest reduction in PU risk was observed in the group without depression and with moderate-to-high levels of VPA （HR = 0.58, 95%CI: 0.48～0.70, P < 0.001） or MPA （HR = 0.56, 95%CI: 0.44～0.71, P < 0.001）. MR analysis confirmed that depression increased the risk of PU （IVW=0.29, 95%CI: 0.13～0.44, P < 0.001）, and was associated with decreased levels of moderate-to-vigorous PA （MVPA: IVW: β = -0.05, 95%CI: -0.08～-0.02, P = 0.001） and VPA （IVW=-0.01, 95%CI: -0.02～0.00, P = 0.046）. MR analysis further demonstrated that MVPA （IVW = -0.48, 95%CI: -0.65 to -0.31, P < 0.001） and VPA （IVW = -1.14, 95%CI: -1.77 to -0.51, P < 0.001） have protective causal effects on PU. Mediation analysis suggested that MVPA may partially mediate the pathway through which depression increases PU risk, with a mediated effect of 0.0200 （P = 0.027）, accounting for 7.01% of the total effect. Subgroup analyses revealed significant heterogeneity in the associations of depression and PA with incident PU across different populations, and multiple sensitivity analyses confirmed the robustness of the findings. Conclusion Moderate-to-high levels of PA among middle-aged and older adults in Europe can effectively reduce the risk of PU. MVPA may exert a protective effect in the pathway through which depression drives PU, underscoring that early engagement in higher levels of PA among individuals with depression may help prevent PU.
- Peptic ulcer,
- Depression,
- Physical activity

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References(29)

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