GASTROENTEROLOGY / CLINICAL RESEARCH
Bidirectional associations of depression, anxiety, sleep disorders, and constipation: insights from Mendelian randomization
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1
Department of Psychiatry, Xiamen Xianyue Hospital, Xianyue Hospital Affiliated with Xiamen Medical College, Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen, Fujian, China
2
Xiamen Cardiovascular Hospital of Xiamen University, Xiamen University, Xiamen, Fujian, China
3
School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, China
Submission date: 2025-03-23
Final revision date: 2025-06-15
Acceptance date: 2025-06-27
Online publication date: 2025-07-02
Corresponding author
Xinchao Chen
School of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian 350122; Department of Psychiatry, Xiamen Xianyue Hospital, Xianyue Hospital Affiliated with Xiamen, Medical College, Fujian Psychiatric Center, Fujian Clinical
Research Center for
Mental Disorders
Xiamen, Fujian 361003,
China
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Mental health disorders and constipation are increasingly prevalent health problems worldwide. Previous studies have reported bidirectional associations between depression, anxiety, sleep disorders, and constipation. However, observational studies have yielded inconsistent results.
Material and methods:
The associations were examined through a two-sample, bidirectional, univariable, and multivariable Mendelian randomization (MR) study. Summary-level data were obtained from the UK Biobank, large consortia, and the FinnGen consortium. The inverse-variance weighted method was applied as the principal analytical approach, and other additional MR methods (maximum likelihood, MR-RAPS, and MR-PRESSO) were used for sensitivity analyses. Multivariable MR analysis was performed to assess the independent effects of selected exposures.
Results:
The univariable MR analyses indicated that major depression (MD) (OR = 1.28; 95% CI: 1.12–1.46), broad depression (BD) (OR = 3.72; 95% CI: 1.55–8.97), depressed affect (OR = 1.41; 95% CI: 1.13–1.76), and worry (OR = 1.42; 95% CI: 1.13–1.77) were associated with an increased risk of constipation. There was no evidence supporting the causal effects of anxious feelings, sleep duration, and sleeplessness on constipation. The reverse MR analyses found no reverse causal association of constipation with depression, anxiety, and sleep disorders. In multivariable MR, only MD still had a robust causal association with constipation, while the effect of worry was attenuated to null, and the effects of BD and depressed affect were completely reversed.
Conclusions:
MD is causally associated with constipation, and worry might also increase the risk of constipation. Future studies are needed to confirm the causality and elucidate the underlying mechanisms.
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