RESUMEN
Background: Observational studies have suggested associations between functional gastrointestinal disorders (FGIDs) and variations in the cerebral cortex. However, the causality of these relationships remains unclear, confounded by anxiety and depression. To clarify these causal relationships and explore the mediating roles of anxiety and depression, we applied univariate, multivariable, and mediation Mendelian randomization (MR) analyses. Method: We utilized genome-wide association study (GWAS) summary data from the FinnGen database and the ENIGMA consortium, identifying genetic variants associated with irritable bowel syndrome (IBS), functional dyspepsia (FD), and cerebral cortex structures. Data on anxiety and depression came from FinnGen and a large meta-analysis. Utilizing a bidirectional univariate MR approach, we explored correlations between FD, IBS, and cortex variations. Then, independent effects were assessed through multivariable MR. A meta-analysis of these results, incorporating data from two cohorts, aimed to increase precision. We also explored the potential mediating roles of anxiety and depression. Results: Our findings indicate a negative causal correlation between FD and the thickness of the rostral anterior cingulate cortex (rACC) across both global and regional adjustments (ß = -0.142, 95% confidence interval (CI): -0.209 to-0.074, P.FDR = 0.004; ß = -0.112, 95%CI: -0.163 to-0.006, P.FDR = 0.003) and a positive causal correlation with the globally adjusted thickness of the superior frontal gyrus (SFG) (ß = 0.107, 95%CI: 0.062 to 0.153, P.FDR = 0.001). The causal correlation with the rACC persisted after multiple variable adjustments (ß = -0.137, 95% CI: -0.187 to-0.087, P.FDR = 1.81 × 10-5; ß = -0.109, 95%CI: -0.158 to-0.06, P.FDR = 0.002). A significant causal association was found between globally adjusted surface area of the caudal anterior cingulate cortex (cACC) and IBS (odds ratio = 1.267, 95%CI: 1.128 to 1.424, P.FDR = 0.02). The analysis showed that neither anxiety nor depression mediated the relationship between FGIDs and cerebral cortex structures. Conclusion: Our research provides significant MR evidence of a bidirectional causal relationship between FGIDs and the cerebral cortex structures. This evidence not only confirms the two-way communication along the brain-gut axis but also illuminates the underlying pathophysiology, paving the way for identifying potential therapeutic approaches.
RESUMEN
OBJECTIVE: To assess the effectiveness of acupuncture for treating depression and anxiety in patients diagnosed with functional dyspepsia (FD). METHODS: PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Data, Sinomed, and VIP Database were searched until April 30, 2023 for Randomized Controlled Trials (RCTs) comparing acupuncture to placebo or drugs for symptom alleviation. Two independent reviewers conducted the study search, data extraction, and bias risk assessment using the Cochrane Risk of Bias tool. Mean difference (MD), risk ratio (RR), and corresponding 95% confidence intervals (CI) were computed. Subgroup and sensitivity analyses were also performed. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was employed to evaluate the evidence level. RESULTS: A total of 16 RCTs involving 1315 participants were included. Acupuncture demonstrated marked superiority over placebo (MD = -7.07, 95%CI: -11.03 to -3.10, very low quality evidence) in mitigating Self-Rating Anxiety Scale (SAS) scores and was found to be more effective in reducing Self-Rating Depression Scale (SDS) scores than either placebo (MD = -4.63, 95%CI: -6.28 to -2.98, low quality evidence) or first-line drugs (MD = -2.71, 95%CI: -5.19 to -0.23, very low quality evidence). In terms of attenuating Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD) scores, acupuncture consistently outperformed both placebo (HAMA: MD = -2.58, 95%CI: -4.33 to -0.83, very low quality evidence; HAMD: MD = -1.89, 95%CI: -3.11 to -0.67, low quality evidence) and first-line drugs (HAMA: MD = -5.76, 95%CI: -10.18 to -1.35, very low quality evidence; HAMD: MD = -5.59, 95%CI: -7.59 to -3.59, very low quality evidence). However, no significant difference was observed between acupuncture and placebo in terms of improvement in Hospital Anxiety and Depression Scale (HADS) scores. CONCLUSIONS: Based on current clinical evidence, acupuncture might have a positive effect on depression and anxiety in patients with FD. Further large-sample, multi-center, high-quality RCTs validation are required, as the conclusion is limited by the quantity and quality of the included studies.