Causal relationships between depression, emotional changes, and hiatal hernia: A Mendelian randomization analysis

Hiatal hernia (HH) is a common gastrointestinal disorder characterized by the displacement of abdominal contents, particularly the stomach, into the thoracic cavity. This condition is frequently associated with gastroesophageal reflux disease (GERD) and can lead to various symptoms, including chronic cough and respiratory issues. Despite its prevalence, the mechanisms linking psychological factors to HH are not well understood. Observational studies have suggested correlations between mental health issues - such as stress, anxiety, and depression - and gastrointestinal disorders, indicating that emotional states may influence the development of HH. This study aims to clarify the causal relationships between mood swings, depression, and the risk of developing HH using Mendelian randomization (MR), a robust method that utilizes genetic variants as instrumental variables (IVs) to infer causality. Data for this MR analysis were obtained from publicly available genome-wide association studies (GWAS). We employed a bidirectional, 2-sample MR approach, using IVs associated with mood swings, depression, feelings of tension, and feelings of misery as exposures, with HH as the outcome. A reverse MR analysis was also conducted, treating HH as the exposure and the aforementioned emotional states as outcomes. The primary analytical method used was inverse variance weighting (IVW), supplemented by sensitivity analyses, including MR-Egger and weighted median methods. Our analysis revealed significant associations: mood swings (OR = 1.014; 95% CI = 1.001-1.027; P = .032), depression (OR = 1.019; 95% CI = 1.006-1.033; P = .003), feelings of tension (OR = 1.012; 95% CI = 1.004-1.020; P = .001), and feelings of misery (OR = 1.007; 95% CI = 1.003-1.010; P = .0001) significantly increased the risk of HH. Importantly, reverse MR analysis indicated no causal influence of HH on these emotional states. This study provides evidence that mood swings, depression, feelings of tension, and feelings of misery are significant risk factors for developing HH. These findings highlight the need to address psychological factors in the clinical management and prevention strategies for HH, potentially improving patient outcomes.