Psychological Processes, Not Physiological Parameters, Are Most Important Contributors to Symptom Severity in Patients With Refractory Heartburn/Regurgitation Symptoms

Background and aims Physiological and psychological factors have been shown to influence esophageal symptom reporting. We aim to evaluate which of these factors are associated with three reflux symptom severity outcomes (Total, Heartburn, and Sleep Disturbance), through a traditional statistical and a complementary machine-learning approach. Methods Consecutive adult patients with refractory heartburn/regurgitation symptoms underwent standard 24-hour pH-impedance monitoring and completed questionnaires assessing past and current gastrointestinal and psychological health. In the traditional statistical approach, hierarchical general linear models assessed relationships of psychological and physiological variables (e.g., total number of reflux episodes) with reflux severity scores. Mediation analyses further assessed pathways between relevant variables. In the machine-learning approach, all psychological and physiological variables were entered into 11 different models and cross-validated model performance was compared between the different models to select the best model. Results 393 participants [mean (SD) age=48.5 (14.1); 60% female] were included. General psychological functioning emerged as an important variable in the traditional statistical approach, as it was significantly associated with all three outcomes and mediated the relationship between childhood trauma and both Total Reflux and Heartburn Severity. In the machine-learning analyses, general psychological variables (e.g., depressive symptoms) were most important for Total Reflux and Sleep Disturbance outcomes, while symptom-specific variables, like visceral anxiety, were more influential for Heartburn Severity. Physiological variables were not significant contributors to reflux symptom severity outcomes in our sample across reflux classifications and statistical methodology. Conclusions Psychological processes, both general and symptom-specific, should be considered as another important factor within the multifactorial processes that impact reflux symptom severity reporting, across the reflux spectrum.