Causal effect of anxiety and depression status on the symptoms of gastroesophageal reflux disease and functional dyspepsia during proton pump inhibitor therapy

Background Although anxiety and depression status is considered related to gastroesophageal reflux disease (GERD) and functional dyspepsia (FD) symptoms, ambiguity primarily arises from the difficulty in determining their cause-effect relationships. We aimed to examine the longitudinal reciprocal causation between anxiety/depression status and GERD/FD symptoms among symptomatic adult patients with GERD. Methods Adult (≥ 20 years) patients with GERD symptoms received PPI treatment for 4 weeks after endoscopy. GERD and FD symptom subscales (GERD-SS/FD-SS) were evaluated using the gastroesophageal reflux and dyspepsia therapeutic efficacy and satisfaction test (GERD-TEST). Anxiety and depression status were evaluated using the hospital anxiety and depression scale (HADS). A cross-lagged analysis using structural equation modeling was conducted to examine causal relationships among psychiatric bias (anxiety and depression scores) and upper gastrointestinal symptoms (GERD-SS and FD-SS scores) over time. Results A total of 182 patients with GERD (men: 120; age: 57.1 ± 12.8 years; body mass index: 24.2 ± 4.1 kg/m 2 ; nonerosive reflux disease/erosive reflux disease: 61/121) were eligible before ( T 1) and after 4 weeks ( T 2) of PPI therapy. The cross-lagged effect model indicated that anxiety at T 1 contributed to the FD-SS at T 2 ( β = 0.18*) and depression at T 1 contributed to the GERD-SS at T 2 ( β = 0.23*) (* p < 0.05). Conclusion Psychiatric bias was a risk factor for refractory GERD and FD. Anxiety and depression status reduced the therapeutic effect of PPIs on GERD and FD symptoms. Therefore, attention is required to detect the anxiety/depression status of patients with GERD/FD symptoms to treat patients appropriately and optimize therapeutic outcomes.