Unveiling the Temporal Pathways Linking Psychological Distress, Disease Symptomatology, and Quality of Life in Inflammatory Bowel Disease

Abstract

Introduction

Inflammatory bowel disease (IBD) is a chronic relapsing condition associated with substantial psychological burden, including elevated anxiety, depression, and perceived stress. Psychological distress is consistently linked to poorer quality of life (QoL), yet the mechanisms underlying this relationship remain incompletely understood. In particular, whether distress affects QoL directly or indirectly through disease symptomatology is still debated. Most mediation studies assume a single temporal ordering, although alternative specifications are often equally plausible. This study compares temporal mediation models to evaluate how temporal assumptions influence conclusions on this relationship in IBD.

Objectives

To investigate the mediating role of disease symptomatology in the association between psychological distress and QoL in patients with IBD, comparing alternative temporal mediation models and evaluating the robustness of findings under different missing-data imputation strategies.

Methods

A longitudinal cohort of 102 patients with IBD was assessed at baseline (T0) and four-month follow-up (T1). Psychological distress was measured with the Depression Anxiety Stress Scale-21 (DASS-21), disease symptomatology with the patient-reported IBD-Control symptom score, and QoL with the EQ-5D-5L. Baron and Kenny’s mediation framework was applied to three alternative specifications: (1) a fully cross-sectional model, all variables at T0; (2) a fully prospective model, distress at T0 and symptomatology/QoL at T1; and (3) a partially prospective model, distress and symptomatology at T0 and QoL at T1. Mediation paths (a, b, c, c’) were estimated for each specification. About 20% of follow-up observations were missing; missing data were handled via predictive mean matching and missForest multiple imputation. As both approaches produced comparable estimates, missForest was retained for the final analyses due to its lower computational burden.

Results

The fully cross-sectional model supported partial mediation of IBD symptoms on the relation distress-quality of life: path a) distress is significantly correlated with IBD symptoms (mediator) ; path b) IBD symptom significantly correlated with QoL, while path c’) a direct effect of distress on QoL remained after accounting for the mediator. The fully prospective specification also identified significant indirect pathways; however, the direct effect of distress on QoL reversed direction, suggesting an unstable mediation structure under this temporal assumption. In contrast, the partially prospective model, linking baseline distress and symptomatology with follow-up QoL, showed significant effects for all mediation paths in the expected direction, providing the most coherent evidence for partial mediation. Results were highly consistent between complete-case and imputed datasets, indicating robustness to the handling of missing follow-up data.

Conclusions

Among the temporal specifications examined, the model linking baseline distress to concurrent symptomatology and subsequent QoL at four-month follow-up provided the most coherent mediation pattern. These findings suggest that psychological distress rapidly influences patients’ perceived symptom burden, which subsequently contributes to poorer QoL over time, while a direct effect of distress on QoL also persists. More broadly, this study shows that mediation results may depend substantially on the temporal specification adopted. Explicitly comparing plausible temporal models should be considered good practice when applying the Baron and Kenny framework to longitudinal observational data, improving the robustness and interpretability of mediation analyses beyond the specific clinical context of IBD.