Gastrointestinal (GI) diseases and mental disorders are common and burdensome conditions that frequently co-occur in patients. While prior studies suggest a bidirectional association between these conditions, the temporal ordering and underlying causal mechanisms remain insufficiently elucidated. Existing research often focuses on narrow disease subtypes, overlooking the broader spectrum of GI and mental disorders. This study aims to investigate the dynamic, longitudinal relationship between these conditions in a large population-based cohort.
The primary objective is to examine the bidirectional temporal and causal associations between GI diseases and mental disorders over time. Secondary objectives include: (1) quantifying the relative causal strength in both directions (GI to mental and mental to GI); (2) identifying key moderating factors, such as age, gender, and socioeconomic status; and (3) exploring potential mediators of these relationships, such as lifestyle factors (e.g., diet, physical activity) and medication use.
Leveraging the UK Biobank’s rich longitudinal dataset, we will apply random intercept cross-lagged panel models (RI-CLPM) to capture the directionality and temporal sequencing of the relationships. To strengthen causal inference and address time-varying confounding, we will additionally use inverse probability weighting (IPW) within marginal structural models (MSM).
By adopting a comprehensive, system-level perspective on multimorbidity, this study will move beyond traditional single-disease frameworks. It seeks to advance etiological understanding and guide future research and intervention design for patients facing the dual burden of GI and mental health conditions.
