# Bidirectional Associations Between Anxiety and Gastrointestinal Disorders: A Retrospective Cohort Study Using the TriNetX Database

## TL;DR

This study finds that anxiety and irritable bowel syndrome are strongly linked in both directions, but the same isn't true for anxiety and inflammatory bowel disease.

## Contribution

Quantifies bidirectional associations between anxiety and GI disorders using a large real-world dataset.

## Key findings

- Anxiety increases IBS risk by 2.7-fold and IBD risk by 1.6-fold.
- IBS increases anxiety risk by 2.2-fold, but IBD does not significantly increase anxiety risk.
- Strong gut-brain axis and neuroimmune interactions are implicated in anxiety and IBS.

## Abstract

Introduction: Irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) are common gastrointestinal (GI) disorders often linked with anxiety and depression. IBS is defined by recurrent abdominal pain and altered bowel habits without a detectable organic disease, whereas IBD involves chronic, relapsing intestinal inflammation. Bidirectional communication through the gut-brain axis, gut dysbiosis, neuroimmune interactions, and shared genetic susceptibility may underlie these associations. This study aims to quantify and compare the bidirectional associations between anxiety and IBS or IBD using a large, real-world multicenter dataset.

Methods: A retrospective cohort study was conducted using TriNetX, a global network of de-identified electronic health records from over 100 healthcare organizations. Adults diagnosed with anxiety disorders, IBS, and IBD between January 1, 2021, and January 1, 2024, were identified along with matched controls. Patients with prior psychiatric disorders, GI conditions, recent GI infections, or relevant medication use were excluded. Propensity score matching balanced cohorts by age, sex, race, ethnicity, smoking status, and history of depression. Outcomes included incident IBS or IBD following anxiety and incident anxiety following IBS or IBD assessed over a follow-up period of five years post-index. Risk ratios, risk differences, and odds ratios with 95% confidence intervals were calculated.

Results: Among matched cohorts, 6,724 individuals (1.1%) with anxiety developed IBS compared with 2,457 (0.4%) in controls (RR 2.737, 95% CI 2.613-2.866; p < 0.001). For IBD, 1,412 patients (0.2%) with anxiety developed the condition versus 908 (0.2%) in controls (RR 1.555, 95% CI 1.431-1.690; p < 0.001). Reciprocally, 8,334 patients (6.6%) with IBS developed anxiety compared with 3,770 (3.0%) in controls (RR 2.211, 95% CI 2.129-2.295; p < 0.001). Among patients with IBD, 2,354 (2.6%) developed anxiety versus 2,383 (2.7%) in controls (RR 0.988, 95% CI 0.934-1.045; p = 0.669).

Conclusion: Anxiety and IBS exhibit strong bidirectional associations, whereas links between anxiety and IBD are weaker and inconsistent. These findings highlight the roles of the gut-brain axis and neuroimmune pathways in these conditions. Screening for psychiatric comorbidities and integrating GI and mental health care, including gut-brain-targeted interventions, may improve outcomes for patients suffering from these conditions.