Brain imaging derived phenotypes: a biomarker for the onset of inflammatory bowel disease and a potential mediator of mental complications

Background and aims: Inflammatory bowel disease (IBD), mainly categorized into Crohn's disease (CD) and ulcerative colitis (UC), is a chronic relapsing gastrointestinal disorder that significantly impairs patients' quality of life. IBD patients often experience comorbidities such as anxiety and depression, and the underlying mechanisms and treatment strategies remain areas of investigation. Methods: We conducted a Mendelian randomization(MR) analysis utilizing brain image derived phenotypes (IDP) from the UK Biobank database to investigate the causal relationships between IBD and alterations in brain structural morphology and connectivity of neural tracts. This study aimed to identify biological evidence linking IBD to psychiatric disorders such as anxiety and depression. Results: Specifically, the volume of grey matter in the Left Frontal Orbital Cortex exhibited a negative association with the onset of Crohn's disease (odds ratio (OR) [95% confidence interval (CI)]: 0.315[0.180 similar to 0.551], adjusted P=0.001), while the volume of the superior frontal cortex in the right hemisphere showed a positive correlation with the development of Ulcerative colitis (OR [95% CI]: 2.285[1.793 similar to 2.911], adjusted P<0.001), and the volume of lateral occipital cortex in the left hemisphere demonstrated a positive relationship with Crohn's disease onset (OR [95% CI]: 1.709[1.671 similar to 1.747], adjusted P<0.001). In the context of reverse causality, the onset of UC or CD has led to alterations in imaging derived phenotypes associated with five disorders (anxiety, depression, schizophrenia, bipolar disorder, pain) and three functions (memory, emotion, language). Conclusion: Our study has demonstrated a causal relationship between IBD and IDPs. IDPs may serve as potential biomarkers for the progression of IBD and as predictive intermediaries for the development of neurological diseases in IBD patients.