No robust cortical morphometry differences and limited morphometry-phenotype associations in a UK Biobank irritable...

Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction that has sparked interest in neural markers. Yet, previous neuroimaging findings remain inconsistent and often fail to replicate, likely due to small sample sizes that overestimate effects and overlook patient heterogeneity. Using normative modeling to quantify cortical deviations from MRI in a UK Biobank digestive health questionnaire (DHQ)-derived IBS phenotype and matched controls (N = 3 413 each) relative to a healthy reference sample (N = 8 661), we found no robust group differences. Further, equivalence tests provided evidence that both group and group × sex effects were statistically equivalent to negligible effect sizes across nearly all regions. Within IBS, negative associations between cortical gray matter deviations and symptom or pain severity were observed for some regions. However, no statistically meaningful IBS-specific effects and no sex moderation were detected. Overall, our findings challenge previously reported structural alterations in IBS, underscoring the need for replicability in adequately powered designs.