Brain structure and function changes in Crohn's disease with or without depression based on multi-modal MRI

Crohn's disease (CD) is frequently comorbid with depression, yet the neural mechanisms underlying this association remain poorly understood. This study aimed to investigate brain structural and functional alterations in CD patients with and without depression, and to examine their relationship with depressive symptoms, inflammation, and disease activity.

Seventy CD patients and sixty healthy controls underwent resting-state functional MRI and structural MRI. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9) and Hamilton Depression Rating Scale-24 (HAMD-24). CD patients were stratified into depressed (CD-D, n = 28) and non-depressed (CD-N, n = 42) groups based on PHQ-9 scores. Voxel-based morphometry (VBM) was used to identify gray matter volume (GMV) differences, with significant regions serving as seeds for functional connectivity (FC) analysis. Associations between imaging metrics and clinical variables (inflammatory markers, disease activity, depression scores) were examined.

Compared to controls, CD patients exhibited reduced GMV in bilateral cerebellar lobule 8, which positively correlated with inflammatory markers (ESR/CRP), and increased GMV in the putamen and precentral gyrus. FC analysis revealed decreased connectivity between cerebellar lobule 8 and regions within sensorimotor, frontoparietal, and default mode networks. However, the changes in brain structure and function in each CD group were not significantly related to depression.

CD is associated with inflammation-related brain structural and functional alterations, which are linked to both disease activity and depressive symptom severity. These findings suggest that depressive symptoms in CD may arise from inflammation-driven brain changes along the gut-brain axis, rather than from depression-specific neural pathology.