Disrupted prefrontal-sensorimotor functional connectivity mediates the association between depression and symptom severity in patients with irritable bowel syndrome

Background: Depressive symptoms are well-established psychological comorbidities significantly associated with the onset and progression of irritable bowel syndrome (IBS). Although alterations in resting-state functional connectivity (rsFC) have been shown in IBS, the potential mediating role of aberrant rsFC in the relationship between depressive symptoms and IBS severity remains unclear. Methods: This exploratory resting-state functional magnetic resonance imaging (rs-fMRI) study recruited participants including 32 IBS patients and 37 HCs. We employed whole-brain functional connectivity strength (FCS) analysis to identify regions with significant rsFC alterations. Subsequently, seed-based whole-brain FC analysis (using FCS-altered regions as seeds) and seed-to-seed FC analysis (based on the AAL atlas) were performed to examine group differences in FC. The mean rsFC value within clusters with significant between-group differences were correlated with clinical scores. Mediation models were constructed to test the mediating role of aberrant FC in the relationship between depressive symptoms and IBS severity. Results: Compared to HCs, IBS patients exhibited significantly reduced FCS in the bilateral prefrontal cortex (PFC). Seed-based whole-brain FC analysis revealed that, relative to HCs, IBS patients had increased FC between the left PFC and primary sensory cortex (SI), but decreased FC between the left PFC and right PFC, as well as between the left PFC and bilateral thalamus. Seed-to-seed FC analysis further showed aberrant connectivity within the default mode network (DMN) in IBS patients, with the left angular gyrus (a key DMN hub) demonstrating disrupted connectivity with multiple regions (e.g., right PFC, left precentral gyrus, and SI). Correlation analyses indicated that left PFC FCS was positively correlated with Self-Rating Depression Scale (SDS) scores and negatively correlated with Irritable Bowel Syndrome Symptom Severity Scale (IBS-SSS) scores in IBS patients; additionally, SDS scores were positively correlated with IBS-SSS scores. Mediation analysis confirmed that left PFC FCS significantly mediated the relationship between SDS (predictor) and IBS-SSS (outcome), while the reverse model showed no significant mediating effect. Conclusions: Our exploratory findings suggest that depressive symptoms in IBS are associated with alterations in functional connectivity (FC), particularly within the prefrontal cortex. Crucially, the identified FC changes might be a potential interplay between depression and symptom severity in IBS.