Aberrant functional connectivity patterns in the pregenual anterior cingulate cortex and anterior midcingulate cortex of patients with irritable bowel syndrome accompanied by depressive symptoms

Irritable bowel syndrome (IBS) is a common brain-gut disorder often accompanied by depressive symptoms, with atrophy and hyperactivity of the anterior cingulate gyrus (ACC) being key drivers of both IBS and its psychiatric comorbidities. This study aimed to investigate the functional connectivity (FC) patterns of pregenual ACC (pgACC) and anterior midcingulate cortex (aMCC) in IBS patients with depressive symptoms (DEP-IBS). A whole-brain FC analysis was conducted using pgACC and aMCC as regions of interest in three groups: 28 DEP-IBS patients, 21 IBS patients without depressive symptoms (nDEP-IBS), and 36 matched healthy controls (HCs). Partial correlation and mediation analyses were performed between abnormal FC and clinical symptoms. The ability of aberrant FC to identify IBS and its psychiatric comorbidity was evaluated using receiver operating characteristic (ROC) curve. DEP-IBS patients exhibited increased pgACC-related FC in the left medial prefrontal cortex (mPFC) and aMCC-related FC in the right middle frontal gyrus, angular gyrus and cerebellum, while showing decreased aMCC-related FC in the right precentral gyrus, superior parietal gyrus and precuneus. Both patient groups demonstrated increased FC between aMCC and left dorsolateral prefrontal cortex (dlPFC), effectively distinguishing them from HCs (AUC = 0.755). The FC between pgACC and left mPFC partially mediated the relationship between gastrointestinal and depressive symptoms, effectively distinguishing DEP-IBS from nDEP-IBS patients (AUC = 0.808). Aberrant FC within the emotional arousal network may serve as a neurobiological marker for IBS with comorbid depression. Furthermore, abnormal FC between the aMCC and the dlPFC may underlie the neural mechanism of IBS.