Characteristic of anterior cingulate cortex connectivity at subregional level in major depressive disorder

The anterior cingulate cortex (ACC) exhibits substantial role underlying the pathophysiology of major depressive disorder (MDD), yet its exact connectivity alteration and the relationship with clinical symptoms remain unclarified. We aimed to systematically investigate ACC subregional functional connectivity alterations with a relatively large sample of MDD and their longitudinal changes associated with clinical state.

From the Huaxi Depression Imaging Cohort Study, we recruited 141 MDD patients and 138 matched healthy controls (HC) with complete clinical information and resting-state functional MRI data, and calculated functional connectivity (FC) of five ACC subregions (subgenual, perigenual, rostral, dorsal, and caudal ACC). A subset of patients who completed follow-up clinical assessments and MRI scanning was further classified into remitted and non-remitted subgroups. ACC subregional FC was compared between MDD and HC, and for longitudinal changes in remitted and non-remitted patients separately. Exploratory correlations between FC alterations and symptom profiles were also assessed.

Compared with HCs, MDD patients demonstrated widespread hyperconnectivity between most ACC subregions and regions within frontoparietal network (FPN) and default mode network (DMN) at baseline. At follow-up, remitted patients showed reduced connectivity between perigenual ACC (pgACC) and dorsolateral/ventrolateral prefrontal cortex (dlPFC/vlPFC), with connectivity approaching HC levels. Non-remitted patients, however, exhibited no significant changes.

Our findings delineate specific dysconnectivity patterns of ACC at the subregional level in MDD and suggest the pgACC-dlPFC/vlPFC connectivity may represent a candidate neuroimaging correlate of remission.