Functional connectivity patterns of the subgenual anterior cingulate cortex in first-episode refractory major depressive disorder

Although accumulating evidence has been elucidating the neuronal basis of refractory/nonrefractory major depressive disorder (rMDD/nrMDD), the results are inconsistent, and little is known about the distinct neural mechanisms underlying rMDD. Here, we explored the convergent/divergent brain networks between first-episode MDD subtypes using the resting-state functional connectivity (RSFC) approach. In total, 33 healthy controls (HCs), 31 first-episode rMDD patients and 33 first-episode nrMDD patients were enrolled and underwent MRI scanning. The left subgenual anterior cingulate cortex (sgACC) was selected as the seed region, and RSFC was employed to evaluate associations between the seed and other regions in the whole brain. Both MDD subtypes exhibited convergent left sgACC-based neural networks, including increased RSFC with the dorsal prefrontal cortex (DPFC) and decreased RSFC with the bilateral orbitofrontal cortex (OFC) and right parahippocampus. rMDD patients exhibited increased left sgACC-OFC RSFC relative to nrMDD patients, and RSFC with the bilateral OFC in rMDD patients was negatively correlated with HAMD scores. These findings confirmed our speculation that convergent and divergent neural networks exist between rMDD and nrMDD. Cortical-limbic circuits, especially the prefrontal–limbic circuit, may serve as the convergent dysfunctional neural circuitry in MDD subtypes. As an important biomarker, a unique OFC-sgACC circuit abnormality was identified in rMDD patients, which might help elucidate the underlying mechanism regarding treatment responses in rMDD patients.