Dissociable patterns of alpha-band connectivity and structural-functional coupling in major depressive disorder with...

Although Major depressive disorder with mixed features (DMF) is recognized as a clinically distinct subtype, its underlying electrophysiological signatures remain unknown. This study aimed to investigate subtype-specific alterations in resting-state alpha band oscillations between DMF and Major depressive disorder without mixed features (nDMF), as well as the relationship of these oscillations with white matter structure.

We collected resting-state magnetoencephalography (MEG) and diffusion tensor imaging (DTI) data from 197 participants. The cohort comprised 86 healthy controls (HC), 35 patients with DMF, and 76 nDMF. We analyzed alpha band functional connectivity across all participants and, in a subsample, examined global and regional structural-functional (SC-FC) coupling. The relationship of these neuroimaging metrics with clinical features was assessed.

DMF patients showed higher alpha-band connectivity between the right supplementary motor area (SMA.R) and right anterior cingulate gyrus (ACC.R) than nDMF patients, and uniquely enhanced SC-FC coupling in the left anterior cingulate gyrus (ACC.L) versus both nDMF and HC groups, which negatively correlated with the subthreshold (hypo)manic symptom items. Conversely, nDMF patients exhibited higher connectivity between the SMA.R and the right middle temporal gyrus (TPOmid.R) than both DMF and HC groups. Both patient groups shared increased connectivity between the SMA.R and the right superior parietal gyrus (SPG.R) relative to HC group.

Our findings support DMF as a neurobiologically distinct subtype, characterized by a dissociable pattern of alpha band connectivity and SC-FC coupling, providing a multimodal framework for refining diagnostic precision in depressive disorders.