BACKGROUND: Major depressive disorder with mixed features (DMF) is a severe condition with high suicide risk and recurrence, and is closely related to the bipolar spectrum. However, its neurobiological differentiation from non-mixed MDD (nDMF) is poorly understood. This study aimed to identify DMF specific aberrations in low-gamma oscillations. METHODS: We recruited 60 DMF patients, 60 nDMF patients, and 60 healthy controls (HCs). Resting-state magnetoencephalography (MEG) was used to assess low-gamma (30-48 Hz) oscillatory power and functional connectivity (FC). Source-level power and network-based statistics were analyzed with adjustment for age, sex, and education. Clinical symptoms were assessed using the Hamilton Depression Rating Scale (HDRS₁7) and the number of subthreshold (hypo) manic symptoms. Correlations between abnormal neural indices and clinical measures were examined within the DMF group. RESULTS: Compared to nDMF and HCs, the DMF group exhibited significantly elevated low-gamma power across sensorimotor, parietal, occipital, and limbic regions. Reduced low-gamma FC was observed within a prefrontal-limbic-motor network, including connections between the left opercular part of inferior frontal gyrus, supplementary motor area, left insula, and amygdala. In DMF patients, low-gamma power in the right mid cingulate and paracingulate gyrus and FC strengths of key connections were negatively correlated with the number of subthreshold (hypo) manic symptom items. CONCLUSION: DMF exhibits a low-gamma signature of local hyperexcitability and long-range desynchronization, reflecting impaired top-down cognitive inhibition and holding potential as a biomarker for bipolar spectrum risk stratification.
Xiong et al. (Fri,) studied this question.