Beta-band oscillatory signatures differentiate melancholic and anxious subtypes of major depressive disorder

Abstract Background Major Depressive Disorder (MDD) is a prevalent and disabling psychiatric disorder. Its clinical heterogeneity undermines diagnostic precision and treatment effectiveness. While DSM-5 defines melancholic and anxious subtypes based on symptoms, their neurophysiological bases remain unclear. Resting-state electroencephalography (EEG) provides a non-invasive approach for investigating neurophysiological heterogeneity in depression. Beta-band oscillations are associated with reward processing, motivation, and cortical arousal, which may differ across subtypes. Methods We analyzed 325 patients with MDD, classified into melancholic ( n = 108), anxious ( n = 102), and non-melancholic and non-anxious ( n = 115) groups. Relative spectral power and phase-locking value (PLV) in beta1 (12–20 Hz) and beta2 (20–30 Hz) bands were compared. Logistic regression and subtype-specific correlation analyses assessed classification and clinical associations. Results Melancholic depression was associated with widespread reductions in beta2 power and higher suicide risk, whereas anxious depression showed altered beta-band functional connectivity, particularly involving left temporal-region connections. Both subtypes shared reduced prefrontal–temporal connectivity. Exploratory classification analyses showed modest discriminative performance after leakage-controlled cross-validation. Associations between beta1 activity and symptom severity were observed only in the anxious subtype. Conclusions Melancholic and anxious depression showed partially distinct beta-band EEG patterns. These findings provide preliminary evidence that beta-band EEG features may capture subtype-related neurophysiological heterogeneity in MDD, with subtype-specific associations between neural activity and symptom severity. Further validation is required before these features can be considered clinically applicable. Trial registration The trial was registered at the Chinese Clinical Trial Registry on 04/23/2022 ( www.chictr.org.cn ChiCTRID ChiCTR2200059053).