A potential biomarker of varying severity in patients with first-episode drug-naïve depressive disorder: Evidence from the alteration of EEG microstates.

BACKGROUND

Depressive disorder (DD) is a heterogeneous disease, and the dynamic of the electroencephalogram (EEG) changes associated with different severities DD remain unclear. Identifying objective biomarkers of disease severity can improve treatment strategies.

METHODS

This cross-sectional study enrolled 117 first-episode drug-naïve DD patients and 36 demographically matched healthy controls (HC). Depressive symptoms were assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17), with patient stratification into mild-to-moderate (MMDD) group and severe (SDD) group based on HAMD-17. Resting-state EEG was analyzed using atomic agglomerative hierarchical clustering, identifying four typical microstates (A-D). Microstate parameters were compared across groups and correlated with the four-factor structure of HAMD-17.

RESULTS

Compared to HC, patients with MMDD and SDD exhibited reduced duration and contribution of microstate A, as well as elevated occurrence and contribution of microstate C, reflecting deficits in emotional regulation and negative cognitive processing. Additionally, participants in the SDD group exhibited a significantly prolonged microstate D duration compared with those in the MMDD group, suggesting a progression from insufficient frontoparietal network activation in MMDD to compensatory hyperactivation in SDD to meet higher emotional and cognitive demands. Microstate transition analysis further revealed reduced brain-state transitions flexibility with increasing depression severity. Notably, microstate D duration negatively correlated with HAMD-17 somatic factor scores, implying its compensatory role in addressing somatic symptoms and mitigating emotional and cognitive impairments.

CONCLUSIONS

These findings support the potential use of EEG microstates, especially C and D, as neurobiological markers for identifying DD severity and guiding early diagnosis and treatment strategies.