EEG microstate alterations in psychotic depression: prolonged microstate C duration and associations with psychotic symptoms.

Abstract

Background: Major Depressive Disorder with psychotic features (MDD-Psy) represents a severe clinical subtype with distinct psychopathology, yet its underlying large-scale brain network dynamics, as measured by resting-state EEG microstates, remain poorly characterized.

Methods: We compared 68 patients with MDD-Psy and 63 patients with MDD without psychotic features (MDD-NonPsy). Clinical assessment included the Kangduo Antidepressant Scale (KDAS) and the Brief Psychiatric Rating Scale (BPRS). Resting-state EEG microstate parameters (duration, time coverage, occurrence, and transition probabilities) were analyzed. Group comparisons employed Mann-Whitney U/t-tests with False Discovery Rate (FDR) correction. Correlations between microstate alterations and psychotic symptom severity were assessed using Spearman's rank correlation with FDR correction.

Results: The groups were comparable in age and sex. The MDD-Psy group exhibited significantly greater severity in thought disturbance, activation, and hostility (all p < 0.001). EEG microstate analysis revealed a significantly prolonged median duration of microstate C, putatively associated with salience-network-related activity in MDD-Psy (91.99 ms) versus MDD-NonPsy (85.56 ms; p-corr = 0.004). Altered transition probabilities characterized MDD-Psy, including increased B→A but decreased B→C and C→A transitions (all p-corr < 0.05). Furthermore, in the combined sample, the duration of microstate C positively correlated with thought disturbance (ρ = 0.243, p-FDR = 0.030), while the reduced B→C transition probability was strongly negatively correlated with both thought disturbance (ρ=-0.393, p-FDR < 0.001) and hostility.

Conclusions: Within patients with major depressive disorder, the psychotic subtype is associated with a distinct pattern of aberrant resting-state brain network dynamics relative to the non-psychotic subtype, characterized by prolonged microstate C duration, commonly linked to salience network dynamics and reconfigured temporal transitions between the salience, visual, and auditory networks. The altered visual-to-salience network transition (B → C) demonstrated the most robust association with core psychotic symptom dimensions, including thought disturbance and hostility. These findings suggest that dysregulated dynamic coupling between perceptual processing and salience evaluation may represent a candidate neurophysiological indicator of psychotic features in depression. However, these results should be considered hypothesis-generating preliminary: the high rate of antipsychotic medication use in the MDD-Psy group, the absence of a healthy control group, and the cross-sectional design preclude tentative causal or specificity claims. Future longitudinal studies incorporating medication-naïve patients, healthy controls, and complementary neurophysiological markers are required to validate the clinical utility of these microstate alterations.

Clinical trial number: Not applicable.