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

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.

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.

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.

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.

Not applicable.