Altered electroencephalographic microstate dynamics in major depressive disorder and their modulation by melatonergic treatment

Background: The modulation of brain dynamics by melatonin antidepressants in patients with major depressive disorder (MDD) remains unclear. Methods: Resting-state electroencephalographic (EEG) was recorded in 84 drug-free patients with MDD and 143 healthy controls. EEG data were collected at baseline and after 8-week agomelatine treatment. K-means clustering identified four canonical microstates (MS-A-D), and topographic analysis of variance assessed group differences. Results: At baseline, patients with MDD showed increased occurrence and coverage of MS-C and MS-D, along with a higher transition probability between these two states, compared to healthy controls. In contrast, the duration and coverage of MS-A and MS-B, as well as their transition probabilities, were reduced in the MDD group. Following treatment, patients with MDD exhibited increased MS-A coverage and a higher transition probability from MS-A to MS-B, while the transition probability between MS-C and MS-D decreased. Several microstate parameters were normalized to those of healthy controls. Notably, MS-B occurrence negatively correlated with baseline anhedonia severity, although no microstate measures predicted changes in anhedonia over time. Conclusions: This study demonstrates altered EEG microstate dynamics in patients with MDD and provides insights into the neural mechanisms underlying MDD. Microstate abnormalities may serve as potential clinical biomarkers for MDD.