EEG microstates as markers of major depressive disorder and predictors of response to SSRIs therapy

Major depressive disorder (MDD) is associated with abnormal neural activities and brain connectivity. EEG microstate is a voltage topology map that reflects transient activations of the brain network. A limited number of studies on EEG microstate in MDD have focused on differences between patients and healthy controls. However, EEG microstate changes in MDD patients before and after drug treatment have not been evaluated. We assessed EEG microstate characteristics and evaluated changes in brain network dynamics in MDD patients before and after drug treatment. Moreover, we evaluated the neuro-electrophysiological mechanisms of antidepressant therapies. 64-channel resting EEG was obtained from 101 patients with first-episode untreated depression (0 week) and 45 healthy controls (HC) from January to December 2020. MDD patients were treated with selective serotonin reuptake inhibitors (SSRI). EEG data for 51 MDD patients who had completed an 8-week follow-up was collected. After pre-processing, EEG data from different groups were subjected to microstate analysis, and the atomize and agglomerate hierarchical clustering (AAHC) was into 4 microstates. Next, EEG signals from each patient were fitted using templates of 4 microstates. Finally, microstate indices were collected and analyzed. Global clustering generated 4 microstates (A, B, C, D) in all subjects, which explained 65–84% of the global variance. Compared to HC, the duration of microstate D reduced while those of microstates A and B increased in MDD patients. After the 8-week treatment period, the duration and coverage of microstate D increased, the frequency of microstate A and transition probability of microstate D to A reduced, while transition probability of microstate B to D and D to B increased in MDD patients. There were no differences in microstate features between HC and MDD at 8 weeks. In patients with first-episode untreated depression, lower average durations of microstate D, relatively higher frequencies of microstate C and lower transition probabilities of microstate D to B correlated with better effects after 8 weeks. The higher occurrence and proportion of microstate C at 8 weeks was positively correlated with the HAMD score and reduction rate. The same observation was reached for the transition probability of microstate A to C. However, the transition probability of microstate D to B showed a negative correlation with the HAMD score at 8 weeks. Microstate D is a potential electrophysiological trait of MDD and can predict treatment outcomes of SSRIs. Therefore, EEG microstate analysis may not only be an objective method for evaluating treatment outcomes of depression, but is also a potential new approach for exploring the neuro-electrophysiological mechanisms of antidepressant therapy. Public title: Multidimensional diagnosis, individualized treatment and management techniques based on clinic-pathological characteristics of depressive disorder; Registration number: ChiCTR1900026600; Date of registration: 2019-10-15; URL: http://www.chictr.org.cn/index.aspx