Effects of escitalopram therapy on resting-state functional connectivity of subsystems of the default mode network in unmedicated patients with major depressive disorder

Abstract

Antidepressants are often the first-line medications prescribed for patients with major depressive disorder (MDD). Given the critical role of the default mode network (DMN) in the physiopathology of MDD, the current study aimed to investigate the effects of antidepressants on the resting-state functional connectivity (rsFC) within and between the DMN subsystems. We collected resting-state functional magnetic resonance imaging (rs-fMRI) data from 36 unmedicated MDD patients at baseline and after escitalopram treatment for 12 weeks. The rs-fMRI data were also collected from 61 matched healthy controls at the time point with the same interval. Then, we decomposed the DMN into three subsystems based on a template from previous studies and computed the rsFC within and between the three subsystems. Finally, repeated measures analysis of covariance was conducted to identify the main effect of group and time and their interaction effect. We found that the significantly reduced within-subsystem rsFC in the DMN core subsystem in patients with MDD at baseline was increased after escitalopram treatment and became comparable with that in the healthy controls, whereas the reduced within-subsystem rsFC persisted in the DMN dorsal medial prefrontal cortex (dMPFC) and medial temporal subsystems in patients with MDD following escitalopram treatment. In addition, the reduced between-subsystem rsFC between the core and dMPFC subsystem showed a similar trend of change after treatment in patients with MDD. Moreover, our main results were confirmed using the DMN regions from another brain atlas. In the current study, we found different effects of escitalopram on the rsFC of the DMN subsystems. These findings deepened our understanding of the neuronal basis of antidepressants' effect on brain function in patients with MDD. The trial name: appropriate technology study of MDD diagnosis and treatment based on objective indicators and measurement. URL: http://www.chictr.org.cn/showproj.aspx?proj=21377 . Registration number: ChiCTR-OOC-17012566.

Fig. 1. Default mode network subsystems.

Panel A shows spatial distributions of the three subsystems of the default mode network from Yeo’s template [54, 55]. Brain regions painted in yellow belong to the core subsystem; brain regions painted in blue belong to the dMPFC subsystem, and brain regions painted in red belong to the MTL subsystem. Panels of B show the lower triangular of the averaged functional connectivity matrices among 24 ROIs of the default mode network in the healthy controls and the patients with MDD at baseline and after 12 weeks. The color bar represents functional connectivity strength. Panel C shows the result of hierarchical clustering analysis for the connectivity matrix of the healthy controls at baseline, which were consistent with Yeo’s default mode subsystems. The meaning of the color of the number is the same as those in Panel A. See Table S2 for the meaning of numbers.

Fig. 2. The interaction effect and main effect on the rsFC within and between the DMN subsystems.

Panel A summarizes the interaction effect and main effect within and between the DMN subsystems. Panel B shows the significant interaction effect on the within-subsystem rsFC of the core subsystem and the between-subsystem rsFC of the core and dMPFC subsystem using violin plots. Panel C shows the significant group main effect on the within-subsystem rsFC in the dMPFC and MTL subsystems using violin plots. **P-values < 0.01; *P-values < 0.05 for post hoc analyses.

Fig. 3. The interaction effect on the ROI-to-ROI rsFC.

The ROI regions painted in yellow belong to the core subsystem; the ROI regions painted in blue belong to the dMPFC subsystem, and the ROI regions painted in red belong to the MTL subsystem.