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

Jian Cui,Xiongying Chen,Rui Liu,Gang Wang,Jingjing Zhou,Zhifang Zhang,Yuan Feng,Yuan Zhou,Yun Wang

doi:10.1038/s41398-021-01754-4

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.

Highlights

Major depressive disorder (MDD) has a high lifetime prevalence nearly up to 20.6% in adults [1], and MDD is regarded as the third non-fatal leading cause of the global burden of disease [2]
We found that the significantly reduced within-subsystem resting-state functional connectivity (rsFC) in the default mode network (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 and medial temporal subsystems in patients with MDD following escitalopram treatment
Our study investigated the effects of escitalopram on the rsFC of the three DMN subsystems in patients with MDD

Summary

Introduction

Major depressive disorder (MDD) has a high lifetime prevalence nearly up to 20.6% in adults [1], and MDD is regarded as the third non-fatal leading cause of the global burden of disease [2]. Antidepressant therapy (i.e., selective 5-HT reuptake inhibitors [SSRIs]) is the first-line treatment for patients with MDD [3]. It is well-known that most antidepressant medications primarily modulate monoaminergic neurotransmitters (such as serotonin [5-HT]), translation of these neurobiological changes into clinically important events remains unclear [4]. Neuroimaging studies in the last decades have found abnormal communications among large-scale brain networks, including the default mode network (DMN), frontoparietal network, and other networks related to emotion or salience processing in patients with MDD [5, 6]. Among the brain networks related to MDD, the DMN draws increasing researchers’ attention in MDD studies. Based on the dataset consisting of 1300 patients with MDD and 1128 healthy controls (HCs) from 25 sites of China, Yan et al [15] found decreased rsFC within the DMN in patients with MDD

Methods

Results

Conclusion