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

AbstractAntidepressants 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.

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Reduced Default Mode Network Functional Connectivity in Patients with Recurrent Major Depressive Disorder

10.1101/321745 ◽

2018 ◽

Author(s):

Chao-Gan Yan ◽

Xiao Chen ◽

Le Li ◽

Francisco Xavier Castellanos ◽

Tong-Jian Bai ◽

...

Keyword(s):

Major Depressive Disorder ◽

Functional Connectivity ◽

Depressive Disorder ◽

Default Mode Network ◽

Resting State ◽

Resting State Fmri ◽

Research Groups ◽

Major Depressive ◽

Default Mode ◽

Normal Controls

ABSTRACTMajor Depressive Disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol prior to aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. Finally, all resting-state fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.SIGNIFICANCE STATEMENTFunctional connectivity within the default mode network in major depressive disorder patients has been frequently reported abnormal but with contradicting directions in previous small sample size studies. In creating the REST-meta-MDD consortium containing neuroimaging data of 1,300 depressed patients and 1,128 normal controls from 25 research groups in China, we found decreased default mode network functional connectivity in depressed patients, driven by patients with recurrent depression, and associated with current medication treatment but not with disease duration. These findings suggest that default mode network functional connectivity remains a prime target for understanding the pathophysiology of depression, with particular relevance to revealing mechanisms of effective treatments.

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Abnormality of Resting-State Functional Connectivity in Major Depressive Disorder: A Study With Whole-Head Near-Infrared Spectroscopy

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.664859 ◽

2021 ◽

Vol 12 ◽

Author(s):

Eisuke Sakakibara ◽

Yoshihiro Satomura ◽

Jun Matsuoka ◽

Shinsuke Koike ◽

Naohiro Okada ◽

...

Keyword(s):

Major Depressive Disorder ◽

Prefrontal Cortex ◽

Infrared Spectroscopy ◽

Functional Connectivity ◽

Depressive Disorder ◽

Resting State ◽

Near Infrared ◽

Healthy Controls ◽

Resting State Functional Connectivity ◽

Major Depressive

Near-infrared spectroscopy (NIRS) is a functional neuroimaging modality that has advantages in clinical usage. Previous functional magnetic resonance imaging (fMRI) studies have found that the resting-state functional connectivity (RSFC) of the default mode network (DMN) is increased, while the RSFC of the cognitive control network (CCN) is reduced in patients with major depressive disorder (MDD) compared with healthy controls. This study tested whether the NIRS-based RSFC measurements can detect the abnormalities in RSFC that have been associated with MDD in previous fMRI studies. We measured 8 min of resting-state brain activity in 34 individuals with MDD and 78 age- and gender-matched healthy controls using a whole-head NIRS system. We applied a previously established partial correlation analysis for estimating RSFCs between the 17 cortical regions. We found that MDD patients had a lower RSFC between the left dorsolateral prefrontal cortex and the parietal lobe that comprise the CCN, and a higher RSFC between the right orbitofrontal cortex and ventrolateral prefrontal cortex, compared to those in healthy controls. The RSFC strength of the left CCN was negatively correlated with the severity of depressive symptoms and the dose of antipsychotic medication and positively correlated with the level of social functioning. The results of this study suggest that NIRS-based measurements of RSFCs have potential clinical applications.

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