Altered resting-state functional connectome in major depressive disorder: a mega-analysis from the PsyMRI consortium

Abstract

Major depressive disorder (MDD) is associated with abnormal neural circuitry. It can be measured by assessing functional connectivity (FC) at resting-state functional MRI, that may help identifying neural markers of MDD and provide further efficient diagnosis and monitor treatment outcomes. The main aim of the present study is to investigate, in an unbiased way, functional alterations in patients with MDD using a large multi-center dataset from the PsyMRI consortium including 1546 participants from 19 centers (www.psymri.com). After applying strict exclusion criteria, the final sample consisted of 606 MDD patients (age: 35.8 ± 11.9 y.o.; females: 60.7%) and 476 healthy participants (age: 33.3 ± 11.0 y.o.; females: 56.7%). We found significant relative hypoconnectivity within somatosensory motor (SMN), salience (SN) networks and between SMN, SN, dorsal attention (DAN), and visual (VN) networks in MDD patients. No significant differences were detected within the default mode (DMN) and frontoparietal networks (FPN). In addition, alterations in network organization were observed in terms of significantly lower network segregation of SMN in MDD patients. Although medicated patients showed significantly lower FC within DMN, FPN, and SN than unmedicated patients, there were no differences between medicated and unmedicated groups in terms of network organization in SMN. We conclude that the network organization of cortical networks, involved in processing of sensory information, might be a more stable neuroimaging marker for MDD than previously assumed alterations in higher-order neural networks like DMN and FPN.

Intrinsic Connectivity Networks of Glutamate-Mediated Antidepressant Response: A Neuroimaging Review

“…The SMN closely coordinates with other ICNs and has been implicated in several functions associated with error detection, motor planning and initiation, motor inhibition, the subjective urge to move, experience of bodily awareness and pain, and the fine-tuning of cognitive and executive functions ( 260 – 264 ). Neuroimaging studies have indicated that nodes of the SMN display reduced activity ( 265 , 266 ) and within-network connectivity ( 86 , 88 , 158 , 267 , 268 ) in MDD patients, which has been further supported by a recent mega-analysis ( 269 ). Sensorimotor interventions, such as music, light, tone, and physical exercise, are also well-known to modulate depressive symptoms ( 270 ).…”

“…Impaired top-down control is thought to be attributed to diminished CEN connectivity, which has been seen in depressed individuals at rest ( 64 , 78 – 80 ) and during tasks involving working memory ( 81 ), executive control ( 82 ), and affective interference ( 83 ). Hypoconnectivity within the SMN has been linked with the symptoms of psychomotor retardation ( 84 , 85 ), and several studies have shown this association among patients with MDD ( 30 , 86 – 88 ). A relatively “new” ICN incorporated into the network model is the CAN, which involves the HPT, AMYG, insula, and brainstem nuclei responsible for the control of bodily autonomic responses ( 61 , 89 ).…”

Functional MRI in major depressive disorder: A review of findings, limitations, and future prospects

“…More specifically, hyperconnectivity within the DMN and hypoactivity within the CEN have frequently been observed in reviews and meta‐analyses. Contradictory, a recent mega‐analysis did not find decreases within the CEN and DMN, whereas another reported DMN hypoactivation 21,22 …”

“…Contradictory, a recent megaanalysis did not find decreases within the CEN and DMN, whereas another reported DMN hypoactivation. 21,22 rs-fMRI has also been studied to identify biomarkers of treatment outcome. Increased FC within areas of the DMN such as the posterior cingulate cortex and medial prefrontal cortex (mPFC) and decreased FC within areas of the cognitive control network such as the insula, ACC, and dlPFC have shown to separate antidepressant treatment-resistant from treatment-responsive MDD patients.…”

Decreased modular segregation of the frontal–parietal network in major depressive disorder

“…For example, a prior restingstate fMRI study has documented aberrant connectivity of the FPN with the SN and DMN leads to imbalance of externally attention process and internally self-reference and furthermore gives rise to emotional dysregulation (21). Another study based on meta-analysis reported hyperconnectivity between the SN and DMN is associated with overreaction to negative stimuli, which results in distorted information processing (22). Reduced connectivity between the executive network (EN) and DMN contributes to higher cognitive dysfunction (23).…”