Reduced nucleus accumbens functional connectivity in reward network and default mode network in patients with recurrent major depressive disorder

Abstract

The nucleus accumbens (NAc) is considered a hub of reward processing and a growing body of evidence has suggested its crucial role in the pathophysiology of major depressive disorder (MDD). However, inconsistent results have been reported by studies on reward network-focused resting-state functional MRI (rs-fMRI). In this study, we examined functional alterations of the NAc-based reward circuits in patients with MDD via meta- and mega-analysis. First, we performed a coordinated-based meta-analysis with a new SDM-PSI method for all up-to-date rs-fMRI studies that focused on the reward circuits of patients with MDD. Then, we tested the meta-analysis results in the REST-meta-MDD database which provided anonymous rs-fMRI data from 186 recurrent MDDs and 465 healthy controls. Decreased functional connectivity (FC) within the reward system in patients with recurrent MDD was the most robust finding in this study. We also found disrupted NAc FCs in the DMN in patients with recurrent MDD compared with healthy controls. Specifically, the combination of disrupted NAc FCs within the reward network could discriminate patients with recurrent MDD from healthy controls with an optimal accuracy of 74.7%. This study confirmed the critical role of decreased FC in the reward network in the neuropathology of MDD. Disrupted inter-network connectivity between the reward network and DMN may also have contributed to the neural mechanisms of MDD. These abnormalities have potential to serve as brain-based biomarkers for individual diagnosis to differentiate patients with recurrent MDD from healthy controls.

Fig. 1. Group differences of meta-analysis.

Compared with healthy controls, patients with recurrent MDD exhibited decreased NAc functional connectivity in the left ventromedial prefrontal cortex.

Fig. 2. Results of mega-analysis.

A The significant between-group differences in the NAc functional connectivity. B The box figures show the distribution of significantly disrupted bilateral NAc functional connectivity in the group comparison. Fusi fusiform gyrus, HC healthy control, L left, NAc nucleus accumbens, PHa parahippocampal gyrus, R right, Re recurrent major depressive disorder, ITG inferior temporal gyrus, VTA ventral tegmental area.

Fig. 3. Visualization of classification by SVM analyses.

A The accuracy, sensitivity, and specificity of the classifications of patients with recurrent MDD versus HCs using all significant NAc FCs as features or using significant NAc FCs within the reward network as features. B Parameter selection result for training set when using (1) all significant NAc FCs as features and (2) using significant NAc FCs within the reward network as features. FC functional connectivity, HC healthy controls, MDD major depressive disorder, NAc nucleus accumbens, SVM support vector machine.