Diagnosis of major depressive disorder using whole-brain effective connectivity networks derived from resting-state functional MRI.

Objective. It is important to improve identification accuracy for possible early intervention of major depressive disorder (MDD). Recently, effective connectivity (EC), defined as the directed influence of spatially distant brain regions on each other, has been used to find the dysfunctional organization of brain networks in MDD. However, little is known about the ability of whole-brain resting-state EC features in identification of MDD. Here, we employed EC by whole-brain analysis to perform MDD diagnosis. Approach. In this study, we proposed a high-order EC network capturing high-level relationship among multiple brain regions to discriminate 57 patients with MDD from 60 normal controls (NC). In high-order EC networks and traditional low-order EC networks, we utilized the network properties and connection strength for classification. Meanwhile, the support vector machine (SVM) was employed for model training. Generalization of the results was supported by 10-fold cross-validation. Main results. The classification results showed that the high-order EC network performed better than the low-order EC network in diagnosing MDD, and the integration of these two networks yielded the best classification precision with 95% accuracy, 98.83% sensitivity, and 91% specificity. Furthermore, we found that the abnormal connections of high-order EC in MDD patients involved multiple widely concerned functional subnets, particularly the default mode network and the cerebellar network. Significance. The current study indicates whole-brain EC networks, measured by our high-order method, may be promising biomarkers for clinical diagnosis of MDD, and the complementary between high-order and low-order EC will better guide patients to get early interventions as well as treatments.