Habenula and left angular gyrus circuit contributes to response of electroconvulsive therapy in major depressive disorder

The habenula (Hb), one of the hottest structures in depression, has been widely demonstrated to be involved in the neurobiology of depression. Although the structural and functional abnormalities of Hb have been reported in major depressive disorders (MDD) patients, the role of Hb in treatment response in MDD remains unclear. In this study, resting-state functional connectivity (RSFC) and Granger causality analysis (GCA) were performed to investigate the intrinsic and causal changes of Hb in MDD after ECT. Moreover, support vector classification was applied to find out whether the changed functional and causal connections of Hb can effectively distinguish the MDD patients from healthy controls. The RSFC and GCA identified increased RSFC strength between bilateral Hb and left angular gyrus (AG), decreased causal connectivity strength from left AG to left Hb, from right Hb to left AG, and bidirectional interactions between left and right Hb in MDD patients after ECT. The changed causal connectivities from left AG to left Hb, and from right Hb to left AG were correlated with the changed depression symptoms and impaired delay memory recall performances. Furthermore, the functional and causal connectivities between left AG and bilateral Hb could serve as a biomarker to differentiate MDD from HCs. These results provided new evidence for the importance of Hb in depression and revealed that the interactions between Hb and left AG contribute to ECT response in MDD. Our findings will facilitate the future treatment of depression with the target of Hb in MDD and other brain disorders.