Disrupted Causal Connectivity Anchored on the Right Anterior Insula in Drug-Naive First-Episode Patients With Depressive Disorder

OBJECT: Major depressive disorder (MDD) has been demonstrated to be associated with abnormalities in neural networks. However, few studies examined information flow in the salience network (SN). This study examined abnormalities in the causal connectivity between the SN and whole brain in drug-naive first-episode patients with MDD in the resting state. METHODS: Based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria, 23 drug-naive first-episode MDD patients and 20 matched healthy individuals were recruited and underwent a resting-state magnetic resonance scan. The acquired functional image data were preprocessed using resting-state functional magnetic resonance imaging (rs-fMRI) data analysis toolkit plus (RESTplus). Then, using the data processing & analysis for brain imaging (DPABI) software and a coefficient-based general component analysis method with the right anterior insula (rAI) as the region of interest (ROI), the causal connectivity of the SN with the whole brain and its correlation with cognitive and mental performance were examined in the resting state. RESULTS: (1) The MDD group showed a significantly higher Hamilton Depression Rating Scale total score and significantly higher scores for anxiety, cognitive disturbance, and block factors compared with normal controls. (2) Compared with control: from whole brain to the rAI, the MDD group showed a lower causal connectivity in the left inferior frontal gyrus; from the rAI to the whole brain, the MDD group showed a lower causal connectivity in the right cingulate gyrus, the right precuneus, and extending to paracentral lobule but higher causal connectivity in the left inferior and middle frontal gyrus. (3) In the MDD group, from rAI to the whole brain, the causal connectivity values for the right cingulate gyrus/precuneus were negatively correlated with the score of Stroop Color-Word Test A, B, and C as well as interference times. CONCLUSION: Our results indicated disrupted causal connectivity among the default mode network (DMN), the central executive network (CEN), and SN in drug-naive first-episode MDD patients. Especially, our results suggest a unique role for rAI in the ordered or hierarchical information processing, presumed to include bottom-up and top-down reciprocal influences among the three networks in MDD.