Disrupted causal connectivity anchored on the anterior cingulate cortex in first-episode medication-naive major depressive disorder

In recent years, major depressive disorder (MDD) has been demonstrated to be associated with abnormalities in neural networks, particularly the prefrontal-limbic network (PLN). However, there are few current studies that have examined information flow in the PLN. In this study, Granger causality analysis (GCA), based on signed regression coefficient, was used to explore changes in causal connectivity in resting-state PLNs of MDD patients. A total of 23 first-episode medication-naïve MDD patients and 20 normal control participants were subjected to resting-state functional magnetic resonance imaging (RS-fMRI) scans. Increased causal effects of the right insular cortex, right putamen and right caudate on the rostral anterior cingulate cortex (rACC) and reduced causal effects of bilateral dorsolateral prefrontal cortex (DLPFC) and left orbitofrontal cortex (OFC) on the rACC were found in MDD patients compared to normal controls. The extensive reduction in the causal effect of the prefrontal cortex (PFC) demonstrates impaired top-down cognitive control in MDD patients. Changes in the causal relationship between the right insula and rACC suggest problems in coordination of the default mode network by the right anterior insular cortex (rAI). These findings provide valuable insight into MDD-related neural network disorders reported in previous RS-fMRI studies and may potentially guide clinical treatment of MDD in the future.