Trait and state alterations in excitatory connectivity between subgenual anterior cingulate cortex and cerebellum in patients with current and remitted depression

Neuroimaging studies have indicated that the altered functional connectivity (FC) of the subgenual anterior cingulate cortex (sgACC) might be potential pathophysiology of major depressive disorder (MDD). However, directed connectivity is proven to be more closely to neurophysiological processes underlying brain activity than FC. This study aimed to identify the alterations underlying directed connectivity of the sgACC in patients with current and remitted MDD. We conducted a cross-sectional neuroimaging study by recruiting 36 patients with current MDD, 20 patients with remitted MDD, and 36 matched healthy controls. Multiple linear regression was employed to estimate bidirectional connectivity between bilateral sgACC and 115 brain regions over 230 time points. Besides, graph theory was applied to further investigate the information transfer across bilateral sgACC and abnormal brain regions. We found that both patients with current and remitted MDD showed a similar abnormality in bidirectional excitatory connectivity between the left sgACC and the right cerebellum. Patients with current MDD exhibited an increase in excitatory connectivity from the left cerebellum to the right sgACC, which was positively correlated with the HAMD score. Meanwhile, significantly decreased betweenness of the left sgACC was detected in all depressive patients. Our findings suggest that the changed bidirectional excitatory connectivity between the left sgACC and the right cerebellum might be a trait alteration and the abnormal increased excitatory connectivity from the left cerebellum to the right sgACC might be a state alteration of MDD. This work may provide a valuable contribution to identify trait and state alterations in the brain for depression.