Linking symptom dimensions to whole-brain functional connectivity of the cerebellar posterior vermis in major depressive disorder

There is a critical need to enhance the therapeutic outcomes for major depressive disorder (MDD). Recent studies have found that the cerebellum is deeply involved in cognitive and emotional functions, with the cerebellar posterior vermis (postVermis), in particular, being a key brain region underlying various symptoms of MDD and a potential target for antidepressant treatment. This study aims to analyze alterations in functional connectivity (FC) between the postVermis and various brain regions in MDD, as well as the relationship between these FC abnormalities and the diverse symptoms of MDD. This study included thirty-six MDD patients and thirty-two healthy controls (HCs). Using the postVermis as the seed region, whole-brain FC analysis was conducted to compare differences between the two groups. Furthermore, the relationship between the strength of abnormal FC and scores on psychological assessment scales was investigated in the MDD group. Compared to HCs, MDD patients exhibited increased FC strength from the postVermis to multiple widely distributed brain regions. Within the MDD group, the strength of FC from the postVermis to the right inferior temporal gyrus, left inferior orbital prefrontal gyrus, right Rolandic operculum, right inferior frontal gyrus (triangular part), left angular gyrus, and right cuneus was negatively correlated with scales scores assessing depressive mood, anxious mood, hopelessness, and sleep quality. This study found a compensatory enhancement of FC from the postVermis to multiple widely distributed brain regions in MDD. A higher level of this compensation was associated with milder symptoms, suggesting that the postVermis is a potential target for antidepressant treatment.