Abnormal core functional connectivity on the pathology of MDD and antidepressant treatment: A systematic review

Rationale/importance: Researches have highlighted communication deficits between resting-state brain networks in major depressive disorder (MDD), as reflected in abnormal functional connectivity (FC). However, it is unclear whether impaired FC is associated with MDD pathology or is simply incidental to MDD symptoms. Moreover, there is no generalized theory to analyze the impact of treatment modalities on MDD. Objectives: To address the issues, we conducted a systematic review of 49 eligible papers to provide insight into the pathological mechanisms of MDD patients by summarizing resting-state FC alterations involving mood and cognitive abnormalities and the effects of medications on them. Results: Mood disorders in MDD were characterized by abnormal FC between the amygdala, insula, anterior cingulate cortex (ACC), and prefrontal cortex (PFC). Cognitive impairment manifests as deficits in executive function, attention, memory, and rumination, primarily modulated by dysfunction between the fronto-parietal network and default mode network. Especially, we proposed the set of core abnormal FC (CA-FC) contributing to mood and cognitive impairment in MDD, currently including ACC-left precuneus/amygdala, rostral ACC-left dorsolateral PFC, left subgenual ACC-left cerebellar, left PFC- anterior subcallosal, and left precuneus-left pulvinar. After treatment, patients with normalized CA-FC showed remission of depressive symptoms. Conclusions: We propose a CA-FC set for possible causative principle of MDD, which unifies the FC results from specific, difficult-to-analyze conditions into one outcome set for screening. Furthermore, CA-FC varies from person to person, and the low success rate of a single treatment may be due to the inability to cover too many CA-FC.