Increased brain nucleus accumbens functional connectivity in melancholic depression

Background: Melancholic depression, marked by typical symptoms of anhedonia, is regarded as a homogeneous subtype of major depressive disorder (MDD). However, little attention was paid to underlying mechanisms of melancholic depression. This study aims to examine functional connectivity of the reward circuit associated with anhedonia symptoms in melancholic depression. Methods: Fifty-nine patients with first-episode drug- naive MDD, including 31 melancholic patients and 28 nonmelancholic patients, were recruited and underwent resting-state functional magnetic resonance imaging (rsfMRI). Thirty-two healthy volunteers were recruited as controls. Bilateral nucleus accumbens (NAc) were selected as seed points to form functional NAc network. Then support vector machine (SVM) was used to distinguish melancholic patients from non-melancholic patients. Results: Relative to non-melancholic patients, melancholic patients displayed increased functional connectivity (FC) between bilateral NAc and right middle frontal gyrus (MFG) and between right NAc and left cerebellum lobule VIII. Compared to healthy controls, melancholic patients showed increased FC between right NAc and right lingual gyrus and between left NAc and left postcentral gyrus; non-melancholic patients had increased FC between bilateral NAc and right lingual gyrus. No significant correlations were observed between altered FC and clinical variables in melancholic patients. SVM results showed that FC between left NAc and right MFG could accurately distinguish melancholic patients from non-melancholic patients. Conclusion: Melancholic depression exhibited different patterns of functional connectivity of the reward circuit relative to non-melancholic patients. This study highlights the significance of the reward circuit in the neuropathology of melancholic depression.