Altered effective connectivity among reward network and triple network in patients with melancholic depression and...

Melancholic depression has more severe clinical manifestations, and its mechanism remains unclear. The deficit of reward network (RN) has been reported to be strongly related to anhedonia of melancholic depression. The triple network, including the default-mode network (DMN), executive control network (ECN), and salience network (SN), was found to exhibit abnormal functional coupling across many mental processes. Whether activities of the RN and its connectivity with the triple network could affect emotional symptoms in melancholic depression is worth exploring.

59 outpatients with first-episode, drug-naïve major depressive disorder (31 melancholic, 28 non-melancholic) and 32 healthy controls were enrolled for resting-state functional magnetic resonance imaging to evaluate the effective connectivity (EC) by using spectral dynamic causal modeling approach. Utilizing the Allen Human Brain Atlas, transcriptome-neuroimaging analysis was applied to identify EC-related gene expression profiles.

Compared with non-melancholic group, there were both increased and decreased ECs between these networks in melancholic group. From network perspective, increased and excitatory ECs were observed from RN to ECN, from ECN to DMN and SN. RN-related PLS1 genes in melancholic patients were related to several biological functions. Pathway enrichment analysis revealed their involvement in the MAPK signaling pathways.

Our findings indicated that the primary mechanism of melancholic depression may involve disrupted functional interactions between the RN and large-scale brain networks, rather than abnormalities confined to isolated intra-network. Besides, our findings revealed correlations between these EC patterns in RN and gene expression profiles, which shed light on the potential genetic mechanisms underlying melancholic depression.