Aberrant topology of the default mode network is associated with phosphatidylcholine and triglyceride levels in major depressive disorder

Abstract

BACKGROUND

The default mode network (DMN) is associated with lipid metabolism. Patients with major depressive disorder (MDD) exhibit concurrent abnormal topological properties of the DMN and dysregulated lipid metabolism. However, there are no studies investigating the mechanisms underlying the associations between these two variables in patients with MDD.

AIM

To investigate the association between abnormal topological properties of the DMN and dysregulated lipid metabolism in patients with MDD.

METHODS

There were 147 participants, including 71 patients with MDD and 76 healthy controls. The 17-item Hamilton Depression Rating Scale (HAMD-17) was used to assess depression severity. Graph theoretical analysis was employed to compare group differences in the topological properties of the DMN across the following bilateral regions: the superior medial frontal gyrus, superior orbital frontal gyrus, posterior cingulate gyrus, parahippocampal gyrus, supramarginal gyrus (SMG), angular gyrus, precuneus, and middle temporal gyrus. Lipidomic techniques were employed to obtain lipid profiles, and orthogonal partial least squares discriminant analysis was performed to compare group differences in lipid profiles. Partial correlation analysis was performed between the abnormal topological properties of the DMN, HAMD-17 scores, and differential lipids.

RESULTS

Abnormal topological properties were observed in the MDD group in the following DMN regions: The right superior medial frontal gyrus (SFGmed.R), right posterior cingulate gyrus, left SMG, right SMG, and left angular gyrus. The betweenness centrality, degree centrality, and efficiency of the SFGmed.R were positively correlated with HAMD-17 scores, whereas the shortest path was negatively correlated with HAMD-17 scores. The betweenness centrality of the left SMG was positively correlated with HAMD-17 scores. The betweenness centrality of the SFGmed.R was positively correlated with phosphatidylcholine O-34:3 and triglyceride O-8:0_18:3_18:5 levels.

CONCLUSION

SFGmed.R is a crucial node within the DMN in MDD patients, and the betweenness centrality of the SFGmed.R is associated with phosphatidylcholine and triglyceride levels. These results may offer novel clues for exploring the pathophysiology and biomarker identification of MDD.

Keywords: Default mode network; Major depressive disorder; White matter; Lipids; Topological properties

Core Tip: The default mode network (DMN) is associated with lipid metabolism. Patients with major depressive disorder (MDD) exhibit abnormalities in the topological properties of the DMN and dysregulation in lipid metabolism. Our study investigated the association between the abnormal topological properties of the DMN and dysregulated lipid metabolism in MDD, revealing that the betweenness centrality of the right superior medial frontal gyrus is associated with phosphatidylcholine and triglyceride. The results may offer novel clues for exploring MDD pathophysiology and biomarker identification.