Transcriptional Patterns of Nodal Entropy Abnormalities in Major Depressive Disorder Patients with and without Suicidal Ideation

Previous studies have indicated that major depressive disorder (MDD) patients with suicidal ideation (SI) present abnormal functional connectivity (FC) and network organization in node-centric brain networks, ignoring the interactions among FCs. Whether the abnormalities of edge interactions affect the emergence of SI and are related to the gene expression remains largely unknown. In this study, resting-state functional magnetic resonance imaging (fMRI) data were collected from 90 first-episode, drug-naive MDD with suicidal ideation (MDDSI) patients, 60 first-episode, drug-naive MDD without suicidal ideation (MDDNSI) patients, and 98 healthy controls (HCs). We applied the methodology of edge-centric network analysis to construct the functional brain networks and calculate the nodal entropy. Furthermore, we examined the relationships between nodal entropy alterations and gene expression. The MDDSI group exhibited significantly lower subnetwork entropy in the dorsal attention network (DAN) and significantly greater subnetwork entropy in the default mode network than the MDDNSI group. The visual learning score of the measurement and treatment research to improve cognition in schizophrenia (MATRICS) consensus cognitive battery was negatively correlated with the subnetwork entropy of DAN in the MDDSI group. The support vector machine model based on nodal entropy achieved an accuracy of 81.87% when distinguishing the MDDNSI and MDDSI. Additionally, the changes in SI-related nodal entropy were associated with the expression of genes in cell signaling and interactions, as well as immune and inflammatory responses. These findings reveal the abnormalities in nodal entropy between the MDDSI and MDDNSI groups, demonstrated their association with molecular functions, and provided novel insights into the neurobiological underpinnings and potential markers for the prediction and prevention of suicide.