Analysis of individualized brain–gut association networks and transcriptional patterns in major depressive disorder

Abstract

The brain‒gut association patterns in major depressive disorder (MDD) and in MDD with suicidal ideation (MDDSI) remain largely unknown. This study included 118 healthy controls and 118 first‐episode, drug‐naive adolescents and young adults with MDD, including 60 MDDSI patients and 58 MDD patients without SI. First, a novel network for investigating individualized brain‒gut associations is proposed based on the algorithm of node importance coupling. Second, the graph convolutional network is applied at the individual level to identify MDD and MDDSI patients, and the GNNExplainer algorithm is used to determine key brain–gut connections. Third, analyses of transcriptional patterns and pathways are conducted to reveal multilevel brain‒gut association characteristics in MDD and MDDSI. The results suggested that associations between proinflammatory gut microbiota and the herpes simplex virus type 1 infection pathway may contribute to the onset of MDD through inflammatory processes. Furthermore, associations between the sulfur metabolism pathway and the insulin signaling pathway may be related to alterations in insulin metabolism and to the significantly increased C‐peptide levels observed in MDDSI patients. Notably, C‐peptide levels were positively correlated with SI. These findings may provide new insights into the potential neuropathological mechanisms of multilevel brain‒gut associations in MDD and MDDSI.