Brain connectomic and transcriptional signatures of suicidal thoughts and behaviors in major depressive disorder

Motivation: Suicide-related connectomic signatures in depression and underlying transcriptional patterns have been poorly understood, most previous findings were limited by small-sample and single-site design. Goal(s): To identify robust brain structural network deficits associated with suicidal thoughts and behaviors (STB) in major depressive disorder (MDD) and to determine related transcriptional profiles. Approach: Based on mutlicenter MRI data of over 700 individuals, group-level connectomic comparisons and connectome-transcriptome association were analyzed. Results: Robust structural connectomic alterations associated with STB in MDD were distributed in the prefrontal, limbic and temporal areas. STB-related connectomic alterations were spatially correlated with genes enriched for cellular metabolism and synaptic signaling. Impact: These findings reveal a robust pattern of brain structural deficits at network level and demonstrate its linkage to gene expression patterns, which provides novel insights into the neurobiological underpinnings and potential markers for prediction and prevention of STB.