Transcriptional Substrates Of Brain Structural And Functional Impairments In Drug-naive First-episode Patients With Major Depressive Disorder

Background: There is evidence that patients with major depression disorder(MDD)are often accompanied by changes in brain structure and function.Nevertheless,little is known regarding the transcriptional substrates underlying certain disease phenotypes.The purpose of this study is to explore transcriptional substrates of brain structural and functional impairments in drug-naive first-episode patients with major depressive disorder(DF-MDD).Methods: Comprehensive and systematic multi-modal neuroimaging meta-analyses were conducted to examine changes in brain structure(GMV)and function(Re Ho,ALFF and f ALFF)in DF-MDD.Gene expression data from the AHBA were processed using a standardized pipeline.Combined with the AHBA,transcriptome-neuroimaging spatial association analyses were performed to identify genes whose expression related to these brain structural and functional changes,followed by a range of gene functional signature analyses.Results: Meta-analyses revealed gray matter atrophy in the insula,temporal pole,cerebellum and postcentral gyrus,and a complex pattern of hyper-function in the temporal pole and hypo-function in the cuneus/precuneus,angular gyrus and lingual gyrus in DF-MDD.Moreover,these brain structural and functional changes were spatially associated with expression of 1194(hub gene 44)and 1733(hub gene 73)genes,respectively.Importantly,there were commonalities and differences in the two gene sets and their functional signatures including functional enrichment,specific expression,behavioral relevance,and constructed protein-protein interaction networks.Conclusion: This study not only corroborate the polygenic nature of MDD,but also suggest common and distinct genetic modulations of brain structural and functional impairments in this disorder.