Transcriptional and Cellular Signatures of Morphometric Similarity Remodeling in Major Depressive Disorder

Little is known about how major depressive disorder (MDD)-related anatomical endophenotypes are driven by transcriptomic profiles. Here, we examined a link between brain-wide gene expression and morphometric similarity (MS) remodeling in two MDD samples. MDD exhibited replicable abnormal MS patterns compared to healthy controls. Using spatially-comprehensive cortical gene expression data, we further identified two types of transcriptional signatures of MS remodeling: i) gene specificity, in which closely linked transcriptionally upregulated genes from postmortem samples in MDD, but not in other brain disorders, were spatially correlated with MDD MS remodeling; and ii) ontological enrichment, which identified reliable neurobiologically-relevant ontology terms and pathways previously described in MDD. Finally, we assigned transcriptional signatures to cell-types, which specified microglia and neurons as contributing most to the transcriptomic relationship of MS remodeling in MDD. Collectively, combined gene transcripts and connectome topology provided insight into how microscale genetic molecular mechanisms cause mesoscale morphometric abnormalities in MDD.

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