Transcriptional signatures of macroscopic cortical structure alternations in major depressive disorder

The onset and symptoms of Major Depressive Disorder (MDD) are associated with abnormalities in macroscopic brain structure. Revealing the relationship between macroscopic brain structure and microscopic transcriptional signatures could promote the understanding of the pathogenesis of MDD. Here, case-control differences in regional Morphometric Inverse Divergence (MIND) were calculated to measure MDD-related morphometric alternations. The relationship between MIND differences and brain-wide gene expression was further examine. The expression of related genes was spatially correlated with MIND differences. Furthermore, genes correlated with MIND changes showed significant enrichments in inflammation- and metabolism-related processes. Dysregulation of astrocyte, microglia and neuronal cells may be an important factor leading to MDD-related MIND alternations. Collectively, these findings link structural abnormalities and microscopic transcriptional signatures, promoting the understanding of the pathogenesis of MDD.