Gene expression has distinct associations with brain structure and function in major depressive disorder

Major depressive disorder (MDD) is associated with structural and functional brain abnormalities. MDD as well as brain anatomy and function are influenced by genetic factors, but the role of gene expression remains unclear. Here we investigated how cortical gene expression contributes to structural and functional brain abnormalities in MDD. We compared the gray matter volume and resting-state functional measures in a Chinese sample of 848 MDD patients and 749 healthy controls, and we then associated these case-control differences with cortical variation of gene expression. While whole gene expression was positively associated with structural abnormalities, it was negatively associated with functional abnormalities. We observed the relationships of expression levels with brain abnormalities for individual genes, and found that transcriptional correlates of brain structure and function showed opposite relations with gene dysregulation in postmortem cortical tissue from MDD patients. We further identified genes that were positively or negatively related to structural abnormalities as well as functional abnormalities. The MDD-related genes were enriched for brain tissue, cortical cells, and biological pathways. These findings suggest that distinct genetic mechanisms underlie structural and functional brain abnormalities in MDD, and highlight the importance of cortical gene expression for the development of cortical abnormalities.