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, this work investigates how cortical gene expression contributes to structural and functional brain abnormalities in MDD. This work compares the gray matter volume and resting‐state functional measures in a Chinese sample of 848 MDD patients and 749 healthy controls, and these case‐control differences are then associated with cortical variation of gene expression. While whole gene expression is positively associated with structural abnormalities, it is negatively associated with functional abnormalities. This work observes the relationships of expression levels with brain abnormalities for individual genes, and found that transcriptional correlates of brain structure and function show opposite relations with gene dysregulation in postmortem cortical tissue from MDD patients. This work further identifies genes that are positively or negatively related to structural abnormalities as well as functional abnormalities. The MDD‐related genes are 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.