Gene Expression has Distinct Associations with Brain Structure and Function in Major Depressive Disorder. Issue 7 (13th January 2023)

• Record Type: Journal Article
• Authors: Liu, Shu; Abdellaoui, Abdel; Verweij, Karin J. H.; van Wingen, Guido A.
• Is Part Of: Advanced science. Volume 10:Issue 7(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-01-13
• Subjects: brain function -- brain structure -- gene expression -- major depressive disorder; Science -- Periodicals; 505
• DOI: 10.1002/advs.202205486
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: 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. Abstract : This paper investigates brain abnormalities in MDD, and observes opposite relationships of structural and functional abnormalities with gene expression in both Asian and European populations. Moreover, the transcriptional correlates of brain abnormalities show significant correlations with gene dysregulation in postmortem tissue samples from MDD patients. These findings suggest that distinct genetic mechanisms underlie brain abnormalities.