Gene Expression has Distinct Associations with Brain Structure and Function in Major Depressive Disorder

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.

Differential gene expression analysis pipelines and bioinformatic tools for the identification of specific biomarkers: A review

“…While FDR offers a balance between discovery and reliability [73] , Bonferroni's method is more conservative and reduces the risk of false positives [74] . To avoid a high number of false positives, it is necessary to correct for multiple testing and select the DEGs, setting a cutoff on the adjusted p-value [75] . Furthermore, the l2FC can be used to rank the genes more representative of differences between two experimental conditions [76] .…”

Locus Coeruleus‐Dorsolateral Septum Projections Modulate Depression‐Like Behaviors via BDNF But Not Norepinephrine

“…Major depressive disorder (MDD) is a common, costly, and debilitating mental health disorder that is tied to an increased suicide risk around the world. [ 1 , 2 , 3 , 4 ] In spite of significant progress, most current treatments for depression are ineffective and cause intolerable side effects. [ 5 , 6 , 7 ] A deeper understanding of depression's pathophysiology and the development of novel treatments is needed.…”