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

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Major depressive disorder (MDD) is linked to brain structural and functional abnormalities.
• Genetic factors influence MDD, brain anatomy, and function, but the role of gene expression is not fully understood.

Purpose of the Study:

• To investigate the contribution of cortical gene expression to structural and functional brain abnormalities in MDD.
• To identify specific genes related to these brain abnormalities in MDD.

Main Methods:

• Comparison of gray matter volume and resting-state functional measures between 848 MDD patients and 749 healthy controls.
• Association of case-control differences with cortical gene expression variations.
• Analysis of gene expression levels in postmortem cortical tissue from MDD patients.

Main Results:

• Whole gene expression positively correlates with structural abnormalities but negatively with functional abnormalities in MDD.
• Transcriptional correlates of brain structure and function exhibit opposing relationships with gene dysregulation.
• Identified specific genes positively or negatively related to both structural and functional abnormalities.
• MDD-related genes are enriched in brain tissue, cortical cells, and specific biological pathways.

Conclusions:

• Distinct genetic mechanisms underlie structural and functional brain abnormalities in MDD.
• Cortical gene expression plays a crucial role in the development of cortical abnormalities associated with MDD.