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Transcriptomic decoding of regional cortical vulnerability to major depressive disorder.
Jiajia Zhu1,2,3, Xiao Chen4,5,6,7, Bin Lu4,5,6,7
1Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
Communications Biology
|August 8, 2024
Summary
This study reveals how genetic risk for major depressive disorder (MDD) impacts brain structure and function. It links specific gene categories to cortical changes, offering insights into MDD
Area of Science:
- Neuroscience
- Psychiatry
- Genetics
Background:
- Cortical abnormalities in major depressive disorder (MDD) are inconsistently reported in small studies.
- The translation of genetic risk for MDD into spatially patterned cortical vulnerability remains unclear.
Purpose of the Study:
- To investigate voxel-wise differences in cortical function and structure in a large cohort of MDD patients.
- To identify gene categories associated with cortical changes in MDD using transcription-neuroimaging spatial correlation and gene enrichment analysis.
Main Methods:
- Utilized multi-modal MRI data from 1660 MDD patients and 1341 controls.
- Employed Allen Human Brain Atlas for analysis.
- Applied transcription-neuroimaging spatial correlation and ensemble-based gene category enrichment analysis.
Main Results:
- MDD patients exhibited circumscribed local functional impairments and widespread global functional connectivity disruptions.
- Functional alterations included hyper-function in associative areas and hypo-function in primary regions.
- Local functional changes correlated with genes related to MDD biological functions (e.g., endoplasmic reticulum stress, MAPK signaling).
- Global connectivity changes associated with MDD-general and brain-specific genes (e.g., neuronal, glial, neurotransmitter pathways).
Conclusions:
- Findings provide insights into the transcriptomic signatures of regional cortical vulnerability in MDD.
- Establishes a link between genetic risk, gene expression patterns, and cortical alterations in MDD.
