Mapping Genetic Associations With Functional Brain Area Alterations in Schizophrenia and Implications for Cortical
Jun-Ding Zhu1,2, Chih-Yun Chung3, Shu-Fei Lin3
1Department of Occupational Therapy, College of Medical Science and Technology, Chung Shan Medical University, Taichung, Taiwan.
Brain and Behavior
|July 21, 2025
Summary
Schizophrenia is linked to reduced gray matter (GM) volume in specific brain areas, particularly in the frontal and temporal lobes. Genetic factors may drive these structural changes during brain development.
Area of Science:
- Neuroimaging
- Genetics
- Developmental Neuroscience
Background:
- Previous research indicates regional gray matter (GM) volume reduction in schizophrenia.
- The specific brain functional areas affected and their genetic underpinnings remain unclear.
Purpose of the Study:
- Identify Brodmann's areas (BAs) with altered GM volume in schizophrenia patients.
- Explore genetic variants associated with these BAs using genome-wide association study (GWAS).
- Investigate the role of identified genes in cortical development.
Main Methods:
- Recruited 194 schizophrenia patients and 330 healthy controls.
- Analyzed T1-weighted MRI scans to assess GM volume in specific BAs.
- Conducted GWAS, single-cell RNA sequencing, and in situ hybridization.
Main Results:
- Found significant GM volume reductions in specific BAs (e.g., BA13, BA23-25, BA27-28, BA31, BA34-35, BA38) in the ventral frontal cortex, anterior temporal lobe, and cingulate cortex.
- Identified multiple genetic variants associated with affected BAs.
- Observed dynamic expression of schizophrenia-associated genes during cortical development.
Conclusions:
- Specific BAs are more susceptible to GM volume reduction in schizophrenia.
- Distinct genetic factors may contribute to these structural abnormalities.
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