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Gene Expression Profiles Associated with Brain Aging are Altered in Schizophrenia
1Department of Pediatrics, Johns Hopkins University, Baltimore, MD, 21287, USA. ssabunc1@jhmi.edu.
Scientific Reports
|April 13, 2019
Summary
Schizophrenia brain aging shows distinct gene expression patterns compared to controls. These differences diminish after age 60, highlighting age-related changes in schizophrenia.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Schizophrenia is a complex psychiatric disorder with suspected neurodevelopmental and neurodegenerative components.
- Gene expression patterns in the brain change with age, but how these aging trajectories differ in schizophrenia is not fully understood.
Purpose of the Study:
- To investigate age-associated transcriptional differences in the postmortem brain of individuals with schizophrenia compared to controls.
- To identify specific age ranges where gene expression diverges between schizophrenia cases and controls.
Main Methods:
- RNA sequencing analysis of 610 postmortem Dorso-Lateral Pre-Frontal Cortex (DLPFC) samples from the CommonMind Consortium (CMC) and psychENCODE cohorts.
- Differential gene expression analysis, including interaction analysis between age and diagnosis.
- Gene set enrichment analysis to identify affected biological pathways.
Main Results:
- Gene expression changes during brain aging differed between schizophrenia cases and controls, with differences diminishing after 60 years of age.
- A specific age group (40-60 years) revealed 556 replicated significant loci with consistent gene expression fold changes across cohorts.
- Disruptions were observed in mitochondrial, RNA splicing, and phosphoprotein gene pathways, with enrichment in schizophrenia-associated genomic regions for overall differentially expressed genes.
Conclusions:
- Aging processes in the brain appear disrupted in schizophrenia pathology.
- Age stratification is crucial for interpreting gene expression studies in schizophrenia research.
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