Post-mortem molecular profiling of three psychiatric disorders.

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Psychiatric disorders are complex, multigenic conditions with significant impact on public health.
• Shared symptoms across disorders suggest common molecular underpinnings and potential therapeutic targets.

Purpose of the Study:

• To compare molecular signatures across three major psychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder) in distinct brain regions.
• To identify differentially expressed genes and regulatory factors implicated in these disorders.

Main Methods:

• RNA sequencing of post-mortem brain tissue (anterior cingulate cortex, dorsolateral prefrontal cortex, nucleus accumbens) from patients and controls.
• Validation of gene expression changes in an independent cohort.
• Metabolomic analysis and transcription factor binding assays (EGR1).

Main Results:

• Significant transcriptional differences were most pronounced in the anterior cingulate cortex of schizophrenia patients.
• The transcription factor EGR1 was found to be downregulated in schizophrenia and may regulate broader transcriptional changes.
• Schizophrenia and bipolar disorder patients showed decreased neuronal gene expression and increased astrocyte gene expression compared to controls.
• GABA levels were disrupted in schizophrenia patients.

Conclusions:

• This study provides a comprehensive transcriptome profile of three psychiatric disorders across multiple brain regions.
• A validated set of differentially expressed genes in schizophrenia was identified, linking transcriptional changes with metabolite profiles.