https://www.nature.com/articles/s41380-024-02568-8
Schizophrenia (SCZ): A neuropsychiatric disorder influenced by genetic and environmental factors, with elusive etiology related to neurotransmitter response1.- Study Aim: To explore the correlation between transcriptome and metabolome in a SCZ model using patient-derived induced pluripotent stem cells (iPSCs)1.
- Methodology: iPSCs were differentiated into cortical neurons, and samples were collected at various developmental stages for RNA-sequencing and targeted metabolomics1.
- Findings:
- Significant perturbations in polyamine and gamma-aminobutyric acid (GABA) biosynthetic pathways during rosette maturation in SCZ lines1.
- Downregulation of glutamate decarboxylase genes GAD1 and GAD2, and their products GAD65/67 and GABA in SCZ samples1.
- Inhibition of ornithine decarboxylase led to decreased GABA levels, suggesting a compensatory activation of the ornithine/putrescine pathway for GABA production1.
- Conclusion: The study indicates an imbalance of cortical excitatory/inhibitory dynamics during early neurodevelopmental stages in SCZ and supports the hypothesis that disruption of inhibitory circuits may be causative for SCZ1.
- Novelty: Establishes a novel in silico approach for integrative correlation of metabolic and transcriptomic data in psychiatric disease models1.