Downregulated NPAS4 in multiple brain regions is associated with major depressive disorder

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Selçuk, Berkay and Aksu, Tuana and Dereli, Onur and Adebali, Ogün (2023) Downregulated NPAS4 in multiple brain regions is associated with major depressive disorder. Scientific Reports, 13 (1). ISSN 2045-2322

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Abstract

Major Depressive Disorder (MDD) is a commonly observed psychiatric disorder that affects more than 2% of the world population with a rising trend. However, disease-associated pathways and biomarkers are yet to be fully comprehended. In this study, we analyzed previously generated RNA-seq data across seven different brain regions from three distinct studies to identify differentially and co-expressed genes for patients with MDD. Differential gene expression (DGE) analysis revealed that NPAS4 is the only gene downregulated in three different brain regions. Furthermore, co-expressing gene modules responsible for glutamatergic signaling are negatively enriched in these regions. We used the results of both DGE and co-expression analyses to construct a novel MDD-associated pathway. In our model, we propose that disruption in glutamatergic signaling-related pathways might be associated with the downregulation of NPAS4 and many other immediate-early genes (IEGs) that control synaptic plasticity. In addition to DGE analysis, we identified the relative importance of KEGG pathways in discriminating MDD phenotype using a machine learning-based approach. We anticipate that our study will open doors to developing better therapeutic approaches targeting glutamatergic receptors in the treatment of MDD.
Item Type: Article
Divisions: Faculty of Engineering and Natural Sciences > Academic programs > Biological Sciences & Bio Eng.
Faculty of Engineering and Natural Sciences
Depositing User: Onur Dereli
Date Deposited: 08 Feb 2024 15:50
Last Modified: 08 Feb 2024 15:50
URI: https://research.sabanciuniv.edu/id/eprint/48894

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