Human Gene Expression Profile Analysis of Insomnia and Pre-Insomnia Disorders: A Cellular Study Publisher



Mansouri V ; Arjmand B ; Asri N ; Razzaghi Z ; Rezaeitavirani M ; Razi F ; Bandarian F ; Robati RM ; Rezaei M
Source: Basic and Clinical Neuroscience Published:2025

Abstract

Introduction: Sleep is a vital process for restoring brain function and is recognized as a fundamental aspect of both physical and mental health. This study aims to assess the molecular mechanisms of insomnia disorder and identify the key dysregulated genes associated with it. Methods: To study molecular mechanisms of insomnia, GSE208668 was selected from the Gene Expression Omnibus (GEO) database. Total RNA from peripheral blood mononuclear cells of 17 individuals with insomnia disorder was analyzed and compared to 25 controls using the GEO2R program. The gene expression profiles were assessed using box plots, uniform manifold approximation and projection (UMAP) plots, expression density diagrams, and Venn diagrams. The significantly differentially expressed genes (DEGs) were evaluated through a directed protein-protein interaction (PPI) network using the CluePedia plugin of Cytoscape software, taking into account co-expression interactions. The central nodes were identified as the most influential and regulated genes. Results: Pre-evaluation analysis revealed that insomnia exhibits heterogeneity and can be divided into two groups. The gene expression profiles of the first group were similar to those of the insomnia group. In contrast, the second group of controls was distinguished from the insomnia group by genes such as TP53, CCND1, IL1B, SOX1, and NOTCH1, which were identified as key actor genes. Additionally, IL10, IL6, TP53, PTGS2, ESR1, PTEN, JUN, CREB1, CDKN1A, CDKN2A, CXCR4, and GATA3 were identified as important regulatory genes. Conclusion: It can be concluded that many individuals may be potentially involved in insomnia disorder as pre-insomnia. The findings demonstrate that pre-insomnia and insomnia share very similar molecular mechanisms. The critical genes TP53, CCND1, IL1B, SOX1, and NOTCH1, along with pathways related to apoptosis, inflammation, immunological response, and changes in sleep quality, are emphasized as particularly relevant to insomnia disorder. Copyright © 2025 The Author(s)