en Behavioral Neuroscience Behavioral Neuroscience Original Original <div style="text-align: justify;"><strong>Introduction</strong>: 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.&nbsp;<br> <strong>Methods</strong>: 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.&nbsp;<br> <strong>Results</strong>: 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.<br> <strong>Conclusion</strong>: 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.</div> Insomnia, Gene expression, Network analysis, Pre-insomnia, Human 929 940 http://bcn.iums.ac.ir/browse.php?a_code=A-10-6876-4&slc_lang=en&sid=1 Vahid Mansouri vm1343@yahoo.com 13700319475328460055667 13700319475328460055667 No Proteomics Research Center, School of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Babak Arjmand mgrc.tums@gmail.com 13700319475328460055668 13700319475328460055668 No Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. Nastaran Asri nastaran.asri26@gmail.com 13700319475328460055669 13700319475328460055669 No Celiac Disease and Gluten-Related Disorders Research Center, School of Medicine, Research Institute for Gastroenterology and Liver Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Zahra Razzaghi z.razaghi@gmail.com 13700319475328460055670 0009-0009-3321-8982 No Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Mostafa Rezaei-Tavirani tavirany@yahoo.com 13700319475328460055671 13700319475328460055671 Yes Proteomics Research Center, School of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Farideh Razi farideh.razi@gmail.com 13700319475328460055672 13700319475328460055672 No Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. Fatemeh Bandarian fbandarian@yahoo.com 13700319475328460055673 13700319475328460055673 No Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. Reza M Robati rezarobati@sbmu.ac.ir 13700319475328460055674 13700319475328460055674 No Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Mitra Rezaei dr_mrezaie@yahoo.com 13700319475328460055675 13700319475328460055675 No Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.