Identification of stress-induced epigenetic methylation onto dopamine D2 gene and neurological and behavioral consequences
Year: 2024
Type: article
Abstract: The D2 dopamine receptor (DRD2) gene has garnered substantial attention as one of the most extensively studied genes across various neuropsychiatric disorders. Since its initial association with severe alcoholism in 1990, particularly through the identification of the DRD2 Taq A1 allele, numerous international investigations have been conducted to elucidate its role in different conditions. As of February 22, 2024, there are 5485 articles focusing on the DRD2 gene listed in PUBMED. There have been 120 meta-analyses with mixed results. In our opinion, the primary cause of negative reports regarding the association of various DRD2 gene polymorphisms is the inadequate screening of controls, not adequately eliminating many hidden reward deficiency syndrome behaviors. Moreover, pleiotropic effects of DRD2 variants have been identified in neuropsychologic, neurophysiologic, stress response, social stress defeat, maternal deprivation, and gambling disorder, with epigenetic DNA methylation and histone post-translational negative methylation identified as discussed in this article. There are 70 articles listed in PUBMED for DNA methylation and 20 articles listed for histone methylation as of October 19, 2022. For this commentary, we did not denote DNA and/or histone methylation; instead, we provided a brief summary based on behavioral effects. Based on the fact that Blum and Noble characterized the DRD2 Taq A1 allele as a generalized reward gene and not necessarily specific alcoholism, it now behooves the field to find ways to either use effector moieties to edit the neuroepigenetic insults or possibly harness the idea of potentially removing negative mRNA-reduced expression by inducing “dopamine homeostasis.”
Source: Gene & Protein in Disease
DOI: 10.36922/gpd.1966
Authors: Kenneth Blum, Abdalla Bowirrat, David Baron, Igor Elman, Milan T. Makale, Jean Lud Cadet, Panayotis K. Thanos, Colin Hanna, Rania Ahmed, Marjorie C. Gondre-Lewis, Catherine A. Dennen, Eric R. Braverman, Diwanshu Soni, Paul Carney, Jag Khalsa, Edward J. Modestino, Debmalya Barh, Debasis Bagchi, Rajendra D. Badgaiyan, Thomas McLaughlin, Rene Cortese, Mauro Ceccanti, Kevin T. Murphy, Ashim Gupta, Miles T. Makale, Keerthy Sunder, Mark S. Gold
Institutions: Eötvös Loránd University, University of Vermont, Ariel University, Western University of Health Sciences, Cambridge Health Alliance, Harvard University, UC San Diego Health System, University of California San Diego, National Institutes of Health, National Institute on Drug Abuse, University at Buffalo, State University of New York, Howard University, Thomas Jefferson University Hospital, University of Missouri, George Washington University, Curry College, Universidade Federal de Minas Gerais, Texas Southern University, Case Western Reserve University, Icahn School of Medicine at Mount Sinai, Regione Lazio, Sapienza University of Rome, University of California, Riverside, Washington University in St. Louis
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Award: G5688951235
OpenAlex ID: W4393471847