Reward Deficiency Syndrome (RDS): A Common Neurogenetic Trait/State of All Addictions: Is this the new DSM?

Authors

  • Kenneth Blum The Kenneth Blum Behavioral & Neurogenetic Institute and RDS Consortium, Austin, TX., USA, Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary, Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel, Israel, Division of Addiction Research & Education, Center for Sports, Exercise, Psychiatry, Western University Health Sciences, Pomona, CA., USA, Division of Personalized Medicine, Center for Advanced Spine Care of Southern Arizona, Tucson, AZ 85712, USA and Programa de Pós-Graduação em Neurologia, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro Brazil
  • Kai Uwe Lewandrowski The Kenneth Blum Behavioral & Neurogenetic Institute and RDS Consortium, Austin, TX., USA, Division of Personalized Medicine, Center for Advanced Spine Care of Southern Arizona, Tucson, AZ 85712, USA, Programa de Pós-Graduação em Neurologia, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro Brazil and Department of Orthopedic Surgery, University of Arizona, School of Medicine, Tucson, AZ 85724, USA
  • Morgan P. Lorio The Kenneth Blum Behavioral & Neurogenetic Institute and RDS Consortium, Austin, TX., USA and Department of Osteopathic Principles and Practice, Orlando College of Osteopathic Medicine, Orlando, FL, USA
  • Albert Pinhasov Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel, Israel
  • Kavya Mohankumar The Kenneth Blum Behavioral & Neurogenetic Institute and RDS Consortium, Austin, TX., USA
  • Alireza Sharafshah The Kenneth Blum Behavioral & Neurogenetic Institute and RDS Consortium, Austin, TX., USA and Cellular and Molecular Research Center - Independent Department at Guilan University of Medical Sciences, School of Medicine, Guilan University of Medical Sciences, Rasht, Guilan, Iran
  • Panayotis K. Thanos The Kenneth Blum Behavioral & Neurogenetic Institute and RDS Consortium, Austin, TX., USA, Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel, Israel and Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, and Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Buffalo, New York, USA
  • Abdalla Bowirrat Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel, Israel
  • Marco Lindeau The Kenneth Blum Behavioral & Neurogenetic Institute and RDS Consortium, Austin, TX., USA
  • Álvaro Dowling The Kenneth Blum Behavioral & Neurogenetic Institute and RDS Consortium, Austin, TX., USA
  • Rafaela Dowling The Kenneth Blum Behavioral & Neurogenetic Institute and RDS Consortium, Austin, TX., USA
  • Joao Paulo Bergamaschi The Kenneth Blum Behavioral & Neurogenetic Institute and RDS Consortium, Austin, TX., USA
  • Alexander PL. Lewandrowski The Kenneth Blum Behavioral & Neurogenetic Institute and RDS Consortium, Austin, TX., USA
  • Edward J. Modestino The Kenneth Blum Behavioral & Neurogenetic Institute and RDS Consortium, Austin, TX., USA and Brain and Behavior Laboratory, Curry College, Milton, MA., USA
  • Mark S Gold The Kenneth Blum Behavioral & Neurogenetic Institute and RDS Consortium, Austin, TX., USA, Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA and Department of Psychiatry, Tulane University School of Medicine, New Orleans, LA., USA 
  • Alphonso Kenison Roy3rd The Kenneth Blum Behavioral & Neurogenetic Institute and RDS Consortium, Austin, TX., USA and Department of Psychiatry, Tulane University School of Medicine, New Orleans, LA., USA
  • David E. Smith The Kenneth Blum Behavioral & Neurogenetic Institute and RDS Consortium, Austin, TX., USA and Department of Pharmacology, College of Medicine, University of San Francisco, San Francisco, CA, USA
  • Catherine A. Dennen The Kenneth Blum Behavioral & Neurogenetic Institute and RDS Consortium, Austin, TX., USA and Department of Family Medicine, Jefferson Health Northeast, Philadelphia, USA
  • Shaurya Mahajan The Kenneth Blum Behavioral & Neurogenetic Institute and RDS Consortium, Austin, TX., USA
  • David Baron The Kenneth Blum Behavioral & Neurogenetic Institute and RDS Consortium, Austin, TX., USA and 4. Division of Addiction Research & Education, Center for Sports, Exercise, Psychiatry, Western University Health Sciences, Pomona, CA., USA
  • Debasis Bagchi Department of Pharmaceutical Sciences, Texas Southern University College of Pharmacy, Houston, TX, USA
  • Sérgio Luís Schimidt The Kenneth Blum Behavioral & Neurogenetic Institute and RDS Consortium, Austin, TX., USA and Division of Personalized Medicine, Center for Advanced Spine Care of Southern Arizona, Tucson, AZ 85712, USA
  • Rossano K A Fiorelli The Kenneth Blum Behavioral & Neurogenetic Institute and RDS Consortium, Austin, TX., USA and Division of Personalized Medicine, Center for Advanced Spine Care of Southern Arizona, Tucson, AZ 85712, USA
  • Rajendra D Badgaiyan The Kenneth Blum Behavioral & Neurogenetic Institute and RDS Consortium, Austin, TX., USA

DOI:

https://doi.org/10.14738/bjhr.1301.19797

Keywords:

Dopamine Homeostasis, Precision Addiction Management, GARS, KB220, Reward Deficiency Syndrome (RDS), Neuroimaging

Abstract

Steven Hyman, former director of the NIMH (2012), noted that neuroscience studies of psychiatric disorders often rely on definitions from the Diagnostic and Statistical Manual of Mental Disorders (DSM), which treats conditions as distinct entities. However, boundaries between disorders are less strict than DSM categories suggest. To address this, Hyman’s group introduced the Research Domain Criteria (RDoC) project, which defines five brain-based domains impaired across psychiatric conditions. Similarly, Blum (1995) proposed Reward Deficiency Syndrome (RDS) as a unifying framework for substance and non-substance addictive behaviors. Currently, over 1,650 PubMed studies link to “reward deficiency,” and 281 specifically to RDS. Recent GWAS and pharmacogenomic (PGX) studies in 88.8 million subjects support dopamine dysregulation as the accurate phenotype of RDS. The Genetic Addiction Risk Severity (GARS®) test has been developed as a predictor of RDS and preaddiction. Psychiatric disorders identified in the DSM-5 share many genetic polymorphisms, often tied to dopaminergic signaling. We propose a biphasic prevention and treatment model for addictions (alcohol, nicotine, glucose, etc.). Acute harm reduction should target postsynaptic Nucleus Accumbens (NAc) dopamine receptors (D1–D5), while long-term therapy should promote dopamine activation/release at the NAc. Failure to balance these may lead to mood instability, aberrant behavior, or suicidal ideation. Individuals with serotonergic/dopaminergic receptor deficits or high COMT activity may self-medicate with substances and behaviors that release dopamine. Evidence suggests that upregulating D2 receptors in genetically vulnerable individuals could mitigate addictive risk. While in vivo D2 agonists downregulate receptors, in vitro studies show constant stimulation can promote receptor proliferation. Gene therapy inducing DRD2 overexpression reduces alcohol and cocaine craving in rodents. Natural dopaminergic repletion therapy may provide a safe, long-term strategy to restore dopaminergic function, improve recovery, and enhance quality of life in RDS-related behaviors.  WC 286

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Published

2026-01-11

How to Cite

Blum, K., Lewandrowski, K. U., Lorio, M. P., Pinhasov, A., Mohankumar, K., Sharafshah, A., Thanos, P. K., Bowirrat, A., Lindeau, M., Dowling, Álvaro, Dowling, R., Bergamaschi, J. P., Lewandrowski, A. P., Modestino, E. J., Gold, M. S., Roy3rd, A. K., Smith, D. E., Dennen, C. A., Mahajan, S., Baron, D., Bagchi, D., Schimidt, S. L., Fiorelli, R. K. A., & Badgaiyan, R. D. (2026). Reward Deficiency Syndrome (RDS): A Common Neurogenetic Trait/State of All Addictions: Is this the new DSM?. British Journal of Healthcare and Medical Research, 13(01), 29–62. https://doi.org/10.14738/bjhr.1301.19797

Issue

Vol. 13 No. 01 (2026): British Journal of Healthcare and Medical Research

Section

Original Articles

License

Copyright (c) 2026 Kenneth Blum, Kai Uwe Lewandrowski, Morgan P. Lorio, Albert Pinhasov, Kavya Mohankumar, Alireza Sharafshah, Panayotis K. Thanos, Abdalla Bowirrat, Marco Lindeau, Álvaro Dowling, Rafaela Dowling, Joao Paulo Bergamaschi, Alexander PL. Lewandrowski, Edward J. Modestino, Mark S Gold, Alphonso Kenison Roy3rd, David E. Smith, Catherine A. Dennen, Shaurya Mahajan, David Baron, Debasis Bagchi, Sérgio Luís Schimidt, Rossano K A Fiorelli, Rajendra D Badgaiyan

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This work is licensed under a Creative Commons Attribution 4.0 International License.