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PERSPECTIVE ARTICLE

Exploring dopamine as the master regulator of brain circuitry and mental health genome

Kenneth Blum1,2,3,4* ,  Eric R. Braverman1 ,  Alireza Sharafshah5 ,  Igor Elman3,6 ,  Kai-Uwe Lewandrowski2,7,8 ,  Abdalla Bowirrat3,9 ,  Albert Pinhasov3 ,  Panayotis K. Thanos3,10 ,  Mark S. Gold11* ,  Catherine A. Dennen12 ,  Edward J. Modestino13 ,  Rajendra D. Badgaiyan9 ,  David Baron4 ,  Brian Fuehrlein14 ,  Daniel Sipple15 ,  John Wesson Ashford16,17 ,  Keerthy Sunder18 ,  Milan Makale19 ,  Kevin Murphy19 ,  Nicole Jafari20 ,  Foojan Zeine21 ,  Aryeh R. Pollack1 ,  Alexander P.L. Lewandrowski1 ,  Jag Khalsa22
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1 Division of Clinical Neurology, The Blum Institute of Neurogenetics and Behavior, Austin, Texas, United States of America
2 Division of Personalized Pain Therapy Research and Education, Center for Advanced Spine Care of Southern Arizona, Tucson, Arizona, United States of America
3 Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel, Israel
4 Division of Addiction Research and Education, Center for Sports, Exercise, and Mental Health, Western University of Health Sciences, Pomona, California, United States of America
5 Cellular and Molecular Research Center, School of Medicine, Guilin University of Medical Sciences, Rasht, Iran
6 Department of Psychiatry and Cambridge Health Alliance, Harvard Medical School, Cambridge, Massachusetts, United States of America
7 Department of Orthopaedics, Fundación Universitaria Sanitas, Bogotá D.C., Colombia
8 Department of Orthopaedics, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
9 Department of Psychiatry, Case Western Reserve University, School of Medicine, Cleveland, Ohio, United States of America
10 Department of Pharmacology and Toxicology, Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, New York, United States of America
11 Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, United States of America
12 Department of Family Medicine, Jefferson Health Northeast, Philadelphia, Pennsylvania, United States of America
13 Department of Psychology, Curry College, Milton, Massachusetts, United States of America
14 Department of Psychiatry, Yale University School of Medicine, New Haven, United States of America
15 M Health Fairview University of Minnesota Medical Center, Minneapolis, Minnesota, United States of America
16 Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, California, United States of America
17 War Related Illness and Injury Study Center, VA Palo Alto Health Care System, Palo Alto, California, United States of America
18 Department of Medicine, Riverside School of Medicine, University of California, Riverside, California, United States of America
19 Department of Radiation Oncology, University of California San Diego, La Jolla, California, United States of America
20 Department of Applied Clinical Psychology, The Chicago School of Professional Psychology, Los Angeles, United States of America
21 Department of Health Science, California State University at Long Beach, Long Beach, California, United States of America
22 Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland, United States of America
GPD, 6557 https://doi.org/10.36922/gpd.6557
Received: 25 November 2024 | Revised: 7 February 2025 | Accepted: 31 March 2025 | Published online: 3 June 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Artificially increasing dopamine transmission is the common mechanism by which substances with addictive potential lead to addiction. A key area of research in neurobiology is the role of dopamine. Significant advancements have been made in uncovering the intracellular signaling pathways that mediate both dopamine’s immediate effects and its long-term influence on brain function. Recent discoveries have also highlighted specific molecules that could serve as potential therapeutic targets for neurological and psychiatric disorders. While understanding several important caveats, we believe dopamine acts as a master regulator of brain circuitry across major chromosomes mapping the mental health genome. This view may have important clinical relevance, emphasizing the critical role of dopaminergic activity across the genome. Importantly, we are cognizant that dopamine does not work in insolation, and its finite actions are due to a highly interactive network (known as the brain reward cascade), involving at least seven other major neurotransmitters.

Keywords
Dopamine
Addiction
Genetics
Brain reward cascade
Psychiatric disorders
Funding
Kenneth Blum is NIH recipient of R41 MD012318/MD/ NIMHD NIH HHS/United States, while Rajendra D. Badgaiyan is the recipient of NIH R01NS073884.
Conflict of interest
Kenneth Blum and Kai-Uwe Lewandrowski are the Editorial Board Members but were not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper. Kenneth Blum holds patents, both domestic and foreign, related to pro-dopamine regulation complexes and genetic testing for addiction risk.
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