{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T09:48:02Z","timestamp":1792403282032,"version":"4.4.0"},"reference-count":103,"publisher":"Scholar Publishing","issue":"01","license":[{"start":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T00:00:00Z","timestamp":1768089600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BJHR"],"abstract":"<jats:p>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\u2019s 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 \u201creward deficiency,\u201d 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\u00ae) 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\u2013D5), 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. \u00a0WC 286<\/jats:p>","DOI":"10.14738\/bjhr.1301.19797","type":"journal-article","created":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T18:55:17Z","timestamp":1768157717000},"page":"29-62","source":"Crossref","is-referenced-by-count":1,"title":["Reward Deficiency Syndrome (RDS): A Common Neurogenetic Trait\/State of All Addictions: Is this the new DSM?"],"prefix":"10.14738","volume":"13","author":[{"given":"Kenneth","family":"Blum","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai Uwe","family":"Lewandrowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan P.","family":"Lorio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Pinhasov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavya","family":"Mohankumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Sharafshah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panayotis K.","family":"Thanos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdalla","family":"Bowirrat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Lindeau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"Dowling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaela","family":"Dowling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joao Paulo","family":"Bergamaschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander PL.","family":"Lewandrowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward J.","family":"Modestino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S","family":"Gold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alphonso Kenison","family":"Roy3rd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine A.","family":"Dennen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaurya","family":"Mahajan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Baron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debasis","family":"Bagchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9rgio Lu\u00eds","family":"Schimidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossano K A","family":"Fiorelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajendra D","family":"Badgaiyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"5756","published-online":{"date-parts":[[2026,1,11]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Alonso SJ, Navarro E, Rodriguez M. 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Proc Natl Acad Sci U S A. 1983 Nov;80(21):6510-2.","DOI":"10.1073\/pnas.80.21.6510"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Blum K, Gardner E, Oscar-Berman M, Gold M. \"Liking\" and \"wanting\" linked to Reward Deficiency Syndrome (RDS): hypothesizing differential responsivity in brain reward circuitry. Curr Pharm Des. 2012b;18(1):113-8. PubMed PMID: 22236117; PubMed Central PMCID: PMC3651846. Scholar Publishing Blum K, Gold M, Demetrovics Z, Archer T, Thanos PK, Baron D, Badgaiyan RD. Substance use disorder a bio-directional subset of reward deficiency syndrome. Front Biosci (Landmark Ed). 2017 Jun 1;22:1534-1548. doi: 10.2741\/4557. PMID: 28410131.","DOI":"10.2174\/138161212798919110"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Blum, K., Khalsa, J., Cadet, J. L., Baron, D., Bowirrat, A., Boyett, B., ... & Gold, M. S. (2021). 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Published online 2016 Dec 29. doi: 10.1080\/10826084.2016.1244551 PMC5589271","DOI":"10.1080\/10826084.2016.1244551"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Blum K, Marcelo Febo, Rajendra D. Badgaiyan, Zsolt Demetrovics, Thomas Simpatico, Claudia Fahlke, Oscar-Berman M, Mona Li, Kristina Dushaj, Mark S. Gold. Common Neurogenetic Diagnosis and Meso-Limbic Manipulation of Hypodopaminergic Function in Reward Deficiency Syndrome (RDS): Changing the Recovery Landscape. Curr Neuropharmacol. 2017a Jan; 15(1): 184\u2013194. Published online 2017 Jan. doi: 10.2174\/1570159X13666160512150918","DOI":"10.2174\/1570159X13666160512150918"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Blum K, Marlene Oscar-Berman, Abdalla Bowirrat, John Giordano, Margaret Madigan, Eric R. Braverman, Debmayla Barh, Mary Hauser, Joan Borsten, Thomas Simpatico. Neuropsychiatric Genetics of Happiness, Friendships, and Politics: Hypothesizing Homophily (\u201cBirds of a Feather Flock Together\u201d) as a Function of Reward Gene Polymorphisms J Genet Syndr Gene Ther. Author manuscript; available in PMC 2013 Jan 17.","DOI":"10.4172\/2157-7412.1000112"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Blum K, Marlene Oscar-Berman, Zsolt Demetrovics, Debmalya Barh, Mark S. Gold. Genetic Addiction Risk Score (GARS): Molecular Neurogenetic Evidence for Predisposition to Reward Deficiency Syndrome (RDS)Mol Neurobiol. 2014a; 50(3): 765\u2013796. Published online 2014 May 31. doi: 10.1007\/s12035-014-8726-5 PMC4225054","DOI":"10.1007\/s12035-014-8726-5"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Blum K, Merritt JH, Reiter RJ, Wallace JE. A possible relationship between the pineal gland and ethanol preference in the rat. Curr Ther Res Clin Exp. 1973 Jan;15(1):25-30. PMID: 4631379. Blum K, Noble EP, Sheridan PJ, Montgomery A, Ritchie T, Jagadeeswaran P, Nogami H, Briggs AH, Cohn JB. Allelic association of human dopamine D2 receptor gene in alcoholism. JAMA. 1990 Apr 18;263(15):2055-60. PMID: 1969501.","DOI":"10.1001\/jama.1990.03440150063027"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Blum K, Thompson B, Demotrovics Z, Femino J, Giordano J, Oscar-Berman M, Teitelbaum S, Smith DE, Roy AK, Agan G, Fratantonio J, Badgaiyan RD, Gold MS. The Molecular Neurobiology of Twelve Steps Program & Fellowship: Connecting the Dots for Recovery. J Reward Defic Syndr. 2015;1(1):46-64. doi: 10.17756\/jrds.2015-008. PMID: 26306329; PMCID: PMC4545669.","DOI":"10.17756\/jrds.2015-008"},{"key":"ref20","unstructured":"Blum K, Topel H. Opioid peptides and alcoholism: genetic deficiency and chemical management. Funct Neurol. 1986 Jan-Mar;1(1):71-83. PMID: 2956168."},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Blum K, Trachtenberg MC, Elliott CE, Dingler ML, Sexton RL, Samuels AI, Cataldie L. Enkephalinase inhibition and precursor amino acid loading improves inpatient treatment of alcohol and polydrug abusers: double-blind placebo-controlled study of the nutritional adjunct SAAVE. Alcohol. 1988 Nov-Dec;5(6):481-93. doi: 10.1016\/0741-8329(88)90087-0. PMID: 3072969.","DOI":"10.1016\/0741-8329(88)90087-0"},{"key":"ref22","unstructured":"Scholar Publishing Blum K, Wallace JE, Briggs AH, Trachtenberg MC. Evidence for the importance of the \"genotype\" theory in alcohol seeking behavior: a commentary. Alcohol Drug Res. 1985-1986;6(6):455-61. Blum K, Han D, Hauser M, Downs BW, Giordano J, Borsten J, Winchell E, Simpatico T, Madigan MA, Barh D. [2013a]. Neurogenetic Impairments of Brain Reward Circuitry Links to Reward Deficiency Syndrome (RDS) as evidenced by Genetic Addiction Risk Score (GARS): A case study. 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