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Kotyuk E, Demetrovics Z, Urbán R, Czakó A, Blum K, Griffiths MD, Potenza MN, Efrati Y. Psychometric properties of the Reward Deficiency Syndrome Questionnaire among a non-clinical sample and its relationship with the characteristics of potentially addictive behaviors. Addict Behav Rep 2025; 21:100598. [PMID: 40248688 PMCID: PMC12005299 DOI: 10.1016/j.abrep.2025.100598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 03/13/2025] [Accepted: 03/20/2025] [Indexed: 04/19/2025] Open
Abstract
Background and aims The addiction literature conceptualizes problematic substance use and addictive behaviors (e.g., gambling disorder, gaming disorder) as having shared etiologies and phenomenologies. The reward deficiency syndrome (RDS) model proposes blunted responses to natural rewards that potentially contribute to the development of addictive behaviors. The 29-item Reward Deficiency Syndrome Questionnaire (RDSQ-29) was developed to assess RDS-related psychological-behavioral characteristics. The aim of the present study was to validate the Hebrew version of the RDSQ-29 and to provide empirical evidence for the relevance of RDS in addictive behaviors and related psychological features. Methods The sample comprised 961 Jewish Israeli young adults from the general community (age 19-27 years; M = 23.40 years [SD = 1.95]) who were assessed for personality characteristics (attachment styles, RDS, compulsive personality), internet gaming disorder (IGD), problematic use of social media use (PUSM), compulsive buying-shopping disorder (CBSD), and gambling disorder (GD). Results The analysis confirmed the validity and factor structure of the RDSQ-29. RDSQ-29 scores showed a significant but weak association with anxiety, avoidance, and compulsive personality. Also, weak to modest relationships were found between RDSQ-29 scores and the severity of the four potential behavioral addictions. Discussion The findings suggest that the Hebrew translation of the RDSQ-29 is a psychometrically sound instrument to assess RDS. Given that different potentially addictive and other problematic behaviors are associated with RDS, its assessment might be useful in prevention or screening.
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Affiliation(s)
- Eszter Kotyuk
- Institute of Psychology, ELTE Eötvös Lorand University, 46 Izabella Street, Budapest H-1064, Hungary
| | - Zsolt Demetrovics
- Institute of Psychology, ELTE Eötvös Lorand University, 46 Izabella Street, Budapest H-1064, Hungary
- Flinders University Institute for Mental Health and Wellbeing, College of Education, Psychology and Social Work, Flinders University, Bedford Park, South Australia, Australia
- Centre of Excellence in Responsible Gaming, University of Gibraltar, Europa Point Campus, Gibraltar
| | - Róbert Urbán
- Institute of Psychology, ELTE Eötvös Lorand University, 46 Izabella Street, Budapest H-1064, Hungary
| | - Andrea Czakó
- Institute of Psychology, ELTE Eötvös Lorand University, 46 Izabella Street, Budapest H-1064, Hungary
- Centre of Excellence in Responsible Gaming, University of Gibraltar, Europa Point Campus, Gibraltar
| | - Kenneth Blum
- Institute of Psychology, ELTE Eötvös Lorand University, 46 Izabella Street, Budapest H-1064, Hungary
- Center for Sports, Exercise & Mental Health, Western University of Health Sciences, Pomona, CA, USA
- Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel, Israel
| | - Mark D. Griffiths
- International Gaming Research Unit, Psychology Department, Nottingham Trent University, Nottingham, UK
| | - Marc N. Potenza
- Departments of Psychiatry, Neuroscience and Child Study Center, Yale University School of Medicine, New Haven, CT, USA
- Connecticut Council on Problem Gambling, Wethersfield, CT, USA
- Connecticut Mental Health Center, New Haven, CT, USA
| | - Yaniv Efrati
- Bar-Ilan University, Faculty of Education, Ramat Gan, Israel
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Green RP, Blum K, Lewandrowski KU, Gold MS, Lewandrowski APL, Thanos PK, Dennen CA, Baron D, Elman I, Sharafshah A, Modestino EJ, Badgaiyan RD. Response to the SAMHSA Clinical Advisory: Considerations for Genetic Testing in the Assessment of Substance Use Disorder Risk. Subst Abuse Rehabil 2025; 16:23-26. [PMID: 39886187 PMCID: PMC11781156 DOI: 10.2147/sar.s514931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Accepted: 01/16/2025] [Indexed: 02/01/2025] Open
Affiliation(s)
| | - Kenneth Blum
- Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel
- Center for Sports, Exercise, Global Mental Health, Western University Health Sciences, Pomona, CA, USA
- Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary
- Center for Advanced Spine Care of Southern Arizona and Surgical Institute of Tucson, Tucson, AZ, USA
| | - Kai Uwe Lewandrowski
- Center for Advanced Spine Care of Southern Arizona and Surgical Institute of Tucson, Tucson, AZ, USA
- Department of Orthopaedics, Fundación Universitaria Sanitas, Bogotá, DC, Colombia
| | - Mark S Gold
- Department of Psychiatry, Washington University, School of Medicine, St. Louis, Missouri, USA
| | - Alexander P L Lewandrowski
- Department of Biological Sciences, Dornsife College of Letters, Arts & Sciences, University of Southern California, Los Angeles, CA, USA
| | - Panayotis K Thanos
- Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel
- Behavioral Neuropharmacology and Neuroimaging Laboratory, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, Clinical Research Institute on Addictions, University at Buffalo, Buffalo, NY, USA
| | - Catherine A Dennen
- Department of Family Medicine, Jefferson Health Northeast, Philadelphia, PA, USA
| | - David Baron
- Center for Sports, Exercise, Global Mental Health, Western University Health Sciences, Pomona, CA, USA
- Department of Psychiatry, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Igor Elman
- Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel
- Department of Psychiatry, Harvard University School of Medicine, Cambridge, MA, USA
| | - Alireza Sharafshah
- Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Edward J Modestino
- Brain & Behavior Laboratory, Department of Psychology, Curry College, Milton, Massachusetts, USA
| | - Rajendra D Badgaiyan
- Department of Psychiatry, Texas Tech University Health Sciences, School of Medicine, Midland, TX, USA
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Blum K, Bowirrat A, Thanos PK, Hanna C, Khalsa J, Baron D, Elman I, Badgaiyan RD, Dennen C, Braverman ER, Carney P, Lewandrowski KU, Sharafshah A, Gold MS. Evidence Based Clinical Analytics Supporting the Genetic Addiction Risk Severity (GARS) Assessment to Early Identify Probands in Preaddiction. EC PSYCHOLOGY AND PSYCHIATRY 2024; 13:1-3. [PMID: 38298272 PMCID: PMC10825809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Subscribe] [Scholar Register] [Indexed: 02/02/2024]
Affiliation(s)
- Kenneth Blum
- Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel
- Center for Sports, Exercise, Global Mental Health, Western University Health Sciences, Pomona, CA, USA
- The Kenneth Blum Behavioral & Neurogenetic Institute, LLC., Austin, TX, USA
- Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary
- Department of Psychiatry, University of Vermont School of Medicine, Burlington, VY, USA
- Department of Psychiatry, Wright University, Boonshoff School of Medicine, Dayton, OH, USA
- Center for Advanced Spine Care of Southern Arizona, Tucson, AZ, USA
| | - Abdalla Bowirrat
- Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel
| | - Panayotis K Thanos
- Behavioral Neuropharmacology and Neuroimaging Laboratory, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, Clinical Research Institute on Addictions, University at Buffalo, Buffalo, NY, USA
- US National Institute on Drug Abuse, NIH, Medical Consequences of Drug Abuse and Infections Branch, National Institute on Drug Abuse, NIH, Bethesda, Maryland, USA
| | - Colin Hanna
- Behavioral Neuropharmacology and Neuroimaging Laboratory, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, Clinical Research Institute on Addictions, University at Buffalo, Buffalo, NY, USA
| | - Jag Khalsa
- US National Institute on Drug Abuse, NIH, Medical Consequences of Drug Abuse and Infections Branch, National Institute on Drug Abuse, NIH, Bethesda, Maryland, USA
| | - David Baron
- Center for Sports, Exercise, Global Mental Health, Western University Health Sciences, Pomona, CA, USA
| | - Igor Elman
- Cambridge Health Alliance, Harvard Medical School, Cambridge, MA, USA
| | - Rajendra D Badgaiyan
- Department of Psychiatry, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Catherine Dennen
- Department of Family Medicine, Jefferson Health Northeast, Philadelphia, PA, USA
| | - Eric R Braverman
- Center for Sports, Exercise, Global Mental Health, Western University Health Sciences, Pomona, CA, USA
| | - Paul Carney
- Division Pediatric Neurology, University of Missouri, School of Medicine, Columbia, MO, USA
| | - Kai-Uwe Lewandrowski
- Department of Orthopaedics, Fundación Universitaria Sanitas, Bogotá, DC, Colombia
- Center for Advanced Spine Care of Southern Arizona, Tucson, AZ, USA
| | - Alireza Sharafshah
- Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Mark S Gold
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
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Lorek M, Kamiński P, Baszyński J, Tadrowski T, Gorzelańczyk EJ, Feit J, Kurhaluk N, Woźniak A, Tkaczenko H. Molecular and Environmental Determinants of Addictive Substances. Biomolecules 2024; 14:1406. [PMID: 39595582 PMCID: PMC11592269 DOI: 10.3390/biom14111406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 10/25/2024] [Accepted: 11/02/2024] [Indexed: 11/28/2024] Open
Abstract
Knowledge about determinants of addiction in people taking addictive substances is poor and needs to be supplemented. The novelty of this paper consists in the analysis of innovative aspects of current research about relationships between determinants of addiction in Polish patients taking addictive substances and rare available data regarding the relationships between these factors from studies from recent years from other environments, mainly in Europe, and on the development of genetic determinants of physiological responses. We try to explain the role of the microelements Mn, Fe, Cu, Co, Zn, Cr, Ni, Tl, Se, Al, B, Mo, V, Sn, Sb, Ag, Sr, and Ba, the toxic metals Cd, Hg, As, and Pb, and the rare earth elements Sc, La, Ce, Pr, Eu, Gd, and Nd as factors that may shape the development of addiction to addictive substances or drugs. The interactions between factors (gene polymorphism, especially ANKK1 (TaqI A), ANKK1 (Taq1 A-CT), DRD2 (TaqI B, DRD2 Taq1 B-GA, DRD2 Taq1 B-AA, DRD2-141C Ins/Del), and OPRM1 (A118G)) in patients addicted to addictive substances and consumption of vegetables, consumption of dairy products, exposure to harmful factors, and their relationships with physiological responses, which confirm the importance of internal factors as determinants of addiction, are analyzed, taking into account gender and region. The innovation of this review is to show that the homozygous TT mutant of the ANKK1 TaqI A polymorphism rs 1800497 may be a factor in increased risk of opioid dependence. We identify a variation in the functioning of the immune system in addicted patients from different environments as a result of the interaction of polymorphisms.
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Affiliation(s)
- Małgorzata Lorek
- Division of Ecology and Environmental Protection, Department of Medical Biology and Biochemistry, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, M. Skłodowska-Curie St. 9, PL 85-094 Bydgoszcz, Poland; (M.L.); (J.B.)
| | - Piotr Kamiński
- Division of Ecology and Environmental Protection, Department of Medical Biology and Biochemistry, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, M. Skłodowska-Curie St. 9, PL 85-094 Bydgoszcz, Poland; (M.L.); (J.B.)
- Department of Biotechnology, Institute of Biological Sciences, Faculty of Biological Sciences, University of Zielona Góra, Prof. Z. Szafran St. 1, PL 65-516 Zielona Góra, Poland
| | - Jędrzej Baszyński
- Division of Ecology and Environmental Protection, Department of Medical Biology and Biochemistry, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, M. Skłodowska-Curie St. 9, PL 85-094 Bydgoszcz, Poland; (M.L.); (J.B.)
| | - Tadeusz Tadrowski
- Department of Dermatology and Venereology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, M. Skłodowska-Curie St. 9, PL 85-094 Bydgoszcz, Poland;
| | - Edward Jacek Gorzelańczyk
- Institute of Philosophy, Kazimierz Wielki University in Bydgoszcz, M.K. Ogiński St. 16, PL 85-092 Bydgoszcz, Poland;
- Faculty of Mathematics and Computer Science, Adam Mickiewicz University in Poznań, Uniwersytet Poznański St., 4, PL 61-614 Poznań, Poland
- Primate Cardinal Stefan Wyszyński Provincial Hospital in Sieradz, Psychiatric Centre in Warta, Sieradzka St. 3, PL 98-290 Warta, Poland
- Department of Theoretical Foundations of Biomedical Sciences and Medical Computer Science, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Jagiellońska St. 15, PL 85-067 Bydgoszcz, Poland
| | - Julia Feit
- Pallmed sp. z o.o., W. Roentgen St. 3, PL 85-796 Bydgoszcz, Poland;
| | - Natalia Kurhaluk
- Department of Animal Physiology, Institute of Biology, Pomeranian University in Słupsk, Arciszewski St. 22 B, PL 76-200 Słupsk, Poland; (N.K.); (H.T.)
| | - Alina Woźniak
- Department of Medical Biology and Biochemistry, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, M. Karłowicz St. 24, PL 85-092 Bydgoszcz, Poland;
| | - Halina Tkaczenko
- Department of Animal Physiology, Institute of Biology, Pomeranian University in Słupsk, Arciszewski St. 22 B, PL 76-200 Słupsk, Poland; (N.K.); (H.T.)
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De Ridder D, Vanneste S. Thalamocortical dysrhythmia and reward deficiency syndrome as uncertainty disorders. Neuroscience 2024; 563:20-32. [PMID: 39505139 DOI: 10.1016/j.neuroscience.2024.11.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 10/18/2024] [Accepted: 11/03/2024] [Indexed: 11/08/2024]
Abstract
A common anatomical core has been described for psychiatric disorders, consisting of the dorsal anterior cingulate cortex (dACC) and anterior insula, processing uncertainty. A common neurophysiological core has been described for other brain related disorders, called thalamocortical dysrhythmia (TCD), consisting of persistent cross-frequency coupling between low and high frequencies. And a common genetic core has been described for yet another set of hypodopaminergic pathologies called reward deficiency syndromes (RDS). Considering that some RDS have the neurophysiological features of TCD, it can be hypothesized that TCD and RDS have a common anatomical core, yet a differentiating associated neurophysiological mechanism. The EEGs of 683 subjects are analysed in source space for both differences and conjunction between TCD and healthy controls, RDS and healthy controls, and between TCD and RDS. A balance between current densities of the pregenual anterior cingulate cortex (pgACC) extending into the ventromedial prefrontal cortex (vmPFC) and dACC is calculated as well. TCD and RDS share a common anatomical and neurophysiological core, consisting of beta activity in the dACC and theta activity in dACC extending into precuneus and dorsolateral prefrontal cortex. TCD and RDS differ in pgACC/vmPFC activity and demonstrate an opposite balance between pgACC/vmPFC and dACC. Based on the Bayesian brain model TCD and RDS can be defined as uncertainty disorders in which the pgACC/vmPFC and dACC have an opposite balance, possibly explained by an inverted-U curve profile of both pgACC/vmPFC and dACC.
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Affiliation(s)
- Dirk De Ridder
- Section of Neurosurgery, Department of Surgical Sciences, Dunedin School of Medicine, University of Otago, New Zealand
| | - Sven Vanneste
- Global Brain Health Institute, Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
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Gold MS, Blum K, Bowirrat A, Pinhasov A, Bagchi D, Dennen CA, Thanos PK, Hanna C, Lewandrowski KU, Sharafshah A, Elman I, Badgaiyan RD. A historical perspective on clonidine as an alpha-2A receptor agonist in the treatment of addictive behaviors: Focus on opioid dependence. INNOSC THERANOSTICS & PHARMACOLOGICAL SCIENCES 2024; 7:1918. [PMID: 39119149 PMCID: PMC11308626 DOI: 10.36922/itps.1918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 08/10/2024]
Abstract
Clonidine operates through agonism at the alpha-2A receptor, a specific subtype of the alpha-2-adrenergic receptor located predominantly in the prefrontal cortex. By inhibiting the release of norepinephrine, which is responsible for withdrawal symptoms, clonidine effectively addresses withdrawal-related conditions such as anxiety, hypertension, and tachycardia. The groundbreaking work by Gold et al. demonstrated clonidine's ability to counteract the effects of locus coeruleus stimulation, reshaping the understanding of opioid withdrawal within the field. In the 1980s, the efficacy of clonidine in facilitating the transition to long-acting injectable naltrexone was confirmed for individuals motivated to overcome opioid use disorders (OUDs), including physicians and executives. Despite challenges with compliance, naltrexone offers sustained blockade of opioid receptors, reducing the risk of overdose, intoxication, and relapse in motivated patients in recovery. The development of clonidine and naltrexone as treatment modalities for OUDs, and potentially other addictions, including behavioral ones, underscores the potential for translating neurobiological advancements from preclinical models (bench) to clinical practice (bedside), ushering in innovative approaches to addiction treatment.
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Affiliation(s)
- Mark S. Gold
- Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Kenneth Blum
- Division of Addiction Research and Education, Center for Sports, Exercise and Global Mental Health, Western University Health Sciences, Pomona, California, United States of America
- The Kenneth Blum Behavioral and Neurogenetic Institute LLC, Austin, Texas, United States of America
- Department of Psychology, Faculty of Education and Psychology, Institute of Psychology, Eötvös Loránd University Budapest, Budapest, Hungary
- Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel
- Division of Personalized Medicine, Cross-Cultural Research and Educational Institute, San Clemente, California, United States of America
- Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, West Bengal, India
- Department of Clinical Psychology and Addiction, Institute of Psychology, Faculty of Education and Psychology, Eötvös Loránd University, Budapest, Hungary
- Department of Psychiatry, University of Vermont, Burlington, Vermont, United States of America
- Department of Psychiatry, Wright University, Boonshoft School of Medicine, Dayton, Ohio, United States of America
- Division of Personalized Medicine, Ketamine Infusion Clinic of South Florida, Pompano, Florida, United States of America
| | - Abdalla Bowirrat
- Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel
| | - Albert Pinhasov
- Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel
| | - Debasis Bagchi
- Department of Nutrigenomic Research, Victory Nutrition International, Inc., Bonita Springs, Florida, United States of America
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, Texas, United States of America
| | - Catherine A. Dennen
- Department of Family Medicine, Jefferson Health Northeast, Philadelphia, Pennsylvania, United States of America
| | - Panayotis K. Thanos
- Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, New York, United States of America
- Department of Psychology, State University of New York at Buffalo, Buffalo, New York, United States of America
| | - Colin Hanna
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, New York, United States of America
- Department of Psychology, State University of New York at Buffalo, Buffalo, New York, United States of America
| | - Kai-Uwe Lewandrowski
- Division of Personalized Pain Therapy Research, Center for Advanced Spine Care of Southern Arizona, Tucson, Arizona, United States of America
- Department of Orthopaedics, Fundación Universitaria Sanitas, Bogotá, Colombia
- Department of Orthopedics, Hospital Universitário Gaffree Guinle Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Alireza Sharafshah
- Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Gilan, Iran
| | - Igor Elman
- Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel
- Department of Psychiatry, School of Medicine, Harvard University, Cambridge, Massachusetts, United States of America
| | - Rajendra D. Badgaiyan
- Department of Psychiatry, Mt. Sinai School of Medicine, New York City, New York, United States of America
- Department of Psychiatry, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America
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Blum K, Baron D, McLaughlin T, Thanos PK, Dennen C, Ceccanti M, Braverman ER, Sharafshah A, Lewandrowski KU, Giordano J, Badgaiyan RD. Summary Document Research on RDS Anti-addiction Modeling: Annotated Bibliography. JOURNAL OF ADDICTION PSYCHIATRY 2024; 8:1-33. [PMID: 38765881 PMCID: PMC11100022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Subscribe] [Scholar Register] [Indexed: 05/22/2024]
Abstract
Annotated bibliography of genetic addiction risk severity (GARS) publications, pro-dopamine regulation in nutraceuticals (KB220 nutraceutical variants), and policy documents. Further research is required to encourage the field to consider "Reward Deficiency Syndrome (RDS) Anti-addiction Modeling" which involves early risk identification by means of genetic assessment similar to GARS, followed by induction of dopamine homeostasis by means of genetically guided pro-dopamine regulation similar to KB220. These results suggest that genetically based treatments may be a missing piece in the treatment of substance use disorder (SUD).
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Affiliation(s)
- Kenneth Blum
- Center for Sports and Mental Health, Western University Health Sciences, Pomona, CA, USA
- The Kenneth Blum Behavioral and Neurogenetic Institute, LLC., Austin, TX, USA
| | - David Baron
- Center for Sports and Mental Health, Western University Health Sciences, Pomona, CA, USA
| | - Thomas McLaughlin
- The Kenneth Blum Behavioral and Neurogenetic Institute, LLC., Austin, TX, USA
| | - Panayotis K. Thanos
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York, Buffalo, NY, USA
| | - Catherine Dennen
- Department of Family Medicine, Jefferson University School of Medicine, Philadelphia, PA, USA
| | - Mauro Ceccanti
- Department of Translational and Precision Medicine, Sapienza University, Rome, Italy
| | - Eric R. Braverman
- The Kenneth Blum Behavioral and Neurogenetic Institute, LLC., Austin, TX, USA
| | - Alireza Sharafshah
- Division of Genetics, Department of Cell and Molecular Biology and Microbiology, School of Science and Biotechnology, University of Isfahan, Isfahan, Iran
| | - Kai-Uwe Lewandrowski
- Department of Orthopaedics, Fundación Universitaria Sanitas Bogotá D.C. Colombia
| | - John Giordano
- The Kenneth Blum Behavioral and Neurogenetic Institute, LLC., Austin, TX, USA
- Division of Recovery Science, JC’S Recovery Center, Hollywood, Florida, USA
| | - Rajendra D. Badgaiyan
- The Kenneth Blum Behavioral and Neurogenetic Institute, LLC., Austin, TX, USA
- Department of Psychiatry, Case Western Reserve University, School of Medicine, Cleveland, OH, USA
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Blum K, Mclaughlin T, Gold MS, Gondre-Lewis MC, Thanos PK, Elman I, Baron D, Bowirrat A, Barh D, Khalsa J, Hanna C, Jafari N, Zeine F, Braverman ER, Dennen C, Makale MT, Makale M, Sunder K, Murphy KT, Badgaiyan RD. Are We Getting High Cause the Thrill is Gone? JOURNAL OF ADDICTION PSYCHIATRY 2023; 7:5-516. [PMID: 38164471 PMCID: PMC10758019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/03/2024]
Abstract
In the USA alone, opioid use disorder (OUD) affects approximately 27 million people. While the number of prescriptions may be declining due to increased CDC guidance and prescriber education, fatalities due to fentanyl-laced street heroin are still rising. Our laboratory has extended the overall concept of both substance and non-substance addictive behaviors, calling it "Reward Deficiency Syndrome (RDS)." Who are its victims, and how do we get this unwanted disorder? Is RDS caused by genes (Nature), environment (Neuro-epigenetics, Nurture), or both? Recent research identifies resting-state functional connectivity in the brain reward circuitry as a crucial factor. Analogously, it is of importance to acknowledge that the cumulative discharge of dopamine, governed by the nucleus accumbens (NAc) and modulated by an array of additional neurotransmitters, constitutes a cornerstone of an individual's overall well-being. Neuroimaging reveals that high-risk individuals exhibit a blunted response to stimuli, potentially due to DNA polymorphisms or epigenetic alterations. This discovery has given rise to the idea of a diminished 'thrill,' though we must consider whether this 'thrill' may have been absent from birth due to high-risk genetic predispositions for addiction. This article reviews this issue and suggests the general concept of the importance of "induction of dopamine homeostasis." We suggest coupling a validated genetic assessment (e.g., GARS) with pro-dopamine regulation (KB220) as one possible frontline modality in place of prescribing potent addictive opioids for OUD except for short time harm reduction. Could gene editing offer a 'cure' for this undesirable genetic modification at birth, influenced by the environment and carried over generations, leading to impaired dopamine and other neurotransmitter imbalances, as seen in RDS? Through dedicated global scientific exploration, we hope for a future where individuals are liberated from pain and disease, achieving an optimal state of well-being akin to the proverbial 'Garden of Eden'.
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Affiliation(s)
- Kenneth Blum
- The Kenneth Blum Behavioral and Neurogenetic Institute, LLC., Austin, TX, USA
- Center for Sports, Exercise, Psychiatry, Western University Health Sciences, Pomona, CA, USA
- Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary
- Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel
- The Sunder Foundation, Palm Springs, CA, USA
- Department of Psychiatry, University of Vermont School of Medicine, Burlington, VY, USA
- Department of Psychiatry, Wright University, Boonshoff School of Medicine, Dayton, OH, USA
- Division of Personalized Medicine, Cross-Cultural Research and Educational Institute, San Clemente, CA, USA
- Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, Purba Medinipur, West Bengal, India
| | - Thomas Mclaughlin
- The Kenneth Blum Behavioral and Neurogenetic Institute, LLC., Austin, TX, USA
| | - Mark S. Gold
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
| | | | - Panayotis K. Thanos
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addiction, Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, Buffalo, NY, USA
| | - Igor Elman
- Cambridge Health Alliance, Harvard Medical School, Cambridge, MA, USA
| | - David Baron
- Center for Sports, Exercise, Psychiatry, Western University Health Sciences, Pomona, CA, USA
| | - Abdalla Bowirrat
- Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel
| | - Debamyla Barh
- Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, Purba Medinipur, West Bengal, India
| | - Jag Khalsa
- Division of Therapeutics and Medical Consequences, Medical Consequences of Drug Abuse and Infections Branch, NIDA-NIH, Special Volunteer, Gaithersburg, MD, USA
| | - Colin Hanna
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addiction, Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University of Buffalo, Buffalo, NY, USA
| | - Nicole Jafari
- Division of Personalized Medicine, Cross-Cultural Research and Educational Institute, San Clemente, CA, USA
- Department of Applied Clinical Psychology, The Chicago School of Professional Psychology, Los Angeles, CA, USA
| | - Foojan Zeine
- Department of Health Science, California State University at Long Beach, Long Beach, CA, USA
- Awareness Integration Institute, San Clemente, CA, USA
| | - Eric R. Braverman
- The Kenneth Blum Behavioral and Neurogenetic Institute, LLC., Austin, TX, USA
| | - Catherine Dennen
- Department of Family Medicine, Jefferson Health Northeast, Philadelphia, PA, USA
| | - Milan T. Makale
- Department of Radiation Medicine and Applied Sciences, UC San Diego, La Jolla, CA, USA
| | - Miles Makale
- Department of Psychology, UC San Diego, La Jolla, CA, USA
| | - Keerthy Sunder
- The Sunder Foundation, Palm Springs, CA, USA
- Department of Psychiatry, University of California Riverside, Riverside, CA, USA
| | - Kevin T. Murphy
- Department of Radiation Oncology, University of California, San Diego, La Jolla, USA
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9
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Alwindi M, Bizanti A. Vesicular monoamine transporter (VMAT) regional expression and roles in pathological conditions. Heliyon 2023; 9:e22413. [PMID: 38034713 PMCID: PMC10687066 DOI: 10.1016/j.heliyon.2023.e22413] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 09/28/2023] [Accepted: 11/10/2023] [Indexed: 12/02/2023] Open
Abstract
Vesicular monoamine transporters (VMATs) are key regulators of neurotransmitter release responsible for controlling numerous physiological, cognitive, emotional, and behavioral functions. They represent important therapeutic targets for numerous pathological conditions. There are two isoforms of VMAT transporter proteins that function as secondary active transporters into the vesicle for storage and release via exocytosis: VMAT1 (SLC18A1) and VMAT2 (SLC18A2) which differ in their function, quantity, and regional expression. VMAT2 has gained considerable interest as a therapeutic target and diagnostic marker. Inhibitors of VMAT2 have been used as an effective therapy for a range of pathological conditions. Additionally, the functionality and phenotypic classification of classical and nonclassical catecholaminergic neurons are identified by the presence of VMAT2 in catecholaminergic neurons. Dysregulation of VMAT2 is also implicated in many neuropsychiatric diseases. Despite the complex role of VMAT2, many aspects of its function remain unclear. Therefore, our aim is to expand our knowledge of the role of VMAT with a special focus on VMAT2 in different systems and cellular pathways which may potentially facilitate development of novel, more specific therapeutic targets. The current review provides a summary demonstrating the mechanism of action of VMAT, its functional role, and its contribution to disease progression and utilization as therapeutic targets.
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Affiliation(s)
- Malik Alwindi
- St George's University Hospital, London SW17 0QT, United Kingdom
| | - Ariege Bizanti
- Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA
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10
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Blum K, Ashford JW, Kateb B, Sipple D, Braverman E, Dennen CA, Baron D, Badgaiyan R, Elman I, Cadet JL, Thanos PK, Hanna C, Bowirrat A, Modestino EJ, Yamamoto V, Gupta A, McLaughlin T, Makale M, Gold MS. Dopaminergic dysfunction: Role for genetic & epigenetic testing in the new psychiatry. J Neurol Sci 2023; 453:120809. [PMID: 37774561 DOI: 10.1016/j.jns.2023.120809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Revised: 08/02/2023] [Accepted: 09/11/2023] [Indexed: 10/01/2023]
Abstract
Reward Deficiency Syndrome (RDS), particularly linked to addictive disorders, costs billions of dollars globally and has resulted in over one million deaths in the United States (US). Illicit substance use has been steadily rising and in 2021 approximately 21.9% (61.2 million) of individuals living in the US aged 12 or older had used illicit drugs in the past year. However, only 1.5% (4.1 million) of these individuals had received any substance use treatment. This increase in use and failure to adequately treat or provide treatment to these individuals resulted in 106,699 overdose deaths in 2021 and increased in 2022. This article presents an alternative non-pharmaceutical treatment approach tied to gene-guided therapy, the subject of many decades of research. The cornerstone of this paradigm shift is the brain reward circuitry, brain stem physiology, and neurotransmitter deficits due to the effects of genetic and epigenetic insults on the interrelated cascade of neurotransmission and the net release of dopamine at the Ventral Tegmental Area -Nucleus Accumbens (VTA-NAc) reward site. The Genetic Addiction Risk Severity (GARS) test and pro-dopamine regulator nutraceutical KB220 were combined to induce "dopamine homeostasis" across the brain reward circuitry. This article aims to encourage four future actionable items: 1) the neurophysiologically accurate designation of, for example, "Hyperdopameism /Hyperdopameism" to replace the blaming nomenclature like alcoholism; 2) encouraging continued research into the nature of dysfunctional brainstem neurotransmitters across the brain reward circuitry; 3) early identification of people at risk for all RDS behaviors as a brain check (cognitive testing); 4) induction of dopamine homeostasis using "precision behavioral management" along with the coupling of GARS and precision Kb220 variants; 5) utilization of promising potential treatments include neuromodulating modalities such as Transmagnetic stimulation (TMS) and Deep Brain Stimulation(DBS), which target different areas of the neural circuitry involved in addiction and even neuroimmune agents like N-acetyl-cysteine.
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Affiliation(s)
- Kenneth Blum
- Division of Addiction Research & Education, Center for Exercise, Sports and Mental Health, Western University Health Sciences, Pomona, CA, USA; The Kenneth Blum Behavioral & Neurogenetic Institute, LLC., Austin, TX, USA; Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel.
| | - J Wesson Ashford
- Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA, USA; War Related Illness & Injury Study Center, VA Palo Alto Health Care System, Palo Alto, CA, USA
| | - Babak Kateb
- Brain Mapping Foundation, Los Angeles, CA, USA; National Center for Nanobioelectronic, Los Angeles, CA, USA; Brain Technology and Innovation Park, Los Angeles, CA, USA
| | | | - Eric Braverman
- The Kenneth Blum Behavioral & Neurogenetic Institute, LLC., Austin, TX, USA
| | - Catherine A Dennen
- Department of Family Medicine, Jefferson Health Northeast, Philadelphia, PA, USA
| | - David Baron
- Division of Addiction Research & Education, Center for Exercise, Sports and Mental Health, Western University Health Sciences, Pomona, CA, USA
| | - Rajendra Badgaiyan
- Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy Memorial VA Hospital, San Antonio, TX, USA; Long School of Medicine, University of Texas Medical Center, San Antonio, TX, USA
| | - Igor Elman
- Center for Pain and the Brain (PAIN Group), Department of Anesthesiology, Critical Care & Pain Medicine, Boston Children's Hospital, Waltham, MA, USA; Cambridge Health Alliance, Harvard Medical School, Cambridge, MA, USA
| | - Jean Lud Cadet
- Molecular Neuropsychiatry Research Branch, NIH National Institute on Drug Abuse, Bethesda, MD, USA
| | - Panayotis K Thanos
- Department of Psychology & Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, NY, USA
| | - Colin Hanna
- Department of Psychology & Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, NY, USA
| | - Abdalla Bowirrat
- Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel
| | | | - Vicky Yamamoto
- Brain Mapping Foundation, Los Angeles, CA, USA; National Center for Nanobioelectronic, Los Angeles, CA, USA; Brain Technology and Innovation Park, Los Angeles, CA, USA; Society for Brain Mapping and Therapeutics, Los Angeles, CA, USA; USC-Norris Comprehensive Cancer Center, Los Angeles, CA, USA
| | | | - Thomas McLaughlin
- Division of Reward Deficiency Research, Reward Deficiency Syndrome Clinics of America, Austin, TX, USA
| | - Mlan Makale
- Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA
| | - Mark S Gold
- Department of Psychiatry, Washington College of Medicine, St. Louis, MO, USA
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11
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Thanos PK, Hanna C, Mihalkovic A, Hoffman A, Posner A, Butsch J, Blum K, Georger L, Mastrandrea LD, Quattrin T. Genetic Correlates as a Predictor of Bariatric Surgery Outcomes after 1 Year. Biomedicines 2023; 11:2644. [PMID: 37893019 PMCID: PMC10603884 DOI: 10.3390/biomedicines11102644] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 08/30/2023] [Accepted: 09/19/2023] [Indexed: 10/29/2023] Open
Abstract
This study analyzed genetic risk assessments in patients undergoing bariatric surgery to serve as a predictive factor for weight loss parameters 1 year after the operation. Thirty (30) patients were assessed for Genetic Addiction Risk Severity (GARS), which analyzes neurogenetic polymorphisms involved in addiction and reward deficiency. Genetic and psychosocial data collected before the operation were correlated with weight loss data, including changes in weight, body mass index (BMI), and percent of expected weight loss (%EWL). Results examined correlations between individual gene risk alleles, 1-year body weight data, and psychosocial trait scores. Spearman's correlations revealed that the OPRM1 (rs1799971) gene polymorphism had significant negative correlation with 1-year weight (rs = -0.4477, p < 0.01) and BMI (rs = -0.4477, p < 0.05). In addition, the DRD2 risk allele (rs1800497) was correlated negatively with BMI at 1 year (rs = -0.4927, p < 0.05), indicating that one risk allele copy was associated with lower BMI. However, this allele was positively correlated with both ∆Weight (rs = 0.4077, p < 0.05) and %EWL (rs = 0.5521, p < 0.05) at 1 year post-surgery. Moreover, the overall GARS score was correlated with %EWL (rs = 0.4236, p < 0.05), ∆Weight (rs = 0.3971, p < 0.05) and ∆BMI (rs = 0.3778, p < 0.05). Lastly, Food Cravings Questionnaire (FCQ) scores were negatively correlated with %EWL (rs = -0.4320, p < 0.05) and ∆Weight at 1 year post-surgery (rs = -0.4294, p < 0.05). This suggests that individuals with a higher genetic addiction risk are more responsive to weight loss treatment, especially in the case of the DRD2 polymorphism. These results should translate clinically to improve positivity and attitude related to weight management by those individuals born with the risk alleles (rs1800497; rs1799971).
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Affiliation(s)
- Panayotis K. Thanos
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Department of Pharmacology and Toxicology, Clinical Research Institute on Addictions, Jacobs School of Medicine and Biosciences, University at Buffalo, Buffalo, NY 14203, USA; (C.H.)
| | - Colin Hanna
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Department of Pharmacology and Toxicology, Clinical Research Institute on Addictions, Jacobs School of Medicine and Biosciences, University at Buffalo, Buffalo, NY 14203, USA; (C.H.)
| | - Abrianna Mihalkovic
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Department of Pharmacology and Toxicology, Clinical Research Institute on Addictions, Jacobs School of Medicine and Biosciences, University at Buffalo, Buffalo, NY 14203, USA; (C.H.)
- Department of Psychology, University at Buffalo, Buffalo, NY 14203, USA
| | - Aaron Hoffman
- Department of Surgery, Methodist Hospital Medical Center, Dallas, TX 75208, USA
| | - Alan Posner
- Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA
| | - John Butsch
- Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA
| | - Kenneth Blum
- Division of Nutrigenomics, SpliceGen, Therapeutics, Inc., Austin, TX 78701, USA;
- Department of Psychiatry, Wright State University Boonshoft School of Medicine and Dayton VA Medical Center, Dayton, OH 45435, USA
- Division of Addiction Research & Education, Center for Exercise Sports & Global Mental Health, Western University Health Sciences, Pomona, CA 91766, USA
- The Kenneth Blum Behavioral & Neurogenetic Institute, LLC., Austin, TX 78701, USA
- Institute of Psychology, ELTE Eötvös Loránd University, 1075 Budapest, Hungary
- Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, Purba Medinipur 721172, West Bengal, India
- Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel 40700, Israel
| | - Lesley Georger
- Department of Natural Sciences and Mathematics, D’Youville University, Buffalo, NY 14201, USA;
| | - Lucy D. Mastrandrea
- UBMD Pediatrics, JR Oishei Children’s Hospital, University at Buffalo, Buffalo, NY 14203, USA (T.Q.)
| | - Teresa Quattrin
- UBMD Pediatrics, JR Oishei Children’s Hospital, University at Buffalo, Buffalo, NY 14203, USA (T.Q.)
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12
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Vanyukov MM. Stigmata that are desired: Contradictions in addiction. ADDICTION RESEARCH & THEORY 2023; 32:83-92. [PMID: 38523739 PMCID: PMC10957146 DOI: 10.1080/16066359.2023.2238603] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 07/17/2023] [Indexed: 03/26/2024]
Abstract
Many experts in the etiology, assessment, and treatment of substance use/addiction view stigma and stigmatization - negatively branding addiction and substance users - as obstacles to the solution of the substance misuse problem. Discussions on this topic impact research and policy, and result in oft-repeated calls to remove the stigma from substance use and users. The goal of the article is to analyze the stigmatization concept as applied to substance use/addiction. It is widely accepted in the literature that stigmatization negatively affects substance users because addiction stigma interferes in both seeking and receiving professional care. It is argued that the societal disapproval of substance use/addiction is inappropriate because it is a mental disorder, involving biological processes. Nonetheless, neither those processes nor negative attitudes to substance use affirm the concept of stigmatization as currently applied. This concept conflates potential mistreatment and malpractice with the prosocial justified societal disapproval of a lethally dangerous behavior. Consequently, the stigmatization concept suffers from internal contradictions, is either misleading or redundant, and may do more harm than the supposed mistreatment of substance users that stigmatization connotes. On the contrary, the justified disapproval of harmful behavior may be a factor raising individual resistance to substance use. Instead of mitigating the effects of that disapproval, it may need to be capitalized on. If it is employed explicitly, conscientiously, and professionally, its internalization may be one of the resistance mechanisms needed to achieve any progress in the still elusive prevention of substance use and addiction.
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Affiliation(s)
- Michael M Vanyukov
- Departments of Pharmaceutical Sciences, Psychiatry, and Human Genetics, University of Pittsburgh, Pittsburgh PA, USA
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13
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Thanos PK, Hanna C, Mihalkovic A, Hoffman AB, Posner AR, Busch J, Smith C, Badgaiyan RD, Blum K, Baron D, Mastrandrea LD, Quattrin T. The First Exploratory Personalized Medicine Approach to Improve Bariatric Surgery Outcomes Utilizing Psychosocial and Genetic Risk Assessments: Encouraging Clinical Research. J Pers Med 2023; 13:1164. [PMID: 37511777 PMCID: PMC10381606 DOI: 10.3390/jpm13071164] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 07/06/2023] [Accepted: 07/10/2023] [Indexed: 07/30/2023] Open
Abstract
It is predicted that by 2030, globally, an estimated 2.16 billion adults will be overweight, and 1.12 billion will be obese. This study examined genetic data regarding Reward Deficiency Syndrome (RDS) to evaluate their usefulness in counselling patients undergoing bariatric surgery and gathered preliminary data on the potential use in predicting short term (6-month) weight loss outcomes. Methods: Patients undergoing bariatric surgery (n = 34) were examined for Genetic Addiction Risk Severity (GARS) [measures the presence of risk alleles associated with RDS]; as well as their psychosocial traits (questionnaires). BMI changes and sociodemographic data were abstracted from Electronic Health Records. Results: Subjects showed ∆BMI (M = 10.0 ± 1.05 kg/m2) and a mean % excess weight loss (56 ± 13.8%). In addition, 76% of subjects had GARS scores above seven. The homozygote risk alleles for MAO (rs768062321) and DRD1 (rs4532) showed a 38% and 47% prevalence among the subjects. Of the 11 risk alleles identified by GARS, the DRD4 risk allele (rs1800955), was significantly correlated with change in weight and BMI six months post-surgery. We identified correlations with individual risk alleles and psychosocial trait scores. The COMT risk allele (rs4680) showed a negative correlation with EEI scores (r = -0.4983, p < 0.05) and PSQI scores (r = -0.5482, p < 0.05). The GABRB3 risk allele (rs764926719) correlated positively with EEI (r = 0.6161, p < 0.01) and FCQ scores (r = 0.6373, p < 0.01). The OPRM1 risk allele showed a positive correlation with the DERS score (r = 0.5228, p < 0.05). We also identified correlations between DERS and BMI change (r = 0.61; p < 0.01). Conclusions: These data support the potential benefit of a personalized medicinal approach inclusive of genetic testing and psychosocial trait questionnaires when counselling patients with obesity considering bariatric surgery. Future research will explore epigenetic factors that contribute to outcomes of bariatric surgery.
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Affiliation(s)
- Panayotis K. Thanos
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA; (C.H.); (A.M.)
- Department of Psychology, University at Buffalo, Buffalo, NY 14203, USA
| | - Colin Hanna
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA; (C.H.); (A.M.)
| | - Abrianna Mihalkovic
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA; (C.H.); (A.M.)
- Department of Psychology, University at Buffalo, Buffalo, NY 14203, USA
| | - Aaron B. Hoffman
- Department of Surgery, Methodist Hospital Medical Center, Dallas, TX 75001, USA; (A.B.H.); (L.D.M.)
| | - Alan R. Posner
- Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA; (A.R.P.); (J.B.)
| | - John Busch
- Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA; (A.R.P.); (J.B.)
| | - Caroline Smith
- UBMD Pediatrics, JR Oishei Children’s Hospital, University at Buffalo, Buffalo, NY 14203, USA;
| | - Rajendra D. Badgaiyan
- Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy Memorial VA Hospital, Long School of Medicine, University of Texas Health Science Center, San Antonio, TX 78229, USA;
| | - Kenneth Blum
- Division of Nutrigenomics, SpliceGen, Therapeutics, Inc., Austin, TX 78701, USA;
- Department of Psychiatry, Wright State University Boonshoft School of Medicine, Dayton, OH 45435, USA;
- Division of Addiction Research & Education, Center for Exercise Sports & Global Mental Health, Western University Health Sciences, Pomona, CA 91766, USA
- The Kenneth Blum Behavioral & Neurogenetic Institute, LLC., Austin, TX 78701, USA
- Institute of Psychology, ELTE Eötvös Loránd University, 23-27, 1075 Budapest, Hungary
- Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, Purba Medinipur 721172, West Bengal, India
- Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel 40700, Israel
| | - David Baron
- Department of Psychiatry, Wright State University Boonshoft School of Medicine, Dayton, OH 45435, USA;
| | - Lucy D. Mastrandrea
- Department of Surgery, Methodist Hospital Medical Center, Dallas, TX 75001, USA; (A.B.H.); (L.D.M.)
| | - Teresa Quattrin
- Department of Surgery, Methodist Hospital Medical Center, Dallas, TX 75001, USA; (A.B.H.); (L.D.M.)
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Muriel J, Escorial M, Margarit C, Barrachina J, Carvajal C, Morales D, Peiró AM. Long-term deprescription in chronic pain and opioid use disorder patients: Pharmacogenetic and sex differences. ACTA PHARMACEUTICA (ZAGREB, CROATIA) 2023; 73:227-241. [PMID: 37307374 DOI: 10.2478/acph-2023-0018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 11/17/2022] [Indexed: 06/14/2023]
Abstract
More than half of patients with opioid use disorder for chronic non-cancer pain (CNCP) reduced their dose through a progressive opioid withdrawal supported by a rotation to buprenorphine and/or tramadol. The aim of this research is to analyse the long-term effectiveness of opioid deprescription taking into account the impact of sex and pharmacogenetics on the inter-individual variability. A cross-sectional study was carried out from October 2019 to June 2020 on CNCP patients who had previously undergone an opioid deprescription (n = 119 patients). Demographic, clinical (pain, relief and adverse events) and therapeutic (analgesic use) outcomes were collected. Effectiveness (< 50 mg per day of morphine equivalent daily dose without any aberrant opioid use behaviour) and safety (number of side-effects) were analysed in relation to sex differences and pharmacogenetic markers impact [OPRM1 genotype (rs1799971) and CYP2D6 phenotypes]. Long-term opioid deprescription was achieved in 49 % of the patients with an increase in pain relief and a reduction of adverse events. CYP2D6 poor metabolizers showed the lowest long-term opioid doses. Here, women showed a higher degree of opioid deprescription, but increased use of tramadol and neuromodulators, as well as an increased number of adverse events. Long-term deprescription was successful in half of the cases. Understanding sex and gender interaction plus a genetic impact could help to design more individualized strategies for opioid deprescription.
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Affiliation(s)
- Javier Muriel
- 1Neuropharmacology applied to Pain (NED) Alicante Institute for Health and Biomedical Research (ISABIAL), c/Pintor Baeza, 12 03010, Alicante, Spain
| | - Mónica Escorial
- 1Neuropharmacology applied to Pain (NED) Alicante Institute for Health and Biomedical Research (ISABIAL), c/Pintor Baeza, 12 03010, Alicante, Spain
- 2Institute of Bioengineering, Miguel Hernández University, Avda. de la Universidad s/n, 03202, Elche, Spain
| | - César Margarit
- 1Neuropharmacology applied to Pain (NED) Alicante Institute for Health and Biomedical Research (ISABIAL), c/Pintor Baeza, 12 03010, Alicante, Spain
- 3Pain Unit, Dr. Balmis General University Hospital, ISABIAL, c/Pintor Baeza, 12 03010, Alicante, Spain
| | - Jordi Barrachina
- 1Neuropharmacology applied to Pain (NED) Alicante Institute for Health and Biomedical Research (ISABIAL), c/Pintor Baeza, 12 03010, Alicante, Spain
- 2Institute of Bioengineering, Miguel Hernández University, Avda. de la Universidad s/n, 03202, Elche, Spain
| | - Cristian Carvajal
- 2Institute of Bioengineering, Miguel Hernández University, Avda. de la Universidad s/n, 03202, Elche, Spain
| | - Domingo Morales
- 4Operations Research Centre, Miguel Hernández University, Avda. de la Universidad s/n, 03202, Elche, Spain
| | - Ana M Peiró
- 1Neuropharmacology applied to Pain (NED) Alicante Institute for Health and Biomedical Research (ISABIAL), c/Pintor Baeza, 12 03010, Alicante, Spain
- 2Institute of Bioengineering, Miguel Hernández University, Avda. de la Universidad s/n, 03202, Elche, Spain
- 3Pain Unit, Dr. Balmis General University Hospital, ISABIAL, c/Pintor Baeza, 12 03010, Alicante, Spain
- 5Clinical Pharmacology Department, Dr. Balmis General University Hospital ISABIAL, c/Pintor Baeza, 12, 03010 Alicante, Spain
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15
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Dennen A C, Blum K, Braverman R E, Bowirrat A, Gold M, Elman I, Thanos K P, Baron D, Gupta A, Edwards D, Badgaiyan D R. How to Combat the Global Opioid Crisis. CPQ NEUROLOGY AND PSYCHOLOGY 2023; 5:93. [PMID: 36812107 PMCID: PMC9937628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Subscribe] [Scholar Register] [Indexed: 02/24/2023]
Abstract
Since 2000 there have been 915,515 people who have died from a drug overdose in the United States (US). This number continues to increase and in 2021 drug overdose deaths reached a record high of 107,622, and opioids specifically were responsible for 80,816 of those deaths. This unprecedented rate of drug overdose deaths is the direct result of increasing rates of illicit drug use in the US. It was estimated that in the US in 2020, approximately 59.3 million individuals had used illicit drugs, 40.3 million had a substance use disorder (SUD), and 2.7 million had opioid use disorder (OUD). Typical treatment for OUD involves an opioid agonist (i.e., buprenorphine or methadone) along with a variety of psychotherapeutic interventions (i.e., motivational interviewing, cognitive-behavioral therapy (CBT), behavioral family counseling, mutual help groups, etc.). In addition to the aforementioned treatment options, there is an urgent need for new therapies and screening methods that are reliable, safe, and effective. Similar to the concept of prediabetes is the novel concept of "preaddiction." Preaddiction is defined as individuals with mild to moderate SUD or those at risk for developing a severe SUD/addiction. Screening for preaddiction could be achieved through genetic testing (i.e., the genetic addiction risk severity (GARS) test) and/or through other neuropsychiatric testing (i.e., Memory (CNSVS), Attention (TOVA), Neuropsychiatric (MCMI-III), Neurological Imaging (qEEG/P300/EP)). The concept of preaddiction, when used in conjunction with standardized and objective diagnostic screening/testing, would halt the rise of SUD and overdoses with early detection and treatment.
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Affiliation(s)
- Catherine Dennen A
- Department of Family Medicine, Jefferson Health Northeast, Philadelphia, PA., USA
| | - Kenneth Blum
- The Kenneth Blum Behavioral & Neurogenetic Institute, LLC., Austin, TX 78701, USA
- Center for Sports, Exercise, Psychiatry, Western University Health Sciences, Pomona, CA., USA
- Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary
- Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel
| | - Eric Braverman R
- The Kenneth Blum Behavioral & Neurogenetic Institute, LLC., Austin, TX 78701, USA
| | - Abdalla Bowirrat
- Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel, Israel
| | - Marks Gold
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO., USA
| | - Igor Elman
- Cambridge Health Alliance, Harvard Medical School, Cambridge, MA., USA
| | - Panayotis Thanos K
- Behavioral Neuropharmacology and Neuroimaging Laboratory, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, Clinical Research Institute on Addictions, University at Buffalo, Buffalo, NY., USA
- Department of Psychology, University at Buffalo, Buffalo, NY., USA
| | - David Baron
- Center for Sports, Exercise, Psychiatry, Western University Health Sciences, Pomona, CA., USA
| | | | | | - Rajendra Badgaiyan D
- Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy Memorial VA Hospital, Long School of Medicine, University of Texas Medical Center, San Antonio, TX 78229, USA
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16
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Ceccanti M, Blum K, Bowirrat A, Dennen CA, Braverman ER, Baron D, Mclaughlin T, Giordano J, Gupta A, Downs BW, Bagchi D, Barh D, Elman I, Thanos PK, Badgaiyan RD, Edwards D, Gold MS. Future Newborns with Opioid-Induced Neonatal Abstinence Syndrome (NAS) Could Be Assessed with the Genetic Addiction Risk Severity (GARS) Test and Potentially Treated Using Precision Amino-Acid Enkephalinase Inhibition Therapy (KB220) as a Frontline Modality Instead of Potent Opioids. J Pers Med 2022; 12:2015. [PMID: 36556236 PMCID: PMC9782293 DOI: 10.3390/jpm12122015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 11/14/2022] [Accepted: 11/25/2022] [Indexed: 12/12/2022] Open
Abstract
In this nonsystematic review and opinion, including articles primarily selected from PubMed, we examine the pharmacological and nonpharmacological treatments of neonatal abstinence syndrome (NAS) in order to craft a reasonable opinion to help forge a paradigm shift in the treatment and prevention of primarily opioid-induced NAS. Newborns of individuals who use illicit and licit substances during pregnancy are at risk for withdrawal, also known as NAS. In the US, the reported prevalence of NAS has increased from 4.0 per 1000 hospital births in 2010 to 7.3 per 1000 hospital births in 2017, which is an 82% increase. The management of NAS is varied and involves a combination of nonpharmacologic and pharmacologic therapy. The preferred first-line pharmacological treatment for NAS is opioid therapy, specifically morphine, and the goal is the short-term improvement in NAS symptomatology. Nonpharmacological therapies are individualized and typically focus on general care measures, the newborn-parent/caregiver relationship, the environment, and feeding. When used appropriately, nonpharmacologic therapies can help newborns with NAS avoid or reduce the amount of pharmacologic therapy required and the length of hospitalization. In addition, genetic polymorphisms of the catechol-o-methyltransferase (COMT) and mu-opioid receptor (OPRM1) genes appear to affect the length of stay and the need for pharmacotherapy in newborns with prenatal opioid exposure. Therefore, based on this extensive literature and additional research, this team of coauthors suggests that, in the future, in addition to the current nonpharmacological therapies, patients with opioid-induced NAS should undergo genetic assessment (i.e., the genetic addiction risk severity (GARS) test), which can subsequently be used to guide DNA-directed precision amino-acid enkephalinase inhibition (KB220) therapy as a frontline modality instead of potent opioids.
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Affiliation(s)
- Mauro Ceccanti
- Società Italiana per il Trattamento dell’Alcolismo e le sue Complicanze (SITAC), ASL Roma1, Sapienza University of Rome, 00185 Rome, Italy
| | - Kenneth Blum
- The Kenneth Blum Behavioral & Neurogenetic Institute, Austin, TX 78701, USA
- Division of Addiction Research & Education, Center for Mental Health & Sports, Exercise and Global Mental Health, Western University Health Sciences, Pomona, CA 91766, USA
- Institute of Psychology, ELTE Eötvös Loránd University, Egyetem tér 1-3, H-1053 Budapest, Hungary
- Department of Psychiatry, School of Medicine, University of Vermont, Burlington, VT 05405, USA
- Department of Psychiatry, Wright State University Boonshoft School of Medicine and Dayton VA Medical Centre, Dayton, OH 45324, USA
- Reward Deficiency Clinics of America, Austin, TX 78701, USA
- Center for Genomics and Applied Gene Technology, Institute of Integrative Omics and applied Biotechnology (IIOAB), Nonakuri, Purba Medinipur, West Bengal 721172, India
- Department of Precision Behavioral Management, Transplicegen Therapeutics, Inc., LLC., Austin, TX 78701, USA
- Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel 40700, Israel
| | - Abdalla Bowirrat
- Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel 40700, Israel
| | - Catherine A. Dennen
- Department of Family Medicine, Jefferson Health Northeast, Philadelphia, PA 19107, USA
| | - Eric R. Braverman
- The Kenneth Blum Behavioral & Neurogenetic Institute, Austin, TX 78701, USA
| | - David Baron
- Division of Addiction Research & Education, Center for Mental Health & Sports, Exercise and Global Mental Health, Western University Health Sciences, Pomona, CA 91766, USA
| | | | - John Giordano
- The Kenneth Blum Behavioral & Neurogenetic Institute, Austin, TX 78701, USA
- Ketamine Infusion Clinic of South Florida, Pompano Beach, FL 33062, USA
| | - Ashim Gupta
- Future Biologics, Lawrenceville, GA 30043, USA
| | - Bernard W. Downs
- The Kenneth Blum Behavioral & Neurogenetic Institute, Austin, TX 78701, USA
| | - Debasis Bagchi
- The Kenneth Blum Behavioral & Neurogenetic Institute, Austin, TX 78701, USA
- Department of Pharmaceutical Sciences, Southern University College of Pharmacy, Houston, TX 77004, USA
| | - Debmalya Barh
- Center for Genomics and Applied Gene Technology, Institute of Integrative Omics and applied Biotechnology (IIOAB), Nonakuri, Purba Medinipur, West Bengal 721172, India
- Department of Genetics, Ecology and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
| | - Igor Elman
- Center for Pain and the Brain (PAIN Group), Department of Anesthesiology, Critical Care & Pain Medicine, Boston Children’s Hospital, Harvard School of Medicine, Boston, MA 02115, USA
| | - Panayotis K. Thanos
- Behavioral Neuropharmacology and Neuroimaging Laboratory, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA
| | - Rajendra D. Badgaiyan
- Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy Memorial VA Hospital, Long School of Medicine, University of Texas Medical Center, San Antonio, TX 78229, USA
| | - Drew Edwards
- Neurogenesis Project, Jacksonville, FL 32223, USA
| | - Mark S. Gold
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA
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Modestino EJ, Blum K, Dennen CA, Downs BW, Bagchi D, Llanos-Gomez L, Elman I, Baron D, Thanos PK, Badgaiyan RD, Braverman ER, Gupta A, Gold MS, Bowirrat A. Theorizing the Role of Dopaminergic Polymorphic Risk Alleles with Intermittent Explosive Disorder (IED), Violent/Aggressive Behavior and Addiction: Justification of Genetic Addiction Risk Severity (GARS) Testing. J Pers Med 2022; 12:1946. [PMID: 36556167 PMCID: PMC9784939 DOI: 10.3390/jpm12121946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 11/09/2022] [Accepted: 11/17/2022] [Indexed: 11/25/2022] Open
Abstract
Scientific studies have provided evidence that there is a relationship between violent and aggressive behaviors and addictions. Genes involved with the reward system, specifically the brain reward cascade (BRC), appear to be associated with various addictions and impulsive, aggressive, and violent behaviors. In our previous research, we examined the Taq A1 allele (variant D2 dopamine receptor gene) and the DAT-40 base repeat (a variant of the dopamine transporter gene) in 11 Caucasian boys at the Brown School in San Marcus, Texas, diagnosed with intermittent explosive disorder. Thirty supernormal controls were screened to exclude several reward-deficit behaviors, including pathological violence, and genotyped for the DRD2 gene. Additionally, 91 controls were screened to exclude ADHD, pathological violence, alcoholism, drug dependence, and tobacco abuse, and their results were compared with DAT1 genotype results. In the schoolboys vs. supercontrols, there was a significant association with the D2 variant and a trend with the dopamine transporter variant. Results support our hypothesis and the involvement of at least two gene risk alleles with adolescent violent/aggressive behaviors. This study and the research presented in this paper suggest that violent/aggressive behaviors are associated with a greater risk of addiction, mediated via various genes linked to the BRC. This review provides a contributory analysis of how gene polymorphisms, especially those related to the brain reward circuitry, are associated with violent behaviors.
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Affiliation(s)
- Edward Justin Modestino
- The Kenneth Blum Behavioral & Neurogenetic Institute, Austin, TX 78701, USA
- Department of Psychology, Curry College, Milton, MA 02360, USA
| | - Kenneth Blum
- The Kenneth Blum Behavioral & Neurogenetic Institute, Austin, TX 78701, USA
- Division of Addiction Research & Education, Center for Psychiatry, Medicine & Primary Care, Western University Health Sciences, Pomona, CA 91766, USA
- Department of Precision Behavioral Management, Geneus Health, San Antonio, TX 78283, USA
- Institute of Psychology, ELTE Eötvös Loránd University, H-1053 Budapest, Hungary
- Department of Psychiatry, University of Vermont, Burlington, VT 05401, USA
- Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur 721172, West Bengal, India
- Department of Psychiatry, Wright State University Boonshoft School of Medicine and Dayton VA Medical Centre, Dayton, OH 45324, USA
- Department of Psychiatry, School of Medicine, University of Vermont, Burlington, VT 05405, USA
- Department of Molecular Biology and Adelson, School of Medicine, Ariel University, Ariel 40700, Israel
| | - Catherine A. Dennen
- Department of Family Medicine, Jefferson Health Northeast, Philadelphia, PA 08033, USA
| | - B. William Downs
- Division of Nutrigenomics, Victory Nutrition International, Lederach, PA 19438, USA
| | - Debasis Bagchi
- Division of Nutrigenomics, Victory Nutrition International, Lederach, PA 19438, USA
- Department of Pharmacy and Health Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USA
| | - Luis Llanos-Gomez
- The Kenneth Blum Behavioral & Neurogenetic Institute, Austin, TX 78701, USA
| | - Igor Elman
- Department of Psychiatry, Harvard Medical School, Boston, MA 02139, USA
| | - David Baron
- Division of Addiction Research & Education, Center for Psychiatry, Medicine & Primary Care, Western University Health Sciences, Pomona, CA 91766, USA
| | - Panayotis K. Thanos
- Department of Psychology & Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Research Institute on Addictions, University at Buffalo, Buffalo, NY 14203, USA
| | - Rajendra D. Badgaiyan
- Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy Memorial VA Hospital, Long School of Medicine, University of Texas Medical Center, San Antonio, TX 78229, USA
| | - Eric R. Braverman
- The Kenneth Blum Behavioral & Neurogenetic Institute, Austin, TX 78701, USA
| | - Ashim Gupta
- Future Biologics, Lawrenceville, GA 30043, USA
| | - Mark S. Gold
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Abdalla Bowirrat
- Department of Molecular Biology and Adelson, School of Medicine, Ariel University, Ariel 40700, Israel
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18
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Blum K, Bowirrat A, Gomez LL, Downs BW, Bagchi D, Barh D, Modestino EJ, Baron D, McLaughlin T, Thanos P, Ceccanti M, Elman I, Badgaiyan RD, Dennen C, Gupta A, Braverman ER, Gold MS. Why haven't we solved the addiction crisis? J Neurol Sci 2022; 442:120404. [PMID: 36084363 DOI: 10.1016/j.jns.2022.120404] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Accepted: 08/25/2022] [Indexed: 11/22/2022]
Abstract
The current addiction crisis has destroyed a multitude of lives, leaving millions of fatalities worldwide in its wake. At the same time, various governmental agencies dedicated to solving this seemingly never-ending dilemma have not yet succeeded or delivered on their promises. We understand that addictive behavioral seeking is a multi-faceted neurobiological and spiritually complicated phenomenon. However, although the substitution replacement approach, especially to treat Opioid Use Disorder (OUD), has importance for harm reduction in the short term, it does not bring about a harm-free recovery or prevention. Instead, we propose a promising novel approach that uses genetic risk testing with induction of dopamine homeostasis and an objective Brain Health Check during youth. Our model involves a six-hit approach known as the "Reward Dysregulation Syndrome Solution System," which can identify addiction risk and target the root cause of addiction, dopamine dysregulation. While we applaud all past sophisticated neurogenetic and neuropharmacological research, our opinion is that in the long term, addiction scientists and clinicians might characterize preaddiction using tests; for example, administering the validated RDSQuestionarre29, genetic risk assessment, a modified brain health check, or diagnostic framing of mild to moderate Substance Use Disorder (SUD). The preaddiction concept could incentivize the development of interventions to prevent addiction from developing in the first place and target and treat neurotransmitter imbalances and other early indications of addiction. WC 222.
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Affiliation(s)
- Kenneth Blum
- Division of Addiction Research & Education, Center for Sports and Mental Health, Western University of Health Sciences, Pomona, CA, USA; Division of Nutrigenomics, The Kenneth Blum Neurogenetic & Behavioral Institute, LLC, Austin, TX., USA; Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary; Department of Psychiatry, University of Vermont, Burlington, VT., USA; Department of Psychiatry, Wright University Boonshoff School of Medicine, Dayton, OH, USA; Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, Purba Medinipur, West Bengal 721172; India; Department of Nutrigenomic Research, Victory Nutrition International, Inc., Bonita Springs, FL, USA.
| | - Abdalla Bowirrat
- Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel 40700, Israel
| | - Luis Llanos Gomez
- Division of Nutrigenomics, The Kenneth Blum Neurogenetic & Behavioral Institute, LLC, Austin, TX., USA
| | - B William Downs
- Department of Nutrigenomic Research, Victory Nutrition International, Inc., Bonita Springs, FL, USA
| | - Debasis Bagchi
- Department of Nutrigenomic Research, Victory Nutrition International, Inc., Bonita Springs, FL, USA; Department of Pharmaceutical Sciences, Texas Southern University College of Pharmacy and Health Sciences, Houston, TX, USA
| | - Debmalya Barh
- Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, Purba Medinipur, West Bengal 721172; India
| | | | - David Baron
- Division of Addiction Research & Education, Center for Sports and Mental Health, Western University of Health Sciences, Pomona, CA, USA
| | - Thomas McLaughlin
- Division of Nutrigenomics, The Kenneth Blum Neurogenetic & Behavioral Institute, LLC, Austin, TX., USA
| | - Panayotis Thanos
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY, USA; Department of Psychology, State University of New York at Buffalo, Buffalo, NY., USA
| | - Mauro Ceccanti
- Alcohol Addiction Program, Latium Region Referral Center, Sapienza University of Rome, Roma, Italy
| | - Igor Elman
- Cambridge Health Alliance, Harvard Medical School, Cambridge, MA, USA
| | - Rajendra D Badgaiyan
- Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy Memorial VA Hospital, Long School of Medicine, University of Texas Health Science Center, San Antonio, TX., USA; Department of Psychiatry, Mt. Sinai School of Medicine, New York, NY., USA
| | - Catherine Dennen
- Department of Family Medicine, Jefferson Health Northeast, Philadelphia, PA, USA
| | - Ashim Gupta
- Future Biologics, Lawrenceville, GA 30043, USA; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
| | - Eric R Braverman
- Division of Nutrigenomics, The Kenneth Blum Neurogenetic & Behavioral Institute, LLC, Austin, TX., USA
| | - Mark S Gold
- Future Biologics, Lawrenceville, GA 30043, USA
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19
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Dennen CA, Blum K, Bowirrat A, Thanos PK, Elman I, Ceccanti M, Badgaiyan RD, McLaughlin T, Gupta A, Bajaj A, Baron D, Downs BW, Bagchi D, Gold MS. Genetic Addiction Risk Severity Assessment Identifies Polymorphic Reward Genes as Antecedents to Reward Deficiency Syndrome (RDS) Hypodopaminergia's Effect on Addictive and Non-Addictive Behaviors in a Nuclear Family. J Pers Med 2022; 12:1864. [PMID: 36579592 PMCID: PMC9694640 DOI: 10.3390/jpm12111864] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 10/19/2022] [Accepted: 10/28/2022] [Indexed: 11/09/2022] Open
Abstract
This case series presents the novel genetic addiction risk score (GARS), which shows a high prevalence of polymorphic risk alleles of reward genes in a nuclear family with multiple reward deficiency syndrome (RDS) behavioral issues expressing a hypodopaminergic antecedent. The family consists of a mother, father, son, and daughter. The mother experienced issues with focus, memory, anger, and amotivational syndrome. The father experienced weight issues and depression. The son experienced heavy drinking, along with some drug abuse and anxiety. The daughter experienced depression, lethargy, brain fog, focus issues, and anxiety, among others. A major clinical outcome of the results presented to the family members helped reduce personal guilt and augment potential hope for future healing. Our laboratory's prior research established that carriers of four or more alleles measured by GARS (DRD1-DRD4, DAT1, MOR, GABABR3, COMT, MAOAA, and 5HTLPR) are predictive of the addiction severity index (ASI) for drug abuse, and carriers of seven or more alleles are predictive of severe alcoholism. This generational case series shows the impact that genetic information has on reducing stigma and guilt in a nuclear family struggling with RDS behaviors. The futuristic plan is to introduce an appropriate DNA-guided "pro-dopamine regulator" into the recovery and enhancement of life.
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Affiliation(s)
- Catherine A. Dennen
- Department of Family Medicine, Jefferson Health Northeast, Philadelphia, PA 08033, USA
| | - Kenneth Blum
- Division of Addiction Research & Education, Center for Sports and Mental Health, Western University of Health Sciences, Pomona, CA 91766, USA
- Division of Nutrigenomics, The Kenneth Blum Behavioral & Neurogenetic Institute, Austin, TX 78701, USA
- Institute of Psychology, ELTE Eötvös Loránd University, Egyetem tér 1–3, 1053 Budapest, Hungary
- Department of Psychiatry, School of Medicine, University of Vermont, Burlington, VT 05405, USA
- Department of Psychiatry, Wright State University Boonshoft School of Medicine and Dayton VA Medical Centre, Dayton, OH 45324, USA
- Center for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, Purba Medinipur 721172, West Bengal, India
| | - Abdalla Bowirrat
- Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel 40700, Israel
| | - Panayotis K. Thanos
- Behavioral Neuropharmacology and Neuroimaging Laboratory, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA
| | - Igor Elman
- Center for Pain and the Brain (P.A.I.N Group), Department of Anesthesiology, Critical Care & Pain Medicine, Boston Children’s Hospital, Boston, MA 02115, USA
| | - Mauro Ceccanti
- Società Italiana per il Trattamento dell’Alcolismo e le sue Complicanze (SITAC), ASL Roma, Sapienza University of Rome, 00185 Rome, Italy
| | - Rajendra D. Badgaiyan
- Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy Memorial VA Hospital, Long School of Medicine, University of Texas Medical Center, San Antonio, TX 78229, USA
| | | | - Ashim Gupta
- Future Biologics, Lawrenceville, GA 30043, USA
| | - Anish Bajaj
- Bajaj Chiropractic Clinic, New York, NY 10010, USA
| | - David Baron
- Division of Addiction Research & Education, Center for Sports and Mental Health, Western University of Health Sciences, Pomona, CA 91766, USA
| | - B. William Downs
- Division of Addiction Research & Education, Center for Sports and Mental Health, Western University of Health Sciences, Pomona, CA 91766, USA
| | - Debasis Bagchi
- Department of Pharmaceutical Sciences, Southern University College of Pharmacy, Houston, TX 77004, USA
| | - Mark S. Gold
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA
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Blum K, Han D, Bowirrat A, Downs BW, Bagchi D, Thanos PK, Baron D, Braverman ER, Dennen CA, Gupta A, Elman I, Badgaiyan RD, Llanos-Gomez L, Khalsa J, Barh D, McLaughlin T, Gold MS. Genetic Addiction Risk and Psychological Profiling Analyses for "Preaddiction" Severity Index. J Pers Med 2022; 12:1772. [PMID: 36579510 PMCID: PMC9696872 DOI: 10.3390/jpm12111772] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Revised: 10/15/2022] [Accepted: 10/16/2022] [Indexed: 01/01/2023] Open
Abstract
Since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism in JAMA, there has been an explosion of genetic candidate association studies, including genome-wide association studies (GWAS). To develop an accurate test to help identify those at risk for at least alcohol use disorder (AUD), a subset of reward deficiency syndrome (RDS), Blum's group developed the genetic addiction risk severity (GARS) test, consisting of ten genes and eleven associated risk alleles. In order to statistically validate the selection of these risk alleles measured by GARS, we applied strict analysis to studies that investigated the association of each polymorphism with AUD or AUD-related conditions, including pain and even bariatric surgery, as a predictor of severe vulnerability to unwanted addictive behaviors, published since 1990 until now. This analysis calculated the Hardy-Weinberg Equilibrium of each polymorphism in cases and controls. Pearson's χ2 test or Fisher's exact test was applied to compare the gender, genotype, and allele distribution if available. The statistical analyses found the OR, 95% CI for OR, and the post risk for 8% estimation of the population's alcoholism prevalence revealed a significant detection. Prior to these results, the United States and European patents on a ten gene panel and eleven risk alleles have been issued. In the face of the new construct of the "preaddiction" model, similar to "prediabetes", the genetic addiction risk analysis might provide one solution missing in the treatment and prevention of the neurological disorder known as RDS.
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Affiliation(s)
- Kenneth Blum
- Division of Addiction Research & Education, Center for Sports, Exercise, and Mental Health, Western University of Health Sciences, Pomona, CA 91766, USA
- Division of Nutrigenomics, The Kenneth Blum Behavioral Neurogenetic Institute, LLC, Austin, TX 78701, USA
- Institute of Psychology, ELTE Eötvös Loránd University, 1075 Budapest, Hungary
- Department of Psychiatry, University of Vermont, Burlington, VT 05405, USA
- Department of Psychiatry, Wright University Boonshoft School of Medicine, Dayton, OH 45324, USA
- Division of Nutrigenomics, Victory Nutrition International, Inc., Harleysville, PA 19329, USA
- Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur 721172, West Bengal, India
- Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel 40700, Israel
| | - David Han
- Department of Management Science and Statistics, University of Texas at San Antonio, San Antonio, TX 78249, USA
| | - Abdalla Bowirrat
- Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel 40700, Israel
| | - Bernard William Downs
- Division of Nutrigenomics, Victory Nutrition International, Inc., Harleysville, PA 19329, USA
| | - Debasis Bagchi
- Division of Nutrigenomics, Victory Nutrition International, Inc., Harleysville, PA 19329, USA
- Department of Pharmaceutical Sciences, College of Pharmacy, Southern University, Houston, TX 77004, USA
| | - Panayotis K. Thanos
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY 14260, USA
- Department of Psychology, State University of New York at Buffalo, Buffalo, NY 14260, USA
| | - David Baron
- Division of Addiction Research & Education, Center for Sports, Exercise, and Mental Health, Western University of Health Sciences, Pomona, CA 91766, USA
- Division of Nutrigenomics, The Kenneth Blum Behavioral Neurogenetic Institute, LLC, Austin, TX 78701, USA
| | - Eric R. Braverman
- Division of Nutrigenomics, The Kenneth Blum Behavioral Neurogenetic Institute, LLC, Austin, TX 78701, USA
| | - Catherine A. Dennen
- Department of Family Medicine, Jefferson Health Northeast, Philadelphia, PA 19107, USA
| | - Ashim Gupta
- Future Biologics, Lawrenceville, GA 30043, USA
| | - Igor Elman
- Department of Psychiatry, Harvard School of Medicine, Cambridge, MA 02115, USA
| | - Rajendra D. Badgaiyan
- Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy Memorial VA Hospital, Long School of Medicine, University of Texas Health Science Center, San Antonio, TX 78229, USA
- Department of Psychiatry, MT. Sinai School of Medicine, New York, NY 10003, USA
| | - Luis Llanos-Gomez
- Division of Nutrigenomics, The Kenneth Blum Behavioral Neurogenetic Institute, LLC, Austin, TX 78701, USA
| | - Jag Khalsa
- Department of Microbiology, Immunology and Tropical Medicine, School of Medicine, George Washington University, Washington, DC 20052, USA
- Medical Consequences of Drug Abuse and Infections Branch, National Institute on Drug Abuse, NIH, Bethesda, MD 20892, USA
| | - Debmalya Barh
- Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur 721172, West Bengal, India
- Department of Genetics, Ecology and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
| | - Thomas McLaughlin
- Division of Nutrigenomics, The Kenneth Blum Behavioral Neurogenetic Institute, LLC, Austin, TX 78701, USA
| | - Mark S. Gold
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA
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21
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Blum K, Dennen CA, Elman I, Bowirrat A, Thanos PK, Badgaiyan RD, Downs BW, Bagchi D, Baron D, Braverman ER, Gupta A, Green R, McLaughlin T, Barh D, Gold MS. Should Reward Deficiency Syndrome (RDS) Be Considered an Umbrella Disorder for Mental Illness and Associated Genetic and Epigenetic Induced Dysregulation of Brain Reward Circuitry? J Pers Med 2022; 12:1719. [PMID: 36294858 PMCID: PMC9604605 DOI: 10.3390/jpm12101719] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 10/11/2022] [Accepted: 10/11/2022] [Indexed: 11/30/2022] Open
Abstract
Reward Deficiency Syndrome (RDS) is defined as a breakdown of reward neurotransmission that results in a wide range of addictive, compulsive, and impulsive behaviors. RDS is caused by a combination of environmental (epigenetic) influences and DNA-based (genetic) neurotransmission deficits that interfere with the normal satisfaction of human physiological drives (i.e., food, water, and sex). An essential feature of RDS is the lack of integration between perception, cognition, and emotions that occurs because of (1) significant dopaminergic surges in motivation, reward, and learning centers causing neuroplasticity in the striato-thalamic-frontal cortical loop; (2) hypo-functionality of the excitatory glutamatergic afferents from the amygdala-hippocampus complex. A large volume of literature regarding the known neurogenetic and psychological underpinnings of RDS has revealed a significant risk of dopaminergic gene polymorphic allele overlap between cohorts of depression and subsets of schizophrenia. The suggestion is that instead of alcohol, opioids, gambling disorders, etc. being endophenotypes, the true phenotype is RDS. Additionally, reward deficiency can result from depleted or hereditary hypodopaminergia, which can manifest as a variety of personality traits and mental/medical disorders that have been linked to genetic studies with dopamine-depleting alleles. The carrying of known DNA antecedents, including epigenetic insults, results in a life-long vulnerability to RDS conditions and addictive behaviors. Epigenetic repair of hypodopaminergia, the causative basis of addictive behaviors, may involve precision DNA-guided therapy achieved by combining the Genetic Addiction Risk Severity (GARS) test with a researched neutraceutical having a number of variant names, including KB220Z. This nutraceutical formulation with pro-dopamine regulatory capabilities has been studied and published in peer-reviewed journals, mostly from our laboratory. Finally, it is our opinion that RDS should be given an ICD code and deserves to be included in the DSM-VI because while the DSM features symptomology, it is equally important to feature etiological roots as portrayed in the RDS model.
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Affiliation(s)
- Kenneth Blum
- The Kenneth Blum Behavioral & Neurogenetic Institute, LLC., Austin, TX 78701, USA
- Center for Behavioral Health & Sports, Exercise, Psychiatry, Western University Health Sciences, Pomona, CA 91766, USA
- Institute of Psychology, ELTE Eötvös Loránd University, Kazinczy u. 23–27, 1075 Budapest, Hungary
- Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel 40700, Israel
| | - Catherine A. Dennen
- The Kenneth Blum Behavioral & Neurogenetic Institute, LLC., Austin, TX 78701, USA
- Department of Family Medicine, Jefferson Health Northeast, Philadelphia, PA 19140, USA
| | - Igor Elman
- Medicine, Boston Children’s Hospital, Boston, MA 02115, USA
- Cambridge Health Alliance, Harvard Medical School, Cambridge, MA 02139, USA
| | - Abdalla Bowirrat
- Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel 40700, Israel
| | - Panayotis K. Thanos
- Behavioral Neuropharmacology and Neuroimaging Laboratory, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, Clinical Research Institute on Addictions, University at Buffalo, Buffalo, NY 14203, USA
- Department of Psychology, University at Buffalo, Buffalo, NY 14260, USA
| | - Rajendra D. Badgaiyan
- Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy Memorial VA Hospital, Long School of Medicine, University of Texas Medical Center, San Antonio, TX 78229, USA
| | - B. William Downs
- Division of Precision Nutrition, Victory Nutrition International, LLC., Lederoch, PA 19438, USA
| | - Debasis Bagchi
- Division of Precision Nutrition, Victory Nutrition International, LLC., Lederoch, PA 19438, USA
- Department of Pharmaceutical Science, College of Pharmacy & Health Sciences, Texas Southern University, Houston, TX 77004, USA
| | - David Baron
- Center for Behavioral Health & Sports, Exercise, Psychiatry, Western University Health Sciences, Pomona, CA 91766, USA
| | - Eric R. Braverman
- The Kenneth Blum Behavioral & Neurogenetic Institute, LLC., Austin, TX 78701, USA
| | - Ashim Gupta
- Future Biologics, Lawrenceville, GA 30043, USA
| | - Richard Green
- The Kenneth Blum Behavioral & Neurogenetic Institute, LLC., Austin, TX 78701, USA
| | - Thomas McLaughlin
- The Kenneth Blum Behavioral & Neurogenetic Institute, LLC., Austin, TX 78701, USA
| | - Debmalya Barh
- Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur 721172, India
| | - Mark S. Gold
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA
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22
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Bajaj A, Blum K, Bowirrat A, Gupta A, Baron D, Fugel D, Nicholson A, Fitch T, Downs BW, Bagchi D, Dennen CA, Badgaiyan RD. DNA Directed Pro-Dopamine Regulation Coupling Subluxation Repair, H-Wave ® and Other Neurobiologically Based Modalities to Address Complexities of Chronic Pain in a Female Diagnosed with Reward Deficiency Syndrome (RDS): Emergence of Induction of "Dopamine Homeostasis" in the Face of the Opioid Crisis. J Pers Med 2022; 12:1416. [PMID: 36143203 PMCID: PMC9503998 DOI: 10.3390/jpm12091416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 08/27/2022] [Accepted: 08/27/2022] [Indexed: 11/16/2022] Open
Abstract
Addiction is a complex multifactorial condition. Established genetic factors can provide clear guidance in assessing the risk of addiction to substances and behaviors. Chronic stress can accumulate, forming difficult to recognize addiction patterns from both genetic and epigenetic (environmental) factors. Furthermore, psychological/physical/chemical stressors are typically categorized linearly, delaying identification and treatment. The patient in this case report is a Caucasian female, aged 36, who presented with chronic pain and partial disability following a surgically repaired trimalleolar fracture. The patient had a history of unresolved attention deficit disorder and an MRI scan of her brain revealed atrophy and functional asymmetry. In 2018, the patient entered the Bajaj Chiropractic Clinic, where initial treatment focused on re-establishing integrity of the spine and lower extremity biomechanics and graduated into cognitive behavior stabilization assisted by DNA pro-dopamine regulation guided by Genetic Addiction Risk Severity testing. During treatment (2018-2021), progress achieved included: improved cognitive clarity, focus, sleep, anxiety, and emotional stability in addition to pain reduction (75%); elimination of powerful analgesics; and reduced intake of previously unaddressed alcoholism. To help reduce hedonic addictive behaviors and pain, coupling of H-Wave with corrective chiropractic care seems prudent. We emphasize the importance of genetic assessment along with attempts at inducing required dopaminergic homeostasis via precision KB220PAM. It is hypothesized that from preventive care models, a new standard is emerging including self-awareness and accountability for reward deficiency as a function of hypodopaminergia. This case study documents the progression of a patient dealing with the complexities of an injury, pain management, cognitive impairment, anxiety, depression, and the application of universal health principles towards correction versus palliative care.
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Affiliation(s)
- Anish Bajaj
- Bajaj Chiropractic Clinic, New York, NY 10010, USA
| | - Kenneth Blum
- Division of Addiction Research & Education, Center for Psychiatry, Medicine, and Primary Care, (Office of the Provost), Western University Health Sciences, Pomona, CA 91766, USA
- The Kenneth Blum Institute on Behavior & Neurogenetics, Austin, TX 78701, USA
| | - Abdalla Bowirrat
- Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel 40700, Israel
| | - Ashim Gupta
- Future Biologics, Lawrenceville, GA 30043, USA
| | - David Baron
- Division of Addiction Research & Education, Center for Psychiatry, Medicine, and Primary Care, (Office of the Provost), Western University Health Sciences, Pomona, CA 91766, USA
| | - David Fugel
- Bajaj Chiropractic Clinic, New York, NY 10010, USA
| | | | - Taylor Fitch
- Bajaj Chiropractic Clinic, New York, NY 10010, USA
| | - B. William Downs
- Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy Memorial VA Hospital, Long School of Medicine, University of Texas Medical Center, San Antonio, TX 78229, USA
| | - Debasis Bagchi
- Department of Pharmaceutical Sciences, Southern University College of Pharmacy, Houston, TX 77004, USA
| | - Catherine A. Dennen
- The Kenneth Blum Institute on Behavior & Neurogenetics, Austin, TX 78701, USA
| | - Rajendra D. Badgaiyan
- Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy Memorial VA Hospital, Long School of Medicine, University of Texas Medical Center, San Antonio, TX 78229, USA
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23
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Blum K, Han D, Gupta A, Baron D, Braverman ER, Dennen CA, Kazmi S, Llanos-Gomez L, Badgaiyan RD, Elman I, Thanos PK, Downs BW, Bagchi D, Gondre-Lewis MC, Gold MS, Bowirrat A. Statistical Validation of Risk Alleles in Genetic Addiction Risk Severity (GARS) Test: Early Identification of Risk for Alcohol Use Disorder (AUD) in 74,566 Case-Control Subjects. J Pers Med 2022; 12:1385. [PMID: 36143170 PMCID: PMC9505592 DOI: 10.3390/jpm12091385] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Revised: 08/12/2022] [Accepted: 08/22/2022] [Indexed: 11/16/2022] Open
Abstract
Since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism in JAMA, there has been an explosion of genetic candidate association studies, including GWAS. To develop an accurate test to help identify those at risk for at least Alcohol Use Disorder (AUD), Blum's group developed the Genetic Addiction Risk Severity (GARS) test, consisting of ten genes and eleven associated risk alleles. In order to statistically validate the selection of these risk alleles measured by GARS, we applied strict analysis to studies that investigated the association of each polymorphism with AUD or AUD-related conditions published from 1990 until 2021. This analysis calculated the Hardy-Weinberg Equilibrium of each polymorphism in cases and controls. If available, the Pearson's χ2 test or Fisher's exact test was applied to comparisons of the gender, genotype, and allele distribution. The statistical analyses found the OR, 95% CI for OR, and a post-risk for 8% estimation of the population's alcoholism prevalence revealed a significant detection. The OR results showed significance for DRD2, DRD3, DRD4, DAT1, COMT, OPRM1, and 5HTT at 5%. While most of the research related to GARS is derived from our laboratory, we are encouraging more independent research to confirm our findings.
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Affiliation(s)
- Kenneth Blum
- Graduate College, Western University Health Sciences, Pomona, CA 91766, USA
- Institute of Psychology, ELTE Eötvös Loránd University, Egyetem tér 1-3, 1053 Budapest, Hungary
- The Kenneth Blum Institute on Behavior & Neurogenetics, LLC., Austin, TX 78701, USA
- Department of Psychiatry, School of Medicine, University of Vermont, Burlington, VT 05405, USA
- Dayton VA Medical Centre, Department of Psychiatry, Boonshoft School of Medicine, Wright State University, Dayton, OH 45324, USA
- Division of Precision Nutrition, Victory Nutrition International, LLC., Lederoch, PA 19438, USA
| | - David Han
- Department of Management Science and Statistics, University of Texas at San Antonio, San Antonio, TX 78249, USA
| | - Ashim Gupta
- Future Biologics, Lawrenceville, GA 30043, USA
| | - David Baron
- Graduate College, Western University Health Sciences, Pomona, CA 91766, USA
| | - Eric R. Braverman
- The Kenneth Blum Institute on Behavior & Neurogenetics, LLC., Austin, TX 78701, USA
| | - Catherine A. Dennen
- Department of Family Medicine, Jefferson Health Northeast, Philadelphia, PA 19114, USA
| | - Shan Kazmi
- Graduate College, Western University Health Sciences, Pomona, CA 91766, USA
| | - Luis Llanos-Gomez
- The Kenneth Blum Institute on Behavior & Neurogenetics, LLC., Austin, TX 78701, USA
| | - Rajendra D. Badgaiyan
- Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy Memorial VA Hospital, Long School of Medicine, University of Texas Medical Center, San Antonio, TX 78229, USA
| | - Igor Elman
- Center for Pain and the Brain (P.A.I.N Group), Department of Anesthesiology, Critical Care & Pain Medicine, Boston Children’s Hospital, Boston, MA 02115, USA
- Cambridge Health Alliance, Harvard Medical School, Cambridge, MA 02139, USA
| | - Panayotis K. Thanos
- Behavioral Neuropharmacology and Neuroimaging Laboratory, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, Clinical Research Institute on Addictions, University at Buffalo, Buffalo, NY 14203, USA
- Department of Psychology, University at Buffalo, Buffalo, NY 14260, USA
| | - Bill W. Downs
- Division of Precision Nutrition, Victory Nutrition International, LLC., Lederoch, PA 19438, USA
| | - Debasis Bagchi
- Division of Precision Nutrition, Victory Nutrition International, LLC., Lederoch, PA 19438, USA
- Department of Pharmaceutical Science, College of Pharmacy & Health Sciences, Texas Southern University, Houston, TX 77004, USA
| | - Marjorie C. Gondre-Lewis
- Department of Psychiatry and Behavioral Sciences, Howard University College of Medicine, Washington, DC 20059, USA
| | - Mark S. Gold
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Abdalla Bowirrat
- Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel 40700, Israel
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24
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White O, Roeder N, Blum K, Eiden RD, Thanos PK. Prenatal Effects of Nicotine on Obesity Risks: A Narrative Review. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:9477. [PMID: 35954830 PMCID: PMC9368674 DOI: 10.3390/ijerph19159477] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 07/25/2022] [Accepted: 07/29/2022] [Indexed: 11/16/2022]
Abstract
Nicotine usage by mothers throughout pregnancy has been observed to relate to numerous deleterious effects in children, especially relating to obesity. Children who have prenatally been exposed to nicotine tend to have lower birth weights, with an elevated risk of becoming overweight throughout development and into their adolescent and adult life. There are numerous theories as to how this occurs: catch-up growth theory, thrifty phenotype theory, neurotransmitter or endocrine imbalances theory, and a more recent examination on the genetic factors relating to obesity risk. In addition to the negative effect on bodyweight and BMI, individuals with obesity may also suffer from numerous comorbidities involving metabolic disease. These may include type 1 and 2 diabetes, high cholesterol levels, and liver disease. Predisposition for obesity with nicotine usage may also be associated with genetic risk alleles for obesity, such as the DRD2 A1 variant. This is important for prenatally nicotine-exposed individuals as an opportunity to provide early prevention and intervention of obesity-related risks.
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Affiliation(s)
- Olivia White
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA; (O.W.); (N.R.)
- Department of Psychology, University at Buffalo, Buffalo, NY 14203, USA
| | - Nicole Roeder
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA; (O.W.); (N.R.)
- Department of Psychology, University at Buffalo, Buffalo, NY 14203, USA
| | - Kenneth Blum
- Division of Addiction Research, Center for Psychiatry, Medicine & Primary Care (Office of Provost), Western University Health Sciences, Pomona, CA 91766, USA;
| | - Rina D. Eiden
- Department of Psychology, Social Science Research Institute, The Pennsylvania State University, University Park, PA 16801, USA;
| | - Panayotis K. Thanos
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA; (O.W.); (N.R.)
- Department of Psychology, University at Buffalo, Buffalo, NY 14203, USA
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25
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Blum K, Brodie MS, Pandey SC, Cadet JL, Gupta A, Elman I, Thanos PK, Gondre-Lewis MC, Baron D, Kazmi S, Bowirrat A, Febo M, Badgaiyan RD, Braverman ER, Dennen CA, Gold MS. Researching Mitigation of Alcohol Binge Drinking in Polydrug Abuse: KCNK13 and RASGRF2 Gene(s) Risk Polymorphisms Coupled with Genetic Addiction Risk Severity (GARS) Guiding Precision Pro-Dopamine Regulation. J Pers Med 2022; 12:1009. [PMID: 35743793 PMCID: PMC9224860 DOI: 10.3390/jpm12061009] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 06/12/2022] [Accepted: 06/16/2022] [Indexed: 11/22/2022] Open
Abstract
Excessive alcohol intake, e.g., binge drinking, is a serious and mounting public health problem in the United States and throughout the world. Hence the need for novel insights into the underlying neurobiology that may help improve prevention and therapeutic strategies. Therefore, our group employed a darkness-induced alcohol intake protocol to define the reward deficiency domains of alcohol and other substance use disorders in terms of reward pathways' reduced dopamine signaling and its restoration via specifically-designed therapeutic compounds. It has been determined that KCNK13 and RASGRF2 genes, respectively, code for potassium two pore domain channel subfamily K member 13 and Ras-specific guanine nucleotide-releasing factor 2, and both genes have important dopamine-related functions pertaining to alcohol binge drinking. We present a hypothesis that identification of KCNK13 and RASGRF2 genes' risk polymorphism, coupled with genetic addiction risk score (GARS)-guided precision pro-dopamine regulation, will mitigate binge alcohol drinking. Accordingly, we review published reports on the benefits of this unique approach and provide data on favorable outcomes for both binge-drinking animals and drunk drivers, including reductions in alcohol intake and prevention of relapse to drinking behavior. Since driving under the influence of alcohol often leads to incarceration rather than rehabilitation, there is converging evidence to support the utilization of GARS with or without KCNK13 and RASGRF2 risk polymorphism in the legal arena, whereby the argument that "determinism" overrides the "free will" account may be a plausible defense strategy. Obviously, this type of research is tantamount to helping resolve a major problem related to polydrug abuse.
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Affiliation(s)
- Kenneth Blum
- The Kenneth Blum Behavioral & Neurogenetic Institute, Austin, TX 78701, USA; (E.R.B.); (C.A.D.)
- Division of Addiction Research & Education, Center for Psychiatry, Medicine & Primary Care (Office of Provost), Western University Health Sciences, Pomona, CA 91766, USA; (D.B.); (M.F.)
- Institute of Psychology, ELTE Eötvös Loránd University, Egyetem tér 1-3, 1053 Budapest, Hungary
- Department of Psychiatry, School of Medicine, University of Vermont, Burlington, VT 05405, USA
- Department of Psychiatry, Wright State University Boonshoft School of Medicine and Dayton VA Medical Centre, Dayton, OH 45324, USA
| | - Mark S. Brodie
- Center for Alcohol Research in Epigenetics, Departments of Physiology and Biophysics, and Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA; (M.S.B.); (S.C.P.)
| | - Subhash C. Pandey
- Center for Alcohol Research in Epigenetics, Departments of Physiology and Biophysics, and Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA; (M.S.B.); (S.C.P.)
| | - Jean Lud Cadet
- Molecular Neuropsychiatry Research Branch, National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD 20892, USA;
| | - Ashim Gupta
- Future Biologics, Lawrenceville, GA 30043, USA;
| | - Igor Elman
- Center for Pain and the Brain (P.A.I.N Group), Department of Anesthesiology, Critical Care & Pain Medicine, Boston Children’s Hospital, Boston, MA 02115, USA;
| | - Panayotis K. Thanos
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY 14203, USA;
- Department of Psychology, State University of New York at Buffalo, Buffalo, NY 14203, USA
| | - Marjorie C. Gondre-Lewis
- Neuropsychopharmacology Laboratory, Department of Anatomy, Howard University College of Medicine, Washington, DC 20059, USA;
| | - David Baron
- Division of Addiction Research & Education, Center for Psychiatry, Medicine & Primary Care (Office of Provost), Western University Health Sciences, Pomona, CA 91766, USA; (D.B.); (M.F.)
| | - Shan Kazmi
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA;
| | - Abdalla Bowirrat
- Department of Molecular Biology and Adelson School of Medicine, Ariel University, Ariel 40700, Israel;
| | - Marcelo Febo
- Division of Addiction Research & Education, Center for Psychiatry, Medicine & Primary Care (Office of Provost), Western University Health Sciences, Pomona, CA 91766, USA; (D.B.); (M.F.)
| | - Rajendra D. Badgaiyan
- Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy Memorial VA Hospital, Long School of Medicine, University of Texas Medical Center, San Antonio, TX 78229, USA;
| | - Eric R. Braverman
- The Kenneth Blum Behavioral & Neurogenetic Institute, Austin, TX 78701, USA; (E.R.B.); (C.A.D.)
| | - Catherine A. Dennen
- The Kenneth Blum Behavioral & Neurogenetic Institute, Austin, TX 78701, USA; (E.R.B.); (C.A.D.)
| | - Mark S. Gold
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA;
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26
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Madigan MA, Gupta A, Bowirrat A, Baron D, Badgaiyan RD, Elman I, Dennen CA, Braverman ER, Gold MS, Blum K. Precision Behavioral Management (PBM) and Cognitive Control as a Potential Therapeutic and Prophylactic Modality for Reward Deficiency Syndrome (RDS): Is There Enough Evidence? INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:6395. [PMID: 35681980 PMCID: PMC9180535 DOI: 10.3390/ijerph19116395] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 05/19/2022] [Accepted: 05/20/2022] [Indexed: 12/20/2022]
Abstract
This brief commentary aims to provide an overview of the available and relatively new precision management of reward deficiencies manifested as substance and behavioral disorders. Current and future advances, concepts, and the substantial evidential basis of this potential therapeutic and prophylactic treatment modality are presented. Precision Behavioral Management (PBM), conceptualized initially as Precision Addiction Management (PAM), certainly deserves consideration as an important modality for the treatment of impaired cognitive control in reward processing as manifested in people with neurobiologically expressed Reward Deficiency Syndrome (RDS).
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Affiliation(s)
- Margaret A. Madigan
- The Kenneth Blum Behavioral & Neurogenetic Institute, LLC., Austin, TX 78701, USA; (M.A.M.); (C.A.D.); (E.R.B.)
| | - Ashim Gupta
- Future Biologics, Lawrenceville, GA 30043, USA;
| | - Abdalla Bowirrat
- Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel 40700, Israel;
| | - David Baron
- Center for Psychiatry, Medicine, & Primary Care (Office of Provost), Division of Addiction Research & Education, Western University Health Sciences, Pomona, CA 91766, USA;
| | - Rajendra D. Badgaiyan
- Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy Memorial VA Hospital, Long School of Medicine, University of Texas Medical Center, San Antonio, TX 78229, USA;
| | - Igor Elman
- Center for Pain and the Brain (P.A.I.N Group), Department of Anesthesiology, Critical Care & Pain Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA;
| | - Catherine A. Dennen
- The Kenneth Blum Behavioral & Neurogenetic Institute, LLC., Austin, TX 78701, USA; (M.A.M.); (C.A.D.); (E.R.B.)
| | - Eric R. Braverman
- The Kenneth Blum Behavioral & Neurogenetic Institute, LLC., Austin, TX 78701, USA; (M.A.M.); (C.A.D.); (E.R.B.)
| | - Mark S. Gold
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA;
| | - Kenneth Blum
- The Kenneth Blum Behavioral & Neurogenetic Institute, LLC., Austin, TX 78701, USA; (M.A.M.); (C.A.D.); (E.R.B.)
- Center for Psychiatry, Medicine, & Primary Care (Office of Provost), Division of Addiction Research & Education, Western University Health Sciences, Pomona, CA 91766, USA;
- Institute of Psychology, ELTE Eötvös Loránd University, Egyetem tér 1-3, 1053 Budapest, Hungary
- Department of Psychiatry, School of Medicine, University of Vermont, Burlington, VT 05405, USA
- Department of Psychiatry, Wright State University Boonshoft School of Medicine, Dayton VA Medical Centre, Dayton, OH 45324, USA
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27
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Vereczkei A, Barta C, Magi A, Farkas J, Eisinger A, Király O, Belik A, Griffiths MD, Szekely A, Sasvári-Székely M, Urbán R, Potenza MN, Badgaiyan RD, Blum K, Demetrovics Z, Kotyuk E. FOXN3 and GDNF Polymorphisms as Common Genetic Factors of Substance Use and Addictive Behaviors. J Pers Med 2022; 12:jpm12050690. [PMID: 35629112 PMCID: PMC9144496 DOI: 10.3390/jpm12050690] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 04/20/2022] [Accepted: 04/21/2022] [Indexed: 12/15/2022] Open
Abstract
Epidemiological and phenomenological studies suggest shared underpinnings between multiple addictive behaviors. The present genetic association study was conducted as part of the Psychological and Genetic Factors of Addictions study (n = 3003) and aimed to investigate genetic overlaps between different substance use, addictive, and other compulsive behaviors. Association analyses targeted 32 single-nucleotide polymorphisms, potentially addictive substances (alcohol, tobacco, cannabis, and other drugs), and potentially addictive or compulsive behaviors (internet use, gaming, social networking site use, gambling, exercise, hair-pulling, and eating). Analyses revealed 29 nominally significant associations, from which, nine survived an FDRbl correction. Four associations were observed between FOXN3 rs759364 and potentially addictive behaviors: rs759364 showed an association with the frequency of alcohol consumption and mean scores of scales assessing internet addiction, gaming disorder, and exercise addiction. Significant associations were found between GDNF rs1549250, rs2973033, CNR1 rs806380, DRD2/ANKK1 rs1800497 variants, and the “lifetime other drugs” variable. These suggested that genetic factors may contribute similarly to specific substance use and addictive behaviors. Specifically, FOXN3 rs759364 and GDNF rs1549250 and rs2973033 may constitute genetic risk factors for multiple addictive behaviors. Due to limitations (e.g., convenience sampling, lack of structured scales for substance use), further studies are needed. Functional correlates and mechanisms underlying these relationships should also be investigated.
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Affiliation(s)
- Andrea Vereczkei
- Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, 1094 Budapest, Hungary; (A.V.); (A.B.); (M.S.-S.)
| | - Csaba Barta
- Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, 1094 Budapest, Hungary; (A.V.); (A.B.); (M.S.-S.)
- Correspondence: (C.B.); (Z.D.)
| | - Anna Magi
- Institute of Psychology, ELTE Eötvös Loránd University, 1075 Budapest, Hungary; (A.M.); (J.F.); (A.E.); (O.K.); (A.S.); (R.U.); (E.K.)
- Doctoral School of Psychology, ELTE Eötvös Loránd University, 1075 Budapest, Hungary
| | - Judit Farkas
- Institute of Psychology, ELTE Eötvös Loránd University, 1075 Budapest, Hungary; (A.M.); (J.F.); (A.E.); (O.K.); (A.S.); (R.U.); (E.K.)
- Nyírő Gyula National Institute of Psychiatry and Addictions, 1135 Budapest, Hungary
| | - Andrea Eisinger
- Institute of Psychology, ELTE Eötvös Loránd University, 1075 Budapest, Hungary; (A.M.); (J.F.); (A.E.); (O.K.); (A.S.); (R.U.); (E.K.)
- Doctoral School of Psychology, ELTE Eötvös Loránd University, 1075 Budapest, Hungary
| | - Orsolya Király
- Institute of Psychology, ELTE Eötvös Loránd University, 1075 Budapest, Hungary; (A.M.); (J.F.); (A.E.); (O.K.); (A.S.); (R.U.); (E.K.)
| | - Andrea Belik
- Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, 1094 Budapest, Hungary; (A.V.); (A.B.); (M.S.-S.)
| | - Mark D. Griffiths
- International Gaming Research Unit, Psychology Department, Nottingham Trent University, Nottingham NG1 4FQ, UK;
| | - Anna Szekely
- Institute of Psychology, ELTE Eötvös Loránd University, 1075 Budapest, Hungary; (A.M.); (J.F.); (A.E.); (O.K.); (A.S.); (R.U.); (E.K.)
| | - Mária Sasvári-Székely
- Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, 1094 Budapest, Hungary; (A.V.); (A.B.); (M.S.-S.)
| | - Róbert Urbán
- Institute of Psychology, ELTE Eötvös Loránd University, 1075 Budapest, Hungary; (A.M.); (J.F.); (A.E.); (O.K.); (A.S.); (R.U.); (E.K.)
| | - Marc N. Potenza
- Departments of Psychiatry, Child Study and Neuroscience, Yale University School of Medicine, New Haven, CT 06511, USA;
- Connecticut Council on Problem Gambling, Wethersfield, CT 06109, USA
- Connecticut Mental Health Center, New Haven, CT 06519, USA
| | - Rajendra D. Badgaiyan
- Department of Psychiatry, Ichan School of Medicine at Mount Sinai, New York, NY 10029, USA;
| | - Kenneth Blum
- Division of Addiction Research & Education, Center for Psychiatry, Medicine, & Primary Care (Office of the Provost), Western University Health Sciences, Pomona, CA 91766, USA;
| | - Zsolt Demetrovics
- Institute of Psychology, ELTE Eötvös Loránd University, 1075 Budapest, Hungary; (A.M.); (J.F.); (A.E.); (O.K.); (A.S.); (R.U.); (E.K.)
- Division of Addiction Research & Education, Center for Psychiatry, Medicine, & Primary Care (Office of the Provost), Western University Health Sciences, Pomona, CA 91766, USA;
- Correspondence: (C.B.); (Z.D.)
| | - Eszter Kotyuk
- Institute of Psychology, ELTE Eötvös Loránd University, 1075 Budapest, Hungary; (A.M.); (J.F.); (A.E.); (O.K.); (A.S.); (R.U.); (E.K.)
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28
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Gondré-Lewis MC, Elman I, Alim T, Chapman E, Settles-Reaves B, Galvao C, Gold MS, Baron D, Kazmi S, Gardner E, Gupta A, Dennen C, Blum K. Frequency of the Dopamine Receptor D3 (rs6280) vs. Opioid Receptor µ1 (rs1799971) Polymorphic Risk Alleles in Patients with Opioid Use Disorder: A Preponderance of Dopaminergic Mechanisms? Biomedicines 2022; 10:870. [PMID: 35453620 PMCID: PMC9027142 DOI: 10.3390/biomedicines10040870] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 03/21/2022] [Accepted: 03/26/2022] [Indexed: 02/05/2023] Open
Abstract
While opioids are a powerful class of drugs that inhibit transmission of pain signals, their use is tarnished by the current epidemic of opioid use disorder (OUD) and overdose deaths. Notwithstanding published reports, there remain gaps in our knowledge of opioid receptor mechanisms and their role in opioid seeking behavior. Thus, novel insights into molecular, neurogenetic and neuropharmacological bases of OUD are needed. We propose that an addictive endophenotype may not be entirely specific to the drug of choice but rather may be generalizable to altered brain reward circuits impacting net mesocorticolimbic dopamine release. We suggest that genetic or epigenetic alterations across dopaminergic reward systems lead to uncontrollable self-administration of opioids and other drugs. For instance, diminished availability via knockout of dopamine D3 receptor (DRD3) increases vulnerability to opioids. Building upon this concept via the use of a sophisticated polymorphic risk analysis in a human cohort of chronic opioid users, we found evidence for a higher frequency of polymorphic DRD3 risk allele (rs6280) than opioid receptor µ1 (rs1799971). In conclusion, while opioidergic mechanisms are involved in OUD, dopamine-related receptors may have primary influence on opioid-seeking behavior in African Americans. These findings suggest OUD-targeted novel and improved neuropharmacological therapies may require focus on DRD3-mediated regulation of dopaminergic homeostasis.
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Affiliation(s)
- Marjorie C. Gondré-Lewis
- Neuropsychopharmacology Laboratory, Department of Anatomy, Howard University College of Medicine, Washington, DC 20059, USA (C.G.)
| | - Igor Elman
- Department of Psychiatry, Cambridge Health Alliance/Harvard Medical School, Cambridge, MA 02139, USA or
| | - Tanya Alim
- Department of Psychiatry and Behavioral Sciences, Howard University College of Medicine, Washington, DC 20059, USA; (T.A.); (E.C.)
| | - Edwin Chapman
- Department of Psychiatry and Behavioral Sciences, Howard University College of Medicine, Washington, DC 20059, USA; (T.A.); (E.C.)
| | - Beverlyn Settles-Reaves
- Neuropsychopharmacology Laboratory, Department of Anatomy, Howard University College of Medicine, Washington, DC 20059, USA (C.G.)
| | - Carine Galvao
- Neuropsychopharmacology Laboratory, Department of Anatomy, Howard University College of Medicine, Washington, DC 20059, USA (C.G.)
| | - Mark S. Gold
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA;
| | - David Baron
- Graduate College, Western University Health Sciences, Pomona, CA 91766, USA;
| | - Shan Kazmi
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA or
| | - Eliot Gardner
- Neuropsychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA;
| | - Ashim Gupta
- Future Biologics, Lawrenceville, GA 30043, USA;
| | - Catherine Dennen
- The Kenneth Blum Behavioral & Neurogenetic Institute, Austin, TX 78701, USA;
| | - Kenneth Blum
- Graduate College, Western University Health Sciences, Pomona, CA 91766, USA;
- The Kenneth Blum Behavioral & Neurogenetic Institute, Austin, TX 78701, USA;
- Department of Clinical Psychology and Addiction, Institute of Psychology, Faculty of Education and Psychology, ELTE Eötvös Loránd University, Egyetem tér 1-3, 1053 Budapest, Hungary
- Department of Psychiatry, School of Medicine, University of Vermont, Burlington, VT 05405, USA
- Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur 721172, West Bengal, India
- Department of Psychiatry, Wright State University Boonshoft School of Medicine and Dayton VA Medical Centre, Dayton, OH 45324, USA
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29
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Kótyuk E, Urbán R, Hende B, Richman M, Magi A, Király O, Barta C, Griffiths MD, Potenza MN, Badgaiyan RD, Blum K, Demetrovics Z. Development and validation of the Reward Deficiency Syndrome Questionnaire (RDSQ-29). J Psychopharmacol 2022; 36:409-422. [PMID: 35102768 DOI: 10.1177/02698811211069102] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The reward deficiency syndrome (RDS) integrates psychological, neurological, and genetic factors of addictive, impulsive, and compulsive behaviors. However, to date, no instrument has been validated to assess the RDS construct. AIMS The present study developed and tested a tool to assess RDS. METHODS Data were collected on two college and university samples. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed on Sample 1 (N = 1726), and confirmatory analysis was conducted on an independent sample (N = 253). Impulsivity and sensation-seeking were assessed. RESULTS Based on EFAs, a 29-item Reward Deficiency Syndrome Questionnaire (RDSQ-29) was developed, containing four subscales (lack of sexual satisfaction, activity, social concerns, and risk-seeking behavior). CFA indicated good fit (comparative fit index (CFI) = 0.941; Tucker-Lewis index (TLI) = 0.933; root mean square error of approximation (RMSEA) = 0.068). Construct validity analysis showed strong relationship between sensation-seeking and the RDS scale. CONCLUSION The RDSQ-29 is an adequate scale assessing psychological and behavioral aspects of RDS. The RDSQ-29 assesses psychological and behavioral characteristics that may contribute to addictions generally.
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Affiliation(s)
- Eszter Kótyuk
- Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary
| | - Róbert Urbán
- Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary
| | - Borbála Hende
- Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary.,Doctoral School of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary
| | - Mara Richman
- Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary
| | - Anna Magi
- Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary.,Doctoral School of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary
| | - Orsolya Király
- Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary
| | - Csaba Barta
- Department of Molecular Biology, Institute of Biochemistry and Molecular Biology, Semmelweis University, Budapest, Hungary
| | - Mark D Griffiths
- International Gaming Research Unit, Psychology Department, Nottingham Trent University, Nottingham, UK
| | - Marc N Potenza
- Departments of Psychiatry, Neuroscience and Child Study Center, Yale University School of Medicine, New Haven, CT, USA.,Connecticut Council on Problem Gambling, Wethersfield, CT, USA.,Connecticut Mental Health Center, New Haven, CT, USA
| | - Rajendra D Badgaiyan
- Department of Psychiatry, Ichan School of Medicine at Mount Sinai, New York, NY, USA
| | - Kenneth Blum
- Division of Addiction Research & Education, Center for Psychiatry, Medicine, & Primary Care (Office of the Provost), Western University Health Sciences, Pomona, CA, USA
| | - Zsolt Demetrovics
- Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary.,Centre of Excellence in Responsible Gaming, University of Gibraltar, Gibraltar
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30
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Martins JS, Joyner KJ, McCarthy DM, Morris DH, Patrick CJ, Bartholow BD. Differential brain responses to alcohol-related and natural rewards are associated with alcohol use and problems: Evidence for reward dysregulation. Addict Biol 2022; 27:e13118. [PMID: 34877771 PMCID: PMC8891069 DOI: 10.1111/adb.13118] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 10/15/2021] [Accepted: 11/04/2021] [Indexed: 12/17/2022]
Abstract
Multiple theoretical perspectives posit that drug use leads to biased valuation of drug-related reward, at the expense of naturally occurring rewarding activities (i.e., reward dysregulation). Recent research suggests that the comparative balance of drug-related and nondrug-related reward valuation is a powerful determinant of substance misuse and addiction. We examined differential neurophysiological responses-indexed with the P3 component of the event-related potential (ERP)-elicited by visual alcohol cues and cues depicting natural reward as a neurobiological indicator of problematic drinking. Nondependent, young adult drinkers (N = 143, aged 18-30 years) completed questionnaire measures assessing alcohol use and problems, and viewed alcohol cues (pictures of alcoholic beverages), high-arousing natural reward cues (erotica, adventure scenes), nonalcoholic beverage cues, and neutral scenes (e.g., household items) while ERPs were recorded. When examined separately, associations of P3-ERP reactivity to alcohol cues and natural reward cues with alcohol use and problems were weak. However, differential P3 response to the two types of cues (i.e., reward dysregulation P3) showed consistent and robust associations with all indices of alcohol use and problems and differentiated high-risk from lower-risk drinkers. The current results support the idea that the differential incentive-motivational value of alcohol, relative to naturally rewarding activities, is associated with increased risk for substance misuse and dependence, and highlight a novel neurophysiological indicator-the reward dysregulation P3-of this differential reward valuation.
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31
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Zajenkowska A, Nowakowska I, Kaźmierczak I, Rajchert J, Bodecka-Zych M, Jakubowska A, Anderson JL, Sellbom M. The interplay between disinhibition and Present-Hedonistic time perspective in the relation between Borderline Personality Organization and depressive symptoms. PERSONALITY AND INDIVIDUAL DIFFERENCES 2022. [DOI: 10.1016/j.paid.2021.111317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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32
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Jordan CJ, Xi ZX. Identification of the Risk Genes Associated With Vulnerability to Addiction: Major Findings From Transgenic Animals. Front Neurosci 2022; 15:811192. [PMID: 35095405 PMCID: PMC8789752 DOI: 10.3389/fnins.2021.811192] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 12/14/2021] [Indexed: 12/21/2022] Open
Abstract
Understanding risk factors for substance use disorders (SUD) can facilitate medication development for SUD treatment. While a rich literature exists discussing environmental factors that influence SUD, fewer articles have focused on genetic factors that convey vulnerability to drug use. Methods to identify SUD risk genes include Genome-Wide Association Studies (GWAS) and transgenic approaches. GWAS have identified hundreds of gene variants or single nucleotide polymorphisms (SNPs). However, few genes identified by GWAS have been verified by clinical or preclinical studies. In contrast, significant progress has been made in transgenic approaches to identify risk genes for SUD. In this article, we review recent progress in identifying candidate genes contributing to drug use and addiction using transgenic approaches. A central hypothesis is if a particular gene variant (e.g., resulting in reduction or deletion of a protein) is associated with increases in drug self-administration or relapse to drug seeking, this gene variant may be considered a risk factor for drug use and addiction. Accordingly, we identified several candidate genes such as those that encode dopamine D2 and D3 receptors, mGluR2, M4 muscarinic acetylcholine receptors, and α5 nicotinic acetylcholine receptors, which appear to meet the risk-gene criteria when their expression is decreased. Here, we describe the role of these receptors in drug reward and addiction, and then summarize major findings from the gene-knockout mice or rats in animal models of addiction. Lastly, we briefly discuss future research directions in identifying addiction-related risk genes and in risk gene-based medication development for the treatment of addiction.
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Affiliation(s)
- Chloe J. Jordan
- Division of Alcohol, Drugs and Addiction, Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA, United States
- *Correspondence: Chloe J. Jordan,
| | - Zheng-Xiong Xi
- Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD, United States
- Zheng-Xiong Xi,
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33
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Fujiwara H, Tsurumi K, Shibata M, Kobayashi K, Miyagi T, Ueno T, Oishi N, Murai T. Life Habits and Mental Health: Behavioural Addiction, Health Benefits of Daily Habits, and the Reward System. Front Psychiatry 2022; 13:813507. [PMID: 35153878 PMCID: PMC8829329 DOI: 10.3389/fpsyt.2022.813507] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 01/05/2022] [Indexed: 11/27/2022] Open
Abstract
In this review, the underlying mechanisms of health benefits and the risk of habitual behaviours such as internet use and media multitasking were explored, considering their associations with the reward/motivation system. The review highlights that several routines that are beneficial when undertaken normally may evolve into excessive behaviour and have a negative impact, as represented by "the inverted U-curve model". This is especially critical in the current era, where technology like the internet has become mainstream despite the enormous addictive risk. The understanding of underlying mechanisms of behavioural addiction and optimal level of habitual behaviours for mental health benefits are deepened by shedding light on some findings of neuroimaging studies to have hints to facilitate better management and prevention strategies of addictive problems. With the evolution of the world, and the inevitable use of some technologies that carry the risk of addiction, more effective strategies for preventing and managing addiction are in more demand than before, and the insights of this study are also valuable foundations for future research.
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Affiliation(s)
- Hironobu Fujiwara
- Department of Neuropsychiatry, Graduate School of Medicine, University of Kyoto, Kyoto, Japan.,Artificial Intelligence Ethics and Society Team, RIKEN Center for Advanced Intelligence Project, Saitama, Japan.,The General Research Division, Osaka University Research Center on Ethical, Legal and Social Issues, Kyoto, Japan
| | - Kosuke Tsurumi
- Department of Neuropsychiatry, Graduate School of Medicine, University of Kyoto, Kyoto, Japan
| | - Mami Shibata
- Department of Neuropsychiatry, Graduate School of Medicine, University of Kyoto, Kyoto, Japan
| | - Kei Kobayashi
- Department of Neuropsychiatry, Graduate School of Medicine, University of Kyoto, Kyoto, Japan
| | - Takashi Miyagi
- Department of Neuropsychiatry, Graduate School of Medicine, University of Kyoto, Kyoto, Japan
| | - Tsukasa Ueno
- Department of Neuropsychiatry, Graduate School of Medicine, University of Kyoto, Kyoto, Japan.,Integrated Clinical Education Center, Kyoto University Hospital, Kyoto, Japan
| | - Naoya Oishi
- Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Toshiya Murai
- Department of Neuropsychiatry, Graduate School of Medicine, University of Kyoto, Kyoto, Japan
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Reward Deficiency Syndrome (RDS): A Cytoarchitectural Common Neurobiological Trait of All Addictions. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph182111529. [PMID: 34770047 PMCID: PMC8582845 DOI: 10.3390/ijerph182111529] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 09/09/2021] [Accepted: 09/10/2021] [Indexed: 02/07/2023]
Abstract
Alcohol and other substance use disorders share comorbidity with other RDS disorders, i.e., a reduction in dopamine signaling within the reward pathway. RDS is a term that connects addictive, obsessive, compulsive, and impulsive behavioral disorders. An estimated 2 million individuals in the United States have opioid use disorder related to prescription opioids. It is estimated that the overall cost of the illegal and legally prescribed opioid crisis exceeds one trillion dollars. Opioid Replacement Therapy is the most common treatment for addictions and other RDS disorders. Even after repeated relapses, patients are repeatedly prescribed the same opioid replacement treatments. A recent JAMA report indicates that non-opioid treatments fare better than chronic opioid treatments. Research demonstrates that over 50 percent of all suicides are related to alcohol or other drug use. In addition to effective fellowship programs and spirituality acceptance, nutrigenomic therapies (e.g., KB220Z) optimize gene expression, rebalance neurotransmitters, and restore neurotransmitter functional connectivity. KB220Z was shown to increase functional connectivity across specific brain regions involved in dopaminergic function. KB220/Z significantly reduces RDS behavioral disorders and relapse in human DUI offenders. Taking a Genetic Addiction Risk Severity (GARS) test combined with a the KB220Z semi-customized nutrigenomic supplement effectively restores dopamine homeostasis (WC 199).
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35
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Blum K, Gold MS, Llanos-Gomez L, Jalali R, Thanos PK, Bowirrat A, Downs WB, Bagchi D, Braverman ER, Baron D, Roy AK, Badgaiyan RD. Hypothesizing Nutrigenomic-Based Precision Anti-Obesity Treatment and Prophylaxis: Should We Be Targeting Sarcopenia Induced Brain Dysfunction? INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18189774. [PMID: 34574696 PMCID: PMC8470221 DOI: 10.3390/ijerph18189774] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 08/27/2021] [Accepted: 08/28/2021] [Indexed: 12/15/2022]
Abstract
Background: The United States Centers for Disease Control and Prevention (CDC) estimates a total obesity rate of 30% for 12 states and a 20% obesity rate nationwide. The obesity epidemic continues to increase in spite of preventative measures undertaken worldwide. Pharmacological treatments promise to reduce total fat mass. However, medications may have significant side effects and can be potentially fatal. Data Retrieval: This brief review, based on a PUBMED search of the key terms "Obesity" and" Sarcopenia," will present evidence to corroborate the existence of Reward Deficiency Syndrome (RDS) in obesity and the involvement of catecholaminergic pathways in substance seeking behavior, particularly as it relates to carbohydrates cravings. Expert Opinion: The genetic basis and future genetic testing of children for risk of aberrant generalized craving behavior are considered a prevention method. Here we present evidence supporting the use of precursor amino acid therapy and modulation of enkephalinase, MOA, and COMT inhibition in key brain regions. Such treatments manifest in improved levels of dopamine/norepinephrine, GABA, serotonin, and enkephalins. We also present evidence substantiating insulin sensitivity enhancement via Chromium salts, which affect dopamine neuronal synthesis regulation. We believe our unique combination of natural ingredients will influence many pathways leading to the promotion of well-being and normal healthy metabolic functioning. Sarcopenia has been shown to reduce angiogenesis and possible cerebral blood flow. Exercise seems to provide a significant benefit to overcome this obesity-promoting loss of muscle density. Conclusion: Utilization of proposed nutrigenomic formulae based on coupling genetic obesity risk testing promotes generalized anti-craving of carbohydrates and can inhibit carbohydrate bingeing, inducing significant healthy fat loss and relapse prevention.
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Affiliation(s)
- Kenneth Blum
- Center for Psychiatry, Medicine & Primary Care (Office of the Provost), Division of Addiction Research & Education, Western University Health Science, Pomona, CA 91766, USA;
- Institute of Psychology, ELTE Eötvös Loránd University, Kazinczy u. 23-27, 1075 Budapest, Hungary
- Division of Nutrigenomics, Genomic Testing Center Geneus Health, San Antonio, TX 78249, USA
- Department of Psychiatry, University of Vermont, Burlington, VT 05401, USA
- Department of Psychiatry, Wright University Boonshoff School of Medicine, Dayton, OH 45377, USA
- Division of Precision Nutrition, Victory Nutrition International, Bonita Springs, FL 34135, USA; (W.B.D.); (D.B.)
- The Kenneth Blum Behavioral & Neurogenetic Institute, Division of Ivitalize Inc., Austin, TX 78701, USA; (L.L.-G.); (R.J.)
- Division of Clinical Neurology, Path Foundation NY, New York, NY 10010, USA;
- Correspondence:
| | - Mark S. Gold
- Department of Psychiatry, School of Medicine, Tulane University, New Orleans, LA 70118, USA; (M.S.G.); (A.K.R.III)
| | - Luis Llanos-Gomez
- The Kenneth Blum Behavioral & Neurogenetic Institute, Division of Ivitalize Inc., Austin, TX 78701, USA; (L.L.-G.); (R.J.)
| | - Rehan Jalali
- The Kenneth Blum Behavioral & Neurogenetic Institute, Division of Ivitalize Inc., Austin, TX 78701, USA; (L.L.-G.); (R.J.)
| | - Panayotis K. Thanos
- Department of Psychology & Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Research Institute on Addictions, University at Buffalo, Buffalo, NY 14260, USA;
| | - Abdalla Bowirrat
- Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel 40700, Israel;
| | - William B. Downs
- Division of Precision Nutrition, Victory Nutrition International, Bonita Springs, FL 34135, USA; (W.B.D.); (D.B.)
| | - Debasis Bagchi
- Division of Precision Nutrition, Victory Nutrition International, Bonita Springs, FL 34135, USA; (W.B.D.); (D.B.)
- Department of Pharmaceutical Sciences, College of Pharmacy & Health Sciences, Texas Southern University, Houston, TX 77004, USA
| | - Eric R. Braverman
- Division of Clinical Neurology, Path Foundation NY, New York, NY 10010, USA;
| | - David Baron
- Center for Psychiatry, Medicine & Primary Care (Office of the Provost), Division of Addiction Research & Education, Western University Health Science, Pomona, CA 91766, USA;
| | - Alphonso Kenison Roy
- Department of Psychiatry, School of Medicine, Tulane University, New Orleans, LA 70118, USA; (M.S.G.); (A.K.R.III)
| | - Rajendra D. Badgaiyan
- Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy Memorial VA Hospital, Long School of Medicine, University of Texas Medical Center, San Antonio, TX 78249, USA;
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36
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Blum K, Badgaiyan RD. Translational and Molecular Cytoarchitectural Genetic Guided Therapy to Induce Dopamine Homeostatic Neuro-signaling in Reward Deficiency and Associated Drug and Behavioral Addiction Seeking: A 60 Year Sojourn the Future is Now. EC PSYCHOLOGY AND PSYCHIATRY 2021; 10:1-4. [PMID: 34708222 PMCID: PMC8547334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Affiliation(s)
- Kenneth Blum
- Graduate College, Western University Health Sciences, Pomona, CA, USA
| | - Rajendra D Badgaiyan
- Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy Memorial VA Hospital and Long School of Medicine, University of Texas Health Science Center, San Antonio, TX, USA
- Department of Psychiatry, MT. Sinai School of Medicine, New York, NY, USA
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Blum K, Khalsa J, Cadet JL, Baron D, Bowirrat A, Boyett B, Lott L, Brewer R, Gondré-Lewis M, Bunt G, Kazmi S, Gold MS. Cannabis-Induced Hypodopaminergic Anhedonia and Cognitive Decline in Humans: Embracing Putative Induction of Dopamine Homeostasis. Front Psychiatry 2021; 12:623403. [PMID: 33868044 PMCID: PMC8044913 DOI: 10.3389/fpsyt.2021.623403] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Accepted: 02/05/2021] [Indexed: 02/01/2023] Open
Abstract
Over years, the regular use of cannabis has substantially increased among young adults, as indicated by the rise in cannabis use disorder (CUD), with an estimated prevalence of 8. 3% in the United States. Research shows that exposure to cannabis is associated with hypodopaminergic anhedonia (depression), cognitive decline, poor memory, inattention, impaired learning performance, reduced dopamine brain response-associated emotionality, and increased addiction severity in young adults. The addiction medicine community is increasing concern because of the high content of delta-9-tetrahydrocannabinol (THC) currently found in oral and vaping cannabis products, the cognitive effects of cannabis may become more pronounced in young adults who use these cannabis products. Preliminary research suggests that it is possible to induce 'dopamine homeostasis,' that is, restore dopamine function with dopamine upregulation with the proposed compound and normalize behavior in chronic cannabis users with cannabis-induced hypodopaminergic anhedonia (depression) and cognitive decline. This psychological, neurobiological, anatomical, genetic, and epigenetic research also could provide evidence to use for the development of an appropriate policy regarding the decriminalization of cannabis for recreational use.
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Affiliation(s)
- Kenneth Blum
- Western University Health Sciences, Pomona, CA, United States
- Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary
- Division of Nutrigenomics, Precision Translational Medicine, LLC., San Antonio, TX, United States
- Division of Nutrigenomics, Genomic Testing Center, Geneus Health, LLC., San Antonio, TX, United States
- Department of Psychiatry, University of Vermont, Burlington, VT, United States
- Department of Psychiatry, Wright University Boonshoff School of Medicine, Dayton, OH, United States
| | - Jag Khalsa
- Department of Microbiology, Immunology and Tropical Medicine, George Washington University, School of Medicine, Washington, DC, United States
| | - Jean Lud Cadet
- Molecular Neuropsychiatry Research Branch, DHHS/NIH/NIDA Intramural Research Program, National Institutes of Health, Baltimore, MD, United States
| | - David Baron
- Western University Health Sciences, Pomona, CA, United States
| | - Abdalla Bowirrat
- Department of Neuroscience, Interdisciplinary Center (IDC), Herzliya, Israel
| | - Brent Boyett
- Bradford Health Services, Madison, AL, United States
| | - Lisa Lott
- Division of Nutrigenomics, Genomic Testing Center, Geneus Health, LLC., San Antonio, TX, United States
| | - Raymond Brewer
- Division of Nutrigenomics, Precision Translational Medicine, LLC., San Antonio, TX, United States
- Division of Nutrigenomics, Genomic Testing Center, Geneus Health, LLC., San Antonio, TX, United States
| | - Marjorie Gondré-Lewis
- Department of Psychiatry and Behavioral Sciences, Howard University College of Medicine, Washington, DC, United States
| | - Gregory Bunt
- Good Samaritan/Day Top Treatment Center, and NYU School of Medicine, New York, NY, United States
| | - Shan Kazmi
- College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, United States
| | - Mark S. Gold
- Department of Psychiatry, Washington University School of Medicine, St Louis, MO, United States
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Identification of a sex-stratified genetic algorithm for opioid addiction risk. THE PHARMACOGENOMICS JOURNAL 2021; 21:326-335. [PMID: 33589790 DOI: 10.1038/s41397-021-00212-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 12/16/2020] [Accepted: 01/20/2021] [Indexed: 11/08/2022]
Abstract
The opioid epidemic has had a devastating impact on our country, with wide-ranging effects on healthcare, corrections, employment, and social systems. Programs have been put in place for monitoring prescriptions, initiating and expanding medications for opioid use disorder, and harm reduction (i.e., naloxone distribution, needle exchanges). However, opportunities for personalization of opioid therapy based on addiction risk have been limited. The goal of the present study was to develop an objective risk assessment algorithm based on genetic markers that are correlated with opioid use disorder (OUD). A total of 180 single-nucleotide polymorphisms (SNPs) were tested in patients with and without OUD. SNPs selected for testing were associated with opioid metabolism and drug reward pathways based on previous studies. Of the 394 patients recruited, 200 had OUD and 194 served as controls without OUD but with prior opioid exposure. Logistic regression analyses stratified by sex identified ten unique SNPs in females and nine unique SNPs in males that were significantly associated with OUD. A Genetics Opioid Risk Score (GenORs) was calculated by counting the number of OUD risk-associated SNPs/genotypes for each patient. To evaluate the discrimination of the GenORs, a receiver operating characteristic (ROC) curve for each sex was generated and determined to be sensitive and specific. This represents the first published example of a sex-based genetic risk score with potential to predict OUD, and the first OUD algorithm to include opioid-associated pharmacokinetic genes.
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Vanneste S, De Ridder D. Chronic pain as a brain imbalance between pain input and pain suppression. Brain Commun 2021; 3:fcab014. [PMID: 33758824 PMCID: PMC7966784 DOI: 10.1093/braincomms/fcab014] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 11/19/2020] [Accepted: 11/23/2020] [Indexed: 12/20/2022] Open
Abstract
Chronic pain is pain that persists beyond the expected period of healing. The subjective experience of chronic pain results from pathological brain network interactions, rather than from persisting physiological sensory input of nociceptors. We hypothesize that pain is an imbalance between pain evoking dorsal anterior cingulate cortex and somatosensory cortex and pain suppression (i.e. pregenual anterior cingulate cortex). This imbalance can be measured objectively by current density ratios between pain input and pain inhibition. A balance between areas involved in pain input and pain suppression requires communication, which can be objectively identified by connectivity measures, both functional and effective connectivity. In patients with chronic neuropathic pain, electroencephalography is performed with source localization demonstrating that pain is reflected by an abnormal ratio between the dorsal anterior cingulate cortex, somatosensory cortex and pregenual anterior cingulate cortex. Functional connectivity demonstrates decreased communication between these areas, and effective connectivity puts the culprit at the dorsal anterior cingulate cortex, suggesting that the problem is related to abnormal behavioral relevance attached to the pain. In conclusion, chronic pain can be considered as an imbalance between pain input and pain suppression.
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Affiliation(s)
- Sven Vanneste
- Global Brain Health Institute, Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland
| | - Dirk De Ridder
- Department of Surgical Sciences, Section of Neurosurgery, Dunedin School of Medicine, University of Otago, 9016 Dunedin, New Zealand
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Blum K, Raza A, Schultz T, Jalali R, Green R, Brewer R, Thanos PK, McLaughlin T, Baron D, Bowirrat A, Elman I, Downs BW, Bagchi D, Badgaiyan RD. Should We Embrace the Incorporation of Genetically Guided "Dopamine Homeostasis" in the Treatment of Reward Deficiency Syndrome (RSD) as a Frontline Therapeutic Modality? ACTA SCIENTIFIC NEUROLOGY 2021; 4:17-24. [PMID: 33681869 PMCID: PMC7931265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
In 2019, the US Center for Disease Control and Prevention provided vital statistics related to drug overdoses in the United State1. They concluded that in the USA the number of deaths at almost 72,000 was due to 66.6% of opioid overdoses. In fact, the rate is alarming and increasing yearly. To make 2021 even more scary is the daunting effect on increased drug usage due to COVID 19 as a pandemic, albeit the new vaccines. Specifically, in 2020, the death rate from opioid overdoses rose to 13% nationally and in some sates 30%. The common neuromodulating aspects of neurotransmission, and its disruption via chronic exposure of drugs and behavioral addictions, requires further intense research focus on developing novel strategies to combat these unwanted genetic and epigenic infractions as accomplished with heroin addiction by our group. The take home message is the plausible acceptance of the well-established evidence for hypodopaminergia, a blunted reward processing system, reduced resting state functional connectivity, genetic antecedents, anti- reward symptomatology, poor compliance with MAT, and generalized RDS. With this evidence it is conceivable that pursuit through intensive future research should involve an approach that incorporates "dopamine homeostasis". This required paradigm shift may consist of many beneficial modalities including but not limited to: exercise, pro-dopamine regulation, nutrigenomics, cognitive behavioral therapy, hedonic hot spot targets brain, rTMRS, deep brain stimulation, diet, genetic edits, genetic guided therapeutics, epigenetic repair, amongst others. It is our opinion that nutrigenomics may assist the millions of people of getting out of a" hypodopaminergic ditch" WC 250.
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Affiliation(s)
- Kenneth Blum
- The Kenneth Blum Behavioral Neurogenetic Institute, Austin, Texas, USA
- Graduate College, Western University Health Sciences, Pomona, California, USA
- Division of Nutrigenomics, Center for Genomic Testing, Geneus Health, LLC., San Antonio, Texas, USA
| | - Ali Raza
- The Kenneth Blum Behavioral Neurogenetic Institute, Austin, Texas, USA
| | - Tiffany Schultz
- The Kenneth Blum Behavioral Neurogenetic Institute, Austin, Texas, USA
| | - Rehan Jalali
- The Kenneth Blum Behavioral Neurogenetic Institute, Austin, Texas, USA
| | - Richard Green
- The Kenneth Blum Behavioral Neurogenetic Institute, Austin, Texas, USA
| | - Raymond Brewer
- The Kenneth Blum Behavioral Neurogenetic Institute, Austin, Texas, USA
| | - Panyotis K Thanos
- Department of Psychology, University of Buffalo, the State University of New York, Buffalo, NY, USA
| | - Thomas McLaughlin
- The Kenneth Blum Behavioral Neurogenetic Institute, Austin, Texas, USA
| | - David Baron
- Graduate College, Western University Health Sciences, Pomona, California, USA
| | - Abdalla Bowirrat
- Department of Neuroscience and Genetics, Interdisciplinary Center Herzliya, Israel
| | - Igor Elman
- Department of Psychiatry, Harvard University College of Medicine, Cambridge, Massachusetts, USA
| | - B William Downs
- The Kenneth Blum Behavioral Neurogenetic Institute, Austin, Texas, USA
| | - Debasis Bagchi
- The Kenneth Blum Behavioral Neurogenetic Institute, Austin, Texas, USA
- Department of Pharmaceutical Sciences, South Texas University College of Pharmacy, Houston, Texas, USA
| | - Rajendra D Badgaiyan
- Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy Memorial VA Hospital, San Antonio, TX, Long School of Medicine, University of Texas Medical Center, San Antonio, TX, USA
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Blum K, Baron D, Jalali R, Modestino EJ, Steinberg B, Elman I, Badgaiyan RD, Gold MS. Polygenic and multi locus heritability of alcoholism: Novel therapeutic targets to overcome psychological deficits. ACTA ACUST UNITED AC 2020; 7. [PMID: 34707891 PMCID: PMC8547332 DOI: 10.15761/jsin.1000240] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Kenneth Blum
- Western University Health Sciences, Pomona, CA, USA.,Institute of Psychology, ELTE Eotvos Lorand University, Budapest, Hungary.,Division of Nutrigenomics, Genomic Testing Center Geneus Health, LLC, San Antonio, TX, USA.,Department of Psychiatry, University of Vermont, VT, USA.,Department of Psychiatry, Wright University Boonshoff School of Medicine, Dayton, OH., USA.,The Kenneth Blum Behavioral Neurogenetic Institute (Division of iVitalize Inc.), Austin, Tx, USA
| | - David Baron
- Western University Health Sciences, Pomona, CA, USA
| | - Rehan Jalali
- The Kenneth Blum Behavioral Neurogenetic Institute (Division of iVitalize Inc.), Austin, Tx, USA
| | | | | | - Igor Elman
- Department of Psychiatry, Harvard School of Medicine, Cambridge, MA, USA
| | - Rajendra D Badgaiyan
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy I Memorial VA Hospital, San Antonio, TX. and Long School of Medicine, University of Texas Medical Center, San Antonio TX, USA
| | - Mark S Gold
- Department of Psychiatry, Washington University School of Medicine, St. Louis, Mo. USA
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Gold MS, Baron D, Bowirrat A, Blum K. Neurological correlates of brain reward circuitry linked to opioid use disorder (OUD): Do homo sapiens acquire or have a reward deficiency syndrome? J Neurol Sci 2020; 418:117137. [PMID: 32957037 PMCID: PMC7490287 DOI: 10.1016/j.jns.2020.117137] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 08/19/2020] [Accepted: 09/08/2020] [Indexed: 12/14/2022]
Abstract
The extant literature confirms that an array of polymorphic genes related to- neurotransmitters and second messengers govern the net release of dopamine in the Nucleus Accumbens (NAc) in the mesolimbic region of the brain. They are linked predominantly to motivation, anti-stress, incentive salience (wanting), and wellbeing. Notably, in 2000 the Nobel Prize was awarded to Carlsson, Greengard, and Kandel for their work on the molecular and cellular function of dopaminergic activity at neurons. This historical psychopharmacological work involved neurotransmission of serotonin, endorphins, glutamate, and dopamine, and the seminal work of Blum, Gold, Volkow, Nestler, and others related to neurotransmitter function and related behaviors. Currently, Americans are facing their second and worst opioid epidemic, prescribed opioids, and easy access drive this epidemic of overdoses, and opioid use disorders (OUDs). Presently the clinical consensus is to treat OUD, as if it were an opioid deficiency syndrome, with long-term to life-long opioid substitution therapy. Opioid agonist administration is seen as necessary to replace missing opioids, treat OUD, and prevent overdoses, like insulin is used to treat diabetes. Treatment of OUD and addiction, in general, is similar to the endocrinopathy conceptualization in that it views opioid agonist MATs as an essential core to therapy. Is this approach logical? Other than as harm reduction, is using opioids to treat OUD therapeutic or harmful in the long term? This historical Trieste provides a molecular framework to understand the current underpinnings of endorphinergic/dopaminergic mechanisms related to opioid deficiency syndrome and generalized reward processing depletion. WC 249.
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Affiliation(s)
- Mark S Gold
- Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, United States.
| | - David Baron
- Graduate School of Biomedical Sciences, Western University Health Sciences, Pomona, CA, United States
| | - Abdalla Bowirrat
- Department of Neuroscience and Genetics, Interdisciplinary Center Herzliya, Israel
| | - Kenneth Blum
- Graduate School of Biomedical Sciences, Western University Health Sciences, Pomona, CA, United States
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43
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Leong SL, Glue P, Manning P, Vanneste S, Lim LJ, Mohan A, De Ridder D. Anterior Cingulate Cortex Implants for Alcohol Addiction: A Feasibility Study. Neurotherapeutics 2020; 17:1287-1299. [PMID: 32323203 PMCID: PMC7641294 DOI: 10.1007/s13311-020-00851-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Abnormal neural activity, particularly in the rostrodorsal anterior cingulate cortex (rdACC), appears to be responsible for intense alcohol craving. Neuromodulation of the rdACC using cortical implants may be an option for individuals with treatment-resistant alcohol dependence. This study assessed the effectiveness and feasibility of suppressing alcohol craving using cortical implants of the rdACC using a controlled one-group pre- and post-test study design. Eight intractable alcohol-dependent participants (four males and four females) were implanted with two Lamitrode 44 electrodes over the rdACC bilaterally connected to an internal pulse generator (IPG). The primary endpoint, self-reported alcohol craving reduced by 60.7% (p = 0.004) post- compared to pre-stimulation. Adverse events occurred in four out of the eight participants. Electrophysiology findings showed that among responders, there was a post-stimulation decrease (p = 0.026) in current density at the rdACC for beta 1 band (13-18 Hz). Results suggest that rdACC stimulation using implanted electrodes may potentially be a feasible method for supressing alcohol craving in individuals with severe alcohol use disorder. However, to further establish safety and efficacy, larger controlled clinical trials are needed.
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Affiliation(s)
- Sook Ling Leong
- Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
- Department of Surgical Sciences, University of Otago, Dunedin, New Zealand.
| | - Paul Glue
- Department of Psychological Medicine, University of Otago, Dunedin, New Zealand
| | - Patrick Manning
- Department of Medicine, University of Otago, Dunedin, New Zealand
| | - Sven Vanneste
- Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland
- Lab for Clinical and Integrative Neuroscience, School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX, USA
| | - Louisa Joyce Lim
- Department of Surgical Sciences, University of Otago, Dunedin, New Zealand
| | - Anusha Mohan
- Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland
| | - Dirk De Ridder
- Department of Surgical Sciences, University of Otago, Dunedin, New Zealand.
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Gondré-Lewis MC, Bassey R, Blum K. Pre-clinical models of reward deficiency syndrome: A behavioral octopus. Neurosci Biobehav Rev 2020; 115:164-188. [PMID: 32360413 DOI: 10.1016/j.neubiorev.2020.04.021] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 04/08/2020] [Accepted: 04/20/2020] [Indexed: 12/15/2022]
Abstract
Individuals with mood disorders or with addiction, impulsivity and some personality disorders can share in common a dysfunction in how the brain perceives reward, where processing of natural endorphins or the response to exogenous dopamine stimulants is impaired. Reward Deficiency Syndrome (RDS) is a polygenic trait with implications that suggest cross-talk between different neurological systems that include the known reward pathway, neuroendocrine systems, and motivational systems. In this review we evaluate well-characterized animal models for their construct validity and as potential models for RDS. Animal models used to study substance use disorder, major depressive disorder (MDD), early life stress, immune dysregulation, attention deficit hyperactivity disorder (ADHD), post traumatic stress disorder (PTSD), compulsive gambling and compulsive eating disorders are discussed. These disorders recruit underlying reward deficiency mechanisms in multiple brain centers. Because of the widespread and remarkable array of associated/overlapping behavioral manifestations with a common root of hypodopaminergia, the basic endophenotype recognized as RDS is indeed likened to a behavioral octopus. We conclude this review with a look ahead on how these models can be used to investigate potential therapeutics that target the underlying common deficiency.
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Affiliation(s)
- Marjorie C Gondré-Lewis
- Department of Anatomy, Howard University College of Medicine, 520 W Street, NW, Washington D.C., 20059, United States; Developmental Neuropsychopharmacology Laboratory, Howard University College of Medicine, 520 W Street, NW, Washington D.C., 20059, United States.
| | - Rosemary Bassey
- Developmental Neuropsychopharmacology Laboratory, Howard University College of Medicine, 520 W Street, NW, Washington D.C., 20059, United States; Department of Science Education, Donald and Barbara Zucker School of Medicine at Hofstra/ Northwell, 500 Hofstra University, Hempstead, NY 11549, United States
| | - Kenneth Blum
- Western University Health Sciences, Graduate College of Biomedical Sciences, Pomona, California, United States
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45
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Blum K, Baron D, McLaughlin T, Gold MS. Molecular neurological correlates of endorphinergic/dopaminergic mechanisms in reward circuitry linked to endorphinergic deficiency syndrome (EDS). J Neurol Sci 2020; 411:116733. [DOI: 10.1016/j.jns.2020.116733] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Revised: 01/19/2020] [Accepted: 02/11/2020] [Indexed: 12/20/2022]
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46
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Swenson S, Blum K, McLaughlin T, Gold MS, Thanos PK. The therapeutic potential of exercise for neuropsychiatric diseases: A review. J Neurol Sci 2020; 412:116763. [PMID: 32305746 DOI: 10.1016/j.jns.2020.116763] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Revised: 02/14/2020] [Accepted: 02/28/2020] [Indexed: 02/06/2023]
Abstract
Exercise is known to have a myriad of health benefits. There is much to be learned from the effects of exercise and its potential for prevention, attenuation and treatment of multiple neuropsychiatric diseases and behavioral disorders. Furthermore, recent data and research on exercise benefits with respect to major health crises, such as, that of opioid and general substance use disorders, make it very important to better understand and review the mechanisms of exercise and how it could be utilized for effective treatments or adjunct treatments for these diseases. In addition, mechanisms, epigenetics and sex differences are examined and discussed in terms of future research implications.
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Affiliation(s)
- Sabrina Swenson
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY, USA
| | - Kenneth Blum
- Western Univesity Health Sciences, Graduate College, Pomona, CA, USA
| | | | - Mark S Gold
- Washington University in St. Louis, School of Medicine, St. Louis, MO, USA
| | - Panayotis K Thanos
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biosciences, State University of New York at Buffalo, Buffalo, NY, USA; Department of Psychology, State University of New York at Buffalo, Buffalo, NY, USA.
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Brewer R, Blum K, Bowirrat A, Modestino EJ, Baron D, Badgaiyan RD, Moran M, Boyett B, Gold MS. Transmodulation of Dopaminergic Signaling to Mitigate Hypodopminergia and Pharmaceutical Opioid-Induced Hyperalgesia. CURRENT PSYCHOPHARMACOLOGY 2020; 9:164-184. [PMID: 37361136 PMCID: PMC10288629 DOI: 10.2174/2211556009999200628093231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 04/16/2020] [Accepted: 05/06/2020] [Indexed: 06/28/2023]
Abstract
Neuroscientists and psychiatrists working in the areas of "pain and addiction" are asked in this perspective article to reconsider the current use of dopaminergic blockade (like chronic opioid agonist therapy), and instead to consider induction of dopamine homeostasis by putative pro-dopamine regulation. Pro-dopamine regulation could help pharmaceutical opioid analgesic agents to mitigate hypodopaminergia-induced hyperalgesia by inducing transmodulation of dopaminergic signaling. An optimistic view is that early predisposition to diagnosis based on genetic testing, (pharmacogenetic/pharmacogenomic monitoring), combined with appropriate urine drug screening, and treatment with pro-dopamine regulators, could conceivably reduce stress, craving, and relapse, enhance well-being and attenuate unwanted hyperalgesia. These concepts require intensive investigation. However, based on the rationale provided herein, there is a good chance that combining opioid analgesics with genetically directed pro-dopamine-regulation using KB220 (supported by 43 clinical studies). This may become a front-line technology with the potential to overcome, in part, the current heightened rates of chronic opioid-induced hyperalgesia and concomitant Reward Deficiency Syndrome (RDS) behaviors. Current research does support the hypothesis that low or hypodopaminergic function in the brain may predispose individuals to low pain tolerance or hyperalgesia.
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Affiliation(s)
- Raymond Brewer
- Department of Nutrigenomics, Genomic Testing Center, Geneus Health, LLC., San Antonio, TX, USA
| | - Kenneth Blum
- Department of Nutrigenomics, Genomic Testing Center, Geneus Health, LLC., San Antonio, TX, USA
- Western University Health Sciences, Pomona, CA., USA
- Division of Neuroscience and Addiction Research, Pathway Healthcare, Birmingham, AL, USA
- Eotvos Loránd University, Institute of Psychology, Budapest, Hungary
- Department of Psychiatry, Wright State University Boonshoft School of Medicine and Dayton VA Medical Center, Dayton, OH, USA
- Department of Psychiatry, University of Vermont, Burlington, VT., USA
| | - Abdalla Bowirrat
- Department of Neuroscience and Genetics, Interdisciplinary Center Herzliya, Israel
| | | | - David Baron
- Western University Health Sciences, Pomona, CA., USA
| | - Rajendra D. Badgaiyan
- Department of Psychiatry, ICHAN School of Medicine, Mount Sinai, New York, NYC. & Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy Memorial VA Hospital, San Antonio, TX, Long School of Medicine, University of Texas Medical Center, San Antonio, TX, USA
| | - Mark Moran
- Department of Nutrigenomics, Genomic Testing Center, Geneus Health, LLC., San Antonio, TX, USA
| | - Brent Boyett
- Division of Neuroscience and Addiction Research, Pathway Healthcare, Birmingham, AL, USA
- Bradford Health Services, Madison, AL., USA
| | - Mark S. Gold
- Department of Psychiatry, Washington University School of Medicine, St. Louis, Mo., USA
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Abijo T, Blum K, Gondré-Lewis MC. Neuropharmacological and Neurogenetic Correlates of Opioid Use Disorder (OUD) As a Function of Ethnicity: Relevance to Precision Addiction Medicine. Curr Neuropharmacol 2020; 18:578-595. [PMID: 31744450 PMCID: PMC7457418 DOI: 10.2174/1570159x17666191118125702] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Revised: 10/31/2019] [Accepted: 11/16/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Over 100 people die daily from opioid overdose and $78.5B per year is spent on treatment efforts, however, the real societal cost is multifold greater. Alternative strategies to eradicate/manage drug misuse and addiction need consideration. The perception of opioid addiction as a social/criminal problem has evolved to evidence-based considerations of them as clinical disorders with a genetic basis. We present evaluations of the genetics of addiction with ancestryspecific risk profiles for consideration. OBJECTIVE Studies of gene variants associated with predisposition to substance use disorders (SUDs) are monolithic, and exclude many ethnic groups, especially Hispanics and African Americans. We evaluate gene polymorphisms that impact brain reward and predispose individuals to opioid addictions, with a focus on the disparity of research which includes individuals of African and Hispanic descent. METHODOLOGY PubMed and Google Scholar were searched for: Opioid Use Disorder (OUD), Genome- wide association studies (GWAS); genetic variants; polymorphisms, restriction fragment length polymorphisms (RFLP); genomics, epigenetics, race, ethnic group, ethnicity, ancestry, Caucasian/ White, African American/Black, Hispanic, Asian, addictive behaviors, reward deficiency syndrome (RDS), mutation, insertion/deletion, and promotor region. RESULTS Many studies exclude non-White individuals. Studies that include diverse populations report ethnicity-specific frequencies of risk genes, with certain polymorphisms specifically associated with Caucasian and not African-American or Hispanic susceptibility to OUD or SUDs, and vice versa. CONCLUSION To adapt precision medicine-based addiction management in a blended society, we propose that ethnicity/ancestry-informed genetic variations must be analyzed to provide real precision- guided therapeutics with the intent to attenuate this uncontrollable fatal epidemic.
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Affiliation(s)
| | | | - Marjorie C. Gondré-Lewis
- Address correspondence to this author at the Department of Anatomy, Howard University College of Medicine, 520 W St NW, Washington DC 20059 USA; Tel/Fax: +1-202-806-5274; E-mail:
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Downs BW, Blum K, Bagchi D, Kushner S, Bagchi M, Galvin JM, Lewis M, Siwicki D, Brewer R, Boyett B, Baron D, Giordano J, Badgaiyan RD. Molecular neuro-biological and systemic health benefits of achieving dopamine homeostasis in the face of a catastrophic pandemic (COVID- 19): A mechanistic exploration. ACTA ACUST UNITED AC 2020; 7. [PMID: 32934824 DOI: 10.15761/jsin.1000228] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
In the face of the global pandemic of COVID 19, approaching 1.75 Million infected worldwide (4/12/2020) and associated mortality (over 108, 000 as of 4/12/2020) as well-as other catastrophic events including the opioid crisis, a focus on brain health seems prudent [1] (https://www.coronavirus.gov). This manuscript reports on the systemic benefits of restoring and achieving dopamine homeostasis to reverse and normalize thoughts and behaviors of Reward Deficiency Syndrome (RDS) dysfunctional conditions and their effects on behavioral physiology; function of reward genes; and focuses on digestive, immune, eye health, and the constellation of symptomatic behaviors. The role of nutrigenomic interventions on restoring normal brain functions and its benefits on these systems will be discussed. We demonstrate that modulation of dopamine homeostasis using nutrigenomic dopamine agonists, instead of pharmaceutical interventions, is achievable. The allied interlinking with diverse chronic diseases and disorders, roles of free radicals and incidence of anaerobic events have been extensively highlighted. In conjunction, the role of dopamine in aspects of sleep, rapid eye movement and waking are extensively discussed. The integral aspects of food indulgence, the influence of taste sensations, and gut-brain signaling are also discussed along with a special emphasis on ocular health. The detailed mechanistic insight of dopamine, immune competence and the allied aspects of autoimmune disorders are also highlighted. Finally, the integration of dopamine homeostasis utilizing a patented gene test and a research-validated nutrigenomic intervention are presented. Overall, a cutting-edge nutrigenomic intervention could prove to be a technological paradigm shift in our understanding of the extent to which achieving dopamine homeostasis will benefit overall health.
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Affiliation(s)
- B W Downs
- Department of Nutrigenomics Research, Victory Nutrition International, Inc., Lederach, PA, USA
| | - K Blum
- Department of Nutrigenomics Research, Victory Nutrition International, Inc., Lederach, PA, USA.,Western University, Health Sciences, Graduate School of Biomedical Sciences, Pomona, CA, USA.,Division of Neuroscience and Addiction Research, Pathway Healthcare, Birmingham, AL, USA.,Eotvos Loránd University, Institute of Psychology, Budapest, Hungary.,Department of Psychiatry, Wright State University Boonshoft School of Medicine and Dayton VA Medical Center, Dayton, OH, USA.,Division of Precision Nutrition, GARS IP., LLC, Hollywood Fl., USA, & Geneus Health, LLC., San Antonio, TX, USA
| | - D Bagchi
- Department of Nutrigenomics Research, Victory Nutrition International, Inc., Lederach, PA, USA.,Department of Pharmacological & Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, TX, USA
| | - S Kushner
- ALM Research & Development, Oldsmar, FL, USA
| | | | - J M Galvin
- Vitality Medical Wellness Institute, PLLC, Charlotte, NC, USA
| | - McG Lewis
- Departments of Anatomy & Psychiatry, Howard University, School of Medicine, Washington, D., USA
| | - D Siwicki
- Division of Precision Nutrition, GARS IP., LLC, Hollywood Fl., USA, & Geneus Health, LLC., San Antonio, TX, USA
| | - R Brewer
- Division of Precision Nutrition, GARS IP., LLC, Hollywood Fl., USA, & Geneus Health, LLC., San Antonio, TX, USA
| | - B Boyett
- Division of Neuroscience and Addiction Research, Pathway Healthcare, Birmingham, AL, USA
| | - D Baron
- Western University, Health Sciences, Graduate School of Biomedical Sciences, Pomona, CA, USA
| | - J Giordano
- National Institute of Holistic and Addiction Studies, Davie, FL, USA
| | - R D Badgaiyan
- Department of Psychiatry, ICHAN School of Medicine, Mount Sinai, New York, NYC. & Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy Memorial VA Hospital, San Antonio, TX, Long School of Medicine, University of Texas Medical Center, San Antonio, TX, USA
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50
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Blum K, Bowirrat A, Baron D, Lott L, Ponce JV, Brewer R, Siwicki D, Boyett B, Gondre-Lewis MC, Smith DE, Panayotis K T, Badgaiyan S, Hauser M, Fried L, A R, Downs BW, Badgaiyan RD. Biotechnical development of genetic addiction risk score (GARS) and selective evidence for inclusion of polymorphic allelic risk in substance use disorder (SUD). ACTA ACUST UNITED AC 2019; 6. [PMID: 33614164 PMCID: PMC7891477 DOI: 10.15761/jsin.1000221] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Research into the neurogenetic basis of addiction identified and characterized by Reward Deficiency Syndrome (RDS) includes all drug and non-drug addictive, obsessive and compulsive behaviors. We are proposing herein that a new model for the prevention and treatment of Substance Use Disorder (SUD) a subset of RDS behaviors, based on objective biologic evidence, should be given serious consideration in the face of a drug epidemic. The development of the Genetic Addiction Risk Score (GARS) followed seminal research in 1990, whereby, Blum’s group identified the first genetic association with severe alcoholism published in JAMA. While it is true that no one to date has provided adequate RDS free controls there have been many studies using case –controls whereby SUD has been eliminated. We argue that this deficiency needs to be addressed in the field and if adopted appropriately many spurious results would be eliminated reducing confusion regarding the role of genetics in addiction. However, an estimation, based on these previous literature results provided herein, while not representative of all association studies known to date, this sampling of case- control studies displays significant associations between alcohol and drug risk. In fact, we present a total of 110,241 cases and 122,525 controls derived from the current literature. We strongly suggest that while we may take argument concerning many of these so-called controls (e.g. blood donors) it is quite remarkable that there are a plethora of case –control studies indicating selective association of these risk alleles ( measured in GARS) for the most part indicating a hypodopaminergia. The paper presents the detailed methodology of the GARS. Data collection procedures, instrumentation, and the analytical approach used to obtain GARS and subsequent research objectives are described. Can we combat SUD through early genetic risk screening in the addiction field enabling early intervention by the induction of dopamine homeostasis? It is envisaged that GARS type of screening will provide a novel opportunity to help identify causal pathways and associated mechanisms of genetic factors, psychological characteristics, and addictions awaiting additional scientific evidence including a future meta- analysis of all available data –a work in progress.
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Affiliation(s)
- K Blum
- Western University Health Sciences Graduate School of Biomedical Sciences, Pomona, CA, USA.,Department of Precision Behavioral Management, Geneus Health, San Antonio, TX, USA.,Division Addiction Services, Dominion Diagnostics, LLC, North Kingston, RI, USA.,Division of Nutrigenomics, Victory Nutrition International. Inc. Lederach, PA, USA.,Divion of Neuroscience & Addiction Research, Pathway HealthCare, LLC, Birmingham, AL.,Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary.,Department of Psychiatry, University of Vermont, Burlington, VM. USA.,Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal, India.,Department of Psychiatry, Wright State University Boonshoft School of Medicine and Dayton VA Medical Centre, Dayton, OH, USA
| | - A Bowirrat
- Departments of Clinical Neuroscience and Population Genetics, Interdisciplinary Center (IDC) Herzliya, Department of Neuroscience, Israel
| | - D Baron
- Western University Health Sciences Graduate School of Biomedical Sciences, Pomona, CA, USA
| | - L Lott
- Department of Precision Behavioral Management, Geneus Health, San Antonio, TX, USA
| | - J V Ponce
- Department of Precision Behavioral Management, Geneus Health, San Antonio, TX, USA
| | - R Brewer
- Department of Precision Behavioral Management, Geneus Health, San Antonio, TX, USA
| | - D Siwicki
- Department of Precision Behavioral Management, Geneus Health, San Antonio, TX, USA
| | - B Boyett
- Divion of Neuroscience & Addiction Research, Pathway HealthCare, LLC, Birmingham, AL
| | - M C Gondre-Lewis
- National Human Genome Center, Howard University, Washington DC, USA.,Departments of Anatomy, and Psychiatry & Behavioral Sciences, Howard University College of Medicine, Washington DC, USA
| | - D E Smith
- Department of Pharmacology, University of California San Francisco School of Medicine, San Francisco, USA
| | - Thanos Panayotis K
- Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Research Institute on Addictions, University at Buffalo, Buffalo, NY, USA
| | - S Badgaiyan
- Department of Precision Behavioral Management, Geneus Health, San Antonio, TX, USA
| | - M Hauser
- Division Addiction Services, Dominion Diagnostics, LLC, North Kingston, RI, USA
| | - L Fried
- Transformations Treatment Center, Del-Ray Beach, FL, USA
| | - Roy A
- Department of Psychiatry, Tulane University School of Medicine, New Orleans, LA, USA
| | - B W Downs
- Division of Nutrigenomics, Victory Nutrition International. Inc. Lederach, PA, USA
| | - R D Badgaiyan
- Department of Psychiatry, Ichan School of Medicine at Mount Sinai, New York, NY., USA.,Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy Memorial VA Hospital, San Antonio, TX, USA.,Long School of Medicine, University of Texas Medical Center, San Antonio, USAInstituto Nacional de Neurología y Neurocirugía
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