Kenneth Blum1,2,3,4,5,6,7,8,9, David Baron1, Lisa Lott7, Jessica V Ponce7, David Siwicki7, Brent Boyett8, Bruce Steinberg10, Edward J Modestino10, Lyle Fried11, Mary Hauser6, Thomas Simpatico4, Bill W Downs9, Thomas McLaughlin12, Raju Hajela13, Rajendra D Badgaiyan14,15. 1. Graduate School of Biomedical Science, Western University Health Sciences, Pomona, CA, USA. 2. Eotvos Loránd University, Institute of Psychology, Budapest, Hungary. 3. Department of Psychiatry, Wright State University Boonshoft School of Medicine and Dayton VA Medical Center, Dayton, OH, USA. 4. Department of Psychiatry, University of Vermont, Burlington, VT, USA. 5. Division of Clinical Neurology, PATH Foundation, New York, NY, USA. 6. Dominion Diagnostics, North Kingston, RI, USA. 7. Division of Precision Addiction Management, Geneus Health, San Antonio, TX, USA. 8. Division of Neuroscience & Addiction Therapy Research, Pathway HealthCare, Birmingham, AL, USA. 9. Victory Nutrition International, Inc., Lederach, PA, USA. 10. Department of Psychology, Curry College, Milton, MA, USA. 11. Transformations Treatment Center, Delray Beach, FL, USA. 12. Center for Psychiatric Medicine, Lawrence, MA, USA. 13. Department of Family Medicine, Cummings School of Medicine, University of Calgary, Calgary, CN, Canada. 14. Department of Psychiatry, South Texas Veteran Health Care System, Audie L. Murphy Memorial VA Hospital, and Long School of Medicine, University of Texas Medical Center, San Antonio, TX, USA. 15. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Abstract
BACKGROUND: The search for an accurate, gene-based test to identify heritable risk factors for Reward Deficiency Syndrome (RDS) was conducted based on hundreds of published studies about the role of dopamine in addictive behaviors, including risk for drug dependence and compulsive/impulsive behavior disorders. The term RDS was first coined by Blum's group in 1995 to identify a group of behaviors with a common neurobiological mechanism associated with a polymorphic allelic propensity for hypodopaminergia. OBJECTIVES: To outline the process used to select risk alleles of reward genes for the Genetic Addiction Risk Score (GARS) test. Consequently, to address the limitations caused by inconsistent results that occur in many case-control behavioral association studies. These limitations are perhaps due to the failure of investigators to adequately screen controls for drug and alcohol use disorder, and any of the many RDS behaviors, including nicotine dependence, obesity, pathological gambling, and internet gaming addiction. METHODS: Review of the literature related to the function of risk alleles of reward genes associated with hypodopaminergia relevant case-control association studies for the selection of alleles to be measured by the Genetic Addiction Risk Score (GARS) test. RESULTS: The prevalence of the DRD2 A1 allele in unscreened controls (33.3%), compared to "Super-Controls" [highly screened RDS controls (3.3%) in proband and family] is used to exemplify a possible solution. CONCLUSION: Unlike one gene-one disease (OGOD), RDS is polygenetic, and very complex. In addition, any RDS-related behaviors must be eliminated from the control group in order to obtain the best possible statistical analysis instead of comparing the phenotype with disease-ridden controls.
BACKGROUND: The search for an accurate, gene-based test to identify heritable risk factors for Reward Deficiency Syndrome (RDS) was conducted based on hundreds of published studies about the role of dopamine in addictive behaviors, including risk for drug dependence and compulsive/impulsive behavior disorders. The term RDS was first coined by Blum's group in 1995 to identify a group of behaviors with a common neurobiological mechanism associated with a polymorphic allelic propensity for hypodopaminergia. OBJECTIVES: To outline the process used to select risk alleles of reward genes for the Genetic Addiction Risk Score (GARS) test. Consequently, to address the limitations caused by inconsistent results that occur in many case-control behavioral association studies. These limitations are perhaps due to the failure of investigators to adequately screen controls for drug and alcohol use disorder, and any of the many RDS behaviors, including nicotine dependence, obesity, pathological gambling, and internet gaming addiction. METHODS: Review of the literature related to the function of risk alleles of reward genes associated with hypodopaminergia relevant case-control association studies for the selection of alleles to be measured by the Genetic Addiction Risk Score (GARS) test. RESULTS: The prevalence of the DRD2 A1 allele in unscreened controls (33.3%), compared to "Super-Controls" [highly screened RDS controls (3.3%) in proband and family] is used to exemplify a possible solution. CONCLUSION: Unlike one gene-one disease (OGOD), RDS is polygenetic, and very complex. In addition, any RDS-related behaviors must be eliminated from the control group in order to obtain the best possible statistical analysis instead of comparing the phenotype with disease-ridden controls.
Entities:
Keywords:
Behavioral genetic research; Reward Deficiency Syndrome (RDS); Single Nucleotide Polymorphisms (SNPs); case controlled studies; genetic addiction association studies; genetic prevalence; hypodopaminergia; study controls; super controls
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Authors: Kenneth Blum; Thomas McLaughlin; Abdalla Bowirrat; Edward J Modestino; David Baron; Luis Llanos Gomez; Mauro Ceccanti; Eric R Braverman; Panayotis K Thanos; Jean Lud Cadet; Igor Elman; Rajendra D Badgaiyan; Rehan Jalali; Richard Green; Thomas A Simpatico; Ashim Gupta; Mark S Gold Journal: J Pers Med Date: 2022-02-21
Authors: Kenneth Blum; Shan Kazmi; Edward J Modestino; Bill William Downs; Debasis Bagchi; David Baron; Thomas McLaughlin; Richard Green; Rehan Jalali; Panayotis K Thanos; Igor Elman; Rajendra D Badgaiyan; Abdalla Bowirrat; Mark S Gold Journal: J Pers Med Date: 2021-03-16
Authors: Kenneth Blum; Bruce Steinberg; Marjorie C Gondre-Lewis; David Baron; Edward J Modestino; Rajendra D Badgaiyan; B William Downs; Debasis Bagchi; Raymond Brewer; Thomas McLaughlin; Abdalla Bowirrat; Mark Gold Journal: Psychol Res Behav Manag Date: 2021-12-17