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In Search of Reward Deficiency Syndrome (RDS)-Free Controls: The “Holy Grail” in Genetic Addiction Risk Testing

Author(s):

Kenneth Blum*, David Baron, Lisa Lott, Jessica Valdez Ponce, David Siwicki, Brent Boyett, Bruce Steinberg, Edward J. Modestino, Lyle Fried, Mary Hauser, Thomas Simpatico, B. William Downs, Thomas McLaughlin and Rajendra D. Badgaiyan   Pages 1 - 15 ( 15 )

Abstract:


Background: The search for an accurate, gene-based test to identify heritable risk Reward Deficiency Syndrome (RDS) was conducted based on hundreds of published studies about the role of dopamine in addictive behaviors, including risk for dependence; both drug and non-drug. The term RDS was first coined by Blum’s group in 1995 to identify a group of behaviors with an in common neurobiological mechanism associated with 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 of case-control behavioral association studies, 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.

Method: Review of the literature related to the function of risk alleles of reward genes associated with hypodopaminergia in relevant case-controlled association studies for the selection of alleles to be measured by the Genetic Addiction Risk Score (GARS) test.

Result: The prevalence of the DRD2 A1 allele in unscreened controls (33.3%), compared to “super-controls” [highly RDS screened controls (3.3%) in proband and family] is used to exemplify a possible solution.

Conclusion: Unlike one gene-one disease (OGOD), RDS is polygenetic, very complex and 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.

Keywords:

Case controlled Studies, Super Controls, Genetic Addiction Association Studies, Genetic Prevalence, Study Controls, Reward Deficiency Syndrome (RDS), Study Controls, Behavioral Genetic Research, Hypodopaminergia, Single Nucleotide Polymorphisms (SNPs)

Affiliation:

Graduate School of Biomedical Science, Western University Health Sciences, Pomona, CA, Graduate School of Biomedical Science, Western University Health Sciences, Pomona, CA, Division of Precision Addiction Management, Geneus Health, San Antonio, TX, Division of Precision Addiction Management, Geneus Health, San Antonio, TX, Division of Precision Addiction Management, Geneus Health, San Antonio, TX, Division of Neuroscience & Addiction Therapy Research, Pathway HealthCare, Birmingham, AL, Department of Psychology, Curry College, Milton, MA, Department of Psychology, Curry College, Milton, MA, Transformations Treatment Center, Delray Beach, FL, Dominion Diagnostics, North Kingston, RI, Department of Psychiatry, University of Vermont, Burlington, VM, Victory Nutrition International, Inc., Lederach, PA, Center for Psychiatric Medicine, Lawrence, MA, 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



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