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

[ Vol. 9 , Issue. 1 ]

Author(s):

Kenneth Blum*, David Baron, Lisa Lott, Jessica V. Ponce, David Siwicki, Brent Boyett, Bruce Steinberg, Edward J. Modestino, Lyle Fried, Mary Hauser, Thomas Simpatico, Bill W. Downs, Thomas McLaughlin, Raju Hajela and Rajendra D. Badgaiyan   Pages 7 - 21 ( 15 )

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.

Keywords:

Behavioral genetic research, case controlled studies, genetic addiction association studies, genetic prevalence, hypodopaminergia, Reward Deficiency Syndrome (RDS), Single Nucleotide Polymorphisms (SNPs), study controls, super controls.

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 Family Medicine, Cummings School of Medicine, University of Calgary, Calgary, CN, 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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