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

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. Method: 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. Result: 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 diseaseridden controls.

A Novel Precision Approach to Overcome the “Addiction Pandemic” by Incorporating Genetic Addiction Risk Severity (GARS) and Dopamine Homeostasis Restoration

“…In previous work, Blum’s group developed the genetic addiction risk severity (GARS) test following seminal research conducted by Blum’s group in 1990, which identified the first genetic association with severe alcoholism published in JAMA [ 27 ]. Although no one has provided sufficient RDS-free controls, and many of these so-called controls (e.g., blood donors) are disputed [ 28 ]. This lack of disease-free case controls remains in the field, and spurious results continue confusion regarding the role of genetics in addiction.…”

“…Specifically, published studies illustrate the GARS test’s use to identify specific neurotransmitter pathways where the risk for a signal breakdown in the BRC occurs and uses semi-customized precision KB220Z variants, matched the individuals’ GARS test result to treat the dysfunction. This synergistic ‘systems biology’ approach provides an increased efficacy in treating RDS [ 28 , 31 , 32 , 33 ]. Dopamine is a major neurotransmitter involved in substance and behavioral addictions; however, there is controversy about managing dopamine clinically to prevent and treat many addictive disorders.…”

Reconceptualizing Addiction: Integrating the Sciences of Addiction & Reward Deficiency Syndrome, Part 1

“…Genetic Addiction Risk Score (GARS) screening for addiction and reward deficiency syndrome, is available to the public, from Geneus Health [32,33]. Genetic testing is an excellent tool for individualized treatment design and as prevention for the next generation [34,35].…”

“…ADHD is well known expression of RDS and is often a co-occurring mental disorder with Substance Use Disorder. Many patients attempt to mitigate ADHD symptomology through self-medication with cocaine or other stimulants [32,33].…”

Offering a Putative “Dopamine Homeostatic” Solution to Overcome the Perils of Reward Deficiency Syndrome (RDS) Epidemic: Emergence of “Precision Behavioral Management (PBM)”

“…The approved drug acamprosate, a NMDA receptor antagonist and a positive allosteric modulator of GABAA receptors also disturbs dopaminergic signaling. Understanding the above premise and the further emerging acceptance of the umbrella term Reward Deficiency Syndrome (RDS) first coined by Blum in 1995, facilitates the common mechanism hypothesis for drug and non-addictive behaviors [7]. Understanding the common neuro modulating aspects of neurotransmission and its disruption via chronic exposure of drugs and behavioral addictions, requires a known Osteopathic approach involving "dopamine homeostasis [8].…”