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

2020 ◽  
Vol 9 (1) ◽  
pp. 7-21 ◽  
Author(s):  
Kenneth Blum ◽  
David Baron ◽  
Lisa Lott ◽  
Jessica V. Ponce ◽  
David Siwicki ◽  
...  
Keyword(s):  
Risk Score ◽  
Association Studies ◽  
Deficiency Syndrome ◽  
Case Control ◽  
Control Group ◽  
Addictive Behaviors ◽  
Internet Gaming ◽  
Risk Alleles ◽  
Addiction Risk ◽  
Reward Deficiency Syndrome

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.

scholarly journals Genetic Addiction Risk Score (GARS): Molecular Neurogenetic Evidence for Predisposition to Reward Deficiency Syndrome (RDS)

2014 ◽  
Vol 50 (3) ◽  
pp. 765-796 ◽  
Author(s):  
Kenneth Blum ◽  
Marlene Oscar-Berman ◽  
Zsolt Demetrovics ◽  
Debmalya Barh ◽  
Mark S. Gold
Keyword(s):  
Risk Score ◽  
Deficiency Syndrome ◽  
Addiction Risk ◽  
Reward Deficiency Syndrome

Genetic addiction risk score analysis: hypodopaminergic polymorphic risk alleles in polydrug addicted males and meso-limbic dopaminergic agonistic activation by neuroadaptagen amino-acid therapy

2011 ◽  
Vol 26 (S2) ◽  
pp. 803-803
Author(s):  
K. Blum ◽  
E. Stice ◽  
Y. Liu ◽  
J. Giordano ◽  
S. Morse ◽  
...  
Keyword(s):  
Amino Acid ◽  
Risk Score ◽  
D2 Receptor ◽  
Controlled Study ◽  
Double Blind ◽  
Heroin Addicts ◽  
Acid Therapy ◽  
Risk Alleles ◽  
Addiction Risk ◽  
The Impact

IntroductionThere is a need to classify patients at genetic risk for drug seeking behavior prior to or upon entry to chemical dependency programs.MethodsThe prevalence of seven risk alleles (DRD2 = A1; SLC6A3 (DAT) = 10R; DRD4 = 3R or 7R; 5HTTLPR = L or LA; MAO = 3R; COMT = G) and corresponding severity risk score (Low (LS) = 1–36%, moderate (MS) = 37–50%, and high (HS) = 51–100%) were calculated. Group 1 consisted of 16 Caucasian male psycho-stimulant addicts, and Group 2 consisted of 10 Chinese male heroin addicts (9 were genotyped). qEEG and fMRI visualized the impact of Neuroadaptagen Amino-Acid Therapy complex on mesolimbic system activation.Results[Findings by Group]74% of the combined groups had a moderate to high genetic addiction risk score (GARS). One acute dose of KB220-IV variant in heroin addicts having brain abnormalities was found to normalize qEEG. Additionally, a randomized double-blind placebo controlled study involving oral KB220-Z variant established qEEG normalization of reward circuitry in abstinent psycho-stimulant abusers (P < 0.03).ConclusionsWe cautiously suggest that long-term activation of dopaminergic receptors will lead to D2 receptor proliferation and enhanced “dopamine sensitivity,” thus reducing aberrant craving behavior especially in carriers of the DRD2 A1 allele. Although supported by 20 clinical trials, KB220-Z awaits PET scanning to determine its chronic effects on D2 receptor numbers.

scholarly journals Molecular Genetic Testing in Pain and Addiction: Facts, Fiction and Clinical Utility

2015 ◽  
Vol 2 (1) ◽  
Author(s):  
Kenneth Blum ◽  
Mary Hauser ◽  
James Fratantonio ◽  
Rajendra D. Badgaiyan
Keyword(s):  
Genetic Testing ◽  
Clinical Utility ◽  
Molecular Genetic ◽  
Deficiency Syndrome ◽  
Pain Tolerance ◽  
Addictive Behaviors ◽  
Molecular Genetic Testing ◽  
Addiction Risk ◽  
Brain Reward ◽  
The Brain

AbstractThe Brain Reward Cascade (BRC) is an interaction of neurotransmitters and their respective genes to control the amount of dopamine released within the brain. Any variations within this pathway, whether genetic or environmental (epigenetic), may result in addictive behaviors as well as altered pain tolerance. While there are many studies claiming a genetic association with addiction and other behavioral infractions, defined as Reward Deficiency Syndrome (RDS), not all are scientifically accurate and in some case just wrong. Albeit our bias, we discuss herein the facts and fictions behind molecular genetic testing in RDS (including pain and addiction) and the significance behind the development of the Genetic Addiction Risk Score (GARSPREDX™), the first test to accurately predict one’s genetic risk for RDS.

scholarly journals Neuropharmacological and Neurogenetic Correlates of Opioid Use Disorder (OUD) As a Function of Ethnicity: Relevance to Precision Addiction Medicine

2020 ◽  
Vol 18 (7) ◽  
pp. 578-595 ◽  
Author(s):  
Tomilowo Abijo ◽  
Kenneth Blum ◽  
Marjorie C. Gondré-Lewis
Keyword(s):  
African American ◽  
Association Studies ◽  
Deficiency Syndrome ◽  
Opioid Use Disorder ◽  
Drug Misuse ◽  
Opioid Overdose ◽  
Genome Wide Association Studies ◽  
Addictive Behaviors ◽  
Opioid Use ◽  
Addiction Medicine

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.

scholarly journals P825 The impact of a SNP-dose–response effect on course of inflammatory bowel disease: a numerical analysis of SNP distribution within the Swiss IBD Cohort Study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S640-S641
Author(s):  
L Biedermann ◽  
L Denoth ◽  
J B Rossel ◽  
M Butter ◽  
S Vavricka ◽  
...  
Keyword(s):  
Cohort Study ◽  
Risk Score ◽  
Association Studies ◽  
Large Population ◽  
Median Number ◽  
Clinical Disease ◽  
Genome Wide Association Studies ◽  
Risk Alleles ◽  
Individual Snps ◽  
The Impact

Abstract Background Several large genome wide association studies have identified an increasing number of IBD risk loci with currently more than 240 established loci and generated robust data on disease association. However, knowledge remains limited on distinctive associations to specific clinical characteristics. The Swiss IBD Cohort Study (SIBDCS) represents a large prospective cohort study with clinically and phenotypically sound data collection since 2006 including genotyping. In this study, we aimed to determine individual associations of known risk loci with clinical features of patients in the SIBDCS, as well as their combined effect on clinical outcomes. Methods Based on 158 analysed SNPs, we investigated the numerical distribution of risk alleles and determined an individual SNP risk score (defined as percentage of risk alleles; i.e. number of risk alleles divided by twice the number of given SNPs multiplied with 100). We then performed linear regression modelling to investigate, whether relevant clinical disease characteristics associate with this SNP risk score. Further, for each given clinical outcome, a model was run with all SNPs as potential predictors, and the number of significant associations per SNP counted. Results In a total of 2304 genotyped patients, we observed a median number of risk alleles of 167, 168 and 167 for IBD overall, CD and UC/IC, respectively with a narrow inter quartile range [11 (q25 = 162, q75 = 173) for IBD and CD; 12 (q25 = 161, q75 = 173) for UC/IC]. A higher SNP risk score was significantly associated with any complications (defined as a composite of any or more of colorectal cancer, colon dysplasia, intestinal lymphoma, osteopenia/-porosis, anaemia, deep venous thrombosis, pulmonary embolism, nephro- or cholelithiasis, malabsorption syndrome, massive haemorrhage, perforation/peritonitis, pouchitis), stenosis in CD patients; pancolitis, conversion to CD, female sex in UC patients; higher clinical disease activity in both CD & UC. Regarding individual SNPs, we identified substantial differences in terms of the frequency of associations to disease-related outcomes with up to 11 for rs4899554 in CD and 7 for rs9557195 in UC, respectively. Conclusion In our large population of IBD patients there is high per patient frequency of hetero- and homozygous SNP risk alleles. The association of higher SNP risk score with several disease-related outcomes indicates a potential interplay of per patient given SNP risk alleles.

scholarly journals Introducing Precision Addiction Management of Reward Deficiency Syndrome, the Construct That Underpins All Addictive Behaviors

2018 ◽  
Vol 9 ◽  
Author(s):  
Kenneth Blum ◽  
Marjorie C. Gondré-Lewis ◽  
David Baron ◽  
Panayotis K. Thanos ◽  
Eric R. Braverman ◽  
...  
Keyword(s):  
Deficiency Syndrome ◽  
Addictive Behaviors ◽  
Reward Deficiency Syndrome

scholarly journals Exploration of Epigenetic State Hyperdopaminergia (Surfeit) and Genetic Trait Hypodopaminergia (Deficit) During Adolescent Brain Development

2021 ◽  
Vol 10 ◽  
Author(s):  
Kenneth Blum ◽  
Abdalla Bowirrat ◽  
Marjorie C. Gondre Lewis ◽  
Thomas A. Simpatico ◽  
Mauro Ceccanti ◽  
...  
Keyword(s):  
Risky Behaviors ◽  
Deficiency Syndrome ◽  
Genetic Trait ◽  
Future Studies ◽  
Risk Alleles ◽  
Epigenetic Events ◽  
Addiction Risk ◽  
The Face ◽  
Addictive Drug ◽  
Adolescent Brain Development

Background: Understanding the risk for all addictive drug and non-drug behaviors, especially, in the unmyelinated Prefrontal Cortex (PFC) of adolescents, is important and complex. Many animal and human studies show the epigenetic impact on the developing brain in adolescents, compared to adults. Some reveal an underlying hyperdopaminergia that seems to set our youth up for risky behaviors by inducing high quanta pre-synaptic dopamine release at reward site neurons. In addition, altered reward gene expression in adolescents caused epigenetically by social defeat, like bullying, can continue into adulthood. In contrast, there is also evidence that epigenetic events can elicit adolescent hypodopaminergia. This complexity suggests that neuroscience cannot make a definitive claim that all adolescents carry a hyperdopaminergia trait. Objective: The primary issue involves the question of whether there exists a mixed hypo or hyper –dopaminergia in this population. Method: Genetic Addiction Risk Score (GARS®) testing of 24 Caucasians, ages 12-19 derived from families with RDS. Results: We have found that adolescents from this cohort, derived from RDS parents, displays a high risk for any addictive behavior (a hypodopaminergia), especially, drug-seeking (95%) and alcohol-seeking (64 %). Conclusion: The adolescents in our study, although more work is required, show a hypodopaminergic trait, derived from a family with Reward Deficiency Syndrome (RDS). Certainly in future studies we will analyze GARS in non-RDS Caucasians between the ages of 12-19. The suggestion is first to identify risk alleles with the GARS test and, then, use well-researched precision, pro-dopamine neutraceutical regulation. This “two-hit” approach might prevent tragic fatalities among adolescents, in the face of the American opioid/psychostimulant, epidemic.

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