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

We have published extensively on the neuro- genetics of brain reward systems with reference to the genes related to dopaminergic function in particular. In 1996, we coined “ Reward Deficiency Syndrome ” (RDS), to portray behaviors found to have gene-based association with hypodopaminergic function. RDS as a useful concept has been embraced in many subsequent studies, to increase our understanding of Substance Use Disorder (SUD), addictions, and other obsessive, compulsive, and impulsive behaviors. Interestingly, albeit others, in one published study, we were able to describe lifetime RDS behaviors in a recovering addict (17 years sober) blindly by assessing resultant Genetic Addic- tion Risk Score (GARS ™ ) data only. We hypothesize that genetic testing at an early age may be an effective preventive strategy to reduce or eliminate pathological substance and behavioral seeking activity. Here, we consider a select number of genes, their polymorphisms, and associated risks for RDS whereby, utilizing GWAS, there is evidence for convergence to reward candidate genes. The evidence presented serves as a plausible brain-print providing relevant genetic information that will reinforce targeted therapies, to improve recovery and prevent relapse on an individualized basis. The primary driver of RDS is a hypodopaminergic trait (genes) as well as epige- netic states (methylation and deacetylation on chromatin structure). We now have entered a new era in addiction med- icine that embraces the neuroscience of addiction and RDS as a pathological condition in brain reward circuitry that calls for appropriate evidence-based therapy and early genetic diagno- sis and that requires further intensive investigation

Hypothesizing repetitive paraphilia behavior of a medication refractive Tourette's syndrome patient having rapid clinical attenuation with KB220Z-nutrigenomic amino-acid therapy (NAAT)

Background and aims: Many patients presenting multiple behaviors including drug and food abuse as well as other pathological repetitive unwanted activities such as gambling, self-mutilation and paraphilias may not be appropriately diagnosed. Here we present a case of a male presenting many of these seemingly diverse behaviors and finally diagnosed with reward deficiency syndrome (RDS) by his attending physician. Methods: The use of the dopamine agonist, ropinirole after two weeks showed improvement in terms of sexual behavior but tolerance set in and was discontinued especially when an infraction occurred with the patient's insurance. In this article, we carefully explore the potential of ropinirole to downregulate dopamine receptors causing adenylate cyclase receptor supersensitivity and tolerance a feature of neurotransmitter cross-talk. Based on previous scientific evidence showing KB220Znutrigenomic amino-acid therapy (NAAT) to rapidly (post one-hour) activate dopaminergic pathways in both the pre-frontal cortex cingulate gyrus (relapse loci) and ventral tegmental area-caudate-accumbens-putamen (craving and emotion loci) the patient was prescribed NAAT. Results and discussion: Within one week of utilization the repetitive paraphilia was eliminated. There were also a number of other positive effects such as enhanced focus that persisted even after the patient stopped using KB220Z suggesting neuroplasticity (e.g. altruistic thoughts). However, these observed profound benefits require more in-depth study, especially in a large cohort against a placebo. While this report focused on a rapid response rather than long-term benefits previously associated with NAAT, it is somewhat encouraging and longer term required follow-up and larger placebo controlled studies are warranted before any definitive conclusions could be gleaned from this case report

Correlation of the Taq1 dopamine D2 receptor gene and percent body fat in obese and screened control subjects: a preliminary report. Food Funct. 3, 40–48. doi: 10.1039/c1fo10089k

While there is a considerable body of literature correlating the role of dopaminergic genes and obesity, body mass index, body type, overeating, carbohydrate binging, energy expenditure and low dopamine D2 receptor (D2R) receptor density, there is a paucity of research concerning the dopamine D2 receptor gene (DRD2) variants and percent body fat. We report here the potential association of DRD2 genotypes and the percent fat phenotype. In this study we genotyped 122 obese/overweight (O/ OW) Caucasian subjects and 30 non-obese Caucasian controls, screened to exclude substance abuse. The subjects were assessed for weight, body mass index (BMI; kg m À2 ) and percent body fat using dual energy X-ray absorptiometry (DEXA). The sample was separated into two independent groups; those with the Taq1 A1 allele (A1/A1 or A1/A2) and those without the A1 allele (A2/A2). The controls had a normal range of body fat (25-31% for females and 18-25% for males). The O/OW subjects had a percent body fat value of over 32% for females and over 25% for males. For the O/OW subjects, the mean BMI was 29.3 AE 6.25 kg m À2 , mean body fat was 42.1 AE 7.5% and mean weight was 82.7 AE 21.7 kg. The DRD2 Taq1 A1 allele was present in 67% of the O/OW subjects compared to 3.3% of super controls (A group), 33.3% of screened (for drug abuse and obesity) controls (B group) and unscreened literature controls 29.4% (P # 0.001). Comparing all cases with more than 34% body fat, utilizing logistic regression analysis, the DRD2 A1 allele accounts for 45.9% of the variance, which is statistically significant (c 2 ¼ 43.47, degrees of freedom (df) ¼ 1, P < 0.0001). These results are consistent with a role for the DRD2 gene in obesity, as measured by percent body fat as well as by weight and BMI