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North Kingstown, RI, United States

Blum K.,Florida College | Blum K.,National Institute for Holist Addiction Studies | Blum K.,University of Vermont | Blum K.,Dominion Diagnostics | And 7 more authors.
Molecular Neurobiology | Year: 2014

We have published extensively on the neurogenetics 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 Addiction 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 epigenetic states (methylation and deacetylation on chromatin structure). We now have entered a new era in addiction medicine 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 diagnosis and that requires further intensive investigation. © 2014, The Author(s). Source

Gaedigk A.,Section of Developmental Pharmacology and Experimental Therapeutics | Fuhr U.,University of Cologne | Johnson C.,Dominion Diagnostics | Berard L.A.,University of Montreal | And 2 more authors.
Pharmacogenomics | Year: 2010

Aims: Allelic variants of cytochrome P450 CYP2D6 (CYP2D6), such as gene deletion, duplication, multiplication and conversion, contribute to the wide range of CYP2D6 activity. Novel gene arrangements were discovered and characterized. Materials & methods: DNA from 32 Caucasian and 59 African-American duplication-positive subjects were analyzed by long-range PCR and genotyping to detect CYP2D7-2D6 hybrid tandem alleles. Novel allelic variants were sequenced and a strategy for the detection and analysis of hybrid genes was refined. Results: CYP2D7-2D6 hybrid tandem alleles were identified in one African-American and four Caucasian subjects. Three novel hybrid genes were found on CYP2D6*1 and CYP2D6*2 duplication backgrounds and designated CYP2D6*76, *77 and *78. CYP2D7to 2D6 conversion occurred in introns 1 and 4, and exon 9. All carried a T-insertion in exon 1 abolishing activity. In Caucasians, four out of 33 (12%) of the duplication-positive alleles were hybrid tandems, three CYP2D6*77 + *2 and one CYP2D6*78 + *2. By contrast, in African-Americans only one of 60 duplication-positive alleles was identified as a hybrid tandem. This allele was designated CYP2D6*76 + *1. Conclusion: Hybrid tandem alleles occur infrequently (<0.25%) in Caucasians, but may explain why not every subject with a CYP2D6 duplication presents with an ultrarapid metabolizer phenotype. © 2010 Future Medicine Ltd. Source

Gyollai A.,Eotvos Lorand University | Griffiths M.D.,Nottingham Trent University | Barta C.,Semmelweis University | Vereczkei A.,Semmelweis University | And 9 more authors.
Current Pharmaceutical Design | Year: 2014

Background and aims: The primary aim of the present review was to summarize the findings of genetic studies conducted on problem and pathological gambling. Method: Literature searches were conducted using PubMed, Medline and the HuGE Navigator databases using the keywords 'gambling' and 'genetic*'. Results: The literature searches identified 21 empirical studies that had analyzed data from eight independent samples. Empirical research utilizing twin data accounted for eight of the studies, while gene association data were presented in 13 studies (including one genome wide-association study [GWAS] study). Twin studies emphasized the significant role of genetic and individual environmental factors in problem and pathological gambling. Gene association studies primarily reported the involvement of the dopaminergic and serotonergic systems. Discussion: Despite the relatively low number of genetic studies, the data clearly indicated the genetic vulnerability of problem and pathological gambling. Studies to date have mainly investigated and verified the role of factors reported to be important in other types of addiction, and it is suggested that pathological gambling should be included as a subtype of 'Reward Deficiency Syndrome' (RDS). It is concluded that future research should attempt to identify possible gambling specific susceptibility factors. © 2014 Bentham Science Publishers. Source

Blum K.,University of Florida | Blum K.,Malibu Beach Recovery Center | Blum K.,University of Vermont | Blum K.,Dominion Diagnostics | And 7 more authors.
Journal of Behavioral Addictions | Year: 2014

Background: Following the first association between the dopamine D2 receptor gene polymorphism and severe alcoholism, there has been an explosion of research reports in the psychiatric and behavioral addiction literature and neurogenetics. With this increased knowledge, the field has been rife with controversy. Moreover, with the advent of Whole Genome-Wide Studies (GWAS) and Whole Exome Sequencing (WES), along with Functional Genome Convergence, the multiple-candidate gene approach still has merit and is considered by many as the most prudent approach. However, it is the combination of these two approaches that will ultimately define real, genetic allelic relationships, in terms of both risk and etiology. Since 1996, our laboratory has coined the umbrella term Reward Deficiency Syndrome (RDS) to explain the common neurochemical and genetic mechanisms involved with both substance and non-substance, addictive behaviors. Methods: This is a selective review of peer-reviewed papers primary listed in Pubmed and Medline. Results: A review of the available evidence indicates the importance of dopaminergic pathways and resting-state, functional connectivity of brain reward circuits. Discussion: Importantly, the proposal is that the real phenotype is RDS and impairments in the brain's reward cascade, either genetically or environmentally (epigenetically) induced, influence both substance and non-substance, addictive behaviors. Understanding shared common mechanisms will ultimately lead to better diagnosis, treatment and prevention of relapse. While, at this juncture, we cannot as yet state that we have "hatched the behavioral addiction egg", we are beginning to ask the correct questions and through an intense global effort will hopefully find a way of "redeeming joy" and permitting homo sapiens live a life, free of addiction and pain. © 2014 Akadémiai Kiadó. Source

Smith D.E.,856 Stanyan Street | Smith D.E.,Center Point | Smith D.E.,Dominion Diagnostics
Journal of Psychoactive Drugs | Year: 2012

Prescription drug abuse is increasingly recognized as the United States' fastest growing drug problem, rising dramatically since the early 2000s, and particularly affecting adolescents and young adults. Federal officials are urging legislation to educate physicians about the use and effects of potent narcotics, which are increasingly being prescribed for chronic pain. ASAM developed strategies in the 1980s to identify the small minority of misprescribers and focused educational and retraining efforts on these individuals. As health reform and more prevalent pain management put more primary care physicians in a gatekeeper role to manage the medical care of addicts, these clinicians must become aware of the abuse potential of the powerful narcotics they prescribe. Increased reference to state-maintained controlled medication databases can also reduce misprescribing. © Taylor & Francis Group, LLC. Source

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