Genetic Addiction Risk Score (GARS): Testing For Polygenetic Predisposition and Risk to Reward Deficiency Syndrome (RDS)

Blum, Kenneth; Fornari, Frank; Downs, Bernard W.; Waite, Roger L.; Giordano, John; Smolen, Andrew; Lui, Yijun; Tain, Jai; Majmundar, Neil; Braverman, Eric R.

doi:10.5772/20067

Cited by 12 publications

(17 citation statements)

References 78 publications

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“…The same pattern of DA-mediated signaling reduction is observed in RDS associated with drug and food addiction 119 and obesity. 138 The marked frequency of ADHD suggests that while genetic mechanisms are likely contributory, other factors are involved in the etiology, including chronic effects of excessive sugar intake, which may lead to alterations in mesolimbic dopamine signaling and could contribute to the symptoms associated with ADHD.…”

Section: Resultssupporting

confidence: 55%

“…A range of other DA, opioid, cannabinoid, norepinephrine, inflammatory pro genes, and related genes have since been added to the list. Attention deficit/hyperactivity disorder is inherited and polygenetic, and, like other behavioral disorders, each gene is responsible for a small percentage of the variance (Table 1 119 ).…”

Section: Proposed Adhd-risk Gene Mapmentioning

confidence: 99%

“…21,34,107 It is reasonable to theorize, awaiting further double-blind comparisons to standard stimulant medication(s), that the use of natural dopaminergic agonist therapy could be beneficial, especially when coupled with early diagnosis, using both candidate gene polymorphisms and psychometric testing. 130–152 Because of the potential for misdiagnosis of ADHD in children when employing only the clinically standardized tools of ADHD diagnosis (eg, interviews), we propose serious consideration be given to genotyping (Table 1 119 ).…”

Section: Future Perspective: Extending Genotyping For Predisposing Rimentioning

confidence: 99%

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Low Dopamine Function in Attention Deficit/Hyperactivity Disorder: Should Genotyping Signify Early Diagnosis in Children?

Gold¹,

Blum²,

Oscar‐Berman³

et al. 2014

Postgraduate Medicine

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Attention deficit/hyperactivity disorder (ADHD) is present in 8% to 12% of children, and 4% of adults worldwide. Children with ADHD can have learning impairments, poor self-esteem, social dysfunction, and an increased risk of substance abuse, including cigarette smoking. Overall, the rate of treatment with medication for patients with ADHD has been increasing since 2008, with > 2 million children now being treated with stimulants. The rise of adolescent prescription ADHD medication abuse has occurred along with a concomitant increase of stimulant medication availability. Of adults presenting with a substance use disorder (SUD), 20% to 30% have concurrent ADHD, and 20% to 40% of adults with ADHD have a history of SUD. Following a brief review of the etiology of ADHD, its diagnosis and treatment, we focus on the benefits of early and appropriate testing for a predisposition to ADHD. We suggest that by genotyping patients for a number of known, associated dopaminergic polymorphisms, especially at an early age, misdiagnoses and/or over-diagnosis can be reduced. Ethical and legal issues of early genotyping are considered. As many as 30% of individuals with ADHD are estimated to either have secondary side-effects or are not responsive to stimulant medication. We also consider the benefits of non-stimulant medication and alternative treatment modalities, which include diet, herbal medications, iron supplementation, and neurofeedback. With the goals of improving treatment of patients with ADHD and SUD prevention, we encourage further work in both genetic diagnosis and novel treatment approaches.

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Section: Resultssupporting

confidence: 55%

Section: Proposed Adhd-risk Gene Mapmentioning

confidence: 99%

Section: Future Perspective: Extending Genotyping For Predisposing Rimentioning

confidence: 99%

See 1 more Smart Citation

Low Dopamine Function in Attention Deficit/Hyperactivity Disorder: Should Genotyping Signify Early Diagnosis in Children?

Gold¹,

Blum²,

Oscar‐Berman³

et al. 2014

Postgraduate Medicine

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“…However testing for polymorphisms of genes that have already been found to associate with PTSD will provide a powerful tool to diagnose suspected veterans after deployment. Results of our research suggest the following genes should be tested: serotoninergic, dopaminergic (DRD2, DAT, DBH), glucocorticoid, GABAergic (GABRB), apolipoprotein systems (APOE2), brain-derived neurotrophic factor, Monamine B, CNR1, Myo6, CRF-1 and CRF-2 receptors, and neuropeptide Y (NPY) [15]. …”

Section: Testing Genetic Antecedentsmentioning

confidence: 99%

Diagnosis and Healing In Veterans Suspected of Suffering from Post- Traumatic Stress Disorder (PTSD) Using Reward Gene Testing and Reward Circuitry Natural Dopaminergic Activation

Blum¹

2012

J Genet Syndr Gene Ther

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There is a need for understanding and treating post-traumatic stress disorder (PTSD), in soldiers returning to the United States of America after combat. Likewise, it would be beneficial to finding a way to reduce violence committed by soldiers, here and abroad, who are suspected of having post-traumatic stress disorder (PTSD). We hypothesize that even before combat, soldiers with a childhood background of violence (or with a familial susceptibility risk) would benefit from being genotyped for high-risk alleles. Such a process could help to identify candidates who would be less suited for combat than those without high-risk alleles. Of secondary importance is finding safe methods to treat individuals already exposed to combat and known to have PTSD. Since hypodopaminergic function in the brain’s reward circuitry due to gene polymorphisms is known to increase substance use disorder in individuals with PTSD, it might be parsimonious to administer dopaminergic agonists to affect gene expression (mRNA) to overcome this deficiency.

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“…Messenger RNA expression causes proliferation of D2 receptors induced by negative feedback mechanisms, in the mesolimbic system signaled by gentle chronic D2 receptor stimulation [31,32]. This neuro-molecular finding serves as the basis for naturally inducing DA release, to produce the same induction of D2-directed mRNA and thus proliferation of D2 receptors in humans and a resultant attenuation of craving behavior [34,35]. This has been proven with work showing a form of gene therapy [36].…”

Section: Introductionmentioning

confidence: 99%

Neurogenetic Impairments of Brain Reward Circuitry Links to Reward Deficiency Syndrome (RDS): Potential Nutrigenomic Induced Dopaminergic Activation

Blum

Giordano

et al. 2012

J Genet Syndr Gene Ther

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Work from our laboratory in both in-patient and outpatient facilities utilizing the Comprehensive Analysis of Reported Drugs (CARD)™ found a significant lack of compliance to prescribed treatment medications and a lack of abstinence from drugs of abuse during active recovery. This unpublished, ongoing research provides an impetus to develop accurate genetic diagnosis and holistic approaches that will safely activate brain reward circuitry in the mesolimbic dopamine system. This editorial focuses on the neurogenetics of brain reward systems with particular reference to genes related to dopaminergic function. The terminology “Reward Deficiency Syndrome” (RDS), used to describe behaviors found to have an association with gene-based hypodopaminergic function, is a useful concept to help expand our understanding of Substance Use Disorder (SUD), process addictions, and other obsessive, compulsive and impulsive behaviors. This editorial covers the neurological basis of pleasure and the role of natural and unnatural reward in motivating and reinforcing behaviors. Additionally, it briefly describes the concept of natural dopamine D2 receptor agonist therapy coupled with genetic testing of a panel of reward genes, the Genetic Addiction Risk Score (GARS). It serves as a spring-board for this combination of novel approaches to the prevention and treatment of RDS that was developed from fundamental genomic research. We encourage further required studies.

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Genetic Addiction Risk Score (GARS): Testing For Polygenetic Predisposition and Risk to Reward Deficiency Syndrome (RDS)

Cited by 12 publications

References 78 publications

Low Dopamine Function in Attention Deficit/Hyperactivity Disorder: Should Genotyping Signify Early Diagnosis in Children?

Low Dopamine Function in Attention Deficit/Hyperactivity Disorder: Should Genotyping Signify Early Diagnosis in Children?

Diagnosis and Healing In Veterans Suspected of Suffering from Post- Traumatic Stress Disorder (PTSD) Using Reward Gene Testing and Reward Circuitry Natural Dopaminergic Activation

Neurogenetic Impairments of Brain Reward Circuitry Links to Reward Deficiency Syndrome (RDS): Potential Nutrigenomic Induced Dopaminergic Activation

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