Limits...
Genetic Addiction Risk Score (GARS): molecular neurogenetic evidence for predisposition to Reward Deficiency Syndrome (RDS).

Blum K, Oscar-Berman M, Demetrovics Z, Barh D, Gold MS - Mol. Neurobiol. (2014)

Bottom Line: In 1996, we coined "Reward Deficiency Syndrome" (RDS), to portray behaviors found to have gene-based association with hypodopaminergic function.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 primary driver of RDS is a hypodopaminergic trait (genes) as well as epigenetic states (methylation and deacetylation on chromatin structure).

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry & McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, USA, drd2gene@gmail.com.

ABSTRACT
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.

Show MeSH

Related in: MedlinePlus

Brain Reward Cascade [14, 15]. In this cascade, stimulation of the serotonergic system in the hypothalamus leads to the stimulation of delta/mu receptors by serotonin to cause a release of enkephalin. Activation of the enkephalinergic system induces an inhibition of GABA transmission at the substania nigra by enkephalin stimulation of mu receptors at GABA neurons. This inhibitory effect allows for the fine-tuning of GABA activity. This provides the normal release of dopamine at the projected area of the NAc [14, 15]
© Copyright Policy - OpenAccess
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4225054&req=5

Fig1: Brain Reward Cascade [14, 15]. In this cascade, stimulation of the serotonergic system in the hypothalamus leads to the stimulation of delta/mu receptors by serotonin to cause a release of enkephalin. Activation of the enkephalinergic system induces an inhibition of GABA transmission at the substania nigra by enkephalin stimulation of mu receptors at GABA neurons. This inhibitory effect allows for the fine-tuning of GABA activity. This provides the normal release of dopamine at the projected area of the NAc [14, 15]

Mentions: Neurotransmitter interactions regulate brain reward circuitry that result in the release of dopamine (DA) in the major loci for feelings of well-being and reward, the nucleus accumbens (NAc) part of the mesolimbic system of the brain. The inter-relationship of at least four important neurochemical pathways: serotonergic, endorphinergic, GABAergic, and dopaminergic constitute the “brain reward cascade” (see Fig. 1) a natural sequence of events that produce feelings of well being. These activities including: the synthesis, vesicle storage, metabolism, release, and function of neurochemicals [1] are regulated by genes, and their expression, in terms of messenger RNA-directed proteins. Thus, genetic testing is a potential window that can be used to identify the specific neurochemistry of individuals and formulate the best treatment options for them [1–13].Fig. 1


Genetic Addiction Risk Score (GARS): molecular neurogenetic evidence for predisposition to Reward Deficiency Syndrome (RDS).

Blum K, Oscar-Berman M, Demetrovics Z, Barh D, Gold MS - Mol. Neurobiol. (2014)

Brain Reward Cascade [14, 15]. In this cascade, stimulation of the serotonergic system in the hypothalamus leads to the stimulation of delta/mu receptors by serotonin to cause a release of enkephalin. Activation of the enkephalinergic system induces an inhibition of GABA transmission at the substania nigra by enkephalin stimulation of mu receptors at GABA neurons. This inhibitory effect allows for the fine-tuning of GABA activity. This provides the normal release of dopamine at the projected area of the NAc [14, 15]
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4225054&req=5

Fig1: Brain Reward Cascade [14, 15]. In this cascade, stimulation of the serotonergic system in the hypothalamus leads to the stimulation of delta/mu receptors by serotonin to cause a release of enkephalin. Activation of the enkephalinergic system induces an inhibition of GABA transmission at the substania nigra by enkephalin stimulation of mu receptors at GABA neurons. This inhibitory effect allows for the fine-tuning of GABA activity. This provides the normal release of dopamine at the projected area of the NAc [14, 15]
Mentions: Neurotransmitter interactions regulate brain reward circuitry that result in the release of dopamine (DA) in the major loci for feelings of well-being and reward, the nucleus accumbens (NAc) part of the mesolimbic system of the brain. The inter-relationship of at least four important neurochemical pathways: serotonergic, endorphinergic, GABAergic, and dopaminergic constitute the “brain reward cascade” (see Fig. 1) a natural sequence of events that produce feelings of well being. These activities including: the synthesis, vesicle storage, metabolism, release, and function of neurochemicals [1] are regulated by genes, and their expression, in terms of messenger RNA-directed proteins. Thus, genetic testing is a potential window that can be used to identify the specific neurochemistry of individuals and formulate the best treatment options for them [1–13].Fig. 1

Bottom Line: In 1996, we coined "Reward Deficiency Syndrome" (RDS), to portray behaviors found to have gene-based association with hypodopaminergic function.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 primary driver of RDS is a hypodopaminergic trait (genes) as well as epigenetic states (methylation and deacetylation on chromatin structure).

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry & McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, USA, drd2gene@gmail.com.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus