Dopamine Genetics and Function in Food and Substance Abuse

Behavioural Pharmacology, 2009

Dopamine plays a key role in reward behavior, yet the association of drug dependence as a chronic, relapsing disorder with the genes encoding the various dopaminergic receptor subtypes remains diYcult to delineate. In the context of subsequent genome-wide association (GWAS) research and post-GWAS investigations, we summarize the novel data that link genes encoding molecules involved in the dopaminergic system (dopamine receptors, transporter and enzymes in charge of its metabolism) to drug addiction. Recent reports indicate that the heritability of drug addiction should be high enough to allow a signiWcant role for a spe-ciWc set of genes, and the available genetic studies, which might not be already conclusive because of the heterogeneity of designs, methods and recruited samples, should support the idea of a signiWcant role of at least one gene related to dopaminergic system. Evolutionary changes in primates and non-primate animals of genes coding for molecules involved in dopaminergic system highlight why addictive disorders are mainly limited to humans. Restricting the analyses to more speciWc intermediate phenotypes (or endophenotypes) such as attention allocation, stress reactivity, novelty seeking, behavioral disinhibition and impulsivity, instead of the broad addictive disorder concept can be instrumental to identify novel genes associated with these traits in the context of genome-wide studies.

2013

Journal of Studies on Alcohol and Drugs, 2016

The article clearly highlights the importance of genetics and the utility of animal models in the study of human addiction. However, there is a tendency to primarily look for genetic susceptibility factors as having effects in the brain, particularly in the cortex and reward areas of the nucleus accumbens. As such, the biological modelling of how gene studies in animals link to human addiction has been intimately linked to the complexity and controversies as to the nature of brain functioning.

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.

Gene Therapy Applications, 2011

Experimental and Therapeutic Medicine, 2021

The hypothesis issued by modern medicine states that many diseases known to humans are genetically determined, influenced or not by environmental factors, which is applicable to most psychiatric disorders as well. This article focuses on two pending questions regarding addiction: Why do some individuals become addicted while others do not? along with Is it a learned behavior or is it genetically predefined? Recent data suggest that addiction is more than repeated exposure, it is the synchronicity between intrinsic factors (genotype, sex, age, preexisting addictive disorder, or other mental illness), extrinsic factors (childhood, level of education, socioeconomic status, social support, entourage, drug availability) and the nature of the addictive agent (pharmacokinetics, path of administration, psychoactive properties). The dopamine-mesolimbic motivation-reward-reinforcement cycle remains the most coherent physiological theory in addiction. While the common property of addictive substances is that they are dopamine-agonists, each class has individual mechanisms, pharmacokinetics and psychoactive potentials.

Journal of genetic syndromes & gene therapy, 2012

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...

2013

The understanding that genes play a significant role in reward dependence and associated behavioral and drug addictions is highlighted in the emergence of Reward Deficiency Syndrome (RDS). Here we show two case reports that unequivocally indicate the definite commonality between food and drug addiction. These human cases not atypically raise the question as to how to treat these two seemingly diverse addictions. We suggest that research directed in an attempt to induce natural activation of dopaminergic reward circuitry as a form of common therapy may indeed be parsimonious.

Journal of Reward Deficiency Syndrome, 2015

Conflict of Interest No conflict of Interest. Author Contribution KB wrote the original manuscript. JF and GA provided important references and clinical input to the original draft. MF and RDB provided information and contribution regarding neuroimaging. TS, ZD and MSG provided clinical interpretation of related matter and added important information to the original draft. All authors approved the final manuscript. GA and JF provided the graphics.

Physiology & Behavior, 2013

Food addiction (FA) is associate with enhanced dopamine signaling.