Hatching the reward deficiency egg: Neurogenetic and nutrigenomic translational research links
Austin, TX – A recent publication in Current Pharmaceutical Design, by Kenneth Blum, PhD and associates entitled: Neuronutrient Amino-Acid Therapy Protects Against Reward Deficiency Syndrome: Dopaminergic Key to Homeostasis and Neuroplasticity may have clinical relevance in providing evidence for the "hatching of the addiction egg" with possible solutions.
Following the first association between the dopamine D2 receptor gene polymorphism and severe alcoholism by Blum & Noble and others in 1990, there has been an explosion of research reports in the psychiatric and behavioral addiction literature and neurogenetics. Since 1996, Blum's 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. Importantly, the proposal is that the real phenotype is RDS and impairments in the brain's reward cascade [BRC], 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. The paper refers to neurogenetic and neuroimaging data and these results have clinical relevance and as such is dedicated to all the people who have lost loved ones in substance-abuse and "reward deficiency syndrome" related tragedies.
The authors raise the questions: Why are we failing at reducing the incidence of 'Bad Behaviors'? Are we aiming at the wrong treatment targets for behavioral disorders? Can we couple Neurogentics with Pro-Dopamine regulation as a paradigm shift, calling it "Reward Deficiency Solution System" providing evidence for its universal adoption possible profound implication in saving lives across the globe? The article explores a 50 year journey explaining the development of neurogenetics and nutrigenomics and its clinical impact.
Blum, the lead author of the article, carefully points out some important scientific features. In particular, Willuhn et al., observed that habitual cocaine use was correlated with reductions in D2/D3 receptors linked to decreased cue activation in occipital cortex and cerebellum. Dopamine agonist therapy maintains dopamine function and this relapse prevention tactic is focused on psychoactive drug and behavioral addictions. Medication Assisted Treatment (MAT) with emphasis on anti-dopamine medications fails in the long-term treatment of Reward Deficiency Syndrome Behaviors (RDS). While the careful use of "dopamine antagonist-therapy" short-term is supported, the research-based concept of "dopamine agonist therapy"[Pro-dopamine Regultion] in long-term is proposed.
According to Blum, – "Neurogenetics and epigenetics are important in understanding treatment response and clinical outcomes. The neuro-mechanisms involving 'dopamine homeostasis' key to understanding recovery from drug and non-drug addictive behaviors is a critical piece missing in many treatment centers across the United States."
For example, patients who carry the DRD2 A1 allele (30-40 less D2 receptors) should consider Neuronutrient-Amino-Acid therapy (KB220 variants) as a prevention modality. DRD2 A1 allele carriers show amplified striatal function of L-amino acid-decarboxylase, prior to dopamine biosynthesis. Another example is the effect of Acute Tyrosine Phenylalanine Depletion (ATPD) on decision-making and reward found in carriers with amino-acid deficiency (ATPD). The review presents information related to a number of neuroimaging studies (qEEG, fMRI and LORETA) on Neuronutriant-Amino-Acid therapy (KB220 variants) showing enhanced functional connectivity and connectivity volume and potential neuroplasticity. Furthermore, the article discusses a panel of gene polymorphisms that induce risk of all RDS behaviors.
According to co-author Dr. Rajendra Badgaiyan, a professor of psychiatry and Director of Neuroimgaing Center, University of Minnesota, stated – "Based on previous research from my laboratory we know that people with RDS, especially ADHD patients, have a reduced baseline dopamine tone and as such are deficent of dopamine function. Utilizing the Genetic Addiction Risk Score (GARS) test as evidence-based significant predictability of the ASI-Media version 'V' for both alcohol severity and drug severity provides a future assessment tool that, if used corectly, could reduce unwanted opioid addiction in those people showing genetic risk."
The article points out the importance of genetic risk for all RDS behaviors and shows that carriers of at least one gene variant, the DRD2 A1 allele, the brain in these high risk individuals is set-up to favor amino-acid therapy by showing amplified striatal function of L-amino acid decarboxylase, prior to dopamine biosynthesis. The authors question if including a reduced resting state functional connectivity in heroin and cocaine abusers (through an understanding of current theories of addiction), for example, counted by KB220z to induce BOLD activation (balancing dopamine function) shown in a number of published studies, would significantly reduce unwanted craving of dependent patients. But with a call for more genetic and neuroimaging studies on the subject of drug addiction and associated behaviors, the real question is: "Have neuroscientists actually hatched the addiction egg?"
Reference: Blum, K; et al. (2016). Neuronutrient Amino-Acid Therapy Protects Against Reward Deficiency Syndrome: Dopaminergic Key to Homeostasis and Neuroplasticity, Curr. Pharm. Des., DOI: 10.2174/1381612822666160719111346
Faizan ul Haq