Have you ever wondered why so many people in America and across the globe are falling victims to the chain of addictive behaviors -part of the worst epidemic in the history of the world?
The answer is in – part both genetic and environmental ( epigenetic) . Recently, researchers found that epigenetic effects on the chromatin structure of our DNA are a legacy that passes from generation to generation.
Scientists like Stephen Hawkins suggest that we are made up of self – assembled molecules generated over 14 billion years. More interesting is that we as Homo sapiens differ in our DNA by only 0.5%. New findings show that each human has on average 60 new mutations compared to their parents. Even more remarkable, the human brain contains billions of neurons working in concert to provide us the gift of “well-being” free of mental disease and stress. The number of neurons in the brain varies dramatically from species to species. One estimate ( published in 2012) puts the human brain at about 85 billion neurons and approximately 85 trillion synapses. It turns out that 20% of our entire body’s energy is budgeted to keep our brain working normally. The differences between individual humans are the 4.25 billion neurons and 4 .25 trillion synapses that make us unique.
This known difference affects the 7.4 billion humans that roam our earth working and living together to achieve some degree of productivity and happiness. However, as the world turns, 21st-century humans are faced daily with reminders of terrorism and horrific diseases that arise because these genetic and epigenetic differences lead to fatalities not just from cancer but from mental impairments that influence billions of neurons and trillions of synapses. This molecular rearrangement of our genome makes each of us unique. For example, how dopamine functions in our reward system may also be unique. One example among other gene variations involving brain reward is that genetic differences account for the presence of Attention Deficit/Hyperactivity Disorder (ADHD), a subtype of Reward Deficiency Syndrome (RDS) in approximately 8 to 12% of children in the United States and 4 % of adults worldwide. You also may be surprised to know that, at birth, an estimated 100,000 million people in the United States carry a form (allele) of just one genetic variation that involves brain dopamine D2 receptors. The allele (DRD2 Taq A1) is associated with 30-4 0% lower D2 receptors in the brain. So what does this mean regarding our romance with getting high-“ turning on” and “ turning off” with potent psychoactive drugs ( e.g. alcohol, cocaine, and opiates) and resultant addiction and fatalities seen in our kids?
In 1990, the first association of a variant (A1) on the dopamine
D2 receptor gene ( DRD2) and severe alcoholism was discovered and published by Noble & Blum et al. in J AMA. L ater experiments showed that individuals who arry this variant have 30 – 40% lower dopamine receptors than DRD2 A2 carriers. Being born with this single gene variation ( DRD2 A1 form) , that causes low dopamine receptors, sets an individual up to have a high addiction risk ( vulnerability) to any substance or behavior that stimulates the neuronal release of dopamine. In fact, in 1996, my laboratory used a mathematical model ( called Bayesian Theorem) , to predict that an individual born with the A1 allele ( variant) has a 74 .4 % risk of developing a RDS behavior like an addiction. People with that allele will have an initial acute response to using a psychoactive drug or experiencing pathological gambling, or whatever behavior stimulates enough neuronal dopamine for them to feel normal possibly for the first time. Unfortunately, chronic consumption experiences lead epigenetic changes that further reduce dopamine receptor numbers and a stronger need to abuse can lead to unwanted, uncontrollable behaviors and even narcotic overdose followed by death.
How were the genes involved in reward found? The chemical messengers ( neurotransmitters) in the brain are like keys that turn on various functions of genes. The neurotransmitters that participate in evoking pleasurable feelings, in the reward circuitry, work in a cascading fashion throughout the brain. These interactions ( the Brain Reward Cascade) may be viewed as activities of subsystems within a larger system, taking place simultaneously or in sequence, merging in cascade fashion toward a specific effect. The goal is the generation of feelings of well-being by the eventual release of just the right amount of dopamine at the reward site. In this scenario, there are at least seven major neurotransmitters and their pathways are involved: serotonin, cannabis, endorphin (enkephalin), GABA, glutamine, acetylcholine, and dopamine. There are thousands of published studies about these reward genes and pathways that influence the function of these named neurotransmitters. This research involved the identification of gene (DNA) variations or alleles that individuals are born with and epigenetic ( environmental RNA) changes that may alter the healthy, intended function of DNA.
Dysfunctional DNA is due to what is referred to as single nucleotide polymorphisms, frequently called SNPs ( pronounced “snips”) . SNPS are the most common type of genetic variation among people. Each SNP represents a difference in a single DNA building block, called a nucleotide. For example, a SNP may replace the nucleotide cytosine (C) with the nucleotide thymine (T) in a certain stretch of DNA. SNPS normally occur throughout a person’s DNA. They occur once in every 300 nucleotides on average, which means there are roughly 10 million SNPs in the human genome. Most commonly, these variations are found in the DNA between genes. They can act as biological markers, helping scientists locate genes that are associated with disease. When SNPs occur within a gene or near
a gene ( in a regulatory region) , they alter the gene’s function. If these SNPS show up in the Brain Reward Cascade-set of genes, the neurotransmission will be dysfunctional resulting in a loss of dopamine regulation or balance ( homeostasis) . Too little dopamine will at birth predispose people to “want”, “like” psychoactive drugs or even behaviors like hypersexuality and gambling. Compromised DNA with risk variations (alleles) can predispose them to become victims to the chain of addictive behaviors.
Following 25 years of extensive research from many scientists worldwide, a panel of eleven reward gene risk variants called the Genetic Addiction Risk Score (GARS) has been developed. When GARS was compared to Addiction Severity Index (ASI) used in many clinical settings, it was found to significantly predict the severity of both alcohol and drug dependency.
In support of early testing for addiction and other RDS subtypes, parents caught up in today’s horrific demographic of 127 people young and old dying from opiate/opioid overdose every day in America need help. Families would have never guessed that their loved ones would die or are now in real danger due to opiate addiction. Bill Moyers published an article in Parade Magazine, in it, he reported that as he traveled around the U nited States, he found too many children with ADHD and that many of those children had subsequent issues like substance abuse. He emphatically called for better ways to identify these children and treat them other than with addictive pharmaceuticals.
When the GARS test is available and approved by the FDA, clinicians and parents will be able to access the vulnerability of chemical dependency patients and more importantly their children to RDS behavior like addiction, ADHD, and autism spectrum disorders. The common thread across all these risk gene variants is that they lead to a low dopamine ( hypodopaminergic) function or deficit. There are arguments against genetic testing because of the fear of labeling and for knowing the risk especially if there was no treatment options. The real issue or challenge, however, is “what can be done if risk alleles are found”? It is understandable that when there is one gene – one disease ( OGOD) involved like in Huntington’s disease, and when, treatment is unavailable, and prevention remains a problem; why know the risk?
Have we found a safe non-addictive solution that will provide the brain a means to balance the neurotransmitters involved in the BRC culminating in true dopamine homeostasis?
In spite of variant genes and epigenetic, environmental insults, holistic approaches like mindfulness, exercise, spirituality, and particularly amino acid therapy ( KB220 formulations) have been shown to reduce relapse and increase brain dopamine homeostasis. I am suggesting that not only should we, in the near future, be able to genetically test our children for unwanted reward gene ris variants that predispose them to dopamine deficiency lack of reward and risk for drug and non-drug addiction but possibly even prevent RDS behaviors.
Genetic risk for substance abuse and other RDS behaviors can be identified by the GARS test and explains why some individuals are vulnerable and others not. With continued research, genetic and epigenetic dopamine deficiencies can be treated, relapse reduced and we can free ourselves from the clutches of powerful addictive behaviors and bring balance and happiness to our lives.
Kenneth Blum, B.Sc. (Pharmacy), M.Sc., Ph.D. & DHL; received his Ph.D. in Neuropharmacology from New York Medical College and graduated from Columbia University and New Jersey College of Medicine. He also received a doctor of humane letters from Saint Martin’s University Lacey, WA. He has published more than 550 abstracts; peer-reviewed articles and 14-books