Addiction And DNA: Do Genes Dictate Our Fate?

Have you ever wondered why US President Donald Trump doesn’t drink alcohol? In an interview with the South China Morning Post, he explained why. One reason is so that he doesn’t lose control. Another was because his older brother Fred repeatedly told him not to. Fred, an airline pilot who struggled with alcohol use disorder, died in 1981. He was 43.

Fred’s demise forms the backdrop to an ongoing debate of whether or not to treat addiction like other inherited diseases. Despite his brother’s history, President Trump’s new health care act does not treat addiction like a disease, instead denying people access to proper treatment. He does not seem to acknowledge that addiction is no longer viewed as a sign of a character flaw, or lack of control, or moral failure.

Global studies show that addiction is a complex disease with various manifestations. Scientists such as the ones at the Jackson Laboratory in Maine are currently working on identifying the genes associated with addiction.

“Addiction is a chronic brain disease similar to other conditions like diabetes, hypertension, or kidney disease,” says Vivek Kumar of the Jackson Laboratory. “If we understand addiction as a neurobiological disease, like many other mental illnesses or chronic diseases, we will take the stigma out of studying and treating addicts.”

Should a family history of addiction be revealed early?

Kumar points out that addicts’ offspring are eight times more likely than the general population to develop an addiction. Trump is aware of this and claims to have educated his kids early about inherited risk.

Some medical professionals like Stanton Peele, psychologist and author of Recover, argue that talking to kids about addiction risk too early may be dangerous. “If you choose to lay that on them as a genetic obligation, you’re wrong. Believing you’re destined to be an addict is a self-fulfilling prophecy.”

Dr. Joseph Lee, medical director for the Hazelden Betty Ford Youth Continual, disagrees with Peele: “If you saw any kind of disease running through families one generation after another, the prudent, moral, scientific thing to do is to invest early so the next generation doesn’t develop problems.” One of Hazelden’s programs, Freedom from Chemical Dependency (FDC), sends specialists to talk to students about family history.

Addiction vulnerability

All addicts have these factors in common: how likely they are to start using a drug, how it affects them, and how likely they are to form a habit.

But what do they have that makes them different from non-addicts? Why are some people more vulnerable to addiction than others? Is addiction caused by the environment or ‘addiction genes’?

These are questions researchers like Dr. Danielle Dick, founder of the College of Behavioral and Emotional Health Institute, are trying to answer. The results of their research greatly impact how addicts are treated.

Dr. Danielle Dick is a professor in Psychology, African American Studies, and Human and Molecular Genetics at Virginia Commonwealth University. With grant funding from the National Institutes of Health (NIH), she studies genetic influences in substance use and mental health, and how genetic predispositions change in different environments.

Dr. Dick started with this premise: “Some of us are born with the sequence of DNA that makes us more at risk for some outcomes.” To address the above questions, she worked with researchers in Finland, England, and the United States.

Test subjects monitored in their teens

In Finland, which has a central population register, Dr. Dick and Finnish researchers studied 12- to 14-year-olds who had just started drinking. They wanted to know what influenced the kids to do so: individual genes or the environment?

The answer: It was all environmental, because for an adolescent to start alcohol consumption, it requires access to the substance. Factors in homes, schools, and neighborhoods impact this accessibility. However, the researchers observed that when these kids went from initial experimentation to more established regular patterns of use, their genes became important while the effects of the previous environmental factors declined.

“So the environment impacts when kids start drinking, but once they do, their genes take over,” explains Dr. Dick. “So wouldn’t it be great if we knew who was most at risk before they ever took that first drink of alcohol?”

The study results divided the Finnish kids into two groups:

1. For those with high levels of parental monitoring (their parents knew what they were up to), the environment was the most important factor that influenced how much those kids were drinking and smoking.
2. For those with low levels of parental monitoring, their genes were the most important element influencing their substance use.

Test subjects monitored before birth

In another study, Dr. Dick teamed with researchers in England who worked with pregnant women in one region over two years. They studied these women’s children before they were born, right into their 20s.

“We wanted to know how early we could predict who was going to become risky adolescent alcohol users,” Dr. Dick explains.

When they gathered reports from moms on their kids before age five, they found two groups that were more likely to drink to cope with depression and anxiety:

1. Kids who had suffered from emotional and behavioural problems since toddler age
2. A bigger group of at-risk kids who were highly sociable and fun-seeking, who demonstrated impulsivity, and who had a propensity for compulsive activities. Dr. Dick’s son belongs to this group.

In the US, Dr. Dick runs a study called Spit for Science. This project aims to discover the causes of substance use and mental health challenges.

The rise of genomics

Thanks to research on the relationship between genes and diseases, plus the Human Genome Project, an entire new field of medicine has surfaced: genomics. It is the branch of molecular biology concerned with the structure, function, evolution, and mapping of genomes. A genome is the complete set of genes or genetic material present in a cell or organism [1]. The Human Genome Project (c.a. 2003) identified all of the genes in human DNA.

Genome medicine helps us understand the role genes play in addiction. Genetic tests also tell us how addictive drugs can affect people depending on their DNA. One day, these tests may be used to predict which treatments are more effective based on one’s genetic profile. This will hopefully lead to more improved, specific treatments for substance use disorder.

Every time a new addiction-specific gene is discovered, two things happen:

1. Researchers can focus on the gene protein to develop a drug to modify its activity. The objective? To correct signals or pathways, and restore proper function to specific parts of brain.
2. Gene therapies can then be developed to treat addiction. For example, one gene therapy generates antibodies to trap methamphetamine, preventing it from reaching the brain. Another produces an enzyme that breaks down cocaine [2].

Seeing double

Scientists are studying twins to explore the role of genetics in addiction. Most agree that genes determine more than half of a person’s vulnerability to addiction. To find out what these are, scientists are comparing identical twins with fraternal ones.

Identical twins are ‘monozygotic’, meaning they come from the same fertilized egg, so they share 100% of their genes. Their 23 chromosome pairs are identical, so they have the same eye colour, hair colour, height, and so on. They often have shared substance abuse issues.

Fraternal twins are ‘dizygotic’—born from the same mother simultaneously, but formed from separate eggs. They share just 50% of their genes, like regular siblings.

“Twin studies explore the roles and interrelationship of genetic and environmental risk factors in the development of drug use, abuse, and dependence,” says Dr. Naimah Weinberg of the Epidemiology, Services, and Prevention Research Division of the National Institute on Drug Abuse (NIDA).

Alexis Edwards, PhD, an assistant professor of genetics at Virginia Commonwealth University (VCU), worked with Kenneth S. Kendler on the Virginia Adult Twin Study of Psychiatric & Substance Use Disorder (VATSPSUD). They conducted research on alcohol problems, depression, and nicotine addiction. Kendler, a psychiatric geneticist, is director of the Virginia Institute for Psychiatric and Behavioral Genetics (VIPBG) and a faculty member in the VCU School of Medicine.

Edwards found genetic makeup links between alcoholism and ADHD, and between nicotine and depression. They compared the mental health of identical and fraternal twins. They studied seven common addiction and psychiatric disorders, including alcohol, nicotine, and other drug addictions.

Edwards has a personal stake in psychiatric genetic information. She has family members with a history of alcoholism and depression. “When you’ve seen first-hand the havoc that addiction brings to relationships,” she said, “you are compelled to try to understand where they come from.” She added that people with substance abuse problems can be infuriating and that she knows this based on personal life experience. “But knowing what I do about the genetics of these problems, I know it’s not their fault.”

Highlights from the Edwards-Kendler study

Links between addiction and prior or concurrent conditions suggest that the disorders may be influenced by common genes. Adolescents with ADHD are likely to have a genetic vulnerability toward alcohol abuse disorders. Now that doctors know hyperactive kids are more at risk for addiction in adolescence and adulthood, they could identify them early and intervene.

Links between the genetics of smoking and depression

• 20% of depressed people smoke compared to 10% of the populace.
• 80% of those with schizophrenia smoke.

“There is a genetic correlation between depression and nicotine dependence,” says Edwards. “However, it’s also possible that smoking actually makes people more likely to experience depression, since we know smokers may be at higher risk for depression.”

University collaboration

One of the largest studies on twins was by the University of Washington and the University of Queensland. Here are some of the highlights:

• 32% of men and 7% of women would experience alcohol dependence at some point in their lifetime.
• Male identical twins: when one twin is alcoholic, there is about a 50% chance that the other would also be an alcoholic.
• Female identical twins: there is a 30% chance that if one is alcoholic, the other would also be an alcoholic.
• Male fraternal twins: about 33% would both be alcoholic at some point. This is not so different from the male alcohol dependence rate in general.
• Female fraternal twins: about 16%.

Is there a marijuana addiction gene?

In July, Danish researchers identified a single variant of the gene CHRNA2 that affects the risk of an individual becoming addicted to cannabis [3]. “The gene doesn’t make someone a pot smoker, but it can increase the risk of addiction for those who try cannabis,” says Ditte Demontis, an associate professor at Aarhus University in Denmark, and leader of the research team. Demontis admits, though, that it is unclear how CHRNA2 does this.

Is there an alcohol addiction gene?

“Researchers have identified six genes that impact our sensitivity to alcohol,” verifies Dr. Marc Schuckit, a psychiatry professor at UCLA San Diego who has been studying genetic links to alcoholism for more than 35 years. In people with other addictions, genes relating to impulse control were discovered. Scientists tried to connect these with subjects’ biological response to substances.

Is there one universal addiction gene?

The current belief is that substance abuse disorders are the result of a combination of environmental influences and genetic factors. “Scientists will never find just a single genetic change that causes addiction,” claims Dr. Glen R. Hanson, former NIDA director and one of the foremost experts on drug addiction. He is responsible for 85% of all research on drug abuse in the world. He is also the director of the Utah Addiction Center.

Dr. Hanson says, “While multiple lines of research show that genes influence substance use, finding the precise genetic cause is tricky. Scientists estimate a person’s genetics account for 40% to 60% of their risk. There are many ways genes can cause one person to be more vulnerable to addiction than another.”

A study by David Goldman et al predicts that “our future understanding of addictions will be enhanced by the identification of genes that have a role in altered substance-specific vulnerabilities, such as variation in drug metabolism or drug receptors, and a role in shared vulnerabilities, such as variation in reward or stress resiliency.”

Are we close to knowing all the genes that influence addiction?

Scientists estimate that there are hundreds of genes involved in addiction, but they have only identified some. “The question is, how many are there?” asks Elissa Chesler, principal investigator at Jackson Laboratory’s Center for Systems Neurogenetics of Addiction, funded by NIDA. “There are the genes that control stress responses, genes that affect how rapidly the drug is metabolized, and genes that affect how readily an addiction forms.”

Kumar’s lab has discovered a cluster of 50 novel genes predictive of addiction. He is currently testing these. We might one day genetically profile people to prevent the emergence of potential addicts.

This is scary because they may be stigmatized even before they develop an addiction. Think racial profiling at US airports. Think Minority Report. Imagine the consequences.

Nurture vs nature

Both impact one’s predisposition to becoming an addict. Addiction experts usually recommend the type of treatment depending on what caused the substance use disorder. If lack of nurture (such as living in a violent home) caused it, rehab and behavioural therapy would be suggested. If nature (having addicted relatives) is the influence, medication might be better.So are we doomed by our heritage? There is no single cause of addiction. But there is hope in continuing research, especially in genetics. Future gene discoveries may lead to more effective treatment and/or prevention strategies.

“No one is born destined to develop substance use disorder,” assures Dr. Hanson. “Just because you are prone to addiction doesn’t mean you’re going to become addicted. It just means you have to be careful.”

So whether your family has a history of addiction or you grew up in an unpleasant environment, the cause of your addiction doesn’t define you. Dr. Dick confirms this: “Our genomes influence our behaviour very early in life, but our environments ultimately shape how those dispositions unfold. Our dispositions are not our destiny.”

What’s important is that the addicted can rise above these factors by seeking professional help and work towards recovery.