Genetic variant increases risk of addiction in the presence of childhood stress

By Dr. Liji Thomas, MDAug 19 2019

What causes some people to become alcoholics or drug abusers when faced with stress, but not others? This question has plagued addiction researchers for decades. Now, in one of the most informative studies dealing with addiction risk, researchers from the OU College of Medicine have found that one specific variant of the catechol‐O‐methyltransferase (COMT, Val158Met, rs4680) gene makes people more likely to become addicted in the presence of a history of childhood stress.

The study involved 480 young adults, in a male: female ratio of 1:1, all in good health, who had a history of stressful experiences in early life to varying degrees. The severity of this factor, also called early-life adversity (ELA), was graded between 0 and 2. The participants were asked about stress in early life, their use of alcohol and other recreational drugs, and were tested for salivary cortisol levels in response to speech and to a stressor (of doing mental arithmetic) as well as for the Val158Met polymorphism of the COMT gene.

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The researchers found that in people who had the gene alleles Met/Met or Val/Met, the ELA was associated with decreasing secretion of cortisol, but in individuals who had the Val/Val genotype, the responses grew in magnitude progressively. However, there was no link between the cortisol response to ELA and the chances of using drugs or alcohol.

The presence of ELA was also predictive of earlier age at first drink, most marked in those who carried the Met allele but smaller in those with the Val/Val allele. People with these genes also showed similar effects when it came to the age at which they first used recreational drugs. These trends are important because drinking before the age of 15 years is a recognized major factor in alcohol addiction.

ELA may be of various types, including divorce or lacking close family relationships. Such stress is poorly handled by people with the COMT Val158Met polymorphism, and they tend to give in to the temptation to try drugs or drink before the age of 15. Thus, this genetic makeup is linked to a higher risk for addiction.

One possible explanation of this phenomenon may have to do with the behavior of dopamine in the brain. The COMT gene is involved in the normal breakdown of a chemical called dopamine, which is associated with the euphoria felt after a drink or with certain drugs like amphetamines. This gene has multiple variants, of which the Val158Met polymorphism is just one. The COMT Val158Met polymorphism changes the way the gene functions.

There are a lot of steady drinkers who never develop addiction, but on the other hand there are a lot of people who can’t handle even one drink without the strong risk of addiction. This difference has made a lot of scientists scratch their head as to the risk factors involved in the development of an addiction, other than exposure and environmental factors. The new study shows that there is also a genetic component to this problem.

However, the current study focuses on the interaction between this gene variant and the result of childhood stress on a person’s addiction potential. Does having this gene make you a predestined alcoholic? Or is it the stress that drives the addiction risk? Neither, according to this research. Rather, it is the interplay of both these factors that increases the risk that the individual may become addicted, primarily by reducing the age at which the first engagement with a potentially addictive substance occurs.

Researcher William R. Lovallo says, “"Early-life adversity doesn't make everyone an alcoholic.  There is no such thing as a gene for addiction. There are genes that respond to our environment in ways that put us at risk. This study showed that people with this genetic mutation are going to have a higher risk for addiction when they had a stressful life growing up.”

Lovallo’s previous double-decade of research in the field of addiction was primarily based on people who had already developed an addiction. The present study displays his determination to go deeper into what causes addiction, which will help frame better and more powerful ways of preventing it.

Lovallo is justifiably proud of his achievement, saying, “Addiction is a real health problem, and to be making progress toward understanding it is one of the most exciting and worthwhile things I've ever done.”

The study was published on May 31, 2019, in the journal Alcoholism: Clinical and Experimental Research.