William R. Lovallo, Ph.D. Reseacher, University of Oklahoma College of Medicine

Genetic Vulnerability to Early Life Stress Contributes to Risky Drinking and Drug Use in Adolescence

MedicalResearch.com Interview with:

William R. Lovallo, Ph.D. Reseacher, University of Oklahoma College of Medicine

Dr. Lovallo

William R. Lovallo, Ph.D.
Reseacher, University of Oklahoma College of Medicine

MedicalResearch.com: What is the background for this study?

Response: We have been interested for some time in why some people are at high risk for alcoholism.  Most work in the field of addictions is focused on persons who are already impacted by their exposure to alcohol or drugs.  We wanted to know what they were like before that phase of their  lives.  So, in 1999 we began the Family Health Patterns Project to study healthy young adults 18-30 years of age with and without family histories of alcoholism but who were not alcoholics themselves.  A family history is the best known, and perhaps strongest, risk factor for future drinking problems.

We asked ourselves are the two family-history groups different?  And if so, how are they different?  There was at that time little literature to build on so we decided to look at as many things as we could.  We began recruiting volunteers for our family-history positive and negative groups and evaluating them with a standard psychiatric interview, personality tests, measures of depressive mood and neuroticism, and measuring physiological reactivity to stress.  In doing so we also began collecting DNA and studying basic genetic variants to see if any of those might be revealing.

MedicalResearch.com: What are the main findings?

Response: In the course of the work, it became apparent that one of the predominant differences in our family-history positive group was that they had experienced much, much more adversity in their childhood and adolescent years.  The most significant form of adversity was disrupted family relationships, including separation from parents, during these formative years.  This early life adversity measure had an important impact on all our other domains of study including stress reactivity, personality, and mood stability.

Because the early environment is clearly so important, and because the person’s FH+ status reflects their genetics, we thought we had the necessary ingredients to do a Gene-by-Environment analysis of our data.  Our colleagues at the National Institute of Alcohol Abuse and Alcoholism did extensive genotyping on these 480 volunteers and this allowed us to examine the specific genetic polymorphism of COMT that we published in this study.

The COMT molecule is an enzyme that breaks down dopamine in the prefrontal cortex and limbic system of the brain.  One genetic variant of the COMT molecule, the Met allele, is less active than the other variant, the Val allele, which is more active.  As a result, persons carrying one or two copies of the MET allele (so called Met/Met and Val/Met carriers) break down dopamine less rapidly than persons carrying two copies of the Val allele.

This difference in dopamine availability is potentially important in how behavior and emotional reactivity is regulated in these groups, and these genetic differences may well signal vulnerability to early stressful experiences.  So, we examined the cortisol response to emotional stress in the lab in our adversity and genotype groups.  We found that persons exposed to greater amounts of early adversity had increasingly diminished cortisol responses to psychological stressors like public speaking and performing mental arithmetic.  This impact of adversity on blunted stress reactivity was only true for persons inheriting one or two copies of the Met variant of COMT.

Simply put, persons with slow breakdown of dopamine in the brain are sensitive to environmental influences.  This sensitivity was reflected in their diminished stress reactions in relation to early maltreatment.  In contrast, the Val/Val carriers appeared to be resistant to their early environment.

This caught our attention because increasing amounts of research are showing that diminished physiological stress reactivity is a signal of risk for addictions.

We then looked at how young our people were when they took their first drink of alcohol and how much recreational drug experimentation they had done.  What we found was that Met-allele carriers exposed to early life adversity started drinking the earliest (under age 15) and experimented with more drugs (2 or more drugs) than any of the other groups.  These are both significant signals of future risk for addiction.

So, we seem to have identified a genetic vulnerability to early life stress that contributes to risky drinking and drug use in adolescence.

MedicalResearch.com: What should readers take away from your report?

Response: The two most important things are to repeat this work with a different population and to probe more deeply into the nature of the stressors these persons may have experienced in their lives.  Ultimately, this work may help us understand the process of addictions to alcohol and drugs.

 MedicalResearch.com: What recommendations do you have for future research as a result of this work? 

Response: This work would not be possible without the extensive support of the National Institutes of Health (NIAAA, grant no. AA12207) and the Department of Veterans Affairs where my lab is located.  I also thank my co-principal investigator, Dr. Ashley Acheson at the University of Arkansas for Medical Sciences, and co-investigator, Dr. David Goldman at NIAAA for their generous collaboration in doing this work.


Lovallo, W.R., Cohoon, A.J., Sorocco, K.H., Vincent, A.S., Acheson, A., Hodgkinson, C.A., Goldman, D.  (2019). Early life adversity and stress reactivity as predictors of alcohol and drug use in COMT (rs4680) Val158Met genotypes.  Alcoholism Clinical and Experimental Research, 43, 1519-1527



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Last Updated on August 20, 2019 by Marie Benz MD FAAD