Early Drinking May Trigger Genes Linked to Alcohol Dependence

Pauline Anderson

September 18, 2009

September 18, 2009 — Early alcohol use may facilitate the expression of genes associated with vulnerability to alcohol dependence (AD), a new study suggests.

The twin study showed that heritable influences on AD symptoms were considerably greater in those who had their first drink when they were younger than 15 years.

This study is one of the first to explore genetic–environmental interactions that might explain the well-researched association between age at first drink (AFD) and AD.

The study results have important public health implications and could be useful for future genetic studies of AD, said corresponding author for the study Arpana Agrawal, PhD, assistant professor, Department of Psychiatry, Washington University School of Medicine, Saint Louis, Missouri.

"From a public health standpoint, later age at first drink may serve to protect against a familial predisposition to subsequent alcohol dependence [and] symptomatology, and from a genetic perspective, investigators may be able to enhance their ability to isolate genes for alcohol dependence by considering them in the context of early [AFD]," she said.

The study is published online ahead of print September 19 in Alcoholism: Clinical & Experimental Research.

For the study, investigators used data on 6257 Australian twins, both men and women, aged 24 to 36 years. The sample included monozygotic and dizygotic pairs as well as twins from incomplete pairs. Researchers interviewed the twins by telephone from 1996 to 2000, using an adaptation of the Semi Structured Assessment for the Genetics of Alcoholism.

First Full Drink

Among other things, the researchers asked the twins how old they were when they had their first full drink of beer, wine, or spirits. The mean age for the first drink was 16.2 years. About 22% of the twins reported taking their first drink at or before the age of 14 years.

Twins who reported drinking at least once a month for 6 months or longer, or drinking to intoxication, were interviewed further to determine AD symptoms. The mean number of Diagnostic and Statistical Manual of Mental Disorders, 4th edition, symptoms in this sample was 0.95 in women and 1.52 in men.

Using various predictive models, some of which controlled for the effects of AFD on AD symptoms and for gene–environment correlations, researchers found that heritable influences on AD symptoms decreased with increasing AFD. Compared with those who consumed their first alcoholic drink after about age 15 years, early-onset drinkers appeared to be more genetically susceptible to later AD, said Dr. Agrawal.

"Starting to drink at an early age in and of itself increased risk for alcohol dependence, and there are a number of other studies that have validated this. What we find here is that in those who drink at an early age, alcohol dependence has a more heritable form," she told Medscape Psychiatry.

Brain Changes

Initiating alcohol use in early adolescence may lead to changes in the developing brain that may modify expression of AD-related genes, said Dr. Agrawal. "It would be very intriguing to use gene expression assays or neuroimaging methods to examine how exposure to alcohol at a very young age — and how much alcohol — directly impacts the developing brain," she said.

In contrast, in twins who initiated alcohol use later in adolescence — after age 18 years — almost all variance on AD symptoms could be attributed to individual environmental factors and/or measurement error. AD problems in people with later AFD appear to be a result of nonshared experiences — for example, a stressful life event such physical or sexual abuse — said Dr. Agrawal.

There are at least 2 possible hypotheses that might explain the association between AFD and later AD, said Dr. Agrawal. One is that certain genes, as well as risk factors such as exposure to deviant peers or parents who drink heavily, predispose young people to drink at an early age and to develop AD later on.

Another hypothesis, which is much harder to test, is that drinking at an early age actually causes AD.

The study adds a few more pieces to the genetic puzzle related to AD. The hope is to eventually identify specific genes that influence the vulnerability to AD, but as with all substance use disorders, AD involves hundreds, if not thousands, of genes, making such efforts extremely difficult.

Try to Delay Drinking

Meanwhile, encouraging adolescents to delay drinking alcohol may serve to buffer the expression of familial predisposition to later alcohol-related problems, said Dr. Agrawal.

"The message has to be at the level of perhaps prevention and intervention programs in schools that encourage children to consider the risk factors associated with drinking at an early age, and presenting it as a possible contributor to later problems with alcohol," she said.

Dr. Agrawal and her colleagues plan to replicate the study using twin sets from the United States and to include older twins. However, they plan some changes. One of the drawbacks of the current study is that the twins were not asked where they took their first drink — whether it was at home, during a religious ceremony, or elsewhere, said Dr. Agrawal.

"In future efforts, as we do more data collection, we need to focus on the context of the drinking behavior because that might contribute to why a proportion of early-onset drinkers develop AD while others do not," she added.

They also plan to look at late-onset drinkers who develop AD and early alcohol drinkers who do not, said Dr. Agrawal. "We're interested in examining what happens to those early-onset drinkers who perhaps have that drink at home (as opposed to with deviant peers perhaps) and who are not exposed to other risk factors."

Mental Health System for Kids a "Shambles"

Asked by Medscape Psychiatry to comment on the study, Mark L. Willenbring, MD, director, Division of Treatment and Recovery Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, said the findings add to the evidence that, either through genes or the environment, drinking at an early age increases the risk for AD later on.

"The idea that there could be epigenetic changes that are permanent or heritable is certainly feasible," he said.

Parents can encourage their children to delay onset of drinking by doing commonsense things like locking their liquor cabinet. Other ways to deter kids from drinking include offering parenting courses and improving the mental health system for children, added Dr. Willenbring.

"One of the biggest problems we have right now is that our mental health system for children and adolescents is in a shambles — there really isn't one. Most people can't get adequate services even if they can pay for them. There's a national shortage of child psychiatrists, insurance coverage is often a problem for these families, and these kids often end up in the juvenile justice system."

The authors have disclosed no relevant financial relationships.

Alcohol Clin Exp Res. Published online September 18, 2009.


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