Adolescent Alcohol Use: Genetics, Pharmacokinetics and Neurobiology

by National Institute of Health

Complex behaviors such as the initiation and use of alcohol result from an intricate interplay between genes and environment. Genes shape physiological and behavioral responses to alcohol that can influence the likelihood that a young person will begin using alcohol and that he or she will progress to problem drinking. Youthful alcohol use also can have an impact on unfolding developmental patterns, and for some, early use becomes the entry point for pathways that lead to problems with alcohol. This article first describes research on genes that may be involved in the development of alcohol problems and how genetic factors may contribute to adolescent alcohol use. It then examines how the changes that occur during adolescent development - in alcohol metabolism, in the brain, and in the endocrine and stress response systems - may affect how a young person experiences alcohol and the likelihood that he or she will develop alcohol use problems. Key words: adolescent; AOD (alcohol and other drug) use initiation; alcohol abuse; alcohol dependence; AOD sensitivity; use initiation; risk factors; protective factors; genetic risk and protective factors; heredity factors; genetics and heredity; environmental factors; heredity vs. environmental factors; human study; twin study; animal study; animal model; puberty; biological development; psychological development; cognitive development; endocrine system; hormones; stress; ethanol metabolism; alcohol metabolism; pharmacokinetics.

Many studies have focused on how physiological and neurobiological responses to alcohol - such as sensitivity to alcohol, change in its rewarding effects, craving, tolerance and withdrawal - factor into the development of alcohol use and alcohol use disorders. The majority of studies to identify genes and neurobiological mechanisms that may contribute to alcohol use and alcohol use disorders in humans have been done with adults. Recent data suggest, however, that the highest prevalence of alcohol dependence in the general population occurs in people ages 18-24, and it is not yet clear to what extent genes involved in the onset of alcohol problems in adults play a similar role in youth. A central goal of research is to understand the genetic and environmental factors, and the interplay between them, that contribute to the development of alcohol abuse and dependence in adolescents.

Human genetic research related to alcohol use has involved studies with twins or with families that have a high prevalence of alcohol-dependent individuals. This work has identified regions of chromosomes that are associated with an altered risk of developing alcohol dependence, and in some cases, individual genes or candidate genes. Analysis of the role these genes and gene regions play in alcohol use is difficult for a number of reasons. As with other complex genetic diseases, multiple genetic factors may contribute to the risk of developing alcohol dependence, but no one factor is associated with a large percent of risk. Different risk factors may be active in different individuals. In the case of alcohol use, studies of both adults and adolescents suggest that the relative contributions of genes and environment change at different stages of problematic drinking; for example, genes have a strong influence over the development of problem use, whereas environment seems to play a greater role in the initiation of alcohol use.

Research using animal models also added to our understanding of the genes that may contribute to alcohol abuse and/or dependence. Animal studies have helped to identify genes involved in the effects of alcohol as well as those involved in the pathways affecting sensitivity to acute alcohol exposure, reward, craving, and withdrawal. Many of the genes that have emerged from this research have roles in other behaviors as well. For example, serotonin has been implicated in alcohol consumption in conjunction with its role in anxiety, which, in some individuals, is particularly manifest during adolescence. Further studies will assess the relative roles of various signaling pathways and their component genes in the development of alcohol-related behavior, and determine which are most influential in adolescents.

Superimposed on genetically shaped aspects of physiology are developmental changes that can measurably affect both the response to alcohol and the chances that someone will drink heavily. Some research, for example, suggests modest changes during adolescence in the pharmacokinetics of alcohol - how it is absorbed, distributed, and eliminated. Gender differences in these processes emerge during puberty and affect blood alcohol levels after drinking.

Animal studies suggest that sensitivity to alcohol is different among adolescents than it is in adults. For example, adolescent rats are less sensitive to the unpleasant effects of intoxication, such as sedation, loss of coordination, and hangover effects, and they consume higher levels of alcohol than do older animals. Possible underlying reasons for the lack of sensitivity include the developmental immaturity of neurotransmitter receptor systems.

Dramatic hormonal changes take place during puberty, affecting growth and sexual development, and the body's stress response systems. These hormonal changes also may affect sensitivity to alcohol. For example, animal research suggests that hormones involved in the response to stress may interact with neurotransmitters in the brain that are associated with the sensation of reward to facilitate drinking.

Clearly, development adds a layer of complexity to understanding the reciprocal interactions between genes and environment, alcohol metabolism, and the neurobiology of the response to alcohol.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.