How genetics can influence learning

November 14, 2001

Alcohol expectancies reflect what one has learned about the results of drinking. Alcohol expectancies are considered a significant risk factor for problem drinking, even among adolescents. In a completely different area of alcohol research, the aldehyde dehydrogenase (ALDH2) gene is considered a genetic factor that may reduce risk for consumption. Individuals with the ALDH2 gene often have a strongly unpleasant response to alcohol. A study in the November issue of Alcoholism: Clinical & Experimental Research integrates these two typically disparate fields of research to investigate if alcohol response is the mechanism by which ALDH2 gene status may affect alcohol expectancies.

"Researchers think of expectancies as a summary of people's learning history about alcohol," said Denis M. McCarthy, assistant project scientist in the department of psychology at the University of California, San Diego and lead author of the study.

"That is, the thoughts you have about the possible outcomes of drinking alcohol. Think of expectancies as an 'information database' people form about alcohol. Then other risk factors - such as personality or genetic factors - feed into this database and influence a person's decision to drink, how much to drink, and whether or when to stop drinking."

Expectancies, then, are influenced by both genetic and environmental factors. Since expectancies are largely considered learning variables, however, researchers have focused primarily on environmental factors that change expectancies, such as seeing one's parents or friends drink.

McCarthy's research is part of a new movement of the past few years that has begun to focus on biological and specific genetic factors that can alter expectancies.

Between one quarter and one half of individuals of Asian heritage possess a genetic variant of the alcohol metabolizing enzyme ALDH2, which has been linked to a deficiency in the low KmALDH2 isoenzyme, which can result in stronger physiological responses to alcohol.

"A significant percentage of these individuals experience a stronger response to alcohol than people without the gene do," said Gregory T. Smith, associate professor of psychology at the University of Kentucky. "In many cases, that stronger response is unpleasant. They may experience things like facial flushing, a higher pulse rate, and hormonal changes. In severe cases, individuals may experience nausea, vomiting, and tachycardia (an abnormally fast heartbeat)." The effects of ALDH2 gene status on response to alcohol have been likened to those of disulfiram (Antabuse™), a drug therapy used to encourage abstinence in alcoholic persons. Not only are the physiological responses very similar, so too are the acting mechanisms - both inhibit the metabolism of acetaldehyde.

"This effect is so strong that people who have two copies of the ALDH2 allele (homozygous)," said McCarthy, "were not able to be included in our study. There is some risk involved in their ingesting even the relatively small amounts of alcohol included in this type of study. The effect is more modest for individuals with one ALDH2 allele (heterozygous), although the physiological response is still pronounced."

The study found that a genetic factor such as ALDH2 status appears to influence what people learn about the benefits of drinking. In particular, the ALDH2 gene appears to work as a protective factor for men by reducing high-risk expectancies. In other words, a genetic factor (such as ALDH2 gene status) affects a physiological variable (alcohol response), which affects alcohol expectancies (learning), which in turn enhances/diminishes risk.

"These findings are important," said Smith, "both for the specific reason that genetics appear to influence learning, and in this case reduce risk, and for the more general reason that they show us the value of integrating what have, historically, been two different fields of study within the alcoholism world."

"Our prior research had found support for the hypothesis that having ALDH2 alleles altered expectancies," said McCarthy. "The goal of the present study was to test how ALDH2 affects expectancies. It is only recently that people have started to look at physiological variables and how they might shape learning and expectancies. Here we tested a physiological mechanism by which ALDH2 status could affect expectancies - through its effect on level of response to alcohol. That the data supported this hypothesis implies that ALDH2 status directly affects expectancies because of the effect it has on level of response to alcohol."

McCarthy noted that the gender differences in both this and the previous study provide interesting hints as to how this process may differ for men and women. Both found ALDH2 status to be related to expectancies for women. This study, however, indicates that this relationship may not be due to ALDH2's effect on alcohol response for women, as it appears to be for men. McCarthy said this is the kind of finding that raises several more questions. For example, does this difference mean that men's level of response to alcohol is more likely to determine what they learn about alcohol? Or that women are more influenced by other factors such as parental modeling of alcohol use? Both he and Smith recommended more intensive research of women.

"There are only a handful of studies demonstrating how a genetic factor can set the stage for what we learn," said McCarthy. "Yet knowledge of genetic factors related to alcoholism risk is steadily increasing. As it does, it becomes important to understand not just what factors are related to alcohol behavior, but how they affect this behavior. This type of study illustrates that genetic influences are part of a larger biopsychosocial process. People are just beginning to understand the way genes affect us; that they can act by making physiological changes, which in turn might influence psychosocial factors in our lives. This model can be seen as a first step in understanding the mechanisms by which a genetic factor can translate into a disorder such as alcoholism."
Co-authors of the Alcoholism: Clinical & Experimental Research paper included: Tamara L. Wall of the Department of Psychiatry at the University of California, San Diego and the Veterans Affairs San Diego Healthcare System; Sandra A. Brown of the Departments of Psychiatry and Psychology at the University of California, San Diego and the Veterans Affairs San Diego Healthcare System; and Lucinda G. Carr of the Indiana University Medical Center.

The study was funded by the National Institutes of Health.

Alcoholism: Clinical & Experimental Research

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