Bridging the gap between genetics and motivations to drink alcohol

January 14, 2004

Alcohol researchers already know that people who expect positive results from drinking - a better mood or social ease - are more likely than other drinkers to develop alcohol problems. Conversely, those who have negative expectations - queasiness, dizziness or fatigue - are less likely to develop alcohol problems. A study in the January issue of Alcoholism: Clinical & Experimental Research has found that a person's genetic makeup may influence their motivation to drink, which can, in turn, enhance behaviors that increase the risk for alcoholism.

"We were interested in learning if beliefs about alcohol provided a partial explanation for how risk for alcoholism is transmitted across generations," said Carol A. Prescott, associate professor of psychiatry and psychology at the Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, and first author of the study. "This transmission could be either environmental, in that young adults model the drinking behavior and motivations of their parents, or through genetic mechanisms, meaning there are physiological reasons alcohol is perceived as more pleasurable by some people and this is transmitted from alcoholic parents to their offspring via genes. For example, we know that people with a family history of alcoholism are more likely to have positive expectations and less likely to have negative ones."

"Although there is much consensus that alcohol abuse and dependence are caused, in part, by genetic factors, there is less certainty concerning what is inherited and how that genetic vulnerability is manifested," added Kenneth J. Sher, Curators' Professor of psychological sciences at The University of Missouri and the Midwest Alcoholism Research Center. "Drinking motives represent a possible genetic mediator of alcoholism risk in multiple ways. For example, if genetic variability predisposes someone to experience greater neuropharmacological reward from alcohol, it could lead to stronger motives to drink for positive reinforcement. Furthermore, genetic vulnerability to depression or anxiety or depression could serve as the foundation for drinking to alleviate negative mood states. Thus, the current study attempts to answer the question of how genetic risk might be related to the various reasons individuals report for why they drink."

Prescott and her colleagues examined data gathered from 2,529 female and 3,709 male adult twins participating in the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. "The data from twin pairs are used to estimate the degree to which individual differences can be attributed to differences among people in their genetic, family environmental and individual-specific environmental causes," explained Prescott.

The researchers used four scales to measure individual differences in drinking motives: drinking to manage mood states, to relieve social anxiety, in social situations, and to improve mental functioning. They also determined lifetime alcohol abuse and/or dependence among the study participants through use of a structured interview that used criteria from the Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition.

"The findings contribute to our understanding of how genetic risk results in alcoholism," said Prescott: "It has long been known that alcoholism runs in families. Twin and adoption studies in the past 20 years have shown that this familiality is in large part due to genetic factors shared by family members. But we don't know very much about how differences among people in their DNA sequences result in differences in risk for drinking problems. This study provides evidence that one way in which genetic factors lead to alcoholism is that genetic factors influence drinking motives, in particular, drinking to alleviate social anxiety. Although motives are still a long way from DNA, they are one step closer to the biology than the clinical disorder of alcoholism."

Prescott noted that there are several ways in which genetic factors may 'intersect' with social drinking. "There is an overlap of the genetic factors which influence risk for alcoholism and those which influence drinking to relieve social anxiety," she said. "Also, alcohol works on the brain in a way quite similar to anti-anxiety drugs, and there are genetic influences on how these drugs affect brain receptors. In addition, personality characteristics such as the need for social stimulation and 'risk taking' are in part inherited. People with these personality traits may be more likely to seek social activities which involve drinking and this in turn increases their risk for alcoholism."

"I think the 'bridging' of genetics and human motivation to drink is critical in understanding how distal genetic influences manifest themselves in variables that are known to be proximal to drinking," said Sher. "Presumably, there are many intermediate links between genes and self-reported motivations to drink, and drinking motivations are undoubtedly closer to the alcohol-use disorder phenotype than to upstream links in the mediational chain such as specific gene products and neuronal receptor function. However, given that the question of whether genes are important has largely been answered, we need to keep refining the question of how they are important and the current study is significant in this regard."

"It's important to note that our results don't prove that motives are causal, only that they are consistent with a causal explanation," said Prescott. "Nonetheless, these findings have important implications for intervention. These results, in combination with others, suggest that drinking motives may have a causal influence on alcoholism. If so, this provides an important point of intervention among individuals at high risk. Motives can be measured prior to the development of drinking problems, and at-risk individuals can be taught strategies for reducing their social anxiety other than using alcohol."

"In my opinion, there are at least three major issues that future research needs to address," said Sher. The first involves improving the measurement of drinking motives, which currently uses self-reports. Yet humans are highly fallible reporters on the question of why they do various things." Sher called the use of "electronic diaries" within natural environments a promising option. "The second issue concerns how drinking motives change over the development and course of alcohol-use disorders across the life span. For example, in our own research we've found that alcohol expectancies influence subsequent drinking, but are also affected by prior drinking. Given the reciprocal nature of the relation between drinking and motivation, the success of any cross-sectional approach to elucidate the interrelationships of gene, drinking motives, and alcohol-use disorders will be limited. The third issue involves the use of molecular approaches. We are only now beginning to examine how allelic variations in specific genes are related to alcohol expectancies and alcohol effects; eventually, we may better understand how genetic variability is manifested in individual differences in alcohol response and how this influences an individual's drinking."
Alcoholism: Clinical & Experimental Research (ACER) is the official journal of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism. Co-authors of the ACER paper included: Rebecca J. Cross of the Department of Hematology/Oncology at Weill Cornell Medical College; Jonathan W. Kuhn and Kenneth S. Kendler of the Virginia Institute for Psychiatric and Behavioral Genetics in the Department of Psychiatry at Virginia Commonwealth University; and John L. Horn of the Department of Psychology at the University of Southern California. The study was funded by the National Institutes of Health.

Alcoholism: Clinical & Experimental Research

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