Alcoholism: Genetics or the Environment?

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Alcoholism: Genetics or the Environment?

It's an alcoholic rat's dream. Instead of stepping up to the bar in a dimly lit establishment and plunking down a couple of bucks like his human counterpart, a rat simply has to scurry over to a corner of his cage and bar-press for his alcoholic buzz.

Depending on the experiment, rats will work for varying concentrations of alcohol -- often until they become so intoxicated they can't move.

And although the rats couldn't care less, they are actually a very important factor in unraveling the genetic and environmental causes of alcoholism in humans. It is generally agreed among researchers from both the medical and social sciences that the risk for alcoholism is determined by an intricate relationship between genetic and environmental factors. But which factors carry the most weight, for whom and why, are still questions without precise answers.

The Cost of Alcoholism

It is clearly important to find out the reasons why 15 million Americans are alcoholics. Alcohol abuse is responsible for three percent (about 100,000) of all deaths in the United States each year, including deaths caused by traffic accidents, health complications, birth defects, violence and crime. Fifty percent of all traffic fatalities are alcohol related, as are 38 percent of all drowning deaths and 50 percent of all homicides. Accidents are the leading cause of adolescent death, taking 25,000 lives annually. Forty percent of those accidental deaths are connected to alcohol.

Although we can't put a dollar sign on a human life, we can count on spending almost $150 billion in 1995 because of alcohol abuse and alcoholism. The costs that we all pay include monies for health care, insurance payments, lost employment and decreased productivity. The big picture is certainly enough to give the whole nation a king-sized hangover.

What is Alcoholism?

For many years there has been a debate over the definition of alcoholism. At stake is not just an entry in a medical reference book, but millions of dollars earmarked for a bona fide "disease," a tag some say doesn't fit. On an individual level, the social stigma of alcoholism can be staggering. If alcoholism were designated a biological factor instead of a character flaw, perhaps some of us might be more willing to accept the problem and then work toward solutions and treatment.

As early as 1960, Dr. E.M. Jellinek, one of the founders of the National Council on Alcoholism, called alcoholism a chronic illness, a biochemical sensitivity to which personality and social factors contribute. Since then, the description has changed repeatedly, based upon new knowledge and social perspectives. Generally, the newer definitions of alcoholism call it a disease with biological and psychological factors, taking into account genetic vulnerability, environmental considerations and behavioral changes.

The Chemistry of Alcohol

It is important to know something about the way ethanol (alcohol) works before any debate about biological or environmental causes can be argued. Ethanol dissolves into both fats and water, a characteristic that allows it to interfere with membrane function, neurotransmitter receptors and the normal operation of the ion channels. Ethanol also plays games with calcium and chloride, as well as with gamma-aminobutyric acid (GABA), the brain's main neurotransmitter. All these factors contribute to alcohol's depressant effect.

One complication, according to Walter A. Hunt, a neuroscientist with the National Institute on Alcohol Abuse and Alcoholism (NIAAA), is that "convincing evidence is lacking for a direct causal relationship between any specific biological change induced by ethanol exposure and a specific behavioral or physiological response to ethanol ingestion. Very little of the information has led yet to an understanding of the social problems accompanying alcohol abuse and alcoholism."

Unlocking the Mysteries of a...Disease?

Unanswered questions don't help the millions who are dying from cirrhosis of the liver, experiencing emotional disorders and encountering alcohol-related violence because of what, in days of more colorful language, was called "the devil's brew." Nor do they ease the concerns of the children of alcoholics, for whom the question of how much heredity contributes is crucial. But ongoing studies are getting closer and closer to unlocking the mysteries surrounding this disease.

Dr. Ting-Kai Li, distinguished professor of medicine and biochemistry with the Indiana University School of Medicine, Division of Endocrinology and Metabolism, has bred lines of alcohol preferring rats (P) and nonpreferring rats (NP) in order to study abnormal alcohol-seeking behavior. According to Dr. Li:

If you start with a very low concentration of alcohol, both P and NP animals will like it because it is a little sweet. Raise the concentration, and it becomes much less palatable. But preferring rats will keep working for it. They'll bar-press for it, which is important to show alcohol is rewarding. If they have to bar-press 5, 10 times, they'll do it. They'll do it thousands of times a day and at concentrations as high as 30 or 40 percent. Of course, as you go higher, their rate of response decreases because their blood alcohol content is higher and they are physically less able to respond.

We believe the most compelling data indicate that animals do it (consume ethanol) for its pharmacological effects, and not because of its taste, smell or caloric properties.

Dr. Li and his colleagues also determined that P rats develop physical dependence with chronic free-choice drinking. By using such tools as condition taste aversion tests, Dr. Li's team also showed that P rats were less sensitive to the aversive effects of alcohol. These neuropharmacological studies with P rats add credence to the theory of heredity-caused alcoholism. Researchers hope their work will lead to prevention measures (through early identification of potential alcoholics) and new medications for the treatment of alcoholism.

Genetically Speaking...

"Nobody believes alcoholism is purely a genetic disorder," however, notes Dr. Henri Begleiter, a professor of psychiatry at the State University of New York, Brooklyn, who is conducting an international project, funded by the NIAAA, studying heredity and alcoholism. "Everyone believes it is a combination, an interaction of genetics and environment. That is very much the case with diseases like hypertension, diabetes and cancer, and alcoholism is very much like those diseases."

No one has been able positively to identify a specific gene that might be the one solely responsible for alcoholism. Dr. Begleiter believes, instead, that there is "more likely a set of genes that are responsible for a variety of behaviors of which alcoholism is a part. But who would deny that the search for a gene is in fact simpler than the search for environmental factors? You have to start somewhere." The Collaborative Study is currently gathering data on the hereditary aspects of the disease by creating a blood-cell bank from known alcoholics and their families.

Over the years, twin and adoption studies have been carried out to help explain the causes of alcoholism. There are reports of separated twins both becoming alcoholics even when one was brought up in a stable, nonalcoholic adoptive family. Identical twins share 100 percent of their genes, while nonidentical twins share 50 percent. The risk for alcoholism is significantly higher for the identical twin of an alcoholic than for the nonidentical twin of an alcoholic, indicating the importance of a genetic factor. Adoption studies have also identified two kinds of alcoholism. Type I appears to be more influenced by environmental factors in genetically susceptible people, while Type II is significantly unaffected by environment but greatly affected by genetics.

The latest round of genetic studies, meticulously researched, according to Dr. Begleiter, provides even more compelling data about the importance of the genetic link in alcoholism. "We are now learning, for example, that there is a strong genetic component in women, that they are equally as high at risk for alcoholism as men," he says.

Other genetic markers of inherited vulnerability include characteristic electrical activity measured by electroencephalography (EEGs) in alcoholics and their children and characteristic levels of certain enzymes, such as monoamine oxidase (MAO) and adenylate cyclase (AC).

One of the most recent and controversial reports has been the work of Dr. Kenneth Blum, professor of pharmacology and Chief, Division of Addictive Diseases, at the University of Texas Health Science Center. Dr. Blum and his associates believe they have found a linkage between the A1 allele of the human dopamine D2 receptor gene and susceptibility to alcoholism. This variant of the D2 receptor, which is related to the brain functions of motivation and reward, is said to be present more often in alcoholics than in nonalcoholics.

Dr. Blum has suggested that an abnormality in the gene may cause susceptibility to at least one subtype of alcoholism. "But there has been a disbelief that we could take such a complicated problem of alcoholism and find one gene that could be associated with [it] at such a high rate," says Dr. Blum.

"The dopamine D2 receptor is highly controversial," says Dr. Begleiter. "Half of the people [doing evaluation] see it; half don't. And many of the studies that have found it have not been replicated. It's very, very troublesome and the full story is not in yet."

Dr. Blum contends also that alcoholism is "a compulsive behavior" and is associated with other substance abuse, nicotine abuse, obsessive carbohydrate consumption and pathological gambling. Although there is disagreement about specifics, if genetics proves to be a significantly stronger determining factor of alcoholism than environment, most researchers agree that science will take a giant step toward controlling alcoholism.

"The biggest problem is denial," said Dr. Blum. "But if we can show someone the gene and say, `Here it is and you have to be more careful about drinking than someone else,' then that's important." He also believes genetic screening eventually could be possible to allow parents to determine if their children would be predisposed to alcoholism. Prevention and cures will be developed, he hopes, through genetic knowledge.

There are, however, real concerns about the possible future misuse of the information that genetic research may uncover. Dr. Begleiter says it would be possible, for example, for insurance companies or employers to discriminate against those who carry the "alcoholic gene." But he emphasizes that the benefits of such knowledge would undoubtedly outweigh any negatives.

Genetic and Environmental Interaction

Despite the strong arguments for the genetic link, environmental factors such as sociocultural norms that contribute significantly to the social use and abuse of alcohol can't be ignored. There are many situations in which the consumption of alcohol is strongly entrenched in an ethnic or religious environment, making the drug readily available and at the very least giving an individual more of an approved opportunity to use and abuse it. Peer pressure to drink, especially among teens and young adults, can be highly influential as well. Stress and life events can have an influence on drinking, which is no surprise to anyone who, after a hard day, collapses in a chair and says, "I need a drink."

Studies in England examining new admissions to an alcohol clinic showed that men often attributed their drinking patterns to involvement in a social network of coworkers. For the most part, the men's drinking was not related to a specific mentally or physically challenging event. It was simply a lifestyle choice. Women, however, said their increased abuse was caused by a particular, distressing event or was a general coping method. They cited such things as divorce or separation, the death of a baby, the death of a spouse or close relative or infertility as reasons for abusing alcohol.

Another recent study, conducted by the National Crime Victims Research and Treatment Center at the Medical University of South Carolina, has shown that women who have been physically assaulted have an increased risk of becoming alcoholics. Post-traumatic stress disorder may also lead to alcoholism, according to the report.

In addition, studies on the genetic and environmental influences on the lifetime alcohol-related problems of older twins completed by the Medical College of Virginia's Department of Psychiatry and reported in the March 1994 issue of the Journal of Studies on Alcohol concluded: "All behavior (including alcoholism) develops in an environmental context, and altering the environment in which genetically influenced behavior unfolds can change the course of that development."

"Drunkards beget drunkards," said the Greek moralist Plutarch.

If only the answer were that simple.

American Council on Science and Health, Inc.

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By Jill Sell

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