Psychology and the NIAAA Research Agenda

In 1970, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) was created to investigate causes and prevention and treatment approaches to the biomedical and behavioral dimensions of alcohol abuse and alcohol dependence. Today NIAAA funds 90 percent of the alcohol research in this country and supports more than 700 grants to scientists in universities, medical schools, hospitals, and other institutions throughout the United States.

Alcohol research strives to understand the factors contributing to the vulnerability to alcoholism. Another major focus of our research is the improvement of current treatment approaches, for example through treatment matching and pharmacotherapy.

Genetic Components of Alcohol Abuse

Twin studies and adoption studies (of infants born to alcoholic parents but adopted into nonalcoholic families) have shown that genetic risk factors can contribute to alcohol abuse. To identify these risk factors, NIAAA has initiated a study called COGA (Cooperative Agreement on Genetics of Alcoholism), which now is taking place in seven research centers. This multidisciplinary study encompasses population genetic — the collection of pedigrees of families with alcoholism — as well as molecular biology to uncover genes that are involved in the heritable portion of the vulnerability to alcoholism.

Two approaches are being used to identify genes that predispose to alcoholism. One is the candidate gene approach, in which an educated guess is made as to which genes might be responsible, based on our understanding of the disease. The second approach involves a thorough search of the whole genome with molecular markers, without proposing specific candidate genes.

The first two years of COGA were devoted to reaching a consensus about the diagnostic instruments for measuring alcoholism. This is important because without a clear distinction of who has the disease and who doesn’t, all the biochemical analyses are of little value. COGA is now in its sixth year and will continue for another four.

Animal Research

The alcohol field is probably ahead of most others in the use of animals for genetic research. Animals have been bred to exhibit, in a predictable fashion, extremes of responses to alcohol. Most important are animals displaying extremes of preference for alcohol. Other alcohol-related traits selected for study with animal model include sensitivity to hypothermia, sensitivity to withdrawal seizures and narcosis. The hope is that by studying behavioral traits in animal and linking them to the genetics or to the chemistry of the brain, we also will learn more about the genes that contribute to the vulnerability to alcoholism in humans and about the disease itself.

NIAAA’s animal research portfolio also emphasizes a powerful new technology, the study of quantitative trait loci (QTL’s). QTL’s are collections of genes that contribute to a condition such as alcoholism, although none of these genes alone is sufficient to cause the disease. Because of recent advances in genetic mapping techniques we are now able to locate and study at lea t those genes that have a prominent role in alcohol depen­dence. We hope to expand these analyses to human studies as well.

Although the genetic studies in humans and animals focus on biochemical analyses, psychologist play a major role in their design and evaluation by providing precise definitions of the behaviors under study. Without this kind of precision, the links between behavior and genetics or neurochemistry cannot be established.

By defining the genetic side of a predisposition to alcoholism we begin to hone in on the environmental side as well, because the two aspects are complementary. One of the fundamental questions that alcohol researchers now face is, how do genes and environment combine to produce the vulnerability to alcohol dependence? The answers to this question will have significant implications for treatment.

Patient-Treatment Matching

Contemporary alcoholism treatment did not develop from the mainstream of medicine or professional health care. Therefore, methods of rigorous treatment assessment, which have long been standard in other areas of medicine, have been applied to alcoholism treatment only in the last 10 or 15 years. These methods include use of controls, blind studies, randomized design, placebos (in pharmacological studies), rigorous definition of outcomes, and attention to the validity of the measurements used.

Until relatively recently, patients entering treatment programs were offered a smorgasbord of treatment options that were added over the years as fashions in treatment changed. NIAAA now is investigating whether, by a precise description of patient characteristics and a precise enunciation of what treatment components consist of, we can match patients to specific modalities so that treatment will become more effective and less costly.

Our major study to determine the effectiveness of patient-treatment matching is Project MATCH. In this multi-site controlled clinical trial, patients are randomly assigned to one of three different categories of verbal therapy: 12-step facilitation, cognitive-behavioral coping skills therapy, or motivational enhancement therapy. Alcohol and other drug use, psychosocial functioning, and other patient characteristics were evaluated both before and at three-month intervals during the 12 months after treatment. We now have 1,700 patients enrolled at nine research sites. The program will be completed late this year, and prelimi­nary results of the study should be available by the end of 1995.

Psychologists have played a key role in much of the design and the implementation of Project MATCH. The field of psychology also has made major contributions to the develop­ment of the statistical techniques that will be used for our analyses of the e data.

Pharmacotherapy

In addition to the evaluation of various verbal therapies, IAAA sponsors studies on pharmacotherapy. Using findings from neuroscience, these studies attempt to determine which medications might help lessen the craving for alcohol. Craving is characteristic of abstinence, and the discomfort of craving often causes or precedes relapse. Studies of the opioid antagonist naltrexone, for example, have shown promise for reducing craving. Of equal importance to the merits of this particular medication is the fact that these studies represent the beginning of a new era in alcohol treatment in which we can learn how to combine both psychological and pharmacological therapy effectively.

Brain Research

Another important area of research, both in NIAAA’s intramural and extramural programs, is the study of alcohol-induced defects in memory and abstraction. Neuropsychology has been a major contributor to this line of investigation. Recently such studies have been augmented with research which focuses on neuroimaging and neurochemistry. An interesting question now being pursued in our intramural program is whether craving is related to any of the defects in memory and abstraction. Since the definition of and mechanisms leading to craving are relevant to all addictions, this area is becoming increasingly important.

The Future of Alcohol Research

In 1992 and 22 years after its creation, NTAAA formally became a part of the National Institutes of Health (NIH). The move to NIH brought new attention to an important issue in alcohol research and in contemporary science in general; that is, whether a reductionist position in biology is justified. The extreme reductionist’s position implies that every important facet of biology, whether physiological or behavioral, ultimately can be explained by the individual’s genetic sequence. Genetic studies obviously have a high priority at NIH and, in view of their importance and recent triumphs, well they should. On the other hand, I doubt that all the aspects of higher organisms ever will be predictable solely on the basis of the nucleotide sequence. I believe that higher levels of organization, such as brain functions or behavior, have properties that are influenced heavily by genetics but are not completely predictable from the genome and are influenced as well by random environmental events.

For the most productive way to understand the vulnerability to alcoholism, both genetic and non-genetic avenues of science should be supported and made attractive to young investigators, because they will illuminate each other. Only the precise study of a behavior can enable the geneticist to find its molecular basis. Conversely, genomic analyses will identify genes whose function is unanticipated and will undoubtedly shed new light on the higher levels of organization. I believe that when genes for the vulnerability to alcoholism are discovered, we may be in for exciting surprises that eventually will lead to the development of new approaches in prevention and treatment.