Through the Times With Marc Schuckit, M.D.

Psychiatric Times

October 2005

Vol. XXII

Issue 11

The complex nature of genetic and environmental influences in alcoholism has intrigued Marc Schuckit, M.D., for 40 years. Schuckit, distinguished professor of psychiatry at the School of Medicine at the University of California, San Diego (UCSD), and the San Diego Veterans Affairs Hospital, was a member of Psychiatric Times' first editorial board and one of its first columnists, often writing about alcohol and other drugs. He also was among the first presenters at the U.S. Psychiatric & Mental Health Congress. In 2000, John Schwartz, M.D., Psychiatric Times' founder, presented him with a Lifetime Achievement Award for his "exemplary career as an outstanding innovative researcher and extraordinary teacher."

Much of that career has centered on understanding the genetics of alcoholism susceptibility and protection, identifying relevant environmental factors, and training clinicians to recognize and treat substance use disorders. At the San Diego VA Healthcare System, Schuckit directs the Alcohol Research Center and the Alcohol and Drug Treatment Program where he supervises residents, medical students and staff. Additionally, he serves as a major contact person regarding alcohol and drug problems for the faculty and staff at UCSD and the San Diego VA. From 1989 to 1994, Schuckit chaired the DSM-IV substance disorders work group and has published papers about the optimal diagnostic criteria for substance use disorders.

Schuckit's interest in psychiatry and substance use disorders began early.

"As a kid in high school, I always liked to hear peoples' stories. So I read novels, and people seemed to like to talk to me about their problems," Schuckit said. "I seemed to have some decent common sense in helping people solve their problems, so it was natural once I decided to go to medical school that psychiatry would be one of the things I would want to do."

After receiving his bachelor of science degree from the University of Wisconsin, he enrolled in Washington University's Medical School in St. Louis, in 1964.

"When I was deciding to go to medical school, I picked the school that had the best reputation and gave me the highest scholarship. By pure luck, I picked the only school that was doing solid, evidence-based research psychiatry. There may have been some other schools doing it, but I didn't know of them. Had I gone to another school, maybe I wouldn't have gone into psychiatry, because other approaches are not as challenging and rewarding to me," Schuckit said.

Other lucky coincidences were Schuckit's first jobs in medical school. Schuckit was hired by sociologist Lee Robins, Ph.D., who was conducting a follow-up study on 30-year-olds who had been in school in St. Louis. Schuckit started interviewing participants, and he found that substance use disorders were very prevalent in that age group.

"I got interested in [studying] alcoholism and drug dependency. Lee Robins was very kind and let me develop a paper using some of the data that were coming through. The paper got accepted, so now I was really hooked on the area. I found it fascinating," he said.

His second job was with a researcher studying the relationship between depression and alcoholism in families.

"By my second year in medical school, I recognized that not only was I happy with the thought of going into psychiatry, but also that it was highly probable I would go into research," Schuckit explained. "Once I had decided on research, why not do it in the area I knew most about? And I have never turned back since I graduated."

Schuckit credits several mentors with helping him progress in his career.

"I happened to have mentors who were not only good at what they did, but they were lovely human beings who cared about my development," he said. Robins helped him discover his love of research, while her husband, Eli Robins, M.D., chairperson of the psychiatry department at Washington University at the time, helped him develop several papers. Two other mentors were George Winokur, M.D., who got Schuckit interested in genetics, and Donald Goodwin, M.D., "one of the best scientific writers" Schuckit ever met, who helped him become "a clear writer."

After Schuckit graduated from medical school, he interned at Cedars Sinai Medical Center in Los Angeles and then returned to Washington University's Renard Hospital for his residency, finishing at UCSD.

From 1972 until 1974, he served in the Navy and was special assistant to the commanding officer of the Navy Medical Neuropsychiatric Research Unit in San Diego. Following his military service, he was an assistant professor of psychiatry at UCSD and chief of the Psychiatric Liaison Service at the VA. Then, he became the first director of the Alcohol and Drug Institute at the University of Washington in Seattle, before returning to San Diego in the 1980s.

Research Steps

Asked to describe his past and current research, Schuckit said it was a series of steps.

"The first step, which occurred in medical school and residency and which led to what I am doing now, was to ask whether alcoholism was genetically influenced. So I looked at children of alcoholics who weren't raised by their biological alcoholic fathers. I found that whether they had any contact with that alcoholic father or not wasn't nearly as important as the fact that their biological father was alcoholic; it was the genes that were likely to be contributing to the risk rather than the childhood environment," he said.

When he was in the Navy, Schuckit conducted some studies looking at how to identify people at high risk for alcoholism. He developed approaches to gathering data from participants with a positive family history.

"I started to play around with the idea that some people react to alcohol differently ... than other people and that the quality of the reaction to alcohol early in your career of drinking might have an impact on whether you drink a lot," he added.

After he left the military, Schuckit began asking patients at UCSD whether alcohol impacted them in a special way early in their drinking careers. To his surprise, most of them reported that alcohol did not do much for them early on, and they could drink everybody else under the table.

Those comments prompted Schuckit to create the theory that he and colleagues have spent many years studying. He explained, "If you drink for the effect that you want when you are a teen-ager, and if it takes more alcohol to get to that effect, you are going to drink more. And when you drink more, your body is going to develop tolerance to alcohol, you are going to hang out with other people who are drinking more and you are going to get into an environment that is encouraging heavy drinking."

In 1978, Schuckit and colleagues began studying 20-year-old men, some of whose fathers were alcoholic, investigating how the sons responded to alcohol. None of the young men were alcohol-dependent at the initiation of the study, but all had some experience with alcohol. Over a 10-year period, 453 men entered the prospective study.

"We gave people the equivalent of about three drinks. It was on a per-kilogram basis, so everybody would get to the same blood alcohol level. Through this experiment, we would then compare at the same blood alcohol level, people who had an alcoholic family history with people who didn't have an alcoholic family history. We found that the people who had an alcoholic parent showed less feeling of intoxication, fewer brain wave changes with intoxication at a given blood alcohol level and less motor performance deterioration. In other words ... they were showing not very much effect at the lower doses of alcohol," he said.

Overall, about 40% of the sons of alcoholics showed low levels of response to alcohol. Then, the question became does the low level of response to alcohol help predict who might become alcoholic-dependent.

"In about 1988, we started to follow up the people we had originally tested in 1978; in 1989, those we had tested in 1979, and so on," Schuckit said. "We found that if they didn't respond very intensely to alcohol when they were 20 years old, they had about a four-times increased risk for developing alcoholism when they were 30" (Schuckit, 1998).

Schuckit and his colleagues then started searching for genes that may contribute to the low response to alcohol. They also studied the original participants and their children to see what in their lives beyond low levels of response relates to their increased risk for alcoholism.

"For example, if you have a low response and have higher life stress, do the two combine to increase your risk? Does having a lot of social support in your environment help diminish the risk, despite the fact that you are a person who requires more alcohol for effect," he said.

Schuckit and colleagues have put into computer models how the level of response to alcohol correlates with and interacts with environmental factors, which account for about 40% to 50% of the risk. They are seeking to not only find the genes contributing to the level of response as a risk but also to determine how the response level interacts with environmental factors to actually produce alcoholism.

They looked at measures of a low response that can be used in adolescence at a time close to the first drinking experience and that do not involve an alcohol challenge. They developed the Self-Rating of the Effects of Alcohol (SRE) Questionnaire. The instrument contains questions related to the number of drinks required for up to four different effects (feeling signs of intoxication or developing a "buzz," slurring speech, stumbling gait, or falling asleep when not wanting to). When the SRE was used with the teen-agers, they were asked to only report drinks for actual effects experienced during the first five times of drinking ("first five" score). A drink was defined as the equivalent of approximately 10 g of ethanol (i.e., a single 12-oz beer, 4 oz of wine or 1.5 oz of 80-proof beverage). In a study published last January, Schuckit et al. (2005b) used the SRE with 487 teen-agers ranging in age from 13 to 19 as a measure of low response. It was part of their genetic analysis.

Most recently, Schuckit et al. (2005a) used data on 1,106 12- to 13-year-old kids who were evaluated in person as part of the Avon Longitudinal Study of Parents and Children. Among those young teen-agers, 80 (7.3%) reported ever having consumed at least one standard drink. Information about their alcohol and other substance use and problems was obtained using a structured interview and low level of response as assessed by the SRE questionnaire.

"The study had to do with a very simple question," said Schuckit. "The question is: At age 12, if you have a low response to alcohol on this questionnaire, do you drink more?" The answer was yes.

The researchers concluded that among the 80 young teen-agers, a low level of response (or the need for more drinks to achieve an effect) correlated best with the maximum number of drinks they ever consumed and had more modest, but still significant, correlations with the drinking frequency over the prior six months and the number of alcohol problems ever experienced.

While Schuckit has focused on a low level of response to alcohol as a risk factor for alcoholism, other researchers are exploring different characteristics that may be genetically influenced.

"In some families, what is being inherited is impulsivity that is increasing the risk for alcoholism, drug dependence, gambling and violence. In other families, there is no increased impulsivity, yet there is alcoholism, and it is probably related to the level of response to alcohol," he said. "What I study, and the genes that I am going to find related to the low response as a risk factor for alcoholism, probably have nothing at all to do with impulsivity. Then, there are genes that relate to how you metabolize alcohol, which have not very much to do with what I am studying and have nothing to do with impulsivity, but do affect the alcoholism risk, and so on."

The long-range implication of his own and others' research on the genetics of alcoholism, Schuckit said, is prevention. If he can find a characteristic that increases the alcoholism risk and then study people who have that characteristic but do not become alcoholic, he could possibly determine what in their environment protects them.

In recognition of his many contributions to research, Schuckit has received numerous awards, including the President's Award from the American Psychiatric Association in 1972, the Distinguished Scientist Award from the Research Society on Alcoholism in 1993, the Middleton Award in 1997, and the Lifetime Achievement Gold Medal Award from the Society of Biological Psychiatry, presented this year.

Beyond Research

Expressing his ideas about training, Schuckit said that one major step toward increasing the diagnosis and treatment of individuals with alcoholism is "to train physicians, nurses, psychologists and other clinicians that their stereotype of what the alcoholic is, is dead wrong."

For example, he explained, the lifetime rate for alcoholism among male graduates of medical schools is roughly the same as for males in the general population, only the graduates are somewhat more functional.

Another aspect of training, he said, is enhancing the clinician's awareness of needing to screen for alcohol and drug dependence in every patient or client who walks into the office.

The diagnosis of alcoholism rests with a good clinical history, according to Schuckit, who noted "There are very good criteria from the DSM or from the ICD ... Just as clinicians know how to diagnose pneumonia and to identify a urinary tract infection, they need to be aware of the substance use disorder criteria as part of their screening," he added.

Schuckit also called for clinicians to incorporate into their screening a 10-item, self-administered questionnaire, the World Health Organization's Alcohol Use Disorder Identification Test (AUDIT), which asks people about life problems related to alcohol and drugs (National Institute on Alcohol Abuse and Alcoholism, 2005).

Lastly, Schuckit hopes clinicians will recognize that there are blood tests that are state markers of heavy drinking. These include γ-glutamyl transferase (GGT) and the carbohydrate-deficient form of transferrin (CDT). These blood tests can identify values that, while still often within the normal range, are high enough to raise the suspicion that an individual might be drinking six or more drinks per day on a regular basis.

Three of Schuckit's books pertain to educating health care professionals and the public about substance use disorders. They are Marc Schuckit's Lectures on Alcohol and Drugs for Health Care Professionals: Instructor's Guide (1998; Addiction Technology Transfer Center of New England); Drug and Alcohol Abuse: A Clinical Guide to Diagnosis and Treatment, Sixth Edition (forthcoming in 2006; Springer) and Educating Yourself About Alcohol and Drugs: A People's Primer (1995; Plenum Press).

Beyond his books, Schuckit has written many book chapters and more than 500 journal articles. He also is the editor of the Journal of Studies on Alcohol and member of the editorial board for several journals, including Addiction and Drug and Alcohol Review.

Even though he juggles many psychiatric and academic pursuits, Schuckit gives top priority to his wife, Judy, and his adult children, Jordan and Dena.

"I was fortunate to always have a wonderful wife who helped me put things into perspective," he said. "There are the real important things in life--your family and the other people you love--and then there are the other important things in life. It has always served me well to try to keep things in that order."

References

National Institute on Alcohol Abuse and Alcoholism (2005), Helping Patient Who Drink Too Much: A Clinician's Guide. Available at: www.niaaa.nih.gov. Accessed Aug. 22.

Schuckit MA (1998), Biological, psychological and environmental predictors of the alcoholism risk: a longitudinal study. J Stud Alcohol 59(5):485-494.

Schuckit MA, Smith TL, Beltran I et al. (2005a), Performance of a self-report measure of the level of response to alcohol in 12- to 13-year-old adolescents. J Stud Alcohol 66(4):452-458.

Schuckit MA, Smith TL, Danko GP et al. (2005b), Evaluation of a level of response to alcohol-based structural equation model in adolescents. J Stud Alcohol 66(2):174-184.