Alcohol: The Genetic Puzzle (3 of 3)

What about other drugs?

Do the same genetic relationships demonstrated in the alcohol adoption studies prove true for other drugs? Was it conceivable that heroin addiction or cigarette smoking could be traits (disorders, really) that men and women inherited?

“There have been a number of animal studies showing genetic differences in sensitivity to nicotine,” said Dr. Neal Benowitz of the Clinical Pharmacology Unit at San Francisco General Hospital, one of the nation’s premier nicotine research centers. And Professor Ovide Pomerleau, the Director of Behavioral Medicine at the University of Michigan Medical School, who collaborated with Cloninger’s group on genetic studies of nicotine and alcohol, told me: “Some people are drawn to smoking, and some people are not. Everybody pretty much goes through the same kind of peer pressures, the same kind of socialization pressures, and then you have some people who emerge as smokers, and some people who don’t. Some people who start smoking give it up easily, and there are others who can’t. Well, why? My answer is that I think there are innate differences in susceptibility.” 

The Cadoret group looked into the question and reported in the Archives of General Psychiatry that alcohol problems in biological relatives appeared to correlate highly with drug abuse in siblings. “Some theorists have suggested that multiple addictions to a wide variety of substances constitute evidence against a genetic interpretation of addiction,” wrote Cadoret. “The present data appear to refute that position, suggesting instead some underlying biochemical foundation involved in all of the substances abused….” 

Dr. Janice Keller Phelps, the drug treatment specialist from Seattle, maintained that “a large number of addicted people I have treated over the years had strong family histories of addiction. Time and again I encountered heroin addicts, cocaine addicts, or speed addicts with one or both parents addicted to alcohol, for example, or with one or more brothers or sisters also addicted—though not necessarily to the same drug. It is known and acknowledged that many alcoholics have one or more alcoholic parents; the large number of children of alcoholics who are not alcoholic but instead are addicted to other substances, however, is not so well recognized.”

In many ways, the genetic findings by Goodwin, Cloninger, and others were as far from the old problems-in-living approach, the Freudian approach, as it was possible to get. As Dr. Edward Sellers, who directed the psychopharmacological research program at the University of Toronto’s Addiction Research Foundation during the 1990s, explained to me: “One simplified way of looking at it is that every cell, every hormone, every membrane in the body has got genetic underpinnings, and while many of the genetic underpinnings are similar in people, in fact there are also huge differences. So on one level, the fact that there is a genetic component to addiction is not very surprising. What is surprising is that you could ever have it show up in a dominant enough way to be something that might be useful in anticipating risk.”

If there existed a set of genes that predisposed people to alcoholism, and possibly other addictions, then these genes had to control the expression of something specific. That’s what genes did. 

However, addiction researchers could not even agree on the matter of where they should be looking for such physical evidence of genetic difference. In the brain? Among the digestive enzymes? Blood platelets? A gene, or a set of genes, coding for…what? Substance H? Production of certain neurotransmitters? What was it they were supposed to be looking for?

What set of genes coded for happiness?

Adapted from The Chemical Carousel: What Science Tells Us About Beating Addiction by Dirk Hanson © 2008.

Graphics Credit: http://www.drugabuse.gov

Profiles in Addiction Science

Henri Begleiter and the P3 wave


At the State University of New York’s Health Science Center in Brooklyn, the late Dr. Henri Begleiter, a professor of psychiatry, began investigating the brain wave activity of alcoholics in the early 1980s. According to Dr. Ting-Kai Li, director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA):

“Starting with the ground-breaking finding, published in Science, that some neurophysiological anomalies in alcoholics were already present in their young offspring before any exposure to alcohol and drugs, he proposed a model that changed the thinking in the field: namely, rather than a consequence of alcoholism, this neural hyperexcitability was a predisposing factor leading to the development of alcoholism and related disorders. This innovative study was replicated throughout the world and launched him on a systematic search to elucidate the genes underlying this predisposition.”

People have heard of alpha waves and theta waves, but there are many other brain waves, evoked by various kinds of stimulation. Scientists can now measure electrical phenomena called evoked potentials (EPs), and event-related potentials (ERPs). For example, certain characteristic waveforms occur when the brain reacts to visual and auditory stimuli--when a person sees flashes of light, for example, or hears a clicking noise. As the signal of the flashing light makes its way from the retina of the eye to the cortex of the brain, electrodes placed on the scalp record the nerve impulses.

Begleiter and his coworkers recorded various event-related potentials, using scalp electrodes. The result was a series of sine wave-like printouts measuring amplitude and elapsed time for any given brain wave. The so-called P3 voltage, a measure of reaction time invoked by such stimuli as flashing lights or clicking noises, especially interested the researchers. Prior testing had shown that people suffering from schizophrenia or attention deficit disorder exhibited low P3 amplitudes. When Begleiter’s team tried recording P3 waves, something odd turned up. Diminished P3 waves were characteristic of an overwhelming majority of practicing alcoholics. As it turned out, the same event-related P3 wave abnormalities could be found in recovering alcoholics--even when they had been abstinent for years.

It was left for Begleiter’s team to round up a group of children ranging in age from six to eighteen, all of whom had an alcoholic parent, and all of whom, as Begleiter’s team documented, showed the same diminished amplitude in P3 waves. None of the children had ever been exposed to alcohol before. Nonetheless, there it was: The P3 waves of these children exhibited exactly the same waveform abnormalities as their actively alcoholic parents.

When Begleiter limited the pool of brain scan volunteers to the sons of fathers who had been diagnosed as Type 2 alcoholics, and compared their P3 waves with the P3 waves of a control group, he was able to correctly identify the children of Type 2 fathers almost 90 per cent of the time. Begleiter had discovered an organic impairment in the brains of non-drinking siblings of alcoholics.

Begleiter’s work caught most genetic researchers by surprise. Numerous laboratories raced to replicate Begleiter’s findings--and consistently succeeded. The P3 deficit was verifiable, and repeatable. Addiction researchers sat up and took notice: Here was compelling evidence of a marker for alcoholism; a specific abnormality in the brain which was apparently passed on genetically in alcoholic families.

“Actually, it’s more than just the P3,” Begleiter told me at the time. A colleague of Begleiter’s, neuroscientist Bernice Porjesz, found that an additional neurological oscillation, the N400 waveform, was markedly different in the children and families of alcoholics. The children with abnormal P3 or N400 waves were more likely to abuse drugs and tobacco in later years. The P3 findings have been thoroughly verified in other laboratories all over the country. There have been no retractions, and little difficulty in duplicating the findings. Begleiter’s markers are solid.