Monday, October 29, 2007

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.

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