The eyes have it: Seeking expressions of the genetic risk for developing alcoholism

October 15, 2002

Genetic factors play a key role in the development of alcoholism. A family history of alcoholism does not, however, guarantee that individual offspring will develop the disease. In an effort to discover identifying "markers" of those at risk for alcoholism, researchers in the October issue of Alcoholism: Clinical & Experimental Research evaluate the influence of a family history of alcoholism on the response of saccadic eye movements to alcohol.

Saccades are high-velocity eye movements made from one point to another, as in reading. Their main function is to bring the image of a target from the visual periphery onto the fovea centralis (center of the retina), where vision is most acute. The saccadic control system is sensitive to alcohol, and saccadic parameters provide reliable measures of alcohol's effects in a dose-dependent manner.

"The premise of our research is that the brain's response to alcohol is related to a genetically influenced risk for alcoholism," said Sean O'Connor, professor of psychiatry at Indiana University School of Medicine and corresponding author for the study. "We used a familial history of alcoholism as a proxy for genetic influence, since specific genes cannot yet be identified. Saccadic eye-movements fulfilled all the criteria for a good measure of the brain's response to alcohol: they are known to be genetically influenced; they are a very reliable measure of brain function as most people will execute these movements in the same way day after day; they are quite sensitive to alcohol; and a lot is known about the systems of neurons that control the movements." O'Connor explained that associating response of saccades to alcohol with the genetic risk for alcoholism is the first step in seeking specific genes increasing that risk.

Researchers evaluated saccadic performance in 54 adults (27 males, 27 females) with a family history of alcoholism, and 49 adults (24 males, 25 females) without a family history of alcoholism. Participants were given alcohol and a placebo in a counter-balanced order. The alcohol was administered intravenously in order to achieve a breath alcohol concentration of 60 mg% in 20 minutes and to maintain it for 160 minutes. Saccadic eye movement was tested before each session (called baseline), and twice during the maintained level of intoxication.

The two groups showed significant overall differences in operational characteristics of the saccadic control system, both at baseline and when the brain was exposed to alcohol. Subjects with a family history of alcoholism were slightly but consistently slower than subjects without a history throughout the sessions, and appeared to "recover" baseline measures despite prolonged and constant exposure to alcohol.

"A key finding of our study is that the adaptive response of saccades to alcohol is associated with a family-history status known to be associated with a genetic influence on the risk for alcoholism," said O'Connor. In other words, brain function among those with a family history of alcoholism returned towards "normal" despite continued exposure to alcohol.

"We are still trying to learn what is actually inherited that affects the risk of alcoholism," said David Crabb, professor of medicine and of biochemistry and molecular biology at Indiana University School of Medicine. "In other words, is the inherited risk related to brain control functions? to the inability to control drinking? to the euphoria of drinking? We need to know this in order to devise therapies that address the actions of alcohol on the brain." He called the study's identification of brain functions (the control of eye movement at a subconscious level) that are both influenced by genetic factors (the family history of alcoholism) and show responses to alcohol "an incremental yet important step toward understanding genetic influences on alcohol's effects on the brain."

Crabb said these findings may one day have practical applications, such as developing a battery of easy-to-use measures of risk. "We could test children of alcoholics," he said. "Perhaps combining the results of the eye movement tests in young people with other measures would predict their risk of alcoholism or other alcohol problems. If we could accurately tell people if they are at a higher or lower risk of alcoholism based on their test results, this could influence some people to reduce their drinking."

O'Connor said it's important for the field of alcohol research to continue to examine the question: "What does alcohol have to do with an increased risk for alcoholism?" His own research plans include quantifying the degree to which genes influence responses to alcohol, examining how other brain functions respond to alcohol, and expanding those studies to include experimental control of how quickly alcohol reaches and leaves the brain.
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Co-authors of the Alcoholism: Clinical & Experimental Research paper included: T. Blekher and R.D. Yee of the Department of Ophthalmology; V.A. Ramchandani and T.-K. Li of the Department of Medicine; L. Flury and T. Foroud of the Department of Medical & Molecular Genetics; and D.A. Kareken of the Department of Psychiatry - all at Indiana University School of Medicine. The study was funded by the National Institute on Alcohol Abuse and Alcoholism, and Research to Prevent Blindness.

Alcoholism: Clinical & Experimental Research

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