Genetically influenced responses to alcohol affect brain activation

A study by researchers at the University of California, San Diego School of Medicine suggests that differences in brain activation in individuals with a low level of response to alcohol may contribute to their inability to recognise modest levels of alcohol intoxication. Their findings could provide the potential to identify individuals who are at risk for developing an alcohol-use disorder before it develops – in essence, providing a marker for this vulnerability.

In a study to be published in the January 2012 issue of Alcoholism: Clinical & Experimental Research and currently available at the journal's Early View, researchers used functional magnetic resonance imaging (fMRI) to examine brain activation in young men and women in San Diego, ages 18 to 25, with both low and high level of response (LR) to alcohol.

''We found significant differences in brain activation between individuals with high and low levels of response to alcohol while performing a cognitive task, possibly reflecting difference in the amount of brain activity used to deal with a cognitive challenge,'' said Marc A. Schuckit, MD, distinguished professor of psychiatry at UC San Diego, who headed the study.

A low level of response to alcohol is a genetically influenced characteristic, or phenotype, that reflects at least in part a low brain response to alcohol, and carries significant risk for the later development of alcoholism.  This study addressed the physiological underpinnings of a low and high LR, finding significant differences in brain activation during a cognitive task, possibly reflecting differences in the amount of brain activity used to deal with a cognitive challenge.

''While some genes that contribute to LR have been provisionally identified, the mechanism through which the low LR operates in the brain has not been extensively studied,'' said Schuckit. ''This report confirms prior reports from our group that used a different cognitive task to show that people with a low LR process information differently from those with a high LR even when tested with placebo.  The differences between LR groups after placebo and alcohol across different cognitive tasks may help explain why low LR subjects might have more problems recognizing the effects of moderate doses of alcohol.  If you aren't able to recognise the effects of lower doses of alcohol, you are more likely to drink heavy amounts per occasion, which both directly and indirectly increases your risk for alcohol problems.''

Schuckit and his colleagues examined 98 (52 females, 46 males) young, healthy drinkers who were not alcohol dependent and who had been identified in prior testing as clearly having low or high LRs to alcohol.  The subjects in the two LR groups were matched to be similar on recent drinking histories, age, gender, race, and histories of smoking and using illicit drugs.  All participants were evaluated during two, event-related fMRI sessions while performing a cognitive task.  The two groups were given either a placebo or an amount of alcohol roughly the equivalent of three standard drinks, in random order.  Treated subjects developed identical blood alcohol levels during the sessions.