Friday, April 21, 2006

Genetic Clues to Alcoholism (or Why Mice Drink)

A study of the brain genetics of alcoholism in mice is unraveling the secrets of this disease in humans.

By Katherine Bourzac

More money and research have probably been dedicated to studying the genetics of alcoholism than any other drug addiction. And so far the results have been disappointing. A recent large-scale study of mice, however, has provided researchers with some surprising new target genes that may be implicated in human alcoholism.

The study, which looked at most of the genes expressed in the brain, also demonstrates the speed and depth of studies of complex genetic diseases made possible by mouse models and increasingly cheaper DNA microarrays.

Researchers led by University of Texas at Austin neurobiologist Susan Bergeson analyzed gene expression data from mice bred for their alcohol preference -- some were teetotalers, others prefered a 10-percent ethanol solution in their water bottles. The researchers examined gene expression across the entire brain of the mice. They found that 3,800 genes differ in expression levels between teetotaler and alcohol-loving mice. In particular, 75 of these genes seem to be associated with the mice's penchant for more or less alcohol. And 36 of the genes are in stretches of the human genome that have been implicated in alcoholism.

The study combined research from scientists who are members of an NIH coalition called the Integrative Neuroscience Initiative on Alcoholism (INIA), and include researchers at the Oregon Health Sciences University, the University of Colorado, Scripps Research Institute, and the Indiana University School of Medicine.

Psychologists and geneticists hope that information about a patient's genetic risk of alcoholism could provide better-tailored treatments. "If you knew why [your patient] was an alcoholic on the neurobiological level, that might help you," says Jonathan Flint, a psychogeneticist at Oxford University's Wellcome Trust Center for Human Genetics.

But so far scientists have been stymied by alcoholism's complexity. "Alcoholism is at its root...almost a canonical example of a complex genetic disease," says Robert Williams, geneticist and professor of anatomy and neurobiology at the University of Tennessee Health Science Center. Risk for alcoholism probably comes from several different genes that each play a small part, he says, and an individual alcoholic's disease is probably caused by different combinations of these genes. This is likely the case because alcohol can interfere with so many chemical pathways in the brain. While many addictive drugs, such as cocaine, have a single target in the brain, ethanol is a "teeny little molecule that can wriggle its way into every network [and] has effects just about everywhere," says Williams.