You don’t have to be a scientist to know that, like height, good teeth, and a strong back, alcoholism runs in families. Years of identical-twin and inheritance studies have confirmed conventional wisdom, but alcoholism’s exact genetic underpinning has, so far, remained a mystery.
Recently, a group of researchers at the University of Illinois at Chicago demonstrated a possible genetic basis for alcoholism. They showed that a strong preference for alcohol can be linked to genetically-low levels of two proteins in the brain—neuropeptide Y (NPY) and cyclic AMP responsive element binding protein (CREB)—and that a deficiency of these proteins relates to anxiety. According to their study, when someone prone to anxiety consumes alcohol, he self-medicates by raising the level of these proteins in the brain, thereby decreasing anxiety.
For the study, published in the October issue of the Journal of Clinical Investigation, professor Subhash Pandey selectively bred two groups of rats: some with a strong preference for alcohol, and some with no preference for alcohol. He found that rats who voluntarily drank more alcohol had low levels of two proteins that affect the amygdala, an area of the brain responsible for emotional processing of sensory input. He also observed that these rats exhibited behavior indicative of anxiety. When these rats drank alcohol, the levels of the proteins increased, and the anxious behavior stopped.
“They may be drinking to self-medicate,” Pandey said in a telephone interview. “These rats are drinking alcohol to increase the levels of [the two proteins].”
Pandey was able to achieve the same soothing effect by directly injecting the rats’ central amygdalas with the protein NPY, or with a chemical that activates the other protein, CREB. He also observed that when he injected a CREB inhibitor into the brains of the rats with no preference for alcohol, those rats then became anxious and started drinking.
After prolonged exposure to alcohol, the rats with no initial preference for alcohol began to exhibit the same anxious behaviors and low protein levels as the alcohol-preferring rats. Those rats had become addicted to alcohol.
Pandey said that humans produce these same proteins, and a protein deficiency would cause high levels of anxiety in people as well as in rats.
“In humans, the high anxiety level causes high alcohol intake,” Pandey said. “This is a very good model for mimicking the human situation.”
Gary Wand, a professor of endocrinology at the Johns Hopkins University School of Medicine, published an editorial on Pandey’s study in the same issue of the Journal of Clinical Investigation. Wand said that past studies on alcoholism have mostly focused on the positive rewards of alcohol: the buzz and sense of well-being a person feels after drinking. Pandey’s study stands out for looking at alcohol use as a remedy for the specific problem of anxiety. Wand believes a genetic disposition to crave either the positive rewards of alcohol, or its anxiety-lowering ability, can lead to alcoholism. However, he holds that environmental factors such as daily life events and early childhood experiences also play a role in determining who will become an alcoholic.
“We know that upwards of 50 percent of the determinants for alcohol dependence are genetic in origin,” Wand said over the phone. “Assuming that there can be genetic differences in how [the two sections of the brain that control reward and anxiety] activate, that can create a vulnerable substrate for abuse. That vulnerable substrate is created in part by genetics and in part by environment.”
Originally published October 3, 2005