Teen binge drinking can set someone up for anxiety and alcohol abuse later in life by impacting brain development and gene regulation at a key developmental time, a new study published in April 2015 in the journal Neurobiology of Disease concludes. The good news, according to the lead researcher: Knowing how gene expression is effected by alcohol binging in youth may put science closer to developing a drug to undo the effect once it emerges in adulthood. “These findings are an important contribution to our understanding of the alcohol-induced brain changes that make alcohol problems in adulthood more likely among young people who abuse alcohol,” says George F. Koob, PhD, director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), which helped fund the study, in a news release. Researchers at the University of Illinois at Chicago (UIC) College of Medicine examined intermittent alcohol exposure in lab rats of adolescent age and followed their behavior into adulthood.
Why These Study Results Are Important
While adolescent drinking is at a historic low, 90 percent of those youths who drink are binge drinking — a risky practice, according to the NIAAA. A binge drinker is defined as a male or female consuming 5 to 6 or more drinks, respectively, per event, and often in a short period. Past research shows that alcohol drinkers who start before age 15 are four times more likely to become alcohol-dependent in the future. The applications of any reversal drug might help any number of the 16 percent of the world who binge drink. The World Health Organization (WHO) says that the increase in binge-drinking contributed to the deaths of 3.3 million people in 2012, according to the WHO’s latest survey.
Youth Drinking and Missed Connections in the Brain
“Our study provides a mechanism for how binge drinking during adolescence may lead to lasting [epigenetic] changes that result in increased anxiety and alcoholism in adults,” said Subhash C. Pandey, PhD, a professor of psychiatry and the director of neuroscience alcoholism research at UIC in the university’s announcement. Intermittent alcohol exposure “degrades the ability of the brain to form the connections it needs to during adolescence. The brain doesn’t develop as it should, and there are lasting behavioral changes associated with this.” In order to most closely model human teenage binge drinking, the researchers gave alcohol to rats of equivalent age (28 days old) for two days in a row, then took them off alcohol for two days, and so on, for 13 days. Researchers examined some of the rats into their adulthood, watching for unusual behavior. The rats were closely observed after being offered both water and alcohol. Rats exposed to alcohol during adolescence displayed changes in behavior that lasted well beyond the end of their binge-drinking consumption. In adulthood, the rats drank more than the control group rats and showed continuing anxious behaviors.
A Refresher in Epigenetics
The NIAAA offers a refresher to help understand the findings. DNA is found in each cell. In order to fit into the nucleus, the long DNA strands wind around proteins called histones, similar in appearance to thread winding on a spool. Earlier studies linked a brain structure called the amygdala with anxiety and alcohol drinking. “When Dr. Pandey and his colleagues analyzed the amygdala of alcohol-exposed rats in their study, they found that the complex of DNA and histone proteins within the amygdala cell nuclei appeared to be tightly wrapped,” the NIAAA explains. “They also found increased levels of a protein called HDAC2, which modifies histones in a way that causes DNA to be wound tighter around them.” Together, these kinds of changes to gene function, but not to the DNA sequence itself, are called epigenetic change. “Genes that lie within DNA that is tightly wrapped around the histones are less active than they are if the DNA is loosely wrapped,” Pandey said. “The looser the DNA is coiled, the more accessible the genes are to the cellular machinery that makes relevant proteins.” These epigenetic changes were associated with reduced expression of a particular gene required for nerve cells to form synaptic connections. The lowered gene expression, said Pandey, is possibly because of the tighter winding of its DNA. And that reduced gene expression lasted well into adulthood, when researchers found the adult rats had diminished nerve connectivity. “This may be the mechanism through which adolescent binge drinking increases the risk for psychiatric disorders, including alcoholism, in adulthood,” Pandey said. “Genes that lie within DNA that is tightly wrapped around the histones are less active than they are if the DNA is loosely wrapped,” Pandey said. “The looser the DNA is coiled, the more accessible are the genes to the cellular machinery that makes relevant proteins.”
A Cancer Drug to Treat Anxiety and Alcohol Abuse?
An experiment during the research suggested a potential pharmacological treatment: Rats exposed to alcohol during their adolescence were, as adults, given a cancer drug that blocks the activity of HDAC2. This cancer drug restored expression of the gene to a degree required for synapses to be made. The DNA was also more loosely coiled than researchers expected, and the rats showed less anxiety and alcohol intake. What’s next, said Pandey, is more research, and among the questions is this: “We aren’t sure if the drug needs to be given long term during adulthood in order to completely reverse the harmful effects of adolescent alcohol exposure.” By Nancy Wride Follow Nancy Wride at @NWride