Alcohol Use: Binge Drinking Kicks Off a Vicious Cycle That Rewrites Genes 

The effects of binge-drinking, as common as it is in the United States — seem to last far beyond a single bender. Outside of the hangover-induced anxiety that haunt the morning after a long night of pounding shots, a recent study conducted by scientists at Rutgers Univesity shows that binge drinking can lead to long-lasting changes in DNA that might actually affect how we approach alcohol in the future.

Previous studies have shown that alcohol can change crucial reward pathways in the brain, triggering a feel-good response that makes heavy drinking a hard pattern to break. But this recent paper in Alcoholism: Clinical and Experimental Research authored by Dipak Sarkar, Ph.D., an animal science professor at Rutgers University, suggests that part of alcohol’s addictive grip can become written in our DNA over time, especially in people who are heavy drinkers or binge drinkers. He was able to show that human binge drinkers and heavy drinkers had significant changes to two genes. Those changes, he says, may actually reinforce how much binge-drinkers crave alcohol, which he tested over three days in a lab in New Haven, Connecticut.

“We have noticed that alcohol drinking not only affects behavior it also alters some of the cellular behaviors including DNA and RNA,” Sarkar tells Inverse. “We found these two genes that are involved in regulating stress function and circadian function were similarly affected.”

To start with, Sarkar took blood samples from three groups of drinkers: moderate drinkers, binge-drinkers, and binge drinkers who “all reported ‘liking beer,’” as he notes in the paper. Specifically, his binge drinkers reported drinking at least seven drinks per week for women and 14 drinks per week for men, plus one additional night of binge drinking per month. To fall into the heavy drinking category, women had to average at least eight drinks per week and men had to average 15.

When he compared the actual DNA molecules from blood samples in those individuals, he found that binge drinkers had slight alterations in the DNA of two genes. The first gene, called POMC, affects stress responses in the brain. Another, called PER2, helps control circadian rhythm — or a cell’s internal clock. The DNA molecules that make up those genes had an extra group of molecules attached (called DNA methylation) that made it harder for cells to actually produce the proteins that those genes code for.

"“We think that it has a profound effect on the body function as well as the behaviors."

Sarkar isn’t the first to suggest that alcohol can literally change our bodies on a cellular level. But his paper does go to lengths to draw the connection between those changes and how heavy drinkers crave alcohol, which he addressed in a behavioral experiment.

In that experiment, he asked his participants to rate their levels of alcohol cravings, and observed how much beer they actually drank when he gave them two glasses for an “alcohol taste test.” The crux of Sarkar’s findings is that he identified a correlation between how much beer people drank, how much they craved alcohol, and how their bodies expressed the POMC and PER2 genes. Based on his analysis he could predict how much someone would drink or crave alcohol based on how their bodies expressed those two genes.

This paper is only enough to establish a strong correlation — he can’t say for sure that the expression of these genes can drive alcohol cravings. He does add that animal studies have shown that when these genes aren’t expressed, mice tend to drink more.

“In the animal studies, we have evidence that these two genes are quite involved in positive reinforcement of alcohol drinking,” he adds. “We think that it has a profound effect on the body function as well as the behaviors. That led us to think that maybe it’s involved in addictive behavior.”

Importantly Sarkar adds it’s not easy to actually induce these changes. He adds that one or two episodes of binge drinking — despite the other side effects they may cause — probably won’t leave any lasting marks on DNA. But for those who struggle with alcohol use, his paper points to a tiny genetic change that could cause a big effect.

Abstract:

Background: Epigenetic modifications of a gene have been shown to play a role in maintaining a long‐lasting change in gene expression. We hypothesize that alcohol’s modulating effect on DNA methylation on certain genes in blood is evident in binge and heavy alcohol drinkers and is associated with alcohol motivation.

Methods: Methylation‐specific polymerase chain reaction (PCR) assays were used to measure changes in gene methylation of period 2 (PER2) and proopiomelanocortin (POMC) genes in peripheral blood samples collected from nonsmoking moderate, nonbinging, binge, and heavy social drinkers who participated in a 3‐day behavioral alcohol motivation experiment of imagery exposure to either stress, neutral, or alcohol‐related cues, 1 per day, presented on consecutive days in counterbalanced order. Following imagery exposure on each day, subjects were exposed to discrete alcoholic beer cues followed by an alcohol taste test (ATT) to assess behavioral motivation. Quantitative real‐time PCR was used to measure gene expression of PER2 and POMC gene levels in blood samples across samples.

Results: In the sample of moderate, binge, and heavy drinkers, we found increased methylation of the PER2 and POMC DNA, reduced expression of these genes in the blood samples of the binge and heavy drinkers relative to the moderate, nonbinge drinkers. Increased PER2 and POMC DNA methylation was also significantly predictive of both increased levels of subjective alcohol craving immediately following imagery (p < 0.0001), and with presentation of the alcohol (2 beers) (p < 0.0001) prior to the ATT, as well as with alcohol amount consumed during the ATT (p < 0.003).

Conclusions: These data establish significant association between binge or heavy levels of alcohol drinking and elevated levels of methylation and reduced levels of expression of POMC and PER2 genes. Furthermore, elevated methylation of POMC and PER2 genes is associated with greater subjective and behavioral motivation for alcohol.