Why Some Drinkers Become Alcoholics

Why is it that half of U.S. college students binge drink, but just a fraction develop long-term drinking problems? Dorit Ron, a neurologist at the University of California, San Francisco, points to a regulatory system in the brain that can break down when people binge drink, leading some into unhealthy alcohol habits. 

When people drink moderately, the body boosts the supply of brain-derived neurotrophic factor, or BDNF. BDNF allows the brain to change over time. It has also been recognized as a player in drug and alcohol addiction.

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Ron has shown that the presence of BDNF in the brain tends to ward off excessive drinking. But binge drinking pushes down BDNF levels in a mouse model of human alcohol abuse, Ron and her colleagues report in a paper published this week in the journal Molecular Psychiatry.

The adaptations in the brain — how the brain changes in response to out-of-control drinking or use of other drugs — those changes are pretty permanent or long-lasting. That’s one reason that people relapse, even people who are very committed and go through rehab.
Dorit Ron, University of California, San Francisco

The blame lies with a bit of microRNA, a genetic substance that helps regulate gene expression, or how genes influence a person’s biology at a given time. 

Ron and her colleagues saw a clear pattern in a part of mouse brains called the medial prefrontal cortex, which plays an important role in decision-making. When the microRNA, called 30a-5p, increased, BDNF levels dropped off. The mice then couldn’t control their alcohol cravings.

“They really binge drink — and the solution is bitter. It doesn’t taste good, but still they escalate and they drink large amounts of alcohol. It’s pretty amazing,” Ron said.

When the scientists limited the microRNA, BDNF levels went back up and the mice went back to drinking alcohol in moderation. The chemical switch may explain why some people get into bad patterns of binge drinking even after it’s no longer fun, and why they find their habits hard to break even if they aren’t physically dependent on alcohol.

A Complicated Genetic Picture

Researchers know that children can inherit a tendency toward alcoholism, and that BDNF in the brain affects alcohol consumption. But how are the two related? Ron’s findings show it’s a complicated relationship.

A previous study found that BDNF levels were lower in alcoholic patients with the disease in their family histories than in those without.

Ron’s research is apparently the first to implicate altered levels of microRNA in alcoholism. The finding may answer the age-old question of why some children of alcoholics drink while others don’t.

“BDNF has long been recognized as an important player in alcohol behavior, and this microRNA approach is an important avenue to investigate,” said Dayne Mayfield, a neurobiologist at the Waggoner Center for Alcohol and Addiction Research at the University of Texas at Austin.

“These microRNAs are really master regulators of many genes, and that’s important in a complex trait disorder like alcoholism,” Mayfield added.

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Mayfield’s own research connecting parts of the genome to addictive behaviors had pointed to the microRNA 30a-5p as one that could play a role.

The Problem with Current Medications for Alcoholism

For Ron, the most pressing need is better medical support for alcoholics who are trying to quit. There are just a few drugs approved to treat alcohol cravings, and they don’t target alcohol specifically. Instead, they shut off the brain’s whole reward system. Life is joyless enough under the influence of these drugs that many patients stop taking them.

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The mechanism Ron’s current study documents is something like a switch, which seems to explain why binge drinking puts people at greater risk of developing alcohol problems. Could we figure out how to flip the switch back to the “moderate drinking” setting with behavior changes? 

That’s hoping for too much, according to Ron. 

“In general, the adaptations in the brain — how the brain changes in response to out-of-control drinking or use of other drugs — those changes are pretty permanent or long-lasting. That’s one reason that people relapse, even people who are very committed [to quitting] and go through rehab,” she said.  

But there’s some good news. The process documented in the paper is specific to alcohol: When BDNF was boosted, the mice still sought out other rewards normally.

Could people also have their alcohol cravings squelched without influencing the whole reward system? Maybe, but microRNA strands often influence the activity of more than one gene. That means scientists will have to find a way to manipulate this microRNA without messing up any other genetic processes.