Bucknell study suggests new genetic risks for alcoholism in women

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LEWISBURG — Gender and the biology of the brain may make some women more likely to reach for a drink when they feel stressed out, and more likely to become dependent on alcohol.

This finding, the outcome of three-year neuroscience study by Bucknell Professor Judith Grisel, psychology, could improve the screening and diagnosis of alcoholism and other addictions. It also adds to the mounting body of evidence about fundamental differences between the brains of men and women — differences that Grisel notes were ignored for decades, leaving a deep gender gap in medical research that persists today.

Funded by the National Institute of Alcoholism and Alcohol Abuse and published in the journal Addiction Biology, the study examined how men’s and women’s brains respond to alcohol depending upon a specific neurotransmitter called beta-endorphin. While the study used mice bred to produce different amounts of the chemical, beta-endorphin is also found in varying amounts in humans, and is a key tool our bodies use to help manage stress. The study was co-authored by Bucknell master’s graduates Todd Nentwig M’17 and Diane Wilson M’14, as well as biology professor Erin Rhinehart of Susquehanna University.

The Binge-drinking Chemical

Grisel and her collaborators found that while male mice with lower levels of beta-endorphin were less likely to binge drink, females with low beta-endorphin levels binged harder and faster, and more quickly escalated to addictive behavior, choosing to continue drinking even when food and water were also available. “We believe the reason is that the low-endorphin females are naturally more stressed, and binge drinking fixes their hyper-stressed state,” Grisel said.

In humans, this association could prove useful in evaluating genetic risk factors for alcoholism in women, as using alcohol to deal with a problem like stress — to self-medicate — is one popularly accepted marker of addiction. “When you’re medicating something with alcohol, it’s likely to cause problems much more quickly than using it for purely social reasons,” Grisel explained, adding that her study backs up a correlation that physicians have previously noted.

“There are clinical findings in humans showing that children of alcoholics have a deficit of beta-endorphin compared to average — before they ever take their first drink of alcohol,” Grisel said.

A Personal mission

The study is the latest step in answering the fundamental question Grisel has made her life’s work. “I’m interested in what’s different about the brains of people who go on to become drug addicts, before they ever get a drug,” Grisel said.

It’s a deeply personal question for the neuroscientist, whose own career was nearly derailed by addiction before it had even begun.

Grisel struggled with alcohol and drug addiction while in college, and had dropped out and become homeless before entering recovery in her early 20s. Spurred at first by a desire to cure her addiction — a motivation she calls arrogant in hindsight — she would go on to finish college and earn her doctorate, concentrating her studies on the neuroscience of addiction. She interweaves stories from this experience with insights from her career as a scientist in her upcoming book, Never Enough: The Experience and Neuroscience Of Addiction. The mass market, popular science book, slated for publication next year by Doubleday, aims to help readers understand both the science and experience of addiction.

“After 30 years of studying addiction, I don’t have the solution, but I hope to shed light on what the problem is,” Grisel said, “why so many people are addicted, what causes it, and how society might help in ways that it doesn’t right now.”

 Remedying medicine’s gender gap

Grisel’s latest findings also work toward a personal goal to which she has devoted some two decades or work: correcting the longstanding gender gap in biomedical science. “For a long time, we just ignored sex differences. Males were the default in science,” Grisel said. “Until this century, virtually all biomedical research done used only males.”

Not taking sex differences into account can have harmful unintended effects, Grisel noted, citing a study she did for a pharmaceutical company to evaluate a new painkiller it had in development, about 15 years ago. Grisel’s study, which used mice, produced seemingly random results that she couldn’t explain or replicate — until she decided to look at how the drug affected males and females differently. The inconsistent data suddenly took on a clear shape: two lines diverging toward the poles of “less pain” and “more pain.” While the drug proved effective in males, it actually intensified the pain felt by females.

“Scientists, including those in the pharmaceutical industry, are beginning to appreciate that all brains are not the same,” Grisel said. “We’ve got a lot of studies now, by me and lots of other people, showing that the neurobiology and neurogenetics of males and females are often different in important ways. We hope that paying more attention to factors like sex will help us to better understand complex disorders, and eventually, alleviate human suffering.”

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