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All in the Slicing and Dicing

News from the Johns Hopkins Department of Psychiatry and Behavioral Sciences

New studies on alcoholism's biology bode change

Mary 'Betsy' McCaul

Betsy McCaul, Ph.D.


Behavioral psychologist Mary“Betsy” McCaul came to study alcohol addiction just as a more honest view of the disorder began to percolate in the public mind. Even though, in the 1960s, that diagnostic staple, the DSM, included alcoholism in its second edition, the disease was lumped in with personality
disorders and considered an all-or-nothing affair. You couldn’t stop drinking, the idea went, because you were weak-willed or antisocial. It’s no surprise, McCaul says, that the main therapy then was antabuse,“basically a punishment whose premise is simple: you drink, you throw up.” It’s taken years to recognize alcoholism as a nuanced disease, grounded in biology as well as environment. And McCaul has fostered that.

McCaul has directed alcohol treatment at the Hopkins Bayview campus, a service that morphed into broader addictions treatment, and the like program at Hopkins Hospital. Today, she heads the latter program while continuing to shine light on alcoholism. Recent studies on the therapy naltrexone, for example, play up the role of reward pathways in the brain in alcohol’s

Q. Early on, you followed college kids from alcohol-dependent families. They were more likely to drink, you found, and having close relatives with the problem made risk higher.

A. Right. We’re very interested in who’s at risk of alcoholism and what’s behind it. We first looked
for revealing behaviors that single out vulnerable people with a family history, but our work has
broadened wonderfully. Now we’re focusing on their biology, on gene-based differences in the
brain that put them at risk.

Q. Since alcohol triggers the brain’s reward system, are you looking there?

A. Yes, and wider. Alcohol is a “dirty” drug because it touches so many neurotransmitter systems— serotonin, for example, and the dopamine-based reward system as well as the opiate-stimulated pathways that feed into it. That’s the good news and bad: our playing field is wide open and trying to narrow it is the devil. Recently my co-researcher, Gary Wand, and I have
focused on brain pathways active during stress—a system superimposed on these others. We’re excited because it may explain the gender differences everyone notices.

Q. What differences?

A. The fact that men who’re impulsive or risk-takers are more likely to get into drug disorders,
but for women, risk is greater if they have depression and anxiety. Anxiety, particularly, looks to be the tail that wags the dog; it begins well before drinking starts. Why would that make women vulnerable? Gary’s studies found that dopamine acts differently on an anxious, stressed brain. Stress alone—or chronic anxiety—seems to make your brain more responsive to the burst of dopamine people experience with drugs. So it might be that anxious women get more relief from alcohol than others. And we’re getting some exciting evidence that different biology underlies men’s addiction.

Q. Do you have an overall picture here? Will it help treatment?


A. Yes. We’re finding that varied pathways lead into addictive disorders, whether from alcohol or
drugs. And the fact that people fall into biological subtypes lets us build more precise treatment programs. Until recently, we’ve had “cookie cutter” approaches; everybody gets the same medicine, the same group therapy. But age and gender for example, seem to matter strongly. Look what happens with a woman troubled by an underlying anxiety disorder when she tries to get off alcohol. Withdrawal itself induces anxious feelings, so this woman will feel dreadful! What if you urge women who already have an underlying social phobia into standard group therapy? When they stop coming, we say they just weren’t motivated. But that’s not the case.

Q. Your ongoing trials aim to define these differences?

A. Yes. Because, ultimately, slicing and dicing treatment is crucial. Besides, being in trials helps people; it’s a no-cost way to get treated, confidentially. “So our subject population is diverse—attorneys, health care providers, people you wouldn't expect.

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