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Darin Dougherty
Darin Dougherty and his colleagues are pleased with the results of the first brain scans ever done on people while they wrestled with their anger. (Staff photo Rose Lincoln/Harvard News Office)

Probing inappropriate rage

Looking into angry brains

By William J. Cromie
Harvard News Office

The scientists were trying to make people mad. While they lay in brain scanning machines, 30 individuals listened to tapes describing what they previously had admitted were the angriest moments of their lives.

There were tales of cheating and romantic breakups, wrongs done to them, even road rages. As the subjects seethed, the scientists measured blood flowing between the thinking and emotional parts of their brains.

Ten of the people suffered from a combination of major depression and anger attacks; ten dealt with depression alone; and ten were as close to normal as the testers could find. What would be the difference between people who controlled their anger pretty well, and those who could not handle it in a socially acceptable way?

These were the first such brain scans ever done with mental patients while they wrestled with their anger. They were done by researchers at Harvard Medical School and Massachusetts General Hospital.

A look into the brains of normal subjects revealed that anger increases blood flow to a reasoning part of their brains, an area over the left eye just behind the forehead, technically called the orbitofrontal cortex. This flow inhibits thoughts of rage. At the same time, blood flow increased activity in the amygdala, an almond-shaped knot of tissue deep in the brain that deals with emotion and vigilance.

diagram of brain
Angry feelings arising in the amygdala are normally cooled by activity in the frontal cortex, part of the thinking region of the brain. However, in some severely depressed people a lack of both recognition and control of anger, can lead to violent rage.

"All of us get angry from time to time," comments Darin Dougherty, an assistant professor who led the research. "At such times, feelings of wrath in the primitive parts of our brains seem to be balanced by inhibitions of our will to act on those feelings."

But in people dealing with both depression and rage, things go a different way. A decrease in blood flow to these areas of the brain reduces both their ability to control impulsive acts and their feelings about the consequences of those acts, say punching someone in the mouth. There is both a lack of emotion and a lack of control. A double hit that adds up to inappropriate, even violent rage.

Those with major depression who are free of anger attacks show a lack of activity in both brain areas; both their feelings and reasoning about anger are deadened.

An angry blow

Studies by different researchers show the same kind of imbalance in other mental illnesses, such as manic-depression, intermittent explosive disorder, and antisocial personality. The latter is a common characteristic of violent behavior directed at both oneself and others.

There's the classic story of Phineas Gage, a 19th century railroad man who - in a freak accident - had a metal tamping rod driven through his skull just above his left eye. Gage survived but his easygoing personality did not. He went from a mild-manned, well-liked, and admired man to a violent, unstable brute, hated and avoided by all who knew him. The tamping rod had destroyed his cerebral center of anger inhibition behind his forehead.

Dougherty estimates that about one-third of the severely depressed people in the United States also suffer bouts of anger, totaling more than a million sad, angry persons in this country alone. When they start feeling irritable and dark, they know depression will follow. When the depression is successfully treated, the anger goes away.

But what happens in their brains when they're not angry anymore? Does their blood start to flow the way it does in so-called normal people? That's a medical mystery that Dougherty and his team want to tackle next. That team includes Scott Rauch, a Harvard Medical School-Massachusetts General Hospital (MGH) psychiatrist who specializes in imaging the brains of people with mood and anxiety disorders, and Maurizio Fava, a Harvard professor who directs the treatment of depression at MGH.

Their next goal is to study angry depressives before and after treatment. "We want to determine what is state and what is trait, what goes away and what stays," Dougherty says. "Once they are successfully treated for depression, do their brains revert to a normal pattern, or do some things stay abnormal? We would also like to do brain scans of other types of patients who exhibit impulsive and violent aggression."

In a report on their research in the August issue of the Achieves of General Psychiatry, Dougherty, Rauch, Fava, and their colleagues note that such aggressive people often have abnormalities in the size as well as functions of their frontal brain and amygdala. One study they mention found that patients with antisocial personalities and a history of violent crime had 17 percent less gray matter in the left frontal part of their brain than those without such a background. Another study concluded that levels of antisocial behavior in violent individuals increased as the size of their amygdalas decreased.

Hard on the heart

At present, excessive anger is treated by anger management techniques like cognitive behavior therapy. The basic research being done by the Harvard-MGH group and others may hasten the day when drugs known as serenics will become available to sooth irritability and calm wrath and rage.

Such drugs could reduce the staggering financial and public health costs of anger. Higher rates of heart attacks and coronary artery disease are closely associated with anger and hostility, the researchers point out. "We are trying to tease out the specific components of the type A personality, the bustling hustler who is more prone to heart disease than more laid-back people," Dougherty says. "Hostility seems to be the biggest trigger of heart disease. Adding outbursts of anger apparently makes things worse."

Depression, anger, and hostility also raise the risk of diabetes. Various studies have shown that such people are less glucose tolerant, that is, less able to process the sugar they consume in their food.

Add to this the social impact on families of yelling, throwing things, and striking children and adults. That can drive others to depression as well as distraction.

"Our findings," Dougherty notes, "underscore the importance of making clear the basic underpinnings of anger and aggression in mental illness and of conducting experimental trials in the search for effective treatments."

To be angry is to revenge the faults of others upon ourselves. -Pope

Copyright 2007 by the President and Fellows of Harvard College