Brain Activity Offers Clues To Origin of Anger

So there he is, Mr. X, angry, his face flushed, his eyes bulging, his fists clenched. To the observer, there is little question of Mr. X's mood, but what is going on in his brain?

The ventral area of his prefrontal cortex is probably trying to move into gear. This brain region is known to be crucial for constraining impulsive outbursts. But chances are that his ventral prefrontal cortex will not be up to the task. After all, persons with a predisposition to anger and aggression have been found to have decreased activity in this brain area.

Now suppose that Mr. X is not only susceptible to anger but has a major depression. What is going on in his brain when he feels angry? Again, his ventral prefrontal cortex is probably functioning below par, a study reported in the August Archives of General Psychiatry suggests.

The lead investigator in the study was Darin Dougherty, M.D., an assistant professor of psychiatry at Harvard Medical School. Another of the investigators was Maurizio Fava, M.D., a professor of psychiatry at Harvard. In 1990, Fava and colleagues introduced the idea that there might be a subtype of major depression characterized by anger attacks.

The new study included 30 subjects—10 with a major depressive disorder plus anger attacks, 10 with a major depressive disorder without anger attacks, and 10 healthy volunteers. All three groups were matched for age and gender. The subjects with a major depressive disorder were not taking medication for it.

Doughtery and his coworkers then used PET scans to measure regional cerebral blood flow in each of the subjects while he or she was listening to an autobiographical narrative script. The script described the two life events that had most enraged him or her. While listening to the script, the subject was asked to “imagine the event portrayed as vividly as possible, as if you are actually participating in the event rather than just `watching yourself' in it.”

When the subjects listening to the scripts started getting angry, blood flow increases in the left ventromedial prefrontal cortex were significantly greater in the healthy control subjects than in the subjects with major depression plus anger attacks. In contrast, blood flow increases in the left ventromedial prefrontal cortex were about the same in the subjects with major depression without anger attacks as in the controls.

What's more, when control subjects listened to the scripts and started fuming, an inverse relationship was found between blood flow changes in the left ventromedial prefrontal cortex and the left amygdala. In contrast, when subjects with major depression plus anger attacks listened to the scripts and started getting angry, there was a positive correlation between blood flow changes in the left ventromedial prefrontal cortex and the left amygdala.

When subjects with major depression without anger attacks listened to the scripts and started getting angry, no link could be found between blood flow changes in the left ventromedial prefrontal cortex and the left amygdala.

Two conclusions can be drawn from these results. First, both the left ventromedial prefrontal cortex and the left amygdala show altered functioning in persons with major depression plus anger attacks when they get angry. Second, the neurobiology of major depressive disorder with anger attacks is distinct from that of major depressive disorder without such attacks.

About a third of patients with major depression are prone to anger attacks, Fava told Psychiatric News. And the results from this study, he believes, “may inform the development of drug interventions for this condition.”

Dougherty and his team will now be conducting further research on the subject. As he explained to Psychiatric News, “Given that most patient populations that exhibit anger and aggression... experience chronic illness and that patients with major depressive disorder plus anger attacks experience a remission of their anger attacks as their depressive symptoms resolve, this latter population may provide a unique opportunity to examine state and trait markers of anger/aggression.”

The study was financed by the National Institute of Mental Health.

An abstract of the report, “Ventromedial Prefrontal Cortex and Amygdala Dysfunction During an Anger Induction Positron Emission Tomography Study in Patients With Major Depressive Disorder With Anger Attacks,” is posted on-line at<http://archpsyc.ama-assn.org/cgi/content/abstract/61/8/795>.▪

Arch Gen Psychiatry 2004 61 795