Depression Plus Anger Prompts Search for Genetic Link

Could there be a subtype of depression characterized by irritability and anger—what the ancient Greeks called “the yellow, choleric, bile type of personality”?

Maurizio Fava, M.D., a professor of psychiatry at Harvard Medical School, thinks that there might be. In fact, a decade or so ago, he described “depression with anger attacks.” Moreover, one of the young psychiatric researchers working with him—Roy Perlis, M.D., an instructor in psychiatry at Harvard Medical School—is getting a study under way to probe for a gene or genes that might underlie this kind of depression.

Perlis announced this effort at the 14th Annual Scientific Symposium of the National Alliance for Research on Schizophrenia and Depression, held in New York City in October.

So far, Perlis explained, he and his colleagues have collected DNA samples from some 150 subjects with either major depression alone or with major depression accompanied by anger attacks, and they plan on ultimately collecting such samples from 300 such individuals. They will then probe the samples to see whether they can find a gene or genes that are peculiar to major depression accompanied by anger attacks.

“I think we may be onto genes that cross criteria in DSM-IV,” he said. “For instance, bipolar patients who are depressed often show anger.”

Someone in the audience asked Perlis whether more men than women experience depression with anger outbursts, since men have higher levels of testosterone than do women and thus tend to be more aggressive. On the contrary, Perlis replied—more women than men seem to experience them. However, when men do experience depression with anger outbursts, he added, they tend to be more violent than women.

Someone else asked whether Perlis and his coworkers planned to measure the testosterone levels of their subjects. While he responded no, he said that it was a good idea.

Perlis likewise reported that he and his coworkers are collaborating with a group of researchers at Massachusetts General Hospital to investigate whether brain-imaging data might distinguish persons with major depression and anger from those with just major depression.

The type of research that Perlis and his colleagues are pursuing is similar to that being pursued by some other psychiatric investigators today, Lewis Judd, M.D., chair of psychiatry at the University of California at San Diego, pointed out at the symposium. In other words, they are attempting to identify subtypes of depression that to date have not been recognized by the psychiatric community. ▪