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School of Medicine
News from the Johns Hopkins Department of Psychiatry and Behavioral Sciences
When Francis Mondimore began to interview patients whose first of many bouts with serious depression came at a fairly tender age—before their 30s—he didn’t expect this response: They were bewildered.
From his years in the clinic, psychiatrist Mondimore had hunches about lasting depression. But they didn’t become truth until he joined the Hopkins arm of a large NIH-sponsored effort to identify genes for recurring major depressive disease. “The Genetics of Recurrent Early-Onset Depression,” or GenRED project, operates on the premise that genes for early-striking disease are probably more obvious than later types. As part of GenRED, Mondimore began assessing patients, recording their history, writing comments. And that’s when his “interview troubles” appeared.
At fault was the list of standard questions: When was your most severe episode of depression? and When did that episode start? When did it stop? “Every few patients, I’d get someone who’d look at me blankly and say, ‘Episode? I don’t know what you mean. There are no episodes; I’ve been depressed as long as I can remember!’ It became clear,” Mondimore explains, “that the questionnaire didn’t capture everyone’s experience. For some, it’s like asking them exactly when friendship stops and love begins.”
And meetings when Mondimore and colleagues would read each others’ interviews and assign diagnoses became equally troublesome. Of three patients with nearly identical histories, says Mondimore, one would get the diagnosis of a very long single episode of major depression. Another would get labeled with the chronic, low-level symptoms of dysthymia. The third had frequently recurring major depression. “Standard psychiatric descriptions would just fall apart,” he says.
“On the other hand, if you looked at the boxes on the study’s questionnaire marked ‘chronic’ or ‘not chronic,’ everyone could agree on that.”
Far more than just a relative handful of patients didn’t fit standard categories, Mondimore says. Both GenRED and an earlier, respected nationwide study showed that a significant number—as many as a quarter of those with major depression—live with it without much pause for years. “It’s not an acute illness for them,” he adds.
So Mondimore, colleague James Potash and a national team examined data from all of GenRED’s 630 families in a new light, picking out only those with the “chronic” box checked. What’s appeared is a new, genuine subtype of major recurring depression, one where genes play an intrinsic part, especially if struggles begin before adolescence. Further, they found, these chronic patients are at greater risk of substance abuse, suicidality and panic disorder.
Does knowing all this affect treatment? “Yes,” says Mondimore. “For one thing, it justifies not trying to taper some patients off antidepressants. But it also means you re-educate them to view their illness more like diabetes, as a problem to be managed over time. If blood sugar levels jump, for example, you don’t ask, ‘has the insulin stopped working?’ You look at what’s going on in a patient’s life, at what needs to change to get better control.”
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