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TRANSLATIONS: Way to Go

News from the Johns Hopkins Department of Psychiatry and Behavioral Sciences

James Potash
Dr. James Potash

As it begins to sink in that “chronic” is a true variety of major depression, don’t expect dramatic change in the way we treat patients, says psychiatrist James Potash, senior researcher on the Hopkins team (see left) that teased the finding from a larger study.

“It ultimately helps patients to have more realistic expectations,” he adds, “and we remind them of the Hopkins dictum for chronic depression: We aim for you to be 80 percent well 80 percent of the time.”

But at this early point, the study’s benefits come more as signposts for research. With a “pure” group of chronically depressed patients, says Potash, we’re now better able to describe their illness and see what we don’t know.

“They’re people swimming below the surface,” he says, citing a colleague’s description. “At times they plunge deep down. At others, they’re only inches away from the top. What they have, then, is chronic low-grade depression—dysthymia—with major depression superimposed. Both, we think, are versions of the same thing.” But are they? And what causes the plunge? Is it stress? Genes? An unfortunate mix? Some patients are resistant to antidepressants—are the chronically depressed more often in that group?

Finding which gene or genes make depression chronic is the step that would lead to answers for hovering questions, as well as suggest new targets for therapy, Potash says. One gene search is under way—GenRED II—at Hopkins and nationally. The first GenRED sought the broad chromosomal areas likely to harbor depression genes. It kindly uncovered just such a “neighborhood” on chromosome 15. Now with GenRED II about to screen several thousand patients, “we hope to return there,” Potash says, “and, in effect, go door to door to pick out specific genes.” New-generation gene chips that can scan up to 500,000 variable sites in a patient’s DNA “give us a gene-hunting power we never dreamed of.” 

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