A Depression Switch?

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A Depression Switch?

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This focus on neurotransmitters is the "bowl of soup" approach that Mayberg speaks of, and it has formed the bulk of depression research for more than two decades. Defining the networks the neurotransmitters move within, however — and in particular identifying Area 25 as a key gateway within the depression network — will let researchers bring their neurochemical knowledge to bear on specific targets.

"With this D.B.S. work," Meyer-Lindenberg says, "they have characterized in detail a system" — or network — "underlying a major disorder. It's not a simplistic thing where you're saying it's all about this one area and you inject a current and everything's fine. It's a very complicated system. But this D.B.S. work shows us that amid this complicated system there is a place of overlap, a common denominator" — Area 25 — "that's a very attractive treatment target." Here, Meyer-Lindenberg says, researchers can try to apply the knowledge they've gained about neurochemistry and genetics. The network theory presents a framework around which to apply these perspectives.

Meyer-Lindenberg's own work shows the power of this approach. Last June he published a study on the serotonin transporter gene, or sert gene, which helps determine serotonin availability. Other research had shown that people with the "short" version of the sert gene run more depression risk. Meyer-Lindenberg found a way to identify how various brain areas were affected by having that short version. Then he took 112 patients, half with the long version and half with the short, scanned their brains and asked the computer to find areas that scanned differently in the two groups. The area showing the most difference was Area 25.

Along with redirecting research, the quieting of Area 25 may also change our conception of depression from a condition in which something is lacking — self-esteem, resilience, optimism, energy, serotonin, you name it — to one in which an active agent makes a person sick.

"Most people think of depression as a deficit state," Mayberg says. "You're low, you're negative. But in fact, talk to a depressed person, and you have this bizarre combination of numbness and what William James called 'an active anguish.' 'A sort of psychical neuralgia,' he said, 'wholly unknown to healthy life.' You're numb but you hurt. You can't think, but you are in pain. Now, how does your psyche hurt? What a weird choice of words. But it's not an arbitrary choice. It's there. These people are feeling a particular, indescribable kind of pain."

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This anguish, Mayberg suggests, is the manifestation of a neural circuit run amok. For doctors, establishing this should focus research and care. For those of us who've never known depression, recognizing it may help us see depression not as a dead absence but as a live affliction. We might even stop indulging the romantic notion of depression as intrinsic to one's identity. For this notion, too, was tested by Mayberg's experiment. When a steady, 4-volt thrum calmed these patients' anguish, they did not lose their identities. They regained them, feeling again the engagements with the world that most define them: flowers for the gardener, lightness for the cyclist and, for Deanna, a long-missed connection to others.

When Deanna, Gary and I finally finished talking, they insisted on driving me to my hotel. Halfway through town, Gary pulled off the main road, drove up a long, sinuous driveway and parked in a lot facing a dark, rambling building.

"This is the hospital," Gary said. "You see where Deanna stayed."

In the winter dark, the secure ward, off to the left, was easily discerned. It was a low wing, the only one with a few lights still on inside. Outside, bright flood lamps illuminated an exercise yard ringed by 20-foot-tall cyclone fencing topped with razor wire.

"And there's the lake," Gary said, motioning behind us. Through trees I could make out its blackness.

We sat several minutes, but no one said much.

"Well," Gary said, putting the minivan in gear. "We'd better get home."

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Source: NY Times

Last updated: 4/06

A Depression Switch?

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