Happiness is a Warm Electrode

Prescription Voltage

Deep-brain stimulation began as a treatment for movement disorders in the mid-1990s, and the surgery has been performed on more than 40,000 patients, most of them Parkinson's sufferers, since then. In those cases, the current normalizes activity in the basal ganglia and thalmus-which dictate motor control, among other things-and can calm their shaking hands and limbs.

But the clinical trial in which Hire is enrolled, along with 16 other patients, is among the first to tackle depression. Other major trials are under way at Emory University and the University of Toronto. Exact numbers are hard to ascertain, but it's estimated that fewer than 50 patients in North America are walking around with wires in their brain.

In some ways, severe depression is a far more challenging disease to treat than Parkinson's. It can manifest in dozens of different ways and arises from a variety of complex factors, some genetic and some environmental. For instance, scientists are just starting to identify a class of what they call vulnerability genes. In essence, they come in two forms: lucky and unlucky. "If you have one version, you are relatively resilient in the face of stress," says Brown University psychiatrist Ben Greenberg, who is collaborating with the Cleveland Clinic group. "But if you have another, the more severe the stress you have in your life, the more likely you are to develop depression."

Most depression therapies address the disease as a kind of communications problem in the brain. When all is healthy, a neuron receives a chemical message from a neighboring neuron and dispatches a corresponding electrical signal along a nerve fiber called an axon. Then, at the other end, the neuron pumps chemicals on to the next cells.

Drugs attempt to improve communication by altering chemical signals. Prozac, the popular antidepressant, blocks the action of a pump that sucks serotonin, a key mood-regulating chemical, out of the gaps between two neurons. This leaves more serotonin in those spaces, supposedly improving the flow of messages between neurons. But why (or whether) this makes people happy remains unclear. Antidepressants may generate billions of dollars in revenue for pharmaceutical companies, but recent studies suggest that pills work only 50 percent of the time-and they don't do much at all for the millions like Hire who are severely depressed.