Vol. 2 No. 2 Specials

There may finally be hope for patients with the chronic mental disorder known as treatment-resistant depression. This particular form of depression is remarkably tenacious; it fails to respond to standard treatments like antidepressants, psychotherapy, and even electroconvulsive therapy. Depression is one of the world’s most widespread health problems, with 4.4 million sufferers in the United States alone. Less well known is that up to 20 percent of these depressive patients show evidence of the insidious treatment-resistant type.

However, the March 2005 issue of Neuron brought a glimmer of hope for the severely depressed. Drs. Andres Lozano and Helen Mayberg of Toronto Western Hospital announced that they had identified a potentially effective therapy for treatment-resistant depression: deep brain stimulation (DBS), a technique that has been used since the 1990s to treat patients with Parkinson’s disease.

It is generally accepted that depression is a disease affecting the integrated pathways that link the cortical, subcortical, and limbic regions of the brain. “We thought that one strategy might be to go in and try to turn down the activity in these areas and to see whether that would have any benefit," says Dr. Lozano. He and Dr. Mayberg specifically targeted the subgenual cingulate region (Cg25) of the brain, also known as Brodmann area 25 (BA25), which they found to be overactive in people suffering from treatment-resistant depression. They hypothesized that sustained electrical stimulation of the Cg25 could ultimately normalize the metabolic activity of that region.

The researchers observed a “striking and sustained remission of depression” in four out of their six subjects, all of whom had been treated with DBS. Brain imaging studies confirmed a reduction in Cg25 metabolic activity. Furthermore, Drs. Lozano and Mayberg noted that other metabolic changes in their subjects’ brains were consistent with the physiological response to medication or psychotherapy in mildly depressive patients.

“This study tells us that this strategy has real potential… Our first target [in the brain] looks like it was a good selection,” Dr. Mayberg remarks. “It may be that there are other areas of the brain that are better, but that remains to be determined.”