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March 21, 2005
Relieve depression through deep brain stimulation?
BY kathi baker
A study published in the March 3 issue of Neuron reports evidence that deep brain stimulation (DBS) could have clinical benefits for individuals suffering from severe depression who have failed other treatments.
The University of Toronto study, led by Helen Mayberg, now a professor in the departments of psychiatry and behavioral sciences and neurology, opens a promising line of research for depressed patients who do not respond to other therapies.
Currently DBS is used to treat such neurological disorders as epilepsy, Parkinson’s disease and dsytonia through high-frequency electrical stimulation of specific areas of the brain responsible for symptoms in each disorder. In previous studies using brain imaging, Mayberg and her colleagues found that the brain’s subgenual cingulate region (Cg25) plays a critical role in modulating sadness and other negative mood states in both healthy and depressed patients. In their latest study, they hypothesized that stimulation of the Cg25 area could provide a significant benefit in treating depression.
“We see depression as a complex disturbance of specific circuits in the brain responsible for regulating mood and emotions,” Mayberg said. “This approach is similar to that taken in Parkinson’s disease where, by careful research of the relevant motor circuits, DBS was developed to modulate these dysfunctional circuits, and is now used to treat the most severely ill patients.
“We hypothesized,” she continued, “that if DBS could locally modulate a critical node with this mood circuit, such modulation would result in clinical improvement—and it appears it did.”
Six patients diagnosed with major depression were entered into the study. They had not responded to any other type of treatment including medication, psychotherapy and electroconvulsive therapy. Guided by magnetic resonance imaging, the team implanted thin wire electrodes in each patient’s brain adjacent to the Cg25 area. The other ends of the wires were connected under the skin of the neck to an implanted pulse generator (similar to a pacemaker) that directed the electrical current. Researchers controlled the intensity of the current, and the electrode implantation and initial testing surgery was performed under local anesthesia.
The researchers were able to track the patients’ clinical response over a six-month period by scanning blood-flow activity through positron emission tomography (PET) and other neuropsychological tests. Four of the six study patients demonstrated significant response, with sustained improvement throughout the six months of the study. In addition to the hypothesized changes in the Cg25 region, PET scans also showed significant response in the frontal cortex, hypothalamus and brainstem, consistent with findings seen with successful response to medication or psychotherapy in less severely ill patients.
“This was a hypothesis-driven, brain-based strategy for the treatment of the most severely ill depressed patients,” Mayberg said. “It was the culmination of 15 years of research using brain-imaging technology that has worked to characterize functional brain abnormalities in major depression and mechanisms of various antidepressant treatments.”
The study’s findings lay the foundation for a larger project to replicate, refine and extend these first results. “If the safety and benefits we have observed are maintained across other future studies, we could see this approach applied in the years to come as a clinical therapy for patients who fail current treatments and continue to suffer with severe depression,” said Andres Lozano, neurosurgeon with Toronto Western Hospital and the study’s co-investigator.
Further work will be carried on by Mayberg and her Emory colleagues. This study was supported by a Distinguished Investigator Award to Mayberg from the National Alliance for Research in Schizophrenia and Depression, and was conducted by a collaboration of scientists from The Rotman Research Institute at Baycrest Centre for Geriatric Care, Toronto Western Hospital and the University of Toronto.