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 S. Mayberg, MD, now a professor in the Departments of Psychiatry and Behavioral Sciences and Neurology at Emory University School of Medicine, opens a promising line of research for depressed patients who do not respond to other therapies.
DBS is currently used as a treatment for such neurological disorders as Epilepsy, Parkinson's disease and Dsytonia. DBS uses high-frequency electrical stimulation targeted to the specific areas of the brain responsible for symptoms in each disorder. In previous studies using brain imaging, Dr. Mayberg and her colleagues found that the subgenual cingulate region (Cg25) of the brain plays a critical role in modulating sadness and negative mood states in both healthy and depressed patients. They hypothesized in their latest study that if stimulation worked for the treatment of other neurological disorders in other parts of the brain, then stimulation of the Cg25 area of the brain could possibly provide a significant benefit in treatment of depression.
"We see depression as a complex disturbance of the specific circuits in the brain responsible for regulating mood and emotions," said Dr. Mayberg. "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 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," explained Dr. Mayberg.
Six patients who had been diagnosed with major depression were entered into the study. These patients did not respond to any other type of treatment including medication, psychotherapy and electroconvulsive therapy. Guided by magnetic resonance imaging (MRI), 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 which directed the electrical current. The intensity of the current was regulated by the researchers. The electrode implantation and initial testing surgery was performed under local anesthesia.
The researchers were able to track the clinical response of the patients over a six-month period by scanning blood flow activity by using positron emission tomography (PET), and neuropsychological tests. A significant response was seen in four of the six study patients, with sustained improvement throughout the six months of the study. In addition to the hypothesized changes in the Cg25 region, The 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," said Dr. Mayberg. "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."