Depression: A New Target for Deep Brain Stimulation?
ABSTRACT & COMMENTARY
By M. Flint Beal, MD
Professor and Chairman of the Department of Neurology at Cornell Medical College
Dr. Beal reports no consultant, stockholder, speaker’s bureau, research, or other relationships related to this field of study.
Synopsis: Chronic stimulation of the white matter tracts adjacent to the subgenual cingulate gyrus was associated with a striking and sustained remission of depression in 4 of 6 patients.
Source: Mayberg HS, et al. Deep Brain Stimulation for Treatment-Resistant Depression. Neuron. 2005;45:651-660.
Major depression is a huge health problem, and ranks among the top causes of worldwide disease burden. It is the leading source of disability in adults in North America younger than age of 50. In many patients, depression is effectively treated with standard pharmacologic interventions, such as selective serotonin reuptake inhibitors. Some patients, however, require combinations of multiple medications and electroconvulsive therapy. Some of these patients still remain depressed despite these interventions. The present studies investigated whether deep brain stimulation in a specific cortical area, which has been linked to depression, would be effective in ameliorating the symptoms of depression. Depression has been linked to the limbic-cortical system network. Functional neuroimaging studies have shown that a critical role is played by the subgenual cingulate (CG25) in both acute sadness and anti-depressant treatment effects. This region may, therefore, play a critical role in mediating depression. A decrease in activity in this area has been reported with clinical response to a number of anti-depressant treatments, including selective serotonin reuptake inhibitors. There has also been a reduction in activity following electroconvulsive therapy. The critical region, CG25, has connections to the brain stem, hypothalamus, and insula, which have been implicated in disturbances of circadian rhythms associated with depression. These include disturbances of sleep, appetite, libido, and neuroendocrine changes. There are reciprocal pathways linking CG25 to orbital frontal, medial prefrontal, and various portions of the anterior and posterior cingulate cortices. These are areas which have been strongly implicated in various aspects of learning, memory, motivation, and reward, which are strongly disturbed in depressed patients.
Deep brain stimulation has been shown to be effective in pathologically over reactive brain circuits. Mayberg and colleagues, therefore, tested whether deep brain stimulation in CG25 would reduce elevated activity and produce clinical benefits in 6 patients with refractory depression. Chronic stimulation of the white matter tracts adjacent to the subgenual cingulate gyrus was associated with a striking and sustained remission of depression in 4 of 6 patients. This was associated with a marked reduction in activity, as well as changes in downstream limbic and cortical areas, as assessed using positron emission tomography.
Commentary
This study is the first to demonstrate that deep brain stimulation can be an effective treatment for refractory depression. Refractory depression can be totally disabling in some patients. Of note, however, only 4 of 6 patients showed a response. It is unclear why in the other 2 patients the treatment was ineffective. The procedure was well-tolerated. Deep brain stimulation may, therefore, become an effective and novel intervention treating patients who have disabling depression.
By M. Flint Beal, MD Professor and Chairman of the Department of Neurology at Cornell Medical College Dr. Beal reports no consultant, stockholder, speakers bureau, research, or other relationships related to this field of study.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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