Deep Brain Stimulation for Treatment-Resistant Depression

Abstract

Treatment-resistant depression is a severely disabling disorder with no proven treatment options once multiple medications, psychotherapy, and electroconvulsive therapy have failed. Based on our preliminary observation that the subgenual cingulate region (Brodmann area 25) is metabolically overactive in treatment-resistant depression, we studied whether the application of chronic deep brain stimulation to modulate BA25 could reduce this elevated activity and produce clinical benefit in six patients with refractory depression. Chronic stimulation of white matter tracts adjacent to the subgenual cingulate gyrus was associated with a striking and sustained remission of depression in four of six patients. Antidepressant effects were associated with a marked reduction in local cerebral blood flow as well as changes in downstream limbic and cortical sites, measured using positron emission tomography. These results suggest that disrupting focal pathological activity in limbic-cortical circuits using electrical stimulation of the subgenual cingulate white matter can effectively reverse symptoms in otherwise treatment-resistant depression.

Subgenual Cingulate Theta Activity Predicts Treatment Response of Repetitive Transcranial Magnetic Stimulation in Participants With Vascular Depression

“…36 reported that active rTMS decreases regional blood flow in the subgenual ACC and is associated with efficacy, and similar findings have been reported using antidepressant medication 12 and deep brain stimulation. 13 The subgenual ACC is also known to become activated during normal sadness 37 and may be overly active in patients with major depression. These findings suggest that higher than normal activity in this specific brain region predicts response to different treatment modalities.38 Although rTMS does not stimulate the subgenual ACC directly, the blood flow studies of Kitou and Koga.…”

“…12 It is unclear whether this is a normalization of high metabolism or a resetting to a new lower level of metabolism in this region. 13 The subgenual ACC has become a target for deep brain stimulation, which has already shown efficacy in treatment-resistant depression. 13 In the present study, we hypothesized that abnormal theta activity occurs within the rostral and/or subgenual regions of the ACC in patients with vascular depression and may predict an antidepressant response to rTMS.…”

Neural circuitry and neuroplasticity in mood disorders: Insights for novel therapeutic targets

“…126,127 In recent years, chronic deep brain stimulation (DBS) in pathologically overactive neural circuits has been found to produce significant therapeutic benefits in those who suffer from Parkinson's disease. 128,129 In a preliminary and uncontrolled yet intriguing experiment, Mayberg et al 130 applied high-frequency DBS to the subgenual cingulate (BA25) of six subjects with severely treatment-refractory depression. All six subjects experienced acute effects intraoperatively including an increased sense of well-being, interest, and calmness as well as an enhanced awareness of the physical surroundings.…”

Sources and effects of electrode impedance during deep brain stimulation

“…In addition, DBS shows promise in the treatment of epilepsy (Hodaie et al, 2002), obsessive-compulsive disorder (Gabriels et al, 2003), and depression (Mayberg et al, 2005). However, the clinical successes of DBS are tempered by our limited understanding of the effects of DBS on the nervous system.…”