Toward an Understanding of the Neural Circuitry of Major Depressive Disorder Through the Clinical Response to Deep Brain Stimulation of Different Anatomical Targets

Deep brain stimulation has been proposed as a treatment for treatment-resistant depression. To date, multiple brain targets have been tested in single case studies and case series. The target regions with the most evidence to support their use are the subcallosal cingulate, ventral capsule/ventral striatum, nucleus accumbens, and medial forebrain bundle. Treatment effects of stimulation at each target share some commonalities, including similar response and remission rates, a relatively slow and progressive time course of treatment response, with a comparatively fast depressive relapse after discontinuation of stimulation. Response is maintained over time, and in some cases improves over years. Similarities may be at least partially attributable to overlap in white matter pathways between targets. Careful attention to mood and somatic effects seen with acute stimulation may differentiate primary vs. secondary treatment effects and mechanisms between the target regions. Understanding which symptoms are primarily affected, and the time course of response and relapse, will shed light on the biological mechanisms underlying DBS effects and depression pathology.