1. ¹Department of Psychiatry and Psychotherapy, University Hospital, Bonn, Germany
2. ²Departments of Psychiatry and Mental Health, The Johns Hopkins University, Baltimore, MD, USA
3. ³Department of Epileptology, University Hospital, Bonn, Germany
4. ⁴Department of Psychology, University of California, Davis, CA, USA
5. ⁵Department of Nuclear Medicine, University Hospital, Bonn, Germany
6. ⁶Department of Functional Neurosurgery, University Hospital, Cologne, Germany

Correspondence: Dr TE Schlaepfer, Department of Psychiatry, University Hospital, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany. Tel: +49 228 287 14715; Fax: +49 228 287 15025; E-mail: schlaepf@jhmi.edu

Received 8 August 2006; Revised 26 February 2007; Accepted 27 February 2007; Published online 11 April 2007.

Abstract

Deep brain stimulation (DBS) to different sites allows interfering with dysfunctional network function implicated in major depression. Because a prominent clinical feature of depression is anhedonia—the inability to experience pleasure from previously pleasurable activities—and because there is clear evidence of dysfunctions of the reward system in depression, DBS to the nucleus accumbens might offer a new possibility to target depressive symptomatology in otherwise treatment-resistant depression. Three patients suffering from extremely resistant forms of depression, who did not respond to pharmacotherapy, psychotherapy, and electroconvulsive therapy, were implanted with bilateral DBS electrodes in the nucleus accumbens. Stimulation parameters were modified in a double-blind manner, and clinical ratings were assessed at each modification. Additionally, brain metabolism was assessed 1 week before and 1 week after stimulation onset. Clinical ratings improved in all three patients when the stimulator was on, and worsened in all three patients when the stimulator was turned off. Effects were observable immediately, and no side effects occurred in any of the patients. Using FDG-PET, significant changes in brain metabolism as a function of the stimulation in fronto–striatal networks were observed. No unwanted effects of DBS other than those directly related to the surgical procedure (eg pain at sites of implantation) were observed. Dysfunctions of the reward system—in which the nucleus accumbens is a key structure—are implicated in the neurobiology of major depression and might be responsible for impaired reward processing, as evidenced by the symptom of anhedonia. These preliminary findings suggest that DBS to the nucleus accumbens might be a hypothesis-guided approach for refractory major depression.