Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression

Thomas E. Schlaepfer, Michael X. Cohen, Caroline Frick, Markus Kosel, Daniela Brodesser, Nikolai Axmacher, Alexius Young Joe, Martina Kreft, Doris Lenartz, Volker Sturm

Research output: Contribution to journalArticlepeer-review

659 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)368-377
Number of pages10
Issue number2
StatePublished - Jan 2008
Externally publishedYes


  • Anhedonia
  • Brain stimulation
  • Cg25
  • Deep brain stimulation
  • Major depression
  • Nucleus accumbens

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health


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