Deep brain stimulation of the human reward system as a putative treatment for refractory major depression

Abstract

Several brain structures play a germane role in the development and maintenance of symptoms in depression. Current studies in treatment-resistant depression (TRD) are targeting the nucleus accumbens (NAc), the medial forebrain bundle, the anterior cingulate cortex (Cg25), and the anterior limb of the internal capsule. The NAc has been studied as a target site for deep brain stimulation (DBS) in depression because of its prominent role in the reward system. The first evidence on a small sample studied for up to 4 years has proven that NAc DBS induces stable, sustained antidepressant effects in 50 % of patients. It is not yet possible to decide on the optimal target for DBS in TRD: the studies are small, long-term data are only available for up to 5 years, and the stimulation amplitude is high compared with neurological indications. The medial forebrain bundle—connecting frontal DBS targets (Cg25) with the NAc—has recently been proposed as new hypothesis-driven target awaiting clinical evidence. The application of NAc DBS for the treatment of bipolar disorder and other psychiatric diseases (e.g., alcohol dependency, opioid addiction, schizophrenia) is currently being investigated. No fundamental ethical objections to the use of DBS in psychiatric disorders have been put forward, but until substantial clinical data are available, mandatory standards are needed to prevent harming patients.