Deep brain stimulation of the human reward system for major depression--rationale, outcomes and outlook

Abstract

Deep brain stimulation (DBS) as a putative approach for treatment-resistant depression (TRD) has now been researched for about a decade. Several uncontrolled studies--all in relatively small patient populations and different target regions-have shown clinically relevant antidepressant effects in about half of the patients and very recently, DBS to a key structure of the reward system, the medial forebrain bundle, has yielded promising results within few days of stimulation and at much lower stimulation intensities. On the downside, DBS procedures in regions are associated with surgical risks (eg, hemorrhage) and psychiatric complications (suicidal attenuation, hypomania) as well as high costs. This overview summarizes research on the mechanisms of brain networks with respect to psychiatric diseases and--as a novelty--extrapolates to the role of the reward system in DBS for patients with treatment-resistant depression. It further evaluates relevant methodological aspects of today's research in DBS for TRD. On the scientific side, the reward system has an important yet clearly under-recognized role in both neurobiology and treatment of depression. On the methodological side of DBS research in TRD, better animal models are clearly needed to explain clinical effects of DBS in TRD. Larger sample sizes, long-term follow-up and designs including blinded sham control are required to draw final conclusions on efficacy and side effects. Practical research issues cover study design, patient tracking, and the discussion of meaningful secondary outcome measures.

Figure 1

DBS targets in depression. Experimental targets (red spheres) for deep brain stimulation in major depression: (a) view from posterolateral right, (b) view from anterolateral right. Note how the medial forebrain bundle (green fiber structure) interconnects the majority of target sites (ALIC, NAcc, SCG, slMFB) as a key structure. Legend: ALIC, anterior limb of internal capsule; Hab, habenula; caudate, caudate nucleus; NAcc, nucleus accumbens (anatomically: accumbens); SCG, subgenual cingulate gyrus; slMFB, superolateral branch of the medial forebrain bundle.