Deep Brain Stimulation of the Human Reward System for Major Depression—Rationale, Outcomes and Outlook
Open accessAbstract
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.
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Deep brain stimulation can modulate brain networks.
“Furthermore, modulation of networks can be achieved through deep brain stimulation (DBS)180-182.”
From Dysregulation of adult hippocampal neuroplasticity in major depression: Pathogenesis and therapeutic implications (2022) · cites this paper as [180]
The medial forebrain bundle was selected as a DBS-target for treatment-resistant depression based on its key function within the reward circuit.
“The medial forebrain bundle (MFB) was selected as a DBS-target for TRD based on its key function within the reward circuit [63,64].”
From Deep brain stimulation for depression. (2022) · cites this paper as [64]
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Schatzberg, A. F. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12716 · Cited by 12 · see citing works
Acute antidepressant effects of deep brain stimulation – Review and data from slMFB-stimulation
Bewernick, B. H., Kayser, S., Gippert, S. M., Coenen, V. A., & Schlaepfer, T. E. (2017) · Personalized Medicine in Psychiatry · doi:10.1016/j.pmip.2017.01.002 · Cited by 12 · see citing works
Self-citationSchumacher, A., Haegele, M., Spyth, J., & Moser, A. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.112277 · Cited by 11 · see citing works
Combination of CT angiography and MRI in surgical planning of deep brain stimulation
Krüger, M. T., Coenen, V. A., Jenkner, C., Urbach, H., Egger, K. E., & Reinacher, P. C. (2018) · Neuroradiology · doi:10.1007/s00234-018-2079-0 · Cited by 10 · see citing works
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Giacolini, T., Alcaro, A., Conversi, D., & Tarsitani, L. (2025) · Frontiers in Psychology · doi:10.3389/fpsyg.2024.1391664 · Cited by 11 · see citing works
Kilian, H. M., Schiller, B., Meyer, D. M., Heinrichs, M., & Schläpfer, T. E. (2024) · Translational Psychiatry · doi:10.1038/s41398-023-02712-y · Cited by 9 · see citing works
- Authors
- Schlaepfer, T. E., Bewernick, B. H., Kayser, S., Hurlemann, R., & Coenen, V. A.
- Affiliations
- Johns Hopkins University (US)
- University Hospital Bonn (DE)
- University Medical Center Freiburg (DE)
- Corresponding author
- Schlaepfer, Thomas E
- Venue
- Neuropsychopharmacology
- Published
- 2014-02-11
- Volume
- 39
- Issue
- 6
- Pages
- 1303-1314
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3988559
- OpenAlex
- W2120569800
- Cited by
- 160
- References
- 101
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 6 · 2023: 8 · 2022: 13 · 2021: 11 · 2020: 10 · 2019: 10 · 2018: 26 · 2017: 16 · 2016: 17 · 2015: 20 · 2014: 10 · 2013: 2
- FWCI
- 2.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medtronic
- Hope for Depression Research Foundation
- Medtronic Europe
- Deutsche Forschungsgemeinschaft
- Volkswagen Foundation
- Rheinische Friedrich-Wilhelms-Universität Bonn
- Topics
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Keywords
- deep brain stimulation, treatment-resistant depression, reward systems, medial forebrain bundle, antidepressant effects, surgical risk, hypomania, animal models of depression, long-term follow-up, secondary outcome measures
- MeSH terms
- Animals, Brain, Major Depressive Disorder, Depressive Disorder, Major, Humans, Neural Pathways, Reward, Deep Brain Stimulation
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