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Deep Brain Stimulation to Reward Circuitry Alleviates Anhedonia in Refractory Major Depression
Open accessAbstract
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.
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“DBS targeting the NAc was shown to exert antidepressant, anxiolytic, and hedonic effects, notably in treatment-resistant depression (Bewernick et al. 2010; Giacobbe et al. 2009; Schlaepfer et al. 2008).”
From Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression (2018) · cites this paper as Schlaepfer et al. 2008
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“deep brain stimulation applied via electrodes situated in the accumbens area/ventral internal capsule improves depressive symptoms in treatmentrefractory depression (Malone et al, 2009;Schlaepfer et al, 2008).”
From Neurocircuitry of Mood Disorders (2010) · cites this paper as Schlaepfer et al, 2008
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“and that deep brain stimulation applied via electrodes situated in the accumbens area/ventral internal capsule reportedly improves depressive symptoms in treatment-refractory depression (Schlaepfer et al. 2008).”
From Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression (2008) · cites this paper as Schlaepfer et al. 2008
In the citing paper
“Treatments with enhanced spatial specificity such as deep brain stimulation (DBS) or transcranial magnetic stimulation (TMS), aimed to restore region-specific hypoactivity, show great promise in alleviating treatment-resistant depression in even the most severe cases (2–10).”
From Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression (2017) · cites this paper as [8]
In the citing paper
“High frequency DBS of the NAc, among other regions, shows great promise in alleviating treatment-resistant depression, though its mechanism is still unclear (5, 8, 10).”
From Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression (2017) · cites this paper as [8]
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“patients responding to DBS of the NAc, a region more associated with reward and positive affect, report acutely improved motivation for pleasurable activities [99].”
From Deep brain stimulation for depression. (2022) · cites this paper as [99]
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“interaction with world targets can also be seen in people who suddenly have their mesolimbic dopamine systems artificially activated for the first time, such as by a newly-implanted brain stimulation electrode.”
From Evolving Concepts of Emotion and Motivation (2018) · cites this paper as Schlaepfer et al., 2008
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“…or in depression associated with obsessive–complusive disorder (Van Laere et al. 2006), and that deep brain stimulation applied via electrodes situated in the accumbens area/ventral internal capsule reportedly improves depressive symptoms in treatment-refractory depression (Schlaepfer et al. 2008).”
Background
Metadata
- Authors
- Schlaepfer, T. E., Cohen, M. X., Frick, C., Kosel, M., Brodesser, D., Axmacher, N., Joe, A. Y., Kreft, M., Lenartz, D., & Sturm, V.
- Affiliations
- Johns Hopkins University (US)
- University Hospital Bonn (DE)
- University Hospital Cologne (DE)
- Corresponding author
- Schlaepfer, Thomas E
- Venue
- Neuropsychopharmacology
- Published
- 2007-04-11
- Volume
- 33
- Issue
- 2
- Pages
- 368-377
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- OpenAlex
- W2141467587
- Cited by
- 1,027
- References
- 61
- Citations by year
- 2026: 18 · 2025: 19 · 2024: 36 · 2023: 42 · 2022: 36 · 2021: 54 · 2020: 81 · 2019: 52 · 2018: 54 · 2017: 45 · 2016: 51 · 2015: 73 · 2014: 75 · 2013: 66 · 2012: 78
- FWCI
- 41.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (acceptedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Keywords
- deep brain stimulation, nucleus accumbens, anhedonia, reward system dysfunction, brain metabolism, FDG-PET, fronto-striatal network, treatment-resistant depression
- MeSH terms
- Depressive Disorder, Double-Blind Method, Humans, Philosophy, Reward, Time Factors, Deep Brain Stimulation, Positron-Emission Tomography
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