Nucleus Accumbens Deep Brain Stimulation Decreases Ratings of Depression and Anxiety in Treatment-Resistant Depression

Bewernick, Bettina H.; Hurlemann, René; Matusch, Andreas; Kayser, Sarah; Grubert, Christiane; Hadrysiewicz, B.; Axmacher, Nikolai; Lemke, Matthias R.; Cooper‐Mahkorn, Déirdre; Cohen, Michael X; Brockmann, Holger; Lenartz, Doris; Sturm, Volker; Schläepfer, Thomas E.

doi:10.1016/j.biopsych.2009.09.013

Cited by 738 publications

(516 citation statements)

References 34 publications

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“…It is important to note, however, that for improvements to be achieved, both these target areas require relatively high stimulation parameters. Furthermore, the stereotactic coordinates of the active electrodes used in both targets are identical in the internal capsule or ventral striatum [78] and the NAcc [115], indicating that the same target is probably involved (the NAcc is located within the ventral striatum).…”

Section: Refractory Depressionmentioning

confidence: 98%

Deep brain stimulation in Parkinson disease—what went wrong?

Krack

Hariz

2010

Nat Rev Neurol

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Section: Refractory Depressionmentioning

confidence: 98%

Deep brain stimulation in Parkinson disease—what went wrong?

Krack

Hariz

2010

Nat Rev Neurol

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“…DBS aims to modulate dysfunctional neuronal networks involved in depression (Krishnan and Nestler, 2010). Three major brain regions have been selected in a hypothesisdriven way for major depression: nucleus accumbens (NAcc) (Bewernick et al, 2010;Schlaepfer and Lieb, 2005), subgenual cingulate cortex (Cg 25 ) Mayberg et al, 2005) and the anterior limb of the capsula interna (ALIC) (Malone et al, 2009). Although the precise mechanism of action is not known yet, significant antidepressant effects have been shown in a 1-year follow-up period in 50-60% of the about 45 treated patients (Bewernick et al, 2010;Lozano et al, 2008;Malone et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Long-Term Effects of Nucleus Accumbens Deep Brain Stimulation in Treatment-Resistant Depression: Evidence for Sustained Efficacy

Bewernick

Kayser

Sturm

et al. 2012

Neuropsychopharmacol

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322

198

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Deep brain stimulation (DBS) to the nucleus accumbens (NAcc-DBS) was associated with antidepressant, anxiolytic, and procognitive effects in a small sample of patients suffering from treatment-resistant depression (TRD), followed over 1 year. Results of long-term follow-up of up to 4 years of NAcc-DBS are described in a group of 11 patients. Clinical effects, quality of life (QoL), cognition, and safety are reported. Eleven patients were stimulated with DBS bilateral to the NAcc. Main outcome measures were clinical effect (Hamilton Depression Rating Scale, Montgomery-Asperg Rating Scale of Depression, and Hamilton Anxiety Scale) QoL (SF-36), cognition and safety at baseline, 12 months (n ¼ 11), 24 months (n ¼ 10), and last follow-up (maximum 4 years, n ¼ 5). Analyses were performed in an intent-to-treat method with last observation carried forward, thus 11 patients contributed to each point in time. In all, 5 of 11 patients (45%) were classified as responders after 12 months and remained sustained responders without worsening of symptoms until last follow-up after 4 years. Both ratings of depression and anxiety were significantly reduced in the sample as a whole from first month of NAcc-DBS on. All patients improved in QoL measures. One non-responder committed suicide. No severe adverse events related to parameter change were reported. First-time, preliminary long-term data on NAcc-DBS have demonstrated a stable antidepressant and anxiolytic effect and an amelioration of QoL in this small sample of patients suffering from TRD. None of the responders of first year relapsed during the observational period (up to 4 years).

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“…The NAc acts as a central regulator of emotional behaviors, and its function is tightly modulated by a number of molecular mechanisms, including histone deactylases, IkK, and DFosB, among others (Christoffel et al, 2011a;Covington et al, 2009;Vialou et al, 2010). Importantly, the NAc is a relevant target for therapeutic exploration in major depressive disorder, as deep brain stimulation of the NAc reduces anxiety and depression in previously treatment-resistant major depressive disorder patients (Bewernick et al, 2010). These findings highlight the critical role of NAc in emotional behaviors and suggest that novel modulators of neuronal function in NAc may improve therapeutic outcomes for psychiatric patients.…”

Section: Introductionmentioning

confidence: 99%

Effects of Inhibitor of κB Kinase Activity in the Nucleus Accumbens on Emotional Behavior

Christoffel

Golden

Heshmati

et al. 2012

Neuropsychopharmacol

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Inhibitor of kB kinase (IkK) has historically been studied in the context of immune response and inflammation, but recent evidence demonstrates that IkK activity is necessary and sufficient for regulation of neuronal function. Chronic social defeat stress of mice increases IkK activity in the nucleus accumbens (NAc) and this increase is strongly correlated to depression-like behaviors. Inhibition of IkK signaling results in a reversal of chronic social defeat stress-induced social avoidance behavior. Here, we more completely define the role of IkK in anxiety and depressive-like behaviors. Mice underwent stereotaxic microinjection of a herpes simplex virus expressing either green fluorescent protein, a constitutively active form of IkK (IkKca), or a dominant negative form of IkK into the NAc. Of all three experimental groups, only mice expressing IkKca show a behavioral phenotype. Expression of IkKca results in a decrease in the time spent in the nonperiphery zones of an open field arena and increased time spent immobile during a forced swim test. No baseline differences in sucrose preference were observed, but following the acute swim stress we noted a marked reduction in sucrose preference. To determine whether IkK activity alters responses to other acute stressors, we examined behavior and spine morphology in mice undergoing an acute social defeat stress. We found that IkKca enhanced social avoidance behavior and promoted thin spine formation. These data show that IkK in NAc is a critical regulator of both depressive-and anxiety-like states and may do so by promoting the formation of immature excitatory synapses.

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Nucleus Accumbens Deep Brain Stimulation Decreases Ratings of Depression and Anxiety in Treatment-Resistant Depression

Cited by 738 publications

References 34 publications

Deep brain stimulation in Parkinson disease—what went wrong?

Deep brain stimulation in Parkinson disease—what went wrong?

Long-Term Effects of Nucleus Accumbens Deep Brain Stimulation in Treatment-Resistant Depression: Evidence for Sustained Efficacy

Effects of Inhibitor of κB Kinase Activity in the Nucleus Accumbens on Emotional Behavior

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