Vagus nerve stimulation in treating depression: A tale of two stories.

Major depressive disorder (MDD) is prevalent. Although standards antidepressants are more effective than placebo, up to 35% of patients do not respond to 4 or more conventional treatments and are considered to have treatment-resistant depression (TRD). Considerable effort has been devoted to trying to find effective treatments for TRD. This review focuses on vagus nerve stimulation (VNS), approved for TRD in 2005 by the Food and Drugs Administration. Stimulation is carried by bipolar electrodes on the left cervical vagus nerve, which are attached to an implanted stimulator generator. The vagus bundle contains about 80% of afferent fibers terminating in the medulla, from which there are projections to many areas of brain, including the limbic forebrain. Various types of brain imaging studies reveal widespread functional effects in brain after either acute or chronic VNS. Although more randomized control trials of VNS need to be carried out before a definitive conclusion can be reached about its efficacy, the results of open studies, carried out over period of 1 to 2 years, show much more efficacy when compared with results from treatment as usual studies. There is an increase in clinical response to VNS between 3 and 12 months, which is quite different from that seen with standard antidepressant treatment of MDD. Preclinically, VNS affects many of the same brain areas, neurotransmitters (serotonin, norepinephrine) and signal transduction mechanisms (brain-derived neurotrophic factor-tropomyosin receptor kinase B) as those found with traditional antidepressants. Nevertheless, the mechanisms by which VNS benefits patients nonresponsive to conventional antidepressants is unclear, with further research needed to clarify this.

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“…Similar results were found after chronic treatment with fluoxetine [124]. This topic has been reviewed recently [125].…”

Section: Effect On Neurogenesis and Neurotrophinssupporting

confidence: 61%

Vagal Nerve Stimulation for Treatment-Resistant Depression

2017

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“…This functional dissociation of taVNS-induced effects is clinically relevant because cost-evidence accumulation is affected by escitalopram, a selective serotonin reuptake inhibitor and common antidepressant drug (Meyniel et al, 2016). Thus, antidepressive effects of VNS (Fang et al, 2016;Grimonprez et al, 2015;Hein et al, 2013;Liu et al, 2016;Tu et al, 2018;Wu et al, 2018;Yuan, Li, Sun, Arias-Carrion, & Machado, 2016) may act via a different neurobehavioral mechanism on the utility of effort than commonly used anti-depressant, pointing to the potential of complementing currently used pharmacological treatment regimes (Argyropoulos & Nutt, 2013).…”

Section: Discussionmentioning

confidence: 99%

Vagus nerve stimulation increases vigor to work for rewards

Neuser

Teckentrup

Kuehnel

et al. 2019

Preprint

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Interoceptive feedback transmitted via the vagus nerve plays a vital role in motivation by tuning actions according to physiological needs. Whereas vagus nerve stimulation (VNS) reinforces actions and enhances dopamine transmission in animals, motivational effects elicited by VNS in humans are still largely elusive. Here, we applied non-invasive transcutaneous auricular VNS (taVNS) on the left or the right ear using a randomized cross-over design (vs. sham). During stimulation, 81 healthy participants had to exert effort to earn food or monetary rewards. We reasoned that taVNS enhances motivation and tested whether it does so by increasing prospective benefits (i.e., vigor) or reducing costs of action (i.e., maintenance) compared to sham stimulation. In line with preclinical studies, taVNS generally enhanced invigoration of effort (p = .004, Bayes factor, BF10 = 7.34), whereas stimulation on the left side primarily facilitated vigor for food rewards (left taVNS: Stimulation × Reward Type, p = .003, BF10 = 11.80). In contrast, taVNS did not affect effort maintenance (ps ≥ .09, BF10 < 0.52). Critically, during taVNS, vigor declined less steeply with decreases in wanting (∆b = -.046, p = .031) indicating a boost in the drive to work for rewards. Collectively, our results suggest that taVNS enhances reward-seeking by boosting vigor, not effort maintenance and that the side of the stimulation affects generalization beyond food reward. We conclude that taVNS may enhance the pursuit of prospective rewards which may pave new avenues for treatment of motivational deficiencies. taVNS increases vigor Neuser et al.3

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“…In patients with TRD, VNS has been shown to improve symptoms of depression 79,80. Imaging studies using either single photon emission computed tomography or blood oxygen level-dependent methods revealed that improvement in depression symptoms induced by VNS was associated with decreased activity in the sgACC, VMPFC, and ACC and increased activity of the superior temporal gyrus 81,82…”

Section: Neurobiology Of Mood Disordersmentioning

confidence: 99%

Neurobiology of hedonic tone: the relationship between treatment-resistant depression, attention-deficit hyperactivity disorder, and substance abuse

Sternat¹,

Katzman²

2016

NDT

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Anhedonia, defined as the state of reduced ability to experience feelings of pleasure, is one of the hallmarks of depression. Hedonic tone is the trait underlying one’s characteristic ability to feel pleasure. Low hedonic tone represents a reduced capacity to experience pleasure, thus increasing the likelihood of experiencing anhedonia. Low hedonic tone has been associated with several psychopathologies, including major depressive disorder (MDD), substance use, and attention-deficit hyperactivity disorder (ADHD). The main neural pathway that modulates emotional affect comprises the limbic–cortical–striatal–pallidal–thalamic circuits. The activity of various components of the limbic–cortical–striatal–pallidal–thalamic pathway is correlated with hedonic tone in healthy individuals and is altered in MDD. Dysfunction of these circuits has also been implicated in the relative ineffectiveness of selective serotonin reuptake inhibitors used to treat anxiety and depression in patients with low hedonic tone. Mood disorders such as MDD, ADHD, and substance abuse share low hedonic tone as well as altered activation of brain regions involved in reward processing and monoamine signaling as their features. Given the common features of these disorders, it is not surprising that they have high levels of comorbidities. The purpose of this article is to review the neurobiology of hedonic tone as it pertains to depression, ADHD, and the potential for substance abuse. We propose that, since low hedonic tone is a shared feature of MDD, ADHD, and substance abuse, evaluation of hedonic tone may become a diagnostic feature used to predict subtypes of MDD, such as treatment-resistant depression, as well as comorbidities of these disorders.

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Vagus nerve stimulation in treating depression: A tale of two stories.

Cited by 20 publications

References 73 publications

Vagal Nerve Stimulation for Treatment-Resistant Depression

Vagal Nerve Stimulation for Treatment-Resistant Depression

Vagus nerve stimulation increases vigor to work for rewards

Neurobiology of hedonic tone: the relationship between treatment-resistant depression, attention-deficit hyperactivity disorder, and substance abuse

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