Hippocampal Gray Volumes Increase in Treatment-Resistant Depression Responding to Vagus Nerve Stimulation

Perini, Giulia; Toffanin, Tommaso; Pigato, Giorgio; Ferri, Giovanni; Follador, Halima; Zonta, Filippo; Pastorelli, Carlo; Piazzon, Giulia; Denaro, Luca; Rolma, Giuseppe; Ermani, Mario; D’Avella, Domenico

doi:10.1097/yct.0000000000000424

Cited by 29 publications

(21 citation statements)

References 49 publications

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“…Altered subcortical brain volumes have been associated with antidepressant response at baseline (Hsieh et al, 2002; Joshi et al, 2016; MacQueen et al, 2008; Vakili et al, 2000; Wade et al, 2016) and longitudinally in response to both psychopharmacological and psychosomatic interventions (Arnone et al, 2013; Frodl et al, 2008; Joshi et al, 2016; Perini et al, 2017; Phillips et al, 2015; Schermuly et al, 2011; Wade et al, 2016). The BDNF rs6265 SNP has also been associated with response to successful interventions ( Chi et al, 2010; Choi et al, 2006; Colle et al, 2015; Hwang et al, 2006; Laje et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

The antidepressant efficacy of subanesthetic-dose ketamine does not correlate with baseline subcortical volumes in a replication sample with major depressive disorder

et al. 2017

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Background This study sought to reproduce, in a larger sample, previous findings of a correlation between smaller raw 3-Tesla (3T) hippocampal volumes and improved antidepressant efficacy of ketamine in individuals with major depressive disorder (MDD). A secondary analysis stratified subjects according to functional BDNF rs6265 (val66met) genotype. Methods Unmedicated subjects with treatment-resistant MDD (n=55) underwent baseline structural 3T MRI. Data processing was conducted with FSL/FIRST and Freesurfer software. The amygdala, hippocampus, and thalamus were selected a priori for analysis. All subjects received a single 0.5mg/kg × 40-minute ketamine infusion. Pearson correlations were performed with subcortical volumes and percent change in MADRS score (from baseline to 230 minutes, 1 day, and 1 week post-infusion). Results Raw and corrected subcortical volumes did not correlate with antidepressant response at any timepoint. In val/val subjects (n=23), corrected left and right thalamic volume positively correlated with antidepressant response to ketamine at 230 minutes post-infusion but did not reach statistical significance. In met carriers (n=14), corrected left and right thalamic volume negatively correlated with antidepressant response to ketamine. Conclusion Baseline subcortical volumes implicated in MDD did not correlate with ketamine’s antidepressant efficacy. Baseline thalamic volume and BDNF genotype may be a combinatorial rapid antidepressant response biomarker.

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Section: Discussionmentioning

confidence: 99%

The antidepressant efficacy of subanesthetic-dose ketamine does not correlate with baseline subcortical volumes in a replication sample with major depressive disorder

et al. 2017

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“…There is evidence that VNS may aid depression treatment, but future work remains before widespread clinical use. There are several other studies examined in this section and referred to in the table but not discussed in detail ( Sackeim et al, 2001 ; Lomarev et al, 2002 ; Mu et al, 2004 ; Nahas et al, 2005 , 2007 ; Zobel et al, 2005 ; Conway et al, 2006 , 2012 ; Pardo et al, 2008 ; Cristancho et al, 2011 ; Kosel et al, 2011 ; Aaronson et al, 2013 ; Hein et al, 2013 ; Fang et al, 2016 ; Rong et al, 2016 ; Perini et al, 2017 ; Tu et al, 2018 ).…”

Section: Vns For Treatment Resistant Depression (Trd)mentioning

confidence: 99%

A Review of Parameter Settings for Invasive and Non-invasive Vagus Nerve Stimulation (VNS) Applied in Neurological and Psychiatric Disorders

et al. 2021

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Vagus nerve stimulation (VNS) is an established form of neuromodulation with a long history of promising applications. Earliest reports of VNS in the literature date to the late 1800’s in experiments conducted by Dr. James Corning. Over the past century, both invasive and non-invasive VNS have demonstrated promise in treating a variety of disorders, including epilepsy, depression, and post-stroke motor rehabilitation. As VNS continues to rapidly grow in popularity and application, the field generally lacks a consensus on optimum stimulation parameters. Stimulation parameters have a significant impact on the efficacy of neuromodulation, and here we will describe the longitudinal evolution of VNS parameters in the following categorical progression: (1) animal models, (2) epilepsy, (3) treatment resistant depression, (4) neuroplasticity and rehabilitation, and (5) transcutaneous auricular VNS (taVNS). We additionally offer a historical perspective of the various applications and summarize the range and most commonly used parameters in over 130 implanted and non-invasive VNS studies over five applications.

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“…In the rat hippocampus, VNS resulted in increased volume, 39 expression of neurotrophic growth factors, 40 neuronal plasticity and cell proliferation, 40,41 synaptic transmission, 42 blood flow, 43 and local theta rhythms. 44 In addition, VNS appears to enhance memory in both rats and humans, likely due to increased activation of hippocampal circuitry.…”

Section: Limbic Circuitrymentioning

confidence: 99%

Connectomic Profiling Identifies Responders to Vagus Nerve Stimulation

Mithani

Mikhail

Morgan

et al. 2019

Annals of Neurology

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Objective: Vagus nerve stimulation (VNS) is a common treatment for medically intractable epilepsy, but response rates are highly variable, with no preoperative means of identifying good candidates. This study aimed to predict VNS response using structural and functional connectomic profiling. Methods: Fifty-six children, comprising discovery (n = 38) and validation (n = 18) cohorts, were recruited from 3 separate institutions. Diffusion tensor imaging was used to identify group differences in white matter microstructure, which in turn informed beamforming of resting-state magnetoencephalography recordings. The results were used to generate a support vector machine learning classifier, which was independently validated. This algorithm was compared to a second classifier generated using 31 clinical covariates. Results: Treatment responders demonstrated greater fractional anisotropy in left thalamocortical, limbic, and association fibers, as well as greater connectivity in a functional network encompassing left thalamic, insular, and temporal nodes (p < 0.05). The resulting classifier demonstrated 89.5% accuracy and area under the receiver operating characteristic (ROC) curve of 0.93 on 10-fold cross-validation. In the external validation cohort, this model demonstrated an accuracy of 83.3%, with a sensitivity of 85.7% and specificity of 75.0%. This was significantly superior to predictions using clinical covariates alone, which exhibited an area under the ROC curve of 0.57 (p < 0.008). Interpretation: This study provides the first multi-institutional, multimodal connectomic prediction algorithm for VNS, and provides new insights into its mechanism of action. Reliable identification of VNS responders is critical to mitigate surgical risks for children who may not benefit, and to ensure cost-effective allocation of health care resources. ANN NEUROL 2019;86:743-753 N early one-third of children with epilepsy are refractory to medications. 1,2 Persistent seizures are associated with mortality, disability, psychosocial isolation, and diminished quality of life. 3-6 Vagus nerve stimulation (VNS) is an effective, safe, and well-tolerated intervention for a subset of patients with treatment-resistant epilepsy. 7-10 Although the goal of VNS is not complete resolution of seizures, many children will show a significant reduction in seizure frequency, as well as a reduction in hospitalizations and psychosocial comorbidities. 11,12 View this article online at wileyonlinelibrary.com.

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Hippocampal Gray Volumes Increase in Treatment-Resistant Depression Responding to Vagus Nerve Stimulation

Abstract: Our data suggest a VNS modulatory effect on hippocampal plasticity as measured by hippocampal gray volume increase in TRD patients. These preliminary findings indicate the fundamental role of hippocampal remodeling as a marker of response to VNS in TRD.

Cited by 29 publications

References 49 publications

The antidepressant efficacy of subanesthetic-dose ketamine does not correlate with baseline subcortical volumes in a replication sample with major depressive disorder

The antidepressant efficacy of subanesthetic-dose ketamine does not correlate with baseline subcortical volumes in a replication sample with major depressive disorder

A Review of Parameter Settings for Invasive and Non-invasive Vagus Nerve Stimulation (VNS) Applied in Neurological and Psychiatric Disorders

Connectomic Profiling Identifies Responders to Vagus Nerve Stimulation

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