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. 2024 Feb 26;25(5):2679.
doi: 10.3390/ijms25052679.

Vagus Nerve Stimulation Modulates Inflammation in Treatment-Resistant Depression Patients: A Pilot Study

Paul Lespérance  1 , Véronique Desbeaumes Jodoin  1 , David Drouin  2 , Frédéric Racicot  3 , Jean-Philippe Miron  1 , Christophe Longpré-Poirier  1 , Marie-Pierre Fournier-Gosselin  3 , Paméla Thebault  4 , Réjean Lapointe  2   4 , Nathalie Arbour  5 , Jean-François Cailhier  2   4   6
Affiliations

Vagus Nerve Stimulation Modulates Inflammation in Treatment-Resistant Depression Patients: A Pilot Study

Paul Lespérance et al. Int J Mol Sci. .

Abstract

Vagal neurostimulation (VNS) is used for the treatment of epilepsy and major medical-refractory depression. VNS has neuropsychiatric functions and systemic anti-inflammatory activity. The objective of this study is to measure the clinical efficacy and impact of VNS modulation in depressive patients. Six patients with refractory depression were enrolled. Depression symptoms were assessed with the Montgomery-Asberg Depression Rating, and anxiety symptoms with the Hamilton Anxiety Rating Scale. Plasmas were harvested prospectively before the implantation of VNS (baseline) and up to 4 years or more after continuous therapy. Forty soluble molecules were measured in the plasma by multiplex assays. Following VNS, the reduction in the mean depression severity score was 59.9% and the response rate was 87%. Anxiety levels were also greatly reduced. IL-7, CXCL8, CCL2, CCL13, CCL17, CCL22, Flt-1 and VEGFc levels were significantly lowered, whereas bFGF levels were increased (p values ranging from 0.004 to 0.02). This exploratory study is the first to focus on the long-term efficacy of VNS and its consequences on inflammatory biomarkers. VNS may modulate inflammation via an increase in blood-brain barrier integrity and a reduction in inflammatory cell recruitment. This opens the door to new pathways involved in the treatment of refractory depression.

Keywords: blood–brain barrier; inflammation; major depression; neuromodulation.

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Conflict of interest statement

Nathalie Arbour declares having been a guest speaker for Novartis in 2017 and 2018. Jean François Cailhier declares having been a panel member organized by Genzyme in 2017 and 2018 and received honorary from Astra-Zeneca for presentation and steering committee in 2021. Paul Lespérance declares having been a guest speaker for LivaNova in 2017 on VNS in resistant depression. Other authors did not have any conflict.

Figures

Figure 1
Figure 1
Individualized variations and dispersion of cytokine/chemokine levels for each VNS patient. Pre-implantation and post-implantation values for IL-7, CXCL8, VEGF-C, Flt-1, CCL2, CCL13, bFGF, CCL17 and CCL22 and bFGF (values in pg/mL). Squares are pre-treatment values, black circles are post-treament values.
Figure 2
Figure 2
Levels of inflammatory proteins previously reported to be modulated in depressive patients. Individualized variations for TNF-α, IL-6 and IFNγ in VNS patients were not significant. Squares are pre-treatment values, black circles are post-treament values.
See this image and copyright information in PMC

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