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

Author:

Lespérance Paul1,Desbeaumes Jodoin Véronique1ORCID,Drouin David2,Racicot Frédéric3,Miron Jean-Philippe1ORCID,Longpré-Poirier Christophe1ORCID,Fournier-Gosselin Marie-Pierre3,Thebault Paméla4,Lapointe Réjean24,Arbour Nathalie5,Cailhier Jean-François246ORCID

Affiliation:

1. Department of Psychiatry, Centre Hospitalier de l’Université de Montréal (CHUM), Université de Montréal, Montreal, QC H2X 0C1, Canada

2. Department of Medicine, Université de Montréal, Montreal, QC H3T 1J4, Canada

3. Division of Neurosurgery, CHUM, Université de Montréal, Montreal, QC H2X 0C1, Canada

4. Centre de Recherche du CHUM (CRCHUM), Institut du Cancer de Montréal, Montreal, QC H2X 0A9, Canada

5. Department of Neurosciences, Université de Montréal and CRCHUM, Montreal, QC H2X 0A9, Canada

6. Department of Medicine, Renal Division, CHUM, Université de Montréal, Montreal, QC H2X 0C1, Canada

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.

Funder

Chair Claude-Bertrand in neurosurgery of the Université de Montréal

Publisher

MDPI AG

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