Vagus Nerve Stimulation and Neurotrophins: a biological psychiatric perspective. Author: Rosso P1, Iannitelli A2, Pacitti F3, Quartini A2, Fico E1, Fiore M1, Greco A4, Ralli M4, Tirassa P5 Affiliation: <sup>1</sup>National Research Council (CNR), Institute of Biochemistry &amp; Cell Biology (IBBC) Rome, Italy. <sup>2</sup>Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy. <sup>3</sup>Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy; Psychiatry Unit San Salvatore Hospital, L'Aquila, Italy. <sup>4</sup>Department of Sense Organs, Sapienza University of Rome, Italy. <sup>5</sup>National Research Council (CNR), Institute of Biochemistry &amp; Cell Biology (IBBC) Rome, Italy. Electronic address: paola.tirassa@cnr.it. Conference/Journal: Neurosci Biobehav Rev. Date published: 2020 Apr 9 Other: Pages: S0149-7634(19)31051-6 , Special Notes: doi: 10.1016/j.neubiorev.2020.03.034. [Epub ahead of print] , Word Count: 187 Since 2004, vagus nerve stimulation (VNS) has been used in treatment-resistant or treatment-intolerant depressive episodes. Today, VNS is suggested as possible therapy for a larger spectrum of psychiatric disorders, including schizophrenia, obsessive compulsive disorders, and panic disorders. Despite a large body of literature supports the application of VNS in patients' treatment, the exact mechanism of action of VNS remains not fully understood. In the present study, the major knowledges on the brain areas and neuronal pathways regulating neuroimmune and autonomic response subserving VNS effects are reviewed. Furthermore, the involvement of the neurotrophins (NTs) Nerve Growth Factor (NGF) and Brain Derived Neurotrophic Factor (BDNF) in vagus nerve (VN) physiology and stimulation is revised. The data on brain NGF/BDNF synthesis and in turn on the activity-dependent plasticity, connectivity rearrangement and neurogenesis, are presented and discussed as potential biomarkers for optimizing stimulatory parameters for VNS. A vagus nerve-neurotrophin interaction model in the brain is finally proposed as a working hypothesis for future studies addressed to understand pathophysiology of psychiatric disturbance. Copyright © 2020. Published by Elsevier Ltd. KEYWORDS: BDNF; NGF; brain plasticity; neurogenesis; psychiatric disorders; stress; vagus nerve PMID: 32278791 DOI: 10.1016/j.neubiorev.2020.03.034