Non-invasive neuromodulation in bipolar depression to improve symptoms and reduce low-grade chronic inflammation and cardiovascular risk.

• Grant number: 23/18278-7
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: May 06, 2024
• End date: May 05, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Helio Cesar Salgado
• Grantee: Thaís Marques da Silva
• Supervisor: Nicola Montano
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Università degli Studi di Milano, Italy
• Associated to the scholarship: 22/07579-3 - Experimental periodontitis in genetically modified mice (VAChT and Super VAChT): cardiovascular and inflammatory aspects, BP.PD

Abstract

The impact of depressive behavior on individuals with bipolar disorder is devastating, markedly increasing the risk of suicide and severely compromising their quality of life. It is well established that depressive disorders are strongly linked to both chronic inflammatory conditions and autonomic disfunction. Elevated inflammation levels have been observed to heighten the susceptibility to depression development. Therefore, targeting the anti-inflammatory pathway emerges as a promising avenue for advancing neuropsychopharmacological research. Additionally, the since the knowledge of the existence of the "Inflammatory Reflex," primarily mediated by the vagus nerve, further underscores the significance of this direction in exploration and treatment of depression. The non-pharmacological treatment of unipolar depression through repetitive transcranial magnetic stimulation (rTMS) or vagus nerve stimulation (VNS) has displayed promising outcomes. These therapies have demonstrated efficacy not just in addressing psychiatric symptoms but also in ameliorating inflammatory and autonomic disorders. However, the low efficacy of rTMS and the invasiveness of implantable VNS devices pose more challenges to its broad clinical application. The present proposal aims to compare the efficacy of rTMS with transcutaneous auricular vagus nerve stimulation (tVNS), a new non-invasive alternative to implantable VNS, as an antidepressant treatment for patients with bipolar depression. The efficacy of the combination of tVNS and rTMS will also be evaluated and compared with each individual technique. Moreover, since both these approaches target the frontal-vagal network, our secondary aim is to test the effects of tVNS on the patients' inflammatory profile, cardiovascular autonomic control, and sleep quality.