Impact of Transcutaneous Vagal Nerve Stimulation on Stress Response in Major Depression

This study will identify the sex-dependent impact of expiratory-gated transcutaneous vagus nerve stimulation (tVNS) on the modulation of the stress response circuitry and associated physiology in major depressive disorder (MDD). We will evaluate a sample of 80 adults with recurrent MDD randomized to receive active or sham expiratory-gated tVNS during a functional magnetic resonance imaging (fMRI) session, with simultaneous mood and physiological assessments. We hypothesize that expiratory-gated tVNS will effectively modulate, in a sex-dependent manner, specific brainstem-cortical pathways of the stress circuitry and attenuate physiological deficits in MDD.

Inclusion Criteria: * Current or past diagnosis of recurrent Major Depressive Disorder Exclusion Criteria: * History of neuroleptic use * Any psychiatric disorder involving a history of psychosis (e.g. schizophrenia, bipolar I disorder) * Active suicidal ideation with intent and/or plan or history of a suicide attempt within the last year * Moderate or severe substance use disorder within the past 12 months * Diagnosis of significant cardiovascular or cerebrovascular disease (e.g. congestive heart failure, stroke, cardiac conduction disorders, history of asystole or non-sustained ventricular tachycardia) * Diseases affecting the CNS (e.g. MS, epilepsy, neurodegenerative diseases, etc.) * Traumatic brain injury with cognitive sequelae * MRI or tVNS contraindications (e.g. claustrophobia, metallic implants or devices) * Pregnancy (uncommon, given the age of this cohort is 50+ years) due to unknown health risks for the fetus