BackgroundTranscutaneous vagus nerve stimulation (tVNS) is a promising therapeutic option for major depressive disorder (MDD) in adults. Alternative third-line treatments for MDD in adolescents are scarce. Here we aimed to assess the effects of acute tVNS on emotion recognition in adolescents with MDD.MethodsAdolescents (14-17 years) with MDD (n = 33) and non-depressed controls (n = 30) received tVNS or sham-stimulation in a cross-sectional, case-control, within-subject cross-randomized controlled trial, while performing different tasks assessing emotion recognition. Correct responses, response times, and errors of omission and commission on three different computerized emotion recognition tasks were assessed as main outcomes. Simultaneous recordings of electrocardiography and electro dermal activity, as well as sampling of saliva for the determination of $α$-Amylase, were used to quantify the effects on autonomic nervous system function.ResultstVNS had no effect on the recognition of gradually or static expressed emotions but altered response inhibition on the emotional Go/NoGo-Task. Specifically, tVNS increased the likelihood of omitting a response toward sad target-stimuli in adolescents with MDD, while decreasing errors (independent of the target emotion) in controls. Effects of acute tVNS on autonomic nervous system function were found in non-depressed controls only.ConclusionsAcute tVNS alters the recognition of briefly presented facial expressions of negative valence in adolescents with MDD while generally increasing emotion recognition in controls.TVNS seems to specifically alter early visual processing of stimuli of negative emotional valence in MDD. These findings suggest a potential therapeutic benefit of tVNS in adolescent MDD that requires further evaluation within clinical trials.