{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:20:02Z","timestamp":1791570002682,"version":"4.3.4"},"reference-count":83,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T00:00:00Z","timestamp":1698019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The discovery of effective treatments for major depressive disorder (MDD) may help target different brain pathways. Invasive vagus nerve stimulation (VNS) is an effective neuromodulation technique for the treatment of MDD; however, the effectiveness of the noninvasive technique, transauricular VNS (taVNS), remains unknown. Moreover, a mechanistic understanding of the neural effects behind its biological and therapeutic effects is lacking. This review aimed to evaluate the clinical evidence and the neural and anti-inflammatory effects of taVNS in MDD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Two searches were conducted using a systematic search strategy reviewed the clinical efficacy and neural connectivity of taVNS in MDD in humans and evaluated the changes in inflammatory markers after taVNS in humans or animal models of depression. A risk of bias assessment was performed in all human studies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Only 5 studies evaluated the effects of taVNS in patients with depression. Although the studies demonstrated the efficacy of taVNS in treating depression, they used heterogeneous methodologies and limited data, thus preventing the conduct of pooled quantitative analyses. Pooled analysis could not be performed for studies that investigated the modulation of connectivity between brain areas; of the 6 publications, 5 were based on the same experiment. The animal studies that analyzed the presence of inflammatory markers showed a reduction in the level of pro-inflammatory cytokines or receptor expression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Data on the clinical efficacy of taVNS in the treatment of MDD are limited. Although these studies showed positive results, no conclusions can be drawn regarding this topic considering the heterogeneity of these studies, as in the case of functional connectivity studies. Based on animal studies, the application of taVNS causes a decrease in the level of inflammatory factors in different parts of the brain, which also regulate the immune system. Therefore, further studies are needed to understand the effects of taVNS in patients with MDD.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ijnp\/pyad058","type":"journal-article","created":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T14:04:35Z","timestamp":1698069875000},"source":"Crossref","is-referenced-by-count":29,"title":["Neural, Anti-Inflammatory, and Clinical Effects of Transauricular Vagus Nerve Stimulation in Major Depressive Disorder: A Systematic Review"],"prefix":"10.1093","volume":"27","author":[{"given":"Joao","family":"Parente","sequence":"first","affiliation":[{"name":"Escola Bahiana de Medicina e Sa\u00fade P\u00fablica , Salvador, Bahia , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Carolyna Gianlorenco","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Federal University of Sao Carlos , Sao Paulo , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Rebello-Sanchez","sequence":"additional","affiliation":[{"name":"Universidade Federal da Bahia , Salvador, Bahia , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minkyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology, Korea University Guro Hospital , Seoul , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Mario Prati","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, Federal University of Sao Carlos , Sao Paulo , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Kyung Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology, Korea University Guro Hospital , Seoul , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyuk","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Graduate School of Medicine, Korea University , Seoul , Republic of Korea"},{"name":"Neurive Co., Ltd. , Gimhae , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Jun","family":"Song","sequence":"additional","affiliation":[{"name":"Neurive Co., Ltd. , Gimhae , Republic of Korea"},{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Medical Center , Seoul , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1703-7526","authenticated-orcid":false,"given":"Felipe","family":"Fregni","sequence":"additional","affiliation":[{"name":"Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School , Boston, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,10,23]]},"reference":[{"key":"2024032719513577500_CIT0001","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1097\/00006842-197507000-00007","article-title":"Behaviorally conditioned immunosuppression","volume":"37","author":"Ader","year":"1975","journal-title":"Psychosom Med"},{"key":"2024032719513577500_CIT0002","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.neuroscience.2012.05.070","article-title":"The projection and synaptic organization of NTS afferent connections with presympathetic neurons, GABA and nNos neurons in the paraventricular nucleus of the hypothalamus","volume":"219","author":"Affleck","year":"2012","journal-title":"Neuroscience"},{"key":"2024032719513577500_CIT0003","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.neuron.2020.06.002","article-title":"The bidirectional relationship of depression and inflammation: double trouble","volume":"107","author":"Beurel","year":"2020","journal-title":"Neuron"},{"key":"2024032719513577500_CIT0004","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.biopsych.2009.09.013","article-title":"Nucleus accumbens deep brain stimulation decreases rating of depression and anxiety in treatment - 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