{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:59:52Z","timestamp":1790848792831,"version":"4.1.0"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>\n                    This narrative review explores the therapeutic potential of hyperbaric oxygen therapy (HBO\n                    <jats:sub>2<\/jats:sub>\n                    ) in treating major depressive disorder (MDD). We highlight the common pathophysiological hypotheses for MDD, the strengths and limitations of current MDD treatments, and the potential for HBO\n                    <jats:sub>2<\/jats:sub>\n                    to be a novel MDD therapeutic through anti-inflammatory and neuroprotective mechanisms. The current review discusses the monoamine, neuronal atrophy, and inflammation hypotheses of MDD pathophysiology origin, as well as how present MDD therapeutics target these MDD pathophysiological traits. While there are a multitude of existing treatments for MDD, including those pharmacological, psychotherapeutic, and neuromoduatory in nature, many treatments possess limitations. The management of difficult-to-treat depression is particularly challenging, highlighting the need for innovative, effective treatments to be developed. HBO\n                    <jats:sub>2<\/jats:sub>\n                    is a potential novel therapy for MDD, exerting antidepressant effects through its ability to promote neurogenesis and anti-inflammatory processes in the central nervous system. Moreover, HBO\n                    <jats:sub>2<\/jats:sub>\n                    has been indirectly correlated with an improvement in depressive symptoms in studies done in the context of treatment for post-traumatic stress disorder (PTSD), traumatic brain injury (TBI), post-stroke recovery, and post-coronavirus disease condition (post-COVID-19). However, there is currently a dearth of direct evidence supporting the indication of HBO\n                    <jats:sub>2<\/jats:sub>\n                    for MDD, and clinical trials that investigate HBO\n                    <jats:sub>2<\/jats:sub>\n                    as a primary treatment for MDD are needed. The current review provides a rationale for further exploration of the potential of HBO\n                    <jats:sub>2<\/jats:sub>\n                    as a novel therapy for MDD.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2026.1931426","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:45:40Z","timestamp":1790847940000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Hyperbaric oxygen therapy as a potential treatment for MDD: a narrative review"],"prefix":"10.3389","volume":"13","author":[{"given":"Yun Chen","family":"Pang","sequence":"first","affiliation":[{"name":"Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto","place":["Toronto, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Giacobbe","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto","place":["Toronto, ON, Canada"]},{"name":"Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto","place":["Toronto, ON, Canada"]},{"name":"Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre","place":["Toronto, ON, Canada"]},{"name":"Kerr Chair in Interventional Psychiatry, Sunnybrook Health Sciences Centre","place":["Toronto, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahad","family":"Alam","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto","place":["Toronto, ON, Canada"]},{"name":"Department of Anesthesia, Sunnybrook Health Sciences Centre","place":["Toronto, ON, Canada"]},{"name":"Department of Anesthesiology and Pain Medicine, University of Toronto","place":["Toronto, ON, Canada"]},{"name":"School of Medicine, Toronto Metropolitan University","place":["Toronto, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"B1","year":"2017"},{"key":"B2","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1590\/1516-4446-2020-0650","article-title":"Prevalence and correlates of major depressive disorder: a systematic review","volume":"42","author":"Guti\u00e9rrez-Rojas","year":"2020","journal-title":"Braz J Psychiatry"},{"key":"B3","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/S2215-0366(21)00395-3","article-title":"Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990\u20132019: a systematic analysis for the global burden of disease study 2019","volume":"9","year":"2022","journal-title":"Lancet Psychiatry"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e073823","DOI":"10.1136\/bmj-2022-073823","article-title":"New and emerging treatments for major depressive disorder","volume":"386","author":"Njenga","year":"2024","journal-title":"Br Med J"},{"key":"B5","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/S0140-6736(22)02080-3","article-title":"Novel and emerging treatments for major depression","volume":"401","author":"Marwaha","year":"2023","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/s41572-023-00454-1","article-title":"Major depressive disorder","volume":"9","author":"Marx","year":"2023","journal-title":"Nat Rev Dis Primers"},{"key":"B7","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1212\/CON.0000000000000604","article-title":"Mood disorders","volume":"24","author":"Rakofsky","year":"2018","journal-title":"Continuum (Minneap Minn)"},{"key":"B8","first-page":"4","article-title":"History and evolution of the monoamine hypothesis of depression","volume":"61","author":"Hirschfeld","year":"2000","journal-title":"J Clin Psychiatry"},{"key":"B9","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/S0165-0327(98)00221-3","article-title":"Mechanism of action of serotonin selective reuptake inhibitors: serotonin receptors and pathways mediate therapeutic effects and side effects","volume":"51","author":"Stahl","year":"1998","journal-title":"J Affect Disord"},{"key":"B10","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1016\/j.euroneuro.2007.03.009","article-title":"What is the meaning of treatment resistant\/refractory major depression (TRD)? 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