{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:32Z","timestamp":1787028512040,"version":"build-2736575974"},"reference-count":178,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T00:00:00Z","timestamp":1684108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Brigham and Women\u2019s Hospital BRI Fund","award":["R21AA030087-01A1"],"award-info":[{"award-number":["R21AA030087-01A1"]}]},{"name":"National Institutes of Health\/the National Institute on Alcohol Abuse and Alcoholism","award":["R21AA030087-01A1"],"award-info":[{"award-number":["R21AA030087-01A1"]}]},{"name":"Intramural Research Fund and the Extramural Division Fund","award":["R21AA030087-01A1"],"award-info":[{"award-number":["R21AA030087-01A1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The increasing comorbidity of alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) associated with traumatic brain injury (TBI) is a serious medical, economic, and social issue. However, the molecular toxicology and pathophysiological mechanisms of comorbid AUD and PTSD are not well understood and the identification of the comorbidity state markers is significantly challenging. This review summarizes the main characteristics of comorbidity between AUD and PTSD (AUD\/PTSD) and highlights the significance of a comprehensive understanding of the molecular toxicology and pathophysiological mechanisms of AUD\/PTSD, particularly following TBI, with a focus on the role of metabolomics, inflammation, neuroendocrine, signal transduction pathways, and genetic regulation. Instead of a separate disease state, a comprehensive examination of comorbid AUD and PTSD is emphasized by considering additive and synergistic interactions between the two diseases. Finally, we propose several hypotheses of molecular mechanisms for AUD\/PTSD and discuss potential future research directions that may provide new insights and translational application opportunities.<\/jats:p>","DOI":"10.3390\/ijms24108805","type":"journal-article","created":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T02:37:51Z","timestamp":1684204671000},"page":"8805","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Molecular Toxicology and Pathophysiology of Comorbid Alcohol Use Disorder and Post-Traumatic Stress Disorder Associated with Traumatic Brain Injury"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8820-7406","authenticated-orcid":false,"given":"Zufeng","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Forensic Medicine, Soochow University, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengliang","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Forensic Medicine, Soochow University, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward W.","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron F.","family":"Sandhu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George E.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialu","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharati","family":"Sinha","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Akbar","sequence":"additional","affiliation":[{"name":"Division of Neuroscience & Behavior, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2867-1650","authenticated-orcid":false,"given":"Pallab","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gandhinagar 382355, Gujarat, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuanhu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Harvard Stem Cell Institute, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3954-3497","authenticated-orcid":false,"given":"Byoung-Joon","family":"Song","sequence":"additional","affiliation":[{"name":"Section of Molecular Pharmacology and Toxicology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9233-2170","authenticated-orcid":false,"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1037\/adb0000348","article-title":"The burden of co-occurring alcohol use disorder and PTSD in U.S. Military veterans: Comorbidities, functioning, and suicidality","volume":"32","author":"Norman","year":"2018","journal-title":"Psychol. 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