Molecular Toxicology and Pathophysiology of Comorbid Alcohol Use Disorder and Post-Traumatic Stress Disorder Associated with Traumatic Brain Injury

Author:

Wang Zufeng12ORCID,Luo Chengliang12,Zhou Edward W.1,Sandhu Aaron F.1,Yuan Xiaojing1,Williams George E.1,Cheng Jialu1,Sinha Bharati1,Akbar Mohammed3,Bhattacharya Pallab4ORCID,Zhou Shuanhu5,Song Byoung-Joon6ORCID,Wang Xin1ORCID

Affiliation:

1. Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA

2. Department of Forensic Medicine, Soochow University, Suzhou 215006, China

3. Division of Neuroscience & Behavior, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20892, USA

4. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gandhinagar 382355, Gujarat, India

5. Harvard Medical School, Harvard Stem Cell Institute, Boston, MA 02115, USA

6. Section of Molecular Pharmacology and Toxicology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20892, USA

Abstract

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.

Funder

Brigham and Women’s Hospital BRI Fund

National Institutes of Health/the National Institute on Alcohol Abuse and Alcoholism

Intramural Research Fund and the Extramural Division Fund

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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