Mechanisms Underlying Hazardous Alcohol Use After Mild Traumatic Brain Injury.

Abstract

Purpose: Alcohol use disorder (AUD) and mild traumatic brain injury (mTBI) have a bidirectional, synergistic, and complicated relationship. Although it is difficult to definitively say that mTBI causes AUD, certain biological mechanisms that occur after trauma are also associated with hazardous alcohol use. Hazardous drinking is defined as any quantity or pattern of alcohol consumption that places people at risk for physical and/or psychological harm. This review explores how the physiological, emotional, and behavioral consequences of mTBI may lead to worse outcomes after hazardous alcohol use and increase the risk for AUD. AUD is one of the most common comorbid conditions that occurs after mTBI, and thus a clear understanding of the mechanistic changes that influence its onset may help to identify preventative and therapeutic measures for individuals who are at risk. This review provides an overview of recently published studies (from 2021 to 2024) and how these new findings fit into the existing literature.

Search methods: This review was conducted by searching "alcohol, traumatic brain injury, TBI" in PubMed, Google Scholar, and Medline databases in October and December 2024. Only articles in English were reviewed. Titles, abstracts, and methods of all articles were read to determine relevance, then the full texts of articles that met inclusion criteria were obtained. The search included articles published after March 2021; relevant papers published before 2021 were identified by consulting previously published reviews on this topic. Articles were excluded if they only discussed (1) moderate/severe TBI, (2) adolescent populations or TBI during adolescence, (3) populations with a history of AUD before TBI, (4) acute outcomes after TBI (less than 2 weeks), or (5) prevalence or effects of TBI while intoxicated. Also excluded were papers that did not specify if TBI preceded or followed hazardous alcohol use or did not discuss the relationship between TBI and alcohol use.

Search results: The search resulted in 196 articles for initial examination. Of those, 155 were excluded and 42 were included. Eight review papers about alcohol use after TBI published from 2009 to 2023 were also examined, which provided foundational and additional background information on publications from 1990 to 2021.

Discussion and conclusions: This review discusses mechanisms that contribute to negative outcomes after mTBI and hazardous alcohol use and to the development of AUD after mTBI. These include inflammation and immune signaling, neuroendocrine alterations, oxidative stress, neurodegeneration, dopamine signaling, and behavioral impairments. Although current literature on the role of the gut-microbiome axis in this context is limited, this topic is also explored.There has been significant research on the biological changes that occur after mTBI and on which mechanisms may precede development of AUD; however, few studies have directly measured the outcomes of alcohol use after mTBI in the same experiment. Future preclinical and clinical research that concurrently studies alcohol use and mTBI could help establish causality for the complex relationship between trauma and alcohol use. Improved knowledge could help identify preventative measures and treatment options to improve quality of life for individuals who experience mTBI and hazardous alcohol use.