PURPOSE:The review surveys the type of machine learning approaches currently used in the alcohol literature, reviews challenges in applying machine learning tools to alcohol data, and explores how overcoming these challenges could advance personalized medicine for alcohol use disorder (AUD). SEARCH METHODS:The authors conducted a search of publications on PubMed, ScienceDirect, and EBSCO Academic Search Premier published from 2015 to April 15, 2025, for articles that used machine learning to analyze alcohol-related outcomes. Search terms were ("drinking" OR "alcohol") AND ("machine learning" OR "deep learning" OR "predict" OR "classify") in the title or abstract. SEARCH RESULTS:The search returned 2,618 manuscripts. Keeping those that predicted alcohol-related outcomes and excluding those that merely used alcohol as a predictor for other outcomes reduced the selection to 567 manuscripts. A final manual selection resulted in 110 original peer-reviewed human research studies that primarily analyzed alcohol consumption behaviors and tested their models on data that they were not trained on. DISCUSSION AND CONCLUSIONS:Predictions focused on alcohol consumption or AUD diagnosis in cohorts with a mean age of 50 years or younger (i.e., when long-term drinking behaviors are being or have been established). Most studies confined the data-driven searches to a single modality and relied on conventional machine learning approaches, which tended to produce accurate and transparent predictions on the relatively small datasets typically collected by AUD studies. The small number of available samples was the most common limitation mentioned by the reviewed articles. Investigators also wished for machine learning models to provide insights about causality. Gaining these insights will be essential to improve diagnosis and treatment of AUD, for which the field must foster multidisciplinary research teams to build rigorous and trustworthy machine learning models and quantitative benchmarks that can capture the multifaceted nature of alcohol use and its comorbidities.
PURPOSE:Resilience is crucial in mitigating the risk of stress-related health issues. Although many people can adapt to adverse stress or trauma, stress exposure can increase the risk of health issues, including obesity, cardiovascular disease, and digestive illnesses. Some individuals may even develop debilitating conditions, such as post-traumatic stress disorder (PTSD). People with PTSD often struggle to adapt, sometimes turning to alcohol to cope, which can lead to alcohol use disorder (AUD), characterized by excessive alcohol-seeking and dependence. Understanding the biological underpinnings of resilience, therefore, is a key to preventing both PTSD and AUD. Recent research has uncovered the neurobiological traits that protect against the development of stress-induced alcohol dependence. Studies have shown that proactive coping and a lack of stress-related symptoms are associated with resilience. Preclinical studies, especially in rodents, have provided deeper insights into how stress impacts alcohol-seeking behaviors. Research has shown that resilience involves adaptive changes at the molecular, cellular, neural circuit, and systems levels. This review aims to integrate this research to better understand what makes people vulnerable to stress and alcohol consumption, highlighting aspects frequently overlooked in clinical models. SEARCH METHODS:This review employed systematic search strategies to achieve a comprehensive and structured assessment of the existing body of literature using the academic databases PubMed, Google Scholar, and Web of Science. Targeted keywords included "stress," "PTSD," "trauma," "alcohol," "AUD," "resilience," "vulnerability," "susceptibility," "sex difference," and "animal models"; Boolean operators (AND, OR, NOT) were used to refine the results. Exclusion criteria included research published before 1990, research that was not peer reviewed, and publications in languages other than English. Additional studies were identified by reviewing the references cited in key articles as well as by identifying subsequent studies that referenced these pivotal works. The search was carried out from April to June 2025 focusing on, but not limited to, experiments involving rodent models. SEARCH RESULTS:The search yielded a total of 347 articles. After screening, 283 articles were removed, either because they met the predefined exclusion criteria or because they were duplicates. This process resulted in 64 articles, forming the core of this comprehensive review. DISCUSSION AND CONCLUSIONS:This review summarizes an overview of recent progress in studies of PTSD and AUD, primarily focusing on the effect of resilience on post-stress alcohol intake in animal models. The findings highlight several biomarkers that may help identify individuals at risk for PTSD, AUD, or their co-occurrence, acknowledging that no single identifier can predict post-trauma outcomes. The identification of these markers is an ongoing process, yet it will be crucial for early diagnosis and risk assessment moving forward.
PURPOSE:There is an urgent need for novel and innovative advancements in alcohol research and treatment. Artificial intelligence (AI) is one such advancement that demonstrates promise, though not without important ethical concerns. This Perspective article examines current applications, ethical considerations, and future implications of integrating AI in alcohol research and treatment. SEARCH METHODS AND RESULTS:A nonsystematic narrative review of peer-reviewed, English-language studies of contemporary applications of AI (specifically, large language models and machine learning) in alcohol research and treatment was conducted in December 2024 through January 2025, using searches of the PubMed, Google Scholar, Web of Science, and PsycInfo databases. Search terms included the following: "alcohol," "alcohol use," "alcohol use disorder," "drinking," "treatment," "screening," "artificial intelligence," "chatbot," "large language models," "research subject recruitment," "research subject enrollment," "electronic health records," "support vector machine," "neural network," "black-box," "random forest," and "machine learning." The article highlights studies that discussed the role of AI in bolstering recruitment and retention for human subjects research and in the application of advanced data analytic techniques for alcohol research. Further, the article examines studies that described current and prospective uses of AI in alcohol use disorder treatment, including assessment and identification of individuals who may benefit from treatment, and as an adjunct to evidence-based treatments for alcohol use disorder. Potential ethical concerns are highlighted alongside potential considerations for the safe and ethical use of AI across these domains. CONCLUSIONS:Based on the identified primary and secondary sources, this review highlights the promises of AI in advancing both alcohol research and treatment, and how its successful implementation is supported by careful and ongoing attention to potential risks. The reviewed studies provide evidence that robust data security protocols, comprehensive informed consent, and ongoing monitoring for potential biases and harms can allow for these tools to advance scientific understanding while improving access to effective and equitable care. However, the current literature and the potential solutions suggested in this Perspective have limitations due to the pace of AI advancements that continue to accelerate at an unprecedent rate. FUTURE DIRECTIONS:Future research can advance the field by explicitly testing and evaluating the utility of these tools in real-world contexts, their risks for bias and privacy violations, and their ethical integration into alcohol research and treatment.
PURPOSE:Alcohol misuse is widely accepted as an independent risk factor for a wide variety of lung diseases, such as pneumonia and acute respiratory distress syndrome. Alcohol induces changes in the regulatory mechanisms of the lung, both at a mechanical and immunological level. Understanding these changes might help discover new targets for drugs and therapeutic approaches for the prevention of respiratory disease following alcohol misuse. SEARCH METHODS:A systematic literature search was conducted on January 25, 2025, in PubMed, Medline, and Embase of manuscripts published between January 2000 and January 2025 using the terms ("alcohol" or "ethanol") AND ("lung," or "respiratory," or "pulmonary") AND ("pneumonia" or "damage" or "leak"). Eligible manuscripts included studies that discussed the effects of ethanol on the lungs. SEARCH RESULTS:A total of 962 publications were identified; after excluding duplicates and research not covering alcohol-related lung effects (e.g., studies investigating liver damage or alcohol-related tissue injury; 814 articles), 148 studies were reviewed. An additional 15 papers from before 2000 were included as historical precedents for the current research cited. Of the 148 studies, 114 were cited in this review; previous review articles and those discussing in utero or prenatal alcohol exposure were excluded (34 articles). DISCUSSION AND CONCLUSIONS:The lungs are particularly susceptible to infections and injury following alcohol misuse. Several key mechanisms by which alcohol misuse drives lung damage have been identified. Alcohol misuse leads to impaired mucus-facilitated clearance of bacterial pathogens, increases the aspiration of microbes from the upper alimentary tract, and suppresses tissue recruitment and function of innate and adaptive immune cells. Alcohol-related reductions in antioxidant levels, trace metals, and metabolites may also contribute to lung disease in people with underlying alcohol misuse. Several regulatory molecules may play crucial roles in alcohol-induced disease processes. Although there are currently no approved therapies to combat the detrimental effects of chronic alcohol consumption on the respiratory system, these molecules may be potential therapeutic targets to guide future investigation. Despite these advancements, limitations and knowledge gaps in the field still exist. For example, few studies have investigated dose- and duration-dependent effects of alcohol on the lung, sex-specific differences in lung responses, and the interaction of alcohol with other coexposures/comorbidities, such as smoking and HIV. In addition, well-defined observational and longitudinal human studies employing robust measures of alcohol use are limited. These gaps represent novel opportunities for more thorough and robust experimental designs of human and animal studies investigating alcohol-associated lung disease.
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.
PURPOSE:Prenatal alcohol exposure (PAE) is a leading cause of persistent neurodevelopmental disability, with additional adverse consequences to the offspring's growth, metabolism, cardiovascular health, and immunity, among others. Alcohol disrupts offspring development through myriad mechanisms, many of which involve direct interactions between alcohol and the embryo and fetus (i.e., the conceptus). This limited narrative review instead focuses on mechanisms that are exogenous to the fetus. Many of these are relatively unexplored and are also mechanistically interrelated. Thus, they represent novel opportunities for the design of interventions that ameliorate alcohol-related pathologies. SEARCH METHODS:Literature from 2020 to October 2024 was searched using the terms "fetal alcohol spectrum disorder"[MeSH] OR "fetal alcohol"[Ti/Ab] with the filter "review." These reviews were inspected to extract nonfetal mechanisms of alcohol. Literature from 2000 to October 2024 was then searched in PubMed, Embase, and Google Scholar for seven mechanisms, using the search terms "fetal alcohol spectrum disorder OR fetal alcohol" AND one of the following: "placenta," "paternal," "metabolism OR insulin OR amino acid," "inflammation OR neuroinflammation OR cytokine," "epigenetic," "iron OR iron deficiency OR anemia," "microbiome." Only primary research articles, both clinical and preclinical, were included. SEARCH RESULTS:The literature scan identified seven mechanisms for which targeted literature searches were conducted. These searches yielded relevant studies that explored mechanisms involving the microbiome (n = 5 studies), inflammation (n = 72 studies), epigenetics (n = 30 studies), paternal alcohol exposure (n = 34 studies), placenta (n = 53 studies), metabolism (n = 37 studies), and functional iron deficiency (n = 23 studies). DISCUSSION AND CONCLUSIONS:Exogenous mechanisms of alcohol's teratogenicity are intertwined. Alcohol remodels the maternal enteric microbiome, with potential consequences to fetal immune function, nutrient availability, and brain development. Microbial endotoxins may further magnify alcohol's proinflammatory actions. This inflammation might also drive a fetal anemia associated with PAE. Alcohol alters maternal and fetal metabolism and could limit fetal nutrient availability. This altered metabolism could also reprogram placental and fetal epigenetics, as could paternal exposure to alcohol. Both epigenetic effects and inflammation can impair placental function and modulate the placenta-brain axis that modulates brain development. The review discusses limitations in the current understanding of these mechanisms and highlights future research avenues that would provide clarity and inform future interventions.
PURPOSE:Individuals with fetal alcohol spectrum disorders (FASD) or neurodevelopmental disorder associated with prenatal alcohol exposure (PAE) can experience a wide range of whole-body health conditions. A survey by the International Adult Leadership Collaboration (ALC) FASD Changemakers found that many adults with FASD have comorbidities relating to metabolic disorders; body composition; cardio-renal, reproductive, and/or immune health; as well as difficulties with hearing/vision and sleep. This review summarizes current knowledge of these health domains and provides an overview of the latest literature on the whole-body effects of PAE/FASD across the life span. SEARCH METHODS:The literature search was conducted on July 8, 2024, using CINAHL, PubMed, and Web of Science databases. To investigate the whole-body health of individuals with PAE, search terms were based on the findings of the ALC FASD Changemakers Health Survey and covered areas relating to sleep; hearing/vision; body composition; and metabolic, cardiovascular, renal, immune, and reproductive health. The search was conducted in two phases. To summarize current knowledge on these topics, the latest systematic reviews and other reviews were identified for each health domain (phase one). In addition, recent primary research articles published since these review searches were completed were identified for each domain (phase two). Inclusion/exclusion was based on article relevance to the physical health challenges reported in the ALC FASD Changemakers Health Survey. SEARCH RESULTS:In phase one, 744 reviews were identified in the initial search, of which 722 articles were excluded and 22 recent and relevant reviews were included. In phase two, 1,102 articles were identified, with 665 screened at the title/abstract level and 169 articles undergoing full-text review. A total of 1,066 articles were excluded. Following the addition of five articles from other sources, 41 recently published primary articles were included in the current review. DISCUSSION AND CONCLUSIONS:A growing body of evidence suggests that individuals with PAE/FASD may experience comorbidities relating to metabolism; body composition; cardio-renal, immune, and/or reproductive health; as well as hearing, vision, and sleep difficulties. These findings support the concept of FASD as a whole-body diagnosis, emphasizing the importance of a holistic approach that supports the overall health and well-being of those with PAE. There are opportunities for future clinical research to focus on further understanding these physical health challenges, how they evolve, and how effective intervention approaches could improve outcomes for individuals with PAE/FASD.
PURPOSE:Sociocultural characteristics, including race/ethnicity and socioeconomic status (SES), may affect individuals' attitudes and norms regarding alcohol use and treatment as well as their access to emerging health knowledge, innovative technologies, and general resources for improving health. As a result of these differences, as well as social determinants of health such as stigma and uneven enforcement, alcohol policies may not benefit all population subgroups equally. This review addresses research conducted within the last decade that examined differential effects of alcohol policies on alcohol consumption, alcohol harm, and alcohol treatment admissions across racial/ethnic and socioeconomic groups. SEARCH METHODS:The authors used the following Boolean phrase search terms to assess the association between race/ethnicity and outcomes: ("alcohol policy" OR "alcohol policies") AND ("race" OR "ethnicity" OR "first nations" OR "African American" OR "Hispanic American" OR "Latino American" OR "Asian American" OR "Native American"). Association with SES was assessed using these terms: ("alcohol policy" OR "alcohol policies") AND ("socioeconomic" OR "class") AND ("effect" OR "impact" OR "outcome"). Both searches were conducted on August 28, 2023, using advanced search in seven EBSCOhost research databases: (1) EBSCO Biomedical Reference Collection: Corporate; (2) EBSCOhost E-Journals; (3) EBSCO MEDLINE Complete; (4) SocINDEX with Full Text; (5) APA PsycInfo; (6) LISTA (Library Information Sciences and Technology Abstracts); and (7) GreenFILE. Inclusion criteria for both searches were: (1) publication dates between 2014 and 2023; (2) peer-reviewed research articles; (3) data disaggregated by racial/ethnic and/or SES subgroups; and (4) English language only. SEARCH RESULTS:The racial/ethnic search produced 64 articles, of which 14 were reviewed as relevant to this study and 50 were excluded. The SES search generated 100 articles, of which 18 were reviewed as relevant to this study and 82 were excluded. Eight of the studies identified by these two searches overlapped (i.e., included both racial/ethnic and SES outcomes), resulting in a total of 24 articles included in this review. DISCUSSION AND CONCLUSIONS:Relying upon data from both U.S. and international research, the identified studies focused on differential effects of financially focused alcohol control policies (e.g., taxation and minimum unit pricing policies) as well as access/availability reduction policies (e.g., those governing outlet density, on-/off-premise sales, and establishment licensing). Several studies concluded that price increases via taxes or minimum unit pricing might be particularly effective in reducing the risk of alcohol-related harms in low-income/low-SES populations. Limitations of the present review include lack of standardization in the ways that SES was measured and the difficulty of measuring policy enforceability. Studies focused on differential effects of alcohol control policies across racial/ethnic groups demonstrated complex associations and the need to conduct further research that identifies better ways to reduce policy-induced health disparities across diverse populations.
PURPOSE:Most research on the structural determinants of substance use and mental health has centered around widely studied factors such as alcohol taxes, tobacco control policies, essential/precursor chemical regulations, neighborhood/city characteristics, and immigration policies. Other structural determinants exist, however, many of which are being identified in the emerging fields of structural stigma, structural racism, and structural sexism. This narrative review surveys the measures and designs used in substance use and mental health studies from these three fields. SEARCH METHODS:The PubMed, PsycINFO, and Scopus databases were searched on May 11, 2023. A focused search approach used terminology for structural racism, stigma, or sexism combined with terminology for substance use or mental health. Peer-reviewed studies were included if they were written in English and assessed associations between objective structural measures and substance use and mental health outcomes. SEARCH RESULTS:Of 2,536 studies identified, 2,487 were excluded. Forty-nine studies (30 related to stigma, 16 related to racism, and three related to sexism) met the inclusion criteria. Information was abstracted about the structural measures, outcome measures, research design, sample, and findings of each study. DISCUSSION AND CONCLUSIONS:The structural determinant measures used in the studies reviewed were diverse. They addressed, for example, community opinions, the gender of legislators, economic vulnerability, financial loan discrimination, college policies, law enforcement, historical trauma, and legislative protections for sexual and gender minorities and for reproductive rights. Most of the structural determinant measures were constructed by combining multiple indicators into indexes or by merging indexes into composite indexes, although some studies relied on single indicators alone. The substance use and mental health outcome measures most frequently examined were related to alcohol and depression, respectively. The studies were conducted in numerous nations and drew samples from an array of groups, including, for example, patients who experienced overdoses from substance use, sexual and gender minorities, racial and ethnic minority groups, women, youth, migrants, and patients subject to involuntary psychiatric hospitalization. Most of the studies used passive-observational (correlational) research designs and, as a result, did not assess whether their structural determinant variables were causally related to substance use and mental health. Nevertheless, the studies reviewed can be used by public health proponents to foster awareness that a wide range of structural determinants correlate with the substance use and mental health of many groups within and across nations.
PURPOSE:Rates of alcohol-related mortality (including deaths attributed to chronic alcohol use as well as acute causes involving alcohol) have been increasing in the United States, particularly for certain population subgroups, such as women. This review summarizes associations of area-level social determinants of health with alcohol-related mortality. These determinants, measured at the community, county, or state level, include alcohol control policies, health care availability, and a community's socioeconomic environment. Examining multiple geographic levels illuminates how macro-level social determinants and local contexts contribute to alcohol-related mortality to inform intervention. Attention to the broad variety of social determinants of alcohol-related mortality could ultimately improve community health. SEARCH METHODS:A literature search of three databases-PubMed, Web of Science, and Cumulative Index to Nursing and Allied Health Literature (CINAHL)-conducted between March 13 and May 16, 2023, identified peer-reviewed studies published from 1990 to May 2023 that modeled at least one area-level social determinant of health as a predictor or correlate of area-level rates of alcohol-related mortality in the United States. Unpublished dissertations, commentaries, editorials, review papers, and articles published in languages other than English were excluded. Two team members reviewed each abstract to verify that the article addressed alcohol-related mortality and included at least one area-level social determinant of health. SEARCH RESULTS:The authors screened 313 abstracts and excluded 210 that did not meet inclusion criteria. The full texts of 103 articles were retrieved. Upon further screening, 30 articles were excluded (two were not obtained), leaving 71 studies for detailed review. DISCUSSION AND CONCLUSIONS:Many studies analyzed fatal alcohol-related motor vehicle crashes or cirrhosis/liver disease mortality. Fewer analyzed other mortality causes related to chronic alcohol consumption. No studies focused on racism and discrimination, community-level prevention activities, or community social services in relation to alcohol-related mortality. Few studies examined major health policy changes or addressed health care system factors. Although the variation across studies complicates systematic comparison of the results, some key themes did emerge from the reviewed studies, such as the beneficial effects of stronger alcohol policies and the importance of socioeconomic conditions as determinants of alcohol-related mortality. Research using a more diverse set of theoretically informed social determinants may help examine whether, how, and for whom racism and discrimination as well as health policies and social services impact alcohol-related mortality. Finally, there is a gap in research linking local community contexts with alcohol-related mortality. Better understanding of subgroup differences, interactions between different contextual factors, and specific mechanisms of action may help identify promising new strategies to improve population health and reduce alcohol-related mortality.
PURPOSE: Sexual and gender minority (SGM) people are at heightened risk for alcohol use, hazardous drinking, and alcohol use disorder compared to heterosexual and cisgender individuals. This paper: (a) presents an oppression framework that integrates intersectionality, stress, stigma, and addiction-based theories to examine the complex and nuanced ways oppression-based stress (e.g., minority stress) leads to sexual orientation and gender identity inequities in alcohol use; (b) conducts a narrative review that summarizes recent and novel advancements in the literature on the impact of oppression-based stressors on alcohol use outcomes across structural, interpersonal, and intrapersonal domains among SGM people; and (c) provides future research and intervention directions for the alcohol field. SEARCH METHODS: A select review of the literature was conducted on July 10, 2023, using multiple electronic databases (i.e., PsycInfo, PubMed, Web of Science) and focusing on studies that had examined the associations between oppression-based stressors and alcohol use outcomes across structural, interpersonal, and intrapersonal levels. Search terms focused on alcohol consumption; SGM people, particularly SGM people of color; and oppression-based stress. Cross-sectional studies that focused on heterosexism-based and anti-bisexual oppression-based stressors at the interpersonal or intrapersonal levels and alcohol use outcomes were excluded as they have been included in prior reviews of the literature. SEARCH RESULTS: The initial and combined search across the databases resulted in 3,205 articles. Of those, the narrative review included 50 peer-reviewed articles that focused on the following four areas of the literature on the associations between oppression- based stressors and alcohol use outcomes: (1) experimental, longitudinal, and experience sampling studies of heterosexism- and anti-bisexual oppression-based stressors (22 articles); (2) any studies of cissexism-based stressors (12 articles); (3) any studies of intersectional oppression among SGM people of color (seven articles, one article overlapped with the first category and another overlapped with the fourth category); and (4) any studies of structural oppression (11 articles). DISCUSSION AND CONCLUSIONS: Results of this narrative review indicate that mounting evidence implicates oppression-based stress in inequities in alcohol use, hazardous drinking, and alcohol use disorder in SGM populations. This reflects SGM people's embodiment of oppression and injustice at the structural, interpersonal, and intrapersonal levels. Given some inconsistent and mixed patterns of findings, future research needs greater specificity in drinking inclusion criteria, robust and well-validated measures, more attention to culturally and developmentally relevant moderating and mediating mechanisms across the lifespan, application of sophisticated methodologies, and integration of intersectional and addiction frameworks.
PURPOSE:Binge drinking (i.e., consuming enough alcohol to achieve a blood ethanol concentration of 80 mg/dL, approximately 4-5 drinks within 2 hours), particularly in early adolescence, can promote progressive increases in alcohol drinking and alcohol-related problems that develop into compulsive use in the chronic relapsing disease, alcohol use disorder (AUD). Over the past decade, neuroimmune signaling has been discovered to contribute to alcohol-induced changes in drinking, mood, and neurodegeneration. This review presents a mechanistic hypothesis supporting high mobility group box protein 1 (HMGB1) and Toll-like receptor (TLR) signaling as key elements of alcohol-induced neuroimmune signaling across glia and neurons, which shifts gene transcription and synapses, altering neuronal networks that contribute to the development of AUD. This hypothesis may help guide further research on prevention and treatment. SEARCH METHODS:The authors used the search terms "HMGB1 protein," "alcohol," and "brain" across PubMed, Scopus, and Embase to find articles published between 1991 and 2023. SEARCH RESULTS:The database search found 54 references in PubMed, 47 in Scopus, and 105 in Embase. A total of about 100 articles were included. DISCUSSION AND CONCLUSIONS:In the brain, immune signaling molecules play a role in normal development that differs from their functions in inflammation and the immune response, although cellular receptors and signaling are shared. In adults, pro-inflammatory signals have emerged as contributing to brain adaptation in stress, depression, AUD, and neurodegenerative diseases. HMGB1, a cytokine-like signaling protein released from activated cells, including neurons, is hypothesized to activate pro-inflammatory signals through TLRs that contribute to adaptations to binge and chronic heavy drinking. HMGB1 alone and in heteromers with other molecules activates TLRs and other immune receptors that spread signaling across neurons and glia. Both blood and brain levels of HMGB1 increase with ethanol exposure. In rats, an adolescent intermittent ethanol (AIE) binge drinking model persistently increases brain HMGB1 and its receptors; alters microglia, forebrain cholinergic neurons, and neuronal networks; and increases alcohol drinking and anxiety while disrupting cognition. Studies of human postmortem AUD brain have found elevated levels of HMGB1 and TLRs. These signals reduce cholinergic neurons, whereas microglia, the brain's immune cells, are activated by binge drinking. Microglia regulate synapses through complement proteins that can change networks affected by AIE that increase drinking, contributing to risks for AUD. Anti-inflammatory drugs, exercise, cholinesterase inhibitors, and histone deacetylase epigenetic inhibitors prevent and reverse the AIE-induced pathology. Further, HMGB1 antagonists and other anti-inflammatory treatments may provide new therapies for alcohol misuse and AUD. Collectively, these findings suggest that restoring the innate immune signaling balance is central to recovering from alcohol-related pathology.
PURPOSE:Chronic alcohol use is a major cause of liver damage and death. In the United States, multiple factors have led to low utilization of pharmacotherapy for alcohol use disorder (AUD), including lack of provider knowledge and comfort in prescribing medications for AUD. Alcohol consumption has direct effects on the gut microbiota, altering the diversity of bacteria and leading to bacterial overgrowth. Growing evidence suggests that alcohol's effects on the gut microbiome may contribute to increased alcohol consumption and progression of alcohol-associated liver disease (ALD). This article reviews human and preclinical studies investigating the role of fecal microbiota transplantation (FMT) in ameliorating alcohol-associated alterations to the liver, gut, and brain resulting in altered behavior; it also discusses the therapeutic potential of FMT. SEARCH METHODS:For this narrative review, a literature search was conducted in September 2022 of PubMed, Web of Science Core Collection, and Google Scholar to identify studies published between January 2012 and September 2022. Search terms used included "fecal microbiota transplantation" and "alcohol." SEARCH RESULTS:Most results of the literature search were review articles or articles on nonalcoholic fatty liver disease; these were excluded. Of the remaining empirical manuscripts, very few described clinical or preclinical studies that were directly investigating the effects of FMT on alcohol drinking or related behaviors. Ultimately, 16 studies were included in the review. DISCUSSION AND CONCLUSIONS:The literature search identified only a few studies that were directly investigating the effect of FMT on ALD or alcohol drinking and related behaviors. Largely proof-of-concept studies, these findings demonstrate that alcohol can alter the gut microbiome and that the microbiome can be transferred between humans and rodents to alter affective behaviors frequently associated with increased alcohol use. Other studies have shown promise of FMT or other probiotic supplementation in alleviating some of the symptoms associated with ALD and drinking. These results show that the implementation of FMT as a therapeutic approach is still in the investigatory stages.
PURPOSE:By 2040, 21.6% of Americans will be over age 65, and the population of those older than age 85 is estimated to reach 14.4 million.Although not causative, older age is a risk factor for dementia: every 5 years beyond age 65, the risk doubles; approximately one-third of those older than age 85 are diagnosed with dementia.As current alcohol consumption among older adults is significantly higher compared to previous generations, a pressing question is whether drinking alcohol increases the risk for Alzheimer's disease or other forms of dementia.SEARCH METHODS: Databases explored included PubMed, Web of Science, and ScienceDirect.To accomplish this narrative review on the effects of alcohol consumption on dementia risk, the literature covered included clinical diagnoses, epidemiology, neuropsychology, postmortem pathology, neuroimaging and other biomarkers, and translational studies.Searches conducted between January 12 and August 1, 2023, included the following terms and combinations: "aging," "alcoholism," "alcohol use disorder (AUD)," "brain," "CNS," "dementia," "Wernicke," "Korsakoff," "Alzheimer," "vascular," "frontotemporal," "Lewy body," "clinical," "diagnosis," "epidemiology," "pathology," "autopsy," "postmortem," "histology," "cognitive," "motor," "neuropsychological," "magnetic resonance," "imaging," "PET," "ligand," "degeneration," "atrophy," "translational," "rodent," "rat," "mouse," "model," "amyloid," "neurofibrillary tangles," "α-synuclein," or "presenilin."When relevant, "species" (i.e., "humans" or "other animals") was selected as an additional filter.Review articles were avoided when possible.SEARCH RESULTS: The two terms "alcoholism" and "aging" retrieved about 1,350 papers; adding phrases-for example, "postmortem" or "magnetic resonance"-limited the number to fewer than 100 papers.Using the traditional term, "alcoholism" with "dementia" resulted in 876 citations, but using the currently accepted term "alcohol use disorder (AUD)" with "dementia" produced only 87 papers.Similarly, whereas the terms "Alzheimer's" and "alcoholism" yielded 318 results, "Alzheimer's" and "alcohol use disorder (AUD)" returned only 40 citations.As pertinent postmortem pathology papers were published in the 1950s and recent animal models of Alzheimer's disease were created in the early 2000s, articles referenced span the years 1957 to 2024.In total, more than 5,000 articles were considered; about 400 are herein referenced.DISCUSSION AND CONCLUSIONS: Chronic alcohol misuse accelerates brain aging and contributes to cognitive impairments, including those in the mnemonic domain.The consensus among studies from multiple disciplines, however, is that alcohol misuse can increase the risk for dementia, but not necessarily Alzheimer's disease.Key issues to consider include the reversibility of brain damage following abstinence from chronic alcohol misuse compared to the degenerative and progressive course of Alzheimer's disease, and the characteristic presence of protein inclusions in the brains of people with Alzheimer's disease, which are absent in the brains of those with AUD.
PURPOSE: Growing evidence supports sleep and circadian rhythms as influencing alcohol use and the course of alcohol use disorder (AUD). Studying sleep/circadian-alcohol associations during adolescence and young adulthood may be valuable for identifying sleep/circadian-related approaches to preventing and/or treating AUD. This paper reviews current evidence for prospective associations between sleep/circadian factors and alcohol involvement during adolescence and young adulthood with an emphasis on the effects of sleep/circadian factors on alcohol use. SEARCH METHODS: The authors conducted a literature search in PsycInfo, PubMed, and Web of Science using the search terms "sleep" and "alcohol" paired with "adolescent" or "adolescence" or "young adult" or "emerging adult," focusing on the title/abstract fields, and restricting to English-language articles. Next, the search was narrowed to articles with a prospective/longitudinal or experimental design, a sleep-related measure as a predictor, an alcohol-related measure as an outcome, and confirming a primarily adolescent and/or young adult sample. This step was completed by a joint review of candidate article abstracts by two of the authors. SEARCH RESULTS: The initial search resulted in 720 articles. After review of the abstracts, the list was narrowed to 27 articles reporting on observational longitudinal studies and three articles reporting on intervention trials. Noted for potential inclusion were 35 additional articles that reported on studies with alcohol-related predictors and sleeprelated outcomes, and/or reported on candidate moderators or mediators of sleep-alcohol associations. Additional articles were identified via review of relevant article reference lists and prior exposure based on the authors' previous work in this area. DISCUSSION AND CONCLUSIONS: Overall, the review supports a range of sleep/ circadian characteristics during adolescence and young adulthood predicting the development of alcohol use and/or alcohol-related problems. Although sleep treatment studies in adolescents and young adults engaging in regular and/or heavy drinking show that sleep can be improved in those individuals, as well as potentially reducing alcohol craving and alcohol-related consequences, no studies in any age group have yet demonstrated that improving sleep reduces drinking behavior. Notable limitations include relatively few longitudinal studies and only two experimental studies, insufficient consideration of different assessment timescales (e.g., day-to-day vs. years), insufficient consideration of the multidimensional nature of sleep, a paucity of objective measures of sleep and circadian rhythms, and insufficient consideration of how demographic variables may influence sleep/circadian-alcohol associations. Examining such moderators, particularly those related to minoritized identities, as well as further investigation of putative mechanistic pathways linking sleep/circadian characteristics to alcohol outcomes, are important next steps.
PURPOSE:This narrative review of research conducted during the first 2 years of the COVID-19 pandemic examines whether alcohol use among cisgender women and transgender and nonbinary people increased during the pandemic. The overarching goal of the review is to inform intervention and prevention efforts to halt the narrowing of gender-related differences in alcohol use. SEARCH METHODS:Eight databases (PubMed, APA PsycInfo, CINAHL, Embase, Scopus, Gender Studies Database, GenderWatch, and Web of Science) were searched for peer-reviewed literature, published between March 2020 and July 2022, that reported gender differences or findings specific to women, transgender or nonbinary people, and alcohol use during the pandemic. The search focused on studies conducted in the United States and excluded qualitative research. SEARCH RESULTS:A total 4,132 records were identified, including 400 duplicates. Of the remaining 3,732 unique records for consideration in the review, 51 were ultimately included. Overall, most studies found increases in alcohol use as well as gender differences in alcohol use, with cisgender women experiencing the most serious consequences. The findings for transgender and nonbinary people were equivocal due to the dearth of research and because many studies aggregated across gender. DISCUSSION AND CONCLUSIONS:Alcohol use by cisgender women seems to have increased during the pandemic; however, sizable limitations need to be considered, particularly the low number of studies on alcohol use during the pandemic that analyzed gender differences. This is of concern as gender differences in alcohol use had been narrowing before the pandemic; and this review suggests the gap has narrowed even further. Cisgender women and transgender and nonbinary people have experienced sizable stressors during the pandemic; thus, understanding the health and health behavior impacts of these stressors is critical to preventing the worsening of problematic alcohol use.
PURPOSE: Early identification of prenatal alcohol exposure (PAE) and of those in need of services resulting from this exposure is an important public health concern. This study reviewed the existing literature on potential biomarkers and screening tools of PAE and its impact. SEARCH METHODS: Electronic databases were searched for articles published between January 1, 1996, and November 30, 2021, using the following search terms: ("fetal alcohol" or "prenatal alcohol" or "FASD" or "alcohol-related neurodevelopmental disorder" or "ARND" or "ND-PAE") and ("screening" or "identification" or "biomarker"). Duplicate articles were electronically eliminated. Titles and abstracts were reviewed for appropriateness, and selected articles were retrieved for further analysis. Additional articles were added that were referenced in the reviewed articles or identified from expert knowledge. Information about the characteristics of the sample, the biomarker or screening tool, and the predictive validity outcome data were abstracted. A narrative analysis of the studies was then performed on the data. SEARCH RESULTS: A total of 3,813 articles were initially identified, and 1,215 were removed as duplicates. Of the remaining articles, 182 were identified as being within the scope of the review based on title and abstract inspection, and 181 articles were successfully retrieved. Of these, additional articles were removed because they were preclinical (3), were descriptive only (13), included only self-report of PAE (42), included only mean group comparison (17), were additional duplicates (2), focused on cost analysis (9), missed predictive validity data (24), or for other reasons (23). The remaining articles (n = 48) were abstracted. An additional 13 manuscripts were identified from these articles, and two more from expert knowledge. A total of 63 articles contributed to the review. DISCUSSION AND CONCLUSIONS: Biomarkers and screening tools of PAE and its impact fall short of ideal predictive validity characteristics. Higher specificity than sensitivity was found for many of the biomarkers and screening tools used to identify PAE and its impact, suggesting that current methods continue to under-identify the full range of individuals impacted by PAE. Exceptions to this were found in recent investigations using microRNAs related to growth and vascular development, proteomic changes associated with PAE, and combinations of markers estimating levels of various cytokines. Replications of these findings are needed across other samples to confirm the limited data available. Future research on biomarkers and screening tools should attend to feasibility and scalability of implementation. This article also recommends a systematic process of evaluation to improve early identification of individuals impacted by PAE so that harm reduction and habilitative care efforts can be implemented.
PURPOSE Although abstinence is recommended in pregnancy, many pregnancies are exposed to alcohol. Observational studies of the effects of low to moderate prenatal alcohol exposure (PAE) and neurodevelopmental outcomes have yielded inconsistent results, with some studies finding an increased risk of adverse neurobehavioral and cognitive outcomes, and other studies finding no changes or reduced risk of the same outcomes. The purpose of this narrative review is to summarize these inconsistencies and apply a methodological framework to discuss how different parameters contribute to the findings. The authors also provide recommendations on how to advance future research in this area. SEARCH METHODS The PubMed, Web of Science, and Embase databases were searched, along with reference lists of selected systematic reviews and meta-analyses. Search terms used were (infant or child or children or adolescent or offspring) AND (low or light or mild or moderate or low-to-moderate) AND (drinking or alcohol or drinks) AND (pregnancy or prenatal or fetal) AND (neurodevelopment or behavioral or psychological or cognitive or developmental) NOT (mice or rat or fish or animal) NOT (meta-analysis or review). Peer-reviewed original research studies were included if they analyzed associations between an exposure defined and characterized as low/light or moderate PAE with offspring neurodevelopmental outcomes. Animal studies, studies that did not provide clear cutoff points to classify PAE categories, studies lacking an abstinence control group, and studies that did not present a multivariable-adjusted measure of association were excluded. SEARCH RESULTS The searches identified 2,422 papers, with 36 papers meeting eligibility criteria. These studies were carried out across nine countries and included samples ranging from approximately 500 to 40,000 participants. Cognitive, academic, socioemotional, and behavioral outcomes were assessed from infancy through age 19. DISCUSSION AND CONCLUSION When the findings from the selected articles were summarized by geographic region, exposure definition, or neurodevelopmental outcome, no consistent observations or patterns emerged between low to moderate PAE and offspring outcomes. Although some studies found positive (i.e., beneficial) associations between low to moderate PAE and outcomes (primarily outcomes related to cognition) and others found negative (i.e., detrimental) associations (primarily for behavioral outcomes), most findings were null (i.e., showed no effect of PAE). The heterogeneity in study results is likely due to methodological issues, including residual confounding, effect measure modification, and exposure misclassification that make synthesis of studies difficult. Alternative study designs, including longitudinal trajectory analysis, sibling design, negative controls, and instrumental variable analyses, may reduce biases and are discussed. To date, the consequences of light to moderate levels of PAE on neurodevelopment remain unresolved; studies that advance methodological rigor will be important contributions to the field.
PURPOSE:Alcohol-related myopathy is one of the earliest alcohol-associated pathological tissue changes that is progressively exacerbated by cumulative long-term alcohol misuse. Acute and chronic alcohol use leads to changes in skeletal muscle mass and function. As discussed in this evidence-based review, alcohol-mediated mechanisms are multifactorial with effects on anabolic and catabolic signaling, mitochondrial bioenergetics, extracellular matrix remodeling, and epigenomic alterations. However, systematic studies are limited, especially regarding the acute effects of alcohol on skeletal muscle.SEARCH METHODS:This review focuses on peer-reviewed manuscripts published between January 2012 and November 2022 using the search terms "alcohol" or "ethanol" and "skeletal muscle" in MEDLINE, PubMed, and Web of Science using EndNote reference management software.SEARCH RESULTS:Eligible manuscripts included full-length research papers that discussed acute and chronic effects of alcohol on skeletal muscle mass and function in both clinical and preclinical studies. The review also includes alcohol-mediated skeletal muscle effects in the context of comorbidities. The three databases together yielded 708 manuscripts. Of these, the authors excluded from this review 548 papers that did not have "alcohol" or "muscle" in the title and 64 papers that were duplicates or did not discuss skeletal muscle. Thus, of all the manuscripts considered for this review, 96 are included and 612 are excluded. Additionally, relevant papers published earlier than 2012 are included to provide context to the review.DISCUSSION AND CONCLUSIONS:Both acute and chronic alcohol use decrease protein synthesis and increase protein degradation. Alcohol also impairs mitochondrial function and extracellular matrix remodeling. However, there is a gap in the literature on the known alcohol-mediated mechanisms, including senescence, role of immune activation, and interorgan communication, on the development of alcohol-related myopathy. With increased life expectancy, changing alcohol use patterns, and increasing frequency of alcohol use among females, current observational studies are needed on the prevalence of alcohol-related myopathy. Additionally, the compounding effects of acute and chronic alcohol use on skeletal muscle with aging or exercise, in response to injury or disuse, and in the context of comorbidities including diabetes and human immunodeficiency virus (HIV), call for further investigation. Though evidence suggests that abstinence or reducing alcohol use can improve muscle mass and function, they are not restored to normal levels. Hence, understanding the pathophysiological mechanisms can help in the design of therapeutic strategies to improve skeletal muscle health.
PURPOSE: This narrative review summarizes and synthesizes the clinical trials and randomized clinical trials that evaluated selected and targeted approaches to reducing preconception and prenatal alcohol exposure (PAE) and alcohol-exposed pregnancy (AEP) since 2011.SEARCH METHODS: A professional hospital librarian completed the primary search using strategies specified within this review, resulting in 94 records returned in PubMed, Ovid MEDLINE, Clinical Key, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. The author completed two supplementary literature searches.SEARCH RESULTS: From the total of 238 records returned from the three searches, 217 records were eliminated. Elimination reasons included other medical problem (119); duplicate entry (34); no content/results (23); secondary analysis (16); focus on effects of PAE (9); treatment of childhood fetal alcohol spectrum disorders (FASD) (6); maternal risk factors (3); and other (7). The remaining 21 studies were included with four overarching themes: (1) case management efforts (n = 4); (2) preconception efforts to reduce AEP (n = 5); (3) motivational interviewing and screening, brief intervention, and referral to treatment (n = 2); and (4) use of technology to deliver the intervention (n = 10).DISCUSSION AND CONCLUSIONS: Case management and home visits did not appear to have strong current empirical support. Study limitations included small sample sizes and no comparison groups, whereas larger efforts did not demonstrate definitive advantages to justify this intensive approach. The studies of preconception efforts, all based on the Project CHOICES approach, had similar outcomes, with the reduction in AEP risk largely due to improved contraception in women of childbearing age who were sexually active and drank alcohol but were not pregnant. It is unknown whether these women refrained from alcohol use when they became pregnant. Two studies of motivational interviewing to reduce prenatal alcohol use did not demonstrate the efficacy of the intervention. Both were small, with less than 200 pregnant women combined; moreover, the study samples had low baseline levels of alcohol use, allowing little opportunity for improvement. Finally, studies evaluating the impact of technological approaches to reducing AEP were reviewed. These exploratory investigations had small sample sizes and provided preliminary evaluations of techniques such as text messages, telephone contact, computer-based screening, and motivational interviewing. The potentially promising findings may inform future research and clinical efforts. Future directions may include research to address the limitations of the evidence to date and should reflect the complexities of FASD that include the biological and social context associated with prenatal alcohol use.
