Alcoholic Research Articles

Evaluation of plasma-derived extracellular vesicles miRNAs and their connection with hippocampal mRNAs in alcohol use disorder

Alcohol use disorder (AUD) is a common mental illness with high morbidity and disability. The discovery of laboratory biomarkers has progressed slowly, resulting in suboptimal diagnosis and treatment of AUD. This study aimed to identify promising biomarkers, as well as the potential miRNA-mRNA networks associated with AUD pathogenesis. RNA sequencing was performed on plasma-derived small extracellular vesicles (sEVs) from AUD patients and healthy controls (HCs) to harvest miRNAs expression profiles. Machine learning (ML) models were built to screen characteristic miRNAs, whose target mRNAs were analyzed using TargetScan, miRanda and miRDB databases. Gene Expression Omnibus (GEO) datasets (GSE181804 and GSE180722) providing postmortem hippocampal gene expression profiles of AUD subjects were mined. A total of 247 differentially expressed (DE) plasma-derived sEVs miRNAs and 122 DE hippocampal mRNAs were obtained. Then, 22 overlapping sEVs miRNAs with high importance scores were gained by intersecting 5 ML models. As a result, we established a putative sEVs miRNA-hippocampal mRNA network that can effectively distinguish AUD patients from HCs. In conclusion, we proposed 5 AUD-representative sEVs miRNAs (hsa-miR-144-5p, hsa-miR-182-5p, hsa-miR-142-5p, hsa-miR-7-5p, and hsa-miR-15b-5p) that may participate in the pathogenesis of AUD by modulating downstream target hippocampal genes. These findings may provide novel insights into the diagnosis and treatment of AUD.

IL17RB genetic variants are associated with acamprosate treatment response in patients with alcohol use disorder: A proteomics-informed genomics study

Acamprosate is a Food and Drug Administration (FDA) approved medication for the treatment of alcohol use disorder (AUD). However, only a subset of patients achieves optimal treatment outcomes. Currently, no biological measures are utilized to predict response to acamprosate treatment. We applied our established pharmaco-omics informed genomics strategy to identify potential biomarkers associated with acamprosate treatment response. Specifically, our previous open-label acamprosate clinical trial recruited 442 patients with AUD who were treated with acamprosate for three months. We first performed proteomics using baseline plasma samples to identify potential biomarkers associated with acamprosate treatment outcomes. Next, we applied our established “proteomics-informed genome-wide association study (GWAS)” research strategy, and identified 12 proteins, including interleukin-17 receptor B (IL17RB), associated with acamprosate treatment response.​ A GWAS for IL17RB concentrations identified several genome-wide significant signals. Specifically, the top hit single nucleotide polymorphism (SNP) rs6801605 with a minor allele frequency of 38% in the European American population mapped 4 kilobase (Kb) upstream of IL17RB, and intron 1 of the choline dehydrogenase (CHDH) gene on chromosome 3 (p: 4.8E-20). The variant genotype (AA) for the SNP rs6801605 was associated with lower IL17RB protein expression. In addition, we identified a series of genetic variants in IL17RB that were associated with acamprosate treatment outcomes. Furthermore, the variantgenotypes for all of those IL17RB SNPs were protective for alcohol relapse. Finally, we demonstrated that the basal level of mRNA expression of IL17RB was inversely correlated with those of nuclear factor-κB (NF-κB) subunits, and a significantly higher expression of NF-κB subunits was observed in AUD patients who relapsed to alcohol use. In summary, this study illustrates that IL17RB genetic variants might contribute to acamprosate treatment outcomes. This series of studies represents an important step toward generating functional hypotheses that could be tested to gain insight into mechanisms underlying acamprosate treatment response phenotypes.(The ClinicalTrials.gov Identifier: NCT00662571).

Coping motives as a mediator of the relationship between child maltreatment and substance use problems in south African adolescents

BackgroundEvidence suggests that adults with a history of child maltreatment (CM) engage in substance misuse driven by ‘coping motives’: maladaptive beliefs that substances help them cope with negative emotions. However, the specificity of this risk pathway is under-researched in younger and non-Western cohorts. ObjectiveThe present study aimed to determine whether coping motives play a distinct role compared to other motives for substance use in mediating the relationship between CM and problematic alcohol and marijuana use in a sample of South African adolescents. Participants and settingA sample of 688 high school students (M age = 15.03 years; 62.5 % female) in Cape Town, South Africa, completed a cross sectional survey. MethodsParticipants completed self-report measures of CM exposure, motives for using alcohol and marijuana (coping, enhancement, social and conformity), and alcohol and marijuana related problems. Participants who endorsed using alcohol (N = 180) or marijuana (N = 136) were included in analysis. A parallel mediation model was conducted for each substance (alcohol and marijuana, respectively) to assess which motives mediated the relationship between CM exposure and substance-related problems. ResultsCM exposure predicted both alcohol-and marijuana related problems. The relationship between CM exposure and alcohol-related problems was partially mediated by coping motives (p < .001, 95%CI 0.028, 0.115) and, to a lesser extent, conformity motives (p < .01, 95%CI 0.001, 0.041), but not by social motives or enhancement motives. The relationship between CM exposure and marijuana-related problems was partially mediated by coping motives (p < .001, 95%CI 0.004, 0.037), but not by conformity, social or enhancement motives. ConclusionsThe findings support the importance of coping motives as a mediator between CM and problematic substance use across different substances of abuse in South African adolescents, and the role of conformity motives in problematic alcohol use. Future research should explore whether these findings hold across other sociocultural contexts, and the utility of interventions to address coping motives for substance use in adolescence.

Epidemiology of alcohol use disorder in the general population of Togo and Benin: the ALCOTRANS study

IntroductionAccess to data concerning mental health, particularly alcohol use disorders (AUD), in sub-Saharan Africa is very limited. This study aimed to estimate AUD prevalence and identify the associated factors in Togo and Benin.MethodsA cross-sectional study was conducted between April and May 2022, targeting individuals aged 18 years and above in the Yoto commune of Togo and the Lalo commune of Benin. Subjects were recruited using a multi-stage random sampling technique. AUD diagnoses were made using the MINI adapted to DSM-5 criteria. Our study collected sociodemographic information, data on psychiatric comorbidities, stigmatization, and assessed cravings, using a series of scales. The association between AUD and various factors was analyzed using multivariable logistic regression.ResultsIn Togo, 55 of the 445 people investigated had AUD (12.4%; [95% CI: 9.5-15.7%]). Among them, 39 (70.9%) had severe AUD and the main associated comorbidities were suicidal risk (36.4%), and major depressive disorder (16.4%). Associated factors with AUD were male gender (aOR: 11.3; [95% CI: 4.8–26.7]), a higher Hamilton Depression Rating Scale (HDRS) score (aOR: 1.2; [95% CI: 1.1–1.3]) and a lower Stigma score measured by the Explanatory Model Interview Catalogue (EMIC) (aOR: 0.9; [95% CI: 0.8–0.9). The stigma scores reflect perceived societal stigma towards individuals with AUD. In Benin, 38 of the 435 people investigated had AUD (8.7%; [95% CI: 6.4–11.7]), and the main associated comorbidities were suicidal risk (18.4%), tobacco use disorder (13.2%) and major depressive episode (16.4%). Associated factors with AUD were male gender (aOR: 6.4; [95% CI: 2.4–17.0]), major depressive disorder (aOR: 21.0; [95% CI: 1.5-289.8]), suicidal risk (aOR: 3.7; [95% CI: 1.2–11.3]), a lower Frontal Assessment Battery (FAB) score (aOR:0.8; [95% CI: 0.8–0.9]) and a lower perceived stigma score (by EMIC )(aOR: 0.9; [95% CI: 0.8–0.9]).ConclusionIn these communes of Togo and Benin, AUD prevalence is notably high. A deeper understanding of the disease and its local determinants, paired with effective prevention campaigns, could mitigate its impact on both countries.

Alterations in Neurotrophins in Alcohol-Addicted Patients during Alcohol Withdrawal.

Alcohol use disorder (AUD) is related to mental and somatic disorders that result in alcohol withdrawal syndrome (AWS), with 30% of AWS cases leading to life-threatening delirium tremens (DTs). Currently, studies do not support using any one biomarker in DTs. Neurotrophins affect neuromodulation, playing a role in the pathogenesis of AUD, AWS, and DTs. This review aims to summarize experimental and clinical data related to neurotrophins and S100B in neuroplasticity, as well as neurodegeneration in the context of AUD, AWS, and DTs. This work used publications that were selected based on the protocol consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. The BDNF level could be a good candidate biomarker for relapse susceptibility, as it is significantly reduced during consumption and gradually increases during abstinence. GDNF influences AUD through its integral role in the function of dopaminergic neurons and ablates the return to alcohol-drinking behavior. NGF protects neurons from ethanol-induced cytotoxic damage and affects recovery from cognitive deficits after brain damage. The NT-3 level is decreased after alcohol exposure and is involved in compensatory mechanisms for cognitive decline in AUD. NT-4 affects oxidative stress, which is associated with chronic alcohol consumption. S100B is used as a biomarker of brain damage, with elevated levels in serum in AUD, and can protect 5-HT neurons from the damage caused by alcohol. BDNF, GDNF, NT-3, NT-4, NGF, and S100B may be valuable markers for withdrawal syndrome. In particular, the most relevant is their association with the development of delirium complications. However, there are few data concerning some neurotrophins in AWS and DTs, suggesting the need for further research.

Genetic risk for trait aggression and alcohol use predict unique facets of alcohol-related aggression.

A propensity for aggression or alcohol use may be associated with alcohol-related aggression. Previous research has shown genetic overlap between alcohol use and aggression but has not looked at how alcohol-related aggression may be uniquely influenced by genetic risk for aggression or alcohol use. The present study examined the associations of genetic risk for trait aggression, alcohol use, and alcohol use disorder (AUD) with alcohol-related aggression using a polygenic risk score (PRS) approach. Using genome-wide association study summary statistics, PRSs were created for trait aggression, alcohol consumption, and AUD. These PRSs were used to predict the phenotype of alcohol-related aggression among drinkers in two independent samples: the University of California at San Francisco (UCSF) Family Alcoholism Study (n = 1,162) and the National Longitudinal Study of Adolescent to Adult Health (Add Health; n = 4,291). There were significant associations between the AUD PRS and lifetime alcohol-related aggression in the UCSF study sample. Additionally, the trait aggression PRS was associated with three or more experiences of hitting anyone else and getting into physical fights while under the influence of alcohol, along with a composite score of three or more experiences of alcohol-related aggression, in the UCSF study sample. No significant associations were observed in the Add Health sample. Limited sex-specific genetic effects were observed. These results provide preliminary evidence that genetic influences underlying alcohol use and aggression are uniquely associated with alcohol-related aggression and suggest that these associations may differ by type and frequency of alcohol-related aggression incidents. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Role of microglia in stress-induced alcohol intake in female and male mice.

Rates of alcohol use disorder (AUD) have escalated in recent years, with a particular increase among women. Women are more susceptible to stress-induced alcohol drinking, and preclinical data suggest that stress can increase alcohol intake in female rodents; however, a comprehensive understanding of sex-specific neurobiological substrates underlying this phenomenon is still emerging. Microglia, the resident macrophages of the brain, are essential for reshaping neuronal processes, and microglial activity contributes to overall neuronal plasticity. We investigated microglial dynamics and morphology in limbic brain structures of male and female mice following exposure to stress, alcohol or both challenges. In a modified paradigm of intermittent binge drinking (repeated "drinking in the dark"), we determined that female, but not male, mice increased their alcohol consumption after exposure to a physical stressor and re-exposure trials in the stress-paired context. Ethanol (EtOH) drinking and stress altered a number of microglial parameters, including overall number, in subregions of the amygdala and hippocampus, with effects that were somewhat more pronounced in female mice. We used the CSF1R antagonist PLX3397 to deplete microglia in female mice to determine whether microglia contribute to stress-induced escalation of EtOH intake. We observed that microglial depletion attenuated stress-induced alcohol intake with no effect in the unstressed group. These findings suggest that microglial activity can contribute to alcohol intake under stressful conditions, and highlight the importance of evaluating sex-specific mechanisms that could result in tailored interventions for AUD in women.

Daily-Level Associations between Situational Familiarity with Location and People and Use of Alcohol-related Protective Behavioral Strategy Among Adolescents and Young Adults.

Despite protective behavioral strategies (PBS) being an important part of alcohol prevention programs, utilization of PBS is sub-optimal, and research is needed to determine factors associated with use and non-use of PBS. The present study examined daily-level associations between situational familiarity (i.e., familiarity with locations and people) and the use of alcohol-related PBS among adolescents and young adults. Participants (analysis N = 564, 55.1% females, 45.2% White, Non-Hispanic, ages 15 to 25, mean = 21.07 years [SD = 2.79]) were part of a longitudinal ecological momentary assessment burst study on cognitions and alcohol use. Mixed effects Poisson models were used to analyze data for engagement in PBS (i.e., serious harm reduction, stopping/limiting, and manner of drinking PBS). Within-person results indicated when participants had elevated (i.e., higher than their own average) familiarity with their location, they were less likely to use serious harm reduction PBS (Rate ratio [RR] = 0.94, p < 0.001) and stopping/limiting PBS (RR = 0.95, p < 0.001). Results showed that on drinking days with elevated familiarity with people, individuals were more likely to use serious harm reduction PBS (RR = 1.03, p = 0.01). There were no significant daily-level associations between familiarity with people or location and manner of drinking PBS. The study suggests PBS use, particularly for serious harm reduction and stopping/limiting strategies, varies among adolescents and young adults based on familiarity with location and people. Alcohol prevention interventions, including just-in-time interventions, should consider how to promote PBS use particularly in familiar locations and with less familiar people.

Diet, lifestyle factors, comorbidities, and hepatocellular carcinoma risk in a middle eastern country: a case-control study

BackgroundHepatocellular Carcinoma (HCC) can be classified as one of the most common malignancies worldwide. There is scarcity of the published data on the risk factors for HCC in the Gulf Cooperation Council countries specifically Kuwait. Therefore, this case-control study sought to examine the risk factors associated with HCC in Kuwait.MethodsFifty-three histopathologically confirmed HCC cases were recruited from the Kuwait Cancer Control Center Registry. One hundred ninety-six controls (1:4 ratio) were selected from medical and/ or surgical outpatient’s clinics at all six public hospitals of Kuwait. A structured questionnaire was used to collect the data both from cases and controls through face-to-face interviews. A multivariable logistic regression model was fitted to the case-control data. Adjusted odds ratios (ORadj) and their 95% confidence intervals (CI) were computed using the parameters’ estimates of the final model and used for interpretation of the model.ResultsThe HCC cases compared with the controls were 41.6 times more likely to have had the history of non-alcoholic fatty liver disease (NAFLD) (ORadj = 41.6; 95% CI: 8.9–193.5; p < 0.001). The cases compared with the controls were more likely to have reported the history of heavy alcohol drinking (ORadj = 14.2; 95% CI: 1.2–173.4; p = 0.038). Furthermore, compared with the controls, the HCC cases tended to frequently consume milk and/or milk substitutes (≥ 3 glass/ week) (ORadj = 7.2; 95% CI: 1.2–43.4). Conversely however, there was a significant protective effect if the participants reportedly have had regularly used olive oil in their routine diet as a source of fat (ORadj = 0.17; 95% CI: 0.04–0.80) or regularly used non-steroid anti-inflammatory drugs (NSAIDs) (ORadj = 0.20; 95% CI: 0.05–0.71).ConclusionsThis study showed that heavy alcohol consumption, NAFLD history, and excessive consumption of milk/ milk substitutes were associated with a significantly increased HCC risk. Conversely however, regular use of olive oil in the diet as a source of fat or regular use of NSAIDs had a significantly protective effect against HCC risk. Adapting healthy dietary habits and preventing/ treating NAFLD may minimize the HCC risk. Future research with a larger sample size may contemplate validating the results of this study and unraveling additional risk factors contributing to HCC risk. The resultant data may help design and implement evidence-based educational programs for the prevention of HCC in this and other similar settings.

Psychometric evaluation of the Chinese version of alcohol relapse risk scale (C-ARRS) in patients with alcohol use disorder

Alcohol use disorder (AUD) is recognized as a chronic relapsing disorder. Alcohol Relapse Risk Scale (ARRS), a multidimensionally self-rating scale, was developed initially by the Japanese to assess the risk of alcohol reuse. The study aimed to validate the reliability and factor structure of the Chinese version of the ARRS (C-ARRS) for patients with AUD. A total of 218 patients diagnosed with AUD according to DSM-5 were recruited for self-administering C-ARRS. We assessed the internal consistency of C-ARRS using Cronbach's α coefficients and examined the factor structure through confirmatory factor analysis (CFA). Additionally, we investigated the concurrent validity by correlating C-ARRS with the Visual Analog Scale of Alcohol Craving (VAS), Penn Alcohol Craving Score (PACS), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) scores. CFA demonstrated inadequate data fit for the original 32-item C-ARRS, prompting the development of a revised 27-item version consisting of 6 subscales with satisfactory model fit estimates. The 27-item C-ARRS exhibited favorable internal consistency, with Cronbach's α ranging from 0.611 to 0.798, along with adequate factor loadings. The 27-item C-ARRS scores displayed significant correlations with the scores of VAS, PACS, BDI and BAI (p < .001). Our results indicated favorable reliability and factor structure of the 27-item C-ARRS. The significant correlation between the 27-item C-ARRS and clinical measures (such as depression, anxiety, and craving) demonstrates satisfactory concurrent validity. These observations collectively support the feasibility of using 27-item C-ARRS to assess the risk of alcohol relapse in patients with AUD.

Mental health nurses' attitudes towards consumers with co-existing mental health and drug and alcohol problems: A descriptive study.

BACKGROUND: Dual diagnosis is a global health concern. This descriptive research assessed mental health nurses' attitudes towards consumers with dual diagnosis in Australian mental health settings. The research question was: What is the attitude of mental health nurses towards consumers with co-existing mental health and drug and alcohol problems? This cross-sectional survey included 103 mental health nurses who work with consumers with dual diagnosis. Participants were recruited from various mental health settings through convenience sampling. The Comorbidity Problems Perceptions Questionnaire was used to assess attitudes. Descriptive data and multiple regression analyses were conducted. We utilized the consensus-based checklist for reporting results of this study. Mental health nurses positively perceived consumers with dual diagnosis. Factors associated with a positive attitude were a higher level of work experience, feeling that one's role is adequate, perceiving one's role as legitimate, receiving increased support in one's position, having high work motivation, possessing high task-specific self-esteem and experiencing higher levels of work satisfaction. Work experience predicted role adequacy. Position predicted role support. The work sector predicted role-related self-esteem. As mental health nurses gain work experience; they develop positive attitudes that boost their self-esteem and sense of importance towards consumers with dual diagnosis. This constructive mindset also positively affects their work motivation and job satisfaction towards consumers with dual diagnosis. Conducting interventional studies is necessary to examine how clinical experiences, work environments, and job positions can impact attitudes, aiming to improve mental health nursing interventions towards consumers with dual diagnosis. The study found that mental health nurses' positive attitudes towards consumers with dual-diagnosis are influenced by their experience and knowledge. Moreover, mental health nurses who feel supported, motivated and confident in their roles are more likely to provide high-quality care to consumers with dual diagnosis. Mental health nurses could provide better care and support if they took a proactive approach and addressed the challenges associated with this consumer population. To be successful in their roles, mental health nurses require access to resources and support from healthcare organizations. As a result, their job satisfaction and attitudes towards consumers with dual diagnosis will be enhanced. In this way, consumers as well as healthcare organizations will benefit.

Examining the role of social vulnerability, neighborhood characteristics, and geospatial patterns of firearm-related injuries and clinical outcomes in Milwaukee county

BackgroundPrevious work has shown socioenvironmental factors can influence firearm injury. Milwaukee County, Wisconsin is a diverse midwestern county with historic disinvestment in marginalized communities yielding stark segregation along racial and ethnic lines. It is also one of the many U.S. counties burdened by surging firearm injuries. The differences among communities within Milwaukee County provides a unique opportunity to explore the intersection of socioenvironmental factors that may affect clinical outcomes and geospatial patterns of firearm injury. MethodsThe trauma registry from the regional adult level 1 trauma center was queried for patients who sustained a firearm-related injury from 2015 to 2022 (N = 2402). The Social Vulnerability Index (SVI) ranking was derived using patient residence addresses to evaluate its association with traumatic injury clinical outcomes (i.e., in-hospital mortality, length of hospital stay, ICU or ventilator treatment, or injury severity score) and risk screening results for alcohol use disorder (AUD), posttraumatic stress disorder (PTSD), and depression. We evaluated hotspots of firearm injury density over time for patient residences and injury locations and distances between locations. A spatially lagged regression model tested the association between firearm injury density and SVI domains, alcohol outlet types, and park coverage. ResultsMost firearm injury patients were younger, male, racial or ethnic minorities from disadvantaged neighborhoods (SVI total; M = 0.86, SD = 0.15). SVI was not associated with any clinical outcomes. Of those screened, 12.9% screened positive for AUD and 44.5% screened at risk for PTSD, depression, or both. Hotspot analysis indicated consistent concentrations of firearm injury density. There were no differences in clinical outcomes between those injured inside or outside the home. Census tracts with lower socioeconomic status, greater off-premises and lower on-premises alcohol outlet density were associated with greater firearm injury density. ConclusionsIn Milwaukee County, firearm injury patients are injured in and often return to the same disadvantaged neighborhoods that may hamper recovery. Results replicate and expand previous work and implicate specific socioenvironmental factors for intervention and prevention of firearm injury.

The impact of abstinence from chronic alcohol consumption on the mouse striatal proteome: sex and subregion-specific differences.

Alcohol misuse is the third leading preventable cause of death in the world. The World Health Organization currently estimates that 1 in 20 deaths are directly alcohol related. One of the ways in which consuming excessive levels of alcohol can both directly and indirectly affect human mortality and morbidity, is through chronic inflammation. Recently, studies have suggested a link between increased alcohol use and the incidence of neuroinflammatory-related diseases. However, the mechanism in which alcohol potentially influences neuroinflammatory processes is still being uncovered. We implemented an unbiased proteomics exploration of alcohol-induced changes in the striatum, with a specific emphasis on proteins related to inflammation. The striatum is a brain region that is critically involved with the progression of alcohol use disorder. Using mass spectrometry following voluntary alcohol self-administration in mice, we show that distinct protein abundances and signaling pathways in different subregions of the striatum are disrupted by chronic exposure to alcohol compared to water drinking control mice. Further, in mice that were allowed to experience abstinence from alcohol compared to mice that were non-abstinent, the overall proteome and signaling pathways showed additional differences, suggesting that the responses evoked by chronic alcohol exposure are dependent on alcohol use history. To our surprise we did not find that chronic alcohol drinking or abstinence altered protein abundance or pathways associated with inflammation, but rather affected proteins and pathways associated with neurodegeneration and metabolic, cellular organization, protein translation, and molecular transport processes. These outcomes suggest that in this drinking model, alcohol-induced neuroinflammation in the striatum is not a primary outcome controlling altered neurobehavioral function, but these changes are rather mediated by altered striatal neuronal structure and cellular health.

Correspondence between the alcohol-P3 event-related potential and alcohol reward phenotypes among young adults.

Behavioral economic theory suggests that the value of alcohol depends upon elements of the choice context, such that increasing constraints on alternatives (e.g., price) or increasing the benefits of alcohol (e.g., social context) may result in greater likelihood of heavy drinking. The P3 event-related potential elicited by alcohol-related cues, a proposed marker of incentive salience, may be an electrophysiological parallel for behavioral economic alcohol demand. However, these indices have not been connected in prior research, and studies typically do not disaggregate social influences in the context of alcohol cue reactivity. The current study recruited heavy drinking young adults (N = 81) who completed measures of alcohol use and alcohol demand, in addition to a 2 (social/nonsocial) × 2 (alcohol/nonalcohol) visual oddball task to elicit the P3. In multilevel models controlling for demographic characteristics, P3 reactivity was greater to alcohol (p < 0.001) and social (p < 0.001) cues than to nonalcohol and nonsocial cues, but without a significant interaction. Higher alcohol consumption (p = 0.02) and lower elasticity of demand (p = 0.01) were associated with greater P3 response to alcohol than nonalcohol cues. The results highlight a brain-behavior connection that may be an important marker for alcohol reward across units of analysis and may be sensitive to changes in the economic choice contexts that influence the likelihood of alcohol use.

Novel medications for problematic alcohol use.

Alcohol-related harm, a major cause of disease burden globally, affects people along a spectrum of use. When a harmful pattern of drinking is present in the absence of significant behavioral pathology, low-intensity brief interventions that provide information about health consequences of continued use provide large health benefits. At the other end of the spectrum, profound behavioral pathology, including continued use despite knowledge of potentially fatal consequences, warrants a medical diagnosis, and treatment is strongly indicated. Available behavioral and pharmacological treatments are supported by scientific evidence but are vastly underutilized. Discovery of additional medications, with a favorable balance of efficacy versus safety and tolerability can improve clinical uptake of treatment, allow personalized treatment, and improve outcomes. Here, we delineate the clinical conditions when pharmacotherapy should be considered in relation to the main diagnostic systems in use and discuss clinical endpoints that represent meaningful clinical benefits. We then review specific developments in three categories of targets that show promise for expanding the treatment toolkit. GPCRs remain the largest category of successful drug targets across contemporary medicine, and several GPCR targets are currently pursued for alcohol-related indications. Endocrine systems are another established category, and several promising targets have emerged for alcohol indications. Finally, immune modulators have revolutionized treatment of multiple medical conditions, and they may also hold potential to produce benefits in patients with alcohol problems.

Drinking patterns among US men and women: Racial and ethnic differences from adolescence to early midlife.

Drinking patterns among young adult men and women in the United States have been understudied, especially among racial and ethnic groups such as Asian Americans and Hispanics. Because alcohol-related racial and ethnic health disparities persist or increase in midlife, identifying peak ages of hazardous drinking could help to reduce disparities. We used the National Longitudinal Study of Adolescent to Adult Health to examine: (1) past 12-month heavy episodic drinking (HED) and total alcohol volume consumption among non-Hispanic White (NHW), Black, Hispanic, and Asian men and women from ages 12 through 41, and (2) age-varying associations of race and ethnicity with drinking. Hispanic and Asian ethnic groups were disaggregated by historical drinking patterns. Time-varying effect models accounted for major demographic confounders. NHW men and women experienced elevated drinking rates in their early 20s, with a second elevation in their 30s. Black men and women did not have elevated drinking until their 30s. Among Hispanic men and women, peak drinking periods varied by gender and subgroup drinking pattern. Peak HED and total consumption emerged in the early 30s for Asian men, while peak HED occurred in the early 20s for Asian women. Drinking at certain ages for some racial and ethnic minoritized men and women did not differ from that in their NHW counterparts. Age periods during which subgroups in the U.S. population experience elevated alcohol consumption vary by ethnicity and gender. Recognition of these group differences could enhance our understanding of intervention timing.

Optogenetic inhibition of light-captured alcohol-taking striatal engrams facilitates extinction and suppresses reinstatement.

Alcohol use disorder (AUD) is a complex condition, and it remains unclear which specific neuronal substrates mediate alcohol-seeking and -taking behaviors. Engram cells and their related ensembles, which encode learning and memory, may play a role in this process. We aimed to assess the precise neural substrates underlying alcohol-seeking and -taking behaviors and determine how they may affect one another. Using FLiCRE (Fast Light and Calcium-Regulated Expression; a newly developed technique which permits the trapping of acutely activated neuronal ensembles) and operant-self administration (OSA), we tagged striatal neurons activated during alcohol-taking behaviors. We used FLiCRE to express an inhibitory halorhodopsin in alcohol-taking neurons, permitting loss-of-function manipulations. We found that the inhibition of OSA-tagged alcohol-taking neurons decreased both alcohol-seeking and -taking behaviors in future OSA trials. In addition, optogenetic inhibition of these OSA-tagged alcohol-taking neurons during extinction training facilitated the extinction of alcohol-seeking behaviors. Furthermore, inhibition of these OSA-tagged alcohol-taking neurons suppressed the reinstatement of alcohol-seeking behaviors, but, interestingly, it did not significantly suppress alcohol-taking behaviors during reinstatement. Our findings suggest that alcohol-taking neurons are crucial for future alcohol-seeking behaviors during extinction and reinstatement. These results may help in the development of new therapeutic approaches to enhance extinction and suppress relapse in individuals with AUD.

Moderate-to-severe cognitive impairment is associated with both recent and chronic alcohol misuse in people with HIV: The New Orleans alcohol use in HIV (NOAH) study.

Human immunodeficiency virus (HIV) profoundly impacts the nervous system, leading to neurological deficits including HIV-associated neurocognitive disorder (HAND). HAND represents the most common neurological comorbidity among people with HIV (PWH), and alcohol use may exacerbate cognitive deficits, especially in vulnerable populations. This study investigated relationships between alcohol use and cognition in an underserved cohort of PWH, on the hypothesis that alcohol misuse exacerbates cognitive deficits. Data collected from participants (n = 259; 66.7% male; mean age 52 ± 10 years) enrolled in the New Orleans Alcohol Use in HIV (NOAH) study were utilized for cross-sectional analysis. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), and alcohol use was comprehensively measured using four metrics: the Alcohol Use Disorders Identification Test (AUDIT), 30-day timeline follow back (TLFB), lifetime drinking history, and phosphatidylethanol (PEth) levels. The average MoCA score among participants was 20.7 ± 4.5, with 86.5% demonstrating cognitive impairment (MoCA < 26). Individuals with MoCA scores below 18 (moderately or severely cognitively impaired) had a higher frequency of recent severe alcohol misuse and greater lifetime alcohol consumption. Participants at increased risk for AUD (AUDIT ≥ 16) also had worse global cognition and memory task performance than those with lower AUDIT scores; this was particularly true among those aged 50 and older. Analysis of the MoCA sub-score data indicated that participants with increased AUD risk had impairments in the cognitive domains of language and memory. Our findings demonstrate a high prevalence of cognitive impairment in the NOAH cohort and suggest that alcohol misuse contributes to global cognitive deficits in PWH, especially among individuals aged 50 and older. Further exploration of the impact of alcohol use on specific cognitive domains, including memory and language, should incorporate additional cognitive tasks. These findings highlight the importance of considering alcohol use and AUD risk as significant factors that may exacerbate cognitive deficits in vulnerable populations, including older PWH.

Prevalence and correlates of alcohol and drug harms to others: Findings from the 2020 U.S. National Alcohol Survey.

Measure prevalence and overlap of secondhand harms from other people's use of alcohol, cannabis, opioid, or other drugs and examine sociodemographic and other correlates of these secondhand harms. This cross-sectional analysis used data from 7,799 respondents (51.6% female; 12.9% Black, 15.6% Hispanic/Latiné; mean age: 47.6) in the 2020 U.S. National Alcohol Survey. Secondhand harms included family/marriage difficulties, traffic accidents, vandalism, physical harm, and financial difficulties. Weighted prevalence estimates provided nationally representative estimates of these harms. Logistic regression assessed associations between individual characteristics and secondhand harms. Lifetime prevalence of secondhand harms from alcohol, cannabis, opioid, or other drugs was 34.2%, 5.5%, 7.6%, and 8.3%, respectively. There was substantial overlap among lifetime harms: almost 30% of those reporting secondhand alcohol harms also reported secondhand drug harms. Significant correlates of secondhand substance harms included female sex (alcohol, other drug); white (alcohol, opioid), American Indian/Alaska Native (opioid), and Black (cannabis) race/ethnicity; and separated/divorced/widowed marital status (opioid). Those reporting family history of alcohol problems had significantly higher odds of reporting secondhand harms across substance types. Individuals who reported frequent cannabis use had higher odds of reporting secondhand alcohol and opioid harms compared to those with no cannabis use, (aOR=1.55; aOR=2.38), but lower odds of reporting secondhand cannabis harms (aOR=0.51). Although less prevalent than secondhand alcohol harms, 14% of participants reported secondhand harms from someone else's drug use and frequently experienced secondhand harms attributed to multiple substances. Population-focused interventions are needed to reduce the total burden of alcohol and drug use.

Gait ataxia in alcohol use disorder: A systematic review.

A severe and long-term alcohol use can have adverse effects on lower limb function. Over time, some individuals may develop gait ataxia, which refers to the impairment of controlled lower body movements that are important for walking and maintaining proper gait. Gait ataxia is well-documented in patients who have been diagnosed with alcohol-related Wernicke-Korsakoff syndrome (WKS); however, less is known on how common ataxia is among patients with alcohol use disorder (AUD) without WKS. To date, no study has systematically reviewed the evidence focusing on patients suffering only from AUD. Our aim was to perform a qualitative synthesis of the existing literature examining behavioral signs of gait ataxia among abstinent patients with AUD. Two facets were created encompassing keywords for "alcohol use disorder" and "measures of gait ataxia." Databases, including EMBASE, APA PsycInfo, Medline, and Cochrane Library, were searched for studies, and a quality assessment was performed. Ten studies were identified (37 ≥ ns ≤ 247), which were all rated as being of moderate (N = 7) to good quality (N = 3). The age range was 31.4-53.4 years (weighted mean age: 53.6 years), and 78.3% of the participants were male. Eight studies found that patients with AUD and without WKS exhibited behavioral signs of gait ataxia. Although there is evidence of gait ataxia among patients with AUD, heterogeneous results and methodological shortcomings such as lack of screening for neurocognitive deficits deem these findings preliminary and highlight the need for more research in the future. (PsycInfo Database Record (c) 2024 APA, all rights reserved).