Alcohol (Hanover, York County, Pa.)最新文献

{"title":"Effect of N-acetylcysteine on neural alcohol cue reactivity and craving in adolescents who drink heavily: A preliminary randomized clinical trial","authors":"ReJoyce Green,&nbsp;Anna E. Kirkland,&nbsp;Brittney D. Browning,&nbsp;Pamela L. Ferguson,&nbsp;Kevin M. Gray,&nbsp;Lindsay M. Squeglia","doi":"10.1111/acer.15402","DOIUrl":"10.1111/acer.15402","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alcohol craving is related to problematic alcohol use; therefore, pharmacotherapies that modulate alcohol craving are of interest. <i>N</i>-acetylcysteine, an over-the-counter antioxidant, is a candidate pharmacotherapy for adolescent alcohol use with the potential to impact craving. Cue-reactivity paradigms using functional magnetic resonance imaging (fMRI) can identify neural regions implicated in craving and serve as a screening tool for novel pharmacotherapy options.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This preliminary study examined the effect of <i>N</i>-acetylcysteine on neural reactivity to alcohol cues and subjective craving among 31 non-treatment-seeking adolescents (17.6–19.9 years old, 55% female) who use alcohol heavily. In a randomized cross-over design, participants completed three fMRI sessions: baseline and after a 10-day course of <i>N</i>-acetylcysteine (1200 mg twice daily) and matched placebo. The primary outcome was neural response to alcohol versus non-alcohol beverage cues after <i>N</i>-acetylcysteine versus placebo, with a secondary outcome of self-reported subjective craving.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the full sample (<i>n</i> = 31), there was no effect of <i>N</i>-acetylcysteine versus placebo on neural alcohol reactivity (<i>p</i>s ≥ 0.49; <span></span><math></math>s = 0.00–0.07) or self-reported acute alcohol craving (<i>p</i> = 0.18, <span></span><math></math> = 0.06). However, <i>N</i>-acetylcysteine did reduce self-reported generalized alcohol craving (<i>p</i> = 0.03, <span></span><math></math> = 0.15). In a subsample of youth who met criteria for past-year alcohol use disorder (<i>n</i> = 19), results remained unchanged.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p><i>N</i>-acetylcysteine may not alter neural reactivity to alcohol cues or acute craving; however, it may reduce general subjective alcohol craving among adolescents who consume alcohol heavily.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 9","pages":"1772-1783"},"PeriodicalIF":3.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unique urine and serum metabolomic signature in patients with excessive alcohol use: An exploratory study","authors":"Zhihong Yang,&nbsp;Hui Gao,&nbsp;Jing Ma,&nbsp;Nathan A. Liang,&nbsp;Sophia P. Liang,&nbsp;Nazmul Huda,&nbsp;Yanchao Jiang,&nbsp;Themis Thoudam,&nbsp;Wanzhu Tu,&nbsp;Jing Su,&nbsp;Maggie Hesler,&nbsp;Kristina Chandler,&nbsp;Suthat Liangpunsakul","doi":"10.1111/acer.15398","DOIUrl":"10.1111/acer.15398","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Excessive alcohol consumption has a multifaceted impact on the body's metabolic pathways and organ systems. The objectives of this study were to characterize global metabolomic changes and identify specific pathways that are altered in individuals with excessive alcohol use.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This exploratory study included 22 healthy controls with no known history of excessive alcohol use and 38 patients identified as using alcohol excessively. A Fibrosis-4 score was used to determine the risk of underlying alcohol-associated liver disease among the excessive drinkers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found significantly altered urinary and serum metabolites among excessive drinkers, affecting various metabolic pathways including the metabolism of lipids, amino acids and peptides, cofactors and vitamins, carbohydrates, and nucleotides. Levels of two steroid hormones—5alpha-androstan-3beta,17beta-diol disulfate and androstenediol (3beta,17beta) disulfate—were significantly higher in both the serum and urine samples of excessive drinkers. These elevated levels may be associated with a higher risk of liver fibrosis in individuals with excessive alcohol use.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Alcohol consumption leads to marked alterations in multiple metabolic pathways, highlighting the systemic impact of alcohol on various tissues and organ systems. These findings provide a foundation for future mechanistic studies aimed at elucidating alcohol-induced changes in these metabolic pathways and their implications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 8","pages":"1519-1528"},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141478087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Infection burden and ALDH2 rs671, East Asian genetic diversity: A reply","authors":"Giovanni Deiana,&nbsp;Ruinan Sun,&nbsp;Jie Huang,&nbsp;Valerio Napolioni,&nbsp;Roberto Ciccocioppo","doi":"10.1111/acer.15403","DOIUrl":"10.1111/acer.15403","url":null,"abstract":"","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 9","pages":"1812-1813"},"PeriodicalIF":3.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychological processes and alcohol reduction in patients with chronic hepatitis C: Results from the HepART trial","authors":"Donna M. Evon,&nbsp;Jia Yao,&nbsp;Catherine Zimmer,&nbsp;Andrew J. Muir,&nbsp;Christian S. Hendershot,&nbsp;Rae Jean Proeschold-Bell","doi":"10.1111/acer.15400","DOIUrl":"10.1111/acer.15400","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>There is a lack of randomized controlled trials of behavioral interventions and process-level research related to alcohol reduction among patients with chronic liver disease (e.g., hepatitis C viral (HCV) infection). We conducted a process-level, secondary analysis of the Hepatitis C-Alcohol Reduction Treatment (HepART) trial to investigate the association between change in psychological processes posited by the Integrated Behavioral Model (IBM) and change in World Health Organization (WHO) drinking risk levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients with HCV who consume alcohol were recruited from hepatology clinics and received provider-delivered SBIRT (Screening, Brief Intervention, Referral to Treatment) or SBIRT+ 6 months of co-located alcohol counseling. Treatment arms were combined for this analysis because no between-group differences were found. At baseline and 6 months, the timeline followback method was used to determine alcohol risk levels according to the 2000 WHO risk categories (based on average grams of alcohol per day). Changes in alcohol consumption and WHO risk levels were quantified and regressed on change in individual psychological processes (e.g., readiness, self-efficacy, motives, attitudes, and strategies) from baseline to 6 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At the baseline assessment, 162 participants were classified as abstinent (5%), low (47%), moderate (16%), high (19%), or very high (13%) WHO risk levels. At 6 months, 38% remained at the same risk level and 48% decreased by at least one level. In univariate analyses, changes in 7 of 12 psychological processes were associated with change in risk levels. Adjusted multivariate analyses demonstrated that change in four processes were significantly associated with change in risk levels, including SOCRATES <i>Taking Steps, Ambivalence</i>, and <i>Recognition scores</i> and alcohol reduction strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings demonstrate significant reductions in quantitative indices of alcohol consumption following opportunistic alcohol interventions in patients with HCV. However, results provided mixed support for associations between change in IBM psychological processes and alcohol consumption.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 8","pages":"1541-1551"},"PeriodicalIF":3.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141461155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social episodic memory in severe alcohol use disorder: Positive encoding bias and negative bias in accessibility of interpersonal information","authors":"Arthur Pabst,&nbsp;Arnaud d'Argembeau,&nbsp;Xavier de Longueville,&nbsp;Philippe de Timary,&nbsp;Pierre Maurage","doi":"10.1111/acer.15344","DOIUrl":"10.1111/acer.15344","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alterations in higher-order social cognition are well documented in individuals with severe alcohol use disorder (SAUD). However, the basic mechanisms underpinning them are not well understood. This knowledge gap hampers the development of targeted therapeutic interventions. Here, we investigated whether individuals with SAUD show abnormalities in social episodic memory processes, which may represent relevant candidate mechanisms for alterations in social cognition.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Recently detoxified patients with SAUD and matched healthy controls (HCs) completed two experimental tasks. We first used a Social Recognition Task in 40 SAUD patients and 40 HCs to measure the participants' ability to implicitly memorize the facial identity and emotion of novel interpersonal cues (i.e., dynamic facial expressions of anger and happiness). We then used a Social Memory Accessibility Task in 29 SAUD patients and 30 HCs) to measure participants' access to and fluency for already existing social memories by asking them to retrieve as many specific positive and negative interpersonal events as possible within equal time limits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the Social Recognition Task, we found that, compared to HCs, patients with SAUD had a globally lower recognition performance for the facial identities of novel social stimuli, but a preserved bias toward positive information. Conversely, in the social memory accessibility task, patients showed greater access to and fluency for negative interpersonal memories than controls (no group differences were observed for positive ones), resulting in a negative accessibility bias.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This exploration of episodic social memory in individuals with SAUD showed (1) a preserved bias for the encoding of positive versus negative novel social information, and (2) greater access to negative than positive interpersonal memories. These results enhance our understanding of socio-affective processing in individuals with SAUD and identify social memory alterations that may contribute to social cognition and interpersonal difficulties.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 7","pages":"1336-1346"},"PeriodicalIF":3.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141461156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The key role of specific DSM-5 diagnostic criteria in the early development of alcohol use disorder: Findings from the RADAR prospective cohort study","authors":"Tim Slade,&nbsp;Siobhan M. O'Dean,&nbsp;Tammy Chung,&nbsp;Louise Mewton,&nbsp;Jim McCambridge,&nbsp;Philip Clare,&nbsp;Raimondo Bruno,&nbsp;Wing See Yuen,&nbsp;Joel Tibbetts,&nbsp;Peter Clay,&nbsp;Alexandra Henderson,&nbsp;Nyanda McBride,&nbsp;Richard Mattick,&nbsp;Veronica Boland,&nbsp;Delyse Hutchinson,&nbsp;Emily Upton,&nbsp;Ashling Isik,&nbsp;Phoebe Johnson,&nbsp;Kypros Kypri","doi":"10.1111/acer.15379","DOIUrl":"10.1111/acer.15379","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Prevention and early intervention of alcohol use disorder (AUD) is a public health priority, yet there are gaps in our understanding of how AUD emerges, which symptoms of AUD come first, and whether there are modifiable risk factors that forecast the development of the disorder. This study investigated potential early-warning-sign symptoms for the development of AUD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data were from the RADAR study, a prospective cohort study of contemporary emerging adults across Australia (<i>n</i> = 565, mean age = 18.9, range = 18–21 at baseline, 48% female). Participants were interviewed five times across a 2.5-year period. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) AUD criteria and diagnoses were assessed by clinical psychologists using the Structured Clinical Interview for DSM-IV (SCID-IV), modified to cover DSM-5 criteria. Hazard analyses modeled the time from first alcoholic drink to the emergence of any AUD criteria and determined which first-emergent AUD criteria were associated with a faster transition to disorder.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>By the final time point, 54.8% of the sample had experienced at least one DSM-5 AUD criterion and 26.1% met criteria for DSM-5 AUD. The median time from first AUD criterion to a diagnosis of AUD was 4 years. Social problems from drinking (hazard ratio [HR] = 3.24, CI₉₅ = 2.14, 4.92, <i>p</i> &lt; 0.001), major role (HR = 2.53, CI₉₅ = 1.58, 4.06, <i>p</i> &lt; 0.001), and drinking larger amounts/for longer than intended (HR = 2.04, CI₉₅ = 1.20, 3.46, <i>p</i> = 0.008) were first-onset criteria associated with a faster transition to AUD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In the context of a prospective general population cohort study of the temporal development of AUD, alcohol-related social problems, major role problems, and using more or for longer than intended are key risk factors that may be targeted for early intervention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 7","pages":"1395-1404"},"PeriodicalIF":3.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.15379","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141461157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and correlates of daily-level reasons not to drink among young adults who use alcohol","authors":"Brooke J. Arterberry,&nbsp;Sarah J. Peterson,&nbsp;Ty S. Schepis,&nbsp;Megan E. Patrick","doi":"10.1111/acer.15349","DOIUrl":"10.1111/acer.15349","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>This study examined reasons not to drink in young adults in relation to demographics, alcohol use patterns, timing (weekend vs. weekday), and typical drinking motives.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Young adults who reported past 30-day alcohol use and at least one nondrinking day (<i>n</i> = 614; mean age = 21.5 years ±0.53) completed a survey of alcohol-related measures (e.g., typical drinking motives) and up to 14 daily surveys that included 12 reasons not to drink assessed on nondrinking days. Multilevel logistic regressions were estimated for each reason not to drink and related covariates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The most common reasons not to drink on a given day were “wasn't interested in drinking” (83.4% of nondrinking days) and “didn't want to get drunk” (81.8% of nondrinking days), with over 96% of participants endorsing each of these at least once. On days (11.6%; by 29.5% of participants) when another drug was used instead of alcohol, 81.8% used cannabis. Sex, race/ethnicity, weekend (vs. weekday), and drinking motives were differentially linked to reasons not to drink. Reporting high-intensity drinking (i.e., ≥10 drinking on a day) versus binge (5–9 drinks on a day) in the past 2 weeks was linked to “had a hangover recently” (odds ratio = 2.85) as a reason not to drink.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Findings suggest that reasons not to drink reflect personal decisions and highlight ways to acknowledge situational barriers (e.g., saving money for food and essentials) that can be emphasized in brief interventions. Furthermore, reasons not to drink and alcohol motives may work in tandem within the motivational model to impact alcohol use behaviors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 7","pages":"1347-1359"},"PeriodicalIF":3.0,"publicationDate":"2024-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.15349","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141461154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The gut-brain axis in individuals with alcohol use disorder: An exploratory study of associations among clinical symptoms, brain morphometry, and the gut microbiome","authors":"Katherine A. Maki,&nbsp;Gwenyth R. Wallen,&nbsp;Thomaz F. S. Bastiaanssen,&nbsp;Li-Yueh Hsu,&nbsp;Michael E. Valencia,&nbsp;Vijay A. Ramchandani,&nbsp;Melanie L. Schwandt,&nbsp;Nancy Diazgranados,&nbsp;John F. Cryan,&nbsp;Reza Momenan,&nbsp;Jennifer J. Barb","doi":"10.1111/acer.15346","DOIUrl":"10.1111/acer.15346","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alcohol use disorder (AUD) is commonly associated with distressing psychological symptoms. Pathologic changes associated with AUD have been described in both the gut microbiome and brain, but the mechanisms underlying gut-brain signaling in individuals with AUD are unknown. This study examined associations among the gut microbiome, brain morphometry, and clinical symptoms in treatment-seeking individuals with AUD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a secondary analysis of data collected during inpatient treatment for AUD in subjects who provided gut microbiome samples and had structural brain magnetic resonance imaging (MRI; <i>n</i> = 16). Shotgun metagenomics sequencing was performed, and the morphometry of brain regions of interest was calculated. Clinical symptom severity was quantified using validated instruments. Gut-brain modules (GBMs) used to infer neuroactive signaling potential from the gut microbiome were generated in addition to microbiome features (e.g., alpha diversity and bacterial taxa abundance). Bivariate correlations were performed between MRI and clinical features, microbiome and clinical features, and MRI and microbiome features.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Amygdala volume was significantly associated with alpha diversity and the abundance of several bacteria including taxa classified to <i>Blautia,</i> <i>Ruminococcus</i>, <i>Bacteroides</i>, and <i>Phocaeicola</i>. There were moderate associations between amygdala volume and GBMs, including butyrate synthesis I, glutamate synthesis I, and GABA synthesis I &amp; II, but these relationships were not significant after false discovery rate (FDR) correction. Other bacterial taxa with shared associations to MRI features and clinical symptoms included <i>Escherichia coli</i> and <i>Prevotella copri.</i></p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We identified gut microbiome features associated with MRI morphometry and AUD-associated symptom severity. Given the small sample size and bivariate associations performed, these results require confirmation in larger samples and controls to provide meaningful clinical inferences. Nevertheless, these results will inform targeted future research on the role of the gut microbiome in gut-brain communication and how signaling may be altered in patients with AUD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 7","pages":"1261-1277"},"PeriodicalIF":3.0,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.15346","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141501972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare and common variants associated with alcohol consumption identify a conserved molecular network","authors":"Brittany S. Leger,&nbsp;John J. Meredith,&nbsp;Trey Ideker,&nbsp;Sandra Sanchez-Roige,&nbsp;Abraham A. Palmer","doi":"10.1111/acer.15399","DOIUrl":"10.1111/acer.15399","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Genome-wide association studies (GWAS) have identified hundreds of common variants associated with alcohol consumption. In contrast, genetic studies of alcohol consumption that use rare variants are still in their early stages. No prior studies of alcohol consumption have examined whether common and rare variants implicate the same genes and molecular networks, leaving open the possibility that the two approaches might identify distinct biology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To address this knowledge gap, we used publicly available alcohol consumption GWAS summary statistics (GSCAN, <i>N</i> = 666,978) and whole exome sequencing data (Genebass, <i>N</i> = 393,099) to identify a set of common and rare variants for alcohol consumption. We used gene-based analysis to implicate genes from common and rare variant analyses, which we then propagated onto a shared molecular network using a network colocalization procedure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Gene-based analysis of each dataset implicated 294 (common variants) and 35 (rare variants) genes, including ethanol metabolizing genes <i>ADH1B</i> and <i>ADH1C</i>, which were identified by both analyses, and <i>ANKRD12</i>, <i>GIGYF1</i>, <i>KIF21B</i>, and <i>STK31</i>, which were identified in only the rare variant analysis, but have been associated with other neuropsychiatric traits. Network colocalization revealed significant network overlap between the genes identified via common and rare variants. The shared network identified gene families that function in alcohol metabolism, including <i>ADH</i>, <i>ALDH</i>, <i>CYP</i>, and <i>UGT</i>. Seventy-one of the genes in the shared network were previously implicated in neuropsychiatric or substance use disorders but not alcohol-related behaviors (e.g. <i>EXOC2</i>, <i>EPM2A</i>, and <i>CACNG4</i>). Differential gene expression analysis showed enrichment in the liver and several brain regions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Genes implicated by network colocalization identify shared biology relevant to alcohol consumption, which also underlie neuropsychiatric traits and substance use disorders that are comorbid with alcohol use, providing a more holistic understanding of two disparate sources of genetic information.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 9","pages":"1704-1715"},"PeriodicalIF":3.0,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.15399","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141501971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blockade of thromboxane A2 signaling attenuates ethanol-induced myocardial inflammatory response in mice","authors":"Weilun Ai,&nbsp;Carol A. Casey,&nbsp;Paras Kumar Mishra,&nbsp;Yazen Alnouti,&nbsp;Sohel Daria,&nbsp;Viswanathan Saraswathi","doi":"10.1111/acer.15391","DOIUrl":"10.1111/acer.15391","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alcohol-associated cardiomyopathy (ACM) is a cardiac muscle disease characterized by inflammation and oxidative stress. Thromboxane-prostanoid receptor (TP-R) plays an important role in the pathogenesis of cardiovascular disease. Herein, we hypothesize that TP-R mediates alcohol-induced early cardiac injury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eight-week-old male C57BL/6 wild-type mice were fed a chronic ethanol (ET) or control diet (CON) for 10 days followed by a single binge of ethanol or maltose-dextrin through oral gavage. A cohort of ethanol-fed mice received SQ 29,548 (SQ), a TP-R antagonist. RNA sequencing, real-time PCR, and western blot analysis were performed on left ventricle to investigate alterations in genes and/or proteins mediating oxidative stress, inflammation, and cardiac remodeling. Sirius Red staining was performed to measure myocardial fibrosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>RNA-sequencing analysis of myocardium from CON and ET groups identified 142 genes that were significantly altered between the two groups. In particular, the gene expression of thioredoxin-interacting protein (TXNIP), a component of NLR family pyrin domain containing 3 (NLRP3) signaling, which mediates oxidative stress and inflammatory response, was upregulated in response to ethanol exposure. The myocardial protein levels of TP-R and thromboxane A2 synthase were increased upon alcohol exposure. Ethanol increased the levels of 4-hydroxynonenal, a marker of oxidative stress, with a concomitant increase in the protein levels of TXNIP and NLRP3, and administration of SQ attenuated these effects. Additionally, ethanol increased the protein levels of pro-inflammatory mediators, including tumor necrosis factor alpha and the NLRP3 downstream product, secretory interleukin 1 beta, and SQ blunted these effects. Finally, the Sirius red staining of the myocardium revealed an increase in collagen deposition in ethanol-fed mice which was attenuated by TP-R antagonism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study demonstrates that ethanol promotes the NLRP3 signaling pathway within the myocardium, leading to a pro-inflammatory milieu that potentially initiates early myocardial remodeling, and TP-R antagonism attenuates this effect.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"48 8","pages":"1529-1540"},"PeriodicalIF":3.0,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.15391","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141501973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}