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

{"title":"Abnormal neurobehavior profiles observed in the newborn period following low-to-moderate prenatal alcohol exposure","authors":"Jessie R. Maxwell,&nbsp;Melissa H. Roberts,&nbsp;Jean Lowe,&nbsp;Xingya Ma,&nbsp;Jillian F. Kotulski,&nbsp;Amy L. Salisbury,&nbsp;Ludmila Bakhireva","doi":"10.1111/acer.70013","DOIUrl":"10.1111/acer.70013","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Prenatal alcohol exposure (PAE) has lifelong consequences on affected individuals, with a range of physical, neurodevelopmental, learning, and behavioral adverse outcomes. There is no method to identify children at risk of these outcomes shortly after birth, resulting in delayed diagnosis and access to therapeutic modalities. The Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale, First Edition (NNNS-I), has demonstrated utility in the risk stratification of substance-exposed infants but has not been previously used to assess infants with PAE. The purpose of this study was to assess the utility of NNNS-I in the identification of infants with low-to-moderate PAE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The Ethanol, Neurodevelopment, Infant, and Child Health (ENRICH-2) prospective cohort included maternal assessments in the second and third trimesters of pregnancy and infant assessments at birth. PAE was evaluated by prospective, repeated Timeline Follow Back interviews and a comprehensive panel of ethanol biomarkers. During the birth hospitalization, certified examiners completed the NNNS-I assessment, which included infant neurobehavioral organization summarized into 12 summary scores. Summary scores and profiles, generated by latent profile analysis (LPA), were compared between PAE and no-PAE groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This analysis included 130 caregiver-infant dyads (71 with PAE and 59 with no-PAE). The absolute alcohol ounces per day in the PAE group were 0.08 ± 0.11, on average, or ~1.1 standard drinks per week. In multivariable analysis, PAE was associated with lower <i>attention</i> (<i>β</i> = −0.79) and higher <i>lethargy</i> (<i>β</i> = −0.86) scores (<i>p</i>'s &lt; 0.05) on NNNS-I after controlling for maternal mental health, marijuana use during pregnancy, and family income. LPA identified three profiles of neurobehavior, with a high-risk profile demonstrating poor infant self-regulation and decreased <i>attention</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Low-to-moderate PAE was associated with neurobehavioral findings identifiable on the NNNS-I assessment, highlighting its potential utility for screening and risk stratification of infants with PAE shortly after birth.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"49 4","pages":"818-828"},"PeriodicalIF":3.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722757","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 network alcohol use is associated with individual-level alcohol use among Black sexually minoritized men and gender-expansive people: Findings from the Neighborhoods and Networks (N2) cohort study","authors":"Cho-Hee Shrader,&nbsp;Dustin T. Duncan,&nbsp;Anthony Santoro,&nbsp;Elvin Geng,&nbsp;Henry R. Kranzler,&nbsp;Deborah Hasin,&nbsp;Donna Shelley,&nbsp;Bryan Kutner,&nbsp;Scott E. Sherman,&nbsp;Yen-Tyng Chen,&nbsp;Mainza Durrell,&nbsp;Rebecca Eavou,&nbsp;Hanson Hillary,&nbsp;William Goedel,&nbsp;John A. Schneider,&nbsp;Justin R. Knox","doi":"10.1111/acer.70009","DOIUrl":"10.1111/acer.70009","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Black sexually minoritized men and gender-expansive people (SGM), including transgender women, have higher levels of alcohol use and experience greater negative consequences from alcohol consumption than the general population. We investigated the role of multilevel factors contributing to alcohol use among these groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed data collected from HIV-negative participants in the Neighborhoods and Network (N2) cohort study in Chicago, IL (<i>N</i> = 138). Participants completed a social network inventory (November 2018–April 2019) and reported alcohol use (frequency, quantity, and frequency of binge drinking) during a quantitative assessment. We used stepwise negative binomial regression to identify associations with social network and individual-level alcohol use while controlling for sociodemographic variables.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Most participants drank alcohol in the past month (68%), with a mean of 2.5 drinks (SD = 1.9) per drinking day. Participants nominated 377 confidants (<i>M</i>_nominated = 2.7), of whom 93% were Black and 78% were friends/family. Among the confidants, 30% drank alcohol at least several times per week. Identifying as Latine (RR = 2.21; 95% CI: 1.44–3.10), having a higher Generalized Anxiety Disorder-7 score (RR = 1.03; 95%CI: 1.00–1.05), living with a problem drinker during one's childhood (RR = 1.80; 95% CI: 1.39–2.34), and having a greater proportion of regular drinkers in one's social network (RR = 1.49; 95% CI: 1.02–2.17) were positively associated with alcohol use.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Black SGM exposed to social network alcohol use during childhood and adulthood reported increased alcohol use. Interventions targeting Black SGM should address social norms around alcohol, intersectional discrimination, and mental health.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"49 4","pages":"783-791"},"PeriodicalIF":3.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722762","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":"History of mental comorbidities and their relationships with drinking milestones, hazardous drug use, suicide attempts, and the ADH1B and ALDH2 genotypes in 4116 Japanese men with alcohol dependence: An exploratory study","authors":"Akira Yokoyama,&nbsp;Tetsuji Yokoyama,&nbsp;Yosuke Yumoto,&nbsp;Tsuyoshi Takimura,&nbsp;Tomomi Toyama,&nbsp;Junichi Yoneda,&nbsp;Kotaro Nishimura,&nbsp;Ruriko Minobe,&nbsp;Takanobu Matsuzaki,&nbsp;Mitsuru Kimura,&nbsp;Sachio Matsushita","doi":"10.1111/acer.70014","DOIUrl":"10.1111/acer.70014","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alcohol dependence (AD) is often comorbid with other mental disorders. We assessed how comorbidities are associated with the clinical features of AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Information on the history of mental comorbidities, hazardous drug use, suicide attempts, and drinking milestones was collected on a semi-structured medical history form from 4116 Japanese male AD inpatients (2007–2018); the subjects' <i>ADH1B</i> and <i>ALDH2</i> genotypes (rs1229984/rs671) were also determined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the total, 889 (21.60%) patients reported a history of mental comorbidities, including mood disorders (15.48%) and insomnia (2.89%); 202 (4.91%) reported a history of hazardous drug use, and 614 (14.92%) reported suicide attempts. Comorbidities were most commonly diagnosed around the time of onset of advanced alcohol use disorder (aAUD). Patients with comorbidities who began drinking regularly showed more rapid progression to aAUD and to the start of treatment for AD. Multivariate odds ratios (MORs [95%CI]) for the fast-metabolizing <i>ADH1B*1/*2</i> and <i>ADH1B*2/*2</i>, protective against AD, were higher in patients with comorbidities [1.43 (1.16–1.76) and 1.35 (1.11–1.66)], drug use [1.64 (1.09–2.46) and 1.60 (1.07–2.38)], and suicide attempts [1.45 (1.13–1.85) and 1.49 (1.17–1.88)] compared with the <i>ADH1B*1/*1</i>. MORs for the inactive protective <i>ALDH2*1/*2</i> were increased only in patients with insomnia [2.65 (1.75–4.02)] compared with the <i>ALDH2*1/*1</i>. MORs for smoking [0.74 (0.58–0.94)] and for age ≤15 years at first drink [0.66 (0.54–0.81)] were lower in patients with comorbidities. MORs for suicide attempts were 2.87 (2.36–3.48) in patients with comorbidities and 3.38 (2.47–4.62) in patients with drug use.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Mental comorbidities and a history of suicide attempts were frequent in Japanese patients with AD. Risk factors for AD (<i>ADH1B*1/*1</i>, smoking, early initiation of drinking) were negatively associated with the risk of comorbidities, suggesting interactions between comorbidities and AD risk factors. Insomnia was positively associated with the inactive <i>ALDH2*1/*2</i>. AD patients with mental comorbidities require multifaceted interventions, including suicide prevention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"49 4","pages":"804-817"},"PeriodicalIF":3.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722759","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":"Trauma-related guilt, shame, and trauma type among patients with co-occurring PTSD and SUD.","authors":"Nathalie N M Faber, Sera A Lortye, Loes A Marquenie, Anna E Goudriaan, Arnoud Arntz, Marleen M de Waal","doi":"10.1111/acer.70028","DOIUrl":"https://doi.org/10.1111/acer.70028","url":null,"abstract":"<p><strong>Background: </strong>Substance use disorder (SUD) frequently co-occurs with posttraumatic stress disorder (PTSD). Feelings of shame and guilt are associated with either disorder but have not been studied in patients with both disorders. Index trauma characteristics are associated with PTSD severity and trauma-related shame. This study examines the effects of trauma-related guilt and shame, and index trauma on SUD and PTSD severity in a clinical sample of individuals with co-occurring SUD and PTSD.</p><p><strong>Methods: </strong>Participants were SUD-treatment-seeking patients with co-occurring PTSD (N = 209) who completed the Clinician-Administered PTSD scale for Diagnostic and Statistical Manual of Mental Disorders (DSM-5; CAPS-5), Alcohol Use Disorder Identification Test (AUDIT), Drug Use Disorders Identification Test (DUDIT), Trauma-Related Guilt Inventory (TRGI) and Trauma-Related Shame Inventory (TRSI). Regression analyses examined the predictive values of PTSD severity, trauma-related guilt, and shame on alcohol and drug use problems, and the predictive values of trauma-related guilt and shame on PTSD severity. One-way ANOVA and follow-up t-tests examined the effects of index trauma on PTSD severity and trauma-related shame.</p><p><strong>Results: </strong>PTSD severity was significantly associated with drug use disorder (DUD) severity and showed a curvilinear relationship to alcohol use disorder (AUD) severity. Trauma-related guilt was not significantly associated with SUD severity, while trauma-related shame was significantly associated with DUD severity (but not AUD severity). Both trauma-related guilt and shame were significantly associated with PTSD severity; however, only trauma-related shame showed an independent association. Interpersonal (especially sexual) index traumas were associated with increased trauma-related guilt and shame, while childhood index traumas were associated with increased PTSD severity.</p><p><strong>Conclusions: </strong>Trauma-related guilt and shame might be important focus points in PTSD treatment, but for SUD problems, this study only showed an association between trauma-related shame and drug use problems. Trauma-related shame seems to be a more important treatment focus point than trauma-related guilt in the treatment of PTSD. It becomes particularly relevant for interpersonal index traumas (especially sexual trauma). Childhood traumas require attention in SUD-PTSD co-occurrence, given the higher severity of PTSD.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712309","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 impact of adolescent drinking on traumatic brain injury-induced cognitive deficits and alcohol preference in adult C57BL/6J mice.","authors":"Yunhui H Xu, Hannah G Sexton, Angela N Henderson-Redmond, Christian Harris, Jason D Huber, Mary-Louise Risher","doi":"10.1111/acer.70027","DOIUrl":"https://doi.org/10.1111/acer.70027","url":null,"abstract":"<p><strong>Background: </strong>Industrial workers and active military personnel within combat roles face heightened risk for blast pressure wave traumatic brain injury (bTBI). Previous studies have shown that experiencing TBI is associated with increased alcohol (EtOH) consumption and illicit substance use. Notably, alcohol use typically begins during late adolescence or early adulthood, a period that precedes many TBI incidents; moreover, early-onset drinking is further associated with heightened risk of developing an alcohol use disorder (AUD) even in the absence of TBI. Adolescent binge drinking can induce lasting cognitive and astrocyte changes, impacting brain recovery and repair. However, the impact of adolescent drinking history on behavioral recovery after bTBI and its role in the subsequent escalation of alcohol consumption remain unexplored. Here, we used a mouse model to investigate how adolescent (PND28-42) and young adult (PND60-90) EtOH consumption affects behavioral outcomes following bTBI. We aim to determine whether the history of adolescent binge drinking contributes to bTBI-induced escalation in EtOH intake, preference, or worsened fear memory and anxiety.</p><p><strong>Methods: </strong>Adolescent mice were subjected to drinking in the dark (DID) EtOH paradigm for 4 weeks, then randomly assigned to sham, mild-bTBI, or severe-bTBI. Behavioral testing was conducted, followed by a second DID.</p><p><strong>Results: </strong>Both EtOH and bTBI independently induced hyperlocomotor activity in a sex-dependent manner. These findings reflect an increase in risk-taking rather than generalized anxiety. Importantly, a history of adolescent EtOH consumption synergistically worsened bTBI-induced impaired fear extinction in both sexes. Changes in EtOH preference post-bTBI are context-dependent, with male mice showing a significant decrease in preference following mild-bTBI and prior EtOH exposure, while females exhibited a trend toward increased preference post-bTBI, with significant increases in preference observed only when comparing pre- to post-bTBI drinking behavior.</p><p><strong>Conclusions: </strong>Both males and females exhibited vulnerability to the combined effects of adolescent EtOH consumption and bTBI on fear extinction, while female mice showed a unique vulnerability to the escalation in EtOH preference.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694621","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":"Blood phosphatidylethanol measurements indicate GLP-1 receptor stimulation causes delayed decreases in alcohol consumption.","authors":"Mathias E Jensen, Mette K Klausen, Marianne L Bergmann, Gitte M Knudsen, Tina Vilsbøll, Christophe Stove, Anders Fink-Jensen","doi":"10.1111/acer.70041","DOIUrl":"https://doi.org/10.1111/acer.70041","url":null,"abstract":"<p><strong>Background: </strong>The investigation of glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RA) as a potential treatment for individuals with alcohol use disorder (AUD) and obesity is currently underway. In this secondary analysis of a randomized placebo-controlled trial, we included AUD patients with comorbid obesity and assessed the effect of the GLP-1RA exenatide versus placebo on alcohol consumption as measured by the alcohol biomarker phosphatidylethanol (PEth).</p><p><strong>Methods: </strong>Thirty AUD patients (9 females, 21 males), with an average age of 53 years and a body mass index (BMI) of at least 30 kg/m², were included in this secondary analysis. Blood samples for PEth were collected at baseline and at weeks 4, 12, 20, and 26. The effect of time and treatment on PEth levels was analyzed using a baseline-adjusted linear mixed model.</p><p><strong>Results: </strong>A significant interaction between time and treatment was observed at Week 26, with PEth levels reduced by -0.9 μmol/L in the exenatide group compared to placebo (95% CI [-1.6 to -0.1], p = 0.03). However, the difference in PEth blood levels between the exenatide and placebo groups was not significant at earlier time points.</p><p><strong>Conclusion: </strong>This secondary analysis indicates that exenatide has a delayed yet significant impact on alcohol consumption in individuals with AUD and obesity, as assessed by PEth levels. These findings warrant further investigation, which is currently underway (NCT05895643).</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694620","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":"Articles of Public Interest","authors":"","doi":"10.1111/acer.70025","DOIUrl":"10.1111/acer.70025","url":null,"abstract":"","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"49 3","pages":"502"},"PeriodicalIF":3.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671780","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":"Chronic alcohol exposure during young adulthood attenuates microglial reactivity and downstream immune response pathways in a mouse model of tauopathy later in life.","authors":"Tiara Wolf, Lauren Moss, Charles Hudson, Alexis M Winters, Salma S Abdelmaboud, Marta Avlas, Jessica Wohlfahrt, Jennifer Guergues, Paula C Bickford, Stanley M Stevens","doi":"10.1111/acer.70034","DOIUrl":"https://doi.org/10.1111/acer.70034","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by the buildup of amyloid-β and tau protein tangles. Alcohol use has been identified as a risk factor for AD; however, the molecular mechanisms underlying this potential causal link remain elusive. An emerging area of research focuses on the role of microglia, the brain's innate immune cells, in AD pathogenesis, with evidence suggesting that alcohol exposure may prime microglia to exhibit an exaggerated immune response when they are subsequently exposed to proinflammatory stimuli.</p><p><strong>Methods: </strong>We used a single 10-day chronic-plus-binge alcohol exposure model in male and female C57BL/6J mice aged 8-10 weeks One month later, tauopathy was induced via adenoviral vector (AAV)-mediated overexpression of h-p301L Tau. After 2.5 months, the mice underwent behavioral and cognitive testing. Two weeks later, microglia were collected using fluorescence-activated cell sorting (FACS) and processed for unbiased, mass spectrometry-based proteomic analysis to determine the molecular pathways related to microglial reactivity.</p><p><strong>Results: </strong>Microglia from mice exposed to alcohol in young adulthood exhibited a blunted immune response when challenged with AAV-mediated delivery and accumulation of human tau later in life. This was characterized by decreased expression of MHC II- and interferon-associated proteins and bioinformatic prediction of inhibited inflammation-related pathways in the absence of gross histological, behavioral, or cognitive deficits. These results demonstrate unique, temporally specific microglial reactivity to tau that is modulated by early adulthood alcohol exposure, implicating a microglial response that could negatively affect the mechanisms necessary for tau clearance and potentially exacerbate tau pathogenesis.</p><p><strong>Conclusions: </strong>This study provides novel insights into the long-term effects of alcohol exposure in early adulthood on microglial function and the complexity of context-dependent microglial involvement in tauopathy. Consideration of early-adulthood environmental factors is critical for understanding and potentially mitigating the risk of neurodegenerative diseases, such as AD.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671769","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":"Peripheral alcohol metabolism dictates ethanol consumption and drinking microstructure in mice.","authors":"Bryan Mackowiak, David L Haggerty, Taylor Lehner, Yu-Hong Lin, Yaojie Fu, Hongkun Lu, Robert J Pawlosky, Tianyi Ren, Wonhyo Seo, Dechun Feng, Li Zhang, David M Lovinger, Bin Gao","doi":"10.1111/acer.70036","DOIUrl":"https://doi.org/10.1111/acer.70036","url":null,"abstract":"<p><strong>Background: </strong>Ethanol metabolism is intimately linked with the physiological and behavioral aspects of ethanol consumption. Ethanol is mainly oxidized by alcohol dehydrogenase (ADH) to acetaldehyde and further to acetate via aldehyde dehydrogenases (ALDHs). Understanding how ethanol and its metabolites work together to initiate and drive continued ethanol consumption is crucial for identifying interventions for alcohol use disorder (AUD). Therefore, the goal of our study was to determine how ADH1, which is mainly peripherally expressed and metabolizes >90% of ingested ethanol, modulates ethanol metabolite distribution and downstream behaviors.</p><p><strong>Methods: </strong>Ethanol consumption in drinking-in-the-dark (DID) and two-bottle choice (2BC) drinking paradigms, ethanol metabolite concentrations, and lickometry were assessed after ADH1 inhibition and/or in Adh1-knockout (Adh1 KO) mice.</p><p><strong>Results: </strong>We found that Adh1 KO mice of both sexes exhibited decreased ethanol consumption and preference compared with wild-type (WT) mice in DID and 2BC. ADH1 inhibitor fomepizole (4-MP) also significantly decreased normal and sweetened ethanol consumption in DID studies. Measurement of ethanol and its metabolites revealed that ethanol was increased at 1 h but not 15 min, peripheral acetaldehyde was slightly decreased at both timepoints, and ethanol-induced increases in acetate were abolished after ethanol administration in Adh1 KO mice compared with controls. Similarly, ethanol accumulation as a function of consumption was 2-fold higher in Adh1 KO or 4-MP-treated mice compared with controls. We then used lickometry to determine how this perturbation in ethanol metabolism affects drinking microstructure. Adh1 KO mice consume most of their ethanol in the first 30 min, like WT mice, but display altered temporal shifts in drinking behaviors and do not form normal bout structures, resulting in lower ethanol consumption.</p><p><strong>Conclusions: </strong>Our study demonstrates that ADH1-mediated ethanol metabolism is a key determinant of ethanol consumption, highlighting a fundamental knowledge gap regarding how ethanol and its metabolites drive ethanol consumption.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671775","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":"Differential impact of recent heavy drinking on first and recurrent acute pancreatitis.","authors":"Christie Y Jeon, Yu Ye, Georgios I Papachristou, James L Buxbaum, Joseph R Pisegna, Cheryl J Cherpitel, Esther A Adeniran, Minoti Apte, Eleanor Chang, Anil K Dasyam, Gayathri D Jalluri, Charlotte A Lansky, Aurelia Lugea, Zarine K Shah, Richard T Waldron, Stephen J Pandol, Dhiraj Yadav","doi":"10.1111/acer.70030","DOIUrl":"https://doi.org/10.1111/acer.70030","url":null,"abstract":"<p><strong>Background: </strong>While alcohol is known to sensitize the pancreas to acute injury, the role of short-term episodic drinking in regular drinkers is unknown.</p><p><strong>Methods: </strong>We conducted a case-crossover study to (1) determine the hazardous period of drinking prior to a first episode of acute pancreatitis (FAP) or recurrent acute pancreatitis (RAP) and (2) evaluate the dose-response association between short-term drinking and FAP/RAP. Patients hospitalized for FAP/RAP with an AUDIT-C score of ≥3 were enrolled. Recent and lifetime drinking history were collected through interviews. Drinking prior to the index pancreatitis attack was compared to that of an asymptomatic control period. Conditional logistic regression quantified the association of heavy drinking and FAP/RAP.</p><p><strong>Results: </strong>Of 141 patients who completed a short-term drinking questionnaire, 77 had RAP, and 64 experienced FAP. We found that both FAP and RAP patients drank at moderate-to-heavy levels regularly, with modest day-to-day variation (intraclass correlation of drinks/day 67%-82%). Alcohol consumption increased 2 days preceding the onset of the index pancreatitis attack as compared to the week prior. Stratifying by prior AP history, heavy drinking in the hazard period was associated with RAP (OR = 3.79, 95% confidence interval [CI] 1.57-9.12). Each drink was associated with 1.22-fold (95%CI 1.10-1.35) increased odds of RAP. Short-term heavy drinking was not associated with a FAP (OR = 1.06, 95%CI 0.43-2.57).</p><p><strong>Conclusion: </strong>In summary, we found that patients with a prior history of AP face a higher risk of RAP due to excess drinking. Drinking intensity did not increase prior to a FAP, which may have been triggered by other cofactors warranting further examination.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665541","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}