{"title":"Texas Research Society on Alcoholism—35th Annual Scientific Meeting","authors":"","doi":"10.1111/acer.70060","DOIUrl":"https://doi.org/10.1111/acer.70060","url":null,"abstract":"","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"49 S1","pages":"565-570"},"PeriodicalIF":3.0,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.70060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244295","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":"Need for international consensus on diagnostic criteria for fetal alcohol spectrum disorders (FASD): Commentary on Myers et al., \"Comparing rates of agreement between different diagnostic criteria for fetal alcohol spectrum disorder: A systematic review\".","authors":"Elizabeth Jane Elliott","doi":"10.1111/acer.70095","DOIUrl":"https://doi.org/10.1111/acer.70095","url":null,"abstract":"","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251071","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}
Cecilia A Hinojosa, Sanne J H van Rooij, Negar Fani, Robyn A Ellis, Henri M Garrison-Desany, Stacey L House, Francesca L Beaudoin, Xinming An, Thomas C Neylan, Gari D Clifford, Sarah D Linnstaedt, Laura T Germine, Scott L Rauch, Karestan C Koenen, Kerry J Ressler, Samuel A McLean, Jennifer S Stevens
{"title":"The reciprocal relationship between posttraumatic stress disorder symptoms and alcohol use in a large multisite longitudinal sample stratified by sex: A random-intercept cross-lagged panel model.","authors":"Cecilia A Hinojosa, Sanne J H van Rooij, Negar Fani, Robyn A Ellis, Henri M Garrison-Desany, Stacey L House, Francesca L Beaudoin, Xinming An, Thomas C Neylan, Gari D Clifford, Sarah D Linnstaedt, Laura T Germine, Scott L Rauch, Karestan C Koenen, Kerry J Ressler, Samuel A McLean, Jennifer S Stevens","doi":"10.1111/acer.70092","DOIUrl":"https://doi.org/10.1111/acer.70092","url":null,"abstract":"<p><strong>Background: </strong>Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) often co-occur. There is a lack of longitudinal studies measuring the naturalistic development of PTSD and alcohol use problems in individuals with recent trauma exposure. This study aimed to compare the temporal relationships between posttraumatic stress symptoms and alcohol use over 6 months following trauma exposure in males and females.</p><p><strong>Methods: </strong>Large-scale longitudinal observational emergency department (ED)-based study of individuals with recent trauma exposure. Individuals with recent trauma exposure (n = 2942, 62% female) were recruited from 29 EDs across the United States within 72 h of trauma exposure from 2017 to 2021. PTSD symptoms, measured via the PTSD Checklist for the DSM-5, and alcohol use measured via the PhenX toolkit, were assessed at five time points: ED visit, 2 weeks, 8 weeks, 3 months, and 6 months following trauma.</p><p><strong>Results: </strong>PTSD symptoms predicted lower future alcohol use between the pretrauma to two-week time points (b = -0.08, p = 0.01) and higher use between the 3- to 6-month time points (b = 0.06, p = 0.01). There were no time points in which alcohol use predicted future PTSD symptoms. When stratifying by sex, male participants showed reciprocal associations, with alcohol use early after trauma predicting PTSD symptoms between 2 and 8 weeks (b = 0.08, p = 0.01), while PTSD symptoms predicted alcohol use between the 3- to 6-month time points (b = 0.10, p = 0.01). Female participants showed a different reciprocal pattern, with pretrauma PTSD symptoms predicting lower alcohol use 2 weeks posttrauma (b = -0.08, p = 0.04), while alcohol use subsequently predicted greater PTSD symptoms from 8 weeks to 3 months (b = 0.04, p = 0.04); these findings did not survive Bonferroni correction.</p><p><strong>Conclusions: </strong>Males and females exhibit complex temporal development patterns of PTSD symptoms and alcohol use that align with the mutual maintenance hypothesis in males but the susceptibility hypothesis in females. These patterns are masked in analyses that do not stratify by sex.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236082","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}
Lauren Smith, William H George, Elizabeth C Neilson
{"title":"Exploring the responsivity of men's perceptions of sexual interest: The impact of sexual consent communications, acute intoxication, and past perpetration of sexual aggression.","authors":"Lauren Smith, William H George, Elizabeth C Neilson","doi":"10.1111/acer.70093","DOIUrl":"https://doi.org/10.1111/acer.70093","url":null,"abstract":"<p><strong>Background: </strong>Several distal and proximal processes have been implicated in sexual aggression (SA) perpetration, including sexual misperception, or the erroneous perception of a potential partner's sexual interest or consent, alcohol intoxication, and past perpetration. Little is known about how these predictors interact in the context of a sexual interaction. Thus, the present study aimed to investigate how men's perceptions of a woman's sexual interest changed over the course of a hypothetical sexual interaction and how their intoxication, past perpetration and the woman's consent cues influenced those perceptions.</p><p><strong>Methods: </strong>Single, male social drinkers aged 21-30 with a history of risky sexual behavior (N = 97) completed an alcohol administration paradigm in which they were randomly assigned to an alcohol condition (sober control vs. intoxicated [BrAC = 0.10%]). Participants read a hypothetical scenario in which a man and woman engaged in nonpenetrative sex and the woman expressed nonconsent nonverbally and verbally. At several points during the scenario, participants rated the woman's sexual interest. Participants also reported their past perpetration.</p><p><strong>Results: </strong>Men's perceptions of the woman's sexual interest significantly decreased following verbal expressions of nonconsent. There were no significant differences between intoxicated and sober participants' ratings of the woman's sexual perception following verbal expressions of nonconsent. Men with a history of perpetration rated the woman's sexual interest following multiple verbal expressions of nonconsent as higher than nonperpetrators.</p><p><strong>Conclusions: </strong>Results suggest that intoxication does not necessarily impede men's ability to adjust their perceptions of a woman's sexual interest following verbal expressions of nonconsent.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236079","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}
Pauline Billaux, Nicolas Cabé, Olivier Desmedt, Joël Billieux, Aleksandra M Herman, Andrzej Jakubczyk, Maciej Kopera, Alice Laniepce, Mateo Leganes-Fonteneau, Paweł Wiśniewski, Côme Lemière, Anne-Lise Pitel, Pierre Maurage
{"title":"Physical sensations of craving in binge drinking and severe alcohol use disorder: A phenomenological approach.","authors":"Pauline Billaux, Nicolas Cabé, Olivier Desmedt, Joël Billieux, Aleksandra M Herman, Andrzej Jakubczyk, Maciej Kopera, Alice Laniepce, Mateo Leganes-Fonteneau, Paweł Wiśniewski, Côme Lemière, Anne-Lise Pitel, Pierre Maurage","doi":"10.1111/acer.70087","DOIUrl":"https://doi.org/10.1111/acer.70087","url":null,"abstract":"<p><strong>Background: </strong>Craving is a key concept in addictive disorders. However, despite seminal results identifying the pivotal role of its physical component, craving remains conceptualized as being centrally underpinned by psychological and cognitive processes. To explore the phenomenological dimension of physical craving in addiction, we measured self-reported body sensations of craving among individuals with subclinical (binge drinking, BD) or clinical (severe alcohol use disorder, SAUD) alcohol use disorders.</p><p><strong>Methods: </strong>We used a body mapping technique, allowing for the free report of the bodily counterparts of psychological phenomena, among 76 binge drinkers and 97 recently detoxified patients with SAUD. We measured the taxonomy, localization, intensity, and pleasantness of the craving bodily sensations.</p><p><strong>Results: </strong>Physical sensations of craving were reported (1) for individuals with BD habits, mostly in the shoulders/thorax (53.95%), mouth (47.37%), and forehead (31.58%), in the form of palpitations, dryness, and tension; (2) for patients with SAUD, most often and with the highest average intensity in the hands (31.96%), forehead (24.74%), and shoulders/thorax (22.68%), in the form of tremors, perspiration, and palpitations. In BD, craving sensations were described as slightly unpleasant to pleasant. Conversely, in SAUD patients, craving was perceived as slightly to very unpleasant.</p><p><strong>Conclusions: </strong>These findings bring forth a novel perspective of the bodily mechanisms involved in craving. They support a dissociation between subclinical and clinical populations of excessive alcohol drinkers, as body sensations related to craving might generate alcohol consumption through positive reinforcement (to extend positive sensations) for subclinical populations and through negative reinforcement (to alleviate unpleasant body sensations) for clinical populations. More widely, we highlight the need to add perceived bodily sensations to the predominantly and exclusively cognitive focus that characterizes the craving research field, since craving is also underpinned by physical sensations.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236080","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}
Maha Najdini, Joris Mathieu, Gérard Shadili, Antoine Frigaux, Maë Ménauges, Carla Mouton, Florence Gressier, Aziz Essadek
{"title":"Substance use prevalence among immigrants by generational status in Europe: A systematic review and meta-analysis.","authors":"Maha Najdini, Joris Mathieu, Gérard Shadili, Antoine Frigaux, Maë Ménauges, Carla Mouton, Florence Gressier, Aziz Essadek","doi":"10.1111/acer.70091","DOIUrl":"https://doi.org/10.1111/acer.70091","url":null,"abstract":"<p><strong>Background: </strong>Immigration has increased globally, particularly in Europe. While past research has looked into substance use among immigrants, there is a gap in understanding how generational status affects these patterns. This systematic review aimed to synthesize existing data on the differences in prevalence rates of substance use among immigrants by generational status to provide a thorough understanding of how substance use rates and trends vary between generations.</p><p><strong>Methods: </strong>We systematically searched PubMed, PsycINFO, Web of Science, Medline, Cochrane, and Embase for cohort studies until June 2024 with no language restrictions. We included studies published between 1990 and 2023, conducted in Europe, that examined substance use prevalence among first-generation immigrants (FGIs) and second-generation immigrants (SGIs). Following the data extraction, the data were pooled using random-effects meta-analyses with odds ratios (OR) and 95% confidence intervals (CI) calculated.</p><p><strong>Results: </strong>We identified 10 records from 157,426 articles screened, covering 2,652,732 individuals. The summary OR for alcohol use was 1.68 (95% CI: 1.32-2.13) with some variability in the results of individual studies, and women of second generation were found to be at higher risk, OR 1.85 (95% CI: 0.54-6.40). The OR for tobacco use was 1.18 (95% CI: 0.45-3.08), based on three effect estimates indicating an absence of significant difference between FGIs and SGIs. Regarding drug use, the OR was 2.50 (95% CI: 2.06-3.03), highlighting a significant association between drug use and SGI status.</p><p><strong>Conclusions: </strong>The findings of this meta-analysis indicate a higher risk of substance use among SGIs compared to FGIs, particularly for drug use and among women for alcohol use. These results highlight the need for further data on consumption patterns across generations to develop effective, culturally tailored intervention and prevention strategies.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236081","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}
Ramesh Bellamkonda, Sundararajan Mahalingam, Ojeshvi Ethiraj, Sathish Kumar Perumal, Madan Kumar Arumugam, Daren L Knoell, Kurt W Fisher, Carol A Casey, Kusum K Kharbanda, Karuna Rasineni
{"title":"Effect of aging on the development and progression of alcohol-associated liver disease.","authors":"Ramesh Bellamkonda, Sundararajan Mahalingam, Ojeshvi Ethiraj, Sathish Kumar Perumal, Madan Kumar Arumugam, Daren L Knoell, Kurt W Fisher, Carol A Casey, Kusum K Kharbanda, Karuna Rasineni","doi":"10.1111/acer.70086","DOIUrl":"https://doi.org/10.1111/acer.70086","url":null,"abstract":"<p><strong>Background: </strong>There is a robust link between chronic alcohol intake and the development of alcohol-associated liver disease (ALD). Over 90% of excessive alcohol drinkers develop hepatic steatosis that can progress to an advanced liver injury state. However, this progression depends on many extrahepatic factors including age, which is also a predictor of ALD-related mortality. This study aimed to identify selected pathological changes in rats of different ages with chronic ethanol administration for the same duration to gain insights into the effects of aging in the development and progression of ALD.</p><p><strong>Methods: </strong>Male Wistar rats of young (4 months), middle (8-12 months), and older (24 months) age were pair-fed for 6 weeks with Lieber-DeCarli control or ethanol diet. At the end of the experimental period, rats were euthanized and serum and tissues (liver, gut, and adipose) were collected for analyses.</p><p><strong>Results: </strong>Chronic ethanol feeding increased serum hepatic injury markers, circulating nonesterified free fatty acids, and hepatic triglycerides across the different age groups compared to their respective controls, with the higher levels seen in the middle-aged and old ethanol-fed rats compared to young ethanol-fed rats. Further, histopathological evaluation and quantitative analysis of inflammatory and fibrotic markers revealed more progressive liver injury in older ethanol-fed rats compared to young and middle-aged counterparts. We also observed increased intestinal permeability, as indicated by lower ileal expression of tight junction proteins and higher serum endotoxin levels in older ethanol-fed rats. Aging alone adversely affected several of these injury markers in older control-fed rats compared to middle-aged and young control-fed rats.</p><p><strong>Conclusion: </strong>Our findings indicate that aging significantly influences the development of liver injury after chronic alcohol intake.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217651","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}
Katherine Walukevich-Dienst, Scott Graupensperger, Marilyn L Piccirillo, Kirstyn N Smith-LeCavalier, Jessica Acolin, Mary E Larimer
{"title":"Are online norms-based alcohol interventions efficacious for college students with higher social anxiety?","authors":"Katherine Walukevich-Dienst, Scott Graupensperger, Marilyn L Piccirillo, Kirstyn N Smith-LeCavalier, Jessica Acolin, Mary E Larimer","doi":"10.1111/acer.70077","DOIUrl":"https://doi.org/10.1111/acer.70077","url":null,"abstract":"<p><strong>Background: </strong>Undergraduates with higher social anxiety symptoms are at risk for co-occurring substance misuse, heavier drinking in certain contexts, and experiencing more negative alcohol-related consequences. Among undergraduates broadly, online norms-based interventions provide consistent and cost-effective reductions in alcohol use and related risks. However, research on norms-based interventions for undergraduates with higher social anxiety symptoms is limited, and less is known about the longitudinal impacts of social anxiety symptoms on the efficacy of online, norms-based alcohol interventions.</p><p><strong>Methods: </strong>Secondary analyses were conducted on data from a large randomized controlled trial (RCT) with undergraduates who reported past-month heavy episodic drinking and were randomized to an attention control or a norms-based intervention. Generalized linear models tested whether baseline social anxiety symptoms moderated the efficacy of receiving a norms-based intervention versus a nonalcohol-focused attention control condition at 3-, 6-, and 12-month follow-up.</p><p><strong>Results: </strong>Social anxiety symptoms moderated intervention efficacy on the number of typical drinks consumed and descriptive norms at 3 months, as well as injunctive norms at 3 and 12 months. However, these effects appeared to be primarily driven by the individuals with higher social anxiety symptoms in the attention control group. Overall, norms-based interventions demonstrated efficacy in reducing the number of typical drinks consumed, descriptive and injunctive norms, and negative consequences up to 12 months later, regardless of social anxiety symptoms.</p><p><strong>Conclusions: </strong>Results demonstrated that online norms-based interventions were similarly efficacious for reducing drinking, negative consequences, and normative beliefs for undergraduates, regardless of social anxiety symptoms. Further, effects were maintained up to 12 months. Thus, existing alcohol-focused brief interventions are efficacious for those with higher social anxiety symptoms, even without adaptation for social anxiety-specific concerns. Individuals with higher social anxiety symptoms who did not receive an active intervention reduced drinking beliefs and behaviors, although reductions were not maintained over time.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210322","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}
Kaitlin R McManus, Erica N Grodin, Elizabeth Burnette, Yenashi Castillo, Karen Miotto, Michael R Irwin, Naomi Eisenberger, Lara A Ray
{"title":"Inflammatory endotoxin challenge in individuals with alcohol use disorder and controls.","authors":"Kaitlin R McManus, Erica N Grodin, Elizabeth Burnette, Yenashi Castillo, Karen Miotto, Michael R Irwin, Naomi Eisenberger, Lara A Ray","doi":"10.1111/acer.70090","DOIUrl":"https://doi.org/10.1111/acer.70090","url":null,"abstract":"<p><strong>Background: </strong>Preclinical and clinical research reveal associations between chronic alcohol use, increases in proinflammatory cytokines (interleukin [IL]-6, IL-8, tumor necrosis factor alpha [TNF-α]), and increases in alcohol consumption, alcohol craving, and negative mood. However, these findings remain largely correlational in clinical samples. Therefore, we conducted a preliminary inflammatory challenge using endotoxin in individuals with alcohol use disorder (AUD) to investigate the immune, behavioral, and brain responses to the inflammatory challenge.</p><p><strong>Methods: </strong>Participants were randomly assigned to receive a bolus intravenous injection of either low-dose endotoxin (0.8 ng/kg of body weight) or placebo (same volume of 0.9% saline). Blood samples, sickness symptoms, physiology, mood, and alcohol craving were collected at baseline and hourly for 4 h postbaseline, with a neuroimaging scan occurring at 3 h postbaseline. Matched control data were used to validate the endotoxin challenge in comparison to the AUD sample.</p><p><strong>Results: </strong>Endotoxin led to an acute blunted pro-inflammatory (i.e., TNF-α, IL-6, and IL-8) response in individuals with AUD compared to controls (all p's < 0.039). Endotoxin led to decreased cue-induced craving in both the behavioral human laboratory (p = 0.03) and neuroimaging (p's < 0.01) assays. Moreover, higher levels of endotoxin-induced IL-6 were most negatively associated with decreased self-reported craving following baseline (p < 0.05) in comparison with lower levels of endotoxin-induced IL-6.</p><p><strong>Conclusions: </strong>This preliminary study provides an acute experimental manipulation of inflammatory processes associated with AUD and suggests that the short-term effects of inflammation in AUD phenomenology are multifaceted and dose-dependent.</p>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200958","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}
Henry R. Kranzler, Zeal Jinwala, Christal N. Davis, Heng Xu, Joanna M. Biernacka, Hang Zhou, Rachel L. Kember, Joel Gelernter, Richard Feinn
{"title":"Moderation of treatment outcomes by polygenic risk for alcohol-related traits in placebo-controlled trials of topiramate","authors":"Henry R. Kranzler, Zeal Jinwala, Christal N. Davis, Heng Xu, Joanna M. Biernacka, Hang Zhou, Rachel L. Kember, Joel Gelernter, Richard Feinn","doi":"10.1111/acer.70052","DOIUrl":"10.1111/acer.70052","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In two 12-week, randomized, placebo-controlled trials (RCTs) in individuals with alcohol use disorder (AUD), topiramate significantly reduced heavy drinking days (HDDs), and alcohol-related problems. In a secondary analysis of those findings, we examined four broad measures of genetic risk—polygenic scores (PGS)—of problematic alcohol use (PAU), drinks per week (DPW), and time to relapse to any drinking (TR) and heavy drinking (THR) as moderators of topiramate's effect on HDDs and alcohol-related problems.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed data from 285 individuals with AUD (65.6% male) of European-like ancestry, who were treated with either topiramate (49.1%) or placebo (50.9%). All patients underwent genome-wide array genotyping, and PGS were calculated using summary statistics from genome-wide association studies of PAU, DPW, and TR and THR (two time-to-event outcomes among patients treated in AUD pharmacotherapy trials). We hypothesized an interaction effect in which greater genetic risk—particularly for PAU—would be associated with a greater therapeutic response to topiramate than placebo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>As shown previously, topiramate significantly reduced both HDDs (odds ratio [OR] = 0.50, <i>p</i> < 0.001) and Short Index of Problems (SIP) scores (<i>b</i> = −3.04, <i>p</i> < 0.001) more than placebo. There were nonsignificant associations of higher PGS with more HDDs (OR = 1.17, 95% CI = 0.98–1.41, <i>p</i> = 0.091) and a greater reduction in HDDs in the topiramate group (OR = 0.80, 95% CI = 0.62–1.03, <i>p</i> = 0.089). There were also significant interaction effects with treatment on SIP score by PGS for PAU (<i>b</i> = −1.64, SE = 0.78, <i>p</i> = 0.033), TR (<i>b</i> = −2.16, SE = 0.72, <i>p</i> = 0.003), and TRH (<i>b</i> = −2.17, SE = 0.72, <i>p</i> = 0.003).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings provide proof of principle for the use of alcohol-related PGS as moderators of the effects of topiramate for treating AUD. Larger RCTs of topiramate are needed to provide adequate statistical power to validate this pharmacogenetic approach to precision AUD treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"49 6","pages":"1297-1305"},"PeriodicalIF":3.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188560","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}