Alcohol (Hanover, York County, Pa.)最新文献_第8页

Intimacy-driven conformity: A between- and within-person perspective on friendship quality and adolescent susceptibility to peer norms about alcohol 亲密驱动的从众：关于友谊质量和青少年对酒精同伴规范的易感性的人际和内部视角。

IF 2.7 Q2 SUBSTANCE ABUSE

Alcohol (Hanover, York County, Pa.)

Pub Date : 2025-10-03 DOI: 10.1111/acer.70179

Nathaniel J. Caluda-Perdue, Rebecca A. Schwartz-Mette, Craig R. Colder

Background

Friendships become increasingly influential in early adolescence, leading to a greater impact of friends' norms on behavior. However, not all youth conform to norms, suggesting other factors may shape this influence. One such factor is friendship quality, which may shape adolescents' motivation to adopt peer norms, especially when those norms come from close, supportive friendships. This study examined how perceptions of friends' alcohol use and approval predict adolescents' intentions to drink, and whether friendship quality moderates these effects while disaggregating between- and within-person effects using a multilevel, longitudinal design.

Methods

Hierarchical linear modeling with a community sample of adolescents (n = 387) across 3 years tested hypotheses by distinguishing within- and between-person associations, capturing both the dynamic nature of friendships and how shifts in perceived norms influence alcohol intentions over time, as well as adolescents' broader tendency to affiliate with peers who approve of or engage in alcohol use. Interactions were tested using cross-product terms.

Results

Results partially supported hypotheses suggesting that friendship quality impacted susceptibility to peer norms regarding perceptions of friends' approval (β = 0.28, p = 0.026) but not use (β = 0.22, p = 0.214). The models supported the decomposition of between- and within-person effects, as both friends' approval (between-person: β = 0.58, p < 0.001; within-person: β = 0.37, p < 0.001) and use (between-person: β = 0.61, p < 0.001; within-person: β = 0.29, p < 0.001) were positively associated with future intentions to drink.

Conclusions

Taken together, results suggest that high-quality friendships amplified the influence of perceived friends' approval on alcohol intentions at the between-person level, but not for perceptions of use. Adolescents may prioritize maintaining their friendships; in turn, they adjust their beliefs and perceptions to preserve these relationships. Furthermore, perceptions of friends' alcohol norms operated similarly at the between- and within-level.

背景：友谊在青春期早期的影响力越来越大，导致朋友的规范对行为的影响更大。然而，并不是所有的年轻人都遵守规范，这表明其他因素可能会形成这种影响。其中一个因素是友谊的质量，它可能会影响青少年接受同伴规范的动机，尤其是当这些规范来自亲密的、支持性的友谊时。这项研究考察了对朋友饮酒和认可的看法如何预测青少年的饮酒意图，以及友谊质量是否会调节这些影响，同时使用多层次的纵向设计来分解人与人之间和人与人之间的影响。方法：对青少年社区样本（n = 387）进行了3年的分层线性建模，通过区分人与人之间的联系来检验假设，捕捉友谊的动态性质，感知规范的变化如何随着时间的推移影响饮酒意图，以及青少年与赞成或参与饮酒的同龄人交往的更广泛倾向。使用交叉乘积项测试相互作用。结果：结果部分支持假设，即友谊质量影响同伴规范对朋友认可感知的易感性（β = 0.28, p = 0.026），但不影响使用（β = 0.22, p = 0.214）。这些模型支持人与人之间和人与人之间效应的分解，因为朋友之间的认可（between-person: β = 0.58, p）。结论：综上所述，结果表明，高质量的友谊在人际层面上放大了感知到的朋友认可对饮酒意图的影响，但对使用的感知没有影响。青少年可能优先考虑维持友谊；反过来，他们调整自己的信念和观念来维持这些关系。此外，对朋友饮酒规范的认知在“间”和“内”水平上也有类似的作用。

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引用次数: 0

Interactions between the bone morphogenetic protein and the planar cell polarity pathways lead to distinctive ethanol-induced facial defects 骨形态发生蛋白与平面细胞极性通路之间的相互作用导致独特的乙醇诱导的面部缺陷。

IF 2.7 Q2 SUBSTANCE ABUSE

Alcohol (Hanover, York County, Pa.)

Pub Date : 2025-10-03 DOI: 10.1111/acer.70175

Raèden Gray, Anna Lloyd, C. Ben Lovely

Background

Fetal alcohol spectrum disorders (FASD) describe a spectrum of ethanol-induced developmental defects. Ethanol susceptibility is modulated by genetics, but the underlying mechanisms remain poorly understood. In all vertebrates, complex cellular events give rise to the body plan, including gastrulation and morphogenesis of the endoderm and cranial neural crest (CNC—gives rise to the facial skeleton). These events are crucial for establishing complex signaling interactions that drive embryo development, including the formation of the facial skeleton. In zebrafish, gastrulation occurs between 6 and 10 h postfertilization (hpf), while endoderm/CNC morphogenesis occurs between 10 and 24 hpf. In previous work, planar cell polarity (PCP) mutants are ethanol-sensitive from 6 to 24 hpf (covering both gastrulation and endoderm/CNC morphogenesis), exhibiting multiple defects in the forming head. This raises the question of whether ethanol during both these time windows drives PCP-ethanol defects. We hypothesize that PCP mutants are ethanol-sensitive from 10 to 24 hpf, after gastrulation. We also hypothesize that bone morphogenetic protein (BMP) signaling (ethanol-sensitive 10–18 hpf) interacts with and sensitizes the PCP pathway to ethanol.

Methods

We treated PCP/BMP mutants with ethanol over various time windows between 6 and 30 hpf and combined morphometric and linear measurements to examine facial development.

Results

We show that PCP mutants are largely ethanol-sensitive from 10 to 24 hpf. We also show that BMP mutants sensitize PCP mutants to ethanol and lead to novel ethanol-independent midline craniofacial defects. Our results suggest that the ethanol-sensitive role of the PCP pathway occurs after gastrulation, during endoderm/CNC morphogenesis, and that the PCP and BMP pathways genetically interact during the morphogenetic events.

Conclusions

Ultimately, our work builds on a mechanistic paradigm of ethanol-induced birth defects we have been developing, connecting the conceptual framework with concrete cellular events that could be ethanol-sensitive beyond facial development.

背景：胎儿酒精谱系障碍（FASD）描述了一系列酒精诱发的发育缺陷。乙醇易感性是由遗传调节的，但潜在的机制仍然知之甚少。在所有脊椎动物中，复杂的细胞事件产生了身体计划，包括原肠胚形成和内胚层和颅神经嵴的形态发生（cnc -产生了面部骨骼）。这些事件对于建立驱动胚胎发育的复杂信号相互作用至关重要，包括面部骨骼的形成。在斑马鱼中，原肠胚形成发生在受精后6至10小时（hpf）之间，而内胚层/CNC形态发生在受精后10至24小时之间。在之前的研究中，平面细胞极性（PCP）突变体在6至24 hpf范围内对乙醇敏感（包括原肠胚和内胚层/CNC形态发生），在形成头部表现出多种缺陷。这就提出了乙醇是否在这两个时间窗口内驱动pcp -乙醇缺陷的问题。我们假设PCP突变体在原肠胚形成后，在10至24 hpf范围内对乙醇敏感。我们还假设骨形态发生蛋白（BMP）信号（乙醇敏感的10-18 hpf）与PCP通路相互作用并使其对乙醇敏感。方法：我们用乙醇处理PCP/BMP突变体，时间窗在6到30 hpf之间，并结合形态测量和线性测量来检查面部发育。结果：我们发现PCP突变体在10至24 hpf范围内对乙醇敏感。我们还发现BMP突变体使PCP突变体对乙醇敏感，并导致新的不依赖乙醇的中线颅面缺陷。我们的研究结果表明，PCP途径的乙醇敏感作用发生在原肠胚形成后，内胚层/CNC形态发生过程中，PCP和BMP途径在形态发生过程中遗传相互作用。结论：最终，我们的工作建立在我们一直在开发的乙醇诱导出生缺陷的机制范例上，将概念框架与具体的细胞事件联系起来，这些细胞事件可能对乙醇敏感，而不是面部发育。

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引用次数: 0

Variations in alcohol craving and negative mood during a clinical trial of ibudilast for alcohol use disorder 在伊布司特治疗酒精使用障碍的临床试验中，酒精渴望和消极情绪的变化。

IF 2.7 Q2 SUBSTANCE ABUSE

Alcohol (Hanover, York County, Pa.)

Pub Date : 2025-10-02 DOI: 10.1111/acer.70178

Lindsay R. Meredith, Erica N. Grodin, Craig K. Enders, Lara A. Ray

Background

Immune medications, including ibudilast, have shown early potential in mitigating alcohol intake in preclinical models and small-scale trials for alcohol use disorder (AUD). To elucidate clinical utility and clinical mechanisms of these novel treatments, research should carefully assess medication-related changes in AUD symptomatology, including craving and negative mood, over time.

Methods

This is a secondary analysis of a 12-week randomized clinical trial of ibudilast for AUD. Participants were 102 individuals (40% female, average age 44 years) seeking treatment for AUD and randomized to ibudilast (50 mg twice-daily) or matched placebo. Clinical symptom measures of alcohol craving, depression, and anxiety were collected monthly. Growth models compared rates of change in clinical symptomatology between treatment groups and tested whether changes were moderated by sex. A subsample (n = 25) completed a functional magnetic resonance imaging scan with an alcohol cue-reactivity task at week four to assess a brain-based craving marker.

Results

At pretreatment, participants reported moderate craving symptoms and nonclinically elevated negative mood symptoms, on average. Participants taking ibudilast showed significantly steeper reductions in craving during the trial, as compared with placebo (1.32 vs. 0.52 points lower per month; p = 0.035). At treatment endpoint, female participants taking ibudilast reported lower craving than female participants taking placebo (p < 0.001). Greater cue-elicited brain activation in bilateral insula, bilateral orbitofrontal cortex, and right precuneus (p's < 0.02) was detected among the placebo subsample, compared to ibudilast. Rates of change for depression and anxiety did not differ between medication conditions, nor were they moderated by sex. Depression symptoms decreased during the trial, while anxiety symptoms remained relatively stable.

Conclusions

Consistent with prior research, ibudilast reduced neurobiological and self-report markers of craving, with female participants showing a stronger treatment response by trial endpoint. Despite shared neuroimmune correlates between negative mood and addiction, ibudilast did not alleviate negative mood symptoms beyond placebo effects.

背景：免疫药物，包括布司特，在酒精使用障碍（AUD）的临床前模型和小规模试验中已经显示出减少酒精摄入的早期潜力。为了阐明这些新疗法的临床效用和临床机制，研究应仔细评估药物相关的AUD症状变化，包括渴望和负面情绪。方法：这是一项为期12周的布司特治疗AUD的随机临床试验的二次分析。参与者为102名寻求AUD治疗的个体（40%为女性，平均年龄44岁），随机分配到布司特组（50mg，每日两次）或匹配的安慰剂组。每月收集酒精渴望、抑郁和焦虑的临床症状测量。生长模型比较了治疗组之间临床症状的变化率，并测试了变化是否因性别而有所缓和。一个子样本（n = 25）在第四周完成了功能磁共振成像扫描和酒精提示反应性任务，以评估基于大脑的渴望标记。结果：在预处理时，参与者平均报告中度渴望症状和非临床升高的负性情绪症状。与安慰剂相比，服用布司特的参与者在试验期间的渴望程度明显下降（每月降低1.32点对0.52点；p = 0.035）。在治疗终点，服用布司特的女性受试者报告的渴望程度低于服用安慰剂的女性受试者(p)。结论：与先前的研究一致，布司特降低了神经生物学和自我报告的渴望指标，女性受试者在试验终点显示出更强的治疗反应。尽管消极情绪和成瘾之间有共同的神经免疫相关性，但布司特并没有减轻消极情绪症状，而不是安慰剂效应。

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引用次数: 0

Alcohol-induced susceptibility to pulmonary bacterial infections: A narrative review 酒精诱导的肺部细菌感染易感性：一个叙述性的回顾。

IF 2.7 Q2 SUBSTANCE ABUSE

Alcohol (Hanover, York County, Pa.)

Pub Date : 2025-10-02 DOI: 10.1111/acer.70176

Tharanja Gobalakrishnan, Prantho M. Dipta, Bernard Aidoo, John Le, Samithamby Jeyaseelan

Alcohol intake is widely accepted in diverse cultures around the world, although heavy and prolonged consumption can be harmful. Alcohol influences multiple organs through interorgan and intercellular signaling cascades. The common health conditions associated with alcohol use disorder (AUD) are pancreatitis, liver cirrhosis, neuropathies, cardiomyopathies, and dementia. By virtue of its anatomical orientation and function, the lung continually encounters microbes, and this can be exacerbated by excessive alcohol consumption. Alcohol abuse is a well-known risk factor for bacterial infection in the lung. Increased susceptibility to bacterial pneumonia is caused by impaired immune responses in individuals with AUD. The key cells to defend against pulmonary infections are innate immune cells, including alveolar macrophages, neutrophils, and adaptive immune cells, such as T and B cells. This review highlights recent advances illuminating the roles of innate immune responses in bacterial pneumonia and the effects of alcohol in bacterial pneumonia. Understanding the molecular mechanisms associated with innate immunity in the lung is essential for developing effective strategies to control pneumonia and alcohol-mediated immunosuppression.

饮酒在世界各地的不同文化中被广泛接受，尽管大量和长期饮酒可能是有害的。酒精通过器官间和细胞间信号级联影响多个器官。与酒精使用障碍（AUD）相关的常见健康状况有胰腺炎、肝硬化、神经病变、心肌病和痴呆。由于肺的解剖方向和功能，它会不断地接触微生物，而过量饮酒会加剧这种情况。众所周知，酗酒是肺部细菌感染的危险因素。对细菌性肺炎的易感性增加是由AUD患者的免疫反应受损引起的。抵御肺部感染的关键细胞是先天免疫细胞，包括肺泡巨噬细胞、中性粒细胞和适应性免疫细胞，如T细胞和B细胞。本文综述了阐明先天免疫反应在细菌性肺炎中的作用和酒精在细菌性肺炎中的作用的最新进展。了解与肺部先天免疫相关的分子机制对于制定有效的策略来控制肺炎和酒精介导的免疫抑制至关重要。

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引用次数: 0

Neural alcohol cue reactivity as a risk factor for future drinking in youth with limited alcohol exposure 神经酒精线索反应是酒精接触有限的青少年未来饮酒的危险因素。

IF 2.7 Q2 SUBSTANCE ABUSE

Alcohol (Hanover, York County, Pa.)

Pub Date : 2025-09-30 DOI: 10.1111/acer.70152

Kathryn C. Jenkins, Shiane Toleson, Alexa House, Kayla Kreutzer, K. Luan Phan, Stephanie M. Gorka

Background

Heightened alcohol cue reactivity is associated with alcohol problems and poor alcohol use disorder outcomes. Theory suggests that this reflects a conditioned response, whereby cues repeatedly paired with chronic alcohol use become more salient. However, few studies have investigated the relative emergence of heightened alcohol cue reactivity. It is possible that this response occurs very early in individual drinking trajectories and may play a role in shaping future alcohol use behavior.

Methods

We tested this hypothesis in a sample of youth (n = 159; ages 16–19) with limited lifetime alcohol exposure (<100 lifetime drinks). Participants completed a baseline cue reactivity task in which they viewed images of alcoholic beverages, high-calorie foods (reward control), and neutral objects. The late positive potential (LPP), measured using electroencephalography, is a positive-going event-related potential measured 400 ms after a visual cue. The LPP was used to index cue reactivity and scored as the average amplitude from parietal site Pz. At baseline and 12 months, participants completed a retrospective calendar of alcohol use. Participants were classified into groups based on lifetime alcohol exposure: (1) ≤ 10 drinks (n = 50), (2) ≤50 drinks (n = 74), (3) >50 drinks (n = 35).

Results

We ran a repeated measures analysis of variance to compare the effects of task condition (alcohol cues/food cues > neutral) and drink groups on LPP amplitude. Our results revealed a significant condition × drink group interaction. Follow-up analyses revealed that, for alcohol cues only, there was a significant group effect. The highest drink exposure group exhibited greater LPP relative only to the low drink exposure group. Next, we examined whether baseline LPP to alcohol cues predicted total drinks consumed 12 months later, while controlling for baseline drinking behavior. Greater LPP to alcohol cues was associated with an increase in drinks consumed at one year.

Conclusions

Heightened alcohol cue reactivity emerges with limited alcohol use and can be predictive of future drinking behaviors.

背景：升高的酒精线索反应与酒精问题和不良的酒精使用障碍结局有关。理论表明，这反映了一种条件反应，即与长期饮酒反复配对的线索变得更加突出。然而，很少有研究调查了酒精线索反应性升高的相对出现。这种反应很可能发生在个人饮酒轨迹的早期，并可能在塑造未来的饮酒行为中发挥作用。方法：我们在终生酒精暴露有限(50次饮酒（n = 35）的青年样本（n = 159；年龄16-19）中检验了这一假设。结果：我们进行了重复测量方差分析来比较任务条件（酒精线索/食物线索>中性）和饮料组对LPP振幅的影响。我们的结果揭示了一个显著的条件x饮料组相互作用。后续分析显示，仅就酒精线索而言，存在显著的群体效应。最高饮酒量组仅比低饮酒量组表现出更大的LPP。接下来，我们检查了基线LPP对酒精线索的预测是否能预测12个月后的总饮酒量，同时控制了基线饮酒行为。对酒精线索的LPP越大，一年内的饮酒量就会增加。结论：酒精提示反应的增强与有限的酒精使用有关，可以预测未来的饮酒行为。

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引用次数: 0

Mutual age-varying influences of binge drinking and cannabis use during emerging adulthood in the NCANDA cohort 在nanda队列中，酗酒和大麻使用在成年初期的相互年龄变化影响。

IF 2.7 Q2 SUBSTANCE ABUSE

Alcohol (Hanover, York County, Pa.)

Pub Date : 2025-09-29 DOI: 10.1111/acer.70139

Jack T. Waddell, Ty Brumback, Fiona C. Baker, Shayna Cheek, Duncan B. Clark, David B. Goldston, Jeremy L. Grove, Bonnie J. Nagel, Kate B. Nooner, Adolf Pfefferbaum, Kilian M. Pohl, Edith V. Sullivan, Susan F. Tapert, Wesley K. Thompson, Sandra A. Brown

Background

Binge drinking peaks during emerging adulthood and is associated with negative developmental outcomes. Within-person changes in cannabis use have been shown to coincide with binge drinking; however, whether within-person changes in binge drinking and cannabis use prospectively predict one another and whether these relations vary by age remain unknown. The current study sought to fill these gaps.

Methods

Data come from National Consortium on Alcohol and Neurodevelopment (NCANDA) participants aged 18–25 years reporting alcohol and cannabis use (N = 526). Parallel-process state–trait mixed effect growth models tested whether: (1) binge drinking across emerging adulthood was correlated with cannabis use (random intercepts); (2) steeper growth in binge drinking across emerging adulthood correlated with growth in cannabis use (random slopes); and (3) age-specific, within-person changes in binge drinking/cannabis use reciprocally predicted one another.

Results

Across individuals, more frequent binge drinking was correlated with more frequent concurrent cannabis use, and steeper increases in binge drinking were correlated with steeper increases in cannabis use during emerging adulthood. Within-person changes in binge drinking and cannabis use covaried. Within-person increases in cannabis use predicted subsequent increases in binge drinking between ages 18 and 21 years but decreases in binge drinking between ages 24 and 25 years. Within-person changes in binge drinking did not predict subsequent changes in cannabis use during emerging adulthood.

Conclusions

Changes in cannabis use coincided with changes in binge drinking, concurrently and subsequently, particularly between ages 18 and 21 years when changes in cannabis use predicted subsequent increases in binge drinking and ages 24 and 25 years when changes in cannabis use predicted decreases in subsequent binge drinking. Incorporating motivational approaches to reduce cannabis use in alcohol interventions may be efficacious in early emerging adulthood.

背景：酗酒在成年初期达到高峰，并与负面的发展结果相关。大麻使用的个人变化已被证明与酗酒相吻合；然而，酗酒和大麻使用的个人内部变化是否可以相互预测，以及这些关系是否因年龄而异，仍然未知。目前的研究试图填补这些空白。方法：数据来自全国酒精和神经发育协会（nanda） 18-25岁报告饮酒和大麻使用的参与者（N = 526）。平行过程状态-特质混合效应增长模型检验了：(1)初成年期酗酒与大麻使用是否相关（随机截取）；(2)成年初期酗酒的急剧增长与大麻使用的增长相关（随机斜率）；(3)酗酒/大麻使用的年龄特异性、个人内部变化相互预测。结果：在个体中，更频繁的酗酒与更频繁的同时使用大麻相关，并且在成年初期，酗酒的急剧增加与大麻使用的急剧增加相关。个人内部酗酒和大麻使用的变化是共同变化的。个人大麻使用量的增加预示着18至21岁之间酗酒人数的增加，但24至25岁之间酗酒人数的减少。个人内部酗酒的变化并不能预测成年初期大麻使用的后续变化。结论：大麻使用的变化与酗酒的变化同时发生和随后发生的变化相吻合，特别是在18至21岁之间，大麻使用的变化预示着随后酗酒的增加，而在24至25岁之间，大麻使用的变化预示着随后酗酒的减少。在酒精干预措施中纳入减少大麻使用的动机方法，可能对刚进入成年期的人有效。

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引用次数: 0

The alcohol cue-exposure paradigm as a screening tool for alcohol use disorder medication development: A critical review 酒精线索暴露范式作为酒精使用障碍药物开发的筛选工具：一个重要的回顾。

IF 2.7 Q2 SUBSTANCE ABUSE

Alcohol (Hanover, York County, Pa.)

Pub Date : 2025-09-29 DOI: 10.1111/acer.70170

Dylan E. Kirsch, Erica N. Grodin, Lorenzo Leggio, Sherry A. McKee, Lindsay R. Meredith, Ethan H. Mereish, Robert Miranda Jr, Steven J. Nieto, Stephanie S. O'Malley, Joseph P. Schacht, Lara A. Ray

The alcohol cue-exposure paradigm has a long and rich history in alcohol use disorder (AUD) research, contributing to the identification of risk factors, the recognition of craving as a core symptom, the understanding of AUD neurobiology, and the development of both pharmacological and behavioral treatments. The goal of this review was to evaluate the utility of the alcohol cue-exposure paradigm as a screening tool for AUD medication development and to provide recommendations for refinement of the paradigm. First, we review evidence supporting the predictive validity and clinical applicability of the alcohol cue-exposure paradigm. Second, we examine current practices in implementing the paradigm in AUD pharmacotherapy studies. Third, we highlight several areas for refinement and offer recommendations for the implementation of this paradigm. Finally, we outline key conclusions and actionable future directions. In summary, while the alcohol cue-exposure paradigm has an established foundation in the study of AUD pharmacotherapies, its future success hinges on a concerted effort to refine and standardize protocols and validate outcome measures in large-scale studies. Addressing these priorities could accelerate the development and regulatory approval of novel treatments for AUD.

酒精线索暴露范式在酒精使用障碍（AUD）研究中有着悠久而丰富的历史，有助于识别危险因素，将渴望视为核心症状，理解AUD神经生物学，以及开发药物和行为治疗方法。本综述的目的是评估酒精提示暴露范式作为AUD药物开发筛选工具的效用，并为改进范式提供建议。首先，我们回顾了支持酒精线索暴露范式的预测有效性和临床适用性的证据。其次，我们检查了目前在AUD药物治疗研究中实施范式的实践。第三，我们强调了需要改进的几个领域，并为该范式的实现提供了建议。最后，我们概述了关键结论和可操作的未来方向。综上所述，尽管酒精提示暴露范式在AUD药物治疗研究中已经建立了基础，但其未来的成功取决于在大规模研究中对方案进行完善和标准化以及验证结果测量的共同努力。解决这些优先事项可以加速AUD新疗法的开发和监管批准。

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引用次数: 0

Predictors of naltrexone prescribing for alcohol use disorder from the emergency department 急诊科纳曲酮治疗酒精使用障碍的预测因素

IF 2.7 Q2 SUBSTANCE ABUSE

Alcohol (Hanover, York County, Pa.)

Pub Date : 2025-09-29 DOI: 10.1111/acer.70145

Jacob A. Lebin, Colin Hensen, Zhixin Lun, Bethany M. Kwan, Elizabeth M. Goldberg, Ellen L. Burnham, Jason A. Hoppe

Background

Excessive alcohol use is a leading cause of preventable death in the United States, with the emergency department (ED) serving as a critical touchpoint for individuals with alcohol use disorder (AUD). Despite clinical guidelines recommending initiation of medication for AUD (MAUD), such as naltrexone, ED prescribing remains rare. The objective of this study is to characterize clinician naltrexone prescribing practices for ED patients with hazardous drinking or AUD and identify patient- and encounter-level predictors of naltrexone prescribing within a large, integrated health system.

Methods

We conducted a retrospective cohort study of adult ED encounters across 12 hospitals from 2022 to 2024. Eligible encounters included patients with a positive Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) screen, indicating hazardous alcohol use or an active AUD, who had no exclusion criteria contraindicating naltrexone and were discharged from the ED. The primary outcome was provision of a naltrexone prescription at ED discharge, and the secondary outcome was prescription fill. We used a multivariable logistic regression model with generalized estimating equation (GEE) to identify predictors of prescribing.

Results

Of 52,701 treatment-eligible ED encounters, only 0.5% resulted in a naltrexone prescription. Prescriptions were more likely in encounters involving younger, male patients with higher AUDIT-C scores, alcohol-related complaints, and those occurring at an academic ED. In the logistic GEE model, academic setting, alcohol withdrawal diagnosis, and greater alcohol misuse severity were independently associated with increased prescribing. Nearly half (45%) of ED naltrexone prescriptions were filled.

Conclusions

Naltrexone prescribing among treatment-eligible patients is rare. Encouragingly, nearly half of patients receiving a prescription proceeded to fill it, highlighting a promising opportunity for ED-based prescribing of naltrexone to initiate AUD treatment. To improve AUD care, systematic ED-based strategies are urgently needed that go beyond universal screening to address barriers to MAUD initiation.

背景：在美国，过度饮酒是可预防死亡的主要原因，急诊科（ED）是酒精使用障碍（AUD）患者的关键接触点。尽管临床指南建议开始治疗AUD (MAUD)，如纳曲酮，ED处方仍然很少。本研究的目的是描述临床医生对患有危险饮酒或AUD的ED患者的纳曲酮处方做法，并在一个大型综合卫生系统中确定纳曲酮处方的患者和患者水平预测因素。方法：我们对2022年至2024年12家医院的成人急诊科就诊情况进行了回顾性队列研究。符合条件的患者包括酒精使用障碍识别测试-消费（AUDIT-C）筛查呈阳性的患者，表明有危险的酒精使用或活跃的AUD，没有排除标准禁止使用纳曲酮，并从急诊科出院。主要结果是在急诊科出院时提供纳曲酮处方，次要结果是处方填充。我们使用多变量逻辑回归模型与广义估计方程（GEE）来识别处方的预测因子。结果：在52701例符合治疗条件的急症患者中，只有0.5%的患者开了纳曲酮处方。较年轻的男性患者，AUDIT-C评分较高，有酒精相关的投诉，以及在学术急诊科就诊的患者更有可能开处方。在logistic GEE模型中，学术环境、酒精戒断诊断和更严重的酒精滥用严重程度与增加的处方独立相关。近一半（45%）的ED纳曲酮处方被配药。结论：纳曲酮处方在符合治疗条件的患者中是罕见的。令人鼓舞的是，近一半接受处方的患者继续填写处方，突出了基于ed的纳曲酮处方启动AUD治疗的有希望的机会。为了改善AUD护理，迫切需要系统的基于ed的策略，超越普遍筛查，以解决MAUD发生的障碍。

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引用次数: 0

Genotype-by-sex interaction analyses for alcohol use disorder across biobanks 跨生物库酒精使用障碍的性别基因型相互作用分析

IF 2.7 Q2 SUBSTANCE ABUSE

Alcohol (Hanover, York County, Pa.)

Pub Date : 2025-09-29 DOI: 10.1111/acer.70173

Hang Zhou, Lu Wang, Zhongzheng Mao, P. J. Michael Deans, Rachel L. Kember, Qingyu Chen, Yasmin Zakiniaeiz, Robert Kohler, MacKenzie R. Peltier, Terril L. Verplaetse, VA Million Veteran Program, Marc N. Potenza, Kristen J. Brennand, Amy C. Justice, Henry R. Kranzler, Joel Gelernter, Sherry A. McKee

Background

Alcohol use and alcohol use disorder (AUD) are significant contributors to morbidity and mortality, with different prevalences between males and females. Despite the established genetic contribution to AUD, sex as a biological variable and the interplay with genetic factors in the disorder remain largely unexplored. This study aimed to address the key question as to how genetic variations interact with biological sex to influence the AUD risk.

Methods

We conducted genome-wide genotype-by-sex (G × S) interaction analyses using multiancestry datasets from the Million Veteran Program (MVP) and UK Biobank (UKB). In total, 1,039,476 participants were analyzed, comprising 150,429 AUD cases and 889,046 controls. AUD cases were defined using ICD-9/10 codes in the MVP and using ICD-10 codes (field ID 41270) along with self-reported history of alcohol addiction (field ID 20406) in the UKB.

Results

In single-ancestry analyses, we identified two loci in African ancestry samples with lead single-nucleotide polymorphisms (SNPs) rs2183020 (p = 1.82 × 10⁻⁸) and rs9304803 (p = 4.66 × 10⁻⁸), and one locus in Admixed American ancestry samples with lead SNP rs9527196 (p = 2.83 × 10⁻⁸). The cross-ancestry meta-analysis identified one additional locus with lead SNP rs62446539 (p = 3.95 × 10⁻⁸). The deep learning method predicted that rs9304803 has B-cell type-specific enhancer activity. Rs2183020 and rs9304803 exhibited expression quantitative trait locus (eQTL) effects on multiple genes across various tissues, including the brain. Further experiments in ethanol-exposed human neurons confirmed expression changes in several of these genes. Phenome-wide association analyses revealed significant associations between rs2183020 and weight/body mass index, and between rs9304803 and prothrombin time (measured as international normalized ratio).

Conclusions

We believe this is the first genome-wide G × S study of AUD, providing novel insights into the genetic basis of sex differences in AUD and advancing our understanding of its biological underpinnings.

背景：酒精使用和酒精使用障碍（AUD）是导致发病率和死亡率的重要因素，男性和女性的患病率不同。尽管已经确定了AUD的遗传因素，但性别作为生物学变量以及与遗传因素的相互作用在很大程度上仍未被探索。本研究旨在解决遗传变异如何与生物性别相互作用以影响AUD风险的关键问题。方法：利用百万退伍军人计划（MVP）和英国生物银行（UKB）的多祖先数据集进行全基因组性别基因型（G × S）相互作用分析。总共分析了1,039,476名参与者，其中包括150,429例AUD病例和889,046例对照。使用MVP中的ICD-9/10代码和英国的ICD-10代码（字段ID 41270）以及自我报告的酒精成瘾史（字段ID 20406）来定义AUD病例。结果：在单祖先分析中，我们在非洲祖先样本中发现了2个位点，其单核苷酸多态性为rs2183020 （p = 1.82 × 10-8）和rs9304803 (p = 4.66 × 10-8)，在混合美国祖先样本中发现了1个位点，其SNP为rs9527196 （p = 2.83 × 10-8）。跨祖先荟萃分析发现了另外一个SNP为rs62446539的位点（p = 3.95 × 10-8）。深度学习方法预测rs9304803具有b细胞类型特异性增强子活性。Rs2183020和rs9304803在包括脑在内的多种组织中表现出多基因的表达数量性状位点（eQTL）效应。在暴露于乙醇的人类神经元中进行的进一步实验证实了其中一些基因的表达变化。全现象关联分析显示，rs2183020与体重/体重指数、rs9304803与凝血酶原时间（以国际标准化比值测量）存在显著相关性。结论：我们认为这是AUD的第一个全基因组G × S研究，为AUD性别差异的遗传基础提供了新的见解，并促进了我们对其生物学基础的理解。

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引用次数: 0

Prenatal alcohol exposure increases the aggressiveness of estrogen-induced pituitary tumors in male rats 产前酒精暴露增加雄性大鼠雌激素诱导的垂体肿瘤的侵袭性。

IF 2.7 Q2 SUBSTANCE ABUSE

Alcohol (Hanover, York County, Pa.)

Pub Date : 2025-09-29 DOI: 10.1111/acer.70169

Shaista Chaudhary, Dipak K. Sarkar

Background

We have recently shown that estrogen-induced prolactin-secreting pituitary tumors are aggressive in prenatal alcohol-exposed female rats. In this study, we investigated whether similar tumor aggressiveness occurs in estrogen-treated prenatal alcohol-exposed male rats.

Methods

Pregnant Fischer 344 rats were fed from gestational days 7 and 21 with a liquid diet containing ethanol 6.7% v/v (AF), pair-fed with an isocaloric liquid diet (PF), or fed chow ad libitum (AD). Alcohol-fed dams exhibited a blood alcohol concentration of 120–150 mg/dL 2 h after the last feeding. Male offspring were orchiectomized at 60 days of age and implanted subcutaneously with estradiol implants. Four months after the estradiol implants, rats were sacrificed, and pituitary tumor tissues were collected. Tumor cells were isolated and cultured for analysis.

Results

Pituitary tumor cells from AF males exhibited stem-like cell properties and showed elevated expression of stem cell regulatory genes and proteins (SOX-2, OCT-4, KLF4, SNAIL-1, and Nestin), tumor aggressiveness markers (MMP-9, CD44, CD34, PTTG, FGFR4, Ki-67, N-Cadherin), and prolactin compared to those from AD and PF controls. AF cells also had a higher cell proliferation rate, increased invasiveness, and colony formation compared to those in AD and PF cells, indicating more aggressive cancer cells than control cells. Notably, AF cells had a higher expression of developmental pluripotency-associated 4 (Dppa4), a gene we recently identified as upregulated in aggressive tumors and in fetal alcohol-exposed animals.

Conclusions

These findings are consistent with our previous observations in estrogen-treated AF female rats. These results support the hypothesis that prenatal alcohol exposure programs the pituitary epithelium toward a mesenchymal stem cell-like phenotype, contributing to the development of aggressive pituitary prolactinomas in both sexes.

背景：我们最近的研究表明，雌激素诱导的泌乳素分泌垂体肿瘤在产前酒精暴露的雌性大鼠中具有侵袭性。在这项研究中，我们研究了雌激素处理的产前酒精暴露雄性大鼠是否发生类似的肿瘤侵袭性。方法：妊娠期Fischer 344大鼠从妊娠第7天和第21天开始分别饲喂含乙醇6.7% v/v （AF）的液体饲粮、等量热量液体饲粮（PF）和自由采食（ad）。最后一次饲喂后2 h，酒精浓度为120 ~ 150 mg/dL。雄性子代于60日龄切除睾丸，皮下植入雌二醇。雌二醇植入4个月后处死大鼠，收集垂体瘤组织。分离培养肿瘤细胞进行分析。结果：与AD和PF对照组相比，AF男性垂体肿瘤细胞表现出干细胞样细胞特性，干细胞调控基因和蛋白（SOX-2、OCT-4、KLF4、snil -1和Nestin）、肿瘤侵袭性标志物（MMP-9、CD44、CD34、PTTG、FGFR4、Ki-67、N-Cadherin）和泌乳素的表达升高。与AD和PF细胞相比，AF细胞也具有更高的细胞增殖率、侵袭性和集落形成，表明癌细胞比对照细胞更具侵袭性。值得注意的是，AF细胞具有较高的发育多能性相关基因4 （Dppa4）表达，我们最近发现该基因在侵袭性肿瘤和胎儿酒精暴露动物中表达上调。结论：这些发现与我们之前在雌激素治疗的AF雌性大鼠中的观察结果一致。这些结果支持了一种假设，即产前酒精暴露使垂体上皮向间充质干细胞样表型发展，促进了两性侵袭性垂体泌乳素瘤的发展。

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引用次数: 0