Alcohol (Hanover, York County, Pa.)最新文献_第10页

Liver molecular networks associated with drinking behavior in nonhuman primates 非人类灵长类动物的肝脏分子网络与饮酒行为有关。

IF 2.7 Q2 SUBSTANCE ABUSE

Alcohol (Hanover, York County, Pa.)

Pub Date : 2025-09-18 DOI: 10.1111/acer.70162

Laura A. Cox, James B. Daunais, Timothy D. Howard, Ge Li, Sobha Puppala, Jeannie Chan, Zeeshan Hamid, Samer Gawrieh, Sun Mi Lee, Betsy Ferguson, Kathleen A. Grant, Michael Olivier

Background

Consumed ethanol is primarily metabolized by the liver, with resulting products of ethanol metabolism, acetaldehyde and salsolinol that influence brain activity and alcohol drinking behavior. Alcohol consumption in humans is highly heritable with numerous associated genetic variants. Functional variants in the ADH and ALDH genes influence liver alcohol metabolism but only account for a small percentage of variance in consumption. We hypothesized that variation in hepatic molecular networks during the induction phase, where animals consume identical amounts of alcohol, predicted variation in drinking behavior during subsequent ad libitum access in nonhuman primates (NHPs).

Methods

We studied male rhesus macaques at baseline and during the uniform consumption phase that became discordant at the later ad libitum phase. The study design increased the likelihood of identifying functional molecular differences between light drinkers (LD) and very heavy drinkers (VHD) before animals exhibited differences in drinking behavior. We analyzed liver biopsies, provided by the Monkey Alcohol and Tissue Research Resource (MATRR), collected at baseline and after 3 months of uniform consumption, using multiomic and histologic methods.

Results

We found hepatic molecular pathways and networks differed between LD and VHD at baseline and in response to identical consumption. Notably, Sirtuin Signaling and a MYC-regulated network were significantly enriched for differentially abundant molecules in both LD and VHD response to uniform alcohol consumption. Potential epigenomic mechanisms regulating response to alcohol consumption were significantly different with LD response primarily through microRNAs, and VHD primarily through DNA methylation. Histological analysis of liver biopsies showed no liver pathologies in either group.

Conclusions

Our findings of differences in molecular networks prior to alcohol consumption suggest genetic variation contributes to drinking phenotypes, and differences in molecular response to uniform alcohol consumption suggest epigenetic mechanisms regulating liver networks also contribute to the development and progression of drinking phenotypes in NHP.

背景：消耗的乙醇主要由肝脏代谢，产生的乙醇代谢产物、乙醛和沙索林醇影响大脑活动和饮酒行为。人类饮酒具有高度遗传性，有许多相关的遗传变异。ADH和ALDH基因的功能变异影响肝脏酒精代谢，但仅占消费量变异的一小部分。我们假设，在诱导阶段，动物消耗相同数量的酒精，肝脏分子网络的变化预测了非人灵长类动物（NHPs）随后随意饮酒行为的变化。方法：我们研究了雄性恒河猴在基线和均匀消耗阶段，在随后的随意阶段变得不协调。研究设计增加了在动物表现出饮酒行为差异之前识别轻度饮酒者（LD）和重度饮酒者（VHD）之间功能分子差异的可能性。我们使用多组学和组织学方法分析了由猴子酒精和组织研究资源（MATRR）提供的肝活检，这些肝脏活检是在基线和均匀消耗3个月后收集的。结果：我们发现LD和VHD的肝脏分子通路和网络在基线和对相同消耗的反应中是不同的。值得注意的是，在LD和VHD对均匀饮酒的反应中，Sirtuin信号和myc调节的网络显著富集了差异丰富的分子。调节对酒精消费反应的潜在表观基因组机制与主要通过microrna调节的LD反应和主要通过DNA甲基化调节的VHD反应有显著差异。两组肝脏活检组织学分析均未见肝脏病变。结论：我们的研究结果表明，饮酒前分子网络的差异表明，遗传变异有助于饮酒表型，而对均匀饮酒的分子反应的差异表明，调节肝脏网络的表观遗传机制也有助于NHP饮酒表型的发展和进展。

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引用次数: 0

Effect of varenicline on major adverse liver outcomes in alcohol-associated liver disease: An exploratory analysis 伐尼克兰对酒精相关性肝病主要不良肝脏结局的影响：一项探索性分析

IF 2.7 Q2 SUBSTANCE ABUSE

Alcohol (Hanover, York County, Pa.)

Pub Date : 2025-09-15 DOI: 10.1111/acer.70160

Pojsakorn Danpanichkul, Yanfang Pang, Donghee Kim, Thanathip Suenghataiphorn, Donghyun Ko, Andrew F. Ibrahim, Vitchapong Prasitsumrit, Kwanjit Duangsonk, Mazen Noureddin, Karn Wijarnpreecha, Suthat Liangpunsakul

Background

Varenicline, a partial agonist of the α4β2 nicotinic acetylcholine receptor, is effective for smoking cessation and has shown promise in treating alcohol use disorder (AUD). However, its impact on patients with concurrent alcohol-associated liver disease (ALD) remains understudied. We aimed to evaluate the association between varenicline use and long-term clinical outcomes in this population.

Methods

We conducted a retrospective cohort study using the TriNetX federated network of deidentified electronic health records. Adults with diagnoses of both ALD and AUD were included. Patients prescribed varenicline were compared to those receiving FDA-approved AUD pharmacotherapies (acamprosate or naltrexone), using 1:1 propensity score matching based on demographics, comorbidities, medications, and laboratory values. The primary outcome was major adverse liver outcomes (MALO); secondary outcomes included all-cause mortality and other liver-related complications. Hazard ratios (HRs) were estimated using Cox proportional hazards models over a five-year follow-up period.

Results

A total of 1278 patients were included after matching. Varenicline use was associated with lower all-cause mortality (14.4% vs. 17.4%; HR 0.75, 95% CI 0.57–0.99) and a significantly reduced risk of hepatic encephalopathy (3.5% vs. 6.7%; HR 0.47, 95% CI 0.28–0.79). Although overall MALO rates were similar between groups (17.3% vs. 17.6%; HR 0.89, 95% CI 0.66–1.20), subgroup analyses revealed reduced MALO incidence among females and all-cause mortality among individuals aged ≥65 years.

Conclusion

In this real-world cohort study, varenicline use was associated with improved survival and a lower risk of hepatic encephalopathy compared to standard AUD pharmacotherapies in patients with co-occurring ALD and AUD. These findings support further investigation of varenicline as a potential therapeutic option, ideally through randomized controlled trials.

背景：Varenicline是一种α4β2烟碱乙酰胆碱受体的部分激动剂，对戒烟有效，并在治疗酒精使用障碍（AUD）方面显示出前景。然而，其对并发酒精相关性肝病（ALD）患者的影响仍未得到充分研究。我们的目的是评估在这一人群中使用伐尼克兰与长期临床结果之间的关系。方法：我们使用TriNetX联合网络进行了一项回顾性队列研究。同时诊断为ALD和AUD的成年人被纳入研究。使用基于人口统计学、合并症、药物和实验室值的1:1倾向评分匹配，将处方伐尼克兰的患者与接受fda批准的AUD药物治疗（阿坎前列酸或纳曲酮）的患者进行比较。主要终点是主要不良肝脏预后（MALO）；次要结局包括全因死亡率和其他肝脏相关并发症。在5年随访期间，使用Cox比例风险模型估计风险比（hr）。结果：匹配后共纳入1278例患者。伐尼克兰的使用与较低的全因死亡率（14.4% vs. 17.4%; HR 0.75, 95% CI 0.57-0.99）和显著降低肝性脑病的风险（3.5% vs. 6.7%; HR 0.47, 95% CI 0.28-0.79）相关。尽管两组间MALO的总体发生率相似（17.3% vs. 17.6%; HR 0.89, 95% CI 0.66-1.20），但亚组分析显示，年龄≥65岁的女性MALO发病率和全因死亡率均有所降低。结论：在这项现实世界的队列研究中，与标准AUD药物治疗相比，在同时发生ALD和AUD的患者中，使用伐尼克兰与提高生存率和降低肝性脑病风险相关。这些发现支持进一步研究伐尼克兰作为潜在的治疗选择，理想情况下通过随机对照试验。

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引用次数: 0

Prenatal alcohol exposure perturbs the development of radial glial cells in the fetal olfactory bulb 产前酒精暴露干扰胎儿嗅球放射状胶质细胞的发育。

IF 2.7 Q2 SUBSTANCE ABUSE

Alcohol (Hanover, York County, Pa.)

Pub Date : 2025-09-10 DOI: 10.1111/acer.70161

Yuka Imamura Kawasawa, Kazue Hashimoto-Torii, Masaaki Torii, Fumiaki Imamura

Background

Prenatal alcohol exposure (PAE) causes fetal alcohol spectrum disorder (FASD) and is associated with various cognitive and sensory impairments, including olfactory dysfunction. While both genetic and environmental factors contribute to olfactory dysfunction, PAE is considered a significant factor affecting brain development, including the olfactory system. In this study, we investigated the impact of PAE on the developing olfactory bulb (OB), specifically focusing on OB RGCs—radial glial cells that give rise to OB projection neurons.

Methods

Ethanol was administered to pregnant mice at embryonic day (E) 11, a time point when OB RGCs generate the highest number of mitral cells—a major class of OB projection neurons. To investigate the impact of PAE on OB RGCs, BrdU was injected 30 min prior to ethanol administration to label OB RGCs in the S phase of the cell cycle. The location and differentiation of BrdU⁺ cells were subsequently examined in the developing OB at E11, E13, and E15. We also assessed whether inhibition of GABA(A) receptors could mitigate the effects induced by PAE.

Results

PAE was found to impair the progression of migration of OB RGC nuclei to the apical side of the ventricular zone for mitosis, indicating the inhibition of the transition from the S phase to the M phase (G2/M arrest). Therefore, PAE delays neurogenesis of OB RGCs. Importantly, our findings suggest that GABAergic signaling mediated by the mTOR signaling plays a critical role in these PAE-induced effects.

Conclusions

These findings provide insights into the mechanisms by which PAE disrupts OB development by impairing neurogenesis of RGC, contributing to a better understanding of the underlying mechanisms of olfactory dysfunction observed in FASD.

背景：产前酒精暴露（PAE）导致胎儿酒精谱系障碍（FASD），并与各种认知和感觉障碍相关，包括嗅觉功能障碍。虽然遗传和环境因素都会导致嗅觉功能障碍，但PAE被认为是影响大脑发育的重要因素，包括嗅觉系统。在这项研究中，我们研究了PAE对发育中的嗅球（OB）的影响，特别是关注OB rgcs -产生OB投射神经元的放射状胶质细胞。方法：在胚胎日(E) 11， OB RGCs产生最高数量的二尖瓣细胞（OB投射神经元的主要类别）的时间点，给妊娠小鼠注射乙醇。为了研究PAE对OB RGCs的影响，在给乙醇前30分钟注射BrdU以标记细胞周期S期的OB RGCs。BrdU+细胞的位置和分化随后在E11、E13和E15处发育的OB中进行了检测。我们还评估了GABA(A)受体的抑制是否可以减轻PAE诱导的影响。结果：PAE可抑制OB RGC核向心室区顶侧有丝分裂的迁移进程，表明其可抑制S期向M期的过渡（G2/M阻滞）。因此，PAE延缓了OB RGCs的神经发生。重要的是，我们的研究结果表明，由mTOR信号介导的gaba能信号在这些pae诱导的效应中起着关键作用。结论：这些发现为PAE通过损害RGC神经发生破坏OB发展的机制提供了见解，有助于更好地理解FASD中观察到的嗅觉功能障碍的潜在机制。

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引用次数: 0

Exploring the role of gender on treatment outcomes in older adults with alcohol use disorder 探讨性别在老年酒精使用障碍治疗结果中的作用。

IF 2.7 Q2 SUBSTANCE ABUSE

Alcohol (Hanover, York County, Pa.)

Pub Date : 2025-09-10 DOI: 10.1111/acer.70164

Jeppe Sig Juelsgaard Tryggedsson, Kjeld Andersen, Silke Behrendt, Michael P. Bogenschutz, Gerhard Buehringer, Anette Søgaard Nielsen

Background

Alcohol use disorder (AUD) among older adults, particularly with respect to gender differences in treatment outcomes, remains underexplored. Our objective was to explore gender differences in AUD treatment outcomes among older adults, focusing on continuous measures (e.g., drinks per day) and binary measures (e.g., abstinence) across a 1-year period.

Methods

We analyzed data from a multinational randomized controlled trial involving 693 older adults (60+) diagnosed with DSM-5 AUD. Participants received motivational enhancement therapy and the community reinforcement approach, across sites in Denmark, Germany, and the United States. Participants were assessed at baseline and after 4, 12, 26, and 52 weeks. Multilevel mixed-effects linear and logistic regressions were used, adjusted for sociodemographic and baseline drinking characteristics.

Results

Both men and women showed significant improvements across all outcomes. At baseline, females reported 0.75 fewer drinks/day, 1.33 fewer drinks/drinking day, and 50% lower odds of low blood alcohol content (BAC) compared to males (OR = 0.50; p < 0.05). Gender–time interactions showed smaller reductions in females' drinks per day and drinks per drinking day (p < 0.05), resulting in similar drinking levels at follow-ups. No gender differences were found at any time points for percent days abstinent and percent heavy drinking days (p ≥ 0.05). A significant gender–time interaction was found for percent days abstinent (p = 0.04), but no consistent direction was observed across time points. For abstinence and no heavy drinking, no gender differences were found (p ≥ 0.05). No interactions between gender and time were found for any binary outcome (p ≥ 0.05).

Conclusions

Among older adults with DSM-5 AUD diagnosis, treatment led to substantial and sustained improvements across genders. While women showed less favorable drinking reductions, adjusted estimates were broadly comparable. Given women's increased physiological vulnerability to alcohol, this may not imply equivalent clinical risk. Still, findings support the potential for meaningful treatment benefits regardless of gender.

背景：老年人中的酒精使用障碍（AUD），特别是在治疗结果的性别差异方面，仍未得到充分探讨。我们的目的是探讨老年人AUD治疗结果的性别差异，重点关注1年期间的连续测量（例如，每天饮酒）和二元测量（例如，禁欲）。方法：我们分析了来自一项多国随机对照试验的数据，该试验涉及693名诊断为DSM-5 AUD的老年人（60岁以上）。参与者在丹麦、德国和美国接受了动机增强疗法和社区强化方法。参与者分别在基线、4周、12周、26周和52周后进行评估。采用多水平混合效应线性和逻辑回归，并根据社会人口统计学和基线饮酒特征进行调整。结果：男性和女性在所有结果上都有显著的改善。在基线时，与男性相比，女性报告的饮酒量减少0.75 /天，饮酒量减少1.33 /饮酒日，低血液酒精含量（BAC）的几率降低50% （OR = 0.50; p）。结论：在DSM-5 AUD诊断的老年人中，治疗导致了男女之间实质性和持续的改善。虽然女性在减少饮酒方面表现得不那么有利，但调整后的估计值大致相当。鉴于女性对酒精的生理脆弱性增加，这可能并不意味着同样的临床风险。尽管如此，研究结果支持了有意义的治疗效果的潜力，而不考虑性别。

{"title":"Exploring the role of gender on treatment outcomes in older adults with alcohol use disorder","authors":"Jeppe Sig Juelsgaard Tryggedsson, Kjeld Andersen, Silke Behrendt, Michael P. Bogenschutz, Gerhard Buehringer, Anette Søgaard Nielsen","doi":"10.1111/acer.70164","DOIUrl":"10.1111/acer.70164","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alcohol use disorder (AUD) among older adults, particularly with respect to gender differences in treatment outcomes, remains underexplored. Our objective was to explore gender differences in AUD treatment outcomes among older adults, focusing on continuous measures (e.g., drinks per day) and binary measures (e.g., abstinence) across a 1-year period.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed data from a multinational randomized controlled trial involving 693 older adults (60+) diagnosed with DSM-5 AUD. Participants received motivational enhancement therapy and the community reinforcement approach, across sites in Denmark, Germany, and the United States. Participants were assessed at baseline and after 4, 12, 26, and 52 weeks. Multilevel mixed-effects linear and logistic regressions were used, adjusted for sociodemographic and baseline drinking characteristics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Both men and women showed significant improvements across all outcomes. At baseline, females reported 0.75 fewer drinks/day, 1.33 fewer drinks/drinking day, and 50% lower odds of low blood alcohol content (BAC) compared to males (OR = 0.50; <i>p</i> < 0.05). Gender–time interactions showed smaller reductions in females' drinks per day and drinks per drinking day (<i>p</i> < 0.05), resulting in similar drinking levels at follow-ups. No gender differences were found at any time points for percent days abstinent and percent heavy drinking days (<i>p</i> ≥ 0.05). A significant gender–time interaction was found for percent days abstinent (<i>p</i> = 0.04), but no consistent direction was observed across time points. For abstinence and no heavy drinking, no gender differences were found (<i>p</i> ≥ 0.05). No interactions between gender and time were found for any binary outcome (<i>p</i> ≥ 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Among older adults with DSM-5 AUD diagnosis, treatment led to substantial and sustained improvements across genders. While women showed less favorable drinking reductions, adjusted estimates were broadly comparable. Given women's increased physiological vulnerability to alcohol, this may not imply equivalent clinical risk. Still, findings support the potential for meaningful treatment benefits regardless of gender.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"49 11","pages":"2553-2566"},"PeriodicalIF":2.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acer.70164","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034752","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}

引用次数: 0

Targeting G9a decreases escalated alcohol drinking in male mice in a model of combined stress and chronic alcohol exposure 在一个综合压力和慢性酒精暴露的模型中，以G9a为靶点可以减少雄性小鼠逐渐增加的酒精摄入量。

IF 2.7 Q2 SUBSTANCE ABUSE

Alcohol (Hanover, York County, Pa.)

Pub Date : 2025-09-09 DOI: 10.1111/acer.70142

Marcelo F. Lopez, Paulina Misztak, Howard C. Becker, Christopher W. Cowan, Ethan M. Anderson

Background

Alcohol use disorder (AUD) is a pervasive problem in society afflicting millions of people worldwide. One reason for the prevalence of AUD is that heavy alcohol drinking can produce alcohol dependence. In addition, alcohol dependence dysregulates the body's stress systems to increase alcohol drinking. Therefore, targeting dependence- and/or stress-related alcohol drinking clinically could reduce heavy drinking in patients with AUD. One key mechanism thought to contribute to behaviors associated with AUD is long-lasting epigenetic alterations of gene expression. We recently showed that the epigenetic regulatory enzyme G9a (also known as euchromatic histone-lysine N-methyltransferase 2 or EHMT2) is downregulated in the nucleus accumbens (NAc) in mice by alcohol dependence produced by the chronic intermittent alcohol (CIE) model. Also, we showed that either viral-mediated NAc G9a knockdown or a systemically administered G9a inhibitor reduced stress-potentiated alcohol drinking by the kappa-opioid agonist U50,488.

Methods

Here, we tested whether NAc G9a knockdown reduces escalated alcohol drinking in a mouse model of combined dependence plus forced swim stress (CIE + FSS) in male mice. We also tested for changes in sucrose drinking, sucrose preference, and water consumption as controls. In addition, we tested whether systemic administration of a G9a inhibitor, UNC0642, could reduce alcohol drinking in the CIE + FSS model.

Results

We found that either NAc G9a knockdown or repeated systemic UNC0642 administration reduced escalated ethanol drinking following CIE + FSS, but without altering control levels of ethanol drinking or sucrose drinking or water drinking in male mice.

Conclusions

These preclinical data suggest that reducing NAc G9a levels, or suppressing its enzymatic activity, can effectively reduce potentiated alcohol drinking produced by stress and/or alcohol dependence. These data suggest that G9a inhibition holds promise as a potential therapeutic for individuals who suffer from AUD.

背景：酒精使用障碍（AUD）是一个普遍存在的社会问题，困扰着全世界数百万人。AUD流行的一个原因是大量饮酒会产生酒精依赖。此外，酒精依赖会使身体的压力系统失调，从而增加饮酒量。因此，临床上针对依赖和/或压力相关的饮酒可以减少AUD患者的重度饮酒。一个被认为有助于AUD相关行为的关键机制是基因表达的长期表观遗传改变。我们最近发现，慢性间歇酒精（CIE）模型产生的酒精依赖导致小鼠伏隔核（NAc）中的表观遗传调节酶G9a（也称为常染色质组蛋白赖氨酸n -甲基转移酶2或EHMT2）下调。此外，我们还发现，病毒介导的NAc G9a敲低或系统给药的G9a抑制剂都可以通过kappa-阿片激动剂U50,488减少应激增强的饮酒。方法：在此，我们测试了NAc G9a敲除是否会减少雄性小鼠联合依赖加强迫游泳应激（CIE + FSS）小鼠模型中的酒精饮酒升级。我们还测试了蔗糖饮用、蔗糖偏好和水消耗的变化作为对照。此外，我们在CIE + FSS模型中测试了全身给药G9a抑制剂UNC0642是否可以减少饮酒。结果：我们发现NAc G9a敲除或重复全身给药UNC0642均可减少CIE + FSS后雄性小鼠的乙醇饮用量，但不改变乙醇饮用量、蔗糖饮用量或饮水量的对照水平。结论：这些临床前数据表明，降低NAc G9a水平，或抑制其酶活性，可以有效减少因压力和/或酒精依赖而产生的饮酒增强。这些数据表明G9a抑制有望成为AUD患者的潜在治疗方法。

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引用次数: 0

Internalizing symptoms are indirectly associated with simultaneous alcohol and cannabis use through specific motives for simultaneous use: A longitudinal study of young adults 内化症状通过同时使用的特定动机与同时使用酒精和大麻间接相关：一项对年轻人的纵向研究。

IF 2.7 Q2 SUBSTANCE ABUSE

Alcohol (Hanover, York County, Pa.)

Pub Date : 2025-09-09 DOI: 10.1111/acer.70147

Jeffrey D. Wardell, Kyra N. Farrelly, Annabelle Moore, Nicolle Fox, Sophie G. Coelho, John A. Cunningham, Roisin M. O'Connor, Christian S. Hendershot

Background

This study examined motivational pathways between internalizing symptoms (i.e., depression, anxiety, stress) and simultaneous alcohol and cannabis use among young adults.

Methods

Participants (N = 151; 64% female, Mean age = 22.07) completed baseline questionnaires assessing internalizing symptoms and simultaneous use motives, and then reported their alcohol and cannabis use each day for 21 days. Participants repeated these procedures again 6 months and 12 months postbaseline. Daily survey responses were used to calculate the number of simultaneous use days involving heavy drinking (4 or more drinks for females; 5 or more drinks for males) and light drinking at each wave for each participant. The total number of negative consequences reported across all simultaneous use days was also calculated for each participant at each wave.

Results

Multilevel mediation analyses revealed that within-person increases in internalizing symptoms (a latent factor consisting of depression, anxiety, and stress indicators) at a given wave were indirectly associated with (a) a greater number of heavy drinking simultaneous use days (controlling for number of cannabis-only days and heavy drinking alcohol-only days) and (b) greater negative consequences on simultaneous use days (controlling for negative consequences on cannabis-only and alcohol-only days). These within-person associations were mediated by increases in positive (i.e., reward/enhancement) motives for simultaneous use. At the between-person level, greater average internalizing symptoms (aggregated across waves) were indirectly associated with more light drinking simultaneous use days via coping motives, and with fewer heavy drinking simultaneous use days via conformity motives (controlling for frequency of single substance use).

Conclusions

Young adults may combine cannabis with heavy episodic drinking more frequently during periods when they experience elevations in internalizing symptoms, mediated by a desire to achieve the positive/enhancing effects of simultaneous use. Findings may inform alcohol and cannabis harm reduction interventions tailored for young adults with internalizing symptoms.

背景：本研究考察了年轻人内化症状（即抑郁、焦虑、压力）与同时使用酒精和大麻之间的动机途径。方法：参与者（N = 151； 64%女性，平均年龄= 22.07）完成评估内化症状和同时使用动机的基线问卷，然后报告他们在21天内每天使用酒精和大麻的情况。参与者在基线后6个月和12个月再次重复这些程序。每天的调查回答被用来计算每个参与者在每次浪潮中同时重度饮酒（女性4次或以上饮酒；男性5次或以上饮酒）和轻度饮酒的天数。在所有同时使用的天数中报告的负面后果的总数也被计算为每个参与者在每个波。结果:多层次中介分析显示，内化症状(一种潜在因素，包括抑郁、焦虑、在给定波的压力指标)间接与(a)更多的大量饮酒同时使用天数（控制大麻天数和大量饮酒酒精天数）和(b)同时使用天数更大的负面后果（控制大麻天数和酒精天数的负面后果）相关。这些人际关系是由同时使用的积极动机（即奖励/增强）的增加所介导的。在人与人之间的水平上，更大的平均内化症状（跨波汇总）与通过应对动机增加的轻度饮酒同时使用天数间接相关，与通过从众动机（控制单一物质使用频率）减少的重度饮酒同时使用天数间接相关。结论：年轻人可能在经历内化症状升高的时期更频繁地将大麻与严重的间歇性饮酒结合起来，这是由同时使用大麻的积极/增强效果的愿望所介导的。研究结果可能为有内化症状的年轻人量身定制减少酒精和大麻危害的干预措施提供信息。

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引用次数: 0

Brain network signatures of spatial memory in adolescents at risk for substance use 有物质使用危险的青少年空间记忆的脑网络特征。

IF 2.7 Q2 SUBSTANCE ABUSE

Alcohol (Hanover, York County, Pa.)

Pub Date : 2025-09-09 DOI: 10.1111/acer.70155

Jennifer T. Sneider, Julia E. Cohen-Gilbert, Emily N. Oot, Anna M. Seraikas, Eleanor M. Schuttenberg, Andie Stallman, Derek A. Hamilton, Sion K. Harris, Helen Sabolek, Poornima Kumar, Lisa D. Nickerson, Marisa M. Silveri

Background

Examining youth before engagement in risky behaviors may help identify neurobiological signatures that prospectively predict susceptibility to initiating and escalating alcohol and other substance use. Given that frontal and medial temporal (e.g., hippocampal) regions continue developing during adolescence, identifying vulnerabilities in these systems is critical.

Methods

This study evaluated baseline brain activation during spatial memory performance using a virtual functional magnetic resonance imaging (fMRI) Morris water task (MWT). Participants were healthy, substance-naïve adolescents aged 13–14 years (n = 51, 27 females) who underwent brain imaging annually for 3 years and were evaluated quarterly for substance use. For the present report, only baseline imaging data were analyzed. During quarterly follow-ups, 22 participants initiated alcohol or other substance use, while 29 remained substance-naïve. Network activation strength was extracted for the retrieval > motor contrast in the dorsal attention network (DAN), salience network (SN), and medial temporal lobe subnetwork of the default mode network (MTL-DMN).

Results

DAN and SN activation strengths were significantly lower in initiators than in noninitiators. No group differences emerged for MTL-DMN activation. While minimal group or sex differences were observed in task performance, greater MTL-DMN activation was associated with better performance across the full sample, whereas better performance was associated with reduced DAN activation only in noninitiators.

Conclusions

Adolescents who later initiated substance use showed distinct baseline network patterns in systems supporting spatial memory and attention (DAN) and task control and salience detection (SN). In contrast, hippocampal network activation (MTL-DMN) was not evident before initiation but may emerge later as a consequence of use. Because substance use status was categorized for group comparisons, early variability may not be fully captured. These findings underscore the need for future longitudinal analyses to disentangle neurobiological markers of risk that precede adolescent substance use from alterations that arise as a result of use.

背景：在青少年从事危险行为之前进行检查可能有助于识别神经生物学特征，从而前瞻性地预测他们对酒精和其他物质使用的易感性。鉴于额叶和内侧颞叶（如海马）区域在青春期继续发育，确定这些系统的脆弱性至关重要。方法：本研究使用虚拟功能磁共振成像（fMRI）莫里斯水任务（MWT）评估空间记忆表现时的基线脑激活。参与者是健康的substance-naïve年龄在13-14岁的青少年（n = 51,27名女性），他们在3年内每年接受一次脑成像检查，并每季度评估一次药物使用情况。在本报告中，仅分析了基线成像数据。在每季度的随访中，22名参与者开始使用酒精或其他物质，29名仍然使用substance-naïve。提取网络激活强度，在背侧注意网络（DAN）、显著性网络（SN）和默认模式网络（MTL-DMN）的内侧颞叶子网络中检索>运动对比。结果：引发剂中DAN和SN的活化强度明显低于非引发剂。MTL-DMN激活没有组间差异。虽然在任务表现中观察到最小的组或性别差异，但在整个样本中，更大的MTL-DMN激活与更好的表现有关，而更好的表现仅与非启动者的DAN激活减少有关。结论：后来开始使用物质的青少年在支持空间记忆和注意（DAN）以及任务控制和显著性检测（SN）的系统中显示出明显的基线网络模式。相比之下，海马网络激活（MTL-DMN）在开始前并不明显，但可能在使用后出现。由于药物使用状况是分组比较分类的，因此可能无法完全捕获早期变异性。这些发现强调了未来纵向分析的必要性，以便将青少年使用药物之前的风险神经生物学标记与使用药物引起的改变分开。

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引用次数: 0

Latent profile analysis of trait impulsivity facets and associations with resilience, problematic alcohol use, and quality of life 特质冲动性方面的潜在特征分析及其与恢复力、问题酒精使用和生活质量的关联。

IF 2.7 Q2 SUBSTANCE ABUSE

Alcohol (Hanover, York County, Pa.)

Pub Date : 2025-09-09 DOI: 10.1111/acer.70158

Heidi H. Meyer, Matthew F. Thompson, Tommy Gunawan, Melanie L. Schwandt, Vijay A. Ramchandani, Nancy Diazgranados, Jeremy W. Luk

Background

Impulsivity is a multidimensional construct that is associated with problematic alcohol use and alcohol use disorder (AUD). Modeling within-person clustering of impulsivity facets has the potential to aid clinical case conceptualization, and examining associations with resilience and well-being outcomes can inform strength-based intervention approaches. In this study, we utilized latent profile analysis (LPA) to capture the clustering of trait impulsivity facets and tested resilience as a mediational pathway linking impulsivity latent profiles to problematic alcohol use and quality of life domains.

Methods

A total of 401 adults (59.9% male and 71.6% with past-year AUD) who completed self-reported measures of trait impulsivity (Barratt Impulsiveness Scale and UPPS-P Impulsive Behavior Scale), resilience, and alcohol-related outcomes were included in this study. Statistical analyses included LPA, linear regression, and path analysis.

Results

LPA identified three profiles that varied by overall impulsivity as well as specific levels of negative and positive urgency: Profile 1—Low Impulsivity/Urgency (36.4%), Profile 2—Medium Impulsivity (45.6%), and Profile 3—High Impulsivity/Urgency (18.0%). The percentages of past-year AUD were 37.7% in Profile 1, 87.4% in Profile 2, and 100% in Profile 3. Latent profiles with higher impulsivity had lower resilience, higher problematic alcohol use, and lower quality of life. Low resilience was a significant mediator of associations between Medium/High Impulsivity profiles and all clinical outcomes, including problematic alcohol use and four quality of life domains.

Conclusions

In this person-centered analysis, individuals who scored high on negative urgency also had elevated scores on positive urgency and several other impulsivity facets. Within-person clustering of impulsivity facets was associated with differential risk for AUD, and latent profile differences in problematic alcohol use and quality of life outcomes were mediated by low resilience. Findings highlight resilience as a potential treatment target that warrants further evaluation in clinical research.

背景：冲动性是一种多维结构，与酒精使用问题和酒精使用障碍（AUD）有关。冲动性方面的个人内部聚类建模有可能帮助临床病例概念化，并且检查与恢复力和幸福感结果的关联可以为基于力量的干预方法提供信息。在本研究中，我们利用潜在特征分析（LPA）来捕捉特质冲动性方面的聚类，并测试弹性作为将冲动性潜在特征与问题酒精使用和生活质量领域联系起来的中介途径。方法：共有401名成年人（59.9%为男性，71.6%为过去一年的AUD）完成了特质冲动性（Barratt冲动性量表和UPPS-P冲动性行为量表）、恢复力和酒精相关结果的自我报告测量。统计分析包括LPA、线性回归和通径分析。结果：LPA确定了三种不同的总体冲动性以及消极和积极紧迫性的具体水平：1-低冲动性/紧迫性（36.4%），2-中等冲动性（45.6%）和3-高冲动性/紧迫性（18.0%）。过去一年澳元的百分比在剖面1中为37.7%，剖面2中为87.4%，剖面3中为100%。冲动性高的潜在特征具有较低的恢复力，较高的问题酒精使用和较低的生活质量。低弹性是中/高冲动性特征与所有临床结果（包括有问题的酒精使用和四个生活质量领域）之间关联的重要中介。结论：在这个以人为中心的分析中，消极紧迫性得分高的个体在积极紧迫性和其他几个冲动方面的得分也较高。冲动方面的个人聚类与AUD的不同风险相关，而问题酒精使用和生活质量结果的潜在剖面差异是由低弹性介导的。研究结果强调，弹性是一个潜在的治疗目标，值得在临床研究中进一步评估。

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引用次数: 0

Directional associations between antisocial behavior and alcohol use disorder symptoms from adolescence through adulthood: A sibling comparison cross-lagged approach 反社会行为与青春期至成年期酒精使用障碍症状之间的定向关联：兄弟姐妹比较交叉滞后方法

IF 2.7 Q2 SUBSTANCE ABUSE

Alcohol (Hanover, York County, Pa.)

Pub Date : 2025-09-09 DOI: 10.1111/acer.70134

Connor J. McCabe, Jarrod M. Ellingson, Jesse D. Hinckley, Michael Stallings, Christian Hopfer, Soo Hyun Rhee, Robin P. Corley, Daniel E. Gustavson, J. Megan Ross, Tamara L. Wall

Background

A well-established link between antisocial behavior (ASB) and problematic alcohol use in adolescence has been demonstrated, yet the direction of this association across the lifespan remains unclear. Although antisocial conduct may increase exposure to known social and environmental risk factors for developing alcohol use disorder (AUD), alcohol use may also impair social functioning and self-regulation that subsequently increases ASB risk. Using a sibling comparison design in a high-risk sample, this study tested bidirectional associations between symptom counts of ASB and AUD from adolescence through adulthood.

Method

Participants were a sample of 783 probands with adolescent-onset ASB and AUD symptoms at baseline and 556 of their siblings assessed during adolescence (18 years and younger), emerging adulthood (19–26 years), and later adulthood (27 years and older). We applied multilevel cross-lagged panel models to assess lagged associations between ASB and AUD symptoms across three waves. Clustering was specified at the family level, with outcomes centered within families.

Results

Greater within-family ASB in adolescence predicted moderate increases in AUD in emerging adulthood (ß = 0.25, p < 0.001); whereas adolescent AUD did not predict subsequent ASB. Within-family associations between AUD and ASB were not found in the emerging-to-later adult periods.

Conclusions

Accounting for family-level confounding, ASB symptoms in adolescence may be a precursor to AUD in emerging adulthood; whereas AUD and ASB symptoms may follow independent trajectories through adulthood. Findings highlight the importance of considering developmental specificity in the prevention and treatment of copresenting AUD and ASB risk.

背景：反社会行为（ASB）与青春期问题酒精使用之间的联系已得到证实，但这种联系在整个生命周期中的方向仍不清楚。虽然反社会行为可能增加已知的社会和环境风险因素对酒精使用障碍（AUD）的影响，但酒精使用也可能损害社会功能和自我调节，从而增加ASB风险。本研究在高风险样本中采用兄弟姐妹比较设计，测试了从青春期到成年期ASB和AUD症状计数之间的双向关联。方法：参与者是783名在基线时具有青少年发病ASB和AUD症状的先证者，以及556名在青春期（18岁及以下）、成年初显期（19-26岁）和成年后期（27岁及以上）进行评估的兄弟姐妹。我们应用多层次交叉滞后面板模型来评估ASB和AUD症状之间的滞后关联。聚类是在家庭水平上指定的，结果以家庭为中心。结论：考虑到家庭水平的混杂因素，青春期的ASB症状可能是成年期早期AUD的前兆，而AUD和ASB症状可能在成年期遵循独立的发展轨迹。研究结果强调了在预防和治疗同时出现的AUD和ASB风险时考虑发育特异性的重要性。

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引用次数: 0

Diagnosing prenatal alcohol exposure and fetal alcohol syndrome in military-connected children: Insights from US military data claims, 2016–2023 诊断与军队有关的儿童的产前酒精暴露和胎儿酒精综合症：来自美国军事数据声明的见解，2016-2023。

IF 2.7 Q2 SUBSTANCE ABUSE

Alcohol (Hanover, York County, Pa.)

Pub Date : 2025-09-07 DOI: 10.1111/acer.70157

Elizabeth H. Lee, Madison Cirillo, Zoe Solomon, Amanda Banaag, Barbara Fuhrman, Rachel Sayko Adams, Tracey P. Koehlmoos

Background

Fetal alcohol spectrum disorder (FASD) is a lifelong neurodevelopmental condition resulting from prenatal alcohol exposure (PAE) during gestation. Conservative estimates of FASD prevalence in United States children are 1%–5%. Early identification could facilitate early intervention, yet fewer than 1% of children with FASD receive a diagnosis. Although heavy alcohol use has been part of military culture for decades, the epidemiology of FASD is unknown in the Military Health System (MHS), where 1.9 million children receive care.

Methods

Using an open cohort design and military claims data for 2016–2023, we calculated period prevalence, annual and cumulative incidence, and average age at first diagnosis for FASD in military children 0–18 years. FASD diagnosis was defined using available diagnostic codes representing a small subset of the broader FASD spectrum of conditions, that is, newborn affected by PAE and fetal alcohol syndrome (FAS). We conducted chi-squared tests and multivariable logistic regression to identify sociodemographic factors associated with these combined diagnoses.

Results

One thousand four hundred seventy six unique children had any diagnosis between 2016 and 2023 (PAE only: 301; FAS only: 1061; both: 114). Period prevalence was 0.42 cases per 1000 children. Cumulative incidence was 0.34 cases per 1000 children for 2017–2023 using 2016 as a 1-year washout. Average age at any diagnosis was 8.3 years. Factors associated with increased likelihood of diagnosis were male sex; being in guardianship; sponsor of senior officer rank; and sponsor affiliated with the Air Force or Other Service branch. Factors associated with decreased likelihood of diagnosis included Black or Other race; being a stepchild; sponsor of junior enlisted or junior officer rank; and sponsor in the Marine Corps.

Conclusions

Like in the US general population, FASD is underdiagnosed in the MHS. Further study of an expanded set of co-occurring conditions under the FASD umbrella may aid in refining estimates of FASD in the MHS.

背景：胎儿酒精谱系障碍（FASD）是由于孕期酒精暴露（PAE）导致的终身神经发育疾病。保守估计FASD在美国儿童中的患病率为1%-5%。早期识别可以促进早期干预，但只有不到1%的FASD儿童得到诊断。虽然大量饮酒几十年来一直是军队文化的一部分，但在190万儿童接受护理的军事卫生系统（MHS）中，FASD的流行病学尚不清楚。方法：采用开放队列设计和2016-2023年军队索赔数据，计算0-18岁军人儿童FASD的时期患病率、年发病率和累计发病率以及平均首次诊断年龄。FASD诊断是使用现有的诊断代码来定义的，这些诊断代码代表了FASD更广泛的病症谱中的一小部分，即受PAE和胎儿酒精综合征（FAS）影响的新生儿。我们进行了卡方检验和多变量逻辑回归，以确定与这些联合诊断相关的社会人口因素。结果：2016年至2023年间，1476名独特的儿童有任何诊断（仅PAE: 301；仅FAS: 1061；两者：114）。期间患病率为每1000名儿童0.42例。以2016年为1年洗脱期，2017-2023年的累积发病率为每1000名儿童0.34例。诊断时的平均年龄为8.3岁。与诊断可能性增加相关的因素是男性；被监护的；保证人具有高级职级；与空军或其他军种有关联的赞助商。与诊断可能性降低相关的因素包括黑人或其他种族；继子；下级士兵或下级军官军衔的保证人；和海军陆战队的赞助人结论：与美国普通人群一样，MHS中FASD的诊断不足。进一步研究FASD保护伞下的一组扩展的共同发生的条件可能有助于改进MHS中FASD的估计。

{"title":"Diagnosing prenatal alcohol exposure and fetal alcohol syndrome in military-connected children: Insights from US military data claims, 2016–2023","authors":"Elizabeth H. Lee, Madison Cirillo, Zoe Solomon, Amanda Banaag, Barbara Fuhrman, Rachel Sayko Adams, Tracey P. Koehlmoos","doi":"10.1111/acer.70157","DOIUrl":"10.1111/acer.70157","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Fetal alcohol spectrum disorder (FASD) is a lifelong neurodevelopmental condition resulting from prenatal alcohol exposure (PAE) during gestation. Conservative estimates of FASD prevalence in United States children are 1%–5%. Early identification could facilitate early intervention, yet fewer than 1% of children with FASD receive a diagnosis. Although heavy alcohol use has been part of military culture for decades, the epidemiology of FASD is unknown in the Military Health System (MHS), where 1.9 million children receive care.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using an open cohort design and military claims data for 2016–2023, we calculated period prevalence, annual and cumulative incidence, and average age at first diagnosis for FASD in military children 0–18 years. FASD diagnosis was defined using available diagnostic codes representing a small subset of the broader FASD spectrum of conditions, that is, newborn affected by PAE and fetal alcohol syndrome (FAS). We conducted chi-squared tests and multivariable logistic regression to identify sociodemographic factors associated with these combined diagnoses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>One thousand four hundred seventy six unique children had any diagnosis between 2016 and 2023 (PAE only: 301; FAS only: 1061; both: 114). Period prevalence was 0.42 cases per 1000 children. Cumulative incidence was 0.34 cases per 1000 children for 2017–2023 using 2016 as a 1-year washout. Average age at any diagnosis was 8.3 years. Factors associated with increased likelihood of diagnosis were male sex; being in guardianship; sponsor of senior officer rank; and sponsor affiliated with the Air Force or Other Service branch. Factors associated with decreased likelihood of diagnosis included Black or Other race; being a stepchild; sponsor of junior enlisted or junior officer rank; and sponsor in the Marine Corps.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Like in the US general population, FASD is underdiagnosed in the MHS. Further study of an expanded set of co-occurring conditions under the FASD umbrella may aid in refining estimates of FASD in the MHS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72145,"journal":{"name":"Alcohol (Hanover, York County, Pa.)","volume":"49 10","pages":"2213-2224"},"PeriodicalIF":2.7,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016614","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}

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