Alcoholism: Clinical and Experimental Research

Cover image for Vol. 40 Issue 5

Early View (Online Version of Record published before inclusion in an issue)

Edited By: Henry R. Kranzler, M.D.

Impact Factor: 3.205

ISI Journal Citation Reports © Ranking: 2014: 5/18 (Substance Abuse)

Online ISSN: 1530-0277

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  1. 1 - 39
  1. Original Articles

    1. Heavy Alcohol Use Among Suicide Decedents Relative to a Nonsuicide Comparison Group: Gender-Specific Effects of Economic Contraction

      Mark S. Kaplan, Nathalie Huguet, Raul Caetano, Norman Giesbrecht, William C. Kerr and Bentson H. McFarland

      Version of Record online: 17 MAY 2016 | DOI: 10.1111/acer.13100

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      The National Violent Death Reporting System and the Behavioral Risk Factor Surveillance System were analyzed by multiple logistic regression to test whether change in acute intoxication among suicide decedents before (2005 to 2007), during (2008 to 2009), and after (2010 to 2011) the Great Recession mirrored heavy alcohol use patterns in a nonsuicide sample. Results show that male suicide decedents experienced a significantly greater increase (+8%) in heavy alcohol use at the onset of the recession (relative to 2005 to 2007) than did the male nonsuicide group (−2%).

    2. Combined Effects of Acamprosate and Escitalopram on Ethanol Consumption in Mice

      Ada Man-Choi Ho, Yanyan Qiu, Yun-Fang Jia, Felipe S. Aguiar, David J. Hinton, Victor M. Karpyak, Richard M. Weinshilboum and Doo-Sup Choi

      Version of Record online: 17 MAY 2016 | DOI: 10.1111/acer.13099

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      Comorbidity between alcohol use disorder and depression is common and poses treatment challenge. Here, we investigated the effects of combining acamprosate and escitalopram on ethanol drinking in mice displaying depression-like behaviors after chronic unpredictable stress. We observed that combined drug treatment reduced ethanol drinking in both stressed and nonstressed mice. Our findings suggest that combining acamprosate and escitalopram may be more effective than monotherapy for individuals with or without depression to reduce alcohol use.

  2. Critical Reviews

    1. Discovery, Development, and Adoption of Medications to Treat Alcohol Use Disorder: Goals for the Phases of Medications Development

      Raye Z. Litten, Daniel E. Falk, Megan L. Ryan and Joanne B. Fertig

      Version of Record online: 17 MAY 2016 | DOI: 10.1111/acer.13093

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      A successful medications development program for the treatment of alcohol use disorder (AUD) requires clearly established goals for each phase of development to ensure that a candidate compound is not trapped in one particular phase. In this article, the phases of medication development are described as they apply to AUD, and specific goals of each phase are identified for the next decade. We hope this will aid the alcohol research community in planning, testing, and developing medications for AUD.

  3. Original Articles

    1. Therapeutic Benefits of Spleen Tyrosine Kinase Inhibitor Administration on Binge Drinking-Induced Alcoholic Liver Injury, Steatosis, and Inflammation in Mice

      Terence N. Bukong, Arvin Iracheta-Vellve, Benedek Gyongyosi, Aditya Ambade, Donna Catalano, Karen Kodys and Gyongyi Szabo

      Version of Record online: 14 MAY 2016 | DOI: 10.1111/acer.13096

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      Binge drinking-induced liver disease is characterized by significant hepatic spleen tyrosine kinase (SYK) activation (pSYKY525/526). Inhibition of SYK activation significantly ameliorated binge drinking-induced alcoholic liver injury, inflammation, and steatosis in mice. These novel findings highlight SYK as a potential target for therapeutic discoveries for binge drinking-induced liver disease in humans.

    2. Ethanol Stimulates Endoplasmic Reticulum Inositol Triphosphate and Sigma Receptors to Promote Withdrawal-Associated Loss of Neuron-Specific Nuclear Protein/Fox-3

      Anna R. Reynolds, Meredith A. Saunders and Mark A. Prendergast

      Version of Record online: 14 MAY 2016 | DOI: 10.1111/acer.13097

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      These findings suggest that, while exposed to ethanol, endoplasmic reticulum (ER)-bound inositol triphosphate (IP3) and sigma (σ)-1 receptors work cooperatively to promote mobilization of calcium from intracellular stores into the cytosol. This is demonstrated by the ability of xestospongin C and BD 1047, respectively, to reverse ethanol-associated changes promoting withdrawal effects. This calcium mobilization contributes to neuroadaptions to prolonged ethanol exposure that promote a well-characterized glutamatergic receptor-mediated ethanol withdrawal-induced excitotoxic cascade in the hippocampus.

  4. Commentary

  5. Erratum

    1. You have free access to this content
      Erratum

      Version of Record online: 12 MAY 2016 | DOI: 10.1111/acer.13117

      This article corrects:

      A Comparison Among 5 Methods for the Clinical Diagnosis of Fetal Alcohol Spectrum Disorders

      Vol. 40, Issue 5, 1000–1009, Version of Record online: 29 MAR 2016

  6. Original Articles

    1. Modeling Fetal Alcohol Spectrum Disorder: Validating an Ex Vivo Primary Hippocampal Cell Culture System

      Elif Tunc-Ozcan, Adriana B. Ferreira and Eva E. Redei

      Version of Record online: 10 MAY 2016 | DOI: 10.1111/acer.13090

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      Hippocampal primary neuronal cultures were established from gestational day 18 fetuses whose mother consumed ethanol, pair-fed, or normal control diets. There were no differences in developmental stage or morphology due to the prenatal treatments in these cultures. These ex vivo hippocampal neuronal cultures showed gene expression profiles that paralleled those obtained from gestational day 21 fetal hippocampi receiving the same prenatal treatments suggesting the ex vivo model applicable to screen candidate drug targets for FASD.

  7. Critical Reviews

    1. Serotonin's Complex Role in Alcoholism: Implications for Treatment and Future Research

      Catherine A. Marcinkiewcz, Emily G. Lowery-Gionta and Thomas L. Kash

      Version of Record online: 10 MAY 2016 | DOI: 10.1111/acer.13076

  8. Original Articles

    1. Associations Between Gestational Age at Birth and Alcohol Use in the Avon Longitudinal Study of Parents and Children

      Elizabeth K. Do, Shawn J. Latendresse, Alexis C. Edwards, Kenneth S. Kendler, Danielle M. Dick and Timothy P. York

      Version of Record online: 7 MAY 2016 | DOI: 10.1111/acer.13080

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      Earlier gestational age at birth predicts never drinking by age 18. Childhood emotional and behavioral health was found to mediate the association between earlier gestational age and never drinking by age 18. This association was not mediated by parental environment during childhood.

  9. Critical Reviews

    1. Sex and the Lab: An Alcohol-Focused Commentary on the NIH Initiative to Balance Sex in Cell and Animal Studies

      Marina Guizzetti, Daryl L. Davies, Mark Egli, Deborah A. Finn, Patricia Molina, Soundar Regunathan, Donita L. Robinson and Farida Sohrabji

      Version of Record online: 7 MAY 2016 | DOI: 10.1111/acer.13072

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      Flow chart of a potential course of action when designing experiments that use both sexes. This figure emphasizes how the researcher retains the power to decide whether to investigate sex differences. After analyzing the results for sex differences, the investigator has the choice of using one or both sexes for future studies by providing a convincing rationale based on scientific findings, questions, and interests. The NIH SABV guidelines discourage the use of a given sex as the “default” model in research.

    2. Adolescent Social Isolation as a Model of Heightened Vulnerability to Comorbid Alcoholism and Anxiety Disorders

      Tracy R. Butler, Anushree N. Karkhanis, Sara R. Jones and Jeffrey L. Weiner

      Version of Record online: 7 MAY 2016 | DOI: 10.1111/acer.13075

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      Although anxiety disorders and alcoholism frequently co-occur, the neural substrates responsible for this comorbidity are unclear. This review highlights recent evidence that, in male rats, adolescent social isolation engenders numerous behavioral risk factors for both disorders, including long-lasting increases in anxiety measures and ethanol self-administration. Initial neurobiological studies have uncovered adaptive changes in mesolimbic circuits that may contribute to these behaviors. These initial studies support the face, construct, and predictive validity of this model and its potential utility in unraveling the neurobiological substrates underlying the relationship between anxiety disorders and alcohol dependence.

  10. Original Articles

    1. Concomitant Caffeine Increases Binge Consumption of Ethanol in Adolescent and Adult Mice, But Produces Additive Motor Stimulation Only in Adolescent Animals

      Brandon M. Fritz, Caroline Quoilin, Chelsea R. Kasten, Michael Smoker and Stephen L. Boehm II

      Version of Record online: 7 MAY 2016 | DOI: 10.1111/acer.13089

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      Consuming a caffeinated ethanol solution increased binge-like ethanol intake in adolescent and adult male C57BL/6J mice. In addition, caffeinated ethanol consumption produced additive locomotor stimulation greater than caffeine or ethanol consumption alone in adolescent mice. However, this effect was not observed in adult animals. This suggests that adolescents may be uniquely sensitive to caffeinated ethanol consumption in a manner that may be associated with the observed elevated risk for hazardous behavior among individuals choosing to consume such beverages.

    2. The Worsening Profile of Alcoholic Hepatitis in the United States

      Tuyet A. Nguyen, Jonathan P. DeShazo, Leroy R. Thacker, Puneet Puri and Arun J. Sanyal

      Version of Record online: 5 MAY 2016 | DOI: 10.1111/acer.13069

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      Trends for hospitalized alcoholic hepatitis (AH) patients from 2000 to 2011. Increasing admissions. On average 10 years younger compared to general admissions. About 3.5 times higher among 40–49 years age group. Increasing trend among baby boomers. Increasing median MELD score and higher proportion with MELD score >22 (severe AH). Increasing comorbidities and higher CCI scores. Response to prednisone and pentoxifylline treatment is suboptimal. Higher risk of death with increasing complications and old age. About 30% mortality even in moderate AH.

    3. FMRP Mediates Chronic Ethanol-Induced Changes in NMDA, Kv4.2, and KChIP3 Expression in the Hippocampus

      Kathryn B. Spencer, Patrick J. Mulholland and L. Judson Chandler

      Version of Record online: 5 MAY 2016 | DOI: 10.1111/acer.13060

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      This study revealed that chronic ethanol exposure enhances translational control of plasticity-related proteins by fragile-X mental retardation protein (FMRP). Shown is a cartoon depicting chronic ethanol-induced homeostatic bidirectional changes in the expression of NMDA and Kv4.2 channels and the role of KChIP3 and FMRP in this process.

    4. Characterization of the Pharmacokinetics of Phosphatidylethanol 16:0/18:1 and 16:0/18:2 in Human Whole Blood After Alcohol Consumption in a Clinical Laboratory Study

      Martin A. Javors, Nathalie Hill-Kapturczak, John D. Roache, Tara E. Karns-Wright and Donald M. Dougherty

      Version of Record online: 30 APR 2016 | DOI: 10.1111/acer.13062

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      The purpose of this study was to characterize the pharmacokinetics of PEth 16:0/18:1 and 16:0/18:2 in blood of 27 participants in a human laboratory study. Blood samples were collected immediately after consumption of low (0.25 and 0.50 g/kg) doses of ethanol and then every 3 days for 2 weeks during abstinence. Our results indicate that ethanol produced increased PEth levels in all participants and PEth levels correlated with absorption of ethanol. Also, the measurement of these 2 PEth homologues may provide additional information to estimate the time from last, previous drinking.

  11. Critical Reviews

    1. Alcohol Use and Breast Cancer: A Critical Review

      Kevin D. Shield, Isabelle Soerjomataram and Jürgen Rehm

      Version of Record online: 30 APR 2016 | DOI: 10.1111/acer.13071

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      The global burden of breast cancer is large and growing, and, accordingly, there is a need for increased attention to breast cancer prevention. This review found that the biological pathways for alcohol-associated breast carcinogenesis are multifold and that even light alcohol consumption is causally related to breast cancer. Furthermore, this review estimated that alcohol caused 144,000 breast cancer cases and 38,000 breast cancer deaths globally in 2012, with 18.8% of these cases and 17.5% of these deaths affecting light drinkers.

  12. Original Articles

    1. Associations Between Cerebellar Subregional Morphometry and Alcoholism History in Men and Women

      Kayle S. Sawyer, Marlene Oscar-Berman, Susan Mosher Ruiz, Daniel A. Gálvez, Nikos Makris, Gordon J. Harris and Eve M. Valera

      Version of Record online: 30 APR 2016 | DOI: 10.1111/acer.13074

    2. Alcohol Increases Delay and Probability Discounting of Condom-Protected Sex: A Novel Vector for Alcohol-Related HIV Transmission

      Patrick S. Johnson, Mary M. Sweeney, Evan S. Herrmann and Matthew W. Johnson

      Version of Record online: 30 APR 2016 | DOI: 10.1111/acer.13079

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      Alcohol intoxication may cause sexual HIV risk behavior (unprotected sex) via delay and/or probability discounting. This study examined effects of acute alcohol administration on 23 recreational drinkers' discounting of hypothetical delayed or probabilistic sexual or monetary outcomes. Alcohol decreased likelihood of waiting to use a condom (Sexual Delay Discounting Task), decreased likelihood of condom use when STI risk was uncertain (Sexual Probability Discounting Task), but had virtually no effect on monetary discounting, suggesting alcohol has domain-specific effects on decision-making.

  13. Critical Reviews

    1. A Mechanistic Review of Cell Death in Alcohol-Induced Liver Injury

      Shaogui Wang, Pal Pacher, Robert C. De Lisle, Heqing Huang and Wen-Xing Ding

      Version of Record online: 30 APR 2016 | DOI: 10.1111/acer.13078

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      1. Cell death and cell survival are closely associated with alcoholic liver disease.
      2. Ethanol metabolism leads to increased oxidative stress resulting in mitochondrial damage and apoptosis in hepatocytes.
      3. Chronic alcohol consumption increases gut permeability and elevated systemic levels of gut-derived endotoxins resulting in increased production of TNF-α from activated Kupffer cells.
      4. Depending on the cIAP levels and caspase-8 activation in hepatocytes, TNF-α either induces apoptosis or necroptosis by activating Bid-mediated mitochondrial apoptotic pathway or ripoptosome or necrosome.
  14. Original Articles

    1. Assessing the Independent and Joint Effects of Unmedicated Prenatal Depressive Symptoms and Alcohol Consumption in Pregnancy and Infant Neurodevelopmental Outcomes

      Gretchen Bandoli, Claire D. Coles, Julie A. Kable, Wladimir Wertelecki, Irina V. Granovska, Alla O. Pashtepa, Christina D. Chambers and the CIFASD

      Version of Record online: 30 APR 2016 | DOI: 10.1111/acer.13081

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      From a sample of pregnant women in Ukraine recruited based upon periconceptional alcohol use, we found prenatal alcohol exposure (PAE) was independently associated with deficits in neurodevelopmental outcomes at 6 and 12 months; however, level of prenatal depressive symptoms was not. We found marginal evidence of synergism of PAE and depressive symptoms in neurodevelopmental assessments. Healthcare providers should be aware of this possible synergism in their efforts to mitigate the neurodevelopmental effects of these co-occurring exposures.

  15. Critical Reviews

  16. Commentary

  17. Original Articles

    1. Alcohol Intake and Reduced Mortality in Patients with Traumatic Brain Injury

      Jin Seong Cho, Sang Do Shin, Eui Jun Lee, Kyoung Jun Song, Hyun Noh, Yu Jin Kim, Seung Chul Lee, Ju Ok Park, Seong Chun Kim and Seung-sik Hwang

      Version of Record online: 21 APR 2016 | DOI: 10.1111/acer.13065

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      Mortality rate due to traumatic brain injury in the alcohol-intake group appears to be lower compared to that in the no-alcohol-intake group after adjusting for main confounding variables.

    2. A Pilot Study of the Safety and Initial Efficacy of Ivermectin for the Treatment of Alcohol Use Disorder

      Daniel J. O. Roche, Megan M. Yardley, Katy F. Lunny, Stan G. Louie, Daryl L. Davies, Karen Miotto and Lara A. Ray

      Version of Record online: 18 APR 2016 | DOI: 10.1111/acer.13064

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      Ivermectin (30 mg) did not increase the number or severity of adverse effects during alcohol administration. However, ivermectin also did not affect cue-induced craving and subjective response to alcohol. These pilot results suggest that ivermectin is safe in combination with an intoxicating dose of alcohol, but do not indicate that this dose of ivermectin produces anti-alcohol effects in humans. Additional studies testing larger samples and alternate dosing regimens are needed to test the potential efficacy of ivermectin as an alcoholism treatment.

    3. Effects of ADH1B and ALDH2 Genetic Polymorphisms on Alcohol Elimination Rates and Salivary Acetaldehyde Levels in Intoxicated Japanese Alcoholic Men

      Akira Yokoyama, Yoko Kamada, Hiromi Imazeki, Emiko Hayashi, Shigenori Murata, Kenji Kinoshita, Tetsuji Yokoyama and Yoshinori Kitagawa

      Version of Record online: 18 APR 2016 | DOI: 10.1111/acer.13073

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      To study the effects of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) genotypes on the alcohol elimination rate (AER) and salivary acetaldehyde levels, we measured the salivary ethanol and acetaldehyde levels twice at a one-hour interval in 99 intoxicated Japanese alcoholic men. The enhanced AER in ADH1B*2 carriers and the increased salivary acetaldehyde levels in ALDH2*1/*2 carriers among intoxicated alcoholics provide possible mechanisms explaining how each genetic polymorphism affects the risk of alcoholism and upper aerodigestive tract cancer.

    4. Destination Memory in Korsakoff's Syndrome

      Mohamad El Haj, Roy P. C. Kessels, Christian Matton, Jean-Eudes Bacquet, Laurent Urso, Gaëlle Cool, Florence Guidez, Stéphanie Potier, Jean-Louis Nandrino and Pascal Antoine

      Version of Record online: 18 APR 2016 | DOI: 10.1111/acer.13070

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      Destination memory refers to the ability to remember to whom information was previously transmitted. Our study tested destination memory in Korsakoff's syndrome. Participants with Korsakoff's syndrome were instructed to tell proverbs to pictures of celebrities. In a subsequent recognition test, they had to indicate whether they had previously told that proverb to that celebrity or not. Results showed compromise of destination memory in Korsakoff's syndrome. Note. Elvis Presley's image is covered by creative commons copyright.

  18. Commentary

  19. Original Articles

    1. Estimation of Unrecorded Alcohol Consumption in Low-, Middle-, and High-Income Economies for 2010

      Jürgen Rehm, Elisabeth Larsen, Candace Lewis-Laietmark, Paul Gheorghe, Vladimir Poznyak, Dag Rekve and Alexandra Fleischmann

      Version of Record online: 15 APR 2016 | DOI: 10.1111/acer.13067

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      Consumption of unrecorded alcohol is common, but there has been relatively little systematic monitoring. As a newly established part of the WHO global monitoring, a Delphi expert was conducted to assess level and characteristics of unrecorded consumption in 46 member states. One hundred experts responded. Main results included a systematic gradient of the proportion of unrecorded alcohol of total consumption by wealth of a country, with unrecorded alcohol being relatively most important in low-income countries (see Figure).

    2. Osteoprotegerin Levels Decrease in Abstinent Alcohol-Dependent Patients

      Peter Malik, Gabriele von Gleissenthall, Rudolf W. Gasser, Roy Moncayo, Johannes M. Giesinger and Sergei Mechtcheriakov

      Version of Record online: 8 APR 2016 | DOI: 10.1111/acer.13063

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      Our main finding is that OPG levels decreased significantly during 8 weeks of abstinence. RANKL levels were normal at baseline and did also not change during the 8-week observation period. RANKL/OPG ratio, being low overall, did decrease slightly, but not significantly, pointing to an excess of bone formation. OC levels increased over 8 weeks. Our results indicate an increase of bone formation during abstinence and could point to the risk for reduced BMD being reversible with abstinence.

  20. Erratum

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    3. You have free access to this content
      Erratum

      Version of Record online: 4 FEB 2016 | DOI: 10.1111/acer.13016

      This article corrects:
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      Erratum

      Version of Record online: 17 JUN 2015 | DOI: 10.1111/acer.12793

      This article corrects:

      Influence of Alcohol Use and Family History of Alcoholism on Neural Response to Alcohol Cues in College Drinkers

      Vol. 37, Issue Supplement s1, E161–E171, Version of Record online: 18 OCT 2012

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      Erratum

      Version of Record online: 13 MAY 2015 | DOI: 10.1111/acer.12768

      This article corrects:

      Commentary: Doxasozin for Alcoholism

      Vol. 37, Issue 2, 191–193, Version of Record online: 27 DEC 2012

    7. You have free access to this content
      Erratum

      Version of Record online: 17 MAR 2015 | DOI: 10.1111/acer.12723

      This article corrects:

      How Is the Liver Primed or Sensitized for Alcoholic Liver Disease?

      Vol. 25, Issue Supplement s1, 171S–181S, Version of Record online: 11 APR 2006

    8. You have free access to this content
      Erratum

      Version of Record online: 14 FEB 2012 | DOI: 10.1111/j.1530-0277.2012.01778.x

      This article corrects:

      fMRI Differences Between Subjects with Low and High Responses to Alcohol During a Stop Signal Task

      Vol. 36, Issue 1, 130–140, Version of Record online: 17 OCT 2011

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