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Publisher: John Wiley and Sons   (Total: 1597 journals)

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Showing 1 - 200 of 1597 Journals sorted alphabetically
Abacus     Hybrid Journal   (Followers: 13, SJR: 0.48, h-index: 22)
About Campus     Hybrid Journal   (Followers: 5)
Academic Emergency Medicine     Hybrid Journal   (Followers: 67, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 49, SJR: 0.547, h-index: 30)
ACEP NOW     Free   (Followers: 1)
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 55, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 177, SJR: 0.101, h-index: 9)
Acta Geologica Sinica (English Edition)     Hybrid Journal   (Followers: 3, SJR: 0.552, h-index: 41)
Acta Neurologica Scandinavica     Hybrid Journal   (Followers: 5, SJR: 1.203, h-index: 74)
Acta Obstetricia et Gynecologica Scandinavica     Hybrid Journal   (Followers: 14, SJR: 1.197, h-index: 81)
Acta Ophthalmologica     Hybrid Journal   (Followers: 7, SJR: 0.112, h-index: 1)
Acta Paediatrica     Hybrid Journal   (Followers: 56, SJR: 0.794, h-index: 88)
Acta Physiologica     Hybrid Journal   (Followers: 6, SJR: 1.69, h-index: 88)
Acta Polymerica     Hybrid Journal   (Followers: 9)
Acta Psychiatrica Scandinavica     Hybrid Journal   (Followers: 37, SJR: 2.518, h-index: 113)
Acta Zoologica     Hybrid Journal   (Followers: 7, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 5)
Addiction     Hybrid Journal   (Followers: 36, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 15, SJR: 2.091, h-index: 57)
Adultspan J.     Hybrid Journal   (SJR: 0.127, h-index: 4)
Advanced Energy Materials     Hybrid Journal   (Followers: 26, SJR: 6.411, h-index: 86)
Advanced Engineering Materials     Hybrid Journal   (Followers: 28, SJR: 0.81, h-index: 81)
Advanced Functional Materials     Hybrid Journal   (Followers: 51, SJR: 5.21, h-index: 203)
Advanced Healthcare Materials     Hybrid Journal   (Followers: 14, SJR: 0.232, h-index: 7)
Advanced Materials     Hybrid Journal   (Followers: 283, SJR: 9.021, h-index: 345)
Advanced Materials Interfaces     Hybrid Journal   (Followers: 6, SJR: 1.177, h-index: 10)
Advanced Optical Materials     Hybrid Journal   (Followers: 7, SJR: 2.488, h-index: 21)
Advanced Science     Open Access   (Followers: 5)
Advanced Synthesis & Catalysis     Hybrid Journal   (Followers: 18, SJR: 2.729, h-index: 121)
Advances in Polymer Technology     Hybrid Journal   (Followers: 14, SJR: 0.344, h-index: 31)
Africa Confidential     Hybrid Journal   (Followers: 21)
Africa Research Bulletin: Economic, Financial and Technical Series     Hybrid Journal   (Followers: 13)
Africa Research Bulletin: Political, Social and Cultural Series     Hybrid Journal   (Followers: 11)
African Development Review     Hybrid Journal   (Followers: 33, SJR: 0.275, h-index: 17)
African J. of Ecology     Hybrid Journal   (Followers: 16, SJR: 0.477, h-index: 39)
Aggressive Behavior     Hybrid Journal   (Followers: 17, SJR: 1.391, h-index: 66)
Aging Cell     Open Access   (Followers: 11, SJR: 4.374, h-index: 95)
Agribusiness : an Intl. J.     Hybrid Journal   (Followers: 3, SJR: 0.627, h-index: 14)
Agricultural and Forest Entomology     Hybrid Journal   (Followers: 16, SJR: 0.925, h-index: 43)
Agricultural Economics     Hybrid Journal   (Followers: 45, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 32, SJR: 1.122, h-index: 120)
Alcoholism and Drug Abuse Weekly     Hybrid Journal   (Followers: 7)
Alcoholism Clinical and Experimental Research     Hybrid Journal   (Followers: 7, SJR: 1.416, h-index: 125)
Alimentary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 34, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 50, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 152, SJR: 0.951, h-index: 61)
American Business Law J.     Hybrid Journal   (Followers: 24, SJR: 0.205, h-index: 17)
American Ethnologist     Hybrid Journal   (Followers: 93, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 30, SJR: 0.211, h-index: 26)
American J. of Hematology     Hybrid Journal   (Followers: 35, SJR: 1.761, h-index: 77)
American J. of Human Biology     Hybrid Journal   (Followers: 13, SJR: 1.018, h-index: 58)
American J. of Industrial Medicine     Hybrid Journal   (Followers: 16, SJR: 0.993, h-index: 85)
American J. of Medical Genetics Part A     Hybrid Journal   (Followers: 17, SJR: 1.115, h-index: 61)
American J. of Medical Genetics Part B: Neuropsychiatric Genetics     Hybrid Journal   (Followers: 4, SJR: 1.771, h-index: 107)
American J. of Medical Genetics Part C: Seminars in Medical Genetics     Partially Free   (Followers: 6, SJR: 2.315, h-index: 79)
American J. of Physical Anthropology     Hybrid Journal   (Followers: 38, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 300, SJR: 5.101, h-index: 114)
American J. of Primatology     Hybrid Journal   (Followers: 14, SJR: 1.197, h-index: 63)
American J. of Reproductive Immunology     Hybrid Journal   (Followers: 4, SJR: 1.347, h-index: 75)
American J. of Transplantation     Hybrid Journal   (Followers: 19, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 10, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 146, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 10, SJR: 0.397, h-index: 18)
Analytic Philosophy     Hybrid Journal   (Followers: 20)
Anatomia, Histologia, Embryologia: J. of Veterinary Medicine Series C     Hybrid Journal   (Followers: 3, SJR: 0.295, h-index: 27)
Anatomical Sciences Education     Hybrid Journal   (Followers: 1, SJR: 0.633, h-index: 24)
Andrologia     Hybrid Journal   (Followers: 2, SJR: 0.528, h-index: 45)
Andrology     Hybrid Journal   (Followers: 2, SJR: 0.979, h-index: 14)
Angewandte Chemie     Hybrid Journal   (Followers: 175)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 238, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 41, SJR: 1.576, h-index: 62)
Animal Genetics     Hybrid Journal   (Followers: 8, SJR: 0.957, h-index: 67)
Animal Science J.     Hybrid Journal   (Followers: 6, SJR: 0.569, h-index: 24)
Annalen der Physik     Hybrid Journal   (Followers: 5, SJR: 1.46, h-index: 40)
Annals of Anthropological Practice     Partially Free   (Followers: 2, SJR: 0.187, h-index: 5)
Annals of Applied Biology     Hybrid Journal   (Followers: 7, SJR: 0.816, h-index: 56)
Annals of Clinical and Translational Neurology     Open Access   (Followers: 1)
Annals of Gastroenterological Surgery     Open Access  
Annals of Human Genetics     Hybrid Journal   (Followers: 9, SJR: 1.191, h-index: 67)
Annals of Neurology     Hybrid Journal   (Followers: 49, SJR: 5.584, h-index: 241)
Annals of Noninvasive Electrocardiology     Hybrid Journal   (Followers: 1, SJR: 0.531, h-index: 38)
Annals of Public and Cooperative Economics     Hybrid Journal   (Followers: 8, SJR: 0.336, h-index: 23)
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5, SJR: 2.389, h-index: 189)
Annual Bulletin of Historical Literature     Hybrid Journal   (Followers: 12)
Annual Review of Information Science and Technology     Hybrid Journal   (Followers: 14)
Anthropology & Education Quarterly     Hybrid Journal   (Followers: 26, SJR: 0.72, h-index: 31)
Anthropology & Humanism     Hybrid Journal   (Followers: 18, SJR: 0.137, h-index: 3)
Anthropology News     Hybrid Journal   (Followers: 15)
Anthropology of Consciousness     Hybrid Journal   (Followers: 11, SJR: 0.172, h-index: 5)
Anthropology of Work Review     Hybrid Journal   (Followers: 11, SJR: 0.256, h-index: 5)
Anthropology Today     Hybrid Journal   (Followers: 94, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 54, SJR: 2.212, h-index: 69)
Anz J. of Surgery     Hybrid Journal   (Followers: 8, SJR: 0.432, h-index: 59)
Anzeiger für Schädlingskunde     Hybrid Journal   (Followers: 1)
Apmis     Hybrid Journal   (Followers: 1, SJR: 0.855, h-index: 73)
Applied Cognitive Psychology     Hybrid Journal   (Followers: 74, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 170, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 53, SJR: 0.868, h-index: 13)
Applied Stochastic Models in Business and Industry     Hybrid Journal   (Followers: 5, SJR: 0.613, h-index: 24)
Aquaculture Nutrition     Hybrid Journal   (Followers: 12, SJR: 1.025, h-index: 55)
Aquaculture Research     Hybrid Journal   (Followers: 31, SJR: 0.807, h-index: 60)
Aquatic Conservation Marine and Freshwater Ecosystems     Hybrid Journal   (Followers: 36, SJR: 1.047, h-index: 57)
Arabian Archaeology and Epigraphy     Hybrid Journal   (Followers: 12, SJR: 0.453, h-index: 11)
Archaeological Prospection     Hybrid Journal   (Followers: 12, SJR: 0.922, h-index: 21)
Archaeology in Oceania     Hybrid Journal   (Followers: 13, SJR: 0.745, h-index: 18)
Archaeometry     Hybrid Journal   (Followers: 31, SJR: 0.809, h-index: 48)
Archeological Papers of The American Anthropological Association     Hybrid Journal   (Followers: 15, SJR: 0.156, h-index: 2)
Architectural Design     Hybrid Journal   (Followers: 29, SJR: 0.261, h-index: 9)
Archiv der Pharmazie     Hybrid Journal   (Followers: 3, SJR: 0.628, h-index: 43)
Archives of Drug Information     Hybrid Journal   (Followers: 5)
Archives of Insect Biochemistry and Physiology     Hybrid Journal   (SJR: 0.768, h-index: 54)
Area     Hybrid Journal   (Followers: 13, SJR: 0.938, h-index: 57)
Art History     Hybrid Journal   (Followers: 272, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 56, SJR: 1.984, h-index: 20)
Arthritis Care & Research     Hybrid Journal   (Followers: 29, SJR: 2.256, h-index: 114)
Artificial Organs     Hybrid Journal   (Followers: 1, SJR: 0.872, h-index: 60)
ASHE Higher Education Reports     Hybrid Journal   (Followers: 15)
Asia & the Pacific Policy Studies     Open Access   (Followers: 17)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 329, SJR: 0.494, h-index: 19)
Asia Pacific Viewpoint     Hybrid Journal   (Followers: 1, SJR: 0.616, h-index: 26)
Asia-Pacific J. of Chemical Engineering     Hybrid Journal   (Followers: 8, SJR: 0.345, h-index: 20)
Asia-pacific J. of Clinical Oncology     Hybrid Journal   (Followers: 6, SJR: 0.554, h-index: 14)
Asia-Pacific J. of Financial Studies     Hybrid Journal   (SJR: 0.241, h-index: 7)
Asia-Pacific Psychiatry     Hybrid Journal   (Followers: 4, SJR: 0.377, h-index: 7)
Asian Economic J.     Hybrid Journal   (Followers: 8, SJR: 0.234, h-index: 21)
Asian Economic Policy Review     Hybrid Journal   (Followers: 4, SJR: 0.196, h-index: 12)
Asian J. of Control     Hybrid Journal   (SJR: 0.862, h-index: 34)
Asian J. of Endoscopic Surgery     Hybrid Journal   (Followers: 1, SJR: 0.394, h-index: 7)
Asian J. of Organic Chemistry     Hybrid Journal   (Followers: 6, SJR: 1.443, h-index: 19)
Asian J. of Social Psychology     Hybrid Journal   (Followers: 6, SJR: 0.665, h-index: 37)
Asian Politics and Policy     Hybrid Journal   (Followers: 12, SJR: 0.207, h-index: 7)
Asian Social Work and Policy Review     Hybrid Journal   (Followers: 5, SJR: 0.318, h-index: 5)
Asian-pacific Economic Literature     Hybrid Journal   (Followers: 5, SJR: 0.168, h-index: 15)
Assessment Update     Hybrid Journal   (Followers: 4)
Astronomische Nachrichten     Hybrid Journal   (Followers: 3, SJR: 0.701, h-index: 40)
Atmospheric Science Letters     Open Access   (Followers: 29, SJR: 1.332, h-index: 27)
Austral Ecology     Hybrid Journal   (Followers: 15, SJR: 1.095, h-index: 66)
Austral Entomology     Hybrid Journal   (Followers: 9, SJR: 0.524, h-index: 28)
Australasian J. of Dermatology     Hybrid Journal   (Followers: 8, SJR: 0.714, h-index: 40)
Australasian J. On Ageing     Hybrid Journal   (Followers: 6, SJR: 0.39, h-index: 22)
Australian & New Zealand J. of Statistics     Hybrid Journal   (Followers: 14, SJR: 0.275, h-index: 28)
Australian Accounting Review     Hybrid Journal   (Followers: 3, SJR: 0.709, h-index: 14)
Australian and New Zealand J. of Family Therapy (ANZJFT)     Hybrid Journal   (Followers: 3, SJR: 0.382, h-index: 12)
Australian and New Zealand J. of Obstetrics and Gynaecology     Hybrid Journal   (Followers: 46, SJR: 0.814, h-index: 49)
Australian and New Zealand J. of Public Health     Hybrid Journal   (Followers: 13, SJR: 0.82, h-index: 62)
Australian Dental J.     Hybrid Journal   (Followers: 6, SJR: 0.482, h-index: 46)
Australian Economic History Review     Hybrid Journal   (Followers: 6, SJR: 0.171, h-index: 12)
Australian Economic Papers     Hybrid Journal   (Followers: 31, SJR: 0.23, h-index: 9)
Australian Economic Review     Hybrid Journal   (Followers: 6, SJR: 0.357, h-index: 21)
Australian Endodontic J.     Hybrid Journal   (Followers: 3, SJR: 0.513, h-index: 24)
Australian J. of Agricultural and Resource Economics     Hybrid Journal   (Followers: 3, SJR: 0.765, h-index: 36)
Australian J. of Grape and Wine Research     Hybrid Journal   (Followers: 5, SJR: 0.879, h-index: 56)
Australian J. of Politics & History     Hybrid Journal   (Followers: 15, SJR: 0.203, h-index: 14)
Australian J. of Psychology     Hybrid Journal   (Followers: 18, SJR: 0.384, h-index: 30)
Australian J. of Public Administration     Hybrid Journal   (Followers: 441, SJR: 0.418, h-index: 29)
Australian J. of Rural Health     Hybrid Journal   (Followers: 6, SJR: 0.43, h-index: 34)
Australian Occupational Therapy J.     Hybrid Journal   (Followers: 75, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 11, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 23, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 38, SJR: 2.126, h-index: 39)
Autonomic & Autacoid Pharmacology     Hybrid Journal   (SJR: 0.371, h-index: 29)
Banks in Insurance Report     Hybrid Journal   (Followers: 1)
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 11, SJR: 0.539, h-index: 70)
Basic and Applied Pathology     Open Access   (Followers: 2, SJR: 0.113, h-index: 4)
Basin Research     Hybrid Journal   (Followers: 5, SJR: 1.54, h-index: 60)
Bauphysik     Hybrid Journal   (Followers: 2, SJR: 0.194, h-index: 5)
Bauregelliste A, Bauregelliste B Und Liste C     Hybrid Journal  
Bautechnik     Hybrid Journal   (Followers: 1, SJR: 0.321, h-index: 11)
Behavioral Interventions     Hybrid Journal   (Followers: 10, SJR: 0.297, h-index: 23)
Behavioral Sciences & the Law     Hybrid Journal   (Followers: 23, SJR: 0.736, h-index: 57)
Berichte Zur Wissenschaftsgeschichte     Hybrid Journal   (Followers: 10, SJR: 0.11, h-index: 5)
Beton- und Stahlbetonbau     Hybrid Journal   (Followers: 2, SJR: 0.493, h-index: 14)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 6, SJR: 0.311, h-index: 26)
Bioelectromagnetics     Hybrid Journal   (Followers: 1, SJR: 0.568, h-index: 64)
Bioengineering & Translational Medicine     Open Access  
BioEssays     Hybrid Journal   (Followers: 10, SJR: 3.104, h-index: 155)
Bioethics     Hybrid Journal   (Followers: 14, SJR: 0.686, h-index: 39)
Biofuels, Bioproducts and Biorefining     Hybrid Journal   (Followers: 1, SJR: 1.725, h-index: 56)
Biological J. of the Linnean Society     Hybrid Journal   (Followers: 18, SJR: 1.172, h-index: 90)
Biological Reviews     Hybrid Journal   (Followers: 5, SJR: 6.469, h-index: 114)
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 41, SJR: 0.12, h-index: 1)
Biology of the Cell     Full-text available via subscription   (Followers: 9, SJR: 1.812, h-index: 69)
Biomedical Chromatography     Hybrid Journal   (Followers: 7, SJR: 0.572, h-index: 49)
Biometrical J.     Hybrid Journal   (Followers: 5, SJR: 0.784, h-index: 44)
Biometrics     Hybrid Journal   (Followers: 37, SJR: 1.906, h-index: 96)
Biopharmaceutics and Drug Disposition     Hybrid Journal   (Followers: 10, SJR: 0.715, h-index: 44)
Biopolymers     Hybrid Journal   (Followers: 18, SJR: 1.199, h-index: 104)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 44, SJR: 0.415, h-index: 55)
Biotechnology and Bioengineering     Hybrid Journal   (Followers: 160, SJR: 1.633, h-index: 146)
Biotechnology J.     Hybrid Journal   (Followers: 15, SJR: 1.185, h-index: 51)
Biotechnology Progress     Hybrid Journal   (Followers: 39, SJR: 0.736, h-index: 101)
Biotropica     Hybrid Journal   (Followers: 20, SJR: 1.374, h-index: 71)
Bipolar Disorders     Hybrid Journal   (Followers: 9, SJR: 2.592, h-index: 100)
Birth     Hybrid Journal   (Followers: 38, SJR: 0.763, h-index: 64)
Birth Defects Research Part A : Clinical and Molecular Teratology     Hybrid Journal   (Followers: 2, SJR: 0.727, h-index: 77)
Birth Defects Research Part B: Developmental and Reproductive Toxicology     Hybrid Journal   (Followers: 8, SJR: 0.468, h-index: 47)
Birth Defects Research Part C : Embryo Today : Reviews     Hybrid Journal   (SJR: 1.513, h-index: 55)

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Journal Cover Alcoholism Clinical and Experimental Research
  [SJR: 1.416]   [H-I: 125]   [7 followers]  Follow
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
   ISSN (Print) 0145-6008 - ISSN (Online) 1530-0277
   Published by John Wiley and Sons Homepage  [1597 journals]
  • Differences in White Matter Microstructure and Connectivity in
           Nontreatment-Seeking Individuals with Alcohol Use Disorder
    • Authors: Evgeny J. Chumin; Joaquín Goñi, Meredith E. Halcomb, Timothy C. Durazzo, Mario Džemidžić, Karmen K. Yoder
      Abstract: BackgroundDiffusion weighted imaging (DWI) has been widely used to investigate the integrity of white matter (WM; indexed by fractional anisotropy, FA) in alcohol dependence and cigarette smoking. These disorders are highly comorbid, yet cigarette use has often not been adequately controlled in neuroimaging studies of alcohol dependent populations. In addition, information on white matter deficits in currently drinking, nontreatment-seeking (NTS) individuals with alcohol dependence is limited. Therefore, the aim of this work was to investigate WM microstructural integrity in alcohol use disorder by comparing matched samples of cigarette smoking NTS and social drinkers (SD).MethodsThirty-eight smoking NTS and nineteen smoking SD subjects underwent DWI as well as structural magnetic resonance imaging. After an in-house preprocessing of the DWI data, FA images were analyzed with Tract-Based Spatial Statistics (TBSS). FA obtained from the TBSS skeleton was tested for correlation with recent alcohol consumption.ResultsSmoking NTS had lower FA relative to smoking SD, predominantly in the left hemisphere (p
      PubDate: 2018-03-15T08:51:04.542998-05:
      DOI: 10.1111/acer.13629
  • Alcohol and epigenetic regulation: Do the products of alcohol metabolism
           drive epigenetic control of gene expression in alcohol-related
    • Authors: Rajanikanth Vadigepalli; Jan B. Hoek
      Abstract: Epigenetic regulation, the persistent change in the gene regulatory state following a transient environmental perturbation, has become increasingly prominent in accounting for the consequences of exposure to addictive substances, including alcohol (ethanol). The purpose of this Virtual Issue is to draw attention to some of the recent advances in our understanding of how consumption of alcohol impacts the epigenetic landscape and causes such persistent changes in the regulation of gene expression and cellular function that affect behavior or disease susceptibility well after the alcohol challenge has occurred. Articles that recently appeared in ACER are placed in the context of the broader relevant literature and emerging opportunities.This article is protected by copyright. All rights reserved.
      PubDate: 2018-03-13T03:12:21.344426-05:
      DOI: 10.1111/acer.13630
  • Glyoxalase (GLO1) inhibition or genetic overexpression does not alter
           ethanol's locomotor effects: implications for GLO1 as a therapeutic target
           in alcohol use disorders
    • Authors: Amanda M Barkley-Levenson; , Frances A Lagarda, Abraham A Palmer
      Abstract: BackgroundGlyoxalase 1 (GLO1) is an enzyme that metabolizes methylglyoxal (MG), which is a competitive partial agonist at GABAA receptors. Inhibition of GLO1 increases concentrations of MG in the brain and decreases binge-like ethanol drinking. The present study assessed whether inhibition of GLO1, or genetic over expression of Glo1, would also alter the locomotor effects of ethanol, which might explain reduced ethanol consumption following GLO1 inhibition. We used the prototypical GABAA receptor agonist muscimol as a positive control.MethodsMale C57BL/6J mice were pretreated with either the GLO1 inhibitor S-bromobenzylglutathione cyclopentyl diester (pBBG; 7.5 mg/kg; Experiment 1) or muscimol (0.75 mg/kg; Experiment 2), or their corresponding vehicle. We then determined whether locomotor response to a range of ethanol doses (0, 0.5, 1.0, 1.5, 2.0, and 2.5) was altered by either pBBG or muscimol pretreatment. We also examined the locomotor response to a range of ethanol doses in FVB/NJ wild type and transgenic Glo1 over expressing mice (Experiment 3). Anxiety-like behavior (time spent in the center of the open field) was assessed in all three experiments.ResultsThe ethanol dose-response curve was not altered by pretreatment with pBBG or by transgenic overexpression of Glo1. In contrast, muscimol blunted locomotor stimulation at low ethanol doses, and potentiated locomotor sedation at higher ethanol doses. No drug or genotype differences were seen in anxiety-like behavior after ethanol treatment.ConclusionsThe dose of pBBG used in this study is within the effective range shown previously to reduce ethanol drinking. Glo1 overexpression has been previously shown to increase ethanol drinking. However, neither manipulation altered the dose response curve for ethanol's locomotor effects, whereas muscimol appeared to enhance the locomotor sedative effects of ethanol. The present data demonstrate that reduced ethanol drinking caused by GLO1 inhibition is not due to potentiation of ethanol's stimulant or depressant effects.This article is protected by copyright. All rights reserved.
      PubDate: 2018-03-12T21:30:57.044181-05:
      DOI: 10.1111/acer.13623
  • Familial Risk for Alcohol Dependence and Brain Morphology: The Role of
           Cortical Thickness Across the Lifespan
    • Authors: Shirley Y. Hill
      Abstract: Henderson and colleagues have provided new data from a large cohort demonstrating that cortical thickness, as one index of brain morphology, differs between adolescents with and without a family history of alcohol dependence. Understanding the relationship between brain structure and cognitive ability that differ in those with a family history of alcohol use disorders and those without relatives with AUD may provide clues about the biological substrate of addiction. To date, most of the studies concerning brain morphological differences by familial risk have focused on volumetric differences.This article is protected by copyright. All rights reserved.
      PubDate: 2018-03-12T21:25:25.628236-05:
      DOI: 10.1111/acer.13621
  • Association between excessive alcohol consumption and echocardiographic
           parameters according to the presence of flushing reaction in Korean men: A
           community based study
    • Authors: Hyeonyoung Ko; Yun-Mi Song, Sang-Chol Lee, Seung Woo Park, Joohon Sung, Kayoung Lee, Eunae Lee
      Abstract: BackgroundThe objective of this study was to investigate the effect of excessive alcohol consumption on heart reflected by various echocardiographic parameters according to the presence or absence of flushing reaction that might reflect acetaldehyde metabolism.MethodsA total of 854 Korean men without significant cardiovascular diseases who underwent echocardiography and participated in the Korean Healthy Twin Study were used as subjects of this study. These subjects were classified into three categories: non-drinker, moderate drinker (≤ 196 g/week), and heavy drinker (> 196 g/week) within two strata of flushing reaction to alcohol drinking. Association between echocardiographic measurements and categories of the amount of alcohol consumption considering flushing reaction were evaluated using mixed linear regression model.ResultsThe proportion of flushers among drinkers was 39.5% (278 of 703). In stratified analysis by flushing reaction, non-flushers showed significantly higher left ventricular mass index (β: 4.605; 95% CI: 0.966, 8.243) and significantly lower ratio of peak early diastolic velocities (E peak) over peak late diastolic velocities of mitral inflow (β: -0.103; 95% CI: -0.198, -0.008) in heavy drinkers compared to non-drinkers. Flushers showed significantly higher left atrial volume index (β: 2.712; 95% CI: 0.456, 4.968) in heavy drinkers and significantly lower ratio of E peak over the peak early diastolic mitral annular velocities (β: -0.493; 95% CI: -0.902, -0.085) in moderate drinkers compared to non-drinkers. However, the interaction according to flushing reaction was only statistically significant for the association between alcohol consumption and left atrial volume index (p for interaction = 0.004).ConclusionAlcohol consumption is associated with changes in cardiac structure and function. Such association might be influenced by acetaldehyde metabolism.This article is protected by copyright. All rights reserved.
      PubDate: 2018-03-10T00:01:25.292134-05:
      DOI: 10.1111/acer.13622
  • Differences in the Synthesis and Elimination of Phosphatidylethanol
           16:0/18:1 and 16:0/18:2 after Acute Doses of Alcohol
    • Authors: Nathalie Hill-Kapturczak; Donald M. Dougherty, John D. Roache, Tara E. Karns-Wright, Martin A. Javors
      Abstract: BackgroundThe purpose of this study was to examine the synthesis and elimination of phosphatidylethanol (PEth) 16:0/18:1 and 16:0/18:2 following the consumption of alcohol among 56 light and heavy drinkers.MethodsA transdermal alcohol monitor was used to promote alcohol absence 7 days prior, and 14 days after, alcohol consumption in the laboratory. Participants consumed a 0.4 or 0.8 g/kg dose of alcohol in15 min. Blood and breath samples were collected before, at various times up to 360 min post-consumption, and 2, 4, 7, 11 and 14 days after alcohol consumption. Initial rates of PEth synthesis, 360 min area under the PEth pharmacokinetic curves (AUC), and elimination half-lives were determined.Results(1) Non-zero PEth levels were observed before alcohol dosing for most participants, despite 7 days of alcohol use monitoring; (2) 0.4 and 0.8 g/kg doses of alcohol produced proportional increases in PEth levels in all but 1 participant; (3) the initial rate of synthesis of both PEth homologues did not differ between the two doses, but was greater for PEth 16:0/18:2 than PEth 16:0/18:1 at both doses; (4) the mean AUC of both PEth homologues was higher at 0.8 g/kg than at 0.4 g/kg; (5) the mean AUC of 16:0/18:2 was greater than that of PEth 16:0/18:1 at both alcohol doses; (6) the mean half-life of PEth 16:0/18:1 was longer than that of PEth 16:0/18:2 [7.8 ± 3.3 (SD) days and 6.4 ± 5.0 (SD) days, respectively]; and (7) there were no sex differences in PEth 16:0/18:1 or 16:0/18:2 pharmacokinetics.ConclusionsThe results of this study support the use of PEth 16:0/18:1 and 16:0/18:2 as biomarkers for alcohol consumption. Because of consistent pharmacokinetic differences, the levels of these two PEth homologues may provide more information regarding the quantity and recentness of alcohol consumption than either alone.This article is protected by copyright. All rights reserved.
      PubDate: 2018-03-05T11:20:22.804431-05:
      DOI: 10.1111/acer.13620
  • Erratum
    • PubDate: 2018-03-05T02:15:33.796299-05:
      DOI: 10.1111/acer.13617
  • Text Messaging to Reduce Alcohol Relapse in Prelisting Liver Transplant
           Candidates: A Pilot Feasibility Study
    • Authors: Kelly S. DeMartini; Michael L. Schilsky, Amanda Palmer, Dwain C. Fehon, Paula Zimbrean, Stephanie S. O'Malley, Hochang B. Lee, Benjamin A. Toll
      Abstract: BackgroundMany liver transplantation programs require documented alcohol sobriety prior to United Network for Organ Sharing (UNOS) listing. This pilot study examined the feasibility of the first mobile, alcohol relapse prevention intervention for liver transplant patients with alcoholic liver disease (ALD).MethodsThis was a randomized 8-week pilot feasibility trial of a text message-based alcohol intervention. In-treatment assessment was conducted at 4 weeks (4W), and immediate posttreatment assessment was conducted at 8W. Participants were liver transplant candidates (N = 15) diagnosed with ALD who reported at least 1 drinking episode in the past year. Primary feasibility outcomes were percent of messages responded to and posttreatment intervention satisfaction ratings. Preliminary clinical efficacy outcomes were any biologically confirmed alcohol consumption, stress, abstinence self-efficacy, and alcohol craving.ResultsOn feasibility outcomes, participants responded to 81% of messages received and reported high rates of intervention satisfaction, looked forward to receiving the messages, and found it easy to complete the intervention. On preliminary efficacy outcomes, zero participants in the text message (TM) had positive urine alcohol tests at 8W. Two of the 6 participants in standard care (SC) tested positive at 8W. No effects were seen on craving. For stress, a condition × time interaction emerged. TM participants had less stress at 4W and 8W compared with SC at baseline. They maintained their stress level during the intervention. For self-efficacy, a trend for condition effect emerged. TM participants had higher self-efficacy than SC participants.ConclusionsParticipants reported high satisfaction with the intervention, looked forward to the messages, and found it easy to complete. Participants who received the intervention had better treatment outcomes than those who received standard care. They maintained higher levels of self-efficacy and lower stress. Mobile alcohol interventions may hold significant promise to help ALD liver transplant patients maintain sobriety.
      PubDate: 2018-03-02T10:00:02.450528-05:
      DOI: 10.1111/acer.13603
  • Alcohol Use Disorder and PTSD: An Introduction
    • Authors: Sudie E. Back; Jennifer L. Jones
      Abstract: Alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) are two of the most common, chronic and debilitating mental health disorders in our society. Epidemiologic data indicate that lifetime rates of AUD and PTSD in the general population are 29.1% and 7.8%, respectively (Grant et al., 2015; Kessler et al., 1995). These two disorders frequently co-occur and are associated with substantial suffering and functional impairment.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-28T09:10:20.855627-05:
      DOI: 10.1111/acer.13619
  • A Randomized Trial of a Personalized Feedback Intervention for Nonstudent
           Emerging Adult At-Risk Drinkers
    • Authors: Cathy Lau-Barraco; Abby L. Braitman, Amy L. Stamates
      Abstract: BackgroundEmerging adulthood is a period of heightened vulnerability for problematic alcohol use. Considerable research has been devoted to reducing alcohol risks in college student populations, although far less effort has focused on their noncollege-attending peers. Research targeting nonstudent emerging adults is critical as this group is at risk of experiencing alcohol-related harms. Consequently, the main objective of the present randomized study was to examine the preliminary efficacy of a brief personalized feedback intervention (PFI) tailored for nonstudent at-risk drinkers. We also examined the influence of gender on intervention outcomes. Finally, we explored participant acceptability of the intervention.MethodsParticipants were 164 (65.9% men) emerging adults (M age = 21.98, SD = 2.02) recruited from the community. They were randomly assigned to either a 50-minute, in-person PFI or an assessment-only control group and were assessed over 9 months postintervention.ResultsResults showed that for short-term change (1 month), the PFI condition reduced drinking significantly more than controls. For longer-term change (1 to 9 months), both conditions continued to show gradual decline in consumption. The groups did not differ in alcohol-related problems, and the intervention was equally effective for both women and men. Regarding acceptability, participants were extremely satisfied with the intervention, perceived the information to be personally relevant, and thought it provided them a new way of looking at their own drinking.ConclusionsOverall, the present research advanced knowledge regarding an understudied and at-risk group of drinkers. This is among one of the first randomized studies to evaluate a brief intervention tailored to the needs of nonstudent emerging adults based on prior formative research with this group. Our data support PFI as a promising intervention approach for nonstudent drinkers in the community. Ultimately, this line of research aims to reduce alcohol-related health disparities associated with inequities in education.The figure reflects modeled trajectories among nonstudent young adult drinkers for overall consumption (panel A) and alcohol-related problems (panel B) by study condition, comparing a personalized feedback alcohol intervention (PFI) against an assessment-only control group. For short-term change (1-month), the PFI condition reduced drinking more than controls but groups did not differ on drinking beyond 1-month and on alcohol-related problems. The intervention was equally effective for both women and men and was highly rated by participants.
      PubDate: 2018-02-27T10:00:02.260655-05:
      DOI: 10.1111/acer.13606
  • Longitudinal associations between alcohol-related cognitions and use in
           African American and European American adolescent girls
    • Authors: Dawn W. Foster; Feifei Ye, Stephanie S. O'Malley, Tammy Chung, Alison E. Hipwell, Carolyn E. Sartor
      Abstract: BackgroundAfrican American (AA) girls initiate alcohol use later and drink less than European American (EA) girls, potentially reflecting differences in the development of drinking behaviors. The current study examined alcohol-related cognitions: expectancies, attitudes, and intention to drink, as possible sources of variation by race in alcohol use. The aim of the current study was to characterize the nature and degree of association between these cognitions and use over time and by race in EA and AA girls.MethodsData were drawn from the longitudinal Pittsburgh Girls Study (PGS, N=2,450), an urban population-based sample of girls and their caregivers recruited when girls were between ages 5 and 8, and assessed annually through adolescence. Cross-lagged panel models were conducted separately by race (56.2% AA, 43.8% EA) to identify patterns of association between alcohol use and cognitions from ages 12-17 in 2,173 girls.ResultsEndorsement of cognitions and use were higher overall in EA than AA girls but the magnitude of cross-lagged path coefficients did not differ significantly by race. In both groups, bidirectional effects emerged between intentions and use, and alcohol use largely predicted cognitions across ages. However, intention to drink was the only alcohol-related cognition that consistently predicted subsequent use (odds ratios ranged from 1.55-2.71).ConclusionsAlthough rates of alcohol use and endorsement of cognitions were greater in EA than AA girls, the anticipated racial differences in longitudinal associations between cognitions and use did not emerge, indicating that variation in associations between use and cognitions does not account for the lower prevalence of alcohol use in AA compared to EA girls. Furthermore, our finding that intention to drink is a consistent, robust predictor of subsequent alcohol use suggests the need to investigate potentially modifiable factors that influence intention to drink across racial groups.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-27T03:57:05.852895-05:
      DOI: 10.1111/acer.13618
  • Beyond Abstinence: Changes in Indices of Quality of Life with Time in
           Recovery in a Nationally Representative Sample of U.S. Adults
    • Authors: John F. Kelly; M. Claire Greene, Brandon G. Bergman
      Abstract: BackgroundAlcohol and other drug (AOD) treatment and recovery research typically have focused narrowly on changes in alcohol/drug use (e.g., “percent days abstinent”) with little attention on changes in functioning or well-being. Furthermore, little is known about whether and when such changes may occur, and for whom, as people progress in recovery. Greater knowledge would improve understanding of recovery milestones and points of vulnerability and growth.MethodsNational, probability-based, cross-sectional sample of U.S. adults who screened positive to the question, “Did you used to have a problem with alcohol or drugs but no longer do'” (Response = 63.4% from 39,809; final weighted sample n = 2,002). Linear, spline, and quadratic regressions tested relationships between time in recovery and 5 measures of well-being: quality of life, happiness, self-esteem, recovery capital, and psychological distress, over 2 temporal horizons: the first 40 years and the first 5 years, after resolving an AOD problem and tested moderators (sex, race, primary substance) of effects. Locally Weighted Scatterplot Smoothing regression was used to explore turning points.ResultsIn general, in the 40-year horizon there were initially steep increases in indices of well-being (and steep drops in distress), during the first 6 years, followed by shallower increases. In the 5-year horizon, significant drops in self-esteem and happiness were observed initially during the first year followed by increases. Moderator analyses examining primary substance found that compared to alcohol and cannabis, those with opioid or other drugs (e.g., stimulants) had substantially lower recovery capital in the early years; mixed race/native Americans tended to exhibit poorer well-being compared to White people; and women consistently reported lower indices of well-being over time than men.ConclusionsRecovery from AOD problems is associated with dynamic monotonic improvements in indices of well-being with the exception of the first year where self-esteem and happiness initially decrease, before improving. In early recovery, women, certain racial/ethnic groups, and those suffering from opioid and stimulant-related problems appear to face ongoing challenges that suggest a need for greater assistance.
      PubDate: 2018-02-23T10:00:01.272202-05:
      DOI: 10.1111/acer.13604
  • Apremilast Alters Behavioral Responses to Ethanol in Mice: I. Reduced
           Ethanol Consumption and Preference
    • Authors: Yuri A. Blednov; Adriana J. Da Costa, Tamara Tarbox, Olga Ponomareva, Robert O. Messing, R. Adron Harris
      Abstract: BackgroundPhosphodiesterase type 4 (PDE4) inhibitors produce widespread anti-inflammatory effects and reduce ethanol consumption in several rodent models. These drugs are potential treatments for several diseases, including central nervous system disorders, but clinical use is limited by their emetic activity. Apremilast is a selective PDE4 inhibitor with fewer gastrointestinal side effects that is FDA approved for the treatment of psoriasis.MethodsWe measured the acute and chronic effects of apremilast on ethanol consumption in male and female C57BL/6J mice using the continuous and intermittent 24-h two-bottle choice drinking models. We also studied the effects of apremilast on preference for sucrose or saccharin, spontaneous locomotor activity, and blood ethanol clearance. Finally, apremilast levels in plasma, liver, and brain were measured one or two hours after injection.ResultsIn the continuous and intermittent drinking tests, apremilast (15-50 mg/kg, p.o.) dose dependently reduced ethanol intake and preference in male and female mice. Higher doses of apremilast (30-50 mg/kg) also reduced total fluid intake in these mice. Chronic administration of apremilast (20 mg/kg) produced a stable reduction of ethanol consumption in both drinking tests with no effect on total fluid intake. The drinking effects were reversible after drug treatment was replaced with vehicle administration (saline) for 2-4 days. Six daily apremilast injections did not alter preference for saccharin or sucrose in male or female mice. Apremilast (20 mg/kg) transiently decreased spontaneous locomotor activity and did not alter blood ethanol clearance. The highest levels of apremilast were found in liver followed by plasma and brain.ConclusionsApremilast produces stable reductions in voluntary ethanol consumption and is rapidly distributed to plasma and tissues (including the brain), suggesting that it may be an improved PDE4 inhibitor for medication development and repurposing efforts to treat alcohol abuse.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-22T09:00:34.15373-05:0
      DOI: 10.1111/acer.13616
  • Apremilast Alters Behavioral Responses to Ethanol in Mice: II. Increased
           Sedation, Intoxication and Reduced Acute Functional Tolerance
    • Authors: Yuri A. Blednov; Adriana J. Da Costa, R. Adron Harris, Robert O. Messing
      Abstract: BackgroundIn our companion paper, we reported that the phosphodiesterase type 4 inhibitor apremilast reduced ethanol intake and preference in different drinking models in male and female C57BL/6J mice. In the current study, we measured the effects of apremilast on other behaviors that are correlated with ethanol consumption.MethodsThe effects of apremilast (20 mg/kg) on the following behaviors were studied in male and female C57BL/6J mice: locomotor response to a novel situation; ethanol- or LiCl-induced conditioned taste aversion (CTA) to saccharin; conditioned place preference (CPP) and conditioned place avoidance (CPA) to ethanol; severity of handling-induced convulsions after ethanol administration; ethanol-induced anxiolytic-like behavior in the elevated plus maze; duration of ethanol-induced loss of the righting reflex (LORR); recovery from ethanol-induced motor impairment on the rotarod; and acute functional tolerance (AFT) to ethanol.ResultsApremilast did not change the acquisition of ethanol-induced CPP, severity of acute withdrawal from ethanol, or ethanol's anxiolytic-like effect. Apremilast did not alter the extinction of ethanol- or LiCl-induced CTA, but may interfere with acquisition of CTA to ethanol. Apremilast increased the acquisition of CPA to ethanol, reduced locomotor responses to a novel situation, and prolonged the duration of LORR and the recovery from acute motor incoordination induced by ethanol. Longer recovery from the ataxic effect of ethanol may be attributed to the reduced development of AFT to ethanol after apremilast pretreatment.ConclusionsOur results suggest that apremilast increases the duration of ethanol intoxication by reducing AFT. Apremilast also reduces some aspects of general reward and increases ethanol's aversive properties, which might further contribute to its ability to reduce ethanol drinking.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-22T09:00:23.980971-05:
      DOI: 10.1111/acer.13615
  • Genomewide association study of alcohol dependence and related traits in a
           Thai population
    • Authors: Joel Gelernter; Hang Zhou, Yaira Z. Nuñez, Apiwat Mutirangura, Robert T. Malison, Rasmon Kalayasiri
      Abstract: BackgroundAlcohol use (both quantity and dependence) is moderately heritable, and genomewide association studies (GWAS) have identified risk genes in European, African, and Asian populations. The most reproducibly identified risk genes affect alcohol metabolism. Well-known functional variants at the gene encoding alcohol dehydrogenase B (ADH1B) and other alcohol dehydrogenases affect risk in European and African-ancestry populations. Similarly, variants mapped to these same genes and a well-known null variant that maps to the gene that encodes aldehyde dehydrogenase 2 (ALDH2) also affect risk in various Asian populations. In this study we completed the first GWAS for three traits related to alcohol use in a Thai population recruited initially for studies of methamphetamine dependence.MethodsAll subjects were evaluated with the Thai version of the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA). A total of 1045 subjects were available for analysis. Three traits were analyzed: flushing, maximum number of alcoholic beverages consumed in any lifetime 24-hour period (“MAXDRINKS”), and DSM-IV alcohol dependence criterion count. We also conducted a pleiotropy analysis with major depression, the only other psychiatric trait where summary statistics from a large-scale Asian-population GWAS are available.ResultsAll three traits showed genomewide-significant association with variants near ALDH2, with significance ranging from 2.01×10-14 (for flushing; lead SNP PTPN11* rs143894582) to pmeta = 5.80 × 10-10 (for alcohol dependence criterion count; lead SNP rs149212747). These lead SNPs flank rs671 and span a region of over a megabase, illustrating the need for prior biological information in identifying the actual effect SNP, rs671. We also identified significant pleiotropy between major depression and flushing.ConclusionsThese results are consistent with prior findings in Asian populations and add new information regarding alcohol use-depression pleiotropy.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-20T04:00:27.792839-05:
      DOI: 10.1111/acer.13614
  • A Test of Multi-Session Automatic Action Tendency Retraining to Reduce
           Alcohol Consumption among Young Adults in the Context of a Human
           Laboratory Paradigm
    • Authors: Robert F. Leeman; Christine Nogueira, Reinout W. Wiers, Janna Cousijn, Kelly Serafini, Kelly S. DeMartini, John A. Bargh, Stephanie S. O'Malley
      Abstract: BackgroundYoung adult heavy drinking is an important public health concern. Current interventions have efficacy but with only modest effects, thus novel interventions are needed. In prior studies, heavy drinkers, including young adults, have demonstrated stronger automatically triggered approach tendencies to alcohol-related stimuli than lighter drinkers. Automatic action tendency retraining has been developed to correct this tendency and consequently reduce alcohol consumption. The current study is the first to test multiple iterations of automatic action tendency retraining, followed by laboratory alcohol self-administration.MethodsA total of 72 non-treatment-seeking, heavy drinking young adults ages 21-25 were randomized to automatic action tendency retraining or a control condition (i.e., “sham training”). Of these, 69 (54% male) completed 4 iterations of retraining or the control condition over 5 days with an alcohol drinking session on Day 5. Self-administration was conducted according to a human laboratory paradigm designed to model individual differences in impaired control (i.e., difficulty adhering to limits on alcohol consumption).ResultsAutomatic action tendency retraining was not associated with greater reduction in alcohol approach tendency or less alcohol self-administration than the control condition.The laboratory paradigm was probably sufficiently sensitive to detect an effect of an experimental manipulation given the range of self-administration behavior observed, both in terms of number of alcoholic and non-alcoholic drinks and measures of drinking topography.ConclusionsAutomatic action tendency retraining was ineffective among heavy drinking young adults without motivation to change their drinking. Details of the retraining procedure may have contributed to the lack of a significant effect. Despite null primary findings, the impaired control laboratory paradigm is a valid laboratory-based measure of young adult alcohol consumption that provides the opportunity to observe drinking topography and self-administration of non-alcoholic beverages (i.e., protective behavioral strategies directly related to alcohol use).This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-16T01:40:22.719048-05:
      DOI: 10.1111/acer.13613
  • Circadian Mechanisms In Alcohol Use Disorder and Tissue Injury
    • Authors: Booker T Davis; Robin M. Voigt, Maliha Shaikh, Christopher B. Forsyth, Ali Keshavarzian
      Abstract: Heavy use of alcohol can lead to addictive behaviors and to eventual alcohol related tissue damage. While increased consumption of alcohol has been attributed to various factors including level of alcohol exposure and environmental factors such as stress, data from behavioral scientists and physiological researchers is revealing roles for the circadian rhythm in mediating the development of behaviors associated with alcohol use disorder as well as the tissue damage that drives physiological disease. In this work, we compile recent work on the complex mutually influential relationship that exists between the core circadian rhythm and the pharmacodynamics of alcohol. As we do so, we highlight implications of the relationship between alcohol and common circadian mechanisms of effected organs on alcohol consumption, metabolism, toxicity, and pathology.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-16T01:35:22.343079-05:
      DOI: 10.1111/acer.13612
  • Effects of early alcohol exposure on functional organization and
           microstructure of a visual tactile integrative circuit
    • Authors: Shiyu Tang; Su Xu, Rao P. Gullapalli, Alexandre E. Medina
      Abstract: BackgroundChildren with fetal alcohol spectrum disorders (FASD) often have deficits associated with multisensory processing. Because ethanol disrupts activity-dependent neuronal plasticity, a process that is essential for refining connections during cortical development, we hypothesize that early alcohol exposure results in alterations in multisensory cortical networks, which could explain the multisensory processing deficits seen in FASD. Here, we use a gyrencephalic animal model to test the prediction that early alcohol exposure alters the functional connectivity and microstructural features of the rostral posterior parietal cortex (PPr), a visual-tactile integrative area.MethodsFerrets were exposed to moderate doses of ethanol during the brain growth spurt period. Functional connectivity and microstructural features were assessed using resting-state functional MRI and ex vivo diffusion kurtosis imaging (DKI) respectively when the animals reached juvenile age and adulthood respectively.ResultsWhile the whole brain volume was smaller in alcohol-treated animals, the relative size of the frontal brain area was larger when compared to control animals. Altered functional connectivity was observed in alcohol-treated animals, where increased connectivity was observed between PPr and the region that provides its major visual inputs (the caudal portion of the parietal cortex), but not with the region that provides its major somatosensory inputs (tertiary somatosensory cortex). DKI revealed reduced microstructural tissue complexity in all investigated sensory areas of alcohol-treated animals.ConclusionsIn this study, we observed alterations in cortical functional connectivity and microstructural integrity in a cortical area involved in multisensory processing in a ferret FASD model. These findings indicate an alteration in cortical networks that may be related to the multisensory processing deficiencies observed in FASD.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-13T14:40:27.126734-05:
      DOI: 10.1111/acer.13611
  • Comparison of Characteristics of Female Drivers with Single and Multiple
           DUI Convictions
    • Authors: Annah K. Bender; Kathleen K. Bucholz, Andrew C. Heath, Vivia V. McCutcheon
      Abstract: BackgroundWomen are increasingly involved in drunk driving and fatal crashes, yet except for the screening performed in criminal justice settings, little is known about their life context, psychiatric histories, and family backgrounds. This study describes a sample of women with histories of arrest for driving under the influence of alcohol (DUI) who were interviewed outside a criminal justice setting and contrasts women with single versus multiple DUI convictions.MethodsWomen with recent documented histories of DUI participated in a study of women's health behaviors. Thirty-six women with 1 DUI and 62 with 2 or more DUIs participated in a diagnostic telephone interview which assessed demographics, alcohol use and problems, psychiatric problems, treatment, and partner violence.ResultsThe sample overall had high rates of co-occurring psychiatric problems, parental alcohol problems, early sexual and physical abuse, and head injuries. Alcohol use severity and the prevalence of head injuries and partner alcohol problems were significantly higher among women with multiple DUIs than women with a single DUI. Measures reflecting life context, such as marital status, number of children, and childhood trauma, were not associated with number of DUIs.ConclusionsFindings suggest that DUI recidivism in women is accounted for primarily by AUD severity and is not influenced by previous life events such as partner violence, psychiatric problems, and family context such as divorce/separation or number of children. Multiple DUIs in women may mark an alcohol severity threshold beyond which few factors account for additional risk.
      PubDate: 2018-02-13T10:00:01.492991-05:
      DOI: 10.1111/acer.13590
  • Nicotine-Use/Smoking Is Associated with the Efficacy of Naltrexone in the
           Treatment of Alcohol Dependence
    • Authors: Raymond F. Anton; Patricia K. Latham, Konstantin E. Voronin, Patrick K. Randall, Sarah W. Book, Michaela Hoffman, Joseph P. Schacht
      Abstract: BackgroundThe opioid antagonist naltrexone is not efficacious for every alcohol treatment seeker. However, various individual factors, such as genetic differences and nicotine-use/smoking status, have been suggested as predictors of naltrexone response. In a randomized clinical trial, we previously reported that nicotine-use/smoking status might be a stronger predictor of naltrexone efficacy than OPRM1 A118G single nucleotide polymorphism (SNP) genotype. In this report, we further characterize the nicotine-users in that trial, examine other drinking outcomes, examine the influence of smoking change on naltrexone effects on drinking, and validate the result in smokers with disialo carbohydrate-deficient transferrin (%dCDT) change as an independent biomarker of response.MethodsIndividuals (n = 146) meeting DSM-IV criteria for alcohol dependence who were genotyped for the OPRM1 A118G SNP and who did, or did not, use nicotine/cigarettes were randomized, in a balanced fashion, to naltrexone (50 mg/d) or placebo and provided medical management (MM) over a 16-week clinical trial. Alcohol use and smoking during the trial were assessed and analyzed.ResultsNicotine-use/smoking status significantly interacted with medication in reducing percent heavy drinking days (PHDD) during the trial (p = 0.003), such that nicotine-users/smokers showed significantly lower PHDD on naltrexone versus placebo (p = 0.0001, Cohen's d = 0.89), while nonusers showed no significant difference between naltrexone and placebo (p = 0.95, Cohen's d = 0.02). Similar effects were shown for drinks per day and percent days drinking. The superiority of naltrexone over placebo on PHDD reduction in nicotine-users/smokers was confirmed with %dCDT (Cohen's d range 0.3 to 0.9 over the study). Naltrexone did not significantly change cigarette use in smokers, and change in use did not influence naltrexone's effect on PHDD.ConclusionsThese data confirm past findings that naltrexone is more efficacious in those who use nicotine/cigarettes. Compared to previous work on the OPRM1 A118G SNP, it appears that nicotine-use might be a more salient predictor of naltrexone treatment response. While naltrexone did not change cigarette use during the study, and smoking change was not related to alcohol reduction, it should be noted that participants were not seeking smoking cessation and MM did not address this issue.In this clinical trial of Alcohol Dependent (AUD) individuals, those that used nicotine/smoked had much reduced drinking when taking the opioid antagonist naltrexone compared to non-nicotine users. Results were confirmed with the specific marker of heavy drinking, %dCDT. The effect on reduced drinking was independent of any effect of naltrexone on nicotine use/smoking, or the amount of pre-treatment drinking. This data suggests that nicotine might enhance alcohol's neurobiological effects (dopamine reward') and that those effects might predispose to successful naltrexone intervention.
      PubDate: 2018-02-12T10:00:02.526421-05:
      DOI: 10.1111/acer.13601
  • Differences in the temporal typology of alcohol hangover
    • Authors: Joris C. Verster; Marith Schrojenstein Lantman, Marlou Mackus, Aurora J.A.E. van de Loo, Johan Garssen, Andrew Scholey
      Abstract: BackgroundAt a group level, hangover severity during the day has been described to follow an inverted U-shaped curve, with gradually increasing severity scores that, after reaching a peak, gradually decrease towards zero. The aim of the current study was to examine if and how individual drinkers’ hangover severity scores vary during the day.MethodsData from a survey (Penning et al. 2012) in which N=732 drinkers reported on their latest alcohol hangover were re-analysed. The temporal pattern of each individual's hangover was first categorised as belonging to one of six types based on pre-defined temporal characteristics.ResultsThree dominant hangover patterns emerged as comprising more than 95% of the sample: (1) a continuous decline hangover (Severity Type 1 hangover, 54.5%), (2) a steady state hangover (Severity Type 2 hangover, 19.1%), and (3) an inverted U-shaped curve hangover (Severity Type 3 hangover, 21.9%). Of these three patterns, severity Type 2 hangovers are associated with significantly less alcohol consumption, and with having the lowest severity scores of individual hangover symptoms. Severity Type 1 hangovers are associated with having the highest severity of individual hangover symptoms. In line with significantly lower levels of alcohol consumption, Severity Type 2 hangovers were significantly more often observed in women when compared to men. Severity Type 1 hangovers were significantly more common in men than in women. Severity Type 3 hangovers, characterized by the increased presence of gastro-intestinal complaints, was equally commonly experienced in men and women.ConclusionThis study revealed that the temporal pattern of hangover severity can follow marked inter-individual variability. Three common temporal patterns were identified, which are uniquely related to the amount of alcohol consumed and the presence and severity of different individual hangover symptoms. Better understanding of individual differences in hangover typology may help to delineate mechanisms underlying alcohol hangover.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-09T03:00:20.950742-05:
      DOI: 10.1111/acer.13610
  • Acute ethanol inhibition of adult hippocampal neurogenesis involves CB1
           cannabinoid receptor signaling
    • Authors: Dal Khatri; Genevieve Laroche, Marion L. Grant, Victoria M. Jones, Ryan P. Vetreno, Fulton T. Crews, Somnath Mukhopadhyay
      Abstract: BackgroundChronic ethanol exposure has been found to inhibit adult hippocampal neurogenesis in multiple models of alcohol addiction. However, acute ethanol inhibition of adult neurogenesis is not well studied. Although many abused drugs have been found to inhibit adult neurogenesis, few have studied cannabinoids or cannabinoids with ethanol, although human use of both together is becoming more common. We used an acute binge alcohol drinking model in combination with select cannabinoid receptor agonists and antagonists to investigate the actions of each alone and together on hippocampal neurogenesis.MethodsAdult male Wistar rats were treated with an acute binge dose of ethanol (5 g/kg, i.g.), CB1R or CB2R agonists, as well as selective CB antagonists, alone or combined. Hippocampal doublecortin, Ki67 and activated cleaved caspase-3 (CC3) immunohistochemistry were used to assess neurogenesis, neuroprogenitor proliferation and cell death respectively.ResultsWe found that treatment with ethanol or the CB1R agonist, ACEA, and the combination significantly reduced doublecortin positive neurons (DCX+IR) in dentate gyrus and increased CC3. Further, using an inhibitor of endocannabinoid metabolism, e.g. JZL195, we also found reduced DCX+IR neurogenesis. Treatment with 2 different CB1R antagonists (AM251 or SR141716) reversed both CB1R agonist and ethanol inhibition of adult neurogenesis. CB2R agonist HU-308 treatment did not produce any significant change in DCX+IR. Interestingly, neither ethanol nor CB1R agonist produced any alteration in cell proliferation in dentate gyrus as measured by Ki67+ cell population, but cleaved caspase-3 positive cell numbers increased following ethanol or ACEA treatment suggesting an increase in cell death.ConclusionTogether, these findings suggest that acute CB1R cannabinoid receptor activation and binge ethanol treatment reduce neurogenesis through mechanisms involving CB1R.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-08T01:55:36.496005-05:
      DOI: 10.1111/acer.13608
  • Effects of Alcohol on the Brain in Cirrhosis: Beyond Hepatic
    • Authors: Brian C Davis; Jasmohan S Bajaj
      Abstract: Recent advances have led to a greater understanding of how alcohol alters the brain, both in acute stages (intoxication and alcohol withdrawal) and in chronic misuse. This review focuses on the current understanding of how alcohol affects the brain in cirrhosis patients with and without hepatic encephalopathy. Chronic alcohol use is associated with nutritional deficiencies, dementia, cirrhosis, and decompensating events such as hepatic encephalopathy. Direct toxicity on brain tissue, induction of neuro-inflammation, and alcohol's alterations of the gut microbiome are possible mechanisms for the clinical features of hepatic encephalopathy associated with alcohol use. Acute management of the alcoholic cirrhosis patient with altered mental status should focus on ruling out other causes, best intensive care, and use of gut-based therapies such as lactulose and rifaximin. Long term management centers on optimizing treatment of concurrent mood disorders, nutritional support, and medical management of complications associated with cirrhosis. Future studies are needed to clarify mechanisms of brain injury in concomitant alcohol misuse and HE in addition to designing treatment interventions in order to improve outcomes in these patients.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-08T01:50:52.277259-05:
      DOI: 10.1111/acer.13605
  • Drinking Level vs. Drinking Pattern and Cigarette Smoking Among Older
    • Authors: Charles J. Holahan; Penny L. Brennan, Kathleen K. Schutte, Carole K. Holahan, J.Gregory Hixon, Rudolf H. Moos
      Abstract: BackgroundThere is a lack of research on the role of alcohol consumption in cigarette smoking among older adults and the few studies on alcohol use and smoking with older adults have failed to distinguish between average level and pattern of drinking as predictors of smoking. The main purpose of this study was to examine the independent contributions of average level vs. pattern of drinking as predictors of cigarette smoking among older adults. A subsidiary purpose was to examine the link between continued smoking and mortality among older smokers.MethodsWe investigated average level and pattern of drinking as predictors of current smoking among 1151 older adults at baseline and of continued smoking and mortality among the subset of 276 baseline smokers tracked across 20 years. We used multiple linear and logistic regression analyses and, to test mediation, bias-corrected bootstrap confidence intervals.ResultsA high level of average drinking and a pattern of episodic heavy drinking were concurrently associated with smoking at baseline. However, only episodic heavy drinking was prospectively linked to continued smoking among baseline smokers. Continued smoking among baseline smokers increased the odds of 20-year mortality and provided an indirect pathway through which heavy episodic drinking related to mortality.ConclusionsSmokers who misuse alcohol are a challenging population for smoking cessation efforts. Older adults who concurrently misuse alcohol and smoke cigarettes provide a unique target for public health interventions.This article is protected by copyright. All rights reserved.
      PubDate: 2018-02-08T01:45:41.839021-05:
      DOI: 10.1111/acer.13607
  • Heavy Episodic Drinking Trajectories Among Underage Young Adult Women: The
           Role of Feminine Norms
    • Authors: Derek Kenji Iwamoto; William Corbin, Jennifer Brady, Margaux Grivel, Lauren Clinton, Aylin Kaya, Carl Lejuez
      Abstract: BackgroundHeavy episodic drinking (HED; 4 or more drinks in a 2-hour period) in U.S. college women has increased by 40% in the past 30 years. This dramatic shift suggests that women are “closing the gender gap” and are drinking at rates similar to men. Multidimensional feminine norms, or beliefs and expectations about what it means to be a woman, are theoretically promising and gender-relevant factors that may help account for within-group differences in problematic drinking patterns among this increasingly at-risk group. The aim of this study was to identify distinct developmental trajectories of HED among underage young adult women and examine the gender-relevant factors that predict these typologies.MethodsGrowth mixture modeling was used to identify latent trajectory classes of HED over the course of a year (3 time points) in 700 underage (Wave 1, Mage = 18, SD = 0.32) young adult women from a Mid-Atlantic university in the United States. Logistic regression analyses evaluated feminine norm endorsement, sorority status, perceived peer norms, expectancies, alcohol-related consequences, and marijuana use as predictors of the latent trajectory classes.ResultsAbout 64.4% of underage women reported engaging in HED. Three HED latent trajectory classes were identified as follows: (i) High Risk, (31%) reported weekly HED over the course of the year; (ii) Monthly HED (33.4%) reported engaging in HED roughly once a month; and (iii) Abstainers (35.6%) reported no HED over the course of the year. The High-Risk class reported significantly more alcohol-related problems and marijuana use than the other trajectory classes. The multidimensional feminine norms of sexual fidelity and appearance were significantly associated with the latent trajectory classes even when controlling for well-established correlates of drinking.ConclusionsHigh-risk drinking typologies were identified in underage women, and these trajectories were related to feminine norms. Prevention and intervention programs targeting gender-relevant factors may help reduce problematic drinking and marijuana use among underage women engaging in problematic patterns of drinking.
      PubDate: 2018-02-07T10:00:02.150353-05:
      DOI: 10.1111/acer.13582
  • Polygenic Risk Score Prediction of Alcohol Dependence Symptoms Across
           Population-Based and Clinically Ascertained Samples
    • Authors: Jeanne E. Savage; Jessica E. Salvatore, Fazil Aliev, Alexis C. Edwards, Matthew Hickman, Kenneth S. Kendler, John Macleod, Antti Latvala, Anu Loukola, Jaakko Kaprio, Richard J. Rose, Grace Chan, Victor Hesselbrock, Bradley T. Webb, Amy Adkins, Tim B. Bigdeli, Brien P. Riley, Danielle M. Dick
      Abstract: BackgroundDespite consistent evidence of the heritability of alcohol use disorders (AUDs), few specific genes with an etiological role have been identified. It is likely that AUDs are highly polygenic; however, the etiological pathways and genetic variants involved may differ between populations. The aim of this study was thus to evaluate whether aggregate genetic risk for AUDs differed between clinically ascertained and population-based epidemiological samples.MethodsFour independent samples were obtained: 2 from unselected birth cohorts (Avon Longitudinal Study of Parents and Children [ALSPAC], N = 4,304; FinnTwin12 [FT12], N = 1,135) and 2 from families densely affected with AUDs, identified from treatment-seeking patients (Collaborative Study on the Genetics of Alcoholism, N = 2,097; Irish Affected Sib Pair Study of Alcohol Dependence, N = 706). AUD symptoms were assessed with clinical interviews, and participants of European ancestry were genotyped. Genomewide association was conducted separately in each sample, and the resulting association weights were used to create polygenic risk scores in each of the other samples (12 total discovery–validation pairs), and from meta-analyses within sample type. We then tested how well these aggregate genetic scores predicted AUD outcomes within and across sample types.ResultsPolygenic scores derived from 1 population-based sample (ALSPAC) significantly predicted AUD symptoms in another population-based sample (FT12), but not in either clinically ascertained sample. Trend-level associations (uncorrected p 
      PubDate: 2018-02-05T10:00:02.305976-05:
      DOI: 10.1111/acer.13589
  • Spatial Epidemiology of Alcohol- and Drug-Related Health Problems Among
    • Authors: William R. Ponicki; Jeffrey A. Henderson, Andrew Gaidus, Paul J. Gruenewald, Juliet P. Lee, Roland S. Moore, Sharice Davids, Nick Tilsen
      Abstract: BackgroundDespite high abstinence rates, American Indians experience elevated rates of many alcohol and other drug problems. American Indians also predominantly reside in poor and rural areas, which may explain some observed health disparities. We investigated whether geographic areas including reservations or large American Indian populations exhibited greater incidence of alcohol- and drug-related hospitalizations.MethodsWe obtained inpatient hospitalization records for 2 Northern Plain states (Nebraska and South Dakota) for the years 2007 to 2012. We constructed zip code counts for 10 categories of hospitalization with diagnoses or injury causation commonly associated with alcohol or drug use. We related these to community sociodemographic characteristics using Bayesian Poisson space–time regression models and examined associations with and without controls for whether each zip code was located within an American Indian reservation.ResultsControlling for other demographic and economic characteristics, zip codes with greater percentage of American Indians exhibited greater incidence for all 10 substance abuse-related health outcomes (9 of 10 well supported); zip code areas within American Indian reservations had greater incidence of self-inflicted injury and drug dependence and abuse, and reduced incidence of alcohol cirrhosis and prescription opioid poisoning. However, the analyses generally demonstrated no well-supported differences in incidence associated with local residence percentages of American Indian versus African American.ConclusionsIn our analyses, ethnicity or heredity alone did not account for alcohol- and drug-related hospitalizations among Native populations. Aspects of social, economic, and political dimensions of Native lives must be considered in the etiology of alcohol- and drug-related problems for rural-dwelling indigenous peoples.American Indian (AI) reservation areas in South Dakota and Nebraska experienced elevated hospitalization rates for many health problems previously linked to substance abuse. Holding other area characteristics constant, zip codes with average percent AI among reservations (67.7%) were predicted to have uniformly higher substance-related hospitalization rates than they would with average non-reservation percent AI (1.5%). This difference was well-supported for 9 of 10 outcomes (as indicated by 95% credible intervals). A complex set of factors help to explain these differences.
      PubDate: 2018-01-30T10:00:02.941375-05:
      DOI: 10.1111/acer.13580
  • Mechanisms Underlying Chronic Binge Alcohol Exposure-Induced Uterine
           Artery Dysfunction in Pregnant Rat
    • Authors: Vishal D. Naik; Katie Davis-Anderson, Kaviarasan Subramanian, Raine Lunde-Young, Matthew J. Nemec, Jayanth Ramadoss
      Abstract: BackgroundA cardinal feature of fetal alcohol syndrome is growth restriction. Maternal uterine artery adaptations to pregnancy correlate with birth weight and survival. We hypothesized that gestational binge alcohol exposure impairs maternal uterine vascular function, affecting endothelial nitric oxide-mediated vasodilation.MethodsPregnant rats grouped as pair-fed control or binge alcohol exposed received a once-daily, orogastric gavage of isocaloric maltose dextrin or alcohol, respectively. On gestational day 20, primary uterine arteries were isolated, cannulated, connected to a pressure transducer, and functional studies were conducted by dual-chamber arteriography. Uterine arteries maintained at constant intramural pressure (90 mm Hg) were maximally constricted with thromboxane, and a dose response for acetylcholine was recorded.ResultsThe alcohol group exhibited significantly impaired endothelium- dependent, acetylcholine-induced uterine artery relaxation (~30%). Subsequently, a dose response was recorded following inhibition of endothelium-derived hyperpolarizing factor (apamin and TRAM-34) and prostacyclin (indomethacin). Acetylcholine-induced relaxation in the pair-fed control decreased by ~46%, and interestingly, relaxation in alcohol group further decreased by an additional ~48%, demonstrating that gestational binge alcohol impairs the nitric oxide system in the primary uterine artery. An endothelium-independent SNP effect was not observed. Immunoblotting indicated that alcohol decreased the level of endothelial excitatory P-Ser1177eNOS (P < 0.05) and total eNOS expression (P < 0.05) compared to both the normal and pair-fed controls. P-Ser1177eNOS level was also confirmed by immunofluorescence imaging.ConclusionThis is the first study to demonstrate maternal binge alcohol consumption during pregnancy disrupts uterine artery vascular function via impairment of the eNOS vasodilatory system.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-24T08:10:29.125406-05:
      DOI: 10.1111/acer.13602
  • Donepezil reverses dendritic spine morphology adaptations and Fmr1
           epigenetic modifications in hippocampus of adult rats after adolescent
           alcohol exposure
    • Authors: Patrick J. Mulholland; Tara L. Teppen, Kelsey M. Miller, Hannah G. Sexton, Subhash C. Pandey, H. Scott Swartzwelder
      Abstract: BackgroundAdolescent intermittent ethanol (AIE) exposure produces persistent impairments in cholinergic and epigenetic signaling and alters markers of synapses in the hippocampal formation, effects that are thought to drive hippocampal dysfunction in adult rodents. Donepezil (Aricept), a cholinesterase inhibitor, is used clinically to ameliorate memory-related cognitive deficits. Given that donepezil also prevents morphological impairment in preclinical models of neuropsychiatric disorders, we investigated the ability of donepezil to reverse morphological and epigenetic adaptations in the hippocampus of adult rats exposed to AIE. Because of the known relationship between dendritic spine density and morphology with the fragile X mental retardation 1 (Fmr1) gene, we also assessed Fmr1 expression and its epigenetic regulation in hippocampus after AIE and donepezil pre-treatment.MethodsAdolescent rats were administered intermittent ethanol for 16 days starting on postnatal day 30. Rats were treated with donepezil (2.5mg/kg) once a day for four days starting 20 days after the completion of AIE exposure. Brains were dissected out after the 4th donepezil dose and spine analysis was completed in dentate gyrus granule neurons. A separate cohort of rats, treated identically, was used for molecular studies.ResultsAIE exposure significantly reduced dendritic spine density and altered morphological characteristics of subclasses of dendritic spines. AIE exposure also increased mRNA levels and H3-K27 acetylation occupancy of the Fmr1 gene in hippocampus. Treatment of AIE-exposed adult rats with donepezil reversed both the dendritic spine adaptations and epigenetic modifications and expression of Fmr1.ConclusionsThese findings indicate that AIE produces long-lasting decreases in dendritic spine density and changes in Fmr1 gene expression in the hippocampal formation, suggesting morphological and epigenetic mechanisms underlying previously reported behavioral deficits after AIE. The reversal of these effects by sub-chronic, post-AIE donepezil treatment indicates that these AIE effects can be reversed by upregulating cholinergic function.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-16T05:15:25.975053-05:
      DOI: 10.1111/acer.13599
  • Neonatal Ethanol Exposure Causes Behavioral Deficits in Young Mice
    • Authors: Wenhua Xu; Andrew B. Hawkey, Hui Li, Lu Dai, Howard H. Brim, Jacqueline A. Frank, Jia Luo, Susan Barron, Gang Chen
      Abstract: BackgroundFetal ethanol (ETOH) exposure can damage the developing central nervous system and lead to cognitive and behavioral deficits, known as fetal alcohol spectrum disorders (FASD). ETOH exposure to mouse pups during early neonatal development was used as a model of ETOH exposure that overlaps the human third trimester “brain growth spurt” - a model that has been widely used to study FASD in rats.MethodsC57BL/6 male and female mice were exposed to ETOH (4 g/kg/day) on postnatal days (PD) 4-10 by oral intubation. Intubated and non-treated controls were also included. Behavioral testing of the offspring, including open field, elevated plus maze and Morris water maze, was performed on PD 20 – 45.ResultsETOH exposure during PD 4-10 resulted in hyperactivity and deficits in learning and memory in young mice with no apparent sex differences.ConclusionBased on these data, this neonatal intubation mouse model may be useful for future mechanistic and genetic studies of FASD and for screening of novel therapeutic agents.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-16T05:10:19.088102-05:
      DOI: 10.1111/acer.13598
  • Loss of Ethanol inhibition of NMDAR-mediated currents and plasticity of
           cerebellar synapses in mice expressing the GluN1(F639A) subunit
    • Authors: Paula A. Zamudio-Bulcock; Gregg E. Homanics, John J. Woodward
      Abstract: BackgroundGlutamatergic N-methyl-D-aspartate receptors (NMDARs) are well known for their sensitivity to ethanol inhibition. However, the specific manner in which ethanol inhibits channel activity and how such inhibition affects neurotransmission, and ultimately behavior, remain unclear. Replacement of phenylalanine 639 with alanine (F639A) in the GluN1 subunit reduces ethanol inhibition of recombinant NMDA receptors. Mice expressing this subunit show reduced ethanol-induced anxiolysis, blunted locomotor stimulation following low dose ethanol administration and faster recovery of motor function after moderate doses of ethanol suggesting that cerebellar dysfunction may contribute to some of these behaviors. In the mature mouse cerebellum, NMDARs at the cerebellar climbing fiber (CF) to Purkinje cell (PC) synapse are inhibited by low concentrations of ethanol and the long term depression (LTD) of parallel fiber (PF) mediated currents induced by concurrent activation of PFs and CFs (PF-LTD) requires activation of ethanol-sensitive NMDA receptors. In this study, we examined cerebellar NMDA responses and NMDA-mediated synaptic plasticity in wild-type and GluN1(F639A) mice.MethodsPatch clamp electrophysiological recordings were performed in acute cerebellar slices from adult wild type and GluN1(F639A) mice. NMDA receptor-mediated currents at the CF-PC synapse and NMDAR-dependent PF-LTD induction were compared for genotype-dependent differences.ResultsStimulation of climbing fibers evoked robust NMDA-mediated EPSCs in PCs that were similar in amplitude and kinetics between wild-type and GluN1(F639A) mice. NMDA-mediated CF-PC excitatory postsynaptic currents (EPSCs) in wild-type mice were significantly inhibited by ethanol (50 mM) while those in mutant mice were unaffected. Concurrent stimulation of CF and PF inputs induced synaptic depression of PF-PC EPSCs in both wild-type and mutant mice and this depression was blocked by the NMDA antagonist DL-APV. The synaptic depression of PF-PC EPSCs in wild-type mice was also blocked by a low concentration of ethanol (10 mM) that had no effect on plasticity in GluN1(F639A) mice.ConclusionsThese results demonstrate that inhibition of cerebellar NMDARs may be a key mechanism by which ethanol affects cerebellar-dependent behaviors.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-11T08:15:23.097573-05:
      DOI: 10.1111/acer.13597
  • Association between paternal alcohol consumption before conception and
           anogenital distance of offspring
    • Authors: Ruilan Xia; Longmei Jin, Dekun Li, Hong Liang, Fen Yang, Jianping Chen, Wei Yuan, Maohua Miao
      Abstract: BackgroundThere are limited studies on the effects of paternal alcohol consumption, before conception, on the reproductive development of offspring. Anogenital distance (AGD), the distance from the center of the anus to the genitals, is a sensitive biomarker of reproductive hormone abnormalities during the critical developmental window. The relationship between paternal alcohol consumption and AGD of human offspring has not been studied yet.MethodsThis cohort study included 1,292 pregnant women recruited in Shanghai. An in-person interview was conducted to collect information on demographic characteristics of couples, and husbands’ lifestyles, including drinking habits. AGD (boys, AGD-AP [anus-penis], AGD-AS [anus-scrotum]; girls, AGD-AC [anus- clitoris], AGD-AF [anus-fourchette]) measurements were performed at birth, and at 6 and 12 months of age. Multiple linear regression analysis was conducted to determine the association between paternal alcohol consumption before conception, and the AGDs of offspring.ResultsData included AGD measurements of infants at birth (N=980), at 6 months (N=592, 60.4%), and at 12 months (N=543, 55.4%). Boys in the paternal alcohol-exposed group had shorter AGDs, irrespective of the areas measured (AGD-AP and AGD-AS) and time of measurements, than those in the unexposed group. However, only the differences in AGD-AP at birth and AGD-AS at 6 months were statistically significant. For girls, the associations were similar at birth; however, the AGD-AC and AGD-AF were longer in the paternal alcohol-exposed group than the unexposed group at 12 months.ConclusionsOur findings provide first, but preliminary evidence that paternal alcohol consumption within 3 months before conception may be associated with shorter AGD in the offspring, especially in boys, which indicates that paternal alcohol drinking may have an adverse effect on their reproductive development. Further studies should be conducted to validate these results.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-06T12:25:36.758056-05:
      DOI: 10.1111/acer.13595
  • MicroRNA-21: Bridging Binge Drinking and Cardiovascular Health
    • Authors: Yingmei Zhang; Jun Ren
      Abstract: Binge drinking is commonly associated with high risk of cardiovascular diseases although the underlying mechanism remains elusive. Advances in genomics and genetics have indicated a number of alcohol-responsive genes in alcohol drinking behavior and alcoholic organ injury. Recent findings revealed a dramatic rise in mircoRNA-10a (miR-10a) and miR-21 levels with binge drinking (Beech et al., 2014). Given the increased knowledge in the past decade on the role of non-coding RNAs in the regulation of cardiovascular function, the identification of novel microRNA and underlying cellular mechanisms in alcoholism and alcoholic organ complication suggests therapeutic promises for the interventions against alcoholic complications.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-06T12:25:34.898585-05:
      DOI: 10.1111/acer.13596
  • Commentary on White and Colleagues: Trends in Alcohol-Related Emergency
           Department Visits in the United States: Results from the Nationwide
           Emergency Department Sample, 2006-2014 (ACER, 2018)
    • Authors: Megan E. Patrick; Yvonne M. Terry-McElrath
      Abstract: Epidemiological research has documented a puzzling disconnect between recent alcohol-related trends in the United States. Studies comparing year-to-year prevalence of alcohol use and binge drinking have shown that drinking has been decreasing among adolescents and young adults (Center for Behavioral Health Statistics and Quality, 2015; Miech et al., 2017; Schulenberg et al., 2017).This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-04T20:45:29.807317-05:
      DOI: 10.1111/acer.13593
  • Alcohol and Opioid Use, Co-Use, and Chronic Pain in the Context of the
           Opioid Epidemic: A Critical Review
    • Authors: Katie Witkiewitz; Kevin E. Vowles
      Abstract: The dramatic increase in opioid misuse, opioid use disorder (OUD), and opioid-related overdose deaths in the United States has led to public outcry, policy statements, and funding initiatives. Meanwhile, alcohol misuse and alcohol use disorder is a highly prevalent public health problem associated with considerable individual and societal costs. This paper provides a critical review of alcohol and opioid misuse, including issues of prevalence, morbidity, and societal costs. We also review research on interactions between alcohol and opioid use, the influence of opioids and alcohol on alcohol use disorder (AUD) and OUD treatment outcomes, respectively, the role of pain in the co-use of alcohol and opioids, and treatment of comorbid OUD and AUD. Heavy drinking, opioid misuse, and chronic pain individually represent significant public health problems. Few studies have examined co-use of alcohol and opioids, but available data suggest that co-use is common and likely contributes to opioid overdose-related morbidity and mortality. Co-use of opioids and alcohol is related to worse outcomes in treatment for either substance. Finally, chronic pain frequently co-occurs with use (and co-use) of alcohol and opioids. Opioid use and alcohol use are also likely to complicate the treatment of chronic pain. Research on the interactions between alcohol and opioids, as well as treatment of the comorbid disorders is lacking. Currently most alcohol research excludes patients with OUD and there is lack of measurement in both AUD and OUD research in relation to pain-related functioning. Research in those with chronic pain often assesses opioid use, but rarely assesses alcohol use or AUD. New research to examine the nexus of alcohol, opioids, and pain, as well as their treatment is critically needed.This article is protected by copyright. All rights reserved.
      PubDate: 2018-01-04T09:40:26.173-05:00
      DOI: 10.1111/acer.13594
  • Issue Information
    • Pages: 473 - 476
      PubDate: 2018-03-01T03:07:13.53696-05:0
      DOI: 10.1111/acer.13455
  • Articles of Public Interest
    • Pages: 477 - 477
      PubDate: 2018-03-01T03:07:07.180008-05:
      DOI: 10.1111/acer.13609
  • Investigating the relationships between alcohol consumption, cannabis use
           and circulating cytokines: a preliminary analysis
    • Authors: Hollis C. Karoly; L. Cinnamon Bidwell, Raeghan Mueller, Kent Hutchison
      Abstract: BackgroundIn recent years, human and animal studies have converged to support altered inflammatory signaling as one molecular mechanism underlying the pathophysiology of alcohol use disorders (AUDs). Alcohol binds to receptors on immune cells, triggering signaling pathways that produce pro-inflammatory cytokines. Chronic inflammation is associated with tissue damage, which may contribute to negative effects of AUD. Conversely, cannabis is associated with decreased inflammatory signaling, and animal studies suggest that cannabinoids may impact alcohol-induced inflammation. Thus, the impact of cannabis on inflammation in AUDs in humans warrants examination.MethodsWe explored the relationship between self-reported alcohol and cannabis use and circulating levels of the pro-inflammatory cytokines IL-6, IL-8 and IL-1β in the blood. Among N=66 regular drinkers (mean age=30.08), we examined circulating cytokines and administered questionnaires assessing alcohol consumption and days of cannabis use over the past 90 days. We examined whether alcohol consumption, cannabis use and gender were associated with changes in circulating cytokines, and whether there was a significant interaction between alcohol and cannabis use predicting blood levels of circulating cytokines.ResultsA positive association between alcohol and IL-6 emerged. We also observed a negative association between cannabis and IL-1β. Follow-up moderation analyses indicated a cannabis by alcohol interaction predicting circulating IL-6, such that cannabis non-users showed a stronger relationship between alcohol and IL-6 compared to cannabis users.ConclusionsThese preliminary findings suggest that cannabinoid compounds may serve to mitigate inflammation associated with alcohol use. In addition, the present results provide data to inform future investigations, with the goal of ultimately leveraging knowledge of the role of inflammation in AUDs to develop more effective treatments focused on novel immune targets.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-29T10:00:23.801758-05:
      DOI: 10.1111/acer.13592
  • Effects of initiating abstinence from alcohol on daily craving and
           negative affect: Results from a pharmacotherapy clinical trial
    • Authors: Kevin A. Hallgren; Brianna C. Delker, Tracy L. Simpson
      Abstract: BackgroundCraving and negative affect are distressing and commonly experienced during alcohol use disorder (AUD) treatment. Patients may assume that initiating abstinence will intensify their cravings and negative affect despite limited empirical data to support this assumption. The present study extends and replicates, under improved methodological conditions, previous work that found reductions in daily craving associated with initiating abstinence.MethodsSeventy-eight adults (80.8% male, 57.1% Caucasian) in a clinical trial testing prazosin for AUD provided daily reports of drinking, craving, and negative affect for up to 12 weeks (mean=64.77 daily reports). Participants were classified into 3 subgroups based on whether and when they initiated 14 days of continuous abstinence, including: (1) ‘abstinence initiators’ who quit drinking during treatment (n=17), (2) ‘already abstainers’ who were abstinent at the start of treatment (n=20), and (3) ‘continued drinkers’ who never initiated abstinence (n=41). The timing and degree of change in craving and negative affect were compared across these groups using multivariate growth curve modeling.ResultsAll participant subgroups reported gradual reductions in craving over the course of treatment, with ‘abstinence initiators’ reporting additional sudden reductions in craving upon initiating abstinence from alcohol. ‘Continued drinkers’ reported higher levels of craving than ‘already abstainers’ throughout the full course of treatment. Negative affect followed a different pattern of change, with ‘abstinence initiators’ experiencing gradual reductions in negative affect after initiating abstinence but no changes prior to or immediately upon initiating abstinence, and with ‘already abstainers’ and ‘continued drinkers’ experiencing no changes in negative affect over time.ConclusionsInitiating abstinence is associated with immediate reductions in craving, followed by gradual reductions in both craving and negative affect. Results provide insight into the timing and magnitude of changes in theoretically and clinically important variables and may help patients anticipate when to expect improvement in craving and negative effect.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-29T10:00:22.180528-05:
      DOI: 10.1111/acer.13591
  • Effect of Gabapentin on Sleep and Event-related Oscillations (EROs) in
           rats exposed to chronic intermittent ethanol vapor and protracted
    • Authors: Manuel Sanchez-Alavez; Derek N Wills, Leslie Amodeo, Cindy L Ehlers
      Abstract: BackgroundDisturbances in sleep architecture, especially reductions in slow wave sleep (SWS), are symptoms commonly observed in individuals with alcohol use disorders (AUDs). Recent clinical trials have demonstrated that the anticonvulsant and analgesic drug Gabapentin may have therapeutic value in normalizing sleep quality in recovering alcoholics. However, the brain mechanisms underlying this improvement in sleep following Gabapentin treatment remain unknownMethodsIn the present study, adult Wistar rats were exposed to 8 weeks of chronic intermittent ethanol vapor (CIE) (blood ethanol concentrations averaged 128.2 + 17.4 mg/dL) or control conditions and then withdrawn. Sleep EEGs and event-related oscillations (EROs) were evaluated at baseline prior to ethanol exposure and 24 hours following ethanol withdrawal. Four weeks following ethanol withdrawal the effects of saline and two doses of Gabapentin (30 mg/kg, 120 mg/kg), on EROs and sleep EEGs, were evaluatedResultsAs compared to baseline, 24 hours following alcohol withdrawal SWS became fragmented as indexed by a significant increase in the number and a decrease in the duration of SWS episodes. Compared to controls, the ethanol exposed group had more ERO energy in the beta frequency band in the parietal cortex. Gabapentin induced a dose dependent decrease in the latency to the first SWS episode, and a reduction in sleep fragmentation. Gabapentin also produced a dose dependent increase in ERO energy in the control group that was significantly attenuated in the ethanol exposed group in the theta, and beta frequency bandsConclusionsTaken together these studies suggest that Gabapentin can reverse some of the alcohol- induced sleep and EEG deficits but does not eliminate all of the enduring brain effects of ethanol exposure.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-29T09:05:23.152889-05:
      DOI: 10.1111/acer.13588
  • Phosphatidylethanol (PEth) Levels among Incarcerated Women: The Influence
           of Pre-incarceration Alcohol Consumption and Length of Abstinence
    • Authors: Kelly E. Moore; Olga J. Santiago Rivera, Bradley Anderson, Jennifer E. Johnson, Judith A. Hahn, Megan E. Kurth, Madhavi K. Reddy, Yael C. Schonbrun, Michael D. Stein
      Abstract: BackgroundPhosphatidylethanol (PEth) is a direct biomarker for alcohol that is formed shortly after alcohol use and may remain detectable in blood for weeks after alcohol consumption. There is little research on alcohol use factors that influence PEth elimination, especially among women.MethodsData were collected from 116 alcohol use-disordered women who were recently incarcerated. We used a two-part model with logistic and linear components to examine whether alcohol consumption in the two weeks prior to incarceration and days since last alcoholic drink (operationalized as abstinence days prior to incarceration + days incarcerated) were associated with PEth detectability (>8ng/mL) and level (ng/mL) in blood. Results: Participants reported drinking an average of 10 drinks per day in the two weeks prior to incarceration. Days since last drink was negatively associated with PEth level (OR = 0.97, 95% CI = 0.93; 0.99) and being PEth detectable (OR = 0.96, 95% CI = 0.91; 0.99). Quantity of alcohol consumed prior to jail admission was associated with PEth detection (OR = 1.08; 95% CI = 1.03; 1.16), but not PEth level.ConclusionsDays since last alcoholic drink and drinks per day both influenced PEth detectability, but only days since last drink predicted PEth level among a large sample of women with alcohol use disorder in the criminal justice system.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-27T18:00:22.470452-05:
      DOI: 10.1111/acer.13587
  • Predictors of Longitudinal Trajectories of Alcohol Consumption in People
           with HIV
    • Authors: Usama Bilal; Mary E. McCaul, Heidi M. Crane, W.Christopher Mathews, Kenneth H. Mayer, Elvin Geng, Sonia Napravnik, Karen L. Cropsey, Michael J. Mugavero, Michael S. Saag, Heidi Hutton, Bryan Lau, Geetanjali Chander
      Abstract: BackgroundTo describe alcohol consumption trajectories in a cohort of People Living With HIV and determine clinical and sociodemographic predictors of each trajectory.MethodsThis is a prospective cohort study of 7906 patients in the 7 Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) sites. Alcohol consumption was categorized as none, moderate, and alcohol misuse. Predictors included age, race/ethnicity, depressive or anxiety symptoms, illicit drug use (opioids, methamphetamines, cocaine/crack), marijuana use, hepatitis C virus (HCV) infection, HIV transmission risk factor, and HIV disease progression. We estimated sex-stratified alcohol consumption trajectories and their predictors.ResultsWe found 7 trajectories of alcohol consumption in men: stable non-drinking and increased drinking (71% and 29% of initial non-drinking); stable moderate, reduced drinking and increased alcohol misuse (59%, 21% and 21% of initial moderate alcohol use); and stable alcohol misuse and reduced alcohol misuse (75% and 25% of initial alcohol misuse). Categories were similar in women, except lack of an increase to alcohol misuse trajectory among women that begin with moderate use. Older men and women were more likely to have stable non-drinking, while younger men were more likely to increase to or remain in alcohol misuse. Minorities, people with depressive or anxiety symptoms, HCV-infected individuals and people who injected drugs were more likely to reduce use. Illicit drug use was associated with a reduction in overall drinking, while marijuana use was associated with stable moderate drinking or misuse.ConclusionsLongitudinal trajectories of increasing alcohol use and stable misuse highlight the need to integrate routine screening and alcohol misuse interventions into HIV primary care.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-19T11:15:27.677904-05:
      DOI: 10.1111/acer.13583
  • Sleep Characteristics and Behavioral Problems among Children of Alcoholics
           and Controls
    • Authors: Maria. M. Wong; Kirk J. Brower, Deirdre A. Conroy, Kathryn Lachance, Elizabeth A. Craun
      Abstract: BackgroundPast research has indicated that both sleep difficulties (Gregory and Sadeh, 2012) and a parental history of alcoholism (Zucker, 2006) increase the risk of behavioral problems. But it is not known whether sleep difficulties differentially increase the risk of problem behaviors among children of alcoholics and controls. We compared multiple measures of sleep and the relationships between sleep and behavioral problems in these two groups of children.MethodsOne hundred and fifteen children aged 8-12 (67% children of alcoholics or COAs; 56% girls; Mage=10.85, SDage=1.51) participated in this study. Data presented here were taken from Time 1 of a larger prospective study designed to understand the relationship between sleep and alcohol use. All participants were naïve to alcohol and other illicit drugs. Participants were asked to wear an actigraph watch on their non-dominant wrists for one week. Parents completed the Pediatric Sleep Questionnaire and the Achenbach Child Behavioral Checklist.ResultsParents of COAs were more likely to rate their children as overtired compared with parents of non-COAs. SEM analyses focusing on overall internalizing and externalizing problems did not reveal any group differences on the relationships between sleep measures and behavioral problems. Regression analyses focusing on specific behavioral problems showed that longer TST, parental ratings of “sleep more” and “sleep less” than other children interacted with COA status to predict specific behavioral problems.ConclusionsSleep difficulties and duration appear to be a general risk factor for behavioral problems in both COAs and non-COAs, yet the relationships between specific sleep parameters and behavioral problems appear to be different between the two groups.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-19T10:45:25.625739-05:
      DOI: 10.1111/acer.13585
  • Effects of withdrawal from chronic intermittent ethanol exposure on sleep
           characteristics of female and male mice
    • Authors: Salvador Huitron-Resendiz; Tali Nadav, Stephanie Krause, Chelsea Cates-Gatto, Ilham Polis, Amanda J Roberts
      Abstract: BackgroundSleep disruptions are an important consequence of alcohol use disorders. There is a dearth of preclinical studies examining sex differences in sleep patterns associated with ethanol dependence despite documented sex differences in alcohol related behaviors and withdrawal symptoms. The purpose of this study was to investigate the effects of chronic intermittent ethanol (EtOH) on sleep characteristics in female and male mice.MethodsFemale and male C57BL6/J mice had access to EtOH/water two bottle choice (2BC) 2hr/day for 3 weeks followed by exposure to EtOH vapor (vapor-2BC) or air (control-2BC) for 5 cycles of 4 days. An additional group never experienced EtOH (naïve). Mice were implanted with EEG electrodes and vigilance states were recorded across 24hr on the fourth day of withdrawal. The amounts of wakefulness (W), slow-wave sleep (SWS), and rapid eye movement (REM) sleep were calculated and spectral analysis was performed by fast Fourier transformation.ResultsOverall, vapor-2BC mice showed a decrease in the amount of SWS four days into withdrawal as well as a decrease in the power density of slow waves, indicating disruptions in both the amount and quality of sleep in EtOH dependent mice. This was associated with a decrease in duration and an increase in number of SWS episodes in males and an increase in latency to sleep in females.ConclusionsOur results revealed overall deficits in sleep regulation in EtOH dependent mice of both sexes. Female mice appeared to be more affected with regard to the triggering of sleep, while male mice appeared more sensitive to disruptions in the maintenance of sleep.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-19T10:45:24.137589-05:
      DOI: 10.1111/acer.13584
  • Pharmacogenetic effects of naltrexone in individuals of East Asian
           descent: Human laboratory findings from a randomized trial
    • Authors: Lara A. Ray; ReJoyce Green, Daniel J.O. Roche, Spencer Bujarski, Emily E. Hartwell, Aaron C. Lim, Taylor Rohrbaugh, Dara Ghahremani, Kent Hutchison, Karen Miotto
      Abstract: BackgroundGenetic variation in the endogenous opioid system has been identified as one potential source of individual variability in naltrexone treatment outcomes. The majority of naltrexone pharmacogenetic studies have focused on a particular single nucleotide polymorphism (SNP) of the mu-opioid receptor gene (OPRM1; rs1799971; commonly known as the Asn40Asp SNP) in Caucasian samples with decidedly mixed results. The goal of this study is to test the pharmacogenetic effects of naltrexone on subjective response to alcohol and self-administration of alcohol in individuals of East Asian descent. We hypothesized that naltrexone, compared with placebo, would potentiate the aversive and sedative effects of alcohol and reduce alcohol self-administration to a greater extent in Asp40 carriers.MethodParticipants (N = 87; Asn40Asn, n = 29; Asn40Asp, n= 34, and Asp40Asp, n = 14) completed two double-blinded and counterbalanced experimental sessions: one after taking naltrexone (50 mg/day) for five days and one after taking matched placebo for five days. In each experimental session, participants received a priming dose of IV alcohol up to the breath alcohol concentration (BrAC) target of 0.06 g/dl which was immediately followed by an alcohol self-administration period (1 hour).ResultsThere were no pharmacogenetic effects observed for alcohol-induced stimulation, sedation, craving for alcohol, or alcohol self-administration in the laboratory. During the self-administration period, Asp40 carriers consumed fewer drinks and had a longer latency to first drink as compared to Asn40 homozygotes.ConclusionsThese findings in East Asians add to the mixed literature on naltrexone pharmacogenetics from predominantly Caucasian samples and highlight the complexity of these effects and their overall limited replicability. It is plausible that a consistent pharmacogenetic effect in tightly controlled preclinical and experimental medicine models “fades” in more complex and heterogeneous settings and samples.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-19T10:45:22.394184-05:
      DOI: 10.1111/acer.13586
  • Brief exposures to the taste of ethanol and quinine promote subsequent
           acceptance of ethanol in a paradigm that minimizes post-ingestive
    • Authors: Gregory C Loney; Paul J Meyer
      Abstract: BackgroundAversion to the orosensory properties of concentrated ethanol solutions is often cited as a primary barrier to initiation of drinking and may contribute to abstention. These aversive properties include gustatory processes which encompass both bitter-like taste qualities and trigeminal-mediated irritation. Chronic-intermittent ethanol access (CIA) results in substantial and persistent increases in ethanol consumption, but the degree to which this facilitation involves sensory responding to ethanol and other bitter stimuli is currently undetermined.MethodsLong-Evans rats were given brief-access licking tests designed to examine the immediate, taste-guided assessment of the palatability of ethanol and quinine solutions. Rats were assessed once in a naïve state and again following previous brief-access exposure, or following four weeks of CIA. The relationship between the sensitivity to the aversive orosensory properties of ethanol and quinine following ethanol access and the impact of antecedent quinine exposure on the acceptance of ethanol were determined in two parallel studies.ResultsBoth brief-access to ethanol and four-week CIA resulted in substantial rightward shifts in the concentration-response function of brief-access ethanol licking indicating that ethanol exposure increased acceptance of the taste of ethanol. The initial sensitivity to the aversive orosensory properties of ethanol and quinine were positively correlated in naïve rats, such that rats that were initially more accepting of quinine were also more accepting of ethanol. Rats that sampled quinine immediately prior to tasting ethanol exhibited successive positive contrast in that they were more accepting of highly concentrated ethanol, relative to a water-control group.ConclusionsIncreased ethanol acceptance following exposure is, at least in part, facilitated by a decrease in its aversive sensory properties. Both long and short term access increases the palatability of the taste of ethanol in brief-access licking tests. Moreover, the sensitivity to the bitterness of quinine was predictive of acceptance of ethanol indicating some commonality in the sensory mechanisms that mediate the initial acceptance of the two stimuli. Accordingly, immediate prior exposure to quinine results in increased acceptance of ethanol suggesting that successive positive contrast between oral stimuli may contribute to increased alcohol consumption.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-14T14:30:44.314051-05:
      DOI: 10.1111/acer.13581
  • Associations between MAOA-uVNTR genotype, maltreatment, MAOA methylation
           and alcohol consumption in young adult males
    • Authors: Megha Bendre; Erika Comasco, Dave Checknita, Jari Tiihonen, Sheilagh Hodgins, Kent W Nilsson
      Abstract: BackgroundEpigenetic mechanisms are candidate moderators of the effect of maltreatment on brain and behavior. Interactions between maltreatment and the Monoamine Oxidase A upstream variable number tandem repeat genotype (MAOA-uVNTR) are associated with alcohol-related problems. However, presently it is not known whether DNA methylation moderates this association. The study focused on fifty-three young adult males and aimed to determine: whether MAOA methylation moderated the association of alcohol-related problems with the interaction of MAOA-uVNTR and maltreatment; and whether alcohol consumption moderated the association of MAOA methylation with the interaction of MAOA-uVNTR and maltreatment.MethodsMAOA-uVNTR genotypes with ≤ 3 and> 3 repeats were categorized as short (S) and long (L), respectively. Data on maltreatment were obtained retrospectively, using self-reported questionnaires. DNA methylation of 16 candidate CpGs within part of the MAOA first exon and intron was assessed and grouped based on principal component analyses. Alcohol-related problems were assessed using the Alcohol Use Disorder Identification Test (AUDIT). Alcohol consumption was measured using AUDIT-C. Moderation effects were assessed and probed using the moderated moderation model and Johnson-Neyman′s method, respectively.ResultsCarriers of the S allele who experienced maltreatment and displayed lower Component 1 (mean of CpGs 13-16 in the first intron) MAOA methylation levels, reported higher AUDIT score, in contrast to L allele carriers. Carriers of the S allele who reported higher AUDIT-C score, and experienced maltreatment, displayed lower Component 3 (mean of CpGs 2-6 in the first exon) MAOA methylation levels than L allele carriers.ConclusionIntronic methylation moderated the association of alcohol-related problems with the interaction of MAOA-uVNTR and maltreatment. Alcohol consumption moderated the association of exonic methylation with the interaction of MAOA-uVNTR and maltreatment. These results suggest that epigenetic factors as well as genotype and maltreatment play a role in the development of alcohol misuse among young adult males.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-09T09:20:42.444379-05:
      DOI: 10.1111/acer.13578
  • Co-administration of low-dose naltrexone and bupropion reduces alcohol
           drinking in alcohol-preferring (P) rats
    • Authors: Emily R. Nicholson; Julian E. Dilley, Janice C. Froehlich
      Abstract: BackgroundThis study examined whether combining naltrexone (NTX) with bupropion (BUP) is more effective in reducing alcohol drinking in alcohol-preferring (P) rats with a genetic predisposition toward high voluntary alcohol intake than is either drug alone.MethodsAlcohol-experienced, adult, male, alcohol-preferring (P) rats were fed NTX alone in a dose of 10.0 mg/kg BW, BUP alone in a dose of 10.0 mg/kg BW, BUP alone in a dose of 20.0 mg/kg BW, NTX (10.0 mg/kg BW) + BUP (10.0 mg/kg BW), or vehicle (VEH) at 1 hour prior to onset of a daily 2-hour alcohol access period for 5 consecutive days.ResultsWhen administered alone, neither NTX (10.0 mg/kg BW) nor BUP, in either of two doses (10.0 mg/kg BW or 20.0 mg/kg BW), reduced voluntary alcohol intake in P rats. However, NTX combined with BUP (10.0 mg/kg NTX + 10.0 mg/kg BUP) and given as a single medication, significantly reduced alcohol consumption throughout prolonged treatment.ConclusionsCombining low doses of NTX and BUP, each of which is ineffective when given alone, increases the efficacy of the medication. Low drug doses circumvent the problem of negative side effects that can occur with higher doses of either drug. A reduction in side effects can facilitate patient compliance and improve clinical outcomes for alcoholics and heavy drinkers who want to reduce their alcohol intake. The results, together with those from our prior studies, demonstrate the strength of a combinatorial pharmacotherapeutic approach to the treatment of alcohol use disorder (AUD).This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-09T09:20:23.792992-05:
      DOI: 10.1111/acer.13577
  • Impact of moderate alcohol discontinuation on insulin action and secretion
           in Latinos with and without hepatitis C
    • Authors: Lindsay A Uribe; Peter Bacchetti, Nicholas Gelman, Esteban Burchard, Mark Fitch, Marc Hellerstein, Mandana Khalili
      Abstract: Background/AimsInsulin resistance (IR) is associated with hepatitis C infection (HCV), and Latinos are both at risk for IR and are disproportionately affected by HCV. Moderate alcohol consumption improves insulin sensitivity and may modify HCV-associated IR. We investigated the impact of moderate alcohol discontinuation on insulin sensitivity and secretion in Latinos using direct measurements.MethodsTwenty-five non-diabetic, non-cirrhotic Latino adults without (n=17) or with (n=8) HCV underwent 3-day metabolic assessment before and after prescription of 6 weeks of moderate alcohol discontinuation. Peripheral IR was measured via steady-state plasma glucose (SSPG) and hepatic IR using endogenous glucose production during a two-step 240-minute insulin suppression test. Insulin secretion was measured using graded glucose infusion test.ResultsBaseline mean age was 46±11 years, 63% male, 29% had HCV, and mean BMI was 27±4 kg/m2. Compared to non-HCV, HCV patients had a higher median SSPG (132 vs 98.8 mg/dL, p=1.0), hepatic IR (13.5 vs 11.3, p=0.24), and insulin secretion (ISR-AUC, 1290 vs 1250 pmol/min, p=0.98). After confirmed alcohol discontinuation, hepatic IR was the only parameter that changed significantly (increased, mean change 2.6±4.8, p=0.02). Higher baseline ALT was also associated with a greater change in hepatic IR (average 4.0 points/ALT doubling, p=0.004), and HCV was associated with a lesser change (average -7.3 points, p=0.002), independent of ALT.ConclusionsShort-term moderate alcohol discontinuation adversely impacted hepatic IR in Latinos which was influenced by level of ALT at baseline independent of etiology. Though reduction in ALT through weight loss and HCV eradication remains a priority in improving IR, the observed non-harmful effect of moderate alcohol use represents a potentially confounding variable that warrants further study.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-08T12:01:16.091181-05:
      DOI: 10.1111/acer.13576
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