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Showing 1 - 200 of 1583 Journals sorted alphabetically
Abacus     Hybrid Journal   (Followers: 11, SJR: 0.48, h-index: 22)
About Campus     Hybrid Journal   (Followers: 5)
Academic Emergency Medicine     Hybrid Journal   (Followers: 54, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 43, SJR: 0.547, h-index: 30)
ACEP NOW     Free  
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 50, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 135, 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: 15, SJR: 1.197, h-index: 81)
Acta Ophthalmologica     Hybrid Journal   (Followers: 5, SJR: 0.112, h-index: 1)
Acta Paediatrica     Hybrid Journal   (Followers: 54, SJR: 0.794, h-index: 88)
Acta Physiologica     Hybrid Journal   (Followers: 7, SJR: 1.69, h-index: 88)
Acta Polymerica     Hybrid Journal   (Followers: 9)
Acta Psychiatrica Scandinavica     Hybrid Journal   (Followers: 35, SJR: 2.518, h-index: 113)
Acta Zoologica     Hybrid Journal   (Followers: 5, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 2)
Addiction     Hybrid Journal   (Followers: 32, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 12, SJR: 2.091, h-index: 57)
Adultspan J.     Hybrid Journal   (SJR: 0.127, h-index: 4)
Advanced Energy Materials     Hybrid Journal   (Followers: 24, SJR: 6.411, h-index: 86)
Advanced Engineering Materials     Hybrid Journal   (Followers: 24, SJR: 0.81, h-index: 81)
Advanced Functional Materials     Hybrid Journal   (Followers: 48, SJR: 5.21, h-index: 203)
Advanced Healthcare Materials     Hybrid Journal   (Followers: 13, SJR: 0.232, h-index: 7)
Advanced Materials     Hybrid Journal   (Followers: 246, 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: 4, SJR: 2.488, h-index: 21)
Advanced Science     Open Access   (Followers: 4)
Advanced Synthesis & Catalysis     Hybrid Journal   (Followers: 17, SJR: 2.729, h-index: 121)
Advances in Polymer Technology     Hybrid Journal   (Followers: 13, SJR: 0.344, h-index: 31)
Africa Confidential     Hybrid Journal   (Followers: 19)
Africa Research Bulletin: Economic, Financial and Technical Series     Hybrid Journal   (Followers: 12)
Africa Research Bulletin: Political, Social and Cultural Series     Hybrid Journal   (Followers: 9)
African Development Review     Hybrid Journal   (Followers: 32, SJR: 0.275, h-index: 17)
African J. of Ecology     Hybrid Journal   (Followers: 14, SJR: 0.477, h-index: 39)
Aggressive Behavior     Hybrid Journal   (Followers: 15, SJR: 1.391, h-index: 66)
Aging Cell     Open Access   (Followers: 9, SJR: 4.374, h-index: 95)
Agribusiness : an Intl. J.     Hybrid Journal   (Followers: 6, SJR: 0.627, h-index: 14)
Agricultural and Forest Entomology     Hybrid Journal   (Followers: 14, SJR: 0.925, h-index: 43)
Agricultural Economics     Hybrid Journal   (Followers: 44, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 28, 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: 33, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 49, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 127, 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: 90, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 28, SJR: 0.211, h-index: 26)
American J. of Hematology     Hybrid Journal   (Followers: 30, SJR: 1.761, h-index: 77)
American J. of Human Biology     Hybrid Journal   (Followers: 12, 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: 15, SJR: 1.115, h-index: 61)
American J. of Medical Genetics Part B: Neuropsychiatric Genetics     Hybrid Journal   (Followers: 3, SJR: 1.771, h-index: 107)
American J. of Medical Genetics Part C: Seminars in Medical Genetics     Partially Free   (Followers: 5, SJR: 2.315, h-index: 79)
American J. of Orthopsychiatry     Hybrid Journal   (Followers: 4, SJR: 0.756, h-index: 69)
American J. of Physical Anthropology     Hybrid Journal   (Followers: 35, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 237, 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: 3, SJR: 1.347, h-index: 75)
American J. of Transplantation     Hybrid Journal   (Followers: 15, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 9, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 116, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 11, SJR: 0.397, h-index: 18)
Analytic Philosophy     Hybrid Journal   (Followers: 15)
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: 153)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 204, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 34, SJR: 1.576, h-index: 62)
Animal Genetics     Hybrid Journal   (Followers: 8, SJR: 0.957, h-index: 67)
Animal Science J.     Hybrid Journal   (Followers: 5, 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: 8, SJR: 0.816, h-index: 56)
Annals of Clinical and Translational Neurology     Open Access   (Followers: 1)
Annals of Human Genetics     Hybrid Journal   (Followers: 9, SJR: 1.191, h-index: 67)
Annals of Neurology     Hybrid Journal   (Followers: 42, SJR: 5.584, h-index: 241)
Annals of Noninvasive Electrocardiology     Hybrid Journal   (Followers: 2, SJR: 0.531, h-index: 38)
Annals of Public and Cooperative Economics     Hybrid Journal   (Followers: 9, 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: 24, SJR: 0.72, h-index: 31)
Anthropology & Humanism     Hybrid Journal   (Followers: 16, SJR: 0.137, h-index: 3)
Anthropology News     Hybrid Journal   (Followers: 14)
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: 93, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 45, SJR: 2.212, h-index: 69)
Anz J. of Surgery     Hybrid Journal   (Followers: 6, 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: 66, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 6, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 133, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 48, 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: 13, 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: 34, SJR: 1.047, h-index: 57)
Arabian Archaeology and Epigraphy     Hybrid Journal   (Followers: 11, 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: 27, SJR: 0.809, h-index: 48)
Archeological Papers of The American Anthropological Association     Hybrid Journal   (Followers: 14, SJR: 0.156, h-index: 2)
Architectural Design     Hybrid Journal   (Followers: 24, SJR: 0.261, h-index: 9)
Archiv der Pharmazie     Hybrid Journal   (Followers: 4, SJR: 0.628, h-index: 43)
Archives of Drug Information     Hybrid Journal   (Followers: 4)
Archives of Insect Biochemistry and Physiology     Hybrid Journal   (SJR: 0.768, h-index: 54)
Area     Hybrid Journal   (Followers: 12, SJR: 0.938, h-index: 57)
Art History     Hybrid Journal   (Followers: 205, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 48, SJR: 1.984, h-index: 20)
Arthritis Care & Research     Hybrid Journal   (Followers: 27, 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: 13)
Asia & the Pacific Policy Studies     Open Access   (Followers: 15)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 319, SJR: 0.494, h-index: 19)
Asia Pacific Viewpoint     Hybrid Journal   (SJR: 0.616, h-index: 26)
Asia-Pacific J. of Chemical Engineering     Hybrid Journal   (Followers: 7, 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: 3, 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: 3, 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   (SJR: 0.394, h-index: 7)
Asian J. of Organic Chemistry     Hybrid Journal   (Followers: 4, SJR: 1.443, h-index: 19)
Asian J. of Social Psychology     Hybrid Journal   (Followers: 5, SJR: 0.665, h-index: 37)
Asian Politics and Policy     Hybrid Journal   (Followers: 13, 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: 2, SJR: 0.701, h-index: 40)
Atmospheric Science Letters     Open Access   (Followers: 29, SJR: 1.332, h-index: 27)
Austral Ecology     Hybrid Journal   (Followers: 12, SJR: 1.095, h-index: 66)
Austral Entomology     Hybrid Journal   (Followers: 10, SJR: 0.524, h-index: 28)
Australasian J. of Dermatology     Hybrid Journal   (Followers: 7, SJR: 0.714, h-index: 40)
Australasian J. On Ageing     Hybrid Journal   (Followers: 7, SJR: 0.39, h-index: 22)
Australian & New Zealand J. of Statistics     Hybrid Journal   (Followers: 13, 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: 42, SJR: 0.814, h-index: 49)
Australian and New Zealand J. of Public Health     Hybrid Journal   (Followers: 11, 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: 4, SJR: 0.171, h-index: 12)
Australian Economic Papers     Hybrid Journal   (Followers: 22, 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: 13, SJR: 0.203, h-index: 14)
Australian J. of Psychology     Hybrid Journal   (Followers: 16, SJR: 0.384, h-index: 30)
Australian J. of Public Administration     Hybrid Journal   (Followers: 382, SJR: 0.418, h-index: 29)
Australian J. of Rural Health     Hybrid Journal   (Followers: 4, SJR: 0.43, h-index: 34)
Australian Occupational Therapy J.     Hybrid Journal   (Followers: 64, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 11, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 19, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 31, 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: 9, 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: 3, 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: 8, SJR: 0.297, h-index: 23)
Behavioral Sciences & the Law     Hybrid Journal   (Followers: 22, SJR: 0.736, h-index: 57)
Berichte Zur Wissenschaftsgeschichte     Hybrid Journal   (Followers: 9, 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: 14, SJR: 1.172, h-index: 90)
Biological Reviews     Hybrid Journal   (Followers: 2, SJR: 6.469, h-index: 114)
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 44, 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: 6, 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: 45, SJR: 0.415, h-index: 55)
Biotechnology and Bioengineering     Hybrid Journal   (Followers: 135, SJR: 1.633, h-index: 146)
Biotechnology J.     Hybrid Journal   (Followers: 13, SJR: 1.185, h-index: 51)
Biotechnology Progress     Hybrid Journal   (Followers: 39, SJR: 0.736, h-index: 101)
Biotropica     Hybrid Journal   (Followers: 17, SJR: 1.374, h-index: 71)
Bipolar Disorders     Hybrid Journal   (Followers: 10, SJR: 2.592, h-index: 100)
Birth     Hybrid Journal   (Followers: 33, 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: 5, 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  [1583 journals]
  • In Memoriam Professor Jean Pierre von Wartburg (1931-2017)
    • Authors: Helmut K. Seitz
      Abstract: On April 11, 2017, Professor Jean Pierre von Wartburg passed away in his home in Bollingen, near Bern, Switzerland. In addition to being one of the pioneers in alcohol research, he was one of the leading scientists in the field of enzymology and alcohol metabolism. Between 1965 and 1990, he was a giant who dominated the field.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-25T07:45:21.882999-05:
      DOI: 10.1111/acer.13423
  • Erratum
    • Abstract: In the article by Xia et al., “Alterations of Rat Corticostriatal Synaptic Plasticity After Chronic Ethanol Exposure and Withdrawal,” 2006, 30:819–824, there was an error in some of the author names. Jian Xun Xia should be Jianxun Xia, Xiao Hu Zhang should be Xiaohu Zhang, Yin Bing Ge should be Yinbing Ge, and Xiao Ru Yuan should be Xiaoru Yuan. We apologize for this error.ReferenceXia J, Li J, Zhou R, Zhang X, Ge Y, Yuan X (2006) Alterations of rat corticostriatal synaptic plasticity after chronic ethanol exposure and withdrawal. Alcohol Clin Exp Res 30:819–824.
      PubDate: 2017-05-23T07:00:37.739696-05:
      DOI: 10.1111/acer.13418
  • Evidence of Altered Mitochondrial Protein Expression After Chronic Ethanol
           Consumption in the Aged Estrogen-Deficient Female Rat Heart
    • Authors: Alexandra M. Garvin; J. L. Miller-Lee, D. R. Sharda, G. M. Kanski, J. C. Hunter, Donna H. Korzick
      Abstract: BackgroundEstrogen loss has been implicated to increase the risk of alcoholic cardiomyopathy in post-menopausal women. The purpose of this study was to identify novel mitochondrial protein targets for the treatment of alcoholic cardiomyopathy in aged women using a state-of-the-art proteomics approach. We hypothesized that chronic ethanol (EtOH) ingestion exacerbates maladaptive mitochondrial protein expression in the aged female heartMethodsAdult (3 mo) and aged (18 mo) F344 ovary-intact or ovariectomized (OVX) rats were randomly assigned an EtOH or control Lieber-DeCarli ‘all liquid’ diet for 20 wks. Proteomic analyses were conducted in mitochondria isolated from left ventricles using isobaric tags for relative and absolute quantification (iTRAQ) 8plex labeling and mass spectrometry (n=3-5/group).ResultsAfter EtOH, significant differences (false discovery rate < 5%) were observed in electron transport chain components (NADH dehydrogenase [ubiquinone] flavoprotein 2) as well as proteins involved in lipid metabolism (2,4 dienoyl-CoA reductase) and cellular defense (catalase), suggesting a possible link to congestive heart failure. Directional changes in protein levels were confirmed by Western blotting. Additionally, EtOH significantly reduced state 3 mitochondrial respiration in all groups, yet only reduced respiratory control index (RCI) in the aged OVX rat heart (p
      PubDate: 2017-05-19T08:00:25.85737-05:0
      DOI: 10.1111/acer.13421
  • The Modulation of the Startle Reflex as Predictor of Alcohol Use Disorders
           in a Sample of Heavy Drinkers: A 4-Year Follow-Up Study
    • Authors: Rosa Jurado-Barba; Almudena Duque, José Ramón López-Trabada, Isabel Martínez-Gras, María Salud García-Gutiérrez, Francisco Navarrete, Francisco López-Muñoz, Miguel Ángel Jiménez-Arriero, Cesar Ávila, Jorge Manzanares, Gabriel Rubio
      Abstract: BackgroundPrevious studies demonstrated that patients with alcohol use disorders (AUDs) show altered startle reflex responses to alcohol-related stimuli. However, there is little information about the role of these altered responses in the development of AUDs. This study examined the startle reflex response to different visual stimuli and the role of these patterns in the development of AUDs in a 4-year follow-up.MethodsTwo hundred and thirty-nine (nondependent) heavy-drinking participants were selected. In the baseline period, the startle reflex responses to alcohol-related, aversive, appetitive, and neutral pictures were assessed. Startle reflex responses to these pictures were used as predictive variables. Status drinking (alcohol dependence and nondependence) assessed at 4-year follow-up was used as outcome measure.ResultsAt the 4-year follow-up assessment, 46% of participants fulfilled DSM-IV alcohol abuse or dependence criteria. Alcohol dependence status was predicted by an attenuated startle reflex response to alcohol-related and aversive pictures.ConclusionsThis study revealed that an attenuated modulation of startle reflex response to alcohol-related and aversive stimuli could be used as a clinical marker to predict the development of AUDs in participants with previous alcohol consumption.The participants are 239 men with a heavy-drinking profile who had not received previous formal treatment for Alcohol Use Disorder (AUD). Results show that in comparison with participants remaining as heavy drinkers and remitted at 4-year follow-up, alcohol-dependent subjects show an attenuated startle reflex response to alcohol-related, aversive, appetitive and neutral pictures. The predictive analysis shows that the startle reflex response to alcohol-related and aversive pictures are significant predictors of alcohol-dependence status at the follow-up 4 years later.
      PubDate: 2017-05-11T16:00:02.452712-05:
      DOI: 10.1111/acer.13399
  • Nalmefene prevents alcohol-induced neuroinflammation and alcohol drinking
           preference in adolescent female mice: role of TLR4
    • Authors: Jorge Montesinos; Anabel Gil, Consuelo Guerri
      Abstract: BackgroundWe previously showed that, by activating innate immune receptors toll-like 4 (TLR4), adolescent intermittent ethanol exposure causes neuroinflammation, myelin damage and behavioral dysfunctions. Recent findings reveal that clinically-used opioid antagonists naltrexone (NT) and naloxone (NX) inhibit opioid-induced TLR4 signaling, and that NT, NX and nalmefene (NF), the 6-methylene derivative of NX, are able to reduce alcohol drinking escalation.MethodsNF (0.1 mg/kg, i.p.) was injected 1 h prior to ethanol (3 g/kg, i.p.) following intermittent treatment in female (PND35) adolescent mice. Inflammatory molecules, myelin proteins and apoptotic markers were assessed in the prefrontal cortex (PFC) and striatum/nucleus accumbens (STR/NAcc). The effect of NF on alcohol drinking preference was evaluated in both the WT and TLR4-knock out adolescent mice. Using astroglial cells, the inhibitory potential of NT, NX and NF on LPS, or the ethanol-triggered TLR4 response, was compared.ResultsOur findings indicate that NF prevents the up-regulation of cytokines (IL-1β, IL-17A, TNF-α), chemokines (MCP-1, MIP-1, KC) and pro-inflammatory mediators (iNOS, COX-2), along with myelin damage and apoptotic events, in both PFC and STR/NAcc. NF also abolishes ethanol-induced escalation of alcohol preference/consumption, but has no effect when administered to TLR4-KO mice. In vitro experiments indicate that NX and NF inhibit TLR4 activation upon LPS or ethanol stimulation. Immunofluorescence studies and lipid rafts isolation show that NF is able to prevent TLR4 translocation to lipid rafts/caveolae in astrocytes.ConclusionsThese results suggest that NF prevents neuroinflammation and brain damage by blocking the TLR4 response, and also support the role of central pro-inflammatory immune signaling in the modulation of alcohol consumption/addiction.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-11T07:46:41.347455-05:
      DOI: 10.1111/acer.13416
  • Aripiprazole Suppression of Drinking in a Clinical Laboratory Paradigm:
           Influence of Impulsivity and Self-Control
    • Authors: Raymond F. Anton; Joseph P. Schacht, Konstantin E. Voronin, Patrick K. Randall
      Abstract: BackgroundAspects of impulsivity have been implicated in the development, or maintenance, of Alcohol Use Disorder (AUD). The brain dopamine system is implicated in both reward processing/memory (typically subcortical) and in brain inhibitory control mechanisms (typically cortical). Using a validated clinical lab paradigm, the dopamine/serotonin “stabilizing” drug, aripiprazole was evaluated in non-treatment-seeking AUD individuals based on their level of impulsivity/ self-control.MethodsNinety-nine individuals (77% male; mean age 27; 7.5 drinks per day; 83% heavy drinking days) meeting DSM-IV criteria for alcohol dependence were randomized to aripiprazole (N=47 evaluable) or placebo (N=48 evaluable) based on their Barratt Impulsiveness Scale (BIS-11) score (above or below 68). Aripiprazole, or similar placebo, was titrated to 15mg over 8 days. Drinking was recorded over 6 days under natural conditions. On day 8, after one day of required abstinence, individuals participated in a bar-lab paradigm that included a priming drink (BAC target 0.02-0.03 g/dL) and free-choice consumption of up to 8 drinks (max BAC 0.1 g/dL) in exchange for a “bar-credit” of $2 per drink (max $16). Endpoints were drinks per day under natural conditions and drinks consumed in the bar-lab after the priming drink.ResultsThere was no significant main effect of aripiprazole or interaction with BIS-11 score during the natural drinking period. However, there was a main effect of aripiprazole on bar-lab drinking (p=0.04) and aripiprazole reduced the total number of drinks consumed more among individuals with low self-control (p=0.034) and increased latency to consume those drinks (p=0.045) more among those with high impulsivity. Relative to placebo, aripiprazole caused more side effects and increased alcohol-induced sedation, but neither significantly influenced its interaction with impulsivity/self-control scores on drinking.ConclusionsThis paradigm forced a choice between immediate drinking reward and delayed monetary reward. In those with high impulsivity and/or low self-control, aripiprazole shifts the balance away from immediate drinking towards a later reward. Medications targeting cortical dopamine/serotonin balance might show clinical benefit of reduced drinking, among individuals with impulsivity/low self-control.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-11T07:46:29.583207-05:
      DOI: 10.1111/acer.13417
  • Association of Anticipated and Laboratory-Derived Alcohol Stimulation,
           Sedation, and Reward
    • Authors: Daniel J. Fridberg; Sandra Y. Rueger, Patrick B.S. Smith, Andrea C. King
      Abstract: BackgroundLaboratory alcohol challenges are the “gold standard” for obtaining accurate measurements of subjective alcohol stimulation, sedation, and reward. However, these approaches are time- and resource-intensive. The present study examined the extent to which self-reported anticipated alcohol stimulation, sedation, and reward corresponded with those same responses measured with the Biphasic Alcohol Effects Scale (BAES), Brief-BAES (B-BAES), and Drug Effects Questionnaire (DEQ) during a controlled laboratory alcohol challenge.MethodsParticipants were 106 light-to-heavy social drinkers (58.5% male; mean ± SD age = 35.8 ± 3.2 years) who completed the Anticipated BAES and DEQ, as well as laboratory-derived versions of these scales 30- and 60-minutes after consuming placebo and 0.8 g/kg alcohol on separate days as part of laboratory sessions in the Chicago Social Drinking Project.ResultsAnticipated BAES/B-BAES and anticipated DEQ alcohol effects were strong predictors of their corresponding laboratory-derived responses during both the rising limb and at peak breath alcohol concentrations. Effects were significant even when accounting for age, sex, past month heavy drinking frequency, and laboratory session order (placebo or alcohol first).ConclusionsThe present study provides strong preliminary support for measuring anticipated alcohol effects with the Anticipated BAES/B-BAES and Anticipated DEQ as a proxy of subjective responses experienced during a controlled laboratory alcohol challenge. The findings lend support for these measures as viable alternatives to other anticipatory scales when laboratory-derived alcohol response measurement is not feasible.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-11T07:46:24.672631-05:
      DOI: 10.1111/acer.13415
  • Determinants of BDNF blood levels in patients with alcohol-use disorder
    • Authors: Philippe Nubukpo; Nicolas Ramoz, Murielle Girard, Dominique Malauzat, Philip Gorwood
      Abstract: BackgroundBlood Brain Derived Neurotrophic Factor (BDNF) levels are influenced by both addiction and mood disorders, as well as somatic conditions, gender, and genetic polymorphisms, leading to widely varying results. Depressive symptoms and episodes are frequently observed in patients with alcohol-use disorder, and vary widely over time, making it a challenge to determine which aspects are specifically involved in variations of serum BDNF levels in this population.MethodsWe assessed 227 patients with alcohol dependence involved in a detoxification program, at baseline and after a follow-up of six months, for the AUDIT score, the length of alcohol dependence, and the number of past detoxification programs. The Beck Depression Inventory and information on current tobacco and alcohol use, suicidal ideation, BMI, age, gender, and psychotropic treatments were also collected. Serum BDNF (ELISA) and two genetic polymorphisms of the BDNF gene (Val33Met and rs962369) were analyzed.ResultsThe presence of the Met allele, two markers of the history of alcohol dependence (γGT and the number of past treatments in detoxification programs), and the presence of a depressive episode (but not depressive score) were significantly associated with the two blood levels of BDNF at baseline and after six months. After controlling for baseline BDNF levels, the presence of the Met allele and an ongoing depressive episode were the only variables associated with changes of BNDF levels after six months.ConclusionsLow serum BDNF levels are associated with characteristics related to alcohol consumption and mood disorders, and variants of the BDNF gene in alcohol-use disorder patients. The factors which most strongly influenced changes in serum BDNF levels following treatment in an alcohol detoxification program were variants of the BDNF gene and ongoing depression.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-09T09:40:48.361199-05:
      DOI: 10.1111/acer.13414
  • FDA and EMA Need Homology on Alcohol Outcome Measures – Semper:
           Simplicitas est purius modum
    • Authors: Bankole A. Johnson
      Abstract: Litten et al. (2017) continue to propose important points, which also emanated from my initial commentary (Johnson, 2017) on the paper by Witkiewitz et al. (2017), which call for: a) homology between the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) criteria to be used for determining efficacy in pharmacotherapy trials for alcohol use disorder (AUD); b) measures that have clinical relevance with respect to the health-related consequences of AUD; and c) the establishment that such measures be sensitive enough to detect clinically significant change in pharmacotherapy trials for AUD.This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-04T07:50:27.99091-05:0
      DOI: 10.1111/acer.13412
  • Letter to Editor in Response to Johnson's Commentary (2017) on the
           Witkiewitz et al. (2017) Article
    • Authors: Raye Z. Litten; Daniel E. Falk, Stephanie S. O'Malley, Katie Witkiewitz, Karl F. Mann, Raymond F. Anton
      Abstract: Dr. Bankole Johnson's commentary (Johnson, 2017) on the recent article by Witkiewitz et al. (2017) was a thoughtful piece, emphasizing several important points that should be considered when developing evidence-based regulatory guidelines for conducting alcohol treatment trials. In particular, Dr. Johnson reiterated the importance of 1) having the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) endorse comparable primary endpoints, 2) developing an endpoint that accurately reflects a reduction in the behavioral and medical risk levels of drinking, and 3) defining more sensitive clinical trial endpoints to detect differences between the experimental medication and placebo groups. The latter point is particularly important because medications showing efficacy in alcohol treatment trials generally have small effect sizes (Falk et al., 2010; Litten et al, 1996 and 2005; Zindel and Kranzler, 2014).This article is protected by copyright. All rights reserved.
      PubDate: 2017-05-04T07:50:25.495154-05:
      DOI: 10.1111/acer.13411
  • Alcohol Use Disorders and Immigration up to the Third Generation in
           France: Findings from a 39,617-Subject Survey in the General Population
    • Authors: Benjamin Rolland; Pierre-Alexis Geoffroy, Baptiste Pignon, Imane Benradia, Hélène Font, Jean-Luc Roelandt, Ali Amad
      Abstract: BackgroundIn the United States, first-generation immigrants (FGIs) show lower prevalence rates of alcohol use disorders (AUDs) than the native population, although they experience more psychosocial risk factors. This epidemiological phenomenon is called an “immigrant paradox.” No previous study has investigated whether immigrants also exhibit a reduced risk of AUDs in Europe. In a study of the general population in France, we have assessed the adjusted risk of AUDs between nonimmigrants and FGIs, second-generation immigrants (SGIs), and third-generation immigrants (TGIs).MethodsA cross-sectional survey based on face-to-face interviews was conducted among 39,617 French subjects recruited using a quota-sampling strategy. The sociodemographic data collected helped determine the subjects’ immigration status. The AUD assessment was performed using the Mini International Neuropsychiatric Interview (version 5.0.0). A multivariable logistic regression model was used to define the independent risk factors for AUDs with backward selection.ResultsThe overall prevalence of AUDs in the sample was 4.34%. AUDs were diagnosed in 3.82% of the native population versus 5.84% of the immigrant population: 4.67% of FGIs, 5.71% of SGIs, and 6.63% of TGIs (p 
      PubDate: 2017-05-02T16:00:01.911784-05:
      DOI: 10.1111/acer.13387
  • Genetic variability in adenosine deaminase-like contributes to variation
           in alcohol preference in mice
    • Authors: Heidi M.B. Lesscher; Alexis Bailey, Louk J.M.J. Vanderschuren
      Abstract: BackgroundA substantial part of the risk for alcohol use disorder (AUD) is determined by genetic factors. We previously used chromosome substitution (CSS) mice, to identify a QTL for alcohol preference on mouse chromosome 2. The aim of this study was to identify candidate genes within this QTL that confer the risk for alcohol preference.MethodsIn order to delineate the neurobiological underpinnings of alcohol consumption, we expanded on the QTL approach to identify candidate genes for high alcohol preference in mice. We narrowed down a QTL for alcohol preference on mouse chromosome 2, that we previously identified using chromosome substitution (CSS) mice, to four candidate genes in silico. Expression levels of these candidate genes in prefrontal cortex, amygdala and nucleus accumbens, brain regions implicated in reward and addiction, were subsequently compared for the CSS-2 and the C57BL/6J host strain.ResultsWe observed increased expression of adenosine deaminase-like (Adal) in all three regions in CSS-2 mice. Moreover, we found that the adenosine deaminase inhibitor EHNA reduced the difference in alcohol preference between CSS-2 and C57Bl/6J mice.ConclusionThe current study identifies Adal as a genetically protective factor against alcohol consumption in mice, in which elevated Adal levels contribute to low alcohol preference.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-27T16:03:21.679483-05:
      DOI: 10.1111/acer.13409
  • Findings from the Families on Track intervention pilot trial for children
           with fetal alcohol spectrum disorders and their families
    • Authors: Christie L. M. Petrenko; Mary E. Pandolfino, Luther K. Robinson
      Abstract: BackgroundIndividuals with fetal alcohol spectrum disorders (FASD) are at high risk for costly, debilitating mental health problems and secondary conditions, such as school disruption, trouble with the law, and substance use. The study objective was to pilot a multi-component intervention designed to prevent secondary conditions in children with FASD and improve family adaptation.MethodsThirty children with FASD or prenatal alcohol exposure (PAE) (ages 4 to 8) and their primary caregivers were enrolled. Families were randomized to either the Families on Track Integrated Preventive Intervention or an active control of neuropsychological assessment and personalized community referrals. The 30-week intervention integrates scientifically validated bi-monthly, in-home parent behavioral consultation and weekly child skills groups. Outcomes measured at baseline and follow-up post-intervention included intervention satisfaction, child emotional and behavioral functioning, child self-esteem, caregiver knowledge of FASD and advocacy, caregiver attitudes, use of targeted parenting practices, perceived family needs met, social support, and self-care. Data analysis emphasized calculation of effect sizes and was supplemented with analysis of variance techniques.ResultsAnalyses indicated that families participating in the intervention reported high program satisfaction. Relative to comparison group outcomes, the intervention was associated with medium to large effects for child emotion regulation, self-esteem, and anxiety. Medium-sized improvements in disruptive behavior were observed for both groups. Medium and large effects were seen for important caregiver outcomes: knowledge of FASD and advocacy, attributions of behavior, use of antecedent strategies, parenting efficacy, family needs met, social support, and self-care.ConclusionsThis pilot study yielded promising findings from the multicomponent Families on Track Integrated Preventive Intervention for child and caregiver outcomes. An important next step is to complete a randomized control trial of the Families on Track program with a larger sample fully representative of this underserved clinical population with built-in study of implementation parameters.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-25T10:21:24.661254-05:
      DOI: 10.1111/acer.13408
  • A Prospective Comparison of How the Level of Response to Alcohol and
           Impulsivity Relate to Future DSM-IV Alcohol Problems in the COGA Youth
    • Authors: Marc A. Schuckit; Tom L. Smith, George Danko, Robert Anthenelli, Lara Schoen, Mari Kawamura, John Kramer, Danielle M. Dick, Zoe Neale, Samuel Kuperman, Vivia McCutcheon, Andrey P. Anokhin, Victor Hesselbrock, Michie Hesselbrock, Kathleen Bucholz
      Abstract: BackgroundAlcohol problems reflect both environmental and genetic characteristics that often operate through endophenotypes like low levels of response (low LRs) to alcohol and higher impulsivity. Relationships of these preexisting characteristics to alcohol problems have been studied, but few analyses have included both low LR and impulsivity in the same model.MethodsWe extracted prospective data from 1,028 participants in the Prospective Youth Sample of the Collaborative Study for the Genetics of Alcoholism (COGA). At Time 1 (age 18) these drinking but non-alcohol dependent males and females completed the Barratt Impulsivity Scale and the Self Report of the Effects of Alcohol Questionnaire regarding drinks required for effects the first 5 times of drinking (SRE5-LR). Two years later, they reported perceived drinking patterns of peers (PEER), their own alcohol expectancies (EXPECT), and their drinking to cope with stress (COPE). Subsequently, at Time 3, participants reported numbers of up to 11 DSM-IV alcohol criterion items experienced in the 2 years since Time 2 (ALC PROBS). Data were analyzed using Structural Equation Modeling (SEM).ResultsIn the SEM, Baseline SRE5-LR and impulsivity were weakly related and did not interact in predicting later ALC PROBS. LR was directly linked to Time 3 ALC PROBS, and to PEER, but had no direct path to EXPECT, with partial mediation to ALC PROBS through PEER to EXPECT and via COPE. Impulsivity did not relate directly to ALC PROBS or PEER, but was directly related to EXPECT and COPE, with effects on ALC PROBS also operating through EXPECT and COPE.ConclusionsLow LRs and impulsivity related to Time 3 ALC PROBS through somewhat different paths. Education- and counseling-based approaches to mitigate future alcohol problems may benefit from emphasizing different potential mediators of adverse alcohol outcomes for youth with low LRs versus those with high impulsivity or both characteristics.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-25T10:00:58.416135-05:
      DOI: 10.1111/acer.13407
  • Role of the Dynorphin/Kappa Opioid Receptor System in the Motivational
           Effects of Ethanol
    • Authors: Rachel I. Anderson; Howard C. Becker
      Abstract: Evidence has demonstrated that dynorphin (DYN) and the kappa opioid receptor (KOR) system contribute to various psychiatric disorders, including anxiety, depression, and addiction. More recently, this endogenous opioid system has received increased attention as a potential therapeutic target for treating alcohol use disorders. In this review, we provide an overview and synthesis of preclinical studies examining the influence of alcohol (ethanol) exposure on DYN/KOR expression and function, as well as studies examining the effects of DYN/KOR manipulation on ethanol's rewarding and aversive properties. We then describe work that has characterized effects of KOR activation and blockade on ethanol self-administration and ethanol dependence/withdrawal-related behaviors. Finally, we address how the DYN/KOR system may contribute to stress-ethanol interactions. Despite an apparent role for the DYN/KOR system in motivational effects of ethanol, support comes from relatively few studies. Nevertheless, review of this literature reveals several common themes: (1) rodent strains genetically predisposed to consume more ethanol generally appear to have reduced DYN/KOR tone in brain reward circuitry; (2) acute and chronic ethanol exposure typically upregulate the DYN/KOR system; (3) KOR antagonists reduce behavioral indices of negative affect associated with stress and chronic ethanol exposure/withdrawal; and (4) KOR antagonists are effective in reducing ethanol consumption, but are often more efficacious under conditions that engender high levels of consumption, such as dependence or stress exposure. These results support the contention that the DYN/KOR system plays a significant role in contributing to dependence- and stress-induced elevation in ethanol consumption. Overall, more comprehensive analyses (on both behavioral and mechanistic levels) are needed to provide additional insight into how the DYN/KOR system is engaged and adapts to influence the motivation effects of ethanol. This information will be critical for the development of new pharmacological agents targeting KORs as promising novel therapeutics for alcohol use disorders and comorbid affective disorders.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-20T02:36:41.978093-05:
      DOI: 10.1111/acer.13406
  • Alcoholic cardiomyopathy: Disrupted protein balance and impaired
           cardiomyocyte contractility
    • Authors: Jennifer L. Steiner; Charles H. Lang
      Abstract: Alcoholic cardiomyopathy (ACM) can develop after consumption of relatively large amounts of alcohol over time or from acute binge drinking. Of the many factors implicated in the etiology of ACM, chronic perturbation in protein balance has been strongly implicated. This review focuses on recent contributions (since 2010) in the area of protein metabolism and cardiac function related to ACM. Data reviewed include that from in vitro and preclinical in vivo animal studies where alcohol or an oxidative metabolite was studied and outcome measures in either cardiomyocytes or whole heart pertaining to protein synthesis or degradation were reported. Additionally, studies on the contractile properties of cardiomyocytes were also included to link signal transduction with function. Methodological differences including the potential impact of sex, dosing and duration/timing of alcohol administration are addressed. Acute and chronic alcohol consumption decreases cardiac protein synthesis and/or activation of proteins within the regulatory mammalian/mechanistic target of rapamycin complex (mTORC1) pathway. Albeit limited, evidence suggests that myocardial protein degradation via the ubiquitin pathway is not altered, while autophagy may be enhanced in ACM. Alcohol impairs ex vivo cardiomyocyte contractility in relation to its metabolism and expression of proteins within the growth factor pathway. Dysregulation of protein metabolism, including the rate of protein synthesis and autophagy, may contribute to contractile deficits and is a hallmark feature of ACM meriting additional sex-inclusive, methodologically consistent studies.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-20T01:10:56.548592-05:
      DOI: 10.1111/acer.13405
  • A 5-year Follow-up of a Cohort of Italian Alcoholics: Hospital Admissions
           and Overall Survival
    • Authors: Gabriele Bardazzi; Ines Zanna, Marco Ceroti, Benedetta Bendinelli, Adriana Iozzi, Saverio Caini, Gabriella Nesi, Calogero Saieva
      Abstract: BackgroundAlcohol-use disorders (AUDs), including alcohol dependence and alcohol abuse defined according to specific DSM-IV and ICD-X criteria, can be potentially lethal, since they are associated with several medical and psychiatric conditions. This study aims to describe the causes of hospitalization of a large cohort of subjects with alcohol dependence (alcoholics) enrolled in Florence (Italy) over a 5-year follow-up period and to evaluate the effect of hospitalization on overall survival.MethodsEleven-hundred-thirty (1,130) alcoholics, newly diagnosed from 1997-2001, were linked to the Regional Mortality Registry for update of vital status as of December 31, 2006 and to the Hospital Discharge electronic archives of the Regional Health System of Tuscany to verify hospital admissions during the 5-year post cohort enrollment follow-up. Kaplan-Meier survival and Cox regression analyses were performed to evaluate any association of hospital admission with overall survival.ResultsA total of 3,916 new hospitalizations occurred during the 5-year follow-up. Most alcoholics (70.6%) reported at least 1 new hospitalization, with a first hospitalization rate of 61.7 per 100 person-years in the first year of follow-up. The mean number of hospitalizations per admitted subject was 4.87 (SD:7.4) and mean length of hospital stay was 8.5 days (SD:11.3). The main causes of hospitalization were mental disorders and diseases of the digestive system, as well as accidents or violence. Among those alcoholics alive after 1 year of follow-up, a significantly increased risk of dying in the following years could be predicted by early hospitalization in the 12 months preceding (HR 1.73; 95% CI 1.15-2.60) or following (HR 3.59; 95% CI 2.31-5.61) enrollment in the cohort.ConclusionsOur results confirm the association of AUDs with several serious medical conditions. This fact may be responsible for a high impact on health resource utilization and high social costs. Early hospitalization significantly predicts vital status at 5 years.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-20T01:10:49.637672-05:
      DOI: 10.1111/acer.13404
  • Dietary Patterns and Alcohol Consumption During Pregnancy: Secondary
           Analysis of Avon Longitudinal Study of Parents and Children
    • Authors: Victoria Coathup; Kate Northstone, Ron Gray, Simon Wheeler, Lesley Smith
      Abstract: BackgroundLarge general population surveys show that heavy regular and episodic alcohol consumption are associated with lower intakes of fruits and vegetables, and higher intakes of processed and fried meat. This is of particular concern regarding pregnant women, as both alcohol intake and inadequate maternal nutrition are independently associated with adverse fetal outcomes. The current study aimed to determine associations between maternal dietary patterns and alcohol consumption during pregnancy.MethodsWomen were participating in the Avon Longitudinal Study of Parents and Children, and provided details of alcohol consumption at 18 weeks’ gestation and diet at 32 weeks’ gestation (n = 9,839). Dietary patterns were derived from the food frequency questionnaire data using principal components analysis. Associations between alcohol consumption and dietary patterns were determined using multiple linear regression, adjusted for various sociodemographic and lifestyle factors.ResultsAfter adjustment, drinking ≥1 unit/d during the first trimester (β = 0.23 [95% CI: 0.08, 0.38]; p = 0.002) and binge drinking (≥4 units in 1 day) during the first half of pregnancy (β = 0.14 [95% CI: 0.07, 0.21]; p 
      PubDate: 2017-04-19T16:00:03.134502-05:
      DOI: 10.1111/acer.13379
  • Does a Crossover Age Effect Exist for African American and Hispanic Binge
           Drinkers? Findings from the 2010 to 2013 National Study on Drug Use and
    • Authors: Tamika C.B. Zapolski; Patrick Baldwin, Devin E. Banks, Timothy E. Stump
      Abstract: BackgroundAmong general population studies, lower rates of binge drinking tend to be found among African Americans and Hispanics compared to Whites. However, among older adult populations, minority groups have been shown to be at higher risk for binge drinking, suggesting the presence of a crossover effect from low to high risk as a function of age. To date, limited research has examined the crossover effect among African American and Hispanic populations compared to non-Hispanic Whites across large developmental time frames or explored variation in risk based on income or gender. This study aimed to fill these gaps in the literature.MethodsData were compiled from the 2010 to 2013 National Survey on Drug Use and Health surveys, which provide annual, nationally representative data on substance use behaviors among individuals aged 12 and older. Hispanic, non-Hispanic African American, and non-Hispanic White respondents were included (N = 205,198) in the analyses.ResultsA crossover effect was found for African American males and females among the lowest income level (i.e., incomes less than $20,000). Specifically, after controlling for education and marital status, compared to Whites, risk for binge drinking was lower for African American males at ages 18 to 24 and for females at ages 18 to 34, but higher for both African American males and females at ages 50 to 64. No crossover effect was found for Hispanic respondents.ConclusionsAlthough African Americans are generally at lower risk for binge drinking, risk appears to increase disproportionately with age among those who are impoverished. Explanatory factors, such as social determinants of health prevalent within low-income African American communities (e.g., lower education, violence exposure, housing insecurity) and potential areas for intervention programming are discussed.
      PubDate: 2017-04-19T16:00:02.066258-05:
      DOI: 10.1111/acer.13380
  • A preliminary investigation of the effect of acute alcohol on dopamine
           transmission as assessed by [11C]-(+)-PHNO
    • Authors: Thulasi Thiruchselvam; Alan A. Wilson, Isabelle Boileau, Bernard Le Foll
      Abstract: BackgroundPrevious positron emission tomography (PET) studies exploring the effect of acute alcohol on dopamine (DA) levels have yielded inconsistent results, with only some studies suggesting increased synaptic DA levels after an alcohol challenge. The D2/D3 agonist radiotracer, [11C]-(+)-propyl-hexahydro-naphtho-oxazin ([11C]-(+)-PHNO), has greater sensitivity to synaptic DA fluctuation than previously used antagonist radiotracers and is in principle more suitable for imaging alcohol-induced changes in DA. Its high affinity for the D3 receptor also enables measuring changes in D3-rich brain areas which have previously been unexplored. The aim of this study was to investigate whether alcohol reduces [11C]-(+)-PHNO binding in the striatum and in D3- rich extra-striatal areas.MethodsEight healthy drinkers underwent two [11C]-(+)-PHNO PET scans following alcohol and placebo in a randomized, single-blind, crossover design. [11C]-(+)-PHNO binding in the striatum and in the extra-striatal regions were compared between the two scans.ResultsAcute alcohol administration did not significantly reduce [11C]-(+)-PHNO binding in either the limbic striatum (d = 0.64), associative striatum (d
      PubDate: 2017-04-19T02:57:07.860266-05:
      DOI: 10.1111/acer.13403
  • Intoxication-Related AmED (Alcohol Mixed with Energy Drink) Expectancies
           Scale: Initial Development and Validation
    • Authors: Kathleen E. Miller; Kurt H. Dermen, Joseph F. Lucke
      Abstract: BackgroundYoung adult use of alcohol mixed with energy drinks (AmEDs) has been linked with elevated risks for a constellation of problem behaviors. These risks may be conditioned by expectancies regarding the effects of caffeine in conjunction with alcohol consumption. The aim of this study was to describe the construction and psychometric evaluation of the Intoxication-Related AmED Expectancies Scale (AmED_EXPI), 15 self-report items measuring beliefs about how the experience of AmED intoxication differs from the experience of noncaffeinated alcohol (NCA) intoxication.MethodsScale development and testing were conducted using data from a U.S. national sample of 3,105 adolescents and emerging adults aged 13-25. Exploratory and confirmatory factor analyses were conducted to evaluate the factor structure and establish factor invariance across gender, age, and prior experience with AmED use. Cross-sectional and longitudinal analyses examining correlates of AmED use were used to assess construct and predictive validity.ResultsIn confirmatory factor analyses, fit indices for the hypothesized four-factor structure (i.e., Intoxication Management [IM], Alertness [AL], Sociability [SO], and Jitters [JT]) revealed a moderately good fit to the data. Together, these factors accounted for 75.3% of total variance. The factor structure was stable across male/female, teen/young adult, and AmED experience/no experience subgroups. The resultant unit-weighted subscales showed strong internal consistency and satisfactory convergent validity. Baseline scores on the IM, SO, and JT subscales predicted changes in AmED use over a subsequent three-month period.ConclusionsThe AmED_EXPI appears to be a reliable and valid tool for measuring expectancies about the effects of caffeine during alcohol intoxication.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-19T02:56:58.614434-05:
      DOI: 10.1111/acer.13402
  • The Validity of the Montgomery-Asberg Depression Rating Scale in an
           Inpatient Sample with Alcohol Dependence
    • Authors: Breanne Hobden; Melanie L. Schwandt, Mariko Carey, Mary R. Lee, Mehdi Farokhnia, Sofia Bouhlal, Christopher Oldmeadow, Lorenzo Leggio
      Abstract: BackgroundThe Montgomery-Asberg Depression Rating Scale (MADRS) is commonly used to examine depressive symptoms in clinical settings, including facilities treating patients for alcohol addiction. No studies have examined the validity of the MADRS compared to an established clinical diagnostic tool of depression in this population. This study aimed to examine: 1) the validity of the MADRS compared to a clinical diagnosis of a depressive disorder (using the Structured Clinical Interview for DSM-IV (SCID)) in patients seeking treatment for alcohol dependence (AD); 2) whether the validity of the MADRS differs by type of SCID-based diagnosis of depression; and 3) which items contribute to the optimal predictive model of the MADRS compared to a SCID diagnosis of a depressive disorder.MethodsIndividuals seeking treatment for AD and admitted to an inpatient unit were administered the MADRS at day 2 of their detoxification program. Clinical diagnoses of AD and depression were made via the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-IV at the beginning of treatment.ResultsIn total, 803 participants were included in the study. The MADRS demonstrated low overall accuracy relative to the clinical diagnosis of depression with an area under the curve of 0.68. The optimal threshold for balancing sensitivity and specificity identified by the Euclidean distance was >14. This cut-point demonstrated a sensitivity of 66%, a specificity of 60%, a positive predictive value of 50% and a negative predictive value of 75%. The MADRS performed slightly better for major depressive disorders compared to alcohol-induced depression. Items related to lassitude, concentration and appetite slightly decreased the accuracy of the MADRS.ConclusionThe MADRS does not appear to be an appropriate substitute for a diagnostic tool among alcohol-dependent patients. The MADRS may, however, still be a useful screening tool assuming careful consideration of cut-off scores.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-19T02:45:34.847039-05:
      DOI: 10.1111/acer.13400
  • Eveningness and later sleep timing are associated with greater risk for
           alcohol and marijuana use in adolescence: Initial findings from the NCANDA
    • Authors: Brant P. Hasler; Peter L. Franzen, Massimiliano de Zambotti, Devin Prouty, Sandra A. Brown, Susan F. Tapert, Adolf Pfefferbaum, Kilian M. Pohl, Edith V. Sullivan, Michael D. De Bellis, Bonnie J. Nagel, Fiona C. Baker, Ian M. Colrain, Duncan B. Clark
      Abstract: BackgroundAbundant cross-sectional evidence links eveningness (a preference for later sleep-wake timing) and increased alcohol and drug use among adolescents and young adults. However, longitudinal studies are needed to examine whether eveningness is a risk factor for subsequent alcohol and drug use, particularly during adolescence, which is marked by parallel peaks in eveningness and risk for the onset of alcohol use disorders. The present study examined whether eveningness and other sleep characteristics were associated with concurrent or subsequent substance involvement in a longitudinal study of adolescents.MethodsParticipants were 729 adolescents (368 females; age 12-21 years) in the National Consortium on Adolescent Neurodevelopment and Alcohol [NCANDA] study. Associations between the sleep variables (circadian preference, sleep quality, daytime sleepiness, sleep timing, and sleep duration) and three categorical substance variables (at-risk alcohol use, alcohol bingeing, and past year marijuana use (y/n)) were examined using ordinal and logistic regression with baseline age, sex, race, ethnicity, socioeconomic status, and psychiatric problems as covariates.ResultsAt baseline, greater eveningness was associated with greater at-risk alcohol use, greater bingeing, and past-year use of marijuana. Later weekday and weekend bedtimes, but not weekday or weekend sleep duration, showed similar associations across the three substance outcomes at baseline. Greater baseline eveningness was also prospectively associated with greater bingeing and past-year use of marijuana at the 1-year follow-up, after covarying for baseline bingeing and marijuana use. Later baseline weekday and weekend bedtimes, and shorter baseline weekday sleep duration, were similarly associated with greater bingeing and past-year use of marijuana at the 1-year follow-up after covarying for baseline values.ConclusionsFindings suggest that eveningness and sleep timing may be under-recognized risk factors and future areas of intervention for adolescent involvement in alcohol and marijuana that should be considered along with other previously-identified sleep factors such as insomnia and insufficient sleep.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-19T02:45:32.570032-05:
      DOI: 10.1111/acer.13401
  • Protective effects of diallyl sulphide against ethanol-induced injury in
           rat adipose tissue and primary human adipocytes
    • Authors: Venkata Harini Kema; Imran Khan, Reshma Jamal, Sandeep Kumar Vishwakarma, Chandrakala Lakki Reddy, Kirti Parwani, Farhin Patel, Dhara Patel, Aleem A Khan, Palash Mandal
      Abstract: BackgroundAlcohol consumption is the fourth leading cause of death and disability worldwide. Several cellular pathways contribute to alcohol mediated tissue injury. Adipose tissue apart from being functioning as an endocrine organ secretes several hormones and cytokines known as adipokines that are known to play a significant role in alcohol induced tissue damage.ObjectiveThis study was designed to test the efficacy of diallyl sulphide (DAS) in regulating the alcohol induced outcomes on adipose tissue.MethodsMale Wistar rats were fed with 36% Lieber-DeCarli liquid diet containing ethanol for 4 weeks. Control rats were pair-fed with isocaloric diet containing maltodextrin instead of ethanol. During the last week of feeding protocol, ethanol fed rat group was given 200mg/Kg body weight of DAS through diet. We also studied DAS effect on isolated human primary adipocytes. Viability of human primary adipocytes on DAS treatment was assessed by MTT assay. Malondialdehyde (MDA), marker of oxidative stress was measured by HPLC and thiobarbituric acid method. Expression of inflammatory genes, lipogenic genes was studied by qRT-PCR and Western blotting. Serum inflammatory gene expression was studied by ELISA.ResultsOur study results showed that DAS could alleviate ethanol induced expression levels of pro-inflammatory and endoplasmic reticulum stress genes as well improve adipose tissue mass and adipocyte morphology in male Wistar rats fed with Lieber de Carli diet containing 6% ethanol. Further, we showed that DAS reduced the expression of lipogenic genes and improved lipid accumulation and adipocyte mass in human primary adipocytes treated with ethanol. Subsequently, we also showed that oxidative stress, as measured by the changes in malondialdehyde levels was reduced in both male Wistar rats and human primary adipocytes treated with ethanol plus DAS.ConclusionOur study results prove that DAS is effective in ameliorating ethanol induced damage of adipose tissue as is evident by the reduction brought about by DAS in oxidative stress, ER stress, and pro-inflammatory gene expression levels. DAS treatment also regulated lipogenic gene expression levels, thereby reducing free fatty acids release. In conclusion, this study has clinical implications with respect to alcohol-induced adipose tissue injury among alcohol users.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-17T02:50:32.138517-05:
      DOI: 10.1111/acer.13398
  • Alcohol Demand, Future Orientation, and Craving Mediate the Relation
           Between Depressive and Stress Symptoms and Alcohol Problems
    • Authors: Kathryn E. Soltis; Meghan McDevitt-Murphy, James G. Murphy
      Abstract: BackgroundElevated depression and stress have been linked to greater levels of alcohol problems among young adults even after taking into account drinking level. The current study attempts to elucidate variables that might mediate the relation between symptoms of depression and stress and alcohol problems, including alcohol demand, future time orientation, and cravingMethodsParticipants were 393 undergraduates (60.8% female, 78.9% White/Caucasian) who reported at least 2 binge drinking episodes (4/5+ drinks for women/men, respectively) in the previous month. Participants completed self-report measures of stress and depression, alcohol demand, future time orientation, craving, and alcohol problemsResultsIn separate mediation models that accounted for gender, race, and weekly alcohol consumption, future orientation and craving significantly mediated the relation between depressive symptoms and alcohol problems. Alcohol demand, future orientation, and craving significantly mediated the relation between stress symptoms and alcohol problemsConclusionsHeavy drinking young adults who experience stress or depression are likely to experience alcohol problems and this is due in part to elevations in craving and alcohol demand, and less sensitivity to future outcomes. Interventions targeting alcohol misuse in young adults with elevated levels of depression and stress should attempt to increase future orientation and decrease craving and alcohol reward value.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-12T04:11:52.628795-05:
      DOI: 10.1111/acer.13395
  • A Double-Blind Randomized Placebo-Controlled Trial of Oral Naltrexone for
           Heavy Drinking Smokers Seeking Smoking Cessation Treatment
    • Authors: Christopher W. Kahler; Patricia A. Cioe, Golfo K. Tzilos, Nichea S. Spillane, Lorenzo Leggio, Susan E. Ramsey, Richard A. Brown, Stephanie S. O'Malley
      Abstract: BackgroundPost hoc analyses of two randomized controlled trials suggest naltrexone may reduce alcohol use and improve smoking cessation outcomes among heavy drinkers receiving smoking cessation treatment. However, no studies have been conducted specifically to examine naltrexone for this purpose or to test whether naltrexone has benefit when added to smoking cessation counseling that explicitly addresses heavy drinking.MethodsWe recruited heavy drinking smokers from the community and randomized them to receive 10 weeks of either (a) 50 mg naltrexone [n = 75] or (b) placebo [n = 75] daily. Participants received 6 weeks of transdermal nicotine patch and 6 sessions of counseling that addressed both heavy drinking and smoking. Participants were followed for 26 weeks after their target quit smoking date.ResultsAcross medication conditions, there were substantial reductions at follow-up in percent heavy drinking days (primary outcome) and average drinks per week (secondary outcome). However, participants receiving naltrexone did not differ significantly from those receiving placebo on percent heavy drinking days (effect size d = -.04, 95% CI [-0.30, 0.22], p = .76) or average drinks per week (d = -.09, 95% CI [-0.35, 0.18], p = .54) during follow-up. Naltrexone compared to placebo was not associated with a significant increase in smoking abstinence rates during follow-up, odds ratio = 0.93, 95% CI [0.46, 1.86], p = .83. The effect of naltrexone on these outcomes was not significantly moderated by current alcohol dependence or gender.ConclusionsResults indicate that heavy drinking smokers, including those with current alcohol dependence, can make substantial reductions in drinking in the context of smoking cessation treatment. However, this study provided no evidence that naltrexone is efficacious for enhancing reductions in drinking or improving smoking cessation in this population. Limitations of this study included lower than desired sample size and modest adherence to study medication.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-12T03:10:27.216771-05:
      DOI: 10.1111/acer.13396
  • Parental monitoring and alcohol use across adolescence in Black and White
           girls: A cross-lagged panel mixture model
    • Authors: Shawn J. Latendresse; Feifei Ye, Tammy Chung, Alison Hipwell, Carolyn E. Sartor
      Abstract: BackgroundThe link between parental monitoring and adolescent alcohol use is well established, but the directionality of this relationship is somewhat elusive. The literature suggests that parental engagement serves a protective function with respect to alcohol use, but that parental monitoring may also diminish in response to recurrent risk behavior. The lower rate of alcohol use despite evidence of lower levels of parental monitoring in Black vs. White youth raises the question of for whom and under what conditions parental monitoring and alcohol use are associated.MethodsData were drawn from a community sample of 1634 female adolescents (954 Black, 680 White) from four age cohorts, assessed annually in an accelerated longitudinal design. The current study uses data spanning ages 12-17; parental monitoring and alcohol use were assessed via self-report, while demographic and adolescent psychosocial risk factors were derived from parent-reports when the girls were age 12. An autoregressive cross-lagged panel mixture model was used to identify discrete patterns of parental monitoring and alcohol use associations across adolescence, and psychosocial factors that differentiate between them.ResultsTwo discrete patterns of co-developing alcohol use and parental monitoring emerged: one with stable bidirectional and autoregressive links (79%), and another differing from the majority profile in terms of the absence (alcohol use to parental monitoring) and direction (parental monitoring to alcohol use) of cross-construct influences (21%). Those in the minority profile were, at age 12, more likely to have received public assistance, resided in single-parent households, reached puberty, and manifest more severe conduct problems.ConclusionsIdentifying subgroups of girls with distinct patterns of co-developing alcohol use and parental monitoring is particularly relevant to the development and implementation of family-level interventions, both in terms of targeting those with known demographic risk factors, and tailoring programs to address behavioral correlates, such as conduct problems.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-09T03:55:29.601693-05:
      DOI: 10.1111/acer.13386
  • Preventing Alcohol-Exposed Pregnancies: A Randomized Controlled Trial of a
           Self-Administered Version of Project CHOICES With College Students and
    • Authors: Linda Carter Sobell; Mark B. Sobell, Kenneth Johnson, Nicholas Heinecke, Sangeeta Agrawal, Burt Bolton
      Abstract: BackgroundAlcohol-exposed pregnancies (AEPs) are a preventable cause of birth defects and developmental disabilities for which many women are at risk. The initial 5-session Project CHOICES intervention was found to prevent AEPs. In the ensuing decade, there have been several additional CHOICES-like studies. The present study, Project Healthy CHOICES, had two objectives: (a) to compare outcomes for students vs. nonstudents; and (b) to test a self-administered mail-based version of the Project CHOICES intervention.MethodsA randomized controlled trial (RCT) compared two interventions for women of child-bearing age (18-44) who were at risk of an AEP: (a) Motivational Feedback based on Project CHOICES, and (b) Information Only. Advertisements recruited 354 women (145 college students; 209 nonstudents) at risk of an AEP. Intervention and study materials were available in English and Spanish. Of the 354 women, 44% were minorities (25% identified as Hispanics).ResultsAt the 6-month follow-up, the interventions did not differ and there was no Intervention by Student interaction. However, over the entire 6-month follow-up, significantly more students (68%) than nonstudents (46%) were not at risk of an AEP (2.1 Odds Ratio; CI = 1.47 – 2.95). For all groups, risk-reduction occurred primarily through effective contraception.ConclusionsThere was no significant difference between the two interventions. However, over the entire 6-month follow-up interval, college students were significantly more likely than nonstudents to not be at risk of an AEP and to use effective contraception. While the student groups had significantly higher reduced risk of AEP outcomes, there was also substantial risk- reduction for women in the Information Only condition. These results suggest that the most effective AEP prevention efforts would be to inform women at risk that they could become pregnant. Because about half of all pregnancies are unplanned, identifying women at risk and preventing the risk of AEPs should be a public health priority.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-07T02:50:57.338331-05:
      DOI: 10.1111/acer.13385
  • Independent and interactive effects of OPRM1 and DAT1 polymorphisms on
           alcohol consumption and subjective responses in social drinkers
    • Authors: Elise M. Weerts; Gary S. Wand, Brion Maher, Xiaoqiang Xu, Mary Ann Stephens, Xiaoju Yang, Mary E. McCaul
      Abstract: BackgroundThe current study examined independent and interactive effects of polymorphisms of the mu opioid receptor gene (OPRM1, A118G) and variable number tandem repeats of the dopamine transporter gene (DAT1, SLC6A3) on alcohol consumption and subjective responses to alcohol in 127 young, healthy, social drinkers.MethodsParticipants completed an in-person assessment, which included self-reported alcohol drinking patterns and blood sampling for DNA, and in a second visit, a cumulative alcohol dosing procedure with subjective ratings across multiple time points and breath alcohol concentrations (0.03-0.1%). DNA was analyzed for OPRM1 AA vs. AG/GG (*G) genotypes, DAT1 10-repeat allele (A10) vs. 9 or lesser alleles (A9), and ancestral informative markers.ResultsThere were significant epistatic interactions between OPRM1 and DAT1 genotypes. Subjective high assessment scale scores after alcohol consumption were highest in *G and A9 carriers, and lowest in *G and A10 carriers. Negative subjective effects were also highest in *G and A9 carriers. Effects were similar in a sensitivity analysis limited to Caucasian subjects. There were independent and epistatic interactions on drinking. The OPRM1 *G allele was independently associated with fewer heavy drinking days. The A9 allele was associated with a greater number of drinking days, which was attenuated in carriers of the *G allele.ConclusionsThese findings highlight the biological importance of interactions between these two genes, and interactions between brain opioid and dopamine systems.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-04T09:55:26.85874-05:0
      DOI: 10.1111/acer.13384
  • Drinker Types, Harm, and Policy-Related Variables: Results from the 2011
           International Alcohol Control Study in New Zealand
    • Authors: Martin Wall; Sally Casswell
      Abstract: BackgroundThe aim was to identify a typology of drinkers in New Zealand based on alcohol consumption, beverage choice, and public versus private drinking locations and investigate the relationship between drinker types, harms experienced, and policy-related variables.MethodsModel-based cluster analysis of male and female drinkers including volumes of alcohol consumed in the form of beer, wine, spirits, and ready-to-drinks (RTDs) in off- and on-premise settings. Cluster membership was then related to harm measures: alcohol dependence, self-rated health; and to 3 policy-relevant variables: liking for alcohol adverts, price paid for alcohol, and time of purchase.ResultsMales and females were analyzed separately. Men fell into 4 and women into 14 clearly discriminated clusters. The male clusters consumed a relatively high proportion of alcohol in the form of beer. Women had a number of small extreme clusters and some consumed mainly spirits-based RTDs, while others drank mainly wine. Those in the higher consuming clusters were more likely to have signs of alcohol dependency, to report lower satisfaction with their health, to like alcohol ads, and to have purchased late at night.ConclusionsConsumption patterns are sufficiently distinctive to identify typologies of male and female alcohol consumers. Women drinkers are more heterogeneous than men. The clusters relate differently to policy-related variables.
      PubDate: 2017-04-03T17:00:02.442949-05:
      DOI: 10.1111/acer.13372
  • “This treatment can really help me” – A longitudinal analysis of
           treatment readiness and its predictors in patients undergoing alcohol and
           drug rehabilitation treatment
    • Authors: Daniela Piontek; Stefan Kurktschiev, Ludwig Kraus, Stefan Hölscher, Fred Rist, Thomas Heinz, Norbert Scherbaum, Stefan Bender, Angela Buchholz
      Abstract: BackgroundThere is evidence that patients entering alcohol or drug treatment have different levels of treatment readiness and change their motivation differently over time. Nonetheless, existing studies mainly use single measures of motivation and do not consider individual differences. The present study addresses two questions: (1) How does treatment readiness change in patients with alcohol and drug use dependence over the course of an in-patient rehabilitation treatment; (2) Can changes in treatment readiness be explained by sociodemographic and substance use related characteristics?MethodsData from n=177 alcohol dependent patients and n=152 drug dependent patients were collected in two in-patient rehabilitation centers in Germany. Three single-item indicators of treatment readiness were assessed weekly over the course of the treatment. Sociodemographic and substance use related characteristics were assessed at baseline. In order to model developments of treatment readiness that may be different for each patient, multilevel analyses for longitudinal data were used.ResultsThe overall effect of time on treatment readiness was not significant, indicating that average motivation across all patients did not change over the course of the treatment. However, individuals showed different initial states and different rates of change. School education, employment status, earlier substance use treatments and craving predicted treatment readiness. Interactions with time were found for craving and marital status.ConclusionsThe results suggest that it is necessary to consider individual differences when evaluating treatment motivation in alcohol and drug dependent patients. The identification of variables predicting motivation may help to improve substance abuse treatment contents and outcomes.This article is protected by copyright. All rights reserved.
      PubDate: 2017-04-03T07:46:02.121554-05:
      DOI: 10.1111/acer.13383
  • Chronic Alcohol Exposure Differentially Alters One-Carbon Metabolism in
           Rat Liver and Brain
    • Authors: James Auta; Huaibo Zhang, Subhash C. Pandey, Alessandro Guidotti
      Abstract: BackgroundEpigenetic mechanisms such as DNA methylation play an important role in regulating the pathophysiology of alcoholism. Chronic alcohol exposure leads to behavioral changes as well as decreased expression of genes associated with synaptic plasticity. In the liver, it has been documented that chronic alcohol exposure impairs methionine synthase (Ms) activity leading to a decrease in SAM/SAH ratio which results in DNA hypomethylation; however it is not known whether similar alterations of S-adenosyl methionine (SAM) and S-adenosyl homocysteine (SAH) levels are also produced in brain.MethodMale adult Sprague Dawley rats were fed chronically with Leiber-DeCarli ethanol (9% v/v) or control diet. The ethanol diet-fed rats were withdrawn for 0 and 24 hrs. The cerebellum (CB) and liver tissues were dissected and used to investigate changes in one-carbon metabolism, SAM and SAH levels.ResultsWe found that chronic ethanol exposure decreased SAM levels, SAM/SAH ratio, MS, methylene tetrahydrofolate reductase (Mthfr) and betaine homocysteine methyltransferase (Bhmt) expression and increased methionine adenosyltransferase-2b (Mat2b) but not Mat2a expression in the liver. In contrast, chronic ethanol exposure decreased SAH levels, increased SAM/SAH ratio and the expression of Mat2a and S-adenosyl homocysteine hydrolase (Ahyc), while the levels of SAM or Bhmt expression in CB remained unaltered. However, in both liver and CB, chronic ethanol exposure decreased the expression of Ms and increased Mat2b expression. All chronic ethanol-induced changes of one-carbon metabolism in cerebellum, but not liver, returned to near-normal levels during ethanol withdrawal.ConclusionThese results indicate a decreased “methylation index” in liver and an increased “methylation index” in CB. The opposing changes of the “methylation index” suggest altered DNA methylation in liver and CB; thus implicating one-carbon metabolism in the pathophysiology of alcoholism.This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-30T10:00:36.388009-05:
      DOI: 10.1111/acer.13382
  • The Public Stigma of Birth Mothers of Children with Fetal Alcohol Spectrum
    • Authors: Patrick W. Corrigan; Juana Lorena Lara, Binoy Biren Shah, Kathleen T. Mitchell, Diana Simmes, Kenneth L. Jones
      Abstract: BackgroundStigma affects not only the person with a stigmatizing condition such as Fetal Alcohol Spectrum Disorders (FASD), but also their family members. The present study examined whether there are stigmatizing attitudes about biological mothers of children with FASD in a crowdsourced sample.MethodsThree hundred and eighty-nine participants were asked to rate levels of difference, disdain, and responsibility on four conditions: serious mental illness (SMI), substance use disorder (SUD), jail experience, and FASD. A budget allocation task was administered as a proxy of discrimination. Prior experience with each of the four conditions was noted to assess familiarity.ResultsResearch participants viewed mothers of children with FASD as more different, disdained, and responsible than women with SMI, SUD and jail experience. Budget allocation towards FASD service programs was significantly lower than all other human service programs. Familiarity with the three comparison conditions moderated most of the stigma ratings, but this effect was not seen in the FASD condition.ConclusionResults supported the notion that mothers of children with FASD are highly stigmatized for their past behavior. The data also suggested that the public might discriminate against this population. Stigma reduction interventions should focus on contact based strategies, rather than education based strategies.This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-30T10:00:30.384973-05:
      DOI: 10.1111/acer.13381
  • Academic Difficulties in Children with Prenatal Alcohol Exposure:
           Presence, Profile, and Neural Correlates
    • Authors: Leila Glass; Eileen M. Moore, Natacha Akshoomoff, Kenneth Lyons Jones, Edward P. Riley, Sarah N. Mattson
      Abstract: BackgroundAcademic achievement was evaluated in children with heavy prenatal alcohol exposure to determine potential strengths and weaknesses, evaluate the utility of different definitions for identifying low academic performance, and explore the neural correlates that may underlie academic performance.MethodsChildren (8 to 16 years) were assessed using the WIAT-II. Patterns of performance were examined in 2 subject groups: children with heavy prenatal alcohol exposure (n = 67) and controls (n = 61). A repeated-measures MANCOVA examining group differences on academic domain (reading, spelling, math) scores was conducted. Post hoc comparisons examined within-group profiles. Numbers and percentage of children with low achievement were calculated using several criteria. In a subsample (n = 42), neural correlates were analyzed using FreeSurfer v5.3 to examine relations between cortical structure (thickness and surface area) and performance.ResultsThe alcohol-exposed group performed worse than controls on all domains and had a unique academic profile, supported by a significant group × academic domain interaction (p 
      PubDate: 2017-03-24T17:00:03.993941-05:
      DOI: 10.1111/acer.13366
  • Trends in Alcohol Consumption Among Older Americans: National Health
           Interview Surveys, 1997 to 2014
    • Authors: Rosalind A. Breslow; I-Jen P. Castle, Chiung M. Chen, Barry I. Graubard
      Abstract: BackgroundThe majority of U.S. older adults consume alcoholic beverages. The older population is projected to almost double by 2050. Substantially more drinkers are likely.PurposeTo describe gender-specific trends (1997 to 2014) in prevalence of drinking status (lifetime abstention, former drinking, current drinking [including average volume], and binge drinking) among U.S. adults ages 60+ by age group and birth cohort.MethodsIn the 1997 to 2014 National Health Interview Surveys, 65,303 respondents ages 60+ (31,803 men, 33,500 women) were current drinkers; 6,570 men and 1,737 women were binge drinkers. Prevalence estimates and standard errors were computed by age group (60+, 60 to 64, 65 to 69, 70 to 74, 75 to 79, 80+) and birth cohort (
      PubDate: 2017-03-24T17:00:02.643103-05:
      DOI: 10.1111/acer.13365
  • Alcohol-Related Blackouts, Negative Alcohol-Related Consequences, and
           Motivations for Drinking Reported by Newly Matriculating Transgender
           College Students
    • Authors: Larry A. Tupler; Daniel Zapp, William DeJong, Maryam Ali, Sarah O'Rourke, John Looney, H. Scott Swartzwelder
      Abstract: BackgroundMany transgender college students struggle with identity formation and other emotional, social, and developmental challenges associated with emerging adulthood. A potential maladaptive coping strategy employed by such students is heavy drinking. Prior literature has suggested greater consumption and negative alcohol-related consequences (ARCs) in transgender students compared with their cisgender peers, but little is known about their differing experiences with alcohol-related blackouts (ARBs). We examined the level of alcohol consumption, the frequency of ARBs and other ARCs, and motivations for drinking reported by the largest sample of transgender college students to date.MethodsA Web survey from an alcohol-prevention program, AlcoholEdu for College™, assessed student demographics and drinking-related behaviors, experiences, and motivations of newly matriculating first-year college students. A self-reported drinking calendar was used to examine each of the following measures over the previous 14 days: number of drinking days, total number of drinks, and maximum number of drinks on any single day. A 7-point Likert scale was used to measure ARCs, ARBs, and drinking motivations. Transgender students of both sexes were compared with their cisgender peers.ResultsA total of 989 of 422,906 students (0.2%) identified as transgender. Over a 14-day period, transgender compared with cisgender students were more likely to consume alcohol over more days, more total drinks, and a greater number of maximum drinks on a single day. Transgender students (36%) were more likely to report an ARB than cisgender students (25%) as well as more negative academic, confrontation-related, social, and sexual ARCs. Transgender respondents more often cited stress reduction, social anxiety, self-esteem issues, and the inherent properties of alcohol as motivations for drinking. For nearly all measures, higher values were yielded by male-to-female than female-to-male transgender students.ConclusionsTransgender compared with cisgender first-year students engage in higher-risk drinking patterns and experience more ARBs and other negative ARCs. Broad institutional efforts are required to address the unique circumstances of transgender men and women and to reduce negative ARCs in college students, regardless of their sex or gender identity.Transgender college students may be at an increased risk of hazardous drinking due to heteronormative societal pressures. Using a Web survey from an alcohol-prevention program, we established that transgender compared with cisgender first-year students engaged in higher-risk drinking patterns and experienced more alcohol-related blackouts and other negative alcohol-related consequences. Transgender respondents more often cited stress reduction, social anxiety, self-esteem issues, and the inherent properties of alcohol as motivations for drinking. Presentations were more severe for male-to-female than female-to-male transgender students.
      PubDate: 2017-03-21T17:00:02.325428-05:
      DOI: 10.1111/acer.13358
  • Commentary on Kerr and Colleagues (): More Evidence that Social and Health
           Limitations in Childhood Increase the Risk of Lifetime Abstention from
    • Authors: Linda Ng Fat
      PubDate: 2017-03-16T07:45:34.94596-05:0
      DOI: 10.1111/acer.13360
  • FOXO1-AMPK-ULK1 Regulates Ethanol-induced Autophagy in Muscle by Enhanced
           ATG14 Association with the BECN1-PIK3C3 Complex
    • Authors: Ly Q. Hong-Brown; C Randell Brown, Maithili Navaratnarajah, Charles H. Lang
      Abstract: BackgroundExcessive alcohol (EtOH) consumption causes imbalances in protein metabolism. EtOH impairs protein synthesis in C2C12 myoblasts via a FoxO1-AMPK-TSC2-mTORC1 pathway and also induces degradation. As the underlying regulatory signaling cascades for these processes are currently poorly defined, we tested the hypothesis that alcohol-induced autophagy is mediated via activation of the PIK3C3 complex that is regulated by FoxO1-AMPK.MethodsC2C12 myoblasts were incubated with EtOH for various periods of time and autophagy pathway-related proteins were assessed by Western blotting and immunoprecipitation. Expression of targeted genes was suppressed using electroporation of specific siRNAs and chemical inhibitors.ResultsIncubation of C2C12 myoblasts with 100 mM EtOH increased the autophagy markers LC3B-II and ATG7, whereas levels of SQSTM1/p62 decreased. The lysosomal inhibitor bafilomycinA1 caused a similar response, although there was no additive effect when combined with ETOH. EtOH altered ULK1 S555 and S757 phosphorylation in a time- and AMPK-dependent manner. The activation of AMPK and ULK1 was associated with increased BECN1 (S93, S14) and PIK3C3/VPS34 (S164) phosphorylation as well as increased total ATG14 and PIK3C3. These changes promoted formation of the ATG14-AMBRA1-BECN1-PIK3C3 pro-autophagy complex that is important in autophagosome formation. EtOH-induced changes were not associated with increased production of PtdIns3P, which may be due to enhanced PIK3C3 complex binding with 14-3-3ϴ. Reduction of AMPK using siRNA suppressed the stimulatory effect of EtOH on BECN1 S93, S14 and PIK3C3 S164 phosphorylation in a time-dependent manner. Likewise, knockdown of AMPK or chemical inhibition of FoxO1 attenuated phosphorylation of ULK1 at both residues. Knockdown of ULK1 or BECN1 antagonized the effect of EtOH on LC3B-II, SQSTM1and ATG7 protein expression.ConclusionsEtOH-induced autophagy is mediated through changes in phosphorylation and interaction of various PIK3C3 complex components. This, in turn, is regulated either directly via FoxO1-AMPK, or indirectly via the FoxO1-AMPK-ULK1 signaling cascade in a mTORC1-independent or-dependent manner.This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-16T02:41:14.205352-05:
      DOI: 10.1111/acer.13377
  • Conditioned Stimulus Form does not explain failures to see
           Pavlovian-Instrumental-Transfer with ethanol-paired Conditioned Stimuli
    • Authors: Richard J. Lamb; Brett C. Ginsburg, Charles W. Schindler
      Abstract: BackgroundPavlovian-Instrumental-Transfer (PIT) examines the effects of associative learning upon instrumental responding. Previous studies examining PIT with ethanol-maintained responding showed increases in responding following presentation of an ethanol-paired Conditioned Stimulus (CS). Recently, we conducted two studies examining PIT with an ethanol-paired CS. One of these found increases in responding, while the other did not. This less robust demonstration of PIT may have resulted from the form of the CS used, as we used a 120-s light stimulus as a CS, while the previous studies used either a 120-s auditory stimulus or a 10-s light stimulus. The present study examined whether using conditions similar to our earlier study, but with either a 120-s auditory or a 10-s light stimulus as a CS, resulted in more robust PIT. We also examined the reliability of our previous failure to observe PIT.MethodsThree experiments were conducted examining whether PIT was obtained using (1) a 120-s light stimulus, (2) a 10-s light stimulus, or (3) a 120-s auditory stimulus as CSs.ResultsWe found PIT was not obtained using (1) a 120-s light stimulus as a CS, (2) a 10-s light stimulus as a CS, or (3) a 120-s auditory stimulus as a CS.ConclusionsThese results suggest that CS form does not account for our earlier failure to see PIT. Rather, factors like rat strain or how ethanol drinking is induced may account for when PIT is or is not observed.This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-14T11:21:01.038885-05:
      DOI: 10.1111/acer.13376
  • Prevalence of Prenatal Alcohol Exposure in the State of Texas as Assessed
           by Phosphatidylethanol in Newborn Dried Blood Spot Specimens
    • Authors: Ludmila N. Bakhireva; Janet Sharkis, Shikhar Shrestha, Tristan J Miranda-Sohrabji, Sonnie Williams, Rajesh C Miranda
      Abstract: BackgroundWhile 2-5% of school-aged children in the U.S. are estimated to be affected by Fetal Alcohol Spectrum Disorders (FASD), the prevalence of prenatal alcohol exposure (PAE) might be substantially under-reported. Our objective was to systematically estimate the prevalence of PAE in Texas by measuring a direct ethanol metabolite, phosphatidylethanol (PEth), in 1,000 infant residual dried blood spots (irDBS) in the Texas Newborn Screening Repository.MethodsAll Public Health Regions were represented proportional to their 2014 birth rate (~0.25% of total births). A cross-sectional study design (unit of observation: individual irDBS cards/infants) with additional ecologic sub-analysis (unit of observation: aggregate measures for each Texas PHR) was utilized. The study used PEth-irDBS to estimate the prevalence of PAE within 1 month before delivery for the state of Texas and each Texas PHR. The ecologic sub-analysis compared different geographical regions’ aggregate prevalence of PAE with a) retail liquor licenses (TABC, 2015), b) median household income by PHR (Texas Association of Counties, 2014), and c) prevalence of birth outcomes commonly associated with FASDResultsThe sample included an equal number of males and females; 47.8% non-Hispanic White, 40.8% Hispanic, 6.6% African American, and 4.8% Asian infants. In the entire sample, 8.4% of irDBS were positive for PEth (>20 ng/ml) indicative of PAE within approximately 1 month before delivery. Large regional differences were observed with mostly urban, high median-income regions demonstrating the highest prevalence.ConclusionsResults of this first systematic statewide PAE prevalence study demonstrate that PAE might be more prevalent than previously thought. Active case ascertainment efforts for FASD coupled with systematic objective assessment of PAE should expand to the national level to better estimate public health needs required to provide adequate services for children affected by PAE.This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-13T04:30:32.663407-05:
      DOI: 10.1111/acer.13375
  • Validating Harmful Alcohol Use as a Phenotype for Genetic Discovery Using
           Phosphatidylethanol and a Polymorphism in ADH1B
    • Authors: Amy C. Justice; Kathleen A. McGinnis, Jan Tate, Ke Xu, William C. Becker, Hongyu Zhao, Joel Gelernter, Henry R. Kranzler
      Abstract: BackgroundAlthough alcohol risk is heritable, few genetic risk variants have been identified. Longitudinal (EHR) data offer a largely untapped source of phenotypic information for genetic studies, but EHR-derived phenotypes for harmful alcohol exposure have yet to be validated. Using a variant of known effect, we used electronic health record (EHR) data to develop and validate a phenotype for harmful alcohol exposure that can be used to identify unknown genetic variants in large samples. Herein, we consider the validity of three approaches to using the three-item Alcohol Use Disorders Identification Test consumption measure (AUDIT-C) as a phenotype for harmful alcohol exposure.MethodsFirst, using longitudinal AUDIT-C data from the Veterans Aging Cohort Biomarker Study (VACS-BC), we compared three metrics of AUDIT-C using correlation coefficients: 1) AUDIT-C closest to blood sampling (closest AUDIT-C), 2) the highest value (highest AUDIT-C), 3) and longitudinal trajectories generated using joint trajectory modeling (AUDIT-C trajectory). Second, we compared the associations of the three AUDIT-C metrics with phosphatidylethanol (PEth), a direct, quantitative biomarker for alcohol in the overall sample using chi-square tests for trend. Lastly, in the sub-sample of African Americans (AAs; n=1,503), we compared the associations of the three AUDIT-C metrics with rs2066702 a common missense (Arg369Cys) polymorphism of the ADH1B gene, which encodes an alcohol dehydrogenase isozyme.ResultsThe sample (n=1,851, 94.5% male, 65% HIV+, mean age 52 years) had a median of 7 AUDIT-C scores over a median of 6.1 years. Highest AUDIT-C and AUDIT-C trajectory were correlated r=0.86. The closest AUDIT-C was obtained a median of 2.26 years after the VACS-BC blood draw. Overall and among AAs, all three AUDIT-C metrics were associated with PEth (all p
      PubDate: 2017-03-11T03:00:36.216289-05:
      DOI: 10.1111/acer.13373
  • Temporal Stability of Heavy Drinking Days and Drinking Reductions among
           Heavy Drinkers in the COMBINE Study
    • Authors: Katie Witkiewitz; Adam D. Wilson, Matthew R. Pearson, Kevin A. Hallgren, Daniel E. Falk, Raye Z. Litten, Henry R. Kranzler, Karl F. Mann, Deborah S. Hasin, Stephanie S. O'Malley, Raymond F. Anton
      Abstract: BackgroundRecently, the Food and Drug Administration (FDA) proposed to expand the options for primary endpoints in the development of medications for alcohol use disorder (AUD) to include either abstinence from alcohol or a non-abstinent outcome: no heavy drinking days (with a heavy drinking day defined as more than 3 drinks per day for women and more than 4 drinks per day for men [>3/>4 cutoff]). The FDA also suggested that 6 months would be the most appropriate length for a clinical trial to demonstrate the stability of this non-abstinent drinking outcome. However, few alcohol clinical trials have examined the stability of non-heavy drinking during and after treatment.MethodsIn a secondary analysis of the COMBINE study data (n=1383), we examined transitions in heavy drinking days during the course of treatment (months 1 through 4), during the transition out of treatment (months 4 through 7), and up to 12 months afterwards (months 13 through 16) using latent variable mixture models.ResultsHeavy drinking and non-heavy drinking were relatively stable in consecutive months (minimum agreement (kappa) = .64 for months 1 to 2). Most individuals were stable low-risk drinkers/abstainers or heavy drinkers by the end of treatment, as characterized by a 10% probability (or less) of transitioning out of either a no heavy drinking state or a heavy drinking state. More than two-thirds of the heavy drinkers who exceeded the heavy drinking threshold during treatment reported, on average, a 64% reduction in drinking frequency and a 38% reduction in drinking intensity from pretreatment drinking levels.ConclusionsThe results show stability of no heavy drinking as an outcome within the first four months of treatment and that the>3/>4 drink cutoff may mask substantial reductions in alcohol consumption among some patients. Future studies should explore the clinical utility of reduction endpoints.This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-10T10:59:35.209204-05:
      DOI: 10.1111/acer.13371
  • Alcoholic Liver Disease on the Rise: Interorgan Cross Talk Driving Liver
    • Authors: Srinivasan Dasarathy; J. Mark Brown
      Abstract: Advanced alcoholic liver disease (ALD) represents a substantial public health burden, threatening the lives of more than ten million people in the United States. Although the direct harmful effects of alcohol in the liver are nearly universally recognized, emerging evidence suggests alcohol also adversely affects other organs such as the intestine, skeletal muscle, adipose tissue, and likely many other tissues. In fact, the extrahepatic effects of alcohol clearly converge to impact the morbidity and mortality associated with chronic alcohol abuse. In the intestine alcohol consumption can profoundly impact both gut barrier function as well as reorganizing intestinal microbial communities. In the skeletal muscle, chronic alcohol consumption promotes sarcopenia by altering protein homeostasis or proteostasis. In parallel, alcohol can impact the normal endocrine and metabolic function of adipose tissue. Collectively, chronic alcohol abuse sustains an interorgan cross talk that provides the multiple hits necessary for progression to end stage liver disease. Here we briefly highlight several recent examples of interorgan cross talk underlying the morbidity and mortality associated with alcohol abuse, and discuss how these recent advances have the potential to impact therapeutic strategies for those suffering with ALD.This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-10T10:59:33.398042-05:
      DOI: 10.1111/acer.13370
  • Ethanol, TLR3, and TLR4 agonists have unique innate immune responses in
           neuron-like SH-SY5Y and microglia-like BV2
    • Authors: Colleen J. Lawrimore; Fulton T. Crews
      Abstract: BackgroundEthanol (EtOH) consumption leads to an increase of proinflammatory signaling via activation of toll-like receptors (TLRs) such as TLR3 and TLR4 that leads to kinase activation (ERK1/2, p38, TBK1), transcription factor activation (NFκB, IRF3) and increased transcription of pro-inflammatory cytokines such as TNFα, IL-1β, and IL-6. This immune signaling cascade is thought to play a role in neurodegeneration and alcohol use disorders. While microglia are considered to be the primary macrophage in brain, it is unclear what if any role neurons play in ethanol-induced proinflammatory signalingMethodsMicroglia-like BV2 and retinoic acid differentiated neuron-like SH-SY5Y were treated with TLR3 agonist Poly(I:C), TLR4 agonist LPS, or EtOH for 10 or 30 minutes to examine proinflammatory immune signaling kinase and transcription factor activation using western blot, and for 24 hours to examine induction of proinflammatory gene mRNA using RT-PCRResultsIn BV2, both LPS and Poly(I:C) increased p-ERK1/2, p-p38, and p-NFκB by 30 minutes, whereas EtOH decreased p-ERK1/2 and increased p-IRF3. LPS, Poly(I:C), and EtOH all increased TNFα and IL-1β mRNA, and EtOH further increased TLR2,7, 8, and MD-2 mRNA in BV2. In SH-SY5Y, LPS had no effect on kinase or proinflammatory gene expression. However, Poly(I:C) increased p-p38 and p-IRF3, and increased expression of TNFα, IL-1β, and IL-6, while EtOH increased p-p38, p-IRF3, p-TBK1 and p-NFκB while decreasing p-ERK1/2 and increasing expression of TLR3,7,8, and RAGE mRNA. HMGB1, a TLR agonist, was induced by LPS in BV2 and by EtOH in both cell types. EtOH was more potent at inducing proinflammatory gene mRNA in SH-SY5Y compared to BV2ConclusionsThese results support a novel and unique mechanism of ethanol, TLR3, and TLR4 signaling in neuron-like SH-SY5Y and microglia-like BV2 that likely contributes to the complexity of brain neuroimmune signaling.This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-08T13:20:28.174311-05:
      DOI: 10.1111/acer.13368
  • A cis-eQTL in OPRM1 is Associated with Subjective Response to Alcohol and
           Alcohol Use
    • Authors: Jacqueline M. Otto; Ian R. Gizer, Joseph D. Deak, Kimberly A. Fleming, Bruce D. Bartholow
      Abstract: BackgroundA functional polymorphism within the mu-opioid receptor (OPRM1) gene, rs1799971 (A118G), previously has been associated with measures of alcohol use and sensitivity to its effects, but findings have been inconclusive. A recent study suggested that a second nearby variant within OPRM1, rs3778150, is robustly associated with heroin dependence, and fully explained a smaller observed association with rs1799971. Given evidence that the rs3778150-C allele is associated with decreased OPRM1 expression levels in the human brain, the current study sought to test the hypothesis that rs3778150 represents a causal variant within OPRM1 that increases risk for a variety of alcohol use phenotypes.MethodsParticipants with genotype and phenotype data from a larger experimental study (N = 152) were assessed on measures of subjective response to alcohol and alcohol use. Measures included (1) the Self-Rating of the Effects of Alcohol (SRE) and the Alcohol Sensitivity Questionnaire (ASQ), (2) the Biphasic Alcohol Effects Scale (BAES) and ratings of subjective intoxication, and (3) average number of drinks per week in the past month.ResultsCompared to rs3778150-T homozygous individuals, carriers of the rs3778150-C allele exhibited significantly lower retrospective self-report levels of alcohol sensitivity. Carriers of the rs3778150-C allele also exhibited lower levels of BAES alcohol-related stimulation during an alcohol challenge, and reported higher levels of drinking in the last 30 days. With the exception of lower levels of BAES alcohol-related sedation, the rs1799971 variant did not show consistent significant association with any of the alcohol phenotypes in the presence of rs3778150.ConclusionsResults suggest that rs3778150 may be causally related to alcohol use phenotypes, and could potentially account for previously observed associations of rs1799971 with substance use phenotypes. Future studies may investigate potential causal relations among genetic variants in OPRM1, subjective response to alcohol, and drinking phenotypes to further delineate the effects of rs3778150.This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-08T13:20:24.063515-05:
      DOI: 10.1111/acer.13369
  • Using Factor Mixture Models to Evaluate the Type A/B Classification of
           Alcohol Use Disorders in a Heterogeneous Treatment Sample
    • Authors: Tom Hildebrandt; Elizabeth E. Epstein, Robyn Sysko, Donald A. Bux
      Abstract: BackgroundThe type A/B classification model for alcohol use disorders (AUDs) has received considerable empirical support. However, few studies examine the underlying latent structure of this subtyping model, which has been challenged as a dichotomization of a single drinking severity dimension. Type B, relative to type A, alcoholics represent those with early age of onset, greater familial risk, and worse outcomes from alcohol use.MethodWe examined the latent structure of the type A/B model using categorical, dimensional, and factor mixture models in a mixed gender community treatment-seeking sample of adults with an AUD.ResultsFactor analytic models identified 2-factors (drinking severity/externalizing psychopathology and internalizing psychopathology) underlying the type A/B indicators. A factor mixture model with 2-dimensions and 3-classes emerged as the best overall fitting model. The classes reflected a type A class and two type B classes (B1 and B2) that differed on the respective level of drinking severity/externalizing pathology and internalizing pathology. Type B1 had a greater prevalence of women and more internalizing pathology and B2 had a greater prevalence of men and more drinking severity/externalizing pathology. The 2-factor, 3-class model also exhibited predictive validity by explaining significant variance in 12-month drinking and drug use outcomes.ConclusionsThe model identified in the current study may provide a basis for examining different sources of heterogeneity in the course and outcome of AUDs.This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-01T02:55:40.53953-05:0
      DOI: 10.1111/acer.13367
  • Heavy prenatal alcohol exposure is related to smaller corpus callosum in
           newborn MRI scans
    • Authors: Sandra W. Jacobson; Joseph L. Jacobson, Christopher D. Molteno, Christopher M. R. Warton, Pia Wintermark, H Eugene Hoyme, Greetje De Jong, Paul Taylor, Fleur Warton, Nadine M. Lindinger, R Colin Carter, Neil C. Dodge, Ellen Grant, Simon K. Warfield, Lilla Zöllei, André J. W van der Kouwe, Ernesta M. Meintjes
      Abstract: BackgroundMRI studies have consistently demonstrated disproportionately smaller corpus callosa in individuals with a history of prenatal alcohol exposure but have not previously examined the feasibility of detecting this effect in infants. Tissue segmentation of the newborn brain is challenging because analysis techniques developed for the adult brain are not directly transferable, and segmentation for cerebral morphometry is difficult in neonates, due to the latter's incomplete myelination. This study is the first to use volumetric structural MRI to investigate prenatal alcohol exposure effects in newborns using manual tracing and to examine the cross-sectional area of the corpus callosum (CC).Methods43 nonsedated infants born to 32 Cape Coloured heavy drinkers and 11 controls recruited prospectively during pregnancy were scanned using a custom-designed birdcage coil for infants, which increases signal-to-noise ratio almost two-fold compared to the standard head coil. Alcohol use was ascertained prospectively during pregnancy, and FASD diagnosis was conducted by expert dysmorphologists. Data were acquired using a multi-echo FLASH protocol adapted for newborns, and a knowledge-based procedure was used to hand-segment the neonatal brains.ResultsCC was disproportionately smaller in alcohol-exposed neonates than controls after controlling for intracranial volume. By contrast, CC area was unrelated to infant sex, gestational age, age at scan, or maternal smoking, marijuana, or methamphetamine use during pregnancy.ConclusionsGiven that midline craniofacial anomalies have been recognized as a hallmark of FAS in humans and animal models since this syndrome was first identified, the CC deficit identified here in newborns may support early identification of a range of midline structural impairments. Smaller CC during the newborn period may provide an early indicator of fetal alcohol-related cognitive deficits that have been linked to this critically important brain structure in childhood and adolescence.This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-01T02:50:47.127545-05:
      DOI: 10.1111/acer.13363
  • Two Brief Measures of Alcohol Use Produce Different Results: AUDIT-C and
           Quick Drinking Screen
    • Authors: Brian Letourneau; Linda Carter Sobell, Mark B. Sobell, Sangeeta Agrawal, Christopher J. Gioia
      Abstract: BackgroundSeveral psychometrically sound measures of alcohol use have been developed to assess drinking. The AUDIT, and its shorter counterpart the AUDIT-C, which contains the first three AUDIT questions, were developed by the World Health Organization and have become the preferred brief measures for screening and evaluating problem severity. This study compared the first three questions on the AUDIT with another psychometrically sound brief measure of alcohol use, the Quick Drinking Screen (QDS).MethodsData were obtained from a randomized controlled trial of a mail-based intervention promoting self-change with 472 alcohol abusers (n = 280, no prior alcohol treatment; n = 192, prior alcohol treatment). Participants’ retrospective self-reports of alcohol consumption were collected using the QDS and the three AUDIT-C questions and compared. Although both measures contain similar questions (2 quantity-frequency and 1 binge drinking), they differ in two important ways: (a) temporal interval over which data are collected, and (b) formatting of response options (i.e., a continuous number vs. categorical).ResultsIntraclass correlations for drinking variables were moderate to moderately high. A repeated measures MANOVA using treatment condition and gender as variables revealed significant differences in absolute values between the two drinking measures with the QDS showing greater consumption on almost all variables. Participants’ numerical answers on the QDS were compared to their categorical answers to the similar alcohol use questions on the AUDIT-C. The comparison revealed that participants’ answers on the AUDIT-C were associated with extreme variability compared to their QDS answers. This variability suggests the AUDIT-C would be unreliable as a quantitative measure of alcohol consumption.ConclusionsThe differences between the three alcohol use questions on the AUDIT-C's and the same questions on the QDS may reflect the imprecision of the AUDIT-C's drinking response categories. Results suggest that the QDS can be used to identify risky drinking and to provide a more informative characterization of a drinker's alcohol consumption than that provided by the AUDIT-C.This article is protected by copyright. All rights reserved.
      PubDate: 2017-03-01T02:50:25.309531-05:
      DOI: 10.1111/acer.13364
  • Genomewide Association Study of Alcohol Dependence Identifies Risk Loci
           Altering Ethanol-response Behaviors in Model Organisms
    • Authors: Amy E. Adkins; Laura M. Hack, Tim B. Bigdeli, Vernell S. Williamson, G Omari McMichael, Mohammed Mamdani, Alexis Edwards, Fazil Aliev, Robin F. Chan, Poonam Bhandari, Richard C. Raabe, Joseph T. Alaimo, GinaMari G. Blackwell, Arden A. Moscati, Ryan S. Poland, Benjamin Rood, Diana G. Patterson, Dermot Walsh, , John B. Whitfield, Gu Zhu, Grant W. Montgomery, Anjali K. Henders, Nicholas G. Martin, Andrew C. Heath, Pamela A.F. Madden, Josef Frank, Monika Ridinger, Norbert Wodarz, Michael Soyka, Peter Zill, Marcus Ising, Markus M Nöthen, Falk Kiefer, Marcella Rietschel, , Joel Gelernter, Richard Sherva, Ryan Koesterer, Laura Almasy, Hongyu Zhao, Henry R. Kranzler, Lindsay A. Farrer, Brion S. Maher, Carol A. Prescott, Danielle M. Dick, Silviu A. Bacanu, Laura D. Mathies, Andrew G. Davies, Vladimir I. Vladimirov, Mike Grotewiel, M. Scott Bowers, Jill C. Bettinger, Bradley T. Webb, Michael F. Miles, Kenneth S. Kendler, Brien P. Riley
      Abstract: BackgroundAlcohol Dependence (AD) shows evidence for genetic liability, but genes influencing risk remain largely unidentified.MethodsWe conducted a genomewide association study in 706 related AD cases and 1748 unscreened population controls from Ireland. We sought replication in 15,496 samples of European descent. We used model organisms to assess the role of orthologous genes in ethanol response behaviors. We tested one primate-specific gene for expression differences in case/control post-mortem brain tissue.ResultsWe detected significant association in COL6A3 and suggestive association in two previously implicated loci, KLF12 and RYR3. None of these signals are significant in replication. A suggestive signal in the long noncoding RNA LOC339975 is significant in case:control meta-analysis, but not in a population sample. Knockdown of a COL6A3 ortholog in C. elegans reduced ethanol sensitivity. Col6a3 expression correlated with handling-induced convulsions in mice. Loss of function of the KLF12 ortholog in C. elegans impaired development of acute functional tolerance. Klf12 expression correlated with locomotor activation following ethanol injection in mice. Loss of function of the RYR3 ortholog reduced ethanol sensitivity in C. elegans and rapid tolerance in Drosophila. The ryanodine receptor antagonist dantrolene reduced motivation to self-administer ethanol in rats. Expression of LOC339975 does not differ between cases and controls but is reduced in carriers of the associated rs11726136 allele in nucleus accumbens.ConclusionsWe detect association between AD and COL6A3, KLF12, RYR3 and LOC339975. Despite non-replication of COL6A3, KLF12 and RYR3 signals, orthologs of these genes influence behavioral response to ethanol in model organisms, suggesting potential involvement in human ethanol response and AD liability. The associated LOC339975 allele may influence gene expression in human nucleus accumbens. Although the functions of long noncoding RNAs are poorly understood, there is mounting evidence implicating these genes in multiple brain functions and disordersThis article is protected by copyright. All rights reserved.
      PubDate: 2017-02-22T15:25:30.785846-05:
      DOI: 10.1111/acer.13362
  • Global transcriptional response of human liver cells to ethanol stress of
           different strength reveals hormetic behavior
    • Authors: Wolfgang Schmidt-Heck; Eva C. Wönne, Thomas Hiller, Uwe Menzel, Dirk Koczan, Georg Damm, Daniel Seehofer, Fanny Knöspel, Nora Freyer, Reinhard Guthke, Steven Dooley, Katrin Zeilinger
      Abstract: BackgroundThe liver is the major site for alcohol metabolism in the body and therefore, the primary target organ for ethanol-induced toxicity. In this study, we investigated the in vitro response of human liver cells to different ethanol concentrations in a perfused bioartificial liver device that mimics the complex architecture of the natural organ.MethodsPrimary human liver cells were cultured in the bioartificial liver device and treated for 24 hours with medium containing 150 mM (low), 300 mM (medium) or 600 mM (high) ethanol, while a control culture was kept untreated. Gene expression patterns for each ethanol concentration were monitored using Affymetrix Human Gene 1.0 ST Genechips. Scaled expression profiles of differentially expressed genes (DEGs) were clustered using Fuzzy c-means algorithm. In addition, functional classification methods, KEGG pathway mapping and also a machine learning approach (Random Forest) were utilized.ResultsA number of 966 (150 mM ethanol), 1,334 (300 mM ethanol), or 4,132 (600 mM ethanol) genes were found to be differentially expressed. Dose-response relationships of the identified clusters of co-expressed genes showed a monotonic, threshold or non-monotonic (hormetic) behavior. Functional classification of DEGs revealed that low or medium ethanol concentrations operate adaptation processes, while alterations observed for the high ethanol concentration reflect the response to cellular damage. The genes displaying a hormetic response were functionally characterized by over-represented ‘cellular ketone metabolism’ and ‘carboxylic acid metabolism’. Altered expression of the genes BAHD1 and H3F3B was identified as sufficient to classify the samples according to the applied ethanol doses.ConclusionsDifferent pathways of metabolic and epigenetic regulation are affected by ethanol exposition and partly undergo hormetic regulation in the bioartificial liver device. Gene expression changes observed at high ethanol concentrations reflect in some aspects the situation of alcoholic hepatitis in humansThis article is protected by copyright. All rights reserved.
      PubDate: 2017-02-22T15:10:30.891706-05:
      DOI: 10.1111/acer.13361
  • Oxytocin Reduces Ethanol Self-Administration in Mice
    • Authors: Courtney E. King; William C. Griffin, Lauryn N. Luderman, Malcolm M. Kates, Jacqueline F. McGinty, Howard C. Becker
      Abstract: BackgroundExcessive ethanol consumption remains an important health concern and effective treatments are lacking. The central oxytocin system has emerged as a potentially important therapeutic target for alcohol and drug addiction. These studies tested the hypothesis that oxytocin reduces ethanol consumption.MethodsMale C57BL/6J mice were given access to ethanol (20% v/v) using a model of binge-like drinking (“drinking-in-the-dark”) that also included the use of lickometer circuits to evaluate the temporal pattern of intake as well as 2-bottle choice drinking in the home cage. In addition, ethanol (12% v/v) and sucrose (5% w/v) self-administration on fixed- and progressive- ratio schedules were also evaluated. A wide range of systemically administered oxytocin doses were tested (0 to 10 mg/kg) in these models.ResultsOxytocin (0, 0.3, 1, 3 or 10mg/kg) dose-dependently reduced ethanol consumption (maximal 45% reducton) in the binge drinking model, with lower effective doses having minimal effects on general locomotor activity. Oxytocin's effect was blocked by pretreatment with an oxytocin receptor antagonist and the pattern of contacts (licks) at the ethanol bottle suggested a reduction in motivation to drink ethanol. Oxytocin decreased 2-bottle choice drinking without altering general fluid intake. Oxytocin also reduced operant responding for ethanol and sucrose in a dose-related manner. However, oxytocin decreased responding and motivation (breakpoint values) for ethanol at doses that did not alter responding for sucrose.DiscussionThese results indicate that oxytocin reduces ethanol consumption in different models of self-administration. The effects are not likely due to a general sedative effect of the neuropeptide. Further, oxytocin reduces motivation for ethanol at doses that do not alter responding for a natural reward (sucrose). While some evidence supports a role for oxytocin receptors in mediating these effects, additional studies are needed to further elucidate underlying mechanisms. Neverthess, these results support the therapeutic potential of oxytocin as a treatment for alcohol use disorder.This article is protected by copyright. All rights reserved.
      PubDate: 2017-02-17T13:01:10.873187-05:
      DOI: 10.1111/acer.13359
  • Issue Information
    • Pages: 871 - 874
      PubDate: 2017-04-25T05:32:23.57144-05:0
      DOI: 10.1111/acer.13189
  • Articles of Public Interest
    • Pages: 875 - 875
      PubDate: 2017-04-25T05:32:25.234552-05:
      DOI: 10.1111/acer.13397
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