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Showing 1 - 200 of 1589 Journals sorted alphabetically
Abacus     Hybrid Journal   (Followers: 12, SJR: 0.48, h-index: 22)
About Campus     Hybrid Journal   (Followers: 5)
Academic Emergency Medicine     Hybrid Journal   (Followers: 65, SJR: 1.385, h-index: 91)
Accounting & Finance     Hybrid Journal   (Followers: 47, SJR: 0.547, h-index: 30)
ACEP NOW     Free   (Followers: 1)
Acta Anaesthesiologica Scandinavica     Hybrid Journal   (Followers: 52, SJR: 1.02, h-index: 88)
Acta Archaeologica     Hybrid Journal   (Followers: 164, 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: 6, SJR: 0.112, h-index: 1)
Acta Paediatrica     Hybrid Journal   (Followers: 56, SJR: 0.794, h-index: 88)
Acta Physiologica     Hybrid Journal   (Followers: 6, SJR: 1.69, h-index: 88)
Acta Polymerica     Hybrid Journal   (Followers: 9)
Acta Psychiatrica Scandinavica     Hybrid Journal   (Followers: 35, SJR: 2.518, h-index: 113)
Acta Zoologica     Hybrid Journal   (Followers: 7, SJR: 0.459, h-index: 29)
Acute Medicine & Surgery     Hybrid Journal   (Followers: 4)
Addiction     Hybrid Journal   (Followers: 35, SJR: 2.086, h-index: 143)
Addiction Biology     Hybrid Journal   (Followers: 14, SJR: 2.091, h-index: 57)
Adultspan J.     Hybrid Journal   (SJR: 0.127, h-index: 4)
Advanced Energy Materials     Hybrid Journal   (Followers: 27, SJR: 6.411, h-index: 86)
Advanced Engineering Materials     Hybrid Journal   (Followers: 26, SJR: 0.81, h-index: 81)
Advanced Functional Materials     Hybrid Journal   (Followers: 51, SJR: 5.21, h-index: 203)
Advanced Healthcare Materials     Hybrid Journal   (Followers: 14, SJR: 0.232, h-index: 7)
Advanced Materials     Hybrid Journal   (Followers: 267, SJR: 9.021, h-index: 345)
Advanced Materials Interfaces     Hybrid Journal   (Followers: 6, SJR: 1.177, h-index: 10)
Advanced Optical Materials     Hybrid Journal   (Followers: 7, SJR: 2.488, h-index: 21)
Advanced Science     Open Access   (Followers: 5)
Advanced Synthesis & Catalysis     Hybrid Journal   (Followers: 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: 21)
Africa Research Bulletin: Economic, Financial and Technical Series     Hybrid Journal   (Followers: 13)
Africa Research Bulletin: Political, Social and Cultural Series     Hybrid Journal   (Followers: 10)
African Development Review     Hybrid Journal   (Followers: 33, SJR: 0.275, h-index: 17)
African J. of Ecology     Hybrid Journal   (Followers: 16, SJR: 0.477, h-index: 39)
Aggressive Behavior     Hybrid Journal   (Followers: 15, SJR: 1.391, h-index: 66)
Aging Cell     Open Access   (Followers: 11, SJR: 4.374, h-index: 95)
Agribusiness : an Intl. J.     Hybrid Journal   (Followers: 3, SJR: 0.627, h-index: 14)
Agricultural and Forest Entomology     Hybrid Journal   (Followers: 16, SJR: 0.925, h-index: 43)
Agricultural Economics     Hybrid Journal   (Followers: 45, SJR: 1.099, h-index: 51)
AIChE J.     Hybrid Journal   (Followers: 32, SJR: 1.122, h-index: 120)
Alcoholism and Drug Abuse Weekly     Hybrid Journal   (Followers: 7)
Alcoholism Clinical and Experimental Research     Hybrid Journal   (Followers: 7, SJR: 1.416, h-index: 125)
Alimentary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 33, SJR: 2.833, h-index: 138)
Alimentary Pharmacology & Therapeutics Symposium Series     Hybrid Journal   (Followers: 3)
Allergy     Hybrid Journal   (Followers: 51, SJR: 3.048, h-index: 129)
Alternatives to the High Cost of Litigation     Hybrid Journal   (Followers: 3)
American Anthropologist     Hybrid Journal   (Followers: 148, 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: 92, SJR: 2.325, h-index: 51)
American J. of Economics and Sociology     Hybrid Journal   (Followers: 29, SJR: 0.211, h-index: 26)
American J. of Hematology     Hybrid Journal   (Followers: 34, 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: 16, SJR: 1.115, h-index: 61)
American J. of Medical Genetics Part B: Neuropsychiatric Genetics     Hybrid Journal   (Followers: 4, SJR: 1.771, h-index: 107)
American J. of Medical Genetics Part C: Seminars in Medical Genetics     Partially Free   (Followers: 6, SJR: 2.315, h-index: 79)
American J. of Physical Anthropology     Hybrid Journal   (Followers: 37, SJR: 1.41, h-index: 88)
American J. of Political Science     Hybrid Journal   (Followers: 278, SJR: 5.101, h-index: 114)
American J. of Primatology     Hybrid Journal   (Followers: 15, 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: 17, SJR: 2.792, h-index: 140)
American J. on Addictions     Hybrid Journal   (Followers: 9, SJR: 0.843, h-index: 57)
Anaesthesia     Hybrid Journal   (Followers: 138, SJR: 1.404, h-index: 88)
Analyses of Social Issues and Public Policy     Hybrid Journal   (Followers: 9, SJR: 0.397, h-index: 18)
Analytic Philosophy     Hybrid Journal   (Followers: 18)
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: 219)
Angewandte Chemie Intl. Edition     Hybrid Journal   (Followers: 222, SJR: 6.229, h-index: 397)
Animal Conservation     Hybrid Journal   (Followers: 41, SJR: 1.576, h-index: 62)
Animal Genetics     Hybrid Journal   (Followers: 8, SJR: 0.957, h-index: 67)
Animal Science J.     Hybrid Journal   (Followers: 6, SJR: 0.569, h-index: 24)
Annalen der Physik     Hybrid Journal   (Followers: 5, SJR: 1.46, h-index: 40)
Annals of Anthropological Practice     Partially Free   (Followers: 2, SJR: 0.187, h-index: 5)
Annals of Applied Biology     Hybrid Journal   (Followers: 7, SJR: 0.816, h-index: 56)
Annals of Clinical and Translational Neurology     Open Access   (Followers: 1)
Annals of Human Genetics     Hybrid Journal   (Followers: 9, SJR: 1.191, h-index: 67)
Annals of Neurology     Hybrid Journal   (Followers: 47, SJR: 5.584, h-index: 241)
Annals of Noninvasive Electrocardiology     Hybrid Journal   (Followers: 1, SJR: 0.531, h-index: 38)
Annals of Public and Cooperative Economics     Hybrid Journal   (Followers: 8, SJR: 0.336, h-index: 23)
Annals of the New York Academy of Sciences     Hybrid Journal   (Followers: 5, SJR: 2.389, h-index: 189)
Annual Bulletin of Historical Literature     Hybrid Journal   (Followers: 13)
Annual Review of Information Science and Technology     Hybrid Journal   (Followers: 14)
Anthropology & Education Quarterly     Hybrid Journal   (Followers: 25, SJR: 0.72, h-index: 31)
Anthropology & Humanism     Hybrid Journal   (Followers: 17, SJR: 0.137, h-index: 3)
Anthropology News     Hybrid Journal   (Followers: 15)
Anthropology of Consciousness     Hybrid Journal   (Followers: 11, SJR: 0.172, h-index: 5)
Anthropology of Work Review     Hybrid Journal   (Followers: 11, SJR: 0.256, h-index: 5)
Anthropology Today     Hybrid Journal   (Followers: 89, SJR: 0.545, h-index: 15)
Antipode     Hybrid Journal   (Followers: 49, SJR: 2.212, h-index: 69)
Anz J. of Surgery     Hybrid Journal   (Followers: 8, SJR: 0.432, h-index: 59)
Anzeiger für Schädlingskunde     Hybrid Journal   (Followers: 1)
Apmis     Hybrid Journal   (Followers: 1, SJR: 0.855, h-index: 73)
Applied Cognitive Psychology     Hybrid Journal   (Followers: 70, SJR: 0.754, h-index: 69)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 7, SJR: 0.632, h-index: 58)
Applied Psychology     Hybrid Journal   (Followers: 207, SJR: 1.023, h-index: 64)
Applied Psychology: Health and Well-Being     Hybrid Journal   (Followers: 49, 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: 14, SJR: 1.025, h-index: 55)
Aquaculture Research     Hybrid Journal   (Followers: 31, SJR: 0.807, h-index: 60)
Aquatic Conservation Marine and Freshwater Ecosystems     Hybrid Journal   (Followers: 36, SJR: 1.047, h-index: 57)
Arabian Archaeology and Epigraphy     Hybrid Journal   (Followers: 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: 15, SJR: 0.156, h-index: 2)
Architectural Design     Hybrid Journal   (Followers: 25, SJR: 0.261, h-index: 9)
Archiv der Pharmazie     Hybrid Journal   (Followers: 3, SJR: 0.628, h-index: 43)
Archives of Drug Information     Hybrid Journal   (Followers: 5)
Archives of Insect Biochemistry and Physiology     Hybrid Journal   (SJR: 0.768, h-index: 54)
Area     Hybrid Journal   (Followers: 12, SJR: 0.938, h-index: 57)
Art History     Hybrid Journal   (Followers: 246, SJR: 0.153, h-index: 13)
Arthritis & Rheumatology     Hybrid Journal   (Followers: 52, 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: 15)
Asia & the Pacific Policy Studies     Open Access   (Followers: 16)
Asia Pacific J. of Human Resources     Hybrid Journal   (Followers: 320, SJR: 0.494, h-index: 19)
Asia Pacific Viewpoint     Hybrid Journal   (Followers: 1, SJR: 0.616, h-index: 26)
Asia-Pacific J. of Chemical Engineering     Hybrid Journal   (Followers: 8, SJR: 0.345, h-index: 20)
Asia-pacific J. of Clinical Oncology     Hybrid Journal   (Followers: 6, SJR: 0.554, h-index: 14)
Asia-Pacific J. of Financial Studies     Hybrid Journal   (SJR: 0.241, h-index: 7)
Asia-Pacific Psychiatry     Hybrid Journal   (Followers: 4, SJR: 0.377, h-index: 7)
Asian Economic J.     Hybrid Journal   (Followers: 8, SJR: 0.234, h-index: 21)
Asian Economic Policy Review     Hybrid Journal   (Followers: 4, SJR: 0.196, h-index: 12)
Asian J. of Control     Hybrid Journal   (SJR: 0.862, h-index: 34)
Asian J. of Endoscopic Surgery     Hybrid Journal   (SJR: 0.394, h-index: 7)
Asian J. of Organic Chemistry     Hybrid Journal   (Followers: 6, SJR: 1.443, h-index: 19)
Asian J. of Social Psychology     Hybrid Journal   (Followers: 5, SJR: 0.665, h-index: 37)
Asian Politics and Policy     Hybrid Journal   (Followers: 12, SJR: 0.207, h-index: 7)
Asian Social Work and Policy Review     Hybrid Journal   (Followers: 5, SJR: 0.318, h-index: 5)
Asian-pacific Economic Literature     Hybrid Journal   (Followers: 5, SJR: 0.168, h-index: 15)
Assessment Update     Hybrid Journal   (Followers: 4)
Astronomische Nachrichten     Hybrid Journal   (Followers: 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: 15, SJR: 1.095, h-index: 66)
Austral Entomology     Hybrid Journal   (Followers: 9, SJR: 0.524, h-index: 28)
Australasian J. of Dermatology     Hybrid Journal   (Followers: 8, SJR: 0.714, h-index: 40)
Australasian J. On Ageing     Hybrid Journal   (Followers: 6, SJR: 0.39, h-index: 22)
Australian & New Zealand J. of Statistics     Hybrid Journal   (Followers: 14, SJR: 0.275, h-index: 28)
Australian Accounting Review     Hybrid Journal   (Followers: 3, SJR: 0.709, h-index: 14)
Australian and New Zealand J. of Family Therapy (ANZJFT)     Hybrid Journal   (Followers: 3, SJR: 0.382, h-index: 12)
Australian and New Zealand J. of Obstetrics and Gynaecology     Hybrid Journal   (Followers: 47, 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: 7, SJR: 0.482, h-index: 46)
Australian Economic History Review     Hybrid Journal   (Followers: 5, SJR: 0.171, h-index: 12)
Australian Economic Papers     Hybrid Journal   (Followers: 31, SJR: 0.23, h-index: 9)
Australian Economic Review     Hybrid Journal   (Followers: 6, SJR: 0.357, h-index: 21)
Australian Endodontic J.     Hybrid Journal   (Followers: 3, SJR: 0.513, h-index: 24)
Australian J. of Agricultural and Resource Economics     Hybrid Journal   (Followers: 3, SJR: 0.765, h-index: 36)
Australian J. of Grape and Wine Research     Hybrid Journal   (Followers: 5, SJR: 0.879, h-index: 56)
Australian J. of Politics & History     Hybrid Journal   (Followers: 14, SJR: 0.203, h-index: 14)
Australian J. of Psychology     Hybrid Journal   (Followers: 18, SJR: 0.384, h-index: 30)
Australian J. of Public Administration     Hybrid Journal   (Followers: 408, SJR: 0.418, h-index: 29)
Australian J. of Rural Health     Hybrid Journal   (Followers: 5, SJR: 0.43, h-index: 34)
Australian Occupational Therapy J.     Hybrid Journal   (Followers: 72, SJR: 0.59, h-index: 29)
Australian Psychologist     Hybrid Journal   (Followers: 12, SJR: 0.331, h-index: 31)
Australian Veterinary J.     Hybrid Journal   (Followers: 21, SJR: 0.459, h-index: 45)
Autism Research     Hybrid Journal   (Followers: 36, SJR: 2.126, h-index: 39)
Autonomic & Autacoid Pharmacology     Hybrid Journal   (SJR: 0.371, h-index: 29)
Banks in Insurance Report     Hybrid Journal   (Followers: 1)
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 11, SJR: 0.539, h-index: 70)
Basic and Applied Pathology     Open Access   (Followers: 2, SJR: 0.113, h-index: 4)
Basin Research     Hybrid Journal   (Followers: 5, SJR: 1.54, h-index: 60)
Bauphysik     Hybrid Journal   (Followers: 2, SJR: 0.194, h-index: 5)
Bauregelliste A, Bauregelliste B Und Liste C     Hybrid Journal  
Bautechnik     Hybrid Journal   (Followers: 1, SJR: 0.321, h-index: 11)
Behavioral Interventions     Hybrid Journal   (Followers: 9, SJR: 0.297, h-index: 23)
Behavioral Sciences & the Law     Hybrid Journal   (Followers: 24, SJR: 0.736, h-index: 57)
Berichte Zur Wissenschaftsgeschichte     Hybrid Journal   (Followers: 10, SJR: 0.11, h-index: 5)
Beton- und Stahlbetonbau     Hybrid Journal   (Followers: 2, SJR: 0.493, h-index: 14)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 6, SJR: 0.311, h-index: 26)
Bioelectromagnetics     Hybrid Journal   (Followers: 1, SJR: 0.568, h-index: 64)
Bioengineering & Translational Medicine     Open Access  
BioEssays     Hybrid Journal   (Followers: 10, SJR: 3.104, h-index: 155)
Bioethics     Hybrid Journal   (Followers: 14, SJR: 0.686, h-index: 39)
Biofuels, Bioproducts and Biorefining     Hybrid Journal   (Followers: 1, SJR: 1.725, h-index: 56)
Biological J. of the Linnean Society     Hybrid Journal   (Followers: 16, SJR: 1.172, h-index: 90)
Biological Reviews     Hybrid Journal   (Followers: 4, SJR: 6.469, h-index: 114)
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 41, SJR: 0.12, h-index: 1)
Biology of the Cell     Full-text available via subscription   (Followers: 9, SJR: 1.812, h-index: 69)
Biomedical Chromatography     Hybrid Journal   (Followers: 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: 44, SJR: 0.415, h-index: 55)
Biotechnology and Bioengineering     Hybrid Journal   (Followers: 141, SJR: 1.633, h-index: 146)
Biotechnology J.     Hybrid Journal   (Followers: 14, SJR: 1.185, h-index: 51)
Biotechnology Progress     Hybrid Journal   (Followers: 39, SJR: 0.736, h-index: 101)
Biotropica     Hybrid Journal   (Followers: 20, SJR: 1.374, h-index: 71)
Bipolar Disorders     Hybrid Journal   (Followers: 9, SJR: 2.592, h-index: 100)
Birth     Hybrid Journal   (Followers: 38, SJR: 0.763, h-index: 64)
Birth Defects Research Part A : Clinical and Molecular Teratology     Hybrid Journal   (Followers: 2, SJR: 0.727, h-index: 77)
Birth Defects Research Part B: Developmental and Reproductive Toxicology     Hybrid Journal   (Followers: 6, SJR: 0.468, h-index: 47)
Birth Defects Research Part C : Embryo Today : Reviews     Hybrid Journal   (SJR: 1.513, h-index: 55)
BJOG : An Intl. J. of Obstetrics and Gynaecology     Partially Free   (Followers: 243, SJR: 2.083, h-index: 125)

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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  [1589 journals]
  • Brief exposures to the taste of ethanol and quinine promote subsequent
           acceptance of ethanol in a paradigm that minimizes post-ingestive
    • Authors: Gregory C Loney; Paul J Meyer
      Abstract: BackgroundAversion to the orosensory properties of concentrated ethanol solutions is often cited as a primary barrier to initiation of drinking and may contribute to abstention. These aversive properties include gustatory processes which encompass both bitter-like taste qualities and trigeminal-mediated irritation. Chronic-intermittent ethanol access (CIA) results in substantial and persistent increases in ethanol consumption, but the degree to which this facilitation involves sensory responding to ethanol and other bitter stimuli is currently undetermined.MethodsLong-Evans rats were given brief-access licking tests designed to examine the immediate, taste-guided assessment of the palatability of ethanol and quinine solutions. Rats were assessed once in a naïve state and again following previous brief-access exposure, or following four weeks of CIA. The relationship between the sensitivity to the aversive orosensory properties of ethanol and quinine following ethanol access and the impact of antecedent quinine exposure on the acceptance of ethanol were determined in two parallel studies.ResultsBoth brief-access to ethanol and four-week CIA resulted in substantial rightward shifts in the concentration-response function of brief-access ethanol licking indicating that ethanol exposure increased acceptance of the taste of ethanol. The initial sensitivity to the aversive orosensory properties of ethanol and quinine were positively correlated in naïve rats, such that rats that were initially more accepting of quinine were also more accepting of ethanol. Rats that sampled quinine immediately prior to tasting ethanol exhibited successive positive contrast in that they were more accepting of highly concentrated ethanol, relative to a water-control group.ConclusionsIncreased ethanol acceptance following exposure is, at least in part, facilitated by a decrease in its aversive sensory properties. Both long and short term access increases the palatability of the taste of ethanol in brief-access licking tests. Moreover, the sensitivity to the bitterness of quinine was predictive of acceptance of ethanol indicating some commonality in the sensory mechanisms that mediate the initial acceptance of the two stimuli. Accordingly, immediate prior exposure to quinine results in increased acceptance of ethanol suggesting that successive positive contrast between oral stimuli may contribute to increased alcohol consumption.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-14T14:30:44.314051-05:
      DOI: 10.1111/acer.13581
  • Associations between MAOA-uVNTR genotype, maltreatment, MAOA methylation
           and alcohol consumption in young adult males
    • Authors: Megha Bendre; Erika Comasco, Dave Checknita, Jari Tiihonen, Sheilagh Hodgins, Kent W Nilsson
      Abstract: BackgroundEpigenetic mechanisms are candidate moderators of the effect of maltreatment on brain and behavior. Interactions between maltreatment and the Monoamine Oxidase A upstream variable number tandem repeat genotype (MAOA-uVNTR) are associated with alcohol-related problems. However, presently it is not known whether DNA methylation moderates this association. The study focused on fifty-three young adult males and aimed to determine: whether MAOA methylation moderated the association of alcohol-related problems with the interaction of MAOA-uVNTR and maltreatment; and whether alcohol consumption moderated the association of MAOA methylation with the interaction of MAOA-uVNTR and maltreatment.MethodsMAOA-uVNTR genotypes with ≤ 3 and> 3 repeats were categorized as short (S) and long (L), respectively. Data on maltreatment were obtained retrospectively, using self-reported questionnaires. DNA methylation of 16 candidate CpGs within part of the MAOA first exon and intron was assessed and grouped based on principal component analyses. Alcohol-related problems were assessed using the Alcohol Use Disorder Identification Test (AUDIT). Alcohol consumption was measured using AUDIT-C. Moderation effects were assessed and probed using the moderated moderation model and Johnson-Neyman′s method, respectively.ResultsCarriers of the S allele who experienced maltreatment and displayed lower Component 1 (mean of CpGs 13-16 in the first intron) MAOA methylation levels, reported higher AUDIT score, in contrast to L allele carriers. Carriers of the S allele who reported higher AUDIT-C score, and experienced maltreatment, displayed lower Component 3 (mean of CpGs 2-6 in the first exon) MAOA methylation levels than L allele carriers.ConclusionIntronic methylation moderated the association of alcohol-related problems with the interaction of MAOA-uVNTR and maltreatment. Alcohol consumption moderated the association of exonic methylation with the interaction of MAOA-uVNTR and maltreatment. These results suggest that epigenetic factors as well as genotype and maltreatment play a role in the development of alcohol misuse among young adult males.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-09T09:20:42.444379-05:
      DOI: 10.1111/acer.13578
  • Co-administration of low-dose naltrexone and bupropion reduces alcohol
           drinking in alcohol-preferring (P) rats
    • Authors: Emily R. Nicholson; Julian E. Dilley, Janice C. Froehlich
      Abstract: BackgroundThis study examined whether combining naltrexone (NTX) with bupropion (BUP) is more effective in reducing alcohol drinking in alcohol-preferring (P) rats with a genetic predisposition toward high voluntary alcohol intake than is either drug alone.MethodsAlcohol-experienced, adult, male, alcohol-preferring (P) rats were fed NTX alone in a dose of 10.0 mg/kg BW, BUP alone in a dose of 10.0 mg/kg BW, BUP alone in a dose of 20.0 mg/kg BW, NTX (10.0 mg/kg BW) + BUP (10.0 mg/kg BW), or vehicle (VEH) at 1 hour prior to onset of a daily 2-hour alcohol access period for 5 consecutive days.ResultsWhen administered alone, neither NTX (10.0 mg/kg BW) nor BUP, in either of two doses (10.0 mg/kg BW or 20.0 mg/kg BW), reduced voluntary alcohol intake in P rats. However, NTX combined with BUP (10.0 mg/kg NTX + 10.0 mg/kg BUP) and given as a single medication, significantly reduced alcohol consumption throughout prolonged treatment.ConclusionsCombining low doses of NTX and BUP, each of which is ineffective when given alone, increases the efficacy of the medication. Low drug doses circumvent the problem of negative side effects that can occur with higher doses of either drug. A reduction in side effects can facilitate patient compliance and improve clinical outcomes for alcoholics and heavy drinkers who want to reduce their alcohol intake. The results, together with those from our prior studies, demonstrate the strength of a combinatorial pharmacotherapeutic approach to the treatment of alcohol use disorder (AUD).This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-09T09:20:23.792992-05:
      DOI: 10.1111/acer.13577
  • Impact of moderate alcohol discontinuation on insulin action and secretion
           in Latinos with and without hepatitis C
    • Authors: Lindsay A Uribe; Peter Bacchetti, Nicholas Gelman, Esteban Burchard, Mark Fitch, Marc Hellerstein, Mandana Khalili
      Abstract: Background/AimsInsulin resistance (IR) is associated with hepatitis C infection (HCV), and Latinos are both at risk for IR and are disproportionately affected by HCV. Moderate alcohol consumption improves insulin sensitivity and may modify HCV-associated IR. We investigated the impact of moderate alcohol discontinuation on insulin sensitivity and secretion in Latinos using direct measurements.MethodsTwenty-five non-diabetic, non-cirrhotic Latino adults without (n=17) or with (n=8) HCV underwent 3-day metabolic assessment before and after prescription of 6 weeks of moderate alcohol discontinuation. Peripheral IR was measured via steady-state plasma glucose (SSPG) and hepatic IR using endogenous glucose production during a two-step 240-minute insulin suppression test. Insulin secretion was measured using graded glucose infusion test.ResultsBaseline mean age was 46±11 years, 63% male, 29% had HCV, and mean BMI was 27±4 kg/m2. Compared to non-HCV, HCV patients had a higher median SSPG (132 vs 98.8 mg/dL, p=1.0), hepatic IR (13.5 vs 11.3, p=0.24), and insulin secretion (ISR-AUC, 1290 vs 1250 pmol/min, p=0.98). After confirmed alcohol discontinuation, hepatic IR was the only parameter that changed significantly (increased, mean change 2.6±4.8, p=0.02). Higher baseline ALT was also associated with a greater change in hepatic IR (average 4.0 points/ALT doubling, p=0.004), and HCV was associated with a lesser change (average -7.3 points, p=0.002), independent of ALT.ConclusionsShort-term moderate alcohol discontinuation adversely impacted hepatic IR in Latinos which was influenced by level of ALT at baseline independent of etiology. Though reduction in ALT through weight loss and HCV eradication remains a priority in improving IR, the observed non-harmful effect of moderate alcohol use represents a potentially confounding variable that warrants further study.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-08T12:01:16.091181-05:
      DOI: 10.1111/acer.13576
  • A novel and selective nociceptin receptor (NOP) agonist
           (AT-312) decreases acquisition of ethanol-induced conditioned place
           preference in mice
    • Authors: Nurulain T. Zaveri; Paul V. Marquez, Michael E. Meyer, Willma E. Polgar, Abdul Hamid, Kabirullah Lutfy
      Abstract: BackgroundNociceptin/Orphanin FQ (N/OFQ), the endogenous peptide agonist for the opioid receptor-like (ORL1) receptor (also known as NOP or the nociceptin receptor), has been shown to block the acquisition and expression of ethanol-induced conditioned place preference (CPP). Here, we report the characterization of a novel small-molecule NOP ligand AT-312 (1-(1-((cis)-4-isopropylcyclohexyl)piperidin-4-yl)-1H-indol-2-yl)methanol) in receptor binding and GTPγS functional assays in vitro. We then investigated the effect of AT-312 on the rewarding action of ethanol in mice using the CPP paradigm. Further, using mice lacking the NOP receptor and their wild-type controls, we also examined the involvement of NOP in the effect of AT-312. Motivational effects of AT-312 alone were also assessed in the CPP paradigm.MethodsFemale mice lacking NOP and/or their wild-type controls received conditioning in the presence or absence of the NOP agonist [AT-312 (1, 3 and 10 mg/kg) or the control NOP agonist SCH221510 (10 mg/kg)] followed by saline/ethanol for 3 consecutive days (twice daily) and tested for CPP in a drug-free state on the next day.ResultsOur in vitro data showed that AT-312 is a high affinity, selective NOP full agonist with 17-fold selectivity over the mu opioid receptor and>200-fold selectivity over the kappa opioid receptor. The results of our in vivo studies showed that AT-312 reduced ethanol CPP at the lowest dose (1 mg/kg) tested but completely abolished ethanol CPP at higher doses (3 or 10 mg/kg) compared to their vehicle-treated control group. AT-312 (3 mg/kg) did not alter ethanol-induced CPP in mice lacking NOP, confirming that AT-312 reduced ethanol CPP through its action at the NOP receptor. AT-312 (3 mg/kg) did not induce reward or aversion when administered alone, showing that the novel small molecule NOP agonist shows efficacy in blocking ethanol-induced CPP via the NOP receptor.ConclusionsTogether, these data suggest that small molecule NOP agonists have the potential to reduce alcohol reward and may be promising as medications to treat alcohol addiction.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-07T06:36:47.348709-05:
      DOI: 10.1111/acer.13575
  • Prenatal alcohol exposure increases histamine H3 receptor-mediated
           inhibition of glutamatergic neurotransmission in rat dentate gyrus
    • Authors: Rafael K. Varaschin; Nyika A. Allen, Martina J. Rosenberg, C. Fernando Valenzuela, Daniel D. Savage
      Abstract: BackgroundWe have reported that prenatal alcohol exposure (PAE)-induced deficits in dentate gyrus (DG) long-term potentiation (LTP) and memory are ameliorated by the histamine H3 receptor inverse agonist ABT-239. Curiously, ABT-239 did not enhance LTP or memory in control offspring. Here, we initiated an investigation of how PAE alters histaminergic neurotransmission in the DG and other brain regions employing combined radiohistochemical and electrophysiological approaches in vitro to examine histamine H3 receptor number and function.MethodsLong-Evans rat dams voluntarily consumed either a 0% or 5% ethanol solution four-hours each day throughout gestation. This pattern of drinking, which produces a mean peak maternal serum ethanol concentration of 60.8 ± 5.8 mg/dL, did not affect maternal weight gain, litter size or offspring birth weight.ResultsRadiohistochemical studies in adult offspring revealed that specific [3H]-A349821 binding to histamine H3 receptors was not different in PAE rats compared to controls. However, H3 receptor-mediated Gi/Go protein-effector coupling, as measured by methimepip-stimulated [35S]-GTPγS binding, was significantly increased in cerebral cortex, cerebellum and DG of PAE rats compared to control. A LIGAND analysis of detailed methimepip concentration-response curves in DG indicated that PAE significantly elevates receptor-effector coupling by a lower affinity H3 receptor population without significantly altering the affinities of H3 receptor subpopulations. In agreement with the [35S]-GTPγS studies, a similar range of methimepip concentrations also inhibited electrically-evoked fEPSP responses and increased paired-pulse ratio, a measure of decreased glutamate release, to a significantly greater extent in DG slices from PAE rats than in controls.ConclusionThese results suggest that a PAE-induced elevation in H3 receptor-mediated inhibition of glutamate release from perforant path terminals as one mechanism contributing the LTP deficits previously observed in the DG of PAE rats, as well as providing a mechanistic basis for the efficacy of H3 receptor inverse agonists for ameliorating these deficits.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-05T02:41:59.007519-05:
      DOI: 10.1111/acer.13574
  • Effects of long-term alcohol drinking on the dopamine D2 receptor: Gene
           expression and heteroreceptor complexes in the striatum in rats
    • Authors: Kristin Feltmann; Dasiel Oscar Borroto-Escuela, Joëlle Rüegg, Luca Pinton, Thatiane Oliveira Sergio, Manuel Narváez, Antonio Jimenez-Beristain, Tomas J Ekström, Kjell Fuxe, Pia Steensland
      Abstract: BackgroundReduced dopamine D2 receptor (D2R) ligand binding has repeatedly been demonstrated in the striatum of humans with alcohol use disorder (AUD). The attenuated D2R binding has been suggested to reflect a reduced D2R density, which in turn has been proposed to drive craving and relapse. However, results from rodent studies addressing the effects of alcohol drinking on D2R density have been inconsistent.MethodsA validated alcohol drinking model (intermittent access to 20% alcohol) in Wistar rats was used to study the effects of voluntary alcohol drinking (at least 12 weeks) on the D2R in the striatum compared to age-matched alcohol-naïve control rats. Reverse transcriptase quantitative PCR was used to quantify isoform-specific Drd2 gene expression levels. Using bisulfite pyrosequencing, DNA methylation levels of a regulatory region of the Drd2 gene were determined. In situ proximity ligation assay was used to measure densities of D2R receptor complexes: D2R-D2R, adenosine A2A receptor (A2AR)-D2R and sigma1 receptor (sigma1R)-D2R.ResultsLong-term voluntary alcohol drinking significantly reduced mRNA levels of the long D2R isoform in the nucleus accumbens (NAc) but did not alter CpG methylation levels in the analyzed sequence of the Drd2 gene. Alcohol drinking also reduced the striatal density of D2R-D2R homoreceptor complexes, increased the density of A2AR-D2R heteroreceptor complexes in the NAc shell and the dorsal striatum and decreased the density of sigma1R-D2R heteroreceptor complexes in the dorsal striatum.ConclusionsThe present results on long-term alcohol drinking might reflect reduced D2R levels through reductions in D2R-D2R homoreceptor complexes and gene expression. Furthermore, based on antagonistic interactions between A2AR and D2R, an increased density of A2AR-D2R heteroreceptor complexes might indicate a reduced affinity and signaling of the D2 receptor population within the complex. Hence, both reduced striatal D2R levels, as well as reduced D2R protomer affinity within the striatal A2AR-D2R complex might underlie reduced D2R radioligand binding in humans with AUD. This supports the hypothesis of a hypodopaminergic system in AUD and suggests the A2AR-D2R heteroreceptor complex as a potential novel treatment target.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-05T02:35:26.220995-05:
      DOI: 10.1111/acer.13568
  • Effects of the acute and chronic ethanol intoxication on acetate
           metabolism and kinetics in the rat brain
    • Authors: Ya-Ju Hsieh; Liang-Chih Wu, Chien-Chih Ke, Chi-Wei Chang, Jung-Wen Kuo, Wen-Sheng Huang, Fu-Du Chen, Bang-Hung Yang, Hsiao-Ting Tai, Sharon Chia-Ju Chen, Ren-Shyan Liu
      Abstract: BackgroundEthanol intoxication inhibits glucose transport and decreases overall brain glucose metabolism; however, humans with long-term ethanol consumption were found to have a significant increase in [1-11C]-acetate uptake in the brain. The relationship between the cause and effect of [1-11C]-acetate kinetics and acute/chronic ethanol intoxication, however, are still unclear.Methods[1-11C]-acetate positron emission tomography (PET) with dynamic measurement of K1 and k2 rate constants was used to investigate the changes in acetate metabolism in different brain regions of rats with acute or chronic ethanol intoxication.ResultsPET imaging demonstrated decreased [1-11C]-acetate uptake in rat brain with acute ethanol intoxication, but this increased with chronic ethanol intoxication. Tracer uptake rate constant K1 and clearance rate constant k2 were decreased in acutely intoxicated rats. No significant change was noted in K1 and k2 in chronic ethanol intoxication, although six of seven brain regions showed slightly higher k2 than baseline. These results indicate that acute ethanol intoxication accelerated acetate transport and metabolism in the rat brain, whereas chronic ethanol intoxication status showed no significant effect.ConclusionsIn vivo PET study confirmed the modulatory role of ethanol, administered acutely or chronically, in [1-11C]-acetate kinetics and metabolism in the rat brain. Acute ethanol intoxication may inhibit the transport and metabolism of acetate in the brain, whereas chronic ethanol exposure may lead to the adaptation of the rat brain to ethanol in acetate utilisation. [1-11C]-Acetate PET imaging is a feasible approach to study the effect of ethanol on acetate metabolism in rat brain.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-05T02:30:23.48819-05:0
      DOI: 10.1111/acer.13573
  • Ovarian Hormones Contribute to High Levels of Binge-Like Drinking by
           Female Mice
    • Authors: Rosalba Satta; Elisa R. Hilderbrand, Amy W. Lasek
      Abstract: BackgroundRecently, the incidence of binge drinking by women has increased. Binge drinking is detrimental to women's health, yet the biological mechanisms that promote excessive drinking by women are not well understood. One method of assessing binge-like ethanol (EtOH) consumption in mice is the drinking in the dark (DID) test, in which mice drink sufficient EtOH to achieve intoxication. In this study, we directly compared male, female, and ovariectomized (OVX) mice for DID and tested whether 17β-estradiol (E2) contributes to DID. We also measured whether DID varies throughout the estrous cycle and if repeated intermittent DID impacts the estrous cycle.MethodsMale, female, and OVX C57BL/6J mice were tested for DID for 2 hours per day on days 1-3 and for 4 hours on day 4 using a single bottle containing 20% EtOH. To measure the effects of E2 on DID, OVX mice were treated with estradiol benzoate (EB) or vehicle daily starting two weeks prior to the drinking test and throughout the DID procedure. In a separate group of experiments, EtOH consumption and estrous cycle phase were measured in freely cycling mice that were drinking EtOH or water 5 days per week for 2 or 6 weeks.ResultsFemale mice consumed more EtOH than male and OVX mice. Treatment with EB increased EtOH consumption by OVX mice compared with vehicle-treated controls. However, EtOH intake did not vary across the estrous cycle, nor did long-term DID alter the estrous cycle.ConclusionsThese results demonstrate that ovarian hormones, specifically E2, contribute to increased EtOH consumption by female mice in the DID test. Although ovarian hormones contribute to this behavior, EtOH consumption is not affected by estrous cycle phase in freely cycling mice. This study provides a framework for understanding the factors that contribute to binge drinking in females.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-05T02:25:27.062672-05:
      DOI: 10.1111/acer.13571
  • Validation of Alcohol Flushing Questionnaires in Determining Inactive
           Aldehyde Dehydrogenase-2 and Its Clinical Implication in Alcohol-Related
    • Authors: Cheol Min Shin; Nayoung Kim, Sung-Il Cho, Joohon Sung, Hee-Jung Lee
      Abstract: BackgroundTo validate alcohol flushing questionnaires in detecting inactive ALDH2 (ALDH2*1/*2 or ALDH2*2/*2).MethodsTwo study sets were established; in study set 1, 210 healthy male subjects (age, 21-59 years) were enrolled; in the study set 2, 756 subjects were enrolled who received esophagogastroduodenoscopy to evaluate their dyspeptic symptoms or as a part of a gastric cancer screening program. Subjects in study set 1 and study set 2 completed modified alcohol flushing questionnaires of the Yokoyama et al (1997) and Yokoyama et al (2003), respectively. Polymerase chain reaction–restriction fragment length polymorphism method was used to determine ALDH2 genotype.ResultsIn study set 1, 29.0% (61 of 210) had inactive ALDH2. The sensitivity and specificity of the original alcohol flushing questionnaire for detecting inactive ALDH2 were 95.1 and 76.5%, respectively. Drinking problems negatively correlated with positive alcohol flushing response and inactive ALDH2 (all p-values < 0.05). In study set 2, the sensitivity and specificity of the alcohol flushing questionnaire for detecting inactive ALDH2 were 78.9 and 82.1%, respectively. Interestingly, drinking ≥ 7 units/week in men or ≥ 3.5 units/week in women significantly increased the risk of benign gastric ulcer among positive alcohol flushers (odds ratio, 8.97; 95% confidence interval, 1.38-58.30), but not among negative alcohol flushers.ConclusionsSimple flushing questionnaires may be administered to Korean population as a screening tool in detecting individuals who carry inactive ALDH2. Alcohol flushing response negatively correlates with drinking problems, and can modify the risk for benign gastric ulcer by alcohol intake.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-05T02:25:25.295302-05:
      DOI: 10.1111/acer.13569
  • Biological systems are a common link between alcohol use disorder and
           co-occurring psychiatric and medical conditions
    • Authors: Sarah L. Hagerty; Jarrod M. Ellingson, Kent E. Hutchison
      Abstract: Alcohol use disorder (AUD) commonly co-occurs with other psychiatric and medical conditions. For example, individuals with AUD are nearly four-times more likely to have Major Depressive Disorder (MDD), six-times more likely to have Bipolar Disorder, and twice as likely to be diagnosed with Post Traumatic Stress Disorder (PTSD) (Kessler et al., 2003). Additionally, medical conditions are commonly comorbid with AUD, and heavy, chronic alcohol use is a risk factor for a host of wide-ranging medical disorders (Rehm et al., 2003, 2009).This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-02T01:50:23.07165-05:0
      DOI: 10.1111/acer.13570
  • Effect of hazardous alcohol use during pregnancy on growth outcomes at
           birth: Findings from a South African cohort study
    • Authors: Bronwyn Myers; Nastassja Koen, Kirsten A. Donald, Raymond T. Nhapi, Lesley Workman, Whitney Barnett, Nadia Hoffman, Sheri Koopowitz, Heather J. Zar, Dan J. Stein
      Abstract: BackgroundCohort studies have noted associations between hazardous alcohol use during pregnancy and infant growth outcomes, but many have not controlled for potential psychosocial confounders. To assess the unique contribution of hazardous alcohol use, we examined its effect on infant growth outcomes while controlling for maternal psychosocial stressors and hazardous tobacco and drug use in a cohort of 986 pregnant South African women enrolled into the Drakenstein Child Health Study between 2012 and 2015.MethodsData on psychosocial stressors and maternal risk behaviors were collected between 28-32 weeks gestation. Participants were categorised as hazardous alcohol users if they obtained moderate or high scores (>10) on the Alcohol, Smoking and Substance Involvement Screening Test at this assessment or retrospectively reported drinking at least two drinks weekly during any trimester of pregnancy. Infant growth outcomes were recorded at delivery. Multivariable regression models examined correlates of hazardous alcohol use and associations between hazardous alcohol use and birth outcomes.ResultsOverall, 13% of mothers reported hazardous alcohol use. Recent exposure to intimate partner violence (adjusted Odds Ratio (aOR) = 2.08; 95% Confidence Interval (CI): 1.37, 3.18) and hazardous tobacco use (aOR = 5.03; 95% CI: 2.97, 8.52) were significant correlates of hazardous alcohol use. After controlling for potential psychosocial confounders, hazardous alcohol use remained associated with lower infant weight for age (B = -0.35, 95% CI: -0.56, -0.14), height for age (B = -0.46, 95% CI: -0.76, -0.17), and head circumference for age z-scores (B = -0.43, 95% CI: -0.69, -0.17).ConclusionsInterventions to reduce hazardous alcohol use among pregnant women in South Africa are needed to prevent alcohol-related infant growth restrictions. As these growth deficits may lead to neurodevelopmental consequences, it is critical to identify alcohol-related growth restrictions at birth and link exposed infants to early interventions for neurodevelopment.This article is protected by copyright. All rights reserved.
      PubDate: 2017-12-02T01:46:31.666891-05:
      DOI: 10.1111/acer.13566
  • Concomitant psychiatric and non-alcohol related substance use disorders
           among hospitalized patients with alcoholic liver disease in the United
    • Authors: Raxitkumar Jinjuvadia; Chetna Jinjuvadia, Pimpitcha Puangsricharoen, Naga Chalasani, David W. Crabb, Suthat Liangpunsakul,
      Abstract: BackgroundDespite that the epidemiological studies on the comorbidity of alcohol misuse and psychiatric disorders have been studied, less is known about the magnitude of these disorders among patients with alcoholic liver disease (ALD). Our aim was to determine the prevalence of psychiatric and substance use disorders among hospitalized ALD patients in the US.MethodsWe utilized a single level clinical classification software to identify patients with ALD and psychiatric/substance use disorders from the 2011 National Inpatient Sample data. The primary outcome was the prevalence of these disorders among hospitalized patients with ALD (n=74,972) compared to those with chronic liver diseasesnot caused by alcohol (n=350,140) and those without underlying liver diseases (n=1,447,063).ResultsThe prevalence of adjustment disorder, anxiety disorder, post-traumatic stress disorder and depression was significantly higher among hospitalized patients with ALD when compared to those with chronic liver diseases not caused by alcohol (all with p values
      PubDate: 2017-12-02T01:45:45.780704-05:
      DOI: 10.1111/acer.13567
  • Exposure to Alcohol Content in Movies and Initiation of Early Drinking
    • Authors: Kristina M. Jackson; Tim Janssen, Nancy P. Barnett, Michelle L. Rogers, Kerri L. Hayes, James Sargent
      Abstract: BackgroundExposure to alcohol content in movies has been shown to be associated with adolescent use of alcohol, including earlier onset. This study examined the influence of movie alcohol exposure on subsequent alcohol onset, considering the social context (whether the movie was viewed with a friend or parent). We examined whether media's influence holds across a spectrum of early drinking milestones: sipping (but not consuming a full drink of) alcohol, consuming a full drink of alcohol, and engaging in heavy episodic drinking (HED).MethodsData were taken from a sample of 882 middle school youth (52% female; 24% non-White) enrolled in an ongoing study on alcohol initiation and progression. Exposure to alcohol content in films was measured using a method that combines content analysis and random assignment of movie titles to youth surveys. The hazard of initiating alcohol use (sip, full drink, HED) as a function of exposure was estimated using survival analysis. Associations were adjusted for demographic, personality, and social influence factors known to be associated with both movie exposure and alcohol use.ResultsExposure to alcohol content was common. Hours of exposure prospectively predicted earlier onset of alcohol involvement across all outcomes. Viewing movies with friends appeared to augment the media exposure effect, in contrast to viewing movies with parents, which was not a significant predictor of initiation.ConclusionsExposure to alcohol in films is involved in the entry into early stages of alcohol involvement. Findings support further investigation into the role of the media in underage drinking, especially in the context of consuming media with friends and peers. Limiting media exposure and/or stronger Federal Trade Commission oversight of movie ratings should be a priority for preventing underage drinking.This study demonstrated that greater exposure to movie alcohol content predicted earlier adolescent drinking initiation, across a spectrum of early-drinking milestones (sipping alcohol, consuming a full drink, engaging in heavy drinking). Viewing movies with friends augmented the exposure effect; viewing with parents did not affect alcohol initiation. Findings suggest that early prevention strategies include limiting movie alcohol exposure, especially with friends and peers, as well as stronger Federal Trade Commission oversight of movie ratings in order to prevent underage drinking.
      PubDate: 2017-11-29T10:00:03.51764-05:0
      DOI: 10.1111/acer.13536
  • MicroRNA-21 contributes to Reduced Microvascular Function in Binge
           Drinking Young Adults
    • Authors: Jing-Tan Bian; Mariann R. Piano, Kumar U. Kotlo, Abeer M. Mahmoud, Shane A. Phillips
      Abstract: BackgroundBinge drinking is associated with increased risk for cardiovascular (CV) disease. MicroRNA-21 (miR21) is upregulated in the setting of excessive alcohol consumption and CV disease. Therefore, the goal of this study was to examine the vasodilatory responses to flow and acetylcholine in the absence and presence of an anti-miR21 inhibitor in the microcirculation of young adult repeated binge drinkers.MethodsGluteal subcutaneous adipose tissue biopsies were obtained from young adults (18-30 yrs, n = 35 vessels from binge drinkers [BDs] and n = 28 vessels from abstainers). Resistance arteries (RAs) were isolated, incubated with anti-miR21 or a negative control to miR-21 (12 hours; 5 nM), and lumen diameters measured with video microscopy. MiRNA-21 of adipose tissues was determined by quantitative PCR (qPCR).ResultsFlow-induced dilation (FID) and acetylcholine (ACh)-induced dilation (AChID) were reduced in BDs as compared to abstainers. The miR-21 inhibitor but not the negative control abrogated these effects in BDs, but did not affect vasodilation in abstainers. Nitric oxide synthase inhibition with L-NAME reduced vasodilation in abstainers but not in BDs. In BDs, vasodilation was reduced by L-NAME in the presence of anti-miR-21 but not the negative control. Scavenging the reactive oxygen species hydrogen peroxide with polyethyleneglyco-catalase reduced dilation in BDs but did not affect the restored dilation by miR-21 inhibitor. Maximum dilation to papaverine (endothelium-independent) was similar between groups and unaffected by pharmacological inhibition. Finally, vascular endogenous miR-21 was increased in BDs compared to abstainers.ConclusionsEndogenous microRNA-21 is increased in RAs of young BDs, leading to reduced flow and acetylcholine-induced vasodilation in the microcirculation.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-25T18:25:24.509696-05:
      DOI: 10.1111/acer.13565
  • Deployment-Related Military Sexual Trauma Predicts Heavy Drinking and
           Alcohol Problems Among Male Reserve and National Guard Soldiers
    • Authors: Jennifer Fillo; Sarah Cercone Heavey, D. Lynn Homish, Gregory G. Homish
      Abstract: BackgroundMilitary sexual trauma (MST) is associated with a range of deleterious mental and physical health consequences; however, far less attention has been paid to the associations between MST and negative health behaviors, such as substance abuse. This study examined 2 focal research questions: (i) What is the prevalence of experiencing MST during deployment among male Reserve and National Guard soldiers' and (ii) to what extent is the degree of MST exposure during deployment associated with frequent heavy drinking and alcohol problems postdeployment'MethodsData from male soldiers who had been deployed (N = 248) were drawn from the baseline wave of Operation: SAFETY (Soldiers And Families Excelling Through the Years) an ongoing study examining health among U.S. Army Reserve and National Guard and their partners. Participants were recruited over a 15-month period (Summer 2014 to Fall 2015) from units in New York State. Deployments occurred prior to the baseline wave of the study. Analyses examined the relation between degree of MST exposure during soldiers’ most recent deployment and (i) frequent heavy drinking and (ii) alcohol problems, measured at baseline, controlling for posttraumatic stress disorder symptoms and age.Results17.3% of the male service members reported experiencing MST during their most recent deployment. Further, greater MST exposure was associated with a greater likelihood of engaging in frequent heavy drinking (adjusted risk ratio [aRR] = 1.03, 95% CI [1.01, 1.05]) and experiencing alcohol problems (aRR = 1.03, 95% CI [1.01, 1.06]) at baseline.ConclusionsFindings demonstrate that MST rates are high among male Reserve and National Guard soldiers, and greater MST exposure is associated with an increased likelihood of engaging in frequent heavy drinking and experiencing alcohol problems among a population already at risk for problematic alcohol use.The nature and consequences of military sexual trauma (MST) in men is understudied. Results revealed that 17.3% of male service members reported experiencing MST during their most recent deployment. Additionally, greater MST exposure was associated with greater likelihood of engaging in frequent heavy drinking and experiencing alcohol problems. These findings demonstrate that MST rates are high among male Reserve and National Guard soldiers, and MST exposure may contribute to one of the most common health problems among recent veterans.
      PubDate: 2017-11-24T10:00:02.004504-05:
      DOI: 10.1111/acer.13528
  • The effects of long-term varenicline administration on ethanol- and
           sucrose-seeking and self-administration in male P rats
    • Authors: Cristine L. Czachowski; Janice C. Froehlich, Michael DeLory
      Abstract: BackgroundVarenicline, a partial agonist at α4β2 and full agonist at α7 nicotinic cholinergic receptors, is FDA approved for treatment of smoking cessation and has been found to reduce alcohol craving in clinical populations. In rodents, varenicline decreases free-choice ethanol intake with somewhat mixed findings in operant paradigms that utilize a combined appetitive/consummatory response.MethodsThe present experiment utilized an operant paradigm that procedurally separates appetitive from consummatory responding and a “reward blocking” approach (i.e., rats were able to consume ethanol during treatment) to better understand the efficacy of varenicline as a treatment for ethanol self-administration and subsequent ethanol-seeking. Separate groups of ethanol- and sucrose reinforced alcohol preferring, male P rats experienced alternating cycles of vehicle (2-week cycles) and varenicline (0.3, 1.0 and 2.0 mg/kg self-administered in a gelatin preparation) treatment (3-week cycles) prior to daily sessions where a single lever-press resulted in 20 minutes of reinforcer access. At the end of each cycle, a single extinction session assessed the seeking response in the absence of drug pretreatment.ResultsVarenicline dose-dependently decreased ethanol intake. Sucrose intake was largely unaffected, with no overall treatment effects and only sporadic days where the medium and high dose differed from vehicle. Neither sucrose nor ethanol-seeking was significantly decreased by varenicline, and there were no treatment effects on either lick or lever-press latency. Overall effect sizes were much greater for both drinking and seeking in the Ethanol Group as compared to the Sucrose Group.ConclusionsVarenicline effectively attenuates ethanol self-administration during treatment, but the experience with ethanol consumption while varenicline is “on board” is not sufficient to alter subsequent ethanol-seeking. The overall pattern of findings indicate that varenicline blocks the rewarding properties of ethanol while not substituting for ethanol, that the non-specific effects on an alternate reinforcer are negligible, and that blood levels of varenicline need to be maintained in order for treatment to remain effective.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-23T00:30:25.970072-05:
      DOI: 10.1111/acer.13562
  • Erratum
    • PubDate: 2017-11-22T07:50:30.565886-05:
      DOI: 10.1111/acer.13557
  • Risk of past year injury related to hours of exposure to an elevated BAC
           and average monthly alcohol volume: Data from four national alcohol
           surveys (2000-2015)
    • Authors: Cheryl J. Cherpitel; Yu Ye, William C. Kerr
      Abstract: BackgroundWhile a strong association exists between alcohol and injury in emergency department (ED) studies, these studies are not representative of the general population.ObjectiveThe association of injury with the number of hours of exposure to a BAC ≥ 0.05 and average monthly volume in drinks, both based on self-report of quantity and frequency of drinking in the last year, in a merged sample of respondents (n=29,571) from four U.S. National Alcohol Surveys (2000-2015) is analyzed.MethodsRisk curves based on categorical step-function and fractional polynomial modeling were analyzed separately by gender, and by age and race/ethnicity for males.ResultsRisk of injury increased at one hour of a BAC exposure of ≥ 0.05 and at an average monthly volume of one drink. Risk of injury for spirits increased to an average daily volume of one drink, but no association was found for injury risk and average volume for either wine or beer. Risk of injury increased with both exposure hours and monthly volume among males, but little association was found for either consumption measure with risk of injury for females. Among males increased risk of injury was greater for whites than for blacks or Hispanics for BAC exposure; Hispanics showed a continued elevated risk up to 8 hours of exposure. After peaking at a monthly volume of one drink, injury risk decreased substantially for blacks, but was more gradual for whites, while risk increased very slightly for Hispanics to about 4 drinks per day. Males aged 18-29 showed the largest increase in risk associated with the number of hours of exposure to a BAC of ≥ 0.05, with risk doubling at one hour of exposure, but subsequently falling.ConclusionsWhile findings here are weaker than those from ED studies and likely due to the context of drinking, risk of injury appears to increase at relatively low levels of consumption, suggesting the importance of preventive efforts to reduce injury not only for heavier drinkers but also for more moderate drinkers.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-21T10:51:34.282498-05:
      DOI: 10.1111/acer.13561
  • Ketogenic Diet suppresses Alcohol Withdrawal Syndrome in Rats
    • Authors: Ditte Dencker; Anna Molander, Morgane Thomsen, Chantal Schlumberger, Gitta Wortwein, Pia Weikop, Helene Benveniste, Nora D Volkow, Anders Fink-Jensen
      Abstract: BackgroundAlcohol use disorder is under-diagnosed and under-treated, and up to 50% of alcohol abstinent patients diagnosed with alcohol dependence relapse within the first year of treatment. Current treatments for the maintenance of alcohol abstinence in patients with alcohol use disorder have limited efficacy, and there is an urgent need for novel treatment strategies. Decreased cerebral glucose metabolism and increased brain uptake of acetate was recently reported in heavy drinkers, relative to controls. Given the switch of metabolic fuel from glucose to acetate in the alcohol-dependent brain, we investigated the potential therapeutic benefit of a ketogenic diet in managing alcohol withdrawal symptoms during detoxification.MethodsMale Sprague Dawley rats fed either ketogenic or regular diets were administered ethanol or water orally, twice daily for 6 days while the diet conditions were maintained. Abstinence symptoms were rated 6, 24, 48, and 72 hours after the last alcohol administration.ResultsMaintenance on a ketogenic diet caused a significant decrease in the alcohol withdrawal symptoms ‘rigidity’ and ‘irritability’.ConclusionOur preclinical pilot study suggests that a ketogenic diet may be a novel approach for treating alcohol withdrawal symptoms in humans.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-21T10:45:34.067805-05:
      DOI: 10.1111/acer.13560
  • Age of Alcohol Initiation and Progression to Binge Drinking in
           Adolescence: A Prospective Cohort Study
    • Authors: Alexandra Aiken; Philip J. Clare, Monika Wadolowski, Delyse Hutchinson, Jackob M. Najman, Tim Slade, Raimondo Bruno, Nyanda McBride, Kypros Kypri, Richard P. Mattick
      Abstract: BackgroundEarly alcohol initiation is common and has been associated with the development of alcohol problems. Yet, past research on the association of age of initiation with later problem drinking has produced inconsistent findings. Using prospective data from the Australian Parental Supply of Alcohol Longitudinal Study cohort, this study examined age of alcohol initiation, and of first drunkenness, and associations with subsequent drinking in adolescence.MethodsA total of 1,673 parent–child dyads recruited through Australian secondary schools completed annual surveys for 5 years (grades 7 to 11). Limiting the sample to those adolescents who had initiated alcohol use by age 17 (n = 839), multinomial logistic regression models were used to examine associations between (i) age of initiation to alcohol use (consuming at least 1 full serve) and (ii) age of first drunkenness, and 2 outcomes: (i) binge drinking (consuming>4 standard drinks on a single occasion), and (ii) the total number of alcoholic drinks consumed in the past year, adjusted for a range of potential child, parent, family, and peer covariates.ResultsFifty percent of adolescents reported alcohol use and 36% reported bingeing at wave 5 (mean age 16.9 years), and the mean age of initiation to alcohol use for drinkers was 15.1 years. Age of initiation was significantly associated with binge drinking and total quantity of alcohol consumed in unadjusted and adjusted models. Age of first drunkenness was associated with total quantity of alcohol consumed in unadjusted models but not adjusted models and was not associated with subsequent bingeing.ConclusionsInitiating alcohol use earlier in adolescence is associated with an increased risk of binge drinking and higher quantity of consumption in late secondary school, supporting an argument for delaying alcohol initiation for as long as possible to reduce the risk for problematic use in later adolescence and the alcohol-related harms that may accompany this use.Early alcohol initiation has been associated with later alcohol problems, however past research has produced inconsistent findings. Using 5 years of prospective cohort data and adjusting for a wide range of potential covariates, this study found that initiating alcohol use earlier in adolescence was associated with an increased risk of binge drinking and higher quantity of consumption in late secondary school. These findings support an argument for delaying alcohol initiation to reduce the risk of problematic use in later adolescence.
      PubDate: 2017-11-21T10:00:02.844185-05:
      DOI: 10.1111/acer.13525
  • Applications and Challenges for the use of Phosphatidylethanol Testing in
           Liver Disease Patients (MINI REVIEW)
    • Authors: Van Long Nguyen; Paul S. Haber, Devanshi Seth
      Abstract: Phosphatidylethanol (PEth) is a direct non-oxidative metabolite of ethanol that may be measured in clinical samples as a marker for monitoring alcohol consumption. It has been used in a wide variety of clinical and non-clinical settings; however, its investigation in relation to liver disease has been limited. This paper aims at providing a short review on the applications and challenges for the incorporation of PEth testing in identifying alcohol intake in this patient population.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-20T09:05:22.700655-05:
      DOI: 10.1111/acer.13558
  • Effects of nicotine on alcohol drinking in female mice selectively-bred
           for high or low alcohol preference
    • Authors: Marcus M. Weera; Molly A. Fields, Danielle N. Tapp, Nicholas J. Grahame, Julia A. Chester
      Abstract: BackgroundStudies show that repeated nicotine use associates with high alcohol consumption in humans, and that nicotine exposure sometimes increases alcohol consumption in animal models. However, the relative roles of genetic predisposition to high alcohol consumption, the alcohol drinking patterns, and the timing of nicotine exposure both with respect to alcohol drinking and developmental stage remain unclear. The studies here manipulated all these variables, using mice selectively bred for differences in free-choice alcohol consumption to elucidate the role of genetics and nicotine exposure in alcohol consumption behaviors.MethodsIn Experiments 1 and 2, we assessed the effects of repeated nicotine (0, 0.5 or 1.5 mg/kg) injections immediately before binge-like (drinking-in-the-dark; Experiment 1) or during free-choice alcohol access (Experiment 2) on these alcohol drinking behaviors (immediately after injections and during re-exposure to alcohol access 14 days later) in adult high- (HAP2) and low-alcohol preferring (LAP2) female mice (co-exposure model). In Experiments 3 and 4, we assessed the effects of repeated nicotine (0, 0.5 or 1.5 mg/kg) injections 14 days prior to binge-like and free-choice alcohol access on these alcohol drinking behaviors in adolescent HAP2 and LAP2 female mice (Experiment 3) or adult HAP2 female mice (Experiment 4).ResultsIn Experiment 1, we found that repeated nicotine (0.5 and 1.5 mg/kg) and alcohol co-exposure significantly increased binge-like drinking behavior in HAP2 but not LAP2 mice during the re-exposure phase after a 14-day abstinence period. In Experiment 2, 1.5 mg/kg nicotine injections significantly reduced free-choice alcohol intake and preference in the 3rd hour post-injection in HAP2 but not LAP2 mice. No significant effects of nicotine treatment on binge-like or free-choice alcohol drinking were observed in Experiments 3 and 4.ConclusionsThese results show that the temporal parameters of nicotine and alcohol exposure, pattern of alcohol access, and genetic predisposition for alcohol preference influence nicotine's effects on alcohol consumption. These findings in selectively bred mice suggest that humans with a genetic history of alcohol-use disorders may be more vulnerable to develop nicotine and alcohol co-use disorders.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-16T11:15:20.987698-05:
      DOI: 10.1111/acer.13555
  • The mammalian circadian clock exhibits chronic ethanol tolerance and
           withdrawal-induced glutamate hypersensitivity, accompanied by changes in
           glutamate and TrkB receptor proteins
    • Authors: Jonathan H Lindsay; Rebecca A Prosser
      Abstract: BackgroundAlcohol tolerance and withdrawal-induced effects are criteria for alcohol use disorders listed by the DSM-V. Although tolerance and withdrawal have been studied over many decades, there is still uncertainty regarding mechanistic distinctions that characterize these different forms of ethanol (EtOH)-induced plasticity. Previously, we demonstrated that the suprachiasmatic nucleus (SCN) circadian clock develops both acute and rapid tolerance to EtOH inhibition of glutamate-induced circadian phase shifts. Here, we demonstrate that chronic EtOH tolerance and withdrawal-induced glutamate hypersensitivity occur in vitro, and that rapid tolerance, chronic tolerance, and glutamate hypersensitivity have distinct cellular changes.MethodsWe use single unit extracellular electrophysiological recordings to determine if chronic tolerance to EtOH inhibition of glutamatergic phase shifts and withdrawal-induced glutamate hypersensitivity develop in the SCN. We use western blotting to compare phosphorylation state and total expression of NMDA receptor subunits and associated proteins in the SCN after mice were exposed to varying EtOH consumption paradigms.ResultsChronic tolerance developed after a minimum of 8 days of 4h/day EtOH access, as indicated by a decreased sensitivity to EtOH inhibition of glutamate-induced phase shifts. We also observed an increased sensitivity to glutamate–induced phase shifts in SCN tissue following withdrawal. We demonstrated an increase in the ratio of NR2B:NR2A NMDA receptor subunit expression after 21 days, but not after 10 days of EtOH drinking. This increase persisted during EtOH withdrawal, along with an increase in NR2B Y1472 phosphorylation, mature BDNF and phosphorylated TrkB.ConclusionsThese results demonstrate that multiple tolerance forms and withdrawal-induced glutamate hypersensitivity occur in the SCN and that these different forms of EtOH-induced plasticity are accompanied by distinct changes in cellular physiology. Importantly, this study further demonstrates the power of using the SCN as a model system to investigate EtOH induced plasticity.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-15T07:31:52.357292-05:
      DOI: 10.1111/acer.13554
  • GRIK1 and GABRA2 Variants Have Distinct Effects on the Dose-Related
           Subjective Response to Intravenous Alcohol in Healthy Social Drinkers
    • Authors: Bao-Zhu Yang; Albert J. Arias, Richard Feinn, John H. Krystal, Joel Gelernter, Ismene L. Petrakis
      Abstract: BackgroundThe heritable risk for alcohol use disorder (AUD) is expressed partly through alterations in subjective alcohol response. In this study, we investigated the effects of 2 AUD-risk-associated single nucleotide polymorphisms, GABRA2 rs279858 and GRIK1 rs2832407, on the subjective response to alcohol administered intravenously to healthy social drinkers in a laboratory setting.MethodsIn total, 93 self-identified European American social drinkers underwent 3 blinded laboratory sessions in which they received intravenous infusions of ethanol at 3 target blood alcohol levels (0.00 mg%, 40 mg%, and 100 mg%) using a “clamp” procedure. The self-reported Biphasic Alcohol Effects Scale (BAES) stimulation and sedation subscales were the primary outcome measures. We examined the effects of these 2 genetic variants on subjective response to alcohol.ResultsFor the BAES stimulation subscale scores, adjusting for age, baseline scores, and time effects, individuals with 2 copies of the GABRA2 rs279858 C “risk” allele for AUD exhibited the greatest stimulant responses to high-dose alcohol compared to the other risk allele counts (dose-by-allele count interaction effect, p = 0.001, post hoc contrast for C-allele, p = 0.012). For the BAES sedation subscale scores, adjusting for the same covariates, we detected a dose-by-allele count interaction effect (p = 0.0044) such that subjects with 2 copies of the GRIK1 C “risk” allele reported the greatest sedative response to the higher alcohol dose.ConclusionsThis study suggests that gene variants contributing to the risk for AUD may alter features of the alcohol dose–response relationship in specific ways. GABRA2 rs279858*C enhances stimulant responses to higher levels of alcohol, while the GRIK1 rs2832407*C-allele increases sedative responses. In summary, GRIK1 and GABRA2 variants have distinct effects on the dose-related subjective response to intravenous alcohol in humans.We investigated the effects of two alcohol use disorder (AUD) risk-associated genetic variants, GABRA2 rs279858 and GRIK1 rs2832407, on the subjective response to alcohol in social drinkers. Individuals carrying the GABRA2 rs279858 C “risk” allele exhibited the greatest stimulant responses to high dose alcohol. Subjects with two copies of the GRIK1 C “risk” allele reported the greatest sedative response. The altered responses in persons with these variants may increase the reward from drinking, perhaps conveying increased risk of AUD.
      PubDate: 2017-11-13T10:00:05.686844-05:
      DOI: 10.1111/acer.13516
  • Low Inherent Sensitivity to the Intoxicating Effects of Ethanol in Rhesus
           Monkeys with Low CSF Concentrations of the Serotonin Metabolite
           5-Hydroxyindoleacetic Acid
    • Authors: Elizabeth K. Wood; Ryno Kruger, Angus Bennion, Bradley M. Cooke, Stephen Lindell, Melanie Schwandt, David Goldman, Christina S. Barr, Stephen J. Suomi, J. Dee Higley
      Abstract: IntroductionType 2 Alcoholism is characterized by low serotonin system functioning and has a high degree of heritability, with offspring of alcoholics often showing a reduced response to the intoxicating effects of ethanol, which is thought to be marker for future alcohol use disorders (AUDs). As such, an important aim of studies investigating the origins of AUDs is understanding the relationship between serotonin system functioning and level of intoxication. A nonhuman primate model was used to evaluate observational ratings of sensitivity to ethanol and to further investigate the relationship between central serotonin activity and behavioral response to ethanol.Materials and MethodsCerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA) were obtained from four cohorts of alcohol-naïve, adolescent rhesus macaques (N=82, 45 females, 37 males). One to three months after the CSF sample, subjects were administered a standardized intravenous (IV) ethanol bolus (males: 2.1 g/kg body weight, females: 2.0 g/kg body weight), placed into an open top, clear Plexiglas™ chamber suspended from the ceiling, and their latency to escape was recorded as a measure of the degree of intoxication. Thereafter, subjects were rated using a Likert scale for the degree of intoxication during a 30-minute observation period.ResultsOur results indicate that latency to escape from the chamber was associated with intoxication ratings (p = 0.0001) following the standardized IV administration of ethanol. Low CSF 5-HIAA concentrations predicted short escape latency (p = 0.006) and were associated with low intoxication ratings (p = 0.02), indicating that low CNS serotonin functioning is related to relative insensitivity to the intoxicating effects of alcohol.DiscussionOur study shows that, in monkeys exposed to alcohol for the first time, objective measures of intoxication are associated with subjective ratings for intoxication and both were associated with CSF 5-HIAA concentrations. Our data confirm and extend the finding that low CNS serotonin functioning is predictive of intrinsic low sensitivity to the intoxicating effects of ethanol.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-10T11:15:45.722759-05:
      DOI: 10.1111/acer.13552
  • Alcohol drinking and blood alcohol concentration revisited
    • Authors: Julian E Dilley; Emily Nicholson, Stephen M. Fischer, Robin Zimmer, Janice C. Froehlich
      Abstract: BackgroundIt is widely assumed that the amount of alcohol in the blood reflects the amount of alcohol consumed. However, several factors in addition to amount of alcohol consumed can influence blood alcohol concentration (BAC). The current study examines the effect of alcohol dose, concentration, and volume on BAC in rats with a high alcohol drinking (HAD) phenotype.MethodsStudy one examined the relationship between the amount of alcohol consumed and BAC. Alcohol-naïve, male, HAD rats (N=7) were given access to alcohol for 2 hrs/day for 9 consecutive days with food and water ad libitum. Alcohol intake and BAC were measured at 30, 60, and 90 minutes after onset of access. Study two examined the effects of altering alcohol dose, concentration, and volume on BAC (as measured by area under the curve). Alcohol-naïve, male, HAD rats (N=39) were infused, via an intragastric cannulus, with 1.16, 2.44, or 3.38 g alcohol/kg BW, produced by varying alcohol volume while holding concentration constant or by holding volume constant while varying concentration. Other rats were infused with 10%, 15%, or 20% v/v alcohol solutions while holding dose constant.ResultsBAC was more strongly correlated with the ratio of alcohol intake (g/kg BW) to total fluid intake (mls) (R=0.85-0.97, p
      PubDate: 2017-11-09T14:05:32.781151-05:
      DOI: 10.1111/acer.13549
  • Incorporating functional genomic information to enhance polygenic signal
           and identify variants involved in gene-by-environment interaction for
           young adult alcohol problems
    • Authors: Jessica E. Salvatore; Jeanne E. Savage, Peter Barr, Aaron R. Wolen, Fazil Aliev, Eero Vuoksimaa, Antti Latvala, Lea Pulkkinen, Richard J. Rose, Jaakko Kaprio, Danielle M. Dick
      Abstract: BackgroundCharacterizing aggregate genetic risk for alcohol misuse and identifying variants involved in gene-by-environment interaction (G×E) effects has so far been a major challenge. We hypothesized that functional genomic information could be used to enhance detection of polygenic signal underlying alcohol misuse, and to prioritize identification of single nucleotide polymorphisms (SNPs) most likely to exhibit G×E effects.MethodsWe examined these questions in the young adult FinnTwin12 sample (n=1170). We used genome-wide association estimates from an independent sample to derive two types of polygenic scores for alcohol problems in FinnTwin12. Genome-wide polygenic scores included all SNPs surpassing a designated p-value threshold. DNase polygenic scores were a subset of the genome-wide polygenic scores including only variants in DNase I hypersensitive sites (DHSs), which are open chromatin marks likely to index regions with a regulatory function. We conducted parallel analyses using height as a non-psychiatric model phenotype in order to evaluate the consistency of effects. For the G×E analyses, we examined whether SNPs in DHSs were overrepresented among SNPs demonstrating significant G × E effects in an interaction between romantic relationship status and intoxication frequency.ResultsContrary to our expectations, we found that DNase polygenic scores were not more strongly predictive of alcohol problems than conventional polygenic scores. However, variants in DNase polygenic scores had per-SNP effects that were up to 1.4 times larger than variants in conventional polygenic scores. This same pattern of effects was also observed in supplementary analyses with height. In G×E models, SNPs in DHSs were modestly overrepresented among SNPs with significant interaction effects for intoxication frequency.ConclusionsThese findings highlight the potential utility of integrating functional genomic annotation information in order to increase the signal-to-noise ratio in polygenic scores and identify genetic variants that may be most susceptible to environmental modification.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-09T14:05:31.059174-05:
      DOI: 10.1111/acer.13551
  • Ethanol and the Cardiovascular System: Friend or Enemy'
    • Authors: Alireza Shirpoor
      Abstract: Alcohol as an old drug and popular beverage has attracted human interest since the beginning of the recorded history. However, in all societies concurrent with alcohol consumption, scientific debates on its risks and benefits have also been generated and continue to this date ((Kloner and Rezkalla,2007). Because of the major role of cardiovascular disease (CAD) in mortality ratesThis article is protected by copyright. All rights reserved.
      PubDate: 2017-11-09T14:05:28.855238-05:
      DOI: 10.1111/acer.13548
  • Role of Gut-Derived Endotoxin on Type I Collagen Production in the Rat
           Pancreas after Chronic Alcohol Exposure
    • Authors: Hongyan Li; Ming Xiu, Shuhua Wang, David R Brigstock, Li Sun, Limei Qu, Runping Gao
      Abstract: BackgroundPancreatic fibrosis is a key pathological feature of alcoholic chronic pancreatitis (ACP). Bacterial endotoxin lipopolysaccharide (LPS) is considered as an important cofactor in the fibrogenesis of ACP. However, there are limitations in the use of exogenous LPS for evaluating the role of endotoxin in ACP pathogenesis. In this study we determined the relationship between the concentration of LPS in the portal vein and pancreatic type I collagen (Col1) content in chronic alcohol-fed rats.MethodsMale Sprague-Dawley rats were divided into two groups and fed with Lieber-DeCarli isocaloric control (CON) liquid diet or Ethanol (EtOH) (15 g/kg/d) liquid diet. 11 CON or EtOH rats were euthanized at the end of week 8, 9 or 10. The plasma LPS from portal vein was determined. Pancreatic inflammatory injury and fibrosis were assessed. Pancreatic stellate cells (PSCs) and macrophages were identified; Pancreatic type I collagen alpha 1 (Col1A1) and TLR4 mRNA and protein were examined; Pancreatic chemokines and transforming growth factor-beta1 (TGF-β1) were determined.ResultsPancreatic inflammatory scores were increased in 10-week EtOH rats compared with CON rats, but there was no significant difference in collagen deposition between two groups. The levels of portal vein LPS and pancreatic TLR4 and Col1A1 mRNA and protein were increased in a time-dependent fashion in EtOH rats, with the highest levels occurring at 10 weeks. Additionally, by 8 weeks, pancreatic TLR4 and Col1A1 mRNA in EtOH rats were statisticaly increased as compared to CON rats, whereas portal vein LPS remained unchanged. The number of PSCs and macrophages and expression of chemokines (MCP-1, MIP-1α and Rantes), TGF-β1, or Col1A1 were significantly increased, each of which was positively correlated with the level of portal vein LPS in 10-week EtOH rats.ConclusionsThese results suggest that LPS is associated with alcohol-induced fibrosis in pancreatitis and targeting of bacterial endotoxin may be a promising therapeutic strategy for ACP.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-09T14:05:22.394533-05:
      DOI: 10.1111/acer.13550
  • Carcinogenic Etheno-DNA Adducts in Alcoholic Liver Disease: Correlation
           with Cytochrome P-4502E1 and Fibrosis
    • Authors: Sebastian Mueller; Teresa Peccerella, Hua Qin, Katharina Glassen, Rüdiger Waldherr, Christa Flechtenmacher, Beate K. Straub, Gunda Millonig, Felix Stickel, Thomas Bruckner, Helmut Bartsch, Helmut Karl Seitz
      Abstract: Background & AimsOne mechanism by which alcoholic liver disease (ALD) progresses is oxidative stress and the generation of reactive oxygen species (ROS), among others due to the induction of cytochrome P-4502E1 (CYP2E1). Experimental data underline the key role of CYP2E1 since ALD could be partially prevented in rats by the administration of the specific CYP2E1 inhibitor chlormethiazole. Since CYP2E1 is linked to the formation of carcinogenic etheno DNA-adducts in ALD patients, a causal role of alcohol induced CYP2E1 in hepatocarcinogenesis is implicated. The purpose of this study was to investigate CYP2E1 induction in ALD, its correlation with oxidative DNA lesions and with hepatic histology.MethodsHepatic biopsies from 97 patients diagnosed with ALD were histologically scored for steatosis, inflammation and fibrosis. CYP2E1 and the exocyclic etheno DNA adduct 1,N6-etheno-2′deoxyadenosine (εdA) were determined immunohistochemically. In addition, in 42 patients 8-hydroxydeoxyguanosine (8-OHdG) was also evaluated using immunohistochemistry.ResultsA significant positive correlation was found between CYP2E1 and εdA (p
      PubDate: 2017-11-09T08:57:22.597419-05:
      DOI: 10.1111/acer.13546
  • Determination of MoCA cutoff score in patients with alcohol use disorders
    • Authors: V. Ewert; S. Pelletier, R. Alarcon, B. Nalpas, Hélène Donnadieu-Rigole, R. Trouillet, P. Perney
      Abstract: BackgroundThe MoCA score is a convenient and promising tool for estimating alcoholic patients’ global cognitive functioning, a major challenge for all specialized alcohol treatment centers. However, whether or not the score should be corrected for education level and whether the proposed cutoff is relevant in patients with alcohol use disorders (AUD) should be determined.DesignWe compared the MoCA scores in patients hospitalized for AUD with and without cognitive impairment (CI) assessed by a battery of neuropsychological tests. Sensitivity, specificity and cutoff of the MoCA score were analyzed using ROC curve analysis.Results31 patients with and 25 without CI were included in the study. There were 40 men and 16 women, with a mean age of 49.5 years. The mean uncorrected MoCA score was 23.1±3.3 in those with and 27.0±1.9 in those without CI. Neuropsychological tests were significantly correlated with the MoCA score. Uncorrected MoCA scores identified more than 80% of the patients with a cutoff score equal to 26; to obtain similar accuracy with the corrected score required using a cutoff score equal to 27.ConclusionOur results confirm that the MoCA test is a convenient and reliable screening tool to measure cognition defects in alcoholic patients. Since using the one-point education adjustment increases the cutoff score by one point, it is suggested to use the non-corrected score and the usual cutoff, i.e. 26. Being easy to administer and only moderately time-consuming, the MoCA score should be used extensively in addiction treatment centers.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-09T08:55:44.639564-05:
      DOI: 10.1111/acer.13547
  • Neuroactive Steroid (3α,5α)3-hydroxypregnan-20-one (3α,5α-THP) and
           Pro-inflammatory Cytokine MCP-1 Levels in Hippocampus CA1 are Correlated
           with Voluntary Ethanol Consumption in Cynomolgus Monkey
    • Authors: Matthew C. Beattie; Christopher S. Reguyal, Patrizia Porcu, James B. Daunais, Kathleen A. Grant, A. Leslie Morrow
      Abstract: BackgroundNeuroactive steroids such as (3α,5α)3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone) are potent neuromodulators that enhance GABAergic neurotransmission and produce inhibitory neurobehavioral and anti-inflammatory effects. Chronic ethanol consumption reduces 3α,5α-THP levels in human plasma, but has brain-region and species-specific effects on CNS levels of 3α,5α-THP. We explored the relationship between 3α,5α-THP levels in the hippocampus and voluntary ethanol consumption in the cynomolgus monkey following daily self-administration of ethanol for 12 months and further examined the relationship to HPA axis function prior to ethanol exposure. We simultaneously explored hippocampus levels of monocyte chemoattractant protein 1 (MCP-1), a pro-inflammatory cytokine that plays an important role in the neuroimmune response to ethanol, following chronic self-administration.MethodsMonkeys were subjected to scheduled induction of water and ethanol consumption (0-1.5 g/kg) over four months, followed by free access to ethanol or water for 22 hours/day over twelve months. Immunohistochemistry was performed using an anti-3α,5α-THP or anti-MCP-1 antibody. Prolonged voluntary drinking resulted in individual differences in ethanol consumption that ranged from 1.2 – 4.2 g/kg/day over 12 months.ResultsProlonged ethanol consumption increased cellular 3α,5α-THP immunoreactivity by 12±2% (p
      PubDate: 2017-11-07T15:20:22.652142-05:
      DOI: 10.1111/acer.13545
  • Alcohol-Induced Impairment of Balance is Antagonized by Energy Drinks
    • Authors: Cecile A. Marczinski; Mark T. Fillmore, Amy L. Stamates, Sarah F. Maloney
      Abstract: BackgroundThe acute administration of alcohol reliably impairs balance and motor coordination. While it is common for consumers to ingest alcohol with other stimulant drugs (e.g., caffeine, nicotine), little is known whether prototypical alcohol-induced balance impairments are altered by stimulant drugs. The purpose of this study was to examine whether the coadministration of a high-caffeine energy drink with alcohol can antagonize expected alcohol-induced increases in body sway.MethodsSixteen social drinkers (of equal gender) participated in 4 separate double-blind dose administration sessions that involved consumption of alcohol and energy drinks, alone and in combination. Following dose administration, participants completed automated assessments of balance stability (both eyes open and eyes closed) measured using the Biosway Portable Balance System. Participants completed several subjective measures including self-reported ratings of sedation, stimulation, fatigue, and impairment. Blood pressure and pulse rate were recorded repeatedly.ResultsThe acute administration of alcohol increased body sway, and the coadministration of energy drinks antagonized this impairment. When participants closed their eyes, alcohol-induced body sway was similar whether or not energy drinks were ingested. While alcohol administration increased ratings of sedation and fatigue, energy drink administration increased ratings of stimulation and reduced ratings of fatigue. Modest increases in systolic and diastolic blood pressure following energy drink administration were also observed.ConclusionsVisual assessment of balance impairment is frequently used to indicate that an individual has consumed too much alcohol (e.g., as part of police-standardized field sobriety testing or by a bartender assessing when someone should no longer be served more alcohol). The current findings suggest that energy drinks can antagonize alcohol-induced increases in body sway, indicating that future work is needed to determine whether this observation regarding neuromotor functioning applies to alcohol in combination with all types of stimulant drugs.Drunk driving is a major public health concern. Since alcohol increases body sway, the visual assessment of balance impairments is used to indicate intoxication (e.g., as part of police standardized field sobriety testing or by bartenders assessing when someone should no longer be served more alcohol). Results of this study indicate that use of an energy drink mixer with alcohol antagonizes alcohol-induced balance impairments even though energy drink mixers do not alter breath alcohol concentrations.
      PubDate: 2017-11-07T10:00:01.301849-05:
      DOI: 10.1111/acer.13521
  • Cortical thickness in adolescents with a family history of alcohol use
    • Authors: Kate E. Henderson; Jatin G. Vaidya, John R. Kramer, Samuel Kuperman, Douglas R. Langbehn, Daniel S. O'Leary
      Abstract: BackgroundIndividuals with a family history (FH+) of alcohol use disorder (AUD) have a higher risk for developing an AUD than those with no family history (FH-) of AUD. In addition, FH+ individuals tend to perform worse on neuropsychological measures and show heightened impulsivity, which may be due to underlying differences in brain structure such as cortical thickness. The primary aim of this study was to investigate differences in cortical thickness in FH+ compared to FH- adolescents. Secondary aims were to: a) investigate differences in executive functioning and impulsivity, and b) examine associations between brain structure and behavior.MethodBrain scans of 95 FH- and 93 FH+ subjects aged 13-18 were obtained using magnetic resonance imaging (MRI). FH+ subjects were required to have at least 1 biological parent with a history of an AUD. FH+ and FH- individuals had limited or no past alcohol use, thereby minimizing potential effects of alcohol. Subjects were evaluated on impulsivity and executive functioning tasks. Thicknesses of cortical lobes and subregions were analyzed using FreeSurfer. Regions showing group differences were examined for group by age interactions and correlations with neuropsychological and personality measures.ResultsFH+ adolescents had thinner cortices in frontal and parietal lobes, notably in the medial orbitofrontal, lateral orbitofrontal, and superior parietal cortices. The difference in cortical thickness between family history groups was strongest among the youngest subjects. FH+ subjects were also more impulsive and had poorer performance on a spatial memory task.ConclusionsThese findings demonstrate frontal and parietal structural differences in FH+ adolescents that might underlie cognitive and behavioral characteristics associated with AUD risk.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-03T07:51:15.395513-05:
      DOI: 10.1111/acer.13543
  • V1b receptor antagonist SSR149415 and naltrexone synergistically decrease
           excessive alcohol drinking in male and female mice
    • Authors: Yan Zhou; Marcelo Rubinstein, Malcolm Low, Mary Jeanne Kreek
      Abstract: BackgroundA recent clinical trial found that pharmacological blockade of V1b receptors reduces alcohol relapse in alcohol-dependent patients. SSR149415 is a selective V1b receptor antagonist that has potential for development as an alcohol dependency treatment. In this study, we investigated whether SSR149415 alone or in combination with the mu-opioid receptor [MOP-r] antagonist naltrexone (NTN) would alter excessive alcohol drinking in mice.MethodsBoth sexes of C57BL/6J (B6) mice were subjected to a chronic intermittent access (IA) drinking paradigm (two-bottle choice, 24-h access every other day) for 3 weeks. Sucrose and saccharin drinking were used as controls for alcohol-specific drug effects. Neuronal proopiomelanocortin (POMC) enhancer (nPE) knockout mice with hypothalamic-specific loss of POMC (including beta-endorphin, the main endogenous ligand of MOP-r) were used as a genetic control for the effects of NTN.ResultsAcute administration of SSR149415 (1-30 mg/kg) reduced alcohol intake and preference in a dose-dependent manner in both male and female B6 mice after IA. To investigate potential synergistic effects between NTN and SSR149415, we tested six different combination doses of SSR149415 and NTN, and found that a combination of SSR149415 (3 mg/kg) and NTN (1 mg/kg) reduced alcohol intake profoundly at doses lower than the individual effective doses in both sexes of B6 mice. We confirmed the effect of SSR149415 on reducing alcohol intake in nPE-/- male mice, consistent with independent mechanisms by which SSR149415 and NTN decrease alcohol drinking.ConclusionThe combination of V1b antagonist SSR149415 with NTN at individual subthreshold doses shows potential in alcoholism treatment, possibly with less adverse effects.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-03T07:50:32.492769-05:
      DOI: 10.1111/acer.13544
  • How do self-assessment of alexithymia and sensitivity to bodily sensations
           relate to alcohol consumption'
    • Authors: Sophie Betka; Gaby Pfeifer, Sarah Garfinkel, Hielke Prins, Rod Bond, Henrique Sequeira, Theodora Duka, Hugo Critchley
      Abstract: BackgroundAlexithymia describes an abnormality of emotional experience that is commonly expressed among individuals with addiction and alcohol abuse disorders. Alexithymic individuals are characterized by difficulties in identifying and describing their emotions. This impairment is linked to the development and maintenance of addiction. Moreover, an emergent theory suggests alexithymia is itself secondary to a failure of interoception (sensitivity to internal bodily signals, including physiological arousal states).MethodsThe present study tested for hypothesized contributory roles of alexithymia and dysfunctional interoception in the expression of binge drinking. Alexithymia, subjective sensitivity to bodily sensations, and alcohol consumption scores were quantified using the Toronto Alexithymia Scale, the Body Perception Questionnaire and the Alcohol Use Questionnaire respectively, in a normative sample (N=600). Regression and bootstrapping mediation analyses were used to test the hypothesis that alexithymia mediated the association between sensitivity to bodily sensations and alcohol consumption.ResultsAlexithymia was positively correlated with sensitivity to bodily sensations and with alcohol consumption. Mediation analysis revealed that alexithymia, and more precisely, difficulty in identifying feelings, mediated the relationship between sensitivity to bodily sensations and alcohol consumption, such that the predictive effect of sensitivity to bodily sensations on alcohol intake became non-significant when controlling for alexithymia.ConclusionsThese results indicate that alexithymia is associated with subjective hypersensitivity to bodily sensations. Moreover, our findings support the theoretical proposal that alexithymia is an expression of impaired processing of bodily sensations including physiological arousal, which underpin the development of maladaptive coping strategies, including alcohol use disorders. Our observations extend a growing literature emphasizing the importance of interoception and alexithymia in addiction, which can inform the development of new therapeutic strategies.This article is protected by copyright. All rights reserved.
      PubDate: 2017-11-02T06:28:49.216696-05:
      DOI: 10.1111/acer.13542
  • Changing Racial/Ethnic Disparities in Heavy Drinking Trajectories through
           Young Adulthood: A Comparative Cohort Study
    • Authors: Edwina Williams; Nina Mulia, Katherine J. Karriker-Jaffe, Camillia K. Lui
      Abstract: BackgroundThere is evidence of racial/ethnic differences in the age at which young adults age-out of heavy drinking. Some studies have found Black and Hispanic drinkers engage in more frequent heavy drinking than Whites beyond adulthood. Yet, the alcohol-related disparities literature has produced contradictory findings on whether an age-crossover effect is evident among racial/ethnic groups; that is, whether racial/ethnic minorities’ drinking levels or trajectories are lower than Whites’ at young ages but later exceed (or crossover) those of Whites. The current study extends this scant literature by assessing whether racial/ethnic differences in heavy drinking have changed over time (possibly accounting for mixed findings from prior research); and tests for an age-crossover effect in heavy drinking using longitudinal data from two cohorts born 20 years apart.MethodsData are from the 1979 (n=10,963) and 1997 (n=8,852) cohorts of the National Longitudinal Survey of Youth. Generalized estimating equations were used to model trajectories of heavy drinking frequency from ages 17–31. Racial/ethnic differences were determined using sex-stratified models and three-way interactions of race/ethnicity with age, age-squared and cohort.ResultsRacial/ethnic differences in heavy drinking trajectories have changed over time in men and women. In the older NLSY cohort, Hispanic men and Black women surpassed White men's and women's heavy drinking frequency by age 31. This crossover was absent in the younger cohort, where trajectories of all racial-sex groups converged by age 31. Normative trajectories have changed in Hispanics and Whites of both sexes, with a delay in age of peak frequency, and greater levels of heavy drinking in the younger cohort of women.ConclusionChanges in heavy drinking trajectories over time suggest the need for targeted interventions during young adulthood. While disparities in young adult heavy drinking were no longer apparent in the more recent birth cohort, continued monitoring is important.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-31T08:05:22.642671-05:
      DOI: 10.1111/acer.13541
  • Earlier Alcohol Use Onset Predicts Poorer Neuropsychological Functioning
           in Young Adults
    • Authors: Tam T. Nguyen-Louie; Georg E. Matt, Joanna Jacobus, Irene Li, Claudia Cota, Norma Castro, Susan F. Tapert
      Abstract: BackgroundNeurodevelopment may be shaped by environmental factors such as alcohol intake. Over 20% of U.S. high school students begin drinking before age 14, and those who initiated drinking before age 14 are 4 times more likely to develop psychosocial, psychiatric, and substance use difficulties than those who began drinking after turning 20. Little is known, however, about how the age of alcohol use onset influences brain development.MethodsThis study prospectively examined the effects of alcohol use onset age on neurocognitive functioning in healthy adolescent drinkers (N = 215). Youth were administered a neuropsychological battery before substance use initiation (M = 13.6 years, SD = 0.8) and on average 6.8 years later (M = 20.2 years, SD = 1.5). Hierarchical linear regressions examined if earlier ages of onset for first and regular (i.e., weekly) alcohol use adversely influenced neurocognition, above and beyond baseline neurocognition, substance use severity, and familial and social environment factors.ResultsAs hypothesized, an earlier age of first drinking onset (AFDO) predicted poorer performance in the domains of psychomotor speed and visual attention (ps
      PubDate: 2017-10-30T09:00:03.541703-05:
      DOI: 10.1111/acer.13503
  • Developmental Etiologies of Alcohol Use and Their Relations to Parent and
           Peer Influences Over Adolescence and Young Adulthood: A Genetically
           Informed Approach
    • Authors: Arielle R. Deutsch; Phillip K. Wood, Wendy S. Slutske
      Abstract: BackgroundDistinct changes in alcohol use etiologies occur during adolescence and young adulthood. Additionally, measured environments known to influence alcohol use such as peers and parenting practice can interact or be associated with this genetic influence. However, change in genetic and environmental influences over age, as well as how associations with measured environments change over age, is understudied.MethodsThe National Longitudinal Study of Adolescent Health (Add Health) sibling subsample was used to examine data-driven biometric models of alcohol use over ages 13 to 27. Associations between friends’ drinking, parental autonomy granting, and maternal closeness were also examined.ResultsThe best-fitting model included a 5-factor model consisting of early (ages 13 to 20) and overall (ages 13 to 27) additive genetic and unique environmental factors, as well as 1 overall common environment factor. The overall additive genetic factor and the early unique environment factor explained the preponderance of mean differences in the alcohol use over this portion of the life span. The most important factors explaining variance attributed to alcohol use changed over age. Additionally, friend use had the strongest associations with genetic and environmental factors at all ages, while parenting practices had almost no associations at any age.ConclusionsThese results supplement previous studies indicating changes in genetic and environmental influences in alcohol use over adolescence and adulthood. However, prior research suggesting that constraining exogenous predictors of genetic and environmental factors to have effects of the same magnitude across age overlooks the differential role of factors associated with alcohol use during adolescence. Consonant with previous research, friend use appears to have a more pervasive influence on alcohol use than parental influence during this age. Interventions and prevention programs geared toward reducing alcohol use in younger populations may benefit from focus on peer influence.Longitudinal, psychometrically-based biometric models indicated that alcohol use over adolescence and young adulthood had adolescent-specific genetic and unique environment influences (ages 13/14–19/20), in addition to A, C, and E factors explaining alcohol use over ages 13/14 to 25/27. Peer use related to all etiologies at almost every age, while parenting practices were not related to almost any etiology at any age.
      PubDate: 2017-10-30T09:00:02.296534-05:
      DOI: 10.1111/acer.13506
  • Phosphatidylethanol (PEth) in Comparison to Self-Reported Alcohol
           Consumption among HIV-infected Women in a Randomized Controlled Trial of
           Naltrexone for Reducing Hazardous Drinking
    • Authors: Yan Wang; Xinguang Chen, Judith A. Hahn, Babette Brumback, Zhi Zhou, Maria J. Miguez, Robert L. Cook
      Abstract: BackgroundBiomarkers can play a key role in supplementing self-report information in alcohol research. In this study, we examined phosphatidylethanol (PEth) in comparison to self-reported alcohol use over time in a randomized controlled trial.Materials and methodsParticipants were women living with HIV enrolled in a randomized placebo controlled trial of naltrexone for reducing hazardous drinking. Drinking behavior was measured using Timeline Followback (TLFB), and PEth as a biomarker using dried blood spots. Data collected at baseline, and months two and seven were analyzed. In addition to calculated Spearman's correlations, mixed effects modeling was used to evaluate the changes in self-reported drinking and PEth respectively, adjusting for body mass index.ResultsA total of 194 participants (83% black, mean age 48) were included in the analysis. PEth levels were significantly correlated with self-reported drinking via TLFB, Spearman's r = .21, at baseline, r = .29 at 2- and r = .28 at 7-month, respectively. No demographic or health factors, except for BMI, was associated with whether self-report was consistent with PEth. Mixed effects model indicated that self-reported drinking showed significantly greater reductions in the naltrexone treatment group than the placebo group at the 2- and 7-month visits, whereas PEth measure only showed this difference at the 7-month follow-up.ConclusionThe magnitude of the correlation between PEth and self-reported alcohol consumption was small. Caution is needed when using either self-report or PEth as a sole outcome measure for alcohol behavior changes in clinical trials.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-28T10:10:25.748764-05:
      DOI: 10.1111/acer.13540
  • Regulation of kisspeptin synthesis and release in the preoptic/anterior
           hypothalamic region of prepubertal female rats: actions of IGF-1 and
    • Authors: Jill K. Hiney; Vinod K. Srivastava, Danielle N. Vaden Anderson, Nicole L. Hartzoge, William L. Dees
      Abstract: BackgroundAlcohol (ALC) causes suppressed secretion of prepubertal luteinizing hormone-releasing hormone (LHRH). Insulin-like growth factor-1 (IGF-1) and kisspeptin (Kp) are major regulators of LHRH and are critical for puberty. IGF-1 may be an upstream mediator of Kp in the preoptic area and rostral hypothalamic area (POA/RHA) of the rat brain, a region containing both Kp and LHRH neurons. We investigated the ability of IGF-1 to stimulate prepubertal Kp synthesis and release in POA/RHA, and the potential inhibitory effects of ALCMethodsImmature female rats were administered either ALC (3g/Kg) or water via gastric gavage at 0730 h. At 0900 h both groups were subdivided where half received either saline or IGF-1 into the brain third ventricle. A second dose of ALC (2g/kg) or water was administered at 1130 h. Rats were killed 6 h after injection and POA/RHA region collectedResultsIGF-1 stimulated Kp, an action blocked by ALC. Upstream to Kp, IGF-1 receptor (IGF-1R) activation, as demonstrated by the increase in insulin receptor substrate 1, resulted in activation of Akt, tuberous sclerosis 2, ras homologue enriched in brain and mammalian target of rapamycin (mTOR). ALC blocked the central action of IGF-1 to induce their respective phosphorylation. IGF-1 and ALC specificity for the Akt activated mTOR pathway were demonstrated by the absence of effects on PRAS40. Furthermore, IGF-1 stimulated Kp release from POA/RHA incubated in vitroConclusionIGF-1 stimulates prepubertal Kp synthesis and release following activation of a mTOR signaling pathway and ALC blocks this pathway at the level of IGF-1R.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-26T08:28:06.762545-05:
      DOI: 10.1111/acer.13539
  • Estimation of the Potential Effectiveness of Lowering the Blood Alcohol
           Concentration (BAC) Limit for Driving from 0.08 to 0.05 Grams per
           Deciliter in the United States
    • Authors: James C. Fell; Michael Scherer
      Abstract: BackgroundIn 2013, the National Transportation Safety Board (NTSB) issued a report recommending that states lower the illegal blood alcohol concentration (BAC) limit for driving from 0.08 to 0.05 g/dl. The NTSB concluded that there is a strong evidence-based foundation for a BAC limit of 0.05 or lower. Most industrialized nations have already enacted a 0.05 illegal BAC limit. This study was undertaken to contribute to the scientific evidence as to whether lowering the BAC limit to 0.05 will be an effective alcohol policy in the United States.MethodsWe accomplished our objective by: (i) conducting a meta-analysis of qualifying international studies to estimate the range and distribution of the most likely effect size from a reduction to 0.05 BAC or lower; (ii) translating this synthesis toward estimating the effects of reducing the current 0.08 BAC limit to 0.05 in the United States; and (iii) estimating the life-saving benefits of the proposed 0.03 reduction in the driving limit from 0.08 to 0.05 BAC.ResultsIn our meta-analysis of studies on lowering the BAC limit in general, we found a 5.0% decline in nonfatal alcohol-related crashes, a 9.2% decline in fatal alcohol-related crashes from lowering the BAC to 0.08, and an 11.1% decline in fatal alcohol-related crashes from lowering the BAC to 0.05 or lower. We estimate that 1,790 lives would be saved each year if all states adopted a 0.05 BAC limit.ConclusionsThis study provides strong evidence of the relationship between lowering the BAC limit for driving and the general deterrent effect on alcohol-related crashes.
      PubDate: 2017-10-24T09:00:02.190337-05:
      DOI: 10.1111/acer.13501
  • Meta-Analyses of Externalizing Disorders: Genetics or Prenatal Alcohol
    • Authors: Leah Wetherill; Tatiana Foroud, Charles Goodlett
      Abstract: BackgroundExternalizing disorders are heritable precursors to alcohol dependence, common in children of alcoholics (COA), and in children with prenatal alcohol exposure (PAE). Pregnancies involving alcohol exposure sufficient to affect the fetus may involve women with genetic risk for alcohol dependence (AD). We hypothesized that known PAE will increase the odds of having an externalizing disorder compared to COA.MethodsThe odds ratios of three externalizing disorders [attention deficit hyperactivity (ADHD), conduct disorder (CD), and oppositional defiant disorder (ODD)] were obtained for two domains: (1) PAE and (2) COA, by estimating the logged odds ratios (LOR) for each study. Permutation tests were implemented to compare LORs for PAE vs COA studies within each disorder, including PAE vs an AD mother and PAE vs an AD father.ResultsIn PAE studies, the odds of ADHD and CD were elevated. Rates of all three disorders were elevated in COA studies. Permutation tests revealed that the mean LOR for ADHD was significantly higher in PAE studies compared to: COA (p=0.01), AD mother (p
      PubDate: 2017-10-23T19:10:28.374973-05:
      DOI: 10.1111/acer.13535
  • Impulsive personality traits mediate the relationship between adult
           attention deficit hyperactivity symptoms and alcohol dependence severity
    • Authors: Allison M. Daurio; Sean A. Aston, Melanie L. Schwandt, Mohammad O. Bukhari, Sofia Bouhlal, Mehdi Farokhnia, Mary R. Lee, Lorenzo Leggio
      Abstract: BackgroundWhile the role of attention deficit hyperactivity disorder (ADHD) as a risk factor for developing alcohol use disorder (AUD) has been established, the underlying pathways connecting the two are still not fully understood. Overlapping constructs such as impulsivity may explain the increased risk for developing AUD in individuals with ADHD.MethodsIn this study, we assessed whether adult ADHD symptoms increase the odds of having a diagnosis of AUD. Furthermore, we tested whether facets of impulsivity explained the relationship between ADHD symptoms and alcohol dependence (AD) severity.ResultsIn a logistic regression of 749 participants (464 = AD, 285 = controls), overall adult ADHD symptoms, and more specifically, symptoms of hyperactivity/restlessness and problems with self-concept, increased the odds of having a diagnosis of AD. Within the AD sample, we found that impulsivity mediated the relationship between adult ADHD symptoms and AD severity. In particular, negative and positive urgency meditated the relationship of overall adult ADHD symptoms, and symptoms of hyperactivity/ restlessness and problems with self-concept with AD severity.ConclusionsThese results highlight the importance of looking at cohorts of ADHD symptoms and facets of impulsivity to assess the risk of developing AUD. They also suggest potential avenues for intervention strategies in individuals with pre-existing adult ADHD symptoms who are seeking treatment for AUD.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-23T19:10:26.426118-05:
      DOI: 10.1111/acer.13538
  • Interactive Effects of Maternal Alcohol Problems and Parental Separation
           on Timing of Daughter's First Drink
    • Authors: Mary Waldron; Nicole K. Watkins, Kathleen K. Bucholz, Pamela A. F. Madden, Andrew C. Heath
      Abstract: BackgroundFew studies examine risk to offspring who experience both parental alcohol problems and parental separation, and still fewer consider gender of the affected parent. We examined interactive effects of maternal versus paternal alcohol problems and parental separation on timing of first alcoholic drink in daughters.MethodsData were drawn from a sample of 3539 European (or other) ancestry (EA) and 611 African ancestry (AA) female twins born between 1975 and 1985, median age 15 at first assessment. Cox proportional hazards regression models were estimated predicting age at first full drink from parental history of alcohol problems (mother only, father only, or both parents), parental separation during childhood, and the interaction of parental alcohol problems and parental separation. Cox models were estimated without and with adjustment for correlated risk factors, separately for EA and AA twins.ResultsFor both EA and AA twins, a significant interaction between parental separation and mother only alcohol problems was observed, suggesting reduced risk of drinking associated with mother only alcohol problems in separated versus intact families.ConclusionsFindings highlight parental separation as an important moderator of risk to children of mothers who have a history of problem drinking, with interactive effects observed consistently across racial group. To identify underlying processes, additional research is needed with more detailed characterization of separated families where mother only has a history of alcohol problems.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-23T19:10:24.111617-05:
      DOI: 10.1111/acer.13537
  • Nifedipine prevents apoptosis of alcohol-exposed first trimester
           trophoblast cells
    • Authors: Alan D Bolnick; Jay M. Bolnick, Hamid-Reza Kohan-Ghadr, Brian A. Kilburn, Michael Hertz, Jing Dai, Sascha Drewlo, D. Randall Armant
      Abstract: BackgroundMaternal alcohol abuse leading to fetal alcohol spectrum disorder (FASD) includes fetal growth restriction (FGR). Ethanol induces apoptosis of human placental trophoblast cells, possibly disrupting placentation and contributing to FGR in FASD. Ethanol facilitates apoptosis in several embryonic tissues, including human trophoblasts, by raising intracellular Ca2+. We previously found that acute ethanol exposure increases trophoblast apoptosis due to signaling from both intracellular and extracellular Ca2+. Therefore, nifedipine, a Ca2+ channel blocker that is commonly administered to treat preeclampsia and preterm labor, was evaluated for cytoprotective properties in trophoblast cells exposed to alcohol.MethodsHuman first trimester chorionic villous explants and the human trophoblast cell line HTR-8/SVneo were pre-treated with 12.5 - 50 nM of the Ca2+ channel blocker nifedipine for 1 hour before exposure to 50 mM ethanol for an additional hour. Intracellular Ca2+ concentrations were monitored in real-time by epifluorescence microscopy, using fluo4-AM. Apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), accumulation of cytoplasmic cytochrome c, and cleavage rates of caspase 3 and caspase 9.ResultsThe increase in intracellular Ca2+ upon exposure to ethanol in both villous explants and HTR-8/SVneo cells was completely blocked (p
      PubDate: 2017-10-19T07:55:21.419568-05:
      DOI: 10.1111/acer.13534
  • Effect of chronic alcohol abuse on anabolic and catabolic signaling
           pathways in human skeletal muscle
    • Authors: Boris S. Shenkman; Svetlana P. Belova, Olga E. Zinovyeva, Nudlya D. Samkhaeva, Timur M. Mirzoev, Natalia A. Vilchinskaya, Erzhena G. Altaeva, Olga V. Turtikova, Tatiana Y. Kostrominova, Tatiana L. Nemirovskaya
      Abstract: BackgroundAnimal studies showed that alcoholic myopathy is characterized by the reduction of myofiber cross sectional area (CSA) and by impaired anabolic signaling. The goal of the current study was to compare changes in CSA and fiber type composition with modifications in anabolic and catabolic signaling pathways at the early stages of alcohol misuse in humans.MethodsSkeletal muscle samples from seven male patients with chronic alcohol abuse (AL; 47.7±2.0 years old; alcohol misuse duration 7.7±0.6 years) were compared with muscle from control group of seven healthy men (C; 39.7±5.0 years old). Biopsies from vastus lateralis muscles were taken and analyzed for the changes in fiber type composition, fiber CSA, and for the alterations in anabolic and catabolic signaling pathways.ResultsAL patients did not have detectable clinical myopathy symptoms or muscle fiber atrophy, but the relative proportion of fast fibers was increased. There was a significant decrease of IGF-I in plasma and IRS-1 protein content in muscle of AL group. Levels of total and phosphorylated p70S6K1, GSK3β, and p90RSK1 were not different between AL and C groups. Muscle of AL patients had increased mRNA expression of HSP70 and HSP90. A marker of anabolic pathway p-4E-BP1 was decreased while catabolic markers (MuRF-1, MAFbx, ubiquitinated proteins) were increased in AL patients when compared with C group.ConclusionsAt the early stages of alcohol misuse in humans, changes in the regulation of anabolic and catabolic signaling pathways precede the development of skeletal muscle atrophy and manifestation of clinical symptoms of alcoholic myopathy.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-16T08:02:42.795497-05:
      DOI: 10.1111/acer.13531
  • Context-specific inhibition is related to craving in alcohol use
           disorders: A dangerous imbalance
    • Authors: Maria Stein; Werner Fey, Thomas Koenig, Jacqueline Oehy, Franz Moggi
      Abstract: BackgroundMost contemporary neuroscientific models of alcohol use disorders (AUD) incorporate an imbalance between enhanced cue reactivity, which results in a strong urge to consume, and the impaired inhibitory control of that urge. While these phenomena have been frequently investigated separately, studies involving both aspects and thus precisely investigating the postulated imbalance are rare. In this study, inhibition was investigated in an addiction-specific context and individual craving levels were also examined.MethodsThis study compared inhibition in alcohol-related and neutral contexts in patients with AUD and healthy controls, while also taking into account the individual amount of craving. All subjects performed a Go-NoGo task involving neutral and alcohol-related NoGo-trials while their brain activity was recorded using multichannel electroencephalography. The map strength and topography of the N2 and P3 components of the NoGo event-related potentials were compared between groups and contexts using whole-scalp randomization-based methods. The effects of interest were further investigated with sLORETA source analysis.ResultsFor the N2 component, the context by craving interaction was strong for map strength and map topography. The source analysis indicated that in subjects with high craving, alcohol-related context led to enhanced and prolonged activation in the posterior cingulate and premotor cortical areas. This interaction was specific for craving, but not for diagnostic classification. The amplitude of the P3 component was reduced in subjects with AUD, which replicated previous findings.ConclusionsIn subjects with strong craving, the conflict reflected in the NoGo-N2 was enhanced in the alcohol-related context. Such enhanced conflict probably makes the successful inhibition of the urge to drink in high-risk situations even more difficult for this subgroup of patients and should therefore be addressed in individualized treatment planning.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-16T08:01:20.091504-05:
      DOI: 10.1111/acer.13532
  • Work is important. Commentary on Finn et al. (2017); Decisions to attend
           and Drink at party events: the effects of incentives and disincentives and
           lifetime alcohol and antisocial problems
    • Authors: Geert Dom
      Abstract: In their recent study Finn et al. explore the effect of contextual factors and antisocial problems in alcohol use decision making(Finn et al., 2017). Both their findings as well as the methodology they use are inspiring. First, the findings point to the importance of including alcohol-related context in task design when studying decision making processes in alcohol use disorders. This could potentially result in more accurate assessments of real life decision making, i.e. tapping into a more ecologically valid decision-making process than when using a single monetary risk or decision-making task. Second, their findings highlight the importance of assessing personality traits when evaluating an individual's decision patterns towards alcohol use. Finally, the findings suggest that a low antisocial problems level and having social responsibilities such as work, might be factors enabling the feasibility of alcohol reduction as a treatment goal.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-16T08:01:17.963068-05:
      DOI: 10.1111/acer.13530
  • Modification of Automatic Alcohol-Approach Tendencies in Alcohol-Dependent
           Patients with Mild or Major Neurocognitive Disorder
    • Authors: Anke Loijen; Mike Rinck, Serge J. W. Walvoort, Roy P. C. Kessels, Eni S. Becker, Jos I. M. Egger
      Abstract: BackgroundTo examine the applicability of an alcohol-avoidance training procedure in patients with alcohol dependence and alcohol-induced neurocognitive disorders, we trained two groups that differed in the degree of cognitive impairment: One group fulfilled the DSM-5 criteria for Alcohol-Induced Mild Neurocognitive Disorder, and one group was diagnosed with Korsakoff's syndrome (Alcohol-Induced Major Neurocognitive Disorder, Confabulatory/Amnesic subtype; DSM-5). The intervention is assumed to match the preserved cognitive capacity for implicit learning in both groups.Methods51 Inpatients with a mild neurocognitive disorder and 54 inpatients with Korsakoff's syndrome were trained. Six training sessions (including pre- and posttests) of a computerized implicit alcohol approach-avoidance task were applied. Neurocognitive variables were available from the standard assessment procedure of the clinic.ResultsTraining of alcohol-avoidance tendencies is feasible in a population with alcohol-related neurocognitive disorders. The alcohol-approach bias decreased for both groups in each session. Better learning results over time were obtained in participants with a larger baseline alcohol-approach tendency. Learning effects were positively related to age and implicit (non-declarative) memory functioning. No relation between training effects and executive or explicit memory functions were found.ConclusionsTraining of an alcohol avoidance tendency can be successfully applied in patients with alcohol-dependence including those with alcohol-induced neurocognitive disorders.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-16T02:30:32.346467-05:
      DOI: 10.1111/acer.13529
  • Beneficial effect of alcohol withdrawal on gut permeability and microbial
           translocation in patients with alcohol use disorder
    • Authors: Hélène Donnadieu-Rigole; Nathalie Pansu, Thibault Mura, Stéphanie Pelletier, Régis Alarcon, Lucie Gamon, Pascal Perney, Florence Apparailly, Jean-Philippe Lavigne, Catherine Dunyach-Remy
      Abstract: BackgroundThe human intestinal microbiota exerts beneficial or harmful effects in several disorders. Many factors, including alcohol consumption, may influence its composition and trigger bacterial translocation. Excessive alcohol consumption increases gut permeability and translocation of endotoxin into peripheral circulation. Although plasma endotoxin concentrations have been measured often, quantitative changes following alcohol withdrawal have never been described in subjects with alcohol use disorder (AUD). The aim of this study was to measure microbial translocation (MT) and gut permeability markers in patients with AUD, to compare these markers to healthy controls (HC) and to monitor markers during the first six weeks of abstinence.MethodsSixty-five patients with AUD and hospitalized for alcohol withdrawal were included. Epidemiological, clinical, biological and addictological data were gathered. Blood samples were collected at baseline, then three and six weeks after alcohol withdrawal. A hundred healthy volunteers were used as controls. Three markers of MT were monitored in plasma samples: sCD14 and LBP were quantified using ELISA, and 16S rDNA was quantified using real time PCR. Zonulin and I-FABP blood levels were also monitored as indirect markers of gut permeability, using ELISA.ResultsAt baseline, LBP, 16S rDNA and I-FABP markers were significantly higher in AUD patients than in HC. Six weeks after alcohol withdrawal plasma levels of sCD14 and LBP decreased significantly. Cannabis consumption and BMI before alcohol withdrawal influenced baseline MT levels and the decrease in MT markers after six weeks. Finally, markers of MT and gut permeability did not correlate with each other before and after alcohol withdrawal.ConclusionsBefore alcohol withdrawal, MT markers were higher in AUD patients than in HC. After six weeks of abstinence an improvement in MT markers was observed. Our data suggest that there is a link between MT, its improvement, BMI and cannabis consumption.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-14T10:25:22.464606-05:
      DOI: 10.1111/acer.13527
  • Dopamine Transporter Gene Methylation is Associated with Nucleus Accumbens
           Activation during Reward Processing in Healthy but not Alcohol-Dependent
    • Authors: Christine Muench; Corinde E. Wiers, Carlos R. Cortes, Reza Momenan, Falk W. Lohoff
      Abstract: BackgroundAlcohol's reinforcement is mediated by dopamine signaling in the ventral striatum, which is modulated by the dopamine transporter (DAT). We hypothesized that methylomic variation in the DAT gene (SLC6A3) affects DAT expression thus contributing to differences in brain reward circuitry in individuals with alcohol dependence (ALC).MethodsBlood from 45 recently detoxified ALC and 45 healthy control (HC) individuals was used to assess DNA methylation across 5 functional regions of SLC6A3. Participants completed the Monetary Incentive Delay task in a 3-Tesla MRI scanner. Employing regression models, we examined effects of SLC6A3 methylation on Nucleus Accumbens (NAc) BOLD responses during anticipation of high/low reward/loss.ResultsResults showed that decreased methylation of the promoter region of SLC6A3 predicted NAc activation during high loss anticipation (p = 0.028) and low loss anticipation (at trend-level; p = 0.057) in HC but not in individuals with ALC. Specifically, percentage of methylation at two CpG sites, located -1001 and -993 base pairs from the transcription start site, accounted for significant variability in NAc activation in the HC group during high (ps ≤ 0.010) and low (ps ≤ 0.006) loss anticipation. There was no effect on reward anticipation. Furthermore, promoter methylation was positively associated with age, which replicates previous findings.ConclusionsOur data suggest that methylation in the promoter region of SLC6A3 predicts NAc activation during the anticipation of monetary loss in HCs. However, this effect was not present in the ALC group, suggesting that epigenetic regulation of striatal DAT expression might be disrupted in ALC, which may contribute to previously reported differences in sensitivity to reward and punishment in this population. Alternatively, it is possible that a similar relationship in the ALC group remained undetected possibly due to methodological limitations inherent in fMRI (e.g., poor spatial resolution, low signal to noise ratio) that generally restrict interpretations regarding mechanisms of epigenetic factors involved in group differences in BOLD responses. Future neuroimaging studies are needed to further elucidate the relationship between SLC6A3 methylation and NAc activation in ALC.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-14T10:25:19.594618-05:
      DOI: 10.1111/acer.13526
  • Commentary on Montag et al. (2017): The Importance of CBPR in FASD
           Prevention with American Indian Communities
    • Authors: Jessica D. Hanson; Tess L. Weber
      Abstract: Prenatal alcohol consumption is a public health concern due to potential lifelong physical and cognitive effects in offspring, often presenting in the form of fetal alcohol syndrome (FAS) or other fetal alcohol spectrum disorders (FASD). FASD is the continuum of lifelong outcomes in those born prenatally exposed to alcohol and includes a diagnosis of fetal alcohol syndrome (FAS), which is diagnosed through facial abnormalities, growth retardation, and delayed brain growth (Hoyme et al., 2016), as well as secondary disabilities such as conduct disorders, mental illness, and psychosocial functioning. Although local, community-specific surveillance data is generally lacking, FASD is of particular concern for many American Indian/Alaska Native (AI/AN) communities, and rates of FAS among Northern Plains AI/ANs range as high as 9 per 1,000 live births (May et al., 2002). Therefore, prevention of FASD and alcohol-exposed pregnancy among AI/AN communities is essential. Previous FASD prevention projects within AI/AN communities have focused almost exclusively on women prior to pregnancy (Hanson et al., 2017), pregnant women (May et al., 2008) or on broad community education (Williams and Gloster, 1999).This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-10T09:40:23.115717-05:
      DOI: 10.1111/acer.13524
  • Response to Afshar et al.'s letter to the editor
    • Authors: Qiuping Ding; Liang Shen
      Abstract: We greatly appreciate Afshar et al.'s interest and comments on our published article entitled “Acute Alcohol Exposure and Risk of Mortality of Patients with Traumatic Brain Injury: A Systematic Review and Meta-analysis”. They noted that methodological issues in our paper should be considered to provide an unbiased conclusion. Considering the limitations of observational studies, we agree with some of Afshar et al.'s suggestions in their letter to the editor. However, we have our own views on the limitations mentioned in the letter.The authors argue that a selection bias exists when using data from trauma centres. They imply that blood alcohol concentration (BAC) is not systematically assessed and that missing values are not missing at random.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-09T15:30:41.739015-05:
      DOI: 10.1111/acer.13517
  • Interaction between the μ-opioid receptor gene and the number of heavy
           drinking peers on alcohol use
    • Authors: Michelle J. Zaso; Stephen A. Maisto, Stephen J. Glatt, John M. Belote, Aesoon Park
      Abstract: BackgroundThe presence of heavy drinking peers may trigger genetic vulnerabilities to alcohol use. Limited correlational findings, albeit mixed as a function of age, suggest that carriers of a μ-opioid receptor (OPRM1) G allele may be more vulnerable than noncarriers to alcohol-promoting perceived peer environments. However, research has not yet examined such genetic susceptibility to actual (rather than perceived) peer environments through an experimental, ad libitum alcohol administration design. The current study examined whether OPRM1 modulates the effects of heavy drinking group size on alcohol consumption and explored potential mediators of such OPRM1-based differences.MethodsCaucasian young adult moderate to heavy drinkers (N = 116; mean age = 22 years [SD = 2.21], 49% female) were randomly assigned to consume alcohol in the presence of none, one, or three heavy drinking peer confederates.ResultsResults showed no significant moderating effects of OPRM1 in the relationship between the number (or presence) of heavy drinking peers and voluntary alcohol consumption (partial η2 = .01). This result remained the same after controlling for sex, age, and typical drinking quantity as well as their two-way interactions with OPRM1 and social drinking condition. In addition, OPRM1 did not moderate the peer influence on any proposed mediating variables, including craving for alcohol and subjective responses to alcohol.ConclusionsFindings suggest no OPRM1-based susceptibility to the number of heavy drinking peers, adding to the existing mixed findings from correlational studies. Future research on OPRM1-related susceptibility to alcohol-promoting peer environments through meta-analytic synthesis and both experimental and prospective, multi-wave designs is needed to resolve these mixed findings.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-09T14:50:29.691969-05:
      DOI: 10.1111/acer.13523
  • Impact of social cognition on alcohol dependence treatment outcome: Poorer
           facial emotion recognition predicts relapse/dropout
    • Authors: Claudia I. Rupp; Birgit Derntl, Friederike Osthaus, Georg Kemmler, W. Wolfgang Fleischhacker
      Abstract: BackgroundDespite growing evidence for neurobehavioral deficits in social cognition in alcohol use disorder (AUD), the clinical relevance remains unclear, and little is known about its impact on treatment outcome. This study prospectively investigated the impact of neurocognitive social abilities at treatment onset and on treatment completion.MethodsFifty-nine alcohol-dependent patients were assessed with measures of social cognition including three core components of empathy via paradigms measuring: 1) emotion recognition (the ability to recognize emotions via facial expression), 2) emotional perspective taking, and 3) affective responsiveness at the beginning of inpatient treatment for alcohol dependence. Subjective measures were also obtained, including estimates of task performance, and a self-report measure of empathic abilities (Interpersonal Reactivity Index). According to treatment outcomes, patients were divided into a patient group with a regular treatment course (e.g., with planned discharge, and without relapse during treatment) or an irregular treatment course (e.g., relapse and/or premature and unplanned termination of treatment, “dropout”).ResultsCompared with patients completing treatment in a regular fashion, patients with relapse and/or dropout of treatment had significantly poorer facial emotion recognition ability at treatment onset. Additional logistic regression analyses confirmed these results, and identified poor emotion recognition performance as a significant predictor for relapse/dropout. Self-report (subjective) measures did not correspond with neurobehavioral social cognition measures, respectively objective task performance. Analyses of individual subtypes of facial emotions revealed poorer recognition particularly of disgust, anger and no (neutral faces) emotion in patients with relapse/dropout.ConclusionsSocial cognition in AUD is clinically relevant. Less successful treatment outcome was associated with poorer facial emotion recognition ability at the beginning of treatment. Impaired facial emotion recognition represents a neurocognitive risk factor that should be taken into account in alcohol dependence treatment. Treatments targeting the improvement of these social cognition deficits in AUD may offer a promising future approach.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-09T14:50:24.42497-05:0
      DOI: 10.1111/acer.13522
  • Alcohol feeding in mice promotes colonic hyperpermeability and changes in
           colonic organoid stem cell fate
    • Authors: Christopher B. Forsyth; Maliha Shaikh, Faraz Bishehsari, Garth Swanson, Robin M. Voigt, Hemraj Dodiya, Peter Wilkinson, Beata Samelco, Shiwen Song, Ali Keshavarzian
      Abstract: BackgroundAlcohol increases intestinal permeability to pro-inflammatory microbial products that promote liver disease, even after a period of sobriety. We sought to test the hypothesis that alcohol affects intestinal stem cells using an in vivo model and ex vivo organoids generated from jejunum and colon from mice fed chronic alcohol.MethodsMice were fed a control or an alcohol diet. Intestinal permeability, liver steatosis/inflammation, and stool short chain fatty acids (SCFA) were measured. Jejunum and colon organoids and tissue were stained for stem cell, cell lineage, and apical junction markers with assessment of mRNA by PCR and RNA-seq. ChIP-PCR analysis was carried out for Notch1 using an antibody specific for acetylated histone 3.ResultsAlcohol-fed mice exhibited colonic (but not small intestinal) hyperpermeability, steatohepatitis and decreased butyrate/total SCFA ratio in stool. Stem cell, cell lineage, and apical junction marker staining in tissue or organoids from jejunum tissue were not impacted by alcohol. Only chromogranin A (Chga) was increased in jejunum organoids by qPCR. However, colon tissue and organoid staining exhibited an alcohol-induced significant decrease in cytokeratin 20+ (Krt20) absorptive lineage enterocytes, a decrease in occludin and E-cadherin apical junction proteins, an increase in Chga, and an increase in the Lgr5 stem cell marker. qPCR revealed an alcohol-induced decrease in colon organoid and tissue Notch1, Hes1, and Krt20 and increased Chga, supporting an alteration in stem cell fate due to decreased Notch1 expression. Colon tissue ChIP-PCR revealed alcohol feeding suppressed Notch1 mRNA expression (via deacetylation of histone H3) and decreased Notch1 tissue staining.ConclusionsData support a model for alcohol-induced colonic hyperpermeability via epigenetic effects on Notch1, and thus Hes1, suppression through a mechanism involving histone H3 deacetylation at the Notch1 locus. This decreased enterocyte and increased enteroendocrine cell colonic stem cell fate and decreased apical junctional proteins leading to hyperpermeability.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-09T14:40:33.763161-05:
      DOI: 10.1111/acer.13519
  • A Single Session of Attentional Bias Modification Reduces Alcohol Craving
           and Implicit Measures of Alcohol Bias in Young Adult Drinkers
    • Authors: Peter Luehring-Jones; Courtney Louis, Tracy A. Dennis-Tiwary, Joel Erblich
      Abstract: BackgroundAttentional bias modification (ABM) techniques for reducing problematic alcohol consumption hold promise as highly-accessible and cost-effective treatment approaches. A growing body of literature has examined ABM as a potentially efficacious intervention for reducing drinking and drinking-related cognitions in alcohol-dependent individuals as well as those at-risk of developing problem drinking habits.MethodsThe present study tested the effectiveness of a single session of visual probe-based ABM training in a cohort of 60 non-treatment-seeking young adult drinkers, with a focus on examining mechanisms underlying training efficacy. Participants were randomly assigned to a single session of active ABM training or a sham training condition in a laboratory setting. Measures of implicit drinking-related cognitions (alcohol Stroop and an Implicit Association Test) and attentional bias (alcohol visual probe) were administered, and subjective alcohol craving was reported in response to in-vivo alcohol cues.ResultsResults showed that active ABM training, relative to sham, resulted in significant differences in measures of implicit alcohol-related cognition, alcohol-related attentional bias, and self-reports of alcohol craving. Mediation analysis showed that reductions in craving were fully mediated by ABM-related reductions in alcohol-Stroop interference scores, suggesting a previously undocumented relationship between the two measures.ConclusionResults document the efficacy of brief ABM to reduce both implicit and explicit processes related to drinking, and highlight the potential intervention-relevance of alcohol-related implicit cognitions in social drinkers.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-09T14:40:23.309855-05:
      DOI: 10.1111/acer.13520
  • Letter to the Editor: Ding Q, Wang Z, Shen M, Su Z, and Shen L. Acute
           Alcohol Exposure and Risk of Mortality of Patients with Traumatic Brain
           Injury: A Systematic Review and Meta-analysis
    • Authors: Majid Afshar; Jennifer S. Albrecht
      Abstract: Ding et al. performed a systematic review and meta-analysis to examine the association of blood alcohol concentration (BAC) with mortality in patients with traumatic brain injury (TBI). The authors identified eighteen observational studies for meta-analysis and reported no association between BAC and death in patients with TBI. Lower levels of BAC (1-100 mg/dL) were associated with greater odds of death than higher levels of BAC, implying a protective effect in higher BAC groups.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-09T14:35:20.448749-05:
      DOI: 10.1111/acer.13518
  • Variation in SWI/SNF chromatin remodeling complex proteins is associated
           with alcohol dependence and antisocial behavior in human populations
    • Authors: Laura D. Mathies; Fazil Aliev, , Andrew G. Davies, Danielle M. Dick, Jill C. Bettinger
      Abstract: BackgroundTesting for direct gene/SNP replication of association across studies may not capture the true importance of a candidate locus; rather, we suggest that relevant replication across studies may be found at the level of a biological process. We previously observed that variation in two members of the SWI/SNF chromatin remodeling complex is associated with alcohol dependence (AD) in the Irish Affected Sib Pair Study for Alcohol Dependence. Here, we tested for association with alcohol-related outcomes using a set of genes functioning in the SWI/SNF complex in two independent samples.MethodsWe used a set-based analysis to examine the 29 genes of the SWI/SNF complex for evidence of association with (1) AD in the adult Collaborative Study on the Genetics of Alcoholism (COGA) case/control sample and (2) antisocial behavior, hypothesized to be a genetically-related developmental precursor, in a younger population sample (Spit for Science).ResultsWe found evidence for association of the SWI/SNF complex with AD in COGA (p=0.0435) and more general antisocial behavior in Spit for Science (p=0.00026). The genes that contributed most strongly to the signal in COGA were SS18L1, SMARCD1, BRD7, SMARCB1 and BCL11A. In the Spit for Science sample, ACTB, ARID2, BCL11A, BCL11B, BCL7B, BCL7C, DPF2, and DPF3 all contributed strongly to the signal.ConclusionsWe detected associations between the SWI/SNF complex and AD in an adult population selected from treatment-seeking probands and antisocial behavior in an adolescent population sample. This provides strong support for a role for SWI/SNF in the development of alcohol-related problems.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-05T09:45:49.733974-05:
      DOI: 10.1111/acer.13514
  • Challenges in patient enrollment and retention in clinical studies for
           alcoholic hepatitis: Experience of the TREAT Consortium
    • Authors: Megan Comerford; Spencer Lourens, Suthat Liangpunsakul, Naga P. Chalasani, Arun J Sanyal, Vijay H. Shah, Patrick S. Kamath, Puneet Puri, Barry P. Katz, Svetlana Radaeva, David W. Crabb
      Abstract: The TREAT Consortium has carried out clinical studies on alcoholic hepatitis (AH) for over four years. We encountered problems with participant recruitment, retention, and eligibility for specific protocols. To improve our ability to carry out such trials, we reviewed recruitment screening logs, end of study logs, and surveyed study coordinators to learn the reasons for missing patients, why patients declined enrollment, and the number of patients eligible for treatment trials. Associations of the recruited subjects’ demographics with their adherence to follow-up appointments were examined. 387 patients (AH and heavy drinking controls) were enrolled in the observational study and 55 AH patients were recruited into treatment trials. About half of patients identified with AH could not be recruited; no specific reason could be determined for about two thirds of these. Among the patients who gave a reason for not participating, the most common reasons were: feeling too sick to participate, desire to concentrate on abstinence, and lack of interest in research. Approximately a quarter of the AH patients met eligibility criteria for treatment trials for moderate or severe AH and we were able to recruit half to two thirds of those eligible. Approximately 35% of participants in the observational study returned for both 6 and 12 month follow-up visits. We did not identify biopsychosocial or demographic correlates of retention in the study. This analysis revealed that attempts at recruitment into trials for AH miss some subjects because of structural issues surrounding their hospital admission, and encounter a high rate of patient refusal to participate. Nonetheless, more than half of the patients who met the eligibility criteria for moderate or severe AH were entered into clinical trials. Retention rates for the observational study are relatively low. These findings need to be accounted for in clinical trial design and power analysis.This article is protected by copyright. All rights reserved.
      PubDate: 2017-10-05T09:45:44.536025-05:
      DOI: 10.1111/acer.13515
  • CREB Mediates Alcohol-Induced Circadian Disruption and Intestinal
    • Authors: Booker T Davis; Robin M. Voigt, Maliha Shaikh, Christopher B. Forsyth, Ali Keshavarzian
      Abstract: BackgroundAlcoholic Liver Disease (ALD) is commonly associated with intestinal permeability. An unanswered question is why only a subset of heavy alcohol drinkers develop endotoxemia. Recent studies suggest that circadian disruption is the susceptibility factor for alcohol-induced gut leakiness to endotoxins. The circadian protein PER2 is increased after exposure to alcohol and siRNA knockdown of PER2 in vitro blocks alcohol-induced intestinal barrier dysfunction. We have shown that blocking CYP2E1 (i.e., important for alcohol metabolism) with siRNA inhibits the alcohol-induced increase in PER2 and suggesting that oxidative stress may mediate alcohol-induced increase in PER 2 in intestinal epithelial cells. The Aim of the current study was to elucidate whether a mechanism incited by alcohol-derived oxidative stress mediates the transcriptional induction of PER2 and subsequent intestinal hyperpermeability.MethodsCaco-2 cells were exposed to 0.2% alcohol with or without pretreatment with modulators of oxidative stress or PKA activity. Permeability of the Caco-2 monolayer was assessed by transepithelial electrical resistance. Protein expression was measured by Western Blot and mRNA with real-time polymerase chain reaction. Wild-type C57BL/6J mice (WT) mice were fed with alcohol diet (29% of total calories, 4.5% v/v) for 8 weeks. Western Blot was used to analyze PER2 expression in mouse proximal colon tissue.ResultsAlcohol increased oxidative stress, caused Caco-2 cell monolayer dysfunction, and increased levels of the circadian clock proteins Per2 and Clock. These effects were mitigated by pre-treatment of Caco-2 cells with an anti-oxidant scavenger. Alcohol-derived oxidative stress activated CREB via the PKA pathway and increased PER2 mRNA and protein. Inhibiting CREB prevented the increase in PER2 and Caco-2 cell monolayer hyperpermeability.ConclusionsTaken together, these data suggest that strategies to reduce alcohol-induced oxidative stress may alleviate alcohol mediated circadian disruption and intestinal leakiness, critical drivers of ALD.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-27T08:00:22.76653-05:0
      DOI: 10.1111/acer.13513
  • The Prospective Association Between Internalizing Symptoms and Adolescent
           Alcohol Involvement and the Moderating Role of Age and Externalizing
    • Authors: Craig R. Colder; Kathleen Shyhalla, Seth Frndak, Jennifer P. Read, Liliana J. Lengua, Larry W. Hawk, William F. Wieczorek
      Abstract: BackgroundAs predicted by self-medication theories that drinking is motivated by a desire to ameliorate emotional distress, some studies find internalizing symptoms (e.g., anxiety, depression) increase risk for adolescent drinking; however, such a risk effect has not been supported consistently. Our prior work examined externalizing symptoms as a potential moderator of the association between internalizing symptoms and adolescent alcohol use (AU) to explain some of the inconsistencies in the literature. We found that internalizing symptoms were protective against early adolescent AU particularly for youth elevated on externalizing symptoms (a two-way interaction). Our sample has now been followed for several additional assessments that extend into young adulthood, and the current study tests whether the protective effect of internalizing symptoms may change as youth age into young adulthood, and whether this age moderating effect varied across different clusters of internalizing symptoms (social anxiety, generalized anxiety, and depression). Internalizing symptoms were hypothesized to shift from a protective factor to a risk factor with age, particularly for youth elevated on externalizing symptoms.MethodA community sample of 387 adolescents was followed for nine annual assessments (mean age =12.1 years at the first assessment and 55% female). Multilevel cross-lagged two-part zero-inflated poisson models were used to test hypotheses.ResultsThe most robust moderating effects were for levels of alcohol use, such that the protective effect of all internalizing symptom clusters was most evident in the context of moderate to high levels of externalizing problems. A risk effect of internalizing symptoms was evident at low levels of externalizing symptoms. With age, the risk and protective effects of internalizing symptoms were evident at less extreme levels of externalizing behavior. With respect to alcohol-related problems, findings did not support age moderation for generalized anxiety or depression, but it was supported for social anxiety.ConclusionsFindings highlight the importance of considering the role of emotional distress from a developmental perspective and in the context of externalizing behavior problems.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-25T10:16:42.017105-05:
      DOI: 10.1111/acer.13512
  • Altered neural oscillations during multisensory integration in adolescents
           with fetal alcohol spectrum disorder
    • Authors: Alfredo D. Bolaños; Brian A. Coffman, Felicha T. Candelaria-Cook, Piyadasa Kodituwakku, Julia M. Stephen
      Abstract: BackgroundChildren with fetal alcohol spectrum disorder (FASD), who were exposed to alcohol in utero, display a broad range of sensory, cognitive, and behavioral deficits, which are broadly theorized to be rooted in altered brain function and structure. Based on the role of neural oscillations in multisensory integration from past studies, we hypothesized that adolescents with FASD would show a decrease in oscillatory power during event-related gamma oscillatory activity (30-100Hz), when compared to typically-developing healthy controls (HC), and that such decrease in oscillatory power would predict behavioral performance.MethodsWe measured sensory neurophysiology using magnetoencephalography (MEG) during passive auditory (A), somatosensory (S), and multisensory (synchronous A/S) stimulation in 19 adolescents (12-21yrs) with FASD and 23 age- and gender-matched HC. We employed a cross-hemisphere multisensory paradigm to assess interhemispheric connectivity deficits in children with FASD.ResultsTime-frequency analysis of MEG data revealed a significant decrease in gamma oscillatory power for both unisensory and multisensory conditions in the FASD group relative to HC, based on permutation testing of significant group differences. Greater beta oscillatory power (15-30 Hz) was also noted in the FASD group compared to HC in both unisensory and multisensory conditions. Regression analysis revealed greater predictive power of multisensory oscillations from unisensory oscillations in the FASD group compared to the HC group. Furthermore, multisensory oscillatory power, for both groups, predicted performance on the Intra-Extradimensional Set Shift Task and the Cambridge Gambling Task.ConclusionsAltered oscillatory power in the FASD group may reflect a restricted ability to process somatosensory and multisensory stimuli during day-to-day interactions. These alterations in neural oscillations may be associated with the neurobehavioral deficits experienced by adolescents with FASD, and may carry over to adulthood.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-25T00:31:06.410475-05:
      DOI: 10.1111/acer.13510
  • Alcohol and Stress Activation of Microglia and Neurons: Brain Regional
    • Authors: T.Jordan Walter; Ryan P. Vetreno, Fulton T. Crews
      Abstract: BackgroundCycles of alcohol and stress are hypothesized to contribute to alcohol use disorders. How this occurs is poorly understood, although both alcohol and stress activate the neuroimmune system – the immune molecules and cells that interact with the nervous system. The effects of alcohol and stress on the neuroimmune system are mediated in part by peripheral signaling molecules. Alcohol and stress both enhance immunomodulatory molecules such as corticosterone and endotoxin to impact neuroimmune cells such as microglia, and may subsequently impact neurons. In this study, we therefore examined the effects of acute and chronic ethanol on the corticosterone, endotoxin, microglial and neuronal response to acute stress.MethodsMale Wistar rats were treated intragastrically with acute ethanol and acutely stressed with restraint/water immersion. Another group of rats was treated intragastrically with chronic intermittent ethanol and acutely stressed following prolonged abstinence. Plasma corticosterone and endotoxin were measured, and immunohistochemical stains for the microglial marker CD11b and neuronal activation marker c-Fos were performed.ResultsAcute ethanol and acute stress interacted to increase plasma endotoxin and microglial CD11b, but not plasma corticosterone or neuronal c-Fos. Chronic ethanol caused a lasting sensitization of stress-induced plasma endotoxin, but not plasma corticosterone. Chronic ethanol also caused a lasting sensitization of stress-induced microglial CD11b, but not neuronal c-Fos.ConclusionsThese results find acute ethanol combined with acute stress enhanced plasma endotoxin, as well as microglial CD11b in many brain regions. Chronic ethanol followed by acute stress also increased plasma endotoxin and microglial CD11b, suggesting a lasting sensitization to acute stress. Overall, these data suggest alcohol and stress interact to increase plasma endotoxin, resulting in enhanced microglial activation that could contribute to disease progression.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-23T10:10:25.773244-05:
      DOI: 10.1111/acer.13511
  • Malondialdehyde-acetaldehyde protein adducts are found exclusively in the
           lungs of smokers with alcohol use disorders and are associated with
           systemic anti-MAA antibodies
    • Authors: Muna Sapkota; Ellen L. Burnham, Jane M. DeVasure, Jenea M. Sweeter, C.D. Hunter, Michael J. Duryee, Lynell W. Klassen, Kusum K. Kharbanda, Joseph H. Sisson, Geoffrey M. Thiele, Todd A. Wyatt
      Abstract: BackgroundMalondialdehyde (MDA) and acetaldehyde (AA) exist following ethanol metabolism and tobacco pyrolysis. As such, lungs of individuals with alcohol use disorders (AUD) are a target for the effects of combined alcohol and cigarette smoke metabolites. MDA and AA form a stable protein adduct, malondialdehyde-acetaldehyde (MAA) adduct, known to be immunogenic, profibrotic, and proinflammatory. MAA adduct is the dominant epitope in anti-MAA antibody formation. We hypothesized that MAA-adducted protein forms in lungs of those who both abuse alcohol and smoke cigarettes, and that this would be associated with systemically elevated anti-MAA antibodiesMethodsFour groups were established: AUD subjects who smoked cigarettes (+AUD/+smoke), smokers without AUD (-AUD/+smoke), AUD without smoke (+AUD/-smoke), and non-AUD/nonsmokers (-AUD/-smoke)ResultsWe observed a significant increase in MAA adducts in lung cells of +AUD/+smoke vs. -AUD/-smoke. No significant increase in MAA adducts was observed in -AUD/+smoke or in +AUD/-smoke compared to -AUD/-smoke. Serum from +AUD/+smoke had significantly increased levels of circulating anti-MAA IgA antibodies. After one week of alcohol that MAA-adducted protein is formed in the lungs of those who smoke cigarettes and abuse alcohol, leading to a subsequent increase in serum IgA antibodies. MAA-adducted proteins could play a role in pneumonia and other diseases of the lung in the setting of AUD and smoking.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-23T10:10:20.262992-05:
      DOI: 10.1111/acer.13509
  • The Corticotropin Releasing Factor Receptor 1 in Alcohol Use Disorder:
           Still a Valid Drug Target'
    • Authors: Matthew B. Pomrenze; Tracy L. Fetterly, Danny G. Winder, Robert O. Messing
      Abstract: Corticotropin releasing factor (CRF) is a neuropeptide that plays a key role in behavioral and physiological responses to stress. A large body of animal literature implicates CRF acting at type 1 CRF receptors (CRFR1) in consumption by alcohol dependent subjects, stress-induced reinstatement of alcohol seeking, and possibly binge alcohol consumption. These studies have encouraged recent pilot studies of CRFR1 antagonists in humans with alcohol use disorder (AUD). It was a great disappointment to many in the field that these studies failed to show an effect of these compounds on stress-induced alcohol craving. Here, we examine these studies to explore potential limitations, and discuss preclinical and human literature to ask whether CRFR1 is still a valid drug target to pursue for the treatment of alcohol use disorder.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-21T08:15:45.73819-05:0
      DOI: 10.1111/acer.13507
  • Alcohol-Induced Behaviors Require a Subset of Drosophila JmjC-Domain
           Histone Demethylases in the Nervous System
    • Authors: Jorge H. Pinzón; Addison R. Reed, Nevine A. Shalaby, Michael Buszczak, Aylin R. Rodan, Adrian Rothenfluh
      Abstract: BackgroundLong-lasting transcriptional changes underlie a number of adaptations that contribute to alcohol use disorders (AUD). Chromatin remodeling, including histone methylation, can confer distinct, long-lasting transcriptional changes, and histone methylases are known to play a role in the development of addiction. Conversely, little is known about the relevance of Jumonji (JmjC) domain-containing demethylases in AUDs. We systematically surveyed the alcohol-induced phenotypes of null mutations in all 13 Drosophila JmjC genes.MethodsWe used a collection of JmjC mutants, the majority of which we generated by homologous recombination, and assayed them in the Booze-o-mat to determine their naïve sensitivity to sedation and their tolerance (change in sensitivity upon repeat exposure). Mutants with reproducible phenotypes had their phenotypes rescued with tagged genomic transgenes, and/or phenocopied by nervous system-specific knock down using RNA interference (RNAi).ResultsFour of the 13 JmjC genes (KDM3, lid, NO66 and HSPBAP1) showed reproducible ethanol-sensitivity phenotypes. Some of the phenotypes were observed across doses, e.g. the enhanced ethanol-sensitivity of KDM3KO and NO66KO, but others were dose-dependent, such as the reduced ethanol sensitivity of HSPBAP1KO, or the enhanced ethanol tolerance of NO66KO. These phenotypes were rescued by their respective genomic transgenes in KDM3KO and NO66KO mutants. While we were unable to rescue lidk mutants, knock down of lid in the nervous system recapitulated the lidk phenotype, as was observed for KDM3KO and NO66KO RNAi-mediated knock down.ConclusionOur study reveals that the Drosophila JmjC-domain histone demethylases Lid, KDM3, NO66, and HSPBAP1 are required for normal ethanol-induced sedation and tolerance. Three of three tested of those four JmjC genes are required in the nervous system for normal alcohol-induced behavioral responses, suggesting that this gene family is an intriguing avenue for future research.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-21T08:15:29.658338-05:
      DOI: 10.1111/acer.13508
  • Maternal alcohol use and nutrition during pregnancy: diet and
    • Authors: R. Colin Carter; Marjanne Senekal, Neil C. Dodge, Lori Bechard, Ernesta M. Meintjes, Christopher D. Molteno, Christopher Duggan, Joseph L. Jacobson, Sandra W. Jacobson
      Abstract: BackgroundDespite known risks of prenatal nutritional deficiencies and studies documenting increased prevalence of poor dietary intake among non-pregnant alcohol abusers, the nutritional status of heavy drinking pregnant women remains largely unstudied. Animal models have found interactions between prenatal ethanol exposure and micronutrients, such as choline, folate, B12, and iron, and human studies have reported that lower maternal weight and body mass confer increased fetal alcohol-related risk.Methods123 heavy drinking Cape Coloured pregnant women and 83 abstaining controls were recruited at their first antenatal clinic visit. At three prenatal study visits, each gravida was interviewed about alcohol, smoking, and drug use and weight, height, and arm skinfolds were measured. Dietary intakes of energy, protein, fat, and 25 major micronutrients were assessed from three 24-hour recall interviews.ResultsThe majority of women gained less than the recommended 0.42 kg/week during pregnancy. While methamphetamine use was associated with smaller biceps skinfolds, an indicator of body fat, alcohol consumption was not related to any anthropometric indicator. Alcohol was related to higher intake of phosphorous, choline, and vitamins B12 and D. Alcohol, cigarette, and methamphetamine use were related to lower vitamin C intake. Insufficient intake was reported by>85% of women for 10 of 22 key nutrients, and>50% for an additional 3 nutrients.ConclusionsAlcohol consumption during pregnancy was not associated with meaningful changes in diet or anthropometric measures in this population, suggesting that poor nutrition among drinkers does not confound the extensively reported effects of prenatal alcohol exposure on growth and neurobehavior. The poor gestational weight gain and high rates of insufficient intake for several nutrients in both the alcohol-exposed and control groups are also of public health importance.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-20T06:15:37.344734-05:
      DOI: 10.1111/acer.13504
  • A Randomized Clinical Trial Examining the Effect of Video-Based Prevention
           of Alcohol and Marijuana Use Among Recent Sexual Assault Victims
    • Authors: Kate Walsh; Amanda K. Gilmore, Patricia Frazier, Linda Ledray, Ron Acierno, Kenneth J. Ruggiero, Dean G. Kilpatrick, Heidi S. Resnick
      Abstract: BackgroundThis study examined whether a brief video intervention (Prevention of Postrape Stress; PPRS) delivered in the emergency department to recent sexual assault (SA) victims reduced alcohol and marijuana use at three points over the course of a six-month follow-up compared to treatment as usual (TAU) and an active control condition (Pleasant Imagery and Relaxation Information; PIRI). Prior assault history, minority status, and pre-SA substance use also were examined as moderators of intervention efficacy.MethodsWomen age 15 and older (N = 154) who participated in a post-SA medical forensic exam were randomly assigned to watch the PPRS video (n=54), the PIRI video (n=48), or receive TAU (n=52) and completed at least one follow-up assessment targeted at 1.5 (T1), 3 (T2), or 6 (T3) months following the exam.ResultsRegression analyses revealed that, relative to TAU, PPRS was associated with less frequent alcohol use at 6 months post-SA among women reporting pre-SA binge drinking and minority women. Relative to TAU, PPRS also was associated with fewer days of marijuana use at T1 among those who did not report pre-SA marijuana use and prior SA. Findings for pre-SA marijuana use were maintained at T3; however, findings for prior SA shifted such that PPRS was associated with fewer days of marijuana use at T3 for women with a prior SA.ConclusionsPPRS may be effective at reducing substance use for some recent SA victims, including those with a prior SA history, a prior substance use history, and minority women.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-20T06:15:21.549456-05:
      DOI: 10.1111/acer.13505
  • Alcohol Reduces Arterial Remodeling by Inhibiting Sonic
           Hedgehog-Stimulated Sca1+ Progenitor Stem Cell Expansion
    • Authors: Emma Fitzpatrick; Xu Han, Weimin Liu, Eoin Corcoran, Denise Burtenshaw, Maryam Alshamrani, David Morrow, Jay-Christian Helt, Paul A. Cahill, Eileen M. Redmond
      Abstract: BackgroundCell and molecular mechanisms mediating the cardiovascular effects of alcohol are not fully understood. Our aim was to determine the effect of moderate Ethanol (EtOH) on Sonic Hedgehog (SHh) signaling in regulating possible Sca1+ progenitor stem cell involvement during pathologic arterial remodeling.Methods and ResultsPartial ligation or sham-operation of the left carotid artery was performed in transgenic Sca1-eGFP mice gavaged with or without ‘daily moderate’ EtOH. The EtOH group had reduced adventitial thickening and less neo-intimal formation, compared to ligated controls. There was expansion of eGFP expressing (i.e., Sca1+) cells in remodeled vessels post-ligation (14d), especially in the neo-intima. Ethanol treatment reduced the number of Sca1+ cells in ligated vessel cross-sections concomitant with diminished remodeling, compared to control ligated vessels. Moreover, EtOH attenuated SHh signaling in injured carotids as determined by immunohistochemical analysis of the target genes patched 1 (Ptch1) and Gli2, and RT-PCR of whole vessel Gli2 mRNA levels. Intraperitoneal injection of ligated Sca1 - eGFP mice with the SHh signaling inhibitor cyclopamine diminished hedgehog target gene expression, reduced the number of Sca1+ cells, and ameliorated carotid remodeling. EtOH treatment of purified Sca1+ adventitial progenitor stem cells in vitro inhibited SHh signaling, and their rSHh-induced differentiation to vascular smooth muscle cells.ConclusionsEtOH reduces SHh - responsive Sca1+ progenitor cell myogenic differentiation/expansion in vitro and during arterial remodeling in response to ligation injury in vivo. Regulation of vascular Sca1+ progenitor cells in this way may be an important novel mechanism contributing to alcohol's cardiovascular protective effects.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-18T02:05:22.557836-05:
      DOI: 10.1111/acer.13499
  • Influence of cocaine-related images and alcohol administration on
           inhibitory control in cocaine users
    • Authors: Erika Pike; Katherine R. Marks, William W. Stoops, Craig R. Rush
      Abstract: BackgroundAlcohol use and impulsivity, including decreased inhibitory control, predict poor treatment outcomes for individuals with cocaine use disorders. This study sought to determine the effects of alcohol administration on inhibitory control following cocaine-related and neutral cues on the Attentional Bias-Behavioral Activation (ABBA) task in cocaine users. We hypothesized that the proportion of inhibitory failures would increase following cocaine cues compared to neutral cues. We further hypothesized that there would be an interaction between alcohol administration and task version, such that alcohol would impair inhibitory control following cocaine, but not neutral cues.MethodsFifty current cocaine users completed this mixed-model, double-blind, placebo-controlled, cross-over study over two experimental sessions. The ABBA task was completed following alcohol administration (0.0 and 0.65 g/kg). Subject-rated drug-effect and physiological measures were collected prior to and after alcohol administration.ResultsProportion of inhibitory failures was increased following cocaine-related cues compared to neutral cues independent of alcohol dose. Alcohol administration also produced prototypical subject-rated drug-effects.ConclusionsA better understanding of the relationship between alcohol consumption and inhibitory control in cocaine users could direct the development of interventions to decrease the risk of relapse in individuals who drink and display impaired inhibitory control.This article is protected by copyright. All rights reserved.
      PubDate: 2017-09-16T10:20:24.363151-05:
      DOI: 10.1111/acer.13500
  • Issue Information
    • Pages: 1981 - 1984
      PubDate: 2017-12-01T05:52:43.142829-05:
      DOI: 10.1111/acer.13196
  • Articles of Public Interest
    • Pages: 1985 - 1985
      PubDate: 2017-12-01T05:52:45.648325-05:
      DOI: 10.1111/acer.13553
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