Alcoholism Clinical and Experimental Research Journal Impact Factor & Information

Publisher: Research Society on Alcoholism (U.S.); National Council on Alcoholism and Drug Dependence (U.S.); International Society for Biomedical Research on Alcoholism, Wiley

Journal description

Founded by the National Council on Alcoholism and Drug Dependence, this journal gives readers direct access to the most significant and current findings on the nature and management of this serious health problem. Each month Alcoholism: Clinical and Experimental Research brings health care professionals and researchers the latest clinical studies and research findings on alcoholism, alcohol-induced syndromes and organ damage. Pertinent current papers in the major categories of basic science, clinical research, and treatment methods are included in each issue.

Current impact factor: 3.31

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 3.311
2012 Impact Factor 3.421
2011 Impact Factor 3.343
2010 Impact Factor 3.468
2009 Impact Factor 3.392
2008 Impact Factor 3.166
2007 Impact Factor 3.175
2006 Impact Factor 2.933
2005 Impact Factor 2.636
2004 Impact Factor 2.508
2003 Impact Factor 2.421
2002 Impact Factor 2.355
2001 Impact Factor 2.674
2000 Impact Factor 2.323
1999 Impact Factor 2.013
1998 Impact Factor 2.14
1997 Impact Factor 1.875
1996 Impact Factor 2.294
1995 Impact Factor 2.31
1994 Impact Factor 2.065
1993 Impact Factor 2.164
1992 Impact Factor 1.961

Impact factor over time

Impact factor

Additional details

5-year impact 3.62
Cited half-life 8.20
Immediacy index 0.64
Eigenfactor 0.02
Article influence 1.03
Website Alcoholism: Clinical and Experimental Research website
Other titles Alcoholism (Baltimore, Md.: Online), Alcoholism, ACER
ISSN 1530-0277
OCLC 44003050
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details


  • Pre-print
    • Author can archive a pre-print version
  • Post-print
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    • 12 months embargo
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    • On author's personal website, institutional repositories, arXiv, AgEcon, PhilPapers, PubMed Central, RePEc or Social Science Research Network
    • Author's pre-print may not be updated with Publisher's Version/PDF
    • Author's pre-print must acknowledge acceptance for publication
    • On a non-profit server
    • Publisher's version/PDF cannot be used
    • Publisher source must be acknowledged with citation
    • Must link to publisher version with set statement (see policy)
    • If OnlineOpen is available, BBSRC, EPSRC, MRC, NERC and STFC authors, may self-archive after 12 months
    • If OnlineOpen is available, AHRC and ESRC authors, may self-archive after 24 months
    • Publisher last contacted on 07/08/2014
    • This policy is an exception to the default policies of 'Wiley'
  • Classification
    ​ yellow

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Ethanol (EtOH) consumption is able to disturb the ovalbumin (OVA)-oral tolerance induction by interfering on the function of antigen presenting cells (APC), down-regulating dendritic cells (DCs) and macrophages and up-regulating B-lymphocytes and their function, which results in an overall allergic-type immune status. In this study, the potential of a priori administration of Lactococcus lactis (LL) in avoiding loss of oral tolerance in EtOH-treated mice was investigated. Female C57BL/6 mice received, by oral route, ad libitum wild-type (WT) LL or heat-shock protein producer (Hsp65) LL for 4 consecutive days. Seven days later, mice were submitted to short-term high-dose EtOH treatment. After 24 hours, stomach, intestine, spleen, mesenteric lymph nodes (mLN) specimens were collected for biomarkers analysis. Following EtOH-treatment protocol, a group of animals underwent single-gavage OVA-tolerance protocol and sera samples collected for antibody analysis. The ingestion of WT LL or Hsp65 LL is able to restore oral tolerance to OVA in EtOH-treated mice, by reducing local and systemic allergic outcomes such as gastric mast cells and gut-interleukin-4, as well as serum IgE. WT LL treatment prevents the decrease of mLN regulatory T cells induced by the EtOH treatment. Moreover, LL treatment preserves APC hierarchy and antigen presentation commitment in EtOH-treated mice, with conserved DC and macrophage activity over B lymphocytes in mLN and preserved macrophage activity over DC and B-cell subsets in the spleen. The present findings suggest that a priori ingestion of LL preserves essential mechanisms associated with oral tolerance induction that are disturbed by EtOH ingestion. Maintenance of mucosal homeostasis by preserving APC hierarchy and antigen presentation commitment could be associated with T-regulatory subset activities in the gastrointestinal tract. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 06/2015; DOI:10.1111/acer.12770
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    ABSTRACT: This current study was undertaken to carefully assess the accuracy of routinely used laboratory tests in detecting excessive/recent alcohol use. We also determined the kinetics of these markers in subjects who underwent an intensive alcohol rehabilitation program. The study cohort consisted of 210 nonexcessive drinkers, 272 excessive drinkers, and 76 with alcoholic cirrhosis. To determine the kinetics of these markers during alcohol abstinence, we followed 45 subjects with history of excessive alcohol use for 12 weeks during the intensive alcohol treatment program. Percentage of carbohydrate deficient transferrin (%CDT) provided the highest diagnostic performance (area under the curve [AUC] 0.77) followed by gamma-glutamyl transferase (GGT) (AUC 0.68) to detect excessive drinkers. The percentage of excessive drinkers with aspartate aminotransferase:alanine aminotransferase (AST:ALT) > 2 was only 2%, whereas 51% of subjects with alcoholic cirrhosis had AST:ALT > 2. In the multivariate analysis, the levels of GGT and %CDT were associated with the level of alcohol consumed during the past 30 days. The levels of GGT, mean corpuscular volume (MCV), and %CDT were significantly lower compared to those at baseline before alcohol rehabilitation, whereas the AST, ALT, and AST:ALT ratio were unchanged. The percent reduction was ~2.7% (for MCV), 19% (for GGT), and 43% (for %CDT) at the end of the 12-week follow-up compared to the baseline. %CDT are useful markers to screen for excessive alcohol use and for follow-up of abstinence. Most subjects with excessive alcohol use do not have a high AST:ALT ratio. Rather, the AST:ALT > 2 is suggestive of alcoholic cirrhosis. The performance of the %CDT to screen for heavy alcohol use is still not ideal. Further research to identify the noninvasive marker(s) (i.e., using proteomic or metabolomics approach) should be considered. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 06/2015; DOI:10.1111/acer.12780
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    ABSTRACT: Alcohol dependence (AD) is a complex psychiatric disorder and a significant public health problem. Twin and family-based studies have consistently estimated its heritability to be approximately 50%, and many studies have sought to identify specific genetic variants associated with susceptibility to AD. These studies have been primarily linkage or candidate gene based and have been mostly unsuccessful in identifying replicable risk loci. Genome-wide association studies (GWAS) have improved the detection of specific loci associated with complex traits, including AD. However, findings from GWAS explain only a small proportion of phenotypic variance, and alternative methods have been proposed to investigate the associations that do not meet strict genome-wide significance criteria. This review summarizes all published AD GWAS and post-GWAS analyses that have sought to exploit GWAS data to identify AD-associated loci. Findings from AD GWAS have been largely inconsistent, with the exception of variants encoding the alcohol-metabolizing enzymes. Analyses of GWAS data that go beyond standard association testing have demonstrated the polygenic nature of AD and the large contribution of common variants to risk, nominating novel genes and pathways for AD susceptibility. Findings from AD GWAS and post-GWAS analyses have greatly increased our understanding of the genetic etiology of AD. However, it is clear that larger samples will be necessary to detect loci in addition to those that encode alcohol-metabolizing enzymes, which may only be possible through consortium-based efforts. Post-GWAS approaches to studying the genetic influences on AD are increasingly common and could greatly increase our knowledge of both the genetic architecture of AD and the specific genes and pathways that influence risk. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 06/2015; DOI:10.1111/acer.12792
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    ABSTRACT: Heavy alcohol drinking is a risk factor for colorectal cancer (CRC); previous studies have shown a linear dose-dependent association between alcohol intake and CRC. However, some studies suggest that moderate alcohol consumption may have a protective effect, similar to that seen in cardiovascular disease. Other factors may interact with alcohol and contribute additional risk for CRC. We aimed to determine the association between moderate alcohol consumption, limited to 30 g of alcohol per day, by beverage type on CRC risk and to assess the effects of other factors that interact with alcohol to influence CRC risk. The PubMed database was used to find articles published between 2008 and 2014 related to alcohol and CRC. Twenty-one relevant articles were evaluated and summarized, including 11 articles reporting on CRC risk associated with moderate intake and 10 articles focusing on genetic interactions associated with alcohol and CRC risk. The association between alcohol and increased risk for CRC was found when intakes exceeded 30 g/d alcohol. Nonsignificant results were consistently reported for intakes <30 g/d. Additional risks for CRC were found to be related to obesity and folate status for regular alcohol consumers. Some significant results suggest that the development of CRC is dependent on the interaction of gene and environment. The association between the amount of alcohol consumed and the incidence of CRC was not significant at moderate intake levels. Moderate alcohol consumption was associated with a reduced CRC risk in study populations with greater adherence to a Mediterranean diet, where wine contributed substantially to the alcoholic beverage consumed. Other factors such as obesity, folate deficiency, and genetic susceptibility may contribute additional CRC risk for those consuming alcohol. To minimize CRC risk, appropriate recommendations should encourage intakes below 30 g of alcohol each day. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 06/2015; DOI:10.1111/acer.12778
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    ABSTRACT: Few epidemiologic studies have examined a full range of adolescent psychiatric disorders in the general population. The association between psychiatric symptom clusters (PSCs) and DSM-IV alcohol use disorders (AUDs) among adolescents is not well understood. This study draws upon the public-use data from the 2000 National Household Survey on Drug Abuse, including a study sample of 19,430 respondents aged 12 to 17. Logistic regression and exploratory structural equation modeling assess the associations between PSCs and DSM-IV AUDs by gender. The PSCs are based on brief screening scales devised from the Diagnostic Interview Schedule for Children Predictive Scales. Several PSCs were found to be significantly associated with DSM-IV AUDs, including separation anxiety, generalized anxiety, depression, oppositional defiant disorder, and conduct disorder among both genders, and panic disorder and obsessive/ compulsive disorder among females. Consistent with the literature, the analysis of PSCs yields 3 factors identical for both genders-2 internalizing factors (fear and anxiety-misery) and 1 externalizing factor. Adolescents who scored higher on the externalizing factor tended to have higher levels of the AUD factor. Female adolescents who scored higher on the internalizing misery factor and lower on the internalizing fear factor also tended to have higher levels of the AUD factor. The associations that we found between PSCs and AUDs among adolescents in this study are consistent with those found among adults in other studies, although gender may moderate associations between internalizing PSCs and AUDs. Our findings lend support to previous findings on the developmentally stable associations between disruptive behaviors and AUDs among adolescents as well as adults in the general population. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
    Alcoholism Clinical and Experimental Research 06/2015; DOI:10.1111/acer.12767
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    ABSTRACT: The production of fibrosis in response to chronic alcohol abuse is well recognized in liver but has not been fully characterized in striated muscle and may contribute to functional impairment. Therefore, the purpose of this study was to use an unbiased discovery-based approach to determine the effect of chronic alcohol consumption on the expression profile of genes important for cell-cell and cell-extracellular matrix (ECM) interactions in both skeletal and cardiac muscle. Adult male rats were pair-fed an alcohol-containing liquid diet or control diet for 24 weeks, and skeletal muscle (gastrocnemius) and heart were collected in the freely fed state. A pathway-focused gene expression polymerase chain reaction array was performed on these tissues to assess mRNA content for 84 ECM proteins, and selected proteins were confirmed by Western blot analysis. In gastrocnemius, alcohol feeding up-regulated the expression of 11 genes and down-regulated the expression of 1 gene. Alcohol increased fibrosis as indicated by increased mRNA and/or protein for collagens α1(I), α2(I), α1(III), and α2(IV) as well as hydroxyproline. Alcohol also increased α-smooth muscle actin protein, an index of myofibroblast activation, but no concomitant change in transforming growth factor-β was detected. The mRNA and protein content for other ECM components, such as integrin-α5, L-selectin, PECAM, SPARC, and ADAMTS2, were also increased by alcohol. Only laminin-α3 mRNA was decreased in gastrocnemius from alcohol-fed rats, while 66 ECM- or cell adhesion-related mRNAs were unchanged by alcohol. For heart, expression of 16 genes was up-regulated, expression of 3 genes was down-regulated, and 65 mRNAs were unchanged by alcohol; there were no common alcohol-induced gene expression changes between heart and skeletal muscle. Finally, alcohol increased tumor necrosis factor-α and interleukin (IL)-12 mRNA in both skeletal and cardiac muscle, but IL-6 mRNA was increased and IL-10 mRNA decreased only in skeletal muscle. These data demonstrate a fibrotic response in striated muscle from chronic alcohol-fed rats which is tissue specific in nature, suggesting different regulatory mechanisms. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 06/2015; DOI:10.1111/acer.12771
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    ABSTRACT: The nonselective opioid receptor antagonist, naltrexone (NAL), reduces alcohol (ethanol [EtOH]) consumption in animals and humans and is an approved medication for treating alcohol abuse disorders. Proopiomelanocortin (POMC)-derived melanocortin (MC) and opioid peptides are produced in the same neurons in the brain, and recent preclinical evidence shows that MC receptor (MCR) agonists reduce excessive EtOH drinking in animal models. Interestingly, there is a growing body of literature revealing interactions between the MC and the opioid systems in the modulation of pain, drug tolerance, and food intake. In the present report, a mouse model of binge EtOH drinking was employed to determine whether the MCR agonist, melanotan-II (MTII), would improve the effectiveness of NAL in reducing excessive binge-like EtOH drinking when these drugs were co-administered prior to EtOH access. Both NAL and MTII blunt binge-like EtOH drinking and associated blood EtOH levels, and when administered together, a low dose of MTII (0.26 mg/kg) produces a 7.6-fold increase in the effectiveness of NAL in reducing binge-like EtOH drinking. Using isobolographic analysis, it is demonstrated that MTII increases the effectiveness of NAL in a synergistic manner. The current observations suggest that activators of MC signaling may represent a new approach to treating alcohol abuse disorders and a way to potentially improve existing NAL-based therapies. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 06/2015; DOI:10.1111/acer.12774
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    ABSTRACT: Subjective perceptions of alcohol intoxication are associated with altered risk for alcohol abuse and dependence. Acute adaptation of these perceptions may influence such risk and may involve genes associated with pleasant perceptions or the relief of anxiety. This study assessed the effect of variation in the GABAA receptor genes GABRG1 and GABRA2 and recent drinking history on the acute adaptation of subjective responses to alcohol. One hundred and thirty-two nondependent moderate to heavy drinkers, aged 21 to 27, participated in 2 single-blind, counterbalanced sessions, approximately 1 week apart. One session was an intravenous alcohol "clamp," during which breath alcohol concentration was held steady at 60 mg/dl (60 mg%) for 3 hours, and the other an identical session using saline infusion. Subjective perceptions of Intoxication, Enjoyment, Stimulation, Relaxation, Anxiety, Tiredness, and Estimated Number of Drinks were acquired before (baseline), and during the first and final 45 minutes of the clamp. A placebo-adjusted index of the subject's acute adaptation to alcohol was calculated for each of the 7 subjective measures and used in a principal component analysis to create a single aggregate estimate for each subject's adaptive response to alcohol. Analysis of covariance tested whether GABRA2 and GABRG1 single nucleotide polymorphism (SNP) genotypes, gender, placebo session, family history of alcoholism, recent drinking history, and the genotype × recent drinking history interaction significantly predicted the adaptive response. Recent drinking history (p = 0.01), and recent drinking history × genotype interaction (p = 0.01) were significantly associated with acute adaptation of the subjective responses to alcohol for the GABRA2 SNP rs279858. Higher recent drinking was found to be associated with reduced acute tolerance to positive, stimulating effects of alcohol in carriers of the rs279858 risk allele. We postulate that the GABRA2 effect on alcohol dependence may, in part, be due to its effect on subjective responses to alcohol. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 06/2015; DOI:10.1111/acer.12749
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    ABSTRACT: We examined associations between parental separation during childhood and offspring alcohol involvement, adjusting for genetic and environmental risks specific to parental alcohol (AD) and cannabis/other illicit drug dependence (DD). The sample consisted of 1,828 offspring of male twins from the Vietnam Era Twin (VET) Registry, who completed a telephone diagnostic interview. Cox proportional hazards regression analyses were conducted predicting onset of first use, transition from first use to first AD symptom, and transition from first use to AD diagnosis from paternal and avuncular AD and DD history, parental separation, and offspring and family background characteristics. Paternal/avuncular DD/AD was based on the DSM-III-R; offspring and maternal AD were based on DSM-IV criteria. Paternal DD/AD predicted increased offspring risk for all transitions, with genetic effects suggested on rate of transitioning to AD diagnosis. Parental separation was predictive of increased risk for early alcohol use, but a reduced rate of transition to both AD symptom onset and onset of AD. No interactions between separation and familial risk (indexed by paternal or avuncular DD/AD) were found. Findings highlight the contribution of both parental separation and paternal substance dependence in predicting timing of offspring alcohol initiation and problems across adolescence into early adulthood. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 06/2015; DOI:10.1111/acer.12766
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    ABSTRACT: Drinking before entering nightclubs (predrinking) seems to be associated with an increase in alcohol-related harm. This study aims to investigate gender differences in predrinking behavior and to evaluate its association with risk behaviors practiced inside nightclubs. Individual-level data were collected by a portal survey of 2,422 patrons at the entrance and 1,833 patrons at the exit of 31 nightclubs located at São Paulo, Brazil. The nightclubs were selected by 2-stage sampling with probability proportional to the establishments' capacity in the first stage and a systematic sample of patrons in the entrance line in the second stage. Breath alcohol concentration (BrAC) was measured at the entrance and exit. Face-to-face interviews identified predrinking characteristics and risk behaviors. Weighted analyses were stratified by gender. Predrinking was practiced by 49.2% (95% confidence interval [CI] = 42.7 to 55.8) of the male patrons and 29.0% (95% CI = 20.6 to 38.9) of the female patrons (p < 0.001) on the day of the interview. When considering only predrinkers, men and women showed similar BrAC at entrance and exit and similar proportion of alcoholic intoxication (BrAC ≥ 0.38 mg/l). In both genders, people who practiced predrinking on the day of the interview were more likely to drink inside the nightclub, compared to those who did not practice predrinking (p < 0.001). Among men, the practice of predrinking increased the chance of "drinking and driving" after leaving the nightclub (odds ratio [OR] = 6.9, 95% CI = 4.1-11.5, p < 0.001). Among women, the practice of predrinking increased the chances of experiencing sexual harassment in the nightclub (OR = 2.9, 95% CI = 1.3 to 6.6, p = 0.010). Predrinking is more prevalent among men; however, men and women who engaged in predrinking have a similar pattern of alcohol consumption and exit BrAC. The fact that risk behaviors and illicit drug use were associated with predrinking but differ between genders suggests that a gender-specific approach should be used in tailored interventions to prevent alcohol-related harm in nightclubs. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 06/2015; DOI:10.1111/acer.12756
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    ABSTRACT: Excessive alcohol use is common in patients presenting with symptoms of depression. The aim of this study was to evaluate how the Alcohol Use Disorders Identification Test (AUDIT) and its most commonly used abbreviated versions perform in detecting at-risk drinking among subjects reporting symptoms of depression. A subsample (n = 390; 166 men, 224 women) of a general population survey, the National FINRISK 2007 Study, was used. Symptoms of depression were measured with the Beck Depression Inventory-Short Form and alcohol consumption with the Timeline Follow-back (TLFB). At-risk drinking was defined as ≥280 g weekly or ≥60 g on at least 1 occasion in the previous 28 days for men, 140 and 40 g, respectively, for women. The AUDIT, AUDIT-C, and AUDIT-3 were tested against the defined gold standard, that is, alcohol use calculated from the TLFB. An optimal cutoff was designated as having a sensitivity and specificity of over 0.75, with emphasis on specificity. The AUDIT and its abbreviations were compared with carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase. At-risk drinking was common. The AUDIT and AUDIT-C performed quite consistently. Optimal cutoffs for men were ≥9 for the AUDIT and ≥6 for AUDIT-C. The optimal cut-offs for women with mild symptoms of depression were ≥5 for the AUDIT and ≥4 for AUDIT-C. Optimal cutoffs could not be determined for women with moderate symptoms of depression (specificity <0.75). A nearly optimal cutoff for women was ≥5 for the AUDIT. The AUDIT-3 failed to perform in women, but in men, a good level of sensitivity and specificity was reached at a cutoff of ≥2. With standard threshold values, the biochemical markers demonstrated very low sensitivity (9 to 28%), but excellent specificity (83 to 98%). Screening for at-risk drinking among patients presenting with symptoms of depression using the full AUDIT is recommended, although the AUDIT-C performed almost equally well. Cut-offs should be adjusted according to gender, but not according to the severity of depressive symptoms. The AUDIT and its abbreviations were superior to biochemical markers. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 06/2015; DOI:10.1111/acer.12763
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    ABSTRACT: Background The medications produced from natural products are widely used as prophylactics for sickness induced by alcohol consumption. One such prophylactic is produced from the Reishi mushroom, Ganoderma lucidum. Because of the antioxidant properties of these preparations, we expect neuroprotective prophylactic effects of Reishi-based medications in alcohol-treated animals.Methods The Reishi (R) suspension was produced as water extract from Altaian mushrooms. Sprague–Dawley male rats were separated into the following 3 experimental groups: Group A + R received R (6 days per week) starting 1 week before alcohol exposure, and during the next 3 weeks, they received both R and alcohol; group A received alcohol; and group C received water. At the end of experiment, we determined the metabolic profile using proton magnetic resonance spectroscopy (1H MRS) of the brain cortex and phosphorus magnetic resonance spectroscopy of the liver. Additionally, the blood cells were collected, and the serum biochemistry and liver histology were performed after euthanasia.ResultsPartial least squares discriminant analysis processing of the brain 1H MRS gave 2 axes, the Y1 axis positively correlated with the level of taurine and negatively correlated with the level of lactate, and the Y2 axis positively correlated with the content of GABA and glycine and negatively correlated with the sum of the excitatory neurotransmitters, glutamate and glutamine. The Y1 values reflecting the brain energetics for the A + R group exceeded the corresponding values for groups C and A. The maximal level of Y2 reflecting the prevalence of inhibitory metabolites in the brain was observed in the rats exposed to alcohol. Moderate alcohol consumption did not cause significant pathological changes in the livers of the experimental animals. However, 20 days of alcohol consumption significantly increased the number of binuclear hepatocytes compared to the control. This effect was mitigated in the rats that received the Reishi extract.Conclusions Regular administration of the Reishi suspension improved the energy supply to the brain cortex and decreased the prevalence of inhibitory neurotransmitters that are characteristic of alcohol consumption. The alcohol-induced increase in liver proliferation was significantly suppressed by regular administration of the G. lucidum water suspension.
    Alcoholism Clinical and Experimental Research 06/2015; DOI:10.1111/acer.12758
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    ABSTRACT: Previous studies have shown that alcohol-dependent (AD) individuals have difficulties inferring other people's emotion, understanding humor, and detecting a faux pas. This study aimed at further understanding the nature of such "Theory of Mind" (ToM) difficulties. A total of 34 recently detoxified AD and 34 paired controls were compared based on 2 nonverbal and video-based false belief tasks. These tasks were designed to identify 3 different types of deficits: (i) a deficit in dealing with the general task demands, (ii) a selective deficit in self-perspective inhibition, and (iii) a deficit in tracking the other person's mental state. (i) and (ii) are compatible with the hypothesis of a prefrontal cortex dysfunction being at the origin of AD individuals' social difficulties, while (iii) would suggest the possible contribution of a dysfunction of the temporo-parietal junction in explaining the social difficulties. Group analyses highlighted that AD individuals performed worse on the 2 false belief tasks than controls. Individual analyses showed, however, that just under half of the AD individuals were impaired compared to controls. Moreover, most of the AD individuals who were impaired showed a deficit in tracking the other person's belief. This deficit was linked to disease-related factors such as illness duration, average alcohol consumption, and craving but not to general reasoning abilities, depression, anxiety, or demographic variables. Just under half of the AD individuals tested showed a ToM deficit, and in most cases, the deficit concerned the tracking of other people's mental states. Such a type of deficit has previously been associated with lesions to the temporo-parietal brain areas, indicating that a prefrontal cortex dysfunction may not be the sole origin of the social cognition deficits observed in alcohol dependence. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 06/2015; 39(6):980-8. DOI:10.1111/acer.12717
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    ABSTRACT: Mutagenesis and labeling studies have identified amino acids from the human α1 glycine receptor (GlyR) extracellular, transmembrane (TM), and intracellular domains in mediating ethanol (EtOH) potentiation. However, limited high-resolution structural data for physiologically relevant receptors in this Cys-loop receptor superfamily have made pinpointing the critical amino acids difficult. Homologous ion channels from lower organisms provide conserved models for structural and functional properties of Cys-loop receptors. We previously demonstrated that a single amino acid variant of the Gloeobacter violaceus ligand-gated ion channel (GLIC) produced EtOH and anesthetic sensitivity similar to that of GlyRs and provided crystallographic evidence for EtOH binding to GLIC. We directly compared EtOH modulation of the α1 GlyR and GLIC to a chimera containing the TM domain from human α1 GlyRs and the ligand-binding domain of GLIC using 2-electrode voltage-clamp electrophysiology of receptors expressed in Xenopus laevis oocytes. EtOH potentiated α1 GlyRs in a concentration-dependent manner in the presence of zinc-chelating agents, but did not potentiate GLIC at pharmacologically relevant concentrations. The GLIC/GlyR chimera recapitulated the EtOH potentiation of GlyRs, without apparent sensitivity to zinc chelation. For chimera expression in oocytes, it was essential to suppress leakage current by adding 50 μM picrotoxin to the media, a technique that may have applications in expression of other ion channels. Our results are consistent with a TM mechanism of EtOH modulation in Cys-loop receptors. This work highlights the relevance of bacterial homologs as valuable model systems for studying ion channel function of human receptors and demonstrates the modularity of these channels across species. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 05/2015; 39(6). DOI:10.1111/acer.12735
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    ABSTRACT: Background: Driving after drinking (DAD) among college students is a significant public health concern, yet little is known about specific theoretical risk factors for DAD, beyond drinking level, among college student drinkers. This study had the following aims: (i) to examine the associations between elevated alcohol demand and DAD, (ii) to determine whether demand decreases in response to a hypothetical driving scenario, (iii) to determine whether drivers who report DAD in the past 3 months would show less of a reduction in demand in response to the hypothetical driving scenario, and (iv) to determine whether delayed reward discounting (DRD) is associated with DAD. Method:Participants were 419 college students who reported at least 1 day of past-month alcohol use. Participants completed 2 alcohol purchase tasks (APTs) that assessed hypothetical alcohol consumption across 17 drink prices with and without a driving scenario, a delay-discounting task, and a series of questions regarding DAD. Results: In logistic regression models that controlled for drinking level, demographics, and sensation seeking, participants reporting higher demand intensity (95% confidence interval [95% CI] [1.04, 2.34]), breakpoint (95% CI [1.23, 2.28]), Omax (95% CI [1.03, 1.53]), and lower elasticity (95% CI [0.15, 1.02]) were more likely to report DAD. Additionally, in analyses of covariance, DAD+ participants exhibited significantly less of a reduction in demand between the standard and the driving APT (intensity, p < 0.01, breakpoint, p = 0.05, and Omax, p < 0.01). A binary logistic regression model with identical covariates revealed that DRD is not associated with DAD. Conclusions: DAD is associated with elevated/inelastic demand and less sensitivity to a hypothetical driving scenario. Drinkers with elevated demand should be prioritized for DAD intervention efforts.
    Alcoholism Clinical and Experimental Research 05/2015; 39(5):896-904.
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    ABSTRACT: Background Alcoholism is known to be associated with cognitive deficits mainly concerning visuospatial capacity, executive function, memory, and attention. These impairments may affect treatment efficacy which should therefore be adapted. We evaluated the potential utility of the Montreal Cognitive Assessment (MoCA) to evaluate cognitive impairment in a large series of alcoholic patients hospitalized for withdrawal and rehabilitation.Methods Consecutive recruitment during a time period of patients admitted to an addiction treatment unit of a teaching hospital. Administration of the MoCA test on admission by trained staff members.ResultsA total of 166 patients aged 49.9 ± 9.2 years were included. Mean duration of administration was 20 minutes. The mean MoCA score was 23.5 ± 3.5 and 68.1% had an impaired value (<26). Age was negatively and education was positively associated with the MoCA score. Significant cognitive deficits concerned visuospatial capacity, attention, fluency, abstraction, and delayed recall. Neither age nor sex was significantly related to the MoCA score, while having a high education level (>12 years) significantly increased the likelihood of having a high MoCA score.Conclusions Owing to their severity and frequency, screening for cognitive deficits is necessary in alcoholics during rehabilitation. MoCA is an appropriate tool for this purpose.
    Alcoholism Clinical and Experimental Research 05/2015; 39(6). DOI:10.1111/acer.12734
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    ABSTRACT: Background Identification of patient subgroups to enhance treatment effects is an important topic in personalized (or tailored) alcohol treatment. Recently, several recursive partitioning methods have been proposed to identify subgroups benefiting from treatment. These novel data mining methods help to address the limitations of traditional regression-based methods that focus on interactions.Methods We propose an exploratory approach, using recursive partitioning methods, for example, interaction trees (IT) and virtual twins (VT), to flexibly identify subgroups in which the treatment effect is likely to be large. We apply these tree-based methods to a pharmacogenetic trial of ondansetron.ResultsOur methods identified several subgroups based on patients' genetic and other prognostic covariates. Among the 251 subjects with complete genotype information, the IT method identified 118 with specific genetic and other prognostic factors, resulting in a 17.2% decrease in the percentage of heavy drinking days (PHDD). The VT method identified 88 subjects with a 21.8% decrease in PHDD. Overall, the VT subgroup achieved a good balance between the treatment effect and the group size.ConclusionsA data mining approach is proposed as a valid exploratory method to identify a sufficiently large subgroup of subjects that is likely to receive benefit from treatment in an alcohol dependence pharmacotherapy trial. Our results provide new insights into the heterogeneous nature of alcohol dependence and could help clinicians to tailor treatment to the biological profile of individual patients, thereby achieving better treatment outcomes.
    Alcoholism Clinical and Experimental Research 05/2015; DOI:10.1111/acer.12759
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    ABSTRACT: Cannabis is the most commonly used drug among those who drink, yet no study has directly compared those who use cannabis and alcohol simultaneously versus concurrently (i.e., separately) in the adult general population. Here, we assess differences in demographics, alcohol-related social consequences, harms to self, and drunk driving across simultaneous, concurrent, and alcohol-only using groups. Secondary analyses of the 2005 and 2010 National Alcohol Survey (N = 8,626; 4,522 female, 4,104 male), a Computer Assisted Telephone Interview survey of individuals aged 18 and older from all 50 states and DC. Blacks and Hispanics are over-sampled. Data were collected using list-assisted Random Digit Dialing. Multinomial and multivariable logistic regressions were used for analyses. The prevalence of simultaneous use was almost twice as high as concurrent use, implying that individuals who use both cannabis and alcohol tend to use them at the same time. Furthermore, simultaneous use was associated with increased frequency and quantity of alcohol use. Simultaneous use was also the most detrimental: compared to alcohol only, simultaneous use approximately doubled the odds of drunk driving, social consequences, and harms to self. The magnitudes of differences in problems remained when comparing drunk driving among simultaneous users to concurrent users. The overall set of results is particularly important to bear in mind when studying and/or treating problems among alcohol/cannabis co-users because they demonstrate that in the general population, co-users are a heterogeneous group who experience different likelihoods of problems relative to co-use patterns. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 05/2015; 39(5):872-9. DOI:10.1111/acer.12698