Alcoholism Clinical and Experimental Research (ALCOHOL CLIN EXP RES)

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: 3.21

Impact Factor Rankings

2016 Impact Factor Available summer 2017
2014 / 2015 Impact Factor 3.205
2013 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 3.72
Cited half-life 8.70
Immediacy index 0.64
Eigenfactor 0.02
Article influence 1.02
Website Alcoholism: Clinical and Experimental Research website
Other titles Alcoholism (Baltimore, Md.: Online), Alcoholism, ACER
ISSN 0145-6008
OCLC 44003050
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details


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    • On author's personal website, institutional repositories, arXiv, AgEcon, PhilPapers, PubMed Central, RePEc or Social Science Research Network
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    • Non-Commercial
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    • 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

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Although negative mood has long been implicated in differences in alcohol seeking by men and women, little research has used precise, well-controlled laboratory experiments to examine how negative mood affects alcohol-seeking behaviors. A total of 34 (19 women) community-dwelling, alcohol-using adults aged 21 to 32 (mean age = 24.86, SD = 3.40, 74.3% Caucasian; Alcohol Use Disorders Identification Test [AUDIT] = 10.1, SD = 3.4) completed 2 counterbalanced intravenous alcohol self-administration sessions: one under negative mood and one under neutral mood. Fourteen individuals (9 women; mean age = 25.00, SD = 2.77) participated in an alcohol “liking” experiment (i.e., free access [FA] drinking) and 20 individuals (10 women; mean age = 24.77, SD = 3.73) participated in an alcohol “wanting” experiment, in which gaining access to alcohol required progressively effortful work. There was no significant difference between men and women on the AUDIT, t(32) = −0.38, p = 0.71. Priming with negative mood induction caused a significant decrease in self-reported mood (mean change = −1.85, t(32) = −6.81, p < 0.001), as intended. In FA, negative mood was associated with a significantly increased peak breath alcohol concentration (BrAC; F = 9.41, p = 0.01), with a trend toward a greater effect in men than in women (F = 2.67, p = 0.13). Negative mood also had a significant effect on peak BrAC achieved in the progressive work paradigm (F = 5.28, p = 0.04), with a significantly stronger effect in men (F = 5.35, p = 0.03) than women; men also trended toward more consistent work for alcohol across both neutral and negative sessions. These preliminary findings demonstrate a gender-specific response on how mood affects alcohol seeking and suggest gender-specific interventions to prevent mood-based alcohol consumption.
    No preview · Article · Feb 2016 · Alcoholism Clinical and Experimental Research
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    ABSTRACT: Alcohol use disorders (AUDs) are common and have worse consequences for racial/ethnic minority groups than whites. AUDs are often underrecognized in clinical settings, but it is unknown whether the prevalence of clinically recognized AUD varies across racial/ethnic groups. We describe the overall and age- and gender-stratified prevalence of clinically documented AUD across 3 racial/ethnic groups in a national sample of Veterans Health Administration (VA) patients. Data from VA's National Patient Care Database identified all patients who used VA care in Fiscal Year 2012 and were documented as black, Hispanic, or white race/ethnicity. The prevalence of clinically recognized AUD based on ICD-9 diagnoses was compared across racial/ethnic groups overall and within gender and age groups using chi-square tests of independence. Among 4,666,403 eligible patients, 810,902 (17.4%) were black, 302,331 (6.5%) were Hispanic, and 3,553,170 (76.1%) were white. The prevalence of clinically recognized AUD was 6.5% overall, and 9.8% (95% CI 9.8 to 9.9) among black, 7.1% (95% CI 7.0 to 7.2) among Hispanic, and 5.7% (95% CI 5.6 to 5.7) among white patients (p < 0.001). This pattern generally held for men, regardless of age group, with the exception of those 18 to 29 years old, for whom no difference was observed across race/ethnicity. Among women, the prevalence of AUD was generally lowest among Hispanic and highest among black patients, with the exception of those 30 to 44 years old, for whom the highest prevalence was among whites. In contrast to findings from the general population, the prevalence of clinically recognized AUD among VA patients is generally highest among black men and women and lowest among white men and Hispanic women. This is the first study to describe the prevalence of clinically recognized AUD across racial/ethnic groups in a large healthcare system. Future research comparing estimates to diagnoses based on structured gold-standard assessments is needed to understand whether AUDs are under- or overidentified.
    No preview · Article · Feb 2016 · Alcoholism Clinical and Experimental Research
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    ABSTRACT: Farm workers in rural areas consume more alcohol than those who reside in urban areas. Occupational exposures such as agricultural work can pose hazards on the respiratory system. It is established that hog barn dust induces inflammation in the airway, including the release of cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-8. We have shown that alcohol alters airway epithelial innate defense through changes in both nitric oxide (NO) and cAMP-dependent protein kinase A (PKA). Simultaneous exposure to hog barn dust and alcohol decreases inflammatory mediators, TNF-α, IL-6, and IL-8, in mice. Previously, mice exposed to both alcohol and hog barn dust showed a depleted amount of lymphocytes compared to mice exposed only to hog barn dust. Weakening of the innate immune response could lead to enhanced susceptibility to disease. In addition, mice that were co-exposed to hog barn dust and alcohol also experienced increased mortality. Because we recently demonstrated that PKA activation inhibits the TNF-α sheddase, TNF-α-converting enzyme (TACE), we hypothesized that an alcohol-mediated PKA pathway blocks TACE activity and prevents the normative inflammatory response to hog barn dust exposure. To delineate these effects, we used PKA pathway inhibitors (adenylyl cyclase [AC], cAMP, and PKA) to modulate the effects of alcohol on dust-stimulated TNF-α release in the bronchial epithelial cell line, BEAS-2B. Alcohol pretreatment blocked TACE activity and TNF-α release in hog barn dust-treated cells. Alcohol continued to block hog barn dust-mediated TNF-α release in the presence of the particulate AC inhibitor, SQ22,536. The soluble adenylyl cyclase inhibitor, KH7, however, significantly increased the inflammatory response to hog barn dust. phosphodiesterase 4 inhibitors significantly elevated cAMP and enhanced alcohol-mediated inhibition of dust-stimulated TNF-α release. In addition, the NO synthase inhibitor, l-NMMA, also reversed the alcohol-blocking effect on dust-stimulated TNF-α. These data suggest that alcohol requires a soluble cyclase-generated cAMP-PKA pathway that is dependent upon the action of NO to inhibit TACE and TNF-α release. These findings support our observations that alcohol functions through a dual NO and PKA pathway in bronchial epithelial cells.
    No preview · Article · Feb 2016 · Alcoholism Clinical and Experimental Research
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    ABSTRACT: Circadian rhythms are essential for adapting to the environment. Chronic alcohol consumption often leads to sleep and circadian disruptions, which may impair the life quality of individuals with alcohol use disorders and contribute to the morbidity associated with alcoholism. We used a pair-feeding liquid diet alcohol exposure protocol (6 weeks duration) in PER1::LUC transgenic rats to examine the effects of chronic alcohol exposure on: (i) diurnal rhythms of core body temperature and locomotor activity, (ii) plasma corticosterone (CORT) concentrations, and (iii) rhythms of ex vivo Period1 (Per1) expression in the suprachiasmatic nucleus (SCN), pituitary, and adrenal glands. We followed multiple circadian outputs not only to examine individual components, but also to assess the relative phase relationships among rhythms. We found that chronic alcohol consumption: (i) reduced 24-hour body temperature and locomotor activity counts in the dark period, (ii) advanced the acrophase of diurnal rhythms of body temperature and locomotor activity, (iii) abolished the phase difference between temperature and activity rhythms, (iv) blunted and advanced the diurnal CORT rhythm, and (v) advanced Per1 expression in the adrenal and pituitary glands but not in the SCN. We found that chronic alcohol altered the phase relationships among diurnal rhythms and between the central (SCN) and peripheral (adrenal and pituitary) molecular clocks. Our findings suggest that desynchrony among internal rhythms is an important and overlooked aspect of alcohol-induced circadian disruptions. The misalignment of phases among rhythms may compromise normal physiological functions and put individuals with chronic alcohol use at greater risk for developing other physical and mental health issues. How this desynchrony occurs and the extent to which it participates in alcohol-related pathologies requires further investigation.
    No preview · Article · Feb 2016 · Alcoholism Clinical and Experimental Research
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    ABSTRACT: Background: Alcohol impairs drinkers' abilities to inhibit inappropriate responses. Certain stimulus conditions have been shown to facilitate behavioral control. Under conditions where individuals are presented with multiple inhibitory signals, the speed and consistency with which they are able to inhibit a response is improved. Recent research has shown that multisensory signals might protect against the disruptive effects of alcohol on mechanisms of behavioral control. This study examined whether multisensory stop signals can be used to improve inhibitory control, possibly by speeding attentional shifts toward inhibitory "stop" signals in the environment. Methods: Twenty adult social drinkers performed a modified cued go/no-go task that measured the ability to inhibit prepotent responses following 0.64 g/kg alcohol and placebo. Response targets were presented as unimodal (visual) and as multisensory (visual + aural) stimuli. Results: Results showed that during unimodal response target trials, participants made more inhibitory failures under 0.64 g/kg alcohol compared to placebo. During multisensory trials, however, there was no significant effect of alcohol on inhibitory control. Conclusions: These findings identify multisensory inhibitory signals as a potentially important environmental factor that can reduce the degree to which alcohol disinhibits behavior possibly by intersensory co-activation between the visual and auditory pathways.
    No preview · Article · Feb 2016 · Alcoholism Clinical and Experimental Research
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    ABSTRACT: Cognitive control deficits, as captured by inhibitory control measures, are indicative of increased impulsivity and are considered a marker for substance use disorder vulnerability. While individuals with alcohol use disorder (AUD) typically exhibit inhibitory control dysfunction, evidence of impaired inhibitory control among harmful drinkers, who are at increased risk of developing an AUD, is mixed. This study examined the response inhibition of binge drinkers using a task that employed neutral, as well as both immediate and delayed reward contingencies, to determine whether reward induced heightened impulsivity in this population. Binge alcohol users (n = 42) and controls (n = 42) were administered a Monetary Incentive Control Task that required participants to successfully inhibit a prepotent motor response to both neutral and immediately rewarding stimuli in order to secure a large delayed reward. Binge drinkers had significantly worse response inhibition than controls irrespective of trial condition and even after controlling for differences in weekly intake. Although both binge and control participants exhibited significantly worse inhibitory control in the presence of immediate reward, the control group showed a greater reduction in inhibition accuracy compared to the binge group in reward relative to neutral conditions. Both groups demonstrated significantly enhanced control when forewarned there was an increased chance response inhibition would be required. Control participants secured the delayed reward more often than binge participants. Despite the variability in the literature, this study demonstrated consistent generalized impulse control deficits among binge-drinking individuals that were unrelated to reward manipulations. These findings point to mechanisms that may confer vulnerability for transition from binge drinking to AUD.
    No preview · Article · Feb 2016 · Alcoholism Clinical and Experimental Research
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    ABSTRACT: Our goal was to investigate the role of behaviors amenable to policy change in mediating the relationship between alcohol consumption in off and on premises, age, and 2 measures of socioeconomic status (education and income). A cross-sectional general population survey was analyzed by using Bayesian path analysis to understand direct and mediating pathways. A total of 1,900 drinkers (past 6 months), aged 18 to 65 years, living in households with landline phones participated in the study. Measures were as follows: typical quantities of alcohol consumed per occasion, frequency of drinking, both off and on premise; gender, age groups; and years of education, personal income, prices paid, time of purchase, and liking for alcohol advertisements. Later times of purchase predicted larger quantities consumed (on and off premise) and more frequent drinking (on premise only). Younger people and males purchased later, and this mediated their heavier consumption. Lower prices paid predicted larger quantities consumed (on premise) and higher frequency of drinking (off premise). Younger and male respondents paid lower prices, and this mediated larger quantities consumed on premise and more frequent drinking off premise. Less well educated paid lower prices, and this mediated drinking more frequently off premise among this group. Liking for alcohol ads predicted drinking larger quantities and higher frequency both off and on premise. Younger and male respondents reported greater liking for ads, and this mediated their consumption of larger quantities and more frequent drinking both on and off premise. Those with higher income drank larger amounts on premise and more frequently on and off, but there were no mediating effects from the policy-relevant variables. Heavier drinking patterns by young people and those less well educated could be ameliorated by attention to alcohol policy.
    No preview · Article · Feb 2016 · Alcoholism Clinical and Experimental Research
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    ABSTRACT: Our aim was to describe alcohol consumption behavior of male Latino migrant farmworkers, compare their alcohol consumption behavior with that of other male Latino immigrants, and determine factors associated with risk for alcohol dependence among Latino immigrant workers. Cross-sectional data were drawn from baseline interviews conducted as part of a larger community-based participatory research project examining the cognitive and neurological outcomes of pesticide exposure. A total of 235 farmworkers and 212 nonfarmworkers completed interviews between May and August 2012. Although 17.5% of the North Carolina Latino farmworkers report never having drunk alcohol, and a total of 34.5% report not having drunk alcohol in the previous 3 months, 48.5% engaged in heavy episodic drinking (HED) in the previous 3 months, and 23.8% frequently engaged in HED during this period. Farmworkers and nonfarmworkers did not differ significantly in alcohol consumption behavior. Farmworkers and nonfarmworkers did differ significantly in each component of the CAGE scale, with 37.9% of farmworkers and 16.0% of nonfarmworkers being at risk for alcohol dependence (p < 0.0001). Significant factors for being at risk for alcohol dependence were stress (odds ratio 1.06, 95% confidence interval 1.03, 1.09) and being a farmworker (odds ratio 3.58, 95% confidence interval 2.12, 6.06). Being married reduced the risk of alcohol dependence (odds ratio 0.45, 95% confidence interval 0.23, 0.87). Latino farmworkers and nonfarmworkers consume relatively large amounts of alcohol and engage in HED at relatively high rates. Latino farmworkers have very high rates of risk for alcohol dependence. Policy changes and public health interventions are needed to address these concerns for a population that is vital to the agricultural economy.
    No preview · Article · Feb 2016 · Alcoholism Clinical and Experimental Research
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    ABSTRACT: Background: Early onset drinking is associated with later heavy drinking and related consequences. Early drinking onset and binge drinking are also independently associated with blackouts, which are periods of amnesia for events during a drinking episode. The objective of this study was to examine how early onset drinking relates to changes in the frequency of experiencing blackouts across 3 years controlling for year-specific binge drinking. Methods: Participants (N = 1,145; 67.9% female) from a 6-year, longitudinal study are included in these analyses. Measures of self-reported age at drinking onset included ages at first drink, first high, and first drunk, which were used to create a latent early onset drinking factor. Frequency of binge drinking and blackouts were assessed annually during Years 4 to 6. Results: Overall, 69.2% of participants reported experiencing blackouts. After controlling for year-specific binge drinking, a growth curve model indicated that early onset drinkers reported more frequent blackouts at Year 4. There were, however, no significant effects of acceleration or deceleration in the frequency of blackouts across the 3 years. Early onset drinkers continued to experience more frequent blackouts compared with those who initiated alcohol use later, despite decreases in binge drinking over time. Conclusions: Early onset drinkers reported more frequent blackouts across all 3 years, indicating that early alcohol initiation predisposes those individuals to continue to experience more frequent blackouts, despite a decrease in their binge drinking. This may be due to various factors, such as altered hippocampal development and functioning resulting from early alcohol exposure.
    No preview · Article · Feb 2016 · Alcoholism Clinical and Experimental Research

  • No preview · Article · Feb 2016 · Alcoholism Clinical and Experimental Research
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    ABSTRACT: The roles of GABA, serotonin, dopamine, and alcohol metabolism pathways in alcohol dependence (AD) are evident from animal models and human studies. Aims of this study were to investigate associations between genes in the 4 pathways and AD. Male subjects from 2 independent samples of Taiwanese Han descent, a family sample of 179 trios and a case–control sample of 262 AD cases and 273 normal controls, were included in this study. The Schedules for Clinical Assessment in Neuropsychiatry was used for phenotype assessment of AD. We genotyped 282 single nucleotide polymorphisms (SNPs) located in 61 candidate genes involving alcohol metabolism, serotonin, and GABA systems among the family sample and replicated the top hits in the case–control sample. Fifteen SNPs located in 10 genes showed signals of associations (FBAT test p < 0.05) with AD in the family sample. Three SNPs, rs1229984 in ADH1B, rs671 in ALDH2, and rs2000292 in HTR1B, were significantly replicated in the case–control sample (p = 5.87 × 10−14, 5.12 × 10−14, and 0.0051, respectively). In the combined meta-analysis, these 3 SNPs and 1 additional SNP, rs698 in ADH1C, showed significant association after correcting for multiple comparisons, and rs1229984 and rs671 showed the strongest association (p < 10−16). Logistic regression conditioning on rs1229984 and rs671 in the case–control sample showed that rs2000292 in HTR1B remained nominally significant. Genes in alcohol metabolism pathway, especially ADH1B and ALDH2, conferred the major genetic risk for AD in Taiwanese Han population. Some genes in GABA and serotonin pathways showed nominal association with AD.
    No preview · Article · Feb 2016 · Alcoholism Clinical and Experimental Research
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    ABSTRACT: Inpatient alcohol detoxifications are only proposed after motivational outpatient encounters because detoxification directly from the emergency department (ED) is believed to be associated with early dropout and poor adherence to outpatient follow-up. The aim of this prospective follow-up study was to test the feasibility of unscheduled (UP) alcohol detoxification directly from the ED and to compare the 1-year follow-up of these patients to that of scheduled (SP) patients. A quasi-naturalistic prospective follow-up study of 120 patients: 60 consecutively admitted patients referred directly by the ED for alcohol detoxification (UP) were compared to 60 consecutively admitted patients who had undergone the usual preparation for an inpatient detoxification program (SP). The length of hospitalization (in days) and attendance to postdischarge outpatient visits during the first year was compared. UP patients were older, less frequently employed, and had more somatic comorbidities compared with SP patients. The UP length of stay was significantly longer (20 ± 16 vs. 14 ± 6, p = 0.04). No difference in their postdischarge attendance was observed; the number of patients attending 1 session (57% UP vs. 65% SP, p = 0.227) and 5 sessions (22% UP vs. 32% SP, p = 0.151) and the mean number of postdischarge visits attended were comparable between the UP and SP groups (2.7 ± 6 vs. 4.5 ± 6; Mann–Whitney U = 1,517, p = 0.124). We did not find that UP patients who had been admitted for alcohol detoxification had a significantly higher dropout rate or lower postdischarge addiction treatment attendance. Because they may have several advantages, detoxification programs directly linked with EDs should be further evaluated.
    No preview · Article · Feb 2016 · Alcoholism Clinical and Experimental Research
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    ABSTRACT: The contribution of epigenetic factors, such as histone acetylation and DNA methylation, to the regulation of alcohol-drinking behavior has been increasingly recognized over the last several years. GADD45b is a protein demonstrated to be involved in DNA demethylation at neurotrophic factor gene promoters, including at brain-derived neurotrophic factor (Bdnf) which has been highly implicated in alcohol-drinking behavior. DNA methyltransferase-1 (Dnmt1), 3a, and 3b, and Gadd45a, b, and g mRNA were measured in the nucleus accumbens (NAc) and ventral tegmental areas of high ethanol (EtOH) consuming C57BL/6J (C57) and low alcohol consuming DBA/2J (DBA) mice using quantitative reverse transcriptase polymerase chain reaction (PCR). In the NAc, GADD45b protein was measured via immunohistochemistry and Bdnf9a mRNA using in situ PCR. Bdnf9a promoter histone H3 acetylated at lysines 9 and 14 (H3K9,K14ac) was measured using chromatin immunoprecipitation, and 5-methylcytosine (5MC) and 5-hydroxymethylcytosine (5HMC) using methylated DNA immunoprecipitation. Alcohol-drinking behavior was evaluated in Gadd45b haplodeficient (+/−) and null mice (−/−) utilizing drinking-in-the-dark (DID) and 2-bottle free-choice paradigms. C57 mice had lower levels of Gadd45b and g mRNA and GADD45b protein in the NAc relative to the DBA strain. C57 mice had lower NAc shell Bdnf9a mRNA levels, Bdnf9a promoter H3K9,K14ac, and higher Bdnf9a promoter 5HMC and 5MC. Acute EtOH increased GADD45b protein, Bdnf9a mRNA, and histone acetylation and decreased 5HMC in C57 mice. Gadd45b +/− mice displayed higher drinking behavior relative to wild-type littermates in both DID and 2-bottle free-choice paradigms. These data indicate the importance of the DNA demethylation pathway and its interactions with histone posttranslational modifications in alcohol-drinking behavior. Further, we suggest that lower DNA demethylation protein GADD45b levels may affect Bdnf expression possibly leading to altered alcohol-drinking behavior.
    No preview · Article · Feb 2016 · Alcoholism Clinical and Experimental Research
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    ABSTRACT: Background: The use of hair ethyl glucuronide (EtG) levels as a biomarker for chronic high intake of ethanol (EtOH) is increasing, and misclassification of alcohol consumption may have large implications for the patient. The aim of this study was to compare levels of hair EtG in patients with reduced kidney function to levels seen in a comparable control group and to investigate whether the hair EtG levels among kidney failure patients who are social drinkers may lead to a false-positive diagnosis of heavy drinking. Methods: A total of 41 patients with reduced kidney function and 42 healthy volunteers were included in the study. Both patients and the healthy volunteers reported moderate alcohol intake. The levels of EtG in hair (corrected for estimated daily intake of EtOH [EDI]) were compared between the 2 groups. Results: There was no significant difference between the groups regarding EDI. Despite this, there were significant higher levels of hair EtG (corrected for EDI) in the patient group compared to the control group (p < 0.001). Eight subjects (20%) in the patient group showed EtG levels in hair above 30 pg/mg, in contrast to no subjects among healthy volunteers (p = 0.002). In the patient group, there was significant correlation between levels of EtG in hair and both estimated glomerulus filtration rate and serum creatinine levels. Conclusions: This study documents an increased risk of obtaining a false-positive diagnosis of heavy drinking among renal disease patients who are social drinkers. Interpretation of EtG levels in hair among patients with reduced kidney function must be performed with caution.
    No preview · Article · Feb 2016 · Alcoholism Clinical and Experimental Research
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    ABSTRACT: Alcoholic hepatitis (AH) is an inflammatory disorder of the liver characterized clinically by jaundice, hepatomegaly, and abdominal pain, and histologically by macrovesicular steatosis and necroinflammation. This clinical review will cover what is known about the pathogenesis, clinical presentation, current treatments, and novel therapies for AH. The pathogenesis and treatment of AH remain areas of active research. Although abstinence is the cornerstone of therapy for all stages of alcoholic liver disease, corticosteroids have shown modest short-term benefits in treatment of severe AH. Improved understanding of the pathogenesis of AH has expanded the range of potential treatments for this devastating disease. Several novel therapies are also currently in various stages of testing through clinical trials.
    No preview · Article · Feb 2016 · Alcoholism Clinical and Experimental Research
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    ABSTRACT: Ethanol (EtOH) exposure in neonate rats during a period comparable to the human third trimester, postnatal days (PD) 4 to 9, leads to persistent deficits in forebrain-dependent cognitive function—modeling the dysfunction seen in individuals diagnosed with fetal alcohol spectrum disorders. EtOH-exposed adult rats are impaired in auditory trace fear conditioning (TFC), a form of Pavlovian conditioning in which a neutral conditioned stimulus (CS; tone) is followed by an aversive unconditioned stimulus (US; footshock), with both stimuli separated in time by a stimulus-free “trace” interval (TI). TFC acquisition depends on N-methyl-d-aspartate NMDA receptor (NMDAR) activation in the dorsal hippocampus (DH), ventral hippocampus (VH), and medial prefrontal cortex (mPFC). Male and female rat pups were sham-intubated (SI) or intragastrically intubated with EtOH (5E; 5 g/kg/d) over PD 4 to 9 and, as adults, submitted to TFC with a 15-second tone CS and 30-second TI. Whole-cell tissue lysates from the DH, VH, and mPFC of TFC rats and DH synaptic/extrasynaptic membrane fractions from experimentally naïve animals were analyzed via Western blot for NMDAR subunit (GluN1, GluN2A, GluN2B) expression. Freezing behavior during CS-alone test trials was significantly reduced in both male and female 5E rats, relative to same-sex controls. Western blot results based on DH tissue samples revealed a greater proportion of GluN2A to GluN2B subunits in 5E rats, relative to SI rats, and significantly reduced synaptic GluN2B and PSD-95 expression. EtOH-induced changes in DH NMDAR subunit expression—particularly synaptic GluN2B, which is critical for TFC—are proposed to weaken long-term memory consolidation and, during behavioral testing, diminish CS-evoked freezing behavior.
    No preview · Article · Feb 2016 · Alcoholism Clinical and Experimental Research
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    ABSTRACT: Prenatal alcohol exposure affects inhibitory control and other aspects of attention and executive function. However, the efficacy of extrinsic reinforcement on these behaviors has not been tested. Alcohol-exposed children (AE; n = 34), children with attention-deficit/hyperactivity disorder (ADHD; n = 23), and controls (CON; n = 31) completed a flanker task with 4 reward conditions (no reward, reward, reward+occasional response cost, equal probability of reward+response cost). Inhibitory control was tested in the no reward conditions using a 3(group) × 2(flanker type) ANCOVA. Response to reinforcement was tested using 3(group) × 4(reward condition) × 4(flanker type) analysis of covariance (ANCOVA). Response time (RT) and accuracy were tested independently. Groups did not differ on demographic variables. The flanker task was successful in taxing interference control, an aspect of executive attention (i.e., responses to incongruent stimuli were slower than to congruent stimuli) and the AE group demonstrated impaired executive control over the other groups. Overall, the AE group had significantly slower RTs compared to the CON and ADHD groups, which did not differ. However, reinforcement improved RT in all groups. While occasional response cost had the greatest benefit in the CON group, the type of reinforcement did not differentially affect the AE and ADHD groups. Accuracy across reward conditions did not differ by group, but was dependent on flanker type and reward condition. Alcohol-exposed children, but not children with ADHD, had impaired interference control in comparison with controls, supporting a differential neurobehavioral profile in these 2 groups. Both clinical groups were equally affected by introduction of reinforcement, although the type of reinforcement did not differentially affect performance as it did in the control group, suggesting that reward or response cost could be used interchangeably to result in the same benefit.
    No preview · Article · Feb 2016 · Alcoholism Clinical and Experimental Research