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
    • Author cannot archive a post-print version
  • Restrictions
    • 12 months embargo
  • Conditions
    • Some journals have separate policies, please check with each journal directly
    • 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
    • Non-Commercial
    • 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: Background The K-complex (KC) is a brain potential characteristic of nonrapid eye movement (NREM) sleep resulting from the synchronous activity of a large population of neurons and hypothesized to reflect brain integrity. KC amplitude is lower in individuals with alcohol use disorder (AUD) compared with age-matched controls, but its recovery with short-term abstinence has not been studied. Therefore, we investigated whether the KC shows significant recovery over the first 4 months of abstinence in individuals with AUD. Methods A total of 16 recently abstinent AUD individuals (46.6 ± 9.3 years) and 13 gender and age-matched healthy controls (41.6 ± 8.3 years) were studied on 3 occasions: the Initial session was within 1 month of the AUD individuals' last drink, then 1 and 3 months later. Overnight electroencephalogram was recorded while participants were presented with tones during stage 2 NREM sleep to elicit KCs. Results At the Initial session, AUD participants showed significantly lower KC amplitude and incidence compared with controls. In the AUD individuals, KC amplitude increased significantly from the Initial to the 1-month session. KC incidence showed a marginally significant increase. Neither KC amplitude nor incidence changed from the 1-month to the 3-month session. No changes in KC amplitude or incidence across sessions were observed in the control group. Conclusions Our results demonstrate partial KC recovery during the first 2 months of abstinence. This recovery is consistent with the time course of structural brain recovery in abstinent AUD individuals demonstrated by recent neuroimaging results.
    Alcoholism Clinical and Experimental Research 08/2015; DOI:10.1111/acer.12769
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    ABSTRACT: Prazosin (PRZ; an α1 -adrenergic receptor antagonist) and naltrexone (NTX; a nonspecific opioid receptor antagonist) each decrease alcohol drinking when administered to rats selectively bred for high voluntary alcohol drinking (alcohol-preferring or "P"), and the combination of PRZ + NTX decreases alcohol drinking more effectively than does either drug alone. As drug responsiveness can depend on history of alcohol drinking and dependence, we investigated whether various schedules of PRZ and NTX administration, alone or in combination, are effective in decreasing alcohol drinking in male P rats with a history of protracted voluntary alcohol drinking, dependence, and repeated withdrawals closely resembling human alcoholism. Male P rats became alcohol-dependent during 1 year of ad libitum 24 h/d access to food, water, and 20% alcohol with repetitive temporary alcohol withdrawals. Four sequential studies then addressed effects of oral PRZ (2 mg/kg) and NTX (10 mg/kg), alone or together, on alcohol drinking during: (i) daily alcohol access with daily drug treatment, (ii) intermittent alcohol access with daily drug treatment, (iii) intermittent alcohol access with occasional drug treatment, and (iv) postdeprivation reinstatement of alcohol access. The combination of PRZ + NTX consistently suppressed alcohol drinking during daily or intermittent alcohol access conditions and when drug treatment was either daily or occasional. PRZ + NTX was consistently more effective than either drug alone. The reduction in alcohol drinking was not due to sedation, motor effects, or malaise. Both daily and "as-needed" treatment with PRZ + NTX are highly effective in suppressing daily, intermittent, and postdeprivation alcohol drinking in male P rats with a protracted history of alcohol dependence and repeated withdrawals. This drug combination may be especially effective for treating individuals with long histories of heavy alcohol abuse, dependence, and repeated relapse, as commonly encountered in clinical practice. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 08/2015; DOI:10.1111/acer.12828
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    ABSTRACT: Many daily functional activities involve goal-directed responses based on open-loop and closed-loop motor control, yet little is known about how children with heavy prenatal alcohol exposure organize and regulate these 2 types of control systems when completing a goal-directed force response. Children with (n = 19) or without (n = 23) heavy prenatal alcohol exposure were required to match a target force (25 and 50% of maximum voluntary force) in a specified target time (200, 800, and 2,000 ms). Target force and produced force were visually displayed on a computer monitor. The analog force-time record was parsed into 2 segments: the period beginning from force initiation to the first reversal in force was designated the open-loop phase, and the remainder of the response was the closed-loop phase. Compared to controls, alcohol-exposed children produced a significantly shorter duration of open-loop control, a higher open-loop phase rate of force development, a shorter time to reach maximum force during the closed-loop phase, and greater absolute target force error. Increasing target force magnitude did not differentially alter the performance of the clinical group. The results indicate that alcohol-exposed children experience deficits in completing goal-directed force responses that likely stem from an alcohol-related insult to the central nervous system. Therapeutic exercises should be designed to recalibrate internal timing systems and improve visuomotor integration. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 08/2015; DOI:10.1111/acer.12827
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    ABSTRACT: The large conductance Ca(2+) - and voltage-activated K(+) channel (BK) is an important player in molecular and behavioral alcohol tolerance. Trafficking and surface expression of ion channels contribute to the development of addictive behaviors. We have previously reported that internalization of the BK channel is a component of molecular tolerance to ethanol (EtOH). Using primary cultures of hippocampal neurons, we combine total internal reflection fluorescence microscopy, electrophysiology, and biochemical techniques to explore how exposure to EtOH affects the expression and subcellular localization of endogenous BK channels over time. Exposure to EtOH changed the expression of endogenous BK channels in a time-dependent manner at the perimembrane area (plasma membrane and/or the area adjacent to it), while total protein levels of BK remain unchanged. These results suggest a redistribution of the channel within the neurons rather than changes in synthesis or degradation rates. Our results showed a temporally nonlinear effect of EtOH on perimembrane expression of BK. First, there was an increase in BK perimembrane expression after 10 minutes of EtOH exposure that remained evident after 3 hours, although not correlated to increases in functional channel expression. In contrast, after 6 hours of EtOH exposure, we observed a significant decrease in both BK perimembrane expression and functional channel expression. Furthermore, after 24 hours of EtOH exposure, perimembrane levels of BK had returned to baseline. We report a complex time-dependent pattern in the effect of EtOH on BK channel trafficking, including successive increases and decreases in perimembrane expression and a reduction in active BK channels after 3 and 6 hours of EtOH exposure. Possible mechanisms underlying this multiphasic trafficking are discussed. As molecular tolerance necessarily underlies behavioral tolerance, the time-dependent alterations we see at the level of the channel may be relevant to the influence of drinking patterns on the development of behavioral tolerance. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 08/2015; DOI:10.1111/acer.12808
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    ABSTRACT: Neural activity within the prefrontal cortex (PFC) is altered by alcohol and alcohol-associated stimuli and is mediated by genetic susceptibility to alcoholism. However, very little is known about how genetic risk of excessive drinking might mediate neural firing in the PFC during alcohol consumption. To determine how genetic risk influences alcohol seeking, intake, and neural activity, a Pavlovian alcohol consumption task was used-the 2-Way Cued Access Protocol (2CAP). Alcohol-preferring "P" rats and relatives of their (heterogeneous) founding Wistar population were used for these studies. After acquisition of 2CAP, extinction of responding for alcohol was evaluated by substituting water for alcohol. Following these experiments, in vivo electrophysiological recordings were obtained during 2CAP from the PFC in a separate cohort of Wistar and P rats implanted with moveable tetrode microdrives. P and Wistar rats increased daily alcohol seeking and intake with P rats consuming roughly twice as much alcohol as Wistar. Both rat populations decreased seeking behavior during extinction. However, P rats displayed persistent increases in seeking after controlling for intake versus Wistar. Higher firing rates (FRs) were observed in P rats prior to 2CAP and throughout alcohol and water consumption compared with Wistars that were matched for alcohol-drinking history. Differences in FR were driven, in part, by a larger percentage of neurons in P rats versus Wistars that increased FR compared with those that decreased, or did not change. These data provide additional evidence of increased alcohol consumption and persistent alcohol seeking in P versus Wistar rats. Differences in PFC neural firing observed in P rats prior to drinking could be heritable and/or related to an enhanced response to alcohol-associated contextual cues. FR differences observed during alcohol drinking might be related to an augmented sensitivity of PFC neurons to orally consumed alcohol. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 08/2015; DOI:10.1111/acer.12804
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    ABSTRACT: Sipping alcohol is common during early adolescence, but research has ignored the distinction between sipping and drinking whole alcohol beverages, conflating the 2, or else simply classifying "sippers" as abstainers. Research has not addressed whether sippers are different to drinkers, in relation to variables known to be associated with adolescent alcohol consumption, or considered whether sipping and drinking behaviors may have quite different associations. Parent-child dyads (N = 1,823) were recruited in 3 states from Australian grade 7 classes. Multinomial logistic analyses compared adolescents who had only had a sip/taste of alcohol (sippers) with adolescents who had consumed at least a whole drink (drinkers) in the past 6 months. The multivariate model assessed a broad range of demographics, parenting practices, peer influences, and adolescent externalizing and internalizing behaviors, and controlled for school clustering. Compared to drinkers, sippers were less likely to come from 1-parent households (odds ratio [OR] = 0.59, 95% confidence interval [CI]: 0.35 to 0.98); less likely to come from low-socioeconomic status (SES) households (OR = 0.54, 95% CI: 0.31 to 0.94); more likely to come from families where parents provide stricter alcohol-specific rules (OR = 1.21, 95% CI: 1.11 to 1.32), stricter monitoring of the child's activities (OR = 1.10, 95% CI: 1.04 to 1.16), more consistent parenting practices (OR = 1.13, 95% CI: 1.05 to 1.23), and more positive family relationships (OR = 1.56, 95% CI: 1.02 to 2.43); and report having fewer substance-using peers (OR = 0.80, 95% CI: 0.70 to 0.91) and greater peer disapproval of any substance use (OR = 1.30, 95% CI: 1.19 to 1.42). After adjustment for confounders, the associations with household composition and SES were no longer significant, but the familial and peer associations remained significant in the multivariate analysis, χ(2) (40) = 1,493.06, p < 0.001. Sipping alcohol has different associations with known predictors of adolescent alcohol use than drinking whole beverages, and sipping may be a distinct or separable behavior. Future research should better define quantities of early consumption and assess the relationship between early sipping and drinking on long-term outcomes separately. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 08/2015; DOI:10.1111/acer.12826
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    ABSTRACT: Binge drinking during adolescence is associated with increased risk for developing alcohol use disorders; however, the neural mechanisms underlying this liability are unclear. In this study, we sought to determine whether binge drinking alters expression or phosphorylation of 2 molecular mechanisms of neuroplasticity, calcium/calmodulin-dependent kinase II alpha (CaMKIIα) and the GluA1 subunit of AMPA receptors (AMPARs) in addiction-associated brain regions. We also asked whether activation of CaMKIIα-dependent AMPAR activity escalates binge-like drinking. To address these questions, CaMKIIαT286 and GluA1S831 protein phosphorylation and expression were assessed in the amygdala and striatum of adolescent and adult male C57BL/6J mice immediately after voluntary binge-like alcohol drinking (blood alcohol >80 mg/dl). In separate mice, effects of the CaMKIIα-dependent GluA1S831 phosphorylation (pGluA1S831 )-enhancing drug tianeptine were tested on binge-like alcohol consumption in both age groups. Binge-like drinking decreased CaMKIIαT286 phosphorylation (pCaMKIIαT286 ) selectively in adolescent amygdala with no effect in adults. Alcohol also produced a trend for reduced pGluA1S831 expression in adolescent amygdala but differentially increased pGluA1S831 in adult amygdala. No effects were observed in the nucleus accumbens or dorsal striatum. Tianeptine increased binge-like alcohol consumption in adolescents but decreased alcohol consumption in adults. Sucrose consumption was similarly decreased by tianeptine pretreatment in both ages. These data show that the adolescent and adult amygdalae are differentially sensitive to effects of binge-like alcohol drinking on plasticity-linked glutamate signaling molecules. Tianeptine-induced increases in binge-like drinking only in adolescents suggest that differential CaMKIIα-dependent AMPAR activation may underlie age-related escalation of binge drinking. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 08/2015; DOI:10.1111/acer.12819
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    ABSTRACT: Genetic variation in a region of chromosome 4p12 that includes the GABAA subunit gene GABRA2 has been reproducibly associated with alcohol dependence (AD). However, the molecular mechanisms underlying the association are unknown. This study examined correlates of in vitro gene expression of the AD-associated GABRA2 rs279858*C-allele in human neural cells using an induced pluripotent stem cell (iPSC) model system. We examined mRNA expression of chromosome 4p12 GABAA subunit genes (GABRG1, GABRA2, GABRA4, and GABRB1) in 36 human neural cell lines differentiated from iPSCs using quantitative polymerase chain reaction and next-generation RNA sequencing. mRNA expression in adult human brain was examined using the BrainCloud and BRAINEAC data sets. We found significantly lower levels of GABRA2 mRNA in neural cell cultures derived from rs279858*C-allele carriers. Levels of GABRA2 RNA were correlated with those of the other 3 chromosome 4p12 GABAA genes, but not other neural genes. Cluster analysis based on the relative RNA levels of the 4 chromosome 4p12 GABAA genes identified 2 distinct clusters of cell lines, a low-expression cluster associated with rs279858*C-allele carriers and a high-expression cluster enriched for the rs279858*T/T genotype. In contrast, there was no association of genotype with chromosome 4p12 GABAA gene expression in postmortem adult cortex in either the BrainCloud or BRAINEAC data sets. AD-associated variation in GABRA2 is associated with differential expression of the entire cluster of GABAA subunit genes on chromosome 4p12 in human iPSC-derived neural cell cultures. The absence of a parallel effect in postmortem human adult brain samples suggests that AD-associated genotype effects on GABAA expression, although not present in mature cortex, could have effects on regulation of the chromosome 4p12 GABAA cluster during neural development. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 08/2015; DOI:10.1111/acer.12807
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    ABSTRACT: "Maturing out" of problem drinking is associated with both role transitions (e.g., getting married) and personality development. However, little is known concerning how these 2 mechanisms jointly influence problem-drinking desistance. This study investigated whether salutary effects of role transitions and personality occur at different points in young-adult development and whether they mediate one another's effects. Participants were initially recruited as first-year undergraduates, with family history of alcoholism overrepresented by design (N = 489). Using 4 waves of data at roughly ages 21, 25, 29, and 34, cross-lagged panel models estimated prospective relations among familial-role transitions (marriage or parenthood), personality (disinhibition, conscientiousness, and neuroticism), and problem drinking. Mixed support was found for the prediction of roles being more strongly associated with earlier maturing out of problem drinking and personality being more strongly associated with later maturing out. Regarding mediation, no evidence was found for the expectation that role effects would be mediated by personality. However, results did support mediation of personality effects by role transitions. Specifically, lower disinhibition and higher conscientiousness in emerging adulthood predicted role adoption, which, in turn, predicted later problem-drinking reductions. Family history of alcoholism also distally influenced these mediation processes. The differential timing of role and personality effects is consistent with the notion of decreasing contextual influences and increasing intrapersonal influences across development. In light of role incompatibility theory, results suggest that, over the course of development, the association of familial roles with problem drinking may increasingly reflect problem-drinking effects on role entry (i.e., role selection) and decreasingly reflect role entry effects on problem drinking (i.e., role socialization). As emerging-adult disinhibition and conscientiousness were associated with an apparent developmental cascade of both direct and indirect effects, findings highlight their potential importance as etiologic mechanisms and intervention targets. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 08/2015; DOI:10.1111/acer.12816
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    ABSTRACT: Emerging research suggests that some bariatric surgery patients are at a heightened risk for developing substance use problems, especially alcohol use problems. An exhaustive literature review was conducted in January 2015 to investigate all articles published that included data on postoperative alcohol use, alcohol use disorders, and illicit drug use among bariatric surgery patients. Twenty-three studies reported on alcohol and/or substance use among bariatric patients. Six studies longitudinally assessed alcohol use behaviors; 3 of these studies found an increase in alcohol use following surgery. Six studies were cross-sectional, and 2 studies assessed medical records. Five studies investigated the prevalence of admissions to substance abuse treatment, and 3 studies combined alcohol and drug use data in a single index. Six studies reported on illicit drug use and reported low-postoperative use. The studies' samples were primarily non-Hispanic white females in their upper 40s, and only 11 of the 23 studies utilized validated assessment instruments. Studies employing longitudinal designs and large sample sizes indicate that bariatric patients who had the gastric bypass procedure are at an elevated risk for alcohol use problems postoperatively. Research also indicates that bariatric surgery patients might be overrepresented in substance abuse treatment facilities. Risk factors for problematic postoperative alcohol use include regular or problematic alcohol use presurgery, male gender, younger age, tobacco use, and symptoms of attention deficient and hyperactivity disorder. As a whole, however, studies indicate bariatric surgery patients demonstrate a low prevalence of problematic alcohol use, and studies about gastric bypass patients are not entirely conclusive. Prospective, longitudinal studies are needed, utilizing standardized and validated alcohol assessment instruments that follow postoperative bariatric patients well beyond 2 years, and account for types of bariatric procedure. Finally, study samples with greater racial/ethnic diversity and wider age ranges are needed. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 08/2015; DOI:10.1111/acer.12805
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    ABSTRACT: Many alcoholics and heavy drinkers undergo repeated cycles of alcohol abstinence followed by relapse to alcohol drinking; a pattern that contributes to escalated alcohol intake over time. In rodents, alcohol drinking that is interspersed with periods of alcohol deprivation (imposed abstinence) increases alcohol intake during reaccess to alcohol. This is termed the "alcohol deprivation effect" or "ADE" and is a model of alcohol relapse in humans. We have previously reported that prazosin reduces alcohol drinking during both brief and prolonged treatment in rats selectively bred for alcohol preference ("P" rats). This study explores whether prazosin prevents alcohol "relapse" in P rats, as reflected by a reduced or abolished ADE. Adult male P rats were given 24-hour access to food and water and scheduled access to alcohol (15 and 30% v/v solutions presented concurrently) for 2 h/d. After 5 weeks, rats underwent imposed alcohol deprivation for 2 weeks, followed by alcohol reaccess for 2 weeks, and this pattern was repeated for a total of 3 cycles. Rats were injected with prazosin (0, 0.5, 1.0, or 2.0 mg/kg body weight, intraperitoneally) once a day for the first 5 days of each alcohol reaccess cycle. Alcohol intake increased on the first day of each alcohol reaccess cycle, demonstrating the formation of an ADE. The ADE was short-lived, lasting only 1 day, during each of the 3 cycles. Prazosin, in all doses tested, prevented the expression of an ADE in all 3 alcohol reaccess cycles. Prazosin decreases alcohol intake in P rats even in a situation that would be expected to increase alcohol drinking, namely following periods of alcohol deprivation. This suggests that prazosin may be effective in reducing alcohol relapse that often occurs during attempts to achieve permanent alcohol abstinence in treatment-seeking alcoholics and heavy drinkers. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 08/2015; 39(8):1538-1546. DOI:10.1111/acer.12789
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    ABSTRACT: Background This study examines the association between perceived neighborhood violence, perceived neighborhood collective efficacy, and binge drinking among Mexican Americans residing on the U.S.–Mexico border.Methods Data were collected from a multistage cluster sample of adult Mexican Americans residing in the U.S.–Mexico border areas of California, Arizona, New Mexico, and Texas (N = 1,307). The survey weighted response rate was 67%. Face-to-face interviews lasting approximately 1 hour were conducted in respondents' homes in English or Spanish. Path analysis was used to test whether collective efficacy mediated the impact of perceived neighborhood violence on binge drinking.ResultsAmong 30+-year-old women, perceived neighborhood collective efficacy mediated the effects of perceived neighborhood violence on binge drinking in a theoretically predicted way: Lower perceptions of violence predicted an increased perception of collective efficacy, which in turn, predicted less binge drinking. Direct effects of violence perceptions on binge were nonsignificant. Younger 18- to 29-year-old women showed a similar (but nonsignificant) pattern of effects. Perceived collective efficacy also mediated the effects of perceived violence on binge drinking among men, but in opposite ways for older and younger men. Older men showed the same mediating effect as older women, but the effect reversed among younger men due to a strong, positive relation between collective efficacy and binge drinking. There were also age differences in the direct effect of violence perceptions on binge drinking: Perceptions of violence predicted more binge drinking among young men, but less among older men.Conclusions These results highlight the complexity of people's responses to neighborhood characteristics in regard to their drinking. Young men in particular seem to react very differently to perceptions of collective efficacy than other groups. However, among both men and women, collective efficacy may come to play an increasingly important protective role in health outcomes with age.
    Alcoholism Clinical and Experimental Research 08/2015; DOI:10.1111/acer.12818
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    ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) is a cancer that is characterized by its high morbidity and mortality rates. While tobacco use and alcohol consumption are 2 major contributing factors for HNSCC carcinogenesis, how the combination of tobacco and alcohol increases HNSCC risk is not understood. We combined the 4-nitroquinoline-1-oxide (4-NQO) oral carcinogenesis and Meadows-Cook alcohol mouse models to elucidate the molecular events and to identify the novel biomarkers associated with oral cancer development. By genome-wide RNA-seq of tongue samples (3 mice per group), we identified changes in transcripts that mediate alcohol metabolism and oxidative stress (Aldh2, Aldh1a3, Adh1, Adh7, and Cyp2a5) in mice treated with 4-NQO followed by ethanol (4-NQO/EtOH) as compared to the vehicle control/untreated (V.C./Untr.) samples. We measured major, global increases in specific histone acetylation and methylation epigenetic marks (H3K27ac, H3K9/14ac, H3K27me3, and H3K9me3) in the oral cavities of V.C./EtOH, 4-NQO/Untr., and 4-NQO/EtOH treatment groups compared to the V.C./Untr. group. We detected changes in histone epigenetic marks near regulatory regions of genes involved in ethanol metabolism by chromatin immunoprecipitation. For instance, the Aldh2 promoter showed increased H3K27me3 marks, and Aldh2 mRNA levels were reduced by 10-fold in 4NQO/EtOH versus V.C./Untr. tongue samples. 4-NQO/EtOH treatment also caused increases in markers of oxidative stress, including 4-HNE, MCT4/SLC16a3, and TOM20, as measured by immunohistochemistry. We delineate a mechanism by which 4-NQO and ethanol can regulate gene expression during the development of HNSCC and suggest that histone epigenetic marks and oxidative stress markers could be the novel biomarkers and targets for the prevention of HNSCC. Copyright © 2015 by the Research Society on Alcoholism.
    Alcoholism Clinical and Experimental Research 08/2015; 39(8):1360-1372. DOI:10.1111/acer.12772