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Background The research of alcohol consumption-related problems is a multidisciplinary field. The aim of this study is to analyze the worldwide scientific production in the area of alcohol-drinking and alcohol-related problems from 2005 to 2009. Methods A MEDLINE and Scopus search on alcohol (alcohol-drinking and alcohol-related problems) published from 2005 to 2009 was carried out. Using bibliometric indicators, the distribution of the publications was determined within the journals that publish said articles, specialty of the journal (broad subject terms), article type, language of the publication, and country where the journal is published. Also, authorship characteristics were assessed (collaboration index and number of authors who have published more than 9 documents). The existing research groups were also determined. Results About 24,100 documents on alcohol, published in 3,862 journals, and authored by 69,640 authors were retrieved from MEDLINE and Scopus between the years 2005 and 2009. The collaboration index of the articles was 4.83 ± 3.7. The number of consolidated research groups in the field was identified as 383, with 1,933 authors. Documents on alcohol were published mainly in journals covering the field of ' Substance- Related Disorders,' 23.18%, followed by ' Medicine,' 8.7%, ' Psychiatry,' 6.17%, and ' Gastroenterology,' 5.25%. Conclusions Research on alcohol is a consolidated field, with an average of 4,820 documents published each year between 2005 and 2009 in MEDLINE and Scopus. Alcohol-related publications have a marked multidisciplinary nature. Collaboration was common among alcohol researchers. There is an underrepresentation of alcohol-related publications in languages other than English and from developing countries, in MEDLINE and Scopus databases. [ABSTRACT FROM AUTHOR]

Background We examined differences in response to self-reported alcohol use items by survey mode, whether self-report differences were the result of modality effects or self-selection, and whether these differences varied across the treatment and control arms of a preventative intervention trial. Methods Data from an existing alcohol prevention trial were used to estimate the effect of survey modality on adolescent's self-reported alcohol use at ages 17 to 18. Estimates were derived from regression models controlling for self-reported alcohol use during 8th grade, measured using a single survey modality, as well as time invariant selection factors. Results No statistically significant survey modality effects were found. No differential effects of survey modality were observed by assigned intervention group. Conclusions We provide initial evidence that adolescent alcohol prevention trials may use multiple survey modalities when necessary to increase response rates without harming interpretation of intervention effects. [ABSTRACT FROM AUTHOR]

Background Low levels of alcohol responses (low LRs) are genetically influenced phenotypes that are identified before alcohol dependence and predict future heavy drinking and alcohol problems. A recent paper described 13 LR-related blood oxygen level-dependent ( BOLD) response contrast patterns observed during an emotional face recognition task that might reflect cognitive processes contributing to LR and that might themselves predict adverse alcohol outcomes ( Paulus et al., Biol Psychiatry 2012; 72: 848). This paper evaluates the predictive implications of those functional magnetic resonance imaging (f MRI) patterns. Methods Of 120 subjects from Paulus and colleagues (2012), 114 (57 low and high LRs; ~50% females) were interviewed 5 years later at age 25. Correlations between baseline f MRI patterns and alcohol-related outcomes were evaluated, and regression analyses were used to determine if BOLD response contrasts incremented over LR in predicting outcomes. Results Baseline f MRI patterns in 5 of 13 baseline regions of interest correlated with adverse outcomes. Such patterns in insular regions, particularly the left anterior insula, and the right frontal gyrus, added to LR in predicting alcohol problems. The relationships remained robust when exact binomial procedures were used, but, reflecting the small sample size, it was not possible to adequately consider Bonferroni corrections. Conclusions The data suggest that f MRI BOLD response contrasts predicted heavier drinking and alcohol problems 5 years later, even after considering baseline low LRs. Future work will focus on whether f MRI results can predict outcomes in larger samples and among young nondrinkers, as well as how the imaging results increase understanding of the processes through which LR operates. [ABSTRACT FROM AUTHOR]

Background Stress and anxiety are widely considered to be causally related to alcohol craving and consumption, as well as development and maintenance of alcohol use disorder ( AUD). However, numerous preclinical and human studies examining effects of stress or anxiety on alcohol use and alcohol-related problems have been equivocal. This study examined relationships between scores on self-report anxiety, anxiety sensitivity, and stress measures and frequency and intensity of recent drinking, alcohol craving during early withdrawal, as well as laboratory measures of alcohol craving and stress reactivity among heavy drinkers with AUD. Methods Media-recruited, heavy drinkers with AUD ( N = 87) were assessed for recent alcohol consumption. Anxiety and stress levels were characterized using paper-and-pencil measures, including the Beck Anxiety Inventory ( BAI), the Anxiety Sensitivity Index-3 ( ASI-3), and the Perceived Stress Scale ( PSS). Eligible subjects ( N = 30) underwent alcohol abstinence on the Clinical Research Unit; twice daily measures of alcohol craving were collected. On day 4, subjects participated in the Trier Social Stress Test; measures of cortisol and alcohol craving were collected. Results In multivariate analyses, higher BAI scores were associated with lower drinking frequency and reduced drinks/drinking day; in contrast, higher ASI-3 scores were associated with higher drinking frequency. BAI anxiety symptom and ASI-3 scores also were positively related to Alcohol Use Disorders Identification Test total scores and AUD symptom and problem subscale measures. Higher BAI and ASI-3 scores but not PSS scores were related to greater self-reported alcohol craving during early alcohol abstinence. Finally, BAI scores were positively related to laboratory stress-induced cortisol and alcohol craving. In contrast, the PSS showed no relationship with most measures of alcohol craving or stress reactivity. Conclusions Overall, clinically oriented measures of anxiety compared with perceived stress were more strongly associated with a variety of alcohol-related measures in current heavy drinkers with AUD. [ABSTRACT FROM AUTHOR]

Background Alcohol-related blackouts are periods of amnesia that reflect the failure of the brain to record memories of what transpires while drinking. This paper examined the incidence, predictors, and behavioral correlates of blackouts among emerging adults and examined whether questions about blackouts could serve as better markers of risk for other alcohol related harms than questions about levels of consumption. Methods In 2012 to 2013, 1,463 (68%) of 2,140 respondents 1-year past high school reported having consumed alcohol. They were asked whether, in the past 6 months because of drinking, they forgot where they were or what they did. The survey also explored demographics, substance use behaviors, and other alcohol-related problems in the past 6 months. Chi-square and logistic regression analyses explored bivariate and multivariate predictors of blackouts and other alcohol-related problems. Results Twenty percent of respondents who ever drank alcohol reported a blackout in the past 6 months. Blackouts were more prevalent among females and those who, in the past 30 days, used multiple drugs, more frequently binged, were drunk, smoked, had lower body weight, and lived in college dorms. After controlling for drinking levels, having a blackout was the strongest independent predictor of most other alcohol problems examined, including in the past 6 months because of drinking, missing class or work, getting behind in work or school, doing something respondents later regretted, arguing with friends, experiencing an overdose, and total number of alcohol problems reported. It was also an independent predictor of hangovers, damaging property, getting hurt, and trouble with police. Conclusions Because blackouts indicate drinking at levels that result in significant cognitive and behavioral impairment, questions about blackouts could serve as important, simple screeners for the risk of experiencing other alcohol related harms. Additional work on this subject is warranted. [ABSTRACT FROM AUTHOR]

Background Despite harmful drinking causing a significant burden on global health, there is a large treatment gap, especially in low- and middle-income countries. A major barrier to care is the lack of adequately skilled human resources to deliver contextually appropriate treatments. This paper describes the systematic process used to develop Counselling for Alcohol Problems ( CAP), a brief psychological treatment (PT) for delivery by lay counselors in routine primary care settings to men with harmful drinking in India. Methods CAP was developed using a methodology involving 3 sequential steps: (i) identifying potential treatment strategies; (ii) developing a theoretical framework for the treatment; and (iii) evaluating the acceptability and feasibility of the treatment. Results CAP is a 3-phase treatment delivered over 1 to 4 sessions based on a motivational interviewing ( MI) stance and involves the following strategies: assessment and personalized feedback, family engagement, drink refusal skills, skills to address drinking urges, problem-solving skills and handling difficult emotions, and relapse prevention and management. Data from a case series were used to inform several adaptations to enhance the acceptability of CAP to the recipients and feasibility of delivery by lay counselors of the treatment, for example expansion of the target group to include alcohol-dependent patients and the extension of the delivery settings to include home-based delivery. There was preliminary evidence of the effectiveness of CAP. Conclusions CAP is an acceptable brief PT for harmful drinking delivered by lay counselors in primary care whose effectiveness is currently being tested in a randomized controlled trial based in primary care in Goa, India. [ABSTRACT FROM AUTHOR]

Background Prenatal alcohol exposure can kill developing neurons, leading to microencephaly and mental retardation. However, not all fetuses are equally vulnerable to alcohol's neurotoxic effects. While some fetuses are severely affected and are ultimately diagnosed with fetal alcohol syndrome (FAS), others have no evidence of neuropathology and are behaviorally normal. These widely different outcomes among alcohol-exposed fetuses are likely due, in part, to genetic differences. Some fetuses possess genotypes that make them much more vulnerable than others to alcohol's teratogenic effects. However, to date, only 1 gene has been identified whose mutation can worsen alcohol-induced behavioral deficits in an animal model of FAS. That gene is neuronal nitric oxide synthase ( nNOS). The purpose of this study was to determine whether mutation of nNOS can likewise worsen alcohol-induced microencephaly and lead to permanent neuronal deficits. Methods Wild-type and nNOS−/− mice received alcohol (0.0, 2.2, or 4.4 mg/g) daily over postnatal days (PDs) 4 to 9. Beginning on PD 85, the mice underwent a series of behavioral tests; the results of which are reported in the companion paper. The brains were then weighed, and stereological cell counts were performed on the cerebral cortex and hippocampal formation, which are the brain regions that mediate the aforementioned behavioral tasks. Results Alcohol caused dose-dependent microencephaly, but only in the nNOS−/− mice and not in wild-type mice. Alcohol-induced neuronal losses were more severe in the nNOS−/− mice than in the wild-type mice in all of the brain regions examined, including the cerebral cortex, hippocampal CA3 subregion, hippocampal CA1 subregion, and dentate gyrus. Conclusions Targeted mutation of the nNOS gene increases the vulnerability of the developing brain to alcohol-induced growth restriction and neuronal losses. This increased neuropathology is associated with worsened behavioral dysfunction. The results demonstrate the critical importance of genotype in determining the outcome of developmental alcohol exposure. [ABSTRACT FROM AUTHOR]

Background Alcohol-related blackouts ( ARBs) are reported by ~50% of drinkers. While much is known about the prevalence of ARBs in young adults and their cross-sectional correlates, there are few prospective studies regarding their trajectories over time during mid-adolescence. This paper reports latent trajectory classes of ARBs between age 15 and 19, along with predictors of those patterns. Methods Latent class growth analysis ( LCGA) was used to evaluate the pattern of occurrence of ARBs across 4 time points for 1,402 drinking adolescents from the Avon Longitudinal Study of Parents and Children ( ALSPAC). Multinomial regression analyses evaluated age-15 demography, substance-related items, externalizing characteristics, and estimated peer substance use as predictors of latent class membership. Results ARBs were reported at age 15 in 30% and at age 19 in 74% of these subjects. Four latent trajectory classes were identified: Class 1 (5.1%) reported no blackouts; for Class 2 (29.5%), ARBs rapidly increased with age; for Class 3 (44.9%), blackouts slowly increased; and for Class 4 (20.5%), ARBs were consistently reported. Using Class 2 (rapid increasers) as the reference, predictors of class membership included female sex, higher drinking quantities, smoking, externalizing characteristics, and estimated peer substance involvement (pseudo R2 = 0.22). Conclusions ARBs were common and repetitive in these young subjects, and predictors of their trajectories over time involved multiple domains representing diverse characteristics. [ABSTRACT FROM AUTHOR]

Background This paper examines the prevalence, the symptom profile, and the drinking and sociodemographic predictors of current (past 12 months) DSM- IV alcohol abuse and dependence among Mexican Americans living along the U. S.- Mexico border and those living in metropolitan areas away from the border. Methods Respondents in the non-border areas (primarily Houston and Los Angeles) constitute a multistage probability sample ( N = 1,288) of these areas, interviewed as part of the 2006 Hispanic Americans Baseline Alcohol Survey ( HABLAS). Respondents in the border area ( N = 1,307) constitute a household probability sample of Mexican Americans living on the border. In both surveys, data were collected during computer-assisted interviews conducted in respondents' homes. The HABLAS and the border sample response rates were 76 and 67%, respectively. Results Although bivariate analyses revealed no overall differences between border and non-border locations, (negative) age trends were more pronounced on the border for male abuse and for dependence among both genders. Among females aged 18 to 29, border residence was linked to significantly higher rates of dependence. In multivariable analyses, the prevalence of male abuse declined more rapidly with age on the border than off the border. Other unique predictors of male abuse were Jewish/other religion and weekly volume of alcohol consumption. Being married or out of the workforce, attaining a higher education, having no religious preference, and weekly volume uniquely predicted female dependence. Age and weekly volume uniquely predicted male dependence. Conclusions The prevalence of alcohol use disorders among Mexican Americans on and off the U. S.- Mexico border largely mirrors previously documented patterns of alcohol consumption in these areas. For young Mexican American women in particular, border residence is linked to heightened vulnerability to alcohol dependence. [ABSTRACT FROM AUTHOR]

Background The instantaneous rate of change of alcohol exposure (slope) may contribute to changes in measures of brain function following administration of alcohol that are usually attributed to breath alcohol concentration ( BrAC) acting alone. To test this proposition, a 2-session experiment was designed in which carefully prescribed, constant-slope trajectories of BrAC intersected at the same exposure level and time since the exposure began. This paper presents the methods and limitations of the experimental design. Methods Individualized intravenous infusion rate profiles of 6% ethanol (EtOH) that achieved the constant-slope trajectories for an individual were precomputed using a physiologically based pharmacokinetic model. Adjusting the parameters of the model allowed each infusion profile to account for the subject's EtOH distribution and elimination kinetics. Sessions were conducted in randomized order and made no use of feedback of BrAC measurements obtained during the session to modify the precalculated infusion profiles. In one session, an individual's time course of exposure, BrAC( t), was prescribed to rise at a constant rate of 6.0 mg% per minute until it reached 68 mg% and then descend at −1.0 mg% per minute; in the other, to rise at a rate of 3.0 mg% per minute. The 2 exposure trajectories were designed to intersect at a BrAC ( t = 20 minutes) = 60 mg% at an experimental time of 20 minutes. Results Intersection points for 54 of 61 subjects were within prescribed deviations (range of ±3 mg% and ±4 minutes from the nominal intersection point). Conclusions Results confirmed the feasibility of applying the novel methods for achieving the intended time courses of the BrAC, with technical problems limiting success to 90% of the individuals tested. [ABSTRACT FROM AUTHOR]

Background: This paper examines differences in drinking and binge drinking between Mexican Americans living along the U.S.-Mexico border and those living in 2 metropolitan areas away from the border (Houston, Texas and Los Angeles, California). Methods: Respondents in the non-border area (Houston and Los Angeles) constitute a multistage probability sample ( N = 1,288), who were interviewed as part of the 2006 Hispanic Americans Baseline Alcohol Survey (HABLAS). Respondents in the border area ( N = 1,307) constitute a household probability sample of Mexican Americans living on the U.S.-Mexico border. In both surveys, data were collected during computer-assisted interviews conducted in respondents' homes. The HABLAS and the border sample response rates were 76 and 67%, respectively. Results: There were no differences between border and non-border Mexican American men in the proportion of drinkers, the proportion who binge drink at least once a year, and volume of alcohol consumption. However, within each location, there were significant differences in drinking by age, indicating that younger men drank more than men who were older. Border women showed significant differences across age-groups in the proportion of drinkers, in binge drinking, and volume of alcohol consumption, which were not seen among non-border women. Conclusions: Women's drinking seems to be more affected than men's by their residence on or off the U.S.-Mexico border. This is seen most clearly among young women 18 to 29 years old, and it is associated with an increased proportion of drinkers, a higher volume of drinking, and an increased proportion of women who report binge drinking. Increased drinking in this group of younger women seems to be associated with drinking in Mexico. [ABSTRACT FROM AUTHOR]

Background: There have been limited trend studies examining variations on the patterns of alcohol consumption among Whites, Blacks, and Hispanics in the United States. The current paper reports national trends in drinking patterns, volume of drinking (number of drinks per month), binge drinking, and drinking to intoxication among Blacks, Whites, and Hispanics over a period of 10 years and identifies sociodemographic predictors of these behaviors across the 3 ethnic groups. Methods: Data are from the 1991 to 1992 National Longitudinal Alcohol Epidemiologic Survey (NLAES; n = 42,862) and the 2001 to 2002 National Epidemiologic Study on Alcohol and Related Conditions (NESARC; n = 43,093). Both surveys used multistage cluster sample procedures to select respondents 18 years of age and older from the U.S. household population. Results: Trends varied across different dimensions of drinking and ethnic groups. There were no statistically significant differences in the mean number of drinks consumed per month among men and women in any of the 3 ethnic groups between 1992 and 2002, but there was a significant rise in the proportion of current drinkers in both genders and in all 3 ethnic groups. Multivariate analysis indicated that, compared to Whites in 1992, Blacks and Hispanics did not increase their volume of drinking, but Whites did. Drinking 5 or more drinks in day at all did not increase between 1992 and 2002, but drinking 5 or more drinks at least once a month was more likely for all groups in 2002 compared to Whites in 1992. Drinking to intoxication at all was more likely among Whites in 2002 than 1992, but drinking to intoxication at least once a month was more likely among Whites and Blacks in 2002 than 1992. Conclusion: The only common trend between 1992 and 2002 across both genders and 3 ethnic groups was a rise in the proportion of drinkers. There was also a rise in drinking 5 or more drinks in a day (Whites, Blacks, and Hispanics) and drinking to intoxication (Whites and Blacks), but this was limited to those reporting such drinking at least once a month. The reasons for these changes are many and may involve complex sociodemographic changes in the population. It is important for the field to closely monitor these cross-ethnic trends in alcohol consumption. [ABSTRACT FROM AUTHOR]

Background Alcohol is a common target of counterfeiting in Russia. Counterfeit alcohol is defined here as the manufacture, distribution, unauthorized placement (forgery) of protected commodity trademarks, and infringement of the exclusive rights of the registered trademark holders of alcoholic beverages. It is often argued that the expansion of the counterfeit product market is due to the steady demand of economically disadvantaged people for low-priced goods. The situation becomes more complicated once deceptive and nondeceptive forms of counterfeiting are taken into account. This study aimed to identify markers of risky behavior associated with the purchase of counterfeit alcohol in Russia. Methods The analysis relied on consumer self-reports of alcohol use and purchase collected nationwide by the Russia Longitudinal Monitoring Survey (RLMS-HSE) in 2012 to 2014. I used a generalized linear mixed-model logistic regression to identify predictors of risky behavior by consumers who purchased counterfeit alcohol, either knowingly or unknowingly, during the 30 days preceding the survey. Results Purchases of counterfeit alcohol declined slightly from 2012 to 2014, mainly due to a decrease in consumers mistakenly purchasing counterfeit products. Predictors of counterfeit alcohol purchases differed between consumers who knowingly and unknowingly purchased counterfeit products. Nondeceptive purchase of counterfeit alcohol was related primarily to an indifference to alcohol brands. Consumers with social networks that include drinkers of nonbeverage alcohol and producers of homemade alcohol were highly likely to consume counterfeit alcohol deliberately. Problem drinking was significantly associated with a higher risk of both deceptive and nondeceptive purchases of counterfeit alcohol. Poverty largely contributed to nondeceptive counterfeiting. Conclusions The literature has overestimated the impact of low prices on counterfeit alcohol consumption. Problem drinking and membership in social networks of consumers of surrogate alcohol (i.e., nonbeverage) are more influential in explaining why people purchase counterfeit alcohol. Further research on these 2 factors is needed to more fully understand the purchase and consumption of counterfeit alcoholic beverages. [ABSTRACT FROM AUTHOR]

Background: Ecological momentary assessment (EMA) studies have provided conflicting evidence for the mood regulation tenet that people drink in response to positive and negative moods. The current study examined mood‐to‐alcohol relationships idiographically to quantify the prevalence and intensity of relationships between positive and negative moods and drinking across individuals. Method: We used two EMA samples: 96 heavy drinking college students (sample 1) and 19 young adults completing an ecological momentary intervention (EMI) for drinking to cope (sample 2). Mood and alcohol use were measured multiple times per day for 4–6 weeks. Mood–alcohol relationships were examined using three different analytic approaches: standard multilevel modeling, group causal modeling, and idiographic causal modeling. Results: Both multilevel modeling and group causal modeling showed that participants in both samples drank in response to positive moods only. However, idiographic causal analyses revealed that only 63% and 21% of subjects (in samples 1 and 2, respectively) drank following any positive mood. Many subjects (24% and 58%) did not drink in response to either positive or negative mood in their daily lives, and very few (5% and 16%) drank in response to negative moods throughout the EMA protocol, despite sample 2 being selected specifically because they endorse drinking to cope with negative mood. Conclusion: Traditional group‐level analyses and corresponding population‐wide theories assume relative homogeneity within populations in mood–alcohol relationships, but this nomothetic approach failed to characterize accurately the relationship between mood and alcohol use in approximately half of the subjects in two samples that were demographically and clinically homogeneous. Given inconsistent findings in the mood–alcohol relationships to date, we conclude that idiographic causal analyses can provide a foundation for more accurate theories of mood and alcohol use. In addition, idiographic causal models may also help improve psychosocial treatments through direct use in clinical settings. [ABSTRACT FROM AUTHOR]

Background: Explicit (self‐report) and implicit (indirect) measures of identification with drinking alcohol—drinking identity—are associated with drinking outcomes cross‐sectionally and longitudinally. A key next step is to identify moderators. The current study evaluated a promising moderator: mindsets of alcoholism. Believing people can change (growth mindset) is associated with adaptive outcomes in domains such as mental health, but research is scant regarding mindsets related to problematic drinking. We evaluated whether individuals' alcoholism mindsets moderated the drinking identity to drinking relation as part of a larger, longitudinal web‐based study of heavy drinkers. Methods: A total of 422 US college graduates (59% women) who were heavy drinkers completed measures assessing drinking identity, mindsets, and drinking outcomes (consumption, problems, and risk of alcohol use disorder). Drinking outcomes were assessed at 2 subsequent assessments occurring 4 and 8 months after the initial assessment. Results: Drinking identity was positively associated with drinking outcomes, and drinking outcomes reduced following college graduation. Alcoholism mindsets were significantly and negatively correlated with all drinking outcomes. Mindsets were only conditionally associated with drinking behaviors over time in models that evaluated mindsets, drinking identity measures, and their interaction. Mindsets moderated the relationship between drinking identity and changes in drinking behaviors, but the relation was specific to explicit drinking identity and consumption. Among participants with stronger drinking identity, those who had stronger (vs. weaker) growth mindsets reported reduction in consumption over time. Conclusions: Growth mindsets of alcoholism appear adaptive for college graduate heavy drinkers with a stronger drinking identity. Mindsets are amenable to interventions; targeting them may be useful in heavy‐drinking college graduates. [ABSTRACT FROM AUTHOR]

Background Prior studies have found that social rejection is associated with increases in negative affect, distress, and hostility. Fewer studies, however, have examined the impact of social rejection on alcohol use, and no known studies have tested whether the impact of social rejection by close others differs from social rejection by acquaintances in its association with subsequent drinking. Methods Participants completed event-contingent reports of their social interactions and alcohol use for 14 consecutive days on smartphones. Multilevel negative binomial regression models tested whether experiencing more social rejection than usual was associated with increased drinking, and whether this association was stronger when participants were rejected by close others (e.g., friends, spouses, family members) versus strangers or acquaintances. Results Results showed a significant interaction between social rejection and relationship closeness. On days characterized by rejection by close others, the likelihood of drinking significantly increased. On days characterized by rejection by acquaintances, by contrast, there was no increase in the likelihood of drinking. There was no main effect of rejection on likelihood of drinking. Conclusions These results suggest that relationship type is a key factor in whether social rejection translates to potentially harmful behaviors, such as increased alcohol use. This finding is in contrast to many laboratory paradigms of rejection, which emphasize rejection and ostracism by strangers rather than known others. In the more naturalistic setting of measuring social interactions on smartphone in daily life, our findings suggest that only social rejection delivered by close others, and not strangers, led to subsequent drinking. [ABSTRACT FROM AUTHOR]

Background Alcohol-dependent liver transplantation ( LT) patients who resume alcohol consumption are at risk for a number of alcohol-related problems including liver injury and liver failure. Post- LT patients are strongly advised to remain abstinent. However, we do not know how well this population complies due to a lack of valid methods (self-report and/or biomarkers) to identify alcohol use. Studies suggest as many as 50% resume alcohol use within 5 years. Phosphatidylethanol ( PEth) is a new cell-membrane phospholipid biomarker to identify alcohol use in the past 28 days. This prospective study followed 213 LT recipients at 2 U.S. liver transplant centers. Methods Sample included 213 LT subjects; 70.9% ( n = 151/213) had a history of alcohol dependence prior to transplantation and 29.1% ( n = 62/213) served as non-alcohol-dependent controls. Subjects participated in face-to-face interviews to assess alcohol use using a 30-day calendar. The protocol called for collecting blood samples at baseline, 6-, and 12-month follow-up. Results Seventy percent (149/213) who reported no alcohol use had consistently negative PEth levels (<8 ng/ml). A total of 26.4% (57/213), 44 alcohol-dependent patients and 13 controls, had a positive PEth test of >8 ng/ml either at baseline and/or during the follow-up period. Alcohol-dependent subjects (23.8%; n = 36/151) and 16.1% ( n = 10/62) controls reported no alcohol use but had at least 1 positive PEth test. Of the 11.2% (24/213) post- LT subjects who reported recent alcohol use, over half (11/24) had a positive PEth. The 13 self-reported alcohol users with a negative PEth level reported insufficient drinking to trigger PEth formation. Conclusions Adoption of PEth as part of routine posttransplant care of LT recipients will enable early identification of patients at risk of alcohol use and facilitate abstinence in patients with a history of alcohol dependence and alcohol-related liver damage. [ABSTRACT FROM AUTHOR]

Background Previous genomewide association studies ( GWASs) have identified a number of putative risk loci for alcohol dependence ( AD). However, only a few loci have replicated and these replicated variants only explain a small proportion of AD risk. Using an innovative approach, the goal of this study was to generate hypotheses about potentially causal variants for AD that can be explored further through functional studies. Methods We employed targeted capture of 71 candidate loci and flanking regions followed by next-generation deep sequencing (mean coverage 78X) in 806 European Americans. Regions included in our targeted capture library were genes identified through published GWAS of alcohol, all human alcohol and aldehyde dehydrogenases, reward system genes including dopaminergic and opioid receptors, prioritized candidate genes based on previous associations, and genes involved in the absorption, distribution, metabolism, and excretion of drugs. We performed single-locus tests to determine if any single variant was associated with AD symptom count. Sets of variants that overlapped with biologically meaningful annotations were tested for association in aggregate. Results No single, common variant was significantly associated with AD in our study. We did, however, find evidence for association with several variant sets. Two variant sets were significant at the q-value <0.10 level: a genic enhancer for ADHFE1 ( p = 1.47 × 10−5; q = 0.019), an alcohol dehydrogenase, and ADORA1 ( p = 5.29 × 10−5; q = 0.035), an adenosine receptor that belongs to a G-protein-coupled receptor gene family. Conclusions To our knowledge, this is the first sequencing study of AD to examine variants in entire genes, including flanking and regulatory regions. We found that in addition to protein coding variant sets, regulatory variant sets may play a role in AD. From these findings, we have generated initial functional hypotheses about how these sets may influence AD. [ABSTRACT FROM AUTHOR]

Background Alcohol consumption patterns on the U.S.-Mexico border and their relationships with DSM-5 alcohol use disorders ( AUD) have been understudied. Yet, the effects of drinking by Mexican-origin individuals may differ between cities on versus off the border both in the United States and in Mexico. We characterize prior 12-month drinking patterns and examine their relationships with AUD, in border and off-border cities of Texas and adjacent Mexican states. Methods Data come from the U.S.-Mexico Study of Alcohol and Related Conditions involving 2,336 Mexican Americans in Texas and 2,460 Mexicans in bordering states of Nuevo Leon and Tamaulipas in Mexico. Drinking pattern was defined as an interaction between volume and maximum amount, or intensity (never vs. ever 5+/4+ [men/women], 8+, and 12+ drinks in a day). DSM-5 AUD was assessed using an adaptation of the Alcohol Section of the World Health Organization Composite International Diagnostic Interview core. Separately by gender, 5 logistic regressions models controlling for age were estimated predicting symptoms in 2 or more AUD criteria domains from volume, heavy pattern and, successively, effects of country, and (by country) residing on vs. off the border, or in each of 3 cities/country. Results A segmentation analysis for Texas males based on rate of experiencing AUD generated several distinct volume groups, each partitioned by an empirically selected maximum, and helped identify a drinking-pattern typology. In gender-stratified models of AUD rates using this typology, adjusting for age, significant volume and intensity effects were seen, more strongly in the United States. Border versus interior differences implied more AUD for given patterns at the border in the United States and the reverse in Mexico, with some city differences also evident. Conclusions Drinking-pattern analyses confirm that border proximity may affect drinking problems but in opposite directions in the United States and Mexico, possibly related to economic and psychological stresses specific to respective communities. [ABSTRACT FROM AUTHOR]

Background In our companion article, we examined the role of MyD88-dependent signaling in ethanol (EtOH) consumption in mice lacking key components of this inflammatory pathway and observed differential effects on drinking. Here, we studied the role of these same signaling components in the acute sedative, intoxicating, and physiological effects of EtOH. Toll-like receptor 4 (TLR4) has been reported to strongly reduce the duration of EtOH-induced sedation, although most studies do not support its direct involvement in EtOH consumption. We examined TLR4 and other MyD88 pathway molecules to determine signaling specificity in acute EtOH-related behaviors. We also studied other GABAergic sedatives to gauge the EtOH specificity and potential role for GABA in EtOH's sedative and intoxicating effects in the mutant mice. Methods Loss of righting reflex ( LORR) and recovery from motor incoordination were studied following acute injection of EtOH or other sedative drugs in male and female control C57 BL/6J mice versus mice lacking CD14, TLR2, TLR4 (C57 BL/10ScN), or MyD88. We also examined EtOH-induced hypothermia and blood EtOH clearance in these mice. Results Male and female mice lacking TLR4 or MyD88 showed reduced duration of EtOH-induced LORR and faster recovery from EtOH-induced motor incoordination in the rotarod test. MyD88 knockout mice had slightly faster recovery from EtOH-induced hypothermia compared to control mice. None of the mutants differed from control mice in the rate of blood EtOH clearance. All of the mutants showed similar decreases in the duration of gaboxadol-induced LORR, but only mice lacking TLR4 were less sensitive to the sedative effects of pentobarbital. Faster recovery from diazepam-induced motor impairment was observed in CD14, TLR4, and MyD88 null mice of both sexes. Conclusions TLR4 and MyD88 were key mediators of the sedative and intoxicating effects of EtOH and GABAergic sedatives, indicating a strong influence of TLR4-MyD88 signaling on GABAergic function. Despite the involvement of TLR4 in EtOH's acute behaviors, it did not regulate EtOH consumption in any drinking model as shown in our companion article. Collectively, our studies demonstrate differential effects of TLR-MyD88 components in the acute versus chronic actions of EtOH. [ABSTRACT FROM AUTHOR]

Background Alcohol marketing is known to be a significant risk factor for underage drinking. However, little is known about youth and adult exposure to alcohol advertising in digital and social media. This study piloted a comparative assessment of youth and adult recall of exposure to online marketing of alcohol. Methods From September to October 2013, a pilot survey of past 30-day exposure to alcohol advertising and promotional content in traditional and digital media was administered to a national sample of 1,192 youth (ages 13 to 20) and 1,124 adults (ages ≥21) using a prerecruited Internet panel maintained by GfK Custom Research. The weighted proportions of youth and adults who reported this exposure were compared by media type and by advertising and promotional content. Results Youth were more likely than adults to recall exposure to alcohol advertising on television (69.2% vs. 61.9%), radio (24.8% vs. 16.7%), billboards (54.8% vs. 35.4%), and the Internet (29.7% vs. 16.8%), but less likely to recall seeing advertising in magazines (35.7% vs. 36.4%). Youth were also more likely to recall seeing advertisements and pictures on the Internet of celebrities using alcohol (36.1% vs. 20.8%) or wearing clothing promoting alcohol (27.7% vs. 15.9%), and actively respond (i.e., like, share, or post) to alcohol-related content online. Conclusions Youth report greater exposure to alcohol advertising and promotional content than adults in most media, including on the Internet. These findings emphasize the need to assure compliance with voluntary industry standards on the placement of alcohol advertising and the importance of developing better tools for monitoring youth exposure to alcohol marketing, particularly on the Internet. [ABSTRACT FROM AUTHOR]

Background Recent reports have demonstrated that binge-like ethanol (EtOH) drinking leads to an increase in hypothalamic orexin ( OX) signaling and that suppressing this signaling via systemic administration of an orexin receptor ( OXR) antagonist blocks this behavior; however, the specific OX pathways that modulate this behavior remain unknown. The goal of this study was to further elucidate the role of the OX system in binge-like EtOH drinking using behavioral, molecular, and pharmacological techniques. Methods The drinking-in-the-dark ( DID) paradigm was used to model binge-like drinking behavior in male C57 BL/6J mice. Experiment 1 examined changes in the OX precursor, prepro-orexin, within the hypothalamus following multiple cycle EtOH or sucrose DID using polymerase chain reaction ( PCR) analysis. In experiments 2a and 2b, we used site-directed infusion of an OXR antagonist to examine the individual contribution of each OXR subtype within the ventral tegmental area ( VTA) and central nucleus of the amygdala (CeA), respectively, in binge-like EtOH or sucrose drinking. Results Findings from our PCR study revealed that multiple cycles of binge-like EtOH drinking did not lead to changes in prepro-orexin mRNA as a function of binge-like EtOH drinking. However, data from site-directed pharmacology studies indicate that the orexin-1 receptor (OX1R) is the predominate receptor subtype within the VTA and CeA that regulates binge-like EtOH drinking. Interestingly, inhibition of OX1Rs did not affect binge-like sucrose intake, which suggests that these OX circuits are specific for EtOH consumption. Conclusions As a whole, these data suggest that the VTA and CeA are important regions in which OX regulates binge-like EtOH drinking behavior. Moreover, these findings identify OXR antagonists as a potential treatment option that may be used to ameliorate problematic drinking behavior while leaving responding to natural rewards relatively intact. [ABSTRACT FROM AUTHOR]

Background Treatment for alcohol use disorders (AUDs) has traditionally been abstinence oriented, but new research and regulatory guidelines suggest that low-risk drinking may also be an acceptable treatment outcome. However, little is known about long-term outcomes for patients who become low-risk drinkers posttreatment. This study explores a posttreatment low-risk drinking outcome as a predictor of future drinking and psychosocial outcomes over 9 years. Methods Study participants were adults with AUDs at treatment entry who received follow-up interviews 6 months posttreatment intake ( N = 1,061) in 2 large randomized studies conducted at Kaiser Permanente Northern California, a large private, nonprofit, integrated health system. Six-month drinking status was defined as abstinent, low-risk (nonabstinent, no 5+ drinking days), or heavy drinking (1 or more days of 5+ drinks). Using logistic regression models, we explored the relationship between past 30-day drinking status at 6 months and odds of being abstinent or a low-risk drinker (compared to heavy drinking), and positive Addiction Severity Index psychosocial outcomes over 9 years (9-year follow-up rate of 73%). Results Abstainers and low-risk drinkers at 6 months had higher odds of recent abstinence/low-risk drinking over 9 years than heavy drinkers; abstainers had better drinking outcomes than low-risk drinkers. Additionally, among those with interview data, 95% of abstainers and 94% of low-risk drinkers at 6 months were abstinent/low-risk drinkers at 9 years; surprisingly, 89% of heavy drinkers at 6 months were also abstinent/low-risk drinkers although still significantly fewer than the other groups. Abstainers and low-risk drinkers at 6 months had better psychiatric outcomes, and abstainers had better family/social outcomes than heavy drinkers; medical outcomes did not differ. Low-risk drinkers and abstainers showed no reliable differences across psychosocial measures. Conclusions The findings suggest that a low-risk drinking outcome may be reasonable over the long-term for some alcohol-dependent individuals receiving addiction treatment. [ABSTRACT FROM AUTHOR]

Background Conditioned responses to alcohol-associated cues can hinder recovery from alcohol use disorder ( AUD). Cue exposure (extinction) therapy ( CET) can reduce reactivity to alcohol cues, but its efficacy is limited by phenomena such as spontaneous recovery and reinstatement that can cause a return of conditioned responding after extinction. Using a preclinical model of alcohol cue reactivity in rats, we evaluated whether the efficacy of alcohol CET could be improved by conducting CET during the memory reconsolidation window after retrieval of cue-alcohol associations. Methods Rats were provided with intermittent access to unsweetened alcohol. Rats were then trained to predict alcohol access based on a visual cue. Next, rats were treated with either standard extinction ( n = 14) or postretrieval extinction ( n = 13). Rats were then tested for long-term memory of extinction and susceptibility to spontaneous recovery and reinstatement. Results Despite equivalent extinction, rats treated with postretrieval extinction exhibited reduced spontaneous recovery and reinstatement relative to rats treated with standard extinction. Conclusions Postretrieval CET shows promise for persistently attenuating the risk to relapse posed by alcohol cues in individuals with AUD. [ABSTRACT FROM AUTHOR]

Background Posttraumatic stress disorder ( PTSD) and alcohol use disorder disproportionately impact certain populations including American Indians/Alaska Natives ( AIAN). While PTSD and alcohol use disorder have been studied both separately and in tandem, less is known about the association in AIAN. The objective was to examine the association between lifetime PTSD and past year alcohol use disorder among AIAN and non-Hispanic Whites ( NHW). Methods Data come from the 2012 to 2013 U.S. National Epidemiologic Survey on Alcohol and Related Conditions- III. We used logistic regression to estimate odds of AUD among adults with and without PTSD by race. Results A total of 19,705 participants, of whom 511 were AIAN and 19,194 were NHW, were included in this study. The percentage of PTSD among AIAN was 22.9% ( n = 117) compared to 11.7% ( n = 2,251) in NHW ( p-value <0.0001). The percentage of past year alcohol use disorder among AIAN was 20.2% ( n = 103) compared to 14.2% ( n = 2,725) in NHW ( p-value <0.0001). The percentage of comorbid past year alcohol use disorder with lifetime PTSD among AIAN was 6.5% ( n = 33) compared to 2.4% ( n = 457) in NHW ( p-value <0.0001). Regarding the joint distribution of PTSD and AUD, AIAN men have greater than 3 times the percentage compared to NHW men (9.5% vs. 3.1%). When stratifying by race (after adjusting for age, sex, depression, and education), among AIAN, the odds of past year alcohol use disorder with (vs. without) lifetime PTSD were 1.76 (95% CI 1.07, 2.90) and among NHW, the odds were 1.59 (95% CI 1.41, 1.80). Conclusions PTSD is significantly associated with alcohol use disorder in the study populations. Despite a lack of pre- PTSD measures of alcohol use disorder, these findings show a trend indicating that AIAN exposed to PTSD are more burdened with alcohol use disorder compared to NHW in the general U.S. population. [ABSTRACT FROM AUTHOR]

Background A limited number of measures exist to assess alcohol problems during adolescence. Item response theory modeling was used to scale a measure of adolescent alcohol problems, including drinking and driving, and then related to alcohol and other psychiatric disorders that occurred over a 15-year period. Methods High school students ( N = 832) completed the 13-item Alcohol Problems Index ( API) at age 18 years as part of a long-term longitudinal study of predictors of alcohol use and alcohol disorders. Frequency of drinking and driving was also measured during adolescence. Lifetime psychiatric disorders, including alcohol disorders, were measured during young adulthood. Rasch modeling was used to scale the severity of alcohol problems, and the scaled total score was used to prospectively predict alcohol disorders. The area under the receiver operating characteristic ( ROC) curve was also computed between the adolescent alcohol problems and alcohol and other psychiatric disorders across a 15-year period. Results The prevalence of alcohol disorders was 38.7% (for alcohol dependence, it was 27.7%). Rasch modeling indicated that the API assessed a range of severity of alcohol problems and that drinking and driving were among the less severe indicators. Age 18 API scores significantly correlated with an alcohol diagnosis (0.34), and ROC curve analysis indicated that for adolescent alcohol problem scores, the diagnostic accuracy (or area under the curve) for an alcohol diagnosis by age 33 was 0.70. Conclusions Our findings supported the unidimensionality and reliability of the API, and statistically significant prospective prediction of young adult alcohol disorders. The measurement of alcohol problems during adolescence, in addition to drinking and driving, may be beneficial in understanding adverse consequences of drinking during adolescence as well as transitions in alcohol use and alcohol disorders across the lifespan. [ABSTRACT FROM AUTHOR]

Background There is a well-known link between attending college and engaging in excessive alcohol use. This study examines in a national sample how the association between student status and excessive alcohol use changes from late adolescence through young adulthood and whether the association of student status with excessive alcohol use is different for students residing with versus away from parents during the school year. Methods This study used cross-sectional data from the National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative sample of noninstitutionalized civilian adults residing in the United States. Our analyses included nonhigh school young adults who were ages 18 to 30 years ( n = 8,645). Excessive alcohol use included past-year (i) high-intensity drinking (men: ≥10 standard drinks; women: ≥8) and (ii) exceeding weekly drinking guidelines (men: >14 drinks per week; women: >7). Students who resided away from their parents and students who lived with their parents during the school year were compared to nonstudents. Results Analyses using time-varying effect modeling showed that the relationship of student status with excessive alcohol use varied as a function of age. Overall student status lost its association with excessive alcohol use in the early 20s, after controlling for demographics and other adult social roles. The association between student status and excessive alcohol use also varied considerably across age and depending on whether the student was residing with or away from parents. Conclusions The association of student status with excessive alcohol use is heterogeneous in terms of both age and living arrangements, suggesting opportunities for interventions targeting problematic alcohol use. Future research should examine additional sources of heterogeneity of students in their risk for excessive alcohol use. [ABSTRACT FROM AUTHOR]

Background All stages of development of alcohol use disorder ( AUD) have not been equally studied. While initiation of drinking has been given considerable attention, other stages have not been as thoroughly investigated. It is not clear whether the same factors are associated consistently across early and late transitions in AUD involvement. High-risk family samples that are enriched for AUD vulnerability and transitions in AUD development offer an opportunity to examine influences across multiple stages of AUD development. Methods Data from adolescents and young adults from high-risk families were used to study 4 transitions in AUD development-time to first drink, first drink to first problem, first drink to first diagnosis, and first problem to first diagnosis. Cox modeling was used to compare associations of parental AUD, parental separation, peer substance use, offspring ever-use of cannabis, trauma exposures, and internalizing and externalizing psychopathology across transitions. Results Hazards of most transitions were elevated for those who had ever used cannabis, those who attributed substance use to their peers, those with externalizing disorders, and those with parents with AUD. Many risk factors were linked to early initiation of alcohol, particularly cannabis use. Internalizing disorders were associated with later stages. Nonassaultive trauma was associated only with early initiation; assaultive trauma was not associated with any transition. Conclusions In this large, ethnically diverse sample of high-risk youth, significant influences across transitions were fairly consistent, with externalizing disorders and cannabis ever-use elevating the likelihood of each stage, and peer and parental (and especially maternal AUD) influences linked to initiation and some later stages. Finally, in light of the increasingly permissive legal and social stances toward cannabis in the United States, the marked elevations of all alcohol outcomes observed for cannabis use underscore the importance of studying the underpinnings of this relationship. [ABSTRACT FROM AUTHOR]

Background Alcohol abuse incurs severe medical conditions, such as thrombocytopenia and hemorrhage, but the pathogenesis is not totally understood. Alcohol has been reported to induce apoptosis in eukaryotic cells, such as hepatocyte, nerve cell, corneal fibroblasts. However, it is still unclear whether alcohol induces platelet apoptosis. Methods Washed human platelets were pretreated with ethanol (EtOH), and apoptotic events and platelet function were detected. In in vivo experiments, C57 BL/6J mice were given EtOH by gavage. Platelet counts, tail bleeding time, and the stomach were examined. Results EtOH dose dependently induces depolarization of mitochondrial inner transmembrane potential, up-regulation of Bax, down-regulation of Bcl-2, and caspase-3 activation. EtOH does not induce surface expression of P-selectin or PAC-1 binding, whereas significantly reduces collagen-, thrombin-, and ADP-induced platelet aggregation. Moreover, EtOH induces c-Jun NH2-terminal kinase activation. In an in vivo mouse model of the acute alcoholism, EtOH significantly reduces the number of circulating platelets, prolongs the tail bleeding time, and causes gastric mucosa hemorrhage. Conclusions These data demonstrate that EtOH induces mitochondria-mediated intrinsic platelet apoptosis, results in the reduction of the number of circulating platelets, and impairs in vivo hemostasis. These findings reveal the possible pathogenesis of hemorrhagic symptoms in patients experiencing acute alcohol intoxication. [ABSTRACT FROM AUTHOR]

Background Both chronic alcohol consumption and alcohol withdrawal lead to neural tissue damage which partly recovers during abstinence. This study investigated withdrawal-associated changes in glutamatergic compounds, markers of neuronal integrity, and gray matter volumes during acute alcohol withdrawal in the hippocampus, a key region in development and maintenance of alcohol dependence in humans and rats. Methods Alcohol-dependent patients ( N = 39) underwent magnetic resonance imaging ( MRI) and MR spectroscopy ( MRS) measurements within 24 hours after the last drink and after 2 weeks of abstinence. MRI and MRS data of healthy controls ( N = 34) were acquired once. Our thorough quality criteria resulted in N = 15 available spectra from the first and of N = 21 from the second measurement in patients, and of N = 19 from healthy controls. In a translational approach, chronic intermittent ethanol-exposed rats and respective controls (8/group) underwent 5 MRS measurements covering baseline, intoxication, 12 and 60 hours of withdrawal, and 3 weeks of abstinence. Results In both species, higher levels of markers of glutamatergic metabolism were associated with lower gray matter volumes in the hippocampus in early abstinence. Trends of reduced N-acetylaspartate levels during intoxication persisted in patients with severe alcohol withdrawal symptoms over 2 weeks of abstinence. We observed a higher ratio of glutamate to glutamine during alcohol withdrawal in our animal model. Conclusions Due to limited statistical power, we regard the results as preliminary and discuss them in the framework of the hypothesis of withdrawal-induced hyperglutamatergic neurotoxicity, alcohol-induced neural changes, and training-associated effects of abstinence on hippocampal tissue integrity. [ABSTRACT FROM AUTHOR]

Background Alcohol use disorder (AUD) is a highly prevalent public health problem associated with considerable individual and societal costs. Abstinence from alcohol is the most widely accepted target of treatment for AUD, but it severely limits treatment options and could deter individuals who prefer to reduce their drinking from seeking treatment. Clinical validation of reduced alcohol consumption as the primary outcome of alcohol clinical trials is critical for expanding treatment options. One potentially useful measure of alcohol treatment outcome is a reduction in the World Health Organization (WHO, International Guide for Monitoring Alcohol Consumption and Related Harm. Geneva, Switzerland, 2000) risk levels of alcohol use (very high risk, high risk, moderate risk, and low risk). For example, a 2-shift reduction in WHO risk levels (e.g., high risk to low risk) has been used by the European Medicines Agency (2010, Guideline on the Development of Medicinal Products for the Treatment of Alcohol Dependence. UK) to evaluate nalmefene as a treatment for alcohol dependence (AD; Mann et al. 2013, Biol Psychiatry 73, 706-13). Methods The current study was a secondary data analysis of the COMBINE study ( n = 1,383; Anton et al., ) to examine the association between reductions in WHO risk levels and reductions in alcohol-related consequences and mental health symptoms during and following treatment in patients with AD. Results Any reduction in WHO risk drinking level during treatment was associated with significantly fewer alcohol-related consequences and improved mental health at the end of treatment and for up to 1 year posttreatment. A greater reduction in WHO risk drinking level predicted a greater reduction in consequences and greater improvements in mental health. Conclusions Changes in WHO risk levels appear to be a valid end point for alcohol clinical trials. Based on the current findings, reductions in WHO risk drinking levels during treatment reflect meaningful reductions in alcohol-related consequences and improved functioning. [ABSTRACT FROM AUTHOR]

Background Standardized alcohol craving scales are rarely used outside of research environments despite recognized clinical utility. Scale length is a key barrier to more widespread application. A brief measure of alcohol craving is needed to improve research and treatment of alcohol use disorders ( AUDs). Grounded in the Elaborated Intrusion Theory of Desire, the Alcohol Craving Experience ( ACE) Questionnaire comprises two 11-item self-report scales that assess past-week frequency and maximum strength of alcohol craving. This study aimed to create a brief version of the ACE while maintaining psychometric integrity and clinical utility. Methods Patients attending a university hospital alcohol and drug outpatient service for the treatment of AUD completed the ACE as part of a questionnaire battery. Three patient samples were utilized: 519 patients with pretreatment and outcome data, 228 patients with pretreatment data, and 66 patients who completed the ACE at treatment sessions 1 and 2. Results The Frequency scale of the ACE possessed greater clinical utility and predictive validity than the Strength scale. Revision of the Frequency measure produced a 5-item 'Mini Alcohol Craving Experience' ( MACE) Questionnaire. Satisfactory validity (construct, predictive, concurrent, convergent, and incremental) and reliability (internal and test-retest) were maintained. A 1 standard deviation increase in pretreatment MACE score was associated with a 54 percentage increase in the odds of patient lapse or dropout. Conclusions The MACE provides a brief, theoretically, and psychometrically robust measure of alcohol craving suitable for use with AUD populations in time-limited clinical and research settings. [ABSTRACT FROM AUTHOR]

Background The chronic intermittent ethanol ( CIE) paradigm is valuable for screening compounds for efficacy to reduce drinking traits related to alcohol use disorder ( AUD), as it measures alcohol consumption and preference under physical dependence conditions. Air control-treated animals allow simultaneous testing of similarly treated, nondependent animals. As a consequence, we used CIE to test the hypothesis that tigecycline, a semisynthetic tetracycline similar to minocycline and doxycycline, would reduce alcohol consumption regardless of dependence status. Methods Adult C57 BL/6J female and male mice were tested for tigecycline efficacy to reduce ethanol (EtOH) consumption using a standard CIE paradigm. The ability of tigecycline to decrease 2-bottle choice of 15% EtOH (15E) versus water intake in dependent ( CIE vapor) and nondependent (air-treated) male and female mice was tested after 4 cycles of CIE vapor or air exposure using a within-subjects design and a dose-response. Drug doses of 0, 40, 60, 80, and 100 mg/kg in saline were administered intraperitoneally (0.01 ml/g body weight) and in random order, with a 1-hour pretreatment time. Baseline 15E intake was re-established prior to administration of subsequent injections, with a maximum of 2 drug injections tested per week. Results Tigecycline was found to effectively reduce high alcohol consumption in both dependent and nondependent female and male mice. Conclusions Our data suggest that tigecycline may be a promising drug with novel pharmacotherapeutic characteristics for the treatment of mild-to-severe AUD in both sexes. [ABSTRACT FROM AUTHOR]

Background Underage college students who obtain and use false identification (fake ID) are at risk for negative outcomes. However, it is currently unclear how uniquely the fake ID itself serves as a vehicle to subsequent harm (i.e., the 'fake ID effect') over and above general and trait-related risk factors (e.g., deviant peers, low self-control). Methods To investigate whether the 'fake ID effect' would hold after accounting for phenotypic risk, we utilized propensity score matching ( PSM) in a cross-sectional sample of 1,454 students, and a longitudinal replication sample of 3,720 undergraduates. Individuals with a fake ID were matched with individuals without a fake ID, in terms of a number of trait-based and social risk factors. These matched groups were then compared on 5 problematic outcomes (i.e., frequent binge drinking, alcohol-related problems, arrests, marijuana use, and hard drug use). Results Findings showed that 'fake ID effects' were substantially-although not fully-diminished following PSM. The 'fake ID effect' remained strongest for alcohol-related arrests. This may relate to issues of enforcement and students' willingness to engage in deviant behavior with a fake ID, or it may be a function of combined processes. Conclusions Overall, the findings suggest that interventions should not only be aimed at reducing the fake ID-related alcohol access specifically, but should also be aimed more generally toward at-risk youths' access to alcohol. Future research might examine whether fake IDs have their strongest potency as moderators of the effects of risky traits-such as impulsiveness-on drinking outcomes. [ABSTRACT FROM AUTHOR]

Background New pharmacotherapies to treat alcohol use disorders ( AUD) are needed. Given the complex nature of AUD, there likely exist multiple novel drug targets. We, and others, have shown that the tetracycline drugs, minocycline and doxycycline, reduced ethanol (EtOH) drinking in mice. To test the hypothesis that suppression of high EtOH consumption is a general property of tetracyclines, we screened several derivatives for antidrinking activity using the Drinking-In-the-Dark ( DID) paradigm. Active drugs were studied further using the dose-response relationship. Methods Adult female and male C57 BL/6J mice were singly housed and the DID paradigm was performed using 20% EtOH over a 4-day period. Mice were administered a tetracycline or its vehicle 20 hours prior to drinking. Water and EtOH consumption was measured daily. Body weight was measured at the start of drug injections and after the final day of the experiment. Blood was collected for EtOH content measurement immediately following the final bout of drinking. Results Seven tetracyclines were tested at a 50 mg/kg dose. Only minocycline and tigecycline significantly reduced EtOH drinking, and doxycycline showed a strong effect size trend toward reduced drinking. Subsequent studies with these 3 drugs revealed a dose-dependent decrease in EtOH consumption for both female and male mice, with sex differences in efficacy. Minocycline and doxycycline reduced water intake at higher doses, although to a lesser degree than their effects on EtOH drinking. Tigecycline did not negatively affect water intake. The rank order of potency for reduction in EtOH consumption was minocycline > doxycycline > tigecycline, indicating efficacy was not strictly related to their partition coefficients or distribution constants. Conclusions Due to its effectiveness in reducing high EtOH consumption coupled without an effect on water intake, tigecycline was found to be the most promising lead tetracycline compound for further study toward the development of a new pharmacotherapy for the treatment of AUD. [ABSTRACT FROM AUTHOR]

Background Executive functioning and episodic memory impairment occur in HIV infection ( HIV) and chronic alcoholism ( ALC). Comorbidity of these conditions ( HIV + ALC) is prevalent and heightens risk of vulnerability to separate and compounded deficits. Age and disease-related variables can also serve as mediators of cognitive impairment and should be considered, given the extended longevity of HIV-infected individuals in this era of improved pharmacological therapy. Methods HIV, ALC, HIV + ALC, and normal controls ( NC) were administered traditional and computerized tests of executive function and episodic memory. Test scores were expressed as age- and education-corrected Z-scores; selective tests were averaged to compute Executive Function and Episodic Memory Composite scores. Efficiency scores were calculated for tests with accuracy and response times. Results HIV, ALC, and HIV + ALC had lower scores than NC on Executive Function and Episodic Memory Composites, with HIV + ALC even lower than ALC and HIV on the Episodic Memory Composite. Impairments in planning and free recall of visuospatial material were observed in ALC, whereas impairments in psychomotor speed, sequencing, narrative free recall, and pattern recognition were observed in HIV. Lower decision-making efficiency scores than NC occurred in all 3 clinical groups. In ALC, age and lifetime alcohol consumption were each unique predictors of Executive Function and Episodic Memory Composite scores. In HIV + ALC, age was a unique predictor of Episodic Memory Composite score. Conclusions Disease-specific and disease-overlapping patterns of impairment in HIV, ALC, and HIV + ALC have implications regarding brain systems disrupted by each disease and clinical ramifications regarding the complexities and compounded damping of cognitive functioning associated with dual diagnosis that may be exacerbated with aging. [ABSTRACT FROM AUTHOR]

Background Highly caffeinated 'energy drinks' ( ED) are commonly consumed and sometimes mixed with alcohol. Associations between ED consumption, risk-taking, and alcohol-related problems have been observed. This study examines the relationship between ED consumption-both with and without alcohol-and drunk driving. Methods Data were derived from a longitudinal study of college students assessed annually via personal interviews. In Year 6 (modal age 23; n = 1,000), participants self-reported their past-year frequency of drunk driving, ED consumption patterns (frequency of drinking alcohol mixed with energy drinks [AmED] and drinking energy drinks without alcohol [ED]), alcohol use (frequency, quantity), and other caffeine consumption. Earlier assessments captured suspected risk factors for drunk driving. Structural equation modeling was used to develop an explanatory model for the association between ED consumption patterns and drunk driving frequency while accounting for other suspected risk factors. Results More than half (57%) consumed ED at least once during the past year. Among ED consumers, 71% drank Am ED and 85% drank ED alone; many (56%) engaged in both styles of ED consumption while others specialized in one or the other (29% drank ED alone exclusively, while, 15% drank Am ED exclusively). After accounting for other risk factors, ED consumption was associated with drunk driving frequency in 2 ways. First, a direct path existed from ED frequency (without alcohol) to drunk driving frequency. Second, an indirect path existed from Am ED frequency through alcohol quantity to drunk driving frequency. Conclusions Among this sample, ED consumption with and without alcohol was common, and both styles of ED consumption contributed independently to drunk driving frequency. Results call for increased attention to the impact of different patterns of ED consumption on alcohol-related consequences, such as drunk driving. [ABSTRACT FROM AUTHOR]

Background Cognitive bias modification ( CBM) can be used to retrain automatic approach tendencies for alcohol. We investigated whether changing cortical excitability with transcranial direct current stimulation ( tDCS) could enhance CBM effects in hazardous drinkers. We also studied the underlying mechanisms by including behavioral (craving, implicit associations, approach tendencies) and electrophysiological (event-related potentials) measurements. Methods The analytical sample consisted of 78 hazardous drinkers (Alcohol Use Disorders Identification Test >8) randomly assigned to 4 conditions in a 2-by-2 factorial design (control/active CBM and sham/active tDCS). The intervention consisted of 3 sessions of CBM, specifically alcohol approach bias retraining, combined with 15 minutes 1 mA tDCS over the left dorsolateral prefrontal cortex. There was a pre- and postassessment before and after the intervention that included experimental tasks (Approach Avoidance Task, Implicit Association Task) and an electroencephalogram with an oddball and cue-reactivity task. Results tDCS decreased cue-induced craving (but not overall craving) on postassessment. CBM did not induce an avoidance bias during assessment. During the training, active and control- CBM only differed in bias score during the first session. We found no enhancement effects of tDCS on CBM. Electrophysiological data showed no clear effects of active tDCS or CBM on the P300. Conclusions There were no electrophysiological or behavioral effects of repeated CBM and/or tDCS, except for an effect of tDCS on craving. Applied in these specific ways these techniques appear to have limited effects in a hazardous drinking population. [ABSTRACT FROM AUTHOR]

Background The construct of relapse is used widely in clinical research and practice of alcohol use disorder (AUD) treatment. The purpose of this study was to test the predictive validity of commonly appearing definitions of AUD relapse in the empirical literature. Methods Secondary analyses of data from Project MATCH and COMBINE were conducted using 7 definitions of 'relapse' based on drinking quantity within a single drinking episode: any drinking; at least 4/5 drinks for women/men; at least 4.3/7.1 drinks for women/men; at least 6/7 drinks for women/men; at least 6 drinks; at least 7/9 drinks for women/men; and at least 8/10 drinks for women/men. Relapse was used to predict alcohol consumption, related consequences, and nonconsumption outcomes (quality of life, psychosocial functioning) at the end of treatment and up to 1 year posttreatment. Results Regression analyses indicated within-treatment relapse definitions significantly predicted end-of-treatment alcohol consumption and alcohol-related consequences. Heavy drinking definitions were generally more predictive than the any drinking definition, but no single heavy drinking definition was consistently a better predictor of outcomes. Relapse definitions were less predictive of longer-term alcohol-related outcomes and both shorter- and longer-term nonconsumption outcomes, including health and psychosocial functioning. Conclusions One particular definition of relapse did not consistently stand out as the best predictor. Advances in AUD research may require reconceptualization of relapse as a multifaceted dynamic process and may consider a wider range of relevant behaviors (e.g., health and psychosocial functioning) when examining the change process in individuals with AUD. [ABSTRACT FROM AUTHOR]

Background Heavy alcohol consumption can be harmful, particularly for individuals with HIV. There is substantial variability in response to interventions that aim to reduce drinking. Neighborhood drinking norms may explain some of this variability among HIV-infected patients. Therefore, we investigated whether neighborhood-level drinking norms modified response to alcohol intervention among HIV-infected heavy drinkers. Methods Heavily-drinking HIV comprehensive care patients ( n = 230) completed 1 of 3 brief alcohol interventions (an educational intervention, a motivational interviewing [ MI] intervention, or an MI intervention with a technological enhancement called HealthCall). Drinking was reported at baseline and end of treatment (60 days). Neighborhood-level drinking norms were obtained from a separate general population study. Results Patients' reductions in drinks per drinking day in response to MI (as compared with the educational control) were more pronounced in neighborhoods with more permissive drinking norms. In contrast, patients' reductions in drinks per drinking day in response to MI plus HealthCall did not significantly vary between neighborhoods with different drinking norms. Norms did not evidence significant interactions with intervention condition for 3 other exploratory drinking outcomes (drinking frequency, binge frequency, and maximum quantity). Conclusions Neighborhood-level drinking norms help explain differential response to an alcohol MI intervention among HIV-infected patients. This study suggests the utility of considering neighborhood context as an effect modifier of alcohol interventions. [ABSTRACT FROM AUTHOR]

Background This was a proof-of-concept study to evaluate the efficacy of LY2940094, a nociceptin/orphanin FQ peptide receptor antagonist, in reducing alcohol consumption in actively alcohol-drinking patients with alcohol dependence. Methods Eighty-eight patients, 21 to 66 years of age, diagnosed with alcohol dependence, reporting 3 to 6 heavy drinking days per week, were randomized (1:1) to 8 weeks of treatment with once-daily oral placebo ( N = 44) or 40 mg/d of LY2940094 ( N = 44). The primary efficacy analysis was the change from baseline in number of drinks per day ( NDD) utilizing mixed-model repeated measures comparing LY2940094 and placebo in Month 2 of the 8-week double-blind treatment period. The probability that the difference relative to placebo in NDD was ≤0 at endpoint was calculated, and a probability ≥80% was considered to be evidence that LY2940094 was associated with the reduction in NDD. Results After 8 weeks of treatment, reduction in mean NDD did not differ between LY2940094 versus placebo (−1.4 vs. −1.5, respectively, 44% probability of greater reduction relative to placebo), but there was a greater reduction in the mean percentage of heavy drinking days in a month with LY2940094 versus placebo (−24.5 vs. −15.7%, respectively, 93% probability of a greater reduction relative to placebo), and an increase in the mean percentage of abstinent days in a month compared to placebo (9.1 vs. 1.9%, respectively, 91% probability of a greater increase relative to placebo). Patients who were treated with LY2940094 showed decreased plasma levels of gamma-glutamyl transferase with probabilities ≥98% for greater reduction compared with placebo at Weeks 1, 4, 6, and 8. Treatment-emergent adverse events in ≥5% of patients treated with LY2940094 included insomnia, vomiting, and anxiety. There were no serious adverse events or significant changes in laboratory assessments or vital signs with LY2940094. Conclusions Although not reducing the NDD, LY2940094, compared to placebo, did reduce heavy drinking days and increased abstinence days in patients with alcohol dependence. [ABSTRACT FROM AUTHOR]

Background Neurobehavioral consequences of heavy prenatal alcohol exposure are well documented; however, the role of age or sex in these effects has not been studied. The current study examined the effects of prenatal alcohol exposure, sex, and age on neurobehavioral functioning in children. Methods Subjects were 407 youth with prenatal alcohol exposure ( n = 192) and controls ( n = 215). Two age groups (child [5 to 7 years] or adolescent [10 to 16 years]) and both sexes were included. All subjects completed standardized neuropsychological testing, and caregivers completed parent-report measures of psychopathology and adaptive behavior. Neuropsychological functioning, psychopathology, and adaptive behavior were analyzed with separate 2 (exposure history) × 2 (sex) × 2 (age) multivariate analyses of variance (MANOVAs). Significant effects were followed by univariate analyses. Results No 3-way or 2-way interactions were significant. The main effect of group was significant in all 3 MANOVAs, with the control group performing better than the alcohol-exposed group on all measures. The main effect of age was significant for neuropsychological performance and adaptive functioning across exposure groups with younger children performing better than older children on 3 measures (language, communication, socialization). Older children performed better than younger children on a different language measure. The main effect of sex was significant for neuropsychological performance and psychopathology; across exposure groups, males had stronger language and visual spatial scores and fewer somatic complaints than females. Conclusions Prenatal alcohol exposure resulted in impaired neuropsychological and behavioral functioning. Although adolescents with prenatal alcohol exposure may perform more poorly than younger exposed children, the same was true for nonexposed children. Thus, these cross-sectional data indicate that the developmental trajectory for neuropsychological and behavioral performance is not altered by prenatal alcohol exposure, but rather, deficits are consistent across the 2 age groups tested. Similarly, observed sex differences on specific measures were consistent across the groups and do not support sexually dimorphic effects in these domains. [ABSTRACT FROM AUTHOR]

Background Relapse is common in alcohol-dependent individuals and can be triggered by alcohol-related cues in the environment. It has been suggested that these individuals develop cognitive biases, in which cues automatically capture attention and elicit an approach action tendency that promotes alcohol seeking. The study aim was to examine whether cognitive bias modification ( CBM) training targeting approach bias could be delivered during residential alcohol detoxification and improve treatment outcomes. Methods Using a 2-group parallel-block (ratio 1:1) randomized controlled trial with allocation concealed to the outcome assessor, 83 alcohol-dependent inpatients received either 4 sessions of CBM training where participants were implicitly trained to make avoidance movements in response to pictures of alcoholic beverages and approach movements in response to pictures of nonalcoholic beverages, or 4 sessions of sham training (controls) delivered over 4 consecutive days during the 7-day detoxification program. The primary outcome measure was continuous abstinence at 2 weeks postdischarge. Secondary outcomes included time to relapse, frequency and quantity of alcohol consumption, and craving. Outcomes were assessed in a telephonic follow-up interview. Results Seventy-one (85%) participants were successfully followed up, of whom 61 completed all 4 training sessions. With an intention-to-treat approach, there was a trend for higher abstinence rates in the CBM group relative to controls (69 vs. 47%, p = 0.07); however, a per-protocol analysis revealed significantly higher abstinence rates among participants completing 4 sessions of CBM relative to controls (75 vs. 45%, p = 0.02). Craving score, time to relapse, mean drinking days, and mean standard drinks per drinking day did not differ significantly between the groups. Conclusions This is the first trial demonstrating the feasibility of CBM delivered during alcohol detoxification and supports earlier research suggesting it may be a useful, low-cost adjunctive treatment to improve treatment outcomes for alcohol-dependent patients. [ABSTRACT FROM AUTHOR]

Background This study is the first to examine the developmental course of high-intensity drinking (i.e., consuming 10+ drinks in a row) across late adolescence and the transition to adulthood. Methods National longitudinal data ( N = 3,718) from Monitoring the Future were used to examine trajectories of 10+ high-intensity drinking from age 18 through 25/26 overall and across sociodemographic subgroups; results were compared with similar analysis of 5+ binge drinking trajectories. Results Results document that 10+ drinkers consume not just a greater quantity of alcohol on a given drinking occasion, but also engage in 5+ drinking more frequently than drinkers who do not report having 10 or more drinks. Developmental patterns for 10+ and 5+ drinking were similar, with peak frequencies reported at age 21/22. Greater peaks in both 10+ and 5+ drinking were documented among men and among college attenders, compared with women and nonattenders, respectively. However, there was a steeper decline in 10+ drinking after age 21/22, indicating that risk for consumption of 10 or more drinks in a row is more clearly focused on the early 20s. Patterns of developmental change in both behaviors were driven largely by college students: No significant age-related change in 10+ drinking was observed among men and women who did not go to college, and no significant age-related change in 5+ drinking was observed among female nonattenders. Conclusions Findings underscore the importance of recognizing high-intensity drinkers as a unique high-risk group, and that college attendance is associated with particularly strong peaks in the developmental course of high-intensity drinking. [ABSTRACT FROM AUTHOR]

Background Quantifying craving longitudinally during the course of withdrawal, early abstinence, and relapse is essential for optimal management of alcohol use disorder ( AUD). In an effort to identify biological correlates of craving, we used proton magnetic resonance spectroscopy (1H- MRS) to investigate the correlation between craving and glutamate levels in the left dorsolateral prefrontal cortex ( LDLPFC) of patients with AUD. Methods Participants underwent 1H- MRS of the LDLPFC with 2-dimensional J-resolved (2 DJ) averaged PRESS. MRS data were processed with LCModel and cerebrospinal fluid ( CSF)-corrected to generate metabolite concentrations. The Penn Alcohol Craving Scale ( PACS) and the 30-day time line follow-back ( TLFB 30) were used to quantify craving for alcohol and drinking patterns, respectively. Results There was a statistically significant positive correlation between CSF-corrected glutamate ([Glu]) levels and PACS scores ( n = 14; p = 0.005). When PACS scores were dichotomized (< or ≥median = 16), [Glu] levels were significantly higher in the high- versus low-craving group ( p = 0.007). In addition, there was a significant negative correlation between CSF-corrected N-acetyl aspartic acid ([ NAA]) levels and mean number of drinks per drinking day in the past month ( n = 13; TLFB 30; p = 0.012). When mean TLFB 30 was dichotomized (< or ≥median = 7.86), [ NAA] levels were significantly lower in subjects that consumed more alcoholic beverages. There was no significant correlation between [Glu] and [ NAA] levels with other measures of drinking behavior and or depression symptom severity. Conclusions While limited by small sample size, these data suggest that glutamate levels in LDLPFC are associated with alcohol craving intensity in patients with AUD. Further study with larger sample size is needed to replicate this finding and evaluate the merits of glutamate spectroscopy as a biological correlate of alcohol craving intensity and a guide to treatment interventions. [ABSTRACT FROM AUTHOR]

Background The current study sought to examine the diagnostic overlap in DSM- IV and DSM-5 alcohol use disorder ( AUD) and determine the clinical correlates of changing diagnostic status across the 2 classification systems. Methods DSM- IV and DSM-5 definitions of AUD were compared using cross-national community survey data in 9 low-, middle-, and high-income countries. Participants were 31,367 respondents to surveys in the World Health Organization's World Mental Health Survey Initiative. The Composite International Diagnostic Interview, version 3.0, was used to derive DSM- IV and DSM-5 lifetime diagnoses of AUD. Clinical characteristics, also assessed in the surveys, included lifetime DSM- IV anxiety; mood and drug use disorders; lifetime suicidal ideation, plan, and attempt; general functional impairment; and psychological distress. Results Compared with DSM- IV AUD (12.3%, SE = 0.3%), the DSM-5 definition yielded slightly lower prevalence estimates (10.8%, SE = 0.2%). Almost one-third ( n = 802) of all DSM- IV abuse cases switched to subthreshold according to DSM-5 and one-quarter ( n = 467) of all DSM- IV diagnostic orphans switched to mild AUD according to DSM-5. New cases of DSM-5 AUD were largely similar to those who maintained their AUD across both classifications. Similarly, new DSM-5 noncases were similar to those who were subthreshold across both classifications. The exception to this was with regard to the prevalence of any lifetime drug use disorder. Conclusions In this large cross-national community sample, the prevalence of DSM-5 lifetime AUD was only slightly lower than the prevalence of DSM- IV lifetime AUD. Nonetheless, there was considerable diagnostic switching, with a large number of people inconsistently identified across the 2 DSM classifications. [ABSTRACT FROM AUTHOR]

Background To counteract the syndemics of HIV and alcohol in Sub-Saharan Africa, international collaborations have developed interventions to reduce alcohol consumption. Reliable and accurate methods are needed to estimate alcohol use outcomes. A direct alcohol biomarker called phosphatidylethanol ( PEth) has been shown to validate heavy, daily drinking, but the literature indicates mixed results for moderate and nondaily drinkers, including among HIV-infected populations. This study examined the associations of the PEth biomarker with self-report alcohol use at 2 time points in 127 HIV-infected outpatient drinkers in western Kenya. Methods Participants were consecutively enrolled in a randomized clinical trial to test the efficacy of a behavioral intervention to reduce alcohol use in Eldoret, Kenya. They endorsed current alcohol use, and a minimum score of 3 on the Alcohol Use Disorders Identification Test-Consumption or consuming ≥6 drinks per occasion at least monthly in the past year. Study interviews and blood draws were conducted at baseline and at 3 months post treatment from July 2012 through September 2013. Alcohol use was assessed using the Timeline Followback questionnaire. Blood samples were analyzed for the presence of the PEth biomarker and were compared to self-reported alcohol use. We also conducted semistructured interviews with 14 study completers in February through March 2014. Results Baseline data indicated an average of moderate-heavy alcohol use: 50% drinking days and a median of 4.5 drinks per drinking day. At baseline, 46% of women (31 of 67) and 8% of men (5 of 60) tested negative for PEth ( p < 0.001). At the 3-month follow-up, 93% of women (25 of 27) and 97% of men (30 of 31) who reported drinking tested positive, while 70% of women (28 of 40) and 35% of men (10 of 29) who denied drinking tested negative for PEth. Interviews were consistent with self-reported alcohol use among 13 individuals with negative baseline results. Conclusions These results add to the growing literature showing lack of agreement between self-report and PEth results among unhealthy and nondaily drinkers, particularly women. More research is needed to determine at what level of consumption over what period of time PEth becomes a reliable and accurate indicator of alcohol use. [ABSTRACT FROM AUTHOR]

Background The Alcohol Use Disorder and Associated Disabilities Interview Schedule- IV ( AUDADIS- IV) and AUDADIS-5 are diagnostic interviews used in major epidemiological and other studies of alcohol use disorder ( AUD). Much of what we know regarding the prevalence of AUD in the United States is based upon this interview. However, past research and meta-analytic evidence suggest that differential operationalization of the AUD criteria across instruments can lead to differential endorsement of symptoms and resulting AUD diagnosis rates. In particular, studies employing the AUDADIS are observed to have markedly higher endorsement rates of withdrawal than other large epidemiological studies. One explanation for this is that when assessing withdrawal, the AUDADIS combines effects from the morning after drinking with those from the days following, thereby conflating hangover and withdrawal. Methods This study addresses whether this operationalization confounds rates of endorsement when compared to simpler, less ambiguous hangover or withdrawal stems. To this aim, 497 college student drinkers were randomized into 1 of 3 stem conditions: (i) hangover ( n = 164), (ii) withdrawal ( n = 167), or (iii) combined AUDADIS- IV ( n = 166). Results Across conditions, participants were more likely to report the occurrence of each withdrawal symptom in the combined stem condition than in the explicit withdrawal stem condition, but not in the explicit hangover stem condition. Within the combined stem condition, probed symptoms were more likely to be reported as a result of a hangover. Conclusions The AUDADIS potentially results in false positives for withdrawal, arguably a pathognomonic symptom of alcoholism and, in turn, likely affects rates of the diagnosis of AUD. [ABSTRACT FROM AUTHOR]

Background Common variants in the gene GATA binding protein 4 ( GATA4) show association with alcohol dependence ( AD). The aim of this study was to identify rare variants in GATA4 in order to elucidate the role of this gene in AD susceptibility. Identification of rare variants may provide a more complete picture of the allelic architecture at this risk locus. Methods Sanger sequencing of all 6 coding exons of GATA4 was performed in 528 patients and 517 controls. Four in silico prediction tools were used to determine the effect of a DNA variant on the amino acid sequence and protein function. Five variants were included in the replication step. Of these, 4 were successfully genotyped in our replication cohort of 655 patients and 1,501 controls. All patients fulfilled DSM- IV criteria for AD, and all individuals were of German descent. Results In the discovery step, 19 different heterozygous variants were identified. Four patient-specific and potentially functionally relevant variants were followed up. Only the variant S379S (c.1137C>T) remained patient specific (1/1,166 patients vs. 0/1,997 controls). None of the variants showed a statistically significant association with AD. Conclusions The present study elucidated the role of GATA4 in AD susceptibility by identifying rare variants via Sanger sequencing and subsequent replication. Although novel patient-specific rare variants of GATA4 were identified, none received support in the independent replication step. However, given previous robust findings of association with common variants, GATA4 remains a promising candidate gene for AD. [ABSTRACT FROM AUTHOR]

Background U.S. border populations have been found to be at high risk for alcohol problems. However, results from the U.S.-Mexico Study on Alcohol and Related Conditions ( UMSARC) revealed surprisingly large variation in alcohol outcomes even among Texas border sites, with alcohol use disorder ( AUD) prevalence ~1.5 to 1.6 times greater in the border city of Laredo compared to both San Antonio and the border site of McAllen/Brownsville. Because a better understanding of this variation is important to identifying environmental influences on AUD, we developed and tested a conceptual model addressing variation in AUD prevalence across Texas UMSARC sites. Methods Surveys involved in-person, household interviews with Mexican-origin residents of the Texas border cities Laredo ( n = 751) and McAllen/Brownsville ( n = 814), with San Antonio as an off-border comparison ( n = 771). Interviews assessed past-year DSM-5 AUD; past-year heavy drinking; coping and enhancement motives; and 7 indicators of substance use climate and stress exposure hypothesized to mediate site effects. Analyses, conducted separately by gender, included regressions and structural equation modeling with Mplus. Results Preliminary analyses revealed that site effects on AUD prevalence were, unexpectedly, exclusive to men, and that Laredan men were similar to McAllen/Brownsville men on demographics, acculturation, and cross-border mobility. However, sites differed dramatically on most of the hypothesized risk factors. Structural equation models confirmed that site effects on AUD were partially mediated via effects of site on indicators of a permissive climate (i.e., permissive drinking norms, high drug availability) and stress exposures (i.e., high exposure to violence/crime, low family support), and via downstream effects on drinking motives and heavy drinking. Conclusions Findings of very high rates of past-12-month AUD among Laredan men (35%) suggest the possibility of significant heterogeneity even within demographically similar border areas and underline the need for additional study of the border region. Findings regarding our conceptual model suggest that this model may constitute a useful initial framework for future research on alcohol problems at the border. However, additional research using representative samples is needed to confirm and expand this model to comprehensively address relevant individual and community factors. [ABSTRACT FROM AUTHOR]