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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 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 It has been argued that the excessive consumption of energy drinks ( EDs) may have serious health consequences, and that may serve as an indicator for substance use and other risky behaviors. The present paper offers a perspective on this topic that remains underexplored on the population of adolescents. Methods Data were collected via self-administered anonymous questionnaires from 870 adolescents aged 15 to 19 years who were recruited from a random sample of public secondary schools in the geographic area of the Calabria Region, in the South of Italy. Results A total of 616 participants completed the survey for a response rate of 70.8%. Nearly 68% of respondents had drunk at least a whole can of ED during their life, and about 55% reported consuming EDs during the 30 days before the survey. Only 13% of interviewed adolescents were aware that drinking EDs is the same as drinking coffee, whereas a sizable percentage believed that drinking EDs is the same as drinking carbonated beverages or rehydrating sport drinks. Forty-six percent of adolescents had drunk alcohol-mixed energy drinks ( AmEDs) during their life, and 63% of lifetime users admitted drinking AmEDs during the 30 days before the survey. Overall, 210 (63.3%) had drunk alcohol alone not mixed with EDs during their life, and more than half (56.3%) reported having consumed it at least once during the 30 days before the survey. Multivariate analysis showed that the factors independently associated with the consumption of AmEDs were the increasing number of sexual partners, being a current smoker, being male, riding with a driver who had been drinking alcohol, and having used marijuana. Conclusions Comprehensive educational programs among youths focusing on potential health effects of EDs, alcohol, and the combination of the two, designed to empower the ability to manage these drinking habits, are strongly advisable. [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: This paper describes a new multicountry collaborative project to assess the impact of alcohol control policy. Longitudinal surveys of drinkers in a number of participating countries and analysis of the policy context allow for the assessment of change over time within countries and comparison between countries. The design of the study is modeled on the International Tobacco Control study and aims to assess the impact of alcohol policies in different cultural contexts on policy-related behaviors and alcohol consumption. A survey instrument and protocol for policy analysis have been developed by the initial participating countries: England, Scotland, Thailand, South Korea, and New Zealand. The first round of data collection is scheduled for 2011-2012. Measurements: The survey instrument (International Alcohol Control [ IAC] survey) measures key policy relevant behaviors: place and time of purchase, amounts purchased and price paid; ease of access to alcohol purchase; alcohol marketing measures; social supply; perceptions of alcohol affordability and availability and salience of price; perceptions of enforcement; people's experiences with specific alcohol restrictions; support for policy and consumption (typical quantity, frequency using beverage and location-specific measures). The Policy Analysis Protocol ( PoLAP) assesses relevant aspects of the policy environment including regulation and implementation. Results: It has proved feasible to design instruments to collect detailed data on behaviors relevant to alcohol policy change and to assess the policy environment in different cultural settings. Conclusions: In a policy arena in which the interest groups and stakeholders have different perceptions of appropriate policy responses to alcohol-related harm, a robust methodology to assess the impact of policy will contribute to the debate. [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 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: This study aims to increase understanding of the relationship between heavy episodic drinking (HED) and fathers' involvement in parenting in five countries. The potential moderating effect of fathers' experiences of childhood trauma is also studied, controlling for the possible confounding of the effect of HED by father's attitudes toward gender equality, father's age and father's education. Method: United Nations Multi‐Country Study on Men and Violence (UNMCS) survey data from 4562 fathers aged 18–49 years from Cambodia, China, Indonesia and Papua New Guinea (PNG) and Sri Lanka were used to assess the relationship between fathering involvement (e.g., helping children with their homework) and self‐reported HED of 6+ drinks in one occasion vs. non‐HED and abstaining. Moderating effects of a 13‐item fathers' childhood trauma (FCT) scale were tested and analyses were adjusted for gender‐inequitable attitudes using the Gender‐Equitable Men scale score. Bivariate and adjusted individual participant meta‐analyses were used to determine effect estimates for each site and across all sites. Results: Fathers' HED was associated with less positive parental involvement after adjusting for gender‐equitable attitudes, FCT, age and education. No overall interaction between HED and FCT was identified. Gender equitable attitudes were associated with fathering involvement in some countries but not overall (p = 0.07). Conclusions: Heavy episodic drinking was associated with reduced positive fathering involvement. These findings suggest that interventions to increase fathers' involvement in parenting should include targeting reductions in fathers' HED. Structural barriers to fathers' involvement should be considered alongside HED in future studies of fathers' engagement with their children. [ABSTRACT FROM AUTHOR]

Background: Research examining emotion dysregulation and alcohol use has increased exponentially over the past decade. However, these studies have been limited by their use of cross‐sectional designs and narrow definitions of emotion dysregulation. To address these significant gaps in the extant literature, this study utilized state‐of‐the‐art methodology (i.e., experience sampling) and statistics (i.e., dynamic structural equation modeling) to examine potential reciprocal associations between negative and positive emotion dysregulation and alcohol use at the momentary level. Methods: Participants were 145 community women (mean age = 40.56, 40.3% white) experiencing intimate partner violence (IPV) and using substances. Surveys assessing negative and positive emotion dysregulation and alcohol use (i.e., number of standard drinks) were administered three times a day for 30 days using phone‐based interactive voice recording. Results: Significant contemporaneous effects indicated that negative and positive emotion dysregulation both co‐occurred with alcohol use. However, levels of negative and positive emotion dysregulation did not predict later alcohol use, nor did alcohol use predict later levels of negative or positive emotion dysregulation. There was significant variability among participants in cross‐lagged effects. Conclusions: Findings showed that negative and positive emotion dysregulation co‐occurred with alcohol use and that there was significant interindividual variability in the cross‐lagged associations between negative and positive emotion dysregulation and alcohol use. Research using idiographic approaches may identify women experiencing IPV for whom negative and positive emotion dysregulation drive alcohol use and alcohol use drives negative and positive emotion dysregulation. [ABSTRACT FROM AUTHOR]

Background: Early recovery from alcohol use disorder (AUD) is commonly associated with high levels of negative affect, stress, and emotional vulnerability, which confer significant relapse risk. Emotion differentiation—the ability to distinguish between discrete emotions—has been shown to predict relapse after treatment for a drug use disorder, but this relationship has not been explored in individuals recovering from AUD. Methods: The current study used thrice daily random and up to thrice daily self‐initiated ecological momentary assessment surveys (N = 42, observations = 915) to examine whether 1) moments of high affective arousal are characterized by momentary differences in emotion differentiation among individuals in the first year of a current AUD recovery attempt, and 2) individuals' average emotion differentiation would predict subsequent alcohol use measured by the timeline follow‐back over a 3‐month follow‐up period. Results: Multilevel models showed that moments (Level 1) of higher‐than‐average negative affect (p < 0.001) and/or stress (p = 0.033) were characterized by less negative emotion differentiation, while moments of higher‐than‐average positive affect were characterized by greater positive emotion differentiation (p < 0.001). At the between‐person level (Level 2), participants with higher stress overall had lower negative emotion differentiation (p = 0.009). Linear regression showed that average negative, but not positive, emotion differentiation was inversely associated with percent drinking days over the subsequent 3‐month follow‐up period (p = 0.042). Neither form of average emotion differentiation was associated with drinking quantity. Conclusions: We found that for individuals in early AUD recovery, affective states are associated with acute shifts in the capacity for emotion differentiation. Further, we found that average negative emotion differentiation prospectively predicts subsequent alcohol use. [ABSTRACT FROM AUTHOR]

Background: Progression through the stages of change is a proposed mechanism underlying the effects of treatment for alcohol use disorder (AUD). However, examining stages of change as a mechanism of treatment effects requires that the measure be invariant across patient subgroups, treatment conditions, and time. In this study, we examined measurement invariance of the University of Rhode Island Change Assessment Scale (URICA) in Project MATCH using an exploratory structural equation modeling (ESEM) approach. Methods: We conducted a secondary analysis of data from Project MATCH (N = 1726; Mage = 40.2, SD = 10.9; 75.7% male; 80% non‐Hispanic white), a multisite randomized clinical trial that tested three AUD treatments: Motivational Enhancement Therapy, Cognitive‐Behavioral Therapy, or Twelve‐Step Facilitation. Participants completed the 24‐item URICA for assessing the stages of change in relation to drinking at baseline and post‐treatment (3 months after baseline). Results: A 4‐factor ESEM provided a good fit to the data and a better fit to the data than a conventional 4‐factor confirmatory factor analysis model. Further, the URICA demonstrated scalar invariance across each patient subgroup at baseline (sex, ethnicity, marital status, education, and parental history of AUD) and treatment condition at follow‐up. However, the URICA was not longitudinally invariant as the metric model resulted in a significant decrement in model fit. Conclusions: Measurement invariance of the URICA over time was not supported. Longitudinally invariant measures of the stages of change are needed to test the proposal that progression through the stages explains treatment effects. [ABSTRACT FROM AUTHOR]

Background: Day drinking, or drinking during the daytime, is a term used colloquially in the media and among college students based on anecdotal evidence. Drinking at tailgate parties, generally thought to be a type of day drinking, tends to be particularly heavy and to achieve levels comparable to drinking on holidays and special occasions. The objective of this study was to assess how many and how often students day drink and whether day drinking days (i.e., days drinking began before 4:00 p.m.) were associated with heavy drinking, legal intoxication, negative alcohol‐related consequences, and three risky substance use behaviors. Methods: We conducted a longitudinal daily diary study of college students who were followed for their first seven semesters of college. The analytic sample includes 7,633 drinking days nested with 619 student drinkers. We used logistic and Poisson multilevel models to test associations between day drinking days and substance use outcomes and negative consequences. Results: Approximately 50% of drinkers drank durinng the day at least once, and day drinking occurred on 9% of drinking days. Greek organization participants reported significantly more day drinking days than non‐participants. Day drinking days were characterized by heavy drinking as evidenced by strong, positive associations between day drinking and drinking to heavy episodic drinking (HED) and high‐intensity drinking (HID) thresholds on a given day. In contrast, students were less likely to reach legal intoxication and experienced fewer negative alcohol‐related consequences on day drinking days than days on which drinking began in the evening or nighttime. Students who reported day drinking more often throughout the study also reported having more days of drinking at the HED and HID thresholds and playing drinking games and mixed alcohol with energy drinks more frequently. Conclusions: Day drinking was common among this sample of college students. Findings suggest that day drinking days may be characterized by heavy drinking and may be a behavior most typically engaged in by heavy drinkers, including members of Greek organizations. [ABSTRACT FROM AUTHOR]

Background: The majority of adolescents and young adults (AYA) who use cannabis also use alcohol. Although cannabis use is increasing in the United States (US), it is not known whether the increase contributes to either increased co‐use of alcohol and cannabis (e.g., complementarity) or replacement of alcohol with cannabis (e.g., substitution). The current study estimated the prevalence of alcohol use by cannabis use status among US AYA ages 12 to 25 in 2018 and trends in alcohol use by cannabis use status from 2002 to 2018. Methods: Data were drawn from the 2002 to 2018 National Survey on Drug Use and Health public use data files. The analytic sample included AYA ages 12 to 25 (2018 sample, n = 26,924; total combined sample 2002 to 2018, n = 576,053). Linear and logistic regression models were used to estimate past‐month alcohol use, daily alcohol use, and average quantity of alcohol consumed among AYA with and without past‐month cannabis use from 2002 to 2018. Results: In 2018, any alcohol use and daily alcohol use were significantly more common among AYA who used cannabis use than those who did not use cannabis. Overall, any alcohol use, daily alcohol use, and average drinks per day declined from 2002 to 2018 among AYA irrespective of recent cannabis use. However, the decline in any alcohol use, daily alcohol use, and average alcohol drinks per day was more rapid among AYA who used cannabis (daily and nondaily) than those who did not use cannabis. The rate of decline in average alcohol drinks per day was also higher among AYA with daily compared to nondaily cannabis use. Conclusions: Even with declines in alcohol use over time, drinking is much more common among AYA who report cannabis than those without recent cannabis use, which is consistent with complementarity. Yet, because the decline in alcohol use has been more rapid among AYA who use cannabis, there is also evidence of substitution. Thus, the current data on alcohol and cannabis use are consistent with both complementarity and substitution. However, these relationships may change as cannabis legalization expands over time. [ABSTRACT FROM AUTHOR]

Background: Because there is high variability among European countries in prevalence levels of various alcohol consumption measures, the informational value of adolescent's alcohol consumption indicators is uncertain. The present study aimed to examine information capacity and measurement invariance of different alcohol consumption indicators in adolescents from countries of the former Soviet (Eastern) Bloc in Central and Eastern Europe (CEE). Methods: Data were collected in 16 CEE countries, as part of the 2013/2014 wave of the Health Behavior in School‐aged Children study. Data from adolescents (age 15) who reported having consumed alcohol at least once in their lifetime were analyzed. Four binary items selected for analysis measured the presence or absence of alcohol consumption in the last 30 days, lifetime drunkenness, weekly drinking frequency, and binge drinking on a typical occasion. Multiple group confirmatory factor analysis and item response theory analysis were used to examine the data. Results: In most of the included countries, alcohol consumption in the last 30 days and lifetime drunkenness were indicative at lower severity levels, while binge drinking and weekly drinking frequency were informative at higher levels of alcohol use severity. A low proportion of the estimated intercepts and factor loadings were noninvariant, which indicated approximate cross‐national invariance of these indicators. Conclusions: Adolescent alcohol consumption indicators are informative for different severity levels and enable cross‐nationally invariant measurement. However, different indicators suggested the presence of diverging drinking cultures in the CEE regions, with the highest discrimination capacity at the lower and higher ends of the continuum of alcohol use severity. [ABSTRACT FROM AUTHOR]

Background: Prenatal alcohol exposure (PAE) is associated with smaller regional and global brain volumes. In rats, gestational choline supplementation mitigates adverse developmental effects of ethanol exposure. Our recent randomized, double‐blind, placebo‐controlled maternal choline supplementation trial showed improved somatic and functional outcomes in infants at 6.5 and 12 months postpartum. Here, we examined whether maternal choline supplementation protected the newborn brain from PAE‐related volume reductions and, if so, whether these volume changes were associated with improved infant recognition memory. Methods: Fifty‐two infants born to heavy‐drinking women who had participated in a choline supplementation trial during pregnancy underwent structural magnetic resonance imaging with a multi‐echo FLASH protocol on a 3T Siemens Allegra MRI (median age = 2.8 weeks postpartum). Subcortical regions were manually segmented. Recognition memory was assessed at 12 months on the Fagan Test of Infant Intelligence (FTII). We examined the effects of choline on regional brain volumes, whether choline‐related volume increases were associated with higher FTII scores, and the degree to which the regional volume increases mediated the effects of choline on the FTII. Results: Usable MRI data were acquired in 50 infants (choline: n = 27; placebo: n = 23). Normalized volumes were larger in six of 12 regions in the choline than placebo arm (t ≥ 2.05, p ≤ 0.05) and were correlated with the degree of maternal choline adherence (β ≥ 0.28, p ≤ 0.04). Larger right putamen and corpus callosum were related to higher FTII scores (r = 0.36, p = 0.02) with a trend toward partial mediation of the choline effect on recognition memory. Conclusions: High‐dose choline supplementation during pregnancy mitigated PAE‐related regional volume reductions, with larger volumes associated with improved 12‐month recognition memory. These results provide the first evidence that choline may be neuroprotective against PAE‐related brain structural deficits in humans. [ABSTRACT FROM AUTHOR]

Background: The current study examined the extent to which within‐person variation in drinking motives differentiates moderate, binge, and high‐intensity drinking; and independent associations of motives and drinking intensity with alcohol use consequences in a sample of young adult drinkers from across the United States. Methods: Participants were past 30‐day drinkers in the U.S. nationally representative Monitoring the Future 12th grade sample in 2018, who also reported alcohol use during a 14‐day data collection burst 1 year later (N = 484 people, mean age 19.3 [SD 0.40], 43% female; N = 1042 drinking days) as part of the Young Adult Daily Life Study in 2019. Weighted multilevel modeling estimated within‐ and between‐person associations of drinking motives, drinking intensity (i.e., moderate [women 1–3, men 1–4 drinks], binge [women 4–7, men 5–9 drinks], and high‐intensity drinking [women 8+, men 10+ drinks]), and number of positive and negative alcohol consequences. Results: On days participants reported greater enhancement and social motives, they were more likely to engage in high‐intensity (vs. binge) drinking and binge (vs. moderate) drinking and experience more positive alcohol consequences. On days participants reported greater enhancement and coping motives, they experienced more negative alcohol consequences. Binge (vs. moderate) drinking on a given day was associated with more positive and negative alcohol consequences; high‐intensity (vs. binge) drinking on a given day was associated with more negative alcohol consequences that day. Moderation analyses indicated that social motives were associated with high‐intensity (vs. binge) drinking only among college students. Conclusions: Stronger drinking motives on a given day were associated with drinking intensity (enhancement and social motives) and negative consequences (enhancement and coping). High‐intensity (vs. binge or moderate) drinking was associated with more negative consequences but not more positive consequences. These results underscore that high‐intensity drinking and consequences vary across days and time‐varying, occasion‐specific risks such as current motivational context are appropriate targets for intervention. [ABSTRACT FROM AUTHOR]

Background: Alcohol may increase gastric cancer risk. Alcohol can be more carcinogenic in persons who possess inactive ALDH2. The aim of this meta‐analysis was to evaluate whether ALDH2 polymorphism can affect alcohol‐induced gastric carcinogenesis. Methods: We searched the PubMed, EMBASE, and Cochrane databases to identify relevant articles published between January 2000 and September 2019. Eligible articles were selected according to inclusion and exclusion criteria. The data were analyzed using Review Manager 5.3. Results: A total of 7 case–control studies on ALDH2 rs671 polymorphism consisting of 3,251 gastric cancer cases and 4,943 controls were included in the analysis. Inactive ALDH2 genotypes (G/A or A/A) were associated with an increased risk of gastric cancer (odds ratio [OR] = 1.26, 95% confidence interval [CI]: 1.04 to 1.52, p = 0.02, I2 = 64%), compared with active ALDH2 (G/G genotype). Subgroup analysis by alcohol consumption showed that inactive ALDH2 increased risk for gastric cancer in moderate to heavy drinkers (OR = 1.85, 95% CI: 1.52 to 2.25, p < 0.01, I2 = 6%) more than in nondrinkers or mild drinkers (OR = 1.19; 95% CI: 1.05 to 1.36, p < 0.01, I2 = 6%). Moderate/heavy alcohol consumption increased gastric cancer risk in individuals with inactive ALDH2 (OR = 2.23, 95% CI: 1.63 to 3.05, p < 0.01, I2 = 30%) more than those with active ALDH2 (OR = 1.40, 95% CI: 0.98 to 2.01, p = 0.07, I2 = 85%). Conclusions: The ALDH2 polymorphism modifies the risk of gastric cancer. Moderate/heavy drinkers are more susceptible to gastric cancer than non‐drinkers or light drinkers with inactive ALDH2. [ABSTRACT FROM AUTHOR]

Background: Alcohol can lead to fatal and nonfatal overdose (OD) through its neurobiological inhibitory effects when used alone or with other drugs. Little research has examined alcohol OD characteristics in the context of concomitant drug use. Methods: This study utilized alcohol OD data (defined as alcohol poisoning, passing out, or blacking out) collected in a large residential addiction treatment facility (N = 660). Latent class analysis identified classes of alcohol OD events based on concomitant drug use at the time of OD. We evaluated correlates of alcohol OD classes, including depression, emergency medical services, and hospitalization, using latent class regression. Results: Only 20% of alcohol ODs involved alcohol alone. Marijuana was the most commonly used drug during the most recent alcohol OD (43.2%), followed by sedatives (27.9%), cocaine or crack (25.9%), prescription opioids (26.1%), and heroin (20%). The final latent class model included 3 classes: no/low drug involvement (61%), moderate drug involvement (33%), and high drug involvement (6%). Relative to the no/low drug involvement class, participants admitted to the hospital were 6.4‐fold more likely to be in the high drug involvement class (95% CI: 2.4 to 16.6) and 2.9‐fold more likely to be in the moderate drug involvement class (95% CI: 1.2 to 7.2). Participants receiving emergency medical services were more likely to be in the high drug involvement class (aOR: 2.2, 95% CI: 2.2, 1.1 to 4.5) and less likely to be in the moderate drug involvement class (aOR 0.39, 95% CI: 0.2 to 0.96). Conclusions: Combining drug classes with alcohol prior to OD was common and associated with a higher likelihood of hospitalization. Overdose prevention efforts should address acute risks of alcohol ingestion with other drugs. [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 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 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 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 The Monkey Alcohol Tissue Research Resource (MATRR) is a repository and analytics platform for detailed data derived from well-documented nonhuman primate (NHP) alcohol self-administration studies. This macaque model has demonstrated categorical drinking norms reflective of human drinking populations, resulting in consumption pattern classifications of very heavy drinking (VHD), heavy drinking (HD), binge drinking (BD), and low drinking (LD) individuals. Here, we expand on previous findings that suggest ethanol drinking patterns during initial drinking to intoxication can reliably predict future drinking category assignment. Methods The classification strategy uses a machine-learning approach to examine an extensive set of daily drinking attributes during 90 sessions of induction across 7 cohorts of 5 to 8 monkeys for a total of 50 animals. A Random Forest classifier is employed to accurately predict categorical drinking after 12 months of self-administration. Results Predictive outcome accuracy is approximately 78% when classes are aggregated into 2 groups, 'LD and BD' and 'HD and VHD.' A subsequent 2-step classification model distinguishes individual LD and BD categories with 90% accuracy and between HD and VHD categories with 95% accuracy. Average 4-category classification accuracy is 74%, and provides putative distinguishing behavioral characteristics between groupings. Conclusions We demonstrate that data derived from the induction phase of this ethanol self-administration protocol have significant predictive power for future ethanol consumption patterns. Importantly, numerous predictive factors are longitudinal, measuring the change of drinking patterns through 3 stages of induction. Factors during induction that predict future heavy drinkers include being younger at the time of first intoxication and developing a shorter latency to first ethanol drink. Overall, this analysis identifies predictive characteristics in future very heavy drinkers that optimize intoxication, such as having increasingly fewer bouts with more drinks. This analysis also identifies characteristic avoidance of intoxicating topographies in future low drinkers, such as increasing number of bouts and waiting longer before the first ethanol drink. [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 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 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 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 Physicians have long reported that patients with chronic pain show higher tendencies for alcohol use disorder ( AUD), and AUD patients appear to have higher pain sensitivities. The goal of this study was to test 2 hypotheses: (i) binge alcohol consumption increases inflammatory pain and mechanical and cold sensitivities; and (ii) tigecycline is an effective treatment for alcohol-mediated-increased pain behaviors and sensitivities. Both female and male mice were used to test the additional hypothesis that important sex differences in the ethanol (EtOH)-related traits would be seen. Methods 'Drinking in the Dark' ( DID) alcohol consuming and nondrinking control, female and male, adult C57 BL/6J mice were evaluated for inflammatory pain behaviors and for the presence of mechanical and cold sensitivities. Inflammatory pain was produced by intraplantar injection of formalin (10 μl, 2.5% in saline). For cold sensation, a 20 μl acetone drop was used. Mechanical withdrawal threshold was measured by an electronic von Frey anesthesiometer. Efficacy of tigecycline (80 mg/kg i.p.) to reduce DID-related pain responses and sensitivity was tested. Results DID EtOH consumption increased inflammatory pain behavior, while it also produced sustained mechanical and cold sensitivities in both females and males. Tigecycline produced antinociceptive effects in males; a pro-nociceptive effect was seen in females in the formalin test. Likewise, the drug reduced both mechanical and cold sensitivities in males, but females showed an increase in sensitivity in both tests. Conclusions Our results demonstrated that binge drinking increases pain, touch, and thermal sensations in both sexes. In addition, we have identified sex-specific effects of tigecycline on inflammatory pain, as well as mechanical and cold sensitivities. The development of tigecycline as an AUD pharmacotherapy may need consideration of its pro-nociceptive action in females. Further studies are needed to investigate the mechanism underlying the sex-specific differences in nociception. [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 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 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 Informed by inconsistent findings regarding the association between injunctive norms (IN) and drinking behaviors, the current study developed a new measure of IN, the Injunctive Norms Drinking and Abstaining Behaviors Questionnaire ( IN- DABQ). This measure addressed several psychometric weaknesses of prior assessment of this construct, specifically, reliance on single-item measures, and assessment of a limited range of drinking behaviors. The new measure also assessed norms for reasons for abstaining from drinking as college students often have simultaneous motives to use and inhibit their drug use. A parallel measure of descriptive norms (DN), the Descriptive Norms Drinking and Abstaining Behaviors Questionnaire ( DN- DABQ), was created to allow for a comparison of the relative predictive effects of descriptive and IN in relation to different drinking outcomes. Methods A college sample ( N = 254, female = 50.42%) was recruited using Amazon's Mechanical Turk. Participants completed an online survey assessing demographic characteristics, social norms for 3 referents, weekly alcohol use, and alcohol-related consequences. Results Exploratory factor analyses indicated 2 factors for the DN- DABQ and 3 factors for the IN- DABQ. The IN Drinking Behaviors factor consistently predicted weekly consumption and alcohol-related consequences across 3 reference groups (typical college student at your school, friends, and closest friends). Conclusions These findings suggest that prior inconsistencies in the relationship between IN and drinking behaviors are likely a function of poor measurement of this construct. Implications for normative feedback interventions are discussed. [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 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 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 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 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]

Background: Fetal alcohol syndrome (FAS) is a well-known consequence of prenatal alcohol exposure. However, women tend to deny or underreport their alcohol use during pregnancy. The aim of this study was to explore the usability of various alcohol biomarkers for FAS screening in a data set without information on self-reported alcohol use. Methods: A nationwide register study with a case-control design was conducted. The target population consisted of all live births in Finland from 1987 to 2005. FAS cases (n = 565) were identified from the Finnish Register of Congenital Malformations. Mothers of FAS cases and their controls were selected in a ratio of 1 to 2 from the Finnish Maternity Cohort (FMC). Background information was obtained from the Finnish Medical Birth Register. Serum samples, collected at the mother's first visit to the maternity care, were obtained from the national FMC biobank. Biomarkers of alcohol consumption, gamma-glutamyltransferase (GGT), carbohydrate-deficient transferrin (%CDT), combination of GGT and CDT (GGT-CDT), and ethylglucuronide (EtG) were analyzed from mothers of FAS cases (n = 385) and their controls (n = 745). Results: Median levels of all biomarkers were significantly higher among the mothers of FAS children than in control mothers. Using previously validated cutoffs for EtG, GGT, %CDT, and GGT-CDT, nearly half (46%) of the mothers with affected offspring could be identified. The predictive association was highest for GGT-CDT combination and significant also for all the other biomarkers. Conclusions: In this explorative case-control study, we demonstrate that the FMC biobank can be used to screen alcohol biomarkers for epidemiological research purposes. According to our results, the use of alcohol biomarkers during the first trimester may help to identify the high-risk pregnancies for FAS. A more systematic use of alcohol biomarkers at maternity care may open new possibilities for screening and intervention of alcohol use among pregnant mothers. [ABSTRACT FROM AUTHOR]

Background: Exposure to ethanol (EtOH) in utero alters the disposition of tangentially migrating GABAergic interneurons in the fetal brain. The medial ganglionic eminence (MGE) gives rise to a large portion of cortical GABAergic interneurons, including the parvalbumin-expressing interneurons that shape and contribute to inhibitory/excitatory (I/E) balance of the intracortical circuit. Here, we investigated in the mouse medial prefrontal cortex (mPFC) the hypothesis that low levels of maternal EtOH consumption from closure of the neural tube embryonic day (E) 9.5 until birth result in an enduring interneuronopathy. Methods: Pregnant mice were subjected to a 2%w/w EtOH consumption regimen starting at neural tube closure and ending at parturition. Neurogenesis in theMGE was assessed by 5-bromo-2-deoxyuridine (BrdU) immunofluorescence at E12.5. The count and distribution of parvalbumin-expressing interneurons were determined in adult animals, and patch clamp electrophysiology was performed to determine GABAergic function and I/E balance. Open-field behavior in adult mice was assessed to determine whether the EtOH-exposed cohort displayed a lasting alteration in exploratory behavior. Results: In embryos exposed to EtOH in utero, we found increased BrdU labeling in the MGE, pointing to increased neurogenesis. Adult mice prenatally exposed to EtOH were hyperactive, and this was associated with an increase in parvalbumin-expressing GABAergic interneurons in the mPFC. In addition, prenatal EtOH exposure altered the balance between spontaneous inhibitory and excitatory synaptic input and attenuated GABAergic tone in layer V mPFC pyramidal neurons in juvenile mice. Conclusions: These findings underscore that altered migration of GABAergic interneurons contributes to the EtOH-induced aberration of cortical development and that these effects persist into adulthood as altered cortical form and function. [ABSTRACT FROM AUTHOR]

Background: Although many studies have analyzed the association of 3'-untranslated region variable- number tandem repeat (VNTR) polymorphism in SLC6A3 with alcohol dependence (AD), the results remain controversial. This study aimed to determine whether this variant indeed has any genetic effect on AD by integrating 17 reported studies with 5,929 participants included. Methods: The A9-dominant genetic model that considers A9-repeat and non-A9 repeat as 2 genotypes and compared their frequencies in alcoholics with that in controls was adopted. Considering the potential influence of ethnicity, differences in diagnostic criteria of AD, and alcoholic subgroups, stratified meta-analyses were conducted. There existed no evidence for the presence of heterogeneity among the studied samples, indicating the results under the fixed-effects model are acceptable. Results: We found a significant association of VNTR A9 genotypes with AD in all ethnic populations (pooled odds ratio [OR] 1.12; 95% confidence interval [CI] 1.00, 1.25; p = 0.045) and the Caucasian population (pooled OR 1.15; 95% CI 1.01, 1.31; p = 0.036). We also found VNTR A9 genotypes to be significantly associated with alcoholism as defined by the DSM-IV criteria (pooled OR 1.18; 95% CI 1.03, 1.36; p = 0.02). Further, we found a significant association between VNTR A9 genotypes and alcoholism associated with alcohol withdrawal seizure or delirium tremens (pooled OR 1.55; 95% CI 1.24, 1.92; p = 1.0 × 10-4). In all these meta-analyses, no evidence of publication bias was detected. Conclusions: We concluded that the VNTR polymorphism has an important role in the etiology of AD, and individuals with at least 1 A9 allele are more likely to be dependent on alcohol than persons carrying the non-A9 allele. [ABSTRACT FROM AUTHOR]

Background The relationship between gestational age at birth (GA) and alcohol use measures in early adulthood was examined in a large U.K. community-based birth cohort (Avon Longitudinal Study of Parents and Children). Methods A series of linear and logistic regression models were used to test for main effects of a continuous measure of GA on a range of alcohol use measures, and moderation of these associations by sex. In addition, mediation analyses assessed the extent to which significant associations between GA and alcohol use operated indirectly, through influences of the parental environment and/or childhood measures of emotional and behavioral health (EBH). Results Earlier GA significantly predicted never drinking by age 18, but was not associated with other measures of alcohol use behavior among young adult drinkers (i.e., Self-Rating of the Effects of Alcohol, Alcohol Use Disorders Identification Test, or DSM- IV- TR Criteria for Alcohol Dependence). The association between earlier GA and never drinking by age 18 was moderated by sex, such that females born early were less likely to have ever had a drink by age 18. In the full sample, childhood measures of EBH were found to mediate the association between earlier GA and never drinking by age 18. This association was not mediated by parenting factors. Conclusions Earlier GA is associated with never drinking alcohol in early adulthood, in females. Emotional and behavioral difficulties experienced in early childhood may mediate the relationship between earlier GA and never drinking by age 18. [ABSTRACT FROM AUTHOR]

Background Alcoholism has been linked to deficits in cognitive, behavioral, and emotional functions, and the cerebellum is important for optimal functioning of these abilities. However, little is known about how individual differences such as gender and drinking history might influence regional cerebellar abnormalities. Methods Volumetric analyses of the cerebellum and its subregions were performed in relation to the interaction of gender and measures of drinking history. Structural magnetic resonance imaging scans of 44 alcoholic individuals (23 men) and 39 nonalcoholic controls (18 men) were obtained. In addition to measuring total cerebellar gray and white matter volumes, we measured 64 individual cerebellar parcellation units, as well as functionally defined a priori regions of interest that have been shown to correspond to functions impaired in alcoholism. Results Total cerebellar white matter volume was smaller in alcoholic relative to nonalcoholic participants. Moreover, volumes of parcellation units varied with drinking history, showing negative associations between years of heavy drinking and the anterior lobe, the vestibulocerebellar lobe, and the spinocerebellar subdivision. The negative association between anterior volume and years of heavy drinking was driven primarily by alcoholic men. Additionally, we observed larger white and gray matter volumes for alcoholic women than for alcoholic men. Conclusions The identification of drinking-related abnormalities in cerebellar subregions lays a foundation that can be utilized to inform how cerebro-cerebellar networks are perturbed in this pathological condition. These results also provide estimates of how gender and individual differences in drinking history can predict cerebellar volumes. [ABSTRACT FROM AUTHOR]

Background The genetic polymorphisms of alcohol dehydrogenase-1B ( ADH1B) and aldehyde dehydrogenase-2 ( ALDH2) are associated with the risk of alcoholism and upper aerodigestive tract cancer in alcoholics. Salivary ethanol ( sEtOH) levels are well correlated with blood Et OH levels. Methods To study the effects of ADH1B and ALDH2 genotypes on the alcohol elimination rate ( AER) and salivary acetaldehyde ( sAcH) levels, we measured the sEtOH and sAcH levels twice at a 1-hour intervals in 99 intoxicated Japanese alcoholic men who had stopped drinking for 4 or more hours. Results The initial sEtOH levels did not differ between the ADH1B*2 group ( n = 50) and the ADH1B*1/*1 group ( n = 49) (median: 0.617 vs. 0.762 mg/ml). The salivary AER (sAER) increased as the sEtOH levels increased ( p < 0.0001). After stratification according to the sEtOH levels (<0.4, 0.4 to 0.99, and ≥1.00 mg/ml), the median sAER of the ADH1B*2 group was 0.075, 0.188, and 0.228 mg/ml/h, respectively, and that of the ADH1B*1/*1 group was 0.037, 0.115, and 0.233 mg/ml/h, respectively. The sAER of the ADH1B*2 group was faster than that of the ADH1B*1/*1 group overall ( p = 0.001) and when the sEtOH category was 0.4 to 0.99 mg/ml ( p < 0.0001). The ADH1B genotype and the sEtOH levels had an interaction effect on the sAER ( p = 0.036). A multiple linear regression analysis with a stepwise procedure selected the ADH1B*2 allele ( p = 0.004) and the sEtOH levels ( p < 0.0001) as positive predictors of sAER. The sAER did not differ according to the ALDH2 genotype. The sAcH levels were higher than the blood AcH levels reported in alcoholics, probably because of AcH production by oral microorganisms. The sAcH of the ALDH2*1/*2 group ( n = 18) was higher than that of the ALDH2*1/*1 group ( n = 81) overall ( p = 0.0008) and when the corresponding sEtOH category was ≥1.00 mg/ml (median: 3.195 vs. 1.776 μg/ml, p = 0.009). A multiple linear regression analysis selected the ALDH2*1/*2 and the sEtOH levels as positive predictors of the sAcH levels ( p < 0.0001). Conclusions The enhanced AER in ADH1B*2 carriers and the increased sAcH levels in ALDH2*1/*2 carriers among intoxicated alcoholics provide possible mechanisms explaining how each genetic polymorphism affects the risk of alcoholism and upper aerodigestive tract cancer. [ABSTRACT FROM AUTHOR]