Showing papers in "Alcoholism: Clinical and Experimental Research in 2013"

Multidimensionality in impulsivity and alcohol use: a meta-analysis using the UPPS model of impulsivity

Abstract: BACKGROUND: Although there is considerable support for the relationship between impulsivity and alcohol use, the use of multidimensional conceptualizations of impulsivity and alcohol use has lead to varying relationship sizes across studies. The aims of the current meta-analysis are to (i) examine variability in the magnitude of the bivariate relationship between impulsivity and alcohol use across studies and (ii) describe the pattern of effects between specific impulsivity traits and alcohol use variables, using the UPPS model of impulsivity. METHODS: Ninety-six studies were meta-analyzed using a random effects model to examine the relationship between general impulsivity and alcohol use, as well as the relationships among separate impulsivity traits based in the UPPS model of impulsivity and specific alcohol use outcomes. RESULTS: Results indicate that, in general, impulsivity and alcohol use are related (r = 0.28); however, this effect size varied significantly across studies (from -0.05 to 1.02). Drinking quantity was most strongly predicted by lack of perseverance (r = 0.32), whereas all traits equally predicted drinking frequency. Drinking problems were most highly related to negative (r = 0.35) and positive (r = 0.34) urgency, and alcohol dependence was most highly related to negative urgency (r = 0.38) and lack of planning (r = 0.37). CONCLUSIONS: Effect sizes between impulsivity and alcohol use vary significantly by UPPS trait used in each study; thus, findings suggest and further reinforce the view in the literature that specific impulsivity-related constructs differentially relate to specific alcohol use outcomes. Language: en

Alcohol and sleep I: effects on normal sleep.

Abstract: This review provides a qualitative assessment of all known scientific studies on the impact of alcohol ingestion on nocturnal sleep in healthy volunteers. At all dosages, alcohol causes a reduction in sleep onset latency, a more consolidated first half sleep and an increase in sleep disruption in the second half of sleep. The effects on rapid eye movement (REM) sleep in the first half of sleep appear to be dose related with low and moderate doses showing no clear trend on REM sleep in the first half of the night whereas at high doses, REM sleep reduction in the first part of sleep is significant. Total night REM sleep percentage is decreased in the majority of studies at moderate and high doses with no clear trend apparent at low doses. The onset of the first REM sleep period is significantly delayed at all doses and appears to be the most recognizable effect of alcohol on REM sleep followed by the reduction in total night REM sleep. The majority of studies, across dose, age and gender, confirm an increase in slow wave sleep (SWS) in the first half of the night relative to baseline values. The impact of alcohol on SWS in the first half of night appears to be more robust than the effect on REM sleep and does not appear to be an epiphenomenon REM sleep reduction. Total night SWS is increased at high alcohol doses across gender and age groups.

Approaching the prevalence of the full spectrum of fetal alcohol spectrum disorders in a south african population-based study

Abstract: BACKGROUND—The prevalence and characteristics of fetal alcohol spectrum disorders (FASD) were determined in this fourth study of first grade children in a South African community. METHODS—Active case ascertainment methods were employed among 747 first grade pupils. The detailed characteristics of children within the continuum of FASD are contrasted with randomly-selected, normal controls on: 1. physical growth and dysmorphology; 2. cognitive/ behavioral characteristics; and 3. maternal risk factors. RESULTS—The rates of specific diagnoses within the FASD spectrum continue to be among the highest reported in any community in the world. The prevalence (per 1,000) is: FAS - 59.3 to 91.0; PFAS – 45.3 to 69.6; and ARND – 30.5 to 46.8. The overall rate of FASD is therefore 136.1 to 208.8 per 1,000 (or 13.6 to 20.9%). Clinical profiles of the physical and cognitive/behavioral traits of children with a specific FASD diagnosis and controls are provided for understanding the full spectrum of FASD in a community. The spectral effect is evident in the characteristics of the diagnostic groups and summarized by the total (mean) dysmorphology scores of the children: FAS

Intranasal Oxytocin Blocks Alcohol Withdrawal in Human Subjects

Abstract: Background: The neuropeptide, oxytocin (OT), has been reported to block tolerance formation toalcohol and decrease withdrawal symptoms in alcohol-dependent rodents. Numerous recent studies inhuman subjects indicate that OT administered by the intranasal route penetrates into and exerts effectswithinthebrain.Methods: In a randomized, double-blind clinical trial, intranasal OT (24 IU/dose, N = 7) orplacebo (N = 4) was given twice daily for 3 days in alcohol-dependent subjects admitted to a researchunit for medical detoxification using Clinical Institute Withdrawal Assessment for Alcohol (CIWA)score-driven PRN administration of lorazepam. Subjects rated themselves on the Alcohol WithdrawalSymptom Checklist (AWSC) each time CIWA scores were obtained. Subjects also completed the PennAlcohol Craving Scale, an Alcohol Craving Visual Analog Scale (ACVAS) and the Profile of MoodStates(POMS)oninpatientdays2and3.Results: All subjects had drunk heavily each day for at least 2 weeks prior to study and had previ-ously experienced withdrawal upon stopping/decreasing alcohol consumption. OT was superior toplacebo in reducing alcohol withdrawal as evidenced by: less total lorazepam required to completedetoxification (3.4 mg [4.7, SD] vs. 16.5 [4.4], p = 0.0015), lower mean CIWA scores on admission day1 (4.3 [2.3] vs. 11.8 [0.4], p < 0.0001) and day 2 (3.4 [2.2] vs. 11.1 [3.6], p < 0.002), lower AWSC scoreson days 1 and 2 (p < 0.02; p = 0.07), and lower ACVAS ratings (p = 0.01) and lower POMS Tension/Anxietysubscalescoresonday2(p < 0.01).Conclusions: This is the first demonstration that OT treatment may block alcohol withdrawal inhuman subjects. Our results are consistent with previous findings in rodents that OT inhibits neuroad-aptationtoandwithdrawalfromalcohol.OTcouldhaveadvantagesoverbenzodiazepinesinmanagingalcohol withdrawal because it may reverse rather than maintain sedative-hypnotic tolerance. It will beimportant to test whether OT treatment is effective in reducing drinking in alcohol-dependent outpa-tients.Key Words: Oxytocin, Alcohol Withdrawal, Detoxification, Dependence, Tolerance, HumanSubjects.

AUDIT-C Scores as a Scaled Marker of Mean Daily Drinking, Alcohol Use Disorder Severity, and Probability of Alcohol Dependence in a U.S. General Population Sample of Drinkers

Abstract: Background: Brief alcohol screening questionnaires are increasingly used to identify alcohol misuse in routine care, but clinicians also need to assess the level of consumption and the severity of misuse so that appropriate intervention can be offered. Information provided by a patient’s alcohol screening score might provide a practical tool for assessing the level of consumption and severity of misuse. Methods: This post hoc analysis of data from the 2001 to 2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) included 26,546 U.S. adults who reported drinking in the past year and answered additional questions about their consumption, including Alcohol Use Disorders Identification Test—Consumption questionnaire (AUDIT-C) alcohol screening. Linear or logistic regression models and postestimation methods were used to estimate mean daily drinking, the number of endorsed alcohol use disorder (AUD) criteria (“AUD severity”), and the probability of alcohol dependence associated with each individual AUDIT-C score (1 to 12), after testing for effect modification by gender and age. Results: Among eligible past-year drinkers, mean daily drinking, AUD severity, and the probability of alcohol dependence increased exponentially across increasing AUDIT-C scores. Mean daily drinking ranged from < 0.1 to 18.0 drinks/d, AUD severity ranged from < 0.1 to 5.1 endorsed AUD criteria, and probability of alcohol dependence ranged from < 1 to 65% across scores 1 to 12. AUD severity increased more steeply across AUDIT-C scores among women than men. Both AUD severity and mean daily drinking increased more steeply across AUDIT-C scores among younger versus older age

Gestational choline supplementation normalized fetal alcohol-induced alterations in histone modifications, DNA methylation, and proopiomelanocortin (POMC) gene expression in β-endorphin-producing POMC neurons of the hypothalamus.

Abstract: Background Prenatal exposure to ethanol reduces the expression of hypothalamic proopiomelanocortin (POMC) gene, known to control various physiological functions including the organismal stress response. In this study, we determined whether the changes in POMC neuronal functions are associated with altered expressions of histone-modifying and DNA-methylating enzymes in POMC-producing neurons, since these enzymes are known to be involved in regulation of gene expression. In addition, we tested whether gestational choline supplementation prevents the adverse effects of ethanol on these neurons.

Further development of a neurobehavioral profile of fetal alcohol spectrum disorders.

Abstract: Background—Heavy prenatal alcohol exposure (AE) results in a broad array of neurobehavioral deficits. Recent research has focused on identification of a neurobehavioral profile or profiles that will improve identification of children affected by AE. The current study aimed to build on our preliminary neurobehavioral profile in order to improve classification accuracy and test the specificity of the resulting profile in an alternate clinical group. Methods—A standardized neuropsychological test battery was administered to three groups of children: subjects with AE (n = 209), typically developing controls (CON, n = 185), and subjects with attention-deficit/hyperactivity disorder (ADHD, n = 74). We assessed a large sample from six sites in the U.S. and South Africa, using standardized methodology. Data were analyzed using three latent profile analyses (LPA) including: (1) subjects with FAS and controls, (2) subjects with

Longitudinal Changes in White Matter Integrity Among Adolescent Substance Users

Abstract: BACKGROUND: The influence of repeated substance use during adolescent neurodevelopment remains unclear as there have been few prospective investigations. The aims of this study were to identify longitudinal changes in fiber tract integrity associated with alcohol- and marijuana-use severity over the course of 1.5 years. METHODS: Adolescents with extensive marijuana- and alcohol-use histories by mid-adolescence (n = 41) and youth with consistently minimal if any substance use (n = 51) were followed over 18 months. Teens received diffusion tensor imaging and detailed substance-use assessments with toxicology screening at baseline and 18-month follow-ups (i.e., 182 scans in all), as well as interim substance-use interviews each 6 months. RESULTS: At an 18-month follow-up, substance users showed poorer white matter integrity in 7 tracts: (i) right superior longitudinal fasciculus, (ii) left superior longitudinal fasciculus, (iii) right posterior thalamic radiations, (iv) right prefrontal thalamic fibers, (v) right superior temporal gyrus white matter, (vi) right inferior longitudinal fasciculus, and (vii) left posterior corona radiata (ps Language: en

Liver transplantation in alcoholic patients: impact of an alcohol addiction unit within a liver transplant center

Abstract: Background Many concerns about liver transplantation in alcoholic patients are related to the risk of alcohol recidivism. Starting from 2002, an Alcohol Addiction Unit (AAU) was formed within the liver transplant center for the management of alcoholic patients affected by end-stage liver disease and included in the waiting list for transplantation. We evaluated retrospectively the impact of the AAU on alcohol recidivism after transplantation. The relationship between alcohol recidivism and the duration of alcohol abstinence before transplant was evaluated as well. Methods Between 1995 and 2010, 92 cirrhotic alcoholic patients underwent liver transplantation. Clinical evaluation and management of alcohol use in these patients was provided by psychiatrists with expertise in addiction medicine not affiliated to the liver transplant center before 2002 (n = 37; group A), or by the clinical staff of the AAU within the liver transplant center starting from 2002 (n = 55; group B). Results Group B, as compared with group A, showed a significantly lower prevalence of alcohol recidivism (16.4 vs. 35.1%; p = 0.038) and a significantly lower mortality (14.5 vs. 37.8%; p = 0.01). Furthermore, an analysis of group B patients with either ≥6 or <6 months of alcohol abstinence before transplantation showed no difference in the rate of alcohol recidivism (21.1 vs. 15.4%; p = ns). Conclusions The presence of an AAU within a liver transplant center reduces the risk of alcohol recidivism after transplantation. A pretransplant abstinence period <6 months might be considered, at least in selected patients managed by an AAU.

Use of AUDIT-Based Measures to Identify Unhealthy Alcohol Use and Alcohol Dependence in Primary Care: A Validation Study

Abstract: Background As programs for screening, brief intervention, and referral to treatment (SBIRT) for unhealthy alcohol use disseminate, evidence-based approaches for identifying patients with unhealthy alcohol use and alcohol dependence (AD) are needed. While the National Institute on Alcohol Abuse and Alcoholism Clinician Guide suggests use of a single alcohol screening question (SASQ) for screening and Diagnostic and Statistical Manual checklists for assessment, many SBIRT programs use alcohol use disorders identification test (AUDIT) “zones” for screening and assessment. Validation data for these zones are limited. This study used primary care data from a bi-ethnic southern U.S. population to examine the ability of the AUDIT zones and other AUDIT-based approaches to identify unhealthy alcohol use and dependence. Methods Existing data were analyzed from interviews with 625 female and male adult drinkers presenting to 5 southeastern primary care practices. Timeline follow-back was used to identify at-risk drinking, and diagnostic interview schedule was used to identify alcohol abuse and dependence. Validity measures compared performance of AUDIT, AUDIT-C, and AUDIT dependence domains scores, with and without a 30-day binge drinking measure, for detecting unhealthy alcohol use and dependence. Results Optimal AUDIT scores for detecting unhealthy alcohol use were lower than current commonly used cutoffs (5 for men, 3 for women). Improved performance was obtained by combining AUDIT cutoffs of 6 for men and 4 for women with a 30-day binge drinking measure. AUDIT scores of 15 for men and 13 for women detected AD with 100% specificity but low sensitivity (20 and 18%, respectively). AUDIT dependence subscale scores of 2 or more showed similar specificity (99%) and slightly higher sensitivity (31% for men, 24% for women). Conclusions Combining lower AUDIT cutoff scores and binge drinking measures may increase the detection of unhealthy alcohol use in primary care. Use of lower cutoff scores and dependence subscale scores may increase diagnosis of AD; however, better measures for detecting dependence are needed.

Missing data in alcohol clinical trials: a comparison of methods.

Abstract: BACKGROUND: The rate of participant attrition in alcohol clinical trials is often substantial and can cause significant issues with regard to the handling of missing data in statistical analyses of treatment effects. It is common for researchers to assume that missing data is indicative of participant relapse, and under that assumption, many researchers have relied on setting all missing values to the worst-case scenario for the outcome (e.g., missing = heavy drinking). This sort of single-imputation method has been criticized for producing biased results in other areas of clinical research, but has not been evaluated within the context of alcohol clinical trials, and many alcohol researchers continue to use the missing = heavy drinking assumption. METHODS: Data from the COMBINE study, a multisite randomized clinical trial, were used to generate simulated situations of missing data under a variety of conditions and assumptions. We manipulated the sample size (n = 200, 500, and 1,000) and dropout rate (5, 10, 25, 30%) under 3 missing data assumptions (missing completely at random, missing at random, and missing not at random). We then examined the association between receiving naltrexone and heavy drinking during the first 10 weeks following treatment using 5 methods for treating missing data (complete case analysis [CCA], last observation carried forward [LOCF], missing = heavy drinking, multiple imputation [MI], and full information maximum likelihood [FIML]). RESULTS: CCA, LOCF, and missing = heavy drinking produced the most biased naltrexone effect estimates and standard errors under conditions that are likely to exist in randomized clinical trials. MI and FIML produced the least biased naltrexone effect estimates and standard errors. CONCLUSIONS: Assuming that missing = heavy drinking produces biased results of the treatment effect and should not be used to evaluate treatment effects in alcohol clinical trials. Language: en

Mixing an energy drink with an alcoholic beverage increases motivation for more alcohol in college students.

Abstract: Background There has been a dramatic rise in the consumption of alcohol mixed with energy drinks (AmED) in social drinkers. It has been suggested that AmED beverages might lead individuals to drink greater quantities of alcohol. This experiment was designed to investigate if the consumption of AmED would alter alcohol priming (i.e., increasing ratings of wanting another drink) compared with alcohol alone.

Continuous objective monitoring of alcohol use: twenty-first century measurement using transdermal sensors.

Abstract: Transdermal alcohol sensors continuously collect reliable and valid data on alcohol consumption in vivo over the course of hours to weeks. Transdermal alcohol readings are highly correlated with breath alcohol measurements, but transdermal alcohol levels lag behind breath alcohol levels by one or more hours owing to the longer time required for alcohol to be expelled through perspiration. By providing objective information about alcohol consumption, transdermal alcohol sensors can validate self-report and provide important information not previously available. In this article, we describe the development and evaluation of currently available transdermal alcohol sensors, present the strengths and limitations of the technology, and give examples of recent research using the sensors.

Sensitivity and Specificity of a Brief Personality Screening Instrument in Predicting Future Substance Use, Emotional, and Behavioral Problems: 18-Month Predictive Validity of the Substance Use Risk Profile Scale

Abstract: Background This study assessed the validity, sensitivity, and specificity of the Substance Use Risk Profile Scale (SURPS), a measure of personality risk factors for substance use and other behavioral problems in adolescence. Methods The concurrent and predictive validity of the SURPS was tested in a sample of 1,162 adolescents (mean age: 13.7 years) using linear and logistic regressions, while its sensitivity and specificity were examined using the receiver operating characteristics curve analyses. Results Concurrent and predictive validity tests showed that all 4 brief scales—hopelessness (H), anxiety sensitivity (AS), impulsivity (IMP), and sensation seeking (SS)—were related, in theoretically expected ways, to measures of substance use and other behavioral and emotional problems. Results also showed that when using the 4 SURPS subscales to identify adolescents “at risk,” one can identify a high number of those who developed problems (high sensitivity scores ranging from 72 to 91%). And, as predicted, because each scale is related to specific substance and mental health problems, good specificity was obtained when using the individual personality subscales (e.g., most adolescents identified at high risk by the IMP scale developed conduct or drug use problems within the next 18 months [a high specificity score of 70 to 80%]). Conclusions The SURPS is a valuable tool for identifying adolescents at high risk for substance misuse and other emotional and behavioral problems. Implications of findings for the use of this measure in future research and prevention interventions are discussed.

Childhood Trauma Exposure and Alcohol Dependence Severity in Adulthood: Mediation by Emotional Abuse Severity and Neuroticism

Abstract: Background Childhood trauma has been linked with a number of negative outcomes later in life, including alcohol dependence (AD). Previous studies have suggested a mediating role for neuroticism in the relationship between childhood trauma and psychopathology. In this study, we investigate the prevalence of multiple types of childhood trauma in treatment-seeking alcohol-dependent patients, and the associations between childhood trauma and AD severity using multiple mediation analysis. Methods The prevalence of 5 types of childhood trauma—emotional abuse, sexual abuse, physical abuse, emotional neglect, and physical neglect—was assessed in treatment-seeking alcohol-dependent patients (n = 280) and healthy controls (n = 137) using the Childhood Trauma Questionnaire. Multiple mediation analyses were used to model associations between childhood trauma measures and alcohol-related outcomes, primarily the severity of AD in the alcohol-dependent sample. Results Childhood trauma was significantly more prevalent and more severe in the alcohol-dependent subjects. In addition, childhood trauma was found to influence AD severity, an effect that was mediated by neuroticism. When individual trauma types were examined, emotional abuse was found to be the primary predictor of AD severity, both directly and through the mediating effects of the impulsivity subfacet of neuroticism. Physical abuse also had a moderate direct effect on AD severity. Mediation analysis did not reveal any association between childhood trauma and Alcohol Use Disorders Identification Test score in the nondependent control sample. Conclusions Childhood trauma is highly prevalent in treatment-seeking alcoholics and may play a significant role in the development and severity of AD through an internalizing pathway involving negative affect. Our findings suggest that alcoholics with a history of childhood emotional abuse may be particularly vulnerable to severe dependence.

Adolescent rearing conditions influence the relationship between initial anxiety-like behavior and ethanol drinking in male Long Evans rats.

Abstract: Background Rodent studies have demonstrated that adolescent social isolation results in many behavioral perturbations, including increases in anxiety-like behaviors. Socially isolated (SI) rats have also been shown to self-administer greater amounts ethanol (EtOH) in some, but not all, studies. Here, we tested whether juvenile social isolation increases EtOH drinking using an intermittent procedure that engenders relatively high intake in normally reared animals. We also compared the behavioral phenotype of rats reared under social isolation or group-housed conditions with adult rats housed under conditions commonly used in EtOH-drinking studies. Methods Male Long Evans rats were procured immediately postweaning and were group housed for 1 week. Subjects were then randomly divided into 2 groups: SI rats, housed individually for 6 weeks and group-housed (GH) rats (4/cage). A third group was procured as young adults and was housed individually upon arrival for 1 week (standard housing condition). Rats were then tested in a plus-maze and novelty assay, and then, all subjects were singly housed and EtOH drinking was assessed. Results SI rats displayed increased anxiety-like behaviors on the plus-maze, a greater locomotor response to a novel environment, and increased EtOH intake, relative to GH rats. Age-matched standard housed (STD) rats exhibited an anxiety-like behavioral profile on the plus-maze that was similar to SI, and not GH rats, and also drank EtOH at levels comparable with SI subjects. In addition, anxiety-like behavior on the plus-maze correlated with intermittent EtOH intake in SI and GH rats. Conclusions These data further support the validity of the rodent juvenile social isolation model for studies directed at elucidating behavioral and neurobiological mechanisms linking anxiety and EtOH drinking. These findings further suggest that housing conditions commonly employed in rodent drinking studies may recapitulate the anxiety-like and EtOH-drinking phenotype engendered by a juvenile social isolation procedure.

Drinking before going to licensed premises: an event-level analysis of predrinking, alcohol consumption, and adverse outcomes.

Abstract: BACKGROUND: Research in the United States and the United Kingdom indicates that drinking before going out (commonly called "predrinking") is common among young people and associated with increased harm. On the basis of Swiss data, this study investigates differences in alcohol consumption and adverse or risky outcomes for evenings when persons consumed alcohol before going to a licensed premise (i.e., predrinking), drank on-premise only, or drank off-premise only. METHODS: Using the recently developed Internet-based cell phone-optimized assessment technique (ICAT), alcohol consumption and drinking location were assessed at 6 time points (5 pm to the next morning) on Thursdays, Fridays, and Saturdays over 5 consecutive weeks by means of participants' cell phones. Overall, 7,828 assessments provided by 183 young adults (53.0% women, mean age [SD] = 23.1 [3.1]) on 1,441 evenings were analyzed by means of cluster-adjusted means and proportion tests and of multilevel structural equation models. The extent to which alcohol consumption mediated the association between predrinking and adverse outcomes was also examined. RESULTS: Higher alcohol consumption occurred on evenings with predrinking (7.1 drinks on average) compared with on-premise only (4.2 drinks) and off-premise only (4.3 drinks) evenings. Adverse outcomes occurred more often on evenings with predrinking (with 23.8% of predrinking nights involving at least 1 outcome) than on evenings with on-premise drinking only (13.9%) and off-premise drinking only (12.0%). Predrinking was indirectly associated with adverse outcomes, mediated by larger amounts of alcohol consumed in the evening. CONCLUSIONS: Because of its association with heavier consumption and related adverse outcomes, predrinking, especially combined with on-premise drinking, represents a major target for prevention. Educational interventions as well as structural measures, such as reduction in late-night off-sale opening hours, and staff training in responsible beverage service, are needed to prevent high total consumption and related adverse consequences among young people. Language: en

Early life adversity contributes to impaired cognition and impulsive behavior: studies from the Oklahoma Family Health Patterns Project.

Abstract: Background: Stressful early life experience may have adverse consequences in adulthood and may contribute to behavioral characteristics that increase vulnerability to alcoholism. We examined early life adverse experience in relation to cognitive deficits and impulsive behaviors with a reference to risk factors for alcoholism. Methods: We tested 386 healthy young adults (18 to 30 years of age; 224 women; 171 family history positive for alcoholism) using a composite measure of adverse life experience (low socioeconomic status plus personally experienced adverse events including physical and sexual abuse and separation from parents) as a predictor of performance on the Shipley Institute of Living scale, the Stroop colorword task, and a delay discounting task assessing preference for smaller immediate rewards in favor of larger delayed rewards. Body mass index (BMI) was examined as an early indicator of altered health behavior. Results: Greater levels of adversity predicted higher Stroop interference scores (F = 3.07, p = 0.048), faster discounting of delayed rewards (F = 3.79, p = 0.024), lower Shipley mental age scores (F = 4.01, p = 0.019), and higher BMIs in those with a family history of alcoholism (F = 3.40, p = 0.035). These effects were not explained by age, sex, race, education, or depression. Conclusions: The results indicate a long-term impact of stressful life experience on cognitive function, impulsive behaviors, and early health indicators that may contribute to risk in persons with a family history of alcoholism.

A Meta-Analysis on the Impact of Alcohol Dependence on Short-Term Resting-State Heart Rate Variability: Implications for Cardiovascular Risk

Abstract: Background Alcohol dependence is associated with an increased likelihood of cardiac events. Reductions in heart rate variability (HRV) may be one mechanism linking dependence with these events. HRV may also be related to poor social functioning and the lack of impulse control commonly observed in alcohol-dependent individuals. However, prior studies on the impact of alcohol dependence on HRV have reported contradictory findings highlighting the need for a meta-analysis. Methods Studies comparing short-term HRV in alcohol-dependent populations and healthy controls who were nondependent were considered for meta-analysis. Only studies reporting findings from participants without cardiovascular disease were included in the analysis. Results Meta-analyses were based on 6 articles that fulfilled inclusion criteria, comprising a total of 177 alcohol-dependent participants and 216 nondependent participants. Alcohol-dependent participants displayed reduced HRV (Hedges' g = −0.6, p > 0.001) in comparison with nondependent participants. No differences were observed between the summary effect sizes obtained from different HRV domains (Q = 1.19, p = 0.55). Conclusions Alcohol dependence is associated with reduced HRV, an effect associated with a medium effect size. Findings highlight the importance of monitoring alcohol-dependent patients for cardiac disease and emphasize the need for cardiovascular risk reduction strategies in these patients.

Not early drinking but early drunkenness is a risk factor for problem behaviors among adolescents from 38 European and North American countries

Abstract: Background: Many studies have reported that the earlier the age at first drink (AFDrink) the higher the later drinking levels and related problems. However, unless adolescents proceed into drunkenness, it is unclear why consuming small quantities at early age should lead to later problems. This study investigates the link between AFDrink and problem behaviors (smoking, cannabis use, injuries, fights, and low academic performance) among 15-year-olds who did and did not proceed into drunkenness. Among those with drunkenness experience, we tested whether AFDrink predicted problem behaviors over and above the age at first drunkenness (AFDrunk). Methods: Multilevel structural equation models were estimated based on a sample of 44,801 alcohol-experienced 15-year-olds from 38 North American and European countries and regions who participated in the Health Behaviour in School-aged Children cross-national survey. Results: Overall, there was a significant association between AFDrink and all 5 problem behaviors. However, this was the case only among those with drunkenness experiences but not among those never drunk. Among the former, AFDrunk was a strong predictor for all 5 problem behaviors, but time from first drink to first drunk did not predict problem behaviors. Conclusions: Not early alcohol initiation but early drunkenness was a risk factor for various adolescent problem behaviors at the age of 15, that is, there was not consistent relationship for the time before the first drunkenness (i.e., since first drinking). Besides targeting early drinking, particular efforts are needed to impede early drunkenness to prevent associated harm in adolescence and beyond.

An update of research examining college student alcohol-related consequences: new perspectives and implications for interventions.

Abstract: The objective of this review is to provide an update on existing research examining alcohol-related consequences among college students with relevance for individual-based interventions. While alcohol-related consequences have been a focus of study for several decades, the literature has evolved into an increasingly nuanced understanding of individual and environmental circumstances that contribute to risk of experiencing consequences. A number of risk factors for experiencing alcohol-related consequences have been identified, including belonging to specific student subgroups (e.g., Greek organizations) or drinking during high-risk periods, such as spring break. In addition, the relationship between students' evaluations of both negative and positive consequences and their future drinking behavior has become a focus of research. The current review provides an overview of high-risk student subpopulations, high-risk windows and activities, and college students' subjective evaluations of alcohol-related consequences. Future directions for research are discussed and include determining how students' orientations toward consequences change over time, identifying predictors of membership in high-risk consequence subgroups and refining existing measures of consequences to address evolving research questions.

Circadian Misalignment, Reward‐Related Brain Function, and Adolescent Alcohol Involvement

Abstract: In this review, we hypothesize that developmental changes in sleep and circadian rhythms that occur during adolescence may contribute to impaired reward-related brain function, and consequently increase the risk of alcohol use disorders (AUDs). Sleep-wake timing tends to shift later during adolescence, driven in part by changes in the endogenous circadian clock. This biologically-driven tendency for later sleep-wake timing conflicts with the earlier sleep-wake schedules demanded by school start times, thus resulting in circadian misalignment. Emerging evidence indicates that circadian misalignment disrupts reward mechanisms. We propose that this disruption of reward mechanisms accelerates the transition from alcohol use to AUDs in vulnerable adolescents. We recognize that adolescent alcohol use is highly contextualized, and thus psychosocial factors that may influence both sleep patterns and alcohol use need to be considered as additional influences or alternative explanations. Furthermore, alcohol use has marked effects on sleep and circadian rhythms (Hasler et al., 2012b, Brower, 2001), adding to the challenge of determining directionality between sleep/circadian disturbance and adolescent alcohol use. We assert here that taking on this challenge is warranted. While psychosocial influences and the effects of alcohol use on sleep and circadian function are also pertinent, we contend that circadian misalignment may be an underappreciated risk factor for adolescent AUDs.

Gender Differences in Lifetime Alcohol Dependence: Results from the National Epidemiologic Survey on Alcohol and Related Conditions

Abstract: Background An extensive clinical literature has noted gender differences in the etiology and clinical characteristics of individuals with alcohol dependence (AD). Despite this knowledge, many important questions remain.

Array-based Profiling of DNA Methylation Changes Associated with Alcohol Dependence

Abstract: Background Epigenetic regulation through DNA methylation may influence vulnerability to numerous disorders, including alcohol dependence (AD). Methods Peripheral blood DNA methylation levels of 384 CpGs in the promoter regions of 82 candidate genes were examined in 285 African Americans (AAs; 141 AD cases and 144 controls) and 249 European Americans (EAs; 144 AD cases and 105 controls) using Illumina GoldenGate Methylation Array assays. Association of AD and DNA methylation changes was analyzed using multivariate analyses of covariance with frequency of intoxication, sex, age, and ancestry proportion as covariates. CpGs showing significant methylation alterations in AD cases were further examined in a replication sample (49 EA cases and 32 EA controls) using Sequenom's MassARRAY EpiTYPER technology. Results In AAs, 2 CpGs in 2 genes (GABRB3 and POMC) were hypermethylated in AD cases compared with controls (p ≤ 0.001). In EAs, 6 CpGs in 6 genes (HTR3A, NCAM1, DRD4, MBD3, HTR2B, and GRIN1) were hypermethylated in AD cases compared with controls (p ≤ 0.001); CpG cg08989585 in the HTR3A promoter region showed a significantly higher methylation level in EA cases than in EA controls after Bonferroni correction (p = 0.00007). Additionally, methylation levels of 6 CpGs (including cg08989585) in the HTR3A promoter region were analyzed in the replication sample. Although the 6 HTR3A promoter CpGs did not show significant methylation differences between EA cases and EA controls (p = 0.067 to 0.877), the methylation level of CpG cg08989585 was nonsignificantly higher in EA cases (26.9%) than in EA controls (18.6%; p = 0.139). Conclusions The findings from this study suggest that DNA methylation profile appears to be associated with AD in a population-specific way and the predisposition to AD may result from a complex interplay of genetic variation and epigenetic modifications.

Alcohol Marketing Receptivity, Marketing-specific Cognitions and Underage Binge Drinking

Abstract: Background: Exposure to alcohol marketing is prevalent and is associated with both initiation and progression of alcohol use in underage youth. The mechanism of influence is not well understood, however. This study tests a model that proposes alcohol-specific cognitions as mediators of the relation between alcohol marketing and problematic drinking among experimental underage drinkers. Methods: This study describes a cross-sectional analysis of 1,734 U.S. 15- to 20-year-old underage drinkers, recruited for a national study of media and substance use. Subjects were queried about a number of alcohol marketing variables including TV time, Internet time, favorite alcohol ad, ownership of alcohol-branded merchandise (ABM), and exposure to alcohol brands in movies. The relation between these exposures and current (30-day) binge drinking was assessed, as were proposed mediators of this relation, including marketing-specific cognitions (drinker identity and favorite brand to drink), favorable alcohol expectancies, and alcohol norms. Paths were tested in a structural equation model that controlled for sociodemographics, personality, and peer drinking. Results: Almost one-third of this sample of ever drinkers had engaged in 30-day binge drinking. Correlations between mediators were all statistically significant (range 0.16 to 0.47), and all were significantly associated with binge drinking. Statistically significant mediation was found for the association between ABM ownership and binge drinking through both drinker identity and having a favorite brand to drink, which also mediated the path between movie brand exposure and binge drinking. Peer drinking and sensation seeking were associated with binge drinking in paths through all mediators. Conclusions: Associations between alcohol marketing and binge drinking were mediated through marketing-specific cognitions that assess drinker identity and brand allegiance, cognitions that marketers aim to cultivate in the consumer.

The Impact of Alcohol and Energy Drink Consumption on Intoxication and Risk-Taking Behavior

Abstract: BACKGROUND: It has been argued that consuming alcohol mixed with energy drinks (AmED) causes a subjective underestimation of intoxication and an increased level of risk-taking behavior To date, however, there is mixed support for AmED-induced reductions in perceived intoxication, and no objective assessment of risk-taking following AmED consumption Consequently, the present study aimed to determine the effect of alcohol and energy drink (ED) consumption on subjective measures of intoxication and objective measures of risk-taking METHODS: Using a placebo-controlled, single-blind, cross-over design, participants (n = 28) attended 4 sessions in which they were administered, in counterbalanced order: 05 g/kg alcohol, 357 ml/kg ED, AmED, and a placebo beverage Participants completed the Biphasic Alcohol Effects Scale and a Subjective Effects Scale at baseline and 30 and 125 minutes postbeverage administration; risk-taking was measured using the Balloon Analogue Risk Task (BART) RESULTS: Participants reported greater subjective intoxication, impairment, and sedation after active relative to placebo alcohol consumption, with no interactive AmED effects However, a significant moderate magnitude increase in stimulation ratings was observed in the AmED relative to alcohol, ED, and placebo conditions There was no independent effect of alcohol, or interactive effect with ED, on the BART A significant, yet small magnitude, increase in risk-taking was evident in active relative to placebo ED conditions CONCLUSIONS: The interactive effect of AmED appears restricted to perceived stimulation, with alcohol-induced increases in subjective intoxication occurring regardless of presence or absence of ED Engagement in risk-taking behavior was only increased by ED consumption; however, this effect was only of small magnitude; at these doses, alcohol consumption, with or without EDs, did not affect risk-taking Further research assessing the dose-dependent effects of AmED on objectively measured risk-taking behavior could clarify whether the ED effect increases with higher doses and whether an interactive effect is observed with higher alcohol doses Language: en

Resting‐State Synchrony in Long‐Term Abstinent Alcoholics

Abstract: Background Alcohol dependence is a disorder with an impulsive and compulsive “drive” toward alcohol consumption and an inability to inhibit alcohol consumption. Neuroimaging studies suggest that these behavioral components correspond to an increased involvement of regions that mediate appetitive drive and reduced involvement of regions that mediate executive control within top-down networks. Little is known, however, about whether these characteristics are present after long periods of abstinence. Methods Resting-state functional magnetic resonance imaging data were collected to examine resting-state synchrony (RSS) differences between 23 long-term abstinent alcoholics (LTAA; 8 women, age: M = 48.46, SD = 7.10), and 23 nonsubstance abusing controls (NSAC; 8 women, age: M = 47.99, SD = 6.70). Using seed-based measures, we examined RSS with the nucleus accumbens (NAcc) and the subgenual anterior cingulate cortex (sgACC). All participants were assessed with the intra/extradimensional set shift task outside of the scanner to explore the relationship between RSS and cognitive flexibility. Results Compared to NSAC, LTAA showed (i) decreased synchrony of limbic reward regions (e.g., caudate and thalamus) with both the anterior cingulate cortex seed and the NAcc seed and (ii) increased synchrony of executive control regions (e.g., dorsolateral prefrontal cortex) with both the NAcc seed and the sgACC seed. RSS differences were significantly correlated with task performance. Conclusions The results are consistent with an interpretation of an ongoing compensatory mechanism in LTAA evident during rest, in which decision-making networks show reduced synchrony with appetitive drive regions and increased synchrony with inhibitory control regions. In addition, RSS differences were associated with cognitive flexibility. These resting-state findings indicate an adaptive mechanism present in long-term abstinence that may facilitate the behavioral control required to maintain abstinence.

Global functional connectivity abnormalities in children with fetal alcohol spectrum disorders.

Abstract: Background Previous studies, including those employing diffusion tensor imaging (DTI), have revealed significant disturbances in the white matter of individuals with fetal alcohol spectrum disorders (FASD). Both macrostructural and microstructural abnormalities have been observed across levels of FASD severity. Emerging evidence suggests that these white matter abnormalities are associated with functional deficits. This study used resting-state functional MRI (fMRI) to evaluate the status of network functional connectivity in children with FASD compared with control subjects. Methods Participants included 24 children with FASD, ages 10 to 17, and 31 matched controls. Neurocognitive tests were administered including Wechsler Intelligence Scales, California Verbal Learning Test (CVLT), and Behavior Rating Inventory of Executive Functioning. High-resolution anatomical MRI data and 6-minute resting-state fMRI data were collected. The resting-state fMRI data were subjected to a graph theory analysis, and 4 global measures of cortical network connectivity were computed: characteristic path length, mean clustering coefficient, local efficiency, and global efficiency. Results Results revealed significantly altered network connectivity in those with FASD. The characteristic path length was 3.1% higher (p = 0.04, Cohen's d = 0.47), and global efficiency was 1.9% lower (p = 0.04, d = 0.63) in children with FASD compared with controls, suggesting decreased network capacity that may have implications for integrative cognitive functioning. Global efficiency was significantly positively correlated with cortical thickness in frontal (r = 0.38, p = 0.005), temporal (r = 0.28, p = 0.043), and parietal (r = 0.36, p = 0.008) regions. No relationship between facial dysmorphology and functional connectivity was observed. Exploratory correlations suggested that global efficiency and characteristic path length are associated with capacity for immediate verbal memory on the CVLT (r = 0.41, p = 0.05 and r = 0.41, p = 0.01, respectively) among those with FASD. Conclusions Resting-state functional connectivity measures provide new insight into the integrity of brain networks in clinical populations such as FASD. Results demonstrate that children with FASD have alterations in core components of network function and that these aspects of brain integrity are related to measures of structure and cognitive functioning.

Stress increases voluntary alcohol intake, but does not alter established drinking habits in a rat model of posttraumatic stress disorder.

Abstract: BACKGROUND: Life-altering anxiety disorders, such as posttraumatic stress disorder (PTSD), can co-occur at high rates with substance use disorders. Alcoholism, compared with other substance use disorders, is particularly common. Rodent studies of acute stress effects on alcohol consumption show that stress can alter ethanol (EtOH) consumption. This study examined voluntary EtOH consumption in male Long-Evans rats that had undergone a stress-enhanced fear learning (SEFL) procedure. METHODS: Adult Long-Evans rats were exposed to a stress that consisted of 15 inescapable foot-shocks (1 mA, 1 second) known to cause a long-lasting nonassociative enhancement of subsequent fear learning. Control animals received no shock. One day later, animals were placed in a novel and very different context and received a single foot-shock. On day 3, animals were returned to the single shock context and freezing was used as a measure of learned fear. The intermittent access 2-bottle choice (2BC) regimen consisted of 1 bottle of water and 1 bottle of experimental solution, either 19% EtOH or 28.4% sucrose-0.08% quinine, for a 24-hour period, 3 days a week, and all other times 2 water bottles. This regimen lasted until stable levels of experimental solution drinking were reached, at which point the experimental solution was removed for 40 days and then returned to measure the resumption of consumption. RESULTS: Rats that received stress prior to EtOH consumed significantly more EtOH than control rats before and after reinstatement. Rats that received stress after drinking was established did not consume significantly more EtOH when the drug was returned. Stress had no significant effect on sucrose-quinine drinking, our calorie and taste control for EtOH. CONCLUSIONS: A single traumatic event sufficient to produce long-lasting enhancement of fear learning increases voluntary EtOH consumption, but does not alter previously acquired EtOH drinking habits or alter the consumption of a calorically equivalent sweet-bitter-tasting solution. Language: en

The association between prenatal alcohol exposure and behavior at 22 years of age.

Abstract: BACKGROUND: Prenatal alcohol exposure (PAE) affects central nervous system development, growth, and morphology at higher exposure levels. Little is known about the effects of PAE at lower exposure levels or in young adults. Research on children with higher levels of PAE has shown that PAE predicts behavior problems. The question remains whether these effects are permanent or ameliorated by maturation into adulthood. METHODS: These data are from a longitudinal study of PAE. Mothers were recruited from a prenatal clinic and interviewed during their fourth prenatal month, seventh month, and delivery. In the postpartum, mothers and offspring were seen at 8 and 18 months, and 3, 6, 10, 14, 16, and 22 years. RESULTS: At 22 years, PAE significantly predicted behavior as measured with the adult self-report. These findings were significant controlling for covariates. Exposure at each trimester predicted increased behavior problems on the Total Score, Internalizing, Externalizing, Attention, and Critical Items scales. Use across pregnancy predicted a higher rate of behavior problems compared to no use and use in the first trimester only. CONCLUSIONS: The effects were dose-response and significant at each trimester of pregnancy. However, duration across pregnancy was a better predictor than drinking during the first trimester only. Binge drinking was not a better predictor of outcome compared to average daily volume (ADV), and within categories of ADV, binge drinking did not predict more problems than nonbinge drinking. Thus, there is no safe level or safe time during pregnancy for women to drink. These data demonstrate that the effects of PAE, even at low to moderate levels, extend into young adulthood and are most likely permanent. Language: en