Neuropharmacology of alcohol addiction

Br J Pharmacol. 2008 May; 154(2): 299–315.

Despite the generally held view that alcohol is an unspecific pharmacological agent, recent molecular pharmacology studies demonstrated that alcohol has only a few known primary targets. These are the NMDA, GABAA, glycine, 5-hydroxytryptamine 3 (serotonin) and nicotinic ACh receptors as well as L-type Ca2+ channels and G-protein-activated inwardly rectifying K+ channels.

Following this first hit of alcohol on specific targets in the brain, a second wave of indirect effects on a variety of neurotransmitter/neuropeptide systems is initiated that leads subsequently to the typical acute behavioural effects of alcohol, ranging from disinhibition to sedation and even hypnosis, with increasing concentrations of alcohol.

Besides these acute pharmacodynamic aspects of alcohol, we discuss the neurochemical substrates that are involved in the initiation and maintenance phase of an alcohol drinking behaviour.

Finally, addictive behaviour towards alcohol as measured by alcohol-seeking and relapse behaviour is reviewed in the context of specific neurotransmitter/neuropeptide systems and their signalling pathways.

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The Impact of Parenthood on Alcohol Consumption Trajectories

Variations as a Function of Timing of Parenthood, Familial Alcoholism and Gender

Dev Psychopathol. 2009; 21(2): 661–682.

The current study tested the impact of the transition to parenthood on growth in alcohol consumption from early adolescence through emerging adulthood.

We measured age-related discontinuity in trajectories of alcohol consumption associated with timing of the parenthood transition, above and beyond the effects of accrued educational status, gender and time-varying marital status.

We also examined the impact of a familial selection factor for the transmission of alcohol use problems, family history density of alcoholism (FHD), on both risk for adolescent parenthood and risk for adolescent parents’ continuity in alcohol consumption after the parent-transition within a mediation structural equation model.

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Physiology and pharmacology of alcohol: the imidazobenzodiazepine alcohol antagonist site on subtypes of GABAA receptors as an opportunity for drug development?

Br J Pharmacol. 2008 May; 154(2): 288–298.

We recently showed that low-dose alcohol enhancement on highly alcohol-sensitive GABAAR subtypes is antagonized by Ro15-4513 in an apparently competitive manner, providing a molecular explanation for behavioural Ro15-4513 alcohol antagonism. The identification of a Ro15-4513/EtOH binding site on unique GABAAR subtypes opens the possibility to characterize this alcohol site(s) and screen for compounds that modulate the function of EtOH/Ro15-4513-sensitive GABAARs.

The utility of such drugs might range from novel alcohol antagonists that might be useful in the emergency room, to drugs for the treatment of alcoholism, as well as alcohol-mimetic drugs to harness acute positive effects of alcohol.

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Short Message Service (SMS) Technology in Alcohol Research—A Feasibility Study

Alcohol and Alcoholism Advance Access published online on May 29, 2009

The aim of this study was to describe the feasibility, advantages and limitations of the combined use of Internet and SMS technology to assess alcohol use, and to test whether an SMS sent in the evening (i.e. prior to a possible drinking event) changed the respondents’ assessment, made on the following day, of the number of drinks consumed.

The new method shares some of the advantages of conventional diaries but overcomes most of the limitations: it is easy to use, cost-effective and suitable for large-scale surveys. Application restrictions and further developments are discussed.

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Request Reprint E-Mail: ekuntsche@sfa-ispa.ch

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Making Sense of Australia's New Alcohol Guidelines

This brief explanatory document is designed for health and human services workers to assist their understanding of: the new NHMRC guidelines ,the ways in which the new guidelines differ from the previous guidelines, how health and human services workers may use the new guidelines in their day-to-day roles.

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Ventral Tegmental Area BDNF Induces an Opiate-Dependent–Like Reward State in Naïve Rats

Science Published Online May 28, 2009

We found that a single infusion of BDNF into the VTA promotes a shift from a dopamine-independent to a dopamine-dependent opiate reward system, identical to that seen when an opiate naïve rat becomes dependent and withdrawn. This shift involves a switch in the GABA-A receptors of VTA GABAergic neurons, from inhibitory to excitatory signaling.

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Request Reprint E-Mail: vargashector@yahoo.com

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Effectiveness of opinion leaders for getting research into practice in the alcohol and other drugs field: Results from a systematic literature review

Drugs: education, prevention and policy, Volume 16, Issue 3 June 2009 , pages 205 - 216

Despite good theoretical underpinnings for the use of opinion leaders to influence change in professionals' behaviour, current evidence of their effectiveness is sparse and inconsistent. There is a need for good quality, well-designed studies that are conducted in an AOD context using opinion leaders who are appropriately identified and adequately supported.

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Request Reprint E-Mail: Petra.Bywood@flinders.edu.au

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Media Influence on Alcohol-Control Policy Support in the U.S. Adult Population: The Intervening Role of Issue Concern and Risk Judgments Journal of Health Communication, Volume 14, Issue 3 April 2009 , pages 262 - 275

Data from a national random-digit dial survey (N = 1,272) were analyzed to examine the influence of news media use on alcohol-control policy support, and to test whether risk judgments and concern about alcohol-related risks mediated effects of news media use variables on support for various types of alcohol-control public policies.

In so doing, we test the proposition that perceptions influenced by routine coverage of events such as crime or accidents may in part explain news effects on public policy support in the domain of health policy.

Analyses indicated that the (positive) influence of attention to news about crime and accidents on support for laws increasing server liability and limiting marketing of alcohol products was mediated by concern about risks of alcohol-related injuries and by perceptions of the alcohol-attributable fraction of homicides and unintended injury fatalities.

Tests of model fit suggest that concern precedes the more cognitive risk judgment in the mediation model.

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Request Reprint E-Mail: slater.59@osu.edu
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Acute alcohol decreases performance of an instrumental response to avoid aversive consequences in social drinkers
Psychopharmacology Online First May 26, 2009

Acute alcohol may decrease the motivation to avoid negative consequences and thus might contribute to risky behaviour and binge drinking.

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Request Reprint E-Mail: t.duka@sussex.ac.uk

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A metacognitive model of problem drinking
Clinical Psychology & Psychotherapy Published Online: 28 May 2009


Previous research has demonstrated significant relationships between metacognition and problem drinking. In this study, we aimed to investigate further these relationships by testing the fit of a metacognitive model of problem drinking in a sample of 174 problem drinkers from a university student population.

In the model presented, it is proposed that positive metacognitive beliefs about alcohol use and negative affect lead to alcohol use as a means of affect regulation. Positive metacognitive beliefs about alcohol use are also associated with a reduction in metacognitive monitoring which further contributes to alcohol use. Once alcohol use is initiated it brings a disruption in metacognitive monitoring leading to a continuation in drinking. Following a drinking episode, alcohol use is appraised as both uncontrollable and dangerous, which in turn strengthens negative metacognitive beliefs about alcohol use. These beliefs are associated with an escalation of negative affect, which acts as a trigger for further drinking.

The specified relationships among these variables were examined by testing the fit of a path model. Results of this analysis indicated a good model fit consistent with predictions. The conceptual and clinical implications of these data are discussed.

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Request Reprint E-Mail: M.Spada@roehampton.ac.uk
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Changing attitudes, knowledge and behaviour

A review of successful initiatives

This report examines how initiatives successfully used in other fields can help inform new strategies for tackling alcohol-related harm.

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Exposure of children and adolescents to alcohol advertising on Australian metropolitan free-to-air television

Addiction Published Online: 12 May 2009

The self-regulation system in Australia does not protect children and youth from exposure to alcohol advertising, much of which contains elements appealing to these groups.

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Request Reprint E-Mail: : l.fielder@curtin.edu

The importance of drinking frequency in evaluating individuals' drinking patterns: implications for the development of national drinking guidelines

Addiction Published Online: 11 May 2009

Given that risk and frequency of binge drinking among Canadians increases with their frequency of drinking, any public recommendation to drink moderately should be made with great caution.

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Request Reprint E-Mail: catherine_paradis@yahoo.ca

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Shoveling Up II: The Impact of Substance Abuse on Federal, State and Local Budgets

In this report, The National Center on Addiction and Substance Abuse(CASA) at Columbia University has identified the total amount spent by federal, state and local governments on substance abuse and addiction--the first timesuch an analysis has ever been undertaken.

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Intravenous Ethanol Infusions Can Mimic the Time Course of Breath Alcohol Concentrations Following Oral Alcohol Administration in Healthy Volunteers

Alcoholism: Clinical and Experimental Research Volume 33 Issue 5, Pages 938 - 944

Despite the use of standardized doses and controlled experimental conditions, there was substantial between-subject variability in the BrAC time course following oral administration of alcohol. The PBPK-model-based infusion method can mimic the BrACs attained with oral alcohol for individual subjects. This method provides a platform to evaluate effects attributable to the route of administration on the response to alcohol, as well as the influence of determinants such as family history of alcoholism on the alcohol response.

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Request Reprint E-Mail vijayr@mail.nih.gov
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Blood Glucose Level, Alcohol Heavy Drinking, and Alcohol Craving During Treatment for Alcohol Dependence: Results From the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) Study
Alcoholism: Clinical and Experimental Research Published Online: 26 May 2009

A link between pretreatment glucose levels and heavy drinking during treatment was found, suggesting a role of glucose in predicting heavy alcohol consumption. Although caution is needed in the interpretation of these results, elevated glucose and heavy drinking may be affected by a common mechanism and manipulations affecting glucose regulation may influence alcohol consumption.

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Request Reprint E-Mail: lorenzo_leggio@brown.edu _________________________________________________

Sensitization of Ventral Tegmental Area Dopamine Neurons to the Stimulating Effects of Ethanol
Alcoholism: Clinical and Experimental Research Published Online: 26 May 2009

The results indicate that repeated local ethanol exposure of the p-VTA produced neuroadaptations in DA neurons projecting to the NAc shell, resulting in a persistent increase in the sensitivity of these neurons to the stimulating effects of ethanol.

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Request Reprint E-Mail: zding@iupui.edu
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Extreme College Drinking and Alcohol-Related Injury Risk

Alcoholism: Clinical and Experimental Research Published Online: 26 May 2009

College health clinics may want to focus limited alcohol injury prevention resources on students who frequently engage in extreme drinking, defined in this study as 8+M/5+F drinks per day, and score high on sensation-seeking disposition.

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Request Reprint E-Mail: marlon.mundt@fammed.wisc.edu

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A Double-Blind Trial of Gabapentin Versus Lorazepam in the Treatment of Alcohol Withdrawal
Alcoholism: Clinical and Experimental Research Published Online: 26 May 2009

Gabapentin was well tolerated and effectively diminished the symptoms of alcohol withdrawal in our population especially at the higher target dose (1200 mg) used in this study. Gabapentin reduced the probability of drinking during alcohol withdrawal and in the immediate postwithdrawal week compared to lorazepam.

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Request Reprint E-Mail: myrickh@musc.edu
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Screening for Hazardous Drinking Using the Michigan Alcohol Screening Test–Geriatric Version (MAST-G) in Elderly Persons With Acute Cerebrovascular Accidents

Alcoholism: Clinical and Experimental Research
Published Online: 26 May 2009

The 10-item SMAST-G and 2-item MMAST-G are brief screening tests that show comparable effectiveness in detecting hazardous drinking in elderly patients with acute CVA compared with the full 24-item MAST-G. Implications for research and clinical practice are discussed.

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Request Reprint E-Mail: djgreene@med.miami.edu

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Externalizing Psychopathology and Risk for Suicide Attempt: Cross-Sectional and Longitudinal Findings From the Baltimore Epidemiologic Catchment Area Study

The Journal of Nervous and Mental Disease: May 2009 - Volume 197 - Issue 5 - pp 293-297

Externalizing psychopathology appears to be an independent short-term risk factor for suicidal behavior interval , but appears less powerful in predicting long-term suicide risk .

These findings underline the importance of assessment of suicidality among individuals presenting with externalizing disorders.

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Request Reprint E-Mail: Ahills@exchange.hsc.mb.ca

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Systematic Review of interventions for children with Fetal Alcohol Spectrum Disorders

BMC Pediatrics 2009, 9:35

There is limited good quality evidence for specific interventions for managing FASD, however seven randomized controlled trials that address specific functional deficits of children with FASD are underway or recently completed.

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The Relationships of the Level of Response to Alcohol and Additional Characteristics to Alcohol Use Disorders Across Adulthood: A Discrete-Time Survival Analysis

Alcoholism: Clinical and Experimental Research Published Online: 26 May 2009

The findings illustrate that LR is a unique risk factor for AUDs across adulthood, and not simply a reflection of a broader range of risk factors. The continued investigation of how LR is related to AUD onset later in life will help inform treatment providers about this high-risk population, and future longitudinal evaluations will utilize DTSA to assess rates of AUD remission as well as the onset of drinking outcomes in adolescent samples.

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Request Reprint E-Mail: rstrim@gmail.com

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Acute and chronic alcohol dose: population differences in behavior and neurochemistry of zebrafish

Genes, Brain and Behavior Published Online: 19 Feb 2009

The results showed genetic differences in numerous aspects of alcohol-induced changes, including, for the first time, the behavioral effects of withdrawal from alcohol and neurochemical responses to alcohol. For example, withdrawal from alcohol abolished shoaling and increased dopamine and 3,4-dihydroxyphenylacetic acid in AB but not in SF fish.

The findings show that, first, acute and chronic alcohol induced changes are quantifiable with automated behavioral paradigms; second, robust neurochemical changes are also detectable; and third, genetic factors influence both alcohol-induced behavioral and neurotransmitter level changes.

Although the causal relationship underlying the alcohol-induced changes in behavior and neurochemistry is speculative at this point, the results suggest that zebrafish will be a useful tool for the analysis of the biological mechanisms of alcohol-induced functional changes in the adult brain.

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Request Reprint E-Mail: robert_gerlai@yahoo.com

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Alcohol use and comorbid anxiety, traumatic stress, and hopelessness among Hispanics
Addictive Behaviors Article in Press 4 May 2009

This study provides evidence of the need for further investigation of stress, trauma, anxiety, hopelessness, and alcohol abuse in Mexican American residents and to inform future prevention and treatment efforts to improve both the physical and mental health of this population.

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Request Reprint E-Mail: awblume@uncc.edu
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Validation of the drinking refusal self-efficacy questionnaire in Arab and Asian samples
Addictive Behaviors Article in Press 22 May 2009

Exploratory and confirmatory factor analysis demonstrated that the DRSEQ-R has a three factor structure. Internal consistency ranged from α .96 to α .86 and validity was good. This study offers evidence of the utility of this measure with Arab and Asian samples.

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Request Reprint E-Mail: tayyibaalmarri@gmail.com
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Cost-Effectiveness of Screening for Unhealthy Alcohol Use with %Carbohydrate Deficient Transferrin: Results From a Literature-Based Decision Analytic Computer Model

Alcoholism: Clinical and Experimental Research Published Online: 4 May 2009

Adding %CDT to questionnaire-based screening for unhealthy alcohol use was cost-effective in our literature-based decision analytic model set in typical primary care conditions. Screening with %CDT should be considered for adults up to the age of 60 when the prevalence of unhealthy alcohol use is 15% or more and screening questionnaires are negative.

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Request Reprint E-Mail: alok.kapoor@BMC.org

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Mood-Related Drinking Motives Mediate the Familial Association Between Major Depression and Alcohol Dependence

Alcoholism: Clinical and Experimental Research Published Online: 4 May 2009

The results are consistent with an indirect role for mood-related drinking motives in the etiology of depression and alcohol dependence, and suggest that mood-related drinking motives may be a useful index of vulnerability for these conditions.

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Request Reprint E-Mail: cprescot@usc.edu

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Can Serotonin Transporter Genotype Predict Craving in Alcoholism?

Alcoholism: Clinical and Experimental Research Published Online: 4 May 2009

These results not only provide support for the hypothesis that alcoholics who are L-carriers have greater alcohol craving and possibly greater propensity for drinking but also propose that there is an important 5-HTT gene-by-environment interaction that alters cue craving response for alcohol.

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Request Reprint E-Mail: aitdaoud@virginia.edu

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Gender differences in 16-year trends in assault- and police-related problems due to drinking

Addictive Behaviors Article in Press 4 May 2009

This study examined the frequency and predictors of physical assault and having trouble with the police due to drinking over 16 years among women and men who, at baseline, were untreated for their alcohol use disorder.

Predictors examined were the personal characteristics of impulsivity, self-efficacy, and problem-solving and emotional-discharge coping, as well as outpatient treatment and Alcoholics Anonymous (AA) participation.

Women and men were similar on rates of perpetrating assault due to drinking, but men were more likely to have had trouble with the police due to drinking. Respondents who, at baseline, were more impulsive and relied more on emotional discharge coping, and less on problem-solving coping, assaulted others more frequently during the first year of follow-up. Similarly, less problem-solving coping at baseline was related to having had trouble with the police more often at one and 16 years due to drinking.

The association between impulsivity and more frequent assault was stronger for women, whereas associations of self-efficacy and problem-solving coping with less frequent assault and police trouble were stronger for men. Participation in AA was also associated with a lower likelihood of having trouble with the police at one year, especially for men.

Interventions aimed at decreasing impulsivity and emotional discharge coping, and bolstering self-efficacy and problem-solving coping, during substance abuse treatment, and encouragement to become involved in AA, may be helpful in reducing assaultive and other illegal behaviors.

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Request Reprint E-Mail: ctimko@stanford.edu

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Happyhour, a Ste20 Family Kinase, Implicates EGFR Signaling in Ethanol-Induced Behaviors

Cell.2009.03.020

The consequences of alcohol use disorders (AUDs) are devastating to individuals and society, yet few treatments are currently available. To identify genes regulating the behavioral effects of ethanol, we conducted a genetic screen in Drosophila and identified a mutant, happyhour (hppy), due to its increased resistance to the sedative effects of ethanol.

Hppy protein shows strong homology to mammalian Ste20 family kinases of the GCK-1 subfamily. Genetic and biochemical experiments revealed that the epidermal growth factor (EGF)-signaling pathway regulates ethanol sensitivity in Drosophila and that Hppy functions as an inhibitor of the pathway.

Acute pharmacological inhibition of the EGF receptor (EGFR) in adult animals altered acute ethanol sensitivity in both flies and mice and reduced ethanol consumption in a preclinical rat model of alcoholism. Inhibitors of the EGFR or components of its signaling pathway are thus potential pharmacotherapies for AUDs.

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Request Reprint E-Mail: ulrike.heberlein@ucsf.edu

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ADOLESCENT ALCOHOL- AND ILLICIT DRUG-USE IN FIRST AND SECOND GENERATION IMMIGRANTS IN SWEDEN

WORKING PAPER No 8 / 2009

In this paper adolescent alcohol- and illicit drug-use among 1st and 2nd generation immigrants from Nordic, non-Nordic European and non-European countries were compared with the Swedish majority population.

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ALCOHOL USE AND SOCIAL INTERACTIONS AMONG ADOLESCENTS

Do peer-effects exist within and/or between the majority population and
immigrants?
WORKING PAPER No 7 / 2009


Are adolescents who attend schools with a high level of alcohol use more
likely to use alcohol themselves? This paper analyzes peer-effects in adolescent alcohol use based on a survey of 13,337 adolescents in Sweden in 2005. The empirical analysis uses multi-level logistic model to handle non-observable heterogeneity between the schools and the results show that attending a school with a high level of alcohol use is a strong predictor of alcohol use for the individual. However, a positive association is only
seen within Swedes and within non-Swedes (1st and 2nd generation immigrants).

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ADOLESCENTS ALCOHOL-USE AND ECONOMIC CONDITIONS

A Multilevel Analysis of Data from a Period with Big Economic Changes

WORKING PAPER No 6 / 2009

This paper examines how the unemployment rate is related to adolescent alcohol use during a time period characterized by big societal changes using repeated cross-sectional adolescent survey data from a Swedish region, collected in 1988, 1991, 1995, 1998, 2002 and 2005. Individual level alcohol use is connected to local level unemployment rate to estimate the relationship using multilevel modeling.

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The recovery revolution: news from the front

William White, Senior Research Consultant, Chestnut Health Systems, Bloomington, USA

This presentation will briefly review the history and status of this movement in the United States to transform systems of care for individuals and families wounded by alcohol and other drug problems.

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Associations Among GABRG1, Level of Response to Alcohol, and Drinking Behaviors

Alcoholism: Clinical and Experimental Research Published Online: 4 May 2009

Analyses revealed that a SNP of the GABRG1 gene (rs1497571) was associated with level of response to alcohol and drinking patterns in this subclinical sample. Follow-up mediational analyses were also conducted to examine putative mechanisms underlying these associations.

These findings replicate and extend recent research suggesting that genetic variation at the GABRG1 locus may underlie the expression of alcohol phenotypes, including level of response to alcohol.

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Request Reprint E-Mail: lararay@psych.ucla.edu

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Minimum drinking age laws and infant health outcomes

Journal of Health Economics Volume 28, Issue 3, May 2009, Pages 737-747

The evidence suggests that lenient drinking laws generate poor birth outcomes in part because they increase the number of unplanned pregnancies.

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Request Reprint E-Mail: Tara.Watson@williams.edu

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