A haplotype analysis is consistent with the role of functional HTR1B variants in alcohol dependence

Animal and human studies have suggested that the serotonergic system plays an important role in alcohol consumption and abuse, mainly due to the serotonin receptor 1B (5-HT_1B) function in the mesolimbic reward pathway. Association studies between the HTR1B gene variants and alcoholism have found significant results. There is also evidence for a complex balancing regulation of the gene by two functional variants in the promoter region (rs11568817 and rs130058), which are in linkage disequilibrium.

The aim of this study is to investigate the role of the most relevant variants (rs11568817, rs130058, rs6296 and rs13212041) of the HTR1B gene in the susceptibility to alcohol dependence. The sample comprised 136 Brazilian alcoholics of European descendent and 237 controls.

The results suggest an association between a functional variant of the gene (rs11568817) and alcohol dependence (p = 0.001). In addition, this association could also be confirmed in an independent sample using imputed data from a GWAS, where marginal significant association (p = 0.03, one-tailed) with the same allele was obtained. The pattern of distribution of haplotypes was significantly different between patients and controls (p < 0.0001), which is consistent with the role of the two functional variants of the promoter region.

In conclusion, our findings point to an association between functional variants in the promoter region of the HTR1B gene and alcohol dependence, supporting previous neurobiological evidences of the involvement of HTR1B variations in alcohol-related phenotypes.

Read Full Abstract

Requset Reprint E-Mail: claiton.bau@ufrgs.br

Child maltreatment increases sensitivity to adverse social contexts: Neighborhood physical disorder and incident binge drinking in Detroit

Exposure to child maltreatment is associated with elevated risk for behavioral disorders in adulthood. One explanation for this life-course association is that child maltreatment increases vulnerability to the effects of subsequent stressors; however, the extent to which maltreatment increases sensitivity to social context has never been examined. We evaluated whether the association between neighborhood physical disorder and binge drinking was modified by child maltreatment exposure.

Data were drawn from the Detroit Neighborhood Health Study, a prospective representative sample of predominately African Americans in the Detroit population. Neighborhood physical disorder was measured via systematic neighborhood assessment. Child maltreatment indicators included self-reported physical, sexual, and emotional abuse. Incident binge drinking was defined as at least one episode of ≥5 drinks (men) or ≥4 drinks (women) in the past 30-day period among those with no binge drinking at baseline (N = 1013).

Child maltreatment and neighborhood physical disorder interacted to predict incident binge drinking (B = 0.16, p = 0.02) and maximum number of past 30-day drinks (B = 0.15, p = 0.04), such that neighborhood physical disorder predicted problematic alcohol use only among individuals with high exposure to child maltreatment.

The results add to the growing literature that African Americans in the US are exposed to an array of stressors that have pernicious consequences for problematic alcohol use. Our results document the need for increased attention to the potential for at-risk alcohol use among populations with a high degree of stress exposure.

Read Full Abstract

Request Reprint E-Mail: kmk2104@columbia.edu

Different genes influence toluene- and ethanol-induced locomotor impairment in C. elegans

The abused volatile solvent toluene shares many behavioral effects with classic central nervous system depressants such as ethanol. Similarities between toluene and ethanol have also been demonstrated using in vitro electrophysiology. Together, these studies suggest that toluene and ethanol may be acting, at least in part, via common mechanisms.

We used the genetic model, Caenorhabditis elegans, to examine the behavioral effects of toluene in a simple system, and used mutant strains known to have altered responses to other CNS depressants to examine the involvement of those genes in the motor effects induced by toluene.

Toluene vapor brings about an altered pattern of locomotion in wild-type worms that is visibly distinct from that generated by ethanol. Mutants of the slo-1, rab-3 and unc-64 genes that are resistant to ethanol or the volatile anesthetic halothane show no resistance to toluene. A mutation in the unc-79 gene results in hypersensitivity to ethanol, halothane and toluene indicating a possible convergence of mechanisms of the three compounds. We screened for, and isolated, two mutations that generate resistance to the locomotor depressing effects of toluene and do not alter sensitivity to ethanol.

In C. elegans, ethanol and toluene have distinct behavioral effects and minimal overlap in terms of the genes responsible for these effects. These findings demonstrate that the C. elegans model system provides a unique and sensitive means of delineating both the commonalities as well as the differences in the neurochemical effects of classical CNS depressants and abused volatile inhalants.

Read Full Abstract

Request Reprint E-Mail: agdavies@vcu.edu

Analyses related to the development of DSM-5 criteria for substance use related disorders: 2. Proposed DSM-5 criteria for alcohol, cannabis, cocaine a

A number of changes have been proposed and investigated in the criteria for substance use disorders in DSM-5. However, although clinical utility of DSM-5 is a high priority, relatively little of the empirical evidence supporting the changes was obtained from samples of substance abuse patients.

Proposed changes were examined in 663 patients in treatment for substance use disorders, evaluated by experienced clinicians using the Psychiatric Research Interview for Substance and Mental Disorders (PRISM). Factor and item response theory analysis was used to investigate the dimensionality and psychometric properties of alcohol, cannabis, cocaine and heroin abuse and dependence criteria, and craving.

The seven dependence criteria, three of the abuse criteria (hazardous use; social/interpersonal problems related to use; neglect of roles to use), and craving form a unidimensional latent trait for alcohol, cannabis, cocaine and heroin. Craving did not add significantly to the total information offered by the dependence criteria, but adding the three abuse criteria and craving together did significantly increase total information for the criteria sets associated with alcohol, cannabis and heroin.

Among adult patients in treatment for substance disorders, the alcohol, cannabis, cocaine and heroin criteria for dependence, abuse (with the exception of legal problems), and craving measure a single underlying dimension. Results support the proposal to combine abuse and dependence into a single diagnosis in the DSM-5, omitting legal problems. Mixed support was provided for the addition of craving as a new criterion, warranting future studies of this important construct in substance use disorders.

Read Full Abstract

Request Reprint E-Mail: dsh2@columbia.edu

News Release - Four new members named to the National Advisory Council on Alcohol Abuse and Alcoholism

U.S. Department of Health and Human Services Secretary Kathleen Sebelius recently appointed four new members to the National Advisory Council on Alcohol Abuse and Alcoholism of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). The council advises the Secretary, the Director of the National Institutes of Health and the director of NIAAA on program and policy matters, offers recommendations on research conducted at NIAAA, and reviews applications for grants and cooperative agreements.

The 15-member council includes outstanding representatives from health and science fields relevant to NIAAA activities, as well as leaders from among the general public in fields including health policy, law, economics, and management.

“We are delighted to welcome this distinguished group of leaders to our advisory council,” said NIAAA Acting Director Kenneth R. Warren, Ph.D. “NIAAA will benefit greatly from their insight and experience.”

The recently appointed council members are:

The Honorable Linda Chezem J.D., who is a professor in the Department of Youth Development and Agriculture Education in the College of Agriculture at Purdue University, West Lafayette, Ind. The first woman to serve as a department head in the College of Agriculture, Chezem teaches at both the undergraduate and graduate levels, as well as in the law school, where her courses include Alcohol Science and Law. She also holds an adjunct appointment in the Department of Medicine at the Indiana University School of Medicine, Indianapolis. Chezem was the first woman to serve as a circuit court judge in Indiana and the second woman to be appointed as presiding judge on the Indiana Court of Appeals. In September 2007, Governor Mitch Daniels appointed her to serve on the Indiana Health Informatics Corporation Board. Among her many awards, Chezem received the Richard M. Fairbanks Circle of Hope Award from the Fairbanks Addiction Treatment Center, the oldest independent drug and treatment center in the United States, for her outstanding contributions to research, education, and treatment of drug and alcohol abuse and addiction.

Fulton Crews, Ph.D., who is the director of the Bowles Center for Alcohol Studies, and the John R. Andrews Professor of Pharmacology and Psychiatry at the School of Medicine at the University of North Carolina at Chapel Hill. Dr. Crews is also director of the NIAAA-supported Comprehensive Alcohol Research Center at the Bowles Center. Respected internationally for his research on addiction, neurodegeneration, depression and alcohol-related neuropathology, Crews is a longtime NIH grantee, and the author of more than 200 scientific articles published in peer reviewed journals and books. Crews serves on many editorial boards, as well as on the board of directors of several agencies. He has served on numerous NIH peer review committees and is the chair of the NIAAA Advisory Council’s Extramural Advisory Working Group. Crews has received numerous awards, including the Norbert Kelly Distinguished Award on Addiction from the Addiction Professionals of North Carolina, an NIAAA Method to Extend Research in Time Award, and the NIAAA Mark Keller Memorial Lecture Award.

Mimi Fleury, a parent who is founder and president of the Community of Concern, North Bethesda, Md., a non-profit organization that focuses on disseminating information to help keep youth free from alcohol and drug use. Her efforts to raise awareness about drinking and drug use among young people have been widely effective, and she has successfully established Community of Concern organizations in 24 states. Fleury’s organization published A Parent’s Guide for the Prevention of Alcohol, Tobacco and Other Drug Use. This booklet received critical acclaim from scientific experts and community organizations, as well as the Caron Foundation Award for Educational Excellence. Fleury received the Parents’ Council of Washington Volunteer of the Year Award for her work on this book.

Craig J. McClain, M.D., who is professor of medicine at the School of Medicine, University of Louisville and the chief of gastroenterology at the Louisville Veterans Administration Medical Center in Kentucky. McClain also serves as chief of research affairs, Division of Gastroenterology, Hepatology, and Nutrition, associate vice president for translational research, and distinguished university scholar. McClain is an internationally distinguished clinician-scientist in the fields of gastroenterology, alcoholic liver disease, nutrition, and infectious diseases including HIV/AIDS. Since 1977, McClain has earned funding from the Veterans Administration, and multiple institutes of the NIH including NIAAA, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institute of Neurological Diseases and Strokes. He has published 300 peer-reviewed articles and 100 manuscripts in books and proceedings. He has been a member of many editorial boards, NIH peer review committees, and was a member of the Center for Scientific Review/NIH Advisory Council. His numerous awards include the Jewish Hospital Distinguished Chair in Hepatology and the NIAAA Method to Extend Research in Time Award. > > > > Read More

Global Actions: March 14, 2012

Key Recent Milestones:

· Russia: ICAP held a Master Class in Moscow for industry stakeholders from Russia and Ukraine as part of its effort to build capacity across the alcohol industry.



Global Actions in Focus: Self-Regulation in the Philippines

As part of the collaboration between The International Center for Alcohol Policies (ICAP) and the World Federation of Advertisers (WFA) on self-regulation, Global Actions in the Philippines has reached two important milestones.

In August 2011, the Philippine local self-regulary organization - the Ad Standards Council (ASC) - introduced a system of pre-clearance of alcohol beverage ads in print form. The decision is intended to ensure that print ads are treated in the same manner that alcohol beverage ads are addressed in other media (TV, radio, outdoor). It reinforces the credibility of beverage alcohol advertising self-regulation in the Philippines. During the course of 2012, the local advertising association (the Philippine Association of National Advertisers – PANA) and the ASC will seek to extend the scope of pre-clearance to include digital advertising with the support of key local stakeholders such as the Internet and Mobile Marketing Association of the Philippines (IMMAP).

A second milestone was reached in the fall of 2011 when ASC launched an ambitious awareness raising campaign across four national TV channels and on radio. The campaign highlighted ASC’s role in the self-regulation process and ran a second time in February 2012. The two ads, Baby Ver. 1 and Suitor Ver. 1 can he viewed on YouTube. Once the campaign has concluded, PANA and ASC will undertake a second national awareness survey in 2012 in order to measure results of the campaign with the pre-campaign survey and report on the impact of the campaign on consumer awareness in the Philippines.

What’s Happening Next:

· Brussels: The European Advertising Standards Alliance (EASA) is holding a self-regulation conference on March 28.

Lifestyle Change and High-Density Lipoprotein Change: The US Department of Veterans Affairs Normative Aging Study

We sought to determine whether lifestyle modifications are associated with high-density lipoprotein cholesterol (HDL-C) change in a cohort with long-term follow-up.

Hypothesis: Changes in alcohol consumption, smoking, or body mass index (BMI) are associated with within-individual changes in HDL-C.

We selected 1420 men with ≥2 HDL-C measurements from the US Department of Veterans Affairs Normative Aging Study (NAS). Changes in HDL-C (in milligrams/deciliter) over a 3-year period were calculated for each pair of exams. For each interval of HDL-C change, lifestyle exposures were categorized: participants maintained a stable BMI >25 kg/m² (reference) or ≤25 kg/m² since the previous exam, or increased or decreased BMI; participants were actively smoking at both exams (reference), nonsmokers at both exams, quit, or initiated smoking between exams; and participants maintained alcohol intake of <2 (reference) or ≥2 drinks daily since the previous exam, or increased or decreased alcohol intake. Longitudinal analysis was used to examine the relationship between the lifestyle change categories and 3-year change in HDL-C for each interval, adjusting for comorbidities, lipids, and cholesterol medication.

Participants were followed for approximately 14.3 years. Increases in HDL-C were associated with maintaining alcohol intake of ≥2 drinks daily (mean HDL-C increase, 0.86; P = 0.02), increasing alcohol intake from <2 to ≥2 drinks daily (mean, 2.53; P = 0.0003), and with maintaining a BMI of ≤25 kg/m² (mean, 0.71; P = 0.04).

Increases in alcohol consumption, maintaining moderate alcohol intake, and maintaining BMI ≤25 kg/m² were associated with significant 3-year increases in HDL-C.

Read Full Abstract

Request Reprint E-Mail: crahilly-tierney@partners.org

Binge Britain in the spotlight

Last summer, the performance artist Bryony Kimmings locked herself in a warehouse in Bethnal Green, east London and got drunk for a week. Not for fun, you understand, but in the name of art: her aim was to explore the links between intoxication and creativity, or to find out whether she was a better artist when she was drunk.

The conclusions reached during her binge make up her theatre piece, 7 Day Drunk. In the show, "created drunk, performed sober", Kimmings relives her experiment in front of an audience, one of whom is handed a pint of vodka and cranberry juice and asked to drink the same amount while watching it as she did while creating it.

Kimmings is not the only performer bringing bar-room culture into the theatre. The Paper Birds trawled the pubs and clubs of London and Leeds to find the raw material for their latest show, Thirsty. They set up a hotline, printed up business cards with the words "Are you drunk? Call this number" and used the voicemails they received as the inspiration for their play about young women and binge drinking, performed to a shouty soundtrack of karaoke classics on a set made out of toilet cubicles. > > > > Read More

Fetal Alcohol Exposure

Fetal alcohol exposure occurs when a woman drinks while pregnant. Alcohol can disrupt fetal development at any stage during a pregnancy—including at the earliest stages before a woman even knows she is pregnant.

Research shows that binge drinking, which means consuming four or more drinks per occasion, and regular heavy drinking put a fetus at the greatest risk for severe problems. But even lesser amounts can cause damage.

Alcohol passes easily from a mother’s bloodstream into her developing baby’s blood. Alcohol present in a developing baby’s bloodstream can interfere with the development of critical organs and body parts, including the brain.

Prenatal alcohol exposure is the leading preventable cause of birth defects in the United States. It can cause a range of developmental, cognitive, and behavioral problems, which can appear at any time during childhood and last a lifetime. > > > > Read More

Sexual Deprivation Increases Ethanol Intake in Drosophila

The brain’s reward systems reinforce behaviors required for species survival, including sex, food consumption, and social interaction. Drugs of abuse co-opt these neural pathways, which can lead to addiction.

Here, we used Drosophila melanogaster to investigate the relationship between natural and drug rewards.

In males, mating increased, whereas sexual deprivation reduced, neuropeptide F (NPF) levels. Activation or inhibition of the NPF system in turn reduced or enhanced ethanol preference.

These results thus link sexual experience, NPF system activity, and ethanol consumption. Artificial activation of NPF neurons was in itself rewarding and precluded the ability of ethanol to act as a reward.

We propose that activity of the NPF–NPF receptor axis represents the state of the fly reward system and modifies behavior accordingly.


Read Full Abstract

Request Reprint E-Mail: : shohatophirg@janelia.hhmi.org (G.S.-O.); ulrike.heberlein@ucsf.edu (U.H.)

Home Office evaluation of Alcohol Arrest Referral pilots: ARRs do not appear cost-effective

The Home Office has published a report on the findings of the two Alcohol Arrest Referral (AAR) pilots. The AAR pilots took place between 2007 and 2010 in twelve police forces, but the evaluation did not find measurable reductions in re-offending or overall cost efficacy, despite evidence of reduced drinking.

The AAR pilots built on the early success of schemes such as the AAR in Dudley and Worcester, which were evaluated by Professor Doug Sharp in 2004. These early schemes appeared succesful and roll out of similar schemes was supported by the 2007 national alcohol strategy. However a 2009 Home Office guide to setting up ARRs warned of the challenges. > > > > Read More

Acute Alcohol Effects on Contextual Memory BOLD Response: Differences Based on Fragmentary Blackout History

Contextual memory, or memory for source details, is an important aspect of episodic memory and has been implicated in alcohol-induced fragmentary blackouts (FBs). Little is known, however, about how neural functioning during contextual memory processes may differ between individuals with and without a history of FB. This study examined whether neural activation during a contextual memory task differed by history of FB and acute alcohol consumption.

Twenty-four matched individuals with (FB+; n = 12) and without (FB−; n = 12) a history of FBs were recruited from a longitudinal study of alcohol use and behavioral risks and completed a laboratory beverage challenge followed by 2 functional magnetic resonance imaging (fMRI) sessions under no alcohol and alcohol (breath alcohol concentration = 0.08%) conditions. Task performance and brain hemodynamic activity during a block design contextual memory task were examined across 48 fMRI sessions.

Groups demonstrated no differences in performance on the contextual memory task, yet exhibited different brain response patterns after alcohol intoxication. A significant FB group by beverage interaction emerged in bilateral dorsolateral prefrontal cortex and posterior parietal cortex with FB− individuals showing greater blood oxygenation level-dependent response after alcohol exposure (p < 0.05).

Alcohol had differential effects on neural activity for FB+ and FB− individuals during recollection of contextual information, perhaps suggesting a neurobiological mechanism associated with alcohol-induced FB.

Read Full Abstract

Request Reprint E-Mail: rwetherill@ucsd.edu

Learning from Positive and Negative Monetary Feedback in Patients with Alcohol Dependence

Chronic and excessive consumption of alcohol is associated with structural, physiological, and functional changes in multiple regions of the human brain including the prefrontal cortex, the medial temporal lobe, and the structures of the reward system. The present study aimed to assess the ability of alcohol-dependent patients (ADP) to learn probabilistic stimulus–reward contingencies and to transfer the acquired knowledge to new contexts. During transfer, the relative preference to learn from positive or negative feedback was also assessed.

Twenty-four recently detoxified ADP and 20 healthy controls engaged in a feedback learning task with monetary rewards. The learning performance per se and transfer performance including positive versus negative learning were examined, as well as the relationship between different learning variables and variables comprising alcohol and nicotine consumption patterns, depression, and personality traits (harm avoidance and impulsivity).

Patients did not show a significant general learning deficit in the acquisition of stimulus–response–outcome associations. Fifteen healthy subjects and 13 patients reached the transfer phase, in which ADP showed generally lower performance than healthy controls. There was no specific deficit with regard to learning from positive or negative feedback. The only near-significant (negative) correlation between learning variables and drug consumption patterns, depression, and personality traits emerged for harm avoidance and positive learning in controls.

Impaired transfer performance suggests that ADP had problems applying their acquired knowledge in a new context. Potential relations to dysfunctions of specific brain structures and implications of the finding for therapy are discussed.

Read Full Abstract

Request Reprint E-Mail: martina.rustemeier@rub.de

Impact of Multiple Types of Childhood Trauma Exposure on Risk of Psychiatric Comorbidity Among Alcoholic Inpatients

This study examined the prevalence of single- and multiple-type childhood trauma exposure (CTE) among alcoholic patients undergoing inpatient detoxification and treatment. The relationships between various types of CTE and lifetime psychiatric comorbidities and suicide attempts were also explored.

A total of 196 alcoholic inpatients were assessed by Structured Clinical Interview for DSM-IV Axis I Disorders and Childhood Trauma Questionnaire (CTQ) for CTE history.

The overall prevalence of CTE in the entire sample was high (55.1%). Specifically, the prevalence of emotional abuse was 21.4%, physical abuse 31.1%, sexual abuse 24.0%, emotional neglect 20.4%, and physical neglect 19.9%. Regarding multiple types of CTE, 31.7 and 18.9% reported at least 2 and at least 3 CTE types, respectively. Strikingly, among those with at least 1 positive CTQ category, more than half reported 2 or more CTE types. A history of emotional abuse increased the risk of mood disorder, in particular major depressive disorder, as well as posttraumatic stress disorder (PTSD). Physical abuse contributed to the prediction of suicide attempts, while sexual abuse was associated with a diagnosis of anxiety disorder, PTSD, and multiple comobidities (e.g., anxiety and mood disorder). The number of reported CTE types or the total score of the CTQ predicted an increased risk of having single or multiple psychiatric comorbidities as well as suicide attempts.

We observed high rates of a broad range of CTE types and a trend for CTE-specific enhancement of risk for various psychiatric outcomes among alcoholic inpatients. Of note, a dose–response relationship between number of CTE types and risk of psychiatric comorbidities as well as suicide attempts was found. We suggest a wide range of CTE should be included when exploring the effects of CTE or developing prevention and treatment strategies among alcoholic subjects.

Read Full Abstract

Request Reprint E-Mail: markus.heilig@mail.nih.gov

Carvedilol Attenuates the Progression of Alcohol Fatty Liver Disease in Rats

Hepatosteatosis is an essential step in liver disease progression. However, the mechanisms that mediate the progression of hepatosteatosis and the optimal inhibitor of them remain largely unclear. The sympathetic nervous system (SNS) is responsible for the lipid metabolism and the accumulation of collagen that occurs in an injured liver. Medicines that inhibit this pathway may be a relevant treatment for the hepatosteatosis, and then reduce the liver injury that progresses through the stage of steatosis to fibrosis.

Using an ethanol-liquid-diet-fed rat model of alcohol fatty liver disease (AFLD), we studied the effects of carvedilol, which can block the SNS completely via β1, β2, and α1 adrenergic receptors, on the sympathetic tone, hepatosteatosis, and fibrosis based on histological, immunohistochemical, Western blot, and reverse transcriptase polymerase chain reaction analyses.

Carvedilol inhibited the ethanol-induced whole-body and hepatic sympathetic activities based on the serum 3-methoxy-4-hydroxyphenylglycol level and hepatic tyrosine hydroxylase expression. Carvedilol attenuated the hepatosteatosis, as evidenced by reduced hepatic triglyceride level and the accumulation of fatty droplets within hepatocytes, down-regulated fatty acid synthase and sterol regulatory element binding protein-1, and up-regulated peroxisome proliferator-activated receptor-α. No fibrosis signs were shown in our rat model. Carvedilol inhibited ethanol-induced the thickening of zone 3 vessel walls, reduced the activation of hepatic stellate cells (HSCs), and decreased the induction of collagen, transforming growth factor β1, and tissue inhibitor of metalloproteinases-1. Tumor necrosis factor α (TNF-α) was expressed on the activated HSCs and inhibited by carvedilol based on the immunohistochemical double staining analysis.

Ethanol metabolism-induced lipogenesis may trigger the SNS-activated HSCs feedback loop, and then induct the activated HSCs and the activated HSCs–derived TNF-α, the mediator of lipogenesis, overproduction. Carvedilol may block this feedback loop via antisympathetic activity and demonstrate its preventive role on the development of hepatosteatosis in rat with AFLD.

Read Full Abstract

Request Reprint E-Mail: czhliu@yamaguchi-u.ac.jp

Quantitative Trait Locus Mapping for Ethanol Teratogenesis in BXD Recombinant Inbred Mice

Individual differences in susceptibility to the detrimental effects of prenatal ethanol (EtOH) exposure have been demonstrated. Many factors, including genetics, play a role in susceptibility and resistance. We have previously shown that C57BL/6J (B6) mice display a number of morphological malformations following an acute dose of EtOH in utero, while DBA/2J (D2) mice are relatively resistant. Here, we present the results of quantitative trait locus (QTL) mapping for EtOH teratogenesis in recombinant inbred strains derived from a cross between B6 and D2 (BXD RIs).

Pregnant dams were intubated with either maltose-dextrin or 5.8 g/kg EtOH on day 9 of gestation (GD9). On GD 18, dams were sacrificed and fetuses and placentae were removed. Placentae and fetuses were weighed; fetuses were sexed and examined for gross morphological malformations. Fetuses were then either placed in Bouin's fixative for subsequent soft-tissue analyses or eviscerated and placed in EtOH for subsequent skeletal examinations. QTL mapping for maternal weight gain (MWG), prenatal mortality, fetal weight (FW) at c-section, placental weight (PW), and several morphological malformations was performed using WebQTL.

Heritability for our traits ranged from 0.06 for PW to 0.39 for MWG. We found suggestive QTLs mediating all phenotypes and significant QTLs for FW and digit and rib malformations. While most QTL regions are large, several intriguing candidate genes emerged based on polymorphisms between B6 and D2 and gene function.

In this first mapping study for EtOH teratogenesis, several QTLs were identified. Future studies will further characterize these regions. Identification of genes and epigenetic modifications mediating susceptibility to the teratogenic effects of alcohol in mice will provide targets to examine in human populations.

Read Full Abstract

Request Reprint E-Mail: cdowning@pharmacy.isu.edu

CAGE, RAPS4, RAPS4-QF and AUDIT Screening Tests for Men and Women Admitted for Acute Alcohol Intoxication to an Emergency Department: Are Standard Thr

A number of screening instruments are routinely used in Emergency Department (ED) situations to identify alcohol-use disorders (AUD). We wished to study the psychometric features, particularly concerning optimal thresholds scores (TSs), of four assessment scales frequently used to screen for abuse and/or dependence, the cut-down annoyed guilty eye-opener (CAGE), Rapid Alcohol Problem Screen 4 (RAPS4), RAPS4-quantity-frequency and AUD Identification Test (AUDIT) questionnaires, particularly in the sub-group of people admitted for acute alcohol intoxication (AAI).

All included patients [AAI admitted to ED (blood alcohol level ≥0.8 g/l)] were assessed by the four scales, and with a gold standard (alcohol dependence⁄abuse section of the Mini International Neuropsychiatric Interview), to determine AUD status. To investigate the TSs of the scales, we used Youden's index, efficiency, receiver operating characteristic (ROC) curve techniques and quality ROC curve technique for optimized TS (indices of quality).

A total of 164 persons (122 males, 42 females) were included in the study. Nineteen (11.60%) were identified as alcohol abusers alone and 128 (78.1%) as alcohol dependents (DSM-IV). Results suggest a statistically significant difference between men and women (P < 0.05) in performance of the screening tests RAPS4 (≥1) and CAGE (≥2) for detecting abuse. Also, in this population, we show an increase in TSs of RAPS4 (≥2) and CAGE (≥3) for detecting dependence compared with those typically accepted in non-intoxicated individuals. The AUDIT test demonstrates good performance for detecting alcohol abuse and/or alcohol-dependent patients (≥7 for women and ≥12 for men) and for distinguishing alcohol dependence (≥11 for women and ≥14 for men) from other conditions.

Our study underscores for the first time the need to adapt, taking into account gender, the thresholds of tests typically used for detection of abuse and dependence in this population.


Read Full Abstract

Request Reprint E-Mail: gbrousse@chu-clermontferrand.fr

The Effects of Prenatal Alcohol Exposure on the Developmental Retina of Mice

Our aim is to investigate the effects of prenatal alcohol exposure (PAE) on the development of retinal bipolar and horizontal cells.

The alterations of the retinal bipolar and horizontal cells in P7, P14 and P30 mice were observed after PAE, with immunofluorescent labeling and DiI diolistic assay.

The retinal development of filial pups was affected by PAE in a dose-dependent and long-term manner. The number of bipolar cells of alcohol groups was significantly lower than that of the control, and the dendritic receptive field of horizontal cells was also significantly smaller than those of the control groups (P < 0.01).

PAE was able to cause retarded development of pup retinal neural cells.



Read Full Abstract

Request Reprint E-Mail: jinbo_deng@henu.edu.cn

Alcohol Misuse Y91 Coding in ICD-11: Rational Terminology and Logical Coding Specifically to Encourage Early Identification and Advice

Alcohol misuse is a common presentation to the Emergency Department (ED). The International Classification of Diseases ICD-10 for alcohol misuse, both under F10 and Y90/Y91, is not straightforward.

The practicalities of coding ED attendances reveal an increasing detachment from ICD-10 (currently under review). Early identification [sometimes using blood alcohol concentrations (BACs)] and brief advice (IBA) can reduce unscheduled alcohol-related ED re-attendance. The UK Government Department of Health has implemented use of the terms ‘Hazardous Drinking’, ‘Harmful Drinking’ and ‘Dependent Drinking’ in its Public Service Agreements aimed at reducing harm by alcohol. Simplifying coding might increase IBA usage.

We suggest that coding improvements in ICD-11 should update Y91 (currently ‘clinical assessment’)—with ICD-10 Y90 remaining for BAC to classify a patient's ‘alcohol status’. Y90 and Y91 together would indicate the urgency for early IBA and/or speciality referral, aiming to reduce the prevalence of ‘Dependent Drinking’.



Read Full Abstract

Request Reprint E-Mail: robintouquet@uk2.net

New board to 'name and shame' alcohol ads

Chaired by former Australian of the Year and children's health advocate Fiona Stanley, the independent Alcohol Advertising Review Board was launched in Perth on Friday, promising to hold advertisers to account for what it says is a growing problem of alcohol abuse across the nation.

The independent body is made up of health professionals and related groups, and supported by the McCusker Centre for Action on Alcohol and Youth (MCAAY) and Cancer Council Western Australia.

MCAAY director Mike Daube said it would counter the industry-based Alcohol Beverages Advertising Code, which he claimed wasn't doing enough to curb excessive drinking and exposure to children. > > > > Read More

Sexually Rejected Flies Turn to Booze

Offer a male fruit fly a choice between food soaked in alcohol and its nonalcoholic equivalent, and his decision will depend on whether he's mated recently or been rejected by a female. Flies that have been given the cold shoulder are more likely to go for the booze, researchers have found. It's the first discovery, in fruit flies, of a social interaction that influences future behavior.

"This is an amazing link," says neurogeneticist Troy Zars of the University of Missouri, Columbia, who was not involved in the study. Understanding the brain pathways responsible, he says, could help explain more broadly how rewarding behavior is reflected in the brain, and how the brain mediates complex behaviors.

Scientists already knew that when fruit flies drink alcohol, reward pathways in their brains are activated, making it a "pleasurable" experience. They also knew that social interactions are among the most rewarding experiences. So researchers led by neuroscientist Galit Shohat-Ophir, who conducted the work at the University of California, San Francisco, but who has now moved to the Howard Hughes Medical Institute's Janelia Farm Research Campus in Ashburn, Virginia, wanted to see whether the two types of rewards were connected in the brain. "This was just a wild experiment to do," she says. "We didn't expect to see such dramatic results." > > > > Read More

Generational Association Studies of Dopaminergic Genes in Reward Deficiency Syndrome (RDS) Subjects: Selecting Appropriate Phenotypes for Reward Depen

Abnormal behaviors involving dopaminergic gene polymorphisms often reflect an insufficiency of usual feelings of satisfaction, or Reward Deficiency Syndrome (RDS). RDS results from a dysfunction in the “brain reward cascade,” a complex interaction among neurotransmitters (primarily dopaminergic and opioidergic).

Individuals with a family history of alcoholism or other addictions may be born with a deficiency in the ability to produce or use these neurotransmitters. Exposure to prolonged periods of stress and alcohol or other substances also can lead to a corruption of the brain reward cascade function.

We evaluated the potential association of four variants of dopaminergic candidate genes in RDS (dopamine D1 receptor gene [DRD1]; dopamine D2 receptor gene [DRD2]; dopamine transporter gene [DAT1]; dopamine beta-hydroxylase gene [DBH]).

We genotyped an experimental group of 55 subjects derived from up to five generations of two independent multiple-affected families compared to rigorously screened control subjects (e.g., N = 30 super controls for DRD2 gene polymorphisms). Data related to RDS behaviors were collected on these subjects plus 13 deceased family members.

Among the genotyped family members, the DRD2 Taq1 and the DAT1 10/10 alleles were significantly (at least p < 0.015) more often found in the RDS families vs. controls. The TaqA1 allele occurred in 100% of Family A individuals (N = 32) and 47.8% of Family B subjects (11 of 23). No significant differences were found between the experimental and control positive rates for the other variants.

Although our sample size was limited, and linkage analysis is necessary, the results support the putative role of dopaminergic polymorphisms in RDS behaviors.

This study shows the importance of a nonspecific RDS phenotype and informs an understanding of how evaluating single subset behaviors of RDS may lead to spurious results. Utilization of a nonspecific “reward” phenotype may be a paradigm shift in future association and linkage studies involving dopaminergic polymorphisms and other neurotransmitter gene candidates.


Read Full Text (PDF)

Why don't northern American solutions to drinking and driving work in southern America?

While individual studies from several South American countries have shown driving while intoxicated to be a problem, there are no objective systematically collected alcohol-associated driving data obtained in most South American countries. This limits their ability to implement and enforce targeted prevention strategies, evaluate whether proven prevention efforts from North America (particularly the United States and Canada) can be transferred to the South, and to sustain momentum for the improvement of road safety by demonstrating that previously implemented legal and policy changes are effective.

The aim of this paper is to discuss the abysmal differences that exist between northern and southern American countries regarding the current status of driving while intoxicated prevention strategies—their implementation, impacts and effects—using Brazil as a case example.

We propose a three-pronged approach to close this northern–southern American gap in driving while intoxicated prevention and intervention: (a) systematic collection on road traffic crash/injury/death as well as risk factor data, (b) passage of laws without loopholes requiring compliance with blood alcohol concentration testing and (c) provision of appropriate training and equipment to the police in concomitance with vigilant enforcement.

Resources and energies must be put towards data collection, implementation of prevention strategies and enforcement in order to decrease the unacceptably high rates of these preventable driving while intoxicated deaths.

Read Full Abstract

Request Reprint E_Mail: fpechans@uol.com.br

Prevention For College Students Who Suffer Alcohol-Induced Blackouts Could Deter High-Cost Emergency Department Visits

Fifty percent of college students who drink report alcohol-induced blackouts, and alcohol abusers in general put a heavy burden on the medical care system.

Using data drawn from a randomized, controlled alcohol intervention trial at five university sites, our study quantified the costs of visits to emergency departments by college students who experienced blackouts from drinking alcohol.

Of 954 students in the study, 52 percent of males and 50 percent of females at the outset of the study had experienced an alcohol-induced blackout in the past year. Of 404 emergency department visits among the study participants over a two-year observation period, about one in eight were associated with blackout drinking. Injuries ranged from broken bones to head and brain injuries requiring computed tomography.

We calculate that on a large university campus having more than 40,000 students, blackout-associated emergency department visit costs would range from $469,000 to $546,000 per year.

We conclude that blackouts are a strong predictor of emergency department visits for college drinkers and that prevention efforts aimed at students with a history of blackouts might reduce injuries and emergency department costs.

Read Full Abstract

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

Alcohol Consumption in Movies and Adolescent Binge Drinking in 6 European Countries

The goal of this study was to investigate whether the association between exposure to images of alcohol use in movies and binge drinking among adolescents is independent of cultural context.

A cross-sectional survey study in 6 European countries (Germany, Iceland, Italy, Netherlands, Poland, and Scotland) was conducted. A total of 16 551 pupils from 114 public schools with a mean (± SD) age of 13.4 (± 1.18) years participated. By using previously validated methods, exposure to alcohol use in movies was estimated from the 250 top-grossing movies of each country (years 2004−2009). Lifetime binge drinking was the main outcome measure.

Overall, 27% of the sample had consumed >5 drinks on at least 1 occasion in their life. After controlling for age, gender, family affluence, school performance, television screen time, sensation seeking and rebelliousness, and frequency of drinking of peers, parents, and siblings, the adjusted β-coefficient for lifetime binge drinking in the entire sample was 0.12 (95% confidence interval: 0.10−0.14; P < .001). The crude relationship between movie alcohol use exposure and lifetime binge drinking was significant in all countries; after covariate adjustment, the relationship was still significant in 5 of 6 countries. A sensitivity analysis revealed that the association is content specific, as there was no significant association between lifetime binge drinking and exposure to smoking in movies.

The link between alcohol use in movies and adolescent binge drinking was robust and seems relatively unaffected by cultural contexts.

Read Full Text (PDF)

Youth Violence and Alcohol/Drug Abuse

The relationship between youth violence and substance abuse

Youth violence and substance abuse often occur together. The Pathways to Desistance study is an OJJDP-sponsored study that followed over 1,300 serious juvenile offenders from Philadelphia and Phoenix for a period of seven years after their conviction. Youth participating in the study were 14 to 17 years old at the time of their conviction and had been convicted of at least one serious crime involving violence, offense against property, or drugs. The sample was 84% male and 80 percent minority and over 40% were convicted of felony crimes against persons (such as murder, sexual assault, and robbery). Participants were extensively interviewed at the beginning of the study as well as several times during the seven years after enrollment in the study.

The overall purpose of the study was to increase understanding of the factors that contribute
to offenders either desisting from or continuing to engage in criminal activity. One key finding
to emerge is that serious/chronic offenders were much more likely than other offenders to
meet diagnostic criteria for a substance use disorder. > > > > Read More

Does moderate drinking harm the fetal brain? Insights from animal models.

Although public health campaigns advise pregnant women to abstain from ethanol, drinking during pregnancy is pervasive.

Here, we highlight recent studies that have clearly demonstrated long-lasting neurobehavioral deficits in the offspring of laboratory animals exposed to moderate levels of ethanol during development.

Alterations in learning, memory, motor coordination, social behavior, and stress responses were identified in these animals. Increased vulnerability to substance abuse was also demonstrated.

These behavioral alterations have been associated with impairments in neurotransmitter systems, neuromodulators, and/or synaptic plasticity in several brain regions.

this review we hope to contribute to a better appreciation of the potential effects of developmental exposure to moderate ethanol levels, leading to better interventions aimed at relieving fetal alcohol spectrum disorders.


Read Full Abstract

Request Reprint E-Mail: fvalenzuela@salud.unm.edu

Alcohol News - 11/2012

The Local.no (Norway) - Use LSD to combat alcoholism: experts

A team of Norwegian researchers has established that the psychedelic drug LSD is an effective medicine for the treatment of alcoholism, arguing that it should be used more widely.

Read more

YLE News (Finland) - Pellervo: class 3 beer restrictions would increase booze cruises

According to a report by the Pellervo Economic Research PTT think tank, transferring sales of class 3 beer to state Alko stores would increase passenger imports of alcoholic beverages by one-third. Other effects would be a reduction in state tax revenues and a greater concentration of retail outlets.

Read more

Helsingin Sanomat (Finland) - Survey shows Finns increasingly in favour of restrictive alcohol policies

Attitudes of the Finnish people toward the consumption and distribution of alcoholic beverages have become increasingly restrictive, according to a survey by the National Institute for Health and Welfare (THL).

Read more

YLE News (Finland) - Peacekeepers accept zero tolerance policy on alcohol

The Association of Finnish Peacekeepers says it accepts the idea of zero tolerance towards the consumption of alcohol during missions abroad. However, the Association adds a decision on the issue rests entirely with the Finnish Defence Forces.

Read more

The Local.se (Norway/Sweden) - Booze and butter boost Norwegians' Swedish spending spree

Norwegians spent more than 13 billion kronor ($1.9 billion) during one-day shopping trips to Sweden last year, meaning almost 6 percent ofNorway's consumer food and beverage trade has migrated to Sweden.

Read more

IUF.org (Lithuania) - Lithuanian courts declare beer an 'essential service' to cover attacks on union rights at Carlsberg Lithuania!

Management attacks on workers and their unions continue at Carlsberg, the world's 4th largest brewery company. A planned strike by union workers at the Carlsberg brewery in Lithuania has been declared illegal by an outrageous court decision which is now the subject of an ILO complaint.

Read more

TIME - Study: Does Alcohol in Movies Drive Teens to Binge Drink?

A new study from six European countries suggests that teens who see more boozy scenes in movies are more likely to binge drink.

Read more

MarketWatch (USA) – Interlocks for First-time DUI Convictions Cut Repeat Offenses; Study of Washington Drivers Supports Mandatory Interlock Laws

People convicted for the first time of alcohol-impaired driving are less likely to reoffend if they have to install alcohol interlocks on their vehicles, a new study by the Insurance Institute for Highway Safety shows.

Read more

Sydney Morning Herald (Australia) - Should packaged alcohol display health warnings?

WINEMAKERS understand why some people like the idea of health warnings on alcohol containers. It's simple, consistent, gets the message onto the product itself and is easy for policy makers to implement and monitor.

Read more

Scotsman (Scotland) – 1 in 3 teenagers binge drinking by age of 13

ONE in three Scottish teenagers is binge drinking by the age of 13, according to shocking new research which lays bare the extent of the nation’s alcohol crisis.

Read more

dailyRx - Alcohol While Pregnant is Worse Than Cocaine or Pot

Children exposed to as little as half an alcoholic drink a day in utero - even if they didn't have fetal alcohol syndrome - appeared to suffer in their achievement test scores.

Read more

Texas Tribune (USA) - TABC Develops Apps to Curb Excessive, Underage Drinking
As college students from across the nation head to Texas beaches for spring break, the Texas Alcoholic Beverage Commission is already making plans to have new tools at its disposal for next year's partiers — mobile phone apps that it hopes will curb excessive and underage drinking.

Read more

BBC News (Scotland) - Scottish Tories drop opposition to minimum alcohol pricing

The Scottish Conservative Party has dropped its opposition to minimum unit pricing for alcohol. Tory leader Ruth Davidson confirmed that her party would now support the Scottish government plans.

Read more

Independent Online (South Africa) - Alcohol ads ban a ‘last, last resort’

There are no definite plans to ban alcohol adverts but all options to curb alcohol abuse are being considered, Deputy Minister of Trade and Industry Elizabeth Thabethe said on Thursday.

Read more

AllAfrica.com (Rwanda) - Debate on Underage Alcohol Consumption Intensifies

As government moves to tackle the problem of alcohol and drug abuse among the youth, a cross section of the public has come out to say that sensitisation on the dangers of excessive alcohol consumption should be put forward.

Read more

Scoop.co.nz (Thailand) - Alcohol & Politics: A Volatile Mix in Thailand

One of Thailand's most powerful politicians has denied accusations that "he was drunk" in Parliament, prompting a lively public debate about alcohol use by politicians and the legal limits on reporting such allegations.

Read more

News-Medical.net (UK) - Middle aged ignoring health messages on alcohol consumption

A new survey finds that adults aged 45 and over are more than three times as likely to drink alcohol almost every day as those under 45. This could mean that the middle aged population is ignoring the serious health risks associated with excessive drinking. The age disparity is most pronounced among women.

Read more

Belfast Telegraph (Northern Ireland) - Minimum alcohol price considered for Nothern Ireland

Tackling the problems associated with the availability of cheap alcohol in Northern Ireland has become a political priority.
Read more

North Country Gazette (USA) - Survey: 10% Of Adults In Recovery From Drugs, Alcohol

Survey data released Tuesday by The Partnership at Drugfree.org and the New York State Office of Alcoholism and Substance Abuse Services (OASAS) show that 10 percent of all American adults, ages 18 and older, consider themselves to be in recovery from drug or alcohol abuse problems.

Read more

Wall Street Journal (EU/US) - Treatment for Alcoholics Set for Europe, But Not U.S.

Lundbeck A/S expects European marketing authorization for its alcohol dependence treatment Selincro within the year, but the Danish pharmaceutical group isn’t aiming to get into the U.S. market any time soon.

Read more

MSN NZ News (New Zealand) - Harm done to Kiwi kids by alcohol a focus

The harm done to Kiwi babies and children by alcohol will be the focus of a conference in Wellington later this month.

Read more

Fox News (Germany) - German town gets tough on drunk cycling

A German university town is throwing the book at drunk cyclists -- by applying drunk driving laws to peddlers. Under the new rules in Munster, 296 miles west of the capital Berlin, anyone caught cycling inebriated faces a ban from bike riding, news website The Local reported Friday.

Read more


Read Full Newsletter