Irish top Europe's binge-drinking league


London Times
March 14, 2007

David Charter, Europe Correspondent

The Irish are Europe's champion binge drinkers, putting even Briain's lager louts in the shade, according to a survey of all 27 EU nations released today.

Officials said it was pure coincidence that the results from the most extensive survey of EU drinking habits were released just before St Patrick’s Day, a traditional excuse for a glass or five.

Binge drinking – defined as imbibing five or more drinks at any one sitting – seems to be a northern European speciality.

The nations with the worst record are Ireland, followed by Finland, then Britain, Denmark and Sweden.

Asked how much they get through each time a bottle is opened or a pint pulled, the Irish confessed that 34 per cent of sessions involve at least five drinks. By the same measure, 27 per cent of Finns and 24 per cent of British drink to excess.

At the other end of the spectrum, the most responsible drinkers seem to come from southern Europe, with just 1 per cent of Bulgarians admitting to binge behaviour, followed by 2 per cent of both Italians and Greeks, and 4 per cent of Portuguese.

St Patrick’s Day on Saturday, the feast day of Ireland’s patron saint, is actually more of a booze day, the findings by Eurobarometer suggest.

Earlier this year Ireland's Catholic bishops warned that alcohol abuse was damaging Irish society.

The survey also shows that almost eight out of 10 Europeans (77 per cent) agree with putting warnings on alcohol bottles and adverts to alert pregnant women and drivers of the dangers of drinking alcohol. France has introduced images on some bottles aimed particularly at pregnant women and Finland is considering similar measures.

Almost three quarters of Europeans (73 per cent) would agree to a lower blood alcohol limit for young and learner drivers.

Markos Kyprianou, the EU Health Commissioner, said: “I am deeply concerned about the data showing that one in five young Europeans regularly binge drink.

"It is clear from this survey that EU citizens support measures to protect specific groups in society, such as pregnant women, drivers and young people, from the harmful effects of alcohol abuse and misuse.”

The survey suggested that while increasing the price of alcohol by as much as a quarter would not deter the majority of drinkers, it did indicate that a price increase would encourage many younger people to drink less.

A total of 44 per cent of the youngest respondents believed they would buy less alcohol if it became substantially more expensive, but the majority of people doubted if the increased cost would be enough to deter most young people, or heavy drinkers in general. Sixty-two per cent said they would not buy fewer alcoholic drinks if the price went up by 25 percent.

It is estimated that alcohol abuse and misuse kills 195,000 people a year across the European Union. Harmful alcohol consumption is responsible for one in four deaths among young men aged 15-29.

The EC pollsters surveyed 25,000 people across Europe to compile the league table.

European Commission Survey (PDF)

Source: Robin GW Room KBS_List 14 March 2007

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Faces & Voices of Recovery
eNewsletter - March 13, 2007

Addiction and Recovery: Communities Take Action! update
Organize and host a house party on St. Patrick’s Day, March 17th and bring the power of recovery to HBO’s Addiction! Thanks to recovery advocates in Chicago, IL (A Safe Haven), Detroit, MI, (Detroit Recovery Project and NCADD-Detroit), Philadelphia, PA (PRO-ACT), Dallas, TX (Association of Persons Affected by Addiction), and Hartford, CT (CCAR) for their terrific premiere events as part of the release of HBO’s Addiction! HBO’s web site and the Communities Take Action web site are now live. More…

Addiction Recovery Insurance Equity Campaign
The fight for addiction recovery insurance equity is heating up in Congress. H.R. 1424, the Paul Wellstone Mental Health and Addiction Equity Act of 2007 was introduced by Representatives Patrick Kennedy (D-MA), Jim Ramstad (R-MN) and 253 co-sponsors. Take action today by sending an email to your member of Congress and asking them to support the bill! More…

Sign up for our March 24th Webinar!
“Restoring Rights to People with Drug Convictions” is the topic of our second online, hour-long recovery advocacy training with “how-to” information on campaigns in Rhode Island and KY to restore voting rights to people with drug convictions. Listen and learn from representatives of the Legal Action Center and Sentencing Project Saturday, March 24th more…

ANNOUNCEMENT
Faces & Voices of Recovery Board of Directors Call for Nominations: Faces & Voices board’s nominating committee is calling for nominations for seven board openings: four regional representatives and three At-large members. All nominations are due by close of business on March 31. The board will elect new members at its May 10, 2007 meeting. More…

RESOURCES
“A New Recovery Advocacy Movement” by Bill White and Pat Taylor is a column that describes some of the nationwide recovery advocacy efforts.

“State Estimates of Substance Use from the 2004-2005” from the National Surveys on Drug Use and Health provides highlights, tables, and national maps with substance use data on individual States.

3-(4-Chloro-2-Morpholin-4-yl-Thiazol-5-yl)-8-(1-Ethylpropyl)-2,6-Dimethyl-Imidazo[1,2-b]Pyridazine: A Novel Brain-Penetrant, Orally Available Corticotropin-Releasing Factor Receptor 1 Antagonist with Efficacy in Animal Models of Alcoholism

The Journal of Neuroscience, March 7, 2007, 27(10):2718-2726;

Andrea Cippitelli,^2,4

Annika Thorsell,²

Anh Dzung Lê,³

Philip A. Hipskind,¹

Chafiq Hamdouchi,¹

Jianliang Lu,¹

Erik J. Hembre,¹

Jeffrey Cramer,¹

Min Song,¹

David McKinzie,¹

Michelle Morin,¹

Roberto Ciccocioppo,⁴ and

Markus Heilig²

¹Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, ²Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism–National Institutes of Health, Bethesda, Maryland 20892, ³Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada M5S 2S1, and ⁴Department of Experimental Medicine and Public Health, University of Camerino, 62032 Camerino, Italy

Correspondence should be addressed to Dr. Markus Heilig, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism–National Institutes of Health, 10 Center Drive, 10/1-5334, Bethesda, MD 20892-1108. Email: Markus.Heilig@mail.nih.gov

Abstract

We describe a novel corticotropin-releasing factor receptor 1 (CRF₁) antagonist with advantageous properties for clinical development, and its in vivo activity in preclinical alcoholism models.

3-(4-Chloro-2-morpholin-4-yl-thiazol-5-yl)-8-(1-ethylpropyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (MTIP) inhibited ¹²⁵I-sauvagine binding to rat pituitary membranes and cloned human CRF₁ with subnanomolar affinities, with no detectable activity at the CRF₂ receptor or other common drug targets. After oral administration to rats, MTIP inhibited ¹²⁵I-sauvagine binding to rat cerebellar membranes ex vivo with an ED₅₀ of 1.3 mg/kg and an oral bioavailability of 91.1%.

Compared with R121919 (2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7-dipropylamino-pyrazolo[1,5-a]pyrimidine) and CP154526 (N-butyl-N-ethyl-4,9-dimethyl-7-(2,4,6-trimethylphenyl)-3,5,7-triazabicyclo[4.3.0]nona-2,4,8,10-tetraen-2-amine), MTIP had a markedly reduced volume of distribution and clearance. Neither open-field activity nor baseline exploration of an elevated plus-maze was affected by MTIP (1–10 mg/kg). In contrast, MTIP dose-dependently reversed anxiogenic effects of withdrawal from a 3 g/kg alcohol dose.

Similarly, MTIP blocked excessive alcohol self-administration in Wistar rats with a history of dependence, and in a genetic model of high alcohol preference, the msP rat, at doses that had no effect in nondependent Wistar rats. Also, MTIP blocked reinstatement of stress-induced alcohol seeking both in postdependent and in genetically selected msP animals, again at doses that were ineffective in nondependent Wistar rats.

Based on these findings, MTIP is a promising candidate for treatment of alcohol dependence.

Alcohol Reports March 6, 2007 Press Release

Collaborative Study on the Genetics of Alcoholism!

The Collaborative Study on the Genetics of Alcoholism (COGA) is a multi-site, multi-disciplinary undertaking with the overall goals of characterizing the familial transmission of alcoholism and related phenotypes and identifying susceptibility genes using genetic linkage. The study is being coordinated by the SUNY Health Science Center at Brooklyn (HSCB) under the leadership of Henri Begleiter. The study was initially funded by the National Institute of Alcohol Abuse and Alcoholism (NIAAA) in 1989.

Interviewing and testing of COGA families is conducted at six university centers: SUNY Health Science Center at Brooklyn, University of Connecticut, Indiana University, University of Iowa, University of California in San Diego, and Washington University. All six sites will carry out the identical study protocol. Most of these institutions continue to be responsible for maintaining scientific and procedural standards as well as quality control in their areas of expertise including Ascertainment, Psychiatric Assessment, Neurophysiology, Molecular Biology, and Genetic Analyses. The scope and scale of COGA also necessitates a complex data management system. The data management and repository functions are shared based on specialty by Washington University (clinical), Indiana University (pedigree), and SUNY (electrophysiology). Washington University doubles as the overall data management and repository coordinating center. In addition, a cell and DNA repository will be managed by Jay Tischfield now at Rutgers University.

COGA website

Publications available as full text

2006

Agrawal A, Edenberg H, Foroud T, Bierut L, Dunne G, Hinrichs A, Nurnberger J, Crowe R, Kuperman S, Schuckit M, Begleiter H, Porjesz B, Dick D. Association of GABRA2 with Drug Dependence in the Collaborative Study of the Genetics of Alcoholism Sample. Behav Genet 2006. Download PDF (full text)

Begleiter H, Porjesz B. Genetics of Human Brain Oscillations - Special Issue on Models and Theories on Brain Function with Special Emphasis on Cognitive Processing. Int J Psychophysiol 2006; 60:162-171. Download PDF (full text)

Wang J, Dunn G, Porjesz B, Begleiter H, Hesselbrock V. Linkage Analyses of IQ in the Collaborative Study on the Genetics of Alcoholism (COGA) Sample. Behav Genet 2006; 36(1):77-86. Download PDF (full text)

Dick D, Bierut L, Hinrichs A, Fox L, Bucholz K, Kramer, Kuperman S, Hesselbrock V, Schukit M, Almasy L, Tischfield J, Porjesz B, Begleiter H, Nurnberger J, Xuei X, Edenberg H, Foroud T. The Role of GABRA2 in Risk for Conduct Disorder and Alcohol and Drug Dependence Across Different Development Stages. Behav Genet - Special Issue on Substance Use 2006 Mar 24 Download PDF (full text)

Dick D, Jones K, Saccone N, Hinrichs A, Wang J, Goate A, Bierut L, Almasy L, Schuckit M, Hesselbrock V, Tischfield J, Foroud T, Edenberg H, Porjesz B, Begleiter H. Endophenotypes Successfully Lead to Gene Identification: Results from the Collaborative Study on the Genetics of Alcoholism. Behav Genet 2006; 36(1):112-126. Download PDF (full text)

Dick D, Plunkett J, Flury L, Xuei X, Goate A, Hesselbrock V, Schuckit M, Crowe R, Edenberg H, Foroud T. Association Between GABRA1 and Drinking Behaviors in the Collaborative Study on the Genetics of Alcoholism Sample. Alcohol Clin Exp Res 2006; 30(7):1101-1110. Download PDF (full text)

Duncan A, Neuman R, Kramer J, Kuperman S, Hesselbrock V, Bucholz K. Lifetime Psychiatric Comorbidity of Alcohol Dependence and Bulimia Nervosa in Women. Drug Alcohol Depend 2006 Jan 30. Download PDF (full text)

Edenberg H, Xuei X, Chen HJ, Tian H, Flury-Wetherill L, Dick D, Almasy L, Bierut L, Bucholz K, Goate A, Hesselbrock V, Kuperman S, Nurnberger J, Porjesz B, Rice J, Schukit M, Tischfield J, Begleiter H, Foroud T. Association of Alcohol Dehydrogenase Genes with Alcohol Dependence: A Comprehensive Analysis. Hum Mol Genet 2006; 15(9):1539-1549. Download PDF (full text)

Gogineni A, King S, Jackson K, Kramer J, Bucholz K, Chan G, Iacono W, Kuperman S, Larkins J, Longabaugh R, McGue M, Polgreen L, Sher K, Stout R, Strong D, Woolard R. Female Offspring of Alcoholic Individuals: Recent Findings on Alcoholism and Psychopathology Risks: Symposium Presented at the Research Society on Alcoholism, 2004, Aruna Gogineni, Chair. Alcohol Clin Res Exp 2006; 30(2):377-387. Download PDF (full text)

Grucza R, Cloninger CR, Bucholz K, Constantino J, Schuckit M, Dick D, Bierut L. Novelty Seeking as a Moderator of Familial Risk for Alcohol Dependence. Alcohol Clin Exp Res 2006; 30(7):1176-1183. Download PDF (full text)

Hinrichs A, Wang J, bufe B, Kwon J, Budde J, Allen R, Bertelsen S, Evans W, Dick D, Rice J, Foroud T, Nurnberger Jr., J, Tischfield J, Kupperman S, Crowe R, Hesselbrock V, Schuckit M, Almasy L, Begleiter H, Porjesz B, Edenberg H, Meyerhof W, Bierut L, Goate A. Functional Variant in a Bitter Taste Receptor (hTAS2R16) Influences Risk for Alcohol Dependence. Am J Hum Genet 2006; 78(1):103-111. Download PDF (full text)

Padmanabhapillai A, Porjesz B, Ranganathan M, Jones K, Chorlian D, Tang Y, Kamarajan C, Rangaswamy M, Stimus A, Begleiter H. Suppression of Early Evoked Gamma Band Response in Male Alcoholics During a Visual Oddball Task. Int J Psychophysiol 2006; 60(1):15-26. Download PDF (full text)

Schuckit M, Windle M, Smith T, Hesselbrock V, Ohannessian C, Averna S, Bauer L, Kramer J, Bucholz K, Sher K. Searching for the Full Picture: Structural Equation Modeling in Alcohol Research. Alcohol Clin Exp Res 2006; 30(2):194-202. Download PDF (full text)

Are there empirically supported and clinically useful subtypes of alcohol dependence?

Addiction. 2006 Sep;101 Suppl 1:97-103

• Hesselbrock VM, E-mail: hesselb@psychiatry.uchc.edu
• Hesselbrock MN.

Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, USA.

AIMS:

This paper provides an overview of several multidimensional empirically derived typologies of alcohol use disorders that have been derived primarily for research purposes in relation to their clinical utility.

METHODS:

Studies using multivariate statistical methods for identifying homogeneous groups of subjects were selected for inclusion. Theoretically based typologies were not included in this review.

RESULTS:

While formal diagnostic criteria typically identify separate categories of alcohol abuse and dependence, several studies using different statistical methods consistently suggest as many as four homogeneous types of alcoholism: a chronic/severe type, a depressed/anxious type, a mildly affected type and an antisocial type.

CONCLUSIONS:

Even though the longitudinal outcomes of few empirically derived subtypes have been examined, alcoholism typologies remain a viable and potentially valuable tool for investigating etiological pathways, the effectiveness of treatments and the long-term course of alcohol use disorders.

SAMHSA to Fund 15 Addiction Technology Transfer Centers (ATTC) Grants



Contact Media Services: (240) 276-2130

Date: 3/12/2007
Media Contact: SAMHSA Press Office
Telephone: 240-276-2130

SAMHSA to Fund 15 Addiction Technology Transfer Centers (ATTC) Grants

The Substance Abuse and Mental Health Services Administration (SAMHSA) is soliciting applications for Addiction Technology Transfer Centers (ATTC). The ATTC program supports the workforce that provides addictions treatment services to 23 million Americans age 12 and older who need treatment for alcohol or illicit drug problems (NSDUH, 2005). The ATTCs assess the training and development needs of the substance use disorders workforce, and develop and conduct training and technology transfer activities to promote the adoption of evidence-based practices in substance use disorders treatment.

It is expected that approximately $7.8 million will be available to fund up to 15 awards.

Awards will be made to 14 Regional Centers and 1 National Coordinating Center. The annual award amount will range from $500,000 to $550,000 per year for up to five years. The actual amount may vary, depending on the availability of funds. Eligible applicants are domestic public or nonprofit entities, states and local governments, federally recognized American Indian/Alaska native tribes and tribal organizations, including public or private universities and colleges, and community and faith-based organizations. The grants will be awarded by SAMHSA’s Center for Substance Abuse Treatment.

WHO CAN APPLY: Eligible applicants are domestic, private and public nonprofit entities, including State and local governments, federally recognized American Indian/Alaska native tribes and tribal organizations, public or private universities and colleges, and community and faith-based organizations.

HOW TO APPLY: Applications for No. TI -07-001 are available by calling SAMHSA’s Clearinghouse at 1-877-SAMHSA7, or by downloading from http://www.samhsa.gov/grants/index.aspx or www.grants.gov. Applicants are encouraged to apply on line using www.grants.gov

APPLICATION DUE DATE: June 1, 2007

ADDITIONAL INFORMATION: Applicants with questions on program issues should contact Catherine Nugent at 240-276-1577 or Cathy.Nugent@samhsa.hhs.gov. For questions on grants management issues, contact Kimberly Pendleton at 240-276-1421 or Kimberly.Pendleton@samhsa.hhs.gov.

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For U.S. Troops at War, Liquor Is Spur to Crime

By PAUL von ZIELBAUER

Published: March 13, 2007

In May 2004, Specialist Justin J. Lillis got drunk on what he called “hajji juice,” a clear Iraqi moonshine smuggled onto an Army base in Balad, Iraq, by civilian contractors, and began taking potshots with his M-16 service rifle. .....(more)

Source: Ernest Kurtz KBS-list

Changing Patterns of Addiction and Public Aid Receipt: Tracking the Unintended Consequences of Welfare Reform

Journal of Health Politics, Policy and Law 2006 31(5):945-980;






Laura A. Schmidt E-mail:laura.schmidt@ucsf.edu

University of California at San Francisco

James Wiley

San Francisco State University

Daniel Dohan

University of California at San Francisco

Denise Zabkiewicz

University of California at Berkeley

Laurie M. Jacobs

Alcohol Research Group

Stuart Henderson

University of California at San Francisco

Matthew Zivot

University of Massachusetts at Amherst

Abstract

Sharp declines in welfare rolls since the passage of welfare reform legislation have led many to label it a social policy success.

Using data from prereform and postreform samples of welfare applicants and recipients, as well as ethnographic data on welfare reform implementation, we examine three hypotheses based on concerns raised during the welfare reform debate about the possible effects of new policies on substance abusers and addicts:

First, they would be "scared off," or discouraged from applying to aid by welfare's new requirements surrounding work and treatment.

Second, they might be "weeded out," or face discrimination in the application process because of concerns about the difficulty of moving them successfully from welfare to work.

Third, they might be "bumped down," or shifted to local aid programs rather than moving from welfare to self-sufficiency.

Our empirical analysis finds no evidence of scaring off or weeding out, and some evidence of bumping down.

Using ethnographic data, we offer some possible explanations for these findings by placing them in the context of policy change and implementation in the years following welfare reform.

FAR's first community-based project is under way in Harrisonburg, VA.

FOUNDATION FOR ALCOHOL RESPONSIBILITY

...Creating a Society in Which Alcohol Is Consumed Responsibly

››Foundation for Alcohol Responsibility

Foundation for Alcohol Responsibility (FAR) was created upon the belief that responsible drinking plays an important and positive role in our society and that it is only the misuse of alcohol that causes problems. It does indeed take a village to prevent intoxication, drunk driving and other alcohol-related incidents. When community members are effectively taught to prevent the irresponsible use of alcohol or to intervene when alcohol is used irresponsibly, alcohol-related deaths and injuries can be prevented. FAR is dedicated to that mission.

FAR is a non-profit 501(c)(3) that provides funding for initiatives to prevent intoxication, drunk driving and other alcohol-related problems as well as promotes the responsible use of alcohol. These initiatives include efforts in training, higher education, enforcement, awareness, and the development of community coalitions.

›› Inaugural Project -- Harrisonburg, Virginia

FAR's first community-based project is under way in Harrisonburg, VA. There, the foundation is sponsoring a multi-phased initiative that will launch on February 21, 2007.

The project will reach community members and provide key stakeholders with alcohol education while arming them with the tools to both consume and serve alcohol responsibly and to intervene in instances of intoxication.

The first phase of the project is aimed at restaurants and bars and will provide them with training and tools to help reduce instances of underage drinkers as well as reduce the number of intoxicated patrons and patrons who drive under the influence. Popular off-premise outlets will be trained also. A mystery-shopper service will be utilized to re-inforce ID checking behaviors and to publicly recognize the establishments that are compliant.

Shortly after the first phase launches, key campus leaders including Greeks, resident advisors, and athletes will receive training. Awareness within the community on responsible alcohol consumption practices will be expanded through advertising in print, on radio and television, and on posters displayed throughout the community.

Phase two of the project is more long term and will include social norms marketing, expanding the training component to reach every freshman college student, and development of the systematic structure to replicate the program year after year. The goal is to use Harrisonburg as a template for other community-based alcohol responsibility initiatives throughout the country.

Foundation for Alcohol Responsibility
P.O. Box 13810
Arlington, VA 22219
703-351-1070

Source: Join Together Weekly News Roundup March 12, 2007

Futures Forum Goes Online With Alcohol And Drugs Project Latest Developments

023/2007 | 9 March 2007

Scotland’s Futures Forum has taken its ‘Fresh Perspectives on Alcohol and Drugs’ online with a dedicated website facility that will allow the 250 leading experts already involved in the project shape the debate as the forum’s year-long inquiry develops.

Following yesterday’s publication of a major report by the Royal Society of Arts Commission on Illegal Drugs, Communities and Public Policy, the Futures Forum website asks today what are the implications for the debate in Scotland.

Frank Pignatelli, Chair of the Alcohol and Drugs Project Board, Scotland’s Futures Forum said:

“There is a need for an open, honest debate in Scotland on the way forward for tackling the issues associated with alcohol and drugs.

“The Futures Forum already has around 250 leading experts from academia, the health service, our police forces and public agencies on board with the project and the number is growing. By taking our inquiry online each has the opportunity to share their knowledge and understanding in a public space.

“Already, we see online in our forum reaction to the radical suggestions made yesterday by the RSA, and over the coming months our project partners will continue to debate and shape the way forward for tackling alcohol and drugs issues in Scotland.”

Members of the public are also able to log on to the Futures Forum website and have their say on Fresh Perspectives on Alcohol and Drugs.

Following the launch of the inquiry in January 2007, the Forum’s website also acts as an electronic library resource where participants in the project can place their research findings over the course of the year.

Other project material, such as the issues identified during the workshop launch sessions at Holyrood on 15 January are available online along with video archives of the chamber sessions from the day.

Professor Pignatelli added:

“Taking the project online means that we are in position to say to everyone with a view on the alcohol and drugs debate, ‘we want to hear from you, we want to listen to your views, we want to share your ideas, we want you to help shape public policy in Scotland.’”

Scotland’s Futures Forum website and the latest on ‘Fresh Perspectives on Alcohol and Drugs’ can be found at: www.scotlandfutureforum.org

Topics raised for debate on the website following the RSA’s report yesterday include:

• issues surrounding the “demonisation” and morality of drugs,

• is it too early to conclude that certain government policies on drugs have “largely been a failure”? – could the same be said about other key political issues such as tackling poverty, homelessness, crime and racism,

• is it correct to say that “just say no” “has manifestly not worked”?

• what is the dividing line between arresting and jailing people who commit ‘drug-related crimes’ as opposed to pursuing a health-based approach?

Source: Daily Dose 12 March 2007

Tiagabine does not attenuate alcohol-induced activation of the human reward system

Psychopharmacology
Volume 191, Number 4 / May, 2007
p. 975-983


Christoph Fehr Email: fehrc@uni-mainz.de

Nina Hohmann¹, G

Gerhard Gründer²,

Thomas F. Dielentheis¹,

Hans-Georg Buchholz³,

Natalie Chechko^{3, 4},

Igor Yakushev³,

Christian Landvogt³,

Peter Bartenstein^{3, 5},

Reinhard Urban⁶ and

Mathias Schreckenberger³

(1)	Department of Psychiatry, University of Mainz, Untere Zahlbacher Strasse 8, 55131 Mainz, Germany

(2)	Department of Psychiatry and Psychotherapy, RWTH Aachen University, Aachen, Germany

(3)	Department of Nuclear Medicine, University of Mainz, Mainz, Germany

(4)	Max Planck Institute for Psychiatry, Munich, Germany

(5)	Department of Nuclear Medicine, University of Munich (LMU), Munich, Germany

(6)	Institute of Legal Medicine, University of Mainz, Mainz, Germany

Abstract

Rationale
The rewarding effects of ethanol and other drugs of abuse are mediated by activation of the mesolimbic dopamine system. Recent neuroimaging studies in primates and humans suggest that cocaine-induced dopamine stimulation might be diminished by drugs augmenting γ-aminobutyric acid A (GABA-A) receptor function such as the GABA transaminase inhibitor vigabatrin.

Objectives
The objective of this study was to test the property of the selective GABA transporter 1 (GAT1) inhibitor tiagabine to block ethanol-induced activation of the mesolimbic reward system in an i.v. ethanol challenge.

Materials and methods
Twenty nonaddicted healthy volunteers underwent an i.v. ethanol challenge after 1 week of tiagabine (15 mg/day) administration. Neuronal activation was measured using [¹⁸F]-fluoro-deoxyglucose positron emission tomography (PET).

Results
Tiagabine did not prevent ethanol-induced stimulation of the mesolimbic reward system but augmented ethanol-induced hypometabolism within areas of the visual system and the cerebellum. Tiagabine alone also decreased neuronal metabolism within parts of the right temporal cortex that are highly enriched with GABA-ergic neurons.

Conclusions
Our ethanol challenge imaging study does not provide supporting evidence that the GAT1 inhibitor tiagabine diminishes the rewarding effects of ethanol. Further PET imaging studies using established anticraving compounds, such as the μ-opioid receptor antagonist naltrexone and antiepileptic drugs affecting the GABA-ergic system more broadly, will provide additional important insights on the interaction between the GABA-ergic and the brain reward system in vivo and the suitability of GABA-ergic drugs as anticraving compounds.

Keywords Tiagabine - GABA - Alcohol - Ethanol - Striatum - Imaging - PET - 18-FDG

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Christoph Fehr Email: fehrc@uni-mainz.de

Social and Behavioral Characteristics of Young Adult Drink/Drivers Adjusted for Level of Alcohol Use

Alcoholism: Clinical and Experimental Research (OnlineEarly Articles).
q7 February 2007

• C. Raymond Bingham¹
• ¹University of Michigan Transportation Research Institute, Ann Arbor, Michigan; and ,
• Michael R. Elliott²
• ²Department of Biostatistics, University of Michigan, Ann Arbor, Michigan., and
• Jean T. Shope¹
• ¹University of Michigan Transportation Research Institute, Ann Arbor, Michigan; and

• ¹University of Michigan Transportation Research Institute, Ann Arbor, Michigan; and ²Department of Biostatistics, University of Michigan, Ann Arbor, Michigan.

Reprint requests: C. Raymond Bingham, University of Michigan Transportation Research Institute, Ann Arbor, MI; E-mail: rbingham@umich.edu

Abstract

Background:

Alcohol consumption and drink/driving are positively correlated and many predictors of alcohol use also predict drink/driving. Past research has not fully distinguished the contributions of personal risk factors from the level of alcohol use in the prediction of drink/driving. As a result, the extent to which predictors are specific to drink/driving, versus due to a mutual association to alcohol use, is unclear.

Methods:

This study examined the unique and shared risk factors for drink/driving and alcohol use, and examined the attributable risk (AR) associated with predictors of drink/driving while adjusting for alcohol use. Study data were from a telephone survey of 3,480 Michigan-licensed young adults who were drinkers. Four groups of drink/drivers were formed based on the prior 12-month maximum severity of drink/driving: (1) never drink/driving; (2) driving at least once within an hour of 1 or 2 drinks; (3) driving within an hour of 3 or more drinks or while feeling the effects of alcohol; and (4) drinking while driving.

Results:

Lower perceived risk of drink/driving, greater social support for drinking and drink/driving, greater aggression and delinquency, more cigarette smoking, and more risky driving behaviors uniquely predicted drink/driving severity in models adjusted for alcohol use. The largest ARs were associated with social support for drinking and drink/driving and perceived risk of drink/driving.

Conclusions:

These results confirm that alcohol use and drink/driving share risk factors, but also indicate that part of the variation in these factors is specific to drink/driving. Implications for interventions to reduce drink/driving are discussed

Background briefing | Professor David Clark
Theories of craving and urges

12 March 2007 | drinkanddrugsnews | p. 15
(PDF)







Professor David Clark describes craving and urges for
and briefly outlines some of the underlying theories.


The terms craving and urges have enjoyed wide popularity in both subjective reports of people
misusing substances and in the clinical literature of addiction.

Craving occurs for substances that cause problematic behaviour and addiction, including
opiates, stimulants, alcohol and nicotine. Moreover, craving has been suggested as a prominent feature maintaining drug and alcohol use and precipitatingrelapse after a period of abstinence.

Craving is regarded as a subjective motivational state in which an individual experiences an intense or overpowering desire to engage in drug-taking or alcohol consumption. It can vary in intensity, sometimes reaching a level that can overwhelm the individual, dominating their thoughts, feelings and actions to the exclusion of all else.

There has been some confusion in the field related to the terms craving and urges. While some
people use the terms interchangeably, others consider a distinction between the two phenomena. For example, Tom Horvarth describes craving as a desire to achieve the psychological state induced by the substance that one has given up – the ‘I want it badly’ feeling. Cravings serve as a cue for urges. An urge is considered to be the impulse or intention to get the substance and use it – it is the ‘I have to do it now’ feeling. Some therapeutic strategies focus on managing the response to urges because they cue the addictive behaviour. Cravings and urges have been intimately linked to classical conditioning processes. Over a long history of drinking or drug-taking, stimuli that have been repeatedly associated with consumption of alcohol or drugs (eg sight of the pub, or the syringe) become conditioned stimuli.

These conditioned stimuli become capable of eliciting the same responses that are produced by
alcohol or drugs themselves. They activate conditioned motivational states that produce craving and urges, physiological reactions, and drug or alcohol seeking behaviour.

Craving and urges can be linked to both positive and negative reinforcement systems. One model proposes that these states arise from the anticipation of the positive reinforcing or pleasurable effects of drugs or alcohol. Watching someone smoke a cigarette and the smell of the
tobacco can remind an ex-smoker of the relaxing effect of smoking and trigger an intense desire to experience this again.

Another model proposes that craving and urges arise from the need to relieve withdrawal or
conditioned withdrawal symptoms. Thus, a person returning to an area where they have experienced withdrawal on many occasions in the past may experience conditioned withdrawal symptoms, which in turn can generate craving.

In contrast, Terry Robinson and Kent Berridge argue that drug or alcohol craving is a psychological process that is distinct from conditioned withdrawal and the anticipation of pleasurable drug or alcohol effects.

They propose that repeated use of these substances can lead to neuroadaptations (increased
sensitivity) in brain dopamine systems that are involved in attributing incentive salience to stimuli. Incentive salience is a psychological process that ‘transforms the perception of stimuli, imbuing them with salience, making them attractive, “wanted” incentive stimuli’.

The sensitisation of these brain dopamine systems causes excessive incentive salience to be
attributed to the act of drug-taking and to stimuli associated with drug-taking, transforming ordinary wanting into excessive drug craving.

Importantly, these researchers make a distinction between ‘wanting’ and ‘liking’; although a person may want a drug, they may not necessarily like it. While some models assume a tight link between drug or alcohol misuse and craving, the cognitive model of Steve Tiffany proposes that drug and alcohol use in addicts can function independently of the processes that control craving.

Tiffany argues that over a long history of drinking (or drug use), many of the actions involved in
acquiring and consuming alcohol become automatic for people with an alcohol problem. Stimulus triggers (eg clock reaching 17.00) activate automatic cognitive processes that result in automatic drinking, with craving playing no controlling role.

However, when the automated alcohol use sequences in a drinker are blocked by an
environmental obstacle, eg favourite pub is closed for renovation, the person must activate nonautomatic processes to cope with the problem.

These non-automated processes, when activated simultaneously with automated alcohol use
sequences, generate craving.

People with a drink problem who are abstaining from alcohol face a continuous barrage of cues and situations that trigger their automated alcohol use sequences. By trying to abstain they are using nonautomated cognitive processes, which in turn generate craving.

This model can account for the fact that addicts often do not identify craving as a major, immediate cause of their relapse.

Tiffany points out that relapses that occur where craving is not identified as a major cause might be the result of automatic alcohol or drug use sequences being activated without concurrent
mobilisation of non-automatic processes directed towards impeding these automated sequences.

Craving and urges for drugs and alcohol cause a repeated, short-term discomfort to a person, which they need to learn to deal with if they are to overcome their substance use problem. While they are a natural part of addiction, they do disappear over time. Strategies have been developed that help people deal with craving and urges; use of these can facilitate behavioural change and the path to recovery.

Source: Daily Dose 12 March 2007

Factors predictive of alcohol use during pregnancy in three rural states
Behavioral and Brain Functions 2007, 3:8
9 February 2007

Gary R Leonardson1 , E-mail: mpr@zipmt.com Roland Loudenburg2 and Judy Struck3 1Mountain Plains Research, 55 Rodeo Trail, Dillion, MT 59725, USA 2Center for Disabilities, Department of Pediatrics, Sanford School of Medicine, The University of South Dakota, P. O. Box 530, Salem, SD 57058, USA 3Center for Disabilities, Department of Pediatrics, Sanford School of Medicine, The University of South Dakota, 1400 West 22nd Street, Sioux Falls, SD 57374, Abstract Background A substance use screening instrument was used to determine factors predictive of drinking during pregnancy. Alcohol consumption during pregnancy can lead to negative birth outcomes. Methods The participants (n = 4,828) for the study were sampled from pregnant women attending prenatal clinics in Montana, South Dakota, and North Dakota. Clinic sites for the administration of the screening instrument were selected in each state, based on geographic and known population characteristics. Univariate and multivariate statistical procedures were used to determine factors predictive of drinking during pregnancy. Results Women who drank tended to: be single, be between 21–25 years old, have had fewer children, have had abortions, and be unemployed. Demographic factors that were protective of drinking when pregnant were married and full-time housewife status. Other variables associated with maternal alcohol use were: past sexual abuse, current or past physical abuse, tobacco use, other drug use, lived with substance users, and had mates who were substance users. Other contributing factors for alcohol use included: feeling sad, believing that drinking any amount of alcohol while pregnant was acceptable, had been in treatment, could use treatment now, and were able to hold four or more drinks. Conclusion Because drinking rates were high and factors correlated with drinking are known, alcohol screening for this population is essential. Full Text (PDF) ____________________________________________________________________

Determining client need in a multi-state fetal alcohol syndrome consortium: from training to practice

Behavioral and Brain Functions 2007, 3:10
15 February 2007


Suzanne Christopher¹ , E-mail: suzanne@montana.edu
Tim Dunnagan¹ ,
George Haynes¹ and
Lili Stiff^2
1Department of Health and Human Development, Herrick Hall, Montana State University, Bozeman, MT 59717, USA
²Department of Health and Human Development, Haley Road, Bozeman, MT 59715, USA


Abstract

Background

A multi-state consortium was developed in the US to conduct baseline data collection and intervention research on fetal alcohol syndrome. Each state employed support specialists whose job it was to reduce or eliminate alcohol consumption in women who were at high risk for drinking alcohol during their pregnancy. The purpose of this paper is to report how support specialists in three primarily rural/frontier states were trained to assess client need and how client need was actually assessed in the field.

Methods

A qualitative process evaluation was conducted using semi-structured interviews. Interviews were conducted with state staff involved in support specialist training and consortium activities and the support specialists themselves. Inductive analyses were conducted with interview data.

Results

Need determination varied by state and for one state within the state. How support specialists were trained to assess need and how need was assessed in the field was mostly congruent.

Conclusion

Process evaluation is an effective method for providing practical and useful answers to questions that cannot be answered by outcome evaluation alone.

Full Text (PDF)

Effects of craving and DRD4 VNTR genotype on the relative value of alcohol: an initial human laboratory study

Behav Brain Funct. 2007; 3: 11. Published online 2007 February 19. James MacKillop,1,2 David P Menges,1 John E McGeary,3,2 and Stephen A Lisman1 1Department of Psychology, State University of New York at Binghamton, PO Box 6000, Binghamton, NY 13902-6000, USA 2Center for Alcohol and Addiction Studies, Brown University, Box G-BH, Providence RI 02906, USA 3Providence Veteran Affairs Medical Center, Providence RI 02909, USA Corresponding author. James MacKillop: james_mackillop@brown.edu ; David P Menges: dmenges@eden.rutgers.edu ; John E McGeary: john_mcgeary@brown.edu ; Stephen A Lisman: slisman@binghamton.edu Received December 1, 2006; Accepted February 19, 2007. Abstract Background Craving for alcohol is a highly controversial subjective construct and may be clarified by Loewenstein's visceral theory, which emphasizes craving's behavioral effects on the relative value of alcohol. Based on the visceral theory, this study examined the effects of a craving induction on the relative value of alcohol as measured by a behavioral choice task. In addition, based on previous evidence of its role in the expression of craving, the influence of DRD4 VNTR genotype (DRD4-L vs. DRD4-S) was also examined. Methods Thirty-five heavy drinkers (54% male; 31% DRD4-L) were randomly assigned to receive either a craving induction (exposure to personally relevant alcohol cues) or a control induction (exposure to neutral cues), which was followed by an alcohol-money choice task. Participants were assessed for craving and positive/negative affect throughout the procedure, and relative value of alcohol was derived from participant choices for alcohol versus money. DRD4 VNTR status was assessed retrospectively via buccal samples using previously established protocols. Results Factorial analysis of the craving induction revealed that it was associated with significant increase in craving (p < .001), but not greater relative value of alcohol. Factorial analyses including DRD4 VNTR genotype of did not suggest an influence on reactivity to the craving induction, although this analysis was substantially compromised by small cell sample sizes. Continuous analyses revealed that craving was significantly associated with the relative value of alcohol (p < .05) and possession of the DRD4-L allele further amplified this relationship (p < .001). Conclusion These results are interpreted as generally supporting Loewenstein's visceral theory of craving and evidence of a functional role of DRD4 VNTR genotype in the expression of craving for alcohol. Methodological limitations, mechanisms underlying these findings, and future directions are discussed. Full Text (PDF)

ALCOHOL DEPENDENCE
Updated January 16. 2007

OMIMTM - Online Mendelian Inheritance in ManTM

Welcome to OMIM, Online Mendelian Inheritance in Man. This database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere, and developed for the World Wide Web by NCBI, the National Center for Biotechnology Information. The database contains textual information and references. It also contains copious links to MEDLINE and sequence records in the Entrez system, and links to additional related resources at NCBI and elsewhere.

#103780
ALCOHOL DEPENDENCE

Alternative titles; symbols

ALCOHOLISM

Gene map locus 13q14-q21, 4q22, 4p13-p12

TEXT

A number sign (#) is used with this entry because of the demonstrated role of multiple genes in determining the genetic susceptibility for alcoholism that is supported by family, twin, and other studies.

INHERITANCE

The tendency for drinking patterns of children to resemble those of their parents has been recognized since antiquity, e.g., in the observations of Plato and Aristotle (Warner and Rosett, 1975). Alcoholism is probably a multifactorial, genetically influenced disorder (Goodwin, 1976). The genetic influence is indicated by studies showing that (1) there is a 25 to 50% lifetime risk for alcoholism in sons and brothers of severely alcoholic men; (2) alcohol preference can be selectively bred for in experimental animals; (3) there is a 55% or higher concordance rate in monozygotic twins with only a 28% rate for like-sex dizygotic twins; and (4) half brothers with different fathers and adopted sons of alcoholic men show a rate of alcoholism more like that of the biologic father than that of the foster father. A possible biochemical basis is a metabolic difference such that those prone to alcoholism have higher levels of a metabolite giving pleasurable effects or those not prone to alcoholism have higher levels of a metabolite giving unpleasant effects. Schuckit and Rayses (1979) found that, after a moderate dose of alcohol, blood acetaldehyde levels were elevated more in young men with alcoholic parents or sibs than in controls. A certain degree of organ specificity in the pathologic effects of alcohol is observed. For example, patients have cardiomyopathy, cirrhosis, or pancreatitis but rarely more than one of these. A genetic basis of organ specificity is evident in Wernicke-Korsakoff syndrome (277730) and pancreatitis from type V hyperlipidemia (238400).

Cloninger (1987) identified 2 separate heritable types of alcoholism. Type 1 alcohol abuse had its usual onset after the age of 25 years and was characterized by severe psychological dependence and guilt. It occurred in both men and women and required both genetic and environmental factors to become manifest. By contrast, type 2 alcohol abuse had its onset before the age of 25; persons with this type of alcoholism were characterized by their inability to abstain from alcohol and by frequent aggressive and antisocial behavior. Type 2 alcoholism was rarely found in women and was much more heritable. Abnormalities in platelet monoamine oxidase activity were found only in type 2 alcoholics (Von Knorring et al., 1985). See comments by Omenn (1988).

Crabb (1990) reviewed biologic markers for increased risk of alcoholism. Aston and Hill (1990) performed complex segregation analysis of 35 multigenerational families ascertained through a pair of male alcoholics. They concluded that liability to alcoholism is, in part, controlled by a major effect with or without additional multifactorial effects. However, mendelian transmission of this major effect was rejected, as was the hypothesis that the major effect is due to a single major locus.

In connection with a collection of 11 research reports on the genetics of alcohol-related traits, Buck (1998) gave a brief review on recent progress toward the identification of genes related to risk for alcoholism.

MAPPING

Nurnberger et al. (2001) reported linkage data indicating that a susceptibility locus for alcoholism and/or depression phenotypes resides on chromosome 1p. Using short tandem repeat (STR) markers and the transmission disequilibrium test in 87 European-American families with one or more alcohol-dependent offspring (93 children and 174 parents), Lappalainen et al. (2004) fine-mapped the region identified by Nurnberger et al. (2001). The strongest evidence for transmission disequilibrium was for marker D1S406 (p = 0.005). Three other markers, all within less than 350 kb, had supporting evidence for transmission disequilibrium: D1S424 (p = 0.01), D1S2804 (p = 0.04), and D1S2776 (p = 0.02). Lappalainen et al. (2004) suggested that one or more genes causing susceptibility to alcohol dependence reside on chromosome 1 in a region approximately delimited by markers D1S1170 and D1S2779.

Event-related brain potentials (ERPs) are recordings of neuroelectric activity, usually in response to some task, made from electrodes on the scalp. ERPs are altered in patients with a variety of psychiatric disorders and in members of their families, compared with the general population. Alcoholic subjects have a reduction of amplitude of the P3 component, a positive peak approximately 300-600 ms after a stimulus, that remains after long periods of abstinence from alcohol (Porjesz and Begleiter, 1985). A similar reduction in P3 amplitude is also seen in young alcohol-naive sons of alcoholic probands (Begleiter et al., 1984). Almasy et al. (2001) presented results of a genomewide linkage screen for amplitude of the N4 and P3 components of the ERP, measured at 19 scalp locations in response to a semantic priming task for 604 individuals in 100 pedigrees ascertained as part of a collaborative study on the genetics of alcoholism. N4 and P3 amplitudes in response to 3 semantic stimuli showed significant heritabilities, the highest being 0.54. Both N4 and P3 amplitudes showed significant genetic correlations across stimulus type at a given lead and across leads within a stimulus, indicating shared genetic influences among the traits. N4 amplitudes showed suggestive evidence of linkage in several chromosomal regions, and P3 amplitudes showed significant evidence of linkage to chromosome 5 and suggestive evidence of linkage to chromosome 4.

Ehlers et al. (2004) used a panel of 791 microsatellite polymorphisms to map susceptibility loci for DSM-III-R alcohol dependence and 2 narrower alcohol-related phenotypes (alcohol use severity phenotype and withdrawal phenotype) in Mission Indian families (466 individuals). Analyses of multipoint variance component lod scores for the dichotomous DSM-III-R phenotype revealed no peak lod scores that exceeded 2.0. For the alcohol use severity phenotype, chromosomes 4 and 12 had peak lod scores that exceeded 2.0, and for the withdrawal phenotype, chromosomes 6, 15, and 16 were found to have peak lod scores that exceeded 2.0. Combined linkage and association analyses suggested that polymorphisms of the alcohol dehydrogenase-1B gene (ALD2; 103720) were partially responsible for the linkage result on chromosome 4 in this population.

Prescott et al. (2006) conducted a genome scan in the Irish Affected Sib Pairs Study of Alcohol Dependence sample set. Most of the probands were ascertained through alcoholism treatment settings and were severely affected. Probands, affected sibs, and parents were evaluated by structured interview. Most of the 474 families in the study were comprised of affected sib pairs (96%). Quantitative results indicated strong linkage for alcohol dependence criteria (defined by DSM IV) to chromosome 4q22-4q32 (peak multipoint lod = 4.59, p = 0.0000021 at D4S1611).

Hill et al. (2004) studied families containing alcoholics (330 individuals) identified through a double proband methodology. Multipoint linkage analyses using 360 markers for 22 autosomes gave strong support for loci on chromosomes 1, 2, 6, 7, 10, 12, 14, 16, and 17.

MOLECULAR GENETICS

Association with the ADH Gene Cluster on Chromosome 4q22

Chai et al. (2005) examined polymorphisms in the ADH2 (103720) and ADH3 (103730) genes on chromosome 4q22 and in the ALDH2 (100650) gene on chromosome 12q24 in 72 alcoholic and 38 nonalcoholic healthy Korean men. Forty-eight of the alcoholic men had Cloninger type 1 and 24 had Cloninger type 2 alcoholism. The frequency of ADH2*1 (103720.0001) and ADH3*2 (103730.0002) alleles was significantly higher in men with type 2 alcoholism than in men with type 1 alcoholism and in healthy men. The frequency of the ALDH2*1 (100650.0001) allele was significantly higher in men with alcohol dependence than in healthy men. Chai et al. (2005) suggested that the genetic characteristics of alcohol metabolism in type 1 alcoholism fall between nonalcoholism and type 2 alcoholism.

Association with the GABA-A Receptor Gene Cluster on Chromosome 5q34

Radel et al. (2005) genotyped a Southwestern Native American sample of 433 individuals and a Finnish sample of 511 individuals, including both alcohol-dependent and unaffected individuals, for 6 SNPs in the GABA-A receptor gene cluster (see 137140) on chromosome 5q34. Sib-pair linkage and case-control association analyses as well as linkage disequilibrium mapping with haplotypes were done. Radel et al. (2005) detected sib-pair linkage of 5q34 GABA-A receptor genes to alcohol dependence in both population samples. Haplotype localization implicated 3 polymorphisms of GABRA6 (137143), including a pro385-to-ser substitution.

Association with the NPY Gene on Chromosome 7p15

Kauhanen et al. (2000) and Lappalainen et al. (2002) found an association between susceptibility to alcoholism and a leu7-to-pro polymorphism in the neuropeptide Y (NPY) gene on chromosome 7p15; see 162640.0001.

Association with the TAS2R16 Gene on Chromosome 7q31

Hinrichs et al. (2006) found a functional variant in a bitter-taste receptor (TAS2R16; 604867.0001) on chromosome 7q31 that influences risk of alcohol dependence. The K172 allele of the K172N SNP showed an increased risk of alcohol dependence, regardless of ethnicity. However, this risk allele was uncommon in European Americans, whereas 45% of African Americans carried the K172 allele, which makes this a much more significant risk factor in that population.

Association with the CHRM2 Gene on Chromosome 7q35

Genomewide linkage analyses using pedigrees from the Collaborative Study of the Genetics of Alcoholism (COGA) provided consistent evidence of an alcoholism susceptibility locus on the long arm of chromosome 7 (Reich et al., 1998; Foroud et al., 2000).

By fine mapping of 488 sib pairs with alcohol dependence, Wang et al. (2004) refined the locus on chromosome 7q to D7S1799 (lod = 2.9). They examined 11 SNPs within and flanking the CHRM2 gene (118493) in 262 families with alcohol dependence from the COGA. Three SNPs showed highly significant association with alcoholism (p = 0.004, 0.004, and 0.007, respectively). Two SNPs were significantly associated with major depressive syndrome (MDD; 608516) (p = 0.004 and 0.017). Haplotype analyses revealed that the most common haplotype, T-T-T (rs1824024, rs2061174, and rs324650), was undertransmitted to affected individuals with alcohol dependence and major depressive syndrome.

Association with the DRD2 Gene on Chromosome 11q23

The candidate gene approach was used by Blum et al. (1990) and by Bolos et al. (1990) to investigate a possible relationship of the dopamine D2 receptor (DRD2; 126450), which maps to chromosome 11q23, to alcoholism. Although Blum et al. (1990) suggested an association between a particular allele at the DRD2 locus, Bolos et al. (1990) could not confirm this. In family studies, Bolos et al. (1990) excluded linkage between alcoholism and the DRD2 locus.

Johann et al. (2005) studied the association of a -141C deletion variant (-141delC) of the DRD2 gene in 1,126 well-characterized, primary chronic alcoholics of German descent according to a phenotype-genotype strategy and found an excess of the -141delC alleles in alcoholics with a paternal and grandpaternal history of alcoholism and in alcoholic subgroups with suicidality or without a history of withdrawal symptoms. Johann et al. (2005) concluded that the -141delC variant of DRD2 might be a protective factor against the development of withdrawal symptoms but might also be a risk factor in a highly burdened subgroup of alcoholics with a paternal and grandpaternal history of alcoholism and might contribute to suicide risk in alcoholics.

Association with the ALDH2 Gene on Chromosome 12

Chai et al. (2005) examined polymorphisms in the ADH2 and ADH3 genes on chromosome 4q22 and in the ALDH2 (100650) gene on chromosome 12q24 in 72 alcoholic and 38 nonalcoholic healthy Korean men. Forty-eight of the alcoholic men had Cloninger type 1 and 24 had Cloninger type 2 alcoholism. The frequency of the ALDH2*1 (100650.0001) allele was significantly higher in men with alcohol dependence than in healthy men. Also see 'Association with the ADH Gene Cluster on Chromosome 4q22.'

Association with the ANKK1 Gene (TaqIA Allele) on Chromosome 11q23

In a study of the TaqIA polymorphism (see ANKK1; 608774) in 884 nonalcoholic Finnish Caucasian males, Hallikainen et al. (2003) found that the self-reported alcohol consumption of the homozygous A1/A1 group was 30% and 40% lower than that of the A1/A2 and A2/A2 groups, respectively (p = 0.042).

Association with the SLC6A4 Gene on Chromosome 17q

Feinn et al. (2005) conducted a metaanalysis of the association of the functional serotonin transporter promoter polymorphism (SLC6A4; 182138.0001) on chromosome 17q with alcohol dependence. The metaanalysis was from data collected from 17 published studies including 3,489 alcoholics and 2,325 controls. The frequency of the short allele was significantly associated with alcohol dependence (OR = 1.18, 95% CI = 1.03-1.33). A greater association with the S allele was seen among individuals with alcohol dependence complicated by either a comorbid psychiatric condition or an early-onset or more severe alcoholism subtype (OR = 1.34, 95% CI = 1.11-1.63).

Following up on a study by Herman et al. (2003) that showed an association between the SLC6A4 short form of the promoter polymorphism and alcohol consumption in a college population, Munafo et al. (2005) studied 755 individuals, aged 33 to 73 years, who were recruited from general practices in the U.K. as part of a study of genetic associations with smoking cessation. Subjects were assessed for age, gender, body mass index, weekly alcohol consumption, ethnicity, and smoking habits. Individuals who were nondrinkers were excluded from the study. Genotyping was done for SLC6A4 long and short promoter polymorphisms. The short allele was significantly associated with increased alcohol consumption (p = 0.03). There was suggestive evidence of a genotype-sex interaction (p = 0.04). Post hoc analysis indicated higher alcohol consumption in men with one or more copies of the short allele, whereas consumption in women was highest among heterozygotes compared to both homozygote groups.

Association with the COMT Gene on Chromosome 22q11

The enzyme catechol-O-methyltransferase (COMT; 116790), encoded by a gene on chromosome 22q11, has a crucial role in the metabolism of dopamine. Lachman et al. (1996) suggested that a common functional genetic polymorphism in the COMT gene, which results in 3- to 4-fold difference in COMT enzyme activity, may contribute to the etiology of mental disorders such as bipolar disorder and alcoholism. Since ethanol-induced euphoria is associated with the rapid release of dopamine in limbic areas, it was considered conceivable that subjects who inherited the allele encoding the low activity COMT variant would have a relatively low dopamine inactivation rate, and therefore would be more vulnerable to the development of ethanol dependence. In 2 Finnish populations of type 1 (late-onset) alcoholics, Tiihonen et al. (1999) found a markedly higher frequency of the low activity allele (L). They estimated that the population etiologic (attributable) fraction for the LL genotype in alcoholism was as high as 13.3%.

ANIMAL MODEL

Liang et al. (2003) demonstrated that in alcohol-preferring and alcohol-nonpreferring rats, a polymorphism in the alpha-synuclein gene (SNCA; 163890) maps to the same location as a QTL for alcohol preference.

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