CONTENTS

A. NIAAA Budget

FY 2005 Appropriation On December 8, 2004 Congress and President Bush finalized the FY 2005 appropriation. The FY 2005 NIAAA appropriation of $438.3 million provides a 2.3 percent increase over the FY 2004 level of $425.4 million. Included in the appropriation is $27.2 million for HIV/AIDS research.

FY 2006 President's Request The FY 2006 President's Request for NIH has not yet been released.

A summary of the FY 2005 Appropriation (in thousands):

B. Director's Activities

International Society for Biomedical Research on Alcoholism On September 30, Dr. Li gave a plenary talk on "Gene-Environment Correlations in Drinking Behavior: A Developmental Perspective," at the International Society for Biomedical Research on Alcoholism (ISBRA) conference in Mannheim, Germany. As part of the ISBRA meeting, he also gave an overview of Dr. Harold Kalant's research career at a symposium on alcohol tolerance honoring Dr. Kalant. Other NIAAA staff chairing sessions or making presentations at ISBRA include Drs. David Lovinger, Kenneth Warren, and Mark Willenbring.

11th U.S.-China Science and Technology Joint Commission Meeting On October 12, officials from U.S. and Chinese science agencies participated in the 11th U.S.-China Science and Technology Joint Commission Meeting. The meeting took place at the U.S. Department of State in Washington, DC. Speakers discussed areas of past collaboration and identified areas of mutual interest for the future. Dr. Li gave a presentation entitled "Alcohol Use Disorders: A Global Challenge."

Maloney-Booker Graduate Lecture in Pharmacology Howard University College of Medicine sponsors the yearly Maloney-Booker Graduate Lecture in Pharmacology in memory of two distinguished Howard pharmacologists, Drs. Arnold H. Maloney and Walter M. Booker. For this year's Maloney-Booker lecture November 10, Dr. Li spoke on "Genes, Environment, and Alcohol Pharmacology: The Development of Alcoholism."

Association for Medical Education and Research in Substance Abuse Dr. Li gave a talk on "Alcohol Research in the Post-Genomics Era" on November 12 at the annual meeting of the Association for Medical Education and Research in Substance Abuse (AMERSA) in Washington, DC. AMERSA's mission is to promote multidisciplinary health professional faculty development in substance abuse.

White House Leadership Conference on Medical Education in Substance Abuse The White House Office of National Drug Control Policy (ONDCP) hosted a Leadership Conference on Medical Education in Substance Abuse on December 1 and 2. The meeting brought together leaders or organizations and agencies seeking to enhance the training of physicians in the prevention, diagnosis, and treatment of drug and alcohol problems and related medical disorders. Dr. Li gave a talk entitled "Health Professions Education: View from the National Institute on Alcohol Abuse and Alcoholism." The talk included a proposal for a collaborative program for the development of core faculty in health professional schools. Peggy Murray served on the expert panel advising the program organizers, and Drs. Mark Willenbring and Howard Moss participated in meeting discussion groups.

Advisory Committee to the Director, NIH Dr. Li gave a talk entitled "Vision and Goals for the National Institute on Alcohol Abuse and Alcoholism: 2003 and Beyond," on December 2 at the semiannual meeting of the Advisory Committee to the Director, NIH.

C. NIAAA Staff

Extramural Staff

Howard Moss, M.D. New NIAAA Associate Director Dr.  Howard Moss has joined NIAAA as Associate Director for Education and Career Development. Dr. Moss, an addiction psychiatrist, comes to NIAAA from the University of Pennsylvania School of Medicine in Philadelphia, where he served as professor of psychiatry and director of the Substance Abuse Fellowship Training Program. As Associate Director for Education, he is charged with leading NIAAA efforts to close the gap between alcohol research and medical practice. Dr. Moss will advise Dr. Li on all areas related to science education and the training and development of scientists participating in alcohol research activities in both the extramural and intramural programs. Among Dr. Moss' duties will be the development of educational programs for physicians and graduate and undergraduate students.

Roberta Wilhelm  Roberta Wilhelm, Chief of NIAAA's Contracts Management Branch since 1987, has retired. Under Ms. Wilhelm's leadership, the contracts budget grew from $2.5 million to a peak of $36 million. In 2003, she was named the recipient of the 4th Martin K. Trusty Excellence in Management Award, established by NIAAA to recognize long-term, outstanding commitment to, and excellence in the management of, programs and administration. She was cited for "outstanding analysis, advice, and recommendations to senior staff." Staff will miss her sound advice and leadership. Ed Kostolansky will be Acting Chief for the next 3 months, followed by Matthew L. Packard while NIAAA conducts a search for a new branch chief.

Barbara Smothers, Ph.D.  Dr. Barbara Smothers, who has been with NIAAA since 1988, has left to take the position of Director of the Division of Extramural Affairs with the National Institute of Nursing Research. Dr. Smothers had worked as a member of NIAAA's extramural review staff and in the Epidemiology Branch prior to joining the Division of Epidemiology and Prevention Research.

Intramural Staff

Wolfgang H. Sommer, M.D., Ph.D.  Dr. Wolfgang Sommer was appointed as a staff clinician (visiting program or VP, 10/31/2004 - 08/31/06) in the Section of Molecular Pathophysiology (SMP), Laboratory of Clinical Studies (LCS). Dr. Sommer will focus on developing a research program in behavioral genomics within LCS. Dr. Sommer possesses experience in molecular biological techniques and an interest in transitional research in areas relevant to alcoholism.

Karin Annika Thorsell, Ph.D.  Dr. Karin Thorsell was appointed as a staff scientist (VP, 12/08/2004 - 11/13/2006) in the SMP, LCS. Dr. Thorsell will establish an in vivo pharmacology unit focusing on animal models of addiction.

Rise B. Goldstein, Ph.D.  Dr. Rise Goldstein was appointed as a staff clinician (12/12/2004 - 12/11/2009) in the Laboratory of Epidemiology and Biometry. Dr. Goldstein's primary research focus will involve national epidemiologic surveys conducted by the laboratory.

New Research Fellows  The following scientists have joined DICBR as fellows: Scott A. Chen, Ph.D., research fellow, LCS (Poolesville), Grezegorz Godlewski, Ph.D., visiting fellow, Section on Neuroendocrinology, Laboratory of Physiologic Studies; Anita Hansson, Ph.D. and Anton Terasmaa, Ph.D., visiting fellows in the Section of Molecular and Pathophysiology, LCS; Dmitriy Krepkiy, Ph.D., visiting fellow in the Section of Nuclear Magnetic Resonance, Laboratory of Membrane Biochemistry and Biophysics; Damian Williams, Ph.D., visiting fellow, Section on Transmitter Signaling, Laboratory of Molecular Physiology; and Henry Yin, Ph.D., postdoctoral fellow in the Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience.

D. Research Priority Emphasis and Core Support Teams

Underage Drinking On September 20, 2004, NIAAA convened the first meeting of the Steering Committee on Underage Drinking Research and Prevention. NIAAA organizers assembled a multidisciplinary group with broad and varied expertise in child and adolescent development, neuroscience, genetics, prevention research, public policy, communications, alcohol research, and other fields. Serving on the steering committee are Richard J. Bonnie, Jane D. Brown, Sandra A. Brown, Ronald E. Dahl, Thomas J. Dishion, Cindy L. Ehlers, Mimi Fleury, Ann S. Masten, Matthew McGue, Frank Middleton, Stacia A. Murphy, Daniel Pine, Sir Michael Rutter, Linda Spear, Michael Windle, and Robert A. Zucker. The committee also includes two members of the Leadership to Keep Children Alcohol Free: Kendel Ehrlich, First Lady of Maryland; and Nancy Freudenthal, First Lady of Wyoming. (The Leadership initiative is a unique national public-private coalition led by State governors' spouses.) The complete steering committee roster, including the committee members' affiliations, is available at niaaa.nih.gov/about/underage.htm.

NIAAA staff provided an overview of the current science on underage drinking, including epidemiology, neuroscience, genetics, and research on prevention and treatment. The committee held a wide-ranging discussion of the need for research on adolescent development and the factors driving underage drinking as well as strategies to prevent youth drinking and its consequences. Data suggest that for a high percentage of individuals who develop alcohol dependence, the disorder has its onset much younger than previously thought, suggesting that dependence is a developmental disorder that begins for many in youth. A key point made in the meeting is the necessity of developing an understanding of youth drinking in the context of adolescent development as a basis for prevention and intervention. To address these issues further, NIAAA will form smaller task groups with additional outside experts to work in conjunction with the steering committee to conceptualize the phenomenon of underage alcohol consumption and identify the best ways to move the research agenda in this area forward. The next meeting of the steering committee is scheduled for March 3 and 4, 2005. For updates on steering committee activities, visit NIAAA's Web site at niaaa.nih.gov/about/underage.htm.

E. NIAAA Research Programs

Intramural Programs

Intramural Staff in New Quarters Division of Intramural Clinical and Biological Research staff now occupy their long-awaited new research laboratories. Staff formerly located in the Flow/Park research facility moved to 5625 Fishers Lane, Rockville MD, adjacent to NIAAA's administrative offices, in late October 2004. Another long-awaited move that began in the fall was that of the Laboratory of Clinical Studies (LCS), Clinical Research Unit and associated labs. This portion of the LCS, under the direction of Dr. Markus Heilig and previously located on the 6S240 Clinical Unit in Building 10 on the NIH campus, is now located on the first floor of the Mark O. Hatfield Clinical Research Center, the newly completed portion of NIH's Clinical Center.

NIH Research Festival Symposium Dr. David Goldman, chief, Laboratory of Neurogenetics, was invited to participate in the 2004 NIH Research Festival Symposium "Complex Genetics and Common Brain Disorders," chaired by Dr. George Uhl, National Institute on Drug Abuse. The symposium focus was to provide an update on brain and nervous system disorders that affect millions of Americans annually and that are thought to be mediated through complex multigene genetics. Speakers presented their research in the context of the overall genetic architectures of these illnesses with a focus on the ways in which their findings relate to the clinical manifestations of the diseases, how their work might help uncover novel neurobiological mechanisms of illnesses, and the implications of polygene discoveries for diagnosis and treatment. Dr. Goldman's presentation was entitled "Complex Genetics of Alcoholism."

Endocannabinoid Presentations Dr. George Kunos, NIAAA Scientific Director, was invited as a panelist to the Masters of Integrative Physiology Advisory Board meeting in New York (sponsored by Sanofi/Aventis) where he presented a talk on the "Role of Endocannabinoids in the Control of Appetitive Behavior." Dr. Kunos was also invited to give a presentation at the Sixth Annual Symposium of the D.B. Brown Obesity Research Chair in Quebec City, Canada. His talk was entitled "The Endocannabinoid System and Its Role in Energy Homeostasis."

Extramural Programs

Office of Scientific Affairs Reorganized NIAAA’s Office of Scientific Affairs (OSA) has become two offices, one retaining the OSA name, and the other designated the Office of Extramural Activities (OEA). OSA will continue to coordinate scientific advisory activities for the institute, including the function of the national advisory council and the Extramural Advisory Board. The office will retain its role in coordination of NIAAA planning activities, including the Government Performance and Reporting Act (GPRA) and the NIH Roadmap. OEA will have responsibility for extramural grant and contract review, including the management of NIAAA’s chartered initial review groups and special emphasis panels, and for all grants management activities. Dr. Kenneth Warren will continue as OSA Director, and Dr. Tina Vanderveen will serve as Director of OEA.

Lisa Neuhold, Ph.D., Editor Human Brain Proteome Dr. Lisa A. Neuhold edited a book titled the "Human Brain Proteome," published by Elsevier Academic Press. This volume, which is part of the International Review of Neurobiology series, summarizes advances in high-throughput proteomic technologies and its application to studying neurological and brain diseases including Alzheimer's disease, alcoholism, trauma/stroke, Huntington's disease, and Parkinson's disease.

Symposium on Mechanisms of Alcohol-Associated Cancers Dr. Vishnu Purohit organized an international symposium on the Mechanisms of Alcohol-Associated Cancers in Bethesda, Maryland, October 6-7, 2004. The symposium was co-sponsored by NIAAA, NIH's Office of Dietary Supplements and Office of Rare Diseases, the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute of Diabetes and Digestive and Kidney Diseases. Division of Metabolism and Health Effects Director Dr. Sam Zakhari was among the speakers opening the symposium. Scientists from this country and the United Kingdom, Germany, Finland, China, and Japan addressed the following issues: 1) general mechanisms of cancers; 2) epidemiology of alcohol-associated cancers; 3) alcohol and oral cancer; 4) cancers of upper aerodigestive tract and the large intestine; 5) acetaldehyde, microbes, and cancers of digestive tract; 6) mechanisms of acetaldehyde-induced DNA damage; 7) alcohol and aldehyde dehydrogenase polymorphisms and cancer; 8) alcohol and hepatocellular carcinoma; 9) alcohol and pancreatic cancer; 10) role of alcohol in breast cancer; 11) marijuana and cancer; 12) nicotine and gastric cancer; 13) role of MAT and SAMe in alcohol-associated liver cancer; 14) alcohol, vitamin A, and cancer; 15) alcohol, iron-associated oxidative stress, and cancer; and 16) alcohol, folate, and cancer. The proceedings of the symposium will be submitted for publication.

American Academy of Addiction Psychiatry  Division of Treatment and Recovery Research Director Dr. Mark Willenbring gave a presentation on co-occurring nicotine and alcohol dependence at the American Academy of Addiction Psychiatry in San Juan, Puerto Rico December 8-11.

Collaborative Research Efforts

Steering Committee Meeting for Rapid Response to College Drinking Problems  The first meeting of the steering committee for the Rapid Response to College Drinking Problems Program met on October 15, 2004. Attendees included the five (U01) researcher grantees, seven (U18) college/university grantees, and staff from the Substance Abuse and Mental Health Services Administration, the National Highway Traffic Safety Administration, and NIAAA. The purpose of the original program announcement, issued in June 2003, was to provide rapid funding for research on interventions to prevent or reduce alcohol-related problems among college students. The program pairs experienced researchers with educational institutions.

So Help Me God: Substance Abuse Religion and Spirituality Conference  NIAAA provided support for this September 2004 conference sponsored by the National Center on Addiction and Substance Abuse (CASA) at Columbia University, New York, NY. NIAAA Deputy Director Dr. Faye Calhoun presented opening remarks. The conference brought together leading scientists, clergy, mental health providers, and heads of theology and medical schools to discuss the relationship between religion and substance abuse and to develop strategies for encouraging faith and medical communities to work together to prevent and treat substance abuse.

Collaborative Minority Institution Alcohol Research Development Program  In December 2004, Caliber Associates completed the retrospective review of NIAAA's Collaborative Minority Institution Alcohol Research Development (CMIARD) Program. NIAAA initiated the CMIARD program in 1997. Through the CMIARD program, scientists at three minority institutions (Charles Drew University School of Medicine, North Carolina Central University, and Howard University) received awards to establish collaborations with experienced alcohol research scientists at research intensive institutions. The report evaluated CMIARD core functional areas including the collaborative partnerships, key administrative support, infrastructure development, and information transfer. The evaluation was very positive; it is being used to inform the second generation of minority centers, called the Collaborative Minority Serving Institution Alcohol Research program (CMSIAR) which began in late 2003. (CMIARD ended in FY 2003.)

Proceedings Published in Alcohol  The volume 34, number 1 issue of the journal Alcohol is the result of a symposium organized by Vishnudutt Purohit, Ph.D., that took place on Oct. 3, 2003. The subject of the symposium was "The Role of Fatty Liver, Dietary Fatty Acid Supplements, and Obesity in the Progression of Alcoholic Liver Disease." A paper in this issue of Alcohol by Drs. Purohit and Denise Russo in the Division of Metabolism and Health Effects and Dr. Paul Coates of NIH's Office of Dietary Supplements provides an overview of the symposium and summaries of the presentations made at the symposium.

New RFA's/PA's

Community Participation in Health Promotion and Disparities Research (PAR-05-026)  NIAAA joined the Agency for Healthcare Research and Quality in issuing this program announcement (PA). The purpose of this PAR is to support research on health promotion, disease prevention, and health disparities that is jointly conducted by communities and researchers. More information is available at https://webarchive.library.unt.edu/eot2008/20080916110810/http://fedgrants.gov/Applicants/HHS/NIH/NIH/PAR-05-026/Grant.html. The NIAAA contact is Dr. Robert Freeman, 301-443-8820, rfreeman@mail.nih.gov.

Decision Making in Health: Behavior Maintenance (PA-05-016)  NIAAA joined the National Cancer Institute in issuing this PA. The purpose of this initiative is to invite applications for research projects that will expand our knowledge of basic decision-making processes underlying initiation and long-term maintenance of healthy lifestyle behaviors that may reduce one's risk of cancer and other chronic diseases, such as cardiovascular disease, diabetes, and addiction. More information is available at https://webarchive.library.unt.edu/eot2008/20080916110810/http://fedgrants.gov/Applicants/HHS/NIH/NIH/PA-05-016/Grant.html. The NIAAA contact is Dr. Robert Freeman, 301-443-8820, rfreeman@mail.nih.gov.

Structural Interventions, Alcohol Use, and Risk of HIV/AIDS (AA-05-003)  This RFA requests research on the effectiveness of structural interventions that reduce the risk of HIV/AIDS transmission by changing the environment of alcohol use. More information is available at https://webarchive.library.unt.edu/eot2008/20080916110810/http://grants.nih.gov/grants/guide/rfa-files/RFA-AA-05-003.html. Dr. Robert Freeman is the scientific contact, 301-443-8820, rfreeman@mail.nih.gov.

Secondary Analysis of NESARC and NSPY Datasets (DA-05-005)  This RFA requests applications to study the epidemiology and etiology of alcohol and drug abuse, the prevention of these behaviors, and the use of alcohol and drug abuse services. Data are to be drawn from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) or the National Survey of Parents and Youth (NSPY). More information is available at https://webarchive.library.unt.edu/eot2008/20080916110810/http://grants1.nih.gov/grants/guide/rfa-files/RFA-DA-05-005.html. Dr. Robert Freeman is the NIAAA contact, 301-443-8820, rfreeman@mail.nih.gov.

Molecular Approaches to Diet and Pancreatic Cancer Prevention NIAAA joined the National Cancer Institute in issuing this PA. This initiative invites innovative preclinical and clinical R01 applications to determine how dietary energy intake and bioactive food components, including alcohol, influence pancreatic cancer development and prevention. More information is available at https://webarchive.library.unt.edu/eot2008/20080916110810/http://grants.nih.gov/grants/guide/pa-files/PA-05-040.html. The NIAAA contact is Dr. Vishnu Purohit, 301-443-2689, vpurohit@mail.nih.gov.

Research Reports

The following are examples of recently published reports from research conducted or supported by NIAAA:

NIAAA Press Releases: New NESARC Findings Reported  NIAAA issued three press releases since the last Council meeting reporting findings based on data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). The first paper reported on the first nationally representative data on the prevalence and co-occurrence of DSM-IV nicotine dependence and DMS-IV alcohol and drug use disorders, mood and anxiety disorders, and personality disorders. Among the findings: adults with nicotine dependence and/or psychiatric disorders consume 70 percent of all cigarettes smoked in the United States. Persons with a current psychiatric disorder-whether or not they are nicotine dependent-make up 30.3 percent of the population and consume 46.3 percent of all cigarettes smoked. Nicotine dependent persons with co-existing psychiatric disorders comprise only about 7 percent of the adult population but smoke about 34 percent of all cigarettes. The results indicate that smoking prevention and treatment efforts should be developed to target vulnerable subgroups at both the population and the individual levels. (Grant, B.F., Hasin, D.S., Chou, P., Stinson, F.S., and Dawson, D.A. Archives of General Psychiatry 61:1107-1115, 2004.)

A second paper reported on an analysis of immigration status in conjunction with psychiatric morbidity in each of four comparison groups: U.S.-born Mexican Americans, Mexican immigrants to the United States, U.S.-born non-Hispanic Whites, and non-Hispanic White immigrants to the United States. The analysis found that Mexican-Americans and non-Hispanic Whites born in the United States have a higher risk for developing psychiatric disorders than their foreign-born counterparts who have immigrated to this country. Also, U.S.-born Mexican Americans were at significantly lower risk of psychiatric morbidity than U.S.-born non-Hispanic whites. Identifying the specific components of various cultures that may reduce possible negative effects of acculturation on mental health or protect against psychopathology holds great promise in helping to guide future prevention and treatment efforts, the authors conclude. (Grant, B.F, Stinson, F.S., Hasin, D.S., Dawson, D.A., Chou, S.P., and Anderson, K. Archives of General Psychiatry 61:1226-1233, 2004.)

A third analysis of NESARC data found that more than one-third (35.9 percent) of U.S. adults with alcohol dependence (alcoholism) that began more than one year ago are now in full recovery. The fully recovered individuals include roughly equal proportions of abstainers (18.2 percent) and low-risk drinkers (17.7 percent). One-quarter of individuals with alcohol dependence that began more than a year ago remain dependent, 27.3 percent are in partial remission (exhibiting some symptoms of alcohol dependence or abuse) and 11.8 percent are asymptomatic but consume alcohol at levels that increase their chances of relapse (for men, more than 14 drinks per week or more than four drinks on any day; for women, more than 7 drinks per week or more than three drinks on any day). The NESARC analysis strengthens previous reports that many do recover from alcoholism; longitudinal studies will be required to understand the natural history of alcohol dependence over time. (Dawson, D.A., Grant, B.F., Stinson, F.S., Chou, P.S., Huang, Boji, and Ruan, W.J. Addiction published online ahead of print January 14, 2005, doi: 10.111/j.1360-0443.2004.00964.x.)

NIAAA Press Release: Youth Alcohol Consumption Remains High A new analysis of youth drinking trends found that while drinking by youth has stabilized over the past decade, it remains at disturbingly high levels. The current study used joinpoint analysis, a recently developed statistical methodology that provides a means of evaluating trends in data collected over time. The analysis used data from three national surveys, the Monitoring the Future study, the Youth Risk Behavior Survey, and the National Household Survey on Drug Abuse. The analyses showed an increase in youth drinking in the late 1970s, followed by a long period of decreases until the early 1990s. The authors note that the decline in underage drinking rates during this period probably reflects the increase in the minimum legal drinking age from 18 to 21. Since the early 1990s, all three surveys included in this analysis indicate relatively stable prevalence rates for underage drinking. (Faden, V.B. and Fay, M.P. Alcoholism: Clinical and Experimental Research 28:1388-1395, 2004.)

Intramural

Alcohol and Reactive Oxygen Species One of the ways heavy alcohol use is known to damage tissues and organs is through the production of reactive oxygen species (ROS), highly reactive molecules which are a side-product of the breakdown of alcohol. A main source, as well as a target, of ROS production are mitochondria, cell organelles involved in the cell's energy metabolism. While the involvement of ROS in alcohol-related damage is established, the specifics of what proteins are affected and how are not. This study used a method of labeling proteins oxidized by ROS to identify a number of the mitochondrial targets of this destructive process. Knowing these target proteins should permit scientists to further investigate and understand the mechanism of alcohol-induced damage that results from the action of ROS. (Suh, S.-K., Hood, B.L., Kim, B.J., Conrads, T.P., Veenstra, T.D., and Song, B.J. Proteomics 4:3401-3412, 2004.)

Serotonin Transporter and Alcohol Risk A genetic variant, or polymorphism, that results in a reduction of the amount of a transporter molecule for the neurotransmitter serotonin has been found to play a role in anxiety and stress responses in both humans and non-human primates. Research also suggests that serotonin is involved with responses to alcohol and alcohol dependence and abuse. In this study, female macaques who both had this gene variant and were peer-reared rather than mother-reared showed a greater preference for alcohol than littermates who either lacked the variant or had it and were mother-reared (peer-raising is a model of early life stress). In addition, animals who were peer-reared, particularly the females with the serotonin transporter gene variant, progressively increased their alcohol consumption during the study. The authors conclude that these findings suggest that this gene variant interacts with early experience to influence vulnerability to alcoholism. Continuing research may provide approaches for using medications that regulate the serotonin system to prevent or help treat problems with alcohol. (Barr, C.S., Newman, T.K., Lindell, S., Shannon, C., Champoux, M., Lesch, K.P., Suomi, S.J., Goldman, D., and Higley, J.D. Archives of General Psychiatry 61:1146-1152, 2004.

IL-6 in Fatty Liver Disease Approximately 20 percent of the general population of developed countries have fatty liver disease, a condition once largely associated with heavy alcohol use, and now also recognized as a consequence of obesity. Fatty liver disease, a deposition of fat in the liver, increases the risk of more serious liver disease and of mortality after major surgery. In this study, ten days of treatment with the immune molecule interleukin-6 (IL-6) improved the condition of fatty livers in three mouse models of the condition, including alcohol-fed mice. The treatment also prevented liver injury after loss and then restoration of blood flow (ischemia/reperfusion). There is no standard treatment for fatty liver; IL-6 may have therapeutic potential for ameliorating fatty liver disease and reducing surgery-related injury. (Hong, F., Radaeva, S., Pan, H.-n., Tian, Z, Veech, R., and Gao, B. Hepatology 40:933-941, 2004.)

Endocannabinoids and Blood Pressure Research on endocannabinoids-naturally occurring substances in the brain that act on the same receptors as the active ingredients as marijuana-is exploring the range of effects of these compounds, including their demonstrated ability to lower blood pressure. In this study, an antagonist of the cannabinoid receptor CB1-a compound that occupies the receptor and prevents its activation by marijuana or endocannabinoids-increased blood pressure in three rat models of hypertension, while treatment that prevented the breakdown of the endocannabinoid anandamide lowered blood pressure in these animals. These treatments only had these effects in animals with hypertension, not in those with normal blood pressure. High blood pressure is an important public health problem, and searching for compounds that prevent the breakdown of endocannabinoids may yield novel drugs that effectively lower blood pressure in people suffering from hypertension without the side effects of currently available medications. (Batkai, S., Pacher, P., Osei-Hyiaman, D., Radaeva, S., Liu, J., Harvey-White, J., Offertaler, L., Mackie, K., Rudd, M.A., Bukoski, R.D., and Kunos, G. Circulation 110:1996-2002, 2004.)

GABA Receptor Genes Accumulating evidence from two directions suggests that genes coding for A-type receptors for the neurotransmitter GABA play a role in vulnerability to alcoholism. Functional information on GABAA receptors implicates them in alcohol responses; genetic studies suggest that genes in the same chromosomal region where GABAA receptor genes are located may be associated with alcoholism risk. In this study two kinds of evidence in two population samples, one Finnish and one Southwestern Native American, strengthen the case that variation in GABAA receptor genes in a cluster on chromosome 5 influences alcoholism risk. In both populations, studies using single nucleotide polymorphisms (pinpoint variations) in this GABAA gene cluster found association between genes in the cluster and alcoholism risk. A complementary approach (linkage disequilibrium mapping) also found that alcoholism-related genes were likely to reside in this stretch of chromosome 5. Evidence for linkage with alcohol dependence was particularly strong in the region containing polymorphisms in the gene for a particular subunit (a6) of the GABAA receptor. Identification of genes involved in alcoholism risk will both aid understanding of addiction, and provide avenues for developing pharmaceutical treatments. (Radel, M.R., Vallejo, R.L, Iwata, N., Aragon, R., Long, J.C., Virkkunen, M., and Goldman, D. Archives of General Psychiatry 62:47-55, 2005.)

Extramural

Gene/Environment Interaction in FAS Children whose mothers drink during pregnancy may have cognitive deficits and physical abnormalities characteristic of fetal alcohol syndrome (FAS). Some of the variation in the severity in these abnormalities may be due to genetic factors, among them the genes that code for the enzymes responsible for the elimination of alcohol after it is consumed. Alternative forms, or alleles, for some of these genes affect the speed with which alcohol is eliminated. Evidence from this study suggests that the presence in mother or child of a particular allele-ADH1B*3-of the gene coding for the enzyme alcohol dehydrogenase is protective with respect to the severity of facial abnormalities in the children of mothers who drank during pregnancy. A gene/environment interaction among three factors-the absence of ADH1B*3 in either mother or child and alcohol use by the mother just before the first prenatal visit-was associated with more severe facial abnormalities in the children. The enzyme encoded by ADH1B*3 breaks down alcohol more rapidly than alternative forms of the enzyme; the authors suggest this is a possible mechanism for its protective effect. (Das, U.G., Cronk, C.D., Mariter, S.S., Simpson, P.M. and McCarver, D.G. Alcoholism: Clinical and Experimental Research 28:1598-1606, 2004.)

Alcohol and Retinoic Acid Some of the effects of FAS resemble those of exposure to retinoic acid (RA), including heart defects, craniofacial malformations, and central nervous system abnormalities. This study looked at cells in the cerebellum, a part of the brain that is particular vulnerable to alcohol, to see whether alcohol affected RA levels in the developing rat. After four days of alcohol administered to rat pups, RA levels climbed significantly. This study shows for the first time that ethanol stimulates the synthesis of retinoic acid, suggesting an indirect mechanism by which alcohol can injure the developing brain. (McCaffery, P., Koul, O., Smith, D., Napoli, J.L., Chen, N., and Ullman, M.D. Developmental Brain Research 153:233-241, 2004.)

NMDA Receptor Responses Linked to Family History The NMDA receptor for the neurotransmitter glutamate is a target for alcohol in the brain; changes in the function of this receptor are thought to be involved in alcohol abuse and dependence. This study found that in healthy individuals with a family history of alcoholism, the response to a compound that, like alcohol, is an antagonist of the receptor (reduces its activity) is attenuated. (Petrakis, I.L., Limoncelli, D., Gueorguieva, R., Jatlow, P. Boutros, N.N., Trevisan, L., Gelernter, J. and Krystal, J.H. American Journal of Psychiatry 161:1776-1782, 2004.)

Treating Bipolar Disorder and Alcoholism Despite the fact that more than half of individuals with bipolar disorder have a substance abuse problem at some point, effective treatment is lacking for those who have both disorders. This study found that therapy with the anticonvulsant and mood stabilizing drug valproate was effective in reducing the number of heavy drinking days in individuals with comorbid bipolar disorder and alcohol dependence. Alcoholism compounds the difficulties of treating individuals with bipolar disorder; this study suggests that valproate has potential as an adjunct to reduce drinking in this group. (Salloum, I.M., Cornelius, J.R., Daley, D.C., Kirisci, L., Himmelhoch, J.M., and Thase, M.E. Archives of General Psychiatry 62:37-45, 2005.)

Neuropeptide Increases Alcohol Consumption in Rats The neuropeptide galanin increases food intake, especially the intake of fat-rich diets. This paper is one of the first demonstrations of an important role for galanin in modulating alcohol intake-in this study, microinjection of galanin into a brain ventricle increased ethanol consumption in rats. At the same time, this finding adds to the growing list of peptides that may have overlapping control of both alcohol and food ingestion. Previous research showed that alcohol consumption can increase galanin levels in the hypothalamus, particularly in the paraventricular nucleus. Therefore, galanin stimulates alcohol intake, which then can increase galanin in the brain, in what might possibly become a vicious cycle under some conditions. The finding that a galanin receptor antagonist reduced alcohol drinking suggests a possible role for galanin receptor antagonists in the treatment of excessive alcohol drinking as well as for obesity. (Lewis, M.J., Johnson, D.F., Waldman, D., Leibowitz, S.F., and Hoebel, B.G. Alcoholism: Clinical and Experimental Research 28:1822-1828, 2004.)

Binge Drinking and Stroke Heavy episodic drinking or binge drinking is associated with increased risk of stroke, a leading cause of death and long-term disability in the United States. Previous studies have shown that alcohol causes constriction of cerebral arteries but the mechanisms have not been identified. Results from this study, using cerebral arterioles from rats, suggests that alcohol in amounts comparable to that seen in binge drinking causes constriction of these blood vessels by reducing the activity of BK channels, calcium-activated channels in the cell membrane that transport potassium and are involved in the control of smooth muscle tone. This finding identified a specific mechanism for alcohol's action on cerebral arteries. (Liu, P., Xi, Q., Ahmed, A., Jaggar, J.H., and Dopico, A.M. Proceedings of the National Academy of Sciences of the U.S.A. 101:18217-18222, 2004.)

Telephone Care for Alcohol and Drug Dependence Because of the frequency of relapse in substance use disorders, some kind of continuing care may be helpful after initial treatment is complete. Few studies have tested interventions designed to manage alcohol and drug problems over the long term, however. This study compared three versions of continuing care treatment for 12 weeks: weekly telephone-based monitoring and brief counseling contacts combined with weekly support group sessions in the first 4 weeks; twice weekly cognitive-behavioral relapse prevention (an approach which includes identifying risky situations and improving coping with these situations); and twice weekly standard counseling. With the entire group of patients, results with the three treatments did not differ in terms of days of abstinence and total abstinence. In the group who were dependent on alcohol only, results with the telephone-based approach were better than standard treatment in all measures, and better on some measures than the relapse prevention approach. These data provide convincing evidence for a telephone-based treatment approach to the long-term management of alcohol and drug problems. (McKay, J.R., Lynch, K.G., Shepard, D.S., Ratichek, S., Morrison, R., Koppenhaver, J., and Pettinati, H.M. Journal of Consulting and Clinical Psychology 72:967-979, 2004.)

GABA Release in Ethanol-Dependent Rats Within the brain, the central nucleus of the amygdala (CeA) is important in regulating alcohol consumption and it plays a role in the anxiety associated with ethanol withdrawal. This study found that chronic ethanol treatment in rats enhanced signaling of the neurotransmitter GABA in the CeA. Testing with acute ethanol showed no evidence of tolerance in CeA in rats exposed to chronic ethanol. Electrophysiological recordings and microdialysis measurements both suggest that chronic ethanol treatment dramatically promotes release of GABA into the synapse. This presynaptic mechanism is likely to play a key role in ethanol dependence and other behavioral consequences of sustained ethanol exposure. (Roberto, M., Madamba, S.G., Stouffer, D.G., Parson, L.H., and Siggins, G.R. The Journal of Neuroscience 24:10159-10166, 2004.)

Alcohol and the Immune System Excess alcohol consumption can suppress the immune system, increasing susceptibility to infection. This study looked at the effect of alcohol on immune responses involving several toll-like receptors (TLRs), a class of receptors that sense potentially disease-causing molecules and initiate an inflammatory response. Alcohol suppressed inflammatory responses of immune cells (macrophages) in mice to substances that generally induce TLR immune activity. The mechanism for this suppression involved enzymes called MAPKs that play a role in the cascades of immune signaling molecules initiated by TLRs. Alcohol has a broad impact on the immune system; an understanding of the mechanisms of this immune suppression is key to developing treatments. (Goral, J. and Kovacs, E.J. The Journal of Immunology 174:456-463, 2002005.)

F. Outreach

National Efforts

National Association of Deans and Directors (NADD) of Schools of Social Work In October, Peggy Murray, chief of the Health Sciences Education Branch, gave a plenary talk on NIH research opportunities and mechanisms to deans of schools of social work throughout the United States at their semi-annual meeting in San Diego, CA. The session was sponsored by NIH's Office of Behavioral and Social Science Research.

Leadership to Keep Children Free Foundation The Leadership to Keep Children Alcohol Free initiative was launched in March of 2000 as a public/private partnership spearheaded by current governors' spouses focused on the prevention of childhood drinking. An emeritus group was created in 2001 for past governors' spouses who wanted to continue their efforts towards this goal. As a means of helping sustain this effort, the emeritus group of the Leadership to Keep Children Alcohol Free recently created the Leadership to Keep Children Alcohol Free Foundation. The foundation received tax exempt status from the IRS in the fall of 2004.

Science Education Outreach NIAAA Science Education Coordinator Jason Lazarow presented teacher workshops at the National Middle School Teachers Association Annual Conference November 4-6 in Minneapolis, MN, and at the National Science Teachers Association Western Regional Conference December 13-20 in Seattle, WA. Mr. Lazarow also presented a workshop in Warsaw, Poland January 18-23 to teachers at Department of Defense schools from across Europe, using NIAAA science education materials. He was a guest science teacher for two bilingual science education classes in Warsaw middle schools.

Local Outreach

Wyoming Call to Action for Underage Drinking Wyoming First Lady Nancy Freudenthal- now co-chair of Leadership to Keep Children Alcohol Free-has created a Call to Action for Wyoming based on scientific information on the negative effects of the early initiation of alcohol use. Wyoming's Call to Action is based on the recommendations of the Institute of Medicine report on underage drinking. Mrs. Freudenthal asks the citizens of Wyoming to remember that everyone can take some action, beginning with a pledge: "I will educate myself, I will take action, I will be the change I want to see." The statewide initiative's primary vehicle is its Web site, www.wfli.org, which offers resources and materials as well as more than 100 links to other sites, reports, resources, and information on youth alcohol use. A portion of the site is dedicated for comments, questions, and requests. The content will change on a weekly basis.

Music + Prevention CD As part of National Recovery Month in September, Hope Taft, Ohio First Lady and a Leadership co-chair, released a CD titled "One to Grow On." The CD mixes children's songs donated by Ohio recording artists with prevention tips to help parents and caregivers maintain open communication with and provide consistent messages to children. The CD was developed by a State workgroup convened by Mrs. Taft, which worked with the Ohio Department of Alcohol and Drug Addiction Services.

Maryland Project Sticker Shock In October, Kendel Ehrlich, First Lady of Maryland and a member of the Leadership, helped kick off "Project Sticker Shock" in Maryland, a campaign to place stickers on cases of beer reminding purchasers that buying or giving alcohol to minors is illegal. At the kickoff, Mrs. Ehrlich joined volunteers working to stick labels on 5,000 beer cases.

G. Multi-Media Products from NIAAA

Publications and Periodicals

Alcohol Research & Health  Upcoming issues focus on screening and brief intervention, young adult drinking, health services research/economics, and NESARC findings. Full text of the published journals is available on the NIAAA website.

Alcohol Alert  Two issues of the Alcohol Alerts have been printed and disseminated: "Alcohol=s Damaging Effects on the Brain," and "Alcoholic Liver Disease." Both Alert issues are available full text on the NIAAA website.

Drinking and Your Pregnancy  This pamphlet, adapted for American Indian women, has been printed and disseminated. It was pretested with the intended audience on several Indian reservations. We have sent 35,000 copies to Dr. Phil May; he and his colleagues will use the pamphlets in their ongoing prevention activities in prenatal clinics, maternal issues groups, health fairs, and recovery groups as well as in case management with high risk mothers. In addition, Dr. May and his colleagues are designing a pre- and post-test questionnaire to evaluate the pamphlet.

News Briefs  NIAAA is working with the Entertainment Industries Council, Inc. to develop two issues of its Spotlight on... series of topical informative news briefs. The first news brief will focus on underage drinking with the second topic to be determined at a later date. The news briefs are disseminated to approximately 4,500 developers, writers, producers, directors, and researchers for television programming.

Alcohol: A Women's Health Issue  This public information booklet has been revised and updated. In addition, the booklet has been adapted for Spanish-speaking women. The latter was pretested in focus groups in New York City and Albuquerque, New Mexico. Both the English and Spanish versions have been submitted to the printers.

Health Practitioner's Guide  The NIAAA Guide is being revised to provide some important updates and refinements. Among the changes are (1) a simplified screening and diagnostic process that will be much easier for clinicians to use, (2) a new section on medications, and (3) suggestions for managing patients with alcohol use disorders who refuse referral to a specialist or who do not respond to referral to behavioral treatment.

Electronic Media

New Radio PSAs  NIAAA has produced five radio public service announcements (PSAs). Three of the PSAs are targeted to eighth graders and two are targeted to parents. Each 30-second PSA is provided in a variety of music formats. The PSAs were pretested in focus groups with the intended audiences and disseminated to 4,500 radio stations in November.

The Cool Spot  The new version of The Cool Spot, NIAAA's web site for middle school students (www.thecoolspot.gov), was formally released in mid-November. The site now has an interactive quiz that encourages visitors to glean some of the site's key learning objectives. So far, statistics show that two-thirds of quiz takers underestimate the annual number of deaths attributed to underage drinking. In addition, more than half of quiz takers over-estimate the percent of 13-year-olds drinking in the past month (the "Reality Check" section of the site provides "norms perception correction" for these visitors). A press release announced the updated site, which has been picked up by the widely used web directory "about.com" and a variety of other sites dedicated to middle school students, parents, teachers, counselors, and health educators. Current and future promotion efforts include (1) technical work to optimize the site's visibility to search engines; (2) an interview with NIH Radio, soon available for download by hundreds of stations; and (3) outreach efforts to "gatekeepers" such as middle school guidance counselors, health teachers, and after-school providers.

H. What's Ahead

Molecular Mechanisms of Alcohol-Induced Hepatic Fibrosis NIAAA in collaboration with NIH's Office of Rare Diseases will be organizing a satellite symposium on the Molecular Mechanisms of Alcohol-Induced Hepatic Fibrosis at the annual meeting of the Research Society on Alcoholism, to be held in Santa Barbara, California, June 25-29, 2005. The symposium will be held on June 25, 2005. At NIAAA, contact Dr. Vishnu Purohit, 301-443-2689, vpurohit@mail.nih.gov.

Prepared: February 2005