CONTENTS

A. NIAAA Budget

FY 2006 Appropriation   Congress passed the legislation for the FY 2006 appropriations on December 22, 2005 and it was signed by President Bush on December 30, 2005. The FY 2006 NIAAA appropriation of $435.9 million provides a 0.5 percent decrease from the FY 2005 level of $438.3 million, including a 1 percent across-the-board recision. Included in the appropriation is $26.9 million for HIV/AIDS research.

FY 2007 President's Request   The FY 2007 budget request for NIAAA is $433.3 million, including HIV/AIDS, a decrease of $2.6 million and 0.5 percent from the FY 2006 comparable level. The budget request for HIV/AIDS research is $26.9 million. The following highlight some of the major components of the FY 2007 budget request:

• Research Project Grants   Under the President's FY 2007 request, the Institute plans to support approximately 165 competing research project grants (RPGs) and fund approximately 22 percent of approved applications. The FY 2007 request holds the average cost of competing RPGs at the FY 2006 level. There will be no inflationary increases for direct, recurring costs in noncompeting continuation RPGs.
• Alcohol Research Centers   The Centers program budget will support 18 research centers at $30.3 million.
• Other Research   $11.9 million is provided to support 90 research career awards in FY 2007. Cooperative agreements will be funded at $6.0 million.
• Research Training   $10.8 million is provided for 267 pre- and post-doctoral trainees in full-time training positions, a level that is flat relative to FY 2006. Stipend levels for post-doctoral NRSA trainees will remain at the FY 2006 level.
• Research and Development Contracts   Research and development contracts are provided $36.8 million, which is 1.4 percent more than the FY 2006 level.
• Intramural Research Program   $44.8 million has been allocated to maintain the intramural research program's overall level of effort with 111 full time equivalents (FTEs) for FY 2007.
• Research, Management, and Support   Research, Management, and Support (RMS) activities are provided $24.2 million with 116 FTEs for FY 2007.

Below is a summary of the FY 2007 President's budget request (dollars in thousands):

Budget Hearings   The NIAAA FY2007 President's budget request was recently presented before both the House and Senate appropriations subcommittees. The Senate Appropriations Subcommittee hearing was held on May 19th; the House Appropriations Subcommittee hearing was held on April 6. Dr. Zerhouni was the primary presenter for all of the NIH institute/centers.

B. Director's Activities

Indiana University Honors   Dr. Li has been honored with the establishment of an endowed chair in his name at the School of Medicine of Indiana University (IUSM). Dr. D. Craig Brater, Vice President of Indiana University and Dean of the School of Medicine, announced establishment of the chair on February 24 at the second of two lectures Dr. Li was invited to give at IUSM as the 2006 Mark Brothers Lecturer. The lectureship recognizes internationally renowned medical scientists of Asian descent, bringing them to the medical school to interact with faculty and students.

Archibald Lecture   On May 8, Dr. Li gave the 2006 Archibald lecture at the Centre for Addiction and Mental Health (CAMH) in Toronto, Canada. The lecture award is named after David Archibald, the founder of Canada's Addiction Research Foundation, now a Division of CAMH. The series provides a forum for distinguished lecturers to stimulate thought in the field of addiction. Dr. Li spoke on "Alcohol Dependence Syndrome: 30 Years Later."

Karolinska University Hospital   Dr. Li was invited to give a talk on alcohol research at the Karolinska University Hospital, Stockholm, Sweden, on May 11. The program in which he participated included talks by researchers at Karolinska and other universities, including Uppsala, Lunds, and Göteborg. Dr. Li's presentation was entitled "Alcoholism: Understanding Its Developmental Trajectory, Treatment, and Recovery."

American Psychiatric Association   On May 23, Dr. Li gave a lecture entitled "What Have We Learned About Alcoholism From Animal Models?" at the 2006 annual meeting of the American Psychiatric Association. This year's meeting took place May 20-25 in Toronto, Canada.

NIH Asian & Pacific Islander American Heritage Program   On Friday, May 26 Dr. Li presented the keynote address at the cultural program for this year's NIH observance of Asian and Pacific Islander American Heritage Month. The theme of the NIH event is "Progress with Pride and Partnership;" the program took place in Masur Auditorium on the NIH campus. The NIH Asian and Pacific Islander American Organization serves as an independent resource and advocate for the ethnic Asian and Pacific Islander American employees at NIH.

C. NIAAA Staff and Organizational Changes

Nancy Brennan   Nancy Brennan retired from NIAAA in June after 42 years of Federal service. Ms. Brennan came to NIAAA in 1998, serving as a senior budget analyst with responsibility for all areas of financial management. Prior to coming to NIAAA, Ms. Brennan held positions with the Internal Revenue Service and with the Department of Defense.

Faye Calhoun, D.P.A.   Dr. Faye Calhoun, NIAAA Deputy Director since 2003, retired in April with 39 years of service to the Department of Health and Human Services (DHHS). Dr. Calhoun came to NIAAA in 1995 as associate director for collaborative research. Before coming to NIAAA, she had worked for the Food and Drug Administration, the National Institute on Occupational Safety and Health, and NIH's Division of Research Grants (now the Center for Scientific Review) where she was Deputy Chief of Review. As NIAAA Deputy Director, she fostered interagency and international research and outreach initiatives as well as interactions with organizations interested in alcohol issues. She was a frequent spokesperson for NIAAA to the scientific community, Congress, and the public. During her tenure at NIAAA, she also oversaw a broad portfolio of projects; these included chairing the Interagency Coordinating Committee on Fetal Alcohol Syndrome, developing a multi-disciplinary international program for fetal alcohol spectrum disorders, and overseeing National Alcohol Screening Day, among many other programs and initiatives. The awards she has received include the 2005 Heart Award from the Association of Addiction Professionals, the 2005 and 1991 Department of Health and Human Service's Secretary's Awards, and the 2001 Seixas Award from the Research Society on Alcoholism.

Janelle Everett   NIH Management Intern Janelle Everett has begun a 3-month rotation in the Communications and Public Liaison Branch (CPLB). Prior to being selected for the Management Intern Program, Ms. Everett worked in the Referral and Program Analysis Branch of the National Institute of Allergy and Infectious Diseases, where she coded grants and contracts according to their scientific subject matter and produced research reports. Ms. Everett received her bachelor's degree in cell and molecular biology and genetics from the University of Maryland, College Park, in 2002. She is currently enrolled in the Master's of Science in Management program at the University of Maryland University College. During her rotation at NIAAA, Janelle is working on several communications and outreach projects.

Mark Goldman, Ph.D.   NIAAA Associate Director Dr. Mark Goldman left the Institute at the end of May to return full time to the University of South Florida (USF), where he has served since 1985 as Distinguished Research Professor and Director of the Alcohol and Substance Abuse Research Institute. Dr. Goldman came to NIAAA in 2003 under the Intergovernmental Personnel Act (IPA) which enables the temporary exchange of skilled employees between NIH and other agencies or institutions of higher education. While maintaining his research at USF, Dr. Goldman served as an advisor to the Institute on the integration of biological and behavioral science, and assisted NIAAA Director Dr. T.-K. Li with reorganization of the Institute into new divisions and transdisciplinary teams that were designed to address high priority research areas. One of these teams, for which he served as co-leader, developed an initiative aimed at underage drinkers 9-15 years old. This initiative was parallel to the college drinking effort for which he also served as co-chair of the NIAAA task force that was responsible for its development. Under his and Dr. Vivian Faden's leadership, the NIAAA Interdisciplinary Team on Underage Drinking Research established a Steering Committee on Underage Drinking Research and Prevention and produced an overview of research on underage drinking that was published as an issue of NIAAA's journal Alcohol Research & Health. The team is moving forward to issue a state-of-the-science report on alcohol use in the context of development that should inform future research. To assist with the successful completion of those initiatives begun during his tenure at NIAAA, Dr. Goldman will maintain a consulting relationship with the Institute in the immediate future.

Robin Kawazoe   Robin Kawazoe has been named Acting Deputy Director of NIAAA pending selection of a permanent Deputy Director following Dr. Faye Calhoun's retirement. Ms. Kawazoe joined NIAAA in 2005 as Senior Advisor to the Director. Prior to coming to NIAAA, she was Director of the Office of Science Policy and Planning in the Office of the Director, NIH.

Carmen Richardson   Carmen Richardson retired in May after 17 years with NIAAA, having served in a variety of roles at the Institute, most recently health programs analyst in the Office of Science Policy and Communications. She came to NIAAA in 1989 as budget and planning officer after having served as budget officer at the National Eye Institute (NEI) from 1980-1989. She had started at NIH as a chemist in 1970, and was an NIH management intern from 1975-1976, and a budget analyst in the Office of the Director, NIH, until going to NEI. Her trans-NIH roles included serving as a member and then chair of the NIH Administrative Training Committee.

Travis Speck   Travis Speck, an NIH Presidential Management Fellow, has begun a 3-month rotation in the Office of Resource Management/Financial Management Branch. Mr. Speck has previously completed a general administration rotation at NIH's Clinical Center and a grants management rotation at the National Institute of Neurological Disorders and Stroke. He received a bachelor's degree in secondary education from Abilene Christian University in Abilene, TX, and his master's degree in public administration from American University in Washington, DC. During his rotation at NIAAA, Mr. Speck is working on a number of projects relating to budget formulation, execution, and presentation.

Wenxing Zha, Ph.D.   Wenxing Zha, Ph.D. has joined NIAAA's Division of Epidemiology and Prevention Research (DEPR). Dr. Zha is a mathematical statistician who comes to NIAAA from the National Center for Health Statistics (NCHS) where she helped design the most recent National Health Interview Survey and also worked on developing complex statistical methodology for survey analysis. Prior to her tenure at NCHS, Dr. Zha worked in several private firms. She holds a Ph.D. in mathematical statistics from the University of Maryland, Baltimore County. Among Dr. Zha's areas of expertise are complex survey design and analysis, survey non-response, and small-area estimation. In DEPR, she will be involved with secondary data analysis of multiple surveys and will also serve as project officer for technically complex methodological grants.

Office of the Director Reorganization   To accommodate changing patterns of administrative responsibilities and retirements and other staff turnovers, NIAAA's Office of the Director was reorganized, effective in April. In brief, the Office of Scientific Affairs and the Office of Research Translation and Communications (ORTC) were consolidated into a new Office of Science Policy and Communications (OSPC), for which Dr. Li will be acting director pending the appointment of a permanent director. OSPC has a Science Policy Branch, Dr. Karen Peterson, Chief; and a Communications and Public Liaison Branch, Diane Miller, Chief. Drs. Kenneth Warren and Howard Moss have been named to two newly established positions-Associate Director for Basic Research (ADBR) and Associate Director for Clinical and Translational Research (ADCTR), respectively. Kenneth Warren, Ph.D. will become the Associate Director for Basic Research (ADBR) in the Office of the Director, moving from the position of Director, Office of Scientific Affairs, which he held for 22 years. Dr. Warren is responsible for strategic planning for the Institute and serving as liaison with NIH on planning activities; overseeing the Extramural Advisory Board; coordinating NIAAA's activities related to the basic science initiatives under the NIH Roadmap; overseeing the Research Strategies Committee; and providing leadership for the Institute's Fetal Alcohol Syndrome activities. Dr. Moss is responsible for building the Institute's translational research program; serving in a liaison capacity between the extramural and intramural research programs; coordinating NIAAA's activities related to the interdisciplinary and clinical research initiatives under the NIH Roadmap; and chairing the NIAAA International Research Coordinating Committee. Committee management activities have been transferred to the Office of Extramural Activities. The changes have been made with the intent to strengthen the OD and enable the staff to provide more support to and coordination of Institute activities.

D. Research Emphasis and Resource Development Teams

Team Leadership   Having completed the first term of the creation of the teams, the leadership of some of NIAAA's transciplinary research and resource development teams has changed. Leaders for all the teams are as follows:

Medications Development: Raye Litten, Mark Egli
Underage Drinking: Vivian Faden, Howard Moss
Mechanisms of Alcohol Action and Injury: Dennis Twombly, Max Guo
Mechanisms of Behavior Change: Mark Willenbring, Bob Freeman
Etiology of Risk: Genes and Environment: Zhaoxia Ren, Marcia Scott
Resource Development and Analysis: Karen Peterson, Lisa Neuhold
Centers and Training: Tom Gentry, Roger Sorenson

E. NIAAA Research Activities

Collaborative Research Efforts

CRADA's With Eli Lilly   The intramural program, through the Laboratory of Clinical and Translational Studies, has developed and implemented two collaborative research and development agreements (CRADAs) with an industry partner, Eli Lilly and Company. One of these is for preclinical evaluation of compounds targeting CRH1 and mGluR2/3 receptors for potential efficacy in alcoholism, using animal models. The other is for early stage clinical evaluation of a compound targeting the NK-1 receptor for efficacy in alcoholism, using modulation of cue and stress-induced craving, fMRI, and neuroendocrine measures as surrogate efficacy markers.

The studies outlined in the preclinical CRADA are close to completion, and the protocol developed under the clinical agreement has started recruitment. These CRADAs are considered to be of strategic importance, as they represent a breakthrough in the willingness of major pharma to enter into partnership with a commitment to develop pharmacotherapy for alcohol dependence. Such collaborative efforts give the intramural program access to unique pharmacological tools to target novel mechanisms for treatment development.

RFAs/PAs

Identification of Alcohol Biomarker Signatures   As an outcome of RFA AA-06-002 "Identification of Alcohol Biomarker Signatures," NIAAA has launched a biomarkers discovery initiative with the funding of eight research programs following their applications in response to the RFA. The studies will use state-of-the-art technologies in genomics, proteomics, metabolomics, and bioinformatics to discover novel diagnostic biomarker signatures for alcohol consumption and alcohol-induced tissue injury.

Underage Drinking   In response to RFA-AA-06-003, "Underage Drinking: Building Health Care System Responses," 18 applications were received. The RFA solicited applications for cooperative agreements (U01s) to enable rural and small urban health care systems to become platforms for research programs on underage drinking. The applications were reviewed in March with funding anticipated (approximately $2 million) for this summer.

Epigenetics   In response to RFA-AA-06-004 and -005, "Alcohol Metabolism and Epigenetic Effects on Tissue Injury," 33 applications were received. These two RFAs, one using the R01 mechanism, the other the exploratory/development research project (R21) mechanism, solicited new studies on the identification and characterization of epigenetic mechanisms influencing alcohol-induced diseases and the mechanisms by which alcohol-induced changes in redox state and oxidative stress alter gene expression to cause tissue injury. The applications will be reviewed in July and funded (approximately $2 million for both RFAs) before the end of FY 2006.

Newly Issued RFAs/PAs

(Please note that NIAAA participates in numerous requests for applications (RFAs) and program announcements (PAs) issued collaboratively with other institutes. Only those new RFAs and PAs issued solely by NIAAA are listed below. Information on funding opportunities in which NIAAA participates can be found on the NIH website at https://webarchive.library.unt.edu/eot2008/20080916093026/http://grants1.nih.gov/grants/index.cfm.

Alcohol Use Disorders: Treatment, Services Research, and Recovery (PA-06-258)   This PA invites applications to support research on behavioral and pharmacological treatment for alcohol use disorders; organizational, financial, and management factors that facilitate or inhibit the delivery of services for alcohol use disorders; and the phenomenon of recovery from alcohol use disorders. The PA can be accessed on the web at https://webarchive.library.unt.edu/eot2008/20080916093026/http://conferences.jbs.biz/womensconference/. For further information, contact Dr. Margaret Mattson at 301-443-0638, mmattson@mail.nih.gov (pharmacotherapy); Dr. Raye Litten, 301-443-0636, jrlitten@mail.nih.gov (behavioral therapy); Dr. Peter Delaney, 301-443-0788, delanyp@mail.nih.gov (services research); or Dr. Cherry Lowman, 301-443-0637, clowman@mail.nih.gov (recovery research).

Developmental/Exploratory Alcohol Research Centers (RFA-AA-07-001)   This RFA uses the Developmental/Exploratory Research Center (P20) mechanism to provide support for a group of researchers to create a cohesive, interdisciplinary team focused on a significant alcohol research theme and to assist them in establishing the necessary collaborations, facilities, and research projects to justify a subsequent application for a Specialized (P50) or a Comprehensive (P60) Alcohol Research Center. The RFA can be accessed online at https://webarchive.library.unt.edu/eot2008/20080916093026/http://grants.nih.gov/grants/guide/rfa-files/RFA-AA-07-001.html. For further information, contact Drs. Peter Delaney, 301-443-0788, delanyp@mail.nih.gov, R. Thomas Gentry, 301-443-6009, tgentry@niaaa.nih.gov, or Antonio Noronha, 301-443-7722, anoronha@mail.nih.gov.

All the NIH institute/centers also participate in the NIH Roadmap, a framework of the priorities NIH as a whole must address in order to optimize its entire research portfolio. The homepage for the Roadmap, including information on funding opportunities, is at
https://webarchive.library.unt.edu/eot2008/20080916093026/http://nihroadmap.nih.gov/.

NIAAA is a participant in the NIH Neuroscience Blueprint, a partnership among the NIH institute/centers to target those neuroscience challenges that are best met collectively. The homepage for the Blueprint, including information on funding opportunities when available, is at https://webarchive.library.unt.edu/eot2008/20080916093026/http://neuroscienceblueprint.nih.gov/.

Research Reports

The following items represent examples of the breadth and quality of research supported by NIAAA.

NIAAA Press Release: Drinking and Diet   In a study of dietary quality of individuals who drink any kind of alcoholic beverage, researchers found that people who drink the largest quantities of alcohol on drinking days-regardless of drinking frequency-have the poorest quality diets, while those who drink the least amount on drinking days-regardless of frequency-have the best quality diets. Dietary quality was not significantly different between those who drank the highest average daily volume compared with those who drank the lowest average daily volume; the investigators suggest that future research on alcohol consumption and diet should focus on alcohol drinking patterns, as measured by quantity and frequency, rather than average daily volume. The investigators used data on 3,700 subjects from the 1999-2000 National Health and Nutrition Examination Survey. The Healthy Eating Index, a measure of diet quality developed by the U.S. Department of Agriculture, was used to rate dietary quality. Previous studies have shown that moderate alcohol consumption is associated with a reduced risk for cardiovascular disease and death. Investigating the relationship between drinking and diet may help clarify to what extent diet may play a role in the relationship between drinking and cardiovascular disease. (Breslow, R.A., Guenther, P.M., and Smothers, B.A. American Journal of Epidemiology 163:359-366, 2006)

NIAAA Press Release: Shared Genetic Factors for Nicotine and Alcohol Abuse   Findings from a study in which rats bred to prefer or avoid alcohol were taught to self-administer nicotine provide evidence that vulnerability to both alcohol and nicotine abuse may be influenced by the same genetic factor. Rats in the study learned to give themselves nicotine injections by pressing a lever. Those bred to consume large amounts of alcohol (P rats) took more than twice as much nicotine as non-preferring or NP rats. While the P rats took more nicotine, and were also more vulnerable to nicotine relapse than NP rats, there was no difference in cocaine self-administration, suggesting that the differences between the rats in nicotine consumption were not due to a general "reward deficit" in P rats. Smoking is three times more common in people with alcoholism than in the general population. Twin studies in humans have suggested that shared genetic factors underlie alcohol and nicotine abuse; this study provides experimental evidence for a shared genetic basis. (Lê, A.D., Li, Z., Funk, D., Shram, Li, T.-K., and Shaham, Y. The Journal of Neuroscience 26:1872-1879, 2006)

NIAAA Press Release: Genes and OCD Risk   A multi-center team that included intramural investigators has found that a pinpoint change in a gene region much studied for its role in psychiatric disorders alters the risk for obsessive-compulsive disorder (OCD). The region adjoins the gene for a transporter molecule for the neurotransmitter serotonin, a key regulator of mood, whose function is already known to be linked to OCD. The research suggests a mechanism underlying this link and clarifies understanding of the functional variation of this gene stretch. Numerous studies have examined the effects on risk for psychiatric disorders of two variants, or alleles, of this stretch, denoted 5-HTTLPR for serotonin transporter (5-HTT) linked polymorphic region. The region plays a role in determining the level of serotonin in the brain and it has an impact on the neuroanatomy of brain regions involved in a variety of psychiatric disorders. These investigators have found that the degree of functional change resulting from a common point variation in one of the two known alleles argues for it being considered a third function-altering allele, and they suggest a mechanism for its effects. Presence of this third allele almost doubles the risk of OCD. A deeper understanding of the 5-HTTLPR site, and the functional impact of common variations, can provide insight into the origins of depression, OCD, and other psychiatric disorders, and possible avenues for treatment. (Hu, X.-Z., Lipsky, R.H., Zhu, G., Akhtar, L.A., Taubman, J., Greenberg, B.D., Xu, K., Arnold, P.D., Richter, M.A., Kennedy, J.L., Murphy, D., and Goldman, D. American Journal of Human Genetics 78:815-826, 2006)

NIAAA Press Release: Microarrays Identify Drinking-Related Genes   Using strains of mice that have either a high or low innate preference for alcohol, a multi-site team of scientists participating in NIAAA's Integrative Neuroscience Initiative on Alcoholism (INIA) identified nearly 4,000 genes that are differentially expressed (translated into protein) in the high vs. the low drinking strains. The work involved the use of microarrays, an approach which enables researchers to carry out comprehensive analyses of gene activity, in this case, in the brains of animals bred to drink alcohol at different levels. When a gene is activated, cellular machinery transcribes certain parts of the gene's DNA into messenger RNA (mRNA), which is the body's template for creating proteins. The complete set of transcribed mRNA in a tissue is termed the "transcriptome." The INIA collaborators examined brain transcriptomes of nine strains of mice, each differing in their voluntary alcohol consumption. A comparison of the mouse data with human genetic studies revealed that genes with significant expression differences reside in chromosomal regions that previously were shown to be associated with human alcoholism. The report provides clues about the molecular mechanisms that underlie the tendency to drink heavily. (Mulligan, M.K., Ponomarev, I., Hitzemann, R.J., Belknap, J.K., Tabakoff, B., Harris, R.A., Crabge, J.C., Blednov, Y.A., Grahame, N.J., Phillips, T.J., Finn, D.A., Hoffman, P.L., Iyer, V.R., Koob, G.F., and Bergeson, S.E. Proceedings of the National Academy of Sciences of the USA 103:6368-6373, 2006)

NIAAA Press Release: Results from COMBINE Reported   The medication naltrexone and up to 20 sessions of alcohol counseling by a behavioral specialist are equally effective treatments for alcohol dependence when delivered with structured medical management, according to results from "Combining Medications and Behavioral Interventions for Alcoholism" (The COMBINE Study). The largest clinical trial ever conducted of pharmacologic and behavioral treatments for alcohol dependence, COMBINE was carried out at 11 academic sites that recruited and randomly assigned 1383 recently abstinent, alcohol-dependent patients to one of nine treatment groups. One group received specialized alcohol counseling, no medication, and no more than four visits with a health professional for general medical advice. Eight treatment groups received medical management (MM), an intervention consisting of nine brief, structured outpatient sessions provided by a health care professional. Four of these groups in addition received naltrexone (100 milligrams a day), acamprosate (3 grams a day), both naltrexone and acamprosate, or placebo pills. The other four groups received in addition specialized alcohol counseling. As in other large clinical trials, the researchers found that most patients showed substantial improvement during treatment and that both the overall level of improvement and the differences between treatment groups diminished during the follow-up period. In the COMBINE study, however, naltrexone continued to show a small advantage for preventing relapse at 1 year after the end of active treatment. Contrary to expectations, the researchers found no effect on drinking of the medication acamprosate and no additive benefit from adding acamprosate to naltrexone. (Anton, R. F. et al, for the COMBINE Study Research Group. Journal of the American Medical Association, 295:2003-2017, 2006)

The JAMA article on COMBINE and the NIAAA news release are provided in the Council members' packets. Dissemination activities included a telephone news briefing by the study's two principal investigator-chairpersons and NIAAA staff that was attended by representatives from most major daily newspapers and some television news groups. In addition, NIAAA held a constituent briefing for Council Liaison Organization members and representatives of other federal agencies. NIAAA staff and investigators presented results at the American Society of Addiction Medicine and the American Psychiatric Association in May. Other presentations are planned for the June meeting of the Research Society on Alcoholism (RSA), the American Psychological Association in August, and other national and international meetings.

Diagnostic Criteria for Alcohol Problems   The current diagnostic system for alcohol use disorders, defined in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), distinguishes two categories of problems with drinking: abuse and dependence. A common view of the abuse and dependence categories is that abuse represents the mild end of the spectrum of alcohol use disorders while dependence represents more severe problems. In an effort to provide information on how the individual abuse and dependence criteria distinguish levels of severity, intramural scientists applied an approach called item response theory to a very large, representative population sample-the dataset from NIAAA's National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). The analysis revealed that the DSM-IV criteria for abuse and dependence form a spectrum of severity, with the criteria for neither one necessarily signifying problems at the mild or severe end of the scale. For example, the abuse criterion "neglect of role," was an indicator of the highest degree of severity, while the dependence criterion "drinking larger amounts/longer than intended," reflected the lowest severity level. Other criteria were intermediate in terms of severity, but as a whole, the criteria tended to define the severe rather than the mild end of the spectrum. The analysis also found that the criteria varied in how informative they were in distinguishing the severity of problems. Further, the criteria performed similarly when applied to age, race-ethnic, and sex subgroups of the population. The authors conclude that this approach can provide an empirical basis for refinements of the DSM-IV and International Classification of Diseases (ICD)-10 diagnostic systems, including the elimination of the abuse/dependence distinction and of less informative diagnostic criteria. (Saha, T.D., Chou, S.P., and Grant, B.F. Psychological Medicine, epub ahead of print, doi:10.1017/S003329170600746X)

Alcohol Metabolism and Alcoholism Risk   Genetic variations in the enzymes that metabolize alcohol can affect the rate at which an individual clears alcohol from blood after drinking. Research has provided evidence for a link between alcoholism risk and a chromosomal region (4q) encompassing a cluster of genes for alcohol dehydrogenase (ADH) enzymes, which carry out the first step in alcohol breakdown. In this study, researchers looked for associations across the entire ADH gene cluster-seven genes-in this region and alcoholism risk in families participating in the Collaborative Study on the Genetics of Alcoholism (COGA). The team found evidence of an association between the gene for ADH4 and alcoholism risk, and weaker evidence for associations with genes for other alcohol dehydrogenases. Prior studies of the genetic variations in these enzymes and their effects on alcoholism risk focused on so-called Class I dehydrogenases and not ADH4, a Class II enzyme. This study broadens the picture of the relationship between ADH genes and alcoholism risk. (Edenberg, H., Xuei, X., Chen, H.-J., Tian, H., Wetherill, L.F., Dick, D.M., Almasy, L., Bierut, L., Bucholz, K.K., Goate, A., Hesselbrock, V., Kuperman, S., Nurnberger, J., Porjesz, B., Rice, J., Schuckit, M., Tischfield, J., Begleiter, H., and Foroud, T. Human Molecular Genetics 15:1539-1549, 2006)

Striatal Synapses and Learning   The processes that control changes in the strength of the signaling connections between neurons underlie learning and memory. The striatum is a part of the brain involved in goal-directed behavior. In this work, intramural scientists collaborated with scientists at other centers to investigate a process known to play a role in how the striatum integrates information from the cortex-the outer layer of the brain, whose functions encompass thought, consciousness, and memory. This process-a persistent weakening (called long-term depression or LTD) of the synapses between cortical and striatal neurons-requires activation of receptors for the neurotransmitter dopamine. Using transgenic mice in which selected striatal neurons were labeled with a fluorescent protein, the collaborators were able to show that the key dopamine receptors were on a different striatal cell type than previously thought, resolving inconsistencies in the previous understanding of this process, and providing a more complete picture of the chain of events involved. Understanding the cellular processes that underlie LTD of synapses between cortical and striatal neurons helps explain what is happening in brain cells when animals respond behaviorally to rewarding stimuli. (Wang, Z., Kai, L., Day, M., Ronesi, J., Yin, H.H., Ding, J., Tkatch, T., Lovinger, D.M., and Surmeier, D.J. Neuron 50:443-452, 2006)

Liver Fibrosis and the Immune System   To a much greater extent than other organs, the liver is richly populated with immune cells. Research has established that the immune system plays an important role in disease-related liver damage but the mechanisms are complex and not yet fully understood. In this work, intramural scientists showed in a mouse model of liver fibrosis (scarring) that a class of immune cells-natural killer or NK cells-plays a role in limiting fibrosis in the diseased liver by inducing apoptosis or programmed cell death of a population of liver cells (activated hepatic stellate cells) that are responsible for laying down the proteins that constitute fibrosis. They also used mice with selective genetic deletions of key immune regulator molecules to trace the regulatory cascade involved in the process. This work helps clarify why suppression of the immune system-by factors that include infection or alcohol consumption-can enhance the progression of liver fibrosis, and why treatment with immune agents such as interferon can have beneficial effects. (Radaeva, S., Sun, R., Jaruga, B., Nguyen, V.T., Tian, Z. and Gao, B. Gastroenterology 130:435-452, 2006)

Endocannabinoids and Alcohol Preference   Research has demonstrated that endocannabinoids-naturally occurring substances in the brain that act on the same receptors as the active ingredients of marijuana-play a role in regulating appetite for alcohol. This intramural study examined inborn levels of an enzyme (FAAH)-which breaks down endocannabinoids-in rats bred to consume large amounts of alcohol (AA rats) and in alcohol-avoiding rats (ANA rats). Expression of the FAAH gene-that is, how much FAAH was produced from its genetic template-was lower in the AA rats in one of three brain regions tested, and as a result, endocannabinoid levels were higher in this region. Consistent with this observation, a chemical inhibitor of FAAH increased alcohol consumption in a strain of rats not selected for alcohol preference; further, an inhibitor of a receptor for endocannabinoids suppressed drinking in AA rats. All of these findings provide evidence that inherited differences in endocannabinoid metabolism in key parts of the brain play a role in inborn tendencies toward alcohol consumption. Targeting these processes could offer a therapeutic approach for treatment of alcoholism. (Hansson, A.C., Bermúdez-Silva, F.J., Malinen, H., Hyytiä, P., Sanchez-Vera, I., Rimondini, R., Rodriguez de Fonseca, F., Kunos, G., Sommer, W.H., and Heilig, M. Neuropsychopharmacology publication online ahead of print doi:10.1038/sj.npp.1301034).

Restoring Neuronal Function After Fetal Alcohol   Fetal alcohol syndrome (FAS) is the leading nonhereditary cause of retardation. The mechanisms by which alcohol causes cognitive defects are not fully understood, but one area of interest is its effects on neuronal (brain cell) plasticity-the ability of neurons to alter connections with other neurons. This work showed that a class of drug (phosphodiesterase inhibitors) that has been shown to enhance neuronal plasticity in normal subjects had the same effect in an animal model of fetal alcohol exposure. The drug being tested restored the ability of visual cells in the brain to alter their responses to visual stimulation after one eye had been covered during a critical developmental stage. This class of compounds may have potential as treatment for cognitive deficits associated with FAS. (Medina, A.E., Krahe, T.E., and Ramoa, A.S. The Journal of Neuroscience 26:1057-1060, 2006)

Fetal Alcohol and Brain Malformation   Normal development of the brain requires ordered migration of immature neurons. One of the ways prenatal alcohol can harm the brain is by disrupting this process. In an animal model of fetal alcohol syndrome, scientists found that alcohol alters neuronal migration through its effects on the levels of specific signaling molecules in the cell (calcium ions and cyclic nucleotides). Treating cells in ways that reversed the effects of alcohol on these signaling processes also reversed its effects on neuronal migration, suggesting avenues for developing ways of preventing alcohol's harmful effects in early development. (Kumada, T., Lakshmana, M.K., and Komuro, H. The Journal of Neuroscience 26:742-756, 2006)

Cell Death in Fetal Alcohol Exposure   In animals models of fetal alcohol exposure, the sensitivity of some brain regions to harm from alcohol changes with gestational age. One possible reason behind fluctuations in this sensitivity is that alcohol may interact with proteins involved in programmed cell death or apoptosis. Apoptotic cell death occurs in different brain regions at varying intervals during development. In this study, a specific type of brain cell in the cerebellum, a part of the brain involved in control of movement, was protected from ethanol-induced cell loss in animals in which a gene for a protein that promotes apoptosis was disabled or "knocked out." Another type of cerebellar cell was not similarly protected in the knock-out mice; alcohol is likely to influence other apoptotic pathways besides the one studied here. (Heaton, M.B., Paiva, M., Madorsky, I., Siler-Marsiglio, K., and Shaw, G. Journal of Neurobiology 66:95-101, 2006)

Proceedings Published: Hepatitis C   Proceedings of a symposium on hepatitis C and alcohol use that took place at the June 2005 RSA meeting in Santa Barbara, California, were published in Alcoholism: Clinical and Experimental Research (4:709-719, 2006). Dr. Samir Zakhari chaired and organized the symposium with Dr. Gyongyi Szabo of the University of Massachusetts, Worcester. Dr. Zakhari also co-authored with Dr. Jay Hoofnagle of NIH's National Institute of Diabetes and Digestive and Kidney Diseases an article in Hepatology (6:1243, 2005) on research opportunities on alcohol and liver damage.

Proceedings Published: Hepatic Fibrosis   Proceedings of a symposium on mechanisms of alcohol-induced hepatic fibrosis held in June 2005 were published in Hepatology (43:872-878, 2006). Dr. Vishnu Purohit of DMHE organized the symposium, which took place in conjunction with the 2005 RSA meeting.

F. Scientific Meetings

Alcohol Use Disorders in Youth   On April 18, the NIAAA interdisciplinary team on underage drinking research convened a meeting in Bethesda with outside experts to identify and discuss critical issues related to the diagnosis of alcohol use disorders in youth. Among the key areas discussed was the extent to which the current criteria developed for adults are informative or misleading when applied to adolescents. The participants also addressed more general questions, such as whether the diagnostic criteria for all age groups should have dimensional as well as categorical items, and what research avenues could be particularly helpful in guiding the rethinking of diagnostic schemes. Underlying the discussion was anticipation of the upcoming revision of the existing Diagnostic and Statistical Manual, Fourth Edition. Discussants identified key short- and long-term issues that will help guide future Institute research efforts in the area of alcohol use diagnosis.

American Society of Addiction Medicine   Dr. Mark Willenbring gave two presentations on medications development at the May 4-7 Annual Medical Scientific Conference of the American Society of Addiction Medicine in San Diego, CA. On February 8, he also made a presentation at Grand Rounds at the University of Michigan Medical School Department of Psychiatry on "Mechanisms of Change in Drinking Behavior."

International Symposium on Alcoholic Liver and Pancreatic Diseases and Cirrhosis NIAAA was one of the sponsors of an International Symposium on Alcoholic Liver and Pancreatic Diseases and Cirrhosis May 18-19, in Marina Del Rey, California. Division of Metabolism and Health Effects (DMHE) Director Dr. Samir Zakhari gave introductory remarks at the meeting and an overview of opportunities for international collaboration in this subject area.

American Psychiatric Association   At the 2006 annual meeting of the American Psychiatric Association (APA) May 20-25 in Toronto, NIAAA collaborated with the association in presenting a special research-based program track, "Rethinking Alcohol Use Disorders: Science, Diagnosis, Treatment, and Policy." The collaborative sessions included more than 50 lectures, workshops, and symposia by nationally recognized experts. Dr. Mark L. Willenbring, Director of the Division of Treatment and Recovery Research (DTRR), organized the Research Track and chaired several sessions. Dr. Li gave a lecture on animal models as part of the series, and other NIAAA representatives participating in the collaborative sessions included Associate Director Dr. Howard Moss, who chaired a session on alcohol use disorders and psychiatric comorbidity; Dr. Bridget Grant, Chief of the Laboratory of Epidemiology and Biometry, who chaired several sessions, including one on planning a research agenda for DSM-V; and DEPR Director Dr. Ralph Hingson , who co-chaired with Dr. Willenbring a session on alcohol use disorders and psychiatric comorbidity.

This spring, the APA publication Psychiatric News ran a series of articles written by Communications and Public Liaison Branch (CPLB) staff previewing NIAAA's alcohol research track at the APA meeting. The articles appeared in several editions of Psychiatric News in the weeks leading up to the conference.

The NIAAA research track at NIAAA was very well attended; response to the program by participants was enthusiastic.

Neuroimaging in Sleep Research   NIAAA joined other member institutes of the Trans-NIH Sleep Research Coordinating Committee to cosponsor a workshop on "Neuroimaging in Sleep Research," May 29-30 in Bethesda. Dr. Adolf Pfefferbaum gave a talk on "In Vivo Magnetic Imaging of Alcohol-Induced Brain Insult."

G. Outreach

Leadership to Keep Children Alcohol Free   Leadership to Keep Children Alcohol Free has welcomed two new members, bringing the total to 40. American Samoa First Lady Mary Ann Taufaasau Mauga-Tulafono, wife of Governor Togiola Tulafono, is the president and CEO of Nayram Samoa, Ltd., a conglomerate of insurance brokers and adjusters. The First Lady served as chair of the board of directors of the Development Bank of American Samoa, and as an adviser to the American Samoa Delegation to the United Nations for the 1999 UN Conference on Small Island Nations' Sustainable Development. An advocate for children's welfare, Mrs. Tulafono has chaired a program in support of early intervention services for toddlers with disabilities.

Virginia First Lady Anne Holton, wife of Governor Tim Kaine, has devoted her career to serving as an advocate for Virginia's families and children. Ms. Holton was a juvenile court judge in the Juvenile and Domestic Relations District Court for the City of Richmond until her husband was elected governor. As a judge, she served as chairperson of the Millennium Team, a task force focused on improving court processing of abuse/neglect foster care cases in Richmond. She also served on the Virginia Child Support Guideline Review Panel and as a member of the Advisory Committee for the Virginia Court Improvement Program, focusing on foster care and adoption issues.

Leadership members actively promoted Town Hall Meetings that took place across the country on or around March 28th. The Town Hall Meetings-sponsored by the Substance Abuse and Mental Health Services Administration (SAMHSA) and the Interagency Coordinating Committee on the Prevention of Underage Drinking, are part of a national effort to increase the understanding of underage drinking and its consequences and to encourage communities to address the problem. Eleven Leadership members participated in town hall meetings within their respective states and an additional five members prepared op-ed pieces or letters to the editors to draw attention to town hall meetings.

Leadership members also participated in this year's Reach-Out Now Teach Ins, sponsored by SAMHSA and Scholastic, Inc. Teach Ins are an opportunity for national and community leaders to use a research-based curriculum to teach fifth and sixth graders and their communities about the dangers of underage alcohol use. Fourteen leadership members led Teach-Ins in their states.

News Media Contacts   Dr. Mark Willenbring did interviews on addiction, alcohol research, and alcoholism treatment and recovery with a number of news outlets, among them HBO, the Wall Street Journal, the New York Times, and CNN.

U.S. Department of Education   On February 23, Jason Lazarow led a 2-hour workshop on science education and prevention for new recipients of the U.S. Department of Education's Discretionary Grants to Reduce Alcohol Abuse Program. The workshop took place in San Diego, CA, as part of a National Technical Assistance Meeting; about 60 grantees attended. Local educational agencies are eligible for the grants, aimed at providing resources to develop and implement innovative and effective alcohol abuse prevention programs for secondary school students.

U.S. Department of Agriculture Jason Lazarow assisted the U.S. Department of Agriculture (USDA) in reviewing prevention and education curricula submitted to USDA for approval and national dissemination. The review took place April 18 at the National 4H Headquarters in Chevy Chase, MD.

College Drinking   On May 19, Roger Hartman gave a presentation on the status of NIAAA's college drinking initiative at the SAMHSA Targeted Capacity Expansion Campus Screening and Brief Intervention (SBI) Grantee Meeting. The targeted capacity SBI grants are designed to expand existing campus-based medical services by integrating into student health programs both screening for substance abuse and brief interventions to motivate students to take actions needed to end alcohol or drug abuse.

On May 25, Mr. Hartman gave a presentation on college drinking at the 2006 Wyoming Alcohol Education Showcase Conference in Jackson Hole, Wyoming.

U.S. Navy Alcohol and Drug Control Officer Summit   On May 23, Roger Hartman gave a presentation on underage drinking at the 2006 U.S. Navy Alcohol and Drug Control Officer Summit in Millington, Tennessee.

Washington-Area Health/Science Presentations   NIAAA staff made a number of presentations in the Washington area on science-related careers and alcohol and health. Dr. Ricardo Brown gave a presentation on science as a career to students at Archbishop Carroll High School in Washington on April 5; Jason Lazarow spoke April 28 at Laurel (MD) High School's Career Day; and Vijay Ramchandani spoke May 5 at Potomac High School in McLean, VA, about alcohol research and the adolescent brain and alcohol. On April 21, Roger Hartman and Linda Doty represented NIAAA at Gallaudet University's Health Fair, and on May 10, Veronica Wilson and Jason Lazarow provided health information for parents at the NIH Parenting Festival.

H. Multi-Media Products from NIAAA

NIH Plain Language Awards   In April, Dr. Mark Willenbring, Maureen Gardner, and Diane Miller received an NIH Plain Language Award in the Outstanding category for the publication, Helping Patients Who Drink Too Much: A Clinician's Guide. In addition, Maureen Gardner and Diane Miller won an Honorable Mention for their work on "The Cool Spot: The Young Teen's Place for Information on Alcohol and Resisting Peer Pressure" (www.thecoolspot.gov).

The Cool Spot   NIAAA's website for young teens, www.thecoolspot.gov, is being updated with a new "Teacher and Volunteer Corner" that will provide lesson plans based on the site's research-based alcohol prevention content. Designed for middle school counselors, health teachers, and after-care providers, the lessons will include a guided reading activity and interactive role-playing lessons on peer pressure tactics and resistance skills.

Communications and Public Liaison Branch (CPLB) staff prepared two separate promotional news items on "The Cool Spot" for distribution through the American School Counselors Association (ASCA). These appeared in the May issue of the ASCA e-newsletter and the ASCA bi-monthly magazine. Each item describes the features of the site, including the new "teacher and volunteer" corner which will be of particular interest to ASCA members.

Helping Patients Who Drink Too Much: A Clinician's Guide   The Guide is being updated to include information about the approval of Vivitrol, the injectable form of naltrexone, and the results of Project COMBINE. In particular, the medical management support aspect of Project COMBINE will be featured through a new brief section, a patient progress form, and a pocket card.

The Clinician's Guide has also been translated into Spanish. Titled Ayudando a Pacientes Que Beben en Exceso - GuRa Para Profesionales de la Salud, the translation is an adaptation by a team of Spanish-speaking communications specialists with input from medical and community health providers, including representatives from the Pan American Health Organization. The Pocket Guide is also available in Spanish. The first copies of the translated Guide were distributed at the May 20-25 annual meeting of the American Psychiatric Association. The Spanish translation is also available on the NIAAA Web site. CPLB will ensure that as updates are made to the English version of the Guide, the new material also will be incorporated into the Spanish translation.

In conjunction with DTRR, CPLB developed a PowerPoint slideshow designed to familiarize audiences with the organization and content of the Clinician's Guide. The animated presentation takes viewers step-by-step through the Guide and showcases the charts, medications data, frequently asked questions, and other resource materials. Presenters can download the free slideshow from the NIAAA Web site and may adapt the slides and graphics to customize their own presentations. CPLB worked with the American Society of Addiction Medicine (ASAM) to advertise the slideshow in the March-April issue of ASAM News. In May, free CDs with the slideshow and related files were distributed at ASAM's Medical-Scientific Conference in San Diego.

Make a Difference: Talk to Your Child About Alcohol   NIAAA's booklet for parents, Make a Difference: Talk to Your Child About Alcohol, was translated into Tagalog and Ilokano, two Filipino languages, by the Hawaii Department of Health's Alcohol and Drug Abuse Division. Acknowledgement that the booklet was developed by NIAAA is included in the inside front covers. A news release announcing the availability of the booklets was issued by Lt. Governor James R. "Duke" Aiona at the Filipino Fiesta Health Fair in Honolulu. Lt. Governor Aiona is a member of the Leadership to Keep Children Alcohol Free.

Alcohol Alerts   Two Alcohol Alerts were printed and disseminated: "Underage Drinking Prevention-A Complex Problem" and "Focus on Young Adult Drinking."

NIAAA Newsletter   In March, CPLB published the Spring edition of the NIAAA Newsletter. It featured an interview with Dr. Li on "Research and the Future" reprinted with permission from the Society for Neuroscience; a notice about the U.S. Surgeon General's invitation for comments on the Call to Action on Preventing Underage Drinking; a description of the Alcohol Research Track planned for the APA Annual Meeting in Toronto; and information on recent grant announcements, new publications, and other upcoming events.

New On the NIAAA Website The NIAAA Five Year Strategic Plan: Alcohol Across A Life Span is available on the NIAAA website and was open for public comment through May 24. The plan can be accessed on the web through the What's New and About NIAAA sections at https://webarchive.library.unt.edu/eot2008/20080916093026/http://pubs.niaaa.nih.gov/publications/StrategicPlan/NIAAASTRATEGICPLAN.htm

A new section on the NIAAA website provides information for making cash donations to the NIAAA gift fund. The fund is used for various activities in support of alcohol research. The section can be accessed on the site under About NIAAA at https://webarchive.library.unt.edu/eot2008/20080916093026/http://www.niaaa.nih.gov/AboutNIAAA/Donations.htm.

Community Anti-Drug Coalitions of America   Led by CPLB, NIAAA collaborated with the Community Anti-Drug Coalitions of American (CADCA) on the latest edition of Practical Theorist, a publication designed to provide overviews of research in a concise, practical format along with strategies for mobilizing communities. This edition, entitled "Using Science to Combat Underage Drinking," was developed with substantial input from Drs. Ralph Hingson, Vivian Faden, Faye Calhoun, and Patricia Powell, and in CPLB, Fred Donodeo Diane Miller, and Dr. Howard Moss. The Practical Theorist is one of many CADCA publications distributed to more than 5,000 coalition members across the country.

In CADCA's continuing series of interviews with experts from NIAAA, the April 20 issue of the e-newsletter "Coalitions Online" included an exchange with Faye Calhoun, NIAAA´s then Deputy Director, about fetal alcohol syndrome (FAS) and how community coalitions can help address FAS in their communities. The issue is available on CADCA's website, https://webarchive.library.unt.edu/eot2008/20080916093026/http://cadca.org/CoalitionsOnline/ (click on "online archives").

Alcohol Research & Health   An issue of Alcohol Research & Health on Health Services Research has been published. The issue on the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) has been sent to the printer. Upcoming issues will focus on alcohol and tobacco, and metabolism. In April, Alcohol Research & Health made the transition to online management of the journal's administrative tasks, including submission and review of manuscripts. The new Web-based system should help in the tracking the progress of articles and streamline the production process.

Beginning with the Alcohol Research & Health, Vol. 28, No. 3 and the Alcohol Alert, No. 67, each reference cited in these publications now features a direct link to the PubMed abstract and the source article if available on PubMed or another government agency or similar online site.

I. What's Ahead

Research Society on Alcoholism   The 2006 meeting of the Research Society on Alcoholism will take place June 23-29 in Baltimore, Maryland. A number of NIAAA staff are organizing and chairing symposia at the meeting; Dr. Li will give an NIAAA update at the opening.

National Conference on Women, Addiction and Recovery   NIAAA, SAMHSA's Center for Substance Abuse Treatment, and the National Institute on Drug Abuse are cosponsoring the 2006 National Conference on Women, Addiction and Recovery: News You Can Use July 12-14, 2006, in Anaheim, California. The conference will advance the field of women's substance abuse treatment by presenting the latest research and discussing how it can be applied and implemented to improve clinical practice and service delivery for women with substance abuse disorders. Drs. Denise Russo and Deidra Roach will participate as workshop chairs. For information and to register go to https://webarchive.library.unt.edu/eot2008/20080916093026/http://conferences.jbs.biz/womensconference/.

International Society for Biomedical Research on Alcoholism   The biennial meeting of the International Society for Biomedical Research on Alcoholism will take place September 10-13, 2006 in Sydney, Australia. Dr. Li will be a keynote speaker and a number of NIAAA staff are organizing and chairing symposia at the meeting.

Prepared:  June 2006