Director's Report on Institute Activities to the 114th Meeting of the National Advisory Council on Alcohol Abuse and Alcoholism

Thursday, February 8, 2007

CONTENTS

A. Reauthorization Legislation and Budget

B. Director's Activities

C. NIAAA Staff and Organization

D. NIAAA Research Programs

E. Scientific Meetings

F. Outreach

G. Multi-Media Products from NIAAA

A. Reauthorization Legislation and Budget

NIH Reform Act In December, Congress passed a reauthorization bill for NIH, the third ever omnibus reauthorization for the agency. Previous omnibus reauthorizations were enacted in 1993 (the NIH Revitalization Act) and 1985 (the Health Research Extension Act). President Bush signed the current reauthorization on January 15. Among the broad topics addressed in the legislation are the coordination and funding of trans-NIH initiatives, the process for reorganizing NIH programs, and the reporting of NIH activities to Congress. NIH Director Elias Zerhouni has called the legislation an affirmation from Congress at a critical time. The Health Reform Act will be discussed in greater detail later in the meeting.

NIAAA Budget

FY 2007 Appropriation NIH continues to operate under a continuing resolution (CR) scheduled to last through February 15, 2007. On December 11th, 2006, then incoming Chairmen of the House and Senate Appropriations Committees, Rep. David Obey, D-WI, and Sen. Robert Byrd, D-WV, announced their proposal to operate under a year-long CR. Should NIAAA operate under a year-long CR, the NIAAA FY 2007 current rate budget is $435.7 million, which is a flat budget from FY 2006. A summary of the FY 2007 current rate budget is reflected below. However, on February 1, the House passed an FY 2007 joint funding resolution that gave a number of programs increases over the FY 2006 budget. The NIH is among these programs, giving the NIH approximately $620 million, or 2 percent, over the prior year's funding. The Senate is scheduling to consider this resolution before the February 15 deadline.

FY 2008 President's Request The FY 2008 budget request for NIAAA is $436.5 million, including HIV/AIDS, an increase of $0.7 million and 0.2 percent over the FY 2007 revised current rate level. The budget request for HIV/AIDS research is $27.3 million. The following highlight some of the major components of the FY 2008 budget request:

• Research Project Grants Under the President's request, the Institute plans to support approximately 211 competing research project grants (RPGs) (an increase of 9 grants over FY 2007) which could equal approximately a 30 percent success rate for competing RPGs. The FY 2008 request holds the average cost of competing RPGs at the FY 2007 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 $27.3 million, the same level as FY 2007.

• Other Research $12 million is provided to support 93 research career awards in FY 2008. Cooperative agreements will be funded at $8.7 million.

• Research Training $11.3 million is provided for 280 pre- and post-doctoral trainees in full-time training positions, which is flat with FY 2007. Stipend levels for post-doctoral NRSA trainees will remain at the FY 2007 level.

• Research and Development Contracts $33.7 million is provided for research and development contracts.

• Intramural Research Program $45 million has been allocated to maintain the intramural research program's overall level of effort with 118 FTE's for FY 2008.

• Research, Management and Support (RMS) RMS activities are provided $24.9 million with 112 FTE's for FY 2008.

Below is a summary of the FY 2008 President's budget request (dollars in thousands):

B. Director's Activities

Joint Commission on Science and Technology Meeting, Beijing As part of an interagency delegation led by John Marburger, Science Advisor to the President, Dr. Li represented the Department of Health and Human Services and the NIH at the Joint Commission on Science and Technology Meeting held in Beijing, China, on October 18-19. Several U.S. agencies participated in the meeting along with representatives from the Chinese Ministry of Science and Technology to discuss collaboration. There is already much China-U.S. cooperation in business, agriculture, and economics, but thus far only limited health-related collaborations. Dr. Li presented data from the World Health Organization on chronic diseases and the toll of substances such as alcohol and tobacco, and morbidity and mortality rates in China. Both sides agreed to the importance of the emerging problems globally attributable to complex diseases such as hypertension, obesity, diabetes, alcohol, and tobacco, and the need to address them in addition to new and emerging infections. Collaboration in research on alternative medicine and traditional Chinese medicine was also discussed.

C. NIAAA Staff and Organization

Extramural

Peter Delany, Ph.D. In January, Peter Delany, program director for health services research, received the first ever annual Legacy Award from the National Association of Deans and Directors of Schools of Social Work (NADD). In the letter notifying him of the award, NADD president Katharine Briar-Lawson cited his initiatives to advance social work research in drug abuse through research infrastructure investments, and his "work as an inspiring guide, mentor, and critical friend to so many of our faculty and doctoral students." Before joining NIAAA in 2005, Dr. Delany had held positions with the Substance Abuse and Mental Health Services Administration and the National Institute on Drug Abuse (NIDA).

Philippe Marmillot, Ph.D. Philippe Marmillot has joined the Extramural Project Review Branch as a scientific review administrator. Dr. Marmillot came to NIAAA from the Veterans Health Administration Medical Center, George Washington University, Washington, DC, where he was an Assistant Research Professor.

Margaret Murray, M.S.W. In November, Margaret Murray received an NIH Merit Award as part of NIH's Social Work Research Working Group. The award was in recognition of "outstanding contributions in developing and implementing a trans-NIH program to support research on social work practice and concepts in health."

Karen Peterson, Ph.D. Karen Peterson has left NIAAA to take a position as senior advisor to the director of the National Institute of Biomedical Imaging and Bioengineering. At NIAAA, she was chief of the Science Policy Branch (SPB), Office of Science Policy and Communications. Dr. Patricia Powell is acting as SPB branch chief. Dr. Abe Bautista is Executive Secretary for NIAAA's Advisory Council.

Svetlana Radaeva, Ph.D. Svetlana Radaeva has joined the Division of Metabolism and Health Effects (DMHE) as a health scientist administrator with a portfolio covering stem cells and liver diseases. Dr. Radaeva joined DMHE from the Section on Liver Biology in NIAAA's Laboratory of Physiologic Studies where her work was dedicated to immunological aspects and molecular pathogenesis of liver diseases. Dr. Radaeva received a Ph.D. in cell biology at the Institute of Developmental Biology at the U.S.S.R. Academy of Sciences. She also received research training in liver pathology and liver cancer development. In 1996 Dr. Radaeva moved to the Department of Pathology at the Virginia Commonwealth University where she characterized the molecular phenotype of cholangiocarcinoma (biliary cancer) in the furan rat model and in humans.

Brenda Sandler Brenda Sandler retired in September following 24 years at NIH, 8 of them with NIAAA. Ms. Sandler was chief of NIAAA's Administrative Services Branch in the Office of Resource Management. She started at NIH in 1982 in the National Institute of Mental Health (NIMH) where she was a secretary and then budget analyst and financial manager for NIMH's intramural program. She joined NIAAA's intramural program in 1998 as chief of the administrative services branch, becoming chief of administrative services for the institute with the reorganization in 2003. Ms. Sandler's awards include the NIH Director's Award in 1995 for "extraordinary contributions to the NIMH intramural program," and the Martin K. Trusty Excellence in Management Award from NIAAA in 2004. She regards as her most important accomplishment her efforts to ensure pay equity for employees at NIAAA.

Patricia Scullion Patricia Scullion has joined NIAAA as chief of the Administrative Services Branch, Office of Resource Management. With 25 years at NIH, Ms. Scullion comes to NIAAA from the National Institute of Allergy and Infectious Diseases (NIAID), which she joined in 2000 as deputy chief, Intramural Administrative Management Branch. In that capacity, she was part of a leadership group that worked closely with the director and deputy director of NIAID's Division of Intramural Research to develop a strategic plan to implement departmental and congressionally-mandated bio-defense initiatives and programs in the division. In 2006, Ms. Scullion accepted a detail to the Office of the Director, NIAID, to lead an institute initiative to establish a competency-based framework to enhance the training, recruitment, retention, and performance management of NIAID's administrative staff and facilitate a stronger connection between NIAID's strategic goals and the work performed by administrators. Prior to working for NIAID, Ms. Sullivan spent almost 20 years with the National Cancer Institute as a training specialist and officer, and then administrative officer.

Mariela Shirley, Ph.D. Mariela Shirley has joined the Division of Epidemiology and Prevention Research (DEPR) as a health scientist administrator whose portfolio covers four primary areas: underage drinking, screening and brief intervention, psychiatric comorbidity, and women's issues. Dr. Shirley comes to NIAAA from NIH's Center for Scientific Review (CSR) where she was the scientific review administrator for the Adult Psychopathology and Disorders of Aging Study Section. Prior to coming to CSR, she was an assistant professor of psychology at the University of North Carolina at Wilmington where she conducted research on individual and treatment-related predictors of relapse and the epidemiology of substance use and readiness for change in primary care.

Alesia Wilbur Alesia Wilbur joined the Office of the Director (OD) as a staff assistant at the end of October. In this capacity, she will serve as the office manager for the OD; monitor and coordinate the administrative support needs of the three staff offices within the OD and the extramural divisions; work with management and administrative staff in gathering information and in preparing analyses focused on organizational efficiency; and carry out other duties in support of the OD and the Institute. Alesia has 17 years of secretarial/administrative/office management experience in the Federal government, and she began working at NIH in 1998.

Ellen Witt, Ph.D. Ellen Witt, along with other members of the Neuroepidemiology Blue Print Initiative entitled, "NIH Toolbox for the Assessment of Neurological and Behavioral Function," received an Award of Merit from the National Institute on Aging for "outstanding service towards the mission of the National Institute on Aging."

Harold Yahr, Ph.D. Harold Yahr, social science analyst in DEPR, retired in January after more than 30 years at NIAAA. Prior to joining NIAAA, he was branch chief of the Organizational Psychology Branch, Office of Personnel Management; assistant professor of sociology at the American University in Washington, D.C.; and research project director in the Center for Urban Studies, City University of New York. Dr. Yahr published in peer-reviewed journals on the prevalence of alcohol abuse and dependence and other drug disorders, and the detection, intervention, and treatment referral of general hospital admissions with alcohol disorders. Dr.Yahr received his Ph.D. in sociology from New York University.

Intramural

New Intramural Laboratory A new Laboratory of Molecular Signaling has been established in the Division of Intramural Clinical and Biological Research, bringing the number of laboratories to 10. Hee-Yong Kim, Ph.D., is the laboratory chief.

Bin Gao, M.D., Ph.D. Bin Gao has been appointed to the editorial board of The Journal of Biological Chemistry.

Klaus Gawrisch, Ph.D. Klaus Gawrisch is the 2007 winner of the Biophysical Society's Avanti Award in Lipids for his groundbreaking work using NMR to characterize the structure and function of lipids.

B.J. Song, Ph.D. B.J. Song has been appointed to the editorial board of the journal Hepatology.

D. NIAAA Research Programs

NIH Director Visits NIAAA NIH Director Elias Zerhouni visited with representatives of NIAAA's extramural research program on October 6 and heard presentations about ongoing research and opportunities. The discussion included overviews by NIAAA staff of the nature and extent of alcohol problems, the taxonomy of alcohol use disorders, gene-environment interactions, the transition from voluntary to addictive drinking behavior, epigenetics of alcohol use, and biosensors.

NIH Pathway to Independence Award Program An NIAAA grantee was among the awardees in the first group of NIH's Pathway to Independence program, announced on November 30 by Dr. Zerhouni. Over 900 applications were received under the K99-R00 program (PA 06-133, released January 2006) in the first three review cycles. Among the 58 new awards announced was an award to NIAAA's nominee, Valentina Sabino from The Scripps Research Institute, La Jolla, CA. NIAAA anticipates awarding up to three K99-R00 grants per year.

The Pathway to Independence Award program offers a 5-year award for postdoctoral scientists to receive both mentored career development support as well as independent research support. The initial 1-2 year mentored phase (K99) allows postdoctoral scholars to complete their supervised research work, publish results, and search for an independent research position. The second, independent phase (years 3 to 5, R00) allows awardees who secure an assistant professorship, or equivalent position, to establish their own research program and ultimately apply for an NIH investigator-initiated (R01) grant. The Pathway to Independence Awards are a component of a larger, ongoing NIH effort to support new scientists as they transition to research independence, and supplements related efforts at NIAAA.

For more information about the Pathway to Independence Awards, or the new NIAAA Career Transition Awards (K22), contact Dr. Dennis Twombly in the Division of Neuroscience and Behavior (301) 443-9334 ( dtwombly@mail.nih.gov).

"New Hot Paper" Designation for Report on College Drinking A 2005 paper on college drinking for which Ralph Hingson was the lead author has been designated a "New Hot Paper" by Essential Science Indicators (ESI)-a service that uses citation data as a way to track scientific productivity and trends. Every two months, ESI lists "New Hot Papers" that are among the most cited papers published in the last two years in various scientific fields. Dr. Hingson's paper is one of eight selected from a wide variety of fields as new hot papers for January 2007. The "New Hot Papers" listing and an interview with Dr. Hingson can be accessed athttp://www.esi-topics.com. The paper, on alcohol-related mortality and morbidity among U.S. college students, was published in theAnnual Review of Public Health (26:259-279, 2005).

Paper on International Collaboration Published Vishnu Purohit is the author of a paper on "International Collaboration on Alcohol Liver Disease and Pancreatitis: Opportunities," that appeared in the Journal of Gastroenterology (21:S110-S111, 2006).

Responses to Past RFAs/PAs

Underage Drinking: Building Health Care System Responses In response to RFA-AA-06-003, 18 applications were received, and 4 were approved for funding. The purpose of the grants funded in this program is to enhance alcohol research expertise and promote infrastructure development in rural primary health delivery systems to facilitate their participation in community-based empirical research on underage drinking. The four grants approved for funding are "Preventing Underage Drinking by Southwest California Indians: Building Capacity," (Pacific Institute for Research and Evaluation); "Northwest Pennsylvania Adolescent Alcohol Research Cooperative," (University of Pittsburgh); "Primary Health Care and Underage Drinking in Rural Iowa," (University of Iowa); and "PARTNER," (Duke University).

Metabolomics In 2005 NIAAA co-sponsored an RFA with NIEHS on "Metabolomics: Application to Environmental Health Research." On December 4, grantees from this RFA met in Chapel Hill, NC, to discuss progress and potential collaborations. Jose Velazquez chaired a session at the NIEHS-NIAAA conference on "Empowering Environmental Health Sciences Research with New Technologies."

Prenatal Alcohol and Sudden Infant Death NIAAA and the National Institute of Child Health and Human Development established the Prenatal Alcohol, Sudden Infant Death Syndrome (SIDS), and Stillbirth Research Network in 2003 to determine the underlying causes of SIDS and stillbirth, and the role prenatal alcohol exposure plays. The Network sought to develop community-linked studies for investigating the role of prenatal alcohol exposure in the risk for SIDS and adverse pregnancy outcomes (seehttp://www.nichd.nih.gov/research/supported/pass.cfm). An RFA was issued for a Phase II study, and it was funded in 2006. This comprehensive study will prospectively follow 12,000 pregnant women from the Northern Plains and South Africa and their infants to one year of age. The study will examine the interaction of alcohol with a variety of maternal and fetal factors.

Collaborative Initiative on Fetal Alcohol Spectrum Disorders NIAAA issued RFA-AA-07-004 (released November 28) to continue and expand the Collaborative Initiative on Fetal Alcohol Spectrum Disorders consortium, which was initially funded in 2003. Fourteen applications were received. This will be a cooperative agreement mechanism to address issues of diagnosis, neurobehavioral phenotype, early case recognition, and interventions.

NIAAA has received, or is expecting, numerous applications in response to RFAs for 2007. In addition to those RFAs listed above, applications for the following have been received:

• Developmental/Exploratory Alcohol Research Centers (RFA-AA-07-001): 20 applications received. 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. 

• Specialized Alcohol Research Centers (RFA-AA-07-002) : 4 applications received. This RFA uses the NIH specialized research center (P50) mechanism to support an integrated, broad-based multidisciplinary, multi-investigator, long-term program of research and research support activities planned around a specific major research theme. 

• Comprehensive Alcohol Research Centers (RFA-AA-07-003 ): 5 applications received. This RFA uses the NIH comprehensive research center (P60) mechanism to support an integrated multidisciplinary, multi-investigator, long-term program of research and research support activities planned around a specific major research theme and the development of an effective research translation/information dissemination component to help accelerate the use of research findings for the benefit of public health.

• Alcohol Education Project Grants (PAR-07-001) : 12 applications received. This notice of Funding Opportunity solicits research education (R25) grant applications from applicant organizations that propose to develop health education activities in the following areas: K-12 science education and undergraduate/graduate education, health professions education, and public health education.

• Collaborative Initiative on Fetal Alcohol Spectrum Disorders (RFA-AA-07-004): 14 applications received. This RFA solicits NIH cooperative agreement (U01 and U24) applications from current awardees and new applicants to continue and expand the previously funded "Collaborative Initiative on Fetal Alcohol Spectrum Disorders," a multidisciplinary consortium of domestic and international projects. 

• Mechanisms of Behavior Change in the Treatment of Alcohol Use Disorders (RFA-AA-07-005) : 19 applications received. This RFA solicits exploratory/developmental (R21) grant applications from applicant organizations to investigate the underlying mechanisms that drive behavior change within the context of behavioral treatments for alcohol dependence. Mechanisms of behavior change refer to the underlying psychological, social, and neurophysiological processes through which therapeutic change occurs.

Research Reports

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

Gene Regulation and Alcohol Preference Alpha-synuclein is a protein that plays a role in regulation of the neurotransmitter dopamine. Evidence from previous studies suggests that alpha-synuclein may be involved in alcohol-related behavior. Levels of expression of the gene for alpha-synuclein have been found to be different in alcohol-preferring and nonpreferring rats prior to alcohol exposure, for example. In this study, investigators looked at the structure of the regulatory regions of the gene; they also tested whether small sequence variations in regulatory regions affected production of alpha-synuclein. The study yielded information on the architecture of the promoter region of the gene, where transcription to RNA begins; in addition, the investigators found that small variations in this region did not affect levels of the protein. A change at the other end of the gene, however, resulted in a longer-lived protein in the alcohol-preferring rats. Understanding how control of the production of alpha-synuclein from its gene template can affect alcohol-related behavior can help clarify whether this protein could furnish a candidate target for the development of medications to intervene in alcohol problems. (Liang, T. and Carr, L.G. Journal of Neuroscience 99:470-482, 2006)

Ethnic Disparities in Treatment Seeking for Alcohol Problems This study used data from the National Alcohol Survey, conducted every 5 years by NIAAA's Alcohol Study Group, to examine differences in the use of alcohol treatment services across the three largest ethnic groups in America. Findings of previous studies had been mixed, with some suggesting that minorities were over-represented in treatment settings. This study found that it was important to take into account the severity of alcohol problems when measuring the use of services; Hispanics and Blacks with higher levels of problem severity, for example, were less likely to have used treatment services than Whites with problems of comparable severity. Additional research is needed to clarify the factors that discourage minority individuals from seeking treatment. (Schmidt, L.A., Ye, Y., Greenfield, T.K., and Bond, J.Alcoholism: Clinical and Experimental Research 31:48-56, 2007)

Withdrawal and the Brain's Stress System Relieving the anxiety that people with alcohol dependence experience when they stop drinking is a powerful motivator for them to resume. The neuropeptide corticotropin-releasing factor (CRF) is an important player in the body's response to novelty and stress. Research suggests that CRF is involved in the anxiety-like behaviors observed in animals during withdrawal from alcohol. In this study, scientists observed the effects on alcohol consumption of rats of an antagonist to CRF receptors administered to different parts of an area of the rat brain known to be involved in stress responses. The rats being tested had been trained to respond to alcohol and included animals in which dependence had been induced (by exposure to alcohol vapor) and nondependent animals; the dependent rats were experiencing acute withdrawal during testing with CRF. The CRF antagonist reduced alcohol consumption in alcohol dependent (but not nondependent) rats when administered to one out of three of the brain areas tested. In the dependent rats, the amount of CRF measured using an antibody to CRF was lower in the same brain area-the central nucleus of the amygdala-in the dependent rats being withdrawn from alcohol. The authors suggest this decrease is the result of a release of CRF from nerve terminals. The work provides information about the anatomy of CRF's function and suggests the possibility of using the CRF system to develop pharmaceutical treatments for alcohol dependence. (Funk, C.K., O'Dell, L.E., Crawford, E.F., and Koob, G.F. The Journal of Neuroscience 26:11324-11332, 2006)

Gene Involved in Stress and Relapse Stress can trigger relapse to heavy drinking after a period of abstinence in people with a history of dependence. NIAAA intramural scientists collaborating with colleagues in Italy and Sweden found that rats from a strain bred to have an unusual appetite for alcohol (alcohol-preferring mice) are more sensitive to stress than is typical for rats. In addition, alcohol-preferring rats who had learned to press a lever for alcohol, then gone through a period when it was unavailable, were more likely to resume alcohol consumption in response to stress when alcohol became available. The investigators looked for differences in the activity of 20 stress-related genes in the brain that might underlie this behavior; they found that the alcohol-preferring rats had a more abundant supply of the gene for a cellular receptor for corticotropin releasing hormone, a peptide that helps orchestrate the stress response. Antalarmin, a substance that counteracts the receptor's activity, suppressed alcohol seeking only in alcohol preferring rats. In these rats, antalarmin also blocked the resumption of drinking following stress. This work provides an example of how the environment interacts with genetics to shape behavior; it also suggests the potential of medication to help prevent relapse. (Hansson, A.C., Cippitelli, A., Sommer, W.H., Fedeli, A., Björk, K., Soverchia, L. Terasmaa, A., Massi, M., Heilig, M., Ciccocioppo, R. Proceedings of the National Academy of Sciences of the U.S.A. 103:15236-15241, 2006)

Dopamine's Role in Motor Disorders The neurotransmitter dopamine is known to be involved in integrating motivation and behavior, including physical activity. One of the consequences of disruptions in dopamine function, such as that seen in Parkinson's disease, is impaired motor function. In this collaborative study, scientists in NIAAA's intramural program and at North Carolina's Duke University Medical Center developed a way to induce rapid changes in dopamine levels in the brains of mice. The rapidity of the changes, in contrast to the gradual loss of dopamine seen in diseases like Parkinson's, made it possible to observe the immediate and direct effects of depletion and restoration of dopamine. The overall activity level of neurons in the cortex and striatum-parts of the brain that are rich in dopamine receptors and function in coordinating behavior-did not change with fluctuations of dopamine. However, the coordination of this neuronal activity, measured as the synchrony in patterns of nerve cell electrical activity, changed rapidly. The authors conclude that dopamine-related disorders like Parkinson's may result more from changes in the coordination of neuronal activity in affected brain regions, rather than changes in activity level, an insight that may help guide development of future treatments. (Costa, R.M., Lin, S.-C., Sotnikova, T.D., Cyr, M., Gainetdinov, R.R., Caron, M.G., and Nicolelis, M.A.L. Neuron 52:359-369, 2006)

Epigenetics and Alcohol Epigenetics refers to heritable variations in gene expression that are not the result of changes in the DNA sequence. In December 2005, NIAAA issued an RFA soliciting innovative and exploratory research on epigenetic changes from alcohol exposure. This editorial provides a timely overview of some of the mechanisms of epigenetic change that are promising targets for alcohol research. Much of this work has clear relevance to alcohol's impact on the liver, but epigenetic processes also have the potential to provide insight into alcohol's effects on diverse systems, including fetal development and the brain. (Shukla, S.D. and Aroor, A.R. World Journal of Gastroenterology 12:5265-5271, 2006)

A Gene Altering Alcohol Sensitivity in Fruitflies Alcohol exerts its behavioral effects through its impact on genes and gene products involved in nervous system function. It is these genes that are likely to influence sensitivity to alcohol, and many of them have been conserved across evolution and species. For this reason, animal models, even fruit flies, are proving useful in the search for genes that affect risk for alcohol problems. Research has already identified analogous genes affecting the alcohol response in fruit flies and mice. This work reports on a newly identified gene in which mutations result in changes in the sensitivity of fruit flies to alcohol. Investigators exposed fruit flies to alcohol vapor and screened for genetic changes in those flies with altered alcohol responses. Flies with changes in a gene designated whir were strongly resistant to sedation by alcohol. The proteins encoded by whir regulate enzymes known to play a role in nervous system development. Different protein transcripts of whir play roles in the stimulant effects of smaller doses of alcohol and in sedation in response to larger doses. Understanding genes involved in the alcohol response in animals provides scientists with targets for genes that influence alcohol risk in humans, and ultimately, clues to developing medications to prevent and treat dependence. (Rothenfluh, A., Threlkeld, R.J., Bainton, R.J., Tsai, L.T., Lasek, A.W., and Heberlein, U. Cell 127:199-211, 2006)

Neurotrophin Receptor Linked to Alcoholism Risk Neurotrophins are proteins that function in the survival of nerve cells and the shaping of their synaptic connections. Research suggests that the neurotrophin BDNF (brain-derived neurotrophic factor) is involved in responses to alcohol. The results of this intramural study provide evidence that the gene for a cellular receptor for BDNF (NTRK2), also has a role in shaping alcohol responses. The study compared the frequencies of pinpoint variations (single nucleotide polymorphisms or SNPs) in individuals with and without antisocial personality disorder and alcohol dependence. Three SNPs were found to be associated with alcohol dependence and abuse. One haplotype of the gene-a stretch of the DNA sequence that tends to be transmitted from generation to generation en bloc-was more frequent in the individuals without alcohol dependence. These results suggest that the NTRK2 gene is involved in shaping responses to alcohol, and thus risk of dependence. (Xu, K., Anderson, T.R., Neyer, K.M., Lamparella, N. Jenkins, G., Zhou, Z., Yuan, Q., Virkkunen, M., and Lipsky, R.H. The Pharmacogenomics Journal. Epub ahead of print January 2, 2007; doi:10.1038/sj.tpj.6500430)

Computer Games Teach Safety to Alcohol-Affected Children Unintentional injuries are a leading cause of death and disability for children. The risk of unintentional injures is increased for children with developmental disabilities, including those with fetal alcohol spectrum disorder, and teaching them to avoid and deal with hazardous situations can be difficult. In this study, children diagnosed with fetal alcohol syndrome played a computer game designed to teach them fire and street safety skills. Verbal testing on these skills preceded the games. Children were tested verbally before and after the games; in addition, following successful completion of the games, they were tested in situations mimicking the hazards about which they were taught. The children's knowledge of the safety skills was significantly better after than before the game-playing. Further, 72 percent were able to generalize skills learned on the computer to real-life situations, suggesting that computer games may be an effective means of teaching safety skills to high-risk children. (Coles, C.D., Strickland, D.C., Padgett, L., and Bellmoff, L. Research in Developmental Disabilities, Epub before print, doi:10.1016/j.ridd.2006.07.001)

Alcohol Metabolism and Apoptosis Apoptosis is a process by which cells initiate cell death as a means of controlling how and which cells proliferate and thus the balance of tissue growth. Research suggests that one of the ways alcohol damages the liver is by triggering apoptosis. In this study, investigators observed the effects of alcohol on a cell line created using liver cells. The results indicate that alcohol increases the rate of apoptosis, at least in part as a result of an interaction with a cell receptor called Fas, a so-called "death receptor" that plays a role in the apoptotic pathway. In addition to providing information on this mechanism of alcohol's impact on apoptosis, the work demonstrated the utility of this cell line in studying alcohol's effects on liver cells. (McVicker, B.L., Tuma, D.J., Kubik, J.L., Tuma, P.L., and Casey, C.A. Alcoholism: Clinical and Experimental Research 30:1906-1915, 2006)

E. Scientific Meetings

Alcohol and Endotoxin Vishnu Purohit organized a symposium on Alcohol, Intestinal Bacterial Growth, Intestinal Permeability to Endotoxin, Medical Consequences, and Dietary Supplements in Rockville on October 11. The symposium was sponsored by NIAAA, NIDDK, and NIH's Office of Dietary Supplements (ODS). Sam Zakhari delivered opening remarks and the symposium was chaired by Frank Hamilton (NIDDK), Christine Swanson (ODS), Elizabeth Kovacs (Loyola University), and Gyongyi Szabo (University of Massachusetts). The following topics were covered: 1) Role of Endotoxin in Alcoholic and Non-Alcoholic Liver Injury; 2) Alcohol, Immune System, and Intestinal Bacterial Growth; 3) Probiotics, Intestinal Bacterial Overgrowth, and Peptidoglycan; 4) The Leaky Epithelial Barrier in Intestinal Diseases; 5) Alcohol, Intestinal Permeability, and Endotoxemia; 6) Effects of Acetaldehyde and L-glutamine on Intestinal Permeability to Endotoxin; 7) Role of Zinc in Preserving Intestinal Integrity in Alcohol-Intoxicated Mice; and 8) Effects of Nitric Oxide and Oats Supplementation on Alcohol-Induced Leaky Gut. The proceedings of the symposium will be submitted to a journal for publication.

Alcohol and Youth Ralph Hingson was the keynote speaker at two international conferences on alcohol and youth. On October 6, he spoke to the Conference to Prevent Drug and Alcohol Abuse Among Youth in St. Petersburg, Russia. The meeting was sponsored by NIDA and St. Petersburg University, Russia. On November 17, he spoke at the International Conference on Alcohol and Young People, sponsored by the University of the West of England, Bristol, England and the Alcohol and Health Research Trust, a private charity.

Society for Research in Psychopathology Mariela Shirley presented a 2-hour workshop on "Peer Review of NIH Research Grant Applications" at the annual Society for Research in Psychopathology meeting in San Diego, CA, October 12-15. This outreach workshop also addressed the NIH referral process, grantsmanship skills, and NIAAA's mission and research priorities.

American Pancreatic Association Vishnu Purohit spoke on research opportunities for young investigators in alcoholic pancreatic diseases at the joint meeting of the American Pancreatic Association and International Association of Pancreatology in Chicago, November 1-4.

National Commission on Digestive Diseases On November 2nd, Sam Zakhari represented NIAAA at the National Commission on Digestive Diseases meeting, to discuss the research portfolio in this area and help formulate a research agenda for NIH. The commission was established in 2005; part of its mission is to conduct an overview of the state-of-the-science in the field of digestive diseases research and develop a 10-year plan for research. The commission reports to the NIH director.

Loyola University On November 17th, Sam Zakhari gave a presentation entitled "Scientific Gaps in the NIAAA Portfolio" at the Alcohol and Immunology Research Interest Group meeting at the Loyola University Medical Center, Chicago.

Consequences of Marijuana Use on Brain and Behavioral Development NIAAA cosponsored a workshop with NIDA on "Consequences of Marijuana Use on Brain and Behavioral Development." The December 15 workshop, held in Bethesda, focused on examining the state-of-the-science regarding consequences of marijuana exposure, use, and abuse on brain and behavioral development. In addition, the influences of tobacco and alcohol were considered, given the prevalence of use of those substances among youth, polydrug use realities, and the overlap of methodological issues for studies of the developmental consequences of all of these substances. The workshop had the following purposes: (1) to delineate and examine specific areas of investigation that are underway, (2) to identify priority areas still in need of research, and (3) to facilitate increased quality and efficiency in ongoing and future studies by information sharing and methodological problem solving among researchers.

Genetics of Social Behavior NIAAA participated with NIDA and (NIMH) in a two-day workshop entitled, "Genetics and Genomics of Social Behavior," and held in Bethesda, January 4-5. The goal of the workshop was to delineate which social behaviors are most relevant to addiction in order to identify relevant genes and gene variants. Resources and gaps in this area were identified and model systems poised to support these investigations were discussed. The discussion encompassed social behaviors, including monogamy, courtship, foraging, maternal care, solitary versus herding behavior, aggression, and risk-taking, and conditions such as autism and depression.

Society for Social Work and Research Peter Delany moderated a panel on early career development and was a discussant on a peer reviewed panel entitled "Evaluating Treatments for Adolescent Substance Abuse" at the annual conference for the Society for Social Work and Research, January 11-14 in San Francisco.

Institut National de la Santè et de la Recherche Mèdicale France's national health research organization, the Institut National de la Santè et de la Recherche Mèdicale (INSERM), sponsored a joint symposium for intramural and extramural U.S. scientists supported by NIAAA and French investigators funded by INSERM on January 16 and 17 at the INSERM headquarters in Paris, France. The meeting, aimed at promoting collaboration between French and U.S. scientists, focused on four broad areas of alcohol research: 1) genetic vulnerability and environmental factors in predicting alcoholism; 2) mechanisms of tolerance and dependence; 3) mechanisms of alcoholic liver disease; and 4) alcohol and brain development.

After scientific presentations and discussion from both sides, a number of promising areas were identified. These include genetic epidemiology studies; understanding the role of human development in the etiology of alcohol disorders; studies of mechanisms of alcohol dependence; the development of "research" diagnostic criteria; the identification of targets for the treatment of chronic liver injury; and the use of noninvasive tests for alcoholic steatohepatitis.

The next step will be to develop a strategic plan for collaboration including the development of human resources; the setting of research priorities based on common interests; establishment of research tools; and the standardization of methodologies, nomenclature, diagnostic criteria, and quantitative criteria. Of particular interest in both countries are the development of young investigators and the support of investigators new to the alcohol field. Dr. Li joined INSERM director Christian Brechot in presenting opening remarks at the meeting. From NIAAA, Howard Moss, George Kunos, Bin Gao, and Peggy Murray also participated in the meeting.

Presentations on New Therapies/Health Services Mark Willenbring gave presentations or participated in symposia at numerous national and international meetings. These included the International Society of Addiction Medicine annual meeting in Oporto, Portugal, September 25-October 2, where he chaired a symposium on "Treating Alcohol Disorders: Recent Advances and Future Directions"; the Addiction Health Services 2006 Conference in Little Rock, AR, October 23-26, where he made a presentation with Peter Delany on health services research at NIAAA; the White House Office of National Drug Control Policy Medical Education Conference in Washington, DC, December 1 at which he spoke on physician education initiatives; and the American Academy of Addiction Psychiatry annual meeting and symposium in St. Pete Beach, FL, December 7-10, where he participated in a workshop on "Performance Monitoring for the Addiction Psychiatrist." Dr. Willenbring also participated in a news conference on new therapies at the Society for Neuroscience annual meeting in Atlanta, GA, October 14-17.

F. Outreach

Leadership to Keep Children Alcohol Free The Leadership to Keep Children Alcohol Free welcomes Lt. Governor James R. "Duke" Aiona, Jr. (HI) and First Lady Mikey Hoeven (ND) as new co-chairs joining First Lady Mary Easley (NC) and First Lady Nancy Freudenthal (WY). Leadership thanks outgoing co-chairs Columba Bush and Hope Taft for their service. In the wake of the November elections, Leadership staff have created a database of newly elected governors and spouses and distributed a brochure on the Leadership to potential new members.

As part of an effort to create a program designed to address the health needs of children related to alcohol use, the Leadership has been working with members of the American Academy of Pediatrics (AAP) Section on Adolescent Health. As a first effort in this program, Mrs. Hope Taft, First Lady of Ohio and co-chair of the Leadership, hosted 48 Ohio pediatricians at the Governor's residence on October 27-28. The Ohio Department of Alcohol and Drug Addiction Services (ODADAS), and the Ohio chapter of AAP joined the Leadership initiative and the Leadership Foundation as co-sponsors of the two one-day meetings. The purpose of these meetings was to introduce "The 5G's," a brief tool for pediatricians for the prevention and assessment of the risk for alcohol use in young children, developed by Richard Heyman, a private practice pediatrician and chair of the AAP's Section on Adolescent Health. In addition to the presentation by Dr. Heyman, Patricia Powell of NIAAA presented the scope of the underage drinking problem and the effects of alcohol use on children and adolescents, and Peter Rogers of Columbus Children's Hospital discussed the consequences of childhood drinking and the benefits of treatment. Over the coming year, Leadership staff will work with additional Leadership members to hold similar meetings with their State's AAP chapters.

The Leadership has established a State Stipend Program to encourage State efforts to prevent childhood drinking and help generate media coverage on the issue. The program provides stipends and media relations support to State initiatives that engage new partners, reach target audiences, and have the potential to become sustainable programs that can be replicated in other communities or States. Support is provided in two forms: a $5,000 financial gift; and senior media relations assistance of 20 to 25 hours from Leadership's consulting firm, PR Solutions. To date four States have been selected to receive stipends, with the next round to be awarded in March. The selected projects include:

• developing and implementing a comprehensive effort to mobilize communities to fight childhood drinking in American Samoa

• adopting a media campaign to educate the community about the issue of social hosting in Kansas

• supporting a youth group that studies alcohol and underage drinking issues and produces reports with recommendations offering a youth perspective in Maine

• expanding a collaborative effort called Sticker Shock, which educates adults about the laws against providing alcohol to minors in New Mexico.

Mary Easley (NC) and Hope Taft (OH) participated in a national audio-conference call in November sponsored by the Underage Drinking Enforcement Training Center (established by the Office of Juvenile Justice and Delinquency Prevention within the U.S. Department of Justice). The call had almost 200 participants who listened to the presentations and then participated in a Q&A session. Finally, members of the Leadership were involved in numerous initiatives in their respective States, among them launching a new underage drinking hotline in Hawaii, and announcing a new media campaign in Maine to raise parents' awareness of their teens' behaviors.

Recognizing the need for long-term sustainability, the Leadership's emeritus group established a nonprofit foundation in October 2004. Through the Foundation, spouses of former and sitting Governors will continue to work together beyond the duration of the federally funded Leadership initiative contract. Theresa Racicot, Emeritus First Lady of Montana, is president of the Foundation; Hawaii Emeritus First Lady Vicky Cayetano is vice-president and Mary Herman, Emeritus First Lady of Maine, is secretary/treasurer. The Foundation recently opened a headquarters office in Washington, DC.

Supercourse In November 2006 a lecture entitled "Alcohol Use, Abuse, and Alcoholism" by Dr. Li was added to the Supercourse, a free, online library of 3000 lectures written by experts such as Nobel Prize winner Leland Hartwell and NIH Director Elias Zerhouni. Dr. Li's lecture includes information about NIAAA and its research priorities, as well an overview of alcohol use around the world and its relationship to health problems, including abuse and addiction. The lecture also includes information about the new Clinician's Guide, as well as updates on current pharmacological and behavioral treatments of alcohol use disorders. The lecture can be downloaded at http://www.pitt.edu/~super1/lecture/lec25521/index.htm.

The Supercourse online library began in 1999 with funding from the National Aeronautics and Space Administration, and has been supported by NIH's National Library of Medicine. Developed by Ronald LaPorte of the Department of Epidemiology at the University of Pittsburg and colleagues, the reach is considerable. For example, Dr. Li's alcohol lecture has been translated into Chinese, Spanish, and Russian and is available to faculty in medicine and the health sciences all over the world. The July 21, 2006, issue of Science states that the collection of lectures "…provides researchers with a starting point for their own talks and supplies instructors around the world with current information."

The lecture was created with the help of Peggy Murray, Howard Moss, and Brenda Hewitt.

U.S. Department of Education Vivian Faden gave a presentation entitled "Update on NIAAA's College Drinking Program" at the U.S. Department of Education National Meeting on Alcohol and Other Drug Abuse and Violence Prevention in Higher Education. The meeting took place in Arlington, VA, October 19-22.

Community of Concern On November 9, Dr. Li and Fred Donodeo attended the Community of Concern's Leadership Symposium in Potomac, MD. The Community of Concern is a partnership of parents, students, schools and other organizations interested in keeping youth alcohol and drug free. The primary goal of the symposium was to educate the parents, administrators, and students about the science related to alcohol abuse and dependence. Dr. Li delivered a presentation on how alcoholism in the United States is a disease of the young (based on the prevalence of past year DSM-IV alcohol dependence by age) and information about how the NIAAA is helping to address this challenge.

Ralph Hingson and Fred Donodeo attended The Community of Concern's "Helping Students Make Healthy Decisions" conference in Alexandria, VA, on November 28. Dr. Hingson was joined in a panel discussion by Beth Kane Davidson, Director, Addiction Treatment Program, Suburban Hospital, and Mimi Fleury, founder and CEO of The Community of Concern. Dr. Hingson addressed some of the myths surrounding the prevalence and consequences of underage drinking, and provided current information on the extent of the problem and possible ways to address it. The Communications and Public Liaison Branch (CPLB) arranged Dr. Hingson's participation in the conference and distribution of NIAAA underage drinking materials to the administrators and parents in attendance.

The Community of Concern began in the late 1990s as a Washington, DC-area consortium whose goal was to distribute the bookletA Parent's Guide for the Prevention of Alcohol, Tobacco and Other Drug Use. Subsequently, hundreds of schools, churches, and community organizations nationwide have become members of the Community of Concern. Members share a commitment to educate parents about drug, tobacco, and alcohol use by youth through distribution of the booklet, use of an interactive course on the website, and sponsoring parent education events. More information on the Community of Concern is available athttp://www.thecommunityofconcern.org/.

Adolescent Drinking Vivian Faden gave presentations on "Adolescent Development and Alcohol Use" to visiting members of the health committee of the Swedish Academy of Sciences on November 30, and to the Department of Education's Grants to Reduce Alcohol Abuse National Training and Technical Assistance Meeting in Atlanta, GA on January 9. Participants at the Atlanta meeting included representatives from 32 States and 10 tribal governments.

National Association of Student Personnel Administrators On February 1, Ralph Hingson gave the keynote address and Roger Hartman moderated a panel of NIAAA grantees doing research on college drinking at the National Association of Student Personnel Administrators Strategies Conference: Alcohol Abuse and Prevention and Intervention, in Atlanta, GA.

HBO "Addiction" Broadcast HBO will air the 90-minute prime-time program "Addiction" at 9:00 PM on March 15. NIAAA's Mark Willenbring is one of several principal spokespersons for the core broadcast and is featured in a supplementary broadcast on treatment advances. NIAAA grantees Bankole Johnson, Robert Meyers, and others appear in the core film, which premieres in Washington, DC, and Los Angeles in early March. The NIAAA Press Office coordinated NIAAA's project participation, assisted with the scripts and general-audience HBO book that will accompany the films, and will coordinate alcohol-oriented media activities. Through this multiplatform project, NIAAA messages on youth drinking and alcohol addiction and recovery will reach many millions of viewers and online visitors and have the potential to influence changes in treatment, policy, and prevention. NIDA, The Robert Wood Johnson Foundation, Join Together, Community Drug Coalitions of America (CADCA), Faces and Voices of Recovery, and other groups also are project partners.

News Media Contacts Mark Willenbring talked with reporters from several media outlets, including the Wall Street Journal on the topic of health policy measures aimed at cautioning persons with a strong family history of alcohol problems against over consumption; the Los Angeles Times on holiday drinking and treatment seeking; NBC News on psychiatric and substance use disorders among returning veterans; and Best Life magazine, a health magazine for men, on how to avoid risky drinking patterns.

Community Anti-Drug Coalitions of America NIAAA, through CPLB, continues its collaborative activities with CADCA. NIAAA has renewed its sponsorship of six Coalitions Online newsletters, which will feature interviews with NIAAA scientists. At the CADCA National Leadership Forum February 12-15 in Washington, DC, Mark Willenbring will be a plenary speaker while Dennis Twombly and Ralph Hingson will lead workshops.

G. Multi-Media Products from NIAAA

Clinician's Guide An updated edition of Helping Patients Who Drink Too Much: A Clinician's Guide was released on January 3. An NIAAA news advisory announced the updated guide. The update, soon to be available in Spanish, offers new tools including:

• A user-friendly, brief program of behavioral support for patients taking medications: Adapted from the Project COMBINE medical management manual, this program was designed to help clinicians in non-specialty settings to support their patients who take medications for alcohol dependence. Delivered by physicians, nurses, and other health practitioners, the program promotes recovery by increasing adherence to medication and supporting abstinence through education and referral to support groups. In the Guide, the program is condensed into two user-friendly forms-for initial and followup sessions-that double as patient progress notes. 

• A medications update : The section on prescribing medications for alcohol dependence contains added information about treatment strategies and options, including Vivitrol®, the recently approved, long-acting injectable naltrexone. 

• A new patient handout : "Strategies for Cutting Down" offers concise guidance for patients who are ready to cut down or quit. It is available in English and Spanish.

• A new online resource: A new page on the NIAAA Web site ( www.niaaa.nih.gov/guide) is devoted to the Guide and related professional support materials, including downloadable forms, publications, and training resources.

At the request of Cephalon, the company that markets Vivitrol®, NIAAA provided 18,000 copies of the Guide, which will be distributed by the company's sales force to clinicians throughout the country. Other dissemination activities will include direct mailings to deans of medical and nursing schools (these schools have ordered the previous Guide by the hundreds) as well as working with the American Medical Association, the American Society of Addiction Medicine, and the American Academy of Addiction Psychiatry, and several other professional organizations to distribute and promote the Guide to their members.

CPLB has also updated its online PowerPoint slideshow on using the Clinician's Guide. The slideshow is intended to familiarize audiences with the updated Guide's organization and content. The animated presentation takes viewers step-by-step through theGuide's process for screening and brief intervention. Instructors and educators may freely download and adapt the slides and graphics to create customized presentations for health professionals.

Editorial development staff at Medscape ( www.medscape.com) have agreed to work with NIAAA's Mark Willenbring, Diane Miller, and Maureen Gardner to develop a Continuing Medical Education (CME) activity based on Helping Patients Who Drink Too Much: A Clinician's Guide. The CME activity is expected to be available in mid-March 2007.

Updating the Guide was an intensive effort carried out in NIAAA by Mark Willenbring, Maureen Gardner, and Diane Miller, along with Greg Roa, who updated the dynamic Guide PowerPoint™ slide show he created. A core group of NIAAA grantees contributed invaluable feedback in several review cycles--Katharine Bradley, Peter Miller, Richard Saitz, Jeffrey Samet, and Paul Seale--along with NIAAA staff members Ann Bradley, Marcus Heilig, Raye Litten, and Howard Moss. In addition, COMBINE grantee Helen Pettinati, members of the NIAAA Nursing Expert Panel, and NIAAA's Margaret Mattson and Gretchen Daehling contributed significantly to the development of the medication management templates.

Alcohol Research & Health An issue of Alcohol Research & Health on tobacco is at the printers. On October 30 the journal's editorial board met and made a number of recommendations related to producing the journal, including changing the cover design to bring it more in line with other scientific journals; having an internal and external scientific editor for each issue; and including a page in each issue directed at the general public and patients. The next two issues, focusing on metabolism, will be sent to the printers in February. 

Alcohol AlertsAn Alcohol Alert on NESARC was printed and distributed.

Cool Spot CPLB continues to upgrade the Cool Spot, the popular interactive website targeting middle school students. In recent months, the team created a "Teacher and Volunteer Corner" with two lesson plans offering innovative ways to teach young people about peer pressure and resistance skills. A wide range of sound effects and recorded voices have also been added throughout the site. The Cool Spot remains very popular. In 2006, it averaged nearly 3,500 visitors per day for a total of 1,272,492 visits for the year. Users typically viewed multiple pages of the website during each visit for a total of 2,901,445 page views for the year.

Make A Difference NIAAA's booklet aimed at parents, Make a Difference: Talk to Your Child About Alcohol, has been updated with new material, including revised statistics, information on alcohol's effects on the brain, and information on the NIAAA Cool Spot website. The updated version is available in print and on the web in English and Spanish.

New Year's Eve Seasonal Fact Sheet Working with the National Highway Transportation Safety Administration, CPLB released an updated New Year's Eve fact sheet in December. The fact sheet, which focuses on myths about drinking and how the body metabolizes alcohol, was featured on more than 70 news, science, automotive, and financial websites. These included Forbes, Popular Mechanics, Auto Spectator, LiveScience, Pressbox UK, StockPoint, Yahoo News, Breitbart Finance, and more than 40 network news affiliates and newspapers across the country. In addition, transportation and law enforcement agencies continue to partner with NIAAA to distribute hard copies of the fact sheet. More than 2,000 copies were distributed by the Montgomery County (MD) Police Department, the Maryland State Highway Administration, and the Maryland Department of Motor Vehicles. All fact sheets in this series contain relevant statistics presented in an easy-to-understand "infograph" style, practical science-based commentary, and web site addresses for additional information.

NIH News in Health In September, CPLB staff worked with the NIH Office of Communications and Public Liaison on a special feature on college drinking in the NIH News in Health newsletter. The feature focused on the need for parents to discuss the issue of high risk college drinking with their adolescent children.