Thursday, September 17, 2009

Contents

A. Legislation, Budget, and Policy

B. Director's Activities

C. NIAAA Staff and Organization

D. Multi-Media Products from NIAAA

E. Outreach

F. News Media Interactions

G. What's Ahead

H. NIAAA Program Announcement and Request for Application Information

I. NIAAA Research Programs

J. Scientific Meetings

A. Legislation, Budget, and Policy

Budget Update

FY 2009

The NIAAA is currently closing out FY 2009. The FY 2009 annual appropriation for the Institute is $450.2 million, an increase of approximately 2.7% over FY 2008.

The NIAAA also received $113.9 million under the American Recovery and Reinvestment Act (ARRA) that is available over the 2 year period ending September 30th, 2010. Using the ARRA apportionment, NIAAA is able to fund additional approved and highly meritorious projects than could be supported under our regular annual appropriation. An estimated 40% of NIAAA’s ARRA funds will support R01 and R21 grant applications and about 28% will support Challenge Grants and Grand Opportunities Grants. NIAAA will use the remaining 32% of the ARRA apportionment to supplement existing grants, contracts, and centers, as well as support faculty recruitment grants (P30).

FY 2010

House Action: On July 24th, the full House approved the FY 2010 Labor, Health and Human Services and Education bill. For the NIH, it would provide $31.259 billion, which is $941 million more than FY 2009 and $500 million more than the President’s budget. A 3.6% increase would be provided for most NIH Institutes and Centers (ICs), including the NIAAA. For NIAAA, the House bill would provide a total of $466.3 million, an increase of $16.1 million over FY 2009 and $11.2 million over the FY 2010 President’s request.

Senate Action: On July 30, the Senate Appropriations Committee approved the Labor, HHS and Education bill. The NIH funding level was $30.759 billion, the same as the FY 2010 President's budget. However, the Senate rejected the targeted increases for cancer and autism and re-spread the President's budget increase to reflect a more consistent IC to IC allocation. In general, most ICs received a 1.7% increase over FY 2009. For NIAAA, the Senate Committee provided a total of $457.9 million. This represents an increase of $7.7 million or 1.7 % over FY 2009 and $2.7 million or 0.6% over the President’s request. A summary comparing the President’s request and the House and Senate approved levels is provided below. Final action awaits the Senate and House Conference.

FY 2011

Preliminary work on the budget for FY 2011 has begun using the FY 2010 President’s budget request as the base. After intermediate stages of review, the President’s budget request for FY 2011 will be presented to Congress in February 2010, at which time it will become available to the public.

B. Director’s Activities

NIAAA Acting Director Kenneth R. Warren, Ph.D. spoke at the following recent meetings:

Research Society on Alcoholism

June 21, 2009

FASD Exploratory Visit to Poland and Signing of Letter of Intent

From September 6-10, 2009 Dr. Warren and Peggy Murray visited Poland and took part in several activities to determine if Poland should be added to the CI-FASD initiative. Researchers at the JagiellonianUniversity in Kraków are doing MRI studies and psychological assessment on 130 children who were exposed to alcohol in utero. Dr. Warren and others from the U.S. (Dr. Kenneth Lyons Jones and Dr. Edward Riley) presented at the symposium, “Effects of Alcohol on the Child’s Development.” The group of Americans also visited a psychological clinic in Zywiec where children are being treated, and made an appearance at the national Polish symposium in honor of International Fetal Alcohol Spectrum Disorders Awareness Day in the small town of Ledziny. Dr. Warren and Ms. Murray also visited the Institute of Pharmacology of the PolishAcademy of Sciences to learn about their basic science projects in addiction. The trip ended in Warsaw at the Ministry of Health with a signing of a Letter of Intent between NIAAA and the Polish State Agency for the Prevention of Alcohol Related Problems to establish collaborative studies with Polish alcohol research centers.

International Symposium on FASD in Berlin, Germany

On September 12, 2009 Dr. Kenneth Warren gave the plenary address at the International Symposium on FASD held at the Famous hospital center, Charité in Berlin. In addition Dr. Warren and Peggy Murray met with German Ministry of Health officials and several groups representing FASD in European countries.

C. NIAAA Staff and Organization

Honors

Dr. Patricia Powell, Chief of the Science Policy Branch in the NIAAA Office of Science Policy and Communications, received the Martin K. Trusty Excellence in Management Award in July. The Trusty Award recognizes long-term outstanding commitment to and excellence in the management of the NIAAA.

Dr. Judith Arroyo and Ms. Robin Kawazoe recently received the NIH Director’s Award in recognition of contributions made in planning and coordinating the first NIH Summit titled “The Science of Eliminating Health Disparities,” which was held December 16-18, 2008.

Dr. Bani Mukhopadhyay and Dr.Yossef Tam, a Research Fellow and Postdoctoral Fellow, respectively, in DICBR will receive Fellows Awards for Research Excellence (FARE) in 2010. The FARE Award program is sponsored by the NIH Fellows Committee, the Scientific Directors, the NIH Office of Research on Women's Health, and the NIH Office of Intramural Training and Education, and recognizes outstanding scientific research performed by intramural postdoctoral fellows. Drs. Mukhopadhyay and Tam are mentored by Dr. George Kunos.

Dr. Sam Zakhari received a Certificate of Appreciation from HHS Secretary Sebelius for “Dedicated Service as an Executive Review Board Member for the Senior Executive Service Candidate Development Program” on June 25th, 2009. Dr. Zakhari also recently received the NIH Director’s Award for Science “In Recognition of His Exceptional Effort and Leadership in Promoting the Advancement of Emerging Scientific Areas in Alcohol Research.”

Dr. Antonio Noronha received the 22nd Annual RSA Seixas Award for Distinguished Service from the Dr. Peter Monti, President of RSA.

New Appointments

William Dunty, Ph.D. , recently joined the Division of Metabolism and Health Effects as a Program Director. Dr. Dunty obtained his PhD degree in cell and developmental biology from the University of North Carolina at Chapel Hill in 2002. His graduate work was conducted in the laboratory of Dr. Kathleen Sulik where he investigated the cellular and molecular bases for the teratogenic effect of ethanol during mouse embryogenesis. He received postdoctoral training in the Cancer and Developmental Biology Laboratory (CDBL) at the NCI-Frederick under Dr. Terry Yamaguchi. His research explored the molecular mechanisms of Wnt signal transduction during normal embryonic development and how aberrant Wnt signaling contributes to the etiology of human gastrointestinal cancers. Dr. Dunty has published numerous papers in peer reviewed publications.

Ms. Pamela Anderson recently joined the Ethics and Management Branch, Office of Resource Management. Ms. Anderson comes to NIAAA through NIH’s Administrative Fellows Program as part of the Management Analysis track. She will be serving as NIAAA’s Telework Coordinator and PMAP Performance Liaison, and over time NIAAA’s Emergency Planning activities will be transitioned to her as well. She will also start training in the area of ethics and will work on developing standard operating procedures for a variety of administrative functions and provide assistance related to risk management and delegations of authority. In addition to her duties at NIAAA, Ms. Anderson will also fully participate in the Administrative Fellows program.

Ms. Jenna Adamczyk joined the Division of Treatment and Recovery Research as a Research Assistant in August 2009. She recently obtained her Bachelors of Science degree from GannonUniversity where she majored in biology and minored in theology. Throughout her four years, she participated in Tri- Beta the National Biology Honor Society, and served on the executive board her final year. During this time she did extensive work in several areas of biology, including marine biology. In addition, Ms. Adamczyk has conducted research on Neogobius Melanostomus predation of Driessenids. Ms. Adamczyk is interested in a career in medicine and, to that end, has participated in Health Careers Academy and volunteered at Shriners Hospital for Children as a peer supporter and assistant in the Department of Physical Therapy.

Mr. Mark Siegal joined the Communications and Public Liaison Branch on September 14 as NIAAA Web Manager. Mr. Siegal comes to NIAAA from the National Library of Medicine, where he worked as a Senior Program Analyst since August, 2006. His responsibilities at NLM included Website management for the Extramural Program. Mr. Siegal received his Master’s degree in Information Systems and Technology from JohnsHopkinsUniversity in March 2009, and his Bachelor’s degree in Communication from CornellUniversity in 2000.

Resignations

Mark Willenbring, M.D., Director of the Division of Treatment and Recovery Research, NIAAA will be retiring from the federal service on October 31, 2009. Since joining NIAAA in 2004, Dr. Willenbring has reinvigorated the clinical research effort at NIAAA, stimulated innovation in research on health behavior across NIH, and become a highly sought after and respected spokesperson for the science behind the treatment of alcohol use disorders. Dr. Willenbring oversaw the completion of the Institute’s only Phase III clinical trial (COMBINE) and created the NIAAA Clinical Investigations Group (NCIG)—a first-of-its-kind, Institute-directed Phase II clinical trials program. Another major contribution to the Institute’s mission was Dr. Willenbring’s leadership on NIAAA’s Mechanisms of Behavior Change Initiative. This initiative shifts the traditional focus at NIAAA on refining existing behavioral interventions to one that addresses how and why change occurs. Dr. Willenbring led the multidisciplinary Research Emphasis Team devoted to this issue, initiated an annual one-day satellite meeting (now in its fifth year) at the Research Society on Alcoholism, and oversaw the development of a Request for Applications (RFA) specifically devoted to mechanisms of behavior change. He has completed the initial steps necessary to launch the second phase of this initiative: an interdisciplinary research consortium that will include behavioral and social scientists, basic researchers in neuroscience and genetics, imaging experts, and mathematicians and computational biologists. The goal of the second phase is to conduct multidisciplinary research on the topic of behavior change. Dr. Willenbring’s accomplishments in this area played an influential role in establishing an NIH-wide Road Map Initiative on the Science of Behavior Change where he has played a leadership role.

Dr. Willenbring is also well known for his work on communicating findings from alcohol research to practitioners and the general public. In 2007, Dr. Willenbring completed a comprehensive update of the Clinician’s Guide, entitled “Helping Patients Who Drink Too Much: A Clinician’s Guide.” This update incorporates new findings and tools from the landmark COMBINE trial. Dr. Willenbring also was instrumental in the development of NIAAA’s on-line resource on alcohol use entitled Rethinking Drinking. Dr. Willenbring’s efforts have established a high level of visibility for NIAAA with the extramural scientific community, professional organizations and the general public in the United States, while the numerous international collaborations he facilitated on behalf of NIAAA have raised the Institute’s profile around the world.

Ms. Diane Miller, long-time NIAAA communications chief, retired at the end of July, 2009.

Mr. Greg Roa, a writer in the Communications and Public Liaison Branch since 2002, left NIAAA in August, 2009 to accept a position at NINDS.

Extramural Staff Activities

Dr. Antonio Noronha co-chaired a symposium with Dr. George Koob entitled “Novel Neurobiological Targets for the Treatment of Alcoholism” at the Satellite Meeting of the International Society of Neurochemistry and the International Drug Abuse Research Society in Seoul, Korea, August 16-22, 2009. He gave a presentation entitled “Alcohol Dependence: A Chronic relapsing behavioral disorder -- An Overview.”

Dr. John Matochik of the NIAAA Division of Neuroscience and Behavior ( DNB) was part of the NIH Blueprint for Neuroscience Research team that developed the Blueprint Grand Challenge initiative on structural and functional connectivity of the human brain. The Human Connectome Project is a five-year $30 million initiative that will use cutting-edge brain imaging modalities to advance understanding of how neural connectivity underlies brain function.

Dr. Matochik and Dr. Lindsey Grandison of DNB participated in a two-day site visit at YaleUniversity in June 2009 of the Interdisciplinary Research Consortium on Stress, Self-Control and Addiction. This interdisciplinary research consortium is funded under the NIH Roadmap for Medical Research “Research Teams of the Future” initiative. Seven of the 10 RL1 research components in the consortium have an NIAAA Program Officer assigned to them.

Dr. Sam Zakhari gave a presentation titled “The Biologic Effects and Damage of Alcohol” during the 38th Annual meeting and Health Conference of the Association of American Indian Physicians on July 23rd, 2009.

Dr. Antonio Noronha and Howard Edenberg co-organized a symposium at the 12th Congress of the European Society for Biomedical Research on Alcoholism (ESBRA) held in Helsinki, Finland, June 7-10, 2009 entitled “Genome wide Association Studies in Alcoholism”. He gave the introductory presentation entitled “Genetics of Alcoholism: What we know this far.”

Dr. Ralph Hingson presented on the “Magnitude and Prevention of College Age and Underage Drinking Problems” at the New Mexico Traffic Safety Summit: Bridging the Gap-Building Partnerships to Save Lives, held in Albuquerque, New Mexico on August 20, 2009.

Dr. Ralph Hingson presented “Strategic Planning for Research at the National Institute on Alcohol Abuse and Alcoholism” at the Center on Alcoholism, Substance Abuse, and Addictions ( University of New Mexico) in Albuquerque, New Mexico on August 19, 2009.

Dr. Ralph Hingson presented “Strategic Planning for Research at the National Institute on Alcohol Abuse and Alcoholism” at the 2009 National Conference of the Office of Safe and Drug-FreeSchools (Department of Education) in Washington, D.C. on August 3, 2009.

Dr. Ralph Hingson presented “Magnitude and Prevention of College Age and Underage Drinking Problems,” at the Community Anti-Drug Coalitions of America’s 8th Annual Mid-Year Training held July 29-30, 2009 in Louisville, KY.

Dr. Ralph Hingson presented to the Interagency Coordinating Committee on the Prevention of Underage Drinking (ICCPUD) about “Recent Findings on Trends in College Age and Underage Drinking and Prevention of College Age and Underage Drinking: Results from Rapid Response Research” at the Federal Trade Commission in Washington, D.C. on July 27, 2009.

Dr. Bob Freeman participated in a “Research and Data Support” poster session at the American Sociological Association Annual Meeting in San Francisco, CA on August 9, 2009. At the same meeting, Dr. Freeman participated in a panel titled “Community-Based Participatory Research: When Academic/Research Institutions Meet the Real World.”

Dr. Ralph Hingson and Dr. Vivian Faden traveled to Seattle, WA, on September 13-14, 2009, to give presentations and represent NIAAA at a board meeting of the National Alcohol Beverage Control Association (NABCA). They presented NIAAA’s mission, NIAAA’s role in alcohol research, and discussed how NIAAA and NABCA can work together to prevent and reduce problematic and underage drinking.

Dr. Ralph Hingson met with medical examiners from multiple states at BoiseStateUniversity in Boise, Idaho on September 14-15, 2009, to discuss how to develop a coroner/medical examiner tool kit for the collection of information on alcohol- and drug-induced deaths.

Dr. Svetlana Radaeva of the Division of Metabolism and Health Effects prepared the NIAAA report to the White House Council on Women and Girls.

Dr. Abe Bautista and Dr. Kendall Bryant presented “HIV funding opportunities and peer review at NIAAA” at the 9th International Symposium on NeuroVirology in Miami Fl on June 2, 2009.

Staff members of the Division of Neuroscience and Behavior participated in the June 9-10, 2009 Extramural Advisory Board meeting on “Stress and Alcohol Relapse.” Staff members wrote chapters for the Extramural Advisory Board Report and gave slide presentations during the meeting.

Dr. Mark Willenbring co-chaired a session at the NIH-sponsored Science of Behavior Change Conference on June 15-15 2009. This landmark conference brought together over 100 basic behavioral researchers to focus on issue surrounding the initiation and maintenance of health-related behavior change. Dr. Willenbring’s session was entitled “Acquisition and Prevention of Behavior.”

Dr. Mark Willenbring was invited to participate in an Agency for Health Care Research and Quality (AHRQ)-sponsored conference on Practice-Based Research Networks. The conference was held on June 24-26 in Bethesda.

Dr. Mark Willenbring was invited to participate at the NIDA-sponsored conference entitled “Narrowing the Research-Practice Divide in Evidence-Based Medicine with the Adoption of Electronic Health Record Systems: Past and Future Directions.” The conference was held on July 13-14 in Rockville, M.D.

Dr. Mark Willenbring gave the opening plenary address at the Cape Cod Symposium on Addictive Disorders held on September 10-13 in Hyannis, MA. The title of his address was “Innovations in Identifying and Treating Heavy Drinkers.”

D. Multi-Media Products from NIAAA

NIAAA Spectrum

The NIAAA Office of Science Policy and Communications has created a new web-based newsletter - The NIAAA Spectrum. With engaging feature articles, short news updates, and colorful graphics, NIAAA Spectrum will offer accessible and relevant information on NIAAA and the alcohol research field for a wide range of audiences. Each issue will include two primary feature stories, a section on news updates from the field, charticles and photo essays, and an interview with a key NIAAA staff member. Each issue will also include a printable PDF option to increase its portability. The NIAAA Spectrum will be published three times a year in conjunction with NIAAA council meetings.

NIAAA Newsletter

The Communications and Public Liaison Branch (CPLB) published the summer 2009 edition of the NIAAA Newsletter at the end of June. The newsletter features:

• Information on the institute’s activities under the American Recovery and Reinvestment Act of 2009.
• The institute’s latest publication and website Rethinking Drinking that offer research-based information on drinking patterns.
• An update on the results of the NIH Scientific Management Review Board’s first meeting, including their discussion of a merger between NIAAA and NIDA.

Alcohol Research & Health

The current issue of Alcohol Research & Health focuses on underage drinking, spotlighting findings that originally appeared in the journal Pediatrics (Vol. 121, Supplement, 2008). This issue includes an introductory developmental perspective on alcohol use, as well as overviews of risk factors for alcohol use and abuse and the effects of alcohol on children in different developmental stages from birth to late adolescence. This issue also covers preventive interventions for underage drinking and treatment for alcohol and other drugs in adolescence.

Alcohol Alert

The new Alcohol Alert on underage drinking corresponds with the Alcohol Research & Health issue on the same subject. This Alert addresses our current understanding of alcohol’s effects on the key stages of human development from birth through age 20.

Rethinking Drinking update

A recent analysis of publications orders shows that a wide range of organizations have placed repeat, bulk orders for the Rethinking Drinking booklet. Repeat orders have come from health centers and hospitals, medical schools, HMOs, Army and Veterans Administration health centers, prevention and mental health clearinghouses and services, universities, district courts and DUI programs, employee assistance programs (EAPs), and churches. On average, orders for 4,000 to 5,000 booklets are placed each week. One large corporate EAP (3M) is building a major outreach effort around Rethinking Drinking, including a presentation for their EAP professionals to use with employees and leaders, along with an order for 8,000 copies.

Under a new NIAAA contract, a strategic communications plan for the Rethinking Drinking booklet and Web site (as well as other facets of NIAAA communications) will be developed in the months ahead. The Rethinking Drinking plan will outline goals, opportunities, challenges, and strategies, and will take into account the Council members’ many suggestions that followed the June 2009 Council presentation on Rethinking Drinking. In the meantime, a new, brief section on alcohol and liver health is being developed and will be added to the Q&A section; this is in response to one Council member’s suggestion as well as several questions from visitors to the Web site.

Progress is continuing at the University of Missouri, where the Rethinking Drinking Web site is being integrated into efforts on two Screening and Brief Intervention (SBIRT) grants from SAMHSA and the Missouri Foundation for Health. The researchers are developing a “shell” to wrap around the Rethinking Drinking Web site that will allow clinic-based providers and patients to log in, communicate, track progress, and evaluate outcomes such as changes in attitudes and beliefs as well as reductions in drinking. They hope to have basic functionality on the research site by early fall.

E. Outreach

NIAAA Hosts Large Contingent of “Jeter’s Leaders”

This past July, for the sixth consecutive year, NIAAA hosted high school students participating in baseball star Derek Jeter’s “Jeters Leaders” program for a day-long series of presentations and interactive activities. For the first time, the students came to NIAAA during summer break to accommodate students from both New York City and Kalamazoo, MI. The Jeter’s Leaders program focuses on leadership training, peer education, and health lifestyles, with an emphasis on alcohol education. A total of 60 students participated in the trip to NIAAA. Following a general orientation at the NIH Visitor’s Center and a tour of NLM’s global health exhibit, the students met with some of NIAAA’s top scientists. Dr. Vivian Faden fielded many questions during her discussion of alcohol and adolescence, followed by Dr. Judy Arroyo’s bi-lingual presentation on alcohol and people of color.

The group also repeated previous year visits with Dr. Markus Heilig, who explained the progression of alcohol use into alcoholism, and with Dr. Christina Barr for a tour of the Poolesville animal facility. A select group of students met with Dr. Dennis Twombly to get advice and instructions on how they could present the interactive Drunken Brain exhibit during peer education discussions with elementary and middle school students. The day ended with a visit to Dr. Fumihito Ono’s zebra fish lab, where the students got a hands-on look (including turns at the microscopes) at how the small zebra fish play such a large role in alcohol research. A lengthy article in the NIH Record on the students’ visit can be found at http://nihrecord.od.nih.gov/newsletters/2009/08_07_2009/story5.htm

NIAAA Hosts Poster Session at CDC Health Communications Conference

Fred Donodeo of the NIAAA Communications and Public Liaison Branch and Susan Kirby of KMS Consulting hosted a poster session on health communications research at the 3rd Annual National Conference on Health Communication, Marketing and Media on August 12. The conference was co-sponsored by CDC and NCI. Entitled “Beer Pong, PubGolf, and Drinking Scrabble,” the poster session described how audience segmentation research, particularly geodemographic marketing data, could be used to identify and target young adult binge drinkers. The poster was based on the article by Howard Moss et.al, “Characterizing and Reaching High-Risk Drinkers Using Audience Segmentation,” which was published recently in Alcoholism: Clinical and Experimental Research.

NIAAA Partners with CDC to Promote College Alcohol Reduction Strategies

NIAAA has entered into a Memorandum-of-Understanding with CDC to evaluate marketing strategies for a college alcohol reduction program. The partnership supports the Safer Universities project, which will evaluate strategies to encourage the widespread adoption of a comprehensive, community-based environmental prevention program on college drinking. That program is grounded in the successful Safer California Universities Project, an on-going project now in its eighth year which was funded by a grant from NIAAA to the Pacific Institute for Research and Evaluation (PIRE). The grant supported the design, implementation, and evaluation of a comprehensive program for colleges in California, focusing on the first weeks of the academic year. NIAAA and CDC will collaborate in promoting the adoption of this program by colleges and communities across the country.

Health Disparities Outreach Efforts

On July 13-17, 2009, Dr. Judith Arroyo conducted outreach to participants in the National Hispanic Youth Initiative (NHYI), a group of Hispanic high school scholars interested in careers in research and medicine. NIAAA supports the NHYI along with other projects that hope to increase the pipeline of researchers from diverse ethnic and racial backgrounds.

On July 20, 2009, Dr. Judith Arroyo presented on “Health Disparities and Hispanic Alcohol Research” at the National Institute of Mental Health (NIMH) summer research institute for representatives of the Hispanic Association of Colleges and Universities to increase interest in alcohol research on the part of investigators at Hispanic Serving Institutions.

On July 22-27, 2009, Dr. Judith Arroyo served on the faculty of the American Psychological Association Summer Minority Research Institute. She helped post-doctoral students working on submitting applications to NIAAA and other NIH institutions.

On July 23, 2009, NIAAA was prominently featured on the breakout program at the Association of American Indian Physicians. Dr. Mary-Anne Enoch, Staff Scientist at the NIAAA Laboratory of Neurogenetics, presented on “Genetics and Environmental Risk Factors for Alcoholism-Pointers for Prevention and Treatment.” Dr. Samir Zakhari, Director of the Division of Metabolism and Health Effects at NIAAA, presented on “The Biologic Effects and Damage of Alcohol.” NIAAA hopes to expand its involvement with this group of physicians that works with the high-risk, underserved Health Disparity population.

F. News Media Interactions

Dr. Mark Willenbring was quoted at length in a Time magazine article on Thursday, August 20, 2009 entitled “When does social drinking become ’at risk’ drinking?”

Dr. Ralph Hingson gave numerous media interviews re college drinking that were prompted by a recent NIAAA press release about a July, 2009 supplement to the Journal of Studies on Alcohol and Drugs that featured NIAAA research on college drinking prevention . Media outlets included the Milwaukee Journal Sentinel and Alcoholism and Drug Abuse Weekly, among others.

G. What’s Ahead

On September 23-24, 2009, Dr. Ralph Hingson will present at the 16th National Conference on Drugs and Crime of the Treatment Alternatives for Safer Communities (TASC, Inc.) in Charlotte, NC, about the magnitude and prevention of college age and underage drinking problems.

Dr. Sam Zakhari co-organized the 4th International Symposium on ALPD and Cirrhosis to be held October 8-9, 2009 in Egypt. He will give a presentation on “The Role of Epigenetics In Alcohol-Induced Tissue Injury.” He was also invited to give two Lectures at the School of Medicine, CairoUniversity, titled: “Interactions between Alcohol and Medications Resulting in Liver Damage” and “Similarities and Differences Between Basic Mechanisms and Clinical Features of ASH and NASH (alcoholic steatohepatitis and non-alcoholic steatohepatitis).”

On November 4, 2009, Dr. Ralph Hingson will discuss the magnitude and prevention of college age and underage drinking problems as part of a session on addiction issues involving young adults and teens at the American Osteopathic Academy of Addiction Medicine’s 2009 Annual Convention and Scientific Seminar in New Orleans, LA.

On November 11, 2009, Dr. Ralph Hingson will give a presentation titled “Does Age Influence Whether Patients See Physicians and Are Asked and Counseled About Alcohol Consumption” at the American Public Health Association’s 137th Annual Meeting and Exposition in Philadelphia, PA.

H. NIAAA Program Announcement and Request for Applications Information

RFA-MH-09-160 (R34) and RFA-MH-09-161 (R21/R33) (Novel Interventions for Neurodevelopment Disorders). NIAAA joined this RFA from NIMH to encourage development of novel interventions to improve functioning in neurodevelopmental disorders such as autism and fetal alcohol syndrome. Dr. John Matochik, DNB and Dr. Dale Hereld, DMHE are the program contacts. Four alcohol-related applications were reviewed and will be considered for funding.

RFA 09-002 (HIV/AIDS and Alcohol Comprehensive Research Center) Primary and secondary reviews on four applications were completed in August, 2009.

RFA-OD-09-006 Building Interdisciplinary Research Careers in Women’s Health (K12).

RFA with NIDA:

NIAAA is participation in 2 RFAs with NIDA for an R01 and R21 “Substance Use and Abuse among U.S. Military Personnel, Veterans and their Families”. The DTRR staff is the NIAAA POC for these 2 RFAs.

Broad Agency Announcement (BAA): “Mechanisms of Behavior Change Initiation (MOBCI) for Drinking Behavior.”
Through this BAA, announced in April, 2009, DTRR solicited proposals for new, high risk approaches to traditionally intractable alcohol-related problems through the development of mechanism-based strategies that induce maladaptive drinkers to initiate and sustain a change from maladaptive drinking behaviors towards more healthful drinking behaviors.

a. Our Goal was to find innovative methods that will result in entirely new improvements in both the theory and methodologies used to understand how to induce sustainable, positive change in maladaptive drinkers.

b. This BAA focuses on the initiation of change as an initial step towards this goal.

c. We began making site visits on 1 Sept 09 with the intent of awarding one project by the end of FY09.

I. NIAAA Research Programs

RESEARCH REPORTS

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

A discrete alcohol pocket involved in GIRK channel activation. Alcohol is known to influence the activity of ion channels, such as the G-protein gated inward rectifier K (potassium) channels, which scientists simply call “GIRK channels.” Learning how alcohol affects these channels could provide important information about how alcohol exerts its effects in the body. In this study, researchers investigated a suspected alcohol-binding pocket within protein molecules that comprise GIRK channels. Amino acid substitutions within the proposed pocket reduced or eliminated its activation by alcohol. These results suggest that compounds designed to interfere with GIRK channel activation might mitigate the effects of alcohol. (Aryal P, Dvir H, Choe S, Slesinger PA. Nature Neuroscience. 2009 Aug;12(8):988-95.)

Working and episodic memory in HIV infection, alcoholism, and their comorbidity: baseline and 1-year follow-up examinations. In this study, researchers found evidence for a selective rather than a global deficit in memory processes in alcohol-dependent individuals with HIV infection. The specific deficit in immediate episodic memory with no corresponding deficit in retention levels suggest a problem in the encoding of information rather than a deficit in information retrieval in such individuals. Understanding the specific memory deficits in individual patients co-morbid for alcohol dependence and HIV infection may help to guide effective behavioral strategies for individuals to use to compensate for their deficits. These strategies could be useful, for example, in assisting individuals to maintain adherence to medication treatment regimes. (Fama R, Rosenbloom MJ, Nichols BN, Pfefferbaum A, Sullivan EV. Alcohol Clin Exp Res. 2009 Jul 28. [Epub ahead of print].)

Estimated blood alcohol concentrations for child and adolescent drinking and their implications for screening instruments. Blood alcohol concentrations (BACs) in children after consumption of different numbers of standard drinks of alcohol have not been estimated previously. The current study used previously published health surveys and scientific reports to derive total body water data and alcohol elimination rates -- key variables in the BAC equation -- for individuals ranging in age from 9 to 17 years. With that information, the researcher modified the equation used for estimating BACs in adults to estimate the BACs that theoretically would result after children and adolescents consume various numbers of drinks. The results indicate that adolescents achieve far higher BAC levels than young adults when consuming similar amounts of alcohol. These findings further highlight the age-specific effects of alcohol and add additional urgency to develop effective screening, education and prevention efforts for adolescents. (Donovan JE. Pediatrics. 2009 June;123(6):e975-81)

Functional CRH variation increases stress-induced alcohol consumption in primates

Corticotropin-releasing factor (CRF), is a key integrator of stress responses. Scientists hypothesize that variation in the CRH gene may contribute to individual differences in susceptibility to stress-related pathology. In rhesus macaques, a single nucleotide polymorphism (SNP) is found within the CRHgene promoter. In this study, researchers assessed whether this variant influenced stress responding in the animals and whether it predicted voluntary alcohol consumption following stress exposure. They found that the gene’s_248 T allele resulted in increased DNA protein interactions relative to the C allele. In vitro, the T allele resulted in CRH promoter activity that was higher following both stimulation with forskolin and treatment with dexamethasone. Endocrine and behavioral responses to social separation stress were higher among carriers of the T allele, particularly among those exposed to early adversity. They also found that T allele carriers with a history of early life adversity consumed more alcohol in a limited-access paradigm. Our data suggest that CRH promoter variation that confers increased stress reactivity increases the risk for alcohol use disorders in stress-exposed individuals. (Barr CS, Dvoskin RL, Gupte M, Sommer W, Sun H, Schwandt ML, Lindell SG, Kasckow JW, Suomi SJ, Goldman D, Higley JD, and Heilig M. PNAS. August 25, 2009 106(34): 14593–14598)

Targeted Naltrexone for Problem Drinkers

Previous studies have suggested that the targeted use of naltrexone is a useful strategy to reduce heavy drinking. In the current study, scientists compared the effects of naltrexone with those of placebo in a sample of problem drinkers who sought to reduce their drinking to safe limits. Individuals in the study were instructed to use their medication either daily or in situations in which they would be at high risk for heavy drinking. At the end of the 12-week trial, the average number of drinks per day had declined significantly among men in the targeted naltrexone group, Drinks per drinking day also declined significantly in the naltrexone group relative to other groups. The researchers conclude that their results support the use of a targeted approach to reduce drinking among heavy drinkers, particularly men, but argue for the use of additional strategies or more efficacious medications than naltrexone to increase the effects of such an intervention. (Kranzler HR, Tennen H, Armeli S, Chan G, Covault J, Arias A, and Oncken C, J Clin Psychopharmacol 2009;29: 350Y357)

A Randomized, Double-Blind, Placebo-Controlled Pilot Study of Naltrexone in Outpatients With Bipolar Disorder and Alcohol Dependence

Alcohol dependence is extremely common in patients with bipolar disorder and is associated with unfavorable outcomes including treatment nonadherence, violence, increased hospitalization, and decreased quality of life. Researchers conducted a pilot study to assess the efficacy of naltrexone in reducing alcohol use and on mood symptoms in outpatients with bipolar I or II disorders and current alcohol dependence with active alcohol use. Patients received either 12 weeks of naltrexone (50 mg⁄ d) add-on therapy or placebo. Both groups received manual-driven cognitive behavioral therapy designed for patients with bipolar disorder and substance-use disorders. The naltrexone group showed trends toward a greater decrease in drinking days, alcohol craving, and some liver enzyme levels than placebo. While these results suggest the potential value and acceptable tolerability of naltrexone for alcohol dependence in bipolar disorder patients, a larger trial is needed to establish efficacy. (Brown ES, Carmody TJ, Schmitz JM, Caetano R, Adinoff B, Swann AC, and Rush AJ. Alcohol Clin Exp Res, Vol 33, No 11, 2009: pp 1–7)

Varenicline Reduces Alcohol Self-Administration in Heavy-Drinking Smokers

Alcohol and tobacco dependence are highly comorbid disorders, with preclinical evidence suggesting a role for nicotinic acetylcholine receptors (nAChRs) in alcohol consumption. Varenicline, a partial nicotinic agonist with high affinity for the42nAChRreceptor, reduced ethanol intake in rodents. In the current study, investigators examined whether varenicline would reduce alcohol consumption and alcohol craving in non-alcohol-dependent heavy drinkers who were daily smokers. In the double-blind, placebo-controlled investigation, a 7-day medication pretreatment period was followed by a priming dose of alcohol And then a 2-hour alcohol self-administration period during which participants could choose to consume up to 8 additional drinks. Varenicline significantly reduced the number of drinks consumed compared to placebo and increased the likelihood of abstaining from any drinking during the self-administration period. Following the priming drink, varenicline attenuated alcohol craving and reduced subjective reinforcing alcohol effects. Adverse events associated with varenicline were minimal and, when combined with alcohol, produced no significant effects on physiologic reactivity, mood, or nausea. The researchers conclude that varenicline should be investigated as a potential treatment for alcohol use disorders. (McKee SA, Harrison ELR, O’Malley SS, Krishnan-Sarin S, Shi J, Tetrault JM, Picciotto MR, Petrakis IL, Estevez N, and Balchunas E. Biol Psychiatry 2009;66:185–190)

Exogenous thioredoxin prevents ethanol-induced oxidative damage and apoptosis in mouse liver

Increased production of reactive oxygen species ( ROS) and tumor necrosis factor alpha (TNF-alpha), as well as hepatocyte apoptosis, contribute to the progression of ethanol-induced liver injury. Despite the clear role of ROS in the pathogenesis of alcoholic liver disease ALD, treatment with antioxidants only partially protects against liver damage. Although antioxidants prevent oxidative damage, they do not directly protect against inflammation or apoptosis. Thioredoxin-1 (Trx) is a multifunctional small protein that has antioxidant properties, as well as specific functions in decreasing inflammatory cytokine production and apoptosis. The current study tested the hypothesis that Trx treatment reduces oxidative stress, inflammatory cytokine expression, and apoptosis in mice exposed to short-term ethanol feeding. Researchers found that Trx effectively decreased ethanol-induced lipid peroxidation and hepatic inflammatory cytokine concentration, as well as prevented apoptosis. The data suggest that treatment with Trx might be a useful for preventing alcohol-induced liver injury. (Cohen JI, Roychowdhury S, Dibello PM, Jacobsen DW, Nagy LE. Hepatology. 2009 May;49(5):1709-17.)

Taurine supplementation prevents ethanol-induced decrease in serum adiponectin and reduces hepatic steatosis in rats

Researchers have demonstrated that ethanol feeding depletes the amino acid taurine from adipose tissue of rats and that supplementation with taurine prevented multiple effects of ethanol on adipose tissue. The current study demonstrated a preventative role of taurine in ethanol-induced changes in adipose tissue of rats, and an attenuation in the development of ethanol-induced hepatic steatosis. Taurine has also been shown to have therapeutic effects in ethanol-induced liver injury in rats. Taurine is considered a nontoxic amino acid and is easily supplemented in daily diets. Indeed, taurine is widely used as a nutritional supplement in infant formulas and energy drinks. Taken together, these data suggest that taurine, widely used as a nutritional supplement in infant formulas and energy drinks, may be a useful nutritional supplement to attenuate alcohol-induced liver damage. The findings also suggest that adipose tissue can be a potentially important target for therapeutic interventions to prevent alcohol-induced fatty liver. (Chen X, Sebastian BM, Tang H, McMullen MM, Axhemi A, Jacobsen DW, Nagy LE.Hepatology. 2008 Dec 30. [Epub ahead of print])

S-adenosyl-L-methionine co-administration prevents the ethanol-elicited dissociation of hepatic mitochondrial ribosomes in male rats

In this animal study, researchers demonstrated that chronic ethanol feeding impacts hepatic mitochondria by depressing respiration, increasing the dissociation of mitochondrial ribosomes (mitoribosomes), and inhibiting mitoribosomal activity. Co-administration of S-adenosyl-L-methionine prevented ethanol-elicited mitoribosome impairment. These results suggest that defects in the mitoribosome may represent a major underlying factor in the mitochondrial dysfunction seen in the early stages of alcohol-induced liver damage. (Sykora P, Kharbanda KK, Crumm SE, Cahill A. Alcohol Clin Exp Res. 2009 Jan;33(1):1-9.)

Validation of the Bayesian Alcoholism Test Compared to Single Biomarkers in Detecting Harmful Drinking

Current tests to detect alcohol dependence or abuse employ single questionnaires or biochemical markers. The current study investigated a Bayesian Alcoholism Test (BAT) that uses biochemical markers in addition to questionnaire information. Researchers found that the BAT has a greater diagnostic accuracy than commonly used single biological markers in detecting harmful alcohol use. Additional research is needed to further validate and refine the BAT in a female population, in subjects with liver disease and in populations with a low prevalence of hazardous and harmful alcohol use. The advent of computerization of clinic records increases the practicality of using algorithms to raise the clinician's awareness of the risk of alcohol problems. (Korzec S, Korzec A, Conigrave K, Gisolf J, Tabakoff B. Alcohol Alcohol. 2009 Jul-Aug;44(4):398-402. Epub 2009 Mar 16.)

Binge drinking upregulates accumbens mGluR5-Homer2-PI3K signaling: functional implications for alcoholism.

The metabotropic glutamate receptor associated protein, Homer2, regulates alcohol-induced neuroplasticity, but it is not clear what downstream signaling cascades are involved in regulating excessive alcohol consumption. Using various gene targeting and pharmacological approaches, researchers demonstrated that binge alcohol drinking could be significantly reduced by either the disruption of the physical interaction between mGluR5 and Homer2 or by antagonists of mGluR5 and PI3K. These results extended the previous funding on the important roles of mGluR5 and Homer2 in regulating alcohol intake and are consistent with the discovery of the association of polymorphisms of glutamate receptor and PI3K regulatory subunit genes with risky alcohol drinking behavior. Collectively, these data provide strong evidence of mGluR-Homer2-PI3K signaling in the nucleus accumbens in regulating binge like alcohol consumption and reveal potential therapeutic targets for therapeutic intervention. ( Cozzoli DK , Goulding SP , Zhang PW , Xiao B , Hu JH , Ary AW , Obara I , Rahn A , Abou-Ziab H , Tyrrel B , Marini C , Yoneyama N , Metten P , Snelling C , Dehoff MH , Crabbe JC , Finn DA , Klugmann M , Worley PF , Szumlinski KK . J Neurosci. 2009; 29(27):8655-68).

J. Scientific Meetings

Research Society on Alcoholism Annual Meeting

The RSA annual meeting took place in June, 2009 in San Diego. NIAAA was again well-represented at this important meeting. For example:

• The NIAAA supported this year’s scientific meeting of the International Society for Research on Impulsivity (ISRI) as a satellite to the RSA meeting. The theme of the ISRI meeting was “ Alcohol and Impulsivity.” The meeting featured a plenary address by Professor Trevor Robbins from the University of Cambridge, along with 15 oral presentations and a poster session with 21 presentations. Funding also provided for 18 travel awards for students and junior investigators to attend the meeting.
• The NIAAA Division of Treatment and Recovery Research hosted the 4th Pre-conference satellite meeting on MOBC entitled Mechanisms of Behavior Change in Behavioral Treatment: Today and Tomorrow. Ninety-three participants attended the meeting.

Dr. Mariela Shirley and Dr. Lindsey Grandison held an RSA Grantsmanship and Mock Review one-day Satellite meeting as a joint effort between NIAAA and the RSA Education Committee.

Dr. Antonio Noronha co-organized 2 symposiums at the RSA meeting: “Epigenetics of Alcohol Effects on the Nervous System” was co-organized with Dr. Dipak Sarkar; “Genome-Wide Association Studies of Alcoholism and Related Phenotypes” was co-organized with Dr. Howard Edenberg.

Dr. M. Katherine Jung, along with Dr. Elizabeth Kovacs of LoyolaUniversity, co-chaired a symposium, “Alcohol Exposure and Mechanisms of Tissue Injury and Repair.”

Dr. Gyongyi Szabo of U. Mass and NIAAA’s Dr. Joe Wang co-organized a symposium on "HCV and Alcohol, Liver and Immune Damage."

Dr. Dale Hereld co-organized and co-chaired the "MicroRNAs: Master Regulators of Ethanol-abuse and Toxicity?" symposium at the 2009 Research Society on Alcoholism meeting in San Diego, CA. In addition, Dr. Hereld delivered the symposium's introductory talk.

Dr. Ralph Hingson presented his poster titled “Early Age of Drinking Onset, Parental Provision of Alcohol to Youth, and the Development of Alcohol Dependence.”

Dr. Sam Zakhari gave a presentation titled “Stem Cells Come of Age” at the RSA satellite symposium on “Alcohol as a Modifier of Biological Responses, Stem Cells: Relevance to Alcohol-Induced Tissue damage and Regeneration.”

Dr. Sam Zakhari co-organized and co-chaired a symposium on “Molecular Mechanisms of Alcoholic Liver Disease: Roles of Innate Immunity” and gave introductory remarks at the RSA meeting.

Dr. Sam Zakhari was a discussant in a symposium on “Alcohol-HIV-Art Biomedical consequences and Interactions.”

Dr. Svetlana Radaeva co-chaired the “Adverse Effects of Alcohol Abuse on Adult Stem Cells” symposium.

Posted: December 10, 2009