Thursday, February 17, 2011

 A. Legislation, Budget, and Policy

Budget Update

FY 2010

In FY 2010, the NIAAA obligated $462.1 million in appropriated money.  As part of the NIH Director’s one-percent transfer authority and consistent with FY 2009 action, $704 thousand was transferred from NIAAA for the Genes and Environment Initiative (GEI). NIAAA awarded 706 research project grants (RPGs), including 189 competing awards.  FY 2010 support levels from our regular appropriated funds for other key extramural funding mechanisms included 21 research centers for $28.0 million; 116 other research grants for $30.0 million, 289 full-time training positions for $11.8 million; and $35.7 million for research and development contracts.

The NIAAA also obligated its remaining $52.9 million from the American Recovery and Reinvestment Act (ARRA) apportionment of $113.8 million.  These funds were used to support the second year of the ARRA funded grant awards made in FY 2009, a limited number of high priority administrative supplements and competing RPGS via payline extension, and 3 new competitive High Impact Research and Research Infrastructure Grants (RC4s).

FY 2011

The NIH is now operating under its 4th Continuing Resolution (CR) for the year, which provides funding through March 4th at the annualized FY 2010 dollar level. The FY 2011 President’s request for FY 2011, which was released last February, provides a 3.2 percent or $1 billion increase for the NIH.  However, House Appropriators have recently proposed the elimination of this increase and other House proposals are suggesting larger cuts that could pull federal spending back to fiscal 2008 levels.  It is likely that another short-term funding measure will be passed before an agreement on a final budget is reached.  NIAAA is proceeding cautiously due to the many uncertainties.

FY 2012

The FY 2012 President’s budget request was released earlier this week.  For the NIH, the total request is $31.8 billion, an increase of +0.5 billion or 1.9% over FY 2010.  For NIAAA, the request is $469.2 million.  This represents a $7.1 million or a 1.5% increase over the FY 2010 comparable level of $462.1 million.

A budget mechanism distribution of NIAAA’s FY 2010 actual obligations, the FY 2011 Continuing Resolution, and the FY 2012 President’s budget request is provided below.  The FY 2010 and 2011 columns of this table reflect some adjustments for comparability to the FY 2012 request.

NATIONAL INSTITUTES OF HEALTH 

National Institute on Alcohol Abuse and Alcoholism

Budget Mechanism - Total 1/

(Dollars in Thousands)

  1/ All items in italics are "non-adds"; items in parenthesis are subtractions
   2/ Includes FTEs which are reimbursed from the NIH Roadmap for Medical Research

B. Director’s Activities

Dr. Warren attended and/or spoke or otherwise participated at the following recent meetings:

IOM Neuroscience Forum                                                                                    Oct. 13-14, 2010

Alcohol Research Center Director's Meeting, Berkley, Ca                                    Oct. 19-20, 2010

First European Conference on FASD – The Netherlands                                           Nov. 3-5, 2010

Annual Meeting of Society for Neuroscience - San Diego, Ca                                   Nov. 12, 2010

American Congress of Neuropsychopharmacology - Miami Beach, Fla                    Dec. 5-9, 2010

International Activities

• On November 2-3 2010, Drs. Kenneth Warren and Peggy Murray participated in a World Health Organization planning meeting in Kerkrade, Netherlands to develop the protocol for the first global study of the prevalence of Fetal Alcohol Spectrum Disorders.  Dr. Warren co-chaired the meeting with Dr. Jurgen Rehm, consultant to WHO and Dr. Vladimir Poznyak, Director of the Programme on Substance Abuse, WHO. Participants included FASD researchers from Russia, Brazil, Chile, South Africa, Australia, Canada and the United States.
• On November 3-5, Drs. Kenneth Warren and Peggy Murray participated in the meeting "Fetal Alcohol Spectrum Disorders: Growing Awareness in Europe" which was held at the historic Rolduc Monastery in the Netherlands.  Dr. Warren gave the plenary address, "The Future Emerging from FASD Research: Impact on Identification, Prevention and Treatment" and chaired a session on Prevention and Public Education.  Dr. Murray made a presentation entitled, "Reaching Health Professionals to Improve Identification, Treatment and Prevention of FASD."
• On January 31, 2011 Drs. Kenneth Warren and Peggy Murray participated in the conference, “Sharing Health: U.S. – Russia Collaboration in the Health Sector”, sponsored by the Center for Strategic and International Studies in Washington, DC.  The meeting was co-chaired by former Senator William Frist and Nikolay Gerasimenko, First Vice Chair of the Committee on Health Protection, Russian State Duma.  Dr. Warren made a presentation on evidence-based alcohol prevention strategies in the U.S. as part of a session on Collaboration to Promote Healthy Lifestyles.  He also described an NIAAA funded study of FASD prevention that is a collaboration between investigators at the University of Oklahoma Health Sciences Center, St. Petersburg State University, and the Pedagological University of the Nizhniy Novogorod Region.

C. Staff / Grantee Honors

At a White House ceremony hosted by President Obama on December 13, 2010, NIAAA grantee Kimberly Nixon, Ph.D., assistant professor at the University of Kentucky College of Pharmacy, received the Presidential Early Career Award for Scientists and Engineers (PECASE), the highest honor bestowed by the United States government on science and engineering professionals in the early stages of their independent research careers.   Dr. Nixon was one of eighteen NIH grantees and two intramural scientists to receive the prestigious award this year.  PECASE candidates are nominated by federal agencies for their pursuit of innovative research and commitment to community service.  In 2007, Dr. Nixon received a 5-year $1.6 million grant from NIAAA to understand how endogenous neural stem cells contribute to recovery during abstinence from alcoholism.

Dr. Pal Pacher, Acting Chief, Section on Oxidative Stress Tissue Injury, Laboratory of Physiologic Studies, has been invited to join the Editorial Board of Free Radical Biology & Medicine, the Official Journal of the Society for Free Radical Biology and Medicine, and the American Journal of Physiology Heart and Circulation Physiology, the Official Journal of the American Physiological Society.  Dr. Pacher was appointed as Associate Editor for The Journal of Gerontology, Series A: Biological Sciences. The journal is the official journal of the Gerontological Society of America.  Dr. Pacher recently entered the top 100 most cited researchers in the World in the field of Pharmacology according to the Institute for Scientific Information.

D. Press Releases

The following press releases are based on research supported by NIAAA:

11/1/2010: NIH-supported mice studies suggest treatment target for alcohol problems
A molecular pathway within the brain’s reward circuitry appears to contribute to alcohol abuse, according to laboratory mouse research supported by the NIAAA.  The mammalian target of rapamycin complex 1, or mTORC1, is a group of proteins found in cells throughout the body. An important part of the cellular machinery, mTORC1 sends signals that help regulate the size and number of cells.  In laboratory studies, researchers measured an increase in mTORC1 cellular products in the nucleus accumbens of mice that had consumed alcohol – an indication that alcohol activates the mTORC1 pathway.  They then showed that rapamycin, an immunosuppressant drug that blocks the mTORC1 pathway, decreased excessive alcohol consumption, binge drinking, and alcohol-seeking behavior in the rodents. The findings show that the mTORC1 pathway is an important contributor to mechanisms that underlie alcohol-seeking behavior and suggest that novel rapamycin-like compounds might be useful treatments for alcohol use disorders.

11/11/2010: NIH-Supported Study finds Strategies to Reduce College Drinking
Highly visible cooperative projects, in which colleges and their surrounding communities target off-campus drinking settings, can reduce harmful alcohol use among college students, according to a report by researchers supported by the NIAAA.  Researchers conducted the Safer California Universities study of college and community alcohol prevention strategies at 14 large public universities in California.  The researchers measured the proportion of drinking occasions in which students got drunk in various settings.  They found significantly greater reductions in the incidence and likelihood of intoxication at off-campus parties and at bars and restaurants for students at the intervention universities.  Students at intervention universities also reported a lower likelihood of drinking to intoxication the last time they attended an off-campus party, a bar or restaurant, or other drinking settings.  The greatest reductions were found at universities with the highest intensity of intervention implementation, achieved through heavy publicity and highly visible enforcement activities.

12/22/2010: NIH-led study identifies genetic variant that can lead to severe impulsivity
A multinational research team led by scientists at the National Institutes of Health has found that a genetic variant of a brain receptor molecule may contribute to violently impulsive behavior when people who carry it are under the influence of alcohol.  In collaboration with researchers in Finland and France, Dr. David Goldman and colleagues studied a sample of violent criminal offenders in Finland.  The researchers sequenced DNA of the violently impulsive subjects and compared those sequences with DNA from an equal number of non-impulsive Finnish control subjects. They found that a single DNA change that blocks a gene known as HTR2B was predictive of highly impulsive behavior. HTR2B encodes one type of serotonin receptor in the brain. Carriers of the HTR2B variant who had committed impulsive crimes had become violent only while drunk from alcohol. The researchers then conducted studies in mice and found that when the equivalent HTR2B gene is knocked out or turned off, mice also become more impulsive.

1/19/2011: Gene variants predict treatment success for alcoholism medication
The effectiveness of an experimental treatment for alcoholism depends on the genetic makeup of individuals who receive it, according to a new study supported by the NIAAA. Researchers at the University of Virginia, Charlottesville, conducted a controlled trial to determine if the medication ondansetron could reduce problem drinking, in alcohol-dependent individuals.  The researchers had previously shown that variations in the gene that encodes the serotonin transporter can significantly influence drinking intensity.  Specifically, serotonin transporter variants designated as LL and TT have been associated with more severe drinking problems.  The researchers have also reported that ondansetron may be an effective therapy for some people with alcoholism.  In this study, they performed genetic analyses to determine which serotonin transporter gene variants were carried by each subject, then randomly assigned each subject to treatment regimens with ondansetron or placebo.  They found that, for subjects with the LL genotype, those receiving ondansetron reduced their average number of daily drinks to less than five, while those receiving placebo continued to have five or more drinks per day.  LL subjects who received ondansetron also had significantly more days of abstinence, relative to those who received placebo.

E. Multi-Media Products from NIAAA

New Publications

• NIAAA Newsletter -- The Communications and Public Liaison Branch (CPLB) published issue 22 (Winter, 2011) of the NIAAA Newsletter.

• NIAAA Spectrum -- Issue 5 of the Institute's online webzine, will be released in February, 2011.

• New Year, Old Myths, New Fatalities -- NIAAA released this fact sheet in December, 2010 as part of its seasonal outreach series. The fact sheet focused on alcohol impairment and alcohol-related traffic deaths during the holidays.  Media pickup was strong, both domestically and internationally, with postings on major Internet news outlets including  CNBC, Yahoo!, Yahoo! UK & Ireland, Reuters, AOL, and MarketWatch, as well as business journals, industry publications, and numerous major television network (FOX, NBC, CBS, ABC) local affiliates nationwide. Overall, the release resulted in a total of 421 clips, representing a total audience of more than 360 million. Additionally, the fact sheet graphic appeared on PR Newswire’s Times Square billboard a total of 17 times with 5 additional postings on their Las Vegas Fashion Show Mall billboard. The fact sheet was further disseminated to members of the Washington Regional Alcohol Program (WRAP) and the Mothers Against Drunk Driving (MADD) National office, which then worked to disseminate the it to states.

F. News Media Interactions

Recent News Media Interviews

Dr. David Goldman, Chief, NIAAA Laboratory of Neurogenetics, was interviewed by numerous media outlets about the study that he and colleagues published in Nature, which identified a genetic variant that can lead to severe impulsivity.  Dr. Goldman had interviews on this topic with:

• BBC Science Radio Unit
• www.ig.com.br (news Web site in Brazil)
• New Scientist magazine
• ABC.com
• Livescience.com

Dr. Goldman was also interviewed by:
• CNN American Morning about research by scientists at the University of North Carolina on CYP2E1, a gene that may have a predictive value for alcoholism.
• The Wall Street Journal regarding alcoholism genetics

Dr. Joseph Hibbeln, NIAAA Laboratory of Membrane Biochemistry and Biophysics, gave an interview regarding Omega 3 fatty acids and mental health to:
• Periodista científica (Spanish popular science magazine)

Dr. Ralph Hingson, NIAAA Division of Epidemiology and Prevention Research, gave interviews to:
• NIH Radio about Bob Saltz’s “Safer California Universities” paper in AJPM.
• Crane’s New York Business Online about the dangers of excessive drinking during the holidays.
• Newsweek.com about college drinking prevention.
• Vogue magazine about moderate drinking.
• Harper’s Magazine about alcohol-related health issues and alcoholism in youth and young adults.

Dr. Antonio Noronha, NIAAA Division of Neuroscience and Behavior, was interviewed by:
• Superinteressante (Super Interesting) Magazine, Brazil, about brain and behavior responses to alcohol.

Dr. Sam Zakhari, NIAAA Division of Metabolism and Health Effects, gave interviews to:
• msnbc.com to explain that alcohol does not help people stay warm in cold weather, and that excessive alcohol consumption can lead to hypothermia.
• arper’s Magazine about alcohol-related health issues and alcoholism in youth and young adults.
• Women’s Health Magazine about immediate effects of alcohol

Dr. Deidra Roach, NIAAA Division of Treatment and Recovery Research, was interviewed by:
• MyHealthNewsDaily.com on the topic of alcohol and women.
• ABC News (on background) about current research on gender and alcohol.

Dr. PJ Brooks, NIAAA Laboratory of Neurogenetics, was interviewed by:
• msnbc.com on the topic of alcohol flushing and esophageal cancer risk in East Asians

Dr. Aaron White, NIAAA Division of Epidemiology and Prevention, gave interviews about the potential harm caused by caffeinated alcoholic drinks to:
• BBC Radio
• BBC.com
• Nature
• Alcoholism & Drug Abuse Weekly

Dr. George Kunos, Scientific Director, NIAAA, was interviewed by:
• SciBX (Science-Business eXchange), about a recent paper in Chemistry and Biology by Dr. Kunos’ intramural research group.

Dr. Raye Z. Litten, Division of Treatment and Recovery Research, was interviewed by:
• The Pink Sheet on the topic of medications development for alcoholism

Dr. Mike Hilton, Division of Epidemiology and Prevention Research, was interviewed by:
• Healthday.com re a study on drinking at sports events.

Dr. Tom Gentry, Division of Metabolism and Health Effects, was interviewed by:
• WHYY Public Radio in Philadelphia about women and drinking.

Dr. Christopher Ramsden, NIAAA Section on Nutritional Neurosciences, was interviewed by:
• Sunday Times of London about a study of omega-6 fatty acids published by Dr. Ramsden and colleagues in the British Journal of Nutrition.

Dr. Pal Pacher, NIAAA Section on Oxidative Stress Tissue Injury, gave an online interview to:
• Reuters Health regarding his recent collaborative study (with National Cancer Institute, Hebrew University of Jerusalem, et al.) published in December 14, 2010 issue of the Journal of the American College of Cardiology entitled “Cannabidiol Attenuates Cardiac Dysfunction, Oxidative Stress, Fibrosis, and Inflammatory and Cell Death Signaling Pathways in Diabetic Cardiomyopathy.”

G. NIAAA Staff and Organization New Appointments

Dr. Dionne Godette joined DEPR as a Health Scientist Administrator on January 31, 2011.  Dr. Godette was an Assistant Professor at the University of Georgia’s College of Public Health beginning in 2006.  Her areas of scientific interest include alcohol, tobacco, and drug abuse prevention and treatment with a particular focus on disparities in alcohol, tobacco, and other substance use among racial and ethnic minorities.  Dr. Godette has conducted research on physiologic consequences of alcohol, tobacco, and other drug use, such as HIV risk behaviors, HIV infection, elevated blood pressure, co-morbid mental health problems, as well as social consequences such as involvement in the criminal justice system and disruption of social relationships.  Dr. Godette earned her Ph.D. in 2004 in Health Behavior/Health Education at the University of North Carolina, Chapel Hill, and her Master’s degree in Community/Agency Counseling in 1995.  She received post-doctoral training at the Harvard School of Public Health as well as the Boston University School of Public Health, where she conducted research on social determinants of health disparities among minority adolescents and young adults.  She has received funding from NIAAA for pre-doctoral education, post-doctoral research, and as a faculty mentor at the University of Georgia.

Departures

Ann Bradley –After 20 years of service, Ann Bradley, NIAAA Press Officer, left the Institute on September 10, 2010, to begin a new job in the DHHS Office of the Secretary, where she will manage public affairs for three components of the Office of Public Health and Science: the Office of Human Research Protections, the Office of Research Integrity, and the Office of Healthcare Quality.

Dr. Deborah Dawson, Laboratory of Epidemiology and Biometry, retired on December 31, 2010.  Dr. Dawson came to NIAAA nearly 20 years ago from the National Center for Health Statistics. At NIAAA she developed and refined her interests in measuring alcohol consumption and its relationships with a variety of harms. Within a few years after her arrival she became a world renowned expert in these areas and her major and significant contributions will be evidenced for years to come. For her many NIAAA friends and colleagues, Deborah was a delight to work with.  She will be missed.

Dr. Margaret E. Mattson, Division of Treatment and Recovery Research, left NIAAA on February 12, 2011 to accept a position at SAMHSA where she will participate in the development of a new series of public health initiatives.  During her 22 years at NIAAA she played a pivotal role in many major projects.   She was the Staff Collaborator for two of NIAAA’s Phase 3 clinical trials, both national multisite studies conducted as Cooperative Agreements, Project MATCH and COMBINE.  As a member of the Medications Development Team, she helped initiate the Institute’s Phase 2 pharmacotherapy clinical trials program, now known as the NIAAA Clinical Research Investigation Group (NCIG), which has become a well established mechanism for conducting studies of promising compounds to treat alcohol use disorders. 

Extramural Staff Activities

Dr. Vivian Faden and Dr. Trish Powell conducted briefings for HRSA and IHS about NIAAA materials – such as the Clinician’s Guide, Rethinking Drinking, the upcoming guide for screening adolescents, and Beyond Hangovers -- that could be useful in the health care delivery systems that they administer.

Mr. Greg Bloss has agreed to serve as Prevention Team leader for the work group that is implementing the NIH Common Fund’s Health Economics program.  The Health Economics program was launched in 2010 to address the evolving needs of the health care sector for economic research, particularly in the context of reforms to the health care system.  The program goals include fostering the collection of data that will be most useful for policy-relevant analysis; examining the economic effects of changes in incentives for consumers, providers and insurers; exploring the ways in which structure and organization on the supply side of the medical market affect health care spending and clinical outcomes; and investigating the potential of preventive measures to improve health and mitigate cost growth.  The program has issued its first four RFAs, including one on “Economics of Prevention.”  Additional initiatives and funding announcements are under development.

Captain Angela Martinelli of NIAAA participated in Continuing Promise 2010 (CP10), a U.S. Navy ship-based training mission that ran from July through November of 2010.  CP10, which utilized the U.S. Navy amphibious ship USS Iwo Jima (LHD-7), conducted direct care and public health missions in the Caribbean and Latin America.  Captain Martinelli’s 4-week mission started in Guatemala, moved on to Nicaragua and Panama, and ended in Columbia, South America.  She served as a member of the Preventive Medicine Team, which visited villages to provide direct care and health education.  Most of her teaching centered on disease prevention with regard to mosquitoes, malaria, dengue, and de-wormed children and animals.

Dr. Abe Bautista co-chaired a session on “Transdisciplinary Approach to Alcohol and Drug Abuse Interactions with HIV/AIDS” at the National Hispanic Science Network Annual Scientific Meeting in New Orleans, LA on October 1, 2010, and presented a lecture on “NIH Peer Review & Grants Opportunities and Responsible Conduct of Research” at Seton Hall University, Columbia University and Rutgers University on November 8, 2010.

Dr. Ralph Hingson gave plenary comments on the magnitude and related problems of underage drinking, at Alcohol Policy 15: Policies for Reducing Problems Associated with Alcohol Availability, held in Washington, DC, on December 7, 2010.

Dr. Ralph Hingson presented “Alcohol, Tobacco, and Other Drug Use: Predictors of Prescription Drug Misuse,” at the American Public Health Association’s 138th Annual Meeting and Exposition, in Denver, CO, on November 9, 2010.

Dr. Robert Freeman organized the “NIAAA Workshop to Consider the Possible Implications of Social Networking and New Electronic Media Usage for Underage and Young Adult Drinking Patterns,” in Bethesda, MD, on September 28, 2010.

Dr. Ralph Hingson delivered remarks on behalf of the NIAAA at the “Meeting with the Surgeon General: Prescription Drug Abuse among Youth,” which took place in Washington, DC, on December 16, 2010.

Dr. Ralph Hingson presented “Alcohol-Impaired Driving and Other Injury Prevention: From Global to Local,” at Brandeis University’s NIAAA Behavioral Seminar, in Waltham, MA, on December 6, 2010.

Dr. Ralph Hingson presented “What Parents Can Do to Reduce Underage Drinking and Driving After Drinking,” at the Safe Community Coalition’s Fall Community Meeting, in McLean VA, on October 21, 2010.

Dr. Ralph Hingson delivered Plenary Comments: “Recent Trends and Findings Regarding the Magnitude and Prevention of College and Underage Drinking Problems,” at the National Meeting on Alcohol and Other Drug Abuse and Violence Prevention in Higher Education.  Organized by the U.S. Department of Education, Office of Safe and Drug-Free Schools, the meeting took place at National Harbor, MD, on October 20, 2010.

Dr. Ralph Hingson participated in a Panel Session: “Recent Trends and Findings Regarding the Magnitude and Prevention of College and Underage Drinking Problems,” at the National Meeting on Alcohol and Other Drug Abuse and Violence Prevention in Higher Education, at the Gaylord National Hotel & Convention Center at the Maryland National Harbor.

Dr. Ralph Hingson delivered the Keynote Address: “What Parents Can Do to Reduce Underage Drinking and Driving After Drinking,” at the Mothers Against Drunk Driving (MADD) 30th Anniversary, in Arlington, VA, on September 25, 2010.

Dr. Ralph Hingson represented NIAAA at the World Health Organization’s (WHO) meeting titled First meeting of the global network of WHO national counterparts in Geneva, Switzerland, from Feb. 8-11, 2011.

Dr. Mariela Shirley presented “NIH OppNet: Basic Behavioral and Social Science Opportunity Network,” at the Prevention Research Center of the Pacific Institute for Research and Evaluation, in Berkeley, California, on October 18, 2010.

Dr. Aaron White was a presenter and panel moderator for: “Overview of the Magnitude and Prevention of and Trends in College Age and Underage Drinking,” at the Community Anti-Drug Coalitions of America (CADCA) 21st National Forum, at National Harbor, MD, on February 8, 2011.

Dr. Kathy Jung gave a presentation entitled “Challenges and Opportunities in Alcohol-Immunology Research” at the November 19, 2010, meeting of the Alcohol-immunology Research Interest Group (AIRIG) at Loyola University Medical Center, Maywood, IL.

Dr. Kathy Jung took part in the “Face-to-face with the NIH” session at the annual meeting of the American Society for Cell Biology, in Philadelphia, PA, on December 14, 2010.

Dr. Sam Zakhari gave a presentation at the Native American Health care Conference in Rancho Mirage, CA, on December 3rd, 2010, titled “Fighting Alcohol and Substance Abuse in Native America.”

Dr. Sam Zakhari gave a presentation at the Annual Meeting of Southern California Research Center for ALPD and Cirrhosis, in December 2010, titled “Funding Opportunities from NIAAA.”

Dr. Sam Zakhari co-organized a Falk Conference on “Liver and Pancreatic Diseases: Consequences of Chronic Alcohol Consumption” in Freiburg, Germany, on October 6, 2010.  He also chaired a session during the meeting.

Dr. Abbas Parsian and Dr. Matt Reilly, in the Division of Neuroscience & Behavior co-organized and co-chaired a one day Symposium/Workshop with from the same Division at the 60th annual meeting of the American Society of Human Genetics held on November 2 - 6, 2010 in Washington, DC. The Symposium was entitled,” Tightening the Genotype-Phenotype Gap: From Genetic Variation to Gene Function”. The purpose of the symposium was to promote research to identify the effects of polymorphisms (SNPs, CNV, VNTR) in established and novel candidate genes and how these effects change function at the molecular, cellular, and behavioral levels related to alcohol disorders.

Dr. Abbas Parsian gave a presentation entitled “Analysis of SNCA-LRRK2 genes interaction in Parkinson’s disease and controls,” in the session on Psychiatric Genetics, Neurogenetics, and Neurodegeneration at the 60th Annual Meeting of American Society of Human on November 3, 2010, Washington, DC.   Dr. Parsian described results from recent investigations focused on the interaction between single nucleotide polymorphisms (SNPs) in the SNCA and LRRK2 regions as they relate to susceptibility to Parkinson’s disease. They found that specific haplotypes in these two genes might contribute to increased risk for Parkinson’s disease. Such gene-gene interaction analysis could be applied to GWAS of alcoholism using detected signals.

Dr. Changhai Cui, together with Dr. Lindsey Grandison and Dr. Antonio Noronha, organized a satellite symposium to the Annual Meeting of Society for Neuroscience, November 12, 2010, San Diego, CA. This symposium, entitled “Neuroimmune Mechanisms of Brain Functions and Alcohol Related Disorders,” provided fundamental insights on the role of neuroimmune molecules in brain functions and the impact of alcohol on the neuroimmune system. Dr. Cui gave an introduction to the symposium by reviewing the recent advancements in the neuroimmune research and alcohol/neuroimmune interactions. She also chaired the session on “Neuroimmune function in neuroplasticity and neuroadaptation” at the symposium.

Dr. Changhai Cui, Dr. Antonio Noronha, and Dr. Lindsey Grandison are developing a special supplemental issue on “Neuroimmune Mechanisms of Brain Function and Alcohol Related Disorders” in the Journal of Brain Behavior and Immunity. This special supplement, which highlights recent advances in both the neuroimmune and alcohol research field, will include review articles based on the presentations at the SFN Satellite Symposium as well as invited contributions from researchers in the alcohol field.  Dr. Fulton Crews is the guest editor for this special supplement. 

NIAAA staff members participated in the OppNet Fall Retreat at the Hyatt Regency Capitol Hill Hotel in Washington, DC. OppNet is the NIH Basic Behavioral & Social Science Opportunity Network.  The two-day retreat solicited input from the extramural research community and NIH program staff on research gaps, opportunities, and potential directions for future initiatives related to basic behavioral and social science research within the mission of the NIH.  Breakout sessions included such topics as cognition and emotion, decision making, animal models for human applications, developmental perspectives, and culture and health.

Jo-Ann Kriebel, Fred Donodeo, Dr. Ivana Grakalic, Diana Urbanas, and Shuly Babitz participated in the first USA Science and Engineering Expo on the National Mall in Washington, DC on October 23 and 24, 2010. This 2-day free event drew an estimated 500,000 visitors and featured famous scientists, demonstrations, and lots of hands-on activities. It included exhibitions from both the public and private sectors such as NIH, NASA, the Department of Energy, Lockheed Martin, and PBS Kids. The NIAAA staffers presented the “Cool Spot Carnival” to show the negative effects that alcohol can have on the brain. The material was based on the NIAAA Web site for kids, www.thecoolspot.gov.  Children visiting the NIAAA booth had the opportunity to try their hand scoring in a football-toss game while wearing “fatal vision goggles” to simulate being under the influence of alcohol. Other Carnival activities included flip-board games that gave youngsters a chance to “pick your no’s”, demonstrating the best way to say “no” to alcohol, and dispel the myth that “everybody is drinking.”

H. NIAAA Program Announcement, Request for Application, and CRADA Information

PA-11-047 (R01), PA-11-048 (R21), and PA-11-049 (R03)
Program Announcement on Women and Sex/Gender Differences in Drug and Alcohol Abuse/Dependence
Dr. Mariela Shirley– NIAAA Scientific Contact

PA-11-061/062 (R01, R21)
Research into the Impact of Economic Fluctuations on Alcohol Consumption, Drinking Patterns, and Prevention and Treatment of Problem Drinking and Related Problems
Dr. Robert Freeman--NIAAA Scientific Contact

PA-11-064 & 065 Neuroimmune Mechanisms of Alcohol Related Disorders (R01 & R21). This announcement encourages Research Project Grant (R01 or R21) applications that propose to study the neuroimmune mechanisms of alcohol related disorders. Studies using animal models and post-mortem human alcoholic brains suggest that alcohol exposure has a significant impact on the neuroimmune system in the brain. However, it remains unclear how the altered neuroimmune system contributes to neuroadaptation and neurodegeneration associated with alcohol exposure. This NOFO seeks research proposals to address the role of neuroimmune factors in response to and in the neuroadaptation of the brain to acute and chronic alcohol exposure. Studies supported by this announcement will provide fundamental insights of neuroimmune mechanisms underlying brain functional and behavioral changes induced by alcohol.

PAR 10-187 Program Project on Alcohol Related Research (P01).  The NIAAA Program Project Initiative provides leadership in conducting and fostering interdisciplinary research on a wide variety of topics including, but not limited to: the nature, causes, consequences, diagnosis, treatment, and prevention of alcohol abuse and alcoholism; and in developing new topics, approaches and methodologies to pursue these areas of research. The receipt date for this NOFO was December 2, 2010.  NIAAA received 8 applications in response to this NOFO. 

NIAAA will continue participation in the Collaborative Research in Computational Neuroscience: Innovative Approaches to Science and Engineering Research on Brain Function (CRCNS) program for FY2011-13.  The CRCNS program is an inter-agency initiative between four Directorates and two Offices of the National Science Foundation and eight Institutes and one Center at the National Institutes of Health.  The purpose of the CRCNS program is to bring together researchers in computational modeling and engineering with experimental neuroscientists to bring the power of computers to the study of nervous system function and to further understand the computational strategies used by the central nervous system to mediate behavioral responses (e.g., decision making).  Dr. John Matochik, DNB, is the program contact.

RFA-10-005 (U01)
Collaboration on FAS Prevalence (CoFASP)
Dr. Marcia Scott --Project Officer.
Drs. Judith Arroyo, Dan Falk, and Dale Hereld--Project Scientists.
Two U01 cooperative agreement awards were issued to Dr. Christina Chambers at the University of California, San Diego and Dr. Philip May at the University of New Mexico.   On January 5, 2011, NIAAA held the inaugural meeting of the CoFASP initiative.  CoFASP will function as a consortium to identify first grade children in defined geographical areas with FASD using common methodology and data harmonization.  In addition to establishing a more precise and representative prevalence estimate through standardized diagnostic criteria for FASD, NIAAA’s goal for this initiative is to establish a publically available database to facilitate future FASD research.

RFA-HD-10-018 (U01)
Limited Competition, Role of Prenatal Alcohol Exposure in SIDS and Stillbirth.
Dr. Dale Hereld—NIAAA Scientific Contact

TPA-10-177 (R01) and TPA-10-178 (R21)
Stress Pathways in Alcohol Induced Organ Injury and Protection
Dr. Andras Orosz--NIAAA Scientific Contacts

TPA-11-113 (R01) and TPA-11-114 (R21)
Circadian Rhythms and Alcohol-induced Tissue Injury

I. NIAAA Research Programs

RESEARCH REPORTS 

The following examples reflect the breadth and quality of research conducted and supported by NIAAA.

Gene variants predict treatment success for alcoholism medication
The effectiveness of an experimental treatment for alcoholism depends on the genetic makeup of individuals who receive it.  Researchers conducted a controlled trial to determine if the medication ondansetron could reduce problem drinking in alcohol-dependent individuals.  Ondansetron works by blocking receptors for the brain chemical serotonin, which mediates many processes in the brain, including the rewarding effects of alcohol.  Previous studies have shown that variations in the gene that encodes the serotonin transporter, a protein that regulates the concentration of serotonin between nerve cells, can significantly influence drinking intensity.  Specifically, serotonin transporter variants designated as LL and TT have been associated with more severe drinking problems.  In the current study, researchers performed genetic analyses to determine which serotonin transporter gene variants were carried by each subject, then randomly assigned each subject to treatment regimens with ondansetron or placebo.  The researchers found that, for subjects with the LL genotype, those receiving ondansetron reduced their average number of daily drinks to less than five, while those receiving placebo continued to have five or more drinks per day.  LL subjects who received ondansetron also had significantly more days of abstinence, relative to those who received placebo.  Ondansetron’s effects were even more pronounced among individuals who possessed both the LL and TT gene variants, while subjects who did not have the LL variant showed no improvement with ondansetron.  The study represents an important milestone in the search for personalized treatments for alcohol dependence.  (Johnson BA, et al., Am J Psychiatry. 2011 Jan 19. [Epub ahead of print]).

Frontocerebellar abnormalities may signal increased risk for alcohol problems
Brain circuits that connect the frontal lobes with the cerebellum are damaged in chronic alcoholics and may contribute to cognitive deficits in these individuals.  But whether these “frontocerebellar” abnormalities are present in individuals at high risk for alcoholism before they start using alcohol is unknown.  To find out, scientists conducted brain imaging studies with young people whose positive family history for alcoholism put them at high risk for the disease.  Using two different brain imaging techniques -- functional connectivity magnetic resonance imaging and diffusion tensor imaging – the researchers found that family history positive adolescents who had never used alcohol had fewer functional connections between areas of the prefrontal cortex and the cerebellum than did youth with no family history for alcoholism.  The researchers also found that the reduction in functional connectivity was associated with reduced white matter structural integrity in other parts of the frontocerebellar circuitry.  Taken together, the findings suggest that frontocerebellar abnormalities may be a biological marker of risk for alcohol use disorders. (Herting, et al., Neuroimage, Volume 54, Issue 4, 14 February 2011, Pages 2582-2589).

Study identifies genetic variant that can lead to severe impulsivity
A genetic variant of a brain receptor molecule may contribute to violently impulsive behavior when people who carry it are under the influence of alcohol.  In collaboration with researchers in Finland and France, NIAAA intramural scientists studied a sample of violent criminal offenders in Finland.  The researchers conducted the study in Finland because of its unique population history and medical genetics. Modern Finns are descended from a relatively small number of original settlers, which has reduced the genetic complexity of diseases in that country.  Studying the genetics of violent criminal offenders within Finland increased the chances of finding genes that influence impulsive behavior.  The researchers sequenced DNA of the impulsive subjects and compared those sequences with DNA from an equal number of non-impulsive Finnish control subjects. They found that a single DNA change that blocks a gene known as HTR2B was predictive of highly impulsive behavior.  HTR2B encodes one type of serotonin receptor in the brain.  Serotonin is a neurotransmitter known to influence many behaviors, including impulsivity. The scientists found that the genetic variant alone was insufficient to cause violently impulsive behavior.  Carriers of the HTR2B variant who had committed impulsive crimes were male, and all had become violent only while drunk from alcohol, which itself leads to behavioral disinhibition.  The researchers then conducted studies in mice and found that when the equivalent HTR2B gene is turned off, mice also become more impulsive.  Taken together, the findings could lead to a better understanding of some aspects of impulsivity and ultimately may lead to strategies for diagnosing and treating some clinically important manifestations of impulsive behavior.  The researchers caution, however, that impulsivity is a complex trait with multiple genetic and environmental causes. (Bevilacqua L, et al., Nature. 2010 Dec 23;468(7327):1061-6.

GABA interaction with serotonin in the dorsal raphe nucleus underlies escalated aggression in mice
Brain serotonin is a major neurochemical mediator of aggression. In this study, scientists examined whether another brain chemical, gamma-aminobutyric acid (GABA), interacts with serotonin in a brain region called the dorsal raphe nucleus (DRN) to influence aggression. The DRN is important because it is the major serotonin pathway to the prefrontal cortex (PFC), a brain area that has been implicated in impulsive aggression. Researchers injected baclofen, a compound that stimulates GABA activity, into the DRN of male mice and found that the mice significantly increased the frequency of their attack bites against other mice. Further, intra-DRN baclofen increased serotonin release in the medial PFC by binding to GABA receptors.  The association between elevated serotonin in the medial PFC and heightened aggression in this study contradicts current thinking that aggression is related to diminished serotonin transmission.  The findings highlight the importance of GABA’s influence on serotonin pathways in the DRN as a mediator of escalated aggression. (Takahashi A, et al., J Neurosci. 2010 Sep 1;30(35):11771-80).

Role for mammalian target of rapamycin complex 1 signaling in neuroadaptations underlying alcohol-related disorders
There are currently few medications for treating of alcoholism and new molecular targets are needed in order to find novel medications.  This study identified one such potential new molecular target -- the mammalian target of rapamycin complex 1 (mTORC1).  Researchers found that alcohol activates the mTORC1-mediated signaling pathway in a critical reward center of the mouse brain, the nucleus accumbens (NAc).  As its name implies, the mTORC1 signaling complex is a target for the FDA-approved immunosuppressant drug, rapamycin.  In a preclinical rodent model of alcohol abuse the authors of this study found that rapamycin decreased expression of alcohol-induced locomotor sensitization and place preference as well as excessive alcohol intake.  These results provide evidence that targeting the mTORC1 signaling cascade could be an innovative strategy for treating alcoholism. (Neasta et al. Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):20093-8.)

The effects of residential proximity to bars on alcohol consumption
A person’s decision to drink alcohol is potentially influenced by both price and availability of alcohol in the local area. In the current study, researchers examined the impact of distance from place of residence to bars on alcohol consumption in four large U.S. cities from 1985 to 2001. They found that increased density of bars within the immediate vicinity of a person’s residence was associated with small increases in alcohol consumption as measured by daily alcohol consumption, drinks per week, and weekly consumption of beer, wine, and liquor. However, when the researchers applied statistical corrections to account for the possibility that heavier-drinking individuals may choose to locate their residences in areas with easy proximity to bars, the relationship between alcohol consumption and the number of bars near a person’s place of residence disappears. The researchers conclude that bar density in the area surrounding an individual’s home has at most a very small positive effect on alcohol consumption, and that restrictions on the numbers of bars in a neighborhood were likely to be relatively ineffective policy tools for influencing alcohol consumption levels.  (Picone G, et al., Int J Health Care Finance Econ 10:347-367, 2010.)

Alcohol retail density and demographic predictors of health disparities: a geographic analysis
To investigate the complex effects that the proximity of alcohol sales outlets may have on health, researchers examined whether the geographic density of alcohol retailers was greater in geographic areas with higher levels of demographic characteristics that predict health disparities.  The researchers obtained the locations of all alcohol retailers in the continental United States and created a map depicting alcohol retail outlet density in the U.S. Using U.S. Census data, they then compared measures of poverty, education, crowding, and race/ethnicity with the alcohol outlet density. They found that, in urban areas, retail alcohol density had significant nonlinear relationships with Black race, Latino ethnicity, poverty, and education.  In high-proportion Latino communities, retail alcohol density was twice as high as the median density. Retail alcohol density had little or no relationship with the demographic factors of interest in suburban, large town, or rural census tracts.  The researchers conclude that a greater density of alcohol retailers was associated with higher levels of poverty and with higher proportions of Blacks and Latinos in urban census tracts. Although no causal inferences can be drawn from this study, the findings suggest that alcohol outlet density disparities could contribute to higher morbidity in certain geographic areas. (Berke EM, et al., Am J Public Health 100:1967-1971, 2010.)

Loss of ethanol aversion and motor stimulation in knock-in mice with ethanol-insensitive {alpha}2-containing GABAA receptors
GABA type A receptors, composed of five subunits that form a chloride channel, are proposed to modulate many of the behavioral effects of alcohol.  However, the specific subunits of this receptor that mediate the actions of alcohol are unclear.  Interestingly, genetic variation in the alpha2 subunit of the receptor is associated with alcohol dependence in humans.  Therefore, the goal of this study was to determine the role of the alpha2 subunit in the actions of alcohol using molecular, electrophysiological, and behavioral techniques.  An alpha2 subunit was created that harbors two point mutations that changes serine 270 to histidine and leucine 277 to alanine.  This mutant subunit shows normal GABA sensitivity but is insensitive to ethanol in a recombinant expression system.  Knockin mice with the mutated alpha2 subunit do not develop conditioned taste aversion to alcohol and fail to show motor stimulation after alcohol administration.   This study demonstrates that the alpha2 subunit mediates specific behavioral effects of alcohol and may provide a mechanistic explanation for the association of this subunit with alcohol dependence in humans.  (Blednov et al., (2011) J Pharmacol Exp Ther 336: 145-154)

Efficacy of web-based personalized normative feedback: a two-year randomized controlled trial
Web-based brief alcohol interventions have the potential to reach a large number of individuals at low cost.  Few studies, however, have evaluated their effectiveness.  In the current study, researchers conducted a two-year study of a Web-based alcohol intervention in a sample of heavy-drinking college students.  Participants included 818 freshmen who reported 1 or more heavy-drinking episodes in the previous month. Assessments occurred every 6 months for a 2-year period. Results showed modest effects on weekly drinking and alcohol-related problems but not on heavy episodic drinking. This study is important as it provides additional evidence that highly cost-effective, web-based approaches to alcohol education and prevention can be effective. (Neighbors C, et al., J Consult Clin Psychol. 2010 Dec;78(6):898-911.)

Autophagy helps reduce acute ethanol-induced liver damage in mice  
Prolonged alcohol abuse is a major cause of liver injury. Little is known, however, about the cellular mechanisms that help protect against the harmful effects of ethanol. In the current study, researchers investigated whether macroautophagy could play a role in limiting ethanol-induced liver injury. Using an ethanol binge model and primary hepatocyte culture in which the ethanol-induced early pathologic events are well-defined, they demonstrated that acute ethanol exposure strongly induced autophagosome synthesis and promoted a selective autophagy process to remove damaged mitochondria and hepatic lipid droplets, thus reducing a major source of reactive oxygen species (ROS) and a major target/amplifier of ROS. These findings imply that a proper autophagy capability in the liver may be crucial to reduce the detrimental effects of ethanol consumption and that enhancement of autophagy may be a possible therapeutic strategy to mitigate the pathology associated with alcoholic liver disease.  (Ding WX, et al., Gastroenterology. 2010 Nov;139(5):1740-52.)

Ethanol interferes with cell cycle genes in neural stem cells
Ethanol inhibits the proliferation of neural precursors by altering mitogenic and anti-mitogenic growth factor signaling and can affect global methylation activity in the fetus. In the current study, researchers explored alcohol's potential to impair neural stem cell (NSC) proliferation by interfering with actions of a mitogenic factor, FGF2, or promoting those of an anti-mitogenic factor, TGFβ2. Genome-wide transcriptional analysis of isolated NSC revealed a relatively small percentage of genes that were significantly affected by alcohol in the presence of either factor.  The majority of these were down-regulated and further analysis revealed associated hypermethylation of the promoter's of many of these genes.  Consistent with these observations, alcohol exposure in the presence of either FGF2 or TGFβ2 elevated DNA methyltransferase (DNMT) activity and DNMT1 protein levels.  Among the genes down-regulated by alcohol, cell cycle genes were highly represented.  These findings strongly suggest that alcohol interferes with normal proliferation of NSC by prompting epigenetic changes, namely DNA methylation, that diminish expression of positive cell-cycle regulators.  These insights may have relevance to alcohol-induced neuropathology in fetal development and at later stages of life. (Hicks SD, et al., J Neurochem 2010; 114:1767-80.)

Mitochondrial cytochrome P450 2E1 induces oxidative damage and augments alcohol-mediated oxidative stress
The ethanol-inducible enzyme Cytochrome P450 2E1 (Cyp2E1) is a primary mediator of liver pathology, increasing both reactive oxidative stress (ROS) and acetaldehyde concentrations.  Recent studies in the laboratory of Dr. Narayan Avadhani have shown that alcohol exposure redirects the intracellular transport of nascent Cyp2E1 protein away from other organelles to the mitochondria, thereby dramatically increasing the amount of mitochondrial-Cyp2E1 (mt-Cyp2E1).  Given that mitochondria are a recognized site of acetaldehyde and ROS-induced pathology; this suggested that mt-Cyp2E1 plays an important role in alcohol-induced pathology.  The results helped confirm this hypothesis by demonstrating that GSH-depletion (an index of ROS) is largely dependent on the presence of mt-Cyp2E1. (Bansal, et al., J Biol Chem 2010; 285(32):24609-19.)