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NIAAA Director's Report on Institute Activities to the 130th Meeting of the National Advisory Council on Alcohol Abuse and Alcoholism
A. Legislation, Budget, and Policy
After a series of continuing resolutions, the Consolidated Appropriations Act, 2012 (P.L. 112-74) was signed by the President on December 23rd. NIH received a total of $30.6 billion after an across the board reduction and the Secretary’s transfer. Major features of the spending bill included the elimination of the National Center for Research Resources (NCRR) and the creation of the National Center for Advancing Translational Sciences (NCATS).
The FY 2012 appropriation for NIAAA provides $459.4 million. This represents a $1.5 million or a 0.3% increase over the FY 2011 comparable level of $457.9 million. NIAAA estimates it will support a total of 659 Research Project Grant (RPG) awards in FY 2012, including 156 competing awards.
For noncompeting grants, the NIH FY 2012 funding policy is to issue awards without cost of living/inflationary adjustments. However, adjustments for special needs (such as equipment and added personnel) will continue to be accommodated. This policy applies to all grants (including RPGs, Centers, Ks and Other Research Grants) where applicable. For competing grants, the average cost is equal to the FY 2011 level.
The FY 2013 President’s budget request was released on Monday, February 13th. For the NIH, the total request is $30.6 billion, the same level as FY 2012. For NIAAA, the request is $457.1 million. This represents a $1.9 million or a 0.4% decrease from the FY 2012 comparable level of $459.0 million. Under this proposal, in FY 2013, NIAAA would support a total of 653 RPG awards, including 156 competing grants with a success rate of 19%. The NIH budget policy for RPGs in FY 2013 is to apply a one percent reduction from the FY 2012 level in noncompeting awards and a one percent reduction from the FY 2012 level in the average cost for competing RPGs.
A budget mechanism distribution of NIAAA’s FY 2011 actual obligations, the FY 2012 Enacted level, and the FY 2013 President’s budget request is provided below. The FY 2011 and 2012 columns of this table reflect some adjustments for comparability to the FY 2013 request.
Preliminary work on the budget for FY 2014 is beginning. After intermediate stages of review, the President’s budget request for FY 2014 will be presented to Congress in February 2013, at which time it will become available to the public.
NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
(dollars in thousands)
|MECHANISM||FY 2011 Actuals Comparable||FY 2012 Enacted Comparable||FY 2013 President's Budget|
|Res. Centers in Minority Instit.|
|Cooperative Clinical Research||1||6,578||1||0||1||6,665|
|Biomedical Research Support|
|Minority Biomed. Res. Support|
|Subtotal, Other Research||124||30,732||132||30,708||132||37,220|
|Total Research Grants||852||329,544||812||321,027||806||321,034|
|Research & Develop. Contracts||69||37,993||70||41,159||70||45,983|
|Res. Management & Support||29,280||29,280||29,280|
|FY 2011 Comparable Adjustments: -$0.377 million for the comparable transfer to NCATS for the Therapeutics and Rare and Neglected Diseases (TRND) Program and -$0.393 million for the comparable transfer to the NLM for the NCBI and Public Access Assessments.|
|FY 2012 Comparable Adjustment: -$0.416 million for the comparable transfer to NCATS for the Therapeutics and Rare and Neglected Diseases (TRND) Program.|
B. Director’s Activities
NIAAA Acting Director Kenneth R. Warren, Ph.D. spoke or otherwise participated at the following recent meetings:
Banff XLIV: Fetal Alcohol Spectrum Disorder Conference
Banff, Alberta, Canada March 18-21, 2012
Dr. Warren gave the keynote presentation at the Workshop banquet, providing an historical perspective on FASD from the 17th century to today.
IOM Neuroscience and Nervous System Disorders Forum
Washington, D.C. March 28-29, 2012
Dr. Warren participated in discussions and provided comments in the Animal Models Working Group on the relevance of current animal models for alcohol dependence.
ICCFASD Spring Meeting
Rockville, Md. April 3-4, 2012
Dr. Warren chaired the meeting.
Meeting with Professor Li Jun of Anhui Medical University
Rockville, Md. April 12, 2012
Dr. Warren signed a letter of intent to cooperate with Anhui Medical University, People’s Republic of China, in several areas of alcohol research including epidemiology, prevention, pharmacotherapy (including pharmacogenetics and herbal medications), liver injury, health economics, and postdoctoral training. Professor Li Juan, Chairman of the University Council, signed on behalf of Anhui Medical University. The signing took place as part of a site visit of several Chinese research scientists from Anhui, arranged by Dr. Bin Gao, Chief, Section on Liver Disease in NIAAA’s Division of Intramural Research.
43rd Annual Medical Scientific Conference, American Society of Addiction Medicine
Atlanta, Ga. April 20-21, 2012
Dr. Warren delivered an Opening Plenary address on NIAAA’s medications development program.
Meeting with Professor Salim Karim,
Rockville, Md. April 27, 2012
Professor Salim Karim has recently been named the new President of the South African Medical Research Council (MRC). On a recent trip to the U.S., Dr. Karim met with Drs. Ken Warren and Peggy Murray to discuss NIAAA’s ongoing research projects in South Africa and to pledge continued support of research collaborations in FASD, Alcohol and HIV, and Prevention of Underage Drinking between NIAAA and MRC-supported investigators.
Expert Panel Meeting - 2012 FASD State Systems Conference
Arlington, Va. May 1, 2012
Dr. Warren provided an update on NIAAA’s FASD activities.
Roundtable Discussion on Veterans, Behavioral Health, and the Criminal Justice System
Washington, D.C. May 3, 2012
Along with elected officials from several states, and key leadership from Federal agencies, Dr. Warren participated in discussions to address a range of issues, including alcohol problems among veterans returning from Iraq and Afghanistan.
Meeting at Johns Hopkins School of Nursing
Baltimore, MD May 25, 2012
Dr. Warren met with Dr. Martha Hill, Dean of the Johns Hopkins University School of Nursing, to sign a letter of intent to cooperate in the development of a distance learning course on the prevention and treatment of alcohol use disorders for BSN nursing programs. Johns Hopkins School of Nursing will take curriculum content developed by NIAAA and create an interactive on-line course to be made available to schools of nursing around the world, as well as grant continuing education credits (CEU’s) to practicing graduate nurses.
52nd New Clinical Drug Evaluation Unit (NCDEU) Meeting
Phoenix, AZ May 29- June 1, 2012
Dr. Warren presented an update on NIAAA’s medications development program in an NIH Directors Forum.
C. NIAAA Staff and Organization
Dr. Pal Pacher, Acting Chief of the Section on Oxidative Stress Tissue Injury in the NIAAA Laboratory of Physiologic Studies, was named a Star Reviewer of the American Journal of Physiology-Heart and Circulatory Physiology for 2011 by the journal’s executive editor, in recognition of the time, effort, and thoughtfulness Dr. Pacher put into his many expert reviews of manuscripts submitted to the journal.
Dr. Larry Baizer of the Division of Neuroscience and Behavior moved to the National Cancer Institute in April, 2012 to become a Program Officer in the NCI Clinical Trials Program.
Ms. Erin Bryant joined the Communications and Public Liaison Branch of the Office of Science Policy and Communications as a science writer and editor on April 23, 2012. Erin previously worked in the Office of Autism Research Coordination at the National Institute of Mental Health (NIMH), writing about research advances in the autism field and preparing reports for a federal advisory committee. Prior to that, she worked as a contractor writing for the Eunice Kennedy Shriver National Institute on Child Health and Human Development (NICHD) and as a health reporter for a local news wire service. She received her master’s in journalism from the Phillip Merrill College of Journalism at the University of Maryland.
Dr. R. Thomas Gentry, Division of Metabolism and Health Effects, will retire at the end of June 2012. Tom joined the Institute in 1996 after fifteen years in research at the Rockefeller University and the Alcohol Research Center at the Bronx VA Medical Center. In retirement, Tom intends to pursue his long-term interest in alcohol pharmacokinetics and teaching. He will continue to serve on the Blue Ribbon advisory panel for the Driver Alcohol Detection System for Safety and will join the Committee on Alcohol, Other Drugs, and Transportation, Transportation Research Board of the National Research Council.
Ms. Judit O’Connor was appointed NIAAA Budget Officer on April 2, 2012. Judit comes to NIAAA from the National Institute of Allergy and Infectious Diseases (NIAID), where she has served as Team Lead/Senior Budget Analyst in the NIAID Budget Office since October 2009. Previous to this position, she worked in the NIH Office of Budget as a budget analyst for two years. She also has experience with the HHS Office of Global Health Affairs and private sector experience working as a senior manager with Development Finance International. Judit received her bachelor’s degree in international trade from the University of Foreign Trade and Economics in Hungary and a Master of Arts in economics from The George Washington University.
Extramural Staff Activities
NIAAA Research Track at American Psychiatric Association (APA) Meeting
NIAAA sponsored a special Research Track entitled Integrating Treatment for Alcohol Problems and Co-Occurring Conditions in Psychiatric Care: Challenges and Successes during the 165th Annual Meeting of the American Psychiatric Association in Philadelphia, Pennsylvania, May 5-9, 2012.
Organized by Dr. Robert Huebner, Director of the Division of Treatment and Recovery Research, the NIAAA-supported sessions featured in this Research Track included lectures, symposia, workshops, and forums by leading scientists interested in alcohol and co-occurring psychiatric disorders.
Highlights of the Research Track included two keynote lectures. The first keynote lecture was by Dr. Bankole Johnson of the University of Virginia School of Medicine titled Musings on Decades of Progress in Alcoholism Treatment Research. The second keynote lecture, presented by NIAAA Council Member Dr. John Krystal of Yale University School of Medicine, was titled Glutamate, Dopamine and Alcoholism: From Vulnerability to Treatment. Both lectures were very well attended.
Other highlights from the Research Track included a number of symposia and workshops that addressed the following topics:
- Use of Technology for Research, Treatment, and Evaluation of Alcohol Dependence
- Integrating the Full Spectrum of Alcohol and Other Drug Problems in Psychiatric and Primary Care
- Medication Use for Treating Alcohol Dependence
- Helping Patients Who Drink Too Much: Using the NIAAA’s Clinician’s Guide
- Alcohol Screening and Brief Intervention of Youth: The NIAAA Practitioner’s Guide
As with the keynote lectures, these sessions were very well attended by conferees—in many cases, it was standing room only.
Also at APA, Dr. Kenneth Warren provided an overview of the NIAAA Research Track at a Press Conference hosted by the President of the APA and other members of the APA leadership.
Dr. Judith Arroyo, NIAAA Minority Health and Health Disparities Coordinator,
- Conducted a technical assistance workshop with representatives from NCI at the University of Arizona at Tempe on January 25-26, to encourage tribal representatives and their University-based partners to submit applications to PAR-11-346 Interventions for Health Promotion and Disease Prevention in Native American Populations (R01).
- Organized NIAAA co-sponsorship (with the National Institute on Drug Abuse (NIDA), the National Institute of Neurologic Disorders and Stroke (NINDS), NICHD, and NIMH) of the ongoing “Neuroscience Health Disparities Seminar Series: Views by Two.” In this installment, Dr. David Flockhart from Indiana University and Dr. Evan Kharasch from Washington University in St. Louis presented “The Role of Race and Ethnicity in the Age of Personalized Medicine” at NIH on April 12, 2012.
- Participated with Ms. Lynn Morin in the NIDA-sponsored Special Populations Research Development Seminar Series in Bethesda, MD, on April 23-24. This workshop included several NIAAA new investigators who were provided with technical assistance in developing concepts for submission to NIH review. Dr. Arroyo provided an overview of research opportunities at NIAAA and she and Ms. Morin provided feedback to potential applicants on drafts of their applications.
Dr. Abe Bautista, Director of the Office of Extramural Activities, gave Introductory Remarks at the “Alcohol NeuroAIDS Symposium” during the Annual Meeting of the Society for Neuroimmune Pharmacology (SNIP) in Honolulu, HI on April 25-28, 2012. He also co-chaired the “Animal Models Symposium” and the “NIH Workshop” at the same meeting.
Dr. P.J. Brooks, an Investigator in the Division of Metabolism and Health Effects, represents NIAAA as a member of the National Academy of Sciences/Institute of Medicine Roundtable on Translating Genomic-Based Research for Health. At the March 14, 2012 Roundtable meeting, Dr. Brooks presented a talk entitled “PARP Inhibitors and BRCA1/2-Associated Breast Cancer.”
Dr. Vivian Faden, Director of the Office of Science Policy and Communications,
- Presented (with Dr. Robert Huebner) “How Coalitions Can Promote Alcohol Screening” at the Community Anti-Drug Coalitions of America’s (CADCA) 22nd National Leadership Forum, National Harbor, MD, February 7, 2012.
- Delivered a plenary talk about the need for increased screening for alcohol in adolescents across all settings, and how the NIAAA Alcohol Screening Guide can assist in the implementation of universal screening at the Joint Meeting on Adolescent Treatment Effectiveness (JMATE) on April 10, 2012, in Washington, DC. Dr. Faden also organized a panel discussion about the screening guide at the JMATE.
- Convened a workshop on April 23-24 at NIAAA to discuss current research on etiology-based/personalized prevention and how it is progressing to advance new approaches to prevention. The workshop brought together eight experts in a range of related fields to discuss what we know so far, including both the challenges and promise of this new approach to prevention. Each expert made a short presentation to the group in their area of expertise. The group then discussed each presentation as well as general themes and considerations in moving the field forward.
Dr. Ralph Hingson, Director of the Division of Epidemiology and Prevention Research, presented “Recent Trends and Findings Regarding the Magnitude and Prevention of Underage Drinking Problems” at the following events:
- National Governors Association (NGA) 2012 Winter Meeting, Governors’ Spouses’ Program, Washington, DC, February 27, 2012.
- Community Anti-Drug Coalitions of America’s (CADCA) 22nd National Leadership Forum, National Harbor, MD, February 7, 2012.
- The Substance Abuse and Mental Health Services Administration’s (SAMHSA) “Making the Grade on College Drinking Prevention” webcast of a national Town Hall Meeting on Underage Drinking Prevention, National Harbor, MD, February 6, 2012.
Dr. Robert Huebner, Director of the Division of Treatment and Recovery Research,
- presented (with Dr. Vivian Faden) “How Coalitions Can Promote Alcohol Screening” at the Community Anti-Drug Coalitions of America’s (CADCA) 22nd National Leadership Forum, National Harbor, MD, February 7, 2012.
- Organized (with Dr. Raye Litten) an all-day symposium at the American Society of Addiction Medicine’s 2012 Medical-Scientific Conference entitled “Update on Medications for Alcohol Dependence and Their Implementation in Practice,” on April 20, 2012 in Atlanta.
Dr. Philippe Marmillot, Scientific Review Officer and the NIAAA ENS/SREA Coordinator-Liaison, served as Scientific Judge during the Research Day at Howard University Health Sciences, Washington DC on April 13, 2012.
Dr. Mariela Shirley, a program officer in the Division of Epidemiology and Prevention Research,
- Served as the NIAAA representative at a planning meeting at the Institute of Medicine on February 8, 2012, for an upcoming “Science of Research on Families” conference.
- Served as the NIAAA representative to a federal expert panel meeting to develop a protective factors conceptual framework for programs of the Administration on Children, Youth and Families (ACYF) in Washington, DC, on March 27, 2012.
Dr. RV Srinivas, Chief of the Extramural Project Review Branch, co-chaired the “Young Investigators Symposium” and participated in the “NIH Workshop” at the Annual Meeting of the Society for Neuroimmune Pharmacology (SNIP) in Honolulu, HI on April 25-28, 2012.
Dr. Sam Zakhari, Director of the Division of Metabolism and Health Effects,
- Presented “Alcoholic Liver Research: From Model T to Ferrari” at the University of Nebraska Medical Center on March 12, 2012.
- Presented “Patterns of Alcohol Intake and Alcoholic Liver Disease: Effects of Binge Drinking on the Liver” at the International meeting of the European Association for the Study of the Liver (EASL) in Barcelona, Spain, on April 18, 2012.
- Presented “What Can NIH do for You?” to biomedical sciences graduate students at University of Massachusetts Medical School at Worcester, MA, on April 27, 2012. He also gave a seminar at the UMass Hepatology Department on “Alcoholic Liver Research: From 1960s to Present.”
Drs. Larry Baizer, Ivana Grakalic, Soundar Regunathan, Matt Reilly, and Diana Urbanas, of the Division of Neuroscience and Behavior, presented the “Cool Spot Carnival,” a hands-on activity for young people that demonstrates the effects of alcohol on adolescent brain development, and the lifelong consequences of underage drinking, to adolescents and teens attending:
- the 13th annual Brain Awareness Week at the National Museum of Health and Medicine in Silver Spring, MD on March 14 and 15, 2012.
Take Your Child to Work Day at the NIH on April 26, 2012.
NIAAA staffers Nanwei Cao, Fred Donodeo, Maureen Gardner, and Jo-Ann Kriebel of the Office of Science Policy and Communications also participated in these activities.
Dr. Changhai Cui of the Division of Neuroscience and Behavior co-chaired a symposium on “Alcohol and NeuroAIDS” at the annual conference of the Society on NeuroImmune Pharmacology, April 25-28, 2012, in Honolulu, HI. Dr. Cui was also a panelist for NIH workshop on grant funding held at the same conference.
Dr. Ivana Grakalic of the Division of Neuroscience and Behavior spoke to youth and their parents about her work and career during the USA Science Festival’s “Encounters with Scientists and Engineers Program” at the Washington, DC Convention Center on April 28, 2012.
Dr. Antonio Noronha, director of the Division of Neuroscience and Behavior,
- Attended, with Dr. Mark Egli, the biannual INIA-West retreat held at the Scripps Research Institute in La Jolla CA, January 13-14, 2012.
- Attended, with Dr. Abbas Parsian, the annual meeting of the Collaborative Studies on the Genetics of Alcoholism (COGA) that was held January 26 – 27, 2012 in St. Louis, MO.
- Attended, with Dr. Soundar Regunathan and Dr. Larry Baizer, the bi-annual retreat of the Neurobiology of Adolescent Drinking in Adulthood (NADIA) consortium on February 21-23, 2012 in La Jolla, CA.
- Attended, with Dr. Lindsey Grandison, the INIA Stress Retreat on March 24, 2012 in Chapel Hill, NC.
- Gave opening remarks at a satellite workshop entitled Epigenetic Inheritance and the Implications for Complex Traits, at the 14th annual meeting of the International Behavioral and Neural Genetics Society (IBANGS) on May 15, 2012 in Boulder Colorado.
Dr. Matthew Reilly of the Division of Neuroscience and Behavior organized a satellite workshop entitled Epigenetic Inheritance and the Implications for Complex Traits, at the 14th annual meeting of the International Behavioral and Neural Genetics Society (IBANGS) on May 15, 2012 in Boulder Colorado.
D. Press Releases
The following press releases describe NIAAA research or related activities:
3/12/2012: Brain fun and games: NIH takes part in Brain Awareness Week
Flying footballs, couch potato mice, and what can happen with explosive-propelled iron spikes are just a few of the interactive tools that scientists from the National Institutes of Health used to teach young people about the amazing human brain at the National Museum of Health and Medicine in Silver Spring, Md., on March 14 and 15.
The NIH activities are part of the museum’s celebration of Brain Awareness Week, an annual worldwide effort coordinated by the Dana Alliance for Brain Initiatives to increase public awareness of the progress and benefits of brain research. The week (March 12–16) brings together universities, hospitals, patient advocacy groups, professional associations, government agencies, service organizations, and schools to celebrate the brain. http://www.niaaa.nih.gov/news-events/news-releases/brain-fun-and-games-nih-takes-part-brain-awareness-week
3/14/2012: Four new members named to the National Advisory Council on Alcohol Abuse and Alcoholism
U.S. Department of Health and Human Services Secretary Kathleen Sebelius recently appointed four new members to the National Advisory Council on Alcohol Abuse and Alcoholism of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). The council advises the Secretary, the Director of the National Institutes of Health and the director of NIAAA on program and policy matters, offers recommendations on research conducted at NIAAA, and reviews applications for grants and cooperative agreements.
The 15-member council includes outstanding representatives from health and science fields relevant to NIAAA activities, as well as leaders from among the general public in fields including health policy, law, economics, and management.
4/5/2012: Dr. Edward P. Riley delivered the 4th Annual Jack Mendelson Honorary Lecture at the National Institutes of Health
Edward P. Riley, Ph.D. delivered the 4th Annual NIAAA Jack Mendelson Honorary Lecture. Riley is a world-renowned expert on Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Spectrum Disorders (FASD). His presentation was called “FASD: It’s What’s Behind the Face that Matters – Effects of Prenatal Alcohol on Brain and Behavior.” Riley is Distinguished Professor of Psychology at San Diego State University (SDSU), and serves as the Director of SDSU’s Center for Behavioral Teratology. He also leads the NIAAA-funded Collaborative Initiative on FASD, which is a multi-site international consortium studying FASD. During his more than 35 years as a psychologist and researcher, Riley has significantly enhanced our understanding of how prenatal exposure to alcohol can affect the developing embryo and fetus.
E. Multi-Media Products from NIAAA
NIAAA Website Redesigned: A brand-new version of NIAAA’s main public website launched in May 2012. The site has been redesigned from the ground up. It features a modern look and feel, user-friendly navigation, and improved content throughout. This has been a collaborative effort between the Communications and Public Liaison Branch, the Information Technology Branch, and many other people across NIAAA and beyond. The new site is available at http://www.niaaa.nih.gov, and feedback may be directed to NIAAA’s web manager Mark Siegal at firstname.lastname@example.org. The site will continue to be enhanced over time based on user feedback, usability testing, and other ideas for new features.
NIAAA Spectrum – Issue 9 of the Institute's online webzine, will be released in June, 2012
Alcohol Research & Health
The Institute’s peer-reviewed journal, Alcohol Research & Health, is being redesigned and renamed in recognition of the evolution of the journal and its purpose in the field. The next issue, focusing on genetics of alcoholism, will bear the journal’s new name: Alcohol Research: Current Reviews. The next issue is expected to be available in print and online in the summer of 2012.
Issue #83 – Preventing Alcohol Abuse and Alcoholism – An Update is now online at: http://pubs.niaaa.nih.gov/publications/AA83/AA83.htm
The Spring 2012 issue of the NIAAA newsletter is now online at: http://pubs.niaaa.nih.gov/publications/Newsletter/Spring2012/newsletter_number24.htm
NIAAA’s Graduation Fact Sheet
For the 2012 graduation season, NIAAA continued its seasonal outreach series with its fact sheet, “Parents: Help Your Teen Party Right at Graduation.” Seasonal fact sheets contain relevant statistics, practical science-based commentary, and NIAAA website information. They are disseminated through electronic media and in print upon request. The graduation fact sheet focused on the adolescent brain and the physiological effects of excessive drinking. It also discussed alcohol poisoning and provided a link to the NIAAA college website. It was featured on more than 250 online media outlets, including Yahoo! (also Yahoo! Canada and Yahoo! Singapore), the Boston Globe, and the Miami Herald, as well as network television affiliates of FOX, NBC, CBS, and ABC. It reached an audience of approximately 70 million.
NIAAA Billboards on Alcohol and Summer Safety
As part of its seasonal outreach efforts this summer, NIAAA is planning to place billboard ads along the popular arteries leading to Delaware and Maryland beaches, as well as on buses in the Metropolitan DC area. The ads will complement and extend the themes and graphics of the summer safety fact sheets, focusing on the dangers of risky drinking when combined with water recreation and other summer activities.
NIAAA Seasonal Fact Sheet Redesign Wins Communications Award
NIAAA has received a 2012 Blue Pencil Award from the National Association of Government Communicators for its redesigned seasonal fact sheet “New Year, Old Myths, New Fatalities.” The fact sheet was one of more than 500 entries, and was selected for an award from the category of “Most Improved Publication.” It is online at: http://pubs.niaaa.nih.gov/publications/RethinkHoliday/NIAAA_NYE_Fact_Sheet_2011.pdf
New and Upcoming papers
Litten RZ, Egli M, Heilig M, Cui C, Fertig JB, Ryan ML, Falk DE, Moss H, Huebner R, Noronha A. Medications development to treat alcohol dependence: a vision for the next decade. Addict Biol. 2012 May;17(3):513-27.
Sarsour K, Johnston JA, Milton DR, Duhig A, Melfi C, Moss HB. Factors Predicting Change in Frequency of Heavy Drinking Days among Alcohol-Dependent Participants in the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Alcohol Alcohol. 2012 Apr 20. [Epub ahead of print]
Goldman D. Our Genes, Our Choices: How Genotype and Gene Interactions Affect Behavior. London, UK: Academic Press; 2012.
Moss HB, Chen CM, Yi H-Y. Measures of Substance Consumption among Substance Users, DSM-IV Abusers, and those with DSM-IV Dependence Disorders in a Nationally Representative Sample. Journal of Studies on Alcohol and Drugs (in press).
Brooks PJ, Zakhari S. Moderate alcohol consumption and breast cancer in women: From epidemiology to mechanisms and interventions. Alcoholism: Clinical and Experimental Research (in press).
Brooks PJ, Zakhari S. Chapter 6: Alcohol metabolism and genetic control. In: Boyle L, Lowefels A, eds. Alcohol: Science, Policy and Public Health, Oxford, UK: Oxford University Press (in press).
F. News Media Interactions
Recent News Media Interviews
Dr. Kenneth R. Warren, NIAAA Acting Director, participated in a media briefing at the opening of the American Psychiatric Association Annual Meeting in Philadelphia on May 5, 2012.
Dr. Joanne Fertig, NIAAA Division of Treatment and Recovery Research, was interviewed by:
- Fran Lowry, Medscape Medical News, on kudzu extract as a potential treatment for alcohol problems: http://www.medscape.com/viewarticle/764263
Dr. Markus Heilig, NIAAA Clinical Director, was interviewed by:
- Diane Rehm, of The Diane Rehm Show, on alcoholism and the science of addiction: http://thedianerehmshow.org/shows/2012-03-26/alcoholism
- Benedict Carey, of The New York Times, about a NIAAA-funded study by UCSF researchers that examined the relationship between stress and alcohol consumption in fruit flies: http://www.nytimes.com/2012/03/16/health/male-fruit-flies-spurned-by-females-turn-to-alcohol.html
- Doug Quenqua, of The New York Times, regarding the development of medications to treat alcoholism: http://www.nytimes.com/2012/05/22/health/tailoring-treatments-for-alcoho...
Dr. Joseph Hibbeln, Acting Chief, NIAAA Section on Nutritional Neurosciences, gave interviews to:
- Laura Russell, The Oregonian, on the health effects of omega-3 fatty acids.
Dr. Ralph Hingson, Director, NIAAA Division of Epidemiology and Prevention Research, was interviewed by:
- Aimee Lee Ball, The New York Times, about college alcohol use and campus violence for an article that will be published in the Times’ Education Life section in the fall of 2012.
Dr. Robert Huebner, Acting Director, NIAAA Division of Treatment and Recovery Research, was interviewed by:
- Alison Knopf, Alcoholism and Drug Abuse Weekly, regarding a NIAAA-funded study that provides more evidence that alcohol screening and brief interventions performed by emergency department practitioners can reduce alcohol consumption and episodes of driving after drinking in hazardous and harmful drinkers: http://onlinelibrary.wiley.com/doi/10.1002/adaw.20330/pdf
- Alison Knopf, Carlat Behavioral Health Report, regarding the use of Alcoholics Anonymous and other mutual help groups in alcohol treatment.
Dr. Raye Litten, Associate Director, NIAAA Division of Treatment and Recovery Research, was interviewed by:
- Doug Quenqua, of The New York Times, regarding the development of medications to treat alcoholism: http://www.nytimes.com/2012/05/22/health/tailoring-treatments-for-alcoho...
Dr. Deidra Roach, of the NIAAA Division of Treatment and Recovery Research, was interviewed about alcohol and women by:
- Holly Corbett of Prevention.com: http://www.prevention.com/health/healthy-living/binge-drinking-how-tell-if-you-have-alcohol-problem/people-close-you-seem-concerned
Dr. Aaron White, Health Science Administrator, NIAAA Division of Epidemiology and Prevention Research, was interviewed by:
- Jan Hopson, Scientific American Mind magazine, on the brain effects of teen and young adult binge drinking, for an article that will be published in an upcoming issue of the magazine.
- Celia Vimont, Join Together, about NIAAA study on increase in hospitalizations for alcohol and drug overdoses: http://www.drugfree.org/join-together/alcohol/doctors-perfectly-positioned-to-help-prevent-drug-and-alcohol-overdoses-expert-says
- Celia Vimont, Join Together, about alcohol and blackouts.
Dr. Sam Zakhari, Director of the NIAAA Division of Metabolism and Health Effects, gave interviews to:
- Brian Dalek, Men's Health Magazine, on the pathology and treatment of hangovers: http://news.menshealth.com/3-hangover-you-mistakes-you-always-make/2012/04/27/
- Pedro Frisneda of El Diario/La Prensa, the largest and oldest Hispanic newspaper in New York City, on the long-term health effects of alcohol: http://www.eldiariony.com/Alcoholismo_peligroso
G. NIAAA Program Announcement and Request for Applications Information
PA-12-146 (R01) and PA-12-147 (R21): Mechanisms of Alcohol Associated Cancers
This Funding Opportunity Announcement (FOA) issued by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Cancer Institute (NCI) invites applications from researchers with broad ranges of expertise to study the mechanisms by which alcohol increases cancer risk. Alcohol has been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC). Target sites for alcohol-related carcinogenesis include the oral cavity, pharynx, esophagus, larynx, breast, liver, and colon. A better understanding of the molecular basis by which alcohol increases cancer risk could lead to improved therapeutic approaches and preventative strategies and would provide guidance on safe levels of alcohol consumption. The goal of this program announcement is to stimulate a broad range of research into the mechanisms by which alcohol contributes to carcinogenesis.
More information: http://grants.nih.gov/grants/guide/pa-files/PA-12-146.html
PA-12-177 (R01) and PA-12-178 (R21): Alcohol Abuse, Sleep Disorders and Circadian Rhythms
This Funding Opportunity Announcement (FOA), issued by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), encourages Research Project Grant (R01) applications proposing to conduct studies on the functional relationships between alcohol abuse, circadian rhythms and sleep disorders. Recent investigations in both humans and animal models have suggested possible connections between circadian processes and alcohol intake, with alcohol affecting the expression of ‘clock’ genes and polymorphisms in these genes influencing levels of ethanol intake. Furthermore, there is considerable evidence that acute and chronic alcohol consumption disrupts patterns of sleep. These disruptions can persist long after cessation of drinking in abstinent alcoholics and may be an important factor in relapse. Disordered sleep, particularly in adolescence, may also be a factor in the development of alcohol dependence. However, despite the clear connections between alcohol and sleep disorders, the precise mechanisms involved in this interaction remain incompletely understood. The objective of this FOA is therefore to promote research in both humans and animal models on the mechanisms underlying the relationships between alcohol, circadian rhythms and sleep disorders with the ultimate goal of improved understanding of the causes of and treatments for alcoholism.
More information: http://grants.nih.gov/grants/guide/pa-files/PA-12-177.html
RFA-NS-13-003 NIH Blueprint for Neuroscience Research Grand Challenge: Discovering Novel Drugs for Disorders of the Nervous System (U01)
NIAAA is participating in this NIH initiative to provide a unique opportunity for investigators working with small molecule compounds to gain access to a robust ‘virtual pharma’ network to discover neurotherapeutic drugs. Successful applicants to this FOA will become collaborative participants in this network, receiving both funding and no-cost access to contracted drug discovery services that are not typically available to the academic research community. Funding will be provided to conduct biological testing of compound analogs in disease assays and models in the investigator’s laboratory. No-cost drug discovery services will also be provided, including medicinal chemistry optimization, IND-directed pharmacology and toxicology, and Phase I clinical testing.
More information: http://grants.nih.gov/grants/guide/rfa-files/RFA-NS-13-003.html
H. NIAAA Research Programs
The following items represent examples of the breadth and quality of research conducted and supported by NIAAA.
Screening and brief interventions performed by ER staff can reduce alcohol consumption and impaired driving.
Research shows that primary health care providers can promote significant, lasting reductions in drinking levels and alcohol-related problems by asking patients about alcohol use and briefly advising them to reduce risky drinking. In a new study, researchers showed that doctors and nurses in an emergency department can also do effective brief interventions for patients who report risky alcohol use. Researchers asked patients who came to the emergency department of a large university hospital about their alcohol use. The nearly 900 adult patients included in the study were found to exceed NIAAA guidelines for low-risk drinking: no more than four drinks in a day and no more than 14 drinks per week for men, and three or fewer drinks per day and no more than seven drinks per week for women. Individuals who received a seven-minute counseling session from a trained emergency practitioner subsequently had significantly lower rates of alcohol consumption and driving after drinking than those who did not, an effect that persisted even a year after the counseling session. (D'Onofrio G, et al. Ann Emerg Med. 2012 Mar 28. [Epub ahead of print])
Study identifies enzyme subunit in liver cells that may contribute to progression of alcoholic liver disease.
NADPH oxidase is a complex enzyme found primarily in immune system cells that produces molecules that protect against bacteria and fungi. Certain liver cells also contain NADPH oxidase. Research has shown that liver-damaging substances such as alcohol can activate NADPH oxidase and stimulate cellular pathways that cause the death of liver cells. Other research evidence suggests that a subunit of NADPH oxidase known as p47phox plays an important role in these effects. The relative roles that liver cell NADPH oxidase and immune cell NADPH oxidase play in alcoholic liver disease has not been determined. However, a recent animal study suggests that the p47phox/NADPH oxidase complex in liver cells could have the primary significance in alcoholic liver injury. Investigators showed that mice completely without the p47phox subunit were protected from alcoholic liver damage, while those that lacked only immune cell p47phox were not. They note that future studies that examine the selective inhibition of p47phox in liver cells could shed more light on the role this enzyme subunit plays in alcoholic liver damage. (Levin I, Petrasek J, Szabo G. Alcohol Clin Exp Res. 2012 Feb 29. http://www.ncbi.nlm.nih.gov/pubmed/22376231)
Study explores hepatic cannabinoid receptor-1 and insulin signaling
Endocannabinoids and cannabinoid receptor-1 (CB1) have been implicated in obesity and its metabolic consequences, such as type 2 diabetes, high levels of cholesterol and other fats in the blood, heart disease, and nonalcoholic fatty liver disease. Studies have shown that compounds that block CB1 lead to weight reduction and improved insulin resistance and dyslipidemia in patients with the metabolic syndrome. In addition, CB1 knockout mice have been shown to be resistant to high-fat diet (HFD)-induced obesity, hepatic steatosis, insulin resistance, and dyslipidemia. Furthermore, knockout mice selectively deficient in hepatocyte CB1 develop HFD-induced obesity but remain insulin sensitive, suggesting a role for hepatic CB1 in total body insulin resistance. NIAAA intramural investigators examined the role of hepatic CB1 in HFD-induced insulin resistance in normal, CB1-deficient mice, and mice with hepatocyte-specific deletion or transgenic overexpression of CB1. These in vivo and in vitro analyses demonstrated that endocannabinoids contribute to diet-induced insulin resistance mediated by the inhibitory effects of hepatic CB1 on both insulin clearance and signaling and provide support for further studies of hepatic CB1 as a therapeutic target in the treatment of obesity-related insulin resistance and its complications. (Liu J, Zhou L, Xiong K, Godlewski G, Mukhopadhyay B, Tam J, Yin S, Gao P, Shan X, Pickel J, Bataller R, O'hare J, Scherer T, Buettner C, Kunos G. Gastroenterology. 2012 May;142(5):1218-1228.e1. Epub 2012 Jan 31. http://www.ncbi.nlm.nih.gov/pubmed/22307032)
Alcohol induces liver neoplasia in a novel alcohol-preferring rat model
A longstanding problem in research on alcohol-induced liver injury is the lack of rodent models that accurately mirror human alcoholic liver disease. For example, current rodent models of hepatocellular carcinoma (HCC), the most common type of liver cancer, require the induction of cancer by a carcinogenic agent in addition to alcohol, a process that complicates experimental interpretations. Investigators recently reported the discovery of a much-needed animal model of liver cancer with alcohol as the sole inducing agent. The researchers found that liver neoplasia arises in alcohol preferring P rats after 18 months of alcohol exposure. Characterization of the carcinoma that arises shows it to be very similar to hepatocellular carcinoma. Insights that can be gained from the mechanism of carcinogenesis will inform the etiology of HCC and may lead to therapeutic approaches. (Yip-Schneider MT et al. Alcohol Clin Exp Res. 2011 35(12):2216-25. http://www.ncbi.nlm.nih.gov/pubmed/21790668)
Varenicline decreases alcohol consumption in heavy-drinking smokers.
Emerging evidence suggests that the α4β2 form of the nicotinic acetylcholine receptor (nAChR) dampens the rewarding effects of alcohol. Varenicline, a compound that partially stimulates this receptor, and which has been approved by the Food and Drug Administration as a treatment for smoking cessation, has also been shown to decrease alcohol consumption in rodents and in non-blinded human laboratory studies.
Investigators conducted a randomized, double-blind, study among heavy-drinking smokers who were seeking treatment for their smoking. The study was designed to determine the effects of varenicline on alcohol craving and consumption. Researchers found that varenicline significantly decreased alcohol consumption among the 64 participants who were randomized to receive the treatment. The investigators note that although varenicline use has previously been associated with suicidality and depression, side effects were low in this study and declined over time in the varenicline treatment group. They conclude that further studies are warranted to assess varenicline efficacy in treatment-seeking alcohol abusers who do not smoke and to ascertain the relationship between varenicline effects on smoking and drinking. (Mitchell JM, Teague CH, Kayser AS, Bartlett SE, Fields HL. Psychopharmacology (Berl). 2012 May 1. [Epub ahead of print] http://www.ncbi.nlm.nih.gov/pubmed/22547331)
Researchers identify candidate metabolic biomarkers of FASD
Efforts to identify biomarkers of Fetal Alcohol Spectrum Disorders have seemingly focused on markers that are present at the time of birth. While there are benefits to knowing from birth which children will need extra care, biomarkers that identify alcohol exposure during gestation would be of greater advantage, with the potential to prevent further exposure to alcohol or perhaps, in the long run, to intervene to prevent developmental abnormalities. Starting with human embryonic stem cells, investigators identified metabolites that are altered by alcohol exposure in embryoid bodies, neural progenitors, and neurons in vitro. Multiple features showed dose-dependent responses to ethanol, at two different stages of neurogenesis. Four confirmed chemical entities were L-thyroxine, 5’-methylthioadenosine, the tryptophan metabolites l-kynurenine and indoleacetaldehyde. Identification of other altered metabolites in the multiple component profile would provide additional useful information. The four identified here provide candidate diagnostic biomarkers of potential FASD development. (Palmer JA, et al. Alcohol Clin Exp Res. 2012 Feb 10. [Epub ahead of print] http://www.ncbi.nlm.nih.gov/pubmed?term=Palmer%20JA%20%5Bau%5D%20fasd).
Malondialdehyde-acetaldehyde-adducted protein inhalation causes lung injury
The compound malondialdehyde forms when reactive oxygen species degrade lipid molecules. The combination of malondialdehyde with the alcohol metabolite acetaldehyde has been associated with development of alcoholic liver disease. Investigators now show that malondialdehyde-acetaldehyde (MAA) adducted proteins induce a pro-inflammatory response in another organ, the lung, resulting in lung injury. In a mouse model, malondialdehyde-acetaldehyde adducts induced the accumulation of inflammatory cells and chemokines in the peribronchiolar area. The authors conclude that MAA-adduct formation may be a potential mechanism for smoke and alcohol induced lung injury, broadening the scope of alcohol associated damage thought to involve autoimmune mechanisms associated with adduct formation. (Wyatt TA, et al. Alcohol 2012 Feb;46(1):51-9. http://www.ncbi.nlm.nih.gov/pubmed/21958604)
Quantitative Trait Locus Mapping for Alcohol Teratogenesis in BxD Recombinant Inbred Mice.
Not all women who consume alcohol during pregnancy have children with fetal alcohol spectrum disorders (FASD) and studies have shown that genetic factors can play a role in ethanol teratogenesis, the production of birth defects in embryos and fetuses. Investigators used two well-characterized mouse strains, B6 and D2, which differ in their sensitivity to the teratogenic effects of prenatal alcohol, to define regions of the genome, or quantitative trait loci (QTLs), that may play a role in determining this alcohol sensitivity. Twenty-nine recombinant inbred strains derived from B6 x D2 crosses were analyzed, yielding QTLs associated with a range of pregnancy outcomes, including maternal weight gain, prenatal mortality, fetal and placental weight as well as digit, kidney, brain ventricle, rib, and vertebral malformations. Further dissection of the identified genomic regions has the potential to reveal specific genes that contribute alcohol teratogenesis. (Downing C, et al. Alcohol Clin Exp Res, 2012 Apr 24. http://www.ncbi.nlm.nih.gov/pubmed?term=Downing%20C%20%5Bau%5D%20FASD)
Kudzu extract reduces alcohol intake in heavy drinkers.
Compounds naturally occurring in the root of the kudzu plant have been used historically to treat alcohol-related problems. Investigators conducted a pilot study to assess the effects of one of these, an isoflavone compound called puerarin, for its ability to modify alcohol intake in humans. The researchers gave puerarin to ten healthy adult volunteers in a placebo-controlled experiment for one week prior to an afternoon drinking session, during which participants had access to up to six bottles of their preferred brand of beer in addition to juice and water. They found that participants who were treated with the kudzu extract drank fewer beers compared to control participants, and also decreased sip size, took more sips to finish a beer, and took longer to consume each beer. After finishing a beer, the puerarin-treated subjects took longer to open their next beer, compared to control subjects. The study is the first demonstration that a single isoflavone compound from the kudzu root can alter alcohol drinking in humans and suggest that puerarin may be a useful adjunct in the treatment of excessive alcohol intake. (Penetar DM, Toto LH, Farmer SL, Lee DY, Ma Z, Liu Y, Lukas SE. Drug Alcohol Depend. 2012 May 9. [Epub ahead of print] http://www.ncbi.nlm.nih.gov/pubmed/22578529)
Serotonin transporter genomic biomarker for quantitative assessment of ondansetron treatment response in alcoholics.
The lack of sensitive biomarkers to quantify transient changes in alcohol consumption level remains a critical barrier for the development of efficacious treatments for alcoholism. In a recent randomized, controlled, trial of alcohol-dependent individuals, investigators demonstrated that ondansetron was efficacious at reducing the severity of drinking (measured as drinks per drinking day; DDD) in alcoholics carrying the LL compared with the LS/SS genotype of the serotonin transporter gene, 5'-HTTLPR. Using blood samples from a sample of these subjects, they determined whether there was a relationship between mRNA expression level of the 5'-HTTLPR genotypes and self-reported alcohol consumption following treatment with either ondansetron or placebo. The researchers found a significant three-way interaction effect of DDD, 5'-HTTLPR genotypes, and treatment on mRNA expression levels. Among ondansetron but not placebo recipients, there was a significant interaction between DDD and 5'-HTTLPR genotype. In the ondansetron group, DDD was associated positively with mRNA levels at a greater rate of expression alteration per standard drink in those with the LL genotype. The findings suggest that the combination of the LL genotype and 5'-HTTLPR mRNA expression levels might be a promising and novel biomarker to quantify drinking severity in alcoholics treated with ondansetron. (Seneviratne C, Johnson BA. Front Psychiatry. 2012;3:23. Epub 2012 Mar 28. http://www.ncbi.nlm.nih.gov/pubmed/22470354)
Study finds social networks are an important factor in alcohol treatment outcomes.
Many studies have shown that social network variables can influence drinking outcomes, but these studies have not determined whether the influence is causal or correlational. Researchers used state-of-the-art statistical methods to evaluate evidence for a causal role for social network characteristics in determining long-term drinking outcomes following treatment. They found that an increase in the number of drinkers in an individual’s social network predicted worse drinking outcomes, measured by percentage of days abstinent and drinks per drinking day, at Months 15 and 39 following treatment. An increase in the number of abstainers in an individual’s social network predicted more percentage of days abstinent for both time periods. The social network variables uniquely predicted 5%-12% of the outcome variance; AA attendance predicted an additional 1%-6%. The findings suggest that social network composition following treatment is an important and plausibly causal predictor of alcohol outcome across 3 years. The effects were consistent across patients exhibiting a broad range of alcohol-related impairment, and support further development of treatments that promote positive social changes and highlight the need for additional research on the determinants of social network changes. (Stout RL, Kelly JF, Magill M, Pagano ME. J Stud Alcohol Drugs. 2012 May;73(3):489-97. http://www.ncbi.nlm.nih.gov/pubmed/22456254)
Sexual Deprivation Increases Ethanol Intake in Drosophila
Evolutionary forces have shaped the brain to seek and respond to things that are critical for survival such as food and sex. This same brain system mediates behaviors that are not adaptive for survival, such as psychoactive drug use, due to the fact that psychoactive drugs can hi-jack the neural circuits essential for reward. In a new study, researchers identified a brain neuropeptide called NPF that has a dual function in controlling both natural rewards such as sex and unnatural rewards such as the consumption of alcohol. This study has important implications for understanding how the brain responds to rewarding experiences and how this system could be targeted to improve medications for the treatment of drug abuse and alcoholism. (Shohat-Ophir et al., (2012) Science 335(6074):1351-5 http://www.ncbi.nlm.nih.gov/pubmed/22422983)
Opiate drug combination therapy reverses ethanol-altered natural killer cell functions and mammary tumor cell growth
Endogenous opioid peptides, such as enkephalins and endorphins control the functions of the neuroendocrine system, enhance immune function and prevent cancer growth by stimulating natural killer (NK) cell activity. These opioid peptides regulate NK cell functions by acting directly on the spleen and by altering the neuroendocrine-immune system function and are also involved in controlling ethanol-modulating effects on innate immune function. Investigators tested the hypothesis that delta and mu opioid receptor ligands administered in combination would increase the function of NK cells to suppress immune response to tumor cells. Such treatment would reduce the NK cells-mediated immune response to tumor cells and prevent chemically-induced mammary tumor growth. Researchers found that chronic treatment with a mu opioid receptor antagonist increases the delta agonist's ability to promote NK cell functions in non-alcohol treated animals and that such treatment reverses alcohol-induced suppression of NK cell activity. The finding suggests that the combination of an opioid antagonist and agonist may have potential therapeutic value for the treatment of immune incompetence, cancer and ethanol-dependent diseases. This is the first time that responses to a combination therapy of opioid drugs on tumor growth have been reported and these findings will have widespread implications in cancer treatment, especially when accompanied by chronic alcohol consumption. (Sarkar DK, et al. J Biol Chem. 2012 May 11;287(20):16734-47. Epub 2012 Mar 27 http://www.ncbi.nlm.nih.gov/pubmed/22451667)
Study advances new approach to measuring cardiac response to alcohol and other challenges.
Investigators developed a new index for assessing the heart’s response to challenges such as stressful events and the consumption of alcohol. The new method measures the redistribution of spectral power of the electrocardiogram toward higher or lower frequencies. Researchers suggest that redistribution toward lower frequencies may be a more adaptive or appropriate cardiac response to challenges. While preliminary, the study found that females tended to shift toward lower frequencies in response to cardiac challenge more so than did males. The redistribution of spectral power may be an important mechanism that the heart uses in an attempt to compensate for altered neural input, for example after consumption of large amounts of alcohol. Therefore, the interaction of cardiac mechanisms with the central nervous system may play an essential role in adaptation to everyday challenges, and may have relevance for understanding the observed gender differences in response to alcohol. (Bates ME, et al. PLoS One 2011;6(12):e28281 http://www.ncbi.nlm.nih.gov/pubmed/22164260)
Binge drinking has different effects on adolescent male and female brains.
This preliminary study is the first to show that binge drinking during adolescence is associated with gender-specific differences in typical frontal cortical thickness. Adolescent females who recently engaged in binge drinking showed about 8% thicker cortices in the left frontal regions than demographically matched controls. This increase in cortical thickness among females was linked to poorer visuospatial, inhibition, and attention performances. In contrast, adolescent males exposed to binge drinking exhibited about 7% thinner cortices than nondrinking males. These brain changes could indicate either different vulnerability markers toward heavy drinking for males vs. females, or differential adverse consequences (Squeglia LM, et al., Psychopharmacology, 220:529-539, 2012 http://www.ncbi.nlm.nih.gov/pubmed/21952669).
Animal study finds that dihydromyricetin blocks alcohol intoxication.
The plant Hovenia has been used in traditional Chinese herbal medicine as a treatment for alcohol hangover for hundreds of years. In a recent study conducted with animals, researchers found that dihydromyricetin (DHM), a flavonoid compound isolated from Hovenia, blocked acute alcohol intoxication and alcohol tolerance, and prevented signs of withdrawal when it was co-administered with ethanol. DHM also greatly reduced alcohol drinking in rats. At the cellular level, the researchers found that DHM inhibited alcohol's effect on GABA(A) receptors in the brain. DHM anti-alcohol effects were blocked by the benzodiazepine (BZ) antagonist flumazenil and DHM competitively inhibited BZ-site [(3)H]flunitrazepam binding suggesting DHM interaction with ethanol involves the BZ sites on GABA(A) receptors. The findings provide a foundation for further preclinical and clinical evaluation of DHM as a pharmacotherapy for alcohol dependence. (Shen Y, et al. J Neurosci. 2012 Jan 4;32(1):390-401. http://www.ncbi.nlm.nih.gov/pubmed?term=Shen%20Y%20%5Bau%5D%20dhm)
Study reveals novel brain mechanism underlying alcohol sensitivity.
The stria terminalis is a brain region that has been linked to the negative affect of alcohol dependence and to stress-induced reinstatement of drinking. Using a molecular approach in which one of the subunits of the NMDA receptor is temporarily deleted, researchers sought to determine the mechanism by which ethanol modifies neuronal activity in the stria terminalis. The investigators reported that the glutamate 2B subunit was essential for the action of ethanol on the glutamate receptors within the bed nucleus of the stria terminalis. In addition, they showed that the response to chronic ethanol involved the glutamate 2B receptors at extrasynaptic sites. The finding represents a novel molecular mechanism by which alcohol acts within a brain area that is critical for regulating the response to alcohol. (Wills, TA, et al. Proc Natl Acad Sci U S A. 109(5):E278-87, 2012 http://www.ncbi.nlm.nih.gov/pubmed/22219357).
Alcohol outlet density is associated with intimate partner violence-related emergency department visits.
Previous research has shown that individual level factors such as heavy drinking and other substance use, and neighborhood level factors such as residence in an area characterized by poverty and social disadvantage, are risk factors for various measures of intimate partner violence (IPV). Although alcohol outlet density has been linked with assaultive violence in community settings, it has not been analyzed in relation to IPV-related Emergency Department (ED) visits. Therefore, investigators examined the effects of alcohol outlet densities on IPV-related ED visits using data obtained over a three-year period from the state of California. Researchers found that the density of bars in a community was positively associated with IPV-related ED visits while the density of off-premise alcohol outlets was negatively associated with IPV-related ED visits. There was no association between density of restaurants and IPV-related ED visits. This is the first study to make use of hospital records to explore the association between alcohol outlet density and IPV-related ED visits, and adds to a growing body of literature showing that alcohol outlet density is linked to many community problems, such as underage and young adult injures, alcohol-related car crashes, suicide, and child maltreatment. (Cunradi CB, Mair C, Ponicki W, Remer L. Alcohol Clin Exp Res. 2012 May;36(5):847-53. http://www.ncbi.nlm.nih.gov/pubmed/22339652)
Study examines husband and wife alcohol use as predictors of intimate partner violence.
Heavy drinking is a known risk factor for the perpetration of intimate partner violence (IPV) by men. However, the role of women's drinking in their perpetration of IPV is less clear, so researchers examined the relative strength of husbands' and wives' alcohol use and alcohol dependence symptoms on the occurrence and frequency of husbands' and wives' IPV perpetration. They found that husband and wife alcohol consumption and alcohol dependence symptoms contributed to the likelihood and frequency of husband IPV, both independently and interactively. Husband, but not wife, alcohol dependence symptoms contributed to the occurrence of any wife IPV, although both partners' alcohol dependence symptoms predicted the frequency of wife aggression. Couples with discrepant drinking were not more likely to perpetrate IPV. The findings for husband IPV support previous research identifying alcohol use of both partners as a predictor. However, for wives, alcohol appears to play less of a role in IPV perpetration, perhaps reflecting that women experience less inhibition against physical aggression in their intimate relationships than do men. The study points to the need for more refined research focusing on the processes that link distal drinking habits or problems to instances of partner violence. (Testa M, Kubiak A, Quigley BM, Houston RJ, Derrick JL, Levitt A, Homish GG, Leonard KE. J Stud Alcohol Drugs. 2012 Mar;73(2):268-76. http://www.ncbi.nlm.nih.gov/pubmed/22333334)
Study probes links between alcohol, anxiety, and aggression.
Researchers assessed the relationship between alcohol intoxication, anxiety, and aggression in a sample of male drinkers from a university community. Trait and state anxiety was measured using the Trait Anxiety Inventory and the Facial Action Coding System, respectively. Participants consumed an alcoholic or nonalcoholic control beverage and completed a shock-based aggression task. Analyses indicated that alcohol-facilitated elevations in anxiety mediated the relation between alcohol consumption and aggression and that trait anxiety and physical provocation moderated this effect.
The data suggest that during the initial stages of an adversarial interaction anxiety mediates the relation between alcohol intoxication and aggression in high, but not low, trait-anxious men. This suggests that while alcohol consumption-related aggression can be mediated by heightened anxiety, trait-anxious men may be particularly susceptible to this effect. In contrast, during the latter stages of an adversarial interaction, alcohol increases aggression but not anxiety. The findings reveal a previously overlooked route by which alcohol’s effect on anxiety may facilitate aggression. (Parrott DJ, Gallagher KE, Zeichner A. Subst Use Misuse. 2012 Jun;47(7):774-86. http://www.ncbi.nlm.nih.gov/pubmed/22452787)
KE diet could be potential tool against obesity.
Ketogenic (KG) diets have shown beneficial effects for a number of neurological disorders, and some studies have also shown benefits of KG diets in obese patients with diabetes. However, typical KG diets are high-fat, no-carbohydrate diets are often unpalatable and lead to poor patient compliance. They also have been associated with undesirable metabolic effects. To circumvent the deleterious side effects of KG diets, NIAAA intramural researchers and their NIH colleagues have synthesized a ketone ester (KE), which, when added to a diet, increases plasma ketone levels without the need for a high-fat diet and without elevating plasma free fatty acids. Given the increased prevalence of obesity, which occurs because of an imbalance in energy intake and expenditure, they evaluated whether elevated blood ketone levels have any effect on energy intake and expenditure. They measured the effects of a diet in which ketone ester (KE)] replaced equicaloric amounts of carbohydrate on 8-wk-old mice. Voluntary food intake was reduced dose dependently with the KE diet. The KE group also exhibited 14% greater resting energy expenditure, but the total energy expenditure measured over a 24-h period was not different. The quantitative insulin-sensitivity check index was 73% higher in the KE group. The results identify KE as a potential antiobesity supplement.-(Srivastava, S., Kashiwaya, Y., King, M. T. Baxa, U., Tam, J., Niu, G., Chen, X., Clarke, K., Veech, R. L. FASEB J. 2012 Feb 23. http://www.ncbi.nlm.nih.gov/pubmed/22362892)