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NIAAA Director's Report on Institute Activities to the 123rd Meeting of the National Advisory Council on Alcohol Abuse and Alcoholism - February 4, 2010
In FY 2009, the NIAAA obligated $449.5 million in appropriated money. As part of the NIH Director’s one-percent transfer authority and consistent with FY 2008 action, $704 thousand was transferred from NIAAA for the Genes and Environment Initiative (GEI). NIAAA awarded 721 research project grants (RPGs), including 191 competing awards. FY 2009 support levels from our regular appropriated funds for other key extramural funding mechanisms included 20 research centers for $27.9 million; 115 other research grants for $26.1 million, 306 full-time training positions for $11.7 million; and $33.4 million for research and development contracts.
The NIAAA also obligated $61.4 million of the $113.8 million provided under the American Recovery and Reinvestment Act (ARRA) that is available over the 2 year period ending September 30 th, 2010. Using the ARRA apportionment, NIAAA was able to fund an additional 61 highly meritorious, unsolicited R01 and R21 applications over the number awarded from our regular annual appropriation. NIAAA also supported new projects under the NIH ARRA grant solicitations including 14 competing supplements, 18 Challenge Awards, and 13 Grand Opportunities (GO) Awards.
After a series of 2 Continuing Resolutions, Congress passed and the President signed the FY 2010 Omnibus Appropriations (HR 3288) on December 16, which provides FY 2010 appropriations for the NIH. NIH received a total of $31 billion, an increase of $692 million or 2.2% over FY 2009.
The FY 2010 appropriation for NIAAA provides $462.3 million. This represents a $12.3 million or a 2.7% increase over FY 2009 and a $7.2 million or 1.6% increase over the President’s budget request.
In addition to our FY 2010 appropriated funds, NIAAA plans to obligate its remaining $52.4 million from the American Recovery and Reinvestment Act (ARRA) apportionment to support the second year of the ARRA funded grant awards made in FY 2009 and to accelerate testing of new drugs for the treatment of alcohol disorders through R&D contracts.
The FY 2011 President’s budget request was released on February 1. For the NIH, the total request is $32 billion, an increase of +1.0 billion or 3.2% over FY 2010. NIAAA President’s Budget request is for $474.6 million. This represents a $12.5 million or a 2.7% increase over the FY 2010 comparable level of $462.2 million.
A budget mechanism distribution of NIAAA’s FY 2009 actual obligations, the FY 2010 appropriation, and the FY 2011 President’s budget request is provided below. The FY 2009 and 2010 columns of this table reflect some adjustments for comparability to the FY 2011 request.
National Institutes of Health
National Institute on Alcohol Abuse and Alcoholism
(Dollars in Thousands)
Budget Mechanism - Total
Recovery Act Actual
Recovery Act Esimated
Noncompeting (including Ad. Supps)
NIAAA Acting Director Kenneth R. Warren, Ph.D. spoke at the following recent meeting:
American College of Neuropsychopharmacology
December 6, 2009
Dr. Mariela Shirley, a program officer in the Division of Epidemiology and Prevention Research, and co-chair of NIAAA’s Alcohol Research Centers and Training Team, was elected to Fellow status by the American Psychological Association in September, 2009.
Roland Boch, Lab Technician in the Laboratory for Integrative Neuroscience received a Distinguished Performance Award from Kelly Services for his work developing software and hardware for intravenous drug self-administration in mice.
Shuly Babitz joined the Communications and Public Liaison Branch on December 6, 2009 as a Writer/Editor. Shuly comes to NIAAA from 30Point Strategies, a strategic communications and thought leadership firm. Shuly wrote speeches and related materials for corporate and philanthropic leaders, as well as for the Assistant Secretary of Energy Efficiency and Renewable Energy at the Department of Energy. Shuly received a Master’s degree in Social and Public Policy from Georgetown University in May 2003, and a Bachelor’s in Philosophy and Religion from Swarthmore College in 1997.
The Division of Intramural Clinical and Biological Research recently welcomed the following new staff: Hoon Jun Shin, Research Associate (previously at Hopkins University) and currently a contractor by Lockheed Martin; Eric Markey, Postbac IRTA graduate from California State University; Paul F. Kramer, Postbac IRTA graduate from Grinnell College
Extramural Staff Activities
Dr. Sam Zakhari , together with Drs. Gyongyi Szabo and Craig McClain, organized an NIH/NIAAA Corner during the Annual Meeting of the American Association for the Study of Liver Disease (AASLD) in Boston, November 1, 2009. The theme was Alcohol and Liver Disease: Recent Insights and New Directions. Dr. Zakhari gave a presentation on Gaps and Research Opportunities on Alcohol and Liver Damage.
Dr. Kathy Jung, Dr Joe Wang and Dr. Sam Zakhari organized a minisymposium entitled " Probiotics: Modulation of Host Immunity and Alcohol-Induced Tissue Injury" on September 18, 2009, in 5625 Fishers Lane. The four invited speakers were Willem J.S. deVilliers, M.D., Ph.D., speaking on "Gut Microbiome and Innate Immunity"; Karen Madsen, Ph.D., speaking on " Probiotics: Overview of Mechanisms of Action"; Ali Keshavarzian, M.D., speaking on "Role of Gut Leakiness and Dysbiosis in Alcohol-Induced Endotoxemia"; and Craig McClain, M.D., speaking on "Altered Gut Flora in Alcoholics and its Potential Role in TLR4-Mediated Organ Injury".
Dr. Antonio Noronha co-organized a symposium with Dr. George Koob of The Scripps Research Institute at the International Drug Abuse Research Society Meeting held in Seoul, South Korea, August 17-21, 2009 entitled “Novel Neurobiological Targets for the Treatment of Alcoholism”. Dr. Noronha gave the Introductory presentation entitled “Alcohol Dependence: A Chronic Relapsing Behavioral Disorder –An Overview”.
Dr. Antonio Noronha presented an “Overview on NIAAAs Collaborative Study on the Genetics of Alcoholism (COGA)” to the NIDA Genetics Consortium Meeting held in Rockville, MD December1-2, 2009.
Dr. Abbas Parsian gave a presentation entitled “Marinesco-Sjogren syndrome ( MSS): Genotype-Phenotype Correlation and Heterogeneity”at the 59 th Annual Meeting of American Society of Human Genetics in Honolulu, Hawaii from October 20-24, 2009. Dr. Parsian’s presentation distinguished the heterogeneity differences between simple and complex human genetic disorders including alcoholism.
Dr. Ralph Hingson gave two presentations at the World Health Organization Meetings on Indicators and Monitoring Systems for Alcohol, Drugs, and Other Psychoactive Substance Use which took place in Valencia, Spain in October, 2009. Dr. Hingson presented “Key Data Sources in the United States for Alcohol Indicators,” and “Alcohol Indicators Recommended for Members States by the World Health Organization (WHO).”
Dr. Ralph Hingson presented “Magnitude and Prevention of College Age and Underage Drinking Problems,” at a Johns Hopkins University symposium on college drinking in Baltimore, MD on October 6, 2009; during a Robert Wood Johnson Foundation webinar on “Underage, High-Risk Drinking” on November 13, 2009; and at a National Alcohol Beverage Control Association (NABCA) Board of Directors Meeting in Seattle, WA, on September 14, 2009.
Dr. Sam Zakhari co-chaired an early morning workshop on Alcoholic Liver Disease (Basic) during the AASLD meeting in November, 2009.
Dr. Sam Zakhari gave a presentation at the Gastro 2009 meeting in London (November 2009) on New Trends in Alcohol Abuse: Binge Drinking and Recreational Drugs: Consequences to Liver and Pancreas.
Dr. Sam Zakhari , in Collaboration with Drs. Scott Friedman and Hide Tsukamoto, co-organized the 4th International Symposium on Alcoholic and Pancreatic Disease, and Cirrhosis, held October 8-9, in Hurghada, Egypt. He also gave a presentation on The Role of Epigenetics in Alcohol-Induced Tissue Injury. He also gave a lecture at Cairo University as a part of The Post-graduate Course on Drug-Induced Liver Damage including Alcohol-induced Acute Hepatitis, Fibrosis and Cirrhosis.
Dr. Ralph Hingson presented “Legal and Community Interventions to Reduce Alcohol and Impaired Driving,” at a seminar entitled Injury and Violence Prevention: Innovative Community Research and Practice, that took place at Johns Hopkins Center for Injury Research and Policy, Baltimore, Maryland, on October 6, 2009.
Dr. Joe Wang was a guest discussant on the Voice of America’s "Alcohol and Health Forum" on December 19, 2009.
Dr. Kathy Jung presented "Challenges and Opportunities in Alcohol-immunology Research" at the meeting of the Alcohol and Immunology Research Interest Group on November 20, 2009, at Loyola University in Maywood, IL.
Dr. Andras Orosz presented the poster “Dual roles of Heat Shock Factor 1 (HSF1) in Cardioprotection, Pathological Hypertrophy and Heart Failure in Transgenic Mice” on the Gordon Research Conference: Stress Proteins In Growth, Development & Disease at Proctor Academy in Andover, New Hampshire in July, 2009.
NIAAA Study Affected by Haitian Earthquake
Members of a research team conducting a NIAAA-supported investigation in Haiti -- one of 27 NIH research projects in that country – have been accounted for, with one serious injury reported among the on-site staff. The investigators are now attempting to contact the 110 participants in the study, in the wake of the devastating earthquake that occurred on January 12. Led by Drs. Robert Malow and Jessy Devieux of Florida International University, in collaboration with Dr. Jean Pape, director of the GHESKIO medical clinic in Port au Prince, the study is examining the efficacy of a Cognitive-Behavioral Stress Management intervention for enhancing safer sex practices, adherence to antiretroviral medication, and reducing alcohol or other drugs (AOD) use among HIV-infected alcohol abusers. Located in the area worst hit by the earthquake, the GHESKIO medical clinic has been moved to an intact military hospital and is open and providing care. Data and computers associated with the ongoing study are reported to be secure.
Popularity of NIAAA Seasonal Outreach Series Soars
For the 2009 Holiday season, NIAAA continued its seasonal outreach series with the release of its New Years Eve fact sheet, Alcohol Related Traffic Deaths Jump on New Year’s Eve. Seasonal fact sheets contain relevant statistics presented in an easy-to-understand "infograph" style, practical science-based commentary, and NIAAA website information. They are disseminated widely through electronic media and in print upon request.
The 2009 New Years Eve fact sheet focused on the physiological effects of excessive drinking, and how many common abilities may be compromised as a result. It also corrected some popular myths about intoxication and impairment that often lead to dangerous celebratory drinking.
The fact sheet was featured on more than 214 websites (up from 90 the previous year, including Reuters, Forbes, Yahoo!, Yahoo!Canada, Yahoo!UK & Ireland, and MarketWatch, as well as business journals, corporate and business publications, and major network television affiliates of FOX, NBC, CBS, and ABC. It also appeared on PR Newswire’s Times Square billboard in New York City on December 30, and on the Las Vegas Fashion Show billboard on December 18-19.
The 2009 fact sheet reached an estimated total audience of more than 170 million, up from an average of 19 million in previous years.
Improved APIS User Interface
NIAAA has recently improved the user interface for its Alcohol Policy Information System (APIS) website. These improvements make it easier to navigate the website and to download state-by-state data on 29 alcohol policy topics. They also provide a more attractive appearance for all the material on the website. Visit the site at: http://www.alcoholpolicy.niaaa.nih.gov/
Preventing Alcohol, Tobacco, and Other Substance-exposed Pregnancies
In December, 2009 the Institute published a report on the symposium entitled “Preventing Alcohol, Tobacco, and Other Substance-exposed Pregnancies”, which was co-hosted by the Work Group on Women, Drinking, and Pregnancy of the Interagency Coordinating Committee on Fetal Alcohol Spectrum Disorders (ICCFASD), NIAAA, and the American Legacy Foundation in Rockville, MD on September 23-24, 2008. The report summarizes key information from each of the twenty-two presentations and from the highly interactive and informative discussions that followed. Plans are in place for wide distribution of the report through collaborating federal agencies and state public health departments.
NIHSeniorHealth Topic on Older Adults and Alcohol
NIAAA, the National Institute on Aging, and the National Library of Medicine collaborated to produce a new topic area for NIH’s SeniorHealth Website. NIHSeniorHealth features basic health and wellness information for older adults in an easily accessible format. The new topic, “Older Adults and Alcohol,” presents information on the ways in which alcohol use and abuse can affect seniors. The new topic will be available at http://nihseniorhealth.gov in mid-to late-February.
Update on Rethinking Drinking
NIAAA continues to receive requests for an average of 3,000 copies of the Rethinking Drinking booklet each week from people who are using the tool in a variety of settings. Among the notable recent requests, the medical director of the Veterans Administration Medical Center in Los Angeles, which evaluates all the returning combat veterans from Iraq and Afghanistan, recently ordered 1,200 copies each of the Rethinking Drinking patient booklet and the NIAAA Clinicians Guide. According to the medical director, the publications are used for patient education and individual therapy. In addition, a labor union health plan in southern California ordered 8,000 copies of Rethinking Drinking to distribute to all active members and retirees. The plan’s employee assistance program vendor will track claims data for substance use services to see if there is a change after distribution. We also recently heard from a Denver health education specialist who is working in an emergency department through an SBIRT grant. She wrote: “The "Rethinking Drinking" booklet is an excellent resource that I use daily to support the brief interventions I have with patients who are making unhealthy drinking decisions.”
NIAAA co-sponsored the annual meeting of the National Hispanic Science Network in Miami, FL, on October 28-31, 2009. Dr. Judith Arroyo co-chaired a plenary session on Adolescent Vulnerability to Alcohol and other Drug Use. This session featured presentations by two NIAAA grantees. Dr. Cindy Ehlers presented on “ Understanding Vulnerability to and Brain Consequences of Adolescent Alcohol and Nicotine Use: Translational Studies in Animal Models and Young Adult Mexican Americans.” Dr. Duncan Clark presented on “Adolescent Brain Development and Vulnerability to Alcohol and Drug Use Disorders.”
Dr. Kathy Jung gave a presentation entitled "NIH and YOU: Building Partnerships in Biomedical & Behavioral Research" in an informational session at the annual meeting of the American Society for Cell Biology in San Diego, CA, December 5-9, 2009.
Dr. Ralph Hingson recently presented “Recent Trends and Findings Regarding the Magnitude and Prevention of College and Underage Drinking Problems,” to several different audiences: during a Webinar sponsored by the Substance Abuse and Mental Health Services Administration on December 17, 2009; at the U.S. Department of Education’s Prevention Training Institute in Irvine, CA, on December 9, 2009; and at the Center for Substance Abuse Prevention of the Substance Abuse and Mental Health Services Administration, in Rockville, MD, on October 14, 2009.
Dr. Ralph Hingson presented “Strategic Planning for Research at the National Institute on Alcohol Abuse and Alcoholism,” as the Plenary Address at the16th National Treatment Accountability for Safer Communities (TASC) Conference on Drugs and Crime, Charlotte, North Carolina, September 24, 2009; at a Coroner/Medical Examiner Roundtable in Boise, Idaho on September 15, 2009, and at an “All-Hands Meeting” of the National Cancer Institute’s Division of Cancer Control and Population Sciences in Rockville, MD, on November 17, 2009.
Dr. Mariela Shirley presented “Underage and College Drinking Problems: Recent Trends” at a Presidential Leadership Group conference in Scottsdale, AZ, on November 14, 2009.
Dr. Robert Freeman recently participated on the NIH Basic Behavioral and Social Science Research Opportunity Network (OppNet) AIDS-Related Funding Opportunity Announcement (FOA) Working Group.
NIAAA issued a press release – “Molecule Repairs Alcohol Metabolism Enzyme” -- on January 10, 2010 on the effects of a small molecule called Alda-1 in correcting defects in the acetaldehyde-metabolizing enzyme ALDH2*2. The study, led by NIAAA-supported researchers Thomas D. Hurley, Ph.D., of Indiana University School of Medicine in Indianapolis, and Daria Mochly-Rosen, Ph.D., of Stanford University School of Medicine, was published in the advance online edition of Nature Structural and Molecular Biology.
Rethinking Holiday Drinking, an NIH/NIAAA Media Briefing, took place on December 16, 2009 at the National Press Club in Washington, DC. The purpose of the briefing was to answer some questions about holiday drinking in light of recent research. Namely,
- Who is at risk of negative outcomes from drinking and why?
- Where does risk kick in?
- Does at-risk drinking indicate that the drinker is an alcoholic?
- How can holiday party guests and hosts recognize risky drinking patterns and prevent short- and long-term consequences of alcohol abuse?
- Dr. Raynard Kington, deputy director of the National Institutes of Health, who provided opening remarks.
- Dr. Kenneth Warren, NIAAA acting director, introduced the concept of risk and how messages to the public about risky drinking patterns may help individuals adjust their patterns to guard against negative outcomes during and after the holiday season.
- Dr. Mark Willenbring, special liaison to NIAAA for clinical research, described recent research results from the fields of genetics, neuroscience and epidemiology that produced new insights about the use and abuse of alcohol among American adults.
- Dr. Ralph Hingson, NIAAA Epidemiology and Prevention Research, discussed individual differences in alcohol response, alterations in judgment and performance caused by excessive drinking, and research-proven preventive interventions to reduce risk to individuals, communities, and society.
The NIAAA is grateful to the National Alliance for Alcohol Research and Education for its assistance in organizing the media briefing.
NIAAA celebrates its 40th anniversary in 2010.
President Nixon signed the bill creating NIAAA on December 31, 1970. The Institute plans to mark this anniversary throughout the year. Commemorative banners are being installed on the main NIH campus, anniversary issues of the NIAAA publications Alcohol Alert and Alcohol Research & Health are planned, and an anniversary symposium will round out the year. Additionally, the NIAAA website will be redesigned and a branding effort to help increase recognition of the Institute and its products is underway. Throughout the year, the NIAAA website will be updated with more information on activities celebrating 40 years of alcohol research.
Dr. Ralph Hingson will speak at the Pediatric Grand Rounds of the Department of Pediatrics at the Children’s Hospital of Philadelphia in Philadelphia, PA on March 10, 2010. Dr. Hingson will discuss alcohol’s role in the epidemiology of teen crashes and effective policies and programs shown through research to reduce and prevent underage drinking and driving.
Dr. Ralph Hingson will deliver the 17th Annual Virginia S. DeHaan Lecture at the Rollins School of Public Health at Emory University in Atlanta, Georgia In March 2010. This lecture series honors the memory of Ms. Virginia S. DeHaan, an outstanding faculty member of the public health community, who pioneered the development of the Health Promotion and Education Track at Emory University. Dr. Hingson’s presentation will discuss alcohol abuse and traffic safety.
RFA-AA-10-006: Neurobiology of Adolescent Drinking in Adulthood (NADIA) The purpose of this initiative is to support a consortium of researchers across different research institutions to clearly define the persistent effects of adolescent alcohol exposure, and to begin to explore the neurobiological mechanisms underlying these effects. This initiative is limited to animal studies only. The receipt date for applications is February 2, 2010.
RFA-AA-10-005: Case Ascertainment to Estimate the U.S. Prevalence of Fetal Alcohol Spectrum Disorders in Young Children (U01) The NIAAA seeks grant applications from institutions that propose to determine within defined geographical areas of the U.S. a prevalence rate for fetal alcohol spectrum disorders (FASD), including fetal alcohol syndrome (FAS), partial FAS and alcohol-related neurodevelopmental disorders, among young children in the United States. The receipt date for applications was December 22, 2009.
RFA-AA-10-002: Resource Core Alcohol Research Centers (P30). The NIAAA P30 mechanism provides funding for centralized resources and facilities shared by alcohol research investigators. The receipt date for this FOA was December 2, 2009.
RFA-AA-10-003: Specialized Alcohol Research Centers (P50) The overall purpose of the NIAAA Alcohol Research Center program is to provide leadership in conducting and fostering interdisciplinary, collaborative research on a wide variety of topics relevant to the Institute’s mission. The receipt date for this FOA was December 2, 2009.
RFA-AA-10-004: Comprehensive Alcohol Research Centers (P60) In addition to a comprehensive research program, the P60 is required to develop an effective research translation or information dissemination component to help accelerate the use of research findings for the benefit of public health. The receipt date for this FOA was December 2, 2009.
RFA-AA-10-007 (R01) and RFA-AA-10-008 (R21): Gut-Liver-Brain Interactions in Alcohol-Induced Pathogenesis
Update on RFA-MH-09-160 (R34) and RFA-MH-09-161 (R21/R33)(Novel Interventions for Neurodevelopment Disorders). NIAAA joined this RFA from NIMH to encourage development of novel interventions to improve functioning in neurodevelopmental disorders such as autism and fetal alcohol syndrome. Dr. John Matochik, DNB and Dr. Dale Hereld, DMHE are the program contacts. NIAAA is quite pleased that four applications related to fetal alcohol spectrum disorders were successful in receiving funding under this RFA.
PA: The Role of Cellular Organelles in Alcohol-Induced Tissue Injury (R01 and R21)
PA: Stress Pathways in Alcohol Induced Organ Injury and Protection (R01 and R21)
Drs. Peter Silverman and Markus Heilig, NIAAA Technology Development Coordinator and Clinical Director, respectively, announce that NIAAA has established a CRADA with SmithKline Beecham (Cork) to conduct a study of GSK561679, a brain penetrant CRH1 antagonist, in women with alcohol dependence. Dr. Heilig is NIAAA PI on the CRADA, the theoretical rationale for which is based on research showing association between stress and/or negative affect and craving for alcohol and relapse. This will be the first study of CRH antagonism in alcoholism.
The following items represent examples of the breadth and quality of research conducted and supported by NIAAA.
Association of SOD2, a Mitochondrial Antioxidant Enzyme, with Gray Matter Volume Shrinkage in Alcoholics.
Chronic alcoholism leads to gray matter shrinkage and induces the formation of superoxide anions that can cause neuronal cell death. The mitochondrial superoxide dismutase 2 (SOD2) enzyme is critical in the metabolism of superoxide. An Ala16Val polymorphism putatively affects SOD2 enzyme activity in vivo. Brain volumes of 76 treatment-seeking alcohol-dependent individuals were measured with MRI, and gray matter, white matter, sulcal, and ventricular CSF volumes were estimated. Presence of one or two copies of the low activity Ala16 allele was a risk factor for lower gray matter volume in alcoholics below the median alcohol consumption (p=0.03) but not in alcoholics above this level. In this exploratory analysis, a putative functional missense variant of SOD2 appears to influence gray matter loss in alcoholics. This may be due to impaired clearance of reactive oxygen species formed as a result of alcohol exposure. The risk/protective effect was observed in alcoholics with lower levels of lifetime alcohol consumption. Highest levels of exposure may overwhelm the protective action of the SOD2 enzyme. (Srivastava V, Buzas B, Momenan R, Oroszi G, Pulay AJ, Enoch MA, Hommer DW, Goldman D. Neuropsychopharmacology advance online publication, 30 December 2009)
Structure and hydration of membranes embedded with voltage-sensing domains .
The NMR Section of NIAAA’s Laboratory of Membrane Biochemistry and Biophysics contributed the solid state NMR experiments to a collaborative project with NINDS, NIST, the University of California at Irvine and the University of Missouri at Columbia. X-ray crystal structures have been determined for many membrane proteins, but direct structural information about proteins in their native membrane environment is a rarity. This study combined neutron diffraction, solid-state NMR spectroscopy and molecular dynamics simulations to provide a detailed picture of the structure and hydration of lipid bilayermembranes containing S1–S4 voltage-sensing domains, which are responsible for nerve impulses. (Krepkiy D, Mihailescu M, Freites JA, Schow EV, Worcester DL, Gawrisch K, Tobias DJ, White SH, Swartz KJ. Nature. 2009 Nov 26;462(7272):473-9)
Phosphodiesterase inhibition increases CREB phosphorylation and restores orientation selectivity in a model of fetal alcohol spectrum disorders
Fetal alcohol spectrum disorders (FASD) are the leading cause of mental retardation in the western world and children with FASD present altered somatosensory, auditory and visual processing. There is growing evidence that some of these sensory processing problems may be related to altered cortical maps caused by impaired developmental neuronal plasticity. Using the ferret visual cortex as a model, investigators previously established that fetal alcohol impairs neuronal plasticity, which could account for altered sensory processing associated with FASD. Here they demonstrate that this impaired plasticity in the visual cortex is accompanied by sustained reductions in the levels of active, phosphorylated CREB (pCREB), an established mediator of plasticity. Furthermore, they demonstrate that subsequent treatment with a phosphodiesterase (PDE) inhibitor, vinpocetine, corrected pCREB levels and, more importantly, dramatically restored neuronal plasticity. These findings suggest that PDE inhibition might be an effective therapeutic strategy for correcting sensory and possibly other neuronal functional deficits in individuals affected by FASD. (Krahe TE, Wang W, Medina AE. PLoS One. 4(8):e6643, 2009)
Genetical genomic determinants of alcohol consumption in rats and humans .
Investigators used a genetical genomic approach, which relies on statistical and informatics techniques, and non-human animal models of alcohol drinking behavior, to identify candidate genes that predispose to varying levels of alcohol intake in rats. They also assessed genetic polymorphisms associated with alcohol consumption in two populations of humans, the ultimate goal being to ascertain whether such an approach could inform interpretation of genetic association studies with human populations. The results emphasize the importance of the signaling pathways identified using the non-human animal models, rather than single gene products, in identifying factors responsible for complex traits such as alcohol consumption. The comparison of rat and human genetic contributors to the trait of alcohol consumption suggested that one can extrapolate from pathways - not necessarily specific genes - found in animals to begin to elucidate cross-species similarities in the genetic basis of behavior. ( Tabakoff B, et al.; WHO/ISBRA Study on State and Trait Markers of Alcoholism. BMC Biol. 2009 Oct 27;7:70.)
Interplay between mitochondrial motility and fusion-fission dynamics. Researchers identified two classes of mitochondrial fusion events in mammalian cells. In addition to complete fusion, they observed transient fusion events, wherein two mitochondria came into close apposition, exchanged soluble inter-membrane space and matrix proteins, and re-separated, preserving the original morphology. Mitochondrial transient fusion represents a novel mechanism by which organelles can undergo exchange of contents necessary for proper functioning while maintaining a desired morphology. This study has provided some mechanistic insights in the mitochondria dynamics, which is important for alcohol’s action in the cell. (Liu X, Weaver D, Shirihai O, Hajnóczky G. EMBO J. 2009 Oct 21;28(20):3074-89.)
Impaired autophagic flux mediates acinar cell vacuole formation and trypsinogen activation in rodent models of acute pancreatitis. The pathogenic mechanisms underlying acute pancreatitis are not clear. Researchers examined the role of autophagy in acute pancreatitis by comparing autophagic responses in in vivo and in vitro rodent models of pancreatitis with the physiological autophagy induced by fasting. They found evidence that acute pancreatitis causes profound autophagy impairment, which is responsible for 2 key manifestations of this disease: the accumulation of large vacuoles in acinar cells and the intra-acinar trypsinogen activation. The findings provide clear evidence that acute pancreatitis has features of a lysosomal disease, which should be taken into consideration in designing strategies to treat or mitigate pancreatitis. (Mareninova OA, et al. J Clin Invest. 2009 Nov;119(11):3340-55)
Binge-pattern alcohol exposure during puberty induces sexually dimorphic changes in genes regulating the HPA axis. Maternal alcohol consumption during critical periods of fetal brain development leads to devastating long-term consequences on adult reproductive physiology, cognitive function, and social behaviors. However, very little is known about the long-term consequences of alcohol consumption during puberty, which is perhaps an equally dynamic and critical period of brain development. An important neurological system that undergoes extensive plasticity during pubertal development is the hypothalamo-pituitary-adrenal (HPA) axis. In this study, researchers contrasted the HPA axis effects of binge alcohol exposure in rats during the peripubertal period to that of acute exposure. They found that the effects of alcohol on the HPA axis are sex-specific and dependent on repeated high-dose exposures. This contribution provides the first characterization of the impact of binge alcohol exposure during adolescence on the HPA axis. It indicates that binge exposure produces a lasting effect on HPA reactivity and an effect different from that induced by acute alcohol exposure. (Przybycien-Szymanska MM, Rao YS, Pak TR. 2010 Am J Physiol Endocrinol Metab. Epub ahead of print 2009 Dec 1.)
Expression of pronociceptin and its receptor is downregulated in the brain of human alcoholics.
Nociceptin is a brain molecule which has been associated with cognitive processes such as learning and memory. Studies in experimental animal models such as rodents have highlighted a role for nociceptin in modulation of the rewarding effects of alcohol consumption. However, the role of the brain nociceptin system in mediating vulnerability to alcoholism in humans has not been demonstrated. To address this, investigators examined how chronic alcohol abuse alters the abundance of pronociceptin and its receptor in human brain. Analyses of postmortem human brains obtained from individuals with a history of alcoholism showed that the expression of pronociceptin and its receptor are reduced in the brains of alcoholics, in two regions which regulate cognitive control over alcohol intake, the hippocampus and amygdala. The findings add to evidence that suggests pharmacotherapies targeted at the nociceptin system could be useful in the treatment of alcoholism. (Kuzmin A, Bazov I, Sheedy D, Garrick T, Harper C, Bakalkin G. Brain Research 1305: S80-S85, 2009)
Effects of alcohol tax increases on alcohol-related disease mortality in Alaska: time-series analyses from 1976 to 2004.
Researchers evaluated the effects of tax increases on alcoholic beverages in 1983 and 2002 on alcohol-related disease mortality in Alaska. This investigation found a statistically significant reduction in alcohol related disease mortality associated with these tax increases. The effect size was large (-29%) and sustained across the 20 years of data included in the analysis. Even after the initial decrease in alcohol related disease mortality subsequent to the initial tax increase, there was evidence of further decrease after the 2002 tax increase. This investigation provides evidence of the potential long term influence of public health policy changes at the environmental level on alcohol related disease separate from any influence on excess injury or mortality due to drinking related automobile crashes, injury and violence, which were not included in these analyses. (Wagenaar AC, Maldonado-Molina MM, Wagenaar BH. Am J Public Health. 2009 Aug;99(8):1464-70.)
Evidence for an interaction between age at first drink and genetic influences on DSM-IV alcohol dependence symptoms
Research suggests that individuals who start drinking at an early age are more likely to subsequently develop alcohol dependence. In this study, researchers examined whether age at first drink moderates genetic and environmental influences, via gene x environment interactions, on DSM-IV alcohol dependence symptoms. Using data on 6,257 adult monozygotic and dizygotic male and female twins from Australia, they found that the risk for alcohol dependence symptoms increased with decreasing age at first drink. Heritable influences on alcohol dependence symptoms were considerably larger in those who reported an age at first drink prior to 13 years of age. In those with later onset of alcohol use, variance in alcohol dependence was largely attributable to nonshared environmental variance (and measurement error). In addition to confirming the known link between age of first drink and future development of an alcohol use disorder, this analysis shows that genetic factors play a more significant role among early drinkers than late drinkers. Both genetic background and age of first drink made contributions to AUD's in this well controlled analysis.
(Agrawal A, et al.. Alcohol Clin Exp Res. 2009 Dec;33(12):2047-56. Epub 2009 Sep 17.)
A systems approach to college drinking: development of a deterministic model for testing alcohol control policies.
The misuse and abuse of alcohol among college students remain persistent problems. Using a systems approach to understand the dynamics of student drinking behavior and thus forecasting the impact of campus policy to address the problem represents a novel approach. Toward this end, researchers developed a deterministic, compartmental model of college drinking, incorporating three processes: (1) individual factors, (2) social interactions, and (3) social norms. The model quantified these processes in terms of the movement of students between drinking compartments characterized by five styles of college drinking: abstainers, light drinkers, moderate drinkers, problem drinkers, and heavy episodic drinkers. Predictions from the model were first compared with actual campus-level data and then used to predict the effects of several simulated interventions to address heavy episodic drinking. The model was found to adequately predict the actual drinking patterns of students from a variety of campuses surveyed in the Social Norms Marketing Research Project study. The model predicted the impact on drinking patterns of several simulated interventions to address heavy episodic drinking on various types of campuses. These findings provide a novel method for testing the likely effectiveness of preventive policy interventions prior to campuses having to expend resources on a trial and error basis. Thus, employment of such methods have great potential to contribute to future research on prevention effectiveness. ( Scribner R, et al. J Stud Alcohol Drugs .2009 Sep; 70(5):805-21.)
A randomized controlled trial of an internet-based intervention for alcohol abusers.
Misuse of alcohol imposes a major public health cost, yet few problem drinkers are willing to access in-person services for alcohol abuse. The development of brief, easily accessible ways to help problem drinkers who are unwilling or unable to seek traditional treatment services could therefore have significant public health benefit. Investigators conducted a randomized controlled evaluation of the internet-based Check Your Drinking (CYD) screener ( http://www.CheckYourDrinking.net). Problem drinkers who were provided access to CYD displayed a six to seven drink reduction in their weekly alcohol consumption (a 30% reduction in typical weekly drinking) at both the 3- and 6-month follow-ups compared to a one drink per week reduction among control group respondents. The CYD is one of a growing number of internet-based interventions with research evidence supporting its efficacy to reduce alcohol consumption. This finding provides additional evidence that the internet could increase the range of help-seeking options available to the problem drinker. (Cunningham JA, et al. Addiction. 2009 Dec;104(12):2023-32.)
Publications by Extramural Staff
D’Onofrio, G., Goldstein, A.B., Denisco, R.A., Hingson, R., Heffelfinger, J.D., Post, L.A. Emergency Medicine Public Health Research Funded by Federal Agencies: Progress and Priorities. Academic Emergency Medicine 16: 1065-1071, 2009.
Brown, S.A., McGue, M., Maggs, J., Schulenberg, J., Hingson, R., Swartzwelder, S., Martin, C., Chung, T., Tapert, S.F., Sher, K., Winters, K.C., Lowman, C., Murphy, S. Underage Alcohol Use: Summary of Developmental Processes and Mechanisms: Ages 16-20. Alcohol Research & Health 32(1): 41-52, 2009.
Chassin L, Collins RL, Ritter J, Shirley MC, Zvolensky MJ, & Kashdan TB. (2010). Vulnerability to substance use disorders across the lifespan. In R. E. Ingram, & J. M. Price (Eds.), Vulnerability to psychopathology (2nd Ed). NY: Guilford; pp. 176-185.
Edler MC, Yang G, Katherine Jung M, Bai R, Bornmann WG, Hamel E. "Demonstration of microtubule-like structures formed with (-)-rhazinilam from purified tubulin outside of cells and a simple tubulin-based assay for evaluation of analog activity." Arch Biochem Biophys. 2009: 487(2):98-104.
Rozenberg J, Rishi V, Orosz A, Moitra J, Glick A, Vinson C.: Inhibition of CREB function in mouse epidermis reduces papilloma formation. Mol Cancer Res. 2009, 7:654-64.
Dr. Dale Hereld, together with extramural investigators Rajesh Miranda, Andrzej Pietrzykowski, Yueming Tang, Pratheesh Sathyan, Dayne Mayfield, Ali Keshavarzian, and Wayne Sampson, co-authored "MicroRNAs: Master regulators of ethanol-abuse and toxicity?," which will appear in Alcoholism: Clinical and Experimental Research in early 2010.
American Public Health Association’s 137th Annual Meeting and Exposition ,
took place in November, 2009 in Philadelphia. NIAAA was well-represented at this important meeting. For example:
Hingson, R. “Does Age Influence Whether Patients See Physicians and Are Asked and Counseled About Alcohol Consumption?” Session: Barriers to Alcohol Treatment.
Breslow, R. Physical activity: Potential confounder in alcohol epidemiologic studies? (Poster presentation).
Nutritional Armor for the Warfighter: Can Omega-3 Fatty Acids Enhance Stress Resilience , a conference organized jointly by Capt. Joseph R. Hibbeln, M.D., NIAAA, and colleagues from the Samueli Institute as well as the Defense Advanced Research Projects Agency (DARPA) on October 13-14, 2009, was highlighted by a presentation by former Surgeon General, Richard Carmona, M.D. An archived videocast of the conference is available at http://videocast.nih.gov/
Alcohol Pharmacotherapy for Persons Living with HIV/AIDS: Building a Framework for Collaboration .
This December, 2009 meeting hosted by DTRR and DEPR brought together the Principal Investigators and other key personnel from four projects funded under RFA-AA-09-007, “Alcohol Pharmacotherapy and the Treatment and Prevention of HIV/AIDS”. These projects address the use of combined behavioral and pharmacotherapies in individuals with co-occurring HIV infection, heavy drinking, alcohol abuse and alcohol dependence. They occupy a unique niche in the NIAAA HIV/AIDS portfolio, being the first NIAAA-sponsored projects to examine the use of combined behavioral and pharmacologic treatments to reduce the impact of heavy drinking, alcohol abuse and dependence on HIV-infected patients. The purpose of the meeting was to develop a blueprint for linking the projects under a cooperative agreement to facilitate the use of common assessment instruments and the sharing and integration of data across involved research sites. In addition to advancing NIAAA goals related to improving treatment outcomes for individuals with co-occurring alcohol use disorders and HIV infection, this initiative is directly responsive to calls for further research on pharmacologic approaches to comorbid HIV infection and substance abuse from other federal agencies and programs, including the White House Office of the Global AIDS Coordinator (OGAC) and the President’s Emergency Plan for AIDS Relief (PEPFAR).