Table of Contents
The NIAAA is currently closing out Fiscal Year (FY) 2014 to coincide with the end of the Fiscal Year calendar, September 30th. As you may recall from previous Council briefings, the FY 2014 appropriation for NIH is $29.9 billion, $1 billion above the FY 2013 appropriation level after taking into account the impact of the 2013 budget sequestration.
For NIAAA, the FY 2014 appropriation provides $445.4 million. This represents a $12.6 million or a 2.9 percent increase over the FY 2013 budget level (also post-sequestration). NIAAA estimates the appropriation will provide support a total of 677 Research Project Grants (RPGs) in FY 2014, including 174 competing awards, compared to 671 RPGs and 166 competing awards in FY 2013.
As noted in the June Director’s Report to Council, on March 4, 2014, President Obama submitted to Congress his FY 2015 budget request for all Federal agencies – the FY 2015 President’s Budget. Included in this request is a proposed FY 2015 budget for the National Institutes of Health (NIH) of $30.4 billion. The NIAAA budget request for FY 2015 is $446.0 million which is $0.6 million or a 0.1 percent increase over the FY 2014 Enacted level.
On July 24, the Senate Appropriations Committee Democratic leadership released the Labor, Health and Human Services, Education, and Related Agencies (Labor-HHS) Appropriations Subcommittee’s FY 2015 draft spending bill and report language. The Labor-HHS subcommittee approved the bill on June 10 following markup, but consideration by the full Senate Appropriations Committee was indefinitely postponed shortly afterward. The subcommittee provides $30.5 billion for NIH, a $606 million (2 percent) increase over FY 2014. For NIAAA, the subcommittee provides $451.4 million, a 1.3 percent increase over FY 2014 budget. The subcommittee report notes that the increases provided in this draft spending bill, combined with the $1 billion increase in provided in FY 2014, fully replaces the FY 2013 sequester reduction to NIH.
In other legislative activity to note, on July 24, 2014, Senator Tom Harkin (D-IA) introduced S. 2658, the Accelerate Biomedical Research Act. As Senator Harkin noted in his press release, austere budget caps have resulted in over 20 percent erosion in the purchasing power of dollars for biomedical research. If current trends continue, the government of China will outpace the U.S. investment in biomedical research over the coming decade, diverting private investment, jobs, and subsequent economic growth. The Accelerate Biomedical Research Act would reverse this trend by instituting a budget cap adjustment to prioritize NIH over the remaining fiscal years of the Budget Control Act. The budget cap adjustment is sufficient to allow the Appropriations Committees to restore the purchasing power the NIH would have had if funding had kept pace with inflation since 2003, the last year of the doubling. The bill includes language that will require the Appropriations Committee to maintain the current funding of $29.9 billion for NIH, above which appropriations will rise up to $46.2 billion at the end of the seven year period from Fiscal Year 2015 to 2021. The additional funding provides an initial bump of ten percent increases in the first two years to quickly mitigate the lingering effects of sequester, followed by a five percent increase each year thereafter.
Preliminary work on the budget for FY 2016 is beginning. After intermediate stages of review, the President’s budget request for FY 2016 will be presented to Congress on March 3, 2015, at which time it will become available to the public.
Below, find the mechanism table comparing the FY 2014 Enacted budget to the FY 2015 President’s Budget request:
(Dollars in Thousands)
|FY 2014||FY 2015|
|Administrative Supplements *||(24)||1,269||(24)||1,269|
|Research Project Grants||677||253,207||682||253,769|
|Res. Centers in Minority Instit.||-||-||-||-|
|Cooperative Clinical Research||1||7,500||1||7,500|
|Biomedical Research Support||-||-||-|
|Minority Biomed. Res. Support||-||340||-||340|
|Subtotal, Other Research||135||37,064||135||37,064|
|Total Research Grants||830||316,063||835||316,625|
|Research & Develop. Contracts||65||38,040||65||38,390|
|Res. Management & Support||130||30,015||131||30,015|
|Total, NIAAA Budget Authority||$444,905||$446,017|
As part of the Collaborative Research on Addiction at NIH (CRAN), a joint undertaking by NIAAA, NIDA, and the NCI, NIAAA contributed $2.269 million dollars, or 25 percent of the total costs, toward the three initiatives undertaken in fiscal year 2014. These initiatives were directed toward broadening research on joint alcohol and other drug use; expanding the scope of alcohol and other drug research within the T32 training programs; and for the award of research applications under the CRAN Social Media RFA.
As a follow up to an open meeting held on May 27-28, the NIH intends to host an open satellite event/meeting at the Society for Neuroscience Annual Meeting in Washington, DC, in November 2014 to receive recommendations on the Adolescent Brain Cognitive Development (ABCD) study. This study is in the planning stages under CRAN. A number of comments have already been received in response to a Request for Information. For further information please see the CRAN website (addictionresearch.nih.gov).
Over the summer months, Dr. George Koob spoke at several scientific meeting including the annual meeting of the College on Problems of Drug Dependence and the Research Society on Alcoholism. He served as a lecturer at the Institute Pasteur in Paris, France, and spoke at the French Embassy in Washington, DC, to commemorate the 50th anniversary of the Institut National de la Santé et de la Recherche Médicale (INSERM). He also gave a plenary talk at the 9th Federation of European Neuroscience Societies (FENS) Forum of Neuroscience in Milan, Italy.
In July, Dr. Koob spoke at a Congressional briefing on “New Horizons in the Treatment of Alcohol Use Disorders.” Dr. Koob spoke about treatment advances for problem drinking and the conceptual framework for stages of the addiction cycle. The briefing was sponsored in part by the Friends of the National Institute on Alcohol Abuse and Alcoholism (NIAAA).
In August, Dr. Koob presented at the Interagency Coordinating Committee on the Prevention of Underage Drinking and spoke at the University of Illinois on “What Science Can Contribute to the Diagnosis, Prevention and Treatment of Alcoholism.”
On September 2, Dr. Koob presented on the “Neurobiology of Alcohol and Drug Addiction” at the California Society of Addiction Medicine’s Addiction Medicine Review Course 2014.
Lori Ducharme, Ph.D., joined DTRR on June 2, 2014 as Program Director for Health Services Research. Trained as an organizational sociologist, she focuses on the structure, quality, and availability of alcohol treatment services, and in particular on moving evidence-based practices into routine service delivery. From 2008-2014, Dr. Ducharme was a program official in the Services Research Branch at NIDA, where she led the development of that Institute’s implementation science portfolio, and served as Science Officer for NIDA’s Criminal Justice Drug Abuse Treatment Studies cooperative. Prior to joining NIH, she was a NIAAA- and NIDA-funded researcher at the University of Georgia, Research Triangle Institute, and Westat.
Richard Doucette recently joined NIAAA as a Workforce Resources Specialist, in the Administrative Services Branch. He comes to us from the National Institute of Mental Health, with expertise in personnel appointment mechanisms, including Intramural Research Training Award (IRTA), Visiting Program (FTE and Non FTE), Title 42, Title 5, Title 42 with T-38 pay, and Tenure – Track and Tenure Appointments.
Rachel Quade joined the Division of Neuroscience and Behavior in August of this year and is the secretary/assistant for the division and Dr. Antonio Noronha. She previously worked with the intramural Laboratory of Molecular Signaling. Rachel has more than 14 years of federal service with NIH, the Department of Transportation, and the Department of Housing and Urban Development. Rachel traveled the globe extensively prior to coming to work at NIH, working with a non-profit organization to provide shoes and hope for disadvantaged children in Africa.
Patricia Scullion retired in early July after working at NIH for over 40 years and serving as NIAAA’s Chief Administrative Officer for seven years. She and her husband recently relocated to Southport, North Carolina.
Jenny Czajkowski recently moved to Boston, Massachusetts, after working at NIH for over 19 years and serving as NIAAA’s Deputy Executive Officer for the past three years. Previously, she was Communications Director for the Center for Information Technology (CIT), and Deputy Director of Customer Support. Over her career at NIH, Jenny served as a dedicated mentor and was involved with the NIH Administrative Training Committee’s intern programs.
Jennifer Norsworthy has left NIAAA and will be working at the Centers for Medicare & Medicaid Services (CMS) at the Center for Program Integrity in the Data Sharing and Partnership Group. Her new office promotes the integrity of the Medicare and Medicaid programs through provider and policy reviews and providing support to states.
New NIAAA Positions
Fred Donodeo, who was serving as Acting Director of the NIAAA Communications and Public Liaison Branch, was recruited and selected as permanent Director of the branch. Mr. Donodeo, who joined NIAAA in 1998, has an extensive background in public affairs, social marketing, and community relations. Before coming to NIAAA, Mr. Donodeo was a Public Affairs Specialist at the National Cancer Institute (NCI), having joined NIH as a Presidential Management Intern. Prior to that, he managed press and public affairs for a New York City government agency. Mr. Donodeo has a B.A. in Sociology/Communications from Fordham University and an M.P.A. from George Washington University.
Dr. George Koob was awarded the 25th annual Neuronal Plasticity Prize of the Fondation Ipsen for his “pioneering works in the domain of neuropsychology of drug addiction.” The award was made on July 8, 2014 at the FENS (Federation of European Neuroscience Societies) in Milan, Italy.
Drs. Pal Pacher and George Kunos have both been selected as Thomson Reuters Highly Cited Researchers in the area of Pharmacology/Toxicology. This is based on highly cited papers published during 2002 to 2012 (highlycited.com).
PAR-14-281: Connectomes Related to Human Disease (U01). The NIH-funded Human Connectome Project has developed very high resolution acquisition protocols for magnetic resonance imaging (MRI) of the brain, particularly for diffusion tensor imaging (DTI) for investigating the structural integrity of the brain’s white matter fiber tracts. The goal of the PAR is to encourage adoption of these high resolution MR imaging protocols developed by the Human Connectome Project by the larger research community. For NIAAA, application of the protocols to a population of interest such as individuals with FAS/FASD would be considered responsive to the goals of the PAR. Dr. John Matochik (DNB) is the program contact.
RFAs re-issued by NIAAA
RFA-AA-15-001: Specialized Alcohol Research Centers (P50). This RFA solicits applications for specialized Alcohol Research Centers to provide leadership in conducting and fostering interdisciplinary, collaborative research on a wide variety of topics relevant to the Institute’s mission. Drs. M. Katherine Jung (DMHE) and Lindsey Grandison (DNB) are the scientific contacts.
RFA-AA-15-002: Comprehensive Alcohol Research Centers (P60). This RFA solicits applications for comprehensive Alcohol Research Centers (ARC) to provide leadership in conducting and fostering interdisciplinary, collaborative research on a wide variety of topics relevant to the Institute’s mission. Each center 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. Drs. M. Katherine Jung (DMHE) and Lindsey Grandison (DNB) are the scientific contacts.
RFA-AA-15-003: Collaborative Partnership on Alcohol and Health Disparity Research Center (AHDRC) (U54). This program announcement is designed to facilitate planning and implementation of collaborative partnerships between institutions that serve medically and scientifically underserved communities and populations (IUCP) and established Alcohol Research Centers (ARC) to promote targeted research to reduce alcohol-related health disparities in underserved populations, as well as promote alcohol research expertise and infrastructure development at IUCPs. Drs. M. Katherine Jung (DMHE) and Judith Arroyo (OD) are the scientific contacts.
PAs re-issued by NIAAA
PAR-14-268: International Research Collaboration on Alcohol and Alcoholism (U01). This program is intended to provide funds for research activities to be undertaken jointly by a U.S. and non-U.S. laboratory that expands the research direction of both institutions in a collaborative manner. Dr. Peggy Murray (OD) is the scientific contact.
atic and animated PSAs through social media and the NBC Times Square billboard. Capitalizing on football images easily associated with the “Big Game,” the PSAs stressed the risks of binge drinking and driving after game-watching parties. People.com ran all static ads online at no cost to NIAAA for the week leading up to the Super Bowl, an estimated donated value of more than $13,500, and prompting nearly 1,000 click-throughs to the NIAAA website. People.com circulated the three ads periodically, maximizing the impact of advertising during one of the most expensive advertising periods of the year.
Dr. Changhai Cui organized a workshop, “Neuroimmune Mechanisms Contributing to Addiction Neurobiology - Brain Function and Alcohol Related Disorders,” held on September 2, 2014 at NIAAA. The purpose of the workshop was to highlight recent progress in the understanding of neuroimmune mechanisms contributing to brain function and alcohol use disorders. The event brought together scientists from both alcohol and other research fields to present recent science advances and identify research gaps/opportunities. NIAAA director, Dr. George Koob, gave opening remarks and highlighted several NIAAA-sponsored studies in this rapidly growing area. He noted that gene expression changes identified in alcohol dependence overlapped with those in neuroimmune pathways and that other drugs of abuse interact with the neuroimmune system, in addition to alcohol. Dr. Antonio Noronha, the director of the Division of Neuroscience and Behavior, moderated the panel discussion session. The video of the workshop has been archived at videocast.nih.gov. More information on the workshop is available at www.niaaa.nih.gov/news-events/meetings-events-exhibits/niaaa-workshop.
Dr. Andrew Holmes gave a plenary lecture, “The Neural Circuitry of Recovery from Traumatic Fear,” at the South African Neuroscience Society Symposium 2014, on July 13, 2014. Dr. Holmes and his group are using models of chronic alcohol exposure and chronic stress to examine how these environmental insults reshape brain circuits to modify behavior, and why they do so in a manner that varies greatly from individual to individual as a function of genetics, sex and age. A major current focus of Dr. Holmes’ work is how alcohol and stress affect the structure and function of circuits interconnecting the prefrontal cortex with limbic and dorsal striatal regions that are critical for the regulation of emotion, cognition, and executive control over drug-seeking.
Dr. George Kunos was an invited plenary speaker at 11th International Congress of the International Society for the Study of Fatty Acids and Lipids (ISSFAL), in Stockholm, Sweden, on June 29.
Dr. Lorenzo Leggio was one of the three invited guest speakers, together with NIDA-funded extramural investigators Drs. Cunningham and Kalivas, at the Research Day entitled “Developing Medications to Treat Addiction: Challenges for Science and Practice” at the Ross University Medical School in Portsmout, Commonwealth of Dominica, West Indies (http://www.rossu.edu/medical-school/2014/06/At-RUSM-Research-Day-Renowned-Experts-Discuss-Developing-Medications-to-Treat-Addiction.cfm).
Dr. Matthew Reilly co-organized a symposium for the 2014 International Behavioral and Neural Genetics Society meeting (IBANGs) entitled: “The Role of Transposable Elements and Non-Coding RNAs in Brain Health and Disease.” This symposium occurred on May 9th, 2014 in Chicago, Illinois. Dr. Reilly gave an introduction to this symposium that covered the state of the neuroscience field in relation to transposable elements and non-coding RNA biology.
Dr. Abbas Parsian, program director for human genetics/genomics in the Division of Neuroscience & Behavior, as a member of NIH GxE planning committee, played a key role in organizing a workshop entitled, “Challenges in Replication of GxE Research in the Behavioral and Social Sciences” that was held on May 22-23, 2014, at NIH campus. The sessions included GxE interactions in behavioral and social sciences, framing the question of GxE replication, examining how animal studies can inform human studies of GxE, experiences from the field, and data concerns. In addition, Dr. Parsian chaired the session on how animal studies can inform human studies of GxE.
Dr. Raye Litten organized and chaired session on “Advances in Treatments for PTSD and Alcohol Comorbidity,” at the annual American Society of Clinical Psychopharmacology (ASCP)/NCDEU meeting in Hollywood, Florida. Dr. Litten also organized and served as discussant for a session on “Missing Data in Alcohol Use Disorder Clinical Trials,” and served as discussant for a session on “Biological Approaches to Treat Substances Use Disorders.”
Dr. Lori Ducharme serves in an advisory role on the national executive committee of the Veteran’s Administration’s Substance Use Disorder Quality Enhancement Research Initiative (SUD QUERI). In June 2014, she participated in a strategic planning meeting at the Menlo Park, VA campus to develop a framework for prioritizing and selecting implementation research topics for the SUD QUERI program.
Dr. Ralph Hingson gave a presentation titled “Recent Trends and Findings Regarding the Magnitude and Prevention of College Drinking and Drug Use Problems” at the Ohio State University’s Generation Rx University Conference in Columbus, Ohio, on August 6, 2014. This talk discussed issues concerning alcohol and drug use by college students.
Dr. Ralph Hingson represented NIAAA at the Community Anti-Drug Coalitions of America’s (CADCA) 2014 Mid-Year Training Institute, in Orlando, Florida, on July 22, 2014. His first presentation was titled “New Research Since the Surgeon General’s Call to Action to Prevent and Reduce Underage Drinking,” which outlined new research on trends in and consequences of underage drinking and interventions to prevent and reduce underage drinking that have emerged since the 2007 Call to Action. His second talk discussed the World Health Organization’s (WHO) global strategy to reduce the harmful use of alcohol. This presentation also discussed best practices in implementing the WHO strategy, with a particular focus on sharing experiences in implementing policy options at national and international levels.
Dr. Ralph Hingson co-authored an editorial with Dr. Wilson Compton titled “Screening and Brief Intervention and Referral to Treatment for Drug Use in Primary Care: Back to the Drawing Board,” published by the Journal of the American Medical Association (JAMA). This editorial reviewed two recent studies of brief intervention for drug use in primary care, also published in JAMA, one by Dr. Richard Saitz, et al., and the other by Dr. Peter Roy-Byrne, et al.
Dr. Dale Hereld of the Division of Metabolism and Health Effects updated the Fetal Alcohol Spectrum Disorders Study Group on NIAAA's FASD-related activities at their annual meeting, which was held in conjunction with the annual RSA meeting in Bellevue, Washington, on June 21, 2014.
The Research Society on Alcoholism (RSA) held its 37th annual scientific meeting June 21-25 in Bellevue, WA. Many NIAAA employees attended the conference and its satellite sessions. Select activities:
- Dr. George Kunos served as a co-chair and invited speaker at the RSA/ISBRA symposium on “Metabolic Reprogramming and Cell Fate Regulation in Alcohol-Associated Diseases.”
- Dr. Lorenzo Leggio chaired and served as discussant at the mini-symposium on the “Potential for Nutraceuticals as Treatments for Alcohol Use Disorder and Alcoholic Liver Disease.”
- Dr. Antonio Noronha gave a presentation at a symposium entitled, “From Cellular to Genomic and Epigenomics to Identify Therapeutic Targets For Alcoholism,” held in conjunction with RSA/ISBRA. His presentation centered on the evolution of the field in terms of alcohol and epigenetic mechanisms, some persistent epigenetic effects across the lifespan, novel epigenetic drug targets as well as new ways of understanding inherited vulnerability of these epigenetic effects.
- Dr. Ellen Witt co-organized and chaired a symposium entitled, “Puberty, Gonadal Hormones, and Sex Differences in Alcohol Abuse and Dependence.” Dr. Witt gave the introduction to this symposium, which presented animal model research used to study the degree to which hormonal changes at puberty may produce sex-specific effects on alcohol-related behaviors.
- Drs. Dan Falk, Brett Hagman, and Robert Huebner presented the “NIAAA Update and Future Directions of Mechanisms of Behavior Change” at the RSA 10th Annual Satellite Session on Mechanisms of Behavior Change.
- Dr. Bob Freeman was a discussant on “Alcohol’s Role in Sexual Assault Perpetration: Innovations in Research.” This panel featured presentations by NIAAA grantees Toni Abbey, Kelly Davis, and Maria Testa. Dr. Freeman also served as a discussant for “Displays of Alcohol-Related Content on Social Networking Sites: Influence, Infodemiology, and Intervention Opportunities.” This panel featured presentations by NIAAA grantee Megan Moreno and several of her students. Dr. Freeman also participated in the RSA’s “Grantsmanship Workshop.”
- Drs. Svetlana Radaeva, Joe Wang, Andras Orosz, and Gary Murray of the Division of Metabolism and Health Effects co-organized two symposia on alcoholic hepatitis highlighting progress from NIAAA’s liver consortia. These symposia presented clinical trials in process, as well as results from the basic research and translational components of the consortia. Dr. Gary Murray served as a discussant for these symposia.
- Dr. Svetlana Radaeva of the Division of Metabolism and Health Effects co-organized the RSA Satellite Session on Liver and Alcohol Genomics.
Dr. George Koob is the first author on the new textbook “Drugs, Addiction, and the Brain,” (ISBN-13: 978-0123869371, Elsevier, 2014) which explores the molecular, cellular, and neurocircuitry systems in the brain that are responsible for drug addiction. Common neurobiological elements are emphasized that provide novel insights into how the brain mediates the acute rewarding effects of drugs of abuse and how it changes during the transition from initial drug use to compulsive drug use and addiction. The book provides a detailed overview of the pathophysiology of the disease. The information provided will be useful for neuroscientists in the field of addiction, drug abuse treatment providers, and undergraduate and postgraduate students who are interested in learning about the diverse effects of drugs of abuse on the brain.
Drs. Antonio Noronha, Changhai Cui, Adron Harris, and John Crabbe were editors on the book “Neurobiology of Alcohol Dependence” (ISBN: 978-0-12-405941-2, Elsevier, 2014). This book presents a comprehensive overview of our current understanding of the neurobiological mechanisms underlying alcohol dependence at the molecular, cellular, circuitry, and behavioral levels. It highlights the profound impact of alcohol on multiple neurocircuits related to reward, stress, habit formation, and executive function. The book also provides critical reviews on the implications of the neuroplasticity of these systems in alcohol dependence, and bridges genetic factors to behavioral phenotypes, emphasizing the importance of both genes and epigenetics contributing to alcohol dependence and alcohol-related traits.
- On October 14, 2014, Dr. Craig McClain will deliver NIAAA’s Mark Keller Honorary Lecture. His presentation is titled, “Nutrition, Gut Barrier Function and Liver Disease. The event will take place 1:30 p.m. to 3:30 p.m., in Masur Auditorium, NIH Clinical Center, Bethesda, Maryland.
Dr. McClain is Distinguished University Scholar at the University of Louisville (U of L), as well as Associate Vice President for Health Affairs/Research, U of L Associate Vice President for Translational Research, Director of the U of L Clinical and Translational Sciences Institute, Director of Research Affairs, Division of Gastroenterology, Hepatology and Nutrition, and Director of Gastroenterology at the Louisville Veterans Affairs Medical Center. He is an internationally distinguished clinician and scientist in the fields of gastroenterology, alcohol abuse, and nutrition.
This annual lecture series honors Mark Keller’s pioneering contributions to the field of alcohol research. For more information, visit the Keller Lecture page.
- NIAAA is sponsoring a satellite symposium on “PTSD, the Amygdala, and Alcohol Use Disorders” at the Society for Neuroscience annual meeting, November 14, 2014, in Washington, DC. This satellite symposium brings together expertise on PTSD, the amygdala, and alcohol use disorders to facilitate the discussion on neurobiological mechanisms underlying co-morbidities of PTSD and alcohol abuse. This meeting is being organized by Drs. Lindsey Grandison, Changhai Cui, and Antonio Noronha.
Aldehyde Dehydrogenase 2 Deficiency Ameliorates Alcoholic Fatty Liver but Worsens Liver Inflammation and Fibrosis in Mice
Significance: ALDH2 knockout mice are more susceptible to alcohol-induced liver inflammation and fibrosis, but surprisingly are resistant to alcohol-induced fatty liver and elevation of blood aminotransferase. These results may have significant clinical implications in that ALDH2-deficient individuals may be resistant to steatosis and blood ALT elevation, but prone to liver inflammation and fibrosis following alcohol consumption.
Aldehyde dehydrogenase 2 (ALDH2) is the major enzyme that metabolizes acetaldehyde produced from alcohol metabolism. Approximately 40-50% of East Asians carry an inactive ALDH2 gene and exhibit acetaldehyde accumulation after alcohol consumption. However, the role of ALDH2 deficiency in the pathogenesis of alcoholic liver injury remains obscure. In the present study, wild-type and ALDH2(-/-) mice were subjected to ethanol feeding and/or carbon tetrachloride (CCl4 ) treatment, and liver injury was assessed. Compared with wild-type mice, ethanol-fed ALDH2(-/-) mice had higher levels of malondialdehyde-acetaldehyde (MAA) adduct and greater hepatic inflammation, with higher hepatic interleukin (IL)-6 expression but surprisingly lower levels of steatosis and serum alanine aminotransferase (ALT). Higher IL-6 levels were also detected in ethanol-treated precision-cut liver slices from ALDH2(-/-) mice and in Kupffer cells isolated from ethanol-fed ALDH2(-/-) mice than those levels in wild-type mice. In vitro incubation with MAA enhanced the lipopolysaccharide (LPS)-mediated stimulation of IL-6 production in Kupffer cells. In agreement with these findings, hepatic activation of the major IL-6 downstream signaling molecule signal transducer and activator of transcription 3 (STAT3) was higher in ethanol-fed ALDH2(-/-) mice than in wild-type mice. An additional deletion of hepatic STAT3 increased steatosis and hepatocellular damage in ALDH2(-/-) mice. Finally, ethanol-fed ALDH2(-/-) mice were more prone to CCl4 -induced liver inflammation and fibrosis than ethanol-fed wild-type mice. ALDH2(-/-) mice are resistant to ethanol-induced steatosis but prone to inflammation and fibrosis by way of MAA-mediated paracrine activation of IL-6 in Kupffer cells. These findings suggest that alcohol, by way of acetaldehyde and its associated adducts, stimulates hepatic inflammation and fibrosis independent from causing hepatocyte death, and that ALDH2-deficient individuals may be resistant to steatosis and blood ALT elevation, but are prone to liver inflammation and fibrosis following alcohol consumption. (Kwon, H., Won,Y., Park,O., Chang, B., Duryee, M., Thiele, G. E., Matsumoto, A., Singh, S., Abdelmegeed, M., Song, B., Kawamoto, T., Vasiliou, V., Thiele, G., Gao, B. Hepatology 2014; July 60:146-157)
Poly (ADP-Ribose) Polymerase-1 Is a Key Mediator of Liver Inflammation and Fibrosis
Significance: This study identifies a key role for nuclear enzyme Poly (ADP-Ribose) Polymerase-1 in mediating liver inflammation, metabolic dysregulation and fibrosis and suggests that inhibitors of this enzyme, which are in clinical trials for cancer, may be beneficial in the treatment of various forms of liver disease associated with mitochondrial dysfunction, inflammation and fibrosis.
Poly (ADP-ribose) polymerase 1 (PARP-1) is a constitutive enzyme, the major isoform of the PARP family, which is involved in the regulation of DNA repair, cell death, metabolism, and inflammatory responses. Pharmacological inhibitors of PARP provide significant therapeutic benefits in various preclinical disease models associated with tissue injury and inflammation. However, our understanding the role of PARP activation in the pathophysiology of liver inflammation and fibrosis is limited. In this study we investigated the role of PARP-1 in liver inflammation and fibrosis using acute and chronic models of carbon tetrachloride (CCl4 )-induced liver injury and fibrosis, a model of bile duct ligation (BDL)-induced hepatic fibrosis in vivo, and isolated liver-derived cells ex vivo. Pharmacological inhibition of PARP with structurally distinct inhibitors or genetic deletion of PARP-1 markedly attenuated CCl4 -induced hepatocyte death, inflammation, and fibrosis. Interestingly, the chronic CCl4 -induced liver injury was also characterized by mitochondrial dysfunction and dysregulation of numerous genes involved in metabolism. Most of these pathological changes were attenuated by PARP inhibitors. PARP inhibition not only prevented CCl4 -induced chronic liver inflammation and fibrosis, but was also able to reverse these pathological processes. PARP inhibitors also attenuated the development of BDL-induced hepatic fibrosis in mice. In liver biopsies of subjects with alcoholic or hepatitis B-induced cirrhosis, increased nitrative stress and PARP activation was noted.The reactive oxygen/nitrogen species-PARP pathway plays a pathogenetic role in the development of liver inflammation, metabolism, and fibrosis. PARP inhibitors are currently in clinical trials for oncological indications, and the current results indicate that liver inflammation and liverfibrosis may be additional clinical indications where PARP inhibition may be of translational potential. (Mukhopadhyay P, Rajesh M, Cao Z, Horváth B, Park O, Wang H, Erdelyi K, Holovac E, Wang Y, Liaudet L, Hamdaoui N, Lafdil F, Haskó G, Szabo C, Boulares AH, Gao B, Pacher P. Hepatology. 2014 May;59(5):1998-2009)
Modulation Of Fatty Acid and Bile Acid Metabolism by Peroxisome Proliferator-Activated Receptor Α Protects Against Alcoholic Liver Disease
Significance: This study compared alcohol-induced changes in liver tissues in alcohol-fed WT and Ppara-null mice in order to determine the roles of PPARα on hepatomegaly, steatosis, inflammation and mitochondrial swelling. The transcriptomics results indicated that PPARα activity was clearly enhanced through the induction of fatty acid b-oxidation. Striking increases in cholic acid and its derivatives and in a proinflammatory factor, Thbs1, were observed only in alcohol-fed Ppara-null mice. These findings further elucidate metabolic changes during chronic alcohol consumption and thus suggest the potential application of PPARα agonists in preventing ALD progression.
Chronic alcohol intake affects liver function and causes hepatic pathological changes. It has been shown that peroxisome proliferator-activated receptor α (PPARα)-null mice developed more pronounced hepatic changes than wild-type (WT) mice after chronic exposure to a diet containing 4% alcohol. The remarkable similarity between the histopathology of alcoholic liver disease (ALD) in Ppara-null model and in humans, and the fact that PPARα expression and activity in human liver are less than one-tenth of those in WT mouse liver make Ppara-null a good system to investigate ALD. METHODS: In this study, the Ppara-null model was used to elucidate the dynamic regulation of PPARα activity during chronic alcohol intake. Hepatic transcriptomic and metabolomic analyses were used to examine alterations of gene expression and metabolites associated with pathological changes. The changes triggered by alcohol consumption on gene expression and metabolites in Ppara-null mice were compared with those in WT mice. RESULTS: The results showed that in the presence of PPARα, 3 major metabolic pathways in mitochondria, namely the fatty acid β-oxidation, the tricarboxylic acid cycle, and the electron transfer chain, were induced in response to a 2-month alcohol feeding, while these responses were greatly reduced in the absence of PPARα. In line with the transcriptional modulations of these metabolic pathways, a progressive accumulation of triglycerides, a robust increase in hepatic cholic acid and its derivatives, and a strong induction of fibrogenesis genes were observed exclusively in alcohol-fed Ppara-null mice. CONCLUSIONS: These observations indicate that PPARα plays a protective role to enhance mitochondrial function in response to chronic alcohol consumption by adaptive transcriptional activation and suggest that activation of this nuclear receptor may be of therapeutic value in the treatment for ALD. (Li HH, Tyburski JB, Wang YW, Strawn S, Moon BH, Kallakury BV, Gonzalez FJ, Fornace AJ Jr. Alcohol Clin Exp Res. 2014 Jun;38(6):1520-31)
Protective Role Of HO-1 and Carbon Monoxide in Ethanol-Induced Cell Death in Hepatocytes and Liver Injury in Mice
Significance: This study explores the pharmacological induction of Heme oxygenase-1 (HO-1) or treatment with carbon monoxide (an end product of HO-1 activity) releasing molecules to prevent and treat ethanol-induced liver injury in a pre-clinical mouse model. Induction of HO-1 or treatment with carbon monoxide during ethanol feeding protected mice from hepatocyte injury and death, reduced expression of inflammatory mediators in the liver and reversed established liver injury, suggesting that increasing HO-1 and/or modulating CO might be important therapeutic strategies for treatment of ALD.
Alcoholic liver disease is associated with inflammation and cell death. Heme oxygenase-1 (HO-1) is a stress-inducible enzyme with anti-apoptotic and anti-inflammatory properties. Here we tested the hypothesis that induction of HO-1 or treatment with a carbon monoxide releasing molecule (CORM) during chronic ethanol exposure protects and/or reverses ethanol-induced liver injury. METHODS: Female C57BL/6J mice were allowed free access to a complete liquid diet containing ethanol or pair-fed control diets for 25 days. Mice were treated with cobalt protoporphyrin (CoPP) to induce HO-1 expression during ethanol feeding or once injury had been established. Mice were also treated with CORM-A1, a CO-releasing molecule (CORM), after ethanol-induced liver injury was established. The impact of HO-1 induction on ethanol-induced cell death was investigated in primary cultures of hepatocytes. RESULTS: Induction of HO-1 during or after ethanol feeding, as well as treatment with CORM-A1, ameliorated ethanol-induced increases in AST and expression of mRNA for inflammatory cytokines. Treatment with CoPP or CORM-A1 also reduced hepatocyte cell death, indicated by decreased accumulation of CK18 cleavage products and reduced RIP3 expression in hepatocytes. Exposure of primary hepatocyte cultures to ethanol increased their sensitivity to TNFα-induced cell death; this response was attenuated by necrostatin-1, an inhibitor of necroptosis, but not by caspase inhibitors. Induction of HO-1 with CoPP or CORM-3 treatment normalized the sensitivity of hepatocytes to TNFα-induced cell death after ethanol exposure. CONCLUSIONS: Therapeutic strategies to increase HO-1 and/or modulate CO availability ameliorated chronic ethanol-induced liver injury in mice, at least in part by decreasing hepatocellular death. (Bakhautdin B, Das D, Mandal P, Roychowdhury S, Danner J, Bush K, Pollard K, Kaspar JW, Li W, Salomon RG, McMullen MR, Nagy LE. J Hepatol. 2014 Jun 16. pii: S0168-8278(14)00402-4. doi: 10.1016/j.jhep.2014.06.007. [Epub ahead of print])
Moderate Alcohol Induces Stress Proteins HSF1 and HSP70 and Inhibits Proinflammatory Cytokines Resulting in Endotoxin Tolerance
Significance: This study examines the interplay between the innate immune response and the cellular stress response in monocytes and macrophages using a binge or moderate alcohol exposure model. Endotoxin stimulation of TLR4 results in activation of NF-kB–mediated transcription of proinflammatory cytokines such as TNF-a, IL-1b, and IL-6. These innate immune responses are compromised by moderate or binge alcohol exposure by activating HSP70 and inducing HSF1, two cardinal components of the cellular stress response. HSP70 binds to the p50 subunit of NF-B inhibiting cytoplasmic-nuclear translocation, while HSF1 represses cytokine gene promoters thus exerting negative effects on TLR4-induced proinflammatory cytokine production. Crosstalk mechanism between alcohol-induced stress proteins and TLR4 signaling molecules results in endotoxin tolerance suggesting that currently available drugs targeting HSF1 and HSP70 could restore normal immune function in alcohol-exposed individuals.
Binge or moderate alcohol exposure impairs host defense and increases susceptibility to infection because of compromised innate immune responses. However, there is a lack of consensus on the molecular mechanism by which alcohol mediates this immunosuppression. In this study, we show that cellular stress proteins HSF1 and hsp70 play a mechanistic role in alcohol-mediated inhibition of the TLR4/MyD88 pathway. Alcohol exposure induced transcription factor HSF1 mRNA expression and DNA binding activity in primary human monocytes and murine macrophages. Furthermore, HSF1 target gene hsp70 mRNA and protein are upregulated by alcohol in monocytes. In vitro pre-exposure to moderate alcohol reduced subsequent LPS-induced NF-κB promoter activity and downstream TNF-α, IL-6 and IL-1β production in monocytes and macrophages, exhibiting endotoxin tolerance. Mechanistic analysis demonstrates that alcohol-induced HSF1 binds to the TNF-α promoter in macrophages at early time points, exerting transrepression and decreased TNF-α expression. Furthermore, association of hsp70 with NF-κB subunit p50 in alcohol-treated macrophages correlates with reduced NF-κB activation at later time points. Hsp70 overexpression in macrophages was sufficient to block LPS-induced NF-κB promoter activity, suggesting alcohol-mediated immunosuppression by hsp70. The direct crosstalk of hsp70 and HSF1 was further confirmed by the loss of alcohol-mediated endotoxin tolerance in hsp70- and HSF1-silenced macrophages. Our data suggest that alcohol-mediated activation of HSF1 and induction of hsp70 inhibit TLR4-MyD88 signaling and are required for alcohol-induced endotoxin tolerance. Using stress proteins as direct drug targets would be clinically relevant in alcohol abuse treatment and may serve to provide a better understanding of alcohol-mediated immunosuppression. (Muralidharan S, Ambade A, Fulham MA, Deshpande J, Catalano D, Mandrekar P. J Immunol. 2014 193(4):1975-87.)
Chronic Alcohol Ingestion in Rats Alters Lung Metabolism, Promotes Lipid Accumulation, and Impairs Alveolar Macrophage Functions
Significance: Alcohol alters immune-specific host defenses, including alveolar macrophage function and damages barrier integrity of the surfactant layer and the epithelial layer in lungs leading to a higher incidence of pneumonia and acute respiratory distress syndrome. This publication reports that alcohol disrupts metabolism in the lung resulting in alteration in pulmonary immune function. Thus, two systems thought to be separate have been shown to act in concert, paralleling the effects of alcohol on liver. Metabolic signaling effecting changes in immune regulation provides support for crosstalk among cell types and biological mediators as a new avenue for alcohol lung research.
Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to inflammatory lung diseases, including infectious pneumonia and acute respiratory distress syndrome. While alcoholism has been shown to alter hepatic metabolism leading to lipid accumulation, hepatitis, and eventually cirrhosis, the effects of alcohol on pulmonary metabolism remain largely unknown. Because both the lung and the liver actively engage in lipid synthesis, we hypothesized that chronic alcoholism would impair pulmonary metabolic homeostasis in ways similar to effects in the liver. We reasoned that perturbations in lipid metabolism might contribute to the impaired pulmonary immunity observed in people who chronically consume alcohol. We studied the metabolic consequences of chronic alcohol consumption in rat lungs in vivo and in alveolar epithelial type II (AEII) cells and alveolar macrophages in vitro. We found that chronic alcohol ingestion significantly alters lung metabolic homeostasis, inhibiting AMP-activated protein kinase, increasing lipid synthesis, and suppressing expression of genes essential to metabolizing fatty acids. Further, we show that these metabolic alterations promoted a lung phenotype that is reminiscent of alcoholic fatty liver and is characterized by marked accumulation of triacylglycerides and free fatty acids within distal airspaces, alveolar macrophages, and to a lesser extent, AEII cells. We provide evidence that metabolic alterations in alcohol-exposed rats are mechanistically linked to immune impairments in the alcoholic lung: the elevations in fatty acids alter alveolar macrophage phenotypes and suppress both phagocytic functions and agonist-induced inflammatory responses. In summary, our work demonstrates that chronic alcohol ingestion impairs lung metabolic homeostasis and promotes pulmonary immune dysfunction. (Romero F, Shah D, Duong M, Stafstrom W, Hoek JB, Kallen CB, Lang CH, Summer R. Am J Respir Cell Mol Biol. 2014 Jun 18. [Epub ahead of print])
Rat Nucleus Accumbens Core Astrocytes Modulate Reward and the Motivation to Self-Administer Ethanol after Abstinence
Significance: This study shows that astrocytes in the Nucleus Accumbens Core (NAcC), a brain region that mediates responding for rewarding stimuli, regulates dependence induced ethanol consumption during a forced abstinence period in a rat model.
Our understanding of the active role that astrocytes play in modulating neuronal function and behavior is rapidly expanding, but little is known about the role that astrocytes may play in drug-seeking behavior for commonly abused substances. Given that the nucleus accumbens is critically involved in substance abuse and motivation, we sought to determine if nucleus accumbens astrocytes influence the motivation to self-administer ethanol following abstinence. We found that the packing density of astrocytes that were expressing glial fibrillary acidic protein increased in the nucleus accumbens core during abstinence from EtOH self-administration. No change was observed in the nucleus accumbens shell. This increased nucleus accumbens core astrocyte density positively correlated with the motivation for ethanol. Astrocytes can communicate with one another and influence neuronal activity through gap-junction hemichannels. Because of this, the effect of blocking gap-junction hemichannels on the motivation for ethanol was examined. The motivation to self-administer ethanol after 3 wks abstinence was increased following microinjection of gap-junction hemichannel blockers into the nucleus accumbens core at doses that block both neuronal and astrocytic channels. In contrast, no effect was observed following microinjection of doses that are not thought to block astrocytic channels or following microinjection of either dose into the nucleus accumbens shell. Additionally, the motivation for sucrose after 3 wks abstinence was unaffected by nucleus accumbens core gap-junction hemichannel blockers. Next, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were selectively expressed in nucleus accumbens core astrocytes to test the effect of astrocyte stimulation. DREADD activation increased cytosolic calcium in primary astrocytes, facilitated responding for rewarding brain stimulation, and reduced the motivation for ethanol after 3 wks abstinence. This is the first work to modulate drug-seeking behavior with astrocyte-specific DREADDs. Taken together, our findings demonstrate that nucleus accumbens core astrocytes can shape the motivation to self-administer ethanol; suggesting that the development of ligands which selectively stimulate astrocytes may be a successful strategy to abate ethanol-seeking behavior. (Bull C, Freitas KC, Zou S, Poland RS, Syed WA, Urban DJ, Minter SC, Shelton KL, Hauser KF, Negus SS, Knapp PE, Bowers MS. Neuropsychopharmacology. 2014 Jun 6 [Epub ahead of print])
Enhancement of Extinction Learning Attenuates Ethanol-Seeking Behavior and Alters Plasticity in the Prefrontal Cortex
Significance: This study demonstrates that a positive allosteric modulator of mGluR5, 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) or CDPPB, facilitates the extinction of ethanol seeking and attenuates cue-induced reinstatement. Extinction learning is associated with differential structural and functional plasticity in the prelimbic (PrL) and infralimbic (IfL) cortex. CDPPB treatment alters the extinction-induced changes in the glutamatergic activities in the IfL, suggesting that mGluR5 may serve as a potential therapeutic target in reducing relapse.
Addiction is a chronic relapsing disorder in which relapse is often initiated by exposure to drug-related cues. The present study examined the effects of mGluR5 activation on extinction of ethanol-cue-maintained responding, relapse-like behavior, and neuronal plasticity. Rats were trained to self-administer ethanol and then exposed to extinction training during which they were administered either vehicle or the mGluR5 positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) or CDPPB. CDPPB treatment reduced active lever responding during extinction, decreased the total number of extinction sessions required to meet criteria, and attenuated cue-induced reinstatement of ethanol seeking. CDPPB facilitation of extinction was blocked by the local infusion of the mGluR5 antagonist 3-((2-methyl-4-thiazolyl)ethynyl) pyridine into the infralimbic (IfL) cortex, but had no effect when infused into the prelimbic (PrL) cortex. Analysis of dendritic spines revealed alterations in structural plasticity, whereas electrophysiological recordings demonstrated differential alterations in glutamatergic neurotransmission in the PrL and IfL cortex. Extinction was associated with increased amplitude of evoked synaptic PrL and IfL NMDA currents but reduced amplitude of PrL AMPA currents. Treatment with CDPPB prevented the extinction-induced enhancement of NMDA currents in PrL without affecting NMDA currents in the IfL. Whereas CDPPB treatment did not alter the amplitude of PrL or IfL AMPA currents, it did promote the expression of IfL calcium-permeable GluR2-lacking receptors in both abstinence- and extinction-trained rats, but had no effect in ethanol-naive rats. These results confirm changes in the PrL and IfL cortex in glutamatergic neurotransmission during extinction learning and demonstrate that manipulation of mGluR5 facilitates extinction of ethanol cues in association with neuronal plasticity. (Gass JT, Trantham-Davidson H, Kassab AS, Glen WB Jr, Olive MF, Chandler LJ. J Neurosci. 2014 May 28; 34(22):7562-74)
MicroRNA-206 in Rat Medial Prefrontal Cortex Regulates Bdnf Expression and Alcohol Drinking
Significance: This elegant series of experiments demonstrates a causal link between an alcohol-responsive microRNA and escalated alcohol consumption in dependent rats.
Escalation of voluntary alcohol consumption is a hallmark of alcoholism, but its neural substrates remain unknown. In rats, escalation occurs following prolonged exposure to cycles of alcohol intoxication, and is associated with persistent, wide-ranging changes in gene expression within the medial prefrontal cortex (mPFC). Here, we examined whether induction of microRNA (miR) 206 in mPFC contributes to escalated alcohol consumption. Following up on a microarray screen, quantitative real-time reverse transcription PCR (qPCR) confirmed that a history of dependence results in persistent (>3weeks) up-regulation of miR-206 expression in the mPFC, but not in the ventral tegmental area, amygdala, or nucleus accumbens. Viral-mediated overexpression of miR-206 in the mPFC of nondependent rats reproduced the escalation of alcohol self-administration seen following a history of dependence and significantly inhibited BDNF expression. Bioinformatic analysis identified three conserved target sites for miR-206 in the 3'-UTR of the rat BDNF transcript. Accordingly, BDNF was downregulated in post-dependent rats on microarray analysis, and this was confirmed by qPCR. In vitro, BDNF expression was repressed by miR-206 but not miR-9 in a 3'-UTR reporter assay, confirming BDNF as a functional target of miR-206. Mutation analysis showed that repression was dependent on the presence of all three miR-206 target sites in the BDNF 3'-UTR. Inhibition of miR-206 expression in differentiated rat cortical primary neurons significantly increased secreted levels of BDNF. In conclusion, recruitment of miR-206 in the mPFC contributes to escalated alcohol consumption following a history of dependence, with BDNF as a possible mediator of its action. (Tapocik JD, Barbier E, Flanigan M, Solomon M, Pincus A, Pilling A, Sun H, Schank JR, King C, Heilig M. J Neurosci. 2014 Mar 26;34(13):4581-8).
Developmental Trajectories for Visuo-Spatial Attention are Altered by Prenatal Alcohol Exposure: A Longitudinal FMRI Study
Significance: This paper from the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD) reports on a longitudinal fMRI study assessing group differences in the change in brain-activation patterns in children and adolescents with FASD. Their findings reveal differences in cortical activation patterns for visuo-spatial attention in those with FASD at similar performance levels across samples of children recruited from three separate study sites in the U.S. and in South Africa. The unexposed control groups displayed an increase in signal intensity over time during visuo-spatial attention tasks while individuals with FASD showed a decrease in brain activation in the frontal, temporal and parietal brain regions further demonstrating the impact of prenatal alcohol exposure on developmental trajectories during late childhood and adolescence and suggesting a possible neural mechanism for attention deficits in children with FASD.
Functional magnetic resonance imaging (fMRI) reveals brain activation abnormalities during visuo-spatial attention and working memory among those with fetal alcohol spectrum disorders (FASD) in cross-sectional reports, but little is known about how activation changes over time during development within FASD or typically developing children. We studied 30 controls and 31 individuals with FASD over 2 years (7-14 years at first participation) with a total of 122 scans, as part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders. Despite comparable performance, there were significant group differences in visuo-spatial activation over time bilaterally in frontal, parietal, and temporal regions. Controls showed an increase in signal intensity in these multiple regions whereas FASD participants showed a decrease in brain activation. Effects were also found in 2 small independent samples from the USA, corroborating the findings from the larger group. Results suggest that the long-lasting effect of prenatal alcohol may impact the maturation of visuo-spatial attention and differentiate those with FASD from controls. Based on this first longitudinal fMRI study in FASD children, our novel findings suggest a possible neural mechanism for attention deficits common among individuals with FASD. (Gautam P, Nuñez SC, Narr KL, Mattson SN, May PA, Adnams CM, Riley EP, Jones KL, Kan EC, Sowell ER. Cereb Cortex. 2014 Aug 4. [Epub ahead of print])
Chronic Binge Alcohol Exposure During Pregnancy Impairs Rat Maternal Uterine Vascular Function
Significance: In a study examining fetal alcohol exposure on maternal uterine artery function, moderate prenatal alcohol results in impaired uterine artery vasodilation exposure in the absence of fetal growth deficiency. Chronic binge-like alcohol exposure in pregnant rats diminished endothelium-dependent acetylcholine (ACh)-mediated uterine artery vasodilation extending previous findings of alcohol’s negative impact on the maternal uterine vasculature and further supporting a role for its maladaptation in the etiology of FASD.
Alcohol exposure during pregnancy results in an array of structural and functional abnormalities called fetal alcohol spectrum disorders (FASD). Alcohol dysregulates the exquisite coordination and regulation of gestational adaptations at the level of the uterine vasculature. We herein hypothesized that chronic binge-like alcohol results in uterine vascular dysfunction and impairs maternal uterine artery reactivity to vasoconstrictors and dilators. METHODS: We utilized a once-daily binge alcohol (4.5 g/kg body weight) exposure paradigm (gestational day 7 to 17) in a pregnant rat model system and investigated primary uterine artery function in response to vasoconstrictors and vasodilators utilizing wire myography. RESULTS: Alcohol (peak blood alcohol concentration, 216 mg/dl) produced uterine vascular dysfunction. Alcohol did not produce altered uterine vascular reactivity to α1 adrenergic agonist phenylephrine or the prostanoid thromboxane. However, alcohol specifically impaired acetylcholine (ACh)-mediated uterine artery vasodilation but exogenous endothelium-independent vasodilators like sodium nitroprusside exhibited no alcohol effect; ACh significantly decreased vessel relaxation (p = 0.003; ↓pD2 [negative log molar ACh concentration producing the half maximum response], -7.004 ± 0.215 vs. -6.310 ± 0.208; EMax [maximal ACh response], 92% vs. 75%). CONCLUSIONS: We conclude that moderate alcohol exposure impairs uterine vascular function in pregnant mothers. Alcohol specifically impairs agonist-induced uterine artery vasodilation. In summary, the maternal uterine compartment may play a significant role in the pathogenesis of FASD. Thus, the mechanistic targets of alcohol at the level of both the mother and the fetus need to be considered in order to develop effective therapeutic treatment strategies for FASD. (Subramanian K, Naik VD, Sathishkumar K, Yallampalli C, Saade GR, Hankins GD, Ramadoss J. Alcohol Clin Exp Res. 2014;38:1832-8)
Gene Expression Signatures Affected by Alcohol-Induced DNA Methylomic Deregulation in Human Embryonic Stem Cells
Significance: This paper describes a useful model to study molecular mechanisms of human disorders that originate during gestation and adds new insights to alcohol’s effects on human embryonic stem cells and dental pump stem cells, from the perspectives of their DNA methylomic and transcriptomic changes.
Stem cells, especially human embryonic stem cells (hESCs), are useful models to study molecular mechanisms of human disorders that originate during gestation. Alcohol (ethanol, EtOH) consumption during pregnancy causes a variety of prenatal and postnatal disorders collectively referred to as fetal alcohol spectrum disorders (FASDs). To better understand the molecular events leading to FASDs, we performed a genome-wide analysis of EtOH's effects on the maintenance and differentiation of hESCs in culture. Gene Co-expression Network Analysis showed significant alterations in gene profiles of EtOH-treated differentiated or undifferentiated hESCs, particularly those associated with molecular pathways for metabolic processes, oxidative stress, and neuronal properties of stem cells. A genome-wide DNA methylome analysis revealed widespread EtOH-induced alterations with significant hypermethylation of many regions of chromosomes. Undifferentiated hESCs were more vulnerable to EtOH's effect than their differentiated counterparts, with methylation on the promoter regions of chromosomes 2, 16 and 18 in undifferentiated hESCs most affected by EtOH exposure. Combined transcriptomic and DNA methylomic analysis produced a list of differentiation-related genes dysregulated by EtOH-induced DNA methylation changes, which likely play a role in EtOH-induced decreases in hESC pluripotency. DNA sequence motif analysis of genes epigenetically altered by EtOH identified major motifs representing potential binding sites for transcription factors. These findings should help in deciphering the precise mechanisms of alcohol-induced teratogenesis. (Khalid O, Kim JJ, Kim HS, Hoang M, Tu TG1, Elie O, Lee C, Vu C, Horvath S, Spigelman I, Kim Y. PLoS One. 2014 Apr 4;9(4):e93510)
The Safe Passage Study: Design, Methods, Recruitment, and Follow-Up Approach
Significance: The Safe Passage Study is a major multi-site study of SIDS and stillbirth, which integrates prospectively collected exposure information with multidisciplinary biological information in the same maternal and fetal/infant dyad using a common protocol. Essential components of the study design and its success are close ties to the community and rigorous systems and processes to ensure compliance with the study protocol and procedures.
The Safe Passage Study is a large, prospective, multidisciplinary study designed to (1) investigate the association between prenatal alcohol exposure, sudden infant death syndrome (SIDS), and stillbirth, and (2) determine the biological basis of the spectrum of phenotypic outcomes from exposure, as modified by environmental and genetic factors that increase the risk of stillbirth, SIDS, and in surviving children, fetal alcohol spectrum disorders. METHODS: The results provided are based on an interim assessment of 6004 women enrolled, out of the 12 000 projected, from the Northern Plains, US, and Cape Town, South Africa, areas known to be of high risk for maternal drinking during pregnancy. Research objectives, study design, and descriptive statistics, including consent, recruitment, and retention information, are provided. RESULTS: Overall visit compliance is 87%, and includes prenatal, delivery/newborn, and postnatal contacts through 1 year post-delivery. Pregnancy outcome ascertainment is 98% prior to medical chart review; less than 2% of women withdraw. Consent for the use of DNA and placental tissue exceed 94%, and consent to participate in the autopsy portion of the study is 71%. (Dukes KA, Burd L, Elliott AJ, Fifer WP, Folkerth RD, Hankins GD, Hereld D, Hoffman HJ, Myers MM, Odendaal HJ, Signore C, Sullivan LM, Willinger M, Wright C, Kinney HC; PASS Research Network. Paediatr Perinat Epidemiol. 2014 Aug 5. doi: 10.1111/ppe.12136. [Epub ahead of print])
Paternal Alcohol Exposure Reduces Alcohol Drinking and Increases Behavioral Sensitivity to Alcohol Selectively in Male Offspring
Significance: This study has important implications for understanding the inheritance of vulnerability to alcoholism by demonstrating that paternal preconception alcohol exposure results in reduced ethanol preference/consumption and altered sensitivity to the anxiolytic and locomotor effects of ethanol in male offspring of ethanol-sired mice (ethanol-sired female mice do not show these behavioral changes).
Alcohol use disorder (AUD) is heritable, but the genetic basis for this disease remains poorly understood. Although numerous gene variants have been associated with AUD, these variants account for only a small fraction of the total risk. The idea of inheritance of acquired characteristics, i.e. "epigenetic inheritance," is re-emerging as a proven adjunct to traditional modes of genetic inheritance. We hypothesized that alcohol drinking and neurobiological sensitivity to alcohol are influenced by ancestral alcohol exposure. To test this hypothesis, we exposed male mice to chronic vapor ethanol or control conditions, mated them to ethanol-naïve females, and tested adult offspring for ethanol drinking, ethanol-induced behaviors, gene expression, and DNA methylation. We found that ethanol-sired male offspring had reduced ethanol preference and consumption, enhanced sensitivity to the anxiolytic and motor-enhancing effects of ethanol, and increased Bdnf expression in the ventral tegmental area (VTA) compared to control-sired male offspring. There were no differences among ethanol- and control-sired female offspring on these assays. Ethanol exposure also decreased DNA methylation at the BdnfÆpromoter of sire's germ cells and hypomethylation was maintained in the VTA of both male and female ethanol-sired offspring. Our findings show that paternal alcohol exposure is a previously unrecognized regulator of alcohol drinking and behavioral sensitivity to alcohol in male, but not female, offspring. Paternal alcohol exposure also induces epigenetic alterations (DNA hypomethylation) and gene expression changes that persist in the VTA of offspring. These results provide new insight into the inheritance and development of alcohol drinking behaviors. (Finegersh A, Homanics GE. PLoS One. 2014 Jun 4;9(6):e99078)
Adolescent Alcohol Exposure Reduces Behavioral Flexibility, Promotes Disinhibition, and Increases Resistance to Extinction of Ethanol Self-Administration in Adulthood
Significance: This study shows that alcohol exposure during adolescence produces deficits in executive function and loss of behavioral control in adulthood when no alcohol is present, and that administration of a positive allosteric modulator of mGluR5 reverses these deficits. Based on these findings, it was suggested that adolescent alcohol exposure promotes development of a behavioral phenotype in adulthood that is similar to the at-risk adolescent phenotype that has been proposed.
The prefrontal cortex (PFC) is a brain region that is critically involved in cognitive function and inhibitory control of behavior, and adolescence represents an important period of continued PFC development that parallels the maturation of these functions. Evidence suggests that this period of continued development of the PFC may render it especially vulnerable to environmental insults that impact PFC function in adulthood. Experimentation with alcohol typically begins during adolescence when binge-like consumption of large quantities is common. In the present study, we investigated the effects of repeated cycles of adolescent intermittent ethanol (AIE) exposure (postnatal days 28–42) by vapor inhalation on different aspects of executive functioning in the adult rat. In an operant set-shifting task, AIE-exposed rats exhibited deficits in their ability to shift their response strategy when the rules of the task changed, indicating reduced behavioral flexibility. There were no differences in progressive ratio response for the reinforcer suggesting that AIE did not alter reinforcer motivation. Examination of performance on the elevated plus maze under conditions designed to minimize stress revealed that AIE exposure enhanced the number of entries into the open arms, which may reflect either reduced anxiety and/or disinhibition of exploratory-like behavior. In rats that trained to self-administer ethanol in an operant paradigm, AIE increased resistance to extinction of ethanol-seeking behavior. This resistance to extinction was reversed by positive allosteric modulation of mGluR5 during extinction training, an effect that is thought to reflect promotion of extinction learning mechanisms within the medial PFC. Consistent with this, CDPPB was also observed to reverse the deficits in behavioral flexibility. Finally, diffusion tensor imaging with multivariate analysis of 32 brain areas revealed that while there were no differences in the total brain volume, the volume of a subgroup of regions (hippocampus, thalamus, dorsal striatum, neocortex, and hypothalamus) were significantly different in AIE-exposed adults compared with litter-matched Control rats. Taken together, these findings demonstrate that binge-like exposure to alcohol during early to middle adolescence results in deficits in PFC-mediated behavioral control in adulthood. (Gass JT, Glen WB, McGonigal JT, Trantham-Davidson H, Lopez MF, Randall PK, Yaxley R, Floresco SB, Chandler, LJ. Neuropsychopharmacology 2014 [Epub ahead of print])
Economic Contraction, Alcohol Intoxication and Suicide: Analysis of the National Violent Death Reporting System
Significance: Alcohol intoxication among suicide decedents increased after the start of the 2008–2009 economic downturn, with male suicide decedents’ risk of intoxication rising immediately after the start of the downturn while female suicide decedents experienced a delayed effect in their risk of alcohol intoxication.
Although there is a large and growing body of evidence concerning the impact of contracting economies on suicide mortality risk, far less is known about the role alcohol consumption plays in the complex relationship between economic conditions and suicide. The aims were to compare the postmortem alcohol intoxication rates among male and female suicide decedents before (2005-2007), during (2008-2009) and after (2010-2011) the economic contraction in the USA. METHODS: Data from the restricted National Violent Death Reporting System (2005-2011) for male and female suicide decedents aged 20 years and older were analysed by Poisson regression analysis to test whether there was significant change in the fractions of suicide decedents who were acutely intoxicated at the time of death (defined as blood alcohol content ≥0.08 g/dL) prior, during and after the downturn. RESULTS: The fraction of all suicide decedents with alcohol intoxication increased by 7% after the onset of the recession from 22.2% in 2005-2007 to 23.9% in 2008-2011. Compared with the years prior to the recession, male suicide decedents showed a 1.09-fold increased risk of alcohol intoxication within the first 2 years of the recession. Surprisingly, there was evidence of a lag effect among female suicide decedents, who had a 1.14-fold (95% CI 1.02 to 1.27) increased risk of intoxication in 2010-2011 compared with 2005-2007. CONCLUSIONS:
These findings suggest that acute alcohol intoxication in suicide interacts with economic conditions, becoming more prevalent during contractions. (Kaplan MS, Huguet N, Caetano R, Giesbrecht N, Kerr WC, McFarland BH. Inj Prev. 2014 Jul 14 [Epub ahead of print])
Racial/Ethnic Disparities in Alcohol-Related Problems: Differences by Gender and Level of Heavy Drinking
Significance: Findings from this study suggest that compared with white men, black and Hispanic men have higher rates of injuries/accidents/health and social consequences related to alcohol; and Hispanic women have slightly higher social consequences than white women. Further, minorities also had greater odds of alcohol-related problems and/or alcohol dependence in models that adjusted for demographics and alcohol content. Compared with whites, black women had greater odds of dependence at all levels of heavy drinking, while both black and Hispanic men had elevated risk of alcohol problems only at lower levels of heavy drinking. Current interventions are not likely to address gender specific alcohol-related disparities nor do they address alcohol-related problems that occur at low levels of heavy drinking.
While prior studies have reported racial/ethnic disparities in alcohol-related problems at a given level of heavy drinking (HD), particularly lower levels, it is unclear whether these occur in both genders and are an artifact of racial/ethnic differences in drink alcohol content. Such information is important to understanding disparities and developing specific, targeted interventions. This study addresses these questions and examines disparities in specific types of alcohol problems across racial-gender groups. METHODS: Using 2005 and 2010 National Alcohol Survey data (N = 7,249 current drinkers), gender-stratified regression analyses were conducted to assess black-white and Hispanic-white disparities in alcohol dependence and negative drinking consequences at equivalent levels of HD. HD was measured using a gender-specific, composite drinking-patterns variable derived through factor analysis. Analyses were replicated using adjusted-alcohol consumption variables that account for group differences in drink alcohol content based on race/ethnicity, gender, age, and alcoholic beverage. RESULTS: Compared with white men, black and Hispanic men had higher rates of injuries/accidents/health and social consequences, and marginally greater work/legal consequences (p < 0.10). Hispanic women had marginally higher rates of social consequences. In main effects models controlling for demographics, light drinking and HD, only black women and men had greater odds of alcohol-related problems relative to whites. Interaction models indicated that compared with whites, black women had greater odds of dependence at all levels of HD, while both black and Hispanic men had elevated risk of alcohol problems only at lower levels of HD. Drink alcohol content adjustments did not significantly alter findings for either gender.
CONCLUSIONS: This study highlights the gender-specific nature of racial/ethnic disparities. Interventions focused on reducing HD might not address disparities in alcohol-related problems that exist at low levels of HD. Future research should consider the potential role of environmental and genetic factors in these disparities. (Witbrodt, J, Mulia, N, Zemore, SE, Kerr, WC. Alcohol Clin Exp Res. 2014 Jun; 38(6):1662-70)
A Moderating Role for Gender in Racial/Ethnic Disparities in Alcohol Services Utilization
Significance: Findings suggest lower alcohol service utilization among Latinos and Blacks compared to Whites, and women compared to men, with the strongest evidence of disparities between the minority groups and Whites occurring among women. The evidence also suggested that social influence factors contribute to gender disparities, particularly among Whites and Blacks.
Few nationally representative studies have examined racial/ethnic disparities in alcohol services utilization. Further, little is known about whether racial/ethnic disparities generalize across genders, and what factors account for these disparities. Thus, we aimed to describe the combined impact of race/ethnicity and gender on alcohol services utilization, and to explore the roles for social influence factors in explaining racial/ethnic and gender disparities. METHODS: Data were pooled across the 2000, 2005, and 2010 National Alcohol Surveys. Outcomes included lifetime utilization of any services, specialty alcohol treatment, and Alcoholics Anonymous. Social influence factors were assessed as lifetime social pressures (i.e., pressures from a partner, friends, and/or family), legal consequences, and work-related consequences. Core analyses included only those with a lifetime alcohol use disorder (AUD). RESULTS: Analyses revealed a pattern of lower services utilization among Latinos and Blacks (vs. Whites) and women (vs. men); further, race-by-gender interactions revealed that Black-White differences were limited to women, and provided some evidence of stronger Latino-White disparities among women (vs. men). Illustrating these patterns, among women, only 2.5% of Latinas and 3.4% of Blacks with a lifetime AUD accessed specialty treatment, versus 6.7% of Whites; among men, corresponding figures were 6.8% for Latinos, 12.2% for Blacks, and 10.1% for Whites. Racial/ethnic differences were typically robust (or stronger) when controlling for demographics and AUD severity. Evidence did not support a role for measured social influence factors in racial/ethnic disparities, but did suggest that these factors contribute to gender disparities, particularly among Whites and Blacks. CONCLUSIONS: Findings for substantial Latino-White and Black-White disparities, especially among women, highlight the need for continuing research on explanatory factors and the development of appropriate interventions. Meanwhile, our evidence for persistent gender disparities and for social influence factors as drivers of these disparities tentatively suggests a need for intensified outreach to female heavy drinkers. (Zemore SE, Murphy, RD, Mulia N, Gilbert PA, Martinez P, Bond J, Polcin DL. Alcohol Clin Exp Res. 2014 Aug;38(8):2286-96)
The Resting Brain of Alcoholics
Significance: This study used an innovative analysis to show the vulnerability to alcohol of several of the resting state or intrinsic networks identified in the human brain. This study provides a novel mechanism to understand functional deficits in alcohol dependence.
Chronic alcohol consumption affects multiple cognitive processes supported by far-reaching cerebral networks. To identify neurofunctional mechanisms underlying selective deficits, 27 sober alcoholics and 26 age-matched controls underwent resting-state functional magnetic resonance imaging and neuropsychological testing. Functional connectivity analysis assessed the default mode network (DMN); integrative executive control (EC), salience (SA), and attention (AT) networks; primary somatosensory, auditory, and visual (VI) input networks; and subcortical reward (RW) and emotion (EM) networks. The groups showed an extensive overlap of intrinsic connectivity in all brain networks examined, suggesting overall integrity of large-scale functional networks. Despite these similar patterns, connectivity analyses identified network-specific differences of weaker within-network connectivity and expanded connectivity to regions outside the main networks in alcoholics compared with controls. For AT and VI networks, better task performance was related to expanded connectivity in alcoholism, supporting the concept of network expansion as a neural mechanism for functional compensation. For default mode, SA, RW, and EC networks, both weaker within-network and expanded outside-network connectivity correlated with poorer performance and mood. Current smoking contributed to some of these abnormalities in connectivity. The observed pattern of resting-state connectivity might reflect neural vulnerability of intrinsic networking in alcoholics and suggests a mechanism to explain signature impairments in EM, RW evaluation, and EC ability. (Müller-Oehring EM, Jung Y-C, Pfefferbaum A, Sullivan EV, Schulte T, Cerebral Cortex [Epub ahead of print June 16, 2014])
Intravenous Ghrelin Administration Increases Alcohol Craving in Alcohol-Dependent Heavy Drinkers: A Preliminary Investigation
Significance: Intravenous administration of exogenous ghrelin increased alcohol craving in alcohol-dependent heavy-drinking individuals. These findings provide preliminary evidence that ghrelin may play a role in the neurobiology of alcohol craving, thus demonstrating a novel pharmacologic target for treatment.
There is a need to identify novel pharmacologic targets to treat alcoholism. Animal and human studies suggest a role for ghrelin in the neurobiology of alcohol dependence and craving. Here, we were the first to test the hypothesis that intravenous administration of exogenous ghrelin acutely increases alcohol craving. METHODS: This was a double-blind, placebo-controlled human laboratory proof-of-concept study. Nontreatment-seeking, alcohol-dependent, heavy-drinking individuals were randomized to receive intravenous ghrelin 1 mcg/kg, 3 mcg/kg or 0 mcg/kg (placebo), followed by a cue-reactivity procedure, during which participants were exposed to neutral (juice) and alcohol cues. The primary outcome variable was the increase in alcohol craving (also called urge) for alcohol, assessed by the Alcohol Visual Analogue Scale. RESULTS: Out of 103 screenings, 45 individuals received the study drug. Repeated measures of analysis of covariance revealed a group effect across ghrelin doses in increasing alcohol craving (p < .05). A dose-specific examination revealed a significant effect of ghrelin 3 mcg/kg versus placebo in increasing alcohol craving (p < .05) with a large effect size (d = .94). By contrast, no significant ghrelin effect was found in increasing either urge to drink juice or food craving (p = ns). No significant differences in side effects were found (p = ns). CONCLUSIONS: Intravenous administration of exogenous ghrelin increased alcohol craving in alcohol-dependent heavy-drinking individuals. Although the small sample requires confirmatory studies, these findings provide preliminary evidence that ghrelin may play a role in the neurobiology of alcohol craving, thus demonstrating a novel pharmacologic target for treatment. (Leggio L, Zywiak WH, Fricchione SR, Edwards SM, de la Monte SM, Swift RM, and Kenna GA. Biol Psychiatry online. 2014 Mar 25. pii: S0006-3223(14)00220-0)
Treatment for Alcohol Problems: Finding and Getting Help
In an effort to expand informational resources for patients and the general public, NIAAA has released a new booklet summarizing treatment options for those who struggle with alcohol problems. It is intended as a resource for the public to understand what treatment choices are available and what to consider when selecting among them. The booklet addresses behavioral treatment options, FDA-approved medications for alcohol dependence, and tips for selecting a provider or program. “Treatment for Alcohol Problems: Finding and Getting Help” will be available online and in print, and NIAAA has developed a promotion plan to publicize the booklet.
College Fall Semester
For its fall seasonal outreach efforts, NIAAA focused on “college heavy” areas in the Southeast, Midwest, and West Coast. In conjunction with the start of the college fall semester, NIAAA placed eight highway billboards in the Los Angeles, Chicago, and Raleigh-Durham/Greenville, North Carolina areas. The billboards, aimed at reminding parents about the consequences of college drinking and the importance of having discussions with their college-bound students, had an estimated potential adult audience of 5,762,159 people.
NIAAA also disseminated its fact sheet titled, “Fall Semester—A Time for Parents to Revisit Discussions About College Drinking” to the media through PR Newswire on August 20 and 25, 2014. The fact sheet was posted by Internet news outlets such as Yahoo!, Reuters, The Boston Globe, and the Miami Herald, as well as business journals, industry publications, and local affiliates of major television networks (FOX, NBC, CBS, ABC) nationwide. The release had a total of 296 media links, representing a total potential audience of 57,620,000 people.
Caption: Highway billboards aimed at reminding parents about the consequences of college drinking appeared in the Southeast, Midwest, and West Coast before the start of the fall semester
Al-Anon Podcast with Dr. Koob
Dr. George Koob was interviewed in September for a podcast by Al-Anon Family Groups, a member of the NIAAA liaison organization community. Dr. Koob discussed the devastating impact that alcohol use disorder can have on a drinker’s family and friends, the effectiveness of today’s treatment options, and the important role that support groups can play. The podcast is posted on the Al-Anon web site, www.al-anon.org.
For the summer safety installment of the seasonal outreach series, NIAAA disseminated its fact sheet titled “Risky Drinking Can Put a Chill on Your Summer Fun” to the media through PR Newswire on June 16 and 30, 2014. The fact sheet was posted by Internet news outlets such as Yahoo!, Reuters, and Market Watch, as well as business journals, industry publications, and numerous major television network (FOX, NBC, CBS, ABC) local affiliates nationwide. Collectively, the releases had a total of 220 media links, representing a total potential audience of 55,427,000 people.
This summer NIAAA shifted its popular East Coast billboard campaign to the West Coast. During July 2014, NIAAA placed five highway billboards in high-traffic areas around San Diego, reminding summer vacationers to avoid risky drinking. The billboards had a potential audience (based on traffic patterns) of 3,336,384 people. Previous analysis showed that East Coast billboards helped increase traffic to NIAAA’s Rethinking Drinking website; the results of the West Coast signs are currently being evaluated.
In other efforts, summer intern Kaitlyn Corey (granddaughter of former NIAAA Director T-K Li), worked with the outreach team in NIAAA’s Communications and Public Liaison Branch (CPLB) to place a billboard in Durham, North Carolina. The co-branded summer billboard was a collaboration between NIAAA and the Together for Resilient Youth (TRY) coalition.
In an expansion of the summer seasonal outreach series, CPLB added proactive news outreach to the existing efforts. As a result, prior to the July 4th holiday, NIAAA Director Dr. George Koob conducted an exclusive interview with the Associated Press. For more details, see the section on recent news media interviews below. A total of 475 news outlets—radio, TV, print, and online in major markets (including ABC News, NBC News, NPR, and Huffington Post) carried the story between July 3 and 7, with a total potential audience of 449,354,797 people. Daily traffic to the Rethinking Drinking website increased by 255% during that time frame.
Fetal Alcohol Spectrum Disorder Awareness Day & Twitter Chat
To recognize FASD Awareness Day, celebrated on September 9, NIAAA issued a news announcement, tweeted informational messages, and ran a carousel graphic (pictured below). The image was also pitched for placement in national news outlets and health magazines. People.com ran NIAAA's web banner at no charge from Friday, September 5 through Tuesday, September 9. Additionally, Parent.com indicated they would cover the topic of FASD on the Parents Perspective blog on September 9. Prenatal alcohol exposure is the leading preventable cause of birth defects and developmental disorders in the United States, and may affect as many as 2 to 5 percent of children.
In addition, as part of its social media activities, NIAAA also hosted a Twitter chat on FASD with the National Organization on Fetal Alcohol Syndrome (NOFAS). Deputy Director Kenneth Warren served as the chat’s scientific expert.
Carousel Image for Fetal Alcohol Spectrum Disorders Awareness Day (Sept. 9)
Graduation Seasonal Outreach
Continuing the popular seasonal outreach series, NIAAA disseminated its fact sheet titled “Parents: Help Your Teens Party Right After Graduation” to the media through PR Newswire in May. The fact sheet was posted by Internet news outlets such as Yahoo!, The Sacramento Bee, The Boston Globe, and the Miami Herald, as well as business journals, industry publications, and numerous major television network (FOX, NBC, CBS, ABC) local affiliates nationwide. The release had a total of 289 media links, representing a total potential audience of 56,839,000 people.
Updated Facts and Statistics Sheet
After a lengthy development process, NIAAA recently revised and expanded its Alcohol Facts and Statistics information sheet. This important document, which will be regularly updated, contains the latest alcohol-related statistical information, covering a variety of subject areas: (www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/alcohol-facts-and-statistics)
The NIAAA Spectrum is published three times a year in conjunction with Council, where a limited supply of printed copies are distributed. NIAAA Spectrum is also available online at www.spectrum.niaaa.nih.gov and a link to the webzine is emailed to all NIAAA grantees.
The current issue of Alcohol Alert: Measuring the Burden of Alcohol, along with the corresponding issue of the NIAAA journal, Alcohol Research: Current Reviews, presents a comprehensive picture of alcohol’s influence on health, social life, and economics.
NIAAA Information on the NIH Campus
At the request of NIH, NIAAA contributed a framed poster the cover of “Make A Difference: Talk to Your Child About Alcohol” as part of an effort to bring the Institutes’ messaging to the NIH visitors and staff. This design was selected by a panel of NIH communications and policy executives.
As of August 6, there were 28,337 subscribers to the Alcohol Alert; 27,237 to Alcohol Research: Current Reviews; 17,907 to the Spectrum; and 17,752 to receive general information.
NIAAA exhibited at the following scientific meetings:
- The American Association of Nurse Practitioners 2014 National Conference in Nashville, TN, June 19-21, 2014.
- The Research Society on Alcoholism 2014 Scientific Meeting in Bellevue, WA, June 21-25, 2014
- The American Psychological Association Meeting in Washington, DC, August 7-10, 2014
RECENT NEWS MEDIA INTERVIEWS
Dr. George Koob was interviewed by Lauran Neergaard, an Associated Press (AP) science and health reporter, about the amount of alcohol in popular summer cocktails. As a result, the AP released a story and accompanying infographic on July 3.
Dr. Koob also gave numerous interviews to representatives of national and international news media on a number of timely topics related to NIAAA’s research and its impact on treatment and prevention of alcohol abuse and alcohol use disorders. These include interviews with the New York Times, Washington Post, Wall Street Journal, and CNN.
NIAAA division directors and other NIAAA experts were also frequent sources of information for reporters from a broad range of domestic and international news organizations.