Friday, February 12, 2016

Table of Contents

• NIAAA BUDGET
• LEGISLATIVE NEWS
• COLLABORATIVE RESEARCH ON ADDICTION AT NIH UPDATE
• DIRECTOR'S ACTIVITIES
• STAFF TRANSITIONS
• HONORS AND AWARDS
• NEW REQUESTS FOR APPLICATIONS AND PROGRAM ANNOUNCEMENTS
• NOTABLE NIAAA STAFF ACTIVITIES
• WHAT'S AHEAD
• NIH RESEARCH HIGHLIGHTS
• NIAAA COMMUNICATIONS ACTIVITIES

 
NIAAA BUDGET

FY 2015

 NIAAA closed out fiscal year (FY) 2015 on September 30, 2015; the final appropriation for NIAAA was $447.2 million. A summary of key funding actions within this appropriation is as follows: 

• NIAAA awarded 668 research project grants (RPGs), including 156 competing awards, which corresponds to a success rate of 18 percent. 
• NIAAA funded 18 research centers for $28.0 million.
• NIAAA funded 135 other research grants for $37.2 million, including career awards, one cooperative clinical agreement, and several resource and conference grant awards.
• NIAAA supported 277 full-time training positions for $12.7 million.
• NIAAA funding for its research and development contract portfolio was $36.6 million.
• NIAAA support for intramural research totaled $49.5 million.

FY 2016

The Consolidated Appropriations Act, 2016 (H.R. 2029) was signed into law on December 18, 2015, funding NIH with a total of $32.3 billion, $2 billion above the FY 2015 enacted level.  In addition to providing a general increase to all NIH Institutes and Centers (ICs), the bill fully funds the Precision Medicine Initiative, continues support for the Gabriella Miller Kids First Act Pediatric Research Program, and includes specific increases for Alzheimer’s disease research, brain research, and antibiotic research.

 The FY 2016 appropriation for NIAAA provides $467.7 million. This represents a $20.5 million or 4.9 percent increase over the FY 2015 budget level. The NIAAA appropriation includes $2.7 million set aside for the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. NIAAA estimates it will support a total of 684 RPGs in FY 2016, including 173 competing awards.

FY 2017

Preliminary work on the budget for FY 2017 has begun. After intermediate stages of review, the President’s budget request will be presented to Congress in February 2016, at which time it will become available to the public.

*FY 2016 budget excludes the $255K AIDS transfer

LEGISLATIVE NEWS

21^st Century Cures Initiative

Led by Rep. Fred Upton, Chairman of the House Energy and Commerce Committee, the goal of this initiative is to enhance and accelerate the discovery, development, and delivery of new treatments and cures. On July 10, 2015, the House passed the bill, which designated $8.75 billion for NIH and $550 million for the U.S. Food and Drug Administration (FDA) over five years. A Senate version of the bill is yet to be released.
 

 COLLABORATIVE RESEARCH ON ADDICTION AT NIH (CRAN) UPDATE
 

 Joint Review of Training Grants

To functionally integrate Institutional National Research Service Award Research Training at NIAAA and the National Institute on Drug Abuse (NIDA), a single special emphasis panel will be set up each year to review germane applications received by the two ICs in response to the parent notice of funding opportunities (NOFOs) (PAR-14-015 (T32) and PA-14-016 (T35)). The panels will be jointly managed by staff from NIAAA and NIDA to ensure that appropriate expertise is involved to review the breadth of research training proposed in the applications. The first set of applications to be reviewed in this manner will be those submitted for the May 25, 2016, (non-AIDS) and September 7, 2016, (AIDS) receipt dates.

 ABCD Study

A major focus of CRAN from September-January has been the start-up of the longitudinal Adolescent Brain Cognitive Development Study (ABCD). The ABCD Study is the largest long-term study of cognitive and brain development in children across the United States to date. The project will recruit 10,000 healthy children ages 9 to 10, before they initiate alcohol or other drug use, and follow them through the period of highest risk for substance use and other mental health disorders (ten years). Scientists will track exposure to substances (including nicotine, alcohol, and marijuana), academic achievement, cognitive skills, mental health, and brain structure and function using state of the art research methods. Awards were made to the coordinating Center (University of California, San Diego, (UCSD)), Data Analysis and Informatics Center (UCSD), and 11 sites across the United States. In addition, NIH staff collaborators, Drs. Antonio Noronha and John Matochik (NIAAA), and Dr. Kevin Conway (NIDA) were named, and a project manager, Dr. Gaya Dowling, was hired. An operations group consisting of Drs. Susan Weiss and Gaya Dowling from NIDA, Dr. Peggy Murray from NIAAA, Drs. Terry Jernigan, Sandra Brown, and Susan Tapert from the UCSD Coordinating Center, and Drs. Hugh Garavan and Anders Dale from the UCSD Data Analytics and Informatics Center, as well as a Steering Committee made up of study leaders and NIH collaborators, has been formed to lead and coordinate the collaboration.

 The first meeting of ABCD investigators and NIH staff collaborators took place in Chicago, Illinois, on October 22–23, 2015, in conjunction with the Society for Neuroscience (SfN) annual meeting. Given the large, multisite structure of the project, a number of standing committees, advisory groups (such as a Community Advisory Council), and working groups made up of study site staff, outside experts, and NIH subject area experts have been formed and begun meeting to work on issues related to study start-up and implementation. These issues include such areas as bioethics and medical oversight, study design and biostatistics, substance use assessment, neurocognition assessment, brain image acquisition and analysis, mobile technologies for assessment, informatics, culture and environment, and resource sharing and publication. The External Advisory Board, chaired by Dr. Michael Charness, has been named and had their first teleconference with ABCD leadership in December 2015 and first face to face meeting January 14–15, 2016. Protocols are being developed and pilot-tested, and are expected to be ready for initial recruitment efforts at schools in the summer of 2016, with full-blown recruitment at all sites by fall 2016.

 Strategic Plan

Other CRAN activities include the development of a strategic plan which describes the nature of collaborative research and topic areas of joint priority for NIAAA, NIDA, and the National Cancer Institute (NCI). As the plan is developed, attention is being paid to how it fits into the updated strategic plans of NIAAA, NIDA, and NCI.

Notice of Funding Opportunities (NOFOs)

Workgroups are being formed with membership from NIAAA, NIDA, and NCI to develop NOFOs in areas such as health services research; bi-directional basic to clinical to epidemiological translational studies of polysubstance use and abuse; and target assessment, engagement and data replicability to improve substance use disorders treatment outcomes.
 

DIRECTOR’S ACTIVITIES

NIAAA’s Director, Dr. George Koob, made a number of notable presentations during October through December 2015.:  

• He spoke at the October 2, 2015, Institute of the Americas Workshop: Gangs, Youths and Demand Reduction in San Diego, California. The title of this presentation was “Fighting Drugs with Drugs: Neurobiology Advances against Addiction.” 
• He spoke at the California Society on Addiction Medicine in San Francisco, California on October 22, 2015. His presentation was titled, “How does Science Inform Diagnosis Prevention, Treatment of Alcoholism.” 
• He was a featured speaker at an October 27, 2015, congressional briefing titled, “CollegeAIM: Evidence-based strategies for targeting high-risk drinking on college campuses.” The briefing was sponsored by the Friends of NIAAA in cooperation with the Congressional Addiction, Treatment, and Recovery Caucus.  
• He spoke at the American Association for the Study of Liver Diseases (AASLD) on November 16, 2015, in San Francisco, California. The subject of his talk was “The Concept of Addiction and the Impact on Clinical Practice.” 
• He delivered the T.K. Li Distinguished Lecture at Duke University in Durham, North Carolina, on November 18, 2015. The title of his lecture was “Alcoholism as a Stress Surfeit Disorder.” 
• He spoke at the annual meeting of the American College of Neuropsychopharmacology in Hollywood, Florida, on December 6, 2015, providing an “Update on Research on Alcohol Use Disorders at NIAAA,” and again on December 8, 2015, providing a workshop summary of the NIAAA/NIDA INSERM (French Institute of Health and Medical Research) Study Group.
•  He gave a plenary talk for the students at the 2015 Summer Program in Neuroscience, Ethics, & Survival Neuroscience Symposium, held in conjunction with the Society for Neuroscience (SfN) annual meeting (October 16–21, 2015).
   

 STAFF TRANSITIONS
 

Mohammed Akbar, Med. Sc.D., joined the Division of Metabolism and Health Effects (DMHE) as a Program Officer in August, 2015. Trained as a Physiologist and Cell Biologist, he focuses on the pharmacological and toxicological aspects of alcoholic liver disease and alcohol-induced tissue injury. Before joining DMHE as a Program Officer, Dr. Akbar was a Staff Scientist in the Laboratory of Molecular Signaling at NIAAA, where he was engaged in studying non-alcoholic and alcohol-induced liver diseases, dietary supplements, oxidative stress, and metabolic syndrome. Prior to joining NIAAA in 1998, he worked as a Research Scientist at the Chugai Research Institute for Molecular Medicine in Japan.

Balazs Nemeth, M.D., joined the Laboratory of Cardiovascular Physiology and Tissue Injury as an NIH Graduate Student (Special Volunteer) in January 2016. He is a Ph.D. student at Semmelweis University, Heart and Vascular Center. His stay at NIH is sponsored by a prestigious Fellowship from CIEE (Center for International Educational Exchange).

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Janos Paloczi, Ph.D., joined the Laboratory of Cardiovascular Physiology and Tissue Injury as Visiting Research Scientist on August 17, 2015. He received his Ph.D. in Theoretical Medical Sciences at the University of Szeged, Hungary, (summa cum laude) in 2015.

Grace Tato comes to the Administrative Services Branch, NIAAA from NCI where she served as an Administrative Officer for the Division of Extramural Activities. She also has experience as a Committee Management Specialist at NCI. She has a wealth of knowledge in the extramural community as she first started as an Extramural Support Assistant. She earned her bachelor’s degree in Environmental Studies from the University of Maryland, Baltimore County. Grace enjoys spending her spare time outdoors with her husband and two dogs, as well as volunteering at the local animal shelter.

Christie Cunningham-Charles comes to the Administrative Services Branch, NIAAA from NCI where she served as an Administrative Officer in the Center for Cancer Research. She was also an Administrative Officer with the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Previously, she was an Administrative Technician with the Office of the Director (OD). She brings with her an abundance of administrative knowledge of the intramural program. She has earned her bachelor’s degree in Criminology and Criminal Justice from the University of Maryland. In her spare time, Christie enjoys spending time with her husband and two children, as well as reading a good book.
 

 Retired

 Dr. Kenneth R. Warren retired in October 2015 after 41 years of federal service, 39 of them at NIAAA. Following his graduate and postdoctoral training in biochemistry, Dr. Warren joined the Walter Reed Army Institute for Research where he focused on metabolic control mechanisms, including birth defects involving metabolic problems. In 1976, Dr. Warren joined NIAAA, where he turned his attention to seminal reports about a newly-described condition known as fetal alcohol syndrome (FAS). Recognizing its public health ramifications, Dr. Warren pioneered NIAAA’s support for FAS research. Dr. Warren’s early passion for FAS studies yielded groundbreaking results. In 1977, he authored the first U.S. Government health advisory on alcohol and pregnancy, and in 1981 he was the chief architect of the Surgeon General’s Advisory on Alcohol Use in Pregnancy—the advisory that brought about the now-familiar warning labels on alcoholic beverage containers. In recognition of his critical role, Dr. Warren received the Public Health Service’s Superior Service Award in 1982. He also helped to develop the updated advisory issued in 2005. 

 During his NIAAA career, Dr. Warren held many leadership roles, first as Branch Chief and then Deputy Director of the former Division of Extramural Research. Later he was Director of the Office of Scientific Affairs as well as Executive Secretary of the Institute’s National Advisory Council. Most recently, he was NIAAA Deputy Director for 7 years. He also served as NIAAA Acting Director for more than 5 years. During that time, Dr. Warren was instrumental in guiding NIAAA during the launch of a major NIH initiative: the Collaborative Research on Addiction at NIH, or CRAN. Dr. Warren received the NIH Director’s Award in 2014 for “outstanding and sustained service to the National Institutes of Health and commitment to alcohol and addictions research.” Dr. Warren has also received numerous honors from the wider alcohol research community including the 1996 Seixas Award from the Research Society on Alcoholism (RSA) and the 2002 Henry Rosett Award from RSA’s Fetal Alcohol Syndrome Study Group. In 2007, the National Organization on Fetal Alcohol Syndrome (NOFAS) inducted Dr. Warren into its Tom and Linda Daschle FASD Hall of Fame, and in 2008 he received the NOFAS Excellence Award. In 2014, Dr. Warren was honored with the RSA Lifetime Achievement Award.

Dr. Ellen Witt joined NIAAA in 1989 and served as Deputy Director of the Division of Neuroscience and Behavior (DNB) since 2008. She came to NIAAA from St. Elizabeth’s Hospital in Washington, D.C., where she was the Clinical Neuropsychologist in the Acute Care Hospital. Prior to that, she was a Research Psychologist in the Clinical Neuropsychology Section in the intramural program of the National Institute on Neurological Disorders and Stroke (NINDS).

After joining NIAAA, Dr. Witt developed many initiatives on the etiology and consequences of alcohol use disorder (AUD), including the areas of behavioral genetics, cognitive and behavioral neuroscience, sleep, and developmental psychobiology. She had a special interest in the effects of adolescent drinking on brain development and spearheaded many initiatives in that area. Most recently she was Staff Collaborator on the National Consortium on Alcohol and Neurobiological Development in Adolescence (N-CANDA), a multisite longitudinal study examining the impact of drinking on adolescent brain development, which is supported by multiple Institutes. In 2005, Dr. Witt received the Meritorious Research Service Commendation from the American Psychological Association and the Board of Scientific Affairs for outstanding contributions to psychological science through service within the federal government in program development and research facilitation. Most recently, she has participated in several trans-NIH initiatives, such as the NIH Toolbox, the NIH Basic Behavioral and Social Science Opportunities Network, and the Trans-NIH Sleep Research Coordinating Committee.

 
Debbie Hendry joined the NIAAA Grants Management Branch (GMB) as a grants management specialist in 1998. She quickly became an invaluable member of the Grants Management team earning the respect of the extramural research community, NIAAA staff, and the NIH-wide grants management community. Ms. Hendry was instrumental in developing effective new internal procedures at NIAAA that benefited all of GMB staff. She was also active on numerous committees and workgroups that serve the greater NIH grants management community.

HONORS AND AWARDS

Dr. Beata Buzas was awarded the NIH/OD Honor Award as part of the NIH Vertebrate Animal Section Update Workgroup on October 22, 2015.

 Dr. Resat Cinar was awarded a 2-year competitive grant from the American Thoracic Association on December 16, 2015, to study the therapeutic potential of a novel antifibrotic medication (see Laboratory of Physiologic Studies entry under Notable NIAAA Staff Activities) to treat a rare and usually fatal disease: Hermansky-Pudlak syndrome with pulmonary fibrosis.

 Dr. Mehdi Farokhnia received a 2015 American Society of Clinical Psychopharmacology (NCDEU) New Investigator Award, a 2015 Japan Neuroscience Society/SfN Exchange Travel Award, and a 2015 NIDA-International Society of Addiction Medicine (ISAM) Fellowship for Young Investigators.

 At the 2015 ISAM, Dr. Mehdi Farokhnia was presented by the ISAM Scientific Program Committee Award as the winner of the abstract with the highest rating for international scientific merit.

 Dr. Bob Freeman received the NIH 2015 Director’s Award on November 16 as a member of the NIH Sexual and Gender Minority Research Coordinating Committee.

 Drs. Peggy Murray, Kenneth Warren, Antonio Noronha, and John Matochik received the NIH Director’s award on September 24, 2015, in recognition of their work on the NIH team that developed, implemented, and awarded the grants for the ABCD Study.

 Dr. Pal Pacher received the prestigious title of Doctor Honoris Causa, from Semmelweis University, Budapest, on November 18, 2015. The award originated at the University of Oxford, England, in the 15^th century and is given for extraordinary achievements in natural and technological sciences, as well as political, law, and philosophical studies.

 Dr. Pal Pacher was included among the 128 highly cited researchers in “Highly Cited Researchers 2015” by Thomson Reuters in the field of Pharmacology and Toxicology, based on total citations of highly cited papers during past 10 years. The list was released in December 2015.http://highlycited.com/#pharmacology.

NEW REQUESTS FOR APPLICATIONS (RFAs) AND PROGRAM ANNOUNCEMENTS (PAs)

NOFOs issued by NIAAA between September 17, 2015 and January 28, 2016:

 Integrative Neuroscience Initiative on Alcoholism (INIA) Consortia (RFA-AA-16-004 Collaborative U01, RFA-AA-16-005 Research Resource U24, RFA-AA-16-006 Administrative Core U24) The purpose of this NOFO is to solicit cooperative agreement applications that are integrated, multidisciplinary, and collaborative, investigating the neuronal mechanisms of excessive alcohol intake with a focus on immune signaling and stress. More specifically, one focus of the initiative will be to examine brain immune signaling mechanisms promoting and controlling excessive alcohol consumption. A second focus will be to examine enduring consequences of stress challenges on adaptations in brain circuitry leading to excessive drinking and to altered stress responsiveness. An additional emphasis to be promoted within this initiative is the identification of drugable genomic targets to lay the foundations for new treatments for alcohol dependence. As in prior years, projects supported under this initiative are expected to integrate approaches at the molecular, cellular, synaptic, physiological, and behavioral level of analysis. Integration will be promoted by supporting two consortia, each comprising an administrative core (RFA-AA-16-006 U24), multiple component projects (RFA-AA-16-004 U01), and relevant scientific resource (RFA-AA-16-005 U24) cores as needed.

 Multi-Site Randomized Controlled Clinical Trial Research Center on Alcohol's Health Effects (U10) (PAR-16-363) This NOFO invites Cooperative Agreement (U10) applications for implementation of investigator-initiated randomized controlled clinical trials on alcohol’s effects on neurological diseases, most especially stroke, and the health issues that are associated with aging. Applicants for the U10 Clinical Trial Implementation Cooperative Agreement must be able to begin the trial without further planning activities when the U10 is awarded. Therefore, investigators who have already completed planning activities through an NIAAA-funded U34 clinical trial planning grant are expected to apply. The randomized controlled clinical trials are expected to be hypothesis-driven, milestone-defined, related to the research missions of both NIAAA and NINDS, and considered high priority by the participating Institutes.

 Limited Competition for the Continuation of CoFASP (Collaboration on Fetal Alcohol Spectrum Disorders Prevalence) Diagnostic Classifications (Collaborative U01) (RFA-AA-16-007). This limited-competition NOFO invites a cooperative agreement (U01) application from projects funded within the Collaboration on Fetal Alcohol Spectrum Disorders [FASD] Prevalence (CoFASP). The purpose of this limited competition is to allow additional follow-up for the development and use of a standardized diagnostic system to evaluate and report clinical characteristics of FASD among affected children and establish prevalence rates.

 NIH-wide NOFOs with NIAAA’s Participation issued between September 17, 2015 and January 28, 2016

 NIAAA is participating in the following BRAIN Initiative NOFOs:

Drug Discovery For Nervous System Disorders (R01, R21) (Issued by the National Institute of Mental Health (NIMH)) (PAR-16-041, R01; PAR-16-042, R21).

Development and Validation of Novel Tools to Analyze Cell- Specific and Circuit-Specific Processes in the Brain (R01) (Issued by NIMH) (RFA-MH-16-775).

Non-Invasive Neuromodulation - New Tools and Techniques for Spatiotemporal Precision (R01) (Issued by NIMH) (RFA-MH-16-810).

Non-Invasive Neuromodulation - Mechanisms and Dose/Response Relationships for Targeted CNS Effects (R01). (Issued by NIMH) (RFA-MH-16-815).

New Technologies and Novel Approaches for Large-Scale Recording and Modulation in the Nervous System (U01) (Issued by NINDS) (RFA-NS-16-006).

Optimization of Transformative Technologies for Large Scale Recording and Modulation in the Nervous System (U01) (Issued by NINDS) (RFA-NS-16-007).

Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous System (UG3/UH3) (Issued by NINDS) (RFA-NS-16-009).

Clinical Studies to Advance Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous System (UH3) (issued by NINDS) (RFA-NS-16-010).

Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous System (U44) (Issued by NINDS) (RFA-NS-16-011).

New Concepts and Early - Stage Research for Large - Scale Recording and Modulation in the Nervous System (R21) (Issued by NEI) (RFA-EY-16-001).

  NIAAA is participating in the following other NIH-wide NOFOs:

 NIH Blueprint Training in Computational Neuroscience: From Biology to Model and Back Again (T90/R90) (Issued by NIDA) (RFA-DA-16-009).

 Neuroimaging Informatics Tools and Resources Clearinghouse (U24) (Issued by NIBIB) (RFA-EB-16-002).

 Behavioral and Integrative Treatment Development Program (R01, R03, R34) (Issued by NIDA) (PA-16-072 (R01); PA-16-073 (R34); PA-16-074 (R03)).

 Administrative Supplements for Research on Sex/Gender Differences (Admin Supp) (Issued by ORWH) (PA-16-066).

 NIH Blueprint for Neuroscience Research Short Courses in Neurotherapeutics Development (R25) (Issued by NINDS) (RFA-NS-16-017).

 Environmental Influences on Child Health Outcomes (Issued by NIH). This NOFO solicits applications for the Environmental influences on Child Health Outcomes (ECHO). This NOFO is composed of five companion NOFOs (listed below) that will establish the elements of the ECHO Consortium:

• RFA-OD-16-003 (U24) – Data Analysis Center
• RFA-OD-16-004 (UG3/UH3) –  Exploratory/Developmental Cooperative Agreement
• RFA-OD-16-005 (U24) – Resource-Related Research Projects – Cooperative  Agreements
• RFA-OD-16-006 (U2C) – Resource-Related Research Projects – Cooperative Agreements
• PA-16-046 – Administrative Supplement

 The ECHO consortium also includes the following mechanisms (U24) (Issued by NIH):

• RFA-OD-16-001 (UGI) –  Clinical Sites for the [Institutional Development Award] IDeA States Pediatric Clinical Trials Network
• RFA-OD-16-002 (U24) – Data Coordinating and Operations Center for the IDeA States Pediatric Clinical Trials Network

 Drug Discovery For Nervous System Disorders (R01, R21) (Issued by NIMH) (PAR-16-041; PAR-16-042).

 SBIR/STTR Commercialization Readiness Pilot (CRP) Program: Technical Assistance (SB1) (Issued jointly by NIH and the U.S. Centers for Disease Control and Prevention (CDC)) (PAR-16-026).

 SBIR/STTR Commercialization Readiness Pilot (CRP) Program: Technical Assistance and Late Stage Development (SB1) (Issued by NINDS) (PAR-16-027).

 Innovation Corps (I-Corps) at NIH Program for NIH and CDC Phase I Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) Grantees (Admin Supp) (Issued by NCI) This NOFO seeks to develop and nurture a national innovation ecosystem that builds upon biomedical research to develop technologies, products and services that benefit society (PA-16-019).

 SBIR Technology Transfer (R43/R44) This NOFO encourages SBIR grant applications from small business concerns (SBCs) for projects to transfer technology out of the NIH intramural research labs into the private sector (Issued by NINDS) ( PA-15-354). 

NOTABLE NIAAA STAFF ACTIVITIES -- SEPTEMBER 2015 -- JANUARY 2016

Drs. George Kunos, Resat Cinar, Malliga Iyer and Kenner Rice of the Laboratory of Physiologic Studies have developed hybrid inhibitors of peripheral CB1 receptors and inducible nitric oxide synthase as potential novel treatment of fibrotic diseases. A patent application covering these compounds has attracted four license applications for therapeutic development, which are under negotiation.

Drs. Kathy Jung and Joe Wang served as scientific review editors and Dr. Jennifer Hobin served as editor in chief for the “Alcohol and the Immune System” issue of NIAAA’s journal, Alcohol Research: Current Reviews, which was released in September 2015.

Dr. Peggy Murray was a key member of the Planning Committee and participated in the White House Symposium, “Medicine Responds to Addiction” on September 18, 2015, in the Executive Office of the President in Washington, D.C. NIAAA, NIDA, NCI, the Substance Abuse and Mental Health Services Administration (SAMHSA), and CDC were co-sponsors of the meeting along with the Office of National Drug Control Policy. The symposium focused on the need for all physicians to be trained in alcohol and other drug abuse and addiction prevention and treatment, and ended with an outline of specific steps that should be taken in medical training and certification to assure appropriate attention to the full set of issues from prevention to end-stage care.

Dr. Mariela Shirley served as an NIH representative panel member and reviewer for the Substance Abuse Research In-Progress Review (IPR) meeting of the Military Operational Medicine Research Program (MOMRP)/Joint Program Committee for Military Operational Medicine (JPC5) of Defense Health Program-funded research. The meeting took place September 29–October 1, 2015, in Frederick, Maryland. The IPR, an in-person annual meeting, ensures an integrated behavioral health research program, and allows the MOMRP/JPC5 to foster collaboration among Defense Health Program-funded researchers, review fiscal responsibility and challenges to conducting research, and enhance scientific excellence.

Dr. Judith Arroyo and NIAAA were invited to participate in the Tribal Consultation Advisory Committee meeting, held at the NIH Wilson Hall on September 29–30, 2015. This committee was established by the NIH in accordance with a Presidential Executive Order in order to ensure that Tribes and American Indian/Alaska Native people have meaningful and timely input in the development of relevant NIH policies, programs, and priorities.

 Dr. Peggy Murray was a plenary speaker at the Krakow Conference on Fetal Alcohol Spectrum Disorders on September 30, 2015, giving a presentation titled, “FASD and the Global Health Policy Agenda.” The conference was organized by the Polish State Agency for the Prevention of Alcohol-Related Problems, together with the Jagiellonian University and the Children’s Hospital of Krakow.

 Dr. Ralph Hingson represented the federal government at the World Health Organization’s (WHO) meeting titled, the Second meeting of the Coordinating Council for the implementation of the WHO Global Strategy to Reduce the Harmful Use of Alcohol, in Edinburgh, United Kingdom, on October 6 and 9, 2015. He also presented his poster titled, “Traffic Risk Behaviors among Emerging Adults Who Drive after Drinking, Marijuana Use, or Other Drug Use” at the 2015 Global Alcohol Policy Conference (GAPC), sponsored by the WHO and other organizations. The WHO meeting and GAPC were held in conjunction.

Dr. George Kunos gave an invited, plenary lecture at the SecondHeidelberg Symposium on Diabetic Complications in Heidelberg, Germany, October 16–17, 2015.

Several NIAAA staff presented and chaired sessions at the mini-convention on “Frontiers in Addiction Research: Neurobiological and Behavioral Consequences of Drug and Alcohol Use during Development” sponsored by NIDA and NIAAA in conjunction with the Annual Meeting of the SfN in Chicago, Illinois, October 17, 2015. The mini-convention focused on the consequences of substance use and exposure on brain maturation, behavior, and cognition during the developmental transition from neonatal exposure through adolescence use, and the factors that predict vulnerability to early substance use. 

• Dr. George F. Koob gave the opening remarks and final discussion.
• Dr. Antonio Noronha, the co-organizer of the mini-convention, co-chaired the session on Joint NIDA-NIAAA Early Career Investigator Showcase.
• Dr. Ellen Witt co-chaired the session on Brain Development, Structure, and Behavior.
• Dr. Changhai Cui co-chaired the session on Genetics, Neurocognition, and Behavioral Phenotypes.
• Dr. Soundar Regunathan co-chaired the session on Molecular, Cellular, and Behavioral Underpinnings of Substance Use Disorder Vulnerability.

Lynn Morin conducted outreach to underrepresented students and investigators at the annual meeting of the SfN October 16–21, 2015, in Chicago, Illinois. Ms. Morin also conducted outreach at the Society for the Advancement of Chicanos and Native Americans in Science, October 26–31, 2015, National Harbor, Maryland; and at the Annual Biomedical Research Conference for Minority Students, November 11–14, 2015, Seattle, Washington.  

Dr. Ralph Hingson presented the plenary address at the National Prevention Network’s (NPN) 2015 Annual Conference in Seattle, Washington, on November 18, 2015. His address was titled, “New Research since the Surgeon General’s Call to Action to Prevent and Reduce Underage Drinking.” The next day, he gave a workshop at the NPN conference titled, “Recent Trends and Findings Regarding the Magnitude and Prevention of College Drinking and Drug Use Problems.”

Drs. Svetlana Radaeva and Gary Murray of DMHE organized a closed session meeting of the principal investigators for the Alcoholic Hepatitis consortium at the AASLD Diseases meeting in November 2015. The goals of this meeting were to 1) update the group on the status of the ongoing consortia-wide project on Common Data Elements and 2) to introduce a new collaborative effort involving the FDA to determine reasonable and mutually agreeable end-points for clinical trials in alcoholic hepatitis. Drs. Lara Dimick and Ruby Mehta, from the Division of Gastroenterology and Inborn Errors Products, FDA, participated in this meeting.

Drs. Lindsey Grandison and Raye Litten organized an-NIAAA sponsored satellite symposium titled, “State-of-the-Science on Treating the Comorbidity of Alcohol Use Disorders and PTSD,” at the annual meeting of the American College of Neuropsychopharmacology, held December 5, 2015, in Hollywood, Florida. Experts in the fields of post-traumatic stress disorder (PTSD), AUD, behavioral therapy and medication development were brought together in order to assess the current status of treating PTSD-AUD comorbidity and recommending strategies and priorities for developing new medications for this comorbid condition.

Dr. Changhai Cui co-organized a BRAIN Initiative investigators pre-meeting on Large-Scale Recording and Manipulation, at NIAAA, Rockville, Maryland, December 9, 2015. This meeting highlighted research projects funded by seven NIH BRAIN Initiative NOFOs on large-scale recording and modulation in the areas of electrodes, optical instruments/imaging, and probes/sensors. Dr. Cui chaired the session on probes and sensors. She also served on the planning team for organizing the multi-agency BRAIN Initiative investigators meeting held in North Bethesda, Maryland, December 10–11, 2015.

Dr. Lori Ducharme of the Division of Treatment and Recovery Research served as co-chair of the “Methods, Measures and Models” track for the Eighth Annual NIH/AcademyHealth Conference on the Science of Dissemination and Implementation in Health, held in Washington, D.C. on December 14–16, 2015. She also moderated a panel on implementation strategies for integrating addiction treatment into primary care, and served as a panelist in a technical assistance workshop for NIH grant applicants.

Dr. Raye Litten co-organized and served as discussant for a conference titled, “State-of-the-Science on Treating the Comorbidity of Alcohol Use Disorders and PTSD” at the American College of Neuropsychopharmacology meeting, Hollywood, Florida, in December 2015.
  

WHAT'S AHEAD? 

Dr. Svetlana Radaeva of DMHE will chair a session in an upcoming post-graduate course on “Emerging Trends in Alcoholic Hepatitis” organized through the AASLD by Drs. Vijay Shah, Craig McClain, and Gyongyi Szabo in Miami, Florida, on January 22–23, 2016.

The NIAAA Wearable Alcohol Biosensor Challenge issued last year by Dr. Kathy Jung of DMHE received eight entries. Judging of the entries is underway, with prizewinners (first prize - $200,000, second prize - $100,000) to be announced this spring.

The SecondScience of Change meeting will be held as a satellite to the annual meeting of the Society of Biological Psychiatry on May 11, 2016, in Atlanta, Georgia. The meeting is focused on neuroimaging mechanisms of change in treatments for addictive behaviors. The meeting is funded by an R13 conference grant from NIAAA (Dr. John Matochik, DNB, is the Program Officer).
 

NIAAA RESEARCH HIGHLIGHTS

Rsu1 Regulates Ethanol Consumption in Drosophila and Humans

Significance:  This paper identifies a novel gene, Ras suppressor 1 (Rsu1), which underlies vulnerability to AUD. The authors use a well-established Drosophila model to determine that Rsu1 is important for alcohol-related behaviors such as alcohol sensitivity and alcohol preference. The most important aspect of this study is the finding that polymorphisms in Rsu1 identified in human adolescents is associated with alterations in brain activation during reward anticipation. In addition, an independent sample of subjects with AUD showed a genetic association with a potential rare variant in Rsu1. This study is a key example of how to advance the identification of genes underlying AUD by using a translational approach.   

Alcohol abuse is highly prevalent, but little is understood about the molecular causes. Here, we report that Ras suppressor 1 (Rsu1) affects ethanol consumption in flies and humans. Drosophila lacking Rsu1 show reduced sensitivity to ethanol-induced sedation. We show that Rsu1 is required in the adult nervous system for normal sensitivity and that it acts downstream of the integrin cell adhesion molecule and upstream of the Ras-related C3 botulinum toxin substrate 1 (Rac1) GTPase to regulate the actin cytoskeleton. In an ethanol preference assay, global loss of Rsu1 causes high naïve preference. In contrast, flies lacking Rsu1 only in the mushroom bodies of the brain show normal naïve preference but then fail to acquire ethanol preference like normal flies. Rsu1 is, thus, required in distinct neurons to modulate naïve and acquired ethanol preference. In humans, we find that polymorphisms in RSU1 are associated with brain activation in the ventral striatum during reward anticipation in adolescents and alcohol consumption in both adolescents and adults. Together, these data suggest a conserved role for integrin/Rsu1/Rac1/actin signaling in modulating reward-related phenotypes, including ethanol consumption, across phyla. (Ojelade SA et al. Proc Natl Acad Sci U S A 2015 Jul 28;112(30):E4085-93) 

Leptin Levels are Reduced by Intravenous Ghrelin Administration and Correlated with Cue-Induced Alcohol Craving

Significance: Increasing evidence supports the role of appetite-regulating pathways in addictions. This study provides evidence of a ghrelin-leptin cross-talk in individuals with AUD and suggests that the relationship between ghrelin and leptin may play a role in alcohol craving. These results hold important clinical value because cue-induced craving may be associated with relapse and may predict alcohol-related outcomes. In addition, while studies have tended to focus on the role of individual appetite-regulating peptides in alcohol consumption, this study paves the way for future translational research on the role of interactions between these peptides in alcohol consumption.

Increasing evidence supports the role of appetite-regulating pathways, including ghrelin and leptin, in alcoholism. This study tested the hypothesis that intravenous (IV) exogenous ghrelin administration acutely decreases endogenous serum leptin levels, and that changes in leptin levels negatively correlate with alcohol craving. This was a double-blind, placebo-controlled human laboratory study. Non-treatment-seeking, alcohol-dependent, heavy-drinkers (n = 45) were randomized to receive IV ghrelin or placebo, followed by a cue reactivity procedure, during which participants were exposed to neutral (juice) and alcohol trial cues. There was a main effect for IV ghrelin administration, compared to placebo, in reducing serum leptin levels [p <.05]. Post hoc analysis showed significant differences in serum leptin levels at the alcohol trial [p <.05] that persisted at the end of the experiment [p <.05]. By contrast, there were no significant differences in serum leptin levels at the juice trial [p = n.s.]. The change of serum leptin level at the alcohol trial correlated with the increase in alcohol urge [p <.05], while urge to drink juice was not correlated with the leptin change at the juice trial [p = n.s.]. These findings provide preliminary evidence of ghrelin – leptin cross-talk in alcoholic individuals and suggest that their relationship may play a role in alcohol craving. (Haass-Koffler CL et al. Transl Psychiatry 2015;5: e646) 

Dissociating Motivational From Physiological Withdrawal in Alcohol Dependence: Role of Central Amygdala K-Opioid Receptors

Significance:  It has long been acknowledged that the acute physiological withdrawal symptoms contribute indirectly, if at all, to the motivation to drink alcohol; preventing or diminishing acute withdrawal is not sufficient to prevent relapse. Instead the post-withdrawal period—characterized by anxiety and negative affect, sleep disturbances, anhedonia, and dysphoria—is associated with heightened vulnerability to relapse and elevated drinking. This study reveals the selective involvement of the kappa-opioid receptor in the motivational post-withdrawal syndrome and not the acute physiological syndrome and lends support to its potential value as a medication target.

Chronic intermittent alcohol vapor exposure leads to increased dynorphin (DYN) A-like peptide expression and heightened kappa-opioid receptor (KOR) signaling in the central nucleus of the amygdala (CeA) and these neuroadaptive responses differentiate alcohol-dependent from non-dependent phenotypes. Important for therapeutic development efforts is understanding the nature of the stimulus that drives dependence-like phenotypes such as escalated alcohol self-administration. Accordingly, the present study examined the impact of intra-CeA KOR antagonism on escalated operant alcohol self-administration and physiological withdrawal symptoms during acute withdrawal and protracted abstinence in rats previously exposed to chronic intermittent alcohol vapor. Following operant training, rats were implanted with intra-CeA guide cannula and exposed to long-term intermittent alcohol vapor exposure that resulted in escalated alcohol self-administration and elevated physiological withdrawal signs during acute withdrawal. Animals received intra-CeA infusions of the KOR antagonist nor-binaltorphimine (nor-BNI; 0, 2, 4, or 6 μg) prior to operant alcohol self-administration sessions and physiological withdrawal assessment during acute withdrawal and protracted abstinence. The results indicated that site-specific KOR antagonism in the CeA ameliorated escalated alcohol self-administration during both acute withdrawal and protracted abstinence test sessions, whereas KOR antagonism had no effect on physiological withdrawal scores at either time point. These results dissociate escalated alcohol self-administration from physiological withdrawal symptoms in relation to KOR signaling in the CeA and help clarify the nature of the stimulus that drives escalated alcohol self-administration during acute withdrawal and protracted abstinence. (Kissler JL, Walker BM. Neuropsychopharmacology 2015 Jun 24) 

TLR2 and TLR4 Expression and Inflammatory Cytokines are Altered in the Airway Epithelium of Those with Alcohol Use Disorders

Significance: Persons with AUD have a far greater incidence of pneumonia than the general population. This study investigates alcohol’s modification of alveolar epithelial cells and the resulting change in the inflammatory state of the airways as a mechanism by which alcohol consumption disturbs pulmonary lines of defense. Using samples obtained from well-characterized human subjects, the authors report that toll-like receptor (TLR) 2 is up-regulated and TLR4 decreased in AUD subjects, compared to nonsmoking/non-AUD subjects, and correlated with their scores on the Alcohol Use Disorders Identification Test. Interleukin (IL)-6 and IL-8 were also increased in bronchial washings from AUD subjects. The combination increases susceptibility to Streptococcus pneumoniae infection.

BACKGROUND: The lung has a highly regulated system of innate immunity to protect itself from inhaled microbes and toxins. The first line of defense is mucociliary clearance, but if invaders overcome this, inflammatory pathways are activated. Toll-like receptors (TLRs) are expressed on the airway epithelium. Their signaling initiates the inflammatory cascade and leads to production of inflammatory cytokines such as interleukin (IL)-6 and IL-8. We hypothesized that airway epithelial insults, including heavy alcohol intake or smoking, would alter the expression of TLRs on the airway epithelium. METHODS:  Bronchoscopy with bronchoalveolar lavage and brushings of the airway epithelium was performed in otherwise healthy subjects who had normal chest radiographs and spirometry. A history of alcohol use disorders (AUDs) was ascertained using the Alcohol Use Disorders Identification Test (AUDIT), and a history of cigarette smoking was also obtained. Age, gender, and nutritional status in all groups were similar. We used real-time polymerase chain reaction (PCR) to quantitate TLR1 to 9 and enzyme-linked immune assay to measure tumor necrosis factor-α, IL-6, and IL-8. RESULTS:  Airway brushings were obtained from 26 nonsmoking/non-AUD subjects, 28 smoking/non-AUD subjects, 36 smoking/AUD subjects, and 17 nonsmoking/AUD subjects. We found that TLR2 is up-regulated in AUD subjects, compared to nonsmoking/non-AUD subjects, and correlated with their AUDIT scores. We also measured a decrease in TLR4 expression in AUD subjects that correlated with AUDIT score. IL-6 and IL-8 were also increased in bronchial washings from AUD subjects. CONCLUSIONS: We have previously demonstrated in normal human bronchial epithelial cells that in vitro alcohol exposure up-regulates TLR2 through a NO/cGMP/PKG-dependent pathway, resulting in up-regulation of inflammatory cytokine production after Gram-positive bacterial product stimulation. Our current translational study confirms that TLR2 is also up-regulated in humans with AUDs. (Bailey KL et al. Alcohol Clin Exp Res 2015 Sep;39:1691-7) 

Short- or long-term high fat diet feeding plus acute ethanol binge synergistically induce steatohepatitis in mice: an important role for CXCL1

Significance: Obesity and alcohol consumption often coexist and work synergistically to promote steatohepatitis; however, the underlying mechanisms remain obscure. This study demonstrates that feeding mice a high-fat diet combined with acute ethanol consumption synergistically induces acute liver inflammation and injury through the elevation of hepatic or serum free fatty acids and subsequent up-regulation of hepatic CXCL1 expression and promotion of hepatic neutrophil infiltration.

Obesity and alcohol consumption often coexist and work synergistically to promote steatohepatitis; however, the underlying mechanisms remain obscure. Here, we demonstrate that feeding mice a high-fat diet (HFD) for as little as 3 days markedly exacerbated acute ethanol binge–induced liver neutrophil infiltration and injury. Feeding mice with an HFD for 3 months plus a single binge of ethanol induced much more severe steatohepatitis. Moreover, 3-day or 3-month HFD-plus-ethanol binge (3d-HFD+ethanol or 3m-HFD+ethanol) treatment markedly up-regulated the hepatic expression of several chemokines, including chemokine (C-X-C motif) ligand 1 (Cxcl1), which showed the highest fold (approximately 20-fold and 35-fold, respectively) induction. Serum CXCL1 protein levels were also markedly elevated after the HFD+ethanol treatment. Blockade of CXCL1 with a CXCL1 neutralizing antibody or genetic deletion of the Cxcl1 gene reduced the HFD+ethanol-induced hepatic neutrophil infiltration and injury, whereas overexpression of Cxcl1 exacerbated steatohepatitis in HFD-fed mice. Furthermore, expression of Cxcl1 messenger RNA was up-regulated in hepatocytes, hepatic stellate cells, and endothelial cells isolated from HFD+ethanol-fed mice compared to mice that were only given the HFD, with the highest fold induction observed in hepatocytes. In vitro stimulation of hepatocytes with palmitic acid up-regulated the expression of Cxcl1 messenger RNA, and this up-regulation was attenuated after treatment with an inhibitor of extracellular signal–regulated kinase 1/2, c-Jun N-terminal kinase, or nuclear factor κB. In addition, hepatic or serum levels of free fatty acids were higher in HFD+ethanol-fed mice than in the control groups. Conclusion: An HFD combined with acute ethanol consumption synergistically induces acute liver inflammation and injury through the elevation of hepatic or serum free fatty acids and subsequent up-regulation of hepatic CXCL1 expression and promotion of hepatic neutrophil infiltration. (Chang B et al. Hepatology 2015 Oct; 62:1070-85)

Unhealthy Alcohol Use is Associated with Monocyte Activation Prior to Starting Antiretroviral Therapy

Significance:  Alcohol use may accelerate HIV disease progression, but the plausible biological mechanisms have not been clearly elucidated. Unhealthy alcohol use was independently associated with a marker of monocyte activation (i.e., higher sCD14) that predicts mortality in treated HIV-infected individuals. Longitudinal research should examine whether unhealthy alcohol use predicts changes in sCD14 prior to and following antiretroviral therapy initiation.

BACKGROUND:  Alcohol use may accelerate HIV disease progression, but the plausible biological mechanisms have not been clearly elucidated. METHODS:  HIV-positive persons who were not on antiretroviral therapy (ART) completed the baseline assessment for a longitudinal study examining the association of alcohol use with HIV disease markers. Oversampling drinkers, baseline samples were tested for markers of monocyte activation (soluble CD14 [sCD14]), inflammation (interleukin-6 [IL-6]-6), and coagulation (d-dimer). We defined "unhealthy alcohol use" as testing positive using the Alcohol Use Disorders Identification Test-Consumption (≥3 for women and ≥4 for men) in the past 3 months or testing positive using a biomarker of heavy drinking, phosphatidylethanol (≥50 ng/ml). Multiple linear regression was used to examine the associations of unhealthy alcohol use with sCD14, log₁₀ IL-6, and d-dimer. RESULTS:  Compared to those who were abstinent from alcohol, unhealthy drinkers had significantly higher sCD14 levels (mean = 1,676 vs. 1,387 ng/ml; mean difference [95% confidence interval (CI)] = 289 [83, 495], p < 0.01). In analyses adjusted for demographic factors, current cigarette smoking, and HIV disease markers, unhealthy drinkers continued to display significantly higher sCD14 levels compared to those who were abstinent from alcohol (adjusted mean = 1,670 vs. 1,406 ng/ml; adjusted mean difference [95% CI] = 264 [47, 480], p = 0.02). Unhealthy alcohol use was not significantly associated with IL-6 or d-dimer levels. CONCLUSIONS:  Unhealthy alcohol use was independently associated with a marker of monocyte activation (i.e., higher sCD14) that predicts mortality in treated HIV infection. Longitudinal research should examine whether unhealthy alcohol use predicts changes in sCD14 prior to and following ART initiation. (Carrico AW et al. Alcohol Clin Exp Res 2015 Dec;39(12):2422-6) 

Association Between Physical Pain and Alcohol Treatment Outcomes: The Mediating Role of Negative Affect

Significance: Physical pain and negative affect have been described as risk factors for alcohol use following alcohol treatment. This study, a secondary analysis of two clinical trials for AUD examined the associations between pain, negative affect, and AUD treatment outcomes. Pain scores were associated with drinking outcomes in both datasets. Pain scores were also positively associated with negative affect, and negative affect mediated the association between pain and drinking outcomes. Social behavior network therapy attenuated the association between pain and drinking.

OBJECTIVE: Physical pain and negative affect have been described as risk factors for alcohol use following alcohol treatment. The current study was a secondary analysis of 2 clinical trials for alcohol use disorder (AUD) to examine the associations between pain, negative affect and AUD treatment outcomes. METHOD: Participants included 1,383 individuals from the COMBINE Study (COMBINE Pharmacotherapies and Behavioral Interventions for Alcohol Dependence; COMBINE Study Research Group, 2003; 31% female, 23% ethnic minorities, average age = 44.4 [SD = 10.2]), a multisite combination pharmacotherapy and behavioral intervention study for AUD in the United States, and 742 individuals from the United Kingdom Alcohol Treatment Trial (UKATT Research Team, 2001; 25.9% female, 4.4% ethnic minorities, average age = 41.6 [SD = 10.1]) a multisite behavioral intervention study for AUD in the United Kingdom. The Form-90 was used to collect alcohol use data, the Short Form Health Survey and Quality of Life measures were used to assess pain, and negative affect was assessed using the Brief Symptom Inventory (COMBINE) and the General Health Questionnaire (UKATT). RESULTS: Pain scores were significantly associated with drinking outcomes in both datasets. Greater pain scores were associated with greater negative affect and increases in pain were associated with increases in negative affect. Negative affect significantly mediated the association between pain and drinking outcomes and this effect was moderated by social behavior network therapy (SBNT) in the UKATT study, with SBNT attenuating the association between pain and drinking. (Witkiewitz K et al. J Consult Clin Psychol 83(6):1044-1057) 

Funding translation in Stress Research

Significance: This paper provides a perspective on how translational research on stress-related mental disorders is being powered by an ever-developing appreciation of the shared neural circuits and genetic architecture that moderate the response to stress across species. It also addresses research approaches that have the potential to deliver a new generation of risk biomarkers and therapeutic strategies for stress-related disorders.

In our ongoing efforts to advance understanding of human diseases, translational research across rodents and humans on stress-related mental disorders stands out as a field that is producing discoveries that illuminate mechanisms of risk and pathophysiology at a brisk rate. Here we offer a Perspective on how a productive translational research dialog between preclinical models and clinical studies of these disorders is being powered by an ever-developing appreciation of the shared neural circuits and genetic architecture that moderate the response to stress across species. Working from these deep foundations, we discuss the approaches, both traditional and innovative, that have the potential to deliver a new generation of risk biomarkers and therapeutic strategies for stress-related disorders. (Hariri A, Holmes A. Nature Neuroscience 2015 Oct;18(10):1347-52) 

Management of Alcohol Use Disorder in Patients Requiring Liver Transplant

Significance: Alcohol is a leading cause of liver failure worldwide. However, treatments for alcoholic liver disease are limited, and the management of patients with AUD who require liver transplant may be challenging. This paper critically reviews and discusses the clinical, public health, and bioethical issues related to the treatment of AUD in patients before and after liver transplant. The review also highlights the critical need to address smoking in this population. (Lee MR, Leggio L. American Journal of Psychiatry 2015 Dec 1;172(12):1182-9) [no abstract]

Can a criminal justice alcohol abstention programme with swift, certain, and moderate sanctions (24/7 Sobriety) reduce population mortality? A retrospective observational study

Significance:  A rigorous evaluation of the 24/7 sobriety program for alcohol-involved offenders in South Dakota found the program was linked to a surprisingly large (4.2%) reduction in all-cause mortality. These findings, drawn from a strong statistical design, suggest but do not show that the program has spillover effects on members of the population who are not enrolled in the program.

Background: In the UK and USA, various jurisdictions have launched new approaches for managing alcohol-involved offenders that might have public health implications. These programmes require participants to abstain from alcohol and submit to frequent alcohol testing with swift, certain, and modest sanctions for violations, with the aim to reduce crime and keep alcohol-involved offenders in the community. In this study we examine whether the 24/7 Sobriety programme in South Dakota, USA—the largest such programme to date—is associated with reductions in mortality. Methods: With a differences-in-differences design, we used variation in the timing of 24/7 Sobriety implementation across South Dakota counties between 2005 and 2011 to estimate the association between programme introduction and county-level mortality. We used monthly, county-level, aggregate counts for mortality from January, 2000, to June, 2011. We assessed total deaths, and deaths due to external injuries, circulatory disorders, digestive disorders, and cancer (as a potential placebo). Findings: Between January, 2005, and June, 2011, 16 932 people (about 3% of the adult population) participated in the 24/7 Sobriety programme. The analysis was based on a sample size of 9 108 county-month observations (ie, 66 counties × 12 months × 11·5 years). Implementation of 24/7 Sobriety was associated with a 4·2% (95% CI 1·5–6·9) reduction in all-cause adult mortality, with the largest associations among women (8·0%, 95% CI 3·9–11·8) and individuals older than 40 years (4·3%, 95% CI 1·4–7·0). Associations were most evident among circulatory disorders. Interpretation: 24/7 Sobriety might have public health benefits, which could extend beyond individuals directly enrolled in the programme. However, further research, including randomised controlled trials and analyses of individual-level data, is needed to corroborate the finding, reassess the size of these associations, and gain insight into causal mechanisms. Should a negative association be replicated, it might represent a substantial advance in our understanding of how criminal justice interventions could help shape public health. (Nicosia N, Kilmer B, Heaton P. The Lancet Psychiatry. To be published online February 2016) 

Sex Differences in Animal Models: Focus on Addiction

Significance:  This review addressed sex differences in preclinical animal models of addiction. Female rats, in general, acquire the self-administration of drugs and alcohol more rapidly, escalate their drug-taking with extended access more rapidly, and show more motivational withdrawal, and greater reinstatement (when tested in animal models of craving). The one exception is that female rats show less motivational withdrawal to alcohol. These sex differences appear to be both organizational (i.e., estradiol-treated neonatal animals show the male phenotype), and activational (i.e., female phenotype depends on the effects of gonadal hormones.) Differences within the estrous cycle are relatively minor and most prevalent during the acquisition of drug taking and less influential once compulsive drug taking is established. A better understanding of how males and females differ will help scientists design experiments to characterize better the presence or absence of sex differences in new phenomena that they are investigating.

The purpose of this review is to discuss ways to think about and study sex differences in preclinical animal models. We use the framework of addiction, in which animal models have excellent face and construct validity, to illustrate the importance of considering sex differences. There are four types of sex differences: qualitative, quantitative, population, and mechanistic. A better understanding of the ways males and females can differ will help scientists design experiments to characterize better the presence or absence of sex differences in new phenomena that they are investigating. We have outlined major quantitative, population, and mechanistic sex differences in the addiction domain using a heuristic framework of the three established stages of the addiction cycle: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation. Female rats, in general, acquire the self-administration of drugs and alcohol more rapidly, escalate their drug taking with extended access more rapidly, show more motivational withdrawal, and (where tested in animal models of "craving") show greater reinstatement. The one exception is that female rats show less motivational withdrawal to alcohol. The bases for these quantitative sex differences appear to be both organizational, in that estradiol-treated neonatal animals show the male phenotype, and activational, in that the female phenotype depends on the effects of gonadal hormones. In animals, differences within the estrous cycle can be observed but are relatively minor. Such hormonal effects seem to be most prevalent during the acquisition of drug taking and less influential once compulsive drug taking is established and are linked largely to progesterone and estradiol. This review emphasizes not only significant differences in the phenotypes of females and males in the domain of addiction but emphasizes the paucity of data to date in our understanding of those differences. (Becker JB, Koob GF. Pharmacol Rev 2016 Apr;68(2):242-63) 

Converging patterns of alcohol use and related outcomes among females and males in the United States, 2002-2012

Significance:  This study used National Survey on Drug Use and Health (NSDUH) data to explore changes in alcohol use and associated outcomes among females and males aged 12 and up between 2002 and 2012. Although men still drink more than women, differences in the drinking patterns have narrowed for current drinking, number of drinking days per month, past year Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) alcohol abuse, and past-year driving under the influence of alcohol. Notably, the average number of drinking days and the percentage of people who drank in the previous 30 days increased for females and decreased for males. Among 18–25 year olds not in college, binge drinking increased among women, but decreased among men. The evidence of increasing alcohol use by females is particularly concerning given that women are at greater risk of a variety of alcohol-related health effects, including liver inflammation, cardiovascular disease, neurotoxicity and cancer.  

Background: This study confirms other recent reports about changing patterns of alcohol use by men and women in the United States. The evidence of increasing alcohol use by females is particularly concerning given that women are at greater risk of a variety of alcohol-related health effects, including liver inflammation, cardiovascular disease, neurotoxicity and cancer.   Females in the United States consume less alcohol and cause and experience fewer alcohol-related harms than males. However, recent research suggests such gaps might be narrowing. The purpose of this study was to explore changes in alcohol use and associated outcomes among females and males in the United States between 2002 and 2012. METHODS: Data from the National Survey on Drug Use and Health were used to assess the prevalence and trends for females and males aged 12+ in lifetime abstinence, age of onset, current drinking, binge drinking, drinking and driving, reaching DSM-IV criteria for an alcohol use disorder, combining alcohol with other drugs such as marijuana, and other variables. Of particular interest was whether differences between females and males narrowed during the decade under study. RESULTS: Differences in the drinking patterns of females and males aged 12+ narrowed between 2002 and 2012 for current drinking, number of drinking

days per month, past year DSM-IV alcohol abuse, and past-year driving under the influence of alcohol. In addition, convergence was noted in 1 or more age subgroups for the prevalence of binge drinking and DSM-IV alcohol dependence and mean age at drinking onset. Divergence in drinking habits did not occur for any measure in any age subgroups with the exception of a greater increase in the prevalence of combining alcohol with marijuana among young adult male drinkers than female drinkers aged 18 to 25. CONCLUSIONS: Between 2002 and 2012, differences in alcohol consumption and related outcomes narrowed for females and males. Reasons for converging patterns of alcohol use are unclear and do not appear to be easily explainable by recent trends in employment status, pregnancy status, or marital status. More research is needed to identify the psychosocial and environmental contributors to these changes and to assess implications for prevention and treatment efforts. (White A, Castle IJ, Chen CM, Shirley M, Roach D, Hingson R. Alcohol Clin Exp Res 2015 Sep;39(9):1712-26) 

A randomized controlled trial targeting alcohol use and sexual assault risk among college women at high risk for victimization

Significance: This study assessed the effectiveness of a web-based, combined sexual assault risk and alcohol use reduction program for college women using a randomized controlled trial. For women with a history of sexual assault, participating in the combined web-based intervention (compared to participating in face-to-face risk reduction programs) reduced sexual assault risk and heavy episodic drinking. Notably, the combined intervention was only effective in reducing sexual re-assault rates and not first sexual assault experiences. These data suggest that web-based personalized feedback programs targeting sexual assault may be a cost-effective option for reducing sexual assault and heavy episodic drinking on college campuses.

Sexual assault risk reduction programs do not target alcohol use despite the widespread knowledge that alcohol use is a risk factor for being victimized. The current study assessed the effectiveness of a web-based combined sexual assault risk and alcohol use reduction program using a randomized control trial. A total of 207 college women between the ages of 18 and 20 who engaged in heavy episodic drinking were randomized to one of five conditions: full assessment only control condition, sexual assault risk reduction condition, alcohol use reduction condition, combined sexual assault risk and alcohol use reduction condition, and a minimal assessment only condition. Participants completed a 3-month follow-up survey on alcohol-related sexual assault outcomes, sexual assault outcomes, and alcohol use outcomes. Significant interactions revealed that women with higher severity of sexual assault at baseline experienced less incapacitated attempted or completed rapes, less severity of sexual assaults, and engaged in less heavy episodic drinking compared to the control condition at the 3-month follow-up. Web-based risk reduction programs targeting both sexual assault and alcohol use may be the most effective way to target the highest risk sample of college students for sexual assault: those with a sexual assault history and those who engage in heavy episodic drinking. (Gilmore AK, Lewis MA, George WH. Behav Res Ther 2015 Nov;74:38-49) 

Press and Publications Activities:

Recent News Media Interviews:  Dr. Koob continues to field numerous interviews from national and international news outlets on timely topics related to NIAAA’s research and its impact on treatment and prevention of AUD. Notable interviews since September include the Washington Post, Wall Street Journal, CNN, U.S. News & World Report, CBS Network News Radio, Huffington Post, and Forbes.com.

.Publication Statistics: As of January 2016, there were 30,296 subscribers to the Alcohol Alert; 29,684 to Alcohol Research: Current Reviews; 19,420 to the NIAAA Spectrum; and 19,056 to receive general information.

Press Releases

 Male and female drinking patterns becoming more alike in the U.S. (November 23, 2015) 

10 percent of US adults have drug use disorder at some point in their lives (November 18, 2015) 

Brief training increases pediatricians’ use of substance abuse and mental health interventions (November 2, 2015) 

Dr. Kathleen K. Sulik to deliver 20^th Annual Mark Keller Honorary Lecture at the National Institutes of Health (October 28, 2015) 

Prevalence of marijuana use among U.S. adults doubles over past decade (October 21, 2015) 

NIH launches landmark study on substance use and adolescent brain development (September 25, 2015) 

NIH releases comprehensive resource to help address college drinking (September 22, 2015) 

Expanded National Drug and Alcohol Facts Week begins January 25 (August 27, 2015) 

 Partnerships, Outreach & Public Liaison Activities 

Winter Holidays Outreach:  

 During the Christmas and New Year’s holidays, NIAAA conducted promotion of its fact sheet titled, The Truth about Holiday Spirits—How to Celebrate Safely This Season, with dissemination via PR Newswire. This effort resulted in 191 pick-ups from outlets including The Boston Globe, Reuters, Yahoo!, numerous television network affiliates nationwide, and blogs, with an estimated potential audience of 83 million. 

NIAAA also conducted social media outreach with a 15-second video public service announcement (PSA) with a related message about underestimating alcohol’s effects on the body during the holidays (see http://bit.ly/1J344cj). The PSA was widely promoted via YouTube, Facebook, and Twitter, and on social media by CBS News-New York, ESPN-New York, the National Council on Alcoholism and Drug Dependence, the Office on Women’s Health, U.S. News & World Report’s executive editor of consumer advice, and health writers/bloggers. The YouTube video received more than 18,000 views, and the Facebook ads were viewed more than 1.4 million times. During and subsequent to the promotion period, traffic to the Rethinking Drinking website increased. 

College Fall Semester and Halloween Outreach  

In conjunction with the start of the college fall semester, NIAAA disseminated its fact sheet titled, Fall Semester—A Time for Parents to Discuss the Risks of College Drinking via PR Newswire, resulting in a total estimated potential audience of 88 million people. For Halloween 2015, NIAAA used social media to target key influencers, parents, women, television and trade news outlets, and general market audiences with NIAAA’s two Halloween graphic static images. The images were tweeted by the NIH Office on Women’s Health, MedlinePlus, Military Spouse Magazine, and a number of other social media influencers, with a potential audience of 1.3 million people. Additionally, the images were shared on Facebook by Dr. Drew and other addiction and mental health groups. 

CollegeAIM—NIAAA’s College Alcohol Intervention Matrix 

In late September, NIAAA released the CollegeAIM guide and website, important new resources to help colleges address student drinking. Developed with input from researchers and college staff, CollegeAIM (which stands for College Alcohol Intervention Matrix) is an easy-to-use and comprehensive tool to identify evidence-based alcohol interventions. The result of a multiyear collaboration, CollegeAIM rates nearly 60 alcohol interventions in terms of effectiveness, costs, and other factors – and presents the information in a user-friendly and accessible way. With this tool, school officials can use research-based information to choose wisely among the many potential interventions to address student drinking. 

With the release of CollegeAIM, NIAAA embarked on a multifaceted promotion and distribution effort that will continue into 2016.

Launch and Distribution Highlights:

A live webcast announcement on September 22, 2015, from the National Press Club - Drs. George Koob and Jonathan Gibralter, President of Wells College, spoke about the CollegeAIM booklet and website, new resources from NIAAA to help higher education officials address the problem of underage and harmful drinking on U.S. campuses. More than 200 reporters, stakeholders, and college staff participated. 

Following the webcast, Drs. Koob and Gibralter were interviewed live on WTOP-FM by Paula Wolfson. 

Creation of dedicated website with print and interactive versions of the CollegeAIM guide, along with additional resources. 

Direct mailing of CollegeAIM print guide to every degree-granting U.S. college and university.

Regional Workshops and Presentations at Conferences: 

In collaboration with members of the NIAAA College Presidents Working Group to Address Harmful and Underage Drinking, regional workshops will review CollegeAIM and how to use it. 

Presented at: Summit of Behavioral Health Issues among College Students (sponsored by SAMHSA); Peace Corps Global Leadership Summit; I-CAN Statewide Summit (Indiana); National Prevention Network; Community Anti-Drug Coalitions of America (CADCA); and NASPA (an association of student affairs administrators in higher education).

Alcohol Biosensor Event at the National Archives

On December 3, 2015, Dr. Koob participated in an evening round table at the National Archives:  “The ‘Drunkometer’ to Digital Apps: How Technology Changes the Way We Drink.” The round table, held as part of the Archives’ “Spirited America” exhibit, explored the cultural history of alcohol consumption in the United States. and the evolution of alcohol-related technology. Dr. Koob discussed the progress of our national challenge prize to develop a wearable alcohol biosensor. The event was moderated by Gary Wolf, writer and contributing editor at Wired magazine and co-founder of Quantified Self. Panelists included Susan Cheever, author of Drinking in America: Our Secret History; and Dr. William Rorabaugh, history professor at the University of Washington. The event can be viewed at http://www.youtube.com/watch?v=d4Bu58H1ZiE.

Mark Keller Honorary Lecture

Dr. Kathleen K. Sulik, shown here with NIAAA Director Dr. George F. Koob, presented the 20^th annual Mark Keller Lecture on November 5, 2015. Dr. Sulik received the Keller Award for her contributions in advancing the understanding of prenatal development and alcohol-induced birth defects. Dr. Sulik, a professor of cell biology and physiology and a member of the Bowles Center for Alcohol Studies at the University of North Carolina, Chapel Hill, spoke on “Embryos and Ethanol: Basic Research to Prevention.”

Partnerships

 Partnered with NIDA on National Drug and Alcohol Facts Week, including Drugs and Alcohol Chat Day on January 26, 2016. 

The CADCA National Leadership Forum on February 2–4, 2016, featured NIAAA-sponsored presentations by Drs. George Koob, Ralph Hingson, and Jason Kilmer from the University of Washington. Dr. Kilmer is one of the researchers who worked on CollegeAIM.

NIAAA Social Media 

The NIAAA Twitter account (@NIAAAnews) currently has more than 13,500 followers and averages about 90,000 impressions (number of times users saw the Tweet on Twitter) per month. Top tweets included NIAAA’s holiday video, blood alcohol content graphic, biosensor challenge announcement, and Halloween images. On December 16, 2015, NIAAA participated in NIDA’s Monitoring the Future Twitter Chat. The #MTF2015 chat is archived at: http://www.storify.com/NIDAnews/nida-hosts-twitter-chat-on-monitoring-the-future-2.

 New NIAAA Video Page 

In December 2015, NIAAA launched a new landing page to host select videos. Current clips include interviews and presentations by Drs. George F. Koob and Vivian Faden, as well as other NIAAA researchers. The videos on the site will spotlight topics such as underage drinking, FASD, treatment options, alcohol biosensors, and college drinking, as well as include LabTV videos and public service announcements. The new video page can be found at: http://www.niaaa.nih.gov/publications/video-bank.   

 Digitizing the NIAAA Library

 The NIAAA library includes physical copies of books, journals, government documents, legislation, as well as individual articles and book chapters. Until recently, this collection was entirely stored at an NIAAA contractor's warehouse. To make the library's resources more accessible, NIAAA has been working with the Substance Abuse Librarians and Information Specialists (SALIS) organization to digitize and upload selected items to the SALIS Collection of the Internet Archives. More than 500 items, including the NIAAA monographs, are now available at: http://www.archive.org/details/salis?and[]=NIAAA.