NIAAA Director's Report on Institute Activities to the 146th Meeting of the National Advisory Council on Alcohol Abuse and Alcoholism

Thursday, September 14, 2017

Table of Contents

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

NIAAA BUDGET

Fiscal Year (FY) 2017

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is currently closing out FY 2017. 

On May 5, 2017, H.R. 244, the Consolidated Appropriations Act of 2017 was passed into law, providing the National Institutes of Health (NIH) with $34.1 billion for FY 2017, a $2 billion increase above the FY 2016 enacted budget level. This funding includes specific increases for Alzheimer’s disease research, antibiotic research, the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, and the Precision Medicine Initiative (now referred to as the All of Us Research Program). The bill provides a general increase to all NIH Institutes and Centers, and it continues support for the Gabriella Miller Kids First Pediatric Research Program.

 NIAAA received $483.4 million, a $16.7 million increase above the FY 2016 enacted budget level. The NIAAA appropriation includes a $1.9 million set-aside for the BRAIN Initiative. NIAAA estimates it will support a total of 686 Research Project Grants in FY 2017.

 Fiscal Year (FY) 2018

 A Continuing Resolution (CR), or short-term spending bill, was signed into law last week that extends NIH funding through December 8, 2017.

*FY 2016 budget excludes the $255K AIDS transfer
**The FY 2017 budget excludes the $950 K transfer 
 

COLLABORATIVE RESEARCH ON ADDICTION AT NIH (CRAN) UPDATE

Adolescent Brain Cognitive Development (ABCD) Study   

The ABCD Study (abcdstudy.org) continues to meet enrollment targets and currently has about 4,500 9- and 10-year-olds enrolled. In July, the study added a data collection site at the University of Rochester, led by principal investigator Dr. John Foxe.

 In June, the study announced it has partnered with the National Institute of Mental Health Data Archive (NDA) to share ABCD Study data with the public on an ongoing basis. The inaugural data release contains basic demographic data (age, sex) and unprocessed neuroimaging data from participants including:

• High-resolution structural data (three-dimensional T1- and T2-weighted scans);
• Advanced diffusion magnetic resonance imaging (MRI) (multiple b-values and directions);
• Resting state functional magnetic resonance imaging (fMRI); and
• Task fMRI (monetary incentive delay, stop-signal, and emotional N-back), along with raw E-Prime task files for each fMRI run.

 Neuroimaging data were collected using a harmonized Human Connectome Project protocol, developed for the ABCD Study, and supported across all three major MRI scanner platforms (Siemens, General Electric, and Philips). The data in this release are in DICOM format, as provided by the MRI scanners, and have not undergone quality control or curation. As such, the fast-track data are most suitable for technical methods development (e.g., scanner harmonization), because the DICOM images would require pre-processing (e.g., distortion correction, movement correction, alignment) to be suitable for data analysis.

 Curated data, including all assessment domains and computational analysis pipelines, will be released annually through the NDA starting in December 2017.

 The CRAN Committee is currently working to develop a Notice of Funding Opportunity (NOFO) that will encourage applications that use ABCD data to answer a range of questions about risk and protective factors for alcohol, drug, and nicotine misuse and the effects of these substances on the developing brain. Other NIH Institutes are exploring participation in the NOFO to support work that addresses additional questions that could be answered with ABCD data.

 CRAN Blog

 The most recent CRAN blog (addictionresearch.nih.gov/blog), was contributed by Doug Tipperman, Tobacco Policy Liaison in the Office of Policy, Planning, and Innovation at the Substance Abuse and Mental Health Services Administration (SAMHSA). It explores the idea that smoking cessation can improve behavioral outcomes in individuals with mental health and/or substance use disorders.

DIRECTOR'S ACTIVITIES

NIAAA Director Dr. George F. Koob, gave a number of important presentations from April 2017 through July 2017. They included: 

• A plenary lecture at the 48^th annual American Society of Addiction Medicine (ASAM) meeting in New Orleans, Louisiana, on April 7, 2017, titled “NIAAA Perspective: Innovations Shaping the Field of Addiction Medicine.” 
• A plenary lecture at the 65^th Nebraska Symposium on Motivation in Lincoln, Nebraska, on April 20, 2017, titled “Motivating Change in Addiction via Modulation of the Dark Side.” 
• A plenary talk at the New York University Department of Psychiatry’s annual Eric Simon Lecture in Basic and Translational Neuroscience Grand Rounds in New York, New York, on May 4, 2017, titled “The Neurobiology of the Dark Side of Addiction.” 
• A plenary lecture at the Fourth International Congress on Alcoholism and Stress in Volterra, Italy, on May 9, 2017, titled “Stress, Negative Reinforcement and Compulsive Drug-Seeking.” 
• A plenary lecture at the French Neuroscience Society Meeting (NeuroFrance 2017) in Bordeaux, France, on May 19, 2017, titled “Neuroplasticity in the Brain Stress Systems in Addiction.” 
• A plenary lecture at the 170^th annual American Psychiatric Association meeting in San Diego, California, on May 20, 2017, titled “The Dark Side of Compulsive Alcohol and Drug Seeking: The Neurobiology of Negative Emotional States.” 
• The keynote address at the 2017 Annual Society for Prevention Research meeting in Washington, DC, on June 1, 2017, titled “Preventing Alcohol Misuse and Related Harms: An NIAAA Update.” 
• An update on NIAAA’s research portfolio at the annual Friends of NIAAA meeting in Washington, DC, on June 5, 2017. 
• A plenary NIAAA update at the College on Problems of Drug Dependence 79^th Annual Scientific Meeting in Montreal, Canada, on June 18, 2017, titled “NIAAA Update: Priorities Going Forward.” 
• A plenary NIAAA update at the 2017 Research Society on Alcoholism (RSA) Annual Meeting in Denver, Colorado, on June 20, 2017, titled “Report from the National Institute on Alcohol Abuse and Alcoholism.” 
• A featured talk titled, “The Changing Patterns of Women’s Drinking and Their Impact on Public Health,” at a June 22, 2017, congressional briefing sponsored by the Friends of NIAAA in cooperation with the Congressional Addiction, Treatment, and Recovery Caucus. 
• An Advances in Addiction Theory session at the Gordon Research Conference: Neurobiology of Addiction in Hong Kong, China, on July 20, 2017, titled “Negative Reinforcement Based Addiction Models: Past, Present and Future.”

STAFF TRANSITIONS

Departing Staff

 Dr. Youngshim Choi, postdoctoral fellow in Dr. B.J. Song’s laboratory, left NIAAA to join the faculty at the Johns Hopkins University as an Assistant Professor on August 1, 2017.

IN MEMORIAM - MATTHEW RILEY, Ph.D.

Dr. Matthew Reilly, a program officer in NIAAA’s Division of Neuroscience and Behavior (DNB) since 2009, passed away unexpectedly on May 15, 2017. He brought great enthusiasm and dedication to his management of a diverse research grant portfolio devoted to gene and protein networks involved in alcohol use disorder (AUD). Through his active leadership in the NIH’s Library of Network-Based Cellular Signatures (LINCS) Program, he developed a keen interest in applying bioinformatics approaches to the discovery of druggable targets for AUD and was very active in this capacity in NIAAA’s medications development efforts. Matt was well known and long appreciated in the alcohol research community. He is sadly missed.

HONORS & AWARDS

A number of NIAAA staff received 2017 NIH Director’s Awards, September 1, 2017: 

• Drs. George F. Koob, Bridget Williams-Simmons, Jennifer A. Hobin, Vivian B. Faden, Patricia Powell and Ralph Hingson for their contributions to the 2016 Surgeon General’s Report, Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs, and Health.
• Ms. Megan Ryan, for serving on the I-Corps Program Expansion team, an entrepreneurial training program for SBIR and STTR companies provided by NIH and the U.S. Centers for Disease Control and Prevention (CDC).
• Mr. Jonathan Folkers, for serving on the NIH Federal Information Technology Acquisition Reform Act (FITARA) Working Group which was recognized for exceptional leadership and resourcefulness in coordinating NIH's implementation of the FITARA.
• Mr. Ho Lam for serving on the Office of Management and Budget (OMB) M-16-02 Implementation Workgroup which was recognized for developing and delivering a successful response to the initial requirements of OMB's desktop and laptop category management policy, M-16-02. 

Dr. Matthew Sloan, Postdoctoral Visiting Fellow in the Section on Human Psychopharmacology, Division of Intramural Clinical and Biological Research (DICBR), was awarded a fellowship from the NIH Center for Compulsive Behaviors (CCB) directed by Dr. Veronica Alvarez (Laboratory on the Neurobiology of Compulsive Behaviors, DICBR). As a CCB Fellow, Dr. Sloan will conduct research examining the behavioral and neurobiological underpinnings of compulsive alcohol use using human laboratory models. 

Dr. Young-Eun Cho in the Section on Clinical Neuropsychopharmacology (CPN) received the Research Society on Alcoholism (RSA) Junior Investigator Award at the 2017 RSA annual meeting. 

Dr. Resat Cinar in the Laboratory of Physiologic Studies received the Award for Research Excellence of the Hermansky-Pudlak Syndrome (HPS) Network, at its 24^th annual HPS Conference on March 11, 2017, in New York, New York. The award was in recognition of his work on a potential new therapeutic compound for lung fibrosis.

Dr. Allison Daurio, a post-baccalaureate fellow in the Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology (SCPN), received a 2017 RSA Student Merit Award. 

Dr. Mehdi Farokhnia, a postdoctoral fellow in SCPN, was a 2017 RSA Gordis Award finalist. 

Four NIAAA postdoctoral fellows are among the recipients of the 2018 NIH Fellows Award for Research Excellence. They are (mentors in parentheses):

• Dr. Mehdi Farokhnia (Dr. Lorenzo Leggio);
• Dr. Ayesha Sengupta (Dr. Andrew Holmes);
• Dr. Shana Silverstein (Dr. Andrew Holmes); and
• Dr. Mingjiang Xu (Dr. Bin Gao).

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

Notice of Funding Opportunities (NOFO) Issued by NIAAA

Alcoholic Hepatitis Clinical and Translational Network (AHN). This NOFO supports applications within the AHN to accelerate the discovery of diagnostic and treatment options for patients with alcoholic hepatitis. The AHN is composed of five components: the Late Phase Clinical Trials and Observational Studies U01 (RFA-AA-18-002), Translational Research U01 (RFA-AA-18-003), Data Coordinating Center U24 (RFA-AA-18-004), Clinical Pilot Trials U01 (RFA-AA-18-005), and Basic/Pre-Clinical Component UH2/UH3 (RFA-AA-18-006). 

NIH Blueprint for Neuroscience Research: Dynamic Neuroimmune Interactions in the Transition from Normal CNS Function to Disorders, R01 (RFA AA-18-007). The objective of this NOFO is to transform the understanding of how dynamic interactions among multiple cell types involved in neuroimmune interactions (e.g., neurons, glia cells, neurovascular units, or other neuroimmune components) mediate the transition from normal central nervous system (CNS) function to disorder conditions. This NOFO solicits projects that combine diverse expertise and use innovative approaches to address these questions at the molecular, cellular, and circuitry levels. 

Secondary Analyses of Existing Alcohol Research Data, R01 (PA-17-467) and R03 (PA-17-468). This NOFO encourages the submission of investigator-initiated research grant applications to support the secondary analysis of existing data sets, with the goal of enhancing our understanding of patterns of alcohol consumption, the epidemiology and etiology, including genetics, of alcohol-related problems.  

Alcohol-Induced Effects on Tissue Injury and Repair, R01 (PA-17-297) and R21 (PA-17-296) This NOFO solicits applications that focus on the molecular and cellular mechanisms of tissue injury and repair associated with alcohol use in humans. 

Understanding Processes of Recovery in the Treatment of Alcohol Use Disorder, R01 (PA-17-285) and R21 (PA-17-284). The NOFO solicits applications that seek to examine processes of recovery and relapse in the treatment of AUD. Applications high in innovation and significance that address the following potential topics are highly encouraged: defining recovery, examining new and innovative methods to examine precipitants of relapse, understanding mechanisms of mutual help and recovery, evaluating recovery systems of care, and examining processes of extended treatment for AUD.

 NIH-Wide NOFOs with NIAAA’s Participation

Discovery of in vivo Chemical Probes for Novel Brain Targets (R01) PAR-17-336

Tobacco Regulatory Science Small Grant Program for New Investigators (R03) RFA-OD-17-012

Tobacco Regulatory Science (R21) RFA-OD-17-014

BRAIN Initiative: New Concepts and Early-Stage Research for Large-Scale Recording and Modulation in the Nervous System (R21) RFA-EY-17-002

Multidisciplinary Studies of HIV/AIDS and Aging (R21) PAR-17-320

Administrative Supplements for Research on Dietary Supplements PA-17-307

Addressing Suicide Research Gaps: Aggregating and Mining Existing Data Sets for Secondary Analyses (R01) RFA-MH-18-400

HIV and Hepatitis B Co-Infection: Advancing HBV Functional Cure through Clinical Research (R01) PA-17-279

In Vitro and Animal Model Studies on HBV/HIV Co-Infection (R01) PA-17-280 and (R21) PA-17-281

Mechanisms and Consequences of Sleep Disparities in the United States (R21) PAR-17-235 and (R01) PAR-17-234

NIAAA Policy Notices

Request for Information (RFI): NIAAA Initiative for Collecting, Archiving, and Sharing Individual-Level Human Subjects Data. This RFI sought public comments on a proposed data-sharing initiative to create a repository of all future NIAAA-funded studies that include human subjects. With such an initiative, all NIAAA-funded researchers would be expected to make individual-level data obtained from NIAAA-funded human subjects research available to the general research community (NOT AA 17-005).

NOTABLE NIAAA STAFF ACTIVITIES -- APRIL 2017 -  JULY 2017

NIAAA Staff Activities at the 2017 Research Society on Alcoholism (RSA) Annual Meeting, June 24–28, 2017, Denver, Colorado

Satellite Meetings:

• “Health Disparities in Alcohol and Other Drug Problems and Health Equity Approaches: Theories, Methods, and Applications on Minority Health & Health Disparities Updates at NIAAA and NIH” (Dr. Judith A. Arroyo, presenter)
• “Mechanisms of Behavior Change (MOBC)” (Drs. Brett Hagman and Robert Huebner, presenters)
• “Advancing Research on Underage Alcohol Use and Social Media Involvement: An RSA Satellite Workshop” (Dr. Robert Freeman, organizer and chair)
• “New Developments in Understanding Alcohol-Related Partner Violence: Evidence from 4 Ongoing Investigations and Implications for Prevention” (Dr. Robert Freeman, organizer and chair)
• “Fetal Alcohol Spectrum Disorder (FASD) Study Group” (Dr. William Dunty, presenter)
• “Alcohol and Immunology Research Interest Group (AIRIG)” (Dr. Joe Wang, introductory speaker, and Dr. M. Katherine Jung, discussant)

 Symposia/Roundtables/Workshops

• “National Consortium on Alcohol & Neurodevelopment in Adolescence (NCANDA): Towards Shaping the Future of Adolescent Alcohol and Addiction Research” (Dr. John Matochik, introductory presenter)
• “Role of Stable and Enduring marks of the Epigenome in the Development of Alcoholism” (Dr. Antonio Noronha co-chair and introductory presenter)
• “The Use of Model Organisms to Understand Human Genetics of Alcoholism” (Dr. Abbas Parsian, co-organizer and presenter)
• “Perineuronal Nets – Weaving New Twists in Alcohol and Drug Use and Dependence” (Drs. Soundar Regunathan and Qi-Ying Liu, co-organizers, and Dr. Elizabeth Powell, discussant)
• “Impact of Brain-Gut-Liver Axis and Alcohol Induced Neuroinflammation on Organ Injury” (Dr. Soundar Regunathan, co-chair and presenter)
• “Novel Research Methods in Delineating Mechanisms of Behavior Change in the Treatment of Alcohol Use Disorder” (Dr. Brett Hagman, organizer, co-chair and presenter)
• “Everything You Ever Wanted to Know About Alcohol Treatment But Were Afraid To Ask: A Primer For Non-Clinicians” (Drs. Anita Bechtholt and Robert Huebner, organizers, and Dr. George F. Koob, chair)
• “Novel IV Alcohol Administration Human Laboratory Paradigms” (Dr. Vijay Ramchandani, co-chair and presenter)
• “Mechanisms and Functional Role of Alcohol-Induced Gut Leakiness in Inflammatory Organ Damage” (Dr. B.J. Song, co-organizer and presenter)
• “Is Dopamine Dead? New Findings Regarding Dopamine’s Role in Alcohol Use and Treatment” (Dr. Lorenzo Leggio, discussant)
• “Diversity in Drinking and Associated Problems Among U.S. Hispanics” (Dr. Judith A. Arroyo, discussant)
• “Cell, Circuit, Context-Dependent Striatal Activities in Alcohol Seeking Behaviors” (Dr. Veronica Alvarez, presenter)
• “Emerging Ways to Leverage Human Laboratory Paradigms to Advance Medication Development for Alcoholism” (Dr. Raye Litten, discussant)
• “The Neglected Catecholamine Noradrenergic Mechanisms in Regulation of Alcohol-Related Behaviors” (Dr. Raye Litten, discussant)
• “New Features in the Expanded APIS Coverage of Recreational Cannabis” (Dr. Mike Hilton, co-organizer and presenter)
• “Applying a Behavioral Risk Modeling Framework to Alcohol-Related Problems in Community Settings” (Mr. Gregory Bloss, organizer and chair)
• “Non-Coding RNAs In Alcoholic Liver Disease: From Biomarkers to Targeted Therapeutics” (Dr. Dale Hereld, chair and introductory speaker)
• "Mechanistic Insights into Alcoholic Promotion of Intestinal and Hepatic Cancers" (Dr. Bill Dunty, discussant)
• “Stress Pathways in Alcohol Use Disorders: A Multifaceted Affair” (Dr. Andras Orosz, chair)
• “Young Scientists Forum on Alcohol-Induced Cellular and Tissue Damage” (Dr. Gary Murray, organizer and chair)
• “Expanding Your Research Possibilities and Collaborations: NIAAA-Supported R24 Resource Programs in Basic Biomedical Research” (Drs. Dale Hereld and Joe Wang, co-organizers and co-chairs, and Dr. Kathy Jung, introductory speaker)
• “Multi-Organ Effects of Alcohol on the Innate Immunity” (Dr. Kathy Jung, introductory speaker).

 Other RSA Activities

• Dr. Lorenzo Leggio, the 2016 RSA Early Career Investigator Awardee, gave a plenary talk titled “Novel pharmacological targets to treat alcohol use disorder: going with your gut?”
• Drs. Marcia Scott, Wenxing Zha and Anita Bechtholt participated in grantsmanship training activities.
• See page 22 for Communications Activities at RSA.

 NIAAA Staff Participation in Symposia/Workshops/Roundtables at Other Scientific Meetings

Sweden Child Week, Gotenburg, Sweden, April 24–28, 2017

• Dr. Kenneth Warren gave a plenary address that provided a 400-year history of FASD and discussed ongoing as well as new research initiatives on FASD.
• Dr. Margaret Murray gave a plenary lecture titled “FASD in the Global Health Agenda” and co-led a workshop on the evidence base for identifying and addressing women’s drinking in prenatal clinics. 

Fourth International Congress on Alcoholism and Stress, Volterra, Italy, May 9–12, 2017

• Dr. George F. Koob was a plenary speaker on the first day of the meeting. (See Director’s Activities on page 5)
• Dr. Vijay Ramchandani chaired a symposium titled “Stress Vulnerability and Alcohol Use and Consequences: From Human Laboratory Studies to Clinical Outcomes,” which included presentations by Dr. Bethany Stangl, NIAAA Research Fellow, and Dr. Melanie Schwandt, Staff Scientist in the NIAAA Office of the Clinical Director.
• Dr. Lorenzo Leggio co-chaired a symposium titled “Feeding- and Stress-Related Neuroendocrine Pathways in Alcohol Use Disorder: Recent Findings” where he also gave a talk on “Ghrelin and GLP-1 as Potential New Pathways Toward Medication Development for Alcohol Use Disorder: Recent Clinical Data.”
• Dr. Antonio Noronha co-chaired a symposium titled “Emerging role of Epigenetic Reprogramming and Synaptic Remodeling in Alcohol Use and Alcoholism”, as well as co-chaired and presented awards at the Young Investigator Symposium, which featured presentations by six young and early-stage investigators. 

NIAAA/INSERM Workshop, Bordeaux, France, May 16, 2017 - NIAAA and the French National Institute of Health and Medical Research (INSERM) held a workshop to promote collaboration between U.S. and French investigators in public health research regarding alcohol. The meeting was highlighted in an editorial in Lancet soon after. (See thelancet.com/public-health, Published online May 24, 2017, http://dx.doi.org/10.1016/S2468-2667(17)30102-0 )

• Drs. George F. Koob, Peggy Murray, and Ralph Hingson represented NIAAA at the meeting.

• Dr. Ralph Hingson chaired a session titled “Reducing Drinking and Driving” at a symposium titled “Reducing the Burden of Harmful Alcohol Use: Opportunities for Collaborative Research,” at which he also gave two talks: “Preventing Impaired Driving from Alcohol and Drugs,” and “Interventions that Work to Prevent Underage Drinking.”

French Neuroscience Society Meeting (NeuroFrance 2017), Bordeaux, France, May 19, 2017

• Dr. George F. Koob gave a plenary lecture. (See Director’s Activities on page 5)
• Dr. Peggy Murray chaired a symposium, “Alcohol Use Disorders Across the Life Span: Effects on Brain and Behavior with Attention to Gender Differences.” 

American Psychiatric Association Annual Meeting, San Diego, California, May 20–24, 2017

• Dr. Andras Orosz chaired a session titled, “Alcohol Use and Older Adults.”  
• Dr. Kathy Jung presented a talk titled “A Wearable Alcohol Biosensor-Benefits and Challenges.” 

American Society of Clinical Psychopharmacology Annual Meeting, Miami Beach, Florida, May 30–June 1, 2017

• Dr. Raye Litten presented “NIAAA’s Medications Development Program to Treat Alcohol Use Disorder: Advances, Goals, and Initiatives” as part of the Federal Agency Directors Plenary Session.
• Dr. Daniel Falk presented “Alcohol Clinical Trials Initiative (ACTIVE) Validation of a Potential Patient-Reported Outcome Measure of Alcohol-Related Consequences (the IMBIBE) and its Use as an Endpoint in Alcohol Pharmacotherapy Trials” as part of the symposium “The Development and Selected Performance of Patient Reported Outcomes (PRO) in Psychopharmacotherapy Trials - Is the Juice Worth the Squeeze? A Review of Initiatives by the FDA, NIH, and the Alcohol Clinical Trials Initiative (ACTIVE).”

World Health Organization (WHO) Forum on Alcohol, Drugs, and Addictive Behaviors, Geneva, Switzerland, June 26–28, 2017.

• Dr. Peggy Murray gave a plenary presentation on the NIAAA-WHO study of the prevalence on FASD in very low-income countries, and moderated a session on alcohol and pregnancy in the global strategy to reduce alcohol-related harms portion of the meeting. Dr. Murray also participated in a meeting with global experts in FASD diagnosis to determine a strategy for working with the International Classification of Diseases (ICD) committee on updating diagnostic criteria for FASD.
• Dr. Ralph Hingson participated in his capacity as a member of the coordinating council for the implementation of the WHO Global strategy to reduce the harmful use of alcohol.

 American Psychological Association Annual Meeting, Washington, DC, August 3–6, 2017

• Dr. Raye Litten served as a discussant for the following symposia: “Reduction in WHO Drinking Risk Level as an Endpoint for Alcohol Clinical Trials” and “Back to the Lab: New Human Laboratory Approaches in Addictions Treatment Development.”
• Dr. Daniel Falk presented “WHO Drinking Risk Level as Endpoints in Clinical Trials” as part of the symposium “Reduction in WHO Drinking Risk Level as Endpoints for Alcohol Clinical Trials.”

Dr. Soundar Regunathan gave introductory remarks detailing NIAAA efforts on FASD research during the symposium titled “Neuropathologic mechanisms, consequences, and intervention in Fetal Alcohol Spectrum Disorders” at the American Society for Neurochemistry annual meeting in Little Rock, Arkansas, on March 20, 2017. 

Dr. Resat Cinar’s abstract was selected for a short talk at the Keystone Symposium on Injury, Inflammation and Fibrosis in Snowbird, Utah, on March 29, 2017. His presentation was titled “Cannabinoid CB1 receptor overactivity contributes to the pathogenesis of IPF: its dual targeting with inducible nitric oxide synthase improves anti-fibrotic efficacy.” 

Dr. Deidra Roach organized and presented at a symposium titled “New Frontiers in the Treatment of Co-Occurring AUD and Anxiety” at the annual conference of the American Society of Addiction Medicine, in New Orleans, Louisiana, on April 6–9, 2017. 

Dr. Soundar Regunathan participated in the Young Investigator Research Forum sponsored by American Association of Sleep Medicine in Bethesda, Maryland, on April 13, 2017. He presented NIAAA priorities on sleep and alcohol research and participated in discussion. 

Dr. Antonio Noronha attended the International Behavioral and Neural Genetics Society (IBANGS) meeting in Madrid, Spain, on May 15–18. He presented NIAAA’s research priorities and NIH’s grant mechanisms for early-stage investigators at a special mentoring session. In addition, he discussed NIAAA’s Research Agenda for Human Genetics Research and the recent report of the Advisory Committee for Genetics Research at NIAAA. 

Dr. Elizabeth Powell represented NIAAA as a member of the Early Career Investigators: Federal Funding Panel, at the Society of Biological Psychiatry 72^nd Annual Meeting, in San Diego, California, on May 18–20, 2017. 

Dr. Anita Bechtholt organized and chaired a symposium titled “Stress and Alcohol Use Disorder: New Findings, New Directions” at the annual meeting of the Association for Psychological Science in Boston, Massachusetts, on May 25–28, 2017. 

Dr. Antonio Noronha presented NIAAA’s Strategic Plan and DNB research priorities at the Opening Ceremony of the Fifth Asia-Pacific Society for Alcohol and Addiction Research-Taiwanese Society of Addiction Science (APSAAR-TSAS) meeting, in Taipei, Taiwan, on May 31–June 3, 2017. He also co-chaired a symposium titled “Animal Study in Addiction” and contributed to the discussion on preclinical targets for medications development at the meeting. 

Dr. Raye Litten served as an Expert Panel Member for the U.S. Department of Defense’s Pathophysiology of Post-Traumatic Stress Disorder: Rethinking Drug Targets Conference, in Shepherdstown, West Virginia, on June 13–15, 2017. 

Mr. Gregory Bloss organized and chaired a session titled “Economic Perspectives on Personalized Medicine” at the International Health Economics Association’s 12^th World Congress, in Boston, Massachusetts, on July 10, 2017. 

Dr. Veronica Alvarez was an invited speaker at the first Gordon Research Conference on the Neurobiology of Addiction, in Hong Kong, China, on July 16–21, 2017. Her talk was titled “Mechanisms Underlying the Vulnerability for Alcohol Abuse.” 

Dr. Bill Dunty participated in the symposium titled “Improving Approaches to System-involved Youth with Fetal Alcohol Spectrum Disorders” at the National Council of Juvenile and Family Court Judges (NCJFCJ) 80^th Annual Conference, in Washington, DC, on July 18, 2017. 

Dr. Andrew Holmes was a keynote speaker at the Computational Approaches to Memory and Plasticity meeting, in Bangalore, India, on July 19–August 3, 2017. His presentation was titled “Anxiety Treatments: Circuit-based Approaches to Identifying New Anxiolytics.” 

Dr. Ralph Hingson organized a half-day course titled “New Research Since the Surgeon General’s Call to Action to Prevent and Reduce Underage Drinking” at the Community Anti-Drug Coalitions Mid-Year Training Institute, in Atlanta, Georgia, on July 26, 2017. 

Dr. Joseph Hibbeln co-organized an international conference for the International Society for Nutritional Psychiatry Research, in Bethesda, Maryland, on July 30–August 2, 2017. 

Other NIAAA Staff Activities

Dr. Antonio Noronha served as Scientific Review Editor and Dr. Jennifer A. Hobin served as Editor-in-Chief of the “Alcohol-Organ Interactions: Injury and Repair” issue of Alcohol Research: Current Reviews, which was released in July 2017. The issue can be accessed online at arcr.niaaa.nih.gov/arcr382/toc38_2.htm.

Drs. George Kunos, Resat Cinar, Malliga Iyer and Kenner Rice have developed a new class of therapeutic compounds (PCT/US2013/069686) that block CB1 receptors with reduced brain penetrance and simultaneously engage a secondary target such as Inducible nitric oxide synthase (iNOS) or AMP kinase for the treatment of metabolic disorders. These compounds have been licensed by a second start-up company (Vital Spark, Inc.) for translation to human use to treat systemic sclerosis and for commercial development.

WHAT'S AHEAD? 

The 2017 National Institute on Drug Abuse (NIDA)-NIAAA Mini-Convention will be held on November 10, 2017, as a satellite event to the annual meeting of the Society for Neuroscience (SfN) in Washington, DC. The theme this year is The Sciences of Astrocytes, Stress Response, and Translational Research. The mini-convention will also feature an Early-Career Investigator Showcase and the Jacob Waletzky Memorial Award Lecture. Drs. John Matochik and Changhai Cui, DNB, are the program contacts for NIAAA. 

The next annual in-person meeting of the ABCD Investigators, Extramural Advisory Board and Observational Study Monitoring Board will take place November 16, 2017, in conjunction with the SfN Annual Meeting, in Washington, DC, on November 11–15, 2017.

NIAAA RESEARCH HIGHLIGHTS

Magnitude and Trends in Heavy Episodic Drinking, Alcohol-Impaired Driving, and Alcohol-Related Mortality and Overdose Hospitalizations Among Emerging Adults of College Ages 18–24 in the United States, 1998–2014

Significance: Alcohol-impaired driving and heavy episodic drinking among 18- to 24-year-olds in the United States appear to have declined since 2005. However, alcohol-related hospitalizations and overdose deaths among this age group have continued to increase since 1998. Moreover, persistent high levels of heavy episodic drinking and related problems among emerging adults underscore a need to expand individually oriented interventions, college/community collaborative programs, and evidence-supported policies to reduce their drinking and related problems. 

OBJECTIVE: This article estimates percentages of U.S. emerging adults ages 18-24 engaging in past-month heavy episodic drinking and past-year alcohol-impaired driving, and numbers experiencing alcohol-related unintentional injury deaths and overdose hospitalizations between 1998 and 2014.

METHOD: We analyzed national injury mortality data from coroner, census, and college enrollment statistics, the National Survey on Drug Use and Health, and the Nationwide Inpatient Sample.

RESULTS: From 1999 to 2005, percentages of emerging adults ages 18-24 reporting past-month heavy episodic drinking rose from 37.1% to 43.1% and then declined to 38.8% in 2014. Alcohol-impaired driving rose from 24% to 25.5% and then declined to 16.0%. Alcohol-related unintentional injury deaths increased from 4,807 in 1998 to 5,531 in 2005 and then declined to 4,105 in 2014, a reduction of 29% per 100,000 since 1998. Alcohol-related traffic deaths increased from 3,783 in 1998 to 4,114 in 2005 and then declined to 2,614 in 2014, down 43% per 100,000 since 1998. Alcohol-related overdose deaths increased from 207 in 1998 to 891 in 2014, a 254% increase per 100,000. Other types of nontraffic unintentional injury deaths declined. Alcohol-overdose hospitalizations rose 26% per 100,000 from 1998 to 2014, especially from increases in alcohol/other drug overdoses, up 61% (alcohol/opioid overdoses up 197%). CONCLUSIONS: Among emerging adults, a trend toward increased alcohol-related unintentional injury deaths, heavy episodic drinking, and alcohol-impaired driving between 1998 and 2005 was reversed by 2014. Persistent high levels of heavy episodic drinking and related problems among emerging adults underscore a need to expand individually oriented interventions, college/community collaborative programs, and evidence-supported policies to reduce their drinking and related problems. (Hingson R, Zha W, Smyth D. Journal of Studies on Alcohol and Drugs 78(4), 540–548, 2017. PMID: 28728636) 

Drinking Beyond the Binge Threshold: Predictors, Consequences, and Changes in the U.S.

 Significance: Recent studies show that, among underage individuals, drinking, binge drinking (drinking five or more drinks on an occasion for men and four or more for women), and related health and social problems are declining. However, this study found that among all other age groups, binge drinking and drinking at levels beyond the binge thresholds have increased. Moreover, drinking two to three times and three or more times the gender-specific binge thresholds were associated with more negative consequences that pose health risks to those drinkers and others. 

Introduction: Binge drinking, five or more drinks on an occasion for men and four or more for women, marks risky alcohol use. However, this dichotomous variable removes information about higher, more dangerous consumption. This paper examines predictors, consequences, and changes over a decade in drinking one to two times, two to three times, and three or more times standard gender-specific binge thresholds, labeled Levels I, II, and III. Methods: In 2001–2002 and 2012–2013, respectively, 42,748 and 36,083 U.S. respondents aged ≥18 years were interviewed in person in cross-sectional waves of the National Epidemiologic Survey on Alcohol and Related Conditions (response rates, 81% and 61%). Respondents were asked their past-year maximum drink consumption per day, categorized as Levels I, II, or III. Predictors and whether Levels II and III were associated with more negative consequences were analyzed in 2012–2013 data. Results: In 2001–2002, 23% of adults reported past-year binge drinking, with 15% peaking at Level I, 5% at Level II, and 3% at Level III. In 2012–2013, those percentages increased significantly to 33% binging, and 20%, 8%, and 5% binging at Levels I, II, and III, respectively. After adjusting for alcohol use disorder, the strongest predictor of Level I, II, and III binging, Level III versus I and non-binge drinkers had higher odds of past-year driving after drinking and, after drinking, experiencing physical fights, injuries, emergency department visits, arrests/detentions, and other legal problems. Conclusions: Level II and III—relative to Level I—binging is associated with more negative alcohol consequences and may be increasing nationally. Research needs to explore prevention and counseling interventions. (Hingson R, Zha W, White A. American Journal of Preventive Medicine. 2017 Jun;52(6):717-727. PMID: 28526355) 

Vulnerability for Alcohol Use Disorder and Rate of Alcohol Consumption

Significance: This human laboratory study, using intravenous alcohol self-administration, demonstrated that the rate of achieving binge-level alcohol exposure is associated with risk factors for alcohol use disorder (AUD), including male sex, family history of alcoholism, and impulsivity, in non-dependent drinkers. Given the association of vulnerability of AUD with rates of binge drinking, rates of consumption should be assessed as part of a thorough clinical evaluation of alcohol use and problems. 

Objective: Although several risk factors have been identified for alcohol use disorder, many individuals with these factors do not go on to develop the disorder. Identifying early phenotypic differences between vulnerable individuals and healthy control subjects could help identify those at higher risk. Binge drinking, defined as reaching a blood alcohol level of 80 mg%, carries a risk of negative legal and health outcomes and may be an early marker of vulnerability. Using a carefully controlled experimental paradigm, the authors tested the hypothesis that risk factors for alcohol use disorder, including family history of alcoholism, male sex, impulsivity, and low level of response to alcohol, would predict rate of binging during an individual alcohol consumption session. Method: This cross-sectional study included 159 young social drinkers who completed a laboratory session in which they self-administered alcohol intravenously. Cox proportional hazards models were used to determine whether risk factors for alcohol use disorder were associated with the rate of achieving a binge-level exposure. Results: A greater percentage of relatives with alcoholism (hazard ratio: 1.04, 95% CI=1.02–1.07), male sex (hazard ratio: 1.74, 95% CI=1.03–2.93), and higher impulsivity (hazard ratio: 1.17, 95% CI=1.00 to 1.37) were associated with a higher rate of binging throughout the session. Participants with all three risk factors had the highest rate of binging throughout the session compared with the lowest risk group (hazard ratio: 5.27,95%CI=1.81–15.30). Conclusions: Binge drinking may be an early indicator of vulnerability to alcohol use disorder and should be carefully assessed as part of a thorough clinical evaluation. (Gowin JL, Sloan ME, Stangl BL, Vatsalya V, Ramchandani VA. American Journal of Psychiatry, 2017 Aug 4:appiajp201716101180. Epub ahead of print. PMID: 28774194) 

A Relationship between the aldosterone - mineralocorticoid receptor pathway and alcohol drinking:  preliminary translational findings across monkeys, rats and humans 

Significance: This study examined the relationships between alcohol craving, drinking, and anxiety and the aldosterone pathway, as assessed by peripheral aldosterone concentrations and the brain expression of its receptor, the mineralocorticoid receptor (MR). The study showed a relationship between higher aldosterone concentrations and higher craving, drinking, and anxiety. On the other hand, lower expression of the MR in the amygdala was associated with higher alcohol drinking and anxiety. These results were consistent across three species: a rat model of alcohol dependence, a non-human primate model of excessive alcohol drinking, and a clinically-relevant sample of patients with alcohol dependence. The study supports future research to investigate the potential causality link between the aldosterone/MR pathway and alcohol use disorder (AUD) to shed light on the potential role of this pathway towards the development of novel pharmacological treatments for AUD. 

Aldosterone regulates electrolyte and fluid homeostasis through binding to the mineralocorticoid receptors (MRs). Previous work provides evidence for a role of aldosterone in alcohol use disorders (AUDs). We tested the hypothesis that high functional activity of the mineralocorticoid endocrine pathway contributes to vulnerability for AUDs. In Study 1, we investigated the relationship between plasma aldosterone levels, ethanol self-administration and the expression of CYP11B2 and MR (NR3C2) genes in the prefrontal cortex area (PFC) and central nucleus of the amygdala (CeA) in monkeys. Aldosterone significantly increased after 6- and 12-month ethanol self-administration. NR3C2 expression in the CeA was negatively correlated to average ethanol intake during the 12 months. In Study 2, we measured Nr3c2 mRNA levels in the PFC and CeA of dependent and nondependent rats and the correlates with ethanol drinking during acute withdrawal. Low Nr3c2 expression levels in the CeA were significantly associated with increased anxiety-like behavior and compulsive-like drinking in dependent rats. In Study 3, the relationship between plasma aldosterone levels, alcohol drinking and craving was investigated in alcohol-dependent patients. Non-abstinent patients had significantly higher aldosterone levels than abstinent patients. Aldosterone levels positively correlated with the number of drinks consumed, craving and anxiety scores. These findings support a relationship between ethanol drinking and the aldosterone/MR pathway in three different species. (Aoun EG, Jimenez V, Vendruscolo LF, Walter NAR, Barbier E, Ferrulli A, Haass-Koffler CL, Darakajian P, Lee MR, Addolorato G, Heeling M, Whiteman R, Koob GF, Grant KA, Leggio L.  Molecular Psychiatry, 2 May 2017, Epub ahead of print. PMID: 28461696)

Alcohol-associated intestinal dysbiosis impairs pulmonary host defense against Klebsiella pneumoniae

Significance: This paper investigates the effect of alcohol-induced dysbiosis (i.e., perturbed microbial imbalance in the gut) on the lung. The authors used a fecal adoptive transfer model to distinguish direct effects of alcohol on lung host defense from effects of an altered microbiome. They transferred microbiota originating from the gastrointestinal systems of alcohol-fed mice into the gastrointestinal systems of germ-free alcohol-naïve mice, and compared the result to mice receiving gut microbiota from untreated healthy mice. Mice recolonized with microbiota from alcohol-fed mice had higher susceptibility to pneumonia and gut barrier damage, even though the recipient animals had not been fed alcohol. Thus, the gut dysbiosis caused by alcohol directly impairs immune function in the lung.

 Background: AUD has been known to increase lung infections and impairs pulmonary host defense. It is also known that alcohol perturbs intestinal flora. However, the underlying mechanism of how alcohol-associated intestinal microbiota dysbiosis impacts pathophysiology and biodefense of distal organs has yet to be revealed. Results: The new study designed a murine fecal adoptive transfer model to study how alcohol-induced dysbiosis affects pulmonary immune defense.  Germ-free, alcohol-naive mice recolonized with dysbiotic microbiota from alcohol-fed mice are more susceptible to K. pneumoniae infection, and have significantly higher bacterial burden in the lung than those recolonized with eubiotic microbiota. Despite lacking alcohol consumption, these adoptively transferred mice recapitulate the dysbiotic characteristics seen in binge-on-chronic alcohol-fed mice, including increased gut barrier damage and impaired immune response, suggesting that alcohol consumption and intestinal dysbiosis may act in a two-hit mode for the increased susceptibility of pneumonia. The work also showed that alcohol consumption alters the composition of intestinal microbial community and the metabolic profile and such changes are maintained in the adoptively transferred mice. Further, alcohol-associated dysbiosis increases CD 4+ and CD8+ T cells sequestration in the gut, accompanied with a decreased macrophages and dendritic cell migration to the lung during infection, resulting a weakened pulmonary immune clearance. This elegantly designed study demonstrated, for the first time, how alcohol-associated microbiota dysbiosis impacts the immune defense of the lung, and lay a ground work for future clinical intervention. (Samuelson DR, Shellito JE, Maffei VJ, Tague ED, Campagna SR, Blanchard EE, Luo M, Taylor CM, Ronis MJJ, Molina PE, Welsh DA. PLoS Pathogens. 2017 Jun 12;13(6): e1006426. PMID: 28604843)

 Intestinal Fungi Contribute to Development of Alcoholic Liver Disease

Significance: The human gastrointestinal tract is home not only to bacteria but also to fungi. In this report, the authors demonstrate that, similar to the role established for gut bacteria, fungi contribute to chronic alcohol-induced liver damage, potentially by inducing an inflammatory response. Furthermore, the authors found that the altered gut fungal community (the mycobiome) in humans and systemic exposure to fungal products correlate well with the mortality of patients with alcoholic cirrhosis. If more evidence confirms this pioneering report that fungi contribute to the worsening of alcoholic liver disease, antifungal agents might be useful as a treatment or adjunct to treatment. 

Chronic liver disease with cirrhosis is the 12th leading cause of death in the United States, and alcoholic liver disease accounts for approximately half of all cirrhosis deaths. Chronic alcohol consumption is associated with intestinal bacterial dysbiosis, yet we understand little about the contribution of intestinal fungi, or mycobiota, to alcoholic liver disease. Here we have demonstrated that chronic alcohol administration increases mycobiota populations and translocation of fungal β-glucan into systemic circulation in mice. Treating mice with antifungal agents reduced intestinal fungal overgrowth, decreased β-glucan translocation, and ameliorated ethanol-induced liver disease. Using bone marrow chimeric mice, we found that β-glucan induces liver inflammation via the C-type lectin-like receptor CLEC7A on Kupffer cells and possibly other bone marrow-derived cells. Subsequent increases in IL-1β expression and secretion contributed to hepatocyte damage and promoted development of ethanol-induced liver disease. We observed that alcohol-dependent patients displayed reduced intestinal fungal diversity and Candida overgrowth. Compared with healthy individuals and patients with non-alcohol-related cirrhosis, alcoholic cirrhosis patients had increased systemic exposure and immune response to mycobiota. Moreover, the levels of extraintestinal exposure and immune response correlated with mortality. Thus, chronic alcohol consumption is associated with an altered mycobiota and translocation of fungal products. Manipulating the intestinal mycobiome might be an effective strategy for attenuating alcohol-related liver disease. (Yang AM, Enamine T, Horwath K, Chen P, Wang L, Llorente C, Bluemel S, Hartmann P, Xu J, Koyama Y, Kosheleva T, Torralba MG, Moncera K, Beeri K, Chen CS, Freese K, Hellerbrand C, Lee SM, Hoffman HM, Mehal WZ, Garcia-Tsao G, Mutlu EA, Keshavarzian A, Brown GD, Ho SB, Bataller R, Stärkel P, Fouts DE, Schnabl, B. Journal of Clinical Investigation. 2017 Jun 30;127(7):2829-2841. PMID: 28530644)

 Adolescent alcohol exposure decreases frontostriatal resting -state functional connectivity in adulthood

Significance: Adolescent alcohol exposure may perpetuate a lack of inhibitory control, leading to long term adolescent behavioral dysfunction into adulthood. Inhibitory control is governed by frontal cortical regions that continue to mature through adolescence into the adult stage. The report uses resting state functional magnetic resonance imaging to track changes in functional connectivity in an adult animal model after adolescent alcohol exposure. The study finds that acute ethanol exposure leads to increased responses to alcohol as an adult and decreased functional connectivity between brain regions that control impulsivity, risk-taking, and drug use. The results indicate that adolescent alcohol use permanently alters brain circuity, leading to increased susceptibility to adult alcohol use disorder. 

Connectivity of the prefrontal cortex (PFC) matures through adolescence, coinciding with emergence of adult executive function and top-down inhibitory control over behavior. Alcohol exposure during this critical period of brain maturation may affect development of PFC and frontolimbic connectivity. Adult rats exposed to adolescent intermittent ethanol (AIE; 5 g/kg ethanol, 25 percent v/v in water, intragastrically, 2-day-on, 2-day-off, postnatal day 25-54) or water control underwent resting-state functional MRI to test the hypothesis that AIE induces persistent changes in frontolimbic functional connectivity under baseline and acute alcohol conditions (2 g/kg ethanol or saline, intraperitoneally administered during scanning). Data were acquired on a Bruker 9.4-T MR scanner with rats under dexmedetomidine sedation in combination with isoflurane. Frontolimbic network regions-of-interest for data analysis included PFC [prelimbic (PrL), infralimbic (IL), and orbitofrontal cortex (OFC) portions], nucleus accumbens (NAc), caudate putamen (CPu), dorsal hippocampus, ventral tegmental area, amygdala, and somatosensory forelimb used as a control region. AIE decreased baseline resting-state connectivity between PFC subregions (PrL-IL and IL-OFC) and between PFC-striatal regions (PrL-NAc, IL-CPu, IL-NAc, OFC-CPu, and OFC-NAc). Acute ethanol induced negative blood-oxygen-level-dependent changes within all regions of interest examined, along with significant increases in functional connectivity in control, but not AIE animals. Together, these data support the hypothesis that binge-like adolescent alcohol exposure causes persistent decreases in baseline frontolimbic (particularly frontostriatal) connectivity and alters sensitivity to acute ethanol-induced increases in functional connectivity in adulthood. (Broadwater MA, Lee S-H, Yu Y, Zhu H, Crews FT, Robinson DL, Shih Y-Y I. Addiction Biology, 2017 Jul 9. PMID: 28691248)

 Metabolomics Biomarkers to Predict Acamprosate Treatment Response in Alcohol-Dependent Subjects

 Significance: This study evaluated the potential accuracy of predictive models that incorporate metabolomic biomarkers to determine response to acamprosate as a treatment for alcohol use disorder (AUD). Baseline serum metabolites and clinical scores were used in multivariable predictive models to determine treatment responders to acamprosate during three months of treatment. A sensitivity of 0.83 (true positives) and a specificity of only 0.31 (false positives) suggested that more potential biomarkers are needed to expand the clinical utility of predictive algorithms for a pharmacological response to AUD. 

Precision medicine for alcohol use disorder (AUD) allows optimal treatment of the right patient with the right drug at the right time. Here, we generated multivariable models incorporating clinical information and serum metabolite levels to predict acamprosate treatment response. The sample of 120 patients was randomly split into a training set (n = 80) and test set (n = 40) five independent times. Treatment response was defined as complete abstinence (no alcohol consumption during 3 months of acamprosate treatment) while nonresponse was defined as any alcohol consumption during this period. In each of the five training sets, we built a predictive model using a least absolute shrinkage and section operator (LASSO) penalized selection method and then evaluated the predictive performance of each model in the corresponding test set. The models predicted acamprosate treatment response with a mean sensitivity and specificity in the test sets of 0.83 and 0.31, respectively, suggesting our model performed well at predicting responders, but not non-responders (i.e. many non-responders were predicted to respond). Studies with larger sample sizes and additional biomarkers will expand the clinical utility of predictive algorithms for pharmaceutical response in AUD. (Hinton DJ, Vazquez MS, Hitschfeld MJ, Ho AMC, Karpyak VM, Biernacka JM, Choi DS. Scientific Reports. 2017 May 31;7(1):2496. PMID: 28566752) 

A preliminary randomized controlled trial of contingency management for alcohol use reduction using a transdermal alcohol sensor 

Significance: Contingency management has been demonstrated to be an effective strategy for promoting abstinence in substance use disorders, but the use of contingency management in alcohol use disorder (AUD) has been restricted by limitations in detecting alcohol consumption. Transdermal detection has shown promise for shaping behavior in AUD. This study shows its utility in a between-subjects comparison using yoked non-contingent reinforcement. These data provide more certainty that positive outcomes are contingency-based and provide support for proceeding to randomized controlled trials in treatment populations using continuous transdermal alcohol detection.  

AIMS: We tested the efficacy of daily contingent reinforcement for reducing alcohol use compared with (yoked) non-contingent reinforcement (NR) using a transdermal alcohol sensor to detect alcohol use. DESIGN: Pilot randomized controlled design with 1 baseline week, 3 intervention weeks and 1-month follow-up. SETTING: New England, USA. PARTICIPANTS: Heavy drinking adults (46.7% female) not seeking treatment were randomized to (1) an escalating schedule of cash reinforcement (CR; n = 15) for days on which alcohol was neither reported nor detected or (2) yoked NR (n = 15). INTERVENTION AND COMPARATOR: Reinforcement for CR participants started at $5 and increased $2 every subsequent day on which alcohol was not detected or reported, to a maximum of $17. Participants received no reinforcement for days on which alcohol use was detected or reported, and the reinforcer value was re-set to $5 the day after a drinking day. NR participants were yoked to the daily reinforcer value of an individual in the CR condition, in order of enrollment. Paired participants in CR and NR therefore received the same amount of money, but the amount for the NR participant was not behavior-related. MEASUREMENTS: The primary outcome was percentage of days without sensor-detected drinking. Secondary outcomes were number of consecutive days with no detected drinking, peak transdermal alcohol concentration (TAC), self-reported drinks per week and drinking below NIH low-risk guidelines. FINDINGS: Controlling for baseline, CR had a higher percentage of days with no drinking detected (54.3%) than NR (31.2%) during intervention weeks [P = 0.05, Cohen's d = 0.74; 95% confidence interval (CI) = 0.007-1.47]. The longest period of consecutive days with no drinking detected was 8.0 for CR versus 2.9 for NR (P = 0.03, d = 0.85; 95% CI = 0.08-1.61). Peak TAC during intervention showed a non-significant group difference (P = 0.20; d = 0.48; 95% CI = 0.00-1.18); a similar result was found for drinks per week (P = 0.12; d = 0.59; 95% CI = 0.00-1.30). Four times more participants in CR drank below NIH low-risk drinking guidelines during intervention than did participants in NR: 31.1 versus 7.1% (P = 0.07; d = 0.71; 95% CI = -0.04 to 1.46). At 1-month follow-up, the highest number of consecutive days without drinking (self-report) did not differ significantly between conditions (P = 0.26), but showed a medium effect size (d = 0.44; 95% CI = -0.32 to 1.18). CONCLUSIONS: Cash incentives linked to a transdermal alcohol sensor can reduce heavy alcohol consumption while the incentives are in operation. (Barnett NP, Celio MA, Tidey JW, Murphy JG, Colby SM, Swift RM. Addiction. 2017 Jun;112(6):1025-1035. Epub 2017 Feb 22. PMID: 28107772) 

Effects of Varenicline on Alcohol Cue Reactivity in Heavy Drinkers

Significance: Clinical trials and human laboratory studies have established that varenicline can reduce rates of alcohol use among heavy drinkers. Less is known about the mechanisms by which varenicline has this effect on drinking behavior. In this human laboratory study, varenicline reduced the alcohol-induced craving in both heavy drinking smokers and non-smokers. Varenicline continues to show promise as a pharmacological treatment for alcohol use disorder. 

Clinical trials and human laboratory studies have established that varenicline can reduce rates of alcohol use among heavy drinkers. Less is known about the mechanisms by which varenicline has this effect on drinking behavior. Reactivity to alcohol cues is often cited as the primary cause of relapse among those being treated for alcohol use disorder, and several front-line treatments for alcohol use disorder work, at least in part, by minimizing cue-induced alcohol craving. The current double-blind, placebo-controlled human laboratory study tested the effects of varenicline on alcohol cue reactivity in a group of heavy-drinking adult smokers and nonsmokers. As part of a larger series of sequential human laboratory experiments testing the effects of varenicline on drinking outcomes, participants were assigned (between-participant) to receive either active varenicline (2 mg/day) or placebo. Following a titration period, participants (n = 77) attended a laboratory session during which they were exposed to alcohol and neutral cues using a standard cue reactivity paradigm. Alcohol cue exposure increased craving for alcohol in both medication groups. However, participants receiving varenicline showed a smaller increase in alcohol craving compared to participants receiving placebo. The medication effect did not differ between smokers and nonsmokers. Among smokers, alcohol cue exposure also increased tobacco craving. Varenicline did not attenuate this effect. Results support the use of varenicline for reducing alcohol use in heavy drinkers and identify a potential mechanism by which varenicline reduces drinking. Varenicline continues to show promise as a pharmacological treatment for alcohol use disorder. (Roberts W, Harrison ELR, and McKee SA, Psychopharmacology. 2017 Jun 9. doi: 10.1007/s00213-017-4667-9. [Epub ahead of print]. PMID: 28600734) 

Effects of Varenicline on Alcohol Self-Administration and Craving in Drinkers with Depressive Symptoms

Significance: The purpose of this study is to examine whether depressive symptoms moderated the effectiveness of varenicline in reducing risk of drinking in individuals with alcohol use disorder (AUD). Those with higher levels of depression showed the largest reduction in drinking and alcohol craving with varenicline. This study suggests a role of varenicline in treating patients with AUD and elevated depressive symptoms.  

Varenicline (VAR) is approved to aid in smoking cessation and has been shown to be effective for reducing alcohol consumption in heavy drinkers. Little is known, however, about treatment moderators that may influence efficacy. The current study reanalyzed data from a human laboratory study (Verplaetse et al., 2016) to determine whether VAR was more effective at reducing alcohol use among drinkers reporting symptoms of depression. Participants were 60 adults meeting DSM-IV criteria for alcohol use disorders (n = 60) who were randomly assigned to receive VAR (1 mg/day, 2 mg/day) or placebo. Following 7 days of medication pretreatment, participants attended a laboratory testing session. They provided self-reported ratings of alcohol craving and performed an ad libitum alcohol consumption task after receiving a priming dose of alcohol (target blood alcohol concentration = 0.030 g/dL). Higher blood VAR plasma levels were associated with less alcohol craving and less drinking among participants with more depressive symptoms. Among participants with fewer depressive symptoms, VAR was associated with more drinking during the ad libitum drinking task. These findings show that depression symptoms may be a moderator of VAR efficacy in alcohol users and provides evidence for the role of nAChRs in depression and alcohol use. (Roberts W, Verplaetse TL, Moore K, Oberleitner L, Picciotto MR, McKee SA, Journal of Psychopharmacology. 2017 Jul;31(7):906-914. PMID: 28351203)
 

NIAAA COMMUNICATIONS ACTIVITIES

 Press and Publications Activities:

Recent News Media Interviews: Dr. Koob and other NIAAA experts continue to speak with a variety of national and international news outlets on timely topics related to NIAAA’s research and its impact on treatment and prevention of AUD. High-profile interviews since May include: 

• Men’s Health
• Mother Jones
• CBS Radio
• Chicago Tribune
• Consumer Reports

 Notable Coverage: 

NBC Sunday Night with Megyn Kelly

On July 23, 2017, a segment on alcohol treatment ran on NBC Sunday Night. The piece featured interviews with Dr. Koob, who was also featured in supplementary material on the NBC website.

 Press Releases: 

• NIH-funded mouse study sheds light on neural risks associated with prenatal alcohol exposure (July 19, 2017)
• NIH findings link aldosterone with alcohol use disorder (July 17, 2017)
• Media Advisory: Intestinal fungi linked to worsening of alcoholic liver disease (May 22, 2017)
• Study finds tens of millions of Americans drink alcohol at dangerously high levels (May 17, 2017)
• New NIAAA strategic plan aims to advance alcohol research across a broad spectrum of areas (May 15, 2017) 

Publication Statistics: In the month of June, NIAAA filled orders for 34,849 copies of its print publications. As of July 31, there were 30,153 GovDelivery/Granicus subscribers to Alcohol Research: Current Reviews; 21,129 to the NIAAA Spectrum; and 20,942 to receive general information.

Social Media Highlights: The NIAAA Twitter account (@NIAAAnews) currently has more than 18,600 followers and averages about 100,000 impressions (number of times users saw each tweet on Twitter) per month. 

Activities at Research Society on Alcoholism (RSA) Annual Meeting: 

• NIAAA expanded its social media coverage of the RSA annual meeting by filming and tweeting short videos from the meeting. Videos featured Ken Sher, RSA President, Marisa Silveri, Chair of RSA’s National Advocacy and Public Education Committee, Dr. George F. Koob, NIAAA Director, and Dr. Robert Huebner, Director of NIAAA’s Division of Treatment and Recovery Research. 
• The symposium on AUD treatment, “Everything You Ever Wanted to Know About Alcohol Treatment but Were Afraid to Ask: A Primer for Non-Clinicians,” in which experts in the treatment field covered the many treatment options and potential pathways through treatment was filmed and is now available on the NIAAA website at niaaa.nih.gov/news-events/news-noteworthy/everything-you-ever-wanted-know-about-treatment-alcohol-use-disorder. 
• The Communications and Public Liaison Branch (CPLB) organized a well-attended showing of the HBO documentary Risky Drinking for RSA attendees. Drs. Koob and Roach, who were featured in the documentary, participated in a question and answer period after the screening.   

 Partnerships, Outreach & Public Liaison Activities:

 Summer Safety Promotion

Dr. George F. Koob participated in a live television interview with WBFF/Fox-45 Morning News (Baltimore, Maryland) on June 17. The interview discussed risky drinking during the summer months and helped promote NIAAA’s online cocktail calculator and the Rethinking Drinking website.

 Dr. George F. Koob and Dr. Lorenzo Leggio conducted a recorded television interview with WMAR/ABC-2 (Baltimore, Maryland) on June 19 from NIAAA’s bar laboratory at the NIH Clinical Center. They discussed NIAAA’s research on treatment for AUD, including possible triggers for craving alcohol; promoted NIAAA’s online resources; and discussed low-risk drinking limits. The segment aired several times during the week of June 26, 2017.

Awards

NIAAA received a Telly Award, which honors excellence in television, digital and streaming video, and non-broadcast productions, for the NIAAA summer safety fact sheet and social media series.

 Graduation Fact Sheet

NIAAA disseminated its fact sheet Parents—Talk with Your High School Graduates about Celebrating Safely via PR Newswire in June. The release had a total of 143 unique postings, representing a total potential audience of 86.4 million people. Outlets posting the release included Yahoo!, the Miami Herald, The Fresno Bee, the Minneapolis Star Tribune, The Buffalo News, and numerous parenting blogs and websites for health professionals.

 Select Partnership Updates

 American Society of Addiction Medicine (ASAM)

• July 25, 2017: ASAM’s Weekly e-Newsletter featured NIAAA’s Spectrum piece, “New Addiction Medicine Certification Available for Physicians.”

New liaison groups added to NIAAA’s roster:

• Friends of Recovery-New York
• National Council on Patient Information and Education
• Addiction Policy Forum
• American Medical Student Association
• Student Coalition on Addiction
• American Academy of Pediatrics

 Web Update:

 CPLB recently redesigned the NIAAA website with a new navigation aid to find “Research Training.”  The new tab is part of the main navigation bar found at the top of each web page.  This shortcut takes visitors to a new section featuring online resources, funding opportunities, and links about NIAAA and NIH-wide training and career development information. The pages were developed and curated by Ms. Lynn Morin, chair of the NIAAA Centers & Training Working Group. Visit the new Research Training landing page at niaaa.nih.gov/research-training-and-career-development.