NATIONAL ADVISORY COUNCIL ON ALCOHOL ABUSE AND ALCOHOLISM September 19–20, 2012

The National Advisory Council on Alcohol Abuse and Alcoholism (NIAAA) convened for its 131st meeting at 5:30 p.m. on September 19, 2012, at the Fishers Lane Conference Center in Rockville, Maryland, in closed session for a review of grant applications and a Merit Award extension.  The meeting recessed at 7:15 p.m.  Dr. Abraham Bautista, Director, Office of Extramural Activities, presided over the closed session, which, in accordance with the provisions of Sections 552b(C)(6), Title 5, U.S.C. and 10(d) of Public Law 92-463, excluded the public for the review, discussion, and evaluation of individual applications for Federal grant-in-aid funds.  Dr. Kenneth Warren, Acting Director, NIAAA, convened the Council in open session on September 20, 2012, at 9:00 a.m.

 

Council Members Present:

Linda L. Chezem, J.D.

Fulton T. Crews, Ph.D.

Suzanne M. de la Monte, M.P.H., M.D.

Cindy Ehlers, Ph.D.

Marianne L. Fleury

Scott L. Friedman, M.D.

Andres G. Gil, Ph.D.

Kathleen Grant, Ph.D.

Andrew C. Heath, Ph.D.

John H. Krystal, M.D.

Craig McClain, M.D.

Edward P. Riley, Ph.D.

Linda P. Spear, Ph.D.

Gyongyi Szabo, M.D., Ph.D.

 

Chairperson: Kenneth R. Warren, Ph.D.

Executive Secretary: Abraham P. Bautista, Ph.D.

Senior Staff:

Ralph Hingson, Sc.D., M.P.H., Vivian B. Faden, Ph.D.; Robert Huebner, Ph.D., Keith Lamirande; Howard Moss, M.D.; Antonio Noronha, Ph.D., Samir Zakhari, Ph.D.

 

Other Attendees at the Open Sessions:

Approximately 45 observers attended the open session, including representatives from constituency groups, liaison organizations, NIAAA staff, and members of the general public.

 

Call to Order of the Open Session, September 20, 2012

Dr. Kenneth Warren called the open session of the 131st meeting of the Council to order at 9:00 a.m. on Thursday, September 20, 2012. He expressed appreciation for contributions to the Council to Dr. Cindy Ehlers, Dr. Scott Friedman, Dr. Andrew Heath, Dr. John Krystal, Dr. Edward Riley, and Dr. Linda Spear, whose tenure on the Council will end soon. Dr. Warren welcomed participants to the meeting, and Council members and NIAAA senior staff introduced themselves.

 

Director’s Report

Dr. Warren highlighted key recent Institute activities, referring to the newly reformatted Director’s Report, whose featured Note from the Director focused on campus and college-age drinking.

• Legislation, budget, and policy.  Dr. Warren explained that NIAAA simultaneously manages three budgets: executing the current year’s budget, planning for implementation of the next year’s budget, and planning for the subsequent year. With FY 2012 slated to end on September 30, NIAAA was completing execution of that year’s awards. For FY 2012 the National Institutes of Health (NIH) received $30.6 billion, and NIAAA received an appropriation of $459.4 million, an increase of 0.3% over the previous year that compared favorably with most agencies’ appropriations. Regarding the FY 2013 budget, Congress was expected to pass a continuing resolution that would maintain funding at slightly more than FY 2012 levels. Both Houses of Congress recommended modest increases in NIAAA’s budget over the President’s budget request; a joint conference will reconcile the versions. Preliminary planning for FY 2014 has begun for an NIH budget that omits line items for NIAAA and NIDA, but that reflects the establishment of the proposed National Institute on Substance Use and Addictive Disorders. NIAAA continues its planning for future research.

• Director’s activities. Dr. Warren highlighted several recent activities, including his presentations at the 7th International Symposium on Alcoholic Liver and Pancreatic Diseases and Cirrhosis in Beijing, and at the International Society for Biomedical Research on Alcoholism 2012 Congress in Japan. Dr. Warren also participated in an NIAAA/Substance Abuse and Mental Health Services Administration consensus panel on recommendations for protocols for treatment of alcohol use disorders.

• NIAAA staff honors and organization.  Dr. Lorenzo Leggio has joined the Intramural Programs of NIAAA and NIDA, a joint appointment, and will serve as Acting Chief of the NIAAA Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology. After more than 25 years of service to NIAAA, Dr. Sam Zakhari, Director of NIAAA’s Division of Metabolism and Health Effects, will retire. Dr. Joseph Hibbeln received the Wilhelm Normann Medal, the highest award of the Deutsche Gesellschaft fϋr Fettwissenschaft e.V. Dr. Pal Pacher was granted tenure by NIH Central Tenure Committee and was awarded the Young Investigator Award by the Board of Directors of International Cannabinoid Research Society. Dr. Mariela Shirley received the American Psychology Association’s 2012 Meritorious Research Service Commendation, and Dr. Yossi Tam won an Early Career Development Grant award from The Obesity Society. More than a dozen NIAAA employees received 2012 NIH Director’s Awards for exceptional contributions to the NIH mission.

• NIAAA communications and media coverage.  NIAAA continued its decade-long tradition of hosting Derek Jeter’s youth leadership program, Jeter’s Leaders, by welcoming 100 high school students for a day of presentations, exhibits, and hands-on activities. In a press release, Mr. Jeter praised his foundation’s relationship with NIAAA. NIAAA recognized September 9 as International Fetal Alcohol Spectrum Disorders Awareness Day by multimedia messaging about the dangers of alcohol for pregnant women. As part of its summer seasonal communication efforts, NIAAA placed strategic clusters of alcohol-safety awareness ads on billboards on roadways to mid-Atlantic beaches and on buses and selected Metro stations in Washington, DC; established an aerial billboard over Delaware and Maryland beaches; and placed an ad with the safety message on New York’s Times Square electronic billboard. Evaluation of audience metrics will inform future efforts.

• Multimedia products. NIAAA’s 2012 Summer Safety Fact Sheet received wide news coverage. NIAAA’s peer-reviewed journal, recently revamped and renamed Alcohol Research: Current Reviews, includes new sections on resources for alcohol use and abuse research, and an introductory letter from the editor. The forthcoming NIAAA Spectrum focuses on college drinking. NIAAA has translated its popular booklet “Rethinking Drinking” into Spanish.   

• Substance Use and Addiction: Reorganization Activities. The portfolio analysis report and the draft strategic plan that will together inform the reorganization of NIAAA, NIDA, and other relevant agencies, are expected to be released in mid-November. The full FY 2012 grant portfolio will be included in the portfolio analysis, likely in narrative summary form with aggregated budget figures associated with the proposed Institutes to which the topic areas will be assigned. Information will be posted on the website feedback.nih.gov, emailed to key stakeholders with the website link, and communicated probably by means of a teleconference briefing for potentially affected Institute/Center advisory councils and possibly town-hall or phone-in meetings with stakeholders. A public comment period will be followed by the NIH Director’s final recommendations in December 2012.

 

Discussion. Dr. Krystal commended the billboard strategy and suggested promoting responsible drinking by harnessing mass media tactics the alcohol industry uses to advertise alcohol. He suggested partnering with professional sports leagues to donate advertising time during major televised games, a strategy that would destigmatize discussions of alcoholism. Dr. Vivian Faden solicited ideas for ways to pursue sports contacts. Dr. Fred Donodeo described NIAAA’s sports-related outreach to football teams, especially the Redskins through CADCA and other liaison groups, regarding in-game messaging on drinking and driving, and working with teams’ youth programs. NIAAA is developing a strategy regarding drinking, driving, and other statistics for messaging related to Super Bowl Sunday. Ms. Mimi Fleury requested that Dr. Hingson’s presentation on adolescents at risk for excess alcohol consumption be made available.

 

Contract Proposal Concept Clearance

Dr. Abe Bautista described measures to avoid conflict of interest regarding discussion of a small business innovation research (SBIR) contract proposal concept. Mr. Greg Bloss described a project to harness the creativity of the private sector to publicize traffic tragedy statistics in hopes that people might attend more to reducing their risks associated with driving.

Discussion. Judge Linda Chezem observed the possibility of duplication of effort of such a project, given the work currently conducted by the National Highway Traffic Safety Administration, Bureau of Statistics, Centers for Disease Control and Prevention, and the Governors’ Highway Safety Association, and suggested considering a more collaborative project. Dr. Andres Gil suggested that NIAAA’s project should focus exclusively on alcohol-related fatalities, with possible value added by focusing on the relative effectiveness of various media and messages to specific target groups. He suggested that universities’ transportation centers might have interest in providing such information to their states. Dr. Warren noted that applicants for SBIRs must submit business models. Dr. Heath questioned whether the proposal might be viable for small businesses. Dr. de la Monte suggested that devising and marketing protective gear and safety features to protect people from traffic tragedies may have commercial appeal. Dr. Kathleen Grant suggested a project to make breathalyzers to start a car or other devices that are cheap, effective, elective, and alcohol specific.

Action. Council members declined to take action on the concept.

 

Consideration of the June 7, 2012, Meeting Minutes and Future Meeting Dates

Council members unanimously approved the minutes of the NIAAA Council meeting held on June 6–7, 2012.  Future Council meetings will take place February 6–7, June 12–13, and September 18–19, 2013; and February 5–6, June 4–5, and September 10–11, 2014.

 

Collaborative Study on the Genetics of Alcoholism (COGA)

Drs. Bernice Porjesz and Howard Edenberg reported on progress of the Collaborative Study on the Genetics of Alcoholism (COGA), NIAAA’s longest-running large-consortium project. Dr. Porjesz, Professor, Department of Psychiatry, State University of New York Downstate Medical Center, explained that COGA, a multidisciplinary, multicenter collaborative study, aims primarily to identify and understand genes that affect the risk for development of alcoholism and related disorders. This represents a difficult task in a complex disease characterized by multiple genes with small effects, phenotypic complexity, heterogeneous disease manifestation, environmental variability, gene-gene interactions, and gene-environment (GxE) interactions. Dr. Porjesz explained that genetic risk does not make getting the disease inevitable. COGA’s strategy to find genes affecting risk has generated an ideal sample for genetic and phenotypic studies that includes many large, densely affected families. The well-characterized sample of more than 16,000 subjects from more than 2,000 large families has undergone extensive phenotyping in many domains at multiple time points. COGA also has assembled subsamples for several studies.

COGA has identified genes related to alcohol dependence that have since been replicated by others, identified precursors to alcohol problems and alcohol spectrum conditions, successfully used neurophysiological phenotypes for genetic studies, and conducted molecular and cellular studies of key genes. Investigators successfully use brain oscillations (during rest and during sensory and cognitive tasks) as endophenotypes (intermediate phenotypes that correlate with alcohol dependence); the oscillations reflect ensembles of neurons firing in synchrony and represent the basic code of neural communication in the brain. Criteria for consideration as an endophenotype include high heritability and the ability to differentiate between alcoholics and controls, and high-risk offspring and controls for analysis. Theta event–related oscillations (ERO), wherein theta and P3 are reduced in abstinent alcoholics and high-risk offspring, are a good endophenotype for studies.

In its recent Family GWAS study, GOGA used brain oscillations as ab endophenotype with a sample of its most informative families and found genome-wide significant results for frontal theta oscillations. Seven SNPs on chromosome 21 exceed genome-wide significance; these are  in the KCNJ6 gene. COGA is finding a synonymous SNP in exon 4 of KCNJ6 that both highly correlates with its top three SNPs and is significantly associated with the frontal theta ERO phenotype at genome-wide levels. KCNJ6 encodes the protein known as the GIRK2, an inward rectifying potassium channel, which plays an important role in regulating the excitability of neurons. GIRK2 is directly activated by ethanol and is involved in both opioid and ethanol-induced analgesia.

The genome-wide finding in KCNJ6 for frontal theta prompted COGA to set priorities for those findings and to genotype the rest of the sample, including members of its prospective study, to examine how genes that manifest in adults also manifest in adolescents for precursor phenotypes and developmental trajectories. COGA is following offspring (ages 12 to 21) recruited from COGA families every 2 years through the critical age of risk with an extensive battery of age-appropriate assessments in multiple domains. This sample is ideal for studies of both GxE and developmental trajectories, including studies of theta ERO, which decreases with brain development. Investigators found that KCNJ6 SNPs have time-specific effects on frontal theta ERO. Among other frontal tasks, COGA introduced a gambling task that showed that during loss, high-risk offspring have low-occurring density in frontal areas and that KCNJ6 SNPs have an effect on theta ERO while these offspring evaluate loss. In the behavioral arena, COGA demonstrated that the strength of KCNJ6 SNPs’ effect on impulsivity, conduct disorder, and externalizing in adolescents depends on the degree of parental monitoring (larger effect with low monitoring), thus demonstrating significant GxE interaction for these alcohol-related precursor phenotypes. 

Dr. Howard Edenberg, Distinguished Professor and Director, Center for Medical Genomics, Indiana University School of Medicine, explained that such key COGA findings as KCNJ6 and ADHs require molecular studies to understand associations and elucidate mechanisms. Different types of studies are conducted for different genes because of the genes’ varying effects in different domains.

GWAS studies, including COGA’s, have focused on common alleles, though most common alleles have small effects. Rare alleles are not constrained in terms of effect size, and COGA hypothesizes that genes whose products are involved in pathways that affect the risk for alcoholism are likely to have both common variants with small effects and rare variants with large effects. COGA’s first step in its functional studies is to find all the variants in its high-risk population by targeted re-sequencing and then to prioritize functionally important variants that appear to affect gene splicing, gene regulation, and DNA methylation. In KCNJ6 different variants may require testing in cell lines and testing with neuronal cells.

Dr. Edenberg explained that the ADH enzymes play an important role in alcohol metabolism by creating the toxic acetaldehyde. ADH1B harbors functional amino acid changes that are protective. The ADH1B*2 allele is common in Asians but rare in Europeans, and not measured in GWAS studies, so COGA genotyped this allele in the extended dataset and found that the ADH1B*2  allele is associated with alcohol dependence in Europeans as it is in Asians, and is protective with similar odds ratio. COGA also demonstrated a protective effect of the ADH1B*3 allele in African Americans. COGA also has conducted some resequencing and is examining other ADH variants. Recent testing on the effects of variants on gene expression in cell lines by transfection reveals an interaction between variations in two different regulatory regions. Investigators are also examining alcohol’s interactions in other cells, and aim to examine neuronal cells made from iPSCs.

COGA has demonstrated an association with the GABRA2 gene (encoding the alpha-2 subunit of the GABA receptor), while others have found variations in the gamma-1 subunit and in the region in between. On a phenotypic level, these associations were concentrated in people who were more severely affected, affected by multiple drugs, earlier age at onset, and conduct disorder in young people. Having conducted limited sequencing years ago to understand the phenotype pattern, COGA currently is resequencing in a much broader region to identify and prioritize the variants. Investigators consider the most promising approach to be deriving neuronal cells from COGA subjects to study the channel properties in cells, to study alcohol effects on channel properties and effects on regulation, gene expression, and splicing. The effect of GABRA2 SNPs on adolescent symptoms of alcohol dependence is greater when there is more peer substance use.

COGA found that nicotinic receptors were associated with alcohol dependence as well as nicotine dependence and cigarettes per day, and also that a different set of SNPs associated with alcohol dependence was associated additionally with a regulatory difference. With resequencing, rare variants were identified and are being examined, but investigators also are examining molecular effects of some changes. In a case where genes can be easily manipulated, COGA expects to look into what happens with genes in mice using viral vectors.

Dr. Edenberg observed that alcoholism develops over time and over repeated exposure to excess alcohol, and that adolescence represents a critical period of vulnerability. COGA hypothesizes that repeated exposure to high amounts of alcohol during adolescence affects epigenetics, which affects gene regulation and vulnerability. COGA’s longitudinal study is in its early stages; the first epigenetic studies will focus on paired samples of blood cells from adolescents before and after regular drinking, comparing DNA methylation, comparing gene expression, and banking plasma/serum for future biomarker studies to reflect the possibility that genes might suggest protein biomarkers. COGA investigators hope their work will lead to science-based approaches for prevention, treatment, and drug development.

Discussion. Dr. Heath suggested that COGA investigators study serum chemistry, fecal sampling, and re-consenting subjects for wider release of data to the scientific community. Noting that many neurotransmitter genes decline during adolescence, Dr. Crews suggested investigating whether the KCN gene declines during the change in wave intensities during development. Dr. Edenberg described parallel studies on rats exposed to alcohol in adolescence and noted his hope to correlate blood and brain changes to help interpret changes of blood measured in COGA subjects. Dr. Crews pondered how many COGA subjects treated for alcohol have been referred to treatment by a judge. In the context of conduct disorder, Dr. Crews suggested investigating a subset of alcoholics who are treated but who also have aspects of alcoholism that get them into trouble. Dr. Edenberg noted that although few among COGA’s sample of young people with conduct disorder symptoms are or have been in treatment, conduct disorder has a heritable component, and studies may have selected for these genetically loaded families. Dr. Porjesz responded to Dr. Health’s comment on COGA’s work on conduct disorder that the COGA sample is populated by a large mix of families, not just high-risk subjects. Dr. Edenberg noted that NESARC’s collection of DNA samples holds promise as a forum to test findings. Dr. Spear suggested obtaining Tanner stage data, and Dr. Health suggested getting age now.  

Dr. Porjesz responded to Dr. Edward Riley that COGA had enrolled some subjects in the prospective study years ago at age 7, thus providing data from younger ages and enabling investigation of possible behavioral precursors to conduct disorder. Dr. Edenberg explained, in response to Dr. Friedman’s question, that COGA accesses and sorts through ENCODE data to identify candidate variants in regions likely to be important. Asked by Dr. Krystal whether COGA has considered alternatives to iPSCs such as nasal epithelial biopsies to get a more well-defined neural phenotype, Dr. Edenberg responded that the COGA investigators aim to differentiate into neurons or proceed directly to neuronal differentiation; they already have iPSCs. Investigators have not considered consenting for nasal biopsies, in part because they would expect resistance from institutional review boards.

 

Alcoholic Liver Fibrosis: Emerging Mechanism and Prospects for Therapy

Dr. Scott Friedman, Professor of Medicine and Director of Liver Diseases, Mt. Sinai School of Medicine, described his research on alcoholic liver fibrosis. Alcohol, a leading cause of end-stage liver disease, likely accounts for 30% of liver transplantations in the United States. Fibrosis generated over decades in the wound-healing process from chronic injury, ultimately blocks blood flow, deteriorates liver function, and culminates in cirrhosis. Patients with cirrhosis or advanced fibrosis have greater risk for primary liver cancer, for which transplantation can be curative, but only in highly selected patients. Liver cancer, the third leading cause of cancer mortality worldwide, represents a consequence of chronic alcohol abuse and cirrhosis.
 
Dr. Friedman described the progression of fibrosis in liver disease, which is first seen along the sinusoid, where the activation of hepatic stellate cells accounts for the accumulation of scar when the liver becomes injured. Whereas they are normally quiescent, upon injury, activated stellate cells proliferate, lose the vitamin A droplets they had stored, and secrete scar molecules. Loss of microvilli in hepatocytes, and distortion of sinusoids impede blood flow to liver cells. Over time liver function deteriorates, and patients no longer make albumin, detoxify drugs, or make clotting factors. Every change in this cell type ultimately leads to either more cells that make scar or to more scar production per cell. Each of these mediators and many others represent targets for antifibrotic therapies. If patients abstain from alcohol, the liver has the capacity to regress scar on its own, but the cells remain highly primed to faster reactivation when primed by further injury. The process may seem to accelerate, perhaps because a larger fraction of cells had been primed for faster reactivation if additional injury were to occur.
 
Dr. Friedman summarized research in the field of fibrosis in alcoholic liver disease. When stellate cells are activated, they lose their vitamin A droplets, which are comprised of retinoids esterified with long-chain fatty acids. As described by Mark Czaja, autophagy, which regulates lipid metabolism, is an important pathway for hepatocytes to provide energy in times of stress. Collaboration by Drs. Friedman and Czaja found that activation of hepatic stellate cells represents an autophagic response by which the cells eat their own lipid droplets to maintain energy homeostasis, while driving fibrogenesis. NIAAA-supported studies have revealed a pathway known as the unfolded protein response, which ultimately involves splicing of the XBP1 gene. This response is increased during activation of stellate cells in mice fed an alcohol-containing diet. In these stellate cells endoplasmic reticulum stress is accompanied by much more autophagy, which provides fuel to produce scar.  In a genetic mouse model where stellate cells are not able to undergo autophagy there is less scarring after liver injury.

Clinical challenges ahead include finding better markers of fibrosis stage and activity, developing strategies to predict who will progress in fibrosis, learning what makes people with cirrhosis decompensate and need a liver transplant, and conducting a successful proof-of-concept antifibrotic trial. Studies show that genetics determines the risk of alcohol abuse. In addition genetics is a likely determinant of risk of injury for individuals who abuse alcohol and also a determinant of risk and the progression of fibrosis in persons with liver injury. He noted the value of markers for genetic risk of fibrosis progression in testing a new drug to block fibrosis.
 
Dr. Friedman asserted that the biotech and pharmaceutical fields are on the cusp of developing antifibrotics to treat the many forms of fibrotic disease that account for 45% of deaths in the industrialized world. In addition to abstinence, emerging therapies relevant for alcohol-induced fibrosis include reducing tissue injury and fostering epithelial repair; turning off stellate cells (which become myofibroblasts) from proliferating and making new blood vessels or blocking their contractility; antagonizing fibrogenic cytokines and signaling (promoting cell death); and waking up latent proteases that can melt scar. NIAAA-supported work has led to clinical trials of a small molecule mimetic of hepatocyte growth factor and antioxidants; antioxidants need to be further developed. Emphasis also is being placed on blocking fibrogenesis. If small molecule antagonists that block peripheral cannabinoid receptors in the liver can be prevented from crossing the blood-brain barrier, they will have an antifibrotic effect and will have clinical potential.
 
Unanswered questions include: Why is fibrosis responsive to treatment in animal models but not in humans? How do we identify the most vulnerable target for therapy of fibrosis? Will treating fibrosis have adverse consequences on normal tissue’s integrity and repair? Which patients with alcoholic liver disease would benefit from antifibrotics?
 
Discussion. Dr. Friedman replied to a question from Dr. de la Monte that exploration is underway of the role of the hepatocyte progenitor cells in becoming exhausted and allowing permissiveness of the mesenchymal elements to cause disease. Dr. Friedman concurred with Dr. Craig McClain that lack of good biomarkers impedes conducting clinical trials. Investigators seek serum or imaging markers that indicate that the machinery to make scar is turned off, even before the scar content changes. Approaches include developing methods to image activated stellate cells and quantify their mass. Dr. Friedman asserted that the absence of markers represents a roadblock to further progress.

 
Blackouts and Poisonings: Troubling Trends on Our Radar

Dr. Aaron White, Division of Epidemiology and Prevention Research, NIAAA, explained that NIAAA places great emphasis on underage and college drinking. Young people drink less often but more heavily than adults. Studies show, for example, that drinking among persons ages12–20 averages around the binge threshold—four drinks for a woman and five for a man within 2 hours—and once young people cross the binge threshold, they often drink much more. Heavy drinking often leads to injuries, sexual assaults, vandalism, violence, unprotected sex, and other consequences, including alcohol-induced amnesia and emergency department visits and hospitalizations for alcohol overdoses. As blood alcohol concentration (BAC) rises, impairment increases in encoding new information about facts and events in one’s life into long-term memory storage, often accompanied by poor decision making, impaired impulse control, and other brain dysfunction.

Erroneous assumptions based on early research that focused on alcoholics led to the belief that blackouts occurred only in alcoholics. Recent studies suggest that blackouts are frequent and common, particularly among young people. In 2002 Dr. White found that about half of 800 students surveyed who ever drunk alcohol had reported having experienced a blackout, and 40% who had drunk in the previous year had a blackout. A later study found that during the summer after high school graduation, 12% of students surveyed had had a blackout in the previous 2 weeks.

People who do not remember what happened must ask others to tell them. A small survey of college students who had blackouts revealed the following adverse events: insulting someone, spending money, sexual activity, arguing fighting, damaging property, unprotected sex, and unwanted sex. Numbers of lifetime blackouts among college students correlated significantly with reduced grade point average, and as amount of drinking in high school rose, age of drinking onset decreased. Recent research by Mundt and colleagues shows that having had blackouts increases the odds of injury in an alcohol-related event.

BAC influences memory: At BAC of about 0.22%, an individual has an even chance of fragmentary or complete blackout. Studies show that some people seem to be predisposed to alcohol-induced memory impairments and that genetics also play a role. Fast-rising BAC due to drinking quickly or drinking on an empty stomach represents a key scenario for blackout. Not yet known are what transpires during blackouts, including sexual assaults and other crimes, and what might be their legal consequences. While males typically are indifferent to blackouts, the episodes frighten females, who then may cut down on drinking. It is possible that these circumstances offer opportunities for brief motivational interventions.

With binge drinking, BAC may rise to the point of overdose or poisoning; a toxic or deadly dose of alcohol is not much higher than a moderately intoxicating dose. DAWN data for alcohol-involved emergency room (ER) visits offer insight into medical treatment among young people for overdoses and poisoning. Among 12–20 year olds in 2009, 190,000 visited the ER for alcohol-related problems. Dr. White has tapped data from the Nationwide Emergency Department Sample (NEDS) and National Inpatient Sample (NIS) to describe how common and how costly is excessive alcohol consumption as measured by ER and hospital visits for accidental overdose or alcohol poisoning. In 2009 persons age 12 and over made 2.3 million ER visits where excessive consumption played a role, and 877,000 were hospitalized, at a cost of $32 billion; for alcohol poisoning, this group made 50,000 ER visits and 58,000 were hospitalized. Young people ages 18–24 made 270,000 ER visits and 58,000 were hospitalized. From 1999 to 2008, the number of 18 to 24 year olds hospitalized for an alcohol overdose–related event increased by 25%, with the largest increase in hospitalization for overdose by combined alcohol and other drugs. According to a CDC WONDER dataset, more than 1,000 people age18–24 died in 2009 of alcohol overdoses, 927 of them by alcohol poisoning—likely a significant underestimation. Although college amnesty programs permit friends to get help for others, the number of cases that do not result in medical care is unknown. It is also not possible to determine prevalence among college students, although military identifiers may be present in datasets. Not much is known to date about other drug involvement or impact on subsequent drinking.

Dr. White pointed out that young people’s drinking patterns generate high blood alcohol levels with potential for serious consequences. Amnesia due to acute consumption is more common than previously thought, and hospitalization for alcohol overdoses is rising among young people. More data are needed about blackouts and overdoses, as well as to identify opportunities for prevention.

Discussion. Responding to a question from Dr. Warren, Dr. White acknowledged the potential for underestimating frequency of blackouts. Most people learn what had transpired from friends who were with them and then they incorporate that information into their narrative. Dr. de la Monte inquired whether blackout is a good defense in law for serious crimes; Dr. White stated that he knew of no case in which blackout was a good defense. Dr. White responded to Dr. Crews’s questions that no long-term follow-up studies have been conducted with students who reported more than four blackouts and that while most studies have enlisted college students as subjects, blackouts are common also in the general population. Ms. Fleury observed that Dr. White’s information would be complementary to parent-education efforts. Dr. White stated that as number of blackouts rises, age of onset declines, but causation is unknown. Dr. White pointed out that young people today get the message about blackouts from popular songs and movies.                   

Dr. Krystal stated that some neurosignatures add information about possible strategies to study this issue rigorously. He suggested determining whether a momentary circuit dysfunction is associated with blackouts or whether it represents something else. Benzodiazepines also induce blackouts. In response to Dr. Ehlers’s question about a relationship between blackouts and memory function, Dr. White stated that memory function typically is normal but may be compromised with alcohol ingestion. He shared his hypothesis that people who black out more may be more sensitive than others to small doses of alcohol on memory. A baseline controlled memory study by Wetherill and Fromme showed no difference between blackout and non-blackout groups, but the assessment may not have been sufficiently rigorous to distinguish between them. Dr. Ehlers speculated that special memory might be more sensitive.

 

Public Comment

Time was set aside for public comment, but no one stepped forward to speak.

 

Adjournment

Dr. Warren adjourned the meeting at 12:35 p.m.

 

CERTIFICATION

I hereby certify that, to the best of my knowledge, the foregoing minutes are accurate and complete.

 

/s/

Kenneth R. Warren, Ph.D.

Acting Director, National Institute on Alcohol Abuse and Alcoholism

and

Chairperson, National Advisory Council on Alcohol Abuse and Alcoholism

 

/s/

Abraham P. Bautista, Ph.D.

Director, Office of Extramural Activities

and

Executive Secretary, National Advisory Council on Alcohol Abuse and Alcoholism