NATIONAL ADVISORY COUNCIL ON ALCOHOL ABUSE AND ALCOHOLISM
Summary of the 118th Meeting
June 4-5, 2008
The National Advisory Council on Alcohol Abuse and Alcoholism convened for its 118th meeting at 5:30 p.m. on June 4, 2008, at the FishersLaneConferenceCenter in Rockville, Maryland, in a closed session. Dr. Abraham Bautista presided over the closed review of grant applications. Dr. Ting-Kai Li, Director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), presided over the open session on June 5, 2008. In accordance with the provisions of Sections 552b(C)(6), Title 5, U.S.C. and 10(d) of Public Law 92-463, the session on June 4, 2008, was closed to the public for the review, discussion, and evaluation of individual applications for Federal grant-in-aid funds.
Council Members Present:
Michael E. Charness, M.D.
Cheryl J. Stephens Cherpitel, M.P.H., Dr.P.H.
David W. Crabb, M.D.
Gen. Arthur T. Dean
Cindy L. Ehlers, Ph.D.
R. Adron Harris, Ph.D.
Deborah S. Hasin, Ph.D.
Victor M. Hesselbrock, Ph.D.
Joannes B. Hoek, Ph.D.
Vimal Kishore, Ph.D.
Lynell W. Klassen, M.D.
Mack C. Mitchell, Jr., M.D.
Peter M. Monti, Ph.D.
Larry I. Palmer, LL.B.
Hideki Tsukamoto, D.V.M., Ph.D.
Chairperson: Ting-Kai Li, M.D.
Executive Secretary: Abraham P. Bautista, Ph.D.
Ralph W. Hingson, Sc.D., M.P.H., Robin I. Kawazoe, Howard Moss, M.D., Antonio Noronha, Ph.D., Kenneth R. Warren, Ph.D., Mark Willenbring, M.D., Samir Zakhari, Ph.D.
Other Attendees on June 5, 2008
Approximately 50 additional 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 Closed Session, June 4, 2008
Dr. Abraham Bautista called the closed session of the 118th meeting of the Council to order at 5:30 p.m. on Wednesday, June 4, 2008, for consideration of grant applications. He reviewed procedures and reminded Council members of regulations pertaining to conflict of interest and confidentiality. Members absented themselves from the discussion and evaluation of applications from their own institutions and in situations involving any real, apparent, or potential conflict of interest. The closed session adjourned at 7:10 p.m.
Call to Order and Introductions, June 5, 2008
Dr. Ting-Kai Li called the open session to order on June 5, 2008, at 9:00 a.m. and welcomed participants. Ex-officio Council member Col. Joyce Adkins, M.P.H., Ph.D., was unable to attend. Members of NIAAA staff and the audience introduced themselves.
Director’s Report/Special Announcements
Referring to the published “Director’s Report,” Dr. Li highlighted the following Institute activities:
§ Legislation, budget, and policy. Two new Current Procedure Terminology (CPT ®) codes, issued by the American Medical Association, will enable physicians to bill for screening and short-term interventions for alcohol and substance use. The Centers for Medicare and Medicaid Services had adopted two codes in 2007, and the AMA added the new CPT codes in January 2008 to apply to private groups, starting with the Federal Employees Health Benefits Program.
On December 26, 2007, after four continuing resolutions, the President signed a bill appropriating funds for NIH for FY 2008. NIAAA’s budget amounts to $436.3 million, a slight increase over FY 2007 levels. The President’s FY 2009 proposed budget requests funding for NIAAA at $436.7 million, an increase of 0.1%. With the cost of living rising more than 0.1 percent annually, however, net funding would decrease considerably. At this level, NIAAA plans to support 191 competing project research grants, at a success rate of 26.5%, down from the previous year, and also 17 research centers, 86 research career awards, and 287 trainees in full-time positions. A slight increase in stipends is projected for pre- and post-doctoral NRSA trainees. Dr. Li stated that although the House held a hearing on the overall NIH budget, the traditional “theme” hearing for NIAAA, NIDA, NIMH, and SAMHSA was not held; no date for a Senate hearing had been set. Dr. Li anticipated no substantive legislative action on the budget until after a new Administration takes office.
§ Director’s activities. At the 18th Annual Leadership Forum sponsored by the Community Anti-Drug Coalitions of America (CADCA), Dr. Li gave a presentation on partnering with community groups to prevent and reduce underage drinking and related problems. He noted that NIAAA currently focuses research on the relationship of stress to alcohol. NIAAA co-sponsored a meeting in Italy in which Drs. Li, Markus Heilig, Antonio Noronha, and Sam Zakhari participated; the conference examined a newer direction in neuroscience and future treatment strategies.
§ NIAAA staff and organization. Dr. Li reported that NIAAA has had a staff turnover rate of around 8% over the past 2 years. He noted that Dr. Ricardo Brown has joined HowardUniversity as Associate Vice President for Research and Professor of Physiology and Biophysics in the College of Medicine. Dr. Vishnu Purohit and Dr. Jose Velasquez have left NIAAA to join other Institutes with increased portfolios and responsibilities. Dr. Tina Vanderveen has retired after many years of service at NIAAA. New appointments include Peter Gao, M.D., M.S., M.B.A., who has joined NIAAA as a program director. Judith Arroyo, Ph.D., serves as NIAAA’s new Minority Health and Health Disparities Coordinator. Patricia Powell, Ph.D., has been named Chief, NIAAA’s Science Policy Branch. Robert Huebner, Ph.D., Ralph Hingson, Sc.D., M.P.H, and Kenneth Warren, Ph.D. have been recognized with significant honors.
§ Research priority emphasis and core support teams. Dr. Li explained that when NIAAA began to integrate research across disciplines in 2003, it established teams to examine new research priorities. NIAAA constituted the Extramural Advisory Board (EAB) as a subcommittee of Council to review all extramural portfolios, chaired by Dr. Fulton Crews. More recently NIAAA has established working groups, to look at smaller aspects of EAB’s recommendations, and also coordinating committees. Dr. Li explained that an important feature of EAB critical reviews is that initiatives are suggested by team members and divisions. He asserted that the system works well.
Dr. Li observed the importance of publications by staff and researchers to demonstrate evidence of their scholarly activity. He highlighted a supplement in Alcoholism: Clinical and Experimental Research devoted to mechanisms of behavioral change, noting that NIAAA is leading this area of research. He also highlighted papers by Dr. Rosalind Breslow on secondary analysis of large datasets and by Drs. Zakhari and Guo on the relationship of systems biology to alcohol research.
§ NIAAA research programs. Dr. Li noted scholarly papers published on new, collaborative research at NIAAA and across NIH Institutes on the following issues:
- Stress-signaling target for alcohol dependence, by Dr. Ted George
- Drinking and mortality, by Dr. Breslow
- Epigenetic effects involved in withdrawal anxiety, by Dr. Suvash Pandey
- Gene variant predicts medication response, by Dr. Ray Anton
- Neuropeptide Y and stress response, by Dr. David Goldman and extramural investigators
- Additional genes associated with alcohol dependence, by Dr. Hesselbrock
- Endocannabinoid studies, including one led by Dr. George Kunos
- Infant bonding and opioid receptors, by Drs. Christina Barr, Heilig, Goldman, and Suomi
- Cell adhesion molecule, by Dr. Charness and colleagues
§ Scientific meetings. Dr. Li observed that Dr. Mark Willenbring made many presentations and participated in many scientific meetings, important activities that bring NIAAA’s research findings to practitioners. A symposium on alcoholic liver and pancreatic diseases is to be held in Spain in July 2008, funded jointly with NIH’s Office of Rare Diseases.
§ Outreach activities. Leadership to Keep Children Alcohol Free, founded in 2002, has evolved into an important activity. Originally a group of governors’ spouses who championed prevention of alcohol abuse in children, the organization has endured beyond politics and changes in gubernatorial administrations. NIAAA helped the organization’s transition to a new foundation to ensure its sustainability. The organization was instrumental in development of the “Surgeon General's Call to Action to Prevent and Reduce Underage Drinking,” which, in partnership with SAMHSA, is being disseminated to States. NIAAA has provided almost the entire evidence base for this activity. NIAAA also motivated the Journal of Pediatrics to publish a supplement on the science of underage drinking in the context of human development.
As an example of outreach activities to increase young people’s interest in science, Derek Jeter’s Leaders Youth Foundation has expressed interest in a return visit by 40 young people to NIAAA’s intramural labs or ClinicalCenter to learn about the Institute’s research program.
§ Multimedia products. Dr. Li highlighted the Communications and Public Liaison Branch’s products, including Alcohol Research & Health. The Clinician’s Guide to screening and brief interventions, accepted worldwide, uses instruments developed by NIAAA and the World Health Organization (WHO). NIAAA has partnered with Medscape to make the course available to health professionals.
§ What’s ahead. The Research Society on Alcohol and the International Society for Biomedical Research on Alcoholism have scheduled a joint meeting for June–July 2008 in Washington, DC.
Presentation of Council Operating Procedures
Dr. Ken Warren, NIAAA Deputy Director, described NIAAA’s “Operating Procedures for Institute Staff Actions for Administrative Supplements and Time Extensions” that would come into play for projects after approval by the Council and award of funds. The parameters involve, among other topics, reasons for which adjustments may be made to awards and circumstances requiring reporting to the Council.
Motion for Council Concurrence : Members of the Council unanimously concurred with the Council Operating Procedures.
Alcohol and Injuries in an International Perspective: What We Know from Emergency Room Studies
Dr. Cheryl J. Cherpitel, Associate Director and Senior Scientist, Public Health Institute, Alcohol Research Group, NationalAlcoholResearchCenter, discussed her 25 years’ work on alcohol and injury. To set the context, she observed that WHO has designated alcohol abuse among the most serious conditions in terms of disease burden, and that unintentional and intentional injuries constitute 40% of the disease burden. Dr. Cherpitel noted that limited knowledge has existed on the social consequences of alcohol use, particularly in less-resourced countries, although recognition is growing worldwide of fatal and nonfatal injuries as a public health problem.
Dr. Cherpitel considers the emergency room (ER) the ideal place to find many people with injuries. Accessing people just after an injury offers opportunities to link the injury with alcohol better than in a retrospective study. Nevertheless, injured individuals with problematic drinking problems who do not go to ERs are not captured in the sample. Non-injured people who go to ERs for treatment of illnesses are included in the sample as a quasi-control group.
The Emergency Room Collaborative Alcohol Analysis Project (ERCAAP) has conducted 17 studies in 8 countries since 1984. Most samples included both injured and non-injured patients, while some had only injured patients. While many studies covered one ER, several had more than one. All studies used a similar questionnaire and methodology. All patients were 18 years old and over at 33 ERs. Response rates ranged from 65% to 93%. Investigators approached patients upon presentation in the ER, obtained informed consent, and subjected patients to breathalyzer tests. They then administered a questionnaire on the reason for the visit, recent alcohol intake, and usual drinking patterns and problems. The WHO Collaborative Study on Alcohol and Injury duplicated ERCAPP’s work, using the same methodology and instrumentation, at a single ER in 12 countries. The sample included only injury patients who arrived within 6 hours after the injury event, a total of about 500 injured patients per sample.
While studies have found the association of alcohol and injury to be reasonably consistent, the magnitude has varied greatly. In order to explore differences in magnitude and heterogeneity in the alcohol-injury relationship, researchers merged the data sets, weighted to account for differences in the studies, for example, to achieve equal representation for all hours of the day and all days of the week. Investigators analyzed the data in terms of individual-level alcohol use variables, looking at both acute and chronic use, by self-report of usual frequency and quantity of drinking and whether heavy episodic drinking took place in the past 12 months. Investigators also looked at organizational variables (public or private ER, or trauma center) and sociocultural variables (legal drinking age, legal level of intoxication while driving, level to which alcohol use is stigmatized, homicide rate, recorded per capita consumption, and detrimental pattern of consumption). A powerful predictor of the association of alcohol and injury in a given area, a detrimental pattern of consumption involves heavy drinking occasions, drinking in public places, and drinking with meals. Scores were derived for a number of countries for postulated detrimental effect associated with the same per-capita consumption level of alcohol.
Dr. Cherpitel described a cross-national meta-analysis of attributable risk of injury from alcohol to estimate the attributable fraction for all-cause injury and for violence-related injury, and to analyze the extent to which contextual variables explained observed differences in attributable fractions across studies. Attributable fraction is the proportion of all cases in the target population attributable to exposure to alcohol, based on exposure rates to alcohol and risk of injury relative to the exposure. Analysis of 14 studies revealed that most attributable fraction was significant for both all-cause injury and violence-related injury to positive blood alcohol level (BAC) at the time of the ER visit, to self-reported consumption, and to drinking five or more drinks on one occasion.
A meta-analysis looked at the pooled effect sizes for attributable fractions and tested for homogeneity across the studies. Where effect sizes were not homogeneous, investigators modeled the variability as a function of the contextual variables. Pooled estimates are relatively modest for all-cause injury and much larger for violence-related injury. A meta-regression for contextual variables on the attributable fraction for all-cause injury for the three exposure variables showed that most were not significant. The greater the level of detrimental drinking pattern, the greater the attributable fraction for all-cause injury from BAC and for level of stigmatized alcohol use. But the greater the legal age of drinking, the larger the attributable fraction for five-plus drinks monthly on all-cause injury. The countries with the lowest legal drinking age ( Spain and Italy) have the lowest detrimental drinking pattern; wine with meals is less problematic. The meta-regression did not permit simultaneous entry of contextual variables; if it were possible to enter the level of detrimental pattern along with legal drinking age, a negative coefficient would be expected.
Dr. Cherpitel summarized the findings: differences in attributable fractions across studies for all-cause injury are explained by variables related to the integration of alcohol in society; using the same meta-regression for violence-related injuries, none of the contextual variables explains the heterogeneity in the attributable fraction for violence-related injury.
Canada and Australia recently have used the data to establish safe drinking guidelines. NIAAA has made it possible to increase the data set, with hopes of doubling the number of study sites to nearly 100 and increasing the number of countries.
Discussion: In response to a question from Dr. Hasin, Dr. Cherpitel stated that a methodological test of BAC and self-report showed poor correlation between the two variables. BAC is a biomarker, but since BAC level was not determined immediately after injury, the two variables cannot be compared in terms of their relationship to the clinical variables. Dr. Cherpitel responded to Dr. Li that overall consent rates averaged 75 percent, and that the next wave will add more contextual variables, including motor vehicular density. Dr. Ehlers inquired about ethnicity in the sample. Dr. Cherpitel responded that the investigators collected ethnic data, which applied relatively less to homogeneous cultures. She noted that at the Alberta and Quebec sites, the few people who presented with violence-related injuries had all been drinking. In reply to Dr. Mitchell, Dr. Cherpitel stated that breath alcohol concentrations were well above the legal level of drinking. Dr. Harris inquired about gender differences, and Dr. Cherpitel stated that while about 40% of participants were female, the percentage varied by country, and of persons with violence-related injuries, 70–80% were male. To a question from Dr. Crabb on per capita consumption, Dr. Cherpitel stated that the studies used WHO-reported recorded consumption plus additional unrecorded consumption. Subsequent studies have focused more on unrecorded consumption.
Dr. Li inquired whether the new studies examine longitudinal changes in incidence of alcohol-related auto injuries, given the greatly increased numbers of automobiles on the road. Dr. Cherpitel stated that new data from several countries and from NIAAA studies in China will be compared to the older data. She noted that geographical proximity is necessary to make sociocultural variables relevant to the ER study, which often is difficult.
Research Planning for Future Psychiatric Classifications
Darrel Regier, M.D., M.P.H., serves as Executive Director, American Psychiatric Institute for Research and Education (APIRE); Director, Division of Research, American Psychiatric Association; and Vice-chair, DSM-V Task Force. Dr. Regier noted that early in the effort to publish the DSM-V (anticipated in 2012), problems were identified with certain characteristics of the mental health diagnostic system as applied in research settings: high rates of comorbidity, high use of the Not Otherwise Specified (NOS) category instead of specific categories, treatment nonspecificity, inability to find laboratory markers/tests; and DSM hindering the research progress (problems in associating homogeneous pathophysiology with specific mental disorders). Since publication of DSM-III in 1980, new developments have included revisions to improve validity, move toward an etiologically based classification, and an abundance of new data in cognitive-behavioral sciences, family studies, molecular genetics, and neuroscience. The question was raised as to whether a paradigm shift was needed in the next DSM version.
Strategies designed to improve the DSM include incorporating research into the classification’s revision, moving beyond a process of clinical consensus and building diagnoses on empirical findings with international and multidisciplinary input. From 1999 to 2002 a series of six white papers was published on research changes that had taken place, gaps were identified, and three additional papers—on infant/young child, sex/gender, and geriatric mental health—were published (see www.psych.org ). With a 2003 NIH grant, APIRE held a series of 13 conferences on individual diagnostic areas that sought to promote international collaboration and stimulate empirical research to improve decision-making on the identified diagnostic deficiencies. Fully 367 participants represented 39 countries, including 16 developing nations. More than half the participants came from outside the U.S., and five conferences were held abroad. The conferences to date have generated four monographs, including “Diagnostic Issues in Substance Use Disorders,” with others in press or preparation. NIAAA and NIDA supported publication of a peer-reviewed supplement in Addiction in 2006. In the area of substance abuse, conferences focused on, for example, comorbidity of mental and addictive disorders and on dimensions (i.e., measurement of distress, disability, and severity) in psychiatric and addictive disorders. Task Force representatives participated in all substance abuse disorders conferences around the world. Dr. Regier noted some resistance in the international substance abuse community to dimensional classification, highlighting the need for international consensus in diagnostic criteria to move the field forward.
David Kupfer, M.D., Thomas Detre Professor and Chair, Department of Psychiatry and General Science, University of Pittsburgh School of Medicine, and Chair, DSM-V Task Force, reviewed the Task Force’s revision principles for DSM-V: optimizing clinical utility, but with recommendations guided by research evidence. Although the Task Force aims to maintain continuity with previous DSM editions, it imposes no a priori constraints on the degree of change from DSM-IV to DSM-V. Increased emphasis is anticipated on development across the lifespan; dimensional concepts; new knowledge on risk factors, prodromes, and prevention; and the ability of the DSM to be relevant upon publication in terms of reflecting new knowledge on, for example, new risk factors and genetics that may be important diagnostically.
Initial activities include considering severity and disability/impairment/functioning as separate dimensions, consistent with other areas of medicine, and reviewing and identifying broad/super-ordinate categories of diagnostics. The Task Force includes 13 workgroups for specific diagnostic areas, broken into subcommittees and supported by advisors. The Substance Use Workgroup membership includes NIAAA staff and a Council member. The workgroup’s first task is to review the DSM-IV for areas to improve and opportunities to move beyond behavioral criteria and incorporate the use of biomarkers. Areas under active discussion and research by subgroups relate to nonsubstance addictions, including gambling and computer games; impulse control disorders; cannabis withdrawal; dimensions versus categories; biomarkers; and terminology.
Together with individual workgroups, the Task Force will assess the readiness of individual disorders to incorporate biological measures and dimensional approaches into diagnostic criteria and the narratives of DSM-V. They will also incorporate the recommendations derived from the 13 research conferences into the DSM-V. The Task Force will coordinate with WHO’s ICD developments in order to achieve harmony. The Task Force has established study groups to reinforce cross-cutting themes, including diagnostic spectra, life span developmental approach, gender and cross-cultural, and psychiatric/general medical interface. Possible validators for diagnostic groupings include neural substrates, familiality, genetic risk factors, specific environmental risk factors, biomarkers, temperamental antecedents, abnormality of cognitive or emotional processing, and high rates of comorbidity, among others.
Although field trials were conducted in developing DSM-IV, the numbers of subjects required and time constraints for DSM-V point to the need for alternative strategies to consider how proposed diagnostic criteria might play out in real situations. A possibility involves individual workgroups with specific diagnostic questions generating “gold standard patients,” with video clips of patients translated into video clips of actors, and presentation of video clips to clinicians, individually and at meetings, to elicit information about how changes in diagnostic criteria might be appropriate. The vignette approach would enable considerations of reliability, validity, sensitivity, and specificity, and would illustrate prototype diagnoses conducive to case books and Web-based training content for DSM-V.
Discussion: Dr. Li commended the concept of DSM-V as a living document, reflecting a paradigm shift that will incorporate an understanding of heterogeneity of phenotype and consideration of severity, multidimensionality, and comorbidity.
Dr. Ehlers suggested conducting secondary analyses of data, an approach to doing field trials with data instead of people. Dr. Kupfer responded that the Task Force now is doing secondary data analysis on gender and cross-cultural issues, but difficulty is anticipated with matching phenotypes. Dr. Regier added that some instruments used to collect phenotypic data, based on earlier DSM versions, had skip-out patterns. Data sets with additional psychopathology, symptoms, and descriptors are more valuable, especially with no skip-outs, as complete assessments of people. With data sets like COGA and others, secondary data analyses are more feasible with some altered measures that could be introduced into DSM-V, particularly with dimensional measures embedded in some data sets. Dr. Hasin stated that a review of genetic markers revealed that none is strong enough to serve as an individual biomarker, but genetic markers could serve as validators for dimensional measures as well as other ways of configuring symptoms assessed in different data sets.
Dr. Willenbring explained that in contrast to most psychiatric disorders, heavy drinking of alcohol itself represents a risk factor for downstream medical consequences, similar to hypertension. NIAAA is looking increasingly at a public health approach across the spectrum of drinking and drinking-related behavior; currently a diagnosis of disorder is not made until symptoms appear, which impedes treatment for heavy drinking, because heavy drinking is not a diagnosis. Dr. Willenbring suggested considering the disorder to be frequent heavy drinking with addiction as a downstream consequence, with the brain as the target organ in that brain dysfunction occurs with frequent heavy drinking.
Early Alcohol Use Behaviors, Including Binge Drinking Among Adolescents from the COGA Sample
Dr. Victor M. Hesselbrock, Professor and Principal Investigator and Scientific Director, AlcoholResearchCenter, University of Connecticut, noted that in the context of DSM-V, the NIAAA-funded Collaborative Study of the Genetics of Alcoholism (COGA) data set can inform potential changes in diagnostic criteria. Dr. Hesselbrock discussed COGA findings regarding prevalence and predictors of early alcohol use behaviors, including binge drinking, by high-risk adolescents. Prevalence research has shown that persons with a family history of alcohol problems are considered to be at high risk themselves.
COGA, a national interdisciplinary, multidisciplinary, and multisite study begun in 1987, focused on probands (index cases) identified through treatment programs as having significant alcohol-related problems. COGA uses an extended family design, with average family size around 9 individuals per family, and an age range of 6 to 102. COGA collected information from 15,000 adults, almost 1,200 adolescents, and 1,200 individuals below age 12. COGA seeks to characterize the familial distribution of alcohol and alcohol-related phenotypes within families using clinical and electrophysiological assessment. In addition, in order to identify susceptibility genes, COGA has begun to conduct genome-wide association studies using SNPs for a variety of alcohol and alcohol-related phenotypes.
Dr. Hesselbrock described the stages of subject ascertainment, including individuals who meet both DSM-III-R criteria for alcohol dependence and Feighner criteria for alcoholism, and who have two first-degree family members living in one of six COGA catchment areas. Stage I probands usually come from low-density families in which they are the only affected person. Stage II probands are members of high-density families with at least two additional first-degree biological relatives affected with alcohol dependence and living in a COGA catchment area. Investigators assessed all willing biological relatives. The COGA Project assessed for current and past psychiatric conditions, family history of psychiatric conditions, personality traits, environmental factors, electrophysiological assessment, and blood sampling that enabled establishment of lymphoblastoid cell lines for many participants.
COGA looks at early drinking as reported retrospectively by parents and then considers whether the same types of conditions are predictive of the development of alcohol problems in adolescents. Data shows that rates of alcohol dependence in COGA adults is considerably higher when regular drinking begins before age 15. When age of first regular drinking is older, rates of alcohol dependence decline for both males and females. Age of onset of regular drinking relates to age of onset of dependence, with little gender difference in terms of DSM-IV–defined dependence. Earlier age of onset of regular drinking is associated with increased lifetime alcohol dependence symptoms, slightly more for males.
COGA’s adolescent sample of 1,130 included young people ages 13-17, average age 15, with equal numbers of males and females, 24% African American and 7% Hispanic. COGA looked at ages of first drink (sip), of whole (standard) drink, and of first intoxication; maximum drinks consumed in 24 hours ever; and binge drinking (three-plus drinks per occasion). Fewer than half the adolescents (503) had ever consumed a whole drink, and 326 had engaged in binge drinking. Gender made little difference in age of taking the first whole drink, and slightly more boys engaged in binge drinking. Binge drinking matches the distribution by ethnicity, and, consistent with epidemiological data, African Americans postpone drinking compared to Caucasians.
Dr. Hesselbrock offered reasons that adolescents cite for drinking, such as like to drink and smoke, more party invitations, feel less shy, and help to find a date. Sixty-one percent of adolescents in the sample have had any drink at all; young people with alcohol abuse and dependence cite these reasons far more than those who have had a sip; and citation of these reasons increases with alcohol exposure. COGA focuses on alcohol use disorders in adolescence and such comorbid psychiatric disorders as conduct problems (11% for the COGA sample and almost double with binge drinking), attention deficit (3.1% for the COGA sample, and up to 4.3% with binge drinking), and major depression (2.8% for the COGA sample, and a significant increase with binge drinking).
Dr. Hesselbrock explained that opportunities for drinking and taking a first sip occur around age 11 on average, with gaps before taking a whole first drink and then before becoming intoxicated and before regular drinking. Binge drinking occurs prior to regular drinking. The largest number of drinks in 24 hours shows great variation, with many individuals drinking heavily. Prime time for early alcohol exposure occurs between ages 12 and 15, with most events occurring within a short time of each other. Having two parents with alcohol dependence is linked to earlier onset of drinking milestones. The earlier an adolescent tries drinking, the larger the number of drinks the individual would consume; the age of first consuming three or more standard drinks on an occasion and the age of first intoxication show significant correlation. Drinking style changes as adolescents grow older: abstinence diminishes from around 90% at age 13 to 24% at age 17, while binge drinking grows from 4% in 13 year olds to 39% by the time they reach age 17. More exposure links to more symptoms; by age 17, diagnosable alcohol abuse appears in 1 in 5 individuals and alcohol dependence in about 6%. The predictive probability of binge drinking among those with first intoxication before age 13 is virtually indistinguishable, but by age 17 the probability increases dramatically for binge drinking. Predictors of binge drinking include age at interview, age of first drink before 13, conduct disorder, and especially age of first drink and of first intoxication before age 13.
As COGA moves into a longitudinal study, all adolescents in the sample are seen at 2-year intervals to reveal the development of drinking, smoking problems, and other psychiatric concerns. Most models of vulnerability for alcohol problems include familial/genetic risk factors, personal/psychological risk factors, environmental factors as mediators or moderators of risk, and a variety of intermediate and long-term outcomes. Capitalizing on the family study, COGA has done linkage and genome-wide association studies among adults. A number of different genes have been linked to a variety of alcohol-related phenotypes. Various biological systems have been examined, and some genes have been replicated.
Dr. Hesselbrock asserted that the real value of COGA will be to examine the association of identified genes with risk for developing alcohol and other related problems. This work is likely to contribute to the DSM-V Task Force’s efforts to identify potential markers and biological systems associated with risk for developing the condition. If COGA were to follow the adults, the study could look at the genes in relationship to recovery, remission, or persistence of the disorder.
Dr. Hesselbrock stated that the COGA data set has demonstrated that the ages of onset of different alcohol-use milestones occur closely together for boys and girls. Regular drinking or early intoxication is predictive of alcohol-related problems, including binge drinking and other troubling heavy alcohol-use parameters, and early onset of alcohol use may be a useful phenotype for genetic analyses.
Discussion: Dr. Mitchell inquired whether there was an inherent reason why the children in the sample start drinking early, or if the problems arise because of drinking before age 13. Dr. Hesselbrock responded that adolescents with early-onset drinking often have conduct disorder and other problem behaviors that are predictive of bad adolescent outcomes. The COGA study is working toward determining whether individuals have biological differences. Working with a set of genes, it will be possible to do individual association studies on whether differences exist in the GABA, serotonin, or muscarinic systems. A surprising difference has emerged in taste sensitivity related to early drinking. Dr. Hesselbrock stated that adolescents drink whatever is available, mostly beer. To a question from Dr. Willenbring, Dr. Hesselbrock responded that regular drinking among adolescents is defined as drinking three or more times a month for 6 months or more, not daily drinking.
Dr. Hingson inquired whether the COGA sees different strengths of relationships with development of dependence, depending on the particular drinking milestones. Dr. Hesselbrock stated that the reason depends on the outcome examined. Alcohol dependence is a questionable diagnosis in adolescence. At present, only 5–6% of the sample has affectation, but the follow-up study is expected to find significant increases. Using a stepwise analysis, good strength of association currently is found between age of first whole drink and moving into age of regular drinking, age of intoxication, and alcohol problems. Dr. Kishore inquired whether recognized programs target middle school–age adolescents. Dr. Hesselbrock responded that many primary prevention programs have been tried in a variety of settings, and while some skepticism exists about the effectiveness of early prevention programs, no longitudinal data supports or denies their effectiveness.
To a question from Dr. Hasin, Dr. Hesselbrock stated that the biennial assessment of 4,500 adolescents between ages 13 and 22 will generate a data set larger than most adolescent studies. In addition to the frequency of assessment, COGA’s advantages include genetic material, direct interviews with parents, standardized assessment throughout the periods of risk of beginning to drink and of developing alcohol-related problems. COGA is following control subjects, but problems have existed in standardizing the controls, for whom data were collected from community families across six sites.
Dr. Harris stated that in gene deletions in mice for initiation of alcohol consumption, the largest effect comes from taste gene deletions. Dr. Hesselbrock noted that NIAAA funds taste preference studies of sucrose, but that bitter taste is also an area of considerable study.
In response to questions from Dr. Hoek, Dr. Hesselbrock stated that the ages of onset of milestones in COGA for adolescents ages 12–15 map well to findings about the general population revealed in the nationwide Monitoring the Future adolescent study. COGA’s follow-up data for ages 16–22 are expected to show a spike, which will map into studies of twins and adoption that show that children of alcoholics are at extreme risk relative to the general population. COGA will examine the gene/environment interplay and begin to answer questions about reasons for higher risk. COGA abstains from serving as an intervention, although each site maintains a set of literature about risk for drinking and treatment options.
Dr. Li inquired about the discrepancy between small gender differences in binge drinking at early ages and large differences in prevalence of alcohol dependence. Dr. Hesselbrock explained that Dr. Reich identified a secular trend in the data set that gender differences in risk rate diminish for individuals born in each new decade. He anticipates that gender differences in prevalence and incidence of alcohol problems will continue to shrink. Dr. Hasin described a NESARC analysis of birth cohorts that showed gender differences in the youngest cohort were less pronounced. In the most recent cohorts, gender differences were even less distinct. A new study with Monitoring the Future data will look at gender differences to get indices of drinking and heavy drinking.
Dr. Arroyo noted that African Americans and Hispanics report the start of problematic drinking later. She inquired whether the COGA sample has sufficient ethnic minorities to examine the models. Dr. Hesselbrock stated that the data so far model the trend of later ages of onset of alcohol use and alcohol problems in African Americans, particularly African American women, and a slight difference between Caucasians and Hispanics. Dr. Arroyo noted this finding’s significant implications. If alcohol sets off genetically based sequelae, if the finding does not hold up, the situation must be reconsidered: Is it a development process, or a psychosocial interaction with developmental and genetic processes? Dr. Hesselbrock concurred, noting that one advantage of COGA is its information on environmental factors combined with information from geocoding on alcohol outlet density, crime statistics, and other concerns that will lend important input to that question.
Dr. Monti asked whether the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) instrument used by COGA indicates whether or not “other substance use” might account for differences in use among ethnic groups. Dr. Hesselbrock stated that investigations are just emerging for adolescents. In adults, some differences that at first blush might be attributable to ethnic differences appear more to be socioeconomic indicators. He also noted that great geographical differences exist in terms of substances and alcohol use.
Consideration of the February 2008 Minutes and Future Meeting Dates
Council members voted unanimously to approve the minutes of the Council meeting of February 6–7, 2008. Dr. Abraham Bautista announced that upcoming Council meetings will convene on September 17–18, 2008; February 4–5, 2009, June 10–11, 2009, September 16–17, 2009; February 3–4, 2010, June 9–10, 2010, September 15–16, 2010; February 16–17, 2011; June 8–9, 2011; and September 14–15, 2011.
Council Member Round Table
Dr. Charness suggested adding to the agenda for a future Council meeting a discussion of NIAAA’s succession planning and the measures in place to groom or recruit potential leaders as senior leadership approach retirement age. Dr. Li responded that NIAAA and all NIH Institutes have engaged in succession planning discussions, workshops, and human resources initiatives for both scientific professionals and administrative personnel. Every job position in the Federal Government is advertised. For scientist positions, competitions are open to everyone, but administrative positions usually are not open, and significant succession planning relates to the latter positions. Dr. Li suggested obtaining expert advice on mentoring personnel for scientific or administrative leadership roles.
Dr. Warren potentially suggested inviting the chair of the NIH committee currently looking at succession planning to speak at a Council meeting. The NIH study is finding that many institutions—including major universities and private-sector entities—have not developed a system for succession planning. The NIH committee also is visiting organizations that have established mentoring systems to identify and prepare individuals with potential to assume leadership roles.
Dr. Charness pointed out APA’s executive career field program that identifies people at a variety of levels and provides training and mentorship. Ms. Kawazoe described the NIH Senior Leadership Program, for which demand exceeds the number of staff able to attend. Dr. Palmer commented that complex organizations often ignore the value to the organization of employing high quality personnel at every level. Gen. Dean suggested that the Department of Defense may serve as a source of guidance. Dr. Zakhari stated that the Department of Health and Human Services has implemented a program to groom personnel for SES positions.
Dr. Li noted that the Peer Review Committee was expected to report shortly on changes to the peer review system.
Liaison Representative Reports and Public Comment
Brian Gilman of the National Organization on Fetal Alcohol Syndrome (NOFAS), stated that for more than a decade his organization has partnered with NIAAA to develop and disseminate materials and promote continuation and expansion of clinical and biological research related to fetal alcohol syndrome. NOFAS disseminates NIAAA brochures and uses the Clinician’s Guide to train clinical staff at community health centers in several States. The organization hopes to work with NIAAA to develop the best way to collect feedback from practitioners who use the materials. Mr. Gilman noted the possibility of early congressional action to reauthorize previous Fetal Alcohol Spectrum Disorders (FASD) legislation or attach specific provisions to other legislation.
Fred Donadeo, NIAAA, read a statement on behalf of Amy Pollick of the Association for Psychological Science, who was unable to attend the meeting. Ms. Pollick acknowledged NIAAA’s sponsorship of the R25 program “Programs of Excellence in Scientifically Validated Behavioral Treatment,” which elevates standards for clinical science training. She noted that a newly developed accreditation body, Psychological Clinical Science Accreditation System, aims to accredit programs to train the next generation of clinical psychology researchers and graduate psychologists in empirically validated treatment methods.
Dr. Li adjourned the meeting at 12:50 p.m.
I hereby certify that, to the best of my knowledge, the foregoing minutes are accurate and complete.
Ting-Kai Li, M.D.
National Institute on
Alcohol Abuse and Alcoholism
National Advisory Council on
Alcohol Abuse and Alcoholism
Abraham P. Bautista, Ph.D.
Extramural Project Review Branch
National Advisory Council on
Alcohol Abuse and Alcoholism
Prepared: September 23, 2008