NIAAA Director’s Report on Institute Activities to The 119th Meeting of the National Advisory Council on Alcohol Abuse and Alcoholism

Thursday, September 18, 2008

CONTENTS

A. Legislation, Budget, and Policy

B. Director’s Activities

C. NIAAA Staff and Organization

D. Transdisciplinary Research Activities

E. NIAAA Research Programs

F. Scientific Meetings

G. Outreach

H. Multi-Media Products from NIAAA

I. What’s Ahead

A. Legislation, Budget, and Policy

On Monday, June 30, 2008 the President signed into law H.R. 2642, Supplemental Appropriations Act, 2008 netting the NIH an additional $150 million of which NIAAA received $2,320,000. The funds will be used to support additional scientific research. More specifically, 50% was allocated to competing research project grants (RPGs); the remaining funds were allocated to the research careers and individual training grants.

On June 19, the House Appropriations Subcommittee on Labor, HHS, and Education held the markup for the FY 2009 Labor, HHS, and Education Appropriation bill, which includes funding for NIH. The Full House Appropriations Committee met to mark up the bill on June 26; however, the Full Committee adjourned without taking action. No further markup has been scheduled at this time. The Subcommittee bill would provide $30,379,524,000 for NIH and $451,688,000 for NIAAA, a 3% increase over the FY 2008 Enacted Base and the FY 2009 President’s Budget request.

The Senate Appropriations Subcommittee on Labor, HHS, and Education marked up the

FY 2009 appropriations bill on June 24 and the full Senate Appropriations Committee marked up the bill on June 26. The Senate Appropriations Committee recommended $30,254,524,000 for the NIH which would increase funds for NIH by a little more than $1 billion over the President’s Request, and would allow NIH funding to keep up with the biomedical inflation rate (BRDPI) for the first time in six years. The legislation gives NIAAA $448,834,000, an increase of approximately 2.5% over the FY 2008 Enacted Base and the FY 2009 President’s Budget Request.

A summary comparing the President’s request, the House level, and the Senate level is below

^* includes $2.32 million supplement

B. Director’s Activities

Addictions Across the Lifespan - Pregnancy through Aging At a conference in Indianapolis on June 20, Dr. Li gave a keynote address entitled “Addiction Across the Lifespan: Family Influences.”

Joint Scientific Meeting of the Research Society on Alcoholism (RSA) and International Society for Biomedical Research on Alcoholism (ISBRA) At the opening session of the joint meeting of the RSA and ISBRA on June 28, Dr. Li gave a presentation entitled “Harmful Drinking: Global Research Issues.” Dr. Li also delivered a lecture entitled “Alcohol Research: Now and the Future,” in the RSA Student Lecture Series, and co-chaired a session on “Alcohol-Induced Brain Damage: New Findings from the Asian-Pacific Region.”

University of Maryland On August 15 Dr. Li spoke at a Translational Research in Molecular Pathology Seminar at the University of Maryland School of Medicine. Dr. Li’s talk was entitled “Translating Alcohol Research to Practice.”

Wake Forest University Dr. Li participated in a seminar for trainees, fellows, and medical students at Wake Forest University School of Medicine on August 25. His presentation was entitled “Animal Models in Alcohol Research: What are We Modeling?”

On August 30 Dr. Li travelled to Berlin, Germany where he spoke at the 7th Charité Conference on Psychiatric Research: Emotional Neuroscience. Dr. Li’s talk was entitled “Research on Animal Models of Alcoholism.”

Office of National Drug Control Policy On September 5, Dr. Li participated in the 2008 White House Leadership Summit on Screening and Brief Intervention (SBI) for Substance Abuse. Dr. Li’s presentation was entitled “Medical, Professional Education: Who Will Train the Trainers?”

Japan Society for Biomedical Research on Alcohol On September 15, Dr. Li delivered the keynote address at a U.S./Japan Joint Workshop on Alcohol-Related Problems in Yokohama, Japan. Dr. Li’s address was entitled “Alcohol-Attributable Diseases and Health Problems: A Risk-Reduction Paradigm.”

C. NIAAA Staff and Organization

New Appointments

Brenda Weis, Ph.D., joined NIAAA in July as a senior advisor to the NIAAA Director. Her duties include coordinating the Institute’s activity in the NIH Roadmap initiatives and trans-NIH projects. She comes to NIAAA from the National Institute of Environmental Health Sciences where she worked for the past 7 years in a variety of positions including Extramural Review Administrator, Program Director for the National Center for Toxicogenomics, and Senior Science Advisor to the Director. Dr. Weis has played a key role in the development and implementation of several trans-NIH programs, including the Pathways to Discovery-Metabolomics Technology Development Initiative; the Genes, Environment, and Health Initiative; and, most recently, the Roadmap Epigenomics Program.

Qi-Ying Liu, M.D., M.S., joined the Division of Neuroscience and Behavior as a Program Director in July. Dr. Liu obtained his M.D. degree from the Henan Medical University, Zhengzhou, China, and M.S. in pharmacology from the Shanghai Institute of Materia Medica, Chinese Academy of Sciences. Before joining NIAAA, Dr. Liu was a Program Officer at the National Center for Complementary and Alternative Medicine (NCCAM) where he oversaw NCCAM’s research in neuroscience, basic/preclinical cardiovascular system, liver, Botanical Research Centers, and alcohol and substance abuse. Prior to NCCAM, Dr. Liu was an Associate Professor at the Blanchette Rockefeller Neurosciences Institute at West Virginia University. Dr. Liu has also held positions at the Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, first as a post-doctoral fellow, and then as a Senior Staff Fellow. Dr. Liu’s areas of expertise include neuropharmacology, neurotoxicity, developmental neurobiology, synaptic plasticity, and neurobiological basis of learning and memory.

Honors

• NIH Director’s Awards were announced at a ceremony on July 21; NIAAA was well-represented among this year’s recipients. Individual awards went to:

• Robin Kawazoe in recognition of administrative management excellence; and

• Dr. George Kunos for leadership of the intramural program and research on endocannabinoids.

In addition, several staff received group awards for service:

• Ann Bradley and Drs. Mark Willenbring, Antonio Noronha, Sam Zakhari, Mark Egli, Raye Litten, and Bridget Grant for their work on the HBO Project;

• Dr. Lorraine Gunzerath as part of the Division of Extramural Activities Support (DEAS) Re-engineering Team;

• Drs. Patricia Powell and Vivian Faden for their efforts on The Surgeon General’s Call to Action; and

• Dr. Brenda Weis as part of an NIH Roadmap Recognition Award.

Members of the Division of Neuroscience and Behavior were honored for significant achievement for work on the NIH Blueprint for Neuroscience.

• Dr. Lisa Neuhold was honored for significant effort that contributed towards the creation of the NIH Blueprint Monoclonal Antibody Program as a member of the BRAINdev Team.

• Dr. Qi-Ying Liu received an award as a member of the Circuits Initiative Team.

• Dr. Lindsey Grandison received an award for dedication to the Blueprint Neurodevelopment Gene Expression Initiative as a member of the Gene Expression Team.

• Dr. Peter Silverman received an award as a member of the Neuroimaging Project Team for successful planning of two Blueprint initiatives.

• Drs. Thomas Greenwell and Dennis Twombly received awards as members of the Neuroplasticity Workshop Team for successful planning and convening a workshop addressing obstacles and opportunities for neuroplasticity research.

• Dr. Thomas Greenwell also received a group award for commitment and contributions to Neuroplasticity Efforts.

• Dr. Mark L. Willenbring and Dr. Robert B. Huebner, of the Division of Treatment and Recovery Research received awards at the annual meeting of the American Psychological Association (APA) on August 15. Dr. Willenbring received the APA’s Division 50 Distinguished Scientific Contributions to Advancing the Understanding of Addictions Award. Dr. Huebner received a Presidential Citation for Distinguished Service to APA Divisions 50 & 28 for his service supporting early career psychologists in addiction, psychopharmacology, and substance abuse research.

• Dr. Tom Gentry has been invited by the Automotive Coalition for Traffic Safety Inc. (ACTS), a nonprofit organization concerned with the advancement and improvement of highway safety, to be a member of the Blue Ribbon Panel for the Development of Advanced In-Vehicle Alcohol Detection Technologies. The ACTS and the National Highway Traffic Safety Administration (NHTSA) have entered into a cooperative research agreement to explore the feasibility, the potential benefits of, and the public policy challenges associated with a more widespread use of in-vehicle technology to prevent alcohol-impaired driving. The Blue Ribbon Panel Panel will provide expert advice to this endeavor.

D. Transdisciplinary Research Activities

Teams, Working Groups, and Coordinating Committees

In the past few months NIAAA has undertaken an update in the organizational structure and function of its Trans-Disciplinary Research Teams. The Teams were originally created in 2003 shortly after the arrival of Dr. Li as Institute Director. These Trans-Divisional Teams have served NIAAA very well over the past 5 years and the products of the Teams have served as the basis for at least six of the ten Extramural Advisory Board (EAB) Reviews. The Teams have also been responsible for the development of many new research initiatives undertaken by the Institute including programs ranging from epigenetics to behavior change.

Several of the existing Teams will continue with their mission unchanged from past years. Other Teams have accomplished their mission and disbanded, while still others have transitioned into a new phase where they are concerned more with implementation of their past efforts than development of new areas and therefore have evolved from “Team” status to that of a “Working Group.” Two of the Working Groups have been newly created (Biomarkers and Fetal Alcohol Spectrum Disorders). The former Research Resources and Technology Team has expanded its scientific scope to include systems biology, with an appropriate change of name to the Informatics and Computation/Systems Biology Team.

The Institute has also recognized the importance of trans-divisional Coordinating Committees and is providing a formal recognition of their function.

Below is the current list of Teams, Working Groups, and Coordinating Committees. See Appendix I for membership rosters.

• Teams
  

  Gene and Environment

  Informatics and Computation/Systems Biology

  Centers and Training

• Working Groups
  

  Underage Drinking

  Mechanisms of Behavior Change

  Medications Development

  Biomarkers

  Fetal Alcohol Spectrum Disorders

• Coordinating Committees
  

  International Research

  Health Disparities

  HIV/AIDS

The NIH Roadmap

The NIH Roadmap for Medical Research was created by the NIH in 2003 to support cross-cutting, trans-NIH programs that fill fundamental knowledge and technology gaps, and encourage innovative, high-risk/high-reward approaches to complex biomedical problems. Roadmap programs are designed specifically to catalyze research efforts across the NIH, and in the scientific community, by providing enabling tools, technologies, knowledge, training, and resources. Funding for the Roadmap program comes from the NIH Common Fund, which was created in 2004 and enacted into law by Congress through the 2006 Reform Act. The annual Roadmap budget has increased substantially over the past 5 years, from $131M in 2004 to $498M in 2008, highlighting its importance in the overall NIH funding environment. Although Roadmap programs are not intended to target specific diseases and environmental stressors, such as alcohol, many of the Roadmap funded projects focus on alcohol, alcohol-related illness, and addiction. The NIAAA has been actively involved in the development and implementation of several key Roadmap initiatives since 2004, and NIAAA involvement and leadership in Roadmap programs has increased substantially over the past 5 years. Currently, the NIAAA has program and management representatives on nearly all of development and implementation teams for the various Roadmap programs as described in Appendix II.

NIAAA Director, Dr. T-K Li has played an important role in Roadmap activities since the inception of this NIH program. In 2004 he was selected as co-chair of the Pathways to Discovery program, which supports research to advance our understanding of how the building blocks of the body – genes, proteins, metabolites – function and interact via complex systems to maintain health and respond to disease. Dr. Li played an instrumental role in crafting the Metabolomics Technology Development initiative which emerged from the Pathways to Discovery Program, one of the first Roadmap initiatives to be funded in 2005.

More recently, Dr. Li and NIAAA staff have played major implementation roles in Roadmap initiatives on Epigenetics, and forthcoming initiatives on the Science of Behavior Change, Pharmacogenomics, and Mitochondrial Function.

The NIH Blueprint for Neuroscience Research

Over the past 4 years NIAAA has participated in the NIH Blueprint for Neuroscience Research, a cooperative effort involving 16 NIH Institutes, Centers, and Offices that support neuroscience research. The NIH Neuroscience Blueprint emerged from the premise that there are fundamental themes in neuroscience research that cross Institute and Center boundaries. While the Blueprint does not target individual disorders, the tools, resources, and infrastructure created through the Blueprint have the potential to accelerate research for all of them, which in turn will lead to advances in prevention and treatment.

By pooling resources and expertise, the Blueprint takes advantage of economies of scale, confronts challenges too large for any single Institute or Center, and develops research tools and infrastructure that serve the entire neuroscience community involved in both basic and clinical research.

The Blueprint has directed its focus toward three broad themes with relevance across all Institutes engaged in neuroscience research: (1) neurodegeneration during disease and aging; (2) neurodevelopment throughout the lifespan; and (3) neuroplasticity, from the molecular level to the behavioral level. Over the past 4 years a large number of Blueprint initiatives and funding opportunities have been initiated under these themes. Some of the specific initiatives that staff from NIAAA’s Division of Neuroscience and Behavior have actively been involved with and which will have a direct impact on the alcohol research field are presented in Appendix III.

E. NIAAA Research Programs

Publications by Extramural Staff

Dr. Moss is a co-author of "Sex Differences in the Heritability of Alcohol Problems," in The American Journal on Addictions 2008;17:319–327.

Dr. Faden is a co-author of “The Relationship of Pubertal Stage, Age and Drinking in Adolescent Boys and Girls,” in press in the Journal of Child and Adolescent Substance Abuse.

Research Reports

The following items represent examples of the breadth and quality of research supported by NIAAA.

MicroRNA Influence the Development of Alcohol Tolerance. MicroRNA are small molecules that play an important role in regulating gene products in most animal and plant species. A new study indicates that microRNA appear to influence the development of alcohol tolerance. Previous studies have shown that a brain cell membrane structure known as the BK channel, which is responsible for movement of calcium and potassium from inside to outside a cell, develops tolerance on exposure to alcohol, particularly in the supraoptic nucleus and the striatum, brain regions important in alcohol's effects. In the current study, researchers examined whether microRNA might be involved in the alcohol tolerance observed in the BK channel. They found that the amount of a specific microRNA molecule known as miR-9 increases in brain cells within minutes of exposure to alcohol. The increase in miR-9 causes a reduction in the number of BK channels that contain the specific binding site for miR-9, while sparing those that lack it. The BK channels that were destroyed exhibited high alcohol sensitivity, while those that remained showed significantly lower sensitivity, consistent with the development of tolerance. These data demonstrate for the first time that a microRNA may play a role is the mechanism of neuronal adaptation to alcohol, by altering gene expression, and perhaps behavior. These findings could also lead to a potential molecular target for therapeutic intervention. (Pietrzykowski AZ, Friesen RM, Martin GE, Puig SI, Nowak CL, Wynne PM, Siegelmann HT, and Treistman SN. (2008). Neuron 59, 274-287.

Multiple-Domain Predictors of Problematic Alcohol Use in Young Adulthood. In this study, researchers sought to identify predictors of problematic young adult alcohol use through analyses of data collected from participants in the NIAAA-sponsored Collaborative Study on the Genetics of Alcoholism (COGA). All participants were evaluated first as children or adolescents, then approximately 5 years later as young adults. Predictors of alcohol symptoms endorsed at the second time point were drawn from five domains representing: (1) Demographic Characteristics, (2) Child/Adolescent Problematic Alcohol Use, (3) Biological Risk, (4) Externalizing Behaviors, and (5) Family Environment. Analyses revealed that 31% of the variance in the number of alcohol symptoms in young adulthood was predicted by a high number of alcohol symptoms in childhood and adolescence, low initial sensitivity to alcohol, and a negative child/adolescent relationship with the father, and suggest the utility of incorporating biological and nonbiological predictors to optimally predict young adult alcohol problems. (Kramer, JR, Chang G, Dick DM, Kuperman S, et al. J. Stud. Alcohol Drugs 69: 649-659, Sep. 2008)

Correspondence Between Secular Changes in Alcohol Dependence and Age of Drinking Onset Among Women in the United States. Researchers evaluated secular trends in ages at onset for drinking to determine whether they can account for secular changes in alcohol dependence, using data from the combined National Longitudinal Alcohol Epidemiologic Survey (NLAES) and National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), two nationally representative surveys that were conducted 10 years apart. Both men and women born between 1944 and 1963 had earlier ages of onset for drinking (AOD) than did the earliest birth cohort analyzed (1934–43). However, the net decrease in AOD was twice as large for women (3.2 years) than that for men (1.6 years). After adjusting for AOD, differences in lifetime prevalence between different birth cohorts of women were rendered nonsignificant, indicating that AOD accounts for a substantial portion of change in the lifetime prevalence of alcohol dependence. These results suggest that a decrease in AOD accounts for much of the increase in lifetime alcohol dependence among women. AOD is likely to be an indicator of dynamic, and therefore modifiable risk behaviors impacting risk for alcohol dependence. (Grucza RA, Norberg K, Bucholz KK, and Bierut LJ. Alcohol Clin Exp Res, 32(8): 1493-501, August 2008.)

Genetic and Environmental Influences on Alcohol, Caffeine, Cannabis, and Nicotine Use from Early Adolescence to Middle Adulthood. Researchers assessed the changing role of genes and environment in the etiology of psychoactive substance use (PSU) from early adolescence through middle adulthood in a retrospective study of adult twin pairs. The researchers recorded levels of use of alcohol, caffeine, cannabis, and nicotine for every year of each study participant’s life. They found that familial environmental factors were critical in influencing use of nicotine, alcohol, and cannabis in early adolescence and gradually declined in importance through young adulthood. Genetic factors, by contrast, had little or no influence on PSU in early adolescence and gradually increased in their effect with increasing age. The sources of individual differences in caffeine use changed much more modestly over time. Substantial correlations were seen among levels of cannabis, nicotine, and alcohol use and specifically between caffeine and nicotine. In adolescence, those correlations were strongly influenced by shared effects from the familial environment. However, as individuals aged, more and more of the correlation in PSU resulted from genetic factors that influenced use of both substances. The findings support an etiologic model for individual differences in PSU in which initiation and early patterns of use are strongly influenced by social and familial environmental factors while later levels of use are strongly influenced by genetic factors. The substantial correlations seen in levels of PSU across substances are largely the result of social environmental factors in adolescence, with genetic factors becoming progressively more important through early and middle adulthood. (Kendler KS, Schmitt E, Aggen SH, Prescott CA. Arch Gen Psychiatry. 2008 Jun;65(6):674-82.)

Racial/Ethnic Disparities in Service Utilization for Individuals With Co-Occurring Mental Health and Substance Use Disorders. NIAAA researchers used the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) to investigate whether black/white disparities in service utilization for mental health and substance use disorders persist or are diminished among individuals with psychiatric comorbidity in the general population. Assessments of lifetime service utilization for problems with mood, anxiety, alcohol, and drugs found that blacks with co-occurring mood or anxiety and substance use disorders were significantly less likely than whites to receive services for mood or anxiety disorders, equally likely to receive services for alcohol use disorders, and more likely to receive some types of services for drug use disorders. Regardless of race/ethnicity, individuals with these co-occurring disorders were almost twice as likely to use services for mood and anxiety disorders than for substance use disorders. The findings indicate a need for prevention and intervention strategies to address the specific mental health needs of blacks with co-occurring disorders, as well as the overall lack of service use for substance use disorders among individuals with co-occurring psychiatric conditions. (Hatzenbuehler ML, Keyes KM, Narrow WE, Grant BF, Hasin DS. J Clin Psychiatry. 2008 Jul;69(7):1112-21.)

Growth Factors and Ethanol Addiction. A new study discovered that a growth factor called glial cell line-derived neurotropic factor (GDNF) may affect high alcohol consumption. The study injected the growth factor into a part of the rat brain that may be associated with alcohol reward (the ventral tegmental area), and found that high alcohol consumption was rapidly reduced in those rats taking high amounts of ethanol. The investigators then taught the rats that levers associated with ethanol no longer had ethanol, a process called extinction. Animals that received GDNF were less likely than animals that received a control injection to reacquire ethanol lever pressing after extinction. The study shows that GDNF may eventually help people who are trying to quit drinking, but can’t. It also provides a new non-neuronal factor derived from the brain for alcoholism therapies.

(Carnicella, S., Kharazia V., Jeanblanc J., Janak P.H., and Ron D. Proceedings of the National Academy of Sciences 105:8114-8119, 2008.)

Cell Proliferation and Abstinence from Ethanol Many studies have shown that alcohol can be detrimental to the brain and cause nerve cell damage. Recently, investigators have shown that nerve cells in the brain can grow back after a period of abstinence from alcohol. The research presented in this paper shows that there is a burst of non-neuronal cells in the brain after abstinence and shortly before the neuron cells are made. The investigators used specific markers to determine the cell type that grew two days after alcohol abstinence, and found that new microglia grew in the hippocampus and the cortex. This study suggests microglia appear to be helpful with brain recovery after alcohol abstinence, and new therapies directed towards cell growth may help treat alcohol-induced brain damage in the future. (Nixon K., Kim D.H., Potts E.N., He J., and Crews F.T. Neurobiology of Disease 31:218-29, 2008.)

BDNF Signaling Cascade and Alcohol Consumption Brain-derived neurotrophic factor (BDNF) in striatum has recently been identified as a major component of a homeostatic pathway controlling ethanol consumption. In this study, investigators demonstrated that exposure of striatal neurons to ethanol results in the activation of the BDNF receptor TrkB, and ultimately in the increased expression of preprodynorphin (Pdyn). It was found that activation of the dynorphin receptor, the kappa opioid receptor (KOR), is required for the BDNF-mediated decrease in ethanol intake, illustrating a function of dynorphin in BDNF’s homeostatic control of ethanol consumption. These results indicate that BDNF regulates ethanol intake by the ensuing production of downstream gene products, including Pdyn. (Logrip, M. L., Janak, P. H., and Ron, D. FASEB J. 22, 2393–2404, 2008).

The Central Amygdala PKCSignaling Pathway In the central amygdala (CeA), ethanol acts via corticotrophin releasing factor (CRF) type 1 receptors to enhance GABA release. Amygdala CRF has been found to mediate anxiety associated with stress and drug dependence, and regulate ethanol intake. Because mutant mice that lack phosphokinase CPKC exhibit reduced anxiety-like behavior and alcohol consumption, it’s possible that PKC lies downstream of CRF1 receptors in the central amygdala (CeA). In this study, it was found that, compared with PKC^/^CeA neurons, PKC^/^ neurons showed increased GABAergic tone due to enhanced GABA release. CRF and ethanol stimulated GABA release in the PKC^/^ CeA, but not in the PKC^/^ CeA. A PKC-specific inhibitor blocked both CRF- and ethanol-induced GABA release in the PKC^/^ CeA, confirming findings in the PKC^/^ CeA. These results identify a PKC signaling pathway in the CeA that is activated by CRF1 receptor stimulation, mediates GABA release at nerve terminals, and regulates anxiety and alcohol consumption. (Bajo, M., Cruz, M.T., Siggins, G.R., Messing, R., and Roberto, M. Proceedings of the National Academy of Sciences of the United States 105, 8410–8415, 2008).

In Vivo Time-Course Changes in Ethanol Levels Sampled with Subcutaneous Microdialysis. In an attempt to overcome limitations (e.g., optimal time-course resolution, multiple sampling) associated with traditional blood alcohol concentration sampling techniques, Dr. McBride and his colleagues examined bioavailability and time-course of ethanol in the subcutaneous space under various ethanol administration using in vivo microdialysis sampling. This novel sampling technique can be as effective as traditional techniques in determining time-course changes of in vivo ethanol concentrations after systemic ethanol injection or during ethanol self-administration. This method also allows multiple sampling during self-administration without disrupting animal behavior.

(Engleman EA, Ingraham CM, Franklin KM, Keith CM, McClaren JA, Schultz JA, Morzorati SL, O'Connor S, Thielen RJ, Murphy JM, McBride WJ. Alcohol Clin Exp Res. 32(3):435-42, 2008).

Ventricular Expansion in Wild-Type Wistar Rats after Alcohol Exposure by Vapor Chamber This study provides a significant methodological advance in demonstrating that rats can be imaged with magnetic resonance imaging with sufficient resolution for structural brain measurements to be made. Studies using small animal models of alcohol use will benefit greatly from the use of non-invasive brain imaging techniques to perform longitudinal and repeatable studies on the effects of alcohol on brain and behavior. This study also provides the first non-invasive evidence that exposure to alcohol in a vapor chamber does indeed cause structural brain alterations and support the use of this method for alcohol administration. (Pfefferbaum A, Zahr NM, Mayer D, Vinco S, Orduna J, Rohlfing T, Sullivan EV. Alcoholism: Clinical and Experimental Research, Epub ahead of print July 15, 2008.

Fate-Mapping Evidence that Hepatic Stellate Cells Are Epithelial Progenitors in Adult Mouse Livers. Hepatic stellate cells (HSCs) are key cellular components of hepatic wound healing and fibrosis. Interestingly, there are several observations that point out that HSCs may also support the regeneration of damaged liver via differentiation along the hepatocyte cell lineage. In this study, the authors tracked the fate of quiescent HSCs during liver injury and regeneration. They found that during both injury-related activation in mice and in vitro spontaneous activation on plastic dishes, HSCs become highly proliferative and begin to co-express markers of mesenchyme and epithelial progenitors. These results support the concept that HSCs are capable of functioning as multipotent progenitors and can give rise to hepatocytes in adult livers, a finding that has important clinical implications. (Yang L, Jung Y, Omenetti A, Witek RP, Choi S, Vandongen HM, Huang J, Alpini GD, Diehl AM. Stem Cells. 2008 Jun 19. [Epub ahead of print])

The Genomic Determinants of Alcohol Preference in Mice. To identify genetic factors influencing the amount of nondependent drinking by animals, the authors did a genomic analysis on three types of animal populations known to display substantial variation in alcohol consumption: selectively bred, high and low alcohol-preferring mice (HAP and LAP); recombinant inbred mice (BXD RI strains), and inbred strains of mice.  They used a meta-analysis to pool the results and then used previously developed methods of filtering differentially expressed genes through behavioral quantitative trait loci (bQTLs) and expression QTLs (eQTLs) to narrow the focus to eight likely candidates.  Their results, particularly the fact that there were no common transcription factor binding sites among the candidate genes, support the conclusion that the expression of the candidate genes may be subject to cis regulation.  This study demonstrated the validity of using whole-brain gene expression data in mice to draw novel conclusions regarding the transcriptional networks that are associated with alcohol preference.  The identification of the role of the olfactory system that can be derived from the interactions of the candidate genes is consistent with previous work, but also generates new knowledge regarding the key role of this sensory system in mediating differences in dose-dependent alcohol consumption that may influence the development of alcohol dependence. (Tabakoff B, Saba L, Kechris K, Hu W, Bhave SV, Finn DA, Grahame NJ, Hoffman PL. Mamm Genome. 2008 Jun 19. [Epub ahead of print])

Acid Sensitive Channel Inhibition Prevents Fetal Alcohol Spectrum Disorders Cerebellar Purkinje Cell Loss. Using a sheep model of fetal alcohol exposure, this study advances the idea that ethanol-induced acidosis plays a critical role in fetal cerebellar Purkinje cell loss and, importantly, demonstrates that administration of doxapram, an inhibitor of pH-sensitive K⁺ channels (TASKs), confers essentially complete protection against this neuronal loss. The mechanism of this doxapram effect is unclear as it could normalize blood pH by inhibiting TASKs of peripheral chemoreceptors cells. Alternatively, the authors suggest that TASK3 inhibition by doxapram may promote cerebellar granule cell excitability and, consequently, their neurotrophic support of the neighboring Purkinje cells. Nevertheless, the neuronal survival conferred by doxapram is remarkable and thus has therapeutic potential for the ethanol-exposed fetus. (Ramadoss J, Lunde ER, Ouyang N, Chen WJ, Cudd TA. Am J Physiol Regul Integr Comp Physiol 2008, 295: R596–R603.)

Glutathione Content as a Potential Mediator of the Vulnerability of Cultured Fetal Cortical Neurons to Ethanol-induced Apoptosis. Neuronal loss in the developing brain exposed to alcohol is believed to result from apoptosis triggered by oxidative stress. This study demonstrates substantial heterogeneity of fetal cortical neurons in terms of their apoptotic vulnerability to ethanol, ethanol-induced ROS levels, and GSH content. Using fluorescent staining methods followed by either microscopy or cell sorting, a strong inverse correlation between GSH levels and evidence of oxidative stress (ROS, HNE adducts) and apoptosis (TUNEL, caspase activation) in ethanol-treated neuronal cells was established. Deliberate reduction of GSH levels with butathione sulfoxamine resulted in increased apoptosis, supporting a causal relationship between GSH content and apoptotic vulnerability. These findings highlight the central importance of oxidative stress in alcohol-induced death of fetal neurons and the potential of antioxidant treatment strategies. (Maffi SK, Rathinam ML, Cherian PP, Pate W, Hamby-Mason R, Schenker S, Henderson GI. J Neurosci Res 2008, 86:1064-76.)

Enhanced Negative Emotion and Alcohol Craving, and Altered Physiological Responses Following Stress and Cue Exposure in Alcohol Dependent Individuals. This study examined whether chronic alcohol abuse is associated with altered stress and alcohol craving responses. Abstinent alcohol-dependent (AD) individuals and social drinkers (SD) were exposed to a brief guided imagery of a personalized stressful, alcohol-related and neutral-relaxing situation, one imagery condition per session, presented in random order across 3 days. Alcohol craving, anxiety and emotion ratings, behavioral distress responses, heart rate, blood pressure, and salivary cortisol measures were assessed. Alcohol patients showed significantly elevated basal heart rate and salivary cortisol levels. Stress and alcohol cue exposure each produced a significantly enhanced and persistent craving state in alcohol patients that was marked by increased anxiety, negative emotion, systolic blood pressure responses, and, in the case of alcohol cue, behavioral distress responses, as compared to SDs. Blunted stress-induced cortisol responses were observed in the AD compared to the SD group. As laboratory models of stress and negative mood-induced alcohol craving are predictive of relapse outcomes, one implication of the current data is that treatments targeting decreases in stress and alcohol cue-induced craving and regulation of stress responses could be of benefit in improving alcohol relapse outcomes. (Sinha R, Fox HC, Hong KA, Bergquist K, Bhagwagar Z, Siedlarz KM. Neuropsychopharmacology. 2008 Jun 18. [Epub ahead of print])

Naltrexone Alone and with Sertraline for the Treatment of Alcohol Dependence in Alaska Natives and Non-natives Residing in Rural Settings: A Randomized Controlled Trial. Access to specialty alcoholism treatment in rural environments is limited and new treatment approaches are needed. In this study, investigators evaluated the efficacy of naltrexone alone and in combination with sertraline among Alaska Natives and other Alaskans living in rural settings. Naltrexone monotherapy demonstrated significantly higher total abstinence (35%) compared with placebo (12%, p = 0027) and longer, but not statistically different, Time to First Heavy Drinking Day. On secondary measures, naltrexone compared with placebo demonstrated significant improvements in percent days abstinent and drinking-related consequences. Naltrexone can be used effectively to treat alcoholism in remote and rural communities, with evidence of benefit for American Indians and Alaska Natives. New models of care incorporating pharmacotherapy could reduce important health disparities related to alcoholism. (O'Malley SS, Robin RW, Levenson AL, GreyWolf I, Chance LE, Hodgkinson CA, Romano D, Robinson J, Meandzija B, Stillner V, Wu R, Goldman D. Alcohol Clin Exp Res. 2008 Jul;32(7):1271-83.)

Effect of Transdermal Nicotine Replacement on Alcohol Responses and Alcohol Self-Administration. Nicotine replacement is commonly used to treat tobacco use in heavy-drinking smokers. However, few studies have investigated the effect of nicotine replacement on subjective and physiological responses to alcohol and alcohol drinking behavior. In this study the authors examined whether transdermal nicotine replacement (0 mg vs 21 mg/day) altered response to a low-dose priming drink and subsequent ad libitum drinking behavior. The study subjects were non-treatment-seeking, non-dependent heavy drinkers who were also daily smokers. Six hours after transdermal patch application, subjective and physiological responses to a priming drink [designed to raise blood alcohol levels (BALs) to 0.03 g/dl] were assessed. This was followed by a 2-hour self-administration period where subjects could choose to consume up to eight additional drinks (each designed to raise BALs by 0.015 g/dl) or to receive monetary reinforcement for drinks not consumed. Six hours after patch application, tobacco craving associated with withdrawal relief was decreased, and systolic blood pressure and heart rate were increased in the active patch condition compared to the placebo patch condition. Subjective intoxication in response to the priming drink was attenuated in the active nicotine patch condition compared to six hours of nicotine deprivation (i.e., placebo patch). During the self-administration period, subjects had longer latencies to start drinking and consequently appeared to consume fewer drinks when administered the active patch compared to the placebo patch. In heavy drinkers, transdermal nicotine replacement compared to mild nicotine deprivation attenuated subjective and physiological alcohol responses and delayed the initiation of drinking. (McKee SA, O'Malley SS, Shi J, Mase T, Krishnan-Sarin S. Psychopharmacology 2008 Feb;196(2):189-200.)

Risky Drinking in College Changes as Fraternity/Sorority Affiliation Changes: A Person-Environment Perspective. This study examined alcohol use among 2,376 continuously enrolled college students who were assessed before enrolling in college and during the first 6 semesters of college. Latent class analysis found 4 groups: constant Greek members (30%), constant nonmembers (64%), late joiners (2%), and droppers (4%). The analysis showed that disaffiliation with Greek systems is associated with decreases in risky drinking and alcohol-conducive environmental factors (peer norms and alcohol availability), whereas affiliation is associated with increases, indicating Greek socialization through socio-cognitive and physical environments. Future Greeks differed from nonmembers in diverse individual characteristics and heavier substance use before college, suggesting multiple selection paths into Greek systems. (Park A, Sher KJ, Krull JL. Psychol Addict Behav. 2008 Jun;22(2):219-29.)

New Data Underscores the Risks of 21^st Birthday Drinking. Despite public recognition of the hazards of 21st birthday drinking, there is little empirical information concerning its prevalence, severity, and risk factors. Data from a sample of 2,518 college students suggest that 21st birthday drinking poses an extreme danger since 83% of study participants reported drinking to celebrate, many at very high levels of consumption. In fact, 12% of birthday drinkers (men and women) reported consuming 21 drinks, and about half of 21^st birthday drinkers exceeded their prior lifetime maximum number of drinks. Current problematic alcohol involvement and its correlates strongly predicted both the occurrence and severity of 21st birthday drinking. These findings point to the need for interventions to minimize the harm associated with this rite of passage. (Rutledge PC, Park A, Sher KJ. J Consult Clin Psychol. 2008 Jun;76(3):511-6.)

A Randomized Trial to Evaluate a Management Training Program to Prevent Illegal Alcohol Sales. This randomized study of alcohol establishments evaluated the effects of a training program for owners/managers of such establishments (Alcohol Risk Management (ARM)) on sales of alcohol to obviously intoxicated customers and on promoting changes in establishment policies and practices. Owners and managers at 231 on-premise alcohol establishments (i.e. bars, restaurants) received either four one-to-one sessions or a single session of ARM. Sales rates to pseudo-intoxicated patrons in the experimental establishments decreased 23% (relative to the control condition) at the first follow-up purchase attempt (P = 0.06) but returned to baseline levels 3 months later. In addition, researchers observed no significant differences at follow-up in reported policies/practices across establishments. The researchers concluded that relying on manager training to promote responsible establishment alcohol policies is not sufficient to prevent illegal alcohol sales to obviously intoxicated patrons. (Toomey TL, Erickson DJ, Lenk KM, Kilian GR, Perry CL, Wagenaar AC. Addiction 103(3): 405-413, 2008.)

Targeting brain angiotensin and corticotrophin-releasing hormone systems interaction for the treatment of mood and alcohol use disorders

The brain renin-angiotensin system (RAS) participates importantly in the regulation of endocrine, autonomic, and behavioral response to stress. Recent data indicate that central action of AT(1) receptor antagonists can reduce anxiety symptoms in experimental animals. Furthermore, central inhibition of RAS activity decreases ethanol intake in an animal model of alcoholism. Pathological anxiety responses and the development of substance dependence are both critically mediated through corticotrophin-releasing hormone (CRH) systems, and the RAS is positioned to interact both with hypothalamic as well as extrahypothalamic CRH systems. The thesis of this paper is that the RAS is part of the neurochemical dysregulation underlying negative affective states, anxiety disorders, and ethanol dependence and that medications targeting the RAS should be considered to augment the treatment of these disorders. (Sommer WH and Saavedra JM. J Molecular Med. 2008; 86(6):723-28.)

Modulation of voluntary ethanol consumption by beta-arrestin 2

Beta-arrestin 2 is a multifunctional key component of the G protein-coupled receptor complex and is involved in mu-opiate and dopamine D2 receptor signaling, both of which are thought to mediate the rewarding effects of ethanol consumption. NIAAA researchers identified elevated expression of the beta-arrestin 2 gene (Arrb2) in the striatum and the hippocampus of ethanol-preferring AA rats compared to their nonpreferring counterpart ANA line. Differential mRNA expression was accompanied by different levels of Arrb2 protein. The elevated expression was associated with a 7-marker haplotype in complete linkage disequilibrium, which segregated fully between the lines, and was unique to the preferring line. Furthermore, a single, distinct, and highly significant quantitative trait locus for Arrb2 expression in hippocampus and striatum was identified at the locus of this gene, providing evidence that genetic variation may affect a cis-regulatory mechanism for expression and regional control of Arrb2. These findings were functionally validated using mice lacking Arrb2, which displayed both reduced voluntary ethanol consumption and ethanol-induced psychomotor stimulation and demonstrate that beta-arrestin 2 modulates acute responses to ethanol and is an important mediator of ethanol reward. (Bjork K, Rimondini R, Hansson AC, Terasmaa A, Hyytia P, Heilig M, Sommer WH.

FASEB J. 2008; 22(7): 2552-60.)

Prevention of alcoholic fatty liver and mitochondrial dysfunction in the rat by long-chain poly unsaturated fatty acids

This study was aimed at studying the mechanisms by which a diet supplemented with docosahexaenoic (DHA,22:6n3,omega-3) and arachidonic (AA,20:4n6,omega-6) acids prevents alcohol-induced fatty liver. Investigators fed male Long-Evans rats an ethanol or control liquid-diet with or without DHA/AA for 9 weeks. Plasma transaminase levels, liver histology, oxidative/nitrosative stress markers, and activities of oxidatively-modified mitochondrial proteins were evaluated. Chronic alcohol administration increased the degree of fatty liver but fatty liver decreased significantly in rats fed the alcohol-DHA/AA-supplemented diet. Alcohol exposure increased oxidative/nitrosative stress with elevated levels of ethanol-inducible CYP2E1, nitric oxide synthase, nitrite and mitochondrial hydrogen peroxide. However, these increments were normalized in rats fed the alcohol-DHA/AA-supplemented diet. The number of oxidatively-modified mitochondrial proteins was markedly increased following alcohol exposure but significantly reduced in rats fed the alcohol-DHA/AA-supplemented diet. The suppressed activities of mitochondrial aldehyde dehydrogenase, ATP synthase, and 3-ketoacyl-CoA thiolase in ethanol-exposed rats were also recovered in animals fed the ethanol-DHA/AA-supplemented diet. These findings indicate that addition of DHA/AA prevents alcohol-induced fatty liver and mitochondrial dysfunction in an animal model by protecting various mitochondrial enzymes, most likely by reducing oxidative/nitrosative stress. (Song BJ, Moon KH, Olsson NU, Salem N. J Hepatology. 2008; 49(2): 262-73.)

Dysregulation of nociceptin/orphanin FQ activity in the amygdala is linked to excessive alcohol drinking in the rat

Alcohol dependence is a complex behavioral disorder in which interactions between stressful life events and heritable susceptibility factors contribute to the initiation and progression of disease. Neural substrates of these interactions remain largely unknown. In this study, researchers examined the role of the nociceptin/orphanin FQ (N/OFQ) system, with an animal model in which genetic selection for high alcohol preference has led to co-segregation of elevated behavioral sensitivity to stress (Marchigian Sardinian alcohol-preferring [msP]). The msP and Wistar rats trained to self-administer alcohol received central injections of N/OFQ. In situ hybridization and receptor binding assays were also performed to evaluate N/OFQ receptor (NOP) function in naive msP and Wistar rats. Researchers found that intracerebroventricular (ICV) injection of N/OFQ significantly inhibited alcohol self-administration in msP but not in nonselected Wistar rats. The NOP receptor messenger RNA expression and binding was upregulated across most brain regions in msP compared with Wistar rats. However, in msP rats [S-35]GTP gamma S binding revealed a selective impairment of NOP receptor signaling in the central amygdala (CeA). Ethanol self-administration in msP rats was suppressed after N/OFQ microinjection into the CeA but not into the bed nucleus of the stria terminalis or the basolateral amygdala. These findings indicate that dysregulation of N/OFQ-NOP receptor signaling in the CeA contributes to excessive alcohol intake in msP rats and that this phenotype can be rescued by local administration of pharmacological doses of exogenous N/OFQ. Data are interpreted on the basis of the anti-corticotropin releasing factor (CRF) actions of N/OFQ and the significance of the CRF system in promoting excessive alcohol drinking in msP rats. (Economidou D, Hansson AC, Weiss F, Terasmaa A, Sommer WH, Cippitelli A, Fedeli A, Martin-Fardon R, Massi M, Ciccocioppo R, Heilig M. Biol Psychiatry. 2008; 64(3): 211-18.)

Incentive-elicited striatal activation in adolescent children of alcoholics

Deficient recruitment of motivational circuitry by non-drug rewards has been postulated as a pre-morbid risk factor for substance dependence (SD). NIAAA investigators tested whether parental alcohol dependence, which confers risk of SD, is correlated with altered recruitment of ventral striatum (VS) by non-drug rewards in adolescence. During functional magnetic resonance imaging, adolescent children of alcoholics (COA; age 12-16 years) with no psychiatric disorders (including substance abuse) and similarly aged children with no risk factors responded to targets to win or avoid losing $0, $0.20, $1, $5 or a variable amount (ranging from $0.20 to $5). In general, brain activation by either reward anticipation or outcome notification did not differ between COA and age/gender-matched controls. Cue-elicited reward anticipation activated portions of VS in both COA and controls. In nucleus accumbens (NAcc), signal change increased with anticipated reward magnitude (with intermediate recruitment by variable incentives) but not with loss magnitudes. Reward deliveries activated the NAcc and mesofrontal cortex in both COA and controls. Losses activated anterior insula bilaterally in both groups, with more extensive right anterior insula activation by losses in controls. NAcc signal change during anticipation of maximum rewards (relative to non-reward) correlated positively with both Brief Sensation-Seeking Scale scores and with self-reported excitement in response to maximum reward cues (relative to cues for non-reward). Among adolescents with no psychiatric disorders, incentive-elicited VS activation may relate more to individual differences in sensation-seeking personality than to presence of parental alcohol dependence alone. Future research could focus on adolescents with behavior disorders or additional risk factors. (Bjork JM, Knutson B, Hommer DW. Addiction. 2008; 103(8): 1308-19.)

Modulation of brain response to emotional images by alcohol cues in alcohol-dependent patients

Alcohol is often used to modulate mood states. Alcohol drinkers report that they use alcohol both to enhance positive affect and to reduce dysphoria, and alcohol-dependent patients specifically state reduction of negative affect as a primary reason for drinking. The current study proposes that alcohol cues may reduce negative affect in alcohol dependent (AD) individuals. Investigators used functional magnetic resonance imaging to examine brain activation in response to combination images that juxtaposed negative or positive International Affective Picture System (IAPS) images with an alcohol or non-alcohol-containing beverage. They found that in the absence of the alcohol cue, AD individuals showed more activation to negative than to positive images and greater activation than controls to negative images. When the IAPS images were presented with the alcohol cue, there was a decreased difference in activation between the positive and negative images among AD individuals, and a decreased difference in response to the negative images between controls and AD individuals. Additionally, in the neutral-beverage conditions, anxiety ratings significantly predicted activation in the right parahippocampal gyrus but did not predict activation when the alcohol cues were presented. In conclusion, the alcohol cues may have modulated cortical networks involved in the processing of emotional stimuli by eliciting a conditioned response in AD individuals, but not in the controls, which may have decreased responsiveness to the negative images. (Gilman JM, and Hommer DW. Addiction Biology; 13(3-4): 423-34.)

F. Scientific Meetings

Research Society on Alcoholism The annual meeting of the Research Society on Alcoholism (RSA) took place on June 28 to July 3 in Washington, D.C. NIAAA staff participated in numerous symposia, workshops, and working groups. For example:

• Bridget Grant co-chaired a symposium on “New Findings on Alcohol Use Disorders in the U.S. General Population”

• Kenneth R. Warren gave a presentation at a Grantsmanship Workshop entitled: “Old Problems, New Solutions: Understanding the Peer Review System in 2008 to Succeed in Obtaining Research Support.” Dr. Warren also presented “NIAAA Current and Future Research Directions in FASD Research” at a meeting of the FASD Study Group at RSA.

• Sam Zakhari co-chaired a symposium on “Systems Biology Approaches to the Study of Alcohol-Induced Tissue Damage and Repair”

• Raye Litten co-chaired a session on “New Biomarkers and Devices to Detect Ethanol Intake – Benefits, Limitations, How and When to Use”

• Mary-Anne Enoch and David Goldman co-chaired a symposium on “Genetics of Alcoholism: Recent Findings Add More Pieces to the Puzzle”

• Antonio Noronha co-chaired a symposium on “Adolescent Brain Development: Ethanol Induced Cellular and Molecular Changes”

• Daniel W. Hommer organized a Workshop on “fMRI Studies of Motivation: Trying to Deconstruct Desire, Craving and Reward in the Brains of Alcoholics”

• P.J. Brooks co-chaired a symposium on “Mechanisms of Carcinogenesis Resulting from Alcohol Consumption”

• Poster presentations and symposium talks discussed the work of numerous intramural NIAAA investigators.

Meeting of the Organization for the Study of Sex Differences

Dr. Ellen Witt co-chaired a symposium with Dr. Cora Wetherington of the National Institute on Drug Abuse, entitled “Sex Differences in the Causes and Consequences of Drug Abuse” on June 6 in New Orleans, as part of the Second Annual Meeting of the Organization for the Study of Sex Differences. This symposium presented data on the role of gonadal and stress hormones in sex differences in the etiology and consequences of drug and alcohol abuse.

Hispanic Association of Colleges and Universities

Dr. Judith Arroyo spoke at a NIH workshop for the Hispanic Association of Colleges and Universities (HACU) Summer Faculty Fellowship program. The topic of her presentation was “Health Disparities and Hispanic Alcohol Research.”

National Hispanic Youth Initiative

Dr. Judith Arroyo also represented NIAAA at a banquet on July 16 celebrating the 20th anniversary of the National Hispanic Youth Initiative, a program to mentor high school students interested in becoming clinician-scientists. The banquet was sponsored by the Interamerican College of Physicians and Surgeons. In July Dr. Arroyo also participated in the American Psychological Association, Minority Fellowship Association, Summer Research Institute, which provides mentoring and feedback to young minority investigators on preparing grant proposals.

Annual Meeting of the Governors Highway Safety Association

Dr. Ralph Hingson presented on Teen Brain Development, Underage Drinking, and the National Minimum Drinking Age Law on September 9.

Enforcing Underage Drinking Laws (EUDL) 10th Annual National Leadership Conference

Dr. Ralph Hingson spoke on Strategic Planning for Research at the National Institute on Alcohol Abuse and Alcoholism on August 21.

Third International Symposium on Alcoholic Liver and Pancreatic Disease and Cirrhosis Drs. Sam Zakhari, George Kunos, Bin Gao, Svetlana Radaeva, and Kenneth Warren each participated and presented at this meeting, held in Bilbao, Spain on July 17-18, 2008. NIAAA Council member Dr. Hide Tsukamoto, a lead organizer of the Second International Symposium, was also a key presenter at this year’s meeting.

G. Outreach

Outreach for "Video Case Studies: Helping Patients Who Drink Too Much"

More than 5,000 clinicians have earned continuing education credit through Medscape ® for NIAAA’s new interactive, online training program based on the Clinician's Guide. The American Academy of Family Physicians (AAFP) recently designated the program an "approved CME" course that can help members to fulfill the AAFP's own CME requirements. In early September, NIAAA launched a second wave of outreach for the training course, focusing on clinicians in practice (through professional organizations) and in training (through professional schools). We created an email blast with a link to a "toolkit page" that offers a downloadable web ad, a flyer, and other features to make it easy for partner associations to promote the training to their students, colleagues, or members. In partnership with the American Medical Association (AMA), NIAAA mailed promotional post cards to 3,000 medical school residency directors. The AMA also ran a free, full-page color advertisement for the course in the September 8, 2008 issue of Archives of Internal Medicine.

NIAAA – Turn 2 Foundation Partnership Continues with Youth Health Exhibition

Continuing our relationship with Derek Jeter’s Turn 2 Foundation, NIAAA played a significant role in designing the foundation’s first ever youth health exhibition last month at the University of Texas – Arlington. Approximately 300 participants from across the U.S. attended the event, which focused on alcohol use and addictions.

In spring 2008, executives at the Turn 2 Foundation asked Fred Donodeo, CPLB, to help design the event and offer suggestions for presentations and exhibitors. Throughout the summer, the foundation reached out to individuals that he and Dr. Dennis Twombly recommended. As a result, the final program featured topics and presentations that reflect and amplify NIAAA research. NIAAA also provided valuable input regarding the optimal organization of information for the students.

A highlight of the health fair was Dr. Twombly’s Drunken Brain Exhibit, which had a central location at the event. Other presentations included “The Developing Brain” (Ken Winters, recommended by Carlton Erickson); “Alcohol and the Heart” (Ricardo Brown); “Young Adults and Drug Use” (Roger Sorensen); and “Alcohol and Energy Drinks” (head of a local hospital trauma center, recommended by Larry Gentilello). The foundation had also received input from NIAAA Advisory Council member Raul Caetano.

Friends of NIAAA Coalition Strengthens Ties to RSA and Plans Fall Congressional Briefing

The Friends of NIAAA Coalition organized a strategic planning meeting at the RSA Annual Meeting in June. Led by Geoff Mumford of the American Psychological Association, the coalition outlined plans for a number of future activities, including a second congressional briefing. A key development at this planning meeting was the increasing presence of RSA in the group. Then-RSA president Ray Anton appointed Carlo DiClemente as the RSA liaison to the coalition, and the group discussed a number of ways that this enhanced relationship can be maximized in future activities. Incoming RSA President Peter Monti also attended the meeting and expressed continued support. The upcoming congressional briefing will be held on October 8, 2008 in the Rayburn Building, Room 354. It will cover the latest alcohol treatment and recovery research and will be led by Mark Willenbring.

Leadership to Keep Children Alcohol Free Activities

Rear Admiral Steven K. Galson, M.D., M.P.H., the Acting U.S. Surgeon General, spoke to audiences in Helena, Butte, and Bozeman, Montana. In addition to presentations to physicians, teens, the prevention community, and college students and administrators, he participated in a roundtable with college prevention specialists and taped public service announcements with First Lady Nancy Schweitzer.

NIAAA Clinicians Welcome NIDA Award Winner

Acting quickly on an invitation from the NIH Director’s Office, NIAAA’s Laboratory of Clinical and Translational Studies (LCTS) participated in an event for a select group of high school students. Three students recently won a prestigious NIDA-sponsored health fair award for their projects on addictions in addition to honors at the Intel International Science and Engineering Fair. As part of their award, the students and their families were invited to meet with Dr. Zerhouni and tour the NIH. Because NIDA laboratories are located in Baltimore, NIAAA was asked to provide a tour of our labs. Markus Heilig, Annika Thorsell, and Fred Donodeo worked with the NIH OD to arrange this tour. Dr. Thorsell, a LCTS staff scientist, led the students on a tour of the NIAAA Clinical Center Laboratory and discussed projects and careers at NIAAA.

H. Multi-Media Products from NIAAA

Alcohol Research & Health An issue of Alcohol Research & Health on alcohol and other drugs was printed and distributed. Drs. Henry R. Kranzler and Angela Martinelli were the scientific review editors for this issue.

Alcohol Alerts Two Alerts were published and distributed: “Systems Biology: The Solution to Understanding Alcohol-Induced Disorders” and “Alcohol and Other Drugs.”

Research Findings on Underage Drinking and the Minimum Legal Drinking Age CPLB, DEPR, and Science Policy Branch (SPB) staff developed this Web-based information source for individuals seeking relevant material regarding recent efforts by a group of college and university presidents to promote a debate on the legal drinking age.

Seasonal Fact Sheet Series Continuing its seasonal outreach series, CPLB released a Back to Campus fact sheet for parents in August. This fact sheet focuses on the importance of having discussions about excessive and underage drinking with college students, particulary during the first six weeks of the fall semester.

NIAAA Newsletter The Communications and Public Liaison Branch (CPLB) published the Summer 2008 edition of the NIAAA Newsletter. It is posted on the Institute’s Web site and distributed via e-mail to more than 800 grantees and Liaison Group members. Featured in this issue were the following –

• new Federal legislation requires that basic results data from some clinical trials must be submitted to the online NIH registry, www.clinicaltrials.gov;

• NIH announced that critical changes are planned to enhance and improve the NIH peer review system;

• Dr. Kathleen Grant will present the Keller Lecture on October 21;

• NIH will host a research summit on “The Science of Eliminating Health Disparities” scheduled December 16-18;

• NIAAA staff recently participated in an outreach program with Jeter’s Leaders, a New York City-based youth group.

NIAAA's Clinician's Guide -- Making a Difference Recently an Ohio HMO found that among 650 primary care providers who received a mailing of NIAAA materials last fall, rates for following up intervention or treatment after alcohol screenings increased from 10 percent to 50 percent. In October 2007, Paramount Health Care distributed the NIAAA "Pocket Guide for Alcohol Screening and Brief Intervention" to their family practice and internal medicine providers. Having adopted NIAAA's full Guide into its clinical practice guidelines, Paramount sent the pocket guides along with cover letters that encouraged clinicians to follow through with intervention and treatment following alcohol screening. The cover letter also included the web address for obtaining the full Guide. An HMO staff member in quality improvement reported that the mailout of NIAAA materials was the sole intervention, and that "they read it, they used it and it shows!" As a result, the HMO's Medical Advisory Council decided to send copies of the full Guide and pocket guide to all of their ob/gyns, who "often serve as the defacto primary care physician to female members."

Focus Testing and Revisions to "Rethinking Drinking" Following two rounds of focus testing, NIAAA communications staff revised text and graphics of this patient brochure, then held a third round of focus testing in July in Baltimore. Throughout focus testing, it became clear that there is a significant need for public education about drinking patterns, health risks, and evidence-based treatment options for dependence.

Focus testing also revealed the persuasive potential of Rethinking Drinking, in that it prompted respondents to reflect on their drinking habits. A few admitted that “maybe I do drink too much sometimes.” Further revisions will be needed to both the text and graphics to present the low-risk drinking limits in a way that the public will understand and accept.

A companion web site to Rethinking Drinking is under development as well. NIAAA staff focus tested a preliminary design for the home page, which was well received. The site will have interactive features, such as change plans that users can email to themselves, as well as links to helpful resources.

A poster session on the development and focus testing of Rethinking Drinking, entitled “Evidence-Based Strategies for Communicating with At-Risk Drinkers,” was presented by CPLB’s Maureen Gardner at the second National Conference on Health Communication, Marketing, and the Media in Atlanta, Georgia on August 13. The conference, attended by 800 communications professionals, was co-sponsored by the CDC’s National Center for Health Marketing and the National Cancer Institute. NIAAA’s Diane Miller and Fred Donodeo were co-authors.

I. What’s Ahead

Mark Keller Honorary Lecture

October 21, 2008, 1:30 p.m.

Presented by Dr. Kathleen A. Grant,

Department of Behavioral Neurosciences,

Oregon Health and Science University,

at the NIH Clinical Center, Bethesda, MD

APPENDIX I: TEAMS, WORKING GROUPS, AND COORDINATING COMMITTEES

Teams

Gene and Environment

• Marcia Scott, Chair
• Nanwei Cao
• Robert Freeman
• Lindsey Grandison
• Q. Max Guo
• Lisa Neuhold
• Antonio Noronha
• Diana Urbanas
• Brenda Weis
• Ellen Witt

Informatics and Computation/ Systems Biology

• Max Guo and Lisa Neuhold, Co-chair
• Nanwei Cao
• Thomas Gentry
• Lindsey Grandison
• Tom Greenwell
• Lorraine Gunzerath
• Kathy Jung
• Etienne Lamoreaux
• Yuhong Lin
• Sharon Majchrzak
• Philippe Marmillot
• Reza Momenan
• Elisa M. Moore
• Antonio Noronha
• Vijay Ramchandani
• Kenneth R. Warren
• Qiaoping Yuan
• Sam Zakhari

Centers and Training

• Lindsey Grandison and Mariela Shirley, Co-chair
• Thomas Gentry
• Robin Kawazoe
• John Matochik
• Thomas Greenwell
• Kathy Jung
• Joe Wang
• Marcia Scott
• Q. Max Guo
• Ivana Grakalic
• Debra Carle
• Philippe Marmillot
• Svetlana Radaeva
• Lorraine Gunzerath

Working Groups

Underage Drinking

• Vivian Faden and Dale Hereld, Co-chair
• John Bowersox
• Fred Donodeo
• Ralph Hingson
• Cherry Lowman
• Margaret Mattson
• Diane Miller
• Howard Moss
• Patricia Powell
• Gregory Roa
• Mariela Shirley
• Dennis Twombly
• Ellen Witt

Mechanisms of Behavior Change

• Bob Heubner and Mark Willenbring, Co-chair
• Page Chiapella
• Cherry Lowman
• Angela Martinelli

Medications Development

• Mark Egli and Raye Litten, Co-chair
• Joanne Fertig
• Margaret Mattson
• Megan Fitzpatrick Ryan
• Mark Willenbring
• Antonio Noronha
• Thomas Greenwell

Biomarkers

• Kathy Jung, Chair
• Sandor Batkai
• Thomas Greenwell
• Tom Gentry
• Q. Max Guo
• Dale Hereld
• Etienne Lamoreaux
• Robert Lipsky
• Raye Litten
• Philippe Marmillot
• Howard Moss
• Margaret Mattson
• Lisa Neuhold
• Shiu-Lin Niu
• Vijay Ramchandani
• Joe Wang

Fetal Alcohol Spectrum Disorders

• John Matochik and Susan Maier, Co-chair
• Roz Breslow
• Kendall Bryant
• Beata Buzas
• Nanwei Cao
• Margaret Davis
• Lindsey Grandison
• Thomas Greenwell
• Q. Max Guo
• Dale Hereld
• Colin Hodgkinson
• Kathy Jung
• Philippe Marmillot
• Margaret Mattson
• Shui-Lin Niu
• Antonio Noronha
• Deidra Roach
• Marcia Scott
• Mariela Shirley
• Ken Warren
• Bridget Williams-Simmons
• Ellen Witt

Coordinating Committees

International Research

• Peggy Murray and Howard Moss, Co-chair
• Ting-Kai Li
• Kenneth Warren
• Robin Kawazoe
• George Kunos

Health Disparities

• Judy Arroyo, Chair
• (other members appointments pending)

HIV/AIDS

• Deidra Roach and Kendall Bryant, Co-chair
• Kenneth Warren
• (other member appointment pending)

APPENDIX II: NIAAA INVOLVEMENT IN THE NIH ROADMAP

The NIH Roadmap for Medical Research was created by the NIH in 2003 to support cross-cutting, trans-NIH programs that fill fundamental knowledge and technology gaps, and encourage innovative, high-risk/high approaches to complex biomedical problems. Roadmap programs are designed specifically to catalyze research efforts across the NIH, and in the scientific community, by providing enabling tools, technologies, knowledge, training, and resources. Funding for the Roadmap program comes from the NIH Common Fund, which was created in 2004 and enacted into law by Congress through the 2006 Reform Act. The annual Roadmap budget has increased substantially over the past 5 years, from $131M in 2004 to $498M in 2008, highlighting its importance in the overall NIH funding environment. Although Roadmap programs are not intended to target specific diseases and environmental stressors, such as alcohol, about 30 active Roadmap projects focus on topics related to alcohol and/or addiction. These projects cover a range of topics including basic mechanisms, clinical research and translation, and new technologies and approaches to imaging, drug discovery, and biocomputing

The NIAAA has been actively involved in the development and implementation of several key Roadmap initiatives since 2004, and NIAAA involvement and leadership in Roadmap programs has increased substantially over the past 5 years. The NIAAA received approximately $3.18M from the Roadmap Common Fund, and $1.7M in 2008, to support alcohol-related projects. Currently, the NIAAA has program and management representatives on nearly all of development and implementation teams for the various Roadmap programs. The following is a summary of NIAAA involvement in the NIH Roadmap.

Summary of NIH Roadmap Programs with Significant NIAAA Involvement and Support from the NIH Common Fund

In 2004, the NIAAA Director, Dr. T-K Li, was selected as co-chair of the Pathways to Discovery program, which supports research to advance our understanding of how the building blocks of the body – genes, proteins, metabolites – function and interact via complex systems to maintain health and respond to disease. Dr. Li played an instrumental role in crafting the Metabolomics Technology Development initiative, one of the first Roadmap initiatives to be funded in 2005.

Dr. Howard Moss (OD) is applying his medical training and expertise in several key Roadmap initiatives aimed at re-engineering the clinical research enterprise to speed the translation of basic research discoveries to clinical treatment. Two of these programs, the Clinical and Translational Science Awards (CTSAs) and the Patient Reported Outcomes Measurement Information Systems (PROMIS), were launched in 2006-2007. The CTSAs bring together researchers in diverse areas of science into clinical centers that provide basic and applied training, research opportunities, access to new research tools and technologies, and application to patient care. Dr. Moss serves on the CTSA Translation Committee whose purpose is to analyze and disseminate approaches used by the CTSAs to create an environment that is supportive of translational research. The CTSAs serve as a potential avenue for promoting research related to alcoholism and alcohol-related diseases. The centers are linked nationally by shared data collection, reporting and management systems. For example, the PROMIS program provides standardized measurement tools and questionnaires for collecting, reporting and sharing patient-reported information on factors such as pain, fatigue, physical functioning, emotional distress, and social role, that impact quality of life and may predispose individuals to alcoholism and alcohol-related illness. Dr. Moss has been instrumental in developing clinically and scientifically meaningful alcohol use indicators that are entered into psychometric models to analyze emotional stress. Dr. Moss also represents the NIAAA on several senior advisory boards for the NIH Roadmap tasked with developing and vetting new Roadmap ideas for consideration by the NIH Director, Institute/Center/Office Directors, and the scientific community.

Program Directors, Dr. Lindsey Grandison and Dr. John Matochik, have played a key role in the Roadmap Interdisciplinary Research (IR) program which fosters the creation of new academic research cultures based on multi-disciplinary approaches to solving complex biomedical problems. The hallmark of the IR program are the 9 multi-project consortia funded under this program. Drs. Grandison and Matochik serve as program leads for the consortium on Interdisciplinary Research on Stress, Self-Control and Addiction, funded in 2007, and led by Dr. Rajita Sinha at Yale University. One of the projects in this consortium addresses norepinephrine-mediated stress pathways in alcohol dependence. Dr. Matochik also represents the NIAAA on the management Oversight Committee for the overall IR consortia program.

In addition, NIAAA program director, Dr. Michael Hilton, manages an R21 project under the IR program that focuses on developing Novel Methods to Study Substance Use in College Students. The project was initiated in 2007 and is led by Dr. Jonathan Covault at the University of Connecticut.

Program Director, Dr. John Matochik, represents the NIAAA on the Roadmap National Centers for Biomedical Computing (NCBC) program which supports the development and dissemination of innovative bioinformatics and computational biology platforms for modeling and imaging complex cellular systems and networks. The NCBCs provide the tools and resources needed to facilitate biomedical research nationwide. Dr. Matochik serves as science officer for one of the 7 multi-faceted NCBC centers, the National Alliance for Medical Image Computing, at Harvard Medical School. He also serves as program director for one of the collaborative projects affiliated with this center, led by James Daunais at Wake Forest University, and initiated in 2007. The project involving magnetic resonance imaging (MRI) to monitor changes in neuronal structure and function in primates from stress-related alcohol consumption.

In 2007, the NIAAA provided funding for a new investigator supported under the NIH Director’s Pioneer Award program launched through the NIH Roadmap. The Pioneer Award program encourages and supports investigators with exceptional creativity who propose using pioneering approaches to address complex biomedical problems. The NIAAA co-funded the award for Laurence Abbott at Columbia University who is developing model systems of neuronal networks to describe complex tasks involved in decision-making, reactions, and memory, and to link events in behavioral plasticity with synaptic plasticity.

Drs. Brenda Weis, Samir Zakhari, and T-K Li have played a key role in the development and implementation of a new Roadmap Epigenomics Program, launched in 2007-2008, to improve our understanding of the epigenetic contributions to human health and disease. The program consists of five research initiatives aimed at developing epigenome-wide maps in human cells and tissues to serve as references for various diseases, development of new technologies for high throughput epigenome-wide analyses and single call imaging, discovery of novel epigenomic markers in mammalian cells, and creation of new antibodies and public data sources for epigenomics. Dr. Weis (OD) and program director, Dr. Samir Zakhari, lead the trans-NIH initiative on the Epigenomics of Human Health and Disease (RFA-RM-08-017) which closes on October 28, 2008. This initiative will likely foster new research on the epigenetic contributions to alcoholism and alcohol-related diseases. Dr. Li serves as ex officio chair of the Epigenomics Working Group which is comprised of more than 40 NIH staff and is tasked with the development, implementation and management of the program. Dr. Weis also serves as program liaison for the NIAAA on the Roadmap Implementation Coordinating Committee.

Lastly, several NIAAA program directors have been involved in development of the newest of Roadmap initiatives – the Transformative R01 (T-R01) program. The T-R01 program represents a $250M NIH investment over 5 years, beginning in 2009. The program seeks to support innovative, high risk/high reward projects that have the potential to transform our understanding of scientific paradigms in biomedical and behavioral science. NIAAA program staff have played a key role in development of the T-R01 program which targets important research areas for NIAAA, including the science of behavior change and functional variation in mitochondria.

APPENDIX III: NIH BLUEPRINT FOR NEUROSCIENCE RESEARCH

The NIH Blueprint for Neuroscience Research is a cooperative effort among the 16 NIH Institutes, Centers, and Offices that support neuroscience research. By pooling resources and expertise, the Blueprint takes advantage of economies of scale, confronts challenges too large for any single Institute or Center, and develops research tools and infrastructure that serve the entire neuroscience community involved in both basic and clinical research.

Nervous system disorders take many forms: mental disorders, such as schizophrenia, depression, and obsessive compulsive disorder; neurological diseases, such as stroke, traumatic brain injury, epilepsy, Parkinson’s disease, and multiple sclerosis; degenerative dementias of aging, such as Alzheimer’s disease and vascular dementia; developmental disorders, such as autism, mental retardation, and attention deficit disorder; inherited and acquired sensory disorders, including visual and hearing loss; chronic pain conditions; alcohol dependence; and drug addiction. Many of these diseases share mechanisms. While the Blueprint does not target individual disorders, the tools, resources, and infrastructure created through the Blueprint have the potential to accelerate research for all of them, which in turn will lead to advances in prevention and treatment.

The NIH Neuroscience Blueprint emerged from the premise that there are fundamental themes in neuroscience research that cross Institute and Center boundaries. The three themes selected were (1) neurodegeneration during disease and aging; (2) neurodevelopment throughout the lifespan; and (3) neuroplasticity, from the molecular level to the behavioral level.

Over the last few years, a large number of Blueprint initiatives and funding opportunities have been initiated under these main themes. Listed below are some of the initiatives that NIAAA staff from the Division of Neuroscience and Behavior has actively been involved with and which will have a direct impact on the alcohol research field.

NIH Blueprint on Neurodevelopment

NIAAA supports research on the effects of alcohol neurodevelopment from gestation through the adolescent period. However, none of this research focuses on large-scale tool development to accelerate research in this area. The Blueprint initiative on Neurodevelopment identified the development of tools and resources in the following areas for advancing neurodevelopment research: 1) improved analysis of developing cells and circuits, 2) genetic resources, and 3) cross-species standardization of assays for behavioral development. Accordingly, initiatives for improving availability of validated monoclonal antibodies, developing new markers for visualizing neurons and measuring circuit function within developing neural circuits, and advanced genetic resources, particularly genetic tools for developmental analysis in non-human primates were developed. Since NIAAA is interested in how alcohol affects neural development in alcohol-exposed fetuses and adolescents, the new markers for circuit development and monoclonal antibodies will be extremely useful in understanding alcohol’s effects on neurodevelopment. Furthermore, nonhuman primate models are particularly relevant for studying alcohol’s effects on the adolescent brain because of the comparatively long adolescent period in this species. Therefore, investigators can examine the carefully controlled effects of alcohol exposure on gene expression in the nonhuman primate adolescent brain.

NIH Blueprint on Neurodegeneration

The Blueprint initiative on Neurodegeneration identified the development of tools and resources in several areas for advancing neurodegeneration research. Four major initiatives were developed that included the development of biomarkers for neurodegeneration, development of novel techniques to deliver therapeutics to the nervous system, and opportunities for postdoctoral fellows and established investigators to receive training in neurodegeneration research. As neurodegeneration is an outcome of chronic alcohol use, these initiatives should provide good tools and information for the alcohol research community to explain and treat alcohol-induced neurodegeneration.

NIH Blueprint on Neuroplasticity

NIAAA supports a spectrum of research on the neuroscience of alcohol action and addiction. Recent research has highlighted the potential role of neuroplasticity in the progressive changes that occur with repeated, episodic alcohol exposure.  The Blueprint initiative on Neuroplasticity identified the development of probes, instrumentation, and other tools for understanding, monitoring, and manipulating neural plasticity. NIAAA participated in the development and funding of these important initiatives that were aimed at 1) the development of new or improved reporters of neural plasticity, 2) methods for manipulating cell and circuit function associated with plasticity, and 3) optical or electrophysiological methods for monitoring neural plasticity.

Projects funded through this initiative are expected to lead to groundbreaking technological developments that can be utilized by a variety of investigators in alcohol research to increase our understanding of alcohol’s effects on key brain changes that underlie the transition from casual drinking to compulsive drinking and alcohol dependence. 

Diffusion Tensor Imaging (DTI) Expansion for Pediatric MRI Study of Normal Brain Development

Nationwide surveys indicate that alcohol drinking is widespread among adolescents. In fact, more than three-fourths of 12^th graders, nearly two-thirds of 10^th graders, and more than two in five 8^th graders have drunk alcohol at some point in their lives (Monitoring the Future website). Even more troublesome is the high prevalence of heavy episodic drinking referred to as “binge” drinking, which occurs among high school students. Given the high frequency of drinking in young teenagers, NIAAA is interested in the effects of alcohol exposure during the preadolescent and adolescent stages on brain development. To date, very few neuroimaging studies have been conducted on the effects of alcohol on maturational brain processes, and those that have studied brain structural changes in youths with alcohol problems have used cross-sectional designs. This BP initiative, which is an ongoing contracted study to develop a database of MRI and correlated clinical/behavioral data from ~ 500 healthy, typically developing children, ages newborn to late adolescence/early adulthood, will allow alcohol investigators to compare their neuroimaging data to a standardized control group.  Imaging modalities include structural MRI, spectroscopy and diffusion tensor imaging (DTI). Blueprint funds expanded the DTI portion of the project. In future years, it may be possible to add-on to this study to obtain family history and alcohol-drinking information from this sample, which would enhance our ability to dissociate preexisting brain changes associated with alcoholism risk from alcohol’s direct effects on the developing brain.

NIH Toolbox for Assessment of Neurological and Behavioral Function

NIAAA supports national longitudinal epidemiological surveys as well as multi-site clinical trials. However, few of these large-scale studies have attempted to assess aspects of neural and behavioral function (cognition, sensation, movement, and emotion), due to the lengthy administration time and lack of adequate validation and reliability of the measures. This BP initiative is developing a comprehensive set of measures for assessing cognition, emotion, sensation and motor functions, using computerized adaptive testing and real-world setting (virtual reality) that will lead to more efficient, flexible, and responsive assessment, and most importantly, comparability across studies. The goal is to have a unified set of measures that can be used across diverse study designs and populations, particularly longitudinal epidemiological studies and clinical trials.  NIAAA investigators will be able to take advantage of these assessment tools for studying epidemiology, prevention and long-term intervention.

NIH Blueprint For NeuroscienceTraining Initiatives:

Course development on the Neurobiology of Disease:

The intent of this initiative is to bring information on diseases and problems of the nervous system, those which are of significant medical concern, into the graduate curriculum of biomedical training programs. The objective is to introduce the significance of these medical issues into the basic biological science training programs so that basic, biomedical scientists will become more effective in pursuing research into the disease processes of the highest medical significance. This BluePrint initiative will have great relevance to the efforts of NIAAA which has recently established training of the next generation of researchers as a high priority. This initiative will allow the presentation to graduate students, who have not yet established their research path, the significance and activities of alcohol research as awards made under this initiative were to institutions where significant alcohol research is being done and where this information will be incorporated into the graduate course on Neurobiology of Disease. The anticipated outcome from this initiative is expected to be a greater recruitment of new researchers into the alcohol field.

Training in Neuroimaging: Integrating First Principles and Applications (T90)on Training in Neuroimaging:

The intent of this initiative is the establishment of training programs in neuroimaging that will bring together expertise from all areas that impinge on neuroimaging. Currently the majority of training occurs in individual laboratories that are using neuroimaging. However this individual approach does not allow for exposure of trainees to multiple methods of imaging such as fMRI, PET, BOLD etc. Nor does it provide adequate training in the relevant physical principles, their shortcomings, appropriate applications, or analytic interpretations. The objective is to bring into neuroimaging those trained in the physical sciences that support imaging, physics, chemistry of ligand development and bioengineering and further to introduce those with expertise in neuroscience to the technical aspects. This BluePrint initiative has great relevance to the interests of NIAAA in the area of neuroimaging. Neuroimaging provides one of the best approaches to examine neural activity noninvasively in human subjects. It provides a mechanism for translational research critical to applying insights from basic research to the clinical situation.

Circuit Retraining

One of the recommendations from the Blueprint Neuroplasticity Workshop was to develop initiatives to study “circuit re-training following focal injury of the brain and spinal cord.” The treatment and/or remediation of neurological problems such as traumatic brain injury, stroke, and alcohol and drug addiction can benefit from scientific advances in understanding how to promote neural circuits (both disrupted circuits and alternative pathways) to restore cognitive and behavioral function. NIAAA staff are involved with the planning of a workshop to bring together outstanding investigators in the field of neural circuit re-training and recovery of function to discuss the current state of the field and how NIH can accelerate developments that lead to effective treatment interventions. Participants nominated for the workshop include long-time NIAAA grantees that will be able to provide a perspective from the alcohol field and also benefit from discussion of ideas from other disciplines.