Director's Report on Institute Activities to 116th Meeting of Advisory Council

Thursday, September 20, 2007

CONTENTS

A. Legislation, Budget, and Policy

B. Director's Activities

C. NIAAA Staff and Organization

D. NIAAA Research Programs

E. Scientific Meetings

F. Outreach

G. Multi-Media Products from NIAAA

H. What's Ahead

A . Legislation, Budget, and Policy

Legislation for NIAAA Name Change As reported at the May 24 advisory council meeting, Congressman Patrick Kennedy and Senator Joseph Biden introduced in March parallel bills in the House and Senate to change the names of NIAAA and the National Institute on Drug Abuse. The Senate Committee on Health, Education, Labor and Pensions reported the bill, S. 1011, to the Senate floor, with an amendment, on August 1. The amendment would change the name of NIH's National Institute of Child Health and Human Development to the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The bill was placed on the Senate legislative calendar to be brought up for a Senate vote; however, a Senator placed an anonymous "hold" on the bill. This means that the Senate may not take up the bill as long as this hold remains. Only the Senator who placed the hold on the bill can release it.

There has been no action on the House bill.

Congressional Activity On June 7, the House Appropriations Subcommittee on Labor, Health and Human Services (HHS), and Education held the mark up for the FY 2008 Labor, HHS, and Education appropriation bill, which includes funding for NIH. The full House Appropriations Committee marked up the bill on July 11. The bill would provide $29,649,887,000 for NIH and $442,870,000 for NIAAA. The subcommittee mark for NIAAA is an approximately 1.6 percent increase over the FY 2007 revised joint resolution (JR) and the FY 2008 revised President's budget (PB) request.

The full Senate Appropriations Committee on Labor, HHS, and Education approved the markup for the FY 2008 appropriation bill on June 21; the legislation would increase funds for NIH by $800 million over the President's request. The Senate Appropriations Subcommittee recommended $29,899,887,000, a $1 billion increase over the FY 2007 appropriation for the NIH and $445,702,000 for NIAAA, an increase of 2.2 percent over the FY 2007 revised joint resolution and 2.1 percent over the FY 2008 revised President's budget request. This amount will allow the NIH, for the first time since FY 2005, to plan on increasing the average costs of new grants and provide the full "committed level" for non-competing grants.

A summary comparing the President's request, the House level and the Senate level is below 
(all dollars in thousands): 

B. Director's Activities

Tomorrow's Medicine Today Medical Missions for Children (MMC) is a New Jersey-based charity with a broad mission to transfer medical knowledge using the latest communications technology. MMC produces four television programs, one of which,Tomorrow's Medicine Today, focuses on NIH research. On June 4, Dr. Li was the featured NIH institute director for the show's taping; NIH Director Elias Zerhouni was the cohost of the show, along with Naomi Weinshenker, a child psychiatrist and medical reporter. Victor Hesselbrock, an NIAAA grantee at the University of Connecticut School of Medicine accompanied Dr. Li for taping.Tomorrow's Medicine Today will be broadcast over the Medical Broadcasting Channel, which is aimed at an audience of healthcare professionals, and on NJ public television.

Research Society on Alcoholism At the opening session of the annual meeting of the Research Society on Alcoholism July 8, Dr. Li gave an update on NIAAA that included an overview of the budget, the current research portfolio, and central issues for ongoing research. Although the budget has been flat, the FY 2007 joint resolution gave NIAAA extra funds over the President's budget. NIAAA has a good success rate compared to other institutes and the institute is doing what it can to fund new investigators. NIAAA will be funding 27 new investigators in FY 2007, which is our target within NIH based on budget size. The presentation included an update of the strategic plan, noting opportunities in multidisciplinary research that have been added; and addressed some key initiatives in translational research, among them the need to develop dimensional criteria for alcohol use disorders and biomarkers. 

Chinese Governmental Delegation at NIH On Sept. 13, Dr. Li welcomed a delegation of Chinese governmental officials for a briefing and tour of the NIH campus. The group consisted of 20 officials, described as "rising stars" in both central and provincial governments in China. The visit to the U.S. was coordinated via the Diplomacy Institute at George Washington University and the participants spent the week visiting other government agencies and offices such as the White House, the U.S. Congress, the Department of State and the Department of Commerce among others. Dr. Li gave a presentation on the work of NIH, the role of Chinese researchers in the NIH institute/centers, and NIH collaborative efforts with China.

C. NIAAA Staff and Organization

Howard Moss, M.D. Howard Moss has been named one of 27 members of the task force that will oversee the development of the fifth edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-V). The DSM is the handbook used by psychiatrists and other mental health professionals to diagnose and classify mental disorders. The task force includes research scientists from psychiatry and other disciplines as well as clinical care providers, and consumer and family advocates. DSM-V is scheduled to be published in 2012.

New Employees 
Thomas Greenwell, Ph.D. Thomas Greenwell has joined the Division of Neuroscience and Behavior (DNB) as a health scientist administrator. Dr. Greenwell received his Ph.D. in neuroscience from Tulane University in New Orleans, Louisiana, with an emphasis in pharmacology and neuroanatomy. His graduate studies characterized the recently discovered endogenous opioids, endomorphin (EM)-1 and -2, and the projections of EM peptidergic neurons to the reward system. This work has aided our understanding of mechanisms of pain and also has implications for the development of therapeutics for pain and drug addiction.  Dr. Greenwell did postdoctoral research at The Scripps Research Institute prior to his appointment at NIAAA. Within the Department of Neuropharmacology, he studied the effects of corticotropin-releasing factor and adrenergic antagonists on heroin self-administration as well as the neuropharmacology of stress behaviors. His research focused on common neurocircuits and their adaptations to alcohol, heroin, and cocaine dependence. Dr. Greenwell manages a program dealing with neuropeptide involvement in alcohol dependence, as well as stress and alcohol interactions. He also represents NIAAA on the NIH Neuroscience Blueprint for Neuroplasticity.

M. Katherine Jung, Ph.D. M. Katherine Jung joined the Division of Metabolism and Health Effects (DMHE) as a program director in August. Dr. Jung comes from the National Cancer Institute, where she worked as a contractor in drug discovery, designing screens to identify new active agents, and investigating mechanisms of drug action of chemotherapeutic agents. Her areas of expertise include molecular biology, molecular genetics, and cell biology, with special interests in mitosis and signal transduction. She received her Ph.D. in biochemistry from Ohio State University. Dr. Jung has over 30 journal publications.

He (Joe) Wang, Ph.D. He (Joe) Wang joined DMHE as a program director in September. Dr. Wang comes from the U.S. Department of Agriculture (USDA), where he worked in the past three years as a microbiologist and project leader at the Plum Island Animal Disease Center in New York. Before joining USDA, Dr. Wang was a tenure-track assistant professor in the Department of Microbiology and Molecular Genetics of Michigan State University, after training in Dr. Liz Blackburn's laboratory at the University of California, San Francisco. His long time interest has been telomerase and reverse transcriptase, and he has made some important contributions in that field. His areas of expertise include molecular biology, biochemistry, genetics, microbiology, virology, and animal disease.

Bridget Williams-Simmons, Ph.D. Bridget Williams-Simmons has joined NIAAA as a full time staff member in the Science Policy Branch following completion of her 2-year internship in the Emerging Leaders Program (ELP). The ELP is one of the recruitment tools used by the Department of Health and Human Services (DHHS) to hire exceptional interns with a variety of backgrounds and provide fast track development highlighting leadership and business skills through experiential learning and training. Before joining the ELP, Dr. Williams-Simmons earned her Ph.D. in biochemistry from Tulane University in New Orleans, where she did research in telomere biology. While in the ELP, she did rotations in NIH's Center for Scientific Review and the National Cancer Institute, as well as the Indian Health Service and the Substance Abuse and Mental Health Services Administration.

Departures 
Diane Lucas, Ph.D. Diane Lucas, health scientist administrator in DMHE, retired in June after 19 years at NIH, 7 of which were at NIAAA. At NIAAA, Dr. Lucas administered a diverse portfolio of grants that included the effects of alcohol on immune function and alcohol interactions with hepatitis C virus and HIV infection. Prior to joining NIAAA, she held positions at the National Heart, Lung, and Blood Institute and in academia.

Marlene Sable Marlene Sable, secretary to the NIAAA director for 21 years, retired in August. Ms. Sable had worked 38 years for NIH and 9 years prior to that in private industry. She first joined NIH in 1969, working in the intramural research program at the National Institute of Mental Health. She also worked for the National Institute on Drug Abuse, and the National Heart, Lung, and Blood Institute before joining NIAAA as secretary to then director Enoch Gordis. A message from the Research Society on Alcoholism to its members announcing her retirement said, "As the front door to NIAAA, she represented the institute with an attitude of courtesy, welcome, helpfulness, and patience." In 1990, Ms. Sable received the Alcohol, Drug Abuse, and Mental Health Administration's (ADAMHA) Administrator's Award for exceptional achievement. She received at the same time an ADAMHA "Coworkers Award," recognizing employees who have been identified by their coworkers as making a special contribution to the agency.

Roger Sorensen, Ph.D. Roger Sorensen has left NIAAA to take a position in the National Institute on Drug Abuse (NIDA). Dr. Sorensen came to NIAAA in 2000 as a Presidential Management Intern within the then Division of Basic Research. In 2002, he became a health science administrator within the Neuroscience and Behavioral Research Branch. Dr. Sorensen oversaw the research portfolio on molecular pharmacology and physiology within the neuroscience division and was the NIAAA representative on many trans-NIH committees, including the use of computational approaches in neurobiology. In July of this year, Roger accepted a position with the Functional Neuroscience Branch at NIDA.

Awards 
Emmy Award for HBO's The Addiction Project Together with HBO, the Robert Wood Johnson Foundation, and the National Institute on Drug Abuse (NIDA), NIAAA received the American Academy of Television Arts and Sciences' Board of Governors Award, the highest honor bestowed by the Academy, for The Addiction Project. The 14-part multiplatform Project originally was launched March 15, 2007 on HBO television stations and elsewhere and prominently featured Mark Willenbring, along with current and past NIAAA-supported researchers including Sam Bacharach, Kathleen Brady, Larry Gentilello, Bankole Johnson, Thomas McLellan, Robert Meyers for William Miller, and Charles O'Brien. The broadcast also featured current NIDA Director and former NIAAA grantee Dr. Nora Volkow. Many other NIAAA staff, especially Ann Bradley, and grantees contributed significant time and expertise. The presentation ceremony for the 2007 Creative Arts Emmy® Awards took place September 8 in Los Angeles. The Governors Award recognizes work that "stands out with the immediacy of current achievement." In the press release announcing the award, Academy chairman Dick Askin said that this project "was a landmark venture that stripped away misconceptions about addiction and offered hope to addicts and their loved ones with information about new and effective treatments." Principal components of the Project may be viewed at https://www.hbo.com/movies/addiction.

FARE Awards A record number of postdoctoral fellows in the Division of Intramural Clinical and Biological Research (DICBR) won the FARE (Fellows Award for Research Excellence) award at NIH. The award recognizes outstanding scientific research performed by intramural postdoctoral fellows. This year's DICBR recipients are Jonathan Brigman (mentor: Dr. Holmes), Kei Hamazaki (Dr. Kim), Rajesh Mohanraj (Dr. Pacher) and Simona Spinelli (Dr. Barr).

Bridget Grant, Ph.D. Bridget Grant has received the 2007 Jellinek Memorial Fund Award, given to a scientist who has made an outstanding contribution to the advancement of knowledge in the alcohol/alcoholism field. This is the premier international award in alcohol research. The category for this year's award is epidemiology and population studies; Dr. Grant's award recognizes outstanding leadership in the design, implementation and analysis of major epidemiologic surveys in the field of alcohol and drug use disorders and psychiatric comorbidities.

Andrew Holmes, Ph.D. Andrew Holmes is the recipient of the 2007 Senior Preclinical Wyeth Award of the British Association for Psychopharmacology.

Bill Huang, Ph.D. Bill Huang, post-doctoral associate of Hee Yong Kim, received the Progress in Lipid Research Young Investigator Award at the 2007 meeting of the American Society for Biochemistry and Molecular Biology held in Washington DC.

Antonio Noronha, Ph.D. Antonio Noronha received the NIH Director's Award on June 13. This group award was for providing extraordinary scientific leadership of the Molecular Libraries and Imaging Roadmap to enable research on new pathways to discovery in health and disease.

Ellen Witt, Ph.D. Ellen Witt received the Blueprint for Neuroscience Research Directors Award for significant achievement in recognition of her outstanding effort and exemplary teamwork as a member of the Neuroepidemiology Project Team and the Neurodevelopment Workshop Project Team on July 16, 2007.

D. NIAAA Research Programs

NIH Roadmap Sam Zakhari is participating in meetings on the epigenetics initiative of NIH's Roadmap effort to develop five RFAs on various aspects of epigenetics in health and disease. Drs. Zakhari and Max Guo also participated in the Human Microbiome Project, another Roadmap initiative. More information available on the NIH Commonfund website.

Publications by Extramural Staff

Consumption Patterns and Liver Disease Drs. Zakhari and Li are co-authors of a paper on "Determinants of Alcohol Use and Abuse: Impact of Quantity and Frequency Patterns on Liver Disease, " in press in Hepatology.

Symposium Summary: Alcoholic Liver Disease Drs. Zakhari and Vishnu Purohit are co-authors with others of "Role of S-Adenosylmethionine, Folate and Betaine in the Treatment of Alcoholic Liver Disease: Summary of a Symposium," in American Journal of Clinical Nutrition 86:14-24, 2007.

Collaborative International Research

Institut National de la Santé et de la Recherche Médicale The successful collaborative initiative with the French Institut National de la Santé et de la Recherche Médicale (INSERM) continues. To date there have been a number of positive outcomes:

• There have been two face to face research development meetings, one in the U.S. (October 2005) and one in France (January 2007).

• There have been two international video conference calls to review progress on the collaborative agenda outlined in the above meetings.

• A French scientist, Michel Nassila, attended the NIAAA Extramural Advisory Board meeting on animal models. Upon returning to France, he made recommendations to alcohol researchers working there on changes to their animal research procedures that are now being implemented.

• John Helzer from the University of Vermont spent time in France analyzing data from the European EsMed (European Study of the Epidemiology of Mental Disorders) data set, looking at questions to inform improvement in diagnostic criteria for DSM-IV.

• A French scientist, Yann Le Strat, attended the NIAAA-sponsored meeting on immortalized cell lines in gene expression on August 27 to 28 in Rockville.

• An affiliated INSERM laboratory has been officially formed with the NIAAA Alcohol Research Center at Scripps Research Institute in San Diego, CA. George Koob and Brigitte Kieffer are the U.S. and French principal investigators, respectively.

• A French post-doc, Sandra Chenraud, will be working in the laboratory of NIAAA grantee Edith Sullivan beginning in October.

Korean National Institutes of Health On May 21, NIAAA was visited by Hae Wo Cho, Director General of the Korean National Institutes of Health (KNIH). She was accompanied by In-Ho Jo, Director, Center of Biomedical Sciences, KNIH, and Won Ho Kim, a senior scientist in the Center for Biomedical Sciences. KNIH is in the process of developing their program of alcohol research and are looking to collaborate in some areas with both the NIAAA intramural and extramural research communities.

As a result of the May 21 meeting, four Korean alcohol research scientists visited NIAAA on July 16, after attending the Research Society on Alcoholism meeting in Chicago. Advantage was taken of this opportunity to have a ½ day symposium with presentations by Korean visitors and U.S. scientists from NIAAA's Division of Intramural Clinical and Biomedical Research. Korean presenters included San Ick Park, Director, Division of Intractable Diseases, KNIH; Sung Gon Kim, Pusan National University; Dae Jin Kim, Catholic Medical University, Bucheon; and Ji-Young Hwang, Senior Scientists at the KNIH. Presenters from the NIAAA intramural program included David Goldman, Hee-Yong Kim, Won-Il Jeong, and Pal Pacher. NIAAA's Peggy Murray and B.J. Song chaired the symposium.

RFAs: Applications

NIAAA has received, or is expecting, numerous applications in response to RFAs for 2007. Below is a summary of applications that have been received and reviewed for the August and October 2007 councils.

• RFA-AA-07-006 Impact of Adolescent Drinking on the Developing Brain (R21): 19 applications

• RFA-AA-07-007 Alcohol, Puberty, and Adolescent Brain Development (R01): 3 applications

• RFA-AA-07-008 Alcohol, Puberty, and Adolescent Brain Development (R21): 5 applications

• RFA-AA-07-009 Medications Development for the Treatment of Alcoholism (SBIR, R43/R44): 2 applications

• RFA-AA-07-010 Medications Development for the Treatment of Alcoholism (STTR, R41/R42): 1 application

• RFA-AA-07-011 Epigenetic Mechanisms in the Neurobiology of Alcohol Tolerance and Dependence (R01): 4 applications

• RFA-AA-07-012 Epigenetic Mechanisms in the Neurobiology of Alcohol Tolerance and Dependence (R21): 2 applications

• RFA-AA-07-013 Animal Models of Endophenotypes and Intermediate Phenotypes for Alcohol-Related Behaviors (RO1): 7 applications

• RFA-AA-07-014 Animal Models of Endophenotypes and Intermediate Phenotypes for Alcohol-Related Behaviors (R21): 8 applications

• RFA-AA-07-015 Mechanisms of Nervous System Dysfunction: Impact of Alcohol Abuse on HIV-1 Neuropathogenesis(R21): 8 applications

• RFA-AA-07-016 Mechanisms of Nervous System Dysfunction: Impact of Alcohol Abuse on HIV-1 Neuropathogenesis(R21): 5 applications

• RFA-AA-07-019 Announcement of a Limited Competition for the Continuation of the Cooperative Agreement on the Interaction of HIV Infection and Alcohol Abuse on Central Nervous System Morbidity (U01): 1 application

• RFA-AA-07-20 Integrative Prevention Research for Alcohol Users At-Risk for HIV/AIDS (R01): 10 applications

• RFA-AA-07-21 Integrative Prevention Research for Alcohol Users At-Risk for HIV/AIDS (R21): 3 applications

Research Reports

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

Gene X Environment Effect Raises Alcoholism Risk The enzyme monoamine oxidase A (MAOA) metabolizes neurotransmitters involved in the response to stress, among them, serotonin, dopamine, and norepinephrine. Inborn variations in the gene for MAOA shape the enzyme's level of activity, which in turn has been found to have an impact on behavior. A recent study found that maltreated boys who possessed a low activity genetic variant were more likely to develop behavior problems than boys with a high activity variant. In this study, women who had been sexually abused in childhood were much more likely to develop alcoholism and antisocial behavior if they had a low activity variant, whereas a high activity variant was protective. In contrast, there was no relationship between alcoholism, antisocial behavior and the MAOA genotype among non-abused women. The women were from a group of American Indian women living in a community in which rates of childhood sexual abuse, alcoholism, and antisocial personality disorder were much higher than the average rates among U.S. women. The MAOA gene provides an example of how the environment can interact with a gene to shape behavior; these and similar findings are helping to explain why some individuals are more resilient to profound childhood trauma than others. (Ducci, F., Enoch, M.-A., Hodgkinson, C., Xu, K., Catena, M., Robin, R.W., and Goldman, D. Molecular Psychiatry online ahead of print June 26, 2007, doi:10.1038/sj.mp.4992934)

Survey Finds Multi-Year Gap Between Alcohol Disorder Onset and Treatment At some time during their lives, more than 30 percent of U.S. adults have met current diagnostic criteria for an alcohol use disorder (AUD), according to an analysis of data from the NIAAA's 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Of those with alcohol dependence, only 24.1 percent have received any type of treatment, broadly defined to include treatment either by a physician or other health professional, or by 12-step programs, crisis centers, employee assistance programs, or others. Of those with alcohol abuse, only 7.0 percent have received treatment. Although average age of alcohol dependence onset in the survey was 22.5 years, average age of first treatment was 29.8-a lag time of 8 years. Average age of alcohol abuse onset was 21.9 years, but average age of first treatment was 32.1-a lag time of 10 years. The authors point out that factors such as clinician lack of knowledge, lack of awareness of the need for screening, and low expectations of treatment results are among the reasons for the persistent low rates of treatment and suggest that a major effort to change public and professional attitudes toward treatment is needed. The NESARC is a representative survey that involved 43,000 face-to-face interviews of noninstitutionalized U.S. civilians aged 18 years and older. The current analysis also provided data on sociodemographic correlates of AUDs, disorder onset and course, AUD-associated disability, and co-occurring disorders. (Hasin, D.S., Stinson, F.S., Ogburn, E., and Grant, B.F. Archives of General Psychiatry 64:830842, 2007)

Researchers Identify Alcoholism Subtypes Analyses of NESARC data on survey respondents who met diagnostic criteria for alcohol dependence revealed five distinct subtypes of the disease. The researchers identified unique subtypes of alcoholism based on respondents' family history of alcoholism, age of onset of regular drinking and alcohol problems, symptom patterns of alcohol dependence and abuse, and the presence of additional substance abuse and mental disorders. The largest group in the country, representing 31.5 percent of alcoholics, was the young adults subtype, characterized by relatively low rates of co-occurring substance abuse and other mental disorders, a low rate of family alcoholism, and low rates of treatment-seeking for their drinking. The other four groups were the young antisocial subtype, 21 percent; the functional subtype, 19.5 percent; the intermediate familial subtype, 19 percent; and the chronic severe subtype, 9 percent. The authors also report that co-occurring psychiatric and other substance abuse problems are associated with severity of alcoholism and entering into treatment, but overall, help-seeking remains relatively rare. (Moss, H.B., Chen, C.M., and Yi, H.-y. Drug and Alcohol Dependence online ahead of print doi:10.1016/j.drugalcdep.2007.05.016)

Anti-glutamate Drugs Effective for Withdrawal In someone who drinks heavily, neurotransmitter function changes to adapt to the constant presence of alcohol. When a heavy drinker then stops abruptly, the adaptive compensation of the brain has no alcohol to counteract it; this results in the features of withdrawal, including seizures. Benzodiazepines-a category of sedative-have been the standard medical treatment for withdrawal but they have drawbacks, including the potential for abuse. This study investigated the effectiveness of three medications-lamotrigine, memantine, and topiramate-for treating alcohol withdrawal. The drugs all reduce the actions of glutamate, an excitatory neurotransmitter whose activity increases with alcohol withdrawal. At least one of these drugs, topiramate, has been used previously to treat withdrawal, but this study showed that despite the fact that each of the drugs acts on glutamate activity in a different way, all were effective in treating withdrawal symptoms. (Krupitsky, E.M., Rudenko, A.A., Burakov, A.M., Slavina, T.Y., Grinenko, A.A., Pittman, B., Gueorguieva, R., Petrakis, I.L., Zvartau, E.E., and Krystal, J.H.Alcoholism: Clinical and Experimental Research 31:604-611, 2007)

Cannabinoids Involved in Cirrhotic Heart Damage Liver cirrhosis can cause a form of cardiomyopathy, or heart muscle damage, in which the heart seems to have adequate function when an affected person is at rest, but fails in response to stress. This intramural study showed in vivo in rats that the impaired function of the heart muscle in cirrhosis involves endocannabinoids-naturally occurring substances in the brain that act on the same receptors as the active ingredients of marijuana. Endocannabinoids have been found to have diverse effects, including lowering blood pressure through decreasing the pumping function of the heart. Previous research using tissue samples from cirrhotic rats has suggested that endocannabinoids may play a role in the decreased contractile response of heart muscle to stress hormones. In this study, rats with chemically induced cirrhosis developed cardiomyopathy, as verified through in vivo measurements of decreased blood pressure and decreased contractile strength and pumping function of the heart. In these rats, injection of a compound that blocks the cannabinoid receptor CB1 raised blood pressure and other positive indicators of heart function. Levels of the endocannabinoid anandamide were increased 2.7-fold in the hearts of cirrhotic vs. healthy rats. The authors note than an increase in endocannabinoids may be related to endotoxemia, the presence of bacterial toxins in the bloodstream that is associated with cirrhosis and that has been shown to increase anandamide synthesis in macrophages (a type of white blood cell) and to cause low blood pressure. This work suggests that agents blocking the CB1 receptor may have therapeutic value for treating cirrhotic cardiomyopathy. (Bátkai, S., Mukhopadhyay, P., Harvey-White, J., Kechrid, R., Pacher, P., and Kunos, G. American Journal of Physiology-Heart and Circulatory Physiologyadvance online publication June 8, 2007, doi:10.1152/ajpheart.00538.2007)

Alcohol and Extreme Prematurity A prospective study of 3,130 pregnant women found that alcohol consumption was a significant risk factor for extreme prematurity, or birth before 32 weeks gestation. Results of previous studies of alcohol use and prematurity have been mixed; this study used ultrasound to ensure accurate assessment of gestational age. Participating mothers were also questioned on other drug use. The number of drinking days was used as the indicator of alcohol consumption; on average, women in the study were drinking about once every 2 to 3 weeks. Alcohol and cocaine use, but not cigarette smoking, were risk factors for extreme but not mild prematurity. (In women over 30, alcohol also increased the risk of mild prematurity.) The rate of extreme prematurity was 41 percent less among women who abstained from alcohol even when they continued to use cocaine and tobacco. Prematurity is an important cause of neonatal illness and mortality; the authors note that future work is needed to examine more closely the relationship between patterns of alcohol consumption and prematurity. (Sokol, R.J., Janisse, J.J., Louis, J.M., Bailey, B.N., Ager, J., Jacobson, S.W., and Jacobson, J.L. Alcoholism: Clinical and Experimental Research31:1031-1037, 2007)

Adolescent Sensitivity to Alcohol Research suggests that adolescent brains are more sensitive to harm from alcohol than those of adults; the mechanism of this sensitivity is a target for research. This study provides evidence that an effect by alcohol on activity of the inhibitory neurotransmitter GABA may be involved (inhibitory neurotransmitters, in general, reduce the activity of neurons). In the hippocampus, a part of the brain that functions in memory and learning, certain cellular receptors for GABA maintain a tonic or steady state inhibitory electrical current. In this study, this inhibitory current was smaller in adult rats than adolescents. However, alcohol enhanced tonic inhibitory currents to a greater extent in adolescent tissues. Previous research has suggested that the type of GABA receptors involved in this process are likely to play a role in memory; this work adds to evidence that age-related differences in sensitivity of these receptors to alcohol may underlie the increased vulnerability to memory impairment by alcohol in adolescents. (Fleming, R.L., Wilson, W.A., and Swartzwelder, H.S. Journal of Neurophysiology 97:3806-3811, 2007)

Alcohol Reverses Direction of Synaptic Changes Changes in the strength of the synaptic connections in nerve cell circuits in the brain form the cellular basis of memory and learning. An intramural study has found that alcohol exposure can reverse the direction of change in synaptic strength following a stimulus in an area of the brain involved in learning goal-directed behavior. In this study, a test stimulus to brain tissue from a section of the striatum of mice caused an increase in the strength of synaptic connections, a change called long-term potentiation. A dose of alcohol equivalent to mild intoxication reversed the effect, causing long-term depression, a decrease in synaptic strength. This change in how the neuronal circuitry responded to a stimulus was observed in a section of the striatum involved with goal-directed actions-the dorsomedial striatum. The work shows in cellular terms how alcohol can disrupt the learning process-associated with this part of the striatum-that normally takes place when an action is predictably rewarded, leading to goal-directed behavior. With the disruption of this process, say the authors, the alternative form of learning, habit formation, may come into more prominent play. One feature of alcoholism is the loss of ability to avoid or limit alcohol consumption, even in the face of diminishing positive and growing negative consequences; an effect by alcohol on learning could help explain this behavioral shift. (Yin, H.H., Park, B.S., Adermark, L, and Lovinger, D.M. European Journal of Neuroscience 24:3226-3232, 2007)

Hepatocyte Loss in Liver Disease Research on the mechanisms of alcoholic liver disease has implicated the cell-signaling molecule TNF- in the loss of hepatocytes (liver cells). Healthy hepatocytes are resistant to TNF- -induced killing; exposure to alcohol makes them vulnerable. This study found that chronic alcohol consumption by mice resulted in a disruption in the balance of compounds involved in a class of chemical reactions (methylation) that is central to cellular and genetic function. In mice exposed to alcohol, the concentration of S-adenosylmethionine (SAM)-a compound that serves as the source of methyl groups in methylation reactions-was decreased, while S-adenosylhomocysteine (SAH) was increased. This altered ratio sensitized liver cells to TNF-induced toxicity. The authors suggest that finding a way to remove SAH may provide a means of treating alcoholic liver disease. (Song, Z., Zhou, Z., Song, M., Uriarte, S., Chen, T., Deaciuc, I., and McClain, C.J. Biochemical Pharmacology 74:521-531, 2007)

Brain Peptides and Alcohol Craving Exposure to cues in the environment that have been linked in the past to alcohol use can trigger intense craving in a person who is dependent on alcohol. The neurological underpinning of this triggering is a target for research. In this study, rats were trained to press a lever for an alcohol-containing solution and then denied alcohol until they gave up seeking it. Rats then exposed to an aroma previously associated with the availability of alcohol resumed lever-pressing for alcohol. Their brains revealed activation of neurons characterized by the presence of two neuropeptides that play roles in appetite control, energy balance, and some research suggests, drug reward. These neuropeptides-CART and orexin-are produced in cells of the hypothalamus, a part of the brain involved in many aspects of homeostasis. The findings are consistent with the notion that drug and alcohol use exploit systems involved with natural rewards; understanding these pathways will provide clues for developing medications to treat addiction. (Dayas, C.V., McGranahan, T.M., Martin-Fardon, R., and Weiss, F. Biological Psychiatry, online ahead of print, doi:10.1016/j.biopsych.2007.02.002)

Dietary Consequences of Alcohol Consumption Past research has found that dietary quality declines as people drink higher quantities of alcohol. A recent analysis of data from the 2001-2002 National Health and Nutrition Examination Survey (NHANES) found that as men, but not women, drank more alcohol, they consumed lower quantities of essential fatty acids, dietary components that are key to health. Fatty acids are components of fats and oils; essential fatty acids are not synthesized by the body, so must be consumed as part of someone's diet. An optimal balance of dietary fatty acids is associated with improved cardiovascular and mental health, as well as benefits to nervous system development. The authors note that the fatty acid content of tissues may affect the development of alcoholic liver disease; further study should help clarify whether the level of dietary fatty acids may play a role in alcohol-related diseases. The NHANES survey is administered by the Centers for Disease Control and Prevention. (Kim, S.Y., Breslow, R.A., Ahn, J., and Salem, N. Alcoholism: Clinical and Experimental Research 31:1407-1414, 2007)

E. Scientific Meetings

Association of Psychological Science Ellen Witt organized and chaired a symposium at the 19th Annual Convention of the Association of Psychological Science, May 22-25, in Washington, DC. The symposium, "Social Neuroscience and Mechanisms of Behavior Changes," presented human and animal research on the neural and physiological mechanisms of affective and social factors that affect alcohol and/or other substance use behaviors. Mark Willenbring discussed how advances in social and affective neuroscience may relate to health behavior change, particularly intervention response and potential for relapse.

Society of Toxicology At the National Capital Area Chapter of the Society of Toxicology spring symposium May 23, Vishnu Purohit gave a talk entitled "Alcoholism and Liver Inflammation." The talk was co-authored by Bin Gao.

Society for Prevention Research Marcia Scott presented an overview of NIAAA research priorities and findings at a pre-conference workshop of the Society for Prevention Research 15th Annual Meeting, May 30 to June 1. The focus of the workshop, "Underlying Mechanisms in Liability for Dysregulatory Behaviors," was to clarify how genetic and environmental factors interrelate in the occurrence of substance use and mental health disorders and interpret findings regarding relevance to prevention research. Also at that meeting, Bob Freeman organized and moderated a panel on "Theory-Based HIV/AIDS and Alcohol Misuse Prevention Interventions Targeting High-Risk Groups in the U.S. and South Africa." Ralph Hingson gave a presentation on the Division of Epidemiology and Prevention Research strategic plan. The meeting took place in Washington, DC.

Advances in Prevention of Alcohol-Related HIV/AIDS Risk Bob Freeman organized and, with Kendall Bryant, moderated a workshop on "Advances in Prevention of Alcohol-Related HIV/AIDS Risk," which was held on May 29 at the Washington Hyatt Regency, Washington, DC.

American Sociological Association Bob Freeman presented a poster on "Funding Opportunities for Sociologists at the NIAAA" at the annual meeting of the American Sociological Association in New York City, August 11 to 14.

Research Society on Alcoholism The annual meeting of the Research Society on Alcoholism took place on July 7 to 11 in Chicago. NIAAA awarded stipends and/or paid registration fees for 46 junior investigators and 106 students attending the meeting. NIAAA staff participated in numerous symposia:

• Sam Zakhari addressed the pre-RSA satellite meeting on "Mechanisms of Alcohol-Mediated Organ and Tissue Damage."

• Roger Hartman chaired the pre-RSA steering committee meeting on the "Rapid Response to College Drinking" initiative. At two subsequent RSA symposia on the initiative, Marcia Scott was a discussant at one, and Ralph Hingson at the second.

• David Lovinger was the organizer/chair of a symposium on "The Role of Dorsal Striatum in Ethanol Actions, Habit Formation and Addiction."

• B.J. Song and Sam Zakhari were organizers/chairs of a symposium on "Alcohol-Induced ER Stress, Protein-Adducts Formation, Oxidative Protein Modifications, and Functional Implications."

• Tom Gentry was a co-organizer of a grantsmanship workshop on NIAAA-supported research. Laurie Foudin and Dennis Twombly led break-out sessions on different grant mechanisms.

• Raye Litten was one of two organizer/chairs of the symposium "On the Development of Topiramate as a Treatment for Alcohol Dependence: The Next Generation of Progress in Pharmacotherapy."

• Bin Gao moderated a paper session on "Ethanol and Liver Related Disease."

• Vivian Faden was organizer and Patricia Powell, chair, of a symposium on "Understanding and Addressing Underage Drinking in the Context of Development."

• Sam Zakhari was one of two organizers/chairs of a symposium on "Stress Inflammation in Alcoholic Liver Injury: Partners in Crime." Dr. Zakhari also gave opening remarks at the symposium on "Epigenetics and Ethanol."

• Markus Heilig was organizer/chair of a symposium on "The CRF System as a Target for Alcoholism Treatment: New Developments."

• Cherry Lowman was one of two organizers/chairs of a symposium on "Conceptual, Methodological, and Practical Innovations in Research on the Effectiveness of Adolescent Substance Abuse Treatment."

• Bin Gao and Vishnu Purohit were organizers/chairs of a symposium on "Molecular Mechanisms of Alcoholic Fatty Liver: Role of Cytokines, Transcriptional Factors, Endocannabinoids." Sam Zakhari gave opening remarks. Dr. Purohit was a discussant at this symposium and two others on mechanisms of alcoholic pancreatitis and acetaldehyde-induced cell injury.

• Peggy Murray chaired a symposium on "Improving Clinical Practice Through Health Professions Education: Results from Four NIAAA Alcohol Education Project Grants."

Symposium talks provided overviews of the work of NIAAA's Interdisciplinary Team on Underage Drinking Research (Vivian Faden) and recommendations for strengthening biomedical research on alcohol and AIDS (Kendall Bryant). Poster presentations and symposium talks discussed the work of numerous intramural NIAAA investigators.

Workshop on Immortalized Cell Lines for Gene Expression Zhaoxia Ren organized a workshop on "Gene Expression in Immortalized Cell Lines: Toward Standardizing Methodologies for GxE Interaction Studies" that took place in Rockville on August 27 to 28. NIAAA sponsored the workshop along with NIH's Gene, Environment, and Health Initiative. Drs. Li and Francis Collins, Director of NIH's National Human Genome Research Institute, gave opening remarks to the participants. The overall goals of the meeting were to review the potential for the use of immortalized cell lines (LCLs) in studying pharmacogenomics and epigenetics, discuss resources of LCLs and limitations, and make recommendations for the standardization of methodologies for using LCLs.

NIH Blueprint Neuroplasticity Workshop The NIH Blueprint Neuroplasticity Workshop was held at the Bethesda Hyatt Regency on Aug 29th-31st. The Blueprint for Neuroscience Research is a collaborative effort among 16 NIH institute/centers, including NIAAA, that have significant neuroscience research portfolios. By pooling resources and expertise, the Blueprint aims to accelerate neuroscience research and to reduce the burden of nervous system disorders. Research over the last few years has demonstrated the remarkable plasticity in the adult nervous system, that is, the capacity to adapt to various experiences. Recent studies have shown that the human brain is capable of forming new connections in response to injury and harbors stem cells that give rise to new brain cells. The neuroplasticity workshop was composed of eminent scientists in the field (among them, David Lovinger) with the purpose of identifying what research tools are needed to overcome roadblocks and accelerate research in this field. The ability to gain knowledge in the area of plasticity has wide-ranging implications for therapeutic interventions in disorders as diverse as stroke, addiction and post-traumatic stress. Several NIAAA staff played key roles in the organization and execution of the workshop: these and included Tom Greenwell, Dennis Twombly, Roger Sorensen, Kenneth Warren and Antonio Noronha.

F. Outreach

Leadership to Keep Children Alcohol Free The Leadership to Keep Children Alcohol Free has recruited Ohio First Lady Frances Strickland as the most recent new member of the Leadership.

In May, Kenneth Moritsugu, Acting U.S. Surgeon General, visited Hawaii for the first in a series of State rollouts to promote the Surgeon General's Call to Action To Prevent and Reduce Underage Drinking. Dr. Moritsugu was hosted by Lieutenant Governor James R. "Duke" Aiona, Jr., co-chair of Leadership to Keep Children Alcohol Free, for a full day of activities. Media interviews were followed by a visit to an inner-city Honolulu elementary school. Dr. Moritsugu, Lt. Governor Aiona, and Leadership Foundation member Hope Taft also met briefly with Hawaii Governor Linda Lingle to discuss the Call to Action. Following this, members of the Hawaii Partnership to Prevent Underage Drinking (HPPUD) had the opportunity to meet with Vicky Cayetano, former First Lady of Hawaii and Vice President of the Leadership Foundation, Dr. Moritsugu, Lt. Governor Aiona, and Mrs. Taft, at which time Dr. Moritsugu announced the release of three companion publications to the Call to Action-A Guide to Action for Families, A Guide to Action for Educators, and A Guide to Action for Communities-and requested HPPUD's assistance in disseminating them. The day's events culminated with a Town Hall meeting sponsored by HPPUD at which 120 university researchers, health care providers, Department of Health officials, policymakers, law enforcement personnel, educators, business representatives, members of the faith-based community, youths, and parents were in attendance.

Dr. Moritsugu also visited Maine to bring the Call to Action to the State. Maine's First Lady Karen Baldacci hosted Dr. Moritsugu's June visit and is leading the State's response. Dr. Moritsugu and Mrs. Baldacci attended a press conference on the steps of the State House, along with Maine Attorney General Steve Rowe and community leaders. Dr. Moritsugu also met with Governor Baldacci and leaders of the Maine senate and house. He later gave the keynote address at the annual New England School of Addiction Studies, which is an intensive week-long experience for participants to further their knowledge, skills, and experience in the field of substance abuse.

On September 12, Dr. Moritsugu gave a presentation on underage drinking, focusing on the Call to Action, as part of the Millennium Seminar series at North Carolina State University. The lecture was part of a full day of activities in Raleigh in which he joined North Carolina first lady and Leadership co-chair Mary Easley at a press conference announcing Media Ready, a new evidence-based, media literacy program aimed at middle schoolers and designed to prevent underage drinking. Before the press event, Dr. Moritsugu met with state legislators, members of the Governor's staff, officials from North Carolina government and other health related organizations, education leaders, and representatives from the court system and law enforcement. At the conclusion of the day, he met with more than 200 leaders of local underage drinking community coalitions and representatives of other agencies and organizations throughout the state that work on the issue of underage drinking.

The following were among the regional activities of Leadership members:

• In June, Hawaii Lt. Governor James Aiona and the Hawaii Partnership to Prevent Underage Drinking announced a coordinated State effort to increase enforcement of Hawaii's laws prohibiting underage drinking.

• In July Leadership Co-Chair Mikey Hoeven, North Dakota's First Lady, was interviewed by KFYR-TV about several public service announcements being aired in North Dakota, developed by the Substance Abuse and Mental Health Services Administration and the Ad Council.

• In July First Lady Mary Easley encouraged more than 400 local Alcohol Beverage Commission (ABC) Board members, law enforcement and alcohol industry representatives to dedicate more attention and resources to underage drinking prevention efforts in North Carolina communities. Mrs. Easley said the boards oversaw $216 million in revenues from alcohol sales and returned $7 million to alcohol education last year.

New York State Summit Ralph Hingson was a featured speaker at a New York State Summit on "Preventing Student Alcohol Abuse: Improving the Campus-Community Culture." The summit was sponsored by The State University of New York and the city of Albany in cooperation with the Commission on Independent Colleges and Universities and the New York State Office of Alcoholism and Substance Abuse Services and took place June 18 and 19 in Albany, NY. Dr. Hingson's talk was entitled "The Culture and Price of Student Drinking." 

Community Anti-Drug Coalitions of AmericaIn the July 19 issue of Coalitions Online, the online newsletter of the Community Anti-Drug Coalitions of American (CADCA), Patricia Powell, Acting Chief of NIAAA´s Science Policy Branch, was featured in an interview on underage drinking, the Surgeon General's Call to Action, and current NIAAA initiatives. The article is available on CADCA's website, http://cadca.org/coalitionsonline/article.asp?id=1569. Coalitions Online reaches more than 13,000 subscribers each month, most of whom are involved in community coalitions to prevent alcohol and other drug abuse.

Ralph Hingson gave a presentation on "Magnitude and Prevention of College and Underage Drinking Problems," at CADCA's 2007 Mid-Year Training Institute. The Institute offers training for groups involved in substance abuse prevention. This year's Institute was held in Tucson, AZ, July 30 to August 2.

G. Multi-Media Products from NIAAA

NIAAA's Clinician's Guide 
Online Video Case Study CME Course on the Guide This online, interactive program will feature four video scenarios that demonstrate the clinical approach in NIAAA's Helping Patients Who Drink Too Much: A Clinician's Guide. The videos were recently filmed in a college health clinic, a hospital setting, and a staged office setting. They depict screening, assessment, and management of at-risk and dependent patients in different stages of readiness to change. Engaging learning activities have been developed for each case study. Next steps include filming the experts who will lead learners through the case studies, completing the course programming, and continuing to work with Medscape to provide continuing education credit.

Online Text-Based CME Course on the Guide Strong interest continues in the online text-based CME course on the Guide, hosted by Medscape. Lately, an average of 180 clinicians per week complete the activity. Between mid-March and the end of July, 7805 clinicians completed the course, earning 4029 CME (physicians) and 6259.5 CE (nurses) credits and 1389 letters of certification.

Guide Reprinting In July we completed an additional print run of 100,000 copies of the 2007 update of the Guide. The first run of 100,000 copies in January 2007 was quickly depleted thanks to outreach mailings and orders from medical schools, HMOs, hospitals, trauma centers, treatment centers, other organizations, and individual clinicians. Next we are planning more extensive outreach to managed care organizations, through a direct mailing to some 1,000 HMOs and PPOs.

Spin-off Publication: Tips for Cutting Down on Drinking The 2007 update of the Guide included a new patient handout, "Strategies for Cutting Down." We've adapted this as a free-standing pamphlet, Tips for Cutting Down on Drinking. The pamphlet also includes content from another Guide handout, "What's a Standard Drink?" It is available in English and Spanish.

Alcohol Alert An Alcohol Alert on metabolism was printed and distributed.

Alcohol Research & Health A two-part issue of Alcohol Research & Health on alcohol metabolism was printed and distributed. Part I focused on mechanisms of action; part II on metabolism as a key to unlocking alcohol's effects. Sam Zakhari was the scientific review editor for these issues of the journal. Joanne Fertig was scientific review editor for the prior issue of Alcohol Research & Health on tobacco.

College Website The NIAAA college website College Drinking: Changing the Culture has been named the recipient of the National Association of Government Communicators (NAGC) 2007 Blue Pencil & Gold Screen Award of Excellence for its new design and layout. This annual international awards program recognizes superior government communication products and their producers. The NAGC is a not-for-profit professional organization for writers, editors, and public affairs specialists at the local, state, and federal levels. In winning this award, the NIAAA college website competed with submissions from across the country and from all levels of government.

NIAAA also learned recently that the college website was a recipient of the World Wide Web Health Awards-Merit Award for 2006. This award program gives a "seal of quality" for electronic health information by the Health Information Resource Center (HIRC), a national clearinghouse for consumer health information programs and materials.

Streaming Video added to NIAAA College Website NIAAA has added a new state-of-the-art feature to the college website. The site will now feature streaming video highlights of major meetings and workshops on college drinking. The first video in this series highlights the recent NIAAA-Fordham University Workshop on College Drinking that took place in May in New York City. Speakers at this conference included Ralph Hingson, Mark Goldman, Vivian Faden, and Robert Saltz along with New York City Councilmember Peter Vallone and Fordham University President Joseph McShane, S.J. As more presentations are added, the streaming video section will allow practitioners, researchers, and the interested public to access an entire library of presentations from these important NIAAA conferences. The NIAAA college website is managed by the Communications and Public Liaison Branch (CPLB) and can be found at www.collegedrinkingprevention.gov. From April 2002 through June 2007, the college website has recorded almost 70 million hits, and currently averages more than 35,000 hits per month.

NIAAA Newsletter In June, CPLB issued the summer 2007 edition of the NIAAA Newsletter. In addition to its regular features on personnel news, new publications, and upcoming events, the Newsletter also offered brief summaries on the following topics:

• coding changes enacted by the Centers for Medicare and Medicaid Services for physicians' use when seeking reimbursement for alcohol and drug screening and brief intervention;

• a Washington, DC, meeting in March for directors of the Alcohol Research Centers;

• a college drinking prevention workshop hosted by Fordham University in May; and

• the appointment in May of four new National Advisory Council members.

The Newsletter is online at http://www.niaaa.nih.gov/news-events/niaaa-newsletter.

NIH News in Health A capsule on the NIAAA press release "Researchers Identify Alcoholism Subtypes" (June 28) appeared in the August issue of the publication NIH News in Health. News in Health goes to health clinics and small newspapers across the country; it can be accessed at http://newsinhealth.nih.gov.

Seasonal Fact Sheet Series Continuing its seasonal outreach series, CPLB released a graduation fact sheet for parents in spring and a Back to Campus fact sheet for parents in August. The graduation fact sheet was featured on more than 25 news-related websites, with almost 6 million visitors per month. These websites included Health Digest, Educate Inc., the Los Angeles Times,Breitbart, and television news affiliated sites in Dallas/Fort Worth and San Francisco among others. The back to campus fact sheet, which will continue to be featured through September, has already generated coverage in more than 20 news-related websites, with almost 5 million visitors per month. These websites included the Los Angeles Times, Health News Digest, Interest! Alert, and television news affiliated sites in Louisiana, Colorado, and California.

H. What's Ahead

Medicine for the Public Markus Heilig will be giving one of NIH's Medicine for the Public lectures on Tuesday, October 2, on "Alcohol Use Disorders: Old Insights, New Treatment." Medicine for the Public is a series of lectures on disease-related topics by NIH scientists. The lecture series, sponsored by the NIH Clinical Center, has been presented every fall since 1978. More information on the lectures is available at http://clinicalcenter.nih.gov/about/news/mfp.shtml.

Keller Lecture Boris Tabakoff will give the 2007 Keller Lecture on October 30. His talk is entitled "Why Mice, Rats and Some Humans Drink Alcohol: A Neurobiologic/Genomics Perspective." Dr. Tabakoff is professor and chairman, Department of Pharmacology, University of Colorado, School of Medicine in Denver. 

Society for NeuroscienceOn November 2, during the annual meeting of the Society for Neuroscience in San Diego, CA, NIDA will present a mini-convention on Frontiers in Addiction Research. At the conclusion of the mini-convention, NIAAA will join NIDA in holding a memorial symposium for Henri Begleiter from 4:30 to 6 p.m. Drs. Li and David Goldman will be among the speakers.