Contents

A.  Legislation, Budget, and Policy

Substance Abuse Insurance Parity  At the end of each year, there is a sunset date for the 1996 Mental Health Parity Act.  That act, passed in 1996, required insurers to include mental health (not substance abuse) coverage under certain conditions, and had an original sunset date of September 30, 2001.  The 2001 sunset date, now December 31 of each year, has been extended by Congress every year.  In 2007 both the Senate (Senators Domenici and Kennedy/S. 558) and House (Congressmen Kennedy and Ramstad/H.R. 1424) had mental health parity bills which would have made substance abuse coverage mandatory under certain (but different under the two bills) conditions.  Neither of those bills became law.  Late in December, Congress merely extended, for another year, the current status quo mental health parity law.      

NIAAA Budget

FY 2008 Appropriation  On Wednesday, December 26, after four continuing resolutions, President Bush signed Public Law 110-161 (Consolidated Appropriations Act, 2008), providing an appropriation for NIH.  Under the 2008 appropriation NIAAA’s budget is $436.2 million, an increase of 0.2 million above the FY 2007 appropriation.  A summary of the FY 2008 appropriation is provided below.

FY 2009 President’s Request  The FY 2009 budget request for the NIAAA is $436.7 million, including HIV/AIDS, an increase of $0.4 million and 0.1 percent over the FY 2008 appropriation.  The budget request for HIV/AIDS research is $27.0 million.  The highlights of some of the major components of the FY 2009 budget request are:

Research Project Grants  Under the President’s Request, the institute plans to support approximately 206 competing research project grants (RPGs) which would equal an approximately 28.6 percent success rate for competing RPGs.  The request would hold the average cost of competing RPGs at the FY 2008 level.  There will be no inflationary increases for recurring direct costs in non-competing continuation RPGs.

Alcohol Research Centers  The centers program budget will support 17 research centers at $27.3 million.

Other Research  $12 million is provided to support 86 research career awards in FY 2009.  Cooperative agreements will be funded at $8.7 million, supporting the Collaborative Study on the Genetics of Alcoholism and Alcohol Associated Outcomes Among HIV+/- Aging Veterans. 

Research Training  Research training is provided $11.3 million for 287 pre- and post-doctoral trainees in full-time training positions, which is flat with FY 2008.  Stipend levels for pre-and post-doctoral NRSA fellows will increase 1 percent in FY 2009 but there will be no other increases for tuition or training related expenses. 

Research and Development Contracts  Research and development contracts are provided $34.4 million.

Intramural Research Program  $47.6 million has been allocated to maintain the intramural research program’s overall level of effort for FY 2009.

Research, Management, and Support (RMS)  RMS activities are provided $26.0 million for FY 2009.

Below is a summary of the FY 2009 President’s budget request (dollars in thousand:                                                                  

B.  Director’s Activities

Asian Pacific Digestive Diseases Week  On October 18, Dr. Li gave the opening lecture at the International Symposium on Alcoholic Liver and Pancreatic Diseases and Cirrhosis, part of the Asian Pacific Digestive Diseases Week in Kobe, Japan.  NIAAA council member Hidekazu Tsukamoto, professor of pathology at the Keck School of Medicine, University of Southern California, was the principal organizer of the symposium.  Dr. Li’s talk was entitled “Alcohol and Organ Damage: Understanding the Mechanisms, Quantifying the Risks.”  At the meeting, Dr. Li received an award from the Japanese Society of Gastroenterology, citing his extensive and long-term contributions to addressing the adverse health effects of alcohol.  Samir Zakhari, director of NIAAA’s Division of Metabolism and Health Effects (DMHE), was a co-organizer of the symposium and chaired a session on oxidant stress and inflammation; intramural scientist Bin Gao, gave a talk on innate immunity and alcoholic liver fibrosis. 

Alcohol Policy and Research in the U.S. and Korea  The Korean National Institute of Health and the Korean Center for Disease Control and Prevention (KCDCP) sponsored a workshop entitled “Second Workshop on Alcohol Diseases: Alcohol Policy and Alcohol Research in the United States and Korea” in Seoul, South Korea October 22.  Dr. Li gave a presentation on “Alcohol Epidemiology: Implications for Diagnosis and Treatment.”  Dr. Zakhari, intramural scientist B.J. Song, and NIAAA deputy director Kenneth Warren also gave presentations at the meeting, which culminated in the signing by Drs. Li and Jon-Koo Lee, director general of the KCDCP, of a Letter of Intent to increase cooperation in the fields of biomedical and behavioral research between the United States and Korea.  Specific research interests noted in the letter of intent include epidemiology of alcohol problems, prevention, alcohol and chronic diseases, clinical trials, development and evaluation of innovative treatment, and pharmacogenetics/pharmacogenomics. 

American Indian and Alaskan Native Heritage Month Symposium  In observance of American Indian and Alaska Native Month, NIH held a research symposium on November 7 featuring NIH-supported investigators speaking on research projects focused on health issues among American Indians in New Mexico, Arizona, and the Pacific Northwest.  Dr. Li introduced the keynote speaker, NIAAA grantee R. Dale Walker, a professor of psychiatry and public health and preventive medicine at Oregon Health and Science University, Portland.  Dr. Walker’s NIAAA-supported research focuses on treatment processes and outcomes among urban American Indians with alcohol-related problems.    

Friends of NIAAA Coalition Hosts Congressional Briefing  A number of key organizations in the NIAAA liaison community, led by the American Psychological Association (APA), have formed a Friends of NIAAA coalition.  Similar “Friends of” groups exist in support of other NIH institutes.  Typically, these stakeholder-organized coalitions comprise patient groups, scientific and professional societies, and concerned individuals committed to supporting biomedical and behavioral research.

On November 15, the newly-established Friends of NIAAA, working in conjunction with the Addiction, Treatment, and Recovery Caucus in the U.S. House of Representatives, organized an educational briefing for Congressional staffers on Capitol Hill. The briefing focused on underage drinking, and speakers included Dr. Li; former NIAAA associate director Mark Goldman, Distinguished Research Professor and Director of the Alcohol and Substance Use Research Institute at the University of South Florida; Sandra A. Brown, professor of psychology and psychiatry at the University of California, San Diego; and Mimi Fleury, founder of the Community of Concern.  Steve Breckler, APA's executive director for science, made introductory remarks.  Seventeen organizations co-sponsored the briefing, which drew ninety-nine attendees, including multiple representatives from twenty-eight House and seven Senate offices.

Members of the Friends of NIAAA coalition reconvened on January 31 to begin planning additional activities for the coming year.  For a more detailed summary of the November 15 briefing, visit http://www.apa.org/ppo/issues/1107drink.html.

International Conference on Applications of Neuroimaging to Alcoholism  Dr. Li gave a keynote lecture entitled “NIAAA Overview of Imaging in Alcoholism” at the 2^nd International Conference on Applications of Neuroimaging in Alcoholism, held January 19 to 20 at Yale University.  The meeting was hosted by the NIAAA-funded Center for the Translational Neuroscience of Alcoholism (John Krystal, principal investigator).  Conference sessions addressed applications to alcoholism of imaging techniques including MRI, fMRI, DTI, MRS, PET, and SPECT. 

C.  NIAAA Staff and Organization

Veronica Alvarez, Ph.D.  Veronica Alvarez joined NIAAA in January as a tenure track scientist and acting chief of the Section on Neuronal Structure within the Laboratory for Integrative Neuroscience.  Dr. Alvarez earned her Ph.D. from the University of Buenos Aires and did postdoctoral research at Oregon Health and Sciences University and at Harvard University.  She will establish and conduct an independent research program focused on neuronal morphology, structural plasticity and neuronal function in relation to development, addiction, and neurological disorders.

Peter Delany, Ph.D.  Capt. Peter Delany has left NIAAA to join the Substance Abuse and Mental Health Services Administration (SAMHSA) as director of the Office of Applied Studies, where he was a senior program management officer before coming to NIAAA in 2006.  At NIAAA, Dr. Delany was a health scientist administrator in the Division of Treatment and Recovery Research responsible for the development and management of NIAAA’s program in health services research. 

Laurie Foudin, Ph.D.   Laurie Foudin, health scientist administrator in DMHE, retired in December.  She came to NIAAA in 1985 as a visiting scientist and became a health scientist administrator the following year.  Dr. Foudin initially oversaw the neuroscience portfolio until the reorganization of the portfolio in 1987.  From 1987 to 1997 she was the Small Business Innovation Research/Small Business Technology Transfer (SBIR/STTR) coordinator for the institute.  From 1988 to 2003 Dr. Foudin oversaw the basic research portfolio on fetal alcohol spectrum disorders (FASD) within the then Division of Basic Research.  She was also a staff collaborator on three FASD-related cooperative agreements: the D.C. Initiative to Prevent Infant Mortality; the Collaborative Initiative on FASD; and the Prenatal Alcohol, SIDS, and Stillbirth Research Network.  Dr. Foudin was the NIAAA representative on many trans-NIH committees, including the NIH Training Advisory Committee from 1997 to 2005 and the Interagency Coordinating Committee on FAS from 2006 until her retirement.

Rebekah Geiger  NIH presidential management fellow (PMF) Rebekah Geiger has begun a three month rotation in the Financial Management Branch (FMB).  Ms. Geiger has an M.S.W. from the University of Michigan and has interests in health insurance cost, health disparities, the role of preventative healthcare in improving global health, and women’s health.  Prior to joining NIH as an at-large PMF, she completed a two-year internship at the Providence Center for the Healing Arts at the Assarian Cancer Center in Novi, Michigan.  While at NIAAA, Ms. Geiger will be working with FMB staff to learn all aspects of the Federal budget process as well as the day-to-day management of the NIAAA budget. 

Max Guo, Ph.D.   Max Guo has been selected as deputy director, DMHE.  Dr. Guo joined NIAAA in 2002 as a program director of genetics and genomics.  Since 2006, he has also served as a co-leader of the NIAAA team on mechanisms of alcohol action and injury team and the SBIR/STTR coordinator for NIAAA.  Dr. Guo has worked effectively in NIAAA’s trans-disciplinary organizational structure to promote the use of new technologies, alternative animal models, and an integrated approach to study alcohol-induced disorders.  In the past several years, Dr. Guo also represented NIAAA on a number of NIH Roadmap activities.  Dr. Guo received his bachelor degree in biology from Peking University of China.  After receiving a Ph.D. degree from Ohio State University in 1992, he did his postdoctoral training on cancer biology with Nobel Laureate J. Michael Bishop at University of California, San Francisco.  Before joining NIAAA in 2002, he was a tenure-track assistant professor of oncology and the director of the Microarray Center at the Sydney Kimmel Comprehensive Cancer Center at Johns Hopkins Medical School. From 2005 to 2006, Dr. Guo also worked as a program director for  genetics, genomics, gene therapy, and biotechnology in the Division of Lung Diseases at the National Heart, Lung, and Blood Institute. 

Roger Hartman  Roger Hartman retired in January after 5 ½ years as a health science administrator at NIAAA, most recently in the Division of Epidemiology and Prevention Research.  Prior to coming to NIAAA, he was a senior health policy analyst for the Office of the Assistant Secretary of Defense (Health Affairs/ TRICARE Management Activity) and served as head of the Treatment and Rehabilitation Branch, U.S. Navy Drug and Alcohol Abuse Program.  He served on active duty, U.S. Navy, from 1969 to 1977, and retired as a Commander, U.S. Naval Reserve in 1990.  His work at NIAAA included college and underage drinking initiatives; alcohol education projects; and activities associated with National Alcohol Screening Day.

Dale Hereld, M.D., Ph.D.  Dale Hereld joined DMHE as a program director in January.  Dale obtained both M.D. and Ph.D. degrees as well as postdoctoral training from the Johns Hopkins University School of Medicine.  He subsequently joined the faculty of the medical school of the University of Texas Health Science Center at Houston, where his research focused on elucidating mechanisms of G protein-coupled receptor function and regulation.  Dr. Hereld's specific areas of expertise include signal transduction and chemotaxis.  His nearly thirty publications have appeared in prominent journals that include Science, Molecular Biology of the Cell, Molecular Microbiology, the Journal of Biological Chemistry, and the Journal of Immunology.  In addition, Dr. Hereld has been the recipient of a Medical Scientist Training Program Award, a Damon Runyon Postdoctoral Research Fellowship, and the American Heart Association-Texas Affiliate's Lyndon Baines Johnson Research Award.

Howard Moss, M.D.  The American Psychiatric Association (APA) has named Howard Moss a Fellow of the association.  Newly designated APA Fellows will be formally recognized at a convocation ceremony during the APA’s annual meeting in Washington, DC, in May. 

Jessica Rodriguez  NIH management intern Jessica Rodriguez has begun a rotation at NIAAA where she will be working with associate director for administration Robin Kawazoe through May 2008.  Ms. Rodriguez has a B.A. in communications focusing on public speech from the University of Maryland, College Park and is pursuing an M.B.A. at the University of Maryland, University College.  She began her career at NIH with the National Institute of Allergy and Infectious Diseases, where she monitored the execution of the immunological and infectious disease grant operating activity.  Prior to joining NIH, she completed a year-long management training program with Chevy Chase Bank followed by multiple branch management positions.

Norman Salem, Ph.D.  Norman Salem, Jr., retired in January after over 30 years at NIAAA and the National Institute of Neurological Disorders and Stroke.  He has been chief of the Laboratory of Membrane Biochemistry and Biophysics within NIAAA’s intramural research program since 1991; prior to that he was a section chief in the Laboratory of Clinical Studies, NIAAA.  During his tenure here, his laboratory was internationally known for work on essential fatty acids, particularly the omega-3 fatty acid, docosahexaenoate (DHA).  Dr. Salem authored or co-authored about 220 publications while at NIH.  He will continue to pursue his interests in essential fatty acids in the biotech industry; he joins Martek Biosciences Corporation as chief scientific officer this month.  He will be responsible for the discovery, medical research, molecular biology, and analytical groups there.  Martek supplies DHA for use in infant formulas in the United States and many other countries and conducts and sponsors research in this area.

Kenneth Warren, Ph.D.  Kenneth Warren has been selected as deputy director, NIAAA.  Dr. Warren has had a long-term career at NIAAA having joined the institute in 1976 as a staff member of the then Division of Research.  Over the next few years he served as executive secretary for NIAAA’s Biomedical Research Review Committee, then chief, Biomedical Research Branch, and deputy director of the Division of Extramural Research.  In 1984, Dr. Warren was named director, Office of Scientific Affairs (OSA), a post he held until 2005.  During the period of his leadership of OSA the office’s numerous responsibilities included peer review, national advisory council and extramural advisory board activities, committee management, grants management, and communications.  From 2002 to 2007, Dr. Warren also served as the institute’s associate director for basic research and over the past year he has also served as acting director, Office of Science Policy and Communications.

Dr. Warren received a Ph.D. in biochemistry from Michigan State University in 1970.  Following postdoctoral work, he took the position in 1974 of chief of the Section of Biochemistry in the Department of Cellular Physiology, Division of Medicine at the Walter Reed Army Institute of Research.

One of Dr. Warren’s accomplishments has been the initial development and long-term fostering of NIAAA’s research program on fetal alcohol syndrome, for which he received a superior service award from the Public Health Service in 1982, and the Henry Rosett Award from the Fetal Alcohol Syndrome Study Group of the Research Society on Alcoholism (RSA) in 2002.  Dr. Warren was also a recipient of the Seixas Award from RSA in 1994.

NOFAS Hall of Fame  The National Organization on Fetal Alcohol Syndrome (NOFAS) has named Dr. Warren to the organization’s Fetal Alcohol Spectrum Disorders (FASD) Hall of Fame.  The NOFAS website (http://www.nofas.org/) provides an overview of Dr. Warren’s long-time efforts in the development and guidance of research on FASD, including his role in the first national research workshop on FAS, national health advisories on the hazards of alcohol use in pregnancy, and Federal and Institute of Medicine reports on alcohol and pregnancy.  He continues to play a lead role in international initiatives on research in South Africa and other countries, and chairs the Interagency Coordinating Committee on Fetal Alcohol Syndrome. 

D.  Research Priority Emphasis and Core Support Teams

Supplement in Pediatrics on Underage Drinking  Based on the work of NIAAA’s Underage Drinking Research Initiative, a series of seven papers were developed by NIAAA staff and the steering committee of more than 25 experts assembled to advise the institute on this initiative.  The papers will be published as a supplement to Pediatrics this spring entitled Underage Drinking: Understanding and Reducing Risk in the Context of Human Development.  This publication will not only reach the 65,000 pediatricians who subscribe to this journal, but many others as well.  (The supplement has been accepted and is scheduled to appear in April.)

Surgeon General Commendation  In September, Vivian Faden and Patricia Powell received a commendation from Acting U.S. Surgeon General Kenneth Moritsugu.  The  commendation reads: “For Outstanding Support and Service to the Office of the Surgeon General as Co-Sponsor and Co-Coordinator of the Surgeon General's Call to Action to Prevent and Reduce Underage Drinking.” 

E.  NIAAA Research Programs

Collaboration with INSERM  NIAAA and the French Institut National de la Santé et de la Recherche Médicale held the third in a series of joint research symposia on October 3.  The symposium, U.S./French Research Collaborations in Alcohol Abuse and Alcoholism, was held at NIAAA (the first was held at NIAAA in October 2005, the second at INSERM headquarters in Paris, France, in January 2007).  These symposia, held under the terms of a letter of intent between NIH and INSERM, have been conducted with the aim of building research collaborations between alcohol investigators in the U.S. and France.  The topic areas covered in this meeting were neuroimaging, epidemiology, molecular toxicity of alcohol in liver and brain, diagnostic criteria for alcohol-use disorders, and fetal alcohol spectrum disorders.  Dr. Li opened the meeting; NIAAA staff Bridget Grant, Howard Moss, Zhaoxia Ren, Kenneth Warren made presentations at the meeting and Sam Zakhari was a discussant. 

To date, results of this meeting include four research proposals under development under the new NIAAA program announcement for international collaborative research, two French post docs in neuroimaging research placed in U.S. alcohol research labs, one U.S. post doc in epidemiology being offered a position in an INSERM research unit in Paris, and a second U.S. candidate being seriously considered for a post doc position at the INSERM/CEA (French Atomic Energy Commission) in Orsay, France.

In January, Dr. Li and Peggy Murray met with Professor Arnold Munich (science counselor to President of the French Republic, Nicolas Sarkozy) Thiery Damerval, deputy director of INSERM, and Jean Francois Delfraissy (director of the French National Agency for AIDS and Infectious Diseases).  The meeting was held on the Bethesda campus of NIH and focused on a review of the successful outcomes from the NIAAA/INSERM collaboration and areas of continued interest in alcohol research for France.

NIAAA Review Branch Reorganization  NIAAA’s Extramural Project Review Branch has been reorganized.  There are now four study sections (AA-4 is new): 

·         AA-1, Biomedical Research Review Subcommittee, scientific review officer (SRO), Philippe Marmillot

·         AA-2, Epidemiology, Prevention and Behavior Research Review Subcommittee, SRO, Lorraine Gunzerath

·         AA-3, Clinical, Treatment and Health Services Research Review Subcommittee, SRO, Katrina Foster

·         AA-4, Neuroscience Review Subcommittee, SRO, Beata Buzas. 

RFAs:  Applications

NIH has received, or is expecting, numerous applications in response to RFAs.  Below is a summary of applications that have been received for 2008 RFAs.

·         RFA-AA-08-003 Exploratory/Developmental Alcohol Research Centers (P20): 11 applications

·         RFA-AA-08-004 Resource Core Alcohol Research Centers (P30):  1 application

·         RFA-AA-08-005 Specialized Alcohol Research Centers (P50):  6 applications

·         RFA-AA-08-006 Comprehensive Alcohol Research Centers (P60):  2 applications

·         RFA-AA-08-001 The Role of Mitochondria in Alcohol-Induced Tissue Injury (R21):  19 applications

·         RFA-AA-08-002 The Role of Mitochondria in Alcohol-Induced Tissue Injury (R01):  23 applications

NIH Roadmap  Dr. Zakhari represents NIAAA on the program staff for the trans-NIH Stem Cell Task Force and Implementation Committee, charged with implementing the President’s stem cell executive order on research on human pluripotent stem cells from non-embryonic sources.  He is co-chairing two subcommittees. 

Publications by Extramural Staff

Recent publications authored or co-authored by extramural staff included the following: 

Svetlana Radaeva (intramural scientist Bin Gao is also a coauthor):  

Hu, W., Ferris, S.P., Tweten, R.K., Wu, G., Radaeva, S., Gao, B., Bronson, R.T., Halperin, J.A., Qin, X. Rapid conditional targeted ablation of cells expressing human CD59 in transgenic mice by intermedilysin. Nature Medicine 14:98-103, 2008.

Samir Zakhari: 

Zakhari, S.  Overview:  How is Alcohol Metabolized by the Body? Alcohol Research & Health 29:245-254, 2007.

Neuman, M.G., Sha, K., Esguerra, R., Zakhari, S., Winkler, R.E., et al.  Inflammation and repair in viral hepatitis C.  Digestive Diseases and Sciences.  (Epub ahead of print, November 10)

Zakhari, S., Li, T.-K.   Determinants of alcohol use and abuse:  Impact of quantity and frequency patterns on liver disease.  Hepatology 46:2032-2039, 2007. 

Research Reports

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

Gene Variant Affects Alcohol Consumption in Mice  Using a combination of genetic analysis techniques and carefully targeted breeding of mice with different levels of alcohol consumption, scientists have identified a gene variant that influences alcohol preference in the animals.  Many genes can potentially contribute to alcohol related behavior, and individual genes may have subtle effects, making it difficult to pinpoint and characterize individual genes involved in the alcohol response.  In this study, scientists crossed strains of mice with the aim of producing animals with different levels of alcohol preference but that were otherwise almost identical genetically.  This permitted identification of a quantitative trait locus—a stretch of DNA that plays a role in determining alcohol preference—and candidate genes within that stretch.  Subsequent analysis included measurement of whether the activity of the candidate genes differed among mouse strains with different levels of alcohol consumption.  Existing databases on gene function helped narrow the search to a gene—Grm7—that encodes a receptor for the neurotransmitter glutamate.  Previous research suggests that the receptor plays a role in information processing and stress responses.  Continuing research will aim to confirm the role of Grm7 in alcohol consumption and to identify a counterpart gene in humans.  Genes affecting alcohol consumption can provide clues to the physiology of alcohol responses and targets for the development of medications to treat alcohol dependence.  (Vadasz, C., Saito, M., Gyetvai, B.M., Oros, M., Szakall, I., Kovacs, K.M., Prasad, V.V.T.S., and Toth, R.  Genomics 90:690-702, 2007) 

Brief Intervention Helps Patients in Hospital Emergency Departments Reduce Drinking  Emergency care seeking patients who underwent a regimen of alcohol screening and brief intervention reported lower rates of risky drinking at three-month follow-up than did those who received only written information about reducing their drinking, according to a nationwide collaborative study supported NIAAA and the SAMHSA.  Investigators at 14 university-based emergency centers throughout the United States used a brief questionnaire to assess the alcohol use patterns of 7,751 emergency patients, regardless of whether they had signs of alcohol use on admission.  They found that more than one-fourth of the patients exceeded the limits for low-risk drinking—defined by NIAAA as no more than four drinks per day for men and three drinks per day for women and not more than 14 drinks per week for men, and seven drinks per week for women.  More than 1,100 patients who exceeded these limits agreed to continue to participate in the study.  The brief intervention in this study consisted of a “brief negotiated interview” designed to review the patient’s current drinking patterns, assess readiness to change, offer advice about low-risk drinking guidelines, and negotiate an agreement with regard to drinking goals.  Three months later, individuals in the intervention group reported drinking three fewer drinks per week than those in the control group, and more than one-third of individuals in the intervention group reported drinking at low-risk levels, compared with about one-fifth of those in the control group.  (Academic ED SBIRT Research Collaborative.  Annals of Emergency Medicine 50:699-710e6, 2007)

Diagnostic Criteria for Alcoholism  A diagnosis of alcoholism is made when a person meets three out of seven diagnostic criteria as specified in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV).  This study reexamined data from NIAAA’s National Epidemiologic Survey on Alcohol and Related Conditions to assess to what extent individual criteria accurately predicted a positive diagnosis and to characterize patterns in the criteria met by those with alcoholism.  The criterion “activities given up” had the most predictive value; about 95 percent of individuals who were positive for this were also diagnosed with alcoholism.  Two others—continued drinking despite physical/psychological problems and time spent in alcohol-related activities—were endorsed by more than 50 percent of those diagnosed with alcoholism.  Counting the number of positive criteria, however, did not necessarily reflect severity of alcoholism.  Analysis of patterns of criteria met by individuals with alcoholism yielded six clusters or sets of criteria that constitute subtypes of alcoholism.  The authors point out that future research can address whether treatment approaches could be tailored to these subtypes.  (Moss, H.B., Chen, C.M., and Yi, H.-y. Alcoholism: Clinical and Experimental Research 32:306-313, 2008)

Endocannabinoids Key to Habit Formation  Using a combination of behavioral training and neurogenetics, intramural scientists have found a particular class of neurotransmitters—the endocannabinoids—to be key to the development of habitual behavior in mice.  By varying the pattern with which animals are rewarded in response to a trained behavior—in this case lever pressing for a food reward—scientists can elicit either goal-directed or habitual responding.  When behavior is goal directed, the intensity with which animals respond in anticipation of rewards decreases when the reward’s value is diminished.  With habitual behavior, the mice continue to respond with the same intensity whether or not the reward value is diminished.  In this study, mice with targeted mutations in the gene for a receptor (CB1) for endocannabinoids failed to develop habitual behavior after the same reward pattern elicited habitual responding in mice with functioning CB1 receptors.  A drug, administered during training, that blocks CB1 receptors also prevented nonmutant mice from developing habitual behavior, adding confirmation that endocannabinoid signaling was key to habit formation.  Previous research has implicated endocannabinoids in addictive behaviors; studies such as the current one can help dissect the neurobiology and behavioral processes that underlie addiction.   (Hilário, M.R.F., Clouse, E., Yin, H.H., and Costa, R.M. Frontiers in Integrative Neuroscience published online November 2, 2007)

Rat Model Suggests Memory Effects by Alcohol in Third Trimester  Alcohol given to newborn rats—a period of development that is analogous to the third trimester of pregnancy—caused permanent reduction in the generation of new neurons from progenitor cells in the hippocampus, a part of the brain that is central to memory formation.  Among the effects manifested by individuals exposed to alcohol prenatally as a result of heavy drinking by their mothers are learning disabilities and problems with short term memory.  Damage by alcohol to the generation of new cells in the hippocampus may be a mechanism underlying these deficits, and this study suggests that such damage could be a result of third-trimester binge-type drinking by pregnant mothers.  (Klintsova, A.Y., Helfer, J.L., Calizo, L.H., Dong, W.K., Goodlett, C.R., and Greenough, W.T. Alcoholism: Clinical and Experimental Research 31:2073-2082, 2007)

Alcohol, Cigarettes, and Naltrexone  Individuals who abuse alcohol are more likely to smoke, and smoke heavily, than those who abstain from alcohol.  This study looked at whether alcohol intoxication affects cigarette craving in heavy drinkers who were also light smokers, and whether the drug naltrexone altered the results.  Participants were given intravenous alcohol; as blood alcohol levels rose to 0.6, craving for cigarettes also rose.  With naltrexone, the craving for cigarettes did not increase as much with rising BAC.  The authors conclude that intoxication, even without external cues for alcohol, increases craving for cigarettes; naltrexone may be helpful as a treatment for people who drink heavily and would like to stop smoking.  (Ray, L.A., Miranda, R., Jr., Kahler, C.W., Leventhal, A.M., Monti, P.M., Swift, R., and Hutchison, K.E. Psychopharmacology 193:449-456, 2007)

Alcohol’s Immune Effects in Liver Disease  Chronic alcohol use accelerates liver fibrosis (scarring) in individuals with hepatitis C infection.  The mechanism of this effect of alcohol is not well understood; it is not entirely the result of accelerated damage to liver tissue.  Results of this intramural study suggest specific mechanisms by which alcohol impairs the immune system’s ability to forestall fibrosis.  The investigators induced liver damage in mice by feeding them carbon tetrachloride, a liver toxin.  Some of the mice also received chronic alcohol.  Liver fibrosis was greater in the alcohol-fed mice; the investigators found that alcohol disrupted signaling by immune molecules that regulate the activity of natural killer (NK) cells, a class of immune cell that plays a key role in limiting liver fibrosis resulting from viral infection.  Alcohol also compromised the ability of the immune system to limit activation of hepatic stellate cells, which generate scar tissue in the liver in response to injury.  Therapies are needed that can interrupt the progression of liver disease; understanding how alcohol compromises immune function in the liver may provide approaches for new treatments.  (Jeong, W.-I., Park, O., and Gao, B. Gastroenterology 134:248-258, 2008)

Insight into Neurotransmitter Sensitivity to GABA  One of the well established effects of alcohol on the brain is its ability to enhance signaling by the neurotransmitter GABA.  GABA is an inhibitory neurotransmitter, acting to slow the activity of neurons.  The effects of alcohol on GABA are inconsistent, however.  This study demonstrated that a specific intracellular signaling molecule, PKCє, could alter the response of cellular receptors to GABA.  PKC is a protein kinase—an enzyme that regulates cell functions by adding phosphate to proteins (protein phosphorylation).  In this study, investigators used genetic technology to develop cells in which PKCє could be selectively inhibited; they also generated mice lacking the gene for PKCє.  They found that PKCє regulates the sensitivity of GABA_A receptors (the type of GABA receptors most sensitive to alcohol) and pinpointed the mechanism for this regulation—phosphorylation of a GABA_A subunit.  Mice lacking PKCє are more sensitive to the effects of alcohol.  The work helps explain the variability of the response of GABA_A receptors to alcohol; the information may provide avenues for future development of targeted medications.  (Qi, Z.-H., Song, M., Wallace, M., Wang, D., Newton, P.M., McMahon, T., Chou, W.-H., Zhang, C., Shokat, K.M., and Messing, R.O. The Journal of Biological Chemistry 282:33052-33063, 2007)

Donor Alcohol Use and Lung Transplants  Nineteen percent of organ donors are reported to have a history of alcohol abuse; such a health history increases the risk of problems after heart transplantation.  These investigators transplanted rat tracheas into recipient rats.  Some donor rats had had alcohol in their diet before the transplantation.  Pre-transplant alcohol exposure increased airway disease in recipients of the tracheas from alcohol-fed rats.  To trigger airway disease, at least a slight immunological mismatch was required between donor and recipient.  When a mismatch was present, alcohol exposure increased levels in the transplanted tissue of TGF-b₁, a regulatory protein that is central to the development of fibrosis in airways.  The authors predict that future research will identify that alcohol abuse in donors is a risk factor for post-transplant lung disease.  (Mitchell, P.O. and Guidot, D.M. American Journal of Respiratory and Critical Care Medicine 176:1161-1168, 2007)

Brain and Behavior in FAS  Using state-of-the-art methods to analyze magnetic resonance images (MRIs), scientists have been able to extract detailed information on the thickness of the cortex in the brains of young people exposed to alcohol before birth as a result of heavy maternal alcohol consumption.  By comparing this information with similar measurements in young people without prenatal alcohol exposure, the investigators were able to show for the first time correlations between alcohol-related changes in cortical thickness and measures of cognitive function.  The work also added detail to previous findings of regional changes in cortical thickness due to alcohol exposure.  The thickness of the cortex—the outer layer of gray matter covering the surface of the brain—is increased in individuals with fetal alcohol spectrum disorder, a term that refers to the range of deficits that can result from prenatal alcohol exposure.  Under normal circumstances, the cortex thins during development; the authors point out that a thicker cortex does not indicate a larger amount of healthy brain tissue.  The study adds to the understanding of how exposure to heavy alcohol before birth disrupts brain development.  (Sowell, E.R., Mattson, S.N., Kan, E., Thompson, P.M., Riley, E.P., and Toga, A.W. Cerebral Cortex published online ahead of print doi:10.1093/cercor/bhm039)

Peptide Counters Damage by Prenatal Alcohol in Mice  A peptide incorporated into the diets of pregnant mice reduced the harmful effects of alcohol on the eyes of their fetuses.  Damage to the eyes of alcohol-exposed fetuses coincides with central nervous system damage.  The peptide (SAL) is a fragment of a nerve growth factor that has been shown to reduce the effects of alcohol on fetuses when delivered to their mothers intraperitoneally, that is, directly into the abdomen.  The authors point out that despite recognition of fetal alcohol syndrome (FAS), incidence of FAS has not decreased.  This study suggests that SAL given orally could be effective in preventing brain damage in children whose mothers consume alcohol while pregnant.  (Parnell, S.E., Chen, S.-y., Charness, M.E., Hodge, C.W., Dehart, D.B., and Sulik, K.K. Alcoholism: Clinical and Experimental Research 31:2059-2064, 2007)

F.  Scientific Meetings

European Presentations: Alcohol Metabolism  Dr. Zakhari gave the keynote lecture at the 11^th annual meeting of the European Society for Biomedical Research on Alcoholism in Berlin, Germany, September 23 to 26.  He was also invited by Charles University, Prague, Czech Republic, to give a seminar on alcohol metabolism and its consequences, and to discuss various projects with grad