A.  Legislation, Budget, and Policy

Federal Employee Health Coverage for Substance Abuse Services  In the Office of Personnel Management’s annual call for benefit and rate proposals from Federal Employees Health Benefits (FEHB) Program carriers in March, the agency called the attention of FEHB carriers to new Current Procedural Terminology (CPT®) codes for screening and short-term intervention for alcohol and substance abuse.  CPT® codes, issued by the American Medical Association (AMA), are used by physicians to report and bill health insurance plans for their services.  The Centers for Medicare and Medicaid Services adopted screening and brief intervention codes in January 2007, while the AMA’s addition of two CPT® codes became effective in January 2008.  The OPM letter to carriers stated that “All carriers should be aware of these new codes to update their systems so that they can more efficiently provide benefits for these types of services.”   OPM stated at least 70 percent of enrollees participate in FEHB plans which will recognize the codes for their claims processing systems when services are delivered by a medical professional. The new coverage will reimburse doctors who screen their patients for a full spectrum of substance use behaviors, including alcohol, illicit drugs, and prescription drug abuse/addiction, and provide appropriate intervention.

NIAAA Budget

FY 2008 Appropriation  On Wednesday, December 26, 2007, 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 $436.3 million, an increase of 0.2 million above the FY 2007 appropriation.  A summary of the FY 2008 appropriation is below.

FY 2009 President’s Request  The FY 2009 budget request for 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 following highlight some of the major components of the FY 2009 budget request:

Research Project Grants  Under the President’s Request, the institute plans to support approximately 191 competing research project grants (RPGs) which would equal an approximately 26.5 percent success rate for competing RPGs.  The FY 2009 request holds the average cost of competing RPGs at the FY 2008 level.  There will be no inflationary increases for direct, recurring 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.

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 trainees 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  Research, management, and support (RMS) activities are provided $26.0 million for FY 2009.

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

Budget Hearings  The NIAAA FY 2009 President’s budget request was presented March 5 before the House Appropriations Subcommittee.  The House hearing schedule followed the format that has been used over the past several years whereby there is an overview hearing followed by a “theme” hearing combining the institute directors of specific institutes/centers requested to attend the hearing.  Dr. Zerhouni was the main presenter at the March 5 House overview hearing.  NIAAA was not asked to participate in a “theme” hearing. 

The Senate Appropriations Subcommittee, originally scheduled to meet April 23^rd, was rescheduled for April 30^th and subsequently cancelled.  There has been no tentative date set for a future hearing.

B. Director’s Activities

Community Anti-Drug Coalitions of America  On February 13, Dr. Li gave a plenary address at the 18^th Annual Leadership Forum of the Community Anti-Drug Coalitions of America (CADCA).  Participants at the meeting, which took place in Washington, D.C., included community anti-drug coalitions from around the country, addiction treatment professionals, researchers, educators, law enforcement professionals, faith-based leaders, government leaders, and youth.  Participants had an opportunity to hear overviews from experts on key substance abuse issues.  Dr. Li’s talk was entitled “Partnering to Prevent and Reduce Underage Drinking and Related Problems.”  Other NIAAA participants included Ralph Hingson, who gave a presentation on prevention of college age and underage drinking; and Dennis Twombly, who gave a workshop presentation on how alcohol affects the adolescent brain.  Acting Surgeon General Steven K. Galson discussed the Surgeon General's Call to Action on Underage Drinking.   

Duke University  Dr. Li gave a seminar to the Duke University Medical Center Department of Psychiatry and the Central Nervous System Division of the Duke Clinical Research Institute in Durham, NC, on March 7.  His presentation was entitled “Recent Advances in Understanding Alcoholism: Diagnosis, Treatment, and Prevention.”

Alcohol and Stress: A Framework for Future Treatment Strategies  NIAAA joined an international group of organizations to sponsor a meeting on Alcohol and Stress: A Framework for Future Treatment Strategies, held in Volterra, Italy, May 6 to 8.  Dr. Li gave the introduction to the meeting; Markus Heilig, Antonio Noronha, and Sam Zakhari also participated, co-chairing symposia, and making presentations.   

C. NIAAA Staff and Organization

Among the doctorate level staff in the extramural program, the turnover rate over the past two years has varied from 7 to 9 percent. 

Staff Departures

Ricardo Brown, Ph.D.  Ricardo Brown left the Division of Metabolism and Health Effects (DMHE) in April to join Howard University as associate vice president for research and professor of physiology and biophysics with tenure in the College of Medicine.  Dr. Brown joined NIAAA in July 2002, after nearly 15 years as an independent investigator.  He also served as Professor and Chairman of the Department of Biology at Morgan State University in Baltimore, Maryland.  In DMHE, he managed the institute’s cardiovascular research and endocrine portfolios.  In addition, over the past 2 years he served as NIAAA’s Coordinator for Minority Health and Health Disparities.  While at NIAAA, Dr. Brown received the NIH Director’s Award as a member of the group that developed the Trans-NIH Type 1 Diabetes Research Strategic Plan (2006) and NIAAA’s EEO Award (2006) in recognition for his community service activities.

Vishnu Purohit, Ph.D.  Vishnu Purohit has left NIAAA to join the National Institute on Drug Abuse as a program director in the Chemistry and Physiological Systems Research Branch of the Division of Basic Neuroscience and Behavioral Research.  Dr. Purohit came to NIAAA in 1991 from the Food and Drug Administration.  At NIAAA, Dr. Purohit was a program director in DMHE, administering a portfolio in the areas of alcoholic liver disease, pancreatitis, cancer, and osteoporosis.  He was the NIAAA representative on many trans-NIH committees, including the Digestive Diseases Interagency Coordinating Committee, Nutrition Coordinating Committee, Dietary Supplement Working Group, Federal Working Group on Bone Diseases, and Cancer Research Portfolio Group.

Jose Velazquez, Ph.D.   Jose Velazquez has accepted a position as director of the Cell Biology Program in the Division of Aging Biology at the National Institute on Aging.  He joined NIAAA 5 years ago and served as chief of what was then the Genetics and Proteomics Research Branch in the Division of Basic Research, team leader for the Technology and Analysis Team, and most recently program director for functional genomics in DMHE.  During his tenure at NIAAA, Dr. Velazquez helped develop research programs in the areas of biomarker discovery, epigenetics, proteomics, mitochondrial function, and metabolomics.

Tina Vanderveen, Ph.D.  Office of Extramural Activities (OEA) Director Tina Vanderveen retired in March after serving in many capacities at NIAAA.  Dr. Vanderveen was recruited to NIAAA in 1978 from the NIH institute that is now NIDDK.  Prior to arriving at NIH she had a 14-year career as a medical nutrition officer in the United States Air Force.  She served in many positions in her long career at NIAAA, including chief of the former Psychosocial Research Branch in what was then the Division of Extramural Research, director of NIAAA’s centers program, deputy director as well as acting director of the former Division of Basic Research, and deputy director of the then Office of Collaborative Research.  She was named OEA director in 2005.  Dr. Vanderveen briefly interrupted her NIAAA career to serve as a special assistant for AIDS in the National Institute on Drug Abuse’s Division of Clinical Research, returning to NIAAA in 1989. 

New Appointments

Judith Arroyo, Ph.D.  Judith Arroyo has been named Minority Health and Health Disparities Coordinator for NIAAA.  Dr. Arroyo came to NIAAA in 2003 from the Center on Substance Abuse, Alcoholism, and Addictions at the University of New Mexico.  She has worked nationally and internationally on Hispanic use of alcohol and other substances, and served as the first chairperson of the US/Mexican Border Governor’s Conference Substance Abuse Commission.  The minority health coordinator provides leadership and guidance to NIAAA staff on all aspects of extramural activities related to minority health and health disparities.  In addition to working in this capacity, she will continue her role as a program director in the Division of Epidemiology and Prevention Research (DEPR). 

Zhigang (Peter) Gao, M.D.   Zhigang (Peter) Gao joined DMHE as a program director in March.  Dr. Gao earned his M.D. degree from the Henan Medical University, Zhengzhou, China, and an M.S. in pharmacology from Henan Institute of Medical Sciences.  He also has an M.B.A. from the Carey Business School of Johns Hopkins University.  He was a postdoctoral fellow at Johns Hopkins and subsequently joined the faculty of the medical school.  Dr. Gao comes to NIAAA from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) where he was a senior research fellow.  His research has been focused on human hematopoietic stem cells, bone marrow derived stem cells, hemoglobin, and vector development for gene therapy.  His specific areas of expertise also include chemotherapeutic drug studies and animal models for oncology research.  Dr. Gao served as an associate editor for the journal Discovery Medicine from 1999-2003. 

Patricia Powell, Ph.D.  Patricia Powell has been named chief of NIAAA’s Science Policy Branch (SPB).  Dr. Powell had been acting chief of SPB since 2006.  She came to NIAAA in 2001 as an American Association for the Advancement of Science/NIH Science Policy Fellow and then joined the NIAAA staff as a health science administrator with the then Office of Scientific Affairs.  Dr. Powell began working with the Leadership to Keep Children Alcohol Free in 2003 and served as one of NIAAA’s representatives to the Office of the Surgeon General for the development of the Call to Action to Prevent and Reduce Underage Drinking. 

Honors

Robert B. Huebner, Ph.D.  Bob Huebner has been selected as a recipient of the 2008 American Psychological Association (APA) Meritorious Research Service Commendation.  This commendation recognizes outstanding contributions to psychological science through service within the federal government and other organizations in program development and research facilitation.  Dr. Huebner’s award recognizes significant contributions to the advancement of psychological science in promoting and supporting important research at NIAAA and NIH in the areas of problem drinking, treatment, and recovery, and the search for mechanisms of behavior change.  Dr. Huebner will receive personal congratulations from the president of APA at the December 2008 meeting of APA’s Board of Directors in Washington, DC. 

Ralph Hingson, Ph.D.  The American Society of Addiction Medicine (ASAM) has named Ralph Hingson the recipient of its R. Brinkley Smithers Distinguished Scientist Lecture and Award.  The citation notes Dr. Hingson’s “innovative analytic and public policy strategies resulting in fundamental advances in prevention science and public policy concerning the use of alcohol and its harmful consequences in many dimensions of our society, especially in the pursuit to keep our youth and highways safer.”  The award was presented during the ASAM annual medical-scientific conference in Toronto, Canada, April 11 to 13; Dr. Hingson’s award lecture was entitled “Magnitude and Prevention of College Age and Underage Drinking Problems.”  

Kenneth R. Warren, Ph.D.   Kenneth Warren, NIAAA’s Deputy Director, was the recipient of the Excellence Award from the National Organization on Fetal Alcohol Syndrome (NOFAS) at the organization’s Leadership Awards Benefit on May 14.  The award cites Dr. Warren for “pioneering FASD research and distinguished contributions” toward understanding and addressing the fetal alcohol syndrome and fetal alcohol spectrum disorders.  As reported in the February 2008 director’s report to the council, Dr. Warren’s name was added to the NOFAS Linda and Tom Daschle Hall of Fame in November, 2007.  Dr. Warren developed NIAAA’s FAS research program over 30 years ago and has been active in FASD activities throughout his career, including serving as the current chair of the government-wide Interagency Coordinating Committee on FAS.

D. Research Priority Emphasis and Core Support Teams

Update on Teams  When NIAAA established transdisciplinary research teams in 2003, the teams’ structure was intended to be flexible, allowing changes to be implemented as scientific opportunities arise and fields of science mature.  NIAAA senior management and staff recently reexamined and updated the structure of the teams, changing the designation of some teams to “working groups” or “coordinating committees.”

• A team explores an area to develop a long-range vision, and it develops and opens a new frontier for alcohol investigation.  In pursuit of these goals, the team may organize conferences and even issue RFAs for exploratory grants.  
• A working group has a more intermediate agenda, and it fosters trans-divisional activities focusing on oversight of the program initiatives implemented by the teams and expanding on those activities, also using the tools of discussions, workshops, RFAs, and program announcements.
• A coordinating committee will address ongoing trans-divisional activities of the institute that do not have a clear endpoint.

  Briefly, the changes and recommendations for the teams include the following: 

• The Gene and Environment (GxE) team will continue.   The Research Resources and Technologies will be combined with efforts in systems biology to create an Informatics and Computational/Systems Biology Team.
• The Mechanisms of Alcohol Action and Injury Team has been successful in implementing important new programs for the institute, including new projects in metabolomics and epigenetics, among others; also, major efforts that involve NIAAA in metabolomics and proteomics have been undertaken in the past few years within the Roadmap.  This team will be discontinued.
• The Centers and Training Team continues to serve a critical function within the operations of the Institute and will continue as a team.
• The  Mechanisms of Behavior Change, Underage, and Medications Development Teams will continue but with the designation working groups.
• Newly created are working groups on Biomarkers, and Fetal Alcohol Spectrum Disorders.
• Coordinating committees on AIDS, international research, and health disparities and minority health have been created.

Supplement on Underage Drinking Published in Pediatrics   An April 2008 supplement of Pediatrics presents seven papers developed by the members of the NIAAA Team on Underage Drinking Prevention and the steering committee of experts assembled to advise the institute on this initiative.  The supplement offers reviews and analyses of current research on biological, behavioral, and environmental changes during childhood and adolescence that foster the initiation, maintenance, and acceleration of illegal use of alcohol by underage youth.  NIAAA staff Vivian Faden, Margaret Mattson, Howard Moss, Ralph Hingson, and Cherry Lowman were coauthors for articles in the supplement.

E. NIAAA Research Programs

RFAs and PAs

NIAAA has received, or is expecting, applications in response to the following recently issued requests for applications (RFAs) and program announcements (PAs):  
         

• RFA AA-08-007 (R01) and 008 (R21)  Behavioral Mechanisms in the Transition to Habitual Alcohol Seeking and Drinking
• RFA AA-08-009 (R01) and 010 (R21) Alcohol Tolerance: Contribution to Consumption
• RFA AA-08-011 (R01) and 012 (R21) International Research on Venue-Based Interventions for HIV/AIDS and Alcohol Use 
• RFA AA-08-013 (R01) and 014 (R21) Alcohol, AIDS, and Liver Disease: Preventable Side-effects of Antiretroviral Therapy
• PAR 08-004 (U01) International Research Collaboration on Alcohol and Alcoholism

Based on the DEPR strategic plan reviewed by the Council in February 2007, four program announcements have been posted, including the following: 

• Epidemiology and Prevention in Alcohol Research
• Research on Alcohol-Related Public Policies such as Those Detailed the Alcohol Policy Information System (APIS)
• Screening and Brief Alcohol Interventions in Underage and Young Adult Populations
• Nutrition and Alcohol-Related Health Outcomes 

 To date, over 30 applications have been received in response to the announcements. 

Publications by Extramural Staff

An NIAAA-sponsored supplement to Alcoholism: Clinical and Experimental Research (ACER) specifically devoted to mechanisms of behavior change was recently published.  This supplement to ACER was entitled “The Search for Mechanisms of Behavior Change in Evidence-Based Behavioral Treatments for Alcohol Use Disorders” (Vol. 31, No. S3).  The supplement is based on the proceedings of a pre-conference satellite meeting that took place at the June 2005 meeting of the Research Society on Alcoholism.  The guest editors for the supplement were Robert Huebner and J. Scott Tonigan of the University of New Mexico.

In an analysis of a survey of infant feeding practices, Rosalind Breslow and coauthors found that a substantial percentage of breastfeeding women consumed alcohol.  The authors conclude that there is a need for nationally representative data on alcohol consumption and alcohol-related feeding practices among breastfeeding women.  (Breslow, R.A., Falk, D.E., Fein, S.B., and Grummer-Strawn, L.M.  Alcohol consumption among breastfeeding women.  Breastfeeding Medicine 2:152-157, 2007) 

Q. Max Guo and Samir Zakhari wrote the overview article that opens the most recent issue of Alcohol Research & Health on systems biology.    (Q. Max Guo and Samir Zakhari, Systems Biology and Its Relevance to Alcohol Research.  Alcohol Research & Health 31:5-10, 2008-05-21) 

Research Reports

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

Stress-Signaling Target for Alcohol Dependence  Relapse to drinking after periods of sobriety is a defining characteristic of alcoholism and is often triggered by stress.  In preclinical and clinical studies, scientists in NIAAA’s intramural program and collaborating centers found that a brain molecule known as the neurokinin 1 receptor, or NK1R, appears to be a central actor in stress-related drinking.  Previous studies have shown that a brain chemical known as substance P (SP) is released in response to stress, produces symptoms of anxiety, and binds preferentially to NK1R.  In this study, the researchers first demonstrated that NK1R plays an integral role in alcohol consumption in animals.  Mice that were genetically engineered to lack NK1 receptors consumed much less alcohol than did normal mice with fully functional NK1R.  Subsequently, in a small clinical study, the researchers showed that an experimental compound designed to block NK1 receptors reduced alcohol craving and improved overall wellbeing among recently detoxified alcohol-dependent individuals who had high levels of anxiety.  Using functional brain imaging, the researchers also showed that the exaggerated sensitivity to negative stimuli seen in alcoholics was dampened with the medication, while the lack of responses to pleasurable stimuli was restored.  Compounds that block NK1R may have considerable potential for treating alcoholism, and potentially other addictions.  (George, D.T., Gilman, J., Hersh, J., Thorsell, A., Herion, D., Geyer, C., Peng, X., Kielbasa, W., Rawlings, R., Brandt, J.E., Gehlert, D.R., Tauscher, J.T., Hunt, S.P., Hommer, D., and Heilig, M.  Science 319:1536-1539, 2008)

Drinking and Mortality  How much and how often people drink—not just the average amount of alcohol they consume over time—independently influence the risk of death from several causes.  Scientists in NIAAA and the National Cancer Institute examined data from a nationwide health survey conducted in 1988.  Almost half of the nearly 44,000 people who participated in the survey identified themselves as current drinkers who had at least 12 drinks of alcohol during the previous year.  By the end of 2002, more than 2,500 of these individuals had died. The researchers found that, in men, frequency and quantity of alcohol consumption had opposite effects on cardiovascular mortality.  The greater the amount of alcohol that men consumed on drinking days, the greater was their risk for death from cardiovascular disease.  For example, men who had five or more drinks on drinking days had a 30 percent greater risk for cardiovascular mortality than men who had just one drink per drinking day.  Alcohol quantity was also associated with increased mortality from cancer among men.  Frequency of drinking, on the other hand, was associated with decreased risk for death from cardiovascular disease among men.  Among women, frequent drinking was associated with a significantly increased risk of cancer, while increased quantity was associated with risk for mortality from all causes.  The researchers conclude that, for drinkers who are not alcohol dependent, “alcohol quantity and frequency might be thought of as modifiable risk factors for mortality.”  (Breslow, R.A. and Graubard, B.I. Alcoholism: Clinical and Experimental Research 32:513-521, 2008)

Epigenetic Effects Involved in Withdrawal Anxiety  Chronic exposure to alcohol changes brain function in ways that, with continued heavy drinking, set the stage for addiction.  Research suggests that alcohol exposure can change gene activity; this study looked at whether an effect by alcohol on genetic material could play a role in withdrawal-related anxiety.  The investigators found that alcohol can cause specific epigenetic changes to genetic material—that is, changes that do not affect the DNA sequence, but alter elements of the genetic material’s structure and as a result change gene activity.  Epigenetic changes were associated with the levels of anxiety of rats that were first maintained on a liquid diet with alcohol, and then denied alcohol.  One type of change noted was the addition or removal of specific chemical groups (acetyl groups) to and from a protein (histone) that forms part of the structure of the DNA chain.  These scientists found evidence that the removal of acetyl groups from histones in the DNA complex was associated with anxiety brought on by alcohol withdrawal.  The changes took place in a part of the brain (the amygdala) implicated in anxiety and alcohol-drinking behaviors.  By blocking the enzyme that removes the acetyl groups, the researchers prevented the development of alcohol withdrawal-related anxiety.  The researchers also investigated the potential role played by these types of changes in the anxiety-reducing effect that occurs with exposure to low levels of alcohol.  Rats injected with a one-time dose of alcohol exhibited less anxiety than control animals.  The changes at the gene level seen with low dose alcohol were the opposite of those seen in withdrawal—an increase in the addition of acetyl groups to histone rather than a decrease.  This study both demonstrates how epigenetic changes can be involved in alcohol-related behavior, and suggests that these mechanisms might serve as the basis for new treatments.  (Pandey, S.C., Ugale, R., Zhang, H., Tang, L., and Prakash, A. The Journal of Neuroscience 28:3729-3737, 2008)

Gene Variant Predicts Medication Response  Drinking alcohol increases the release of endogenous opioids, compounds that originate in the body and promote a sense of pleasure or well-being.  The drug naltrexone blocks brain receptors for endogenous opioids, reducing alcohol’s pleasurable effects, making it easier for patients to remain abstinent or stop quickly in the event of a slip.  According to an analysis of participants in the 2001-2004 COMBINE (Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence) Study, among patients taking naltrexone, those with a specific variant of an opioid receptor gene (OPRM1) drank less and experienced better overall clinical outcomes than patients without the variant.  About 87 percent of patients with the variant who received naltrexone experienced good outcomes, compared with about 49 percent of those who received a placebo.  About 55 percent of patients without the variant experienced a good outcome regardless of whether they received naltrexone or placebo.  Good outcome was defined as abstinence or moderate drinking without related problems.  In addition to naltrexone or placebo, all patients received medical management and some also received a combined behavioral intervention.  The researchers found that, compared with patients who do not carry the variant, white variant carriers who received naltrexone fared substantially better than other groups on all measures, including almost a 6 times greater likelihood of good clinical outcome. Extending the clinical outcome measure to variant carriers of all ethnicities reduced the benefit to just over a 3 times greater likelihood of good outcome. The researchers found no gene-medication interaction in patients who received specialized alcohol counseling, leading to them to conclude that genotyping for the variant may be most useful when naltrexone is used without intensive counseling.  (Anton, R.F., Oroszi, G., O’Malley, S., Couper, D., Swift, R., Pettinati, H., and Goldman, D. Archives of General Psychiatry 65:135-144, 2008)

Drinking Experience Predicts Drug-Related Risk  Research suggests that among people who drink, those who begin drinking at very young ages are at higher risk of future problems with alcohol.  This study analyzed data from the 1991-1992 National Longitudinal Alcohol Epidemiologic Survey, a national survey involving interviews with 42,862 respondents age 18 and older.  The analysis looked at whether, among all drinkers, those who began drinking at an early age, or experienced dependence, were more likely to subsequently use drugs or develop drug dependence.  The study also looked at whether, among drinkers who used drugs, these two factors—early onset of drinking, and dependence—predicted driving under the influence of drugs and involvement in motor-vehicle crashes because of drugs.  Among all drinkers, those who began drinking at the youngest ages were also at the highest risk of using drugs and experiencing drug dependence.  Independent of early drinking onset, alcohol dependence was also associated with increased risk of drug use.  Among those who both drank and used drugs, early alcohol use was also associated with higher rates of driving under the influence of drugs, and being involved in motor vehicle crashes because of drugs.  The authors conclude that the prevention of early alcohol and dependence treatment plays a part in the prevention of drug use and drug-related crashes.  (Hingson, R.W., Heeren, T., and Edwards, E.M. Journal of Studies on Alcohol and Drugs 69:192-201, 2008)

Gene Variants Affect Stress Responses  The extent to which someone is emotionally resilient in the face of stress is a product of both genes and experience.  Resilience influences vulnerability to psychiatric disorders, including addictions.  In this work, intramural scientists collaborating with scientists at other centers found that gene variants that affect the expression of the signaling molecule neuropeptide Y (NPY) altered brain responses to stress and emotion in human subjects.  Previous research had found that NPY’s release reduces anxiety.  Using functional brain imaging, these investigators found that individuals with the gene variant that yielded the lowest level of NPY reacted with heightened emotionality to images of threatening facial expressions.  People with the low level NPY variant were also found to have a diminished ability to tolerate moderate levels of sustained muscular pain.  In a preliminary finding, the low level NPY gene variant was found to be more common than other variants among a small sample of individuals with anxiety disorders.  Finally, low level NYP expression was linked to high levels of trait anxiety—an indication of an individual’s level of anxiety under normal circumstances.  These findings provide an illustration of how genetics underlie individual variation in resiliency to stress.  (Zhou, Z., Zhu, G., Hariri, A.R., Enoch, M.-A., Scott, D., Sinha, R., Virkkunen, M., Mash, D.C., Lipsky, R.H., Hu, X.-Z., Hodgkinson, C.A., Xu, K., Buzas, B., Yuan, Q., Shen, P.-H., Ferrell, R.E., Manuck, S.B., Brown, S.M., Hauger, R.L., Stohler, C.S., Zubieta, J.-K., and Goldman, D.  Nature 452:997-1001, 2008)

COGA Finds Additional Genes Associated with Alcohol Dependence  Genetic factors have been shown to play an important role in the development of alcohol dependence. Several genes, including GABRA2, ADH4 and CHRM2, have been found to be associated with alcohol dependence in the Collaborative Study on the Genetics of Alcoholism (COGA); these associations have been replicated in multiple independent studies.  In recent COGA studies, four additional genes have been associated with the risk for alcohol dependence:

•            TACR3, the gene for tachykinin receptor 3.  Tachykinins are neuropeptides; the receptor encoded by this gene plays an important role in the response to ethanol and cocaine.  Variations in the TACR3 gene have been strongly associated with severe alcohol dependence as well as cocaine dependence.  (Foroud, T., Wetherill, L.F., Kramer, J., Tischfield, J.A., Nurnberger, J.I. Jr., Schuckit, M.A., Xuei, X., Edenberg, H.J.  Alcoholism: Clinical and Experimental Research.  Epub ahead of print, doi: 10.1111/j.1530-0277.2008.00663.x)
•            OPRK, a gene that encodes the κ-opioid receptor.  A variant in a regulatory stretch of the gene reduces transcription of the gene by half and is significantly associated with alcohol dependence. (Edenberg, H.J., Wang, J., Tian,H., Pochareddy, S., Xuei, X., Wetherill, L., Goate, A., Hinrichs, T., Kuperman, S., Nurnberger, J.I. Jr., Schuckit, M., Tischfield, J.A., Foroud, T. Human Molecular Genetics.  Epub ahead of print, doi:10.1093/hmg/ddn068)