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The National Institute on Alcohol Abuse and Alcoholism (NIAAA) supports and conducts biomedical and behavioral research on the causes, consequences, treatment, and prevention of alcoholism and alcohol-related problems. NIAAA also provides leadership in the national effort to reduce the severe and often fatal consequences of these problems by:
December 31, 1970 - NIAAA was established under authority of the Comprehensive Alcohol Abuse and Alcoholism Prevention, Treatment, and Rehabilitation Act of 1970 (P.L. 91-616) with authority to develop and conduct comprehensive health, education, training, research, and planning programs for the prevention and treatment of alcohol abuse and alcoholism.
May 14, 1974 - Passage of P.L. 93-282, establishing NIAAA, NIMH, and NIDA as coequal institutes within the Alcohol, Drug Abuse and Mental Health Administration.
July 26, 1976 - Expansion of NIAAA's research authority to include behavioral and biomedical etiology of the social and economic consequences of alcohol abuse and alcoholism under authority of the Comprehensive Alcohol Abuse and Alcoholism Prevention, Treatment and Rehabilitation Act amendments of 1976 (P.L. 94-371).
August 1981 - Passage of the Omnibus Budget Reconciliation Act of 1981 (P.L. 97-35), transferring responsibility and funding for alcoholism treatment services to the states through the creation of an Alcohol, Drug Abuse, and Mental Health Services block grant administered by ADAMHA and strengthened NIAAA's research mission.
October 27, 1986 - Creation of a new Office for Substance Abuse Prevention in ADAMHA by the Anti-Drug Abuse Act of 1986 (P.L. 99-570) consolidated the remainder of NIAAA's nonresearch prevention activities with those of NIDA and permitted NIAAA's total commitment to provide national stewardship to alcohol research.
July 10, 1992 - NIAAA became a new NIH research institute under authority of ADAMHA Reorganization Act (P.L. 102-321).
May 3, 1995 - NIAAA celebrated its 25th anniversary.
NIAAA supports research and research training through a program of extramural grant support to scientists at leading U.S. research institutions, through interdisciplinary National Alcohol Research Centers Program grants, and through active intramural research. Additionally, NIAAA is involved in a number of important collaborations within NIH and the international community. Findings from these research endeavors are made available and accessible through a variety of research dissemination activities.
NIAAA's extramural research support is aimed at building a solid base of biomedical and behavioral knowledge for improved prevention and treatment of alcohol-related problems. Scientists from a variety of disciplines, including social and behavioral sciences, biology, and medicine participate in the extramural program. Current directions in extramural research span diverse areas such as genetic predisposition to alcoholism, the neurosciences, alcohol and pregnancy research, the development of pharmacological and behavioral interventions to treat alcohol abuse and alcoholism and its effects, and alcohol-related public health policies. Selected extramural program highlights are provided below.
Genetics. Alcoholism has been recognized for centuries as a familial disorder, and over the last 30 years, NIAAA-supported twin, family, and adoption studies have indicated major roles of for both genetic and environmental factors in its etiology. Twin and family studies are defining more precisely those aspects of the risk for alcoholism that are inherited. Vulnerability to alcoholism is influenced by multiple genes and gene variants. The precise number, identity, and modes of action of most of these genes and gene variants are as yet unknown. In order to identify these genes the NIAAA supports genetic linkage/disequilibrium and association studies in affected individuals and their families drawn from diverse populations from various ethnic backgrounds (e.g. Caucasian, Ashkenazi Jews, Asian, Hispanic, and African American). The Collaborative Study on the Genetics of Alcoholism (COGA), the largest of such studies, initiated in 1989, has recently identified candidate genes and published data providing suggestive evidence for the locations of several other relevant genes and gene variants, based on detailed diagnostic evaluations of more than 20,000 individuals drawn from families with a high incidence of alcoholism, and genotyping of more than 3,000 individuals selected from that sample population.
NIAAA also supports studies using naturally occurring and induced genetic variation in animals as a tool for elucidating mechanisms of actions of genes associated with various features of the alcohol response, such as sensitivity, stimulation, aggression, tolerance, sedation, and withdrawal. For several decades , lines or strains of genetically well defined inbred, selectively bred, and genetically heterogeneous rodents have been used to define quantitative trait loci (QTL), small sections of chromosomes , associated with variation in many alcohol-related behavioral traits and physiological and biochemical variation relevant to the alcohol response. Mapping of QTL's has resulted in the identification of more than a hundred chromosomal regions associate d with alcohol - related traits, as well as , identified candidate genes and gene variants associated with alcohol dependence. Many currently funded studies are focused on changing genes and their expression by addition, deletion, alteration, and stimulation of specific genes. Recent technological advances that allow temporal control of gene expression are expected to prove extremely useful in elucidating the effects of different genes on the response to alcohol and interactions among genes and between different genotypes and environments.
The recent completion of the sequencing of genetic maps for humans and mice and soon to be completed maps for rats, non-human primates, and other species provide us with new approaches to the study of the effects of variation in genes on alcohol-related behaviors. The NIAAA continues to encourage data sharing and bioinformatics approaches to increase understanding of genetic variation in alcohol response by promoting sharing, use, analysis, and interpretation of experimental results by many different scientists. In addition, the merging of data from different experimental approaches, such as gene expression data and gene association studies, is expected to have a dramatic effect on our ability to understand how specific genes and gene families affect responses to alcohol.
Identification of genes predisposing to risk for alcoholism and the physiological pathways mediating the development of this disorder will provide us with clues to biomarkers for risk and injury and medications for prevention, treatment, and mitigation of alcohol-induced injury. Moreover, knowledge of the genes predisposing to alcoholism will permit the design of more powerful studies to determine which gene-gene and gene-environment interactions influence this disease.
The NIAAA also supports studies to determine the respective contributions of the environment and genetics to differential susceptibility of alcohol-related medical disorders such as liver cirrhosis, pancreatitis, cardiomyopathy, fetal alcohol syndrome disorders, and cancers induced by alcohol or worsened by alcohol exposure.
Neuroscience and Behavior . NIAAA supports basic research to identify the neurobiological mechanisms within the brain and nervous system on which affected by or underlying alcohol abuse and alcoholism have an impact or which underlie alcohol p roblems , and the ir resulting behavioral manifestations. This research encompasses multiple levels of study, from determining the molecular targets of alcohol in the brain and characterizing the effects of alcohol on cellular responses and synaptic function, to identifying and understanding the neural pathways and circuits that mediate the effects of acute and chronic alcohol exposure. At the whole animal level, this research seeks to describe the effects of alcohol on cognitive and motor functions, and on the development of behaviors that result from, and lead to, excessive alcohol consumption. Noninvasive, functional imaging techniques are being used in animal and human studies to identify the brain regions influenced by alcohol.
Areas of program interest to the NIAAA fall into two broad categories; 1) the effects of acute and chronic alcohol consumption on the structure and function of the brain and nervous system, and 2) changes in behavioral responses to alcohol as a result of excessive, prolonged consumption, including craving, tolerance, and dependence. Basic research seeks to understand alcohol's effects on neuronal processes, such as intracellular signaling and signal transduction, the physiology and pharmacology of ion channels and neurotransmitter receptors, pre-synaptic and post-synaptic function, local circuit interactions, and gene transcription and regulation in neural systems. Additional studies concern research on the behavioral pharmacology of alcohol's actions, structural and functional neuroadaptations in response to chronic, excessive alcohol intake, and cognitive decline and deficits associated with alcohol abuse.
The study of fetal alcohol syndrome disorders, alcohol-induced neurodegeneration and brain damage, altered cognitive and motor functions that result from excessive alcohol use, the role of the body's normal stress response system in initiating and maintaining alcohol drinking behaviors, and abnormal social functioning, aggression, and other negative behavioral consequences of excessive use of alcohol are several research areas of current interest to NIAAA. Other areas of interest include studies on the molecular, cellular, neuroimmune, and behavioral consequences resulting from different patterns (binge, chronic, chronic-intermittent) of alcohol consumption, on the effects of alcohol drinking on the adolescent brain and throughout the aging process, and using neurocomputational approaches that integrate these data to describe alcohol's actions within the brain and nervous system. Currently research is underway to determine if the adolescent brain is more vulnerable than the adult brain to the negative consequences of alcohol consumption. Indeed, epidemiological studies indicate that the earlier in life individuals initiate drinking the greater the likelihood that they will become alcohol dependent. NIAAA is encouraging studies to better understand this vulnerability. This includes the development of non-human primate models to study the adolescent period.
Alcohol and Pregnancy. NIAAA supports research to determine why and how alcohol consumption during pregnancy results in adverse consequences for the fetus, the most serious of which is fetal alcohol syndrome (FAS), a disorder that includes reduced growth; facial abnormalities; and neurological, cognitive, and behavioral impairment. Laboratory studies have identified several cellular and molecular mechanisms that contribute to these defects. These studies may help to identify biomarkers for early diagnosis and may provide a basis for possible preventive therapies.
Epidemiological and clinical studies to determine environmental and other factors (e.g., cultural norms and genetic predisposition) that place women at risk of giving birth to a FAS child are supported in order to develop and target prevention and intervention efforts more effectively. The development of methods to confirm exposure to the fetus can aid in the identification of high risk mothers and target high risk infants for evaluation by medical specialists. NIAAA also supports and encourages research that develops and/or evaluates community-, clinic-, and family-based strategies to prevent drinking by pregnant women, especially those in high risk populations.
The effects of binge and low-level or moderate drinking on prenatal development are of special concern because these patterns of drinking are so prevalent. Longitudinal human studies have shown that behavioral problems can occur at these levels of prenatal exposure. Neuroimaging studies of children with FAS or nervous system manifestations of the syndrome, in conjunction with neurobehavioral tests, are providing clues about the nature of neurodevelopmental deficits and may lead to better diagnosis and treatment of these disorders.
NIAAA chairs the Interagency Coordinating Committee on Fetal Alcohol Syndrome (ICCFAS), which was created in October 1996 in response to a report by an expert committee of the Institute of Medicine (IOM). The IOM report, entitled Fetal Alcohol Syndrome: Diagnosis, Epidemiology, Prevention, and Treatment, recommended that NIAAA chair a Federal effort to coordinate FAS activities since the responsibility for addressing the many issues relevant to FAS transcends the mission and resources of any single agency or program. Currently the ICCFAS includes representatives from the Department of Education, the Department of Justice, and seven agencies of the Department of Health and Human Services. Since 1996 individual agencies have made substantial progress in expanding or adapting existing programs to address FAS and other fetal alcohol spectrum disorders.
NIAAA is launching a five year Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD), a program to inform and develop effective interventions and treatment approaches for the full spectrum of neurological disorders caused by fetal alcohol exposure. CIFASD will comprise highly integrated, multidisciplinary research projects in five domains, including basic science, neurobehavior, morphology/neuroanatomy, neuropharmacology, and early intervention. It is anticipated that CIFASD will create unprecedented opportunities for collaboration and integration of resources that will significantly accelerate the translation of important scientific discoveries to clinical practice.
Medications Development. NIAAA is strongly committed to the development of pharmacological interventions to diminish the craving for alcohol, reduce risk of relapse, and safely detoxify dependent individuals undergoing treatment. Pharmacologic agents are at various stages of development ranging from preclinical research to clinical application for the treatment of alcoholism. The two most promising medications are naltrexone and acamprosate. Naltrexone, an opioid antagonist, has been approved by FDA as a safe and effective adjunct to psychosocial treatment for alcoholism. Acamprosate, a medication that interacts with the glutamate receptor, has been shown effective in increasing rates of abstinence. NIAAA has recently initiated an 11-site clinical trial evaluating the combination of naltrexone and acamprosate, both alone and together, with behavioral therapies.
Since alcohol-seeking behavior is complex and involves several neurotransmitter systems and neurohormones, NIAAA is exploring a range of medications to modify drinking behavior, including ondansetron, a serotonin3 (5-HT3) blocker; memantine, a glutamate NMDA blocker; and kudzu, an herbal preparation. Related topics of interest are medication compliance, differential effect of pharmacotherapies on subtypes of alcoholics, effects of medications when combined with psychosocial interventions, and medications in combination. The medications development program also seeks to develop compounds for potentially fatal alcohol-related medical disorders, such as alcoholic-liver disease, alcoholic cardiomyopathy, alcoholic pancreatitis, as well as to promote tissue regeneration in organs damaged by alcohol.
Alcohol-related Medical Disorders . Chronic alcohol use affects every organ and system of the body and can lead to life threatening medical disorders, including liver cirrhosis, pancreatitis, and cardiomyopathy. Heavy alcohol use is also an important factor for co-morbid conditions, such as hepatitis C, osteoporosis, type 2 diabetes, and certain cancers. The NIAAA supports a wide range of research to elucidate the genetic, metabolic, and immunologic mechanisms of alcohol-induced tissue injury that contribute to the initiation and progression of these disorders.
Basic research studies are identifying the molecular pathways through which alcohol causes organ damage with the goal of identifying the targets for drug discovery to prevent or treat alcohol-related disorders. The potential for tissue repair and regeneration following damage from chronic heavy drinking through stem cell therapy, gene targeting, and metabolic manipulations is being explored.
Epidemiological and clinical studies are supported to determine differences in the prevalence and severity of alcohol-related disorders among different populations and the associated environmental and genetic risk factors. The identification of biomarkers for the early stages of disease, using genomic, proteomic, and metabolomic approaches, will facilitate treatment before diseases become irreversible. The NIAAA also supports clinical studies of promising treatments based upon findings from basic mechanistic studies.
The NIAAA also supports research to elucidate the mechanism of alcohol's potential beneficial effects on coronary heart disease.
The knowledge gained from the research described above will be used to develop new therapeutic strategies to prevent or slow the progression of diseases caused by excessive drinking.
Treatment. NIAAA continues to emphasize research to improve treatment of alcohol abuse and alcoholism. NIAAA-supported studies have demonstrated that brief interventions delivered in primary care health settings are effective for reducing alcohol consumption in heavy drinkers. NIAAA is committed to supporting clinical trials evaluating a broad range of therapies from mutual help groups; behavioral therapies, such as skills training; and psychological therapies, such as motivation intervention and family therapy. Adolescent treatment deserves special emphasis since fewer clinical trials of adolescent treatment have been done than of adult therapies.
Community Prevention Trials. NIAAA funds community-based controlled intervention trials to prevent alcohol-related trauma (including violence), underage drinking, and drinking and driving. One project tests a school/parent/community-focused intervention among economically and ethnically diverse populations, while others test media advocacy strategies, traditional mass media approaches, policy changes, strategies to enhance voluntary and enforced compliance with underage drinking laws, and a variety of community-mobilization techniques. Results to date indicate that: 1) interventions simultaneously focused on schools, parents, and the community-at-large can delay and lessen underage drinking; 2) community organizing efforts can decrease sales (and distribution) of alcohol to youth; 3) community initiatives involving enhanced law enforcement, media and educational campaigns, and public and private collaboration can significantly reduce drinking and driving and alcohol-involved fatal crashes; and 4) enhanced law enforcement and attendant publicity can increase the perceived risk of arrest, which appears to be a critical mediating catalyst for decreased alcohol-related crashes. New methodologies permit prevention researchers to target high-risk neighborhoods within larger cities.
College-Focused Epidemiologic and Prevention Research. A large number of studies are addressing alcohol problems on college campuses, including "binge" drinking. Epidemiologic studies are exploring various aspects of drinking by college students. These studies include: 1) a longitudinal cohort study of college students looking at the transition to college and drinking problems and analyzing drinking trajectories across the college years, and 2) a study investigating the role of alcohol in college students' decisions about engaging in risky sexual behavior. Studies are also testing the efficacy and effectiveness of preventive interventions designed to reduce drinking and problem drinking among college students. These intervention studies focus on: group-counseling and feedback approaches to prevent risky drinking in fraternities and sororities; campus-wide social-norms marketing approaches to reduce high-risk drinking; motivational counseling and feedback strategies targeted at high-risk individuals; laboratory and environmental techniques that challenge positive expectancies about the benefits of alcohol; the relative and additive effectiveness of social norms marketing, direct-mail personal feedback, and skills-training interventions; educational strategies that target parents of college bound freshmen; and comprehensive campus/community policies and programs dealing with alcohol availability, promotion, and formal regulation and control. Some of this research is co-funded by the Department of Education and the Substance Abuse and Mental Health Services Administration.
Other Prevention Areas. Other composites of grants that are addressing special areas of emphasis include four studies that are measuring the impact of alcohol advertising on youth and adults in terms of their expectancies regarding the benefits and risks of drinking, their intentions to drink, and their actual drinking behavior. Five other studies are testing, through randomized controlled trials, the effectiveness of various sanctions and treatments to prevent recidivism for DWI (drinking while intoxicated). Priority areas that need further development include studies of interventions to prevent work-related alcohol problems, alcohol-related violence, and alcohol-related sexual risk taking that can lead to HIV/AIDS; family-focused preventive interventions; and tests of promising and proven prevention strategies among ethnic minorities.
Health Services Research. NIAAA supports a program of health services research endeavors that seeks to expand understanding of how alcohol treatment and prevention services are organized, managed, financed, and delivered and how these factors influence the availability, quality, cost, utilization, effectiveness, and efficiency of these services. NIAAA-supported studies have demonstrated that brief interventions delivered in primary care, emergency, and other medical settings to alcohol abusers who might not otherwise receive treatment are effective in reducing alcohol consumption and subsequent alcohol-related problems. Similarly, other NIAAA-supported studies have begun to demonstrate that brief and other interventions with alcohol abusers can yield a significant cost benefit savings to society. Other alcohol health services research studies continue to examine the effects of widespread shifts to managed care services, the economic impact of alcohol treatment, and disparities in the availability of alcohol services across racial, ethnic, gender, geographic, and insurance categories. Current research emphases include expanded economic analyses of treatment, improvements in adopting research findings in clinical practice, and secondary analyses of existing health services data.
Epidemiology. Alcohol epidemiology provides the foundation for monitoring the health of the population, developing and evaluating prevention and treatment services for alcohol problems, and establishing alcohol-related social policies. NIAAA conducts and supports research to study the distribution and determinants of alcohol use, abuse, dependence and the associated health and social consequences.
Surveillance activities such as collecting alcohol sales information, U.S. vital statistics, and hospital records are supported to track alcohol consumption and its related problems over time and location. Population-based survey research is encouraged to examine the context, volume, and specific drinking patterns that lead to particular alcohol-related problems as well as the impact of age, gender, race/ethnicity, and other sociodemographic factors. Analytic epidemiological studies which formulate and test hypotheses about genetic, environmental, and other factors that influence injury or disease occurrence are also supported.
Research is funded on the role of alcohol and injuries. The most extensive research has been supported in the role of alcohol in motor vehicle injuries and deaths; however research on the role of alcohol in other injuries, both intentional and unintentional, is also ongoing. The epidemiology of the medical consequences of alcohol use and abuse is an important area of research. Such research includes epidemiologic studies of co-occurring disorders, particularly psychiatric comorbidity and other drug abuse/dependence as well as studies of the risks and benefits of moderate alcohol consumption. Methodological studies are also fostered to improve measurement and assessment in all of the above areas of research.
Institutional Training Program. NIAAA Institutional Research Training Grants are authorized under the NIH National Research Service Awards program. Training grants are supported to help ensure that highly trained scientists will be available in adequate numbers and in appropriate research disciplines to meet the Nation's alcohol research needs. Institutions select promising students for predoctoral and/or postdoctoral training in research areas pertinent to understanding the causes, consequences, treatment, and prevention of alcohol-related problems. Special attention is given to recruiting minority individuals and women. Opportunities exist for basic and clinical research training in a variety of disciplines, including social, behavioral, biomedical, and biological sciences.
HIV/AIDS Program. NIAAA has developed a broad behavioral and biomedical portfolio of HIV/AIDS research in response to the changing nature of the AIDS epidemic among alcohol using, abusing, and dependent individuals. This portfolio addresses emerging scientific opportunities for studying the role of alcohol use in HIV-infected and uninfected drinkers. As the epidemic in the United States continues to evolve, minority women and young gay men are increasingly becoming infected. There is an urgent need to limit the spread of HIV/AIDS among substance abusers in these populations by developing a range of targeted preventive interventions. These interventions include behavioral and social interventions and biomedical approaches. The disproportionate impact of HIV infection among alcohol and substance abusers presents additional challenges to biomedical, behavioral, and, clinical researchers to understand the interplay of individual, cultural, economic, and environmental factors in the treatment of AIDS both in the U.S. and abroad.
Health Disparities Research and Training Program. Epidemiological, psychosocial, and biomedical research suggests that some minority groups suffer more severe adverse effects from alcohol than do other populations. Thus, we need to know why alcohol problems are distributed disproportionately across racial and ethnic groups. Groups of particular concern include African Americans, Hispanics/Latinos, American Indians/Alaska Natives, Asian Americans, and Native Hawaiians and other Pacific Islanders. We also recognize significant variability between subgroups within populations.
Major components of our strategy to address Health Disparities include: promoting alcohol research on issues that affect minority populations; building capacity to conduct alcohol research at minority serving institutions by providing mentoring, training and research support; promoting research career development among minority researchers, educators, health care professionals, and clinicians; and transferring research knowledge to health care professionals and others who serve minority communities for use in practice settings and conveying those practitioners' experiential/clinical knowledge to alcohol researchers who are looking at health disparities issues.
Alcohol Health and Science Education Programs. There is a critical need for research-based knowledge regarding alcohol use and health consequences at all levels of the U. S. education system. This includes K-12, college and graduate programs in the health professions.
The Institute supports several initiatives to better prepare health professionals to identify, prevent, and treat alcohol problems in their patient populations. This is accomplished by developing and disseminating research-based curricula and state-of-the-art faculty training programs. Curricula have been developed for primary care physicians, obstetricians, gynecologists, pediatricians, and social workers. Curricula for pharmacists and nurses are planned for the future.
The NIAAA also develops, disseminates, implements, and evaluates innovative educational programs regarding the science of alcohol for K-12 science education and public education programs. Courses and related materials to educate about scientific advances in the knowledge of alcoholism and related problems are developed for patients, families, the general public, primary and secondary school educators/students, college educators/students, and scientists.
Alcohol Screening. The Institute's screening programs have a number of important goals: to increase public and professional involvement in identifying individuals who would benefit most from alcohol prevention and treatment; to increase the visibility of alcohol problems and the importance of incorporating screening into routine practice in medical and other health professional settings in the U.S., and to heighten awareness of the consequences of at-risk drinking.
The centerpiece of our screening efforts is National Alcohol Screening Day. National Alcohol Screening Day (NASD) provides an opportunity for all Americans to receive basic information about alcohol consumption so that each can make an informed decision on whether to drink and if so, then how much. The theme is "Alcohol and Your Health: Where do you draw the line?" Screening is performed annually during the month of April in thousands of public, college, primary care, clinic, and government settings across the U. S. Persons found to be drinking at at-risk levels receive a brief intervention and those screening positive for a possible diagnosis of abuse or dependence are referred for further evaluation.
There are special populations who will benefit more from the screenings and targeted health messages such as the elderly, women of childbearing age, individuals with a family history of alcohol problems, college students, and individuals with existing medical conditions that are exacerbated by alcohol use or those on certain medications.
International Programs. NIAAA sponsors several projects that team established U.S. investigators with their foreign counterparts to develop new alcohol research, medical education, and research training activities. These collaborative studies serve as the foundation for larger, more intensive studies in populations where the incidence or prevalence of disease is higher than in the U.S. and where other factors, such as well documented family histories and controls permit study designs that will produce more generalizable results.
The institute is actively involved with binational commissions in Russia and South Africa that have facilitated partnerships with U.S. investigators and their counterparts in these two countries. For example, the NIAAA's active role in the Health Working Group for South Africa has led to significant progress in the areas of fetal alcohol syndrome (FAS) research and efforts to develop research on prevention and treatment of alcoholism. The South African Government, recognizing that FAS is particularly prevalent in the Western Cape Province, is working with NIAAA on FAS research projects and prevention strategies.
The NIAAA, as a designated World Health Organization Collaborating Center for Research and Training on Alcohol Use Disorders, also supports scientific exchanges to increase the research capacity of scientists in several foreign countries, including Finland, Japan, Poland, Mexico, Russia, South Africa, Italy, Hungary, and others.
The overall goal of the NIAAA's Division of Intramural Clinical and Biological Research is to understand the mechanisms by which alcohol produces intoxication, dependence, and damage to vital body organs, and to develop tools to prevent and treat those biochemical and behavioral processes. Areas of study include identification and assessment of genetic and environmental risk factors for the development of alcoholism; the effects of alcohol on the central nervous system, including how alcohol modifies brain activity and behavior; metabolic and biochemical effects of alcohol on various organs and systems of the body; noninvasive imaging of the brain structure and activity related to alcohol use, development of animal models of alcoholism; and the diagnosis, prevention, and treatment of alcoholism and associated disorders.
The Division has been expanding its research portfolio: 1) by conducting studies to assess the role of particular molecular targets of alcohol in acute intoxication and alcohol-seeking behavior; 2) through structural biological analysis of membrane proteins that are targets for alcohol actions; 3) by establishing a research program in liver biology to explore the role of cytokines and cytokine signaling proteins in alcoholic liver disease and viral hepatitis; 4) by studying protein kinase signaling cascades to enhance understanding of the pathogenesis and progression of alcoholic liver disease and a variety of disorders caused by alcohol; 5) by pursuing preliminary findings that indicate that alcohol highly and potently stimulates P13 kinase in vascular endothelial cells in culture and, thus, may play a role in the beneficial effects of moderate alcohol consumption in cardiovascular disease; and 6) by establishing a transgenic/knockout mouse facility to develop new research models to understand the genetic basis of alcohol drinking behavior and alcoholism. The Division has established a sabbatical program to bring prominent extramural scientists into the program and allowing intramural scientists to carry out research at extramural institutions.
NIAAA utilizes a combination of clinical and basic research facilities, which enables a coordinated interaction between basic research findings and clinical applications in pursuit of these goals. An 11-bed inpatient ward and a large outpatient program are located in the NIH Clinical Center.
Clinical Research. Among the studies carried out by the clinical program are 1) sophisticated electrophysiological, neuropsychological, and brain imaging studies on alcoholics, individuals at risk, and carefully matched controls; 2) the first clinical trial to test the efficacy and safety of a cannabinoid CB1 receptor antagonist for the treatment of alcohol craving; 3) the use of various specific serotonin receptor antagonists to compare differences in serotonin receptor concentration between alcoholic and normal subjects in both nonhuman primate and human populations; 4) investigations of the mechanisms underlying alcohol-related neurotoxicity, as well as the effects of this toxicity on the autonomic nervous system; 5) research on biochemical concomitants of violent behavior in alcoholics and on variables associated with increased vulnerability of developing alcoholism-related behavior; 6) exploring whether the "cognitive style" used by alcoholics is a risk factor for the development of alcoholism; 7) characterizing the role of various neurotransmitter systems in the etiology of alcoholism; and 8) exploration of possible biochemical determinants that might differentiate subtypes of alcoholism.
A new chief of the Laboratory of Clinical Studies has recently been appointed. Markus Heilig, M.D., Ph.D., currently the head of clinical drug abuse research at the Karolinska Institute in Stockholm, Sweden, will initiate new treatment trials for alcoholism using ligands acting at receptors for various neuropeptides and excitatory amino acids.
Genetics of Alcoholism. This research focuses on investigating and identifying the vulnerability and protective genes that underlie alcoholism's heritability. Studies also have implications for the role of genes in behavior.
Two approaches are being used to identify behavior genes. The first approach uses positional cloning. The second approach uses large-scale screening of candidate genes expressed in the brain for identifying DNA sequence variants. These approaches have the strength of being complementary: the same groups of individuals important in performing the genetic linkage scan are also examined for the effects of gene variants identified through direct gene analysis. In addition, the results of the genetic linkage studies are used to provide candidate genes for identifying new DNA sequence variants.
Genetic and other determinants of alcoholism in population isolates including American Indian communities and Finland are being investigated. Evidence was found for two potential alcoholism-vulnerability genes in an Indian tribe with a high rate of alcoholism.
Other studies investigate the role of neurotransmitters, including corticotropin-releasing hormone (CRH) and serotonin, which are known for their important role in behavioral inhibition and anxiety. Studies also are examining other substances (endogenous opioids, neurotransmitter receptor proteins, and biosynthetic enzymes) that are also critical for alcohol reinforcement and for other behaviors. Toward the goal of determining the genetic basis of behavior, we identified a substantial collection of gene variants in neurogenetic candidate genes and have shown that several are functional in vitro and also effect in vivo biology.
Alcoholic Liver Disease. Researchers in a newly established Section on Liver Biology are exploring the role of cytokines and cytokine signaling proteins in alcoholic liver disease and in non-alcoholic fatty liver. Studies are also aimed at identifying the molecular mechanisms that underlie the synergistic hepatotoxic effect of chronic alcoholism and viral hepatitis.
Alcohol and Essential Fatty Acids. NIAAA researchers are investigating the biological functions of essential fatty acids and the adverse effects of alcohol on these functions. A clinical study of alcoholics has indicated that there is a loss of essential polyunsaturated fatty acids in the tissues and blood cells of these patients. Such losses are believed to be related to the tissue damage that occurs in almost every organ system in alcoholics but particularly in the liver and brain. Alcohol is perhaps the only dietary constituent that is capable of depleting the omega-3 fatty acids from the brain, and this may lead to the degeneration of neural cells and a loss in brain and visual function. An interdisciplinary approach is taken in these studies.
Losses of organ polyunsaturated fats as a consequence of chronic alcohol abuse, the underlying metabolic mechanisms and modulating nutritional factors, and the consequences for membrane function as assessed by biochemical and biophysical means are an integral part of this work. Fluorescence spectroscopy and magnetic resonance imaging are the principal tools used to study the functions of polyunsaturated phospholipids in membranes. Mass spectrometry is used for sensitive analysis of fatty acid metabolites in humans. Studies are also being conducted on the lipid requirements of the nervous system during early development, and the full range of experimental and clinical approaches available in the laboratory are employed in this effort.
Molecular Mechanisms of Alcohol Action in the Brain. Recent NIAAA research studies have demonstrated that alcohol affects signal transduction systems involved in the regulation of nerve cell excitability and the transmission of information at synapses. Using newly developed physiological and molecular biological techniques, institute scientists are working toward determining the molecular mechanisms of alcohol's interaction with these signal transduction systems. Scientists also will investigate the molecular alterations of neural function associated with alcohol tolerance, dependence, and withdrawal. This information will improve our understanding of the molecular basis of alcohol dependence and lead to development of treatments and prevention strategies.
NIAAA maintains an active communications program aimed at informing the general public, health care practitioners, researchers, policy makers, and others involved in managing alcohol-related programs about research findings with applicability to alcohol treatment and prevention efforts. Our scientific communications include vehicles such as:
Online Resources. Research findings and resources are also shared with the alcohol and general health care communities through the NIAAA Website, http://www.niaaa.nih.gov. The Alcohol and Alcohol Problems Science Database, known as ETOH, appears online at http://etoh.niaaa.nih.gov.
Containing nearly 130,000 records from the 1960s to the present, ETOH is a comprehensive bibliographic database of literature on all aspects of alcohol research: psychology, psychiatry, physiology, biochemistry, epidemiology, sociology, neuroscience, treatment, prevention, education, safety, criminal justice, legislation, employment, labor and industry, and public policy. ETOH is updated monthly and includes a thesaurus for searching and retrieving information.
A second database, "Quick Facts," provides access to alcohol-related epidemiologic data and facilitates communication among NIAAA staff and others interested in NIAAA programs and data.
Clinical trials related to alcohol research can be found via the online database, http://ClinicalTrials.gov. For each clinical trial, the following information is provided: location of clinical trials, their design and purpose, criteria for participation, and the treatment under study.
Currently, NIAAA's Website features publications (many available as full text documents), news releases, grant and contract information, conferences and workshops, databases, frequently asked questions for the public, and other alcohol-related resources.
|This page was last reviewed on June 21, 2005 .|
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