NIH 1998 Almanac/The Organization/NIAAA/
National Institute on Alcohol Abuse and Alcoholism : Programs and Activities
NIAAA supports research 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 an active intramural research program on the NIH
campus in Bethesda, Md. Additionally, NIAAA is involved in a number of important
collaborations within NIH and the international community. Findings from these several
research areas are made available and accessible through a wide variety of research
dissemination activities.
Extramural Research
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 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 25 years, NIAAA-supported twin, family, and adoption studies have
indicated major roles of both genetic and environmental factors in its etiology. Today,
twin studies are defining more precisely those aspects of alcoholism which are genetically
inherited. Vulnerability to alcoholism is influenced by multiple genes, whose precise
number, identity, and modes of action are as yet unknown. NIAAA supports genetic linkage
and association studies in affected individuals and their families, in order to identify
these genes. The largest such study, initiated in 1989, has recently published suggestive
evidence for the locations of several such genes, based on detailed diagnostic evaluations
of more than 14,000 individuals drawn from families densely affected by alcoholism, and
genetic typing of more than 2,000 individuals selected from this sample.
In addition to human genetic studies, NIAAA supports a vigorous program of genetic
analysis of alcohol-related behavior in animals. NIAAA-funded selective breeding studies
on mice and rats have shown that many alcohol-related behavioral traits (for example,
consumption, sedation, withdrawal, hypothermia, locomotor stimulation) are genetically
influenced, and that, for the most part, different genes influence the different traits.
Much of the current genetic research is focused on mapping and identifying the individual
genes, or quantitative trait loci (QTL) influencing these traits. Since gene
identification proceeds more rapidly in animals than in humans, and since human
counterparts of animal genes can readily be tested for potential relationship to
alcoholism, the animal genetic studies are expected to speed the discovery of human genes
influencing vulnerability to alcoholism. More recently, investigators have been using
mutations targeted to specific components of nerve cells, in order to test the role of
these components in mediating alcohol’s effects on the nervous system.
Identification of genes predisposing to alcoholism will greatly facilitate elucidation
of the physiological pathways mediating the development of this disorder. Each step in
each pathway so identified is a potential target for prevention and treatment. Moreover,
knowledge of the genes predisposing to alcoholism will permit the design of more powerful
studies to determine which environmental factors 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, and fetal alcohol syndrome.
Alcohol and Pregnancy. NIAAA supports research to determine why and how alcohol
consumption during pregnancy can have many 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 and behavioral impairment. Laboratory studies have
identified several cellular and molecular mechanisms that contribute to these defects,
which may lead to possible preventive therapies.
Epidemiological and clinical studies to determine the environmental and other factors
(e.g., stress and genetic predisposition) that place women at risk of giving birth to an
FAS child are supported in order to target prevention and intervention efforts more
effectively. The development of biomarkers 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. Research to develop and evaluate effective strategies for educating health
care professionals and their patients and preventing drinking during pregnancy are also
supported.
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 and some manifestations of the
syndrome, in conjunction with neurobeha-vioral tests, are providing clues about the nature
of neurodevelopmental deficits and may lead to better diagnosis and treatment of these
disorders.
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.
Naltrexone, an opioid antagonist, has been approved by FDA as a safe and effective
adjunct to psychosocial treatment for alcoholism.
Since alcohol-seeking behavior is complex and involves several neurotransmitter systems
and neurohormones, NIAAA is exploring a range of additional medications to modify drinking
behavior. Serotonin uptake inhibitors have shown considerable promise in animal models and
may assist alcoholics with collateral depression. Related topics of interest are
medication compliance, differential effect of pharmacotherapies on subtypes of alcoholics,
and effects of medications when combined with psychosocial interventions.
Neurosciences. NIAAA funds research designed to learn the neural mechanisms
underlying alcohol abuse and alcoholism. This research includes determining the relevant
molecular targets of alcohol in the brain and understanding which and how specific neural
circuits mediate the various actions of acute and chronic alcohol exposure. A variety of
state-of-the-art methodologies are being used in this endeavor. Molecular biology and
genetic techniques are becoming an integral part of this research. The development and use
of transgenic animals will become increasing important in linking actions of ethanol on
specific targets and neural circuits with its behavioral effects. In addition,
noninvasive, functional imaging techniques are used in animal and human studies to
identify neural circuits influenced by ethanol. Such studies coupled with multisite
electrophysiological recordings in the brain will provide more specific information on
cellular mechanisms underlying activation or inhibition of neural circuits after ethanol
ingestion.
Recent evidence suggests that the adolescent brain is more vulnerable than are adults
to the negative consequences of alcohol consumption. Indeed, epidemiological studies
indicate that the earlier in life individuals begin to seriously drink, the greater the
likelihood that they will become alcoholic. NIAAA is encouraging studies to better
understand this vulnerability. This includes the development of nonhuman primate models to
study the adolescent period, which is quite short in rodents.
Neuroscience research provides basic knowledge needed to begin designing medications
for potential use as therapeutic agents. The program encourages development of lead
compounds for eventual testing in clinical studies.
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 family therapy. Adolescent treatment deserves special
emphasis since fewer clinical trials of adolescent treatment have been done than of adult
therapies. One initiative is a cooperative grant evaluating optimal combinations of
behavioral/psychological therapies and medications.
Community Prevention Trials. NIAAA supports an integrated group of
community-based controlled prevention trials. The problems to be prevented include
alcohol-related trauma, underage drinking, and drinking and driving. All the trials test
the impact of environmental interventions (e.g., enhanced law enforcement and community
coalitions). One project tests a school- and parent-based intervention, while others test
media advocacy strategies or traditional mass media. Experimental and quasi-experimental
designs are used. Two studies evaluate the effectiveness of naturally occurring
interventions using the methodologies of natural experiments. Results to date indicate
that community strategies that focus on schools, parents, and the community. Also, enduced
law enforcement, media and educational campaigns, and public/private collaboration can
significantly reduce drinking and driving, related driving risks, and traffic injuries and
death.
National Alcohol Research Centers
Program. NIAAA administers 14 diverse Alcohol Research Centers nationwide through
the institute's National Alcohol Research Center Grants Program. This program is
interrelated with and complementary to all other research support mechanisms and
scientific activities that investigate the causes, diagnosis, treatment, control,
prevention, and consequences of alcohol abuse and alcoholism. The program provides
long-term (typically 5 years) support for interdisciplinary research that focuses on
particular aspects of alcohol abuse, alcoholism, or other alcohol-related problems. This
program encourages outstanding scientists from many disciplines to provide a full range of
expertise, approaches, and advanced technologies for developing knowledge in these areas.
A primary goal of any NIAAA-funded center is to become, through excellence in science
research, a significant regional or national research resource. In addition, each center
affords research training opportunities for persons from various disciplines and
professions. Current areas of alcohol center focus are the genetic determinants of alcohol
ingestion; epidemiology of alcohol problems; environmental approaches to prevention;
effects of alcohol on cellular neurobiology; alcohol and the cell; etiology and treatment
of alcohol dependence; alcohol and aging; genetic approaches to the neuropharmacology of
alcohol; biobehavioral manifestations of adolescent alcohol abuse; genetics of
neuroadaptation to ethanol; clinical and medical epidemiology; and etiology and
pharmacological treatment of alcoholism.
Intramural Research
The overall goal of the NIAAA Intramural Research Program 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.
Studies on the effects of ethanol on cell membrane receptors, ion channels, and
expression of genes coding for these important proteins are yielding intriguing insights
into basic mechanisms of ethanol’s action. Combined with studies on region specific
effects of ethanol on the release of neurotransmitters, these investigations will
elucidate how ethanol produces reward, dependence, tolerance, and brain damage. Behavioral
studies on animals, using mainly mice and monkeys, combined with molecular genetics and
behavioral manipulations during development, examine important protective and causal
factors for alcohol abuse and dependence.
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 inpatient ward and a large outpatient program are located in
the NIH Clinical Center.
Genetics of Alcoholism. This research focuses on investigating the genetic
determinants of the risk for alcoholism. Studies on impulsive and violent alcoholics show
that there is a clinical subgroup of alcoholics with polydrug abuse and antisocial
personality features who also display deficits in serotonin function. The goal of this
research is to understand how natural variants of genes involved in serotonergic
neurotransmission affect human behavior. Two approaches are used: molecular cloning and
expression studies of genes involved in serotonin function, and intensive behavioral and
neuropsychological studies of human families and animal strains with natural variants of
serotonin genes.
In conducting this research NIAAA scientists examine a variety of populations to
determine how genetics and environment interact in the development of alcoholism and
concomitant psychopathologies including drug abuse, antisocial personality, anxiety, and
mood disorders. Techniques include family transmission studies and genetic linkage
analyses using selected candidate genes and a large number of polymorphic markers.
To identify genes for complex, heterogeneous psychiatric diseases, it is helpful to
define genetic characteristics which could correlate more precisely with genotypes.
Neurophysiologic differences in alcoholism may serve this purpose these differences
include a diminished amplitude of a specific electrophysiological trait--called the P300
evoked potential--and the low voltage alpha component of the electroencephalogram.
Approaches include family transmission studies and a genetic linkage study to map the
genes determining the variants. Psychiatric interviews are conducted to correlate
neurophysiological phenotype with clinical phenotype and behavior.
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.
International Activities
The Office of Collaborative Research Activities initiates and fosters collaborative
activities with other NIH institutes, government agencies, and other organizations
interested in alcohol-related problems. These activities include cosponsorship of
workshops and research projects as well as efforts to disseminate research findings. The
office administers and manages an international program to further the institute’s
domestic goals.
Mutually beneficial collaborative research efforts have been developed with other
countries and international organizations. Research information is exchanged on a regular
basis with over 30 countries. This office also coordinates the institute’s science
education initiative. Special projects in collaboration with educators of K-12 students
are in progress.
Among its many recent collaborative national and international activities, NIAAA has
cosponsored projects with other institutes and organizations studying birth defects, liver
disease, AIDS, women’s health, minority health, aging, and health services research.
NIAAA has supported sicentific eschanges to increase the research capability of scientists
in several foreign countries or to support collaborative research with grantees. The
institute has responded to requests for joint research efforts, developed productive
cooperative projects, or supported grantees to work with scientists in Finland, Poland,
Mexico, Russia, the Czech Republic, Canada, Spain, and many other countries.
Research Dissemination
NIAAA maintains an active communication program aimed at sharing with health care
practitioners, policy makers, others involved in managing alcohol-related programs about
research findings with applicability to alcohol treatment and prevention efforts, and the
general public. Our scientific communications vehicles include publications such as:
- Special reports to Congress on alcohol and health, triennial reports from the
secretary of Health and Human Services to the Congress, which describe research findings
and advances in the alcohol field;
- Alcohol Health & Research World, a quarterly peer-reviewed journal
available by subscription;
- Alcohol Alert, a publication designed to quickly disseminate research findings to
health professionals; and
- Monographs on special topics or containing papers from NIAAA-sponsored workshops on
critical research areas such as women and alcohol, and alcohol and the cardiovascular
system.
- Public education materials such as brochures, pamphlets, and fact sheets that provide
information on various topics.
Research findings are also shared with the alcohol and general health care communities
through two online database services supported by the institute. The first of these, the
"Quick Facts" electronic bulletin board, provides access to alcohol-related
epidem-iologic data and facilitates communication among NIAAA staff and others interested
in NIAAA programs and data.
Scientists, clinicians, and others interested in alcohol-related research also have
direct access to NIAAA’s comprehensive "Alcohol and Alcohol Problems Science
Database" through Ovid Technologies, Inc.--a commercial vendor and through the
NIAAA's home page on the World Wide Web (http://etoh.niaaa.nih.gov). The database title is
ETOH, named after EtOH, one of the chemical designations for ethyl alcohol. ETOH covers
literature from the late 1960’s to the present, contains over 100,000 bibliographic
records, and covers all aspects of alcohol research: psychology, psychiatry, physiology,
biochemistry, epidemiology, sociology, neuroscience, treatment, prevention, education,
accidents and safety, criminal justice, legislation, employment, labor and industry, and
public policy. The database also contains entries on books, monographs, government
reports, dissertations, and conference papers.
Currently, NIAAA’s WWW features publications (many available as full text
documents), news releases, grant and contract information, frequently asked questions, and
other alcohol-related resources.
