|
|
|
 |
|
|
DEPARTMENT
OF HEALTH AND HUMAN SERVICES
|
| 2001
Actual |
2002
Appropriation |
2002
Current Estimate |
2003
Estimate |
Increase or Decrease |
|
| Current Law BA | $340,537,000 | $384,238,000 | $384,071,000 | $416,773,000 | $32,702,000 |
| Accrued Costs | 1,740,000 | 1,875,000 | 1,875,000 | 1,714,000 | (161,000) |
| Proposed Law BA | 342,277,000 | 386,113,000 | 385,946,000 | 418,487,000 | 32,541,000 |
| FTE | 231 | 262 | 262 | 261 | (1) |
This document provides justification for the Fiscal Year 2003 activities
of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), including
HIV/AIDS activities. A more detailed description of NIH-wide Fiscal Year
2003 HIV/AIDS activities can be found in the NIH section entitled "Office
of AIDS Research (OAR).
The President's appropriations request of $418,487,000 for this account includes current law adjusted by assuming Congressional action on the proposed Managerial Flexibility Act of 2001.
Introduction
Second only to tobacco, alcohol is among the most abused substances in the United States. Alcohol abuse and alcohol dependence cost U.S. society an estimated $185 billion annually, according to the 1998 update of The Economic Costs of Alcohol and Drug Abuse in the United States, 1992 (a publication of the Department of Health and Human Services, National Institutes of Health).
Unlike other drugs of abuse, alcohol can damage any tissue in the body, with major consequences. It not only injures the brain, resulting in changes in its functions, but also damages other organs and systems. For example, alcohol damages the liver and alters functions of the immune and endocrine systems, with far-reaching effects.
The mission of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) is to develop optimal prevention and treatment strategies for alcohol-use disorders, as well as their medical consequences. As part of this mission, we disseminate our findings to clinicians and the public, to ensure that our results reach people who suffer from alcohol-use disorders or are at risk of developing them.
The Basis of Alcohol Research
Alcoholism is caused by a variety of factors, both biological and psychosocial. In the genetic arena, scientists now know that about half of the risk for alcoholism can be attributed to multiple genes. These genes produce key substances in biochemical pathways that contribute to drinking behaviors and physiological responses to alcohol, such as organ damage, including brain damage, and the lasting injuries alcohol inflicts on the fetal nervous system. Among our most important work is elucidation of the many physiological steps in these pathways and identification of the genes involved in them. We are making significant advances in our understanding.
In the nervous system, alcohol can trigger "hardwiring" changes that lead to physical dependence. These changes in brain function lay the physiological foundation for the behaviors of alcoholism, and involve nerve-cell responses at the genetic, molecular, and cellular levels. We have responded to the challenge of integrating findings from these many levels of research by establishing the Integrative Neuroscience Initiative on Alcoholism (INIA). This collaborative, interdisciplinary consortium ensures that we optimize the utility of data from diverse sources, to enable us to fully understand the physiological bases of alcoholism and their consequences. Within the cascades of biological events that we thus identify lie points of opportunity; for example, proteins we could pharmaceutically block so that alcohol no longer affected their actions.
Equally important is the study of psychosocial factors, since environment plays a role in moderating or exacerbating the biological influences that predispose people to alcohol-use disorders. We identify these factors and design interventions not only at the individual level, but also at the community and policy level, to change environments conducive to inappropriate drinking -- through outreach programs or policies that regulate youths' access to alcohol, for example.
On this broader scale, our
prevention research includes social and policy issues. For example, drinking
among college students is a complex problem entrenched in campuses and
communities. Minority groups provide another example. Certain minority
groups appear to respond differently to alcohol, physically and behaviorally,
than does the general population. Our epidemiology research identifies
these kinds of public-health issues, and these findings lead to basic
and behavioral research that investigates root causes and potential interventions.
Outreach
We bring our research findings to the public in a variety of ways. Our Research to Practice Initiative is an excellent example. In collaboration with the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment, we arrange with States to engage their treatment providers and administrators. After exchanging information about our current research findings and the practitioners' obstacles to providing treatment, we place experts in temporary residencies in treatment programs that have identified specific areas of need.We bring our findings to the public via Alcohol Screening Day, a nationwide event that enables people to receive free screening for alcohol problems and, if needed, referrals. We also are dealing with the difficult issue of college drinking through our Advisory Council's Subcommittee on College Drinking. The Subcommittee, a collaboration between researchers and college presidents, has been meeting since 1998 and has commissioned 23 papers and developed two panel reports to determine how to prevent drinking by students.
Drinking by youth is not limited to college students, and we are reaching children and adolescents through our Leadership to Keep Children Alcohol-Free. Thirty-three State governors' spouses have joined this project to reduce drinking by young people; a crucial effort, given our research findings that early initiation of drinking portends higher risk of alcoholism later in life. We also are preparing to release public service announcements on underage drinking.
This report presents highlights
of some of our accomplishments of the past year and describes how we can
build on previous findings to advance further toward effective prevention
and treatment.
|
Story
of Discovery Free radicals are molecules that perform important beneficial functions in our bodies, but that also can wreak biological havoc in us. Under certain conditions, they contribute to a host of illnesses. Among them is alcoholic liver disease (ALD), which accounts for about half of all deaths from cirrhosis, the tenth leading cause of mortality in the U.S. Alcohol researchers have built on decades of work on free radicals (and other mechanisms that contribute to ALD) to reach a better understanding of how to prevent alcohol's devastating effects on the liver. Our own bodies make most free radicals from oxygen, as a normal byproduct of metabolism. Fortunately, our cells also make antioxidants, substances that neutralize free radicals. When free radicals form in excess of our antioxidants' ability to neutralize them, however, tissue damage ensues. Alcohol is among the substances that triggers formation of free radicals, which are molecules that have an extra, unpaired electron. The unpaired electron is very reactive and can disrupt chemical bonds that hold other molecules together, changing their structures and functions. The changes in these altered molecules can lead to unpaired electrons in them, too, leading to disruption of yet more molecules, and so on. This chain reaction is beneficial to some biological systems, but destructive to others, some of them critical. Antioxidants counteract these activities by taking unpaired electrons from free radicals. Certain enzymes (proteins that regulate the timing and placement of chemical reactions) serve this protective antioxidant function, but other enzymes generate free radicals, instead. Alcohol damages the liver not only by stimulating production of free radicals, but also by inhibiting liver cells' antioxidant production. |
|
Building on the Background
Other scientists would add to the picture of the devastating damage free radicals can cause. They soon found that free radicals damage DNA, leading to genetic mutations, and, later, that free radicals damage proteins that regulate hundreds of crucial activities in cells, causing the cells to function abnormally. Scientists had found that free radicals cause tissue damage, and where, but a critical question remained: How to prevent it. In the 1970s, scientists made a discovery that would lay the groundwork for answering this question, and research on free radicals surged. They found that an enzyme, superoxide dismutase (SOD), removed a specific free radical from biological systems. The researchers now had a tool enabling them to conduct experiments to find out if they could remove free radicals to protect tissues from damage. In the 1980s, scientists made a major leap with the discovery that blood-starved tissues - the kind of damage seen in heart attacks - sustain additional damage when blood flow is restored to them. The flush of restored blood brings with it a new burst of oxygen, whose metabolism causes a surge of free radicals to form. Scientist found that giving antioxidants attenuated the damage. Focus on Alcohol In the alcohol field, researchers knew that some type of association existed between alcoholic liver disease (ALD) and free radicals. What they didn't know was how alcohol increased free-radical production and whether free radicals were a cause or an effect of ALD. Evidence that free radicals play a major role in causing ALD is mounting. In the 1980s, alcohol researchers developed animal models to show that, at the whole-organ level, the association between ALD and free radicals existed. Other research suggested that one of the systems through which alcohol increased free radicals might involve enzymes, including one called "CYP2E1" that metabolizes alcohol. Further investigations showed that when CYP2E1 metabolizes alcohol, free radicals do form, and that cells make more CYP2E1 on exposure to alcohol. These findings were very suggestive, but scientists needed to link them more directly to strengthen the case for a cause-and-effect association between free radicals and ALD. That study came about 10 years ago, when alcohol researchers injected into the main cells of the liver, in vitro, the gene that produces CYP2E1, causing the cells to make the enzyme. When the scientists incubated these CYP2E1-producing liver cells with alcohol, the cells produced more free radicals and sustained damage. The investigators thus more directly linked alcohol with free-radical production and liver damage at the cellular level. They went even further: Adding antioxidants to the liver cells attenuated injury and reduced levels of free radicals. |
|
Strengthening the Connection
In recent years, investigators conducted four studies that greatly strengthened the evidence that free radicals are a cause, not an effect, of ALD. The collective strength of the studies is that they used four different approaches that independently reached the same conclusion: Alcohol-induced free-radical production activates biological mechanisms that lead to liver injury. In each of the studies, researchers gave animals alcohol for extended periods, which normally triggers free-radical production. This time, however, the scientists either blocked enzymes that generate free radicals in the liver, boosted the animals' ability to produce antioxidant enzymes, or restored depleted levels of the animals' own naturally occurring antioxidants by giving them antioxidant precursors. The scientists used four different genetic or pharmacological techniques to achieve these effects. Each of these interventions reduced free-radical production, attenuated mechanisms in the biological chain of events through which free radicals damage the liver, and reduced liver injury itself. The Final Word? This one mechanism of alcohol-induced liver injury, free-radical formation, is not the sole vehicle for alcohol's liver damage, and antioxidants might not be a magic bullet, especially if used indiscriminantly, without medical supervision. Neither free radicals nor antioxidants operate in a vacuum; they interact with other biological systems, and antioxidants have their own negative effects, under certain circumstances. What these decades of research have produced is not the final word on how to prevent and treat ALD, but major strides in getting there. Through this body of work, particularly the research of the last decade, free radicals are emerging as a principal vehicle through which alcohol damages the liver, and antioxidants look increasingly promising as a potential treatment. |
Science Advances
Shared
Pathology Appears to Precede Early Drinking, Alcoholism,
and Other Behavioral Disorders
NIAAA researchers recently discovered a striking association between early age at first alcohol use and development of alcoholism at some point in life. This finding raised another question: Is early alcohol use per se a cause of alcoholism, or are both alcoholism and early initiation of drinking reflections of some other childhood vulnerability that underlies a variety of subsequent problems? A new study shows that early age at first drink--11 to 14 years of age-- correlates with a number of signs of psychopathology and behavioral disorders, such as attention-deficit disorder and impulsiveness, that appear in early childhood, before the first drinking experience. In addition, adolescents who began drinking early were more likely than others to have reduced amplitude of a brainwave called "P3," an abnormality that serves as a marker of risk of alcoholism. The latter finding suggests that the common vulnerability that appears to underlie these various problems may be, at least in part, physically based.
A particularly suggestive aspect of the new findings is that the signs of psychopathology and impulsive behaviors researchers measured -- signs like nicotine and drug dependence, antisocial personality disorder, and behavioral conduct disorder -- predicted which 11-year-olds would try alcohol by age 14. This indicates that these behaviors pre-dated the early drinkers' alcohol use, strengthening the case for a common vulnerability that underlies a range of problems, including both early drinking and alcoholism.
Even though these findings suggest a common basis for an array of problems, they don't necessarily exclude early drinking itself as a factor that contributes to development of alcoholism. In addition, young people who drink are at risk of the harm associated with drunk driving, risky sexual behavior, and violence, regardless of why they drink. Other research also suggests that alcohol interferes with neurological development in adolescents. For these and other reasons, preventing children from drinking remains paramount. The challenge these findings raise for researchers is to definitively establish that there is a common basis for the wide range of problems examined in this study and to identify the mechanisms that underlie it. In so doing, they will identify potential targets for pharmaceutical or behavioral interventions.
Hepatitis G Virus Improves Survival Rate of People with HIV
Because alcohol is a major cause of liver damage, alcohol researchers conduct studies on hepatitis -- a liver disease -- and related issues. Alcohol researchers now report that people infected with both human immunodeficiency virus (HIV) and hepatitis G, an apparently harmless type of hepatitis virus, survive longer than people infected with HIV alone. The in vitro part of their study showed that hepatitis G virus keeps HIV from making copies of itself in the kind of immune-system cells (mononuclear cells) where HIV usually replicates.
Hepatitis G infection is common among people with HIV. In this 4-year follow-up of HIV patients, 56.4 percent of those without hepatitis G died, compared to a considerably smaller number, 28.5 percent, of those who had concurrent hepatitis G infection.
When HIV multiplies in mononuclear cells, it prevents them from performing their normal function: fighting a variety of bacteria and viruses. The researchers who conducted this study found that, in hindering HIV's ability to replicate, hepatitis G doesn't appear to damage mononuclear cells or prevent them from making proteins crucial to their function.
Previous, smaller studies, primarily of HIV-infected hemophiliacs, suggested that hepatitis G slowed the progression of HIV disease. This much larger study, which was reported in the New England Journal of Medicine1, examined survival rates, instead of HIV disease progression, and included subjects who had been infected with HIV by any one of a number of modes of transmission. The lower mortality among people co-infected with HIV and hepatitis G held true regardless of mode of HIV transmission, type of HIV treatment, age, race, sex, or severity of HIV disease at the outset of the study (as measured by relative depletion of certain immune indicators; that is, CD4+ count).
In previous studies of hepatitis G, this virus hasn't resulted in illness or death, and the Food and Drug Administration does not require that blood donors be screened for it. Once we know the mechanisms through which hepatitis G inhibits HIV replication, we can attempt to design pharmaceuticals that mimic the desired components of hepatitis G's actions.
Choline, Growth Factors Prevent Alcohol's Brain Damage in Mammal Fetus
Alcohol is, by far, the greatest inducer of birth defects, compared with any of the illegal drugs in use today2. It causes fetal alcohol syndrome (FAS) in some children of women who drink during pregnancy, which results in life-long, debilitating neurological damage and behavioral deficits. At present, no treatments exist for infants exposed to alcohol through maternal drinking. Two new findings suggest potential avenues for treating FAS children while they're still in the uterus or after birth.
For the first time in a living mammal model, scientists have shown that genetic manipulations that increase production of nerve growth factor protect a fetal brain region normally sensitive to damage from alcohol. Nerve growth factor is among the substances that regulate survival of fetal brain cells and their differentiation into specialized cells of the nervous system. Alcohol interferes with these developmental processes.
Increasing other neurological growth factors may prove to protect other alcohol-sensitive fetal brain regions. If we find that this is the case, we may be able to develop therapeutic in-utero treatments that maintain effective levels of these growth factors.
Scientists also have new evidence, in an animal model, that it may be possible to offset at least some of the neurological deficits of FAS after birth. Scientists fed pregnant rats alcohol, then gave their offspring supplements of choline -- an essential nutrient, in humans -- for 3 weeks after birth. This period corresponds to the third trimester of human pregnancy, during which important developmental neurological events, including a "brain-growth spurt," occur. Baby rats that got choline supplements performed learning and memory tasks better than those that didn't get supplements. The benefits of choline were long-lasting and may be permanent.
Choline and the by-products of its metabolism are known to perform important functions in the nervous system. They're among the factors that enable nerve cells to send electrical messages to each other, to help regulate memory and muscle control. They contribute to cells' ability to send and receive chemical messages to and from each other and their environments. Choline also plays a role in the integrity of the membrane that surrounds nerve cells, which enables the cells to perform crucial functions.
Boosting Gene's Level in Specific Brain Area Reduces Alcohol Consumption
Scientists temporarily increased levels of the gene that makes the protein DRD2, in a specific area of the brain, causing rats to temporarily overproduce the protein. During this period of DRD2 overproduction, the rats -- even those that had been bred to have a preference for alcohol - voluntarily reduced the amount of alcohol they drank by a substantial amount. Alcoholics have lower-than-normal levels of DRD2 in their brains, and, with this finding, we have evidence that strategies to increase DRD2 levels may one day have therapeutic potential for alcoholism. While the methods used in this study - delivering the gene for DRD2 into the brain via a partially inactivated virus - can't be used in humans, it offers preliminary evidence that future, refined methods of increasing gene levels may one day have utility in reducing drinking.
In both rats and humans, DRD2 acts as a receptor, on nerve cells, for chemical messages conveyed by the neurotransmitter dopamine, one of the mechanisms through which nerve cells communicate with each other. Dopamine is thought to be among the substances that mediate alcohol's rewarding effects in the nervous system, and DRD2 is thought to be the receptor that "receives" and transmits these effects among nerve cells. Alcohol is known to alter dopamine levels in the nucleus accumbens, an area of the brain that appears to be a key locus of alcohol's addictive actions. The scientists who conducted this study delivered DRD2 genes only to this specific region.
Because the neurotransmitter system in which DRD2 is involved is just one of a multitude of biological systems that contribute to the brain's response to alcohol, scientists can't simply say that forcing the gene for DRD2 to overproduce it is the answer to alcoholism. A number of these other systems also are undergoing intensive study and are potential candidates for strategies to reduce alcohol use. By identifying these systems and adding to the picture of how they interact with each other to lead to alcoholism, researchers are discovering points for intervention.
Alcoholics Have Changes in Brain's "White-Matter" Genes
Chronic alcohol use sometimes causes shrinkage of the frontal lobe of the brain, a result of alcohol-induced loss of the brain's "white matter." This white matter, myelin, is a kind of insulation that wraps around certain nerve cells, to enable them to transmit electrical messages at the speed required. Researchers now have found that alcoholics have markedly decreased activity of the genes that produce myelin proteins in the brain's frontal lobe.
The portion of the frontal-lobe that the researchers examined, the cortex, plays an important role in decision making and judgment, functions that often are impaired in alcoholics. The changes that the researchers found in the myelin-producing genes of this region appear to be among the mechanisms through which alcohol exerts its toxic effects on brain cells.
Investigators arrived at these findings by applying a recent genetics technique, microarray technology, which detects changes in activity of thousands of genes at once, to autopsy samples from the frontal cortices of alcoholics and nonalcoholics. In 163 of the 4,000 genes studied, activity differed by 40 percent between the two groups, with pronounced reduction of activity of the myelin-producing genes.
Whether alcohol directly affects
myelin-producing genes or disrupts other factors that contribute to the
normal function of these genes remains to be determined.
1Xiang J, Wunschmann S, Diekema J, Klinzman D, Patrick KD, George SL, Stapleton JT. Effect of Coinfection with GB Virus C on Survival Among Patients with HIV Infection. New England Journal of Medicine, 345(10). 2001.
2Report by the Institute of Medicine. Fetal Alcohol Syndrome: Diagnosis, Epidemiology, Prevention, and Treatment, National Academy Press, 1996.
New Initiatives
Medication Development for Alcoholism Treatment - Medications recently identified by alcohol researchers have been successful in treating alcoholism in some people, but not in others. Among the most urgent needs in alcohol research is development of medications that are effective in a broader range of people. Medication development is a complex process that spans a wide range of activities, from basic science to clinical research, at the genetic, molecular, cellular, animal, and human levels. We are establishing an initiative that will discover new pharmacological agents to treat alcoholism and alcohol-related diseases, and will clinically test the compounds that show promise.
Research to identify the molecular sites of alcohol's actions will be crucial to this initiative. Scientists will develop agents that target these molecular sites, and will test them in in vitro, animal, and human laboratory studies. Investigators will test currently available compounds, synthesize new ones, and determine what makes successful agents work, in order to apply these characteristics to synthesis of improved versions.
Prevention of Alcohol Abuse on College Campuses - Alcohol consumption by college students results in deaths, injuries, crimes, and sexual assaults. It disrupts the lives and studies not only of students who drink, but also of their nondrinking peers, and has a negative impact on the college environment and surrounding community. We are undertaking an initiative that will (1) provide a better understanding of how and why alcohol-related problems develop among college students, through epidemiology and natural-history studies, and (2) develop improved preventive interventions.
To identify cost-effective prevention strategies, investigators will conduct randomized, controlled trials at multiple campuses, as follows: (1) Researchers will test combinations of environmental and policy strategies and those that focus on high-risk individuals and groups. (2) Research on studies of promising interventions already put in place by campus administrations will continue. (3) Colleges are adopting preventive interventions proven effective through replication. Researchers will evaluate these interventions' effectiveness in new campus environments and more diverse student populations.
Advanced Instrumentation for Alcohol Research - Advanced instrumentation is critically important to furthering our understanding of how alcohol causes diseases in major organs, including the brain, and the development of alcohol dependence. We know that several physiological processes form the underpinnings of alcoholism, but we do not yet know how these processes develop at the molecular level.
Certain instruments will enable scientists to examine directly alcohol's interactions with the brain's neurotransmitter systems, which are significantly affected by alcohol, in real time. In so doing, researchers can couple molecular events with behavioral events. This kind of direct examination can be conducted only with advanced instruments, including nuclear magnetic resonance (NMR) equipment (4.7 T medium bore NMR for functional nuclear magnetic studies of primates, small-bore large NMR for functional NMR studies of rodents, and small-bore positron-emission tomography - miniPET instruments). New "proteomic" equipment can identify specific proteins that genes in the brain and other organs produce as they adapt to the presence of alcohol. Proteomic studies require advanced mass spectroscopic instruments.
FAS: A Multi-site, Collaborative Initiative on Fetal Alcohol Syndrome - Children with fetal alcohol syndrome and alcohol-related neurodevelopmental disorder have serious neurological deficits and other physical problems that impair daily function and often persist throughout life. In the U.S., these conditions primarily affect Native Americans, Native Alaskans, and African Americans. To develop preventive therapies and treatments, researchers must identify the molecular mechanisms through which alcohol damages the fetal nervous system, and correlate these damaged areas with behavioral deficits. Recent technologies make this goal attainable. A NIAAA initiative will support individual investigators, multi-site collaborations, and collaborations between basic-science investigators and clinical scientists in FAS research. This initiative will ensure that laboratory findings reach the clinical research setting and that they reach the populations most affected.
Emerging biomedical technologies (non-invasive imaging, microarrays and targeted gene delivery) and newly developed neurobehavioral assessment techniques will accelerate research aimed at (1) preventing alcohol's molecular actions in the fetal nervous system from damaging it; (2) treating or reversing alcohol-induced damage once it has occurred; and (3) interventions for affected children.
Genetic Studies of Vulnerability to Alcohol - A number of steps in biochemical pathways of the brain that influence the development of alcoholism have not yet been identified. Our goal is to identify genes that hold the blueprints for proteins that mediate these steps. A new NIAAA initiative consists of two complementary approaches to meeting this goal, as follows. The proteins thus identified will provide new targets for development of improved strategies to prevent and treat alcoholism and alcohol-induced tissue damage.
(A) One method of identifying these genes is to determine which genes differ between alcoholics and normal subjects. A new mapping method, linkage-disequilibrium scanning, pinpoints the locations of these genes accurately enough that they can be individually tested for their influence on alcoholism. The new initiative will use linkage-disequilibrium scanning in large samples of alcoholic control subjects and capitalizes on resources that have been developed or are about to become available. Linkage-disequilibrium scanning has been made possible by the availability of several very large samples of subjects already evaluated for alcoholism, along with their DNA samples; a genome-wide map of 3,000,000 single nucleotide polymorphisms (SNPs); and new methods for genetic typing (MALDI-TOF) that are orders of magnitude faster and cheaper than older methods.
(B) Another method of identifying the genes in question is to inactivate selected genes and observe how this inactivation affects the animals' behavioral responses to alcohol. The proposed initiative will conduct these kinds of gene-knockout studies of alcohol-related behaviors in rats. Similar gene-knockout studies have been conducted in mice; however, their usefulness is limited by our relatively modest understanding of mouse behavior, neuroanatomy, neurochemistry, and neurophysiology. Our understanding of these subjects is much better-developed in rats. NIH has funded the development of gene knockout technology in rats, and it is expected to become available soon.
Integrative Neuroscience Initiative on Alcoholism (INIA) - When nerve cells are chronically exposed to alcohol, their normal activities can change permanently. These changes in brain function - neuroadaptation - form the physiological basis of alcoholism, and involve nerve-cell responses at the genetic, molecular, and cellular level. We are integrating findings from these multiple levels of research on neuroadaptation through our Integrative Neuroscience Initiative on Alcoholism (INIA). As described on page 2 of this document, INIA is a collaborative, interdisciplinary consortium that enables us to optimize the utility of data from diverse sources, to enable us to fully understand the physiological basis of alcoholism. Our goal is to generate information that will lead to development of therapies that target optimal points for intervention.
Recent neuroscience advances will enable us to expand INIA, to conduct research that will address major barriers to progress. One of our most pressing needs is to obtain a "road map" of the anatomy of neural circuits, networks of nerve cells involved in neuroadaptation. New techniques can identify and define anatomical connections between nerve cells, the synapses involved in neuron-to-neuron communication. This research will identify the neural circuits and pathways that alcohol activates. The results will be crucial in describing neuroadaptive changes in communication, among nerve cells, that lead to alcohol dependence.
The INIA expansion also will fill our need for neurocomputational and theoretical modeling (recently made possible by computer-based advances) that can predict neuroadaptive responses to alcohol. These models will enable us to incorporate experimental data, allowing us to analyze simulations of alcohol-induced changes to brain structure and function.
Biomarkers of Alcohol-Induced Tissue Injury - Excessive alcohol use can damage any type of tissue in the body, making it unique among substances of abuse. Medical consequences include liver disease, some kinds of cancer, immune suppression, brain damage, heart-muscle damage, and birth defects. Clinicians and researchers need reliable biomarkers for detecting alcohol-induced changes in cellular parameters that initiate tissue injuries. The lack of objective measures to detect the earliest stages of disease hinders diagnosis, prevention, and treatment. Development of such biomarkers is a high priority in alcohol research.
The goals of this initiative are to (1) identify metabolic changes that precede clinically detectable signs of alcohol-induced tissue damage, (2) develop genetic biomarkers that predict susceptibility to organ damage and fetal injury, and (3) link indicators of initial damage to development of frank disease.
Dysfunction in several cellular processes implicated in alcohol-induced medical disorders provide a number of opportunities for identifying biomarkers. These processes include production of biologically damaging molecules called "reactive oxygen species"; modification of hormones, by-products of metabolism, and fat-and-protein particles that perform crucial physiological functions; and alteration of proteins that regulate cellular functions. Other processes include the immune-system's inflammatory response, which is beneficial under normal circumstances, but which, in excess, damages tissues and organs. Alcohol is associated with activation of inflammatory cells, changes in immune-system proteins involved in inflammation, and imbalances in immune cells and in the signals that regulate their activity.
Disparities in Adverse Effects of Alcohol - This initiative will identify underlying mechanisms of gender and ethnicity differences in the etiology of alcoholism and alcohol-related tissue damage. Understanding these differences is a prerequisite for developing effective treatments for alcoholism and alcohol-induced organ damage in women and ethnic minorities.
Evidence suggests that susceptibility to alcoholism and alcohol-induced organ damage is linked, in part, to gender and ethnicity. Women are more susceptible than men to alcohol-induced damage to the liver, heart, and brain. African Americans and Hispanics have higher rates of alcohol-related medical problems, including cirrhosis, pancreatitis, alcohol-related acute respiratory distress syndrome, and fetal alcohol syndrome (FAS), than do Caucasians. Native Americans have a significantly higher incidence of FAS than Caucasians and African Americans.
Alcoholism and associated behavioral disorders also are influenced by ethnicity. Some Native American groups have high rates of alcoholism and a genetically regulated neurophysiological trait that may contribute to increased risk of alcoholism. Some Asian groups are less susceptible to alcoholism because they have variations in alcohol-metabolizing enzymes. African-American alcoholics have more severe sleep abnormalities, compared to Caucasian alcoholics.
Among the goals of this initiative are to (1) determine effects of dietary differences and patterns of drinking on increased susceptibility of women and ethnic minorities to alcohol-related organ damage; (2) study genetic predisposition to alcoholism and biomedical consequences in minority populations; (3) study Native Americans, to assess behavioral, neuroendocrine, and electrophysiological risk factors for alcoholism; (4) determine whether sociocultural factors interact with genetic variations in metabolizing enzymes to produce ethnic or gender differences in drinking behavior in minority populations; (5) investigate factors that predispose African-American alcoholics to more severe sleep abnormalities than those of other populations.
Other Areas of Interest
Advancement of Behavioral Therapies - Behavioral (nonpharmacological) therapies currently are the most widely used method of treating alcohol dependence and alcohol abuse. Despite progress in success rates of behavioral treatments, we intend to expand clinicians' ability to engage, retain, and treat adults and adolescents with alcohol-use disorders by developing and testing new behavioral therapies. A new generation of improved behavioral techniques could be of use not only as stand-alone treatments, but also as therapies combined with new medications.
Mathematical Models of How the Brain Adapts to Alcohol - In recent years, neuroscientists have created highly informative computer-based models of the molecular and cellular mechanisms that underlie nervous-system function. Alcohol research would benefit greatly from using these models to simulate hypotheses of how nerve-cell adaptations to long-term alcohol use form the physiological basis of alcoholism. Ultimately, an initiative based on these techniques could lead to information about whether the nerve-cell adaptations that underlie alcoholism are preventable.
Interventions to Delay Initiation and Progression of Drinking in Adolescents - Children who experiment with alcohol early in childhood are more likely than others to develop alcohol dependence and other alcohol problems as adolescents or adults. The same is true of children with specific temperamental characteristics that manifest as conduct disorders as early as age 3. Teenagers who abuse alcohol in high school are more likely to experience alcohol problems in college. We seek to test preventive strategies in (1) children with conduct disorders and (2) children and teenagers who already have experimented with alcohol, who are less responsive than others to school- and family-based prevention programs.
Alcohol's Effects on Neurotransmission - New discoveries in neuroscience now enable researchers to investigate an understudied, but crucial, aspect of alcohol's effects on nerve cells. Alcohol disrupts the molecular machinery that regulates transmission of chemical messages across the gap - the synapse - between the cells. When undisturbed, this neurotransmission ensures normal information-processing by the brain. Most research in the alcohol field has focused on mechanisms at the receiving end (postsynaptic terminal) of the chemical messages. However, mechanisms that regulate the source of the messages, at the presynaptic terminal, are equally important. New discoveries will enable us to conduct research on long- and short-term changes that alcohol causes in the presynaptic terminal. Gaining a complete picture of how alcohol disrupts the neurotransmission process is essential, since this disruption leads to physiologic adaptations, in nerve cells, that underlie alcoholism.
Genetic Studies in Invertebrates; a Link to Mechanisms of Human Alcohol-Related Behavior - Since about half of the risk for alcoholism is genetic, one of our most important goals is to identify genes that influence this disease. Although the technology is available, we lack a cost-effective strategy that provides us with evidence that specific subsets of human genes are highly likely to predispose people to alcoholism and thus are candidates for testing. A rapid, cost-effective way of identifying human genes that merit further testing for association with alcoholism is to first identify them in invertebrates - specifically, fruit flies and nematodes, which have 60 percent of the genes known to be mutated in human disease. A number of factors support the utility and potential of this kind of research. Powerful tools for genetic studies in these species recently were enhanced by the completion of their genomic sequences. Recent completion of the human genome sequence and a genetic map of 1.4 million single-nucleotide polymorphisms have made possible, in principle, genetic association studies with all of the genes in the human genome.
Primate Studies: Alcohol's Effects on Cognition, Impulsivity, Social Behavior, and Stress - The link between dysfunction of the brain's frontal lobe and alcoholism, and a number of psychopathologies, is becoming increasingly apparent. The frontal lobe regulates cognitive functions, such as decision making and motivation, with input from the cerebellum. Because children of alcoholics tend to have the psychopathologies associated with frontal-lobe dysfunction, researchers are asking whether it is a risk factor for alcoholism. We intend to stimulate research on the frontal lobe and cerebellum and lead to strategies for treating cognitive deficits in chronic alcoholics and children at risk of alcoholism. Recent advances in neuroimaging technology and anatomical and physiological techniques now enable scientists to conduct the kind of research required, in human and nonhuman primates.
In FY 2003, NIAAA will expand its collaboration with the Substance Abuse and Mental Health Services Administration in developing its health services research portfolio to enable a more rapid translation of research findings into the delivery of substance abuse treatment and prevention services.
Budget Policy
The Fiscal Year 2003 budget request for the NIAAA is $418,487,000, including AIDS, an increase of $32,541,000 and 8.4 percent over the FY 2002 level.
A five year history of FTEs and Funding Levels for NIAAA are shown in the graphs below. Note that Fiscal Years 2000 and 1999 are not comparable for the Managerial Flexibility Act of 2001 legislative proposal.
One of NIH's highest priorities
is the funding of medical research through research project grants (RPGs).
Support for RPGs allows NIH to sustain the scientific momentum of investigator-initiated
research while providing new research opportunities. The Fiscal Year 2003
request provides average cost increases for competing RPGs equal to the
Biomedical Research and Development Price Index (BRDPI), estimated at
4.0 percent. Noncompeting RPGs will be funded at committed levels which
include increases of 3 percent on average for recurring direct costs.
Future promises for advancement in medical research rest in part with new investigators with new ideas. In the Fiscal Year 2003 request, NIAAA will support 247 pre- and postdoctoral trainees in full-time training positions, the same number as in FY 2002. Stipend levels for NRSA trainees will increase by 4 percent over Fiscal Year 2002 levels.
The Fiscal Year 2003 request includes funding for 15 research centers, 112 other research grants, including 85 clinical career awards, and 49 R&D contracts. The R&D contracts mechanism also includes support for 9 contracts for the Extramural Clinical and Pediatric Loan Repayment Programs. Intramural Research and Research Management and Support receive increases of 9 percent over FY 2002.
The mechanism distribution
by dollars and percent change are displayed below:
National Institute on Alcohol Abuse and Alcoholism
SIGNIFICANT
ITEMS IN HOUSE AND SENATE
APPROPRIATIONS COMMITTEE REPORT
FY
2002 House Appropriations Committee Report Language
(H.R.
Report 107-229)
Item
Alcohol-Induced Liver Disease -- Alcoholic liver disease remains a major cause of morbidity and mortality in the United States. The development of effective interventions to prevent alcoholism and/or prevent alcohol-induced liver injury would enhance health and result in savings to health care costs. The Committee encourages NIAAA, in collaboration with NIDDK, to enhance research on studies of the pathogenesis and treatment of alcoholic liver disease through all available mechanisms, as appropriate. (P. 86)
Action Taken or to Be Taken
It is essential that we understand the molecular mechanisms through which alcohol damages the liver, to enable us to develop optimal treatments for alcoholic liver disease (ALD). In 2000, we funded nearly $13 million in research, which is ongoing, on chronic liver disease, in addition to conducting our own intramural research. We are expanding our work in this area. Our intramural program has a newly established Section on Liver Biology, which focuses on molecular mechanisms involved in alcoholic liver disease, with special emphasis on the role of immune-system proteins called "cytokines."
In October 2001, we issued a Request for Applications (RFA) for grants to develop treatments for alcohol-use disorders and their medical consequences, including alcoholic liver disease. Also in 2001, NIAAA sponsored a symposium on biological mechanisms through which alcoholic hepatitis develops, which has led to plans to develop a Program Announcement on this topic. We will invite NIDDK to collaborate with us in this effort. A symposium sponsored by NIAAA and the Office of Dietary Supplements has led to plans for a collaborative RFA on S-Adenosyl-L-Methonine (SAMe) as a potential treatment for ALD. The collaborators include NIAAA and NCCAM, and NIDDK will be invited to participate.
FY
2002 Senate Appropriations Committee Report Language
(Senate
Report 107-84)
Item
Alaska Native substance abuse. -- The Committee urges NIAAA to sponsor a Research to Practice Forum with the Substance Abuse and Mental Health Services Administration and the State of Alaska, to focus on bridging the gap between researchers and practitioners and translating scientific research into clinical applications, and encourages NIAAA to support the implementation of any recommendations developed at the forum. (p. 159)
Action taken or to be taken
NIAAA and SAMHSA's Center for Substance Abuse Treatment have held preliminary discussions with Alaska officials about conducting a Research to Practice Forum in their State. The first phase of the program, the Research to Practice Forum, would enable Alaskan clinical supervisors and directors to incorporate current research findings into their programs. The clinical supervisors and directors also would inform researchers about obstacles to practice in the clinical setting.
In the next phase, the Researcher in Residence program, participating sites across the State would implement recommendations from the Forum. They would identify areas of need for clinical improvement, and NIAAA staff would recruit researchers with expertise in those areas. These experts would serve residencies at the requesting sites. Based on our success in moving from Phase I to Phase II in New York and North Carolina, we expect to implement the same strategy in Alaska, with attention to cultural and environmental differences.
Item
Alcohol consumption and hepatitis C. -- It is well established that alcohol consumption in patients with hepatitis C increases the damage caused by the disease. Less well known is the mechanism by which this happens, as well as why alcohol inhibits the success of standard treatments for the disease. Both of these areas are important for dealing with this disease, and the Committee strongly encourages the Institute to pursue them both individually and collectively with other interested Institutes. (p. 160)
Action Taken or to Be Taken
Collaborative research between NIAAA's Intramural Program and NIDDK has focused on the molecular mechanism by which alcohol consumption aggravates liver injury in patients with hepatitis C. This work has revealed that an interaction between alcohol and a protein component of the hepatitis C virus synergistically activates inflammatory signals in the liver. Our intramural scientists also have discovered a mechanism by which alcohol inhibits the actions of interferon alpha, a naturally occurring antiviral protein, which may account for the resistance of alcoholic patients with HCV to interferon therapy.
NIAAA and other Institutes have joined in funding six grants, now underway, resulting from a Program Announcement (PA) on HCV infection and alcoholic liver disease, issued in 1999.
We have joined a number of other Institutes in cosponsoring two Requests for Applications (RFAs) relevant to alcohol and HCV. The first was for Hepatitis C Cooperative Research Centers; the second solicited small-business applications to develop inexpensive models for HCV research, which has been hampered by a lack of appropriate animal models and in vitro culture systems.
We also have joined other Institutes in cosponsoring multi-faceted initiatives on HCV and other infections, such as HIV; for example, the RFA entitled Viral Hepatitis and HIV in Drug and Alcohol Users.
Our outreach activities have included a Veterans Administration meeting on HCV, where we presented our initiatives on alcohol and HCV interactions. Veterans in VA hospitals have a high rate of alcohol abuse and alcoholism, and this population offers a valuable population for study. At a recent meeting of the Research Society on Alcoholism, NIAAA and other leaders in the field of alcohol research gathered to discuss the impact of alcohol use on HCV.
In 2002, we will cosponsor a consensus-development conference on HCV, which will include scientists not only from NIH, but also from other eminent research institutes. Currently, our scientists serve on the trans-NIH HCV working group that is preparing the conference. We also will sponsor a workshop on alcoholism and viral hepatitis. A program announcement, Mechanisms of Alcohol-Induced Tissue Injury, includes language intended to stimulate research on alcohol and HCV, and we will continue to support grants on this and on interactions of HIV and HCV. In addition, we have apprised NIAAA-funded investigators of the recently established NIH Hepatitis C Repository and have encouraged them not only to use the valuable resources it provides, but to contribute resources to it, for use by the greater scientific community.
Item
Alcoholic liver disease. -- The Committee recognizes that alcoholic liver disease (ALD) is a major cause of morbidity and mortality in the United States today. Developing effective interventions for this disease is of paramount importance. The Committee is pleased that the Institute has begun to focus greater attention on this problem, and it encourages NIAAA to consider sponsoring additional research on treatment. (p. 160)
Action Taken or to Be Taken
Please refer to page 1 of this document for NIAAA's response to this item regarding alcoholic liver disease.
Item
Alcohol treatment services. -- Given the rapid growth of managed behavioral health care, the Committee is concerned that more needs to be known about how alcohol treatment services are delivered under managed care arrangements and the specific characteristics of behavioral health components of health insurance plans and managed care organizations. The Committee is supportive of the NIAAA Advisory Council's comprehensive plan for health services, particularly its recommendation to prioritize research to understand the effects of managed care on treatment services. The Committee acknowledges NIAAA's progress in implementing this recommendation and encourages the Institute to consider supporting additional research in this area. (p. 160)
Action Taken or to Be Taken
We have expanded our research on how managed care affects alcohol treatment services, as our Advisory Council recommended in its report, Improving the Delivery of Alcohol Treatment and Prevention Services: A Plan for Alcohol Health Research. During the four years since the Council issued its report, in 1997, we have supported 23 grants and three contracts, at a total of more than $15.0 million, in this area of research. During FY 2001 alone, we funded 14 grants, at a total of $3.3 million. Funding for research that focuses explicitly on alcohol treatment under managed care systems has increased by 57 percent since FY 1996. Our spending on general health services research has risen by 28 percent since FY 1996.
Item
Behavioral research to identify high-risk youth. -- Studies show that people who begin drinking early in life have a dramatically higher risk of later becoming alcoholic than do those who begin later. Other studies show that personality characteristics that are evident as early as age 3 predict alcoholism in adulthood. Given these data, developing effective methods for identifying high-risk youth, as well as appropriate prevention strategies, is particularly important. The Committee urges NIAAA to expand efforts on this promising line of research. (p. 160)
Action Taken or to Be Taken
In children, certain "conduct" disorders -- impulsiveness and attention-deficit hyperactivity disorder (ADHD), for example -- and early initiation of drinking appear to be associated with greater risk of alcohol problems at some point in life. Our goal is to prevent initiation and progression of drinking among adolescents, to prevent them from developing alcohol-related problems in youth and adulthood. We recently expanded our research in this area. Currently, we are funding a longitudinal study that will relate a diagnosis of ADHD in young children to development of drinking problems in adolescence or young adulthood. A previous NIAAA-funded study, Project Northland, significantly prevented drinking in a population of rural youth. We are now funding a major study that will test Project Northland's effectiveness in economically and ethnically diverse urban neighborhoods. In addition, we are planning workshops that will assess specific needs for research in the following areas: (1) children with conduct disorders, (2) children of alcoholics, and (3) children and teenagers who already have experimented with alcohol, who are less responsive than others to current school- and family-based prevention programs.
Item
College drinking. -- The Committee continues its strong support of the NIAAA Advisory Council's Subcommittee on College Drinking and its efforts to create a unique dialogue among college presidents, administrators and alcohol researchers. The Committee appreciates the progress made by NIAAA in building community partnerships to help expand the research on college drinking and in developing research-based interventions for preventing the harm caused by misuse of alcohol. Further, the Committee understands that NIAAA will soon begin the first national, longitudinal survey to assess alcohol consumption and contributing characteristics of adolescents and college-age youth. The Committee encourages NIAAA to continue and expand these activities. (p. 160)
Action Taken or to Be Taken
In 2001, we added two new studies on prevention of alcohol abuse among college students to the 15 studies we currently are funding in this area. We also issued a Request for Applications for 2002, to stimulate research on the epidemiology and prevention of college drinking. NIAAA's Subcommittee on College Drinking presented research findings at the U.S. Department of Education's national conference, and notified the education field that new college-drinking publications and programs are forthcoming.
The Subcommittee compiled valuable data on college drinking during its three years of research and in 2002 will present them in publications for specific audiences. These publications will inform NIAAA and policy makers about gaps in knowledge that need to be addressed through research, to improve campus prevention and treatment programs. The publications also will provide college presidents, policy makers, and researchers with science-based advice about the effectiveness of current interventions.
Also scheduled for publication are the scientific papers that served as the basis for the Subcommittee's final report. Among them is a paper that consolidated data on this topic for the first time, revealing that drinking among college students is a larger, more destructive problem than previously known. Experts currently refer to disparate databases in describing the magnitude and nature of the problem.
With the release of the final Subcommittee report, in March 2002, we will hold a series of regional workshops, to share information and recommendations with college and university presidents. A website will provide access to the Subcommittee's findings and reports.
Item
Health disparities. -- The Committee encourages the NIAAA to place a priority on studying the disparities in risk of alcoholism and treatment availability and accessibility among various ethnic and racial groups. Additionally, the Committee urges the Institute to consider establishing a mentoring program with the specific objective of providing quality research training for all racial groups. (p. 160)
Action Taken or to Be Taken
The NIAAA recently updated its strategic plan to increase research on alcohol-related health disparities. The revised plan identifies action steps, sets timetables, and includes measurable milestones for examining differences in alcohol-related problems in minority populations. It includes actions that will engage established scientists in building minority-serving institutions' capacity to conduct alcohol research and to serve minority individuals.
In FY 2001, we awarded seven grants for studies on consumption and potential consequences of high-alcohol-content, low-cost beverages, such as malt liquor. Six projects are studying minority communities and individuals. A Request for Applications to study all of the issues in the Institute's strategic plan will result in more grant awards this fiscal year. We also plan to support more research on influence of race/ethnicity and sociocultural factors on health-services delivery and effectiveness of treatment for alcohol abuse and alcoholism.
Among our most successful mentoring efforts is the NIAAA Collaborative Minority Alcohol Research Development program, in which strong partnerships have resulted in studies at several minority-serving institutions. Similarly, our Developmental Grants for Minority Collaborative Projects requires formal mentoring relationships.
The Institute will continue to conduct workshops to attract faculty from minority-serving institutions to alcohol research. A recent component of the annual meeting of the Research Society on Alcoholism offered guidance in project development and grantsmanship. Other initiatives include programs in long-distance and face-to-face mentoring in prevention research, discussions on conducting clinical alcohol research, and sessions to stimulate collaborative projects.
The NIAAA Intramural Program will host high school, college or graduate students, and high school teachers from minority institutions, for summer projects. The teachers will be assigned to specific laboratories and will learn the basics of biological research under the mentorship of the laboratory director or other senior scientists.
Item
Multidisciplinary Approaches - The examination of alcohol misuse and alcohol use disorders must include the effective integration of multiple disciplines and strong interdisciplinary coordination. Thus, the Committee urges that sufficient funding be directed toward those endeavors which seek to apply multidisciplinary approaches to relevant questions of etiology, consequences and recovery. Specifically, the Committee urges support for efforts directed toward integrating animal and human data as well as the multiple sources of human data. (p. 161)
Action Taken or to Be Taken
Alcohol research is multidisciplinary by nature, since it examines complex responses of the nervous system at the genetic, molecular, cellular, and behavioral levels. All of these levels involve alcohol-induced changes in brain function that, in combination, lay the physiological foundations of alcoholism. To ensure that we capture and optimize the utility of data from the diverse animal and human studies required, we have established a collaborative, interdisciplinary consortium: the Integrative Neuroscience Initiative on Alcoholism (INIA). In 2002, we will issue a follow-up Request for Applications designed to attract to INIA investigators who are not currently in the alcohol field, but who have expertise in highly relevant new technologies in the areas listed above.
Item
Prevention and treatment of violence. -- The Committee is supportive of NIAAA's efforts to understand the relationships between alcohol use and violence. The Committee encourages NIAAA to consider supporting more research in this area, particularly to understand individual characteristics and environmental conditions, situations, and circumstances under which alcohol use and violent behavior are connected. The Committee also encourages the NIAAA to consider supporting additional research on the prevention and treatment of violence by persons with alcohol problems. (p. 161)
Action Taken or to Be Taken
In FY 2001, the NIAAA funded 33 grants, at approximately $8.5 million, for the study of alcohol-related violence. We continue to participate in a NIH-wide consortium, initiated in FY 2000, on reducing violence among youth and hosted a working group on alcohol-related intervention research.
Included in our ongoing and new research are several studies of the role of alcohol consumption in rape and sexual assault. The goal of this research is to develop effective intervention to prevent rape and other violent abuse in adolescent dating, in part by reducing alcohol use. A supplement to one of these studies assesses the problem among ethnically diverse populations. We also are studying alcohol's impact on decision making during marital situations that involve provocation, threat, and high levels of anger.
Several of our studies are taking environmental and community approaches to reducing alcohol-related violence. One is developing and testing a training program that will help bar managers, waiters, and waitresses reduce alcohol-related aggression in drinking environments. Another focuses on the relationships of the spatial density of alcohol outlets to alcohol-related violence.
A newly funded study is examining the influence of motherhood on the lifestyles of female gang members.
In 2001, we continued several interagency activities. We participated in a NIH-wide consortium, initiated in FY 2000, on reducing violence among youth. We also received co-funding, from NIMH, for a large grant that includes the study of alcohol abuse and other deviant and criminal behavior throughout the life-span and transmission of these behaviors from one generation to the next. The National Institute of Justice collaborated with us in publishing a special issue of the NIAAA's journal, Alcohol Research and Health, that focused on alcohol and violence.
Item
Risk and Resiliency - The Committee sees a critical need to identify adequate resources regarding risk and resiliency, including both genetic and psychosocial factors and age-appropriate education and prevention materials which can be empirically evaluated. (p. 161)
Action Taken or to Be Taken
Key questions in alcohol research are (1) what are the genetic and psychosocial factors that put people at risk of alcoholism? and (2) what are the genetic and psychosocial factors that make people resilient; that is, less likely to become alcoholic or more likely to be able to recover from alcoholism? Most of the research that we do, from genetics and molecular biology to behavioral research, contributes, directly or indirectly, to our ability to identify factors that influence risk and resiliency. In 2000, we convened a major workshop on remediation of cognitive deficits in alcoholics and children at risk. This workshop coordinated information on biological and psychological factors involved in risk and resiliency, to help establish directions for future research on these topics.
Regarding education and prevention materials, NIAAA produces a wealth of information that targets both adults and youth, specifically. For example, in addition to distributing written material to the public, we are airing public-service announcements, cosponsoring a Governors' spouses initiative on preventing alcohol abuse among youth, sponsoring a National Alcohol-Screening Day, and joining with college presidents to prevent drinking on campus. We are educating practitioners about current research findings on risk and resiliency, among other topics, at our Research-to-Practice forums.
NIAAA investigators have tested and are testing preventive interventions in schools and throughout communities. Results of these studies provide parents, legislators, and community leaders with science-based information on what kinds of educational, preventive efforts are most effective for youth and adults. For example, NIAAA-funded investigators are adapting an intervention package that proved effective in delaying alcohol use among rural adolescents for testing among youth in ethnically and economically diverse urban areas. A number of intervention studies among high-risk college students also address issues of risk and resiliency.
Item
Technology advances. -- Advances in a range of technologies, such as genetic applications and brain imaging, may benefit the study of alcoholism. The Committee encourages the NIAAA to allocate adequate funding not only for the application of these technologies, but also for providing training to current and new investigators in these technologies. (p. 161)
Action Taken or to Be Taken
We are allocating funding for advanced technologies and for training investigators in their uses. These efforts will contribute important capabilities to our Integrative Neuroscience Initiative on Alcoholism (please refer to the item regarding multidisciplinary approaches on page 7 of this document). Certain instruments will enable us to examine directly alcohol's interactions with the brain's neurotransmitter systems, which are significantly affected by alcohol, in real time. In so doing, we can couple molecular events with behavioral events. This kind of direct examination can be conducted only with advanced instruments, including recent technology that has improved the capabilities of nuclear magnetic resonance equipment. New kinds of "proteomic" equipment can identify specific proteins that genes in the brain and other organs produce as they adapt to the presence of alcohol, adaptations that form the physiologic basis of alcoholism. These kinds of studies with advanced mass-spectroscopic instruments will provide data about the structure of complex molecules - valuable information for alcohol research.
Prepared: February 2002
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
5635 Fishers Lane, MSC 9304
Bethesda, Maryland 20892-9304
Please send comments or suggestions to the .
