Members of the Committee, thank you for your concern about alcohol, drug, and mental health problems, issues that rank very high in their impact on public health and on the Nation. I thank my distinguished colleagues for their contributions in these areas and for sharing in our discussion today. I am Dr. Ting-Kai Li, Director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA).

Alcohol alone accounts for $185 billion in costs to the Nation each year, a result not only of its behavioral effects, but also of its profound potential as a toxin that contributes to cancer and other physical illnesses. Alcohol is readily available to most people and is widely and openly used, and 18 million American adults are physically dependent on this substance. Alcohol use raises not only behavioral and medical issues, but also a host of policy and industry issues. The President has requested $441,911,000 for alcohol research in his fiscal year 2005 budget.

DATA INDICATE NEED FOR SHIFT IN RESEARCH AND SERVICES

Recent NIAAA research, together with results from other studies that have enhanced our understanding of the developmental processes of adolescence, have led us to revise our entire perspective on alcohol dependence (alcoholism) and, potentially, other disorders that co-occur. Historically, alcoholism has been characterized as a disease of mid-to-late adulthood, because the disease becomes readily apparent to health professionals only after patients have manifested its multiple adverse consequences over many years. By then, the disease is usually in its late, severe, chronic form.

By contrast, new data reveal that several mental disorders and addictions commonly associated with adulthood actually have their most striking rates of onset during childhood and adolescence - the physiologically and socially vulnerable developmental years. Alcoholism, major depression and other mental disorders, cannabis dependence, and tobacco addiction tend to co-occur in a relatively short time-frame during youth. The new data strongly suggest that youth, encompassing the time of maximum vulnerability, must necessarily be the critical window of opportunity for prevention.

Hence, a coordinated shift in emphasis of the research and service communities is urgently in order, to focus on prevention and early intervention for these diseases during development. Particularly important are efforts to (1) understand how best to identify these diseases as they emerge early in life; (2) determine which prevention and treatment strategies are effective for specific populations of children and adolescents, and (3) ensure that strategies proven by research to be effective receive timely dissemination and practical application in real-world settings.

The shift in emphasis toward youth has already begun, not only in the research community, but also in the service community. At the request of Secretary Thompson, the Substance Abuse and Mental Health Services Administration (SAMHSA) has formed a government-wide group to review recommendations from a recent National Institute of Medicine report that calls for a nationwide strategy to combat underage drinking. The NIAAA is assisting SAMHSA in this effort. Other partners include the Office of Safe and Drug-Free Schools, the Centers for Disease Control and Prevention, the National Highway Traffic Safety Administration, the Office of Juvenile Justice and Delinquency Prevention, the Office of National Drug Control Policy, and the Office of the Surgeon General. SAMHSA also is a partner in NIAAA's Leadership to Keep Children Alcohol Free, which has recruited 33 Governors' spouses to spearhead a national primary-prevention campaign.

SAMHSA and NIAAA also have been collaborating on treatment for youth. In 1998, NIAAA and SAMHSA's Center for Substance Abuse Treatment signed an Interagency Agreement to cosponsor a program of research on treatment of adolescents with alcohol-use disorders. Fourteen research projects were funded under this collaborative program, the majority of which were randomized clinical studies that are in the final follow-up and initial analysis stages.

The new findings that call for this major shift in emphasis toward youth emerged independently from two major NIAAA studies that took different approaches, strengthening the validity of the results. The National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) examined age of onset of alcoholism and other disorders in the general population. The Collaborative Studies on the Genetics of Alcoholism (COGA) refined the research by focusing on people at high risk of developing these disorders.

VULNERABILITY OF CHILDREN AND ADOLESCENTS

Development is a time not only of growth, but also of vulnerability. The number and kinds of nerve cells in the brain are changing, and connections between brain cells are reforming. At the same time that this physiological upheaval is underway, when reasoned decision-making competes strongly with emotions for control of behavior, adolescents also face changes in their social roles. Taking risks - an effort to cope with these changes - is a hallmark of adolescence.

During this convergence of physiological and social transitions, adolescents make decisions that will determine their developmental trajectories for the rest of their lives. They decide how to assert their independence and how to function in social groups, for example, and they take risks and make choices that contribute largely to whether or not they will be successful in their careers and relationships.

These transitions are not pathological, per se; they are part of the developmental process required for confronting and learning the responsibilities of adulthood. We are biologically and socially compelled to go through them. It is how well we navigate them that holds the potential for pathology - for outcomes that can be the beginning of a life of well-being and achievement or of a downward spiral of compounding, adverse consequences.

Both genetic and environmental factors exert powerful influences on the success, or lack of success, with which we navigate the transitions of development. The new data offer strong, corroborated evidence that people who suffer from alcoholism, major depression, cannabis dependence, and tobacco addiction are casualties of this developmental process. Inattention to these casualties compromises our most important American resource, the future generations of our people.

Other data reveal the magnitude of these disorders, and illustrate the health and financial burden that could be reduced through effective prevention efforts. The 2002 report of the World Health Organization (WHO) lists tobacco use, alcoholism, and illicit drug use among the 10 leading preventable risk factors for years of healthy life lost to death and disability in developed countries. Tobacco and alcohol rank number one and number three, respectively. In 2001, the WHO reported that depression was the leading factor in burden of disease among adolescent and middle-age people in the U.S., Canada, and Western Europe.

ALCOHOLISM

Among these diseases, early prevention of alcoholism alone would represent a considerable reduction in human suffering and financial burden. Among adolescent and middle-age people in the U.S., Canada, and Western Europe, alcohol accounts for more than twice the burden of disease attributable to traffic accidents and more than three times that of drug-use disorders, according to WHO statistics released in 2001.

Previous NIAAA studies had shown that people who first drink early in adolescence have a four-fold greater risk of becoming alcoholic at some point in life than do people who begin later in adolescence. The new results of NIAAA's NESARC and COGA studies - the studies indicating that depression, alcoholism, cannabis dependence, and tobacco addiction, among others, are developmental diseases - built on that finding, revealing that this risk overwhelmingly manifests itself during the developmental years. New cases of alcoholism peak sharply at age 18, while occurrence of new cases drops dramatically after age 25. No subsequent age group experiences an occurrence of new cases of alcoholism that even remotely approaches the surge in the 18-to 25-year-old group. (Cannabis dependence follows a similar trajectory, while significant numbers of new cases of depression and tobacco addiction continue to occur even after the strong surge in onset that occurs among youth.)

Alcohol is the primary psychoactive substance of abuse by American children. About 78 percent of 12 th graders, 67 percent of 10 th graders, and 47 percent of 8 th graders have used alcohol, according to the National Institute on Drug Abuse's Monitoring the Future survey. Youth who report having been drunk at least once include 62 percent of 12 th graders, 44 percent of 10 th graders, and 21 percent of 8 th graders. Roughly half of those percentages say that they drank heavily (five or more drinks in a row) in the past 2 weeks.

Several activities related to prevention of underage drinking already are underway at NIAAA. Approximately $50 million are being devoted to studies of underage drinking in FY 2004, including studies on the neurobiological mechanisms of adolescent alcohol abuse. Investigators also are examining whether a community-based preventive intervention developed for rural youth is effective for children in diverse neighborhoods. An initiative on preventing alcohol-related problems among college students also is underway, based on recommendations by the NIAAA Task Force on College Drinking.

An additional $2 million will be added in FY 2005 for a major new initiative on youth in rural and small urban areas. Youth in both of these regions have high rates of alcohol use and are understudied.

Among the questions alcohol research faces regarding youth are: How does alcohol interact with the changing physiology of the child and adolescent brain, and with environmental influences, to promote alcohol dependence? What are the mechanisms that underlie the co-occurrence and surge in onset of alcoholism, depression, cannabis dependence, and nicotine addiction during the developmental years? Most importantly, what points in these processes and mechanisms are targets for intervention?

A crucial research approach to these and other relevant questions is to conduct longitudinal cohort studies of co-occurring mental and substance-use disorders, framed in a developmental context and involving communities and health-care professionals. This will be the focus of the next generation of NIAAA studies. NIAAA is moving in this direction with its new initiative focused on drinking among youth in rural and small urban areas. In addition to SAMHSA, the Department of Education, the National Institute on Drug Abuse, the National Institute of Mental Health, the National Institute of Child Health and Human Development, and other Federal agencies and organizations will be invited to collaborate.

To this end, NIAAA first convened an advisory conference with representatives of academic health centers from rural and small urban areas, to explore the feasibility of a partnership. The NIAAA determined that these centers will be valuable assets in conducting the research intended, due to the wide variety of requisite disciplines they have in place and to their ability to recruit community partners. In addition, primary care networks tend to be better established in rural and small urban regions.

Longitudinal studies conducted under this initiative will follow participants from early childhood, include biological and environmental aspects of development, and examine the use of alcohol, tobacco, and illegal drugs, mental health disorders, and related problems. Among the goals of the initiative is not only to develop effective, feasible prevention and treatment strategies for diverse communities, but also to enhance the capabilities of the communities themselves to research, develop, and implement these strategies. NIAAA anticipates that SAMHSA will play a central role in the latter.

RELATED NIAAA RESEARCH

Because alcohol's actions are ubiquitous - it acts on several of the neurotransmitter systems in the brain and affects all tissues and organs in the body - NIAAA's research covers a wide range of topics. For example, alcohol has toxic effects that can affect people throughout the life-span, from fetuses to the elderly. Cancer and liver disease are two examples of adverse consequences. Paradoxically, alcohol appears to confer protection against some kinds of chronic diseases, in some people.

Studies of variations in genes and the proteins they produce are important to NIAAA research on alcohol metabolism and its role in alcoholism and organ damage, and to NIAAA research on the neurotransmitter systems known to play a role in propensity for drinking. The timing of protein production and the amount of proteins that genes produce can change at different stages of life - including the developmental years - and under different conditions. Studies of these topics are absolutely essential to NIAAA's medication development program, another area of increased emphasis. They reveal potential molecular targets for compounds that can block alcohol's detrimental effects, and several such compounds have been identified as candidates for testing. With studies pointing to youth as the critical window of opportunity for preventing alcoholism, the coming years also will see a shift in this kind of research, toward medications that can block the disease in its early stages.

Prepared: June 2004

Members of the Committee, thank you for your concern about alcohol, drug, and mental health problems, issues that rank very high in their impact on public health and on the Nation. I thank my distinguished colleagues for their contributions in these areas and for sharing in our discussion today. I am Dr. Ting-Kai Li, Director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Recent NIAAA research, together with results from other studies that have enhanced our understanding of the developmental processes of adolescence, have led us to revise our entire perspective on alcohol dependence (alcoholism) and, potentially, other disorders that co-occur. Historically, alcoholism has been characterized as a disease of mid-to-late adulthood, because the disease becomes readily apparent to health professionals only after patients have manifested its multiple adverse consequences over many years. By then, the disease is usually in its late, severe, chronic form.

Recent NIAAA research, together with results from other studies that have enhanced our understanding of the developmental processes of adolescence, have led us to revise our entire perspective on alcohol dependence (alcoholism) and, potentially, other disorders that co-occur. Historically, alcoholism has been characterized as a disease of mid-to-late adulthood, because the disease becomes readily apparent to health professionals only after patients have manifested its multiple adverse consequences over many years. By then, the disease is usually in its late, severe, chronic form.