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Testimony on NIMH's FY 1998 Budget
Director, National Institute of Mental Health
National Institutes of Health
U.S. Department of Health and Human Services

Before the House Appropriations Committee, Subcommittee on Labor, Health and Human Services, Education and Related Agencies
March 6, 1997

It is my pleasure to appear before you to discuss the research programs of the National Institute of Mental Health (NIMH). My first year as Director of the NIMH has reinforced my perception that this is a period of extraordinary scientific opportunity for understanding the brain, its role in behavior, and what goes wrong in the brain to produce mental illness. The knowledge we are gaining should improve our capacities to treat and, eventually, prevent an array of mental disorders.

In this statement, I will comment briefly on the burden of mental disorders; highlight key scientific accomplishments and opportunities; and describe several administrative steps we are taking to speed our progress as efficiently as possible.

Schizophrenia, major depression and manic depressive illness, severe anxiety disorders, obsessive compulsive disorder, anorexia nervosa, and other severe mental illnesses affect some 5 million adults. Additional millions of Americans suffer other disorders that occur across the lifespan, from childhood autism to dementias in the aged. All told, mental disorders cost the United States more than $148 billion each year. The U.S. experience is not atypical. A study sponsored by the World Bank and World Health Organization recently forecast that by the year 2020, as we effectively meet the challenge of infectious disease in developing countries, major depression alone will rival chronic ischemic heart disease as the single leading cause of disability worldwide (Table 1). The study makes it clear, moreover, that the courses of the top five diseases from all causes are heavily influenced by human behavior. Given the immense public health burden of brain disease and its impact on our Nation's productivity, I am encouraged that mental illness has emerged as a prominent theme in our Nation's efforts to set health care priorities, as evident, for example, in the debate concerning insurance parity. Americans are increasingly aware that serious mental illness is not a moral failing or weakness, but a disorder of a specific organ, the brain, just as coronary artery disease is a disorder of a specific organ, the heart. Mental illnesses are brain disorders that will be understandable in terms of molecular and cellular processes in the brain and the brain's interaction with the environment. With this recognition, the stigma once associated with mental illness is fading.

Independent analyses show that research is an effective response to the economic and social burden of mental illness and to the needs of patients and their families. For example, a study published in the journal Science documents savings of $145 billion to the U.S. economy since 1970 when the FDA approved lithium for treating manic depressive illness. Clozapine maintenance treatment for schizophrenia, approved by the FDA in 1990, yields annual savings of $1.4 billion for the estimated 60,000 patients receiving this medication. These treatments, and the resultant savings, reflect a return on a sustained research investment.

Modern mental health research relies on many of the same methodologies and technologies used in other areas of medicine, but applies them to an array of questions that extend from the cell to society: from studies of the genetics of complex human disorders, to molecular neurobiology, to brain circuits and behavior, to clinical trials of new treatments, to sophisticated services research designs needed to understand the effectiveness of treatments in complex, real-world settings.

The human brain is the most complex structure in our known universe. If we are to understand the roots of mental illness, we must press on with fundamental investigations of the brain. The truly novel and effective treatments of tomorrow will be based on the investments in basic science that we make today. The dividends of our investment are seen in recent NIMH-supported basic science advances:

• We have identified a molecule--a protein found on the surfaces of nerve cells--that early in brain development appears to guide specific emerging cells to become part of the brain's limbic system, which is involved in the control of emotion and motivation. Any alterations in such guidance systems in the developing brain could lead to a cascade of abnormal circuit formation and could be the cause of illnesses such as schizophrenia or autism.
  
  
• Another accomplishment is the deciphering of a cellular mechanism that may be responsible for pruning of excess cortical neurons that are purposely over-produced in early phases of brain development. Here too, the discovery helps to flesh out a suspected developmental cause of the brain defects in schizophrenia.
  
  
• In yet another discovery, scientists using advanced molecular techniques in the mouse, coupled with basic behavioral science, have identified a gene that controls daily biological rhythms. A behavioral test, which exploits the tendency of mice to be highly active during the night and less active in daytime, enabled isolation of a mutation in a gene named clock, which controls the duration of daily biological rhythms. This work, and related research in the fruit fly, is clarifying a complex chain of events that regulate our sleep/wake cycle, a cycle that is disrupted in mood disorders, and also is crucial to understanding human problems ranging from sleep disorders to jet lag.

Such advances make it clear that innovative animal models and the molecular biological approaches constitute an essential foundation of our "bottom up" efforts to understand larger-scale brain systems, their role in behavior, and what it is that goes awry in brain function that leads to mental disorder.

Human genetics is a vital component of our efforts. As molecular genetics comes of age in medical science, we see that disorders such as schizophrenia and manic depressive illness are complex disorders, much like diabetes and hypertension. We know that certain genetic patterns, while not directly causing an illness, can lay a foundation for increased vulnerability to illness. We know that individual vulnerability to mental disorders and other complex traits is due to the interaction of multiple genes rather than to a flaw, or mutation, in a single gene. Moreover, it appears that no single genetic mutation is necessarily shared by all individuals with a given disorder--indeed, there likely are multiple genetic pathways to vulnerability. Environmental factors may then interact with the genetic vulnerability to lead to the onset of a specific illness.

Modern genetics also permits us to understand brain-behavior relationships in animal models. Scientists now can manipulate the mouse genetic code by adding or deleting single genes, and soon will be able to deactivate genes in specific brain locations at a predetermined time in the animal's development. These same approaches will help us understand human disease vulnerability genes whenever we find them.

Of course, what we glean from molecular genetics and other basic research will be most relevant to clinical concerns only when we understand these processes against a backdrop of social context, interpersonal interactions, individual psychology, and neural circuits. Thus, each advance in understanding genetic mechanisms opens opportunities for basic and clinical investigation. To ensure that we capitalize fully on these opportunities, the NIMH attaches high priority to research that translates basic findings into the realm of clinical investigation and application. NIMH-funded research on childhood and adolescent mental disorders illustrates our commitment to clinical and treatment research. As many as 20 percent of young Americans between the ages of 7 and 14--approximately 10 million children--suffer from mental health problems severe enough to compromise their ability to function.

While any interruption to normal developmental processes is of concern to us, we attach particularly high priority to research on autism, a severe disorder of communication and behavior that affects more than 100,000 Americans. Family and twin studies point to a genetic cause in autism, particularly when multiple cases occur in a family. Among siblings of an autistic person, the prevalence rate for the disorder is 75 times higher than in the general population. The importance of finding the genes responsible for autism lies in their value in diagnosis as well as in providing essential information about the regulation of brain development. NIMH researchers at three different locations now are studying families using a combination of strategies, and the likelihood of identifying susceptibility genes in the next several years is high. As this search progresses, neuroimaging studies are providing evidence of abnormalities in several brain regions in persons with autism. Such findings strengthen hypotheses that a genetically-triggered disturbance in brain development early in fetal life is responsible for the devastation of autism. Our research complements an NIH-wide effort focused on autism, with other concentrated activities in the neurology, child health, and communicative disorders institutes.

For all childhood mental disorders, we must have a full range of interventions; that is, treatments based on behavioral approaches such as psychotherapy as well as medications. In one recent project, investigators developed a 16-week cognitive-behavioral intervention specific to the needs of children with anxiety. Untreated, childhood anxiety disorders tend to persist into adulthood and are associated with a range of psychological and social impairments. The psychotherapeutic approach reduced anxiety, and these benefits were maintained for more than three years.

Such advances do not permit us to rest on our laurels. Recognizing that resources are limited, in my first year at NIMH, we have worked to identify and prioritize research challenges. Let me report briefly on progress in three major areas to strengthen our programs and make them even more cost-effective.

First, our Intramural Research Program Planning Committee, which was created in response to congressional interest in the revitalization of intramural research across the NIH campus, has completed its work, and I have begun to implement the nearly 80 recommendations it developed. These call for making many labs smaller; apportioning funds in a way that will offer incentives for translational research; creating incentives for excellence; and freeing up resources so we can recruit and support the most outstanding young and mid-career investigators. A top quality intramural program can create a superb complement to our extramural program by bringing together a critical mass of both basic and clinical researchers and, by stability of funding combined with rigorous review, permitting them to undertake long-term-, higher risk-, and interdisciplinary projects.

Secondly, with extensive consultation from our extramural community, I have undertaken a fundamental restructuring of our extramural research funding divisions. The first impetus for this change is fundamentally scientific--that is, our divisional structure, developed for a previous scientific era, today impedes our efforts to encourage and make necessary scientific connections--for example, between basic and clinical neuroscience. Changes we are making also will yield greater administrative efficiency; a structure that more closely reflects the contemporary scientific process will permit us to use our administrative funds in the most streamlined and effective manner.

A third area of change concerns the role of our National Advisory Mental Health Council. The breadth of interests and expertise of our Council members is impressive, as is the intensity of their commitment to mental health issues. I have been immensely gratified by the enthusiastic and productive response of our Council members to my invitation to take a more active working role in conducting in-depth, hands-on reviews of the operations of various NIMH's programs: Our science communications and prevention research portfolio are now being examined by Council work groups and more will follow.

Let me conclude by returning to the most important aspect of our work, which is the science. Our efforts in the coming year will be aimed at new initiatives in the genetics of vulnerability to mental disorders, using the tools of molecular biology and neurobiology together to understand the function of the normal brain and how things go wrong with mental disorders, and development of programs to translate what we learn from basic brain and behavioral research to clinical applications. In addition we will begin reforming our approach to clinical trials and adapting what we learn to people in the real world. An important task for the mental health services research community will be to study the impact of managed care on the mentally ill, a particularly vulnerable population.

For the scientific activities I have highlighted here and for related programs, NIMH requests $629,739,000 for fiscal year 1998. Thank you Mr. Chairman. I will be pleased to answer any questions.