The National Institute of Mental Health (NIMH) was authorized in 1946 and established within the National Institutes of Health. There, it launched a first-of-a-kind, comprehensive research program on mental illness and health. Throughout its history, NIMH has played a pioneering role in developing the foundations of contemporary neuroscience and behavioral science. The research accomplishments and opportunities presented here reflect NIMH's core mission: supporting and conducting research that seeks to understand, treat, and prevent mental illnesses.

Misunderstood, often feared, and still stigmatized, the most severe mental illnesses affect some 5 million American adults, causing inestimable suffering to these patients and their families. But these severely ill patients--suffering from schizophrenia, manic-depressive illness, major depression, panic disorder, and obsessive-compulsive disorder--represent only a part of a broader problem from which few families are immune, for mental disorders can and do occur from childhood to old age, irrespective of gender or race. Overall, one in ten Americans experience some disability from a diagnosable mental illness in the course of any given year.

The Costs of Mental Illness and the Savings from Research

While numbers cannot convey the distress accompanying mental disorders, the economic impact can be calculated. Mental disorders cost the United States more than $150 billion each year for treatment, for the costs of social service and disability payments made to patients, and for lost productivity and premature mortality. Schizophrenia alone costs the Nation some $30 billion annually.

Now, at a time when the costs of the United States' health care system are the subject of extensive national discussion, NIMH's research is demonstrating that diagnosing, treating, and preventing mental illnesses can play a critical role in reducing the Nation's health care bill.

Some examples:

• Lithium therapy for manic depressive illness is estimated to have saved the U.S. economy more than $145 billion since 1970.

• Clozapine treatment for schizophrenia, approved by the FDA in 1990, saves an average of $23,000 in treatment costs per patient annually, largely by reducing need for hospitalization.

• An analysis conducted for the Senate Appropriations Committee projected that appropriate and timely treatment of severe mental disorders would produce a 10 percent decrease in the use and cost of medical services by people with these illnesses, yielding savings greater than the cost of providing these treatment services.

• A clinical and educational program designed to boost the skills and coping resources of individuals who provide care for an immediate family member with Alzheimer's disease produced savings of over $17,000 in hospitalization costs per patient and reduced the isolation and fatigue experienced by the caretaker. As families assume an increasingly large role in providing care and assistance to relatives with a mental illness, research is underway to develop similar programs for persons and families struggling with other mental illnesses.

• A program designed to detect and treat depression, reversible delirium, and other mental disorders in elderly patients hospitalized with hip fractures reduced the average hospital stay by two days, with savings of five to eight times the extra cost of evaluating and treating these patients. It is likely that elderly patients admitted to the hospital for other physical ailments could benefit from such programs, with similar cost reductions.

The United States' investment in mental health research--one that reflects less than 1 percent of the yearly costs of mental illnesses--shows clearly that reducing the costs and correcting the shortcomings of our health care system requires policies which acknowledge that mental illnesses can be diagnosed precisely and treated effectively.

Mental illnesses are complex disorders, involving our capacities to think, feel, and to act. By necessity, the research focus of the NIMH is broad, encompassing exploration of the fundamental biology of the brain and basic processes of behavior as well as the interaction between biology and environment. Since NIMH was founded, its research has led to major advances in effective therapies and preventive strategies, as well as important insights into the biological and psychological foundations of behavioral disorders that have an impact on developmental processes, health status, and quality of life.

In recent years, the study of the brain, behavior, and mental illnesses has been strengthened greatly by revolutionary advances in molecular biology, biomedical imaging, structural chemistry, immunology, psychology, and computer science. The future holds exciting promise of further progress.

The Diseases

Schizophrenia, the most chronic and disabling of the severe mental disorders, typically develops in the late teens or early twenties. Just as adult life begins, illness intervenes, curtailing career plans, ending relationships, tormenting not only the people directly affected but also their families and friends. More than 2 million Americans are affected by schizophrenia in any given year, and only one in five recovers completely. Even with available treatment, most continue to suffer chronically or episodically from their illness throughout a large part of their lives. One measure of the anguish of schizophrenia may be inferred from its lethality; an estimated 1 of every 10 people with the illness dies by suicide.

The overt symptoms of psychosis in schizophrenia are hallucinations (hearing voices, seeing visions), delusions (false beliefs about commonly held views of reality), and bizarre thought patterns. These are the "positive" symptoms that typically lead to psychiatric treatment and hospitalization. Often neglected are schizophrenia's "negative" symptoms--social isolation and withdrawal, blunting of emotional expressiveness, poor communication skills, and decreased motivation and self-care. These negative symptoms are just as disabling.

NIMH-funded investigators using state-of-the-art imaging techniques recently have discovered specific, subtle abnormalities in the brains of patients with schizophrenia that may provide new insights into the origins of the disease. An intriguing finding of developmental neurobiologists is that schizophrenia may be a developmental disorder that results when neurons form inappropriate connections during fetal development. These errors may lie dormant until puberty, when changes in the brain that occur normally during this critical stage of maturation interact adversely with the faulty connections. This research has spurred efforts to identify prenatal factors which may have some bearing on the apparent developmental anomaly. In other studies, investigators using brain imaging techniques have found evidence of early biochemical changes that may precede the onset of disease symptoms; prompting examination of the neural circuits which are most likely to be involved in producing those symptoms. Scientists working at the molecular level, meanwhile, are exploring the genetic basis for abnormalities in brain development and in the neurotransmitter systems regulating brain function.

Affective (Mood) Disorders affect nearly 18 million Americans age 18 and older each year. The two most severe forms of affective disorder are major depression and manic-depressive, or bipolar, illness. Major depression is marked by persistent depressive thought and mood, accompanied by physiological disturbances in sleep, appetite, and energy level. Acuity of thought, memory, and concentration are also affected. Pessimism or self-deprecation can evolve to delusions of worthlessness.

In bipolar illness, depressive episodes alternate intermittently with manic ones marked initially by heightened energy and mood, sharpened and unusually creative thinking, irritability, and increased self-confidence. In full mania, these symptoms progress to grandiose delusions and psychotic, disruptive behavior. For the great majority of patients, depression and bipolar illness are recurrent disorders. In a subtype termed seasonal affective disorder, recurrent depressions are most common during winter.

Researchers at NIMH recently identified a biochemical mechanism involved in lithium's remarkable effects in modifying the symptoms of both mania and depression. Neuroscientists now are using this information in their search for the origins of manic depressive illness and also in efforts to design new medications for those whose symptoms do not respond to lithium. In a broader effort, researchers funded by NIMH are surveying the entire human genome for genes linked to mood disorders. To date, they have located two plausible candidate genes whose functions fit with known biochemical data about depression and manic depressive illness.

The various Anxiety Disorders share a central, primary symptom of intense anxiety. However, differences in other key symptoms suggest, as does recent research, that each anxiety disorder originates in distinctly different neuronal and psychological mechanisms. Four of the most serious anxiety disorders are:

• Obsessive-compulsive disorder (OCD), characterized by recurrent, unwanted thoughts and conscious, ritualized, seemingly purposeless acts.

• Phobias--persistent, irrational fears of an object or situation and the compelling desire to avoid the object of fear.

• Panic disorder, marked by sudden attacks of terror and irrational fear, an overwhelming sense of impending doom, and bodily symptoms such as racing heartbeat, gasping for air, sweating, weakness, dizziness, and feelings of unreality.

• Post-traumatic stress disorder (PTSD)--though most closely associated with wartime experiences, can follow any traumatic event, such as rape or other violent acts, natural disasters, or accidents. Recollections of the event, sometimes occurring years later, intrude in everyday life and appear in disturbing dreams. Disabling symptoms commonly develop, such as avoiding important activities, feeling emotionally numb, and experiencing sleep difficulties, hypervigilance, or other symptoms of physiological arousal.

As a result of NIMH funding, clinicians now have new, effective therapies for anxiety disorders that were once largely untreatable. For example, a new family of antidepressant medications, when combined with sophisticated behavioral therapy, reduces symptoms in 80 percent of those with OCD. Only a few years ago, there was little hope of relief from the crippling symptoms of OCD. Recent research has underscored the therapeutic value of combining medication with behavioral therapy in treating panic disorder and PTSD. Investigators hope to extend these promising findings to develop combination treatments for other anxiety disorders.

Other priorities for NIMH include disorders that affect special groups of Americans, such as children and adolescents, women, the elderly, individuals infected with HIV, and individuals who care for relatives with debilitating physical or psychological problems. These disorders include eating disorders; suicide; dementias, such as Alzheimer's disease and HIV-associated dementia; the psychological aftermath of physical and sexual abuse; and, conduct disorder.

From Bench to Bedside:

NIMH-Funded Research Highlights and Opportunities

The Brain and Behavior

Since 1990, NIMH's research efforts have been instrumental to the United States' Decade of the Brain, a focus on brain research proclaimed in 1990 by President Bush. The Human Brain Project is a multi-agency effort that is using state-of-the-art computer science technologies to organize the immense amounts of data being generated through neuroscience and related disciplines, and to make this information more readily accessible to researchers, students, and others. Through this and other initiatives, NIMH-supported investigators have made great strides in understanding how the brain develops from a few primitive cells, and how the resulting billions of cells communicate with one another to produce thoughts, emotions, and behaviors.

Of all the organs in the body, the brain is the most inaccessible to study. Accordingly, NIMH has played a pivotal role in developing brain imaging and analytical instrumentation that has helped make the United States the world leader in biomedical technology. Today, researchers use these technologies--positron emission tomography (PET), magnetic resonance imaging (MRI), nuclear magnetic resonance spectroscopy (NMR), and multiple channel electroencephalography, among others--to monitor the operation of neural circuits in the brain as they interact with one another to produce complex behaviors.

One result of these studies is that researchers are gaining a clearer picture of how the brain processes new information and creates memories. These studies also provide information about the root causes of mental illnesses and behavioral disorders, such as depression, phobias, post-traumatic stress syndrome, developmental learning disorders, and Alzheimer's disease. By understanding how the brain's activity differs in these conditions, mental health researchers hope to develop new ways of compensating for abnormal neural activity and thereby alleviating the symptoms of these disorders.

Just as basic neuroscience research is essential to development of effective biological treatments for mental illnesses, basic behavioral research is essential to the development of effective therapies for depression, panic disorders, phobias, conduct disorders, and the social dysfunction associated with schizophrenia. Behavioral science research also has been essential in developing and demonstrating the effectiveness of specific programs to reduce the spread of HIV infection and is helping to identify the many risk factors contributing to the increase in violence in today's society.

Treatment Development

In the 1960s, specific and often dramatic responses of major mental disorders to medications afforded evidence of a biological component to these conditions and triggered the explosive growth of neuroscience, in large part under NIMH's aegis. By using the tools of modern molecular biology, NIMH-funded investigators have discovered a host of new neurotransmitters, receptors, and other important molecules that are involved in the actions of drugs, both therapeutic and illicit. For example, a concerted effort by a number of NIMH-funded researchers is painting a detailed picture of how the neurotransmitter serotonin mediates diverse biochemical effects in the brain. As this neurotransmitter is thought to play a critical role in most of the severe mental illnesses, the new knowledge should greatly enhance our understanding of these diseases and the search for effective therapies for them.

Already, the outpouring of knowledge about the neurochemistry of the brain has led to the development of safer and more effective medications for certain mental disorders than were available only a decade ago. The new generation of psychotherapeutic drugs includes clozapine (Clozaril), an antipsychotic medication which addresses the negative, as well as the positive symptoms of schizophrenia, and thus helps certain patients adjust more smoothly to community living. An entire family of compounds known as serotonin-selective reuptake inhibitors, which includes fluoxetine (Prozac), have produced dramatic results in treating depression, panic disorder, obsessive-compulsive disorder, bulimia, and perhaps even alcoholism and obesity. These medications are revolutionizing the treatment of severe mental illnesses. To build further on these successes, NIMH is funding new avenues of research that will not only help turn basic research into effective medications, but accelerate their progress through critical stages of clinical evaluation and regulatory approval.

NIMH-funded research has demonstrated, too, the value of behavioral therapies in treating mental illnesses, particularly anxiety disorders. Recent work suggests, for example, that behavioral therapies based on sound scientific data are particularly effective in alleviating the symptoms of panic disorder. Rigorously designed behavioral therapy also has been shown to produce long-lasting effects in treating phobias and post-traumatic stress disorder.

Treatment research supported by NIMH is being used to develop new approaches to lower the costs of health care and improve patient outcomes. Recent research has led to the development of a new model of psychotherapy outcome that employers, insurers, and managed-care specialists are now using to monitor the effectiveness of psychotherapy. Under this model, "effective outcome" is defined in terms that balance employers' needs and interests with those of patients, alleviating a patient's symptoms of distress (to reduce overall medical expenditures); improving functioning (to boost job productivity); and enhancing employees' sense of well-being (to promote positive attitudes, job satisfaction, and high morale). The model assures that patients receive the specific type of treatment needed to solve their particular problem in the shortest time possible. Other treatment research findings have been effective in preventing behavioral and physical health problems in older Americans.

Depression and other severe psychiatric problems affect some 3 percent of children and adolescents, and millions more suffer other psychiatric and behavioral conditions. Suicide among adolescents and young adults remains tragically high. Recently, NIMH-funded investigators reported that a brief treatment technique known as interpersonal therapy achieved successful outcomes among a group of adolescents who had been depressed and had suicidal thoughts. Further study of this promising approach is ongoing. NIMH also has launched a sophisticated clinical trial focused on attention-deficit/hyperactivity disorder (ADHD), a common yet severe mental disorder of childhood. Institute-funded investigators at six sites are examining the relative efficacy of three treatment approaches: medications alone; a multi-faceted psychosocial intervention that involves a child's parents and schoolteachers in providing treatment tailored to a child's needs; and a combination of these two interventions. With a fourth group of children with ADHD, the investigators are examining the effectiveness of state-of-the-art treatments routinely available in six local communities.

Prevention Research Initiative

NIMH has targeted efforts to expand the scientific basis of preventive interventions focused on mental and behavioral disorders. The Institute is conducting, at several sites across the United States that encompass all socioeconomic strata in the population, two large-scale trials aimed at preventing serious conduct disorders and overly aggressive behavior in children. Preliminary findings indicate that early intervention, at relatively low cost, can reduce antisocial behavior and head off more serious conduct problems in adolescence. Another research program, involving teachers and parents, is demonstrating that it may be possible to prevent many instances of child abuse, and in the process, strengthen the bonds among family members.

The Future

From individual to society, from infancy to old age, the reality of mental illnesses are felt with devastating impact. They confound, they disable, and they impoverish patients and their families alike. Yet, the scientific achievements realized through NIMH's support show that mental illnesses are definable, treatable, and, to an extent, preventable. Furthermore, research has demonstrated that treatment is increasingly precise and cost-effective.

Information provided by NIH.