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National Institutes of Health

The National Institute of Mental Health Strategic Plan

NIMH Vision

NIMH envisions a world in which mental illnesses are prevented and cured.

NIMH Mission

The mission of NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure.

For the Institute to continue fulfilling this vital public health mission, it must foster innovative thinking and ensure that a full array of novel scientific perspectives are used to further discovery in the evolving science of brain, behavior, and experience. In this way, breakthroughs in science can become breakthroughs for all people with mental illnesses.

In support of this mission, NIMH will generate research and promote research training to fulfill the following four objectives:

The National Institute of Mental Health Strategic Plan

Envisioning a world in which mental illnesses are prevented and cured

Director’s Message

The National Institute of Mental Health (NIMH) has just entered its seventh decade as the nation’s scientific leader in the fight against mental illness. The landscape of mental health research has changed considerably over these decades. A critical acceleration began in the 1970’s and 1980’s when researchers began making rapid strides toward understanding the science of human behavior and the ways in which medicines can be used to treat illnesses. In the 1990’s, the “Decade of the Brain” yielded insights into fundamental aspects of how the brain works including new ways of visualizing the brain with imaging technologies. This era also led to advanced methods for studying the interaction between the brain, behavior, and the environment. These advances, in turn, have set the stage for the current era which might be called the “Decade of Discovery.” Many of the scientific opportunities in this discovery era were scarcely imagined 10 years ago. For NIMH to continue fulfilling its vital public health mission, the Institute needs to remain adaptive and explore fully the changing scientific landscape, ensuring that breakthroughs in science become breakthroughs for people with mental disorders.

When scientists think about this changing landscape, we usually focus on new and novel technologies and innovative models for approaching science. New maps and new mapping tools for the human genome, for instance, have transformed our understanding of how individuals genetically vary from each other and how these variations can put some people at increased risk for certain illnesses. Neuroimaging tools to visualize the brain have given us an unprecedented view of brain activity, providing a new understanding of its development and a picture of how specific networks of cells change with experience. One goal of this Strategic Plan is to translate these and other advances to what the National Institutes of Health (NIH) calls the “4 P’s” of research: increasing the capacity to Predict who is at risk for developing disease; developing interventions that Preempt (or interrupt) the disease process; using knowledge about individual biological, environmental, and social factors for Personalized interventions; and ensuring that clinical research involves Participation from the diversity of people and settings involved in health care.

It is important to note that the changing landscape is found outside scientific laboratories as well. Demographically, America is a different nation than it was 10 years ago: we are more diverse, we are aging, and we are increasingly challenged by the costs and complexities of health care. A major goal of this Strategic Plan is to enhance the impact of research on the enormous public health burden that mental illnesses have across the lifespan. Our success cannot be measured solely by our traditional “outputs”: the numbers of grants, papers, or discoveries supported. In addition, NIMH must measure success by “outcomes”: how well the research we support provides the evidence base for mental health care providers to preempt illness for those at risk (including prevention targeted to those individuals most at risk), enhance recovery for those affected, serve diverse and previously under-served populations, and reduce premature mortality among persons with mental illness.

The urgency of this cause cannot be over-stated. The President’s New Freedom Commission on Mental Health, which examined the need for reform of the mental health care system, concluded that the problems of fragmentation, access, and quality of mental health care were so great that nothing less than transformation would suffice. With several large-scale clinical trials completed by NIMH, we can add that for too many people with mental disorders even the best of current care is not good enough. To fully address these issues, we must continue to (a) discover the fundamental knowledge about brain and behavior and (b) use such discoveries to develop better tools for diagnosis, preemptive interventions, more effective treatments, and improved strategies for delivering services for those who provide direct mental health care. These activities point toward NIMH’s ultimate goal, which is not merely to reduce symptoms among persons with mental illness, but also to promote recovery among this population and tangibly improve their quality of life.

There is an unavoidable tension between the urgent need for transformation and the longer-term nature of scientific progress. Scientific progress is generally slow and incremental—too slow and too incremental for families who need more effective treatments today. Yet, progress has been made and it has been accelerating over the past decade. This Plan is our commitment to continue the accelerated pace of scientific progress by generating, over the next 5 years, the best mental health research that will have the greatest public health impact and continue to fuel the transformation of mental health care.

Thomas R. Insel, M.D.
Director, NIMH

NIMH Vision

NIMH envisions a world in which mental illnesses are prevented and cured.

NIMH Mission

To transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure.


As the lead Federal agency for research on mental and behavioral disorders, the National Institute of Mental Health (NIMH) envisions a world in which mental illnesses are prevented and cured.

In consideration of this vision, the mission of NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure. The burden that this research addresses is enormous. In a given year, an estimated 13 million American adults (approximately 1 in 17) have a seriously debilitating mental illness.1 , 2 Mental health disorders are the leading cause of disability in the United States and Canada, accounting for 25 percent of all years of life lost to disability and premature mortality (Disability Adjusted Life Years or DALYs).3 Moreover, suicide is the 11th leading cause of death in the United States, accounting for the deaths of approximately 30,000 Americans each year.4 Schizophrenia, bipolar disorder, depression, post-traumatic stress disorder, eating disorders, autism, and other disorders are serious, often life-threatening, illnesses for which we need reliable diagnostic tests, new treatments, and effective strategies for prevention.

This public health mandate demands that we harness powerful scientific tools to achieve better understanding, treatment, and ultimately, prevention of these disabling conditions. To fulfill its mission, the Institute:

Important discoveries in areas such as genetics, neuroscience, and behavioral science largely account for the substantial gains in knowledge that have helped us to understand the complexities of mental illnesses and behavioral disorders over the past 15 years. The elaboration of observed behavior, which includes such aspects as cognition, emotions, social interactions, learning, motivation, and perception, are the observable “tips of the iceberg” in reflecting the expanse of complexity further revealed in studying genes, proteins, cells, systems, and circuits. To inspire and support research that will continue to make a difference for those living with mental illness, and ultimately promote recovery, we developed this Strategic Plan to guide what has become an increasingly complex research effort (see Appendix A for details on the strategic planning process). The Plan seeks to bring into sharper focus questions and perspectives that will transform the diagnosis, treatment, and prevention of mental disorders.

With this goal in mind, NIMH identified four overarching Strategic Objectives:

The four Strategic Objectives can be viewed as a cumulative progression of the Institute’s priorities for the next 5 years. This strategy begins with promoting discovery in the brain and behavioral sciences in order to better understand the workings of the brain that can be translated to the study of mental disorders. In effect, our efforts to understand how changes in the brain can lead to mental illness will inform (and be informed by) fundamental research to understand the trajectories of mental illnesses across the lifespan and across diverse populations. By learning more about the trajectories by which mental illnesses develop, we hope to stimulate innovative psychosocial and biomedical approaches that can preempt or change these trajectories before mental illness occurs. Finally, we will retain a strong focus on public health impact and create better methods for ensuring that our research reaches all whose lives are affected by mental illness, as well as those who are dedicated to their care.

It is important to also highlight several core research themes that are essential to advancing and accomplishing the Strategic Objectives. First, in order for research on mental disorders to more fully harness the scientific power of brain-behavior science, sound efforts must be made to redefine mental disorders into dimensions or components of observable behaviors that are more closely aligned with the biology of the brain. Such an effort will result in a research-based description of the key elements of mental disorders, providing even greater traction on the potential mechanisms that can cause mental suffering and targets for more effective preemption and treatment.

Second, it is imperative that NIMH continue to lead efforts that foster data and resource sharing. As we strive to capture and understand the complexity of mental disorders, the data and resources generated by our research also entail greater complexity and diversity. We are committed to working with the scientific community to support the broad sharing of data and the resources necessary to accelerate scientific progress

Third, all advances rest on our ability to support and train future generations of mental health scientists. Future research scientists will use different neurobehavioral, clinical, and services skill sets as the field advances and transforms itself across traditional academic boundaries. It is equally clear that training must inspire creativity, innovation, and a thirst to make a difference in the lives of those with mental disorders. Balancing these needs and finding improved ways to mentor and train the most talented young researchers are fundamental to the future of mental health research. For this reason, the National Advisory Mental Health Committee (NAMHC) is developing a separate document that will outline the Institute’s future research training priorities.

Based on these three research themes, the Strategic Objectives and underlying strategies outlined in this document serve as a guide to the Institute for advancing mental health science and ensuring that research-based interventions and information are made widely available. They also seek to complement the President’s New Freedom Commission on Mental Health report by outlining new research-based tools for transforming the mental health services provided by partner Federal agencies, particularly those of the Substance Abuse and Mental Health Services Administration (SAMHSA).6 Ultimately, this Strategic Plan represents NIMH’s commitment to studying and providing the research evidence that can be used to transform the treatment of mental disorders, paving the way for prevention, recovery, and cure.

Strategic Objective 1: Promote Discovery in the Brain and Behavioral Sciences to Fuel Research on the Causes of Mental Disorders.

We will support basic, translational, and clinical research to gain a more complete understanding of the genetic, neurobiological, behavioral, environmental, and experiential factors that contribute to mental disorders.

This is a time of great scientific excitement in mental health research. Building on new discoveries from genetics, neuroscience, and behavioral science, we are better poised to understand how the brain, behavior, and the environment interact to lead to mental disorders. Mental illnesses are now studied as brain disorders, specifically as disorders of brain circuits. The current era of neuroscience promises to reveal much about their origins, development, and manifestations. In addition to translating neuroscience discoveries to the clinic, we are also in a phase of using clinical findings (e.g., genetic or brain imaging data) from those with mental disorders to guide research on neurobiology.

Research has made significant progress in identifying a wide array of the genetic, neurobiological, and behavioral components that comprise mental disorders. For example, studies have shown that certain genetic variations can increase risk for developing a mental disorder. Environmental and experiential influences, such as traumatic stress, may interact with specific genetic variations during sensitive periods of development. This complex interaction between genetics, environment, experiences, and development may compound risk for mental disorders by altering the structure and function of neural pathways relevant to some forms of adaptive behavior.

With new insights come new challenges. It is becoming increasingly clear that the genetic underpinnings of mental disorders are highly complex, likely involving the interaction between many risk genes. An enormous variety of experiences and environmental factors may influence development, and the ability of these factors to confer risk may change across the lifespan. It is challenging to demonstrate how interactions between genes, environment, experiences, and development contribute to the formation and function of neural circuits. We still know little about how information is stored in neural circuits. In addition, the very definition of mental disorders as complex clusters of behaviors makes it difficult to deconstruct behavioral components and link them to underlying neural circuitry.

Improving our understanding of the underlying causes of mental disorders will provide the necessary foundation for better diagnosis and interventions. To clarify and integrate these neurobiological, behavioral, environmental, and experiential components, NIMH will engage in a number of strategies:

Strategy 1.1: Develop an integrative understanding of basic brain-behavior processes that provide the foundation for understanding mental disorders.

To further clarify how changes in neural activity contribute to mental disorders, it will be necessary to know more about the basic neuroscience of neural circuit formation and how these circuits interact to contribute to observable behaviors. These efforts will require teams to integrate findings from studies of genomics, neuroscience, behavior, and the environment. This research will serve as the foundation for translation to clinical studies. To facilitate these discoveries, NIMH will:

Strategy 1.2: Identify the genetic and environmental factors associated with mental disorders.

Research has demonstrated that genes exert a significant influence on the risk for many disorders, including autism, schizophrenia, and bipolar disorder. However, studies are further revealing the complexity of the genetic, behavioral, experiential, and environmental factors that contribute to mental disorders. A single disorder might result from the interaction of combined, small effects of many different genetic variations, none of which is powerful enough to cause the disorder by itself. Alternatively, it is possible that a disorder might result from diverse, single gene mutations that result in similar physiological changes. Additional research will help ascertain whether a specific gene variation contributes to the cause of a disorder, a subgroup within a disorder, or a symptom that might be shared across multiple disorders. With the sequencing of the human genome, improved understanding of how genes are expressed, and new technologies to measure variation in the genome, we have an unprecedented opportunity to define how genes confer risk for the major mental disorders, potentially yielding new diagnostic and therapeutic targets.

Genes appear to explain only part of the risk for developing these disorders. Research has also demonstrated the importance of environmental and experiential factors in conferring risk for many mental disorders. These factors vary in scope and complexity, ranging from exposure to toxic substances in utero to social and family circumstances. Due to this wide variation, environmental and experiential influences are challenging to define and measure. In addition, some experiential influences, such as stress, may be risk factors for multiple disorders.

Epigenetic mechanisms—ways that the environment influences genes to control their function—will likely prove very important in the cause of these complex disorders. To add to this complexity, it is likely that the interplay between genes and the environment changes over the lifespan. To improve identification of the genetic and environmental factors associated with mental disorders, we will:

Strategy 1.3: Identify and integrate biological markers (biomarkers) and behavioral indicators associated with mental disorders.

Biomarkers are biological indicators of a physiological or disease process. Examples of biomarkers can include genetic mutations, altered levels of a specific protein in blood or spinal fluid, and brain abnormalities observed in neuroimaging tests. Detecting biomarkers may predict risk for developing a mental disorder or may aid in the identification, diagnosis, and treatment of individuals with the disorder. Currently, very few biomarkers have been identified for mental disorders due in part to their complexity and an incomplete understanding of the neurobiological basis of mental disorders. Mental disorders also have observable behaviors associated with them (e.g., startle reactions, compulsions, social avoidance) that, like biomarkers, once identified can indicate a possible underlying disorder and assist mental health professionals with proper diagnosis and treatment. To accelerate the identification of biomarkers and behavioral indicators for mental disorders, it will be important to:

Strategy 1.4: Develop, for research purposes, new ways of classifying mental disorders based on dimensions of observable behavior and neurobiological measures.

Currently, the diagnosis of mental disorders is based on clinical observation—identifying symptoms that tend to cluster together, determining when the symptoms appear, and determining whether the symptoms resolve, recur, or become chronic. However, the way that mental disorders are defined in the present diagnostic system does not incorporate current information from integrative neuroscience research, and thus is not optimal for making scientific gains through neuroscience approaches. It is difficult to deconstruct clusters of complex behaviors and attempt to link these to underlying neurobiological systems. Many mental disorders may be considered as falling along multiple dimensions (e.g., cognition, mood, social interactions), with traits that exist on a continuum ranging from normal to extreme. Co-occurrence of multiple mental disorders might reflect different patterns of symptoms that result from shared risk factors and perhaps the same underlying disease processes.

To clarify the underlying causes of mental disorders, it will be necessary to define, measure, and link basic biological and behavioral components of normal and abnormal functioning. This effort will require integration of genetic, neuroscience, imaging, behavioral, and clinical studies. By linking basic biological and behavioral components, it will become possible to construct valid, reliable phenotypes (measurable traits or characteristics) for mental disorders. This will help us elucidate the causes of the disorder, while clarifying the boundaries and overlap between mental disorders. In order to understand mental disorders in terms of dimensions and/or components of neurobiology and behaviors, it will be important to:

Sidebars: Strategic Objective 1

1. Beyond Nature vs. Nurture

Genomics has become central to biomedical research, yet genes may explain only a piece of the risk for developing a disorder. While rare, single gene mutations are at the root of hereditary disorders, such as cystic fibrosis and Huntington’s disease, most mental disorders are not caused by mutations in one gene. Rather, these disorders are “complex” or polygenic—meaning that they are associated with variations in multiple genes, likely in combination with environmental and experiential factors. Genetic variations are not the sole “cause” of the disorder; they increase risk by changing proteins, cells, and circuits important for behavior and cognition. Already we can see how differences in genetic sequence are associated with differences in brain circuits or brain function, even in people who do not have a disorder. One challenge for the next 5 years will be explaining the mechanisms by which these genomic differences lead to variations in cells and circuits with resulting changes in behavior or cognition. Another challenge will be explaining the non-genomic risks for developing a disorder.

In the past, the debate has been between nature (genetics) and nurture (environment) as causes of mental disorders. Today we recognize the complex interplay between nature and nurture by asking: how does experience interact with biological susceptibility to increase risk or resilience? For example, certain experiences, such as childhood maltreatment, may interact with a person’s genetic vulnerability, increasing the risk for developing PTSD or depression in adulthood.7 , 8 Other influences, such as receiving positive social support, may offset the negative effects of these risk genes and can buffer against developing a mental disorder later in life.9

Understanding the mechanisms by which our experiences are integrated into our biology will rely largely on the developing field of epigenetics—the study of how environmental influences regulate gene expression. Our DNA is decorated with protein complexes that modify how and when genes are expressed. Experiences, such as traumatic stress, do not alter the DNA sequence but can modify these protein complexes, leading to either enhanced or silenced expression of specific genes. Epigenetic modifications may provide the platform through which the environment interacts with the genome, serving as a means for learning and adaptation. Critical issues for future studies of gene-environment interactions will be to define the range of environmental exposures (e.g., maternal environment, infections, toxins, stress, social interaction) that might affect the genome throughout life and to determine how environmental factors are translated into changes in gene expression. These studies will trace the imprints of experience on our DNA, revealing, perhaps years later, how nature and nurture are entwined.

2. Tracing the Brain’s Circuitry

The human brain has approximately 100 billion neurons connected through complex networks, making it extremely challenging to trace the brain’s wiring plan. However, by combining innovative visualization approaches, we may better understand how these circuits interact physically and functionally. Perhaps the most important breakthroughs have come from new techniques for studying neural circuits.

One way to follow neuronal connections is to label the neurons with fluorescent probes. Until recently, however, these probes have been limited to a handful of colors, restricting the number of neurons that can be discerned at one time. A new genetic method labels neurons in mice with a rainbow of fluorescent shades. Instead of teasing out the wiring of the brain by one or two cells at a time, this new technique, called “Brainbow”, provides the means for tracing whole populations of neurons at once.10

In another advance, neuroscientists have genetically modified neurons to express light-activated proteins—named ChR2 and NpHR—found in certain light-responsive algae and bacteria.11 , 12 These neurons can be turned on and off with different colors of light, allowing scientists to manipulate an entire cell-defined circuit in a behaving animal.

While studies in humans lack the cellular precision of studies in mice, diffusion tensor imaging (DTI) maps the paths and directions of neuronal fibers (white matter) responsible for long-distance communication between regions of the human brain. A recent application of DTI has uncovered abnormal wiring in the brains of people with Williams Syndrome, a rare genetic neurodevelopmental disorder.13 The researchers suspect the abnormalities result from neurons migrating to the wrong destinations during development.

These new techniques, whether in mice or humans, should provide insight into how abnormal wiring may give rise to brain disorders. Increasingly, to understand the neural basis of mental disorders, we will be combining techniques that integrate across levels of functioning—from cells to circuits to behavior.

Strategic Objective 2: Chart Mental Illness Trajectories to Determine When, Where, and How to Intervene.

We will chart the course of mental disorders over the lifespan in order to understand ideal times and methods for intervention to preempt or treat mental disorders, and hasten recovery.

Mental disorders are a group of chronic, changing conditions. The symptoms often begin to appear in childhood and adolescence and ebb and flow over the course of an individual’s life. Research demonstrates that the symptoms of many medical disorders (e.g., Parkinson’s, Alzheimer’s, coronary artery disease) represent a late stage of a process that began years earlier. As with many other medical illnesses, science promises to redefine mental disorders along a trajectory moving across stages of risk: from early symptoms, to full symptoms or syndromes, to remission, relapse, and recovery. NIMH aims to compare trajectories of healthy development to those of mental disorders in order to better understand the first instance or instances when development moves off course. Doing so will allow us to pinpoint the best times and techniques to preempt the onset of symptoms or halt and reverse the progression and recurrence of illness. By predicting, detecting, and intervening early in the disease process, we can dramatically improve an individual’s likelihood of a life without suffering from a mental disorder.

Charting the course of mental disorders requires attention to genetic, neurobiological, behavioral, experiential, and environmental factors that confer a risk of developing a mental disorder. Individual characteristics, such as age, sex, race, ethnicity, culture and socioeconomic background, are critical considerations in this research. Either singly or in combination, these different factors and characteristics may not only increase the likelihood an individual will develop a mental disorder, but also affect how well that person will respond to interventions and his or her tendency to experience adverse side effects. The results of these efforts will enable NIMH to foster more personalized, preemptive, and effective therapeutic interventions.

To advance research on the trajectories of mental illnesses across the lifespan, NIMH will undertake the following strategies:

Strategy 2.1: Define the developmental trajectories of mental disorders.

Genetic variation interacts with experiential and environmental factors dynamically, varying across stages of development. We can view mental disorders as following trajectories throughout the lifespan, beginning with risk and evolving as symptoms or syndromes, which in turn can follow cycles of remission and relapse. Our challenge is to redefine disorders by understanding them as unfolding developmental processes, recognizing that these disease processes can have different consequences at different life stages. To understand the origin and development of mental disorders, we need a firm understanding of how normal brain development shapes behavior as well as how experience, in turn, shapes brain development. In support of this effort, NIMH will:

Strategy 2.2: Enhance understanding of how cultural diversity may influence the developmental trajectories of mental illness.

We will enrich the types of data used in the study of mental illnesses to enable more thorough and precise analyses of cultural and ethnic factors that may be involved in risk, resilience, and recovery from illness.

Strategy 2.3: Develop tools to better define and identify risk and protective factors for mental illness across the lifespan.

An understanding of the developmental trajectory of illnesses opens the possibility that we could intervene and alter trajectories, thereby preempting suffering associated with disease. By using the example of efforts in other fields of medicine that have adopted this approach (e.g., cardiology with regard to coronary artery disease), we will facilitate research to identify risk at the individual level (as opposed to population level) and to develop a new set of interventions. To develop such tools and methods to intervene in the trajectory of illness, NIMH plans to:

Sidebars: Strategic Objective 2

1. Mapping the trajectory of mental disorders using imaging technologies

Recent longitudinal studies have mapped the patterns of brain development in healthy youth and in those with mental illness. The results of these studies will guide us as we chart the initiation and progression of mental illness across the lifespan, further clarifying pathways for intervention. Although some loss of neurons and their connections is normal as the brain matures, adolescents with childhood onset schizophrenia show four times the normal rate of gray matter loss in the front of the brain.14 By contrast, children with bipolar disorder show a more complicated pattern of gray matter gains in areas in the left hemisphere and losses in the right hemisphere, and in mood regulating circuitry in the mid-front part of the brain.15 Pediatric bipolar disorder and childhood onset schizophrenia appear to involve different underlying neural circuits, even though the two illnesses share some symptoms and several genetic risk factors. Meanwhile, youth with attention deficit hyperactivity disorder (ADHD) have delayed patterns of brain maturation—three years in some regions, on average.16 The delay in ADHD is most prominent in the frontal lobe, important for the ability to control thinking, attention, and planning.

2. Early detection of risk factors for mental disorders

Early detection of risk factors for illnesses leads to early intervention, which can make all the difference in the quality of life of affected individuals and their families. Recent research has shown that about half of children with autism spectrum disorders (ASD) can be diagnosed soon after their first birthday, while others with the disorder may appear to develop normally until that age and then regress during their second year.17 In the past, clinicians were rarely able to diagnose ASD before age three, potentially missing the most important period for intervention. Building upon these new findings, NIMH envisions criteria that clinicians can use to diagnose ASD in one-year-olds with the potential for recovery by age three.

Following a different trajectory, the psychotic phase of some mental illnesses emerges when an individual is in their late teens or early twenties. In recent work, NIMH-funded researchers have been able to detect illnesses like schizophrenia in up to 80 percent of youth who will develop the disorder (median age of 16) well before the emergence of psychosis.18 Knowing these risk factors — particularly combinations of them—could help clinicians detect and treat schizophrenia years before the psychotic phase with the potential of avoiding or, at least forestalling, the most disabling part of the illness.

Strategic Objective 3: Develop New and Better Interventions for Mental Disorders that Incorporate the Diverse Needs and Circumstances of People with Mental Illness.

We will improve existing approaches and devise new ones for the prevention, treatment, and cure of mental illness, allowing those who may suffer from these disorders to live full and productive lives.

The rapid discovery rate for new factors affecting the trajectories of illness suggests that new targets for psychosocial and biomedical interventions should be examined in a systematic way. We need new and better methods to intervene at all points along the trajectories of mental illnesses to preempt the occurrence of disease or, when that is not possible, to hasten recovery.

Traditionally, intervention research, whether preventive or therapeutic, has focused on the absence or reduction of symptoms of mental illness. Alleviating symptoms, although important, does not necessarily address the totality of a person’s life, including how well he or she functions in their community and workplace. While an intervention may potentially prevent or alleviate the symptoms of a mental illness, there is also the possibility that it may not help; in some cases it might even further impair a person’s ability to function in everyday life. Moreover, an effective preventive strategy or treatment regimen may prove to be too difficult or expensive for proper use by providers. Intervention research, then, must emphasize efficacious recovery as its ultimate goal.

In general, traditional intervention research has focused on comparing how groups of individuals receiving an experimental intervention fare against a comparison group that does not receive that intervention. This approach has given us information about treatments for selected groups of people but not necessarily about how to choose the best treatment for a specific individual. We need personalized medicine: tailoring pharmacological, behavioral, and other forms of treatment to the needs of each individual. A new generation of clinical trials is needed to gather a wider array of data and examine the kinds of questions that can be used for personalized decision-making in medicine.

We need innovative approaches to help providers of mental health interventions ensure that every person who may fall along the trajectory of mental disorder can be helped to preempt or recover from illness. To do so, we will broaden our concept of intervention research to address how these interventions affect an individual’s ability to live a full life, as well as the impact on the providers and settings in which the interventions are delivered (e.g., medical settings, schools). We will also need to address relationships between mental disorders and other illnesses, such as substance abuse and heart disease. In addition to shifting the intervention focus to treating the whole person, it provides substantial opportunity for the reduction of mental illness-related mortality. Ultimately, our intervention research will focus on new targets, resulting in preventive and treatment strategies that allow individuals and their families, their health providers, and their social support systems to find the means to preempt or stop the progression of mental illness.

To further develop interventions that are personalized and work in multiple and diverse settings such as clinical practices, hospitals, schools, and communities, NIMH will employ the following strategies:

Strategy 3.1: Further develop innovative interventions and designs for intervention studies.

The body of work in mental health intervention research is vast and has led to numerous advances in the prevention and treatment of mental disorders. Future research needs to build on this existing scientific knowledge. Additionally, we must adopt innovative approaches to develop personalized preventive and therapeutic approaches for those in need.

Strategy 3.2: Expand and deepen the focus to personalize intervention research.

Adopting novel approaches in clinical research is essential to investigating new, brain-behavior-environmental targets for intervention research in conjunction with a broader focus on an individual’s functioning as a whole. When developing interventions, we will:

Strategy 3.3: Strengthen the application of mental health interventions in diverse care settings by examining community and intervention delivery approaches and how they may affect intervention outcomes.

Mental health interventions are delivered by a wide variety of providers in different settings. For example, preventive interventions may be implemented in schools, in the workplace, or by communities at large. Treatment interventions can be delivered, for instance, by primary care doctors, social workers, clinical psychologists, or psychiatrists. In order for intervention development research to succeed, it must incorporate the perspectives of these various providers and take into account the diverse systems in which interventions are delivered.

Strategy 3.4: Identify and systematically study elements of personalized mental health care.

Each individual at risk for or suffering from a mental illness presents a unique set of characteristics, whether they are genetic, environmental, experiential, developmental, or a combination of these factors. As previously noted, mental health interventions must adapt to the needs and circumstances of each individual they are designed to help. Therefore, an environment in which mental health care adopts a personalized approach where individual characteristics (e.g., biological, cultural, socioeconomic) are considered is expected to optimize outcomes. Similarly, patient preference is a powerful indicator of how well someone will adhere to treatment and must also be part of a personalized approach to mental health intervention.

Sidebars: Strategic Objective 3

1. Advances in understanding fear extinction: PTSD

Recent NIMH-supported research has made significant strides in understanding the nature of anxiety-related disorders such as posttraumatic stress disorder (PTSD), leading to the potential for the development of new, more effective interventions for those suffering with this disorder. While research has been examining the details of the brain’s “fear circuitry” and how it relates to anxiety disorders for decades, more recently investigations have been focusing on the mechanisms by which the brain adapts to and extinguishes fear.19 An exciting discovery is the recent recognition that fear extinction in the brain is an active learning process, not a passive process of forgetting.20 Researchers have identified a specific chemical that binds to brain cell receptors (NMDA partial agonist d-cycloserine) which may help to improve extinction learning.21 This line of research has moved from using models in the laboratory to successful tests in people with a fear of heights.22 Additional studies are now underway to examine how this knowledge can be used to help those suffering from anxiety disorders such as PTSD. This research provides hope that our new understanding of the neuronal and cellular mechanisms of fear extinction can be applied to the development of new pharmacologic and behavioral therapies to promote more rapid recovery among those suffering with this disorder.

2. Advances in the personalization of mental health interventions

NIMH continues to support novel research that seeks to understand how interventions developed to alleviate the burden of mental illnesses can be tailored to ensure the best treatment for a specific individual. While effective treatments are available, there is considerable individual variation in treatment response depending on a range of biological and psychosocial factors. From the perspective of treatment, we know that all mental disorders are highly variable across people (e.g., not everyone displays depression in exactly the same way). We are just learning how to predict which treatment will be best for any given individual.

Recent research has shown specific genetic variations to be linked to non-response and to suicidal thinking that sometimes occurs among people taking the most commonly prescribed class of antidepressants (selective serotonin reuptake inhibitors, or SSRIs).23 , 24 These newly identified gene variations may prove useful in identifying patients who need closer monitoring, alternative treatments and/or specialty care when being treated with SSRIs.

Going forward, NIMH clinical research will not only assess overall group differences, but also individual patterns of intervention response. The goal is a personalized approach to treatment. Ultimately, we hope that patients and their clinicians will decide on the best treatment based on clinical presentation, personal and family history, and a range of biomarkers including genetic variation and brain imaging results that will predict the optimal medical or psychosocial intervention. By shifting our research towards detecting individual predictors of response, NIMH hopes to provide clinicians with the information they need to choose the best available treatment for each patient.

Strategic Objective 4: Strengthen the Public Health Impact of NIMH-Supported Research.

Through research, evaluation, and collaboration, we will further develop the capacity of the Institute to help close the gap between the development of new, research-tested interventions and their widespread use by those most in need.

NIMH’s mission depends inherently on our ability to understand the nature and developmental course of these disorders, enabling the development of research-based interventions for treatment and prevention. The Institute’s role, however, does not end there. To pave the way toward prevention, recovery, and cure, we must find ways to ensure that the interventions and information we generate can be used by patients, families, health care providers, and the wider community involved in mental health care.

Our sister agency, SAMHSA, supports the delivery of services to build resilience and facilitate recovery in communities across the United States. NIMH supports research, not services. However, an important part of our mission is to support research that will optimize services. For instance, NIMH research identifies factors that may enhance access to mental health services, improves the quality of and lowers the cost of care, and strengthens the means by which new interventions are broadly disseminated and implemented. NIMH also pursues numerous dissemination efforts. Since our founding, NIMH has consistently sought the most effective and efficient methods to communicate our findings to the research community, the providers of mental health services, and the public at large.

Yet, how will we know if we are succeeding? Are the products of our research reaching those most in need of it? Are we providing the right information at the right time to the right people? To answer these crucial questions, we must closely monitor our research portfolio and our dissemination activities, and evaluate them in the context of impacting public health.

Finally, to achieve our public health mission, we must rely on our alliances with those who are also concerned with the prevention, recovery, and cure of mental illnesses. By building new or strengthening already existing partnerships with our many stakeholders—whether they are patients, families, service providers, advocacy groups, our sister agencies in the Public Health Service, or others—we can better understand the needs, questions, and concerns of those intended to benefit from the research we support. Working together more closely and efficiently will help to advance the science of mental health and lead to a quicker realization of our common goals. NIMH planning with regard to this objective is more fully described in the 2006 report of the NAMHC’s Workgroup on Services and Clinical Epidemiology Research entitled “The Road Ahead: Research Partnerships to Transform Services.”

To strengthen the public health impact of NIMH-supported research, the Institute will:

Strategy 4.1: Improve understanding of the factors that affect access to service, quality and cost of services, and the means by which newly discovered effective mental health interventions are disseminated and implemented.

To ensure that our research findings are translated into clinical practice, we must examine the context in which they will be delivered, and provide a knowledge base that better enables patients, their care takers and health providers to adopt proven strategies to promote mental health and treat mental disorders. To do so, NIMH will:

Strategy 4.2: Improve the research and dissemination activities of the Institute through monitoring and evaluation.

Through improved research monitoring and evaluation efforts, we will be better positioned to ensure that supported research is aligned with the Institute’s scientific priorities. Also, as new research findings unfold and communication mediums continue to change, the Institute’s dissemination strategies will need to be regularly evaluated and adjusted to ensure that our stakeholders are receiving the information they want and need. To do so, NIMH plans to:

Strategy 4.3: Strengthen partnerships between NIMH and its stakeholder groups.

The success of the Institute’s mission depends on the effective collaboration of all stakeholders in the field of mental health. This requires strengthening our current partnerships and working to build new ones so that we can understand the needs, capabilities, and limitations of the field as we work together to move forward.

Strategy 4.4: Strengthen NIMH’s relationships with other Federal agencies that address mental health issues.

Sidebars: Strategic Objective 4

1. Cost effectiveness of intervening

The cost of mental illness is staggering, with estimates of $100 billion each year for the direct costs of care and significantly more for indirect costs, including $193 billion alone for lost earnings among individuals with serious mental illnesses.25 , 26 NIMH continues to support a number of studies that demonstrate to policymakers, employers, health providers, and other decision-makers the tremendous cost savings that arise from investing in effective interventions for these disorders. For example, research has found that workplace depression screening, outreach, and enhanced treatment improves employees’ health and productivity, leading to lower costs overall to the employer.27

The cost savings of interventions may be demonstrated at all stages in life, including childhood. Targeted preventive interventions that help reduce conduct problems in children are cost-effective when compared to the personal and societal costs of delinquency and crime that can arise from untreated childhood conduct disorders. By demonstrating the long-term benefits of implementing evidence-based mental health interventions, NIMH research can provide compelling evidence of ways to improve the personal and economic components of mental health care.

2. Providing a knowledge base to move evidence-based interventions into practice.

Despite their proven ability to alleviate mental illness, many tested interventions take far too long to be adopted into common practice, with some never reaching those most in need of them. Numerous barriers exist to prevent the successful integration of evidence-based interventions within clinical and community practice. Improving the fit between effective interventions and the care settings in which they are delivered is an important focus of NIMH services research. NIMH researchers, for example, are exploring new strategies to advance the dissemination and implementation of efficacious interventions in individual practices, on the community level, and even the state level. One such project involves working with the state of California to test the effectiveness of a theory-driven model to promote the adoption, implementation, and sustainability of an evidence-based intervention for children in foster care into county-wide systems.

In addition, NIMH researchers are seeking new methods for delivering evidence-based interventions to hard-to-reach populations, often making use of innovative technologies. For example, a recent study demonstrated that an Internet-based, self-managed cognitive behavioral therapy can help reduce symptoms of PTSD and depression.28

Finally, to ensure that evidence-based interventions have maximal benefit to public mental health, NIMH researchers are studying the best approaches for adapting proven interventions to the needs of diverse populations. For example, Critical Time Intervention (CTI), an intervention to prevent homelessness among persons with mental illness when they move from one living situation to another, has proven to be both effective29 and cost-effective30 for men moving from the shelter to the community. It has also been shown to be effective for formerly homeless veterans returning to their communities after psychiatric hospitalization.31 A current study is seeking to adapt CTI for men and women moving from incarceration to the community. Taken together, this body of knowledge will maximize the impact that scientific discoveries can have in the service of public health.

Appendix A

Development Process for the NIMH Strategic Plan

This Strategic Plan was developed using a multi-stage process that solicited input from NIMH’s staff and stakeholders. The first stage involved developing the Institute’s Vision and Mission Statements, as well as the Institute’s overarching scientific objectives. These objectives, developed with assistance of the NAMHC, are broad goals that capture the diversity of topics the Institute must focus on in order to achieve its mission. The seven scientific objectives, successively building in scale from the most basic neuroscience and behavioral science to the broad societal dissemination of mental health research and treatment best practices, are to:

  1. Understand the neuronal and behavioral basis of mental disorders and how they deviate from normal processes.
  2. Develop reliable, valid diagnostic tests and biomarkers for mental disorders.
  3. Define the genetic and environmental risk architecture of mental disorders.
  4. Develop interventions to prevent occurrence and/or reduce relapse of mental disorders.
  5. Develop more effective treatments that have minimal side effects, reduce symptoms, and improve daily living.
  6. Conduct clinical trials that will provide practitioners with treatment options to deliver more effective personalized care across diverse populations and settings.
  7. Create improved pathways for dissemination of science to mental health care and service efforts.

The second stage in the Strategic Plan’s development involved identifying the current state of the science for each of the seven scientific objectives, as well as gaps and opportunities for research advancement. This was accomplished through a series of Institute-wide brainstorming sessions, the results of which identified the four objectives that serve as the basis for this Strategic Plan.

Once an initial draft of the Plan was complete, it was posted on NIMH’s website and public feedback was encouraged (see Appendix B). The draft Plan was also presented to the NAMHC in order to solicit council members’ comments. The draft Strategic Plan was then edited based upon the received feedback, its text and layout were finalized, and the finished draft was publicly released.

Appendix B

Public Comment on the NIMH Strategic Plan

A draft version of the NIMH Strategic Plan was made available to the public, via the NIMH website and postal mail, between November 20, 2007, and December 21, 2007. In total, the Institute received emails and letters from more than 550 individuals, groups, and organizations regarding a broad range of mental health-related topics. We would like to thank everyone who took the time to provide feedback on the draft Strategic Plan. Numerous edits were made to the Plan during its finalization process based on the comments that were received. Public comments were also forwarded to the Institute’s research divisions so that NIMH staff members could be made further aware of the public’s concerns and suggestions.

1 Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. Prevalence, severity, and comorbidity of twelve-month DSM-IV disorders in the National Comorbidity Survey Replication (NCS-R). Arch Gen Psychiatry. 2005 Jun;62(6):617-27. PMID: 15939839

2 U.S. Census Bureau Population Estimates by Demographic Characteristics. Table 2: Annual Estimates of the Population by Selected Age Groups and Sex for the United States: April 1, 2000 to July 1, 2004 (NC-EST2004-02) Source: Population Division, U.S. Census Bureau Release Date: June 9, 2005.

3 The World Health Organization. The World Health Report 2004: Changing History, Annex Table 3: Burden of disease in DALYs by cause, sex, and mortality stratum in WHO regions, estimates for 2002. Geneva, Switzerland: The World Health Organization, 2004.

4 Centers for Disease Control and Prevention, National Center for Injury Prevention and Control. Web-based Injury Statistics Query and Reporting System (WISQARS). (

5 While the Institute invests significantly in research on the intersections between mental health and AIDS, it is important to note that this investment is guided by a National Institutes of Health (NIH)-wide Strategic Plan coordinated through the NIH Office on AIDS Research ( ). Therefore, research on the mental health aspects of AIDS is not addressed in this Plan.

6 President’s New Freedom Commission on Mental Health. Achieving the Promise: Transforming Mental Health Care in America. Final Report. DHHS Pub. No. SMA-03-3832. Rockville, MD: 2003. (

7 Binder EB, Bradley RG, Liu W, Epstein MP, Deveau TC, Mercer KB, Tang Y, Gillespie CF, Heim CM, Nemeroff CB, Schwartz AC, Cubells JF, Ressler KJ.Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA. 2008 Mar;299(11):1291-305.

8 Kaufman J, Yang BZ, Douglas-Palumberi H, Houshyar S, Lipschitz D, Krystal JH, Gelernter J.Social supports and serotonin transporter gene moderate depression in maltreated children. Proc Natl Acad Sci U S A. 2004 Dec;101(49):17316-21.

9 Kaufman J, Yang BZ, Douglas-Palumberi H, Houshyar S, Lipschitz D, Krystal JH, Gelernter J.Social supports and serotonin transporter gene moderate depression in maltreated children. Proc Natl Acad Sci U S A. 2004 Dec;101(49):17316-21.

10 Livet J, Weissman TA, Kang H, Draft RW, Lu J, Bennis RA, Sanes JR, Lichtman JW. Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system. Nature. 2007 Nov 1;450(7166):56-62.

11 Zhang F, Wang LP, Brauner M, Liwald JF, Kay K, Watzke N, Wood P, Bamberg E, Nagel G, Gottschalk A, Deisseroth K. Multimodal fast optical interrogation of neural circuitry. Nature. 2007 Apr 5;446(7136):633-9.

12 Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K. Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci. 2005 Sep;8(9):1263-8.

13 Marenco S, Siuta MA, Kippenhan JS, Grodofsky S, Chang WL, Kohn P, Mervis CB, Morris CA, Weinberger DR, Meyer-Lindenberg A, Pierpaoli C, Berman KF. Genetic contributions to white matter architecture revealed by diffusion tensor imaging in Williams syndrome. Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):15117-22.

14 Thompson PM, Vidal C, Giedd JN, Gochman P, Blumenthal J, Nicolson R, Toga AW, Rapoport JL. Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia. Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11650-5.

15 Gogtay N, Ordonez A, Herman DH, Hayashi KM, Greenstein D, Vaituzis C, Lenane M, Clasen L, Sharp W, Giedd JN, Jung D, Nugent TF 3rd, Toga AW, Leibenluft E, Thompson PM, Rapoport JL. Dynamic mapping of cortical development before and after the onset of pediatric bipolar illness. J Child Psychol Psychiatry. 2007 Sep;48(9):852-62.

16 Shaw P, Eckstrand K, Sharp W, Blumenthal J, Lerch JP, Greenstein D, Clasen L, Evans A, Giedd J, Rapoport JL. Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19649-54.

17 Landa RJ, Holman KC, Garrett-Mayer E. Social and communication development in toddlers with early and later diagnosis of autism spectrum disorders. Arch Gen Psychiatry. 2007 Jul;64(7):853-64.

18 Cannon TD, Cadenhead K, Cornblatt B, Woods SW, Addington J, Walker E, Seidman LJ, Perkins D, Tsuang M, McGlashan T, Heinssen R. Prediction of Psychosis in High Risk Youth: A Multi-Site Longitudinal Study in North America. Arch Gen Psychiatry. 2008 Jan;65(1):28-37.

19 Milad MR, Quirk GJ. Neurons in medial prefrontal cortex signal memory for fear extinction. Nature. 2002; 420:70 –74.

20 Bouton ME. Context and behavioral processes in extinction. Learn Mem. 2004; 11:485– 494.

21 Walker DL, Ressler KJ, Lu K-T, Davis M. Facilitation of conditioned fear extinction by systemic administration or intra-amygdala infusions of D-cycloserine as assessed with fear-potentiated startle in rats. J Neurosci. 2002; 22:2343–2351.

22 Ressler KJ, Rothbaum BO, Tannenbaum L, et al. Cognitive enhancers as adjuncts to psychotherapy: use of D-cycloserine in phobic individuals to facilitate extinction of fear. Arch Gen Psychiatry. 2004 Nov; 61(11):1136-1144.

23 Paddock S, Laje G, Charney D, Rush JA, Wilson AF, Sorant AJM, Lipsky R, Wisniewski SR, Manji H, McMahon FJ. Association of GRIK4 With Outcome of Antidepressant Treatment in the STAR*D Cohort. Am J Psychiatry 164(8): 1181-1188.

24 Laje G, Paddock S, Manji H, Rush AJ, Wilson AF, Charney D, McMahon FJ. Genetic Markers of Suicidal Ideation Emerging During Citalopram Treatment of Major Depression. Am J Psychiatry. 2007 Oct;164(10): 1530-1538.

25 Mark TL, Levit KR, Coffey RM, McKusick DR, Harwood HJ, King EC, Bouchery E, Genuardi JS, Vandivort-Warren R, Buck JA, Ryan K. National Expenditures for Mental Health Services and Substance Abuse Treatment, 1993-2003. SAMHSA Publication No. SMA 07-4227. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2007. (

26 Kessler RC. Heeringa S, Lakoma MD, Petukhova M, Rupp AE, Schoenbaum M, Wang PS, Zaslavsky AM. The individual-level and sociatial-level effects of mental disorders on earnings in the United States: Results from the National Comorbidity Survey Replication. Am J Psychiatry. 2008 Jun; 165(6):703-711.

27 Wang PS, Simon GE, Avorn J, Azocar F, Ludman EJ, McCulloch J, Petukhova MZ, Kessler RC. Telephone screening, outreach, and care management for depressed workers and impact on clinical and work productivity. JAMA. 2007 Sept; 298(12): 1401-1411.

28 Litz BT, Engel CC, Bryant R, Papa A. A Randomized Controlled Proof-of-Concept Trial of an Internet-Based, Therapist-Assisted Self-Management Treatment for Posttraumatic Stress Disorder. Am J Psychiatry. 2007 Nov;164(11):1676-84

29 Susser E, Valencia E, Conover S, Felix A, Tsai W, Wyatt R. Preventing recurrent homelessness among mentally ill men: A “critical time” intervention after discharge from a shelter. Am J Public Health. 1997; 87(2): 256-262.

30 Jones K, Colson PW, Holter MC, Lin S, Valencia E. Susser E, Wyatt RJ. Cost-effectiveness of critical time intervention to reduce homelessness among persons with mental illness. Psychiatr Serv. 2003;54(6): 884-890.

31 Kasprow WJ, Rosenheck RA. Outcomes of critical time intervention case management of homeless veterans after hospitalization. Psychiatr Serv. 2007; 58(7): 929-935.

Previous Reports

For related NIMH reports, visit the National Advisory Mental Health Council home page.