Updated: June 2022

NATIONAL INSTITUTE OF MENTAL HEALTH

STRATEGIC PLAN FOR RESEARCH 

Updated: May 2023
NIMH Strategic Plan for Research i

Message from the Director Table of Contents

Table of Contents

Message from the Director............................................................................................................................................1

Overview of NIMH .........................................................................................................................................................3

Serving as an Efficient and Effective Steward of Public Resources ...............................................................................5

Scientific Stewardship ...............................................................................................................................................5

Setting Research Priorities....................................................................................................................................5

Monitoring and Measuring Programs...................................................................................................................5

Emphasizing Rigor and Reproducibility.................................................................................................................6

Fostering Resource and Data Sharing ..................................................................................................................6

Enhancing Oversight and Monitoring of Clinical Trials.........................................................................................6

Creating and Strengthening Partnerships ............................................................................................................7

Management and Accountability..............................................................................................................................7

Cultivating a Respectful and Inclusive Workplace at NIMH..................................................................................7

Promoting Innovation...........................................................................................................................................7

Enhancing Risk Management................................................................................................................................8

Improving Administrative Processes.....................................................................................................................8

Promoting Workforce Development and Diversity...............................................................................................8

Accomplishing the Mission............................................................................................................................................9

Challenges and Opportunities.....................................................................................................................................10

Coronavirus Disease 2019 (COVID-19) Pandemic ...................................................................................................10

Suicide Prevention...................................................................................................................................................11

Early Intervention in Psychosis................................................................................................................................12

Mental Health Equity ..............................................................................................................................................13

HIV Research ...........................................................................................................................................................13

Digital Health Technology .......................................................................................................................................14

Genetics...................................................................................................................................................................15

Neural Circuits.........................................................................................................................................................15

Cross-Cutting Research Themes..................................................................................................................................17

A Comprehensive Research Agenda .......................................................................................................................17

Prevention...............................................................................................................................................................17

Global Mental Health ..............................................................................................................................................18

Environmental Exposures........................................................................................................................................18
NIMH Strategic Plan for Research ii

Message from the Director Table of Contents

Comorbidities..........................................................................................................................................................19

Translation ..............................................................................................................................................................19

Computational Approaches.....................................................................................................................................20

Harnessing the Power of Data.................................................................................................................................21

Research Workforce................................................................................................................................................21

Goal 1: Define the Brain Mechanisms Underlying Complex Behaviors.......................................................................23

Objective 1.1: Elucidate the brain mechanisms underlying cognitive, affective, and social processes..................24

Objective 1.2: Identify the genomic and non-genomic factors associated with mental illnesses ..........................25

Objective 1.3: Identify and characterize the neural circuit mechanisms contributing to human behavior and their 

disruption in mental illnesses..................................................................................................................................27

Goal 2: Examine Mental Illness Trajectories Across the Lifespan................................................................................30

Objective 2.1: Characterize the trajectories of brain, cognitive, affective, and behavioral development across the 

lifespan and in diverse populations.........................................................................................................................31

Objective 2.2: Identify and understand risk factors, biomarkers, and behavioral indicators of mental illnesses and 

of intervention responses across the lifespan ........................................................................................................32

Goal 3: Strive for Prevention and Cures ......................................................................................................................34

Objective 3.1: Develop new interventions based on discoveries in genomics, engineering, neuroscience, and 

behavioral science...................................................................................................................................................35

Objective 3.2: Develop strategies for tailoring existing interventions to optimize outcomes................................36

Objective 3.3: Test interventions for effectiveness in community practice settings..............................................38

Goal 4: Advance Mental Health Services to Strengthen Public Health .......................................................................41

Objective 4.1: Improve the efficiency, effectiveness, and reach of mental health services through research ......41

Objective 4.2: Expedite adoption, sustained implementation, and continuous improvement of evidence-based 

mental health services ............................................................................................................................................43

Objective 4.3: Develop innovative service delivery models to dramatically improve the outcomes of mental 

health services received in diverse communities and populations.........................................................................44

Strategic Planning Process...........................................................................................................................................48

Updates to the Plan.................................................................................................................................................49

References...................................................................................................................................................................50
NIMH Strategic Plan for Research 1

Message from the Director

Message from the Director

It is an exciting time to be at the helm of the National Institute of Mental Health (NIMH), the lead 

federal agency charged with setting and supporting the national agenda for mental health research. 

Scientific advances are rapidly transforming neuroscience and mental health care. Just in the last five 

years, we have made considerable progress. In basic science, the genetic revolution has begun to pay off 

for mental health research—after facing some challenges, we have now identified hundreds of places in 

the genome irrefutably linked to mental illnesses such as schizophrenia, autism, and depression. Thanks 

to the NIH Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative, we have 

new tools and resources that allow unprecedented insight into the exquisite complexities of the living 

brain. In translational sciences, we celebrated the U.S. Food and Drug Administration (FDA) approval of 

two of the first truly novel antidepressants in decades—esketamine for treatment-resistant depression, 

and brexanolone for postpartum depression. And in intervention research, NIMH-sponsored studies 

proving the effectiveness of coordinated specialty care for first episode psychosis led to nationwide 

implementation of this evidence-based care model through state-supported mental health clinics.

The future is bright. We’ve enacted the NIMH Strategic Plan for Research, aiming to build on these 

advances. Over the next few years, we look forward to further implementation of suicide prevention 

efforts based on recent NIMH findings. These findings include studies demonstrating the benefit of 

universal screening in emergency departments for suicidal thoughts and behaviors, and the benefits and 

challenges of predicting suicide risk using electronic health records and other digital tools. NIMH is also 

investing in practice-based research that examines mental health care delivery in real-world settings. For 

example, NIMH is pioneering the Early Psychosis Intervention Network (EPINET), a research network 

that will use data from community-based first episode psychosis clinics to enhance the delivery, 

evaluation, and continual improvement of evidence-based care. These continuous advances drive the 

enthusiastic and energetic efforts of the research workforce devoted to our mission. And, more 

importantly, they offer hope and solutions to individuals with mental illnesses, as well as their families 

and communities. 

Since the advent of this plan in 2020, we have faced significant challenges. Early in the coronavirus 

disease 2019 (COVID-19) pandemic, symptoms of depression, anxiety, and substance use increased for 

many, and although those symptoms resolved for most, some continue to have elevated symptoms. At 

the same time, minoritized and marginalized communities were disproportionately impacted by greater 

rates of illness and death tragically due to SARS-CoV-2 infection as well as with broader mental health 

consequences of the social, behavioral, and economic impacts of the pandemic. Those infected with 

SARS-CoV-2 can also experience an increase in new mental illness both in the short- and long-term. 

Regardless of direct infection, reports suggest mental health symptoms have remained elevated 

compared to pre-pandemic data. Groups differentially impacted by COVID-19, including Black, Latinx, 

American Indian/Alaska Native, LGBTQ+, and other minoritized and marginalized communities, continue 

to experience greater challenges.
NIMH Strategic Plan for Research 2

Message from the Director

NIMH has relied on its strategic plan to adapt to these challenges. We continue to collaborate with other 

institutes, centers, and offices across NIH, funding more than 40 projects to understand the mental 

health impacts of the pandemic, including the impact of public health mitigation approaches, and 

critically to evaluate scalable, deployable interventions that are desperately needed to respond to the 

increased mental health needs of diverse populations. All of these efforts are in line with our strategic 

priorities, particularly in the context of ongoing mental health disparities. 

As NIMH Director, I am committed to dismantling structural racism in biomedical research. At NIMH, we 

aim to identify and address the extent to which our policies, practices, and culture serve to perpetuate 

the status quo and are working to promote anti-racist ideas and actions both within NIMH and in the 

research communities we support. We started by examining how our application review process affects 

the diversity of our scientific workforce. For example, some of our early efforts are focused on 

understanding and employing solutions to reduce disparities in award rates for grant applications 

supporting Black investigators. We are also making changes to improve diversity, equity, inclusion, and 

accessibility (DEIA) within the NIMH workplace. In response to an internal assessment, NIMH is creating 

new opportunities for dialogue, training, and engagement to advance DEIA efforts. I recognize that 

these efforts, among others in alignment with the NIH-Wide Strategic Plan for DEIA and the UNITE 

initiative, are just the start to making lasting change. 

The NIMH Strategic Plan for Research maps our path. From basic research aimed at understanding how 

the brain produces behavior, to translational efforts to uncover novel treatment targets, to clinical 

studies testing novel approaches in community settings, we have charted numerous routes linking these

challenges and opportunities. Each has the potential to deliver significant advances in mental health 

care. NIMH’s broad portfolio aims to ensure that our research will have public health impacts across a 

range of timeframes—from the near-term to the far-off future. At NIMH, we are proud of how far we 

have come, humbled by the distance yet to be traveled, and empowered by the hope that drives us 

forward. 

Joshua A. Gordon, M.D., Ph.D.

Director, National Institute of Mental Health
NIMH Strategic Plan for Research 3

Overview of NIMH

Overview of NIMH

The National Institute of Mental Health (NIMH) is the lead federal agency for research on mental 

illnesses. NIMH is one of the 27 institutes and centers that make up the National Institutes of Health 

(NIH), the largest biomedical research agency in the world. 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. 

To carry out this mission, NIMH, as established by the Mental Health Act of 1946 and in accordance with 

Title IV of the Public Health Service Act, conducts and supports biomedical and behavioral research, 

health services research, research training, and health information dissemination with respect to the 

causes, diagnosis, treatment, management, and prevention of mental illnesses. As mental health is an 

important part of overall health, NIMH invests in research on adaptive and maladaptive behaviors to 

better understand mental function and dysfunction. 

NIMH supports research and research training through extramural activities and conducts research and 

research training through intramural activities. Through its extramural program, NIMH currently 

supports more than 3,500 research grants and contracts annually at universities, academic health 

centers, and other research institutions across the country and around the world. The NIMH Extramural 

Research Program is organized into four scientific funding Divisions—the Division of Neuroscience and 

Basic Behavioral Science, the Division of Translational Research, the Division of Services and Intervention 

Research, and the Division of AIDS Research. NIMH staff manage and administer the extramural 

research grants and contracts that support cutting-edge scientific discovery in basic, translational, 

comparative effectiveness, and implementation science that aims to transform understanding,

prevention, and treatment of mental illnesses across the lifespan, from prenatal development to late 

life. 

Staff in the NIMH Intramural Research Program (IRP) plan and conduct basic, clinical, and translational 

research to advance understanding of the diagnosis, causes, treatment, and prevention of psychiatric 

disorders. NIMH IRP investigators utilize the unique resources of the NIH to conduct state-of-the-art 

research in an environment conducive to the training and development of clinical and basic scientists

that often complements extramural research activities. The NIMH IRP supports approximately 600 

scientists, who work on the NIH campus in Bethesda, MD. NIMH intramural scientists range from 

molecular biologists working in laboratories to clinical researchers working with patients in the NIH 

Clinical Center, the world’s largest hospital dedicated to clinical research. The variety of scientific 

expertise facilitates interdisciplinary studies and promotes translational research, linking basic research 

discoveries to clinical care. 

To deliver high quality, impactful research and promote translation of such research into clinical 

practice, services delivery, and policy, NIMH developed the Strategic Plan for Research to advance our 

mission and guide research over a five-year period. The NIMH Strategic Plan for Research builds on the 

successes of previous NIMH Strategic Plans, provides a framework for research to leverage new 
NIMH Strategic Plan for Research 4

Overview of NIMH

opportunities for scientific exploration, and addresses new challenges in mental health. In this Strategic 

Plan for Research, NIMH outlines four high-level Goals as follows:

• Goal 1: Define the Brain Mechanisms Underlying Complex Behaviors

• Goal 2: Examine Mental Illness Trajectories Across the Lifespan

• Goal 3: Strive for Prevention and Cures

• Goal 4: Advance Mental Health Services to Strengthen Public Health 

These four Goals form a broad roadmap for the institute’s research priorities over the next five years, 

beginning with fundamental science of the brain and behavior, and extending through evidence-based 

services that improve public health outcomes.

Please Note: The terms “mental illnesses,” “mental disorders,” and “psychiatric disorders” are used 

interchangeably throughout this document. These terms are meant to include an array of disorders 

within NIMH’s scope of interest. Reference to a specific disorder (i.e., as an example or a highlight) or 

research area does not imply prioritization, unless otherwise noted. Furthermore, NIMH respects the 

known comorbidity and heterogeneity of symptoms across mental disorders and recognizes that 

knowledge gained from studying one may inform understanding of and treatment for others. 
NIMH Strategic Plan for Research 5

Stewardship Stewardship

Serving as an Efficient and Effective Steward of Public Resources

Scientific Stewardship

Setting Research Priorities

At the agency level, NIH sets research priorities by managing a dynamic balance among existing and 

emerging public health needs, scientific opportunities, budgetary considerations, and the range of 

science in its portfolio. At the institute level, priorities are outlined within the NIMH Strategic Plan for 

Research. At NIMH, a balanced portfolio starts with excellent science that includes diverse subject 

matter (basic, translational, and applied sciences), diverse timeframes (research with potential impact in 

the short-, medium-, and long-terms), diverse study populations, and a diverse workforce. NIMH 

research priorities are also informed by strategic planning. Strategic planning at NIMH is comprehensive, 

responsive, and adaptive to the often serendipitous nature of scientific progress. Planning also includes 

input from a variety of stakeholders, including NIMH leadership and staff, the National Advisory Mental 

Health Council, as well as federal and private partners, both domestic and global.

NIMH also sets priorities in accordance with NIH-wide strategic plans and research plans of partnering 

organizations. Such plans include the NIH-Wide Strategic Plan, the Advancing Science for the Health of 

Women: The Trans-NIH Strategic Plan for Women’s Health Research, the NIH Minority Health and Health 

Disparities Strategic Plan, the NIH Strategic Plan for Tribal Health Research, the Office of Disease 

Prevention Strategic Plan, the NIH Strategic Plan for Data Science, and the NIH-wide Strategic Plan for 

COVID-19 Research, among others. NIMH also has a substantial investment in supporting HIV research; 

this investment is guided by the NIH Strategic Plan for HIV and HIV-Related Research, coordinated 

through the NIH Office of AIDS Research. Additionally, NIMH has contributed to the creation of several 

strategic plans and reports that include more detail on specific topics, which also inform NIMH priorities. 

These documents include but are not limited to: the White House Report on Mental Health Research 

Priorities; the Interagency Autism Coordinating Committee (IACC) Strategic Plan for Autism Spectrum 

Disorder; the Interdepartmental Serious Mental Illness Coordinating Committee Report to Congress; the

Grand Challenges in Global Mental Health Initiative; A Prioritized Research Agenda for Suicide 

Prevention: An Action Plan to Save Lives, a collaboration with the National Action Alliance for Suicide 

Prevention; and, the Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative

strategic plan, BRAIN 2025: A Scientific Vision, and Working Group reports and plans, including the

BRAIN Initiative 2.0: From Cells to Circuits, Toward Cures and the BRAIN Initiative and Neuroethics: 

Enabling and Enhancing Neuroscience Advances for Society. 

Monitoring and Measuring Programs

NIMH continuously reviews and evaluates its scientific research and training programs to ensure 

responsible management of public funds and measure progress toward accomplishing our mission. For 
NIMH Strategic Plan for Research 6

Stewardship Stewardship

example, NIMH regularly conducts portfolio analyses to identify research gaps and opportunities. 

NIMH’s monitoring and evaluation efforts continue to evolve to keep pace with changing methods to 

analyze information, and new requirements mandated by NIH, the Department of Health and Human 

Services (HHS), and Congress. Program monitoring and evaluation informs the development,

implementation, and reporting of NIMH efforts and accomplishments.

Emphasizing Rigor and Reproducibility

Funding excellent science is essential to the research enterprise. As such, NIMH emphasizes the 

importance of both rigor and reproducibility. Research studies must have a sufficiently rigorous design 

and be sufficiently powered, such that they can be replicated. This means NIMH ensures the sample

sizes within studies are appropriate so they are adequately powered for meaningful effect sizes; ensures

the statistical analysis plans included in grant applications contain sufficient information for reviewers to 

properly evaluate them; ensures expertise in review sections and program staff to properly assess 

statistical methodologies; and, encourages the use of data sharing platforms that can enable third-party 

confirmation and mega-analyses that consolidate data from multiple studies.

Fostering Resource and Data Sharing 

Access to biospecimens and data sharing efficiently expands research capacity and maximizes NIMH’s 

investments by promoting hypothesis generation, increasing the potential for testing novel questions by 

integrating and harmonizing existing data, and encouraging reproducibility. NIMH continues to support 

programs that provide access to biospecimens, such as the NIH NeuroBioBank, a national resource for 

investigators utilizing human post-mortem brain tissue and related biospecimens. Existing NIMH 

investments in the NIMH Data Archive and other data archives have made it easier for NIMH applicants 

to meet NIH expectations for a Data Management and Sharing Plan (NIH Data Management and Sharing 

policy). NIMH also strongly encourages investigators to use common data elements, such as those 

available in the PhenX Toolkit, and requires the use of a small set of common data elements for NIMHfunded research on mental health and HIV. 

Enhancing Oversight and Monitoring of Clinical Trials

NIMH is committed to responsible stewardship, accountability, oversight, and transparency of clinical 

trials. NIMH continues to enhance oversight and monitoring of clinical trials to strengthen clinical 

research, ensure compliance, uphold inclusion standards, and safeguard research participants and their 

data. For example, to ensure studies are meeting their recruitment goals, NIMH expanded the Policy for

the Recruitment of Participants in Clinical Research to apply to all clinical trials, regardless of size. 

Furthermore, the NIH Inclusion Policy and Guidelines strengthen the commitment to clinical trials being 

conducted through a health equity lens and that diverse participants are included in clinical trials to 

better ensure evidence can be generalized back to communities.
NIMH Strategic Plan for Research 7

Stewardship Stewardship

Creating and Strengthening Partnerships 

Collaborations and partnerships across the research pipeline are vital components of NIMH efforts to 

achieve its public health mission. NIMH collaborates with other NIH institutes and centers, as well as 

HHS (e.g., the Centers for Disease Control and Prevention (CDC), the Centers for Medicare and Medicaid 

Services (CMS), the U.S. Food and Drug Administration (FDA), the Health Resources and Services 

Administration (HRSA), the Substance Abuse and Mental Health Services Administration (SAMHSA), the 

Indian Health Service (IHS), the Administration for Community Living (ACL), the Office of the Assistant 

Secretary for Planning and Evaluation (ASPE), the Administration for Children and Families (ACF)), and 

other federal agencies (e.g., the Department of Defense (DoD), the Department of Veterans Affairs 

(VA)). NIMH also works with public, private, non-profit, and research partners, both domestic and 

international, including those in the biotech and pharmaceutical industries. To broaden the 

dissemination and impact of research, NIMH works with external stakeholders—policymakers, advocacy 

groups, providers, and people with lived experience, including family members—who are also 

committed to the prevention, treatment, recovery, and cure of mental illnesses. Collaboration, 

communication, and coordination occur at various stages of research and continue to improve 

dissemination and implementation of evidence-based strategies, practices, and programs. 

Management and Accountability

Cultivating a Respectful and Inclusive Workplace at NIMH

In alignment with the NIH-Wide Strategic Plan for Diversity, Equity, Inclusion, and Accessibility (DEIA), 

NIMH is committed to creating and maintaining a work environment that promotes civility and 

respectful behavior and does not tolerate harassment or discrimination. The contributions of each and 

every member of the NIMH community are vital to transform the understanding, prevention, and 

treatment of mental illnesses. An environment where all people feel welcome, respected, valued, and 

heard is essential for individuals to contribute to their fullest potential. Over the past few years, NIMH 

completed an in-depth, third-party assessment of its internal workforce and has been actively engaging

with staff to improve processes, resources, communication, and accountability with the ultimate goal of 

enhancing workplace culture and climate. Further, NIMH is involved in NIH-wide efforts, such as the NIH 

UNITE initiative, to identify and take actions to address structural racism within the NIH and across the 

biomedical research community. 

Promoting Innovation 

The fields of science and technology are constantly evolving. Beyond scientific innovation, NIMH also 

embraces innovative administrative management practices to ensure the institute can adapt rapidly to 

changing needs and requirements while managing existing resources in a complex environment. In 
NIMH Strategic Plan for Research 8

Stewardship Stewardship

addition, NIMH is committed to encouraging a diverse research and scientific support workforce 

equipped with the knowledge and skills required to execute NIMH’s mission. 

Enhancing Risk Management

NIMH proactively identifies and mitigates internal and external risks to support the institute's mission. 

Working with HHS and NIH leadership, NIMH continues to improve procedures to develop standardized, 

automated, metric-oriented, and consistent business practices to mitigate risk. NIMH will leverage the 

values of collaboration, transparency, and accountability throughout our functional areas to proactively 

adapt risk-management mitigation procedures when confronted with emerging issues. 

Improving Administrative Processes

NIMH is committed to innovative and agile process improvement and aims to optimize, automate, and 

streamline business processes to ensure quality and consistency. As an example, NIMH regularly 

conducts internal workflow analyses to identify opportunities to reduce administrative burden. NIMH 

strives to implement business process management initiatives to maintain accountability and support 

our staff. NIMH will also continue to support efforts aimed at leveraging data to manage the needs of 

the institute and drive decision-making processes. 

Promoting Workforce Development and Diversity

To keep pace with advancing science, the NIMH workforce needs resources and training to ensure it has 

the knowledge, skills, and technologies to support its activities. NIMH encourages and supports the 

development of an inclusive, diverse, and well-trained research workforce. In addition, to preserve 

institutional knowledge, NIMH employs innovative approaches to encourage career development, retain 

expertise, and reward outstanding performance with an eye toward achieving equity and inclusion.
NIMH Strategic Plan for Research 9

Accomplishing the Mission Accomplishing the Mission

Accomplishing the Mission

NIMH developed the Strategic Plan for Research to advance the institute’s mission and guide research 

over a five-year period. The sections of this plan specifically address areas of crucial importance as NIMH 

strives to accomplish its mission. First, Challenges and Opportunities confronts the challenges that may 

lie ahead and describes some of the unique opportunities for scientific exploration to overcome these 

challenges and advance the understanding of mental illnesses. Second, Cross-Cutting Research Themes

are topics that are integral to the Goals of the Strategic Plan for Research and will influence the direction 

of mental health research as we move forward. Finally, the four Goals of the Strategic Plan for Research

form a broad roadmap for the institute’s research priorities, beginning with the fundamental science of 

the brain and behavior, and extending through evidence-based services that improve public health 

outcomes. Each of the four Goals include Objectives, followed by Strategies, which include research 

areas of specific interest that will help drive progress toward achieving our mission. The topics 

throughout the plan are not exhaustive. Prior to submitting an application, investigators are encouraged 

to contact NIMH program staff to discuss proposed aims and relevance to NIMH’s Goals and overall 

priorities.

NIMH will assess and monitor its performance in achieving the Goals presented in this plan by gathering 

and analyzing metrics associated with its core mission. Findings will be integrated to inform and refine 

the direction of the plan over time. The institute will share these findings and updates to the plan with 

stakeholders regularly, such as through NIMH's Strategic Plan Progress Reports.

In the context of prioritizing excellent science, the overall strategy for funding science is to support a 

broad spectrum of both investigator-initiated and institute-solicited research across the NIMH portfolio. 

Full implementation of the NIMH Strategic Plan for Research will help transform the prevention, 

diagnosis, and treatment of mental illnesses.
NIMH Strategic Plan for Research 10

Challenges and Opportunities

Challenges and Opportunities

The urgency of NIMH’s mission stems from the significant burden mental illnesses impose on 

individuals, their families, and society. In any given year, it is estimated that more than one in five U.S. 

adults live with a mental illness1 and the burden of mental illness is predicted to rise worldwide in 

coming decades.

2,3 Mental illnesses cut across age, sex, race, ethnicity, and socioeconomic status. 

Mental illnesses occur more commonly in people with other chronic illnesses, such as heart disease,

diabetes, cancer, and HIV.

4,5 In fact, people with a mental illness may have an increased risk for chronic 

illnesses,6 and effective treatment for mental illnesses can reduce that risk.7 Individuals with mental 

illnesses are also disproportionately represented among homeless and incarcerated populations.

8

Furthermore, serious mental illnesses significantly impair one’s ability to function in daily life, are 

associated with personal loss of earnings,9 have a negative global financial impact,10 and are among the 

leading causes of poor health and early mortality worldwide.4,11 Tragically, suicide remains an urgent 

public health crisis in the United States.12 Although the national suicide rate declined between 2018 and 

2020, the rate rose again in 2021 and is, at least in part, driven by disparities among certain minoritized 

groups.

13 The burden of mental illnesses demands that we harness scientific knowledge and tools to 

achieve better understanding, prevention, and treatment of these disabling conditions. In this section, 

we outline our plans to leverage considerable research opportunities to address the many challenges of

mental health and mental health research. 

Coronavirus Disease 2019 (COVID-19) Pandemic

To address the ongoing challenges that SARS-CoV-2 and the COVID-19 pandemic pose to our health and 

well-being, NIH is working urgently in unprecedented ways to understand and mitigate health threats. 

The NIH Strategic Plan for COVID-19 Research provides a framework for funding research across the 

scientific spectrum, primarily focusing on the direct testing, therapeutic, and preventive approaches 

needed to address SARS-CoV-2 and its long term consequences. As part of the strategic response to 

COVID-19, NIMH is actively engaged with the NIH Researching COVID to Enhance Recovery (RECOVER)

initiative, which seeks to understand, prevent, and treat post-acute sequelae of SARS-CoV-2 infection. 

NIMH is also participating in multiple Rapid Acceleration of Diagnostics (RADx®) initiatives, including 

the RADx® Underserved Populations (RADx-UP) program, which aims to lay the foundation to reduce 

disparities for those underserved and vulnerable populations who are disproportionately affected by the 

COVID-19 pandemic. NIMH is also involved in several other NIH-wide efforts, including the Social, 

Behavioral, and Economic Impacts of COVID-19 and Maternal and Child Health workgroups. Emerging 

data indicate that people with serious mental illness have been hard hit by the pandemic. Individuals 

with schizophrenia or depression are more than seven times more likely to contract COVID-19 and are 

more than twice as likely to die from it if they do fall ill, compared with individuals who do not have a 

mental illness.

14-16 NIMH-supported researchers are examining the effects of COVID-19 on mental health 

and developing and testing ways to improve delivery of care and treatment of mental illnesses in the 

context of a pandemic. This work is critical to meet the increased mental health needs for all who have 
NIMH Strategic Plan for Research 11

Challenges and Opportunities

been impacted by the pandemic, particularly as access to mental health services remain insufficient for 

the demand. In addition, NIMH staff continue to develop resources and share coping strategies to help 

people during the pandemic. More information about NIH’s response to the COVID-19 pandemic and 

guidance for researchers can be found on the NIH COVID-19 webpage.

Suicide Prevention

Given the troubling rise in the national suicide rate in the past decades, suicide prevention research 

remains an urgent priority for NIMH. From 1999 through 2018, U.S. suicide rates had shown small but 

consistent increases. The overall national suicide rate decreased between 2018 (14.2 per 100,000) and 

2020 (13.5 per 100,000); however, the suicide rate rose again in 2021 (14.1 per 100,000). This is, in part, 

due to rising rates among some racially and ethnically minoritized groups, and explanations for these 

disparities are being explored.

12,13 NIMH’s portfolio includes projects aimed at identifying individuals and 

populations most at risk for suicide, understanding the causes of suicide risk, developing suicide 

prevention interventions, and testing the effectiveness of these interventions and services in real-world 

settings. NIMH intramural and extramural research efforts have resulted in the development of

screening tools and clinical pathways for implementation in real-world settings to identify those at risk 

for suicide. Our current collaborative efforts are testing the benefits of various strategies for risk 

detection and intervention. Because many suicide decedents in the United States have accessed health

care services in the 12 months preceding death, health care systems can play a vital role in identifying 

individuals at risk and preventing suicide attempts.17 NIMH research has focused on emergency 

departments as a critical focal point, demonstrating that brief screening tools can improve providers’ 

ability to identify individuals at risk for suicidal behavior.18,19 Pairing this screening with a low-cost 

intervention, such as safety planning and follow-up phone calls, results in significant decreases in 

subsequent suicide attempts in the following year.18 NIMH-supported research has also led to the 

development of a computerized adaptive screener, which may make it easier for providers to screen 

more people and could help emergency departments quickly facilitate a connection with mental health 

services. NIMH continues to support research to identify how and why these screening and follow-up 

interventions work, and how these evidence-based tools can be scaled up for broader implementation

to prevent suicide attempts and deaths. To more rapidly test and implement novel suicide risk reduction 

strategies, NIMH is supporting Practice-based Suicide Prevention Research Centers that will advance 

research, implementation, and training in specific content areas. Given that firearms account for over 

50% of suicides annually in the United States, NIMH is funding research on preventing firearm injury and 

mortality. In addition, accumulating evidence suggests that various preventive interventions delivered 

early in life can change children’s mental health and substance use trajectories in a positive manner, 

including decreased risk for suicidal ideation and behaviors in adolescence and adulthood. NIMH 

continues to focus on understanding how disparities in suicide arise and can be addressed including 

among sexual and gender minority youth and adults who have elevated rates of suicide ideation and 

attempts across age, race, and ethnic groups. Understanding disparities in suicides among Black, 
NIMH Strategic Plan for Research 12

Challenges and Opportunities

American Indian and Alaska Native, and Asian youth, as well as pre-teens, older adults, and rural 

residents, continues to be an important area of focus. 

Early Intervention in Psychosis

In 2008, NIMH launched the Recovery After an Initial Schizophrenia Episode (RAISE) project, a largescale research initiative with the goal to help reduce the likelihood of long-term disability that people 

with schizophrenia often experience and help them lead productive, independent lives. The RAISE 

studies aimed to answer questions about the feasibility, effectiveness, and scalability of early 

intervention services for people experiencing first episode psychosis in the United States, with an 

emphasis on coordinated specialty care (CSC), a team-based, integrated, multi-element treatment 

approach to early psychosis. Baseline findings from the RAISE studies documented areas in need of 

improvement, including the long duration of untreated psychosis,20 variable adherence to treatment 

guidelines,21 and poor attention to comorbid medical conditions associated with premature mortality.22

In addition, the RAISE studies demonstrated that early intervention improves clinical outcomes among 

youth and young adults with first episode psychosis, and that CSC is a feasible and cost-effective 

approach to early intervention in first episode psychosis.23,24,25 Through collaborations with other federal 

agencies, NIMH transformed these findings into real-world change.

26,27 CSC is now the standard of care 

for early psychosis, with more than 360 CSC programs across the country. In 2019 alone, CSC programs

helped over 22,000 young people confronting the tremendous challenge of a first episode of psychosis 

by ensuring they had access to the best possible evidence-based care.

NIMH leveraged this expansion of CSC programs in the United States through the Early Psychosis 

Intervention Network (EPINET). The goal of EPINET is to accelerate advances in early psychosis care, 

recovery outcomes, and scientific discovery through a national early psychosis learning health care 

partnership. In this “learning health care system,” data that are routinely collected in CSC programs, as 

part of clinical practice, drive continuous improvement in client care and further scientific inquiry. 

Through EPINET, NIMH supports eight regional scientific hubs that include more than 100 CSC clinics in 

17 states, as well as a national data coordinating center that standardize, collect, and aggregate data 

across community clinics and use computational methods to study CSC quality and treatment 

effectiveness. By studying large, nationally representative datasets, EPINET may offer crucial insights 

into how best to tailor early psychosis care for individuals and provide information to guide 

improvements in diagnosis and intervention.

NIMH has joined the Accelerating Medicines Partnership® (AMP®) to form a public-private partnership 

between the NIH, the U.S. Food and Drug Administration (FDA), the European Medicines Agency, and 

multiple public and private organizations to establish the AMP Schizophrenia (AMP SCZ) initiative. AMP 

is managed through the Foundation for the National Institutes of Health (FNIH). The goal of the initiative 

is to generate tools for future studies that will improve success in developing early stage pharmacologic

interventions for people who are at risk of developing schizophrenia and other psychotic disorders. AMP 

SCZ has established a research network focused on identifying biological markers of disease progression, 
NIMH Strategic Plan for Research 13

Challenges and Opportunities

outcome measures and clinical endpoints. The initiative has also established a Data Processing, Analysis, 

and Coordinating Center to allow researchers to integrate and analyze data from new and key existing 

cohorts at clinical high risk for psychosis, with all data and analyses made publicly available through the 

NIMH Data Archive. Findings from these studies may enable researchers to develop algorithms that 

predict the course of illness for individuals with clinical high risk for psychosis and allow clinical trials to 

test new pharmacologic interventions to prevent the onset of psychosis.

Mental Health Equity

Mental health equity is the state in which all people have a fair and just opportunity to experience their 

highest level of mental health and emotional well-being. Racial and ethnic minorities, sexual and gender 

minorities, socioeconomically disadvantaged populations, and underserved rural populations experience 

striking disparities in burden of mental illness, access to and engagement in care, and recovery.

Moreover, people from minoritized and marginalized communities are disproportionately affected by 

existing disparities that have been exacerbated by recent acts of racism and discrimination and 

converging public health crises (e.g., COVID-19, HIV, and opioid epidemics).

28 In accordance with the 

21st Century Cures Act, NIMH staff work closely with the National Institute on Minority Health and 

Health Disparities (NIMHD), the Office of Research on Women’s Health (ORWH), and other NIH 

institutes, centers, and offices to ensure activities take into account the health needs of minoritized 

individuals and women and are focused on reducing health disparities. In our efforts to achieve mental 

health equity, NIMH developed an Approach to Mental Health Disparities Research which outlines five 

priority research areas to address mental health disparities, and an NIMH Strategic Framework for 

Addressing Youth Mental Health Disparities. NIMH supports research that addresses the needs of 

individuals and communities across age, race, ethnicity, language, gender identity, sexual orientation, 

geography, and social determinants of health (e.g., education, economic stability, quality of housing, 

access to health care, experience of discrimination), as well as their intersectionality (a framework that 

addresses the multiple dimensions of individuals’ identity and social systems as they intersect with one 

another and relate to inequality).

29 Of particular priority is research that identifies mechanisms 

contributing to the persistence of mental health disparities, and tests interventions aimed at reducing 

disparities, improving outcomes, and promoting equity. Further, to build a valid evidence base for 

effective prevention, treatment, and mental health services, NIMH strives to foster a culture of inclusion

that values and fosters partnerships between study participants, communities, and researchers from all 

backgrounds.

HIV Research

The prevalence of mental illnesses is higher in people with or at risk for HIV compared to the general 

population. Mental illnesses can be a barrier to HIV prevention, testing, linkage to treatment, treatment 

engagement, and retention in care. Mental illnesses are associated with poor health outcomes such as 

lower medication adherence, higher HIV incidence rates, and increased disease burden. There are also 
NIMH Strategic Plan for Research 14

Challenges and Opportunities

many co-occurring biological, psychosocial, and structural factors, as well as social determinants such as 

stigma, violence, and stress, that influence the development and course of mental illnesses and HIV. 

Mental health research is an integral component of HIV-related research across the lifespan. As such, 

NIMH supports a broad research portfolio in the United States and around the world to prevent HIV 

acquisition in high incidence populations and improve treatment and care among people with HIV,

including those with comorbid mental and substance use disorders.

NIMH utilizes basic science to understand the pathogenic mechanisms of HIV-associated central nervous 

system (CNS) disorders, while translational research supports the development of therapeutic strategies 

to treat HIV-CNS comorbidities, including cognitive disorders and mental illnesses. In addition, NIMH 

supports efforts focused on eradicating the virus from the CNS, a prerequisite to finding a safe, effective, 

and complete cure for HIV. To complement efforts in basic and translational science, NIMH also 

advances behavioral and social science research to examine individual, interpersonal, community, 

institutional/health system, and environmental factors; peer and community-based strategies; structural 

and psychosocial determinants; and, data science, methodologies, and technological approaches critical 

in HIV prevention and treatment. NIMH supports implementation science to enable researchers to bring 

evidence-based interventions to the greatest number of people who may benefit, and develop 

innovative communication and dissemination approaches that facilitate trust and use of those 

interventions, particularly among people with HIV in resource-limited settings. NIMH also places a high 

priority on HIV research that can impact individuals from high-incidence populations across the lifespan,

both domestically and globally, including racial and ethnic minorities, sexual and gender minorities, 

mobile populations, adolescents, women, and infants.

Digital Health Technology

Recent advances in technology continue to evolve and create new opportunities to improve access, 

availability, utilization, and quality of mental health care services. The pace of research and clinical use 

of digital health approaches has been dramatically accelerated by the COVID-19 pandemic. The growth 

of digital health technologies, which blend mobile health and health information technology (such as 

smartphones, wearable sensors, electronic health records), gives the public, health care providers, and 

researchers new ways to access information and to measure and manage health and productivity. 

Ongoing NIMH-supported research leverages mobile and other emerging technologies to develop, test, 

and deliver targeted preventive and treatment interventions for disorders such as anxiety, insomnia,

and depression. Approaches include just-in-time interventions that can be pushed out using 

smartphones or other technology based on information about the person’s current state and needs. 

Additional innovations employ patient- and clinician-facing digital monitoring devices, smartphones, and 

other applications or dashboards that facilitate monitoring and early detection of changes in patient 

status that might signal the need for additional or more intensive services to forestall relapse or 

hospitalizations. NIMH is also interested in digital biomarkers and outcome assessments for inclusion in 

clinical trials for monitoring responses to interventions. While the technology frontier offers promising 
NIMH Strategic Plan for Research 15

Challenges and Opportunities

opportunities for therapeutics (e.g., drug development, brain stimulation, behavioral therapies) and 

mental health care, much work remains to address questions about efficacy and effectiveness, bias, 

regulation, privacy, and additional ethical considerations. As technology is increasingly utilized in mental 

health research and care, innovation is needed to bridge the digital divide and ensure that lower 

resourced settings are included. 

Genetics 

Tremendous progress has been made in psychiatric genetics. Genome-wide association studies (GWAS)

as well as rare variant association analyses, both of which required global-scale collaborations to 

assemble immense sample sizes, uncovered statistically rigorous and fully replicated genetic links to 

schizophrenia, autism, depression, and other psychiatric disorders. In considering the complexity of the 

genetic landscape, the Report of the National Advisory Mental Health Council Workgroup on Genomics

provided recommendations for the future of genomics research: 1) utilize statistically rigorous, 

unbiased, and well-powered studies; 2) harness innovative approaches that address both common and 

rare genetic variants; and, 3) leverage universal datasets that capture genetic and phenotypic variation 

across diverse human populations. NIMH is focused on expanding the ancestral diversity of genetic 

samples and increasing our understanding of the genetic determinants of mental illnesses like 

obsessive-compulsive disorder, anorexia nervosa, and other disorders where additional work is needed. 

A significant goal is to better understand how molecular, neural, environmental, and psychosocial 

mechanisms interact with the genetic and epigenetic links that have been identified. Acquiring this new 

knowledge will likely cross levels of analysis, from genes to cells to circuits to behavior.

Neural Circuits

Neuroscience has provided us with the tools to look deeply into the function of neural circuits, and 

directly test hypotheses about brain-behavior relationships using noninvasive brain stimulation 

technologies. Over the past decade, technologies—such as optogenetics, chemogenetics, viral tracing, 

and high-resolution optical imaging—aimed at measuring and modulating the activity of specific circuits, 

have facilitated the attainment of a vast knowledge base about the circuits that control behavior and 

mental processes. Noninvasive neuromodulation devices allow scientists to change function within 

circuits for therapeutic benefit, and this approach led to the U.S. Food and Drug Administration (FDA) 

approval of transcranial magnetic stimulation (TMS) for the treatment of depression and obsessivecompulsive disorder. This knowledge, in turn, may enable the development of diagnostic and treatment 

strategies that detect and normalize circuit dysfunction in people with mental illnesses. In addition, 

invasive neural recording devices (e.g., deep brain stimulation with dual stimulation and recording

electrodes) that are used to treat a variety of clinical conditions in humans may enable researchers to

explore neural circuity underlying complex human behavior and mental illnesses. To drive progress in 

circuit neuroscience, NIMH, in part through the NIH Brain Research Through Advancing Innovative 

Neurotechnologies® (BRAIN) Initiative, aims to reveal how complex neural circuits dynamically interact 
NIMH Strategic Plan for Research 16

Challenges and Opportunities

to influence mental functions. NIMH is committed to understanding which circuits are altered in mental 

illnesses and how; which circuit elements can be changed to reverse or compensate for these 

alterations; and, at which points in time during the course of illness these manipulations are most 

effective.
NIMH Strategic Plan for Research 17

Cross-Cutting Research Themes

Cross-Cutting Research Themes

Several significant research themes cut across and are integral to the Goals of the NIMH Strategic Plan 

for Research. These themes highlight areas where NIMH-funded science may have the greatest impact, 

bridge research gaps, and offer novel approaches to accelerate advances and promote equity in mental 

health research. This section summarizes these major themes that, along with the challenges and 

opportunities facing the mental health field, inspired this Strategic Plan for Research.

A Comprehensive Research Agenda

Excellent and comprehensive science requires an inclusive approach focused on varied topic areas, 

extending research participation and partnerships, and advancing the research agenda across multiple 

timeframes. To ensure there is the potential to improve clinical care over the short-, medium-, and longterm, study designs should engage diverse populations and perspectives, methods, tools, and models.

Diversity in these areas of research, such as engaging multiple perspectives, enables us to address 

complex basic, translational, and applied questions, including those at the intersection of the brain, 

behavior, and community. All vertebrate animal and human studies should factor sex as a biological 

variable into research designs and reporting. Depending on the research question, researchers should 

consider how genetic background will advance the quality and interpretability of the outcomes. Clinical 

research studies should include participants from diverse racial and ethnic backgrounds, and across 

gender identities, geographical context, socioeconomic status, neurotype, and age—offering 

meaningfully representative samples best suited to address public health concerns and provide the most 

rigorous foundation to inform care and policy. 

Prevention

NIMH has a developmentally focused, theory-based prevention research program that spans the life 

course from prenatal though late-life, at different levels of intervention (e.g., universal, selective, 

indicated, tiered), and in different settings (e.g., homes, schools, health care settings, 

communities). While the targeted developmental stage may change, the primary focus of interventions 

is on reducing risk and increasing protective factors that can modify proximal outcomes (e.g., parenting, 

self-regulation, skill development) and long-term, distal outcomes (e.g., depression, anxiety, suicide 

ideation and behaviors). Transition periods (e.g., biological, normative, social) offer important 

opportunities for the implementation of preventive interventions at different developmental 

stages. NIMH supports research focused on developing and testing scalable preventive interventions, 

including prevention trials conducted in a variety of contexts and settings where preventive services are 

offered, and implementation research that tests strategies that can be used to promote the adoption 

and sustained implementation of effective preventive interventions in communities. 
NIMH Strategic Plan for Research 18

Cross-Cutting Research Themes

Global Mental Health

Mental illnesses are a global concern, presenting shared opportunities to advance science across 

international boundaries. NIMH investments in effectiveness and implementation research in low- and 

middle-income countries are producing innovative strategies for expanding access to mental health care 

and improving care quality and outcomes in a range of settings worldwide. Notably, several researchers 

are taking interventions developed for low-resource settings in the global context and applying them in 

the United States to address the tremendous burden of illness and limited health care capacity during 

the COVID-19 pandemic. At the same time, new global opportunities are emerging to advance our 

understanding of how genetics (or population genetics), cultural backgrounds, societal and familial 

structures, and environmental exposures can be integrated within basic and translational mental health 

research. Findings from this research will enhance our knowledge of mental health and illness; point to 

new targets for better preventive and treatment interventions; and, lead to novel approaches for 

addressing mental health needs worldwide, including those of currently underserved populations. NIMH 

also supports research on the implementation of new and evolving tools and technologies to facilitate 

and improve mental health screening, assessment, prediction, prevention, and treatment across 

systems of care. International collaborations with researchers, providers, advocates, individuals living 

with mental illness and their families, and global health and development agencies are also improving

NIMH’s ability to address mental illnesses in the United States, especially for those from geographically, 

socioeconomically, and culturally diverse populations.

Environmental Exposures

Numerous factors in the environment can influence the development of mental illnesses. The 

environment includes natural and built components, individual factors such as the microbiome, and 

social factors such as family interactions, peer relationships, and social determinants of health. Social 

determinants may include structural racism, housing instability, food insecurity, socioeconomic status, 

and others. These environmental factors, which vary within and across populations and settings, can 

affect biological systems important in regulating functions of the body and mental processes. We are 

making significant strides toward understanding how environmental factors affect brain development 

and shape behavior. For example, as part of the Adolescent Brain Cognitive DevelopmentSM Study (ABCD

Study®), which has enrolled over 10,000 children across the country, researchers are examining how 

biology and environment interact and relate to developmental outcomes, such as physical health and 

mental health. NIMH also continues to vigorously support efforts to study the biological and 

psychological impacts of trauma, mechanisms of prenatal risk, and numerous other environmental 

factors that may contribute to mental illnesses. In collaboration with the NIH Helping to End Addiction 

Long-term® (HEAL) Initiative, NIMH supports the HEALthy Brain and Child Development (HBCD) Study to 

understand the impact of prenatal and postnatal exposure to drugs and other adverse environmental 

conditions on brain development and risk of substance use, mental disorders, and other adverse

outcomes. NIMH is also participating in the NIH Climate Change and Health Initiative, an urgent, cross-
NIMH Strategic Plan for Research 19

Cross-Cutting Research Themes

cutting effort to reduce health threats from climate change and build health resilience in individuals, 

communities, and nations around the world, especially among those at highest risk.

Comorbidities

Comorbidities—the co-occurrence of mental and/or other physical disorders, including substance use 

disorders—may affect both the development and clinical course of mental illnesses through their effects

on basic biological processes. For example, some treatments for people with HIV may affect 

inflammation in the CNS, metabolism, and the microbiome—factors that also impact the development 

of mental illnesses. Examining the interactions between mental illnesses and co-occurring conditions will 

provide additional insight into the causes and facilitators of mental illnesses, as well as provide 

pathways to improve the provision of interventions and services to ultimately prevent and treat mental 

illness and comorbidities and achieve better outcomes for people with mental illnesses. NIMH works 

with other NIH institutes and centers to support research to address treatable medical comorbidities 

linked to premature mortality associated in people with serious mental illness. For example, through the 

NIH HEAL Initiative®, NIMH leads a portfolio of research to help improve the provision of services for 

people with co-occurring opioid use disorder and mental disorders and/or suicide risk. 

Translation

Engaging Novel Frameworks for Studying Mental Disorders. High rates of psychiatric comorbidity and 

heterogeneity of symptoms occur when patients are characterized using solely the current diagnostic 

categories, which rely on self-reported or observable symptoms. To extend research beyond diagnostic 

boundaries, NIMH’s evolving Research Domain Criteria (RDoC) framework integrates many approaches 

and levels of information to advance our understanding of mental illnesses. These levels of information 

span from cellular to behavioral measures, with attention to developmental trajectories and the impact 

of environmental and social factors. The RDoC framework is also well-suited to computational 

approaches, such as those described below, which incorporate multiple multimodal sources of 

information to improve mental health outcomes. Through the RDoC framework, NIMH encourages the 

identification of neurobehavioral mechanisms of specific domains of function. Beyond improving 

research sample characterization using objectively measurable factors, this approach holds promise for 

uncovering mechanisms of mental illnesses, identifying putative therapeutic targets, and paving the way 

for novel preventive and treatment interventions.

Advancing Interventions. Historically, novel prevention and treatment development has been slow, 

expensive, and high risk. To facilitate progress across the basic-to-clinical research pipeline, NIMH 

employs an experimental therapeutics approach to clinical trials requiring studies to define intervention

targets and milestones. With NIMH’s experimental therapeutics approach, studies not only evaluate the 

clinical effect of an intervention, but also generate information about the mechanisms contributing to a 

disorder or an intervention response.
NIMH Strategic Plan for Research 20

Cross-Cutting Research Themes

Accelerating Public Health Impact. The translation of new interventions into routine practice and 

population-level benefits has also been far too slow. To accelerate the adoption and implementation of 

evidence-based interventions and strategies into routine mental health care and other settings, NIMH 

invests in studies that anticipate real-world implementation during intervention development. 

Additionally, NIMH takes an experimental approach to testing mechanisms of effective care delivery in 

real-world settings, engages stakeholders throughout the research process, and attends to pragmatic 

questions about implementation like financing, scalability, and sustainability. This is especially important 

when considering the challenges of delivering care to underserved communities and in low-resource 

settings.

Computational Approaches

Computational approaches are aimed at developing mathematical and modeling frameworks to improve 

the understanding, prevention, and treatment of mental illnesses. Computational approaches can allow 

us to mechanistically describe and empirically test how high-level behavioral phenotypes emerge from 

complex neurobiological processes at the micro-, meso-, and macro-scale levels of the brain. For 

example, computational models can put into explicit mathematical terms testable hypotheses regarding 

how alterations in genes might causally affect circuit function through disruptions of neuronal and 

synaptic dynamics. Similarly, computational models can suggest how circuit dysfunction impacts neural 

development and plasticity, and how that dysfunction manifests in behavior leading to progressive, 

chronic disorders. In addition to modeling frameworks incorporating biophysical realism, more datadriven computational approaches can take advantage of large datasets, categorizing brain dysfunction in 

ways that can lead to better diagnoses, improved biomarkers, and tailored preventive and treatment 

interventions. Using big data and theoretical approaches in clinical research can help bridge the gap 

between integrative multi-omics (e.g., epigenomics, transcriptomics, proteomics), neuroimaging, and

digital phenotyping to traverse the complex path from genomics to therapeutics. Using computational 

approaches to assist in the development of explanatory theoretical models that integrate information 

across diverse experimentally tested domains (such as biological, psychological, social, and cultural 

environments; see the RDoC framework) can help define a critical path forward for understanding 

mechanisms and advancing new treatments. Within clinical research, computational methods (e.g., data

mining, machine learning, predictive analytics) may also be used to analyze electronic health records or 

other clinical data to identify modifiable risk factors, derive quantitative predictions to inform the 

optimal timing of interventions, and evaluate the outcomes of treatment trajectories. For instance, 

mathematical modeling approaches may predict which patients might respond best to which of the 

many existing treatments for depression, optimizing treatment selection and speeding recovery. These 

and other computational advances hold the promise of objective, data-driven diagnosis and treatment 

recommendations for serious mental illnesses. NIMH is dedicated to supporting computational 

approaches that integrate knowledge gained at genetic, molecular, cellular, circuit, behavioral, and 

health care system levels, and ask high-impact basic neuroscience, translational, and service and 

intervention questions. 
NIMH Strategic Plan for Research 21

Cross-Cutting Research Themes

Harnessing the Power of Data

Advances in data acquisition and the availability of aggregated, harmonized datasets, coupled with new 

computational modelling tools like machine learning, are revolutionizing the efficiency with which 

researchers turn data into knowledge. These advances will ultimately help us better understand the 

complex factors affecting prevention and treatment outcomes, and will optimize mental health care 

quality and effectiveness. NIMH is committed to providing modernized data infrastructure for use by the 

research community, capitalizing on advances in data science and information technology; setting 

policies to address storing data efficiently and securely for productive and ethical data use; and,

connecting with the NIH data ecosystem and other data systems to make NIMH data usable to the 

broader community, consistent with findability, accessibility, interoperability, and reusability (FAIR) 

principles. In addition to providing the infrastructure, NIMH is working with other major mental health 

research funders around the world to establish a set of measures (e.g., PhenX Toolkit), that all mental 

health researchers may use as they collect data. This effort is expected to allow researchers to better 

integrate data from different laboratories. Further, the development, validation, optimization, and 

expansion of digital mental health tools will improve our understanding of mental illnesses in real time, 

help track the course of illness, and improve mental health care. NIH’s Data Sharing Policy encourages 

widespread data sharing and collaborations with experts in other areas of science, including behavioral 

and social scientists, implementation scientists, ethicists, engineers, informaticists, and computer 

scientists, to add significant value to research and accelerate the pace of discovery. 

Research Workforce

Scientific advancement requires investment in future generations of mental health researchers. 

Indeed, research shows that diverse teams working together and capitalizing on innovative ideas and 

distinct perspectives outperform homogenous teams. As such, NIMH encourages investigators to 

consider diverse perspectives in designing their investigative teams, and emphasizes the importance of 

the diversity of perspectives across all phases of career development.

Training. Supporting outstanding scientists who will advance the field of mental health research is a 

priority for NIMH. NIMH uses institutional and individual funding mechanisms to support research 

training, education, and career development across a range of career stages from undergraduate

education through early stage faculty positions. The institute maintains a robust investment in the 

career development of investigators in all priority research areas described in NIMH’s Strategic Plan for 

Research and is committed to the inclusion of individuals who enrich the diversity of perspectives in 

research.

Inclusion and Diversity. By prioritizing inclusion and diversity, NIMH remains steadfast in its 

commitment to improving recruitment, training, advancement, and retention of researchers from 

diverse backgrounds, including those from groups underrepresented in the biomedical and behavioral 
NIMH Strategic Plan for Research 22

Cross-Cutting Research Themes

sciences, across areas of research funded by NIMH. For example, at the institutional level, NIMH 

supports the NIH Blueprint Program for Enhancing Neuroscience Diversity through Undergraduate 

Research Education Experiences (BP-ENDURE) that is focused on preparing undergraduates to enter and 

successfully complete neuroscience Ph.D. programs. Likewise, NIMH participates in the Maximizing 

Opportunities for Scientific and Academic Independent Careers (MOSAIC) effort to enhance diversity 

within the academic biomedical research workforce by providing support and mentorship to facilitate 

the transition of promising postdoctoral researchers from diverse backgrounds into independent faculty 

careers in research-intensive institutions. NIMH also encourages the neuroscience community to take 

advantage of the NIH-wide Faculty Institutional Recruitment for Sustainable Transformation (FIRST) 

Program, supported by the NIH Common Fund. Further, NIMH is participating in the BRAIN Initiative

effort to support the establishment of facilities at minority-serving institutions and Institutional 

Development Award-eligible institutions for improved access to key neuroscience research resources.

NIMH is also participating in an effort to evaluate the impact of the recent Plan for Enhancing Diverse 

Perspectives (PEDP), a required element for some NIH applications to outline strategies to advance the 

scientific and technical merit of the proposed project through expanded inclusivity. In addition, NIMH 

offers several funding opportunities and supplement programs to enhance the diversity of the 

workforce. To better understand barriers and facilitators to achieving racial and ethnic equity in funding 

success, NIMH also hosted virtual listening sessions during which extramural researchers shared their 

experiences navigating the NIH grant application process.
NIMH Strategic Plan for Research 23

Goal 1

Goal 1: Define the Brain Mechanisms Underlying Complex Behaviors

Through basic science, researchers endeavor to answer fundamental questions about the mechanisms 

(e.g., brain, behavioral, environmental, psychosocial) that contribute to cognition, perception, 

motivation, and social behavior. We have seen extraordinary progress in basic science over the past 

several years, including in neuroscience. New tools have enabled precise mapping and the ability to 

modulate brain circuits across model systems, from cells in a dish to the human brain. New techniques 

have improved the resolution of structural and functional imaging in humans. New sensor technologies 

are transforming the study of behavior. These new tools, techniques, and technologies will help us piece 

together the many complex connections among genes, the brain, and behavior. Researchers are also 

exploring how these aspects of mental function become altered in mental illnesses.

The vast number of cells and connections in the brain make understanding its function in complex 

behavior particularly challenging. New tools and technologies are helping us create a detailed map of 

the circuits involved in complex behavior, including those associated with mental illnesses. For example, 

to address the range of individual variation in brain circuits, the Human Connectome Project provided a 

reference atlas of neuronal connectivity—or a connectome—of 1,200 healthy brains. Researchers are 

now mapping long-distance brain connections and looking at their variability in unprecedented detail. 

These efforts are underway across development and across mental illnesses. 

The genomics revolution, fueled by technological advances, has revealed insights into the genetic 

architecture of mental illnesses. Over the past several years, large, replicated genomic studies have 

revealed many common and rare variants associated with the most heritable conditions (e.g., 

schizophrenia, bipolar disorder, autism). We are also making strides in identifying the genetic and 

nongenetic factors that control gene expression and play other roles in mental health and illness. While 

we have gone from few clues to many, we still cannot fully explain the root causes of mental illnesses. 

Researchers have begun the task of sorting through the complex patterns of genomic variation and 

environmental moderators to define and elucidate how these variations confer risk and resilience. We 

now know hundreds of identifying locations in the genome where genetic variation raises risk for 

psychiatric disorders. Because most participants in these studies have been of European descent, the 

findings may not be applicable to all. NIMH is expanding efforts to increase the diversity of the study 

participants across our genomics research to better benefit people of all racial and ethnic groups.

Researchers are also exploring the role of nongenomic factors (e.g., the environment, experience, the 

microbiome) and their impact on the risk for mental illnesses, including their impact on gene expression. 

We seek to understand how the interplay of molecular, cellular, circuit-level, genetic, and environmental 

factors influence the development of mental illnesses through animal and human studies.

Multidisciplinary approaches integrating statistics, mathematics, physics, computer science, and 

engineering will help us begin to explain how our brain predicts, interprets, alters, and responds to a 

complex world. Through basic science, we will achieve a more refined understanding of the brain 

mechanisms underlying complex behaviors, which will drive progress toward the novel interventions of 

tomorrow.
NIMH Strategic Plan for Research 24

Goal 1

The following Objectives further define this Goal: 

Objective 1.1: Elucidate the brain mechanisms underlying cognitive, affective, and 

social processes

To truly transform our understanding of mental illnesses, we need to identify the roles of all brain cell 

types and circuits in the myriad aspects of mental processes. Knowing how brain cells work together in 

circuits to drive cognitive, affective, and social processes will inform future circuit-based preventive and 

treatment interventions. New tools and techniques that span units of analysis (e.g., genes, molecules, 

cells, circuits, physiology, behavior) will transform our understanding of the brain, thus fostering our

understanding of mental illnesses. 

To better elucidate the brain mechanisms underlying cognitive, affective, and social processes, NIMH 

will support research that employs the following Strategies:

Strategy 1.1.A: Characterizing the genomic, molecular, cellular, and circuit components 

contributing to brain organization and function

Interest areas include:

1. Determining the phenotypic properties and dynamic interactions of neurons, astrocytes, 

oligodendrocytes, microglia, immune cells, and other cell types and how they contribute to 

brain organization and function.

2. Exploring the genomic, molecular, and physiological factors in cell-to-cell variation and 

determining the functional consequences of this variation.

3. Applying advanced neuroanatomical and functional approaches to map neural circuits at micro-, 

meso- and macro-scales.

Strategy 1.1.B: Identifying the developmental, functional, and regulatory mechanisms relevant 

to cognitive, affective, and social domains, across units of analysis

Interest areas include:

1. Elucidating the developmental processes that lead to the establishment of functional brain 

networks subserving these domains, including modifying factors (e.g., genomic, experiential) 

affecting these trajectories.

2. Identifying the mechanisms that mediate normal cellular communication and plasticity at the 

level of molecular control, signal transduction, synapses, circuits, and/or behavior. Examining

how alterations of these mechanisms may disrupt function; such mechanisms may involve nonneural components (e.g., immune system, microbiome, blood-brain barrier, vasculature). 

3. Developing and validating experimentally grounded theories for how the brain computes within 

these domains across spatiotemporal scales and levels of neurobiological abstraction (e.g., 

coordinated neural activity patterns and network state changes). 
NIMH Strategic Plan for Research 25

Goal 1

4. Applying novel behavioral assays of the domains that are causally linked to specific mechanisms 

at multiple units of analysis (e.g., genetic, molecular, cellular, circuit, physiological, behavioral, 

systems). These approaches will be prioritized over studies relying on traditional behavioral 

tests that presume congruence with human symptoms of mental illnesses and do not give 

insight into the function of the circuit(s) under investigation. 

5. Evaluating the preclinical utility of modifying cellular, synaptic, or circuit function for therapeutic 

benefit.

Strategy 1.1.C: Generating and validating novel tools, techniques, and measures to quantify 

changes in the activity of molecules, cells, circuits, and connectomes

Interest areas include:

1. Developing novel assays that can be used to interrogate key regulators of cellular 

communication using in situ and circuit-based models for screening, target discovery, and 

development of novel probes of cell function.

2. Advancing human cell-based assays using induced pluripotent stem cells (iPSCs) for studying the 

molecular factors in mental illnesses, with an emphasis on optimizing robustness, scalability,

reproducibility, and fidelity to in vivo human cell phenotypes, maturation, three-dimensional 

organization, and/or circuit function.

3. Developing novel, age-appropriate imaging assays with higher spatial and temporal resolution 

for visualization and analyses of brain structure, maturation, connectivity, and function, with 

particular emphasis on advancing real-time measurement approaches.

4. Developing innovative computational tools for the analysis and interpretation of neural activity 

including single unit, local field potentials, and other electrophysiological temporal dynamic 

patterns.

5. Developing and validating novel, objective physiological and behavioral measures as research 

tools to assess synaptic plasticity and circuit function in experimental systems, and as assays for 

assessing therapeutic targets in humans. 

6. Advancing objective, quantitative assays to track, manipulate, and analyze behavior at high 

temporal resolution in a range of species, ages, and settings, and across multiple modalities and 

systems. 

7. Developing noninvasive assays for interrogating and manipulating brain circuit function for 

therapeutic purposes.

8. Advancing novel assays to develop biomarkers of disease and for therapeutic discovery.

Objective 1.2: Identify the genomic and non-genomic factors associated with 

mental illnesses

A full understanding of the multifaceted contributors to risk for mental illnesses requires examination of 

genomic, epigenomic, and other factors, including the environment and experience, worldwide. 

Understanding how these factors contribute to adaptive and maladaptive behaviors, mental function 
NIMH Strategic Plan for Research 26

Goal 1

and dysfunction, and mental illnesses is critical for developing improved diagnostics and interventions 

that are effective for diverse individuals and populations. The genetic architecture of mental illnesses is 

extraordinarily complex. While the field of genomics has achieved remarkable advances in the past few 

years, the exact mechanisms that place certain individuals and populations at higher risk than others 

remain unknown. We need comprehensive approaches to understand genomic and non-genomic risk 

factors, and such investigations must consider diverse populations from around the world. To facilitate 

the transition of knowledge to practice, we need novel study designs, advanced genomic technologies, 

and innovative statistical and bioinformatic methods. These approaches will help us to revolutionize the 

analysis and interpretation of genetic associations and will speed the transition of this knowledge to 

practice.

To more effectively identify the genomic and non-genomic factors associated with mental illnesses, 

NIMH will support research that employs the following Strategies: 

Strategy 1.2.A: Discovering gene variants and other genomic elements that contribute to the 

development of mental illnesses in diverse populations

Interest areas include:

1. Performing large, well-powered, whole genome and exome-, epigenome-, and other “ome”-

wide studies in appropriate tissues.

2. Elucidating genetic architecture and heritability across the full allele frequency spectrum.

3. Mapping and identifying causal variants within risk loci.

4. Analyzing co-heritability and shared genetic risk architecture using cross-trait analyses.

5. Collecting and genomically characterizing ancestrally diverse cohorts.

Strategy 1.2.B: Advancing our understanding of the complex etiology of mental illnesses using

molecular epidemiologic approaches that incorporate individual genetic information in large 

cohorts

Interest areas include:

1. Conducting robust, well-powered, and unbiased genome-wide x phenome-wide association 

studies by leveraging large-scale genetic and phenotypic/exposure data from biobanks, health 

systems, and other population-scale cohorts. 

2. Conducting Mendelian randomization studies that identify modifiable exposures mediating or 

mitigating risk for mental illnesses.

3. Developing epidemiologic studies that incorporate individual polygenic risk scores, and other 

genetic markers of risk, and leveraging existing large, population-based cohorts, including 

ethnically and ancestrally diverse cohorts, registries, and/or health systems to conduct analyses 

that advance understanding of the complex etiologies, trajectories, comorbidities, and 

treatment responses of severe mental illnesses.
NIMH Strategic Plan for Research 27

Goal 1

Strategy 1.2.C: Elucidating how human genetic variation affects the coordination of molecular, 

cellular, and physiological networks supporting higher-order functions and emergent properties 

of neurobiological systems

Interest areas include:

1. Creating human molecular reference maps from defined cell types and circuits. 

2. Elucidating the relationship between genomic features, such as gene regulatory elements and 

chromatin structure, and the spatiotemporal dynamics of gene and protein expression in 

healthy individuals and those with mental illnesses.

3. Assembling reference, multi-omic molecular maps (e.g., epigenomic, transcriptomic, proteomic) 

across development, regions, and cell types of the human brain. 

4. Mapping quantitative trait loci (e.g., expression, methylation, histone acetylation, chromatin 

accessibility) across development, regions, and cell types of the human brain.

5. Identifying the developmental periods, signaling pathways, cell types, and neural systems 

driving disease pathogenesis in humans.

Strategy 1.2.D: Developing novel tools and techniques for the analysis of large-scale genetic, 

multi-omic data as it applies to mental health

Interest areas include:

1. Increasing the power and reliability of association studies including whole genome, exome-, 

epigenome-, phenome-, and other “ome”-wide studies. 

2. Integrating multi-omic datasets from tissues and single cells. 

3. Integrating phenotype data spanning multiple units (e.g., genetic variation, gene expression, 

electrophysiology, neuroimaging, behavior). 

4. Focusing on robust genome-wide and brain-wide association studies, genome-wide x phenomewide interaction studies, and genome-wide epistasis detection.

Objective 1.3: Identify and characterize the neural circuit mechanisms 

contributing to human behavior and their disruption in mental illnesses

Most of what we currently know about human brain circuits comes from studying healthy functioning. 

To understand changes in neural structure and function related to mental illnesses, we must apply the 

research tools we have in hand to characterize the neural circuits implicated in mental illnesses across 

diverse populations. It is becoming increasingly possible to map both proximal and distal neural 

connectivity in the brain, enabling an understanding of the relationships between neuronal structure 

and function at the systems level. To develop comprehensive understanding of neural connectivity in 

mental illnesses, we must extend existing structural and functional mapping to the cellular level. 

Connectomic studies of the brain are bringing us innovative tools and technologies. Emerging

developments include robust molecular markers for synapses, new tracers for identifying circuit inputs 

and outputs, high density electrode arrays, and novel microscopy techniques to reconstruct brain 
NIMH Strategic Plan for Research 28

Goal 1

circuits. New technologies are faster, less expensive, and scalable for anatomic reconstruction of neural 

circuits at all biological scales. Focused studies of circuit disruption in mental illnesses will be essential to 

translate knowledge gained from these technologies into novel targets for therapeutics. 

To better characterize and analyze the neural circuit mechanisms involved in mental illnesses, NIMH will 

support research that employs the following Strategies: 

Strategy 1.3.A: Utilizing connectomic approaches to identify brain networks and circuit 

components that contribute to various aspects of mental function and dysfunction

Interest areas include:

1. Conducting brain-wide analyses to determine which neural circuits drive network patterns 

associated with a pathology.

2. Characterizing network components at the molecular, single-cell, morphological, 

microenvironmental, or circuit level that contribute to risk for mental illnesses.

3. Conducting connectomic studies during brain development, from prenatal to late adulthood.

Strategy 1.3.B: Determining through brain-wide analysis how changes in the physiological 

properties of molecules, cells, and circuits contribute to mental illnesses

Interest areas include:

1. Investigating how molecular, cellular, and/or circuit-level changes in the brain, or changes in 

response to environmental factors affect the coordination of neural activity patterns (very largescale samples) during cognitive function, emotional regulation, and social cognition at one or

more stage of development, from prenatal to late adulthood.

Strategy 1.3.C: Developing molecular, cellular, and circuit-level biomarkers of impaired neural 

function in humans 

Interest areas include:

1. Validating translatable biomarkers using analysis of neural circuits; combining approaches, such 

as those that assess or detect synaptic integrity, plasticity, and function; as well as immune 

signaling activity and cells that affect neural circuits.

2. Integrating molecular and genomic data from large-scale multi-omic studies with connectomics 

and functional approaches in humans to formulate multilevel hypotheses regarding circuit 

function and dysfunction in mental illness.

3. Testing the causal nature of circuit-based hypotheses in animal, computational, and human 

experimental systems.
NIMH Strategic Plan for Research 29

Goal 1

Strategy 1.3.D: Developing innovative technologies—including new imaging, computational, 

electrophysiological, pharmacological, and genetic tools—to interrogate and modulate circuit 

activity and structure altered in mental illnesses

Interest areas include:

1. Creating or improving methods to investigate the connectivity of brain networks, at total or very 

large scale and during one or more stages of development that are relevant to mental illnesses, 

including age-appropriate, novel imaging tools for visualization and analyses of brain structure 

and function.

2. Pioneering strategies to use circuit-based technologies to identify circuit-specific intervention

targets.

3. Developing novel technologies to modulate specific circuit elements with the potential for 

translation into humans.
NIMH Strategic Plan for Research 30

Goal 2

Goal 2: Examine Mental Illness Trajectories Across the Lifespan

Many mental illnesses first present in childhood, adolescence, or young adulthood, yet mental illnesses 

are likely the late behavioral manifestations of changes that began years earlier. These early alterations 

may influence the course of brain and behavioral development and establish the trajectories of mental 

illnesses. To better understand these trajectories, we need to develop a comprehensive picture of 

typical and atypical brain and behavioral development across the lifespan. At the same time, novel 

biomarkers and behavioral indicators hold promise for identifying who is at risk at the earliest possible 

point, when development or aging is going off course, or which preventive and treatment interventions 

will produce the best outcomes for which individuals. We also need to understand the factors 

contributing to risk of, resilience to, and protection from development of mental illness. 

Multi-level approaches will be critical in clarifying the complex relationships between biological and 

behavioral processes, social determinants of health, and environmental influences. At the level of 

individual factors, examining biological and behavioral processes across the lifespan will transform our 

understanding of the neurodevelopmental origins and progression of mental illnesses. Research to 

identify the earliest markers or signs that distinguish typical from atypical brain and/or functional 

development will be instrumental in predicting illness trajectories and outcomes decades later. NIMH 

encourages deep phenotyping and integrative approaches to correlate developmental patterns across 

multiple levels of investigation (e.g., molecules, cells, circuits, networks, behavior). 

At the level of contextual factors, examining how theses social determinants and environmental factors

impact risk and resilience to mental illnesses, burden of disease, access to care, and mental health 

outcomes will advance our understanding of mental health disparities. NIMH encourages communityengaged approaches to help elucidate the mechanisms by which social determinants of health and 

environmental factors impact mental health and ensure that the identification and interpretation of 

findings reflect the diverse priorities and experiences of populations participating in research.

As we chart developmental and aging trajectories across the lifespan, it is important to identify sensitive 

periods—critical timepoints to intervene to reduce risk for and to prevent the onset of mental illnesses

and improve outcomes. These sensitive periods may be meaningful because they represent 

developmental stages of rapid brain maturation, physiological or epigenetic processes, and significant

life experiences. Interpreting trajectories and identifying sensitive periods for intervention will be 

enhanced through a life course perspective that considers developmental events as they are impacted 

by the complex interplay of individual and contextual factors. Unraveling these complexities will be key 

to developing novel therapeutic and prevention strategies that hold the promise of reducing both the 

burdens of mental illness and disparities in mental health outcomes.

The following Objectives further define this Goal:
NIMH Strategic Plan for Research 31

Goal 2

Objective 2.1: Characterize the trajectories of brain, cognitive, affective, and 

behavioral development across the lifespan and in diverse populations

Across the lifespan, the brain and the cognitive, behavioral, and affective functioning it supports 

undergo dramatic changes, in part as a result of myriad experiences. Yet, our understanding of how 

biology, psychological development, and experience interact to affect brain development—and, 

ultimately, social, behavioral, medical, and other outcomes—is still incomplete. Discoveries through 

basic and translational research further our fundamental understanding of how mental illnesses develop 

early or later in life and through the course of illness. By characterizing the trajectories of typical and 

atypical brain, cognitive, affective, and behavioral development across the lifespan and in diverse 

populations and contexts, we can identify factors that protect from, increase risk for, or give rise to 

mental illnesses. Greater understanding is needed to determine periods when the brain is at increased 

sensitivity to biological and environmental influences and optimal periods for intervention. Exposures 

during sensitive periods may include viruses and toxins; stressful life events or adversity; environmental 

factors such as light, temperature, or noise; and, social factors such as violence, discrimination, or 

harassment based on race, ethnicity, sexual orientation, or gender. It is important to also consider the 

dynamic and non-linear nature of development and aging, account for cumulative effects of risk and 

protective factors, simultaneously evaluate multiple domains of function, and incorporate life course 

perspectives.

To better understand developmental and aging trajectories and the progression of mental illnesses, 

NIMH will support research that employs the following Strategies:

Strategy 2.1.A: Elucidating the mechanisms contributing to the trajectories of brain 

development and behavior

Interest areas include:

1. Characterizing the interdependence and functional development of simultaneously occurring, 

yet unevenly progressing, trajectories in different brain regions and circuits across the lifespan. 

2. Determining the biological (e.g., epigenetic processes, neuroinflammation, allostatic load) and 

psychological mechanisms by which experience, social determinants, and environment affect 

neural and behavioral development. 

3. Examining individual differences and the inter-relatedness of biological, behavioral, and 

environmental (including social, cultural, and structural) contributors to heterogeneity in risk for

and resilience from mental illnesses across the lifespan, trajectories of illnesses, prevention, and 

treatment interventions. Studies may use multi-level modeling to incorporate an intersectionality 

framework in mental health research.

4. Developing novel statistical, computational, and analytical techniques to integrate behavioral, 

genomic, multi-modal imaging, clinical, environmental, and other data types across repeated 

assessments and across independent datasets.
NIMH Strategic Plan for Research 32

Goal 2

Strategy 2.1.B: Characterizing the emergence and progression of mental illnesses, and 

identifying sensitive periods for optimal intervention

Interest areas include:

1. Conducting longitudinal studies that track changes in behavior, cognition, and affect; brain 

maturation, psychosocial and physical development; and, environmental exposures, to 

characterize the progression from early markers to subsequent impairment in domains of 

functioning. NIMH encourages the use of large and diverse samples, adequately sampled for 

underserved, minoritized, and underrepresented groups and with sufficient power to examine 

mediators and moderators including structural, systemic, and interpersonal racism and 

discrimination. 

2. Identifying the biological mechanisms (e.g., molecular, cellular, circuit) involved in healthy and 

dysfunctional neurodevelopmental trajectories, including processes that underlie sex and 

gender differences in incidence, age of onset, and severity of mental illnesses.

3. Identifying and characterizing sensitive periods for brain, cognitive, social, and affective 

development during which core facets of functioning (e.g., RDoC constructs, including social and 

environmental influences) can be targeted for optimal intervention to prevent, pre-empt, 

and/or effectively treat mental illnesses across diverse populations. 

4. Translating knowledge about sensitive periods and their critical mechanisms to manipulate 

developmental trajectories of neural circuits and associated behaviors, to prevent or minimize 

disease trajectories and promote optimal outcomes, or to provide evidence to inform policies 

directed at social and environmental determinants of health associated with mental illness risk 

and severity.

Objective 2.2: Identify and understand risk factors, biomarkers, and behavioral 

indicators of mental illnesses and of intervention responses across the lifespan

The best time to address a mental illness is before the appearance of symptoms. Preventive

interventions will rely on biomarkers and other indicators that give health care providers the ability to 

predict the onset of illness for individuals, not just populations, at risk. Currently, the mental health field 

lacks predictors that could inform a diagnosis, guide intervention, or predict response to intervention 

and the future course of illness. Further, understanding the mechanisms involved in risk and protective

factors may shed light on novel intervention targets. Targets can include molecular processes; synapticand circuit-level regions or networks; neural systems; intrapersonal factors (e.g., psychological, 

cognitive, emotional, behavioral); interpersonal processes; and, environmental factors. We need to 

identify clinically useful biomarkers, behavioral indicators, and measures of social-environmental 

exposures with high predictive value to guide the use of preventive interventions across diverse 

populations, environments, and developmental processes. 

To lay the foundation for predicting outcomes and optimizing preventive and treatment interventions, 

NIMH will support research that employs the following Strategies:
NIMH Strategic Plan for Research 33

Goal 2

Strategy 2.2.A: Determining early risk and protective factors, and related mechanisms, to serve 

as novel intervention targets 

Interest areas include:

1. Identifying early manifestations of core functional domains (see RDoC framework) particularly 

during infancy, early childhood, and adolescence that predict the onset and course of mental 

illnesses.

2. Examining mechanisms of sequential, additive, and/or interactive combinations of risk, 

resilience, and protective factors that span modalities and units of analysis and predict 

progression along the illness trajectory.

3. Identifying novel intervention targets based on knowledge of neurobehavioral, psychological, 

and contextual mechanisms and trajectories, and the optimal time points for intervention.

4. Demonstrating that putative targets are mutable and potentially modifiable.

5. Using qualitative and mixed methods approaches to identify risk and protective factors, 

especially community and cultural strengths, that could be engaged by preventive and 

treatment interventions.

Strategy 2.2.B: Developing reliable and robust biomarkers and assessment tools to predict 

illness onset and course across diverse populations 

Interest areas include:

1. Identifying specific, clinically relevant, developmentally, culturally appropriate, and validated 

biomarkers of risk, onset, progression, recovery, and relapse phases of illnesses. 

2. Using multiple modalities and standardized methods to identify robust mediators, moderators, 

and predictors of resilience, illness course, and differential trajectories.

3. Harnessing computational approaches to define and refine biomarkers, and to demonstrate 

potential clinical utility.

4. Capitalizing on big data and computational approaches to identify the existence and potential 

drivers of mental health disparities and to quantify population-attributable risk for socialenvironmental factors.

5. Developing fine-grained, objective, and quantitative behavioral assessment tools in animals and 

humans to evaluate dysfunction in domains relevant to the trajectories of mental illnesses. 

6. Developing evidence-based risk assessment instruments that encompass multiple domains, are 

sensitive to developmental and aging stages, and have high predictive power for the onset or 

recurrence of mental illnesses.

7. Developing, testing, and refining tools and methodologies that integrate multimodal clinical, 

behavioral, and biological risk factors to prevent the onset of chronic conditions and optimize 

outcome.
NIMH Strategic Plan for Research 34

Goal 3

Goal 3: Strive for Prevention and Cures

We need to develop better ways to prevent and treat mental illnesses. To achieve that goal, we need 

validated targets for interventions; new methods of intervention; improved methods to match 

interventions to individuals and populations, including minoritized and marginalized communities; and,

strategies for scaling interventions for the greatest public health impact. A target may be a disease 

mechanism, a factor related to a disease mechanism, or a factor that confers significant risk. 

Appropriate targets will depend on the intervention modality and the conceptual framework underlying 

hypotheses about its mechanism of action. Interventions may encompass prevention and treatment, 

consider all therapeutic modalities (e.g., pharmacologic, psychosocial, behavioral, device-based,

biologics), and include structural changes (e.g., policies). Many protective/promotive factors are at 

intrapersonal and interpersonal levels, such as presence of a trusted adult or cultural connectedness. 

The socio-ecological levels beyond the individual level play a large role in risk factors that underlie 

mental health disparities and also strength-based strategies to overcome disparities. Research should 

strive to identify strategies for influencing modifiable factors for the development, testing, and 

implementation of prevention and treatment interventions, including approaches that are relevant and 

acceptable to communities impacted by health disparities.

Robust clinical studies require testable hypotheses on how an intervention will engage a relevant target. 

Interventions should aim to modify targets, based on a hypothesis that such modification will result in 

improved symptoms, behavior, or functional outcomes. Evaluating the relationship between 

modification of targets and clinical outcomes allows us to fine-tune our understanding of mental 

illnesses and helps us to prioritize the most promising interventions. This idea underlies NIMH’s 

experimental therapeutics approach by which interventions serve not only as potential therapies or 

preventive strategies, but also as probes to generate objective information about mechanisms of illness 

and/or resilience. Through the experimental therapeutics approach, information from a research study 

has scientific value, irrespective of the intervention’s success. 

Precision in mental health care means that individuals and populations will receive preventive and 

treatment interventions that are optimally matched to their characteristics and needs, across disease 

stages, diagnostic categories, cultures, environments, and the lifespan. Optimizing interventions will not 

only require consideration of symptoms and functioning, but also a broader consideration of etiologies, 

intervention, preferences of patients and families, and the contexts of intervention delivery. 

NIMH supports the development and testing of preventive as well as treatment interventions, 

recognizing that many mental illnesses begin well before adulthood and often before symptoms appear 

or daily functioning is impaired. We need preventive interventions for delivery early in the course of 

illness and early in life for at-risk individuals, plus treatment interventions to mitigate mental illnesses 

and associated dysfunction at the earliest possible opportunity. NIMH encourages the development and 

testing of preventive and early interventions that can be delivered in a developmentally appropriate

manner (e.g., at known sensitive periods and at key transitions) as early in life as possible and early in 

the illness course, to prevent or forestall mental illnesses and associated dysfunction.
NIMH Strategic Plan for Research 35

Goal 3

The following Objectives further define this Goal:

Objective 3.1: Develop new interventions based on discoveries in genomics,

engineering, neuroscience, and behavioral science

The experimental therapeutics approach focuses not only on testing whether new interventions show 

clinical benefit, but, more importantly, on a staged approach where researchers initially establish 

confidence that the intervention is acting on the presumed target in humans, through a dose-dependent 

mechanism. If successful, larger clinical trials would serve to reconfirm target engagement and further 

assess clinical impact of the potential intervention. If the interventions do not work in the expected 

manner, negative results are likewise scientifically informative and fundamental. In the case of an 

intervention engaging the target but failing to demonstrate a clinical effect, the target would be 

disqualified. If the intervention fails to adequately engage the target, the intervention would be 

disqualified from further consideration.

The experimental therapeutics framework also recognizes that clinical targets may differ qualitatively 

and quantitatively throughout the life course. Therefore, there needs to be a strong scientific premise 

for selecting clinical targets within a particular age range. Additionally, the dose of an intervention that 

is safe and effective for target engagement may be age- or developmental stage-dependent and should 

be systematically established in advance of efficacy testing. It is also recognized that multiple targets 

may need to be engaged to exert beneficial outcomes.

To more effectively develop new preventive and treatment interventions based on novel genomic, 

engineering, neurobiological, and behavioral advancements, NIMH will support research that employs 

the following Strategies:

Strategy 3.1.A: Developing novel interventions using a mechanism-informed, experimental 

therapeutics approach 

Interest areas include:

1. Enhancing the predictive value of preclinical assays used to select targets, drug candidates,

circuit-based or cognitive/behavioral interventions, devices, and biologics for clinical

development.

2. Developing strategies to identify any missing elements in preclinical data to better inform future 

clinical trial designs. 

3. Identifying preventive and treatment intervention targets appropriate to an individual’s age and 

stage of illness, and testing interventions to modify those targets to prevent or improve 

symptoms. Putative targets should be based on scientific discoveries that advance our 

understanding of the mechanisms and trajectories of mental resilience and illnesses.

4. Developing promising preventive and treatment intervention strategies that target specific 

molecular, cellular, neural circuit, psychological, intrapersonal, and interpersonal mechanisms

driving core domains of cognitive, behavioral, and affective function that are disrupted in 
NIMH Strategic Plan for Research 36

Goal 3

mental illnesses, including those that cut across diagnostic categories. Strategies may include 

pharmacological, psychosocial, device-based, or biologic therapeutic candidates that engage the 

target of interest. Studies may also evaluate the functional impact of target engagement and

off-target effects and determine the optimal dose and dosing regimen needed to achieve 

functional impact. 

5. Developing novel preventive interventions based on an understanding of risk and protection at 

the level of the individual and within a developmental and environmental context, and testing 

whether targeting proximal risk and protective factors, or intervening factors that reduce risk, 

result in promoting health and preventing illness.

Strategy 3.1.B: Developing and implementing measurement strategies to facilitate mechanismbased intervention development and testing 

Interest areas include:

1. Developing and validating quantitative behavioral and neurophysiological measures of target 

engagement in humans and animals as translational assays linked to functional domains 

disrupted in and across mental illnesses.

2. Developing and optimizing reliable and objective measures of target engagement and 

intervention on brain (molecular, cellular, circuit) function, side effects, clinical symptoms, and 

functional outcomes that can be implemented in clinical trials.

3. Testing novel behavioral markers and their associated neural activity patterns as potential 

stratification measures. Such testing might include computational and bioinformatics 

approaches and remote sensors. 

4. Optimizing and validating real world outcome measures, including participant-reported 

outcomes, for use across clinical and non-clinical populations. Such measures may take into 

account illness phase, age, sex, race, ethnicity, culture, education, socioeconomic background,

and other factors.

5. Developing and assessing novel mobile technology and digital health tools to enable objective 

measurement of behavior and intervention effects on symptom expression, functional 

outcomes, and quality of life in naturalistic environments. 

6. Developing valid proxy measures or markers that are relatively brief and cost-effective for use in 

outcomes research.

7. Applying quantitative methods, algorithms, and metrics to assess the value and efficiency of 

intervention strategies.

Objective 3.2: Develop strategies for tailoring existing interventions to optimize 

outcomes

Clinical trials have traditionally focused on diagnostic status and symptom severity. Inattention to the 

complex topography of intervention targets, and to individual differences in psychopathology and

intervention needs and preferences, can limit the value of findings and their potential uptake in routine 
NIMH Strategic Plan for Research 37

Goal 3

practice. Strategies should focus on functional outcomes, considered within the context of an 

individual’s development stage, environment, and culture. 

Personalized mental health interventions mean that people should receive preventive and treatment 

interventions optimally matched to their needs. Optimizing interventions and technologies will not only 

require consideration of symptoms, phases of illness, and functioning, but also a broader consideration 

of genetic, developmental, psychosocial, cultural, and environmental factors, and functional deficits and 

needs. Optimal care will also require consideration of the characteristics of population stratification or 

the candidate interventions and characteristics of providers and settings. Efficient research designs are 

needed to examine approaches for optimizing interventions for individuals, families, communities,

populations, and settings.

To better tailor existing interventions to optimize outcomes, NIMH will support research that employs 

the following Strategies:

Strategy 3.2.A: Investigating personalized intervention strategies across disease progression 

and development 

Interest areas include:

1. Investigating heterogeneity in, and mechanisms of, response to existing efficacious preventive 

and treatment interventions to inform personalized interventions that address specific 

outcomes. 

2. Investigating strategies for sequencing or integrating interventions that are optimal for 

individuals in the context of phases of disease progression, stages of development, and other 

characteristics. 

3. Establishing the safety and efficacy of efficacious therapeutic interventions developed for adult 

populations in children and the elderly, as well as women at various phases of the reproductive 

cycle (including menarche, the menstrual cycle, all stages of pregnancy, and menopause), while 

testing targets, target engagement, and/or biomarkers of efficacy specific to these populations.

4. Running prospective studies of known efficacious interventions to identify moderator variables

and objective biomarkers, digital phenotypes, composite biomarkers, and/or multi-modality 

derived biotypes.

5. Developing multi-modal intervention strategies that combine the simultaneous application of 

established or novel pharmacological, psychosocial, biologic, and/or neuromodulation 

interventions to selectively access specific therapeutic targets through synergistic action.

Strategy 3.2.B: Developing and refining computational approaches and research designs that 

can be used to inform and test personalized interventions 

Interest areas include:

1. Developing and refining research methods that can be used to advance personalized 

interventions, including computational algorithms for prescriptive approaches and innovative 

trial designs.
NIMH Strategic Plan for Research 38

Goal 3

2. Reanalyzing or conducting meta-analyses using individual or aggregated clinical trials, patient 

registries, electronic health records, or other existing clinical datasets to identify moderators 

that might serve as tailoring variables for interventions. 

3. Applying innovative computational approaches (e.g., machine learning, artificial intelligence, 

pattern classification techniques, predictive analytics) to multiple streams of data (e.g., routinely 

collected standardized measures in electronic health records, sensor-based data, social 

media/device use metrics, community-level data) using existing data sources to inform targets 

and timing for interventions and to facilitate clinical decision-making.

4. Developing and using innovative trial designs and data collection strategies to test personalized 

strategies that incorporate tailoring variables (e.g., clinical data, biomarkers, behavioral markers 

derived from passive sensing of naturalistic behaviors, patient response history) into participant 

assignment.

5. Promoting research designs that address the needs of underserved, minoritized, and 

marginalized groups. Such studies may include computational approaches that address biases in 

the data used to develop models (e.g., systemic under diagnosis in certain racial or ethnic 

groups) and use gold standard data that are diverse, appropriately over-sampled for minoritized

groups, and that do not train the model to perpetuate existing health disparities. 

Objective 3.3: Test interventions for effectiveness in community practice settings

Effectiveness research aims to generate information about the implementation of interventions and 

services in real-world settings. Effectiveness research is most useful for informing practice or policy 

decisions when it addresses a condition that has substantial public health significance; when it justifies 

the practical benefit of the intervention over existing approaches; when it is conducted in diverse, 

representative populations and contexts; when interventions are potentially scalable and could be 

disseminated into current practice; and, when it assesses a broad array of stakeholder-relevant 

outcomes.

Effectiveness research is best implemented through efficient and innovative platforms and designs that 

advance treatment personalization in community settings. Deployment-focused models of intervention 

and services research, which consider the key characteristics of the settings and providers where 

interventions and services will be implemented, are critical. Consistent with the NIMH experimental 

therapeutics approach to intervention development and testing, there is a need for effectiveness trials 

that contribute to our overall understanding of intervention change mechanisms. Not only are these 

effectiveness trials beneficial when they test the impact of interventions on clinical endpoints; they are 

beneficial when they explicitly examine whether the intervention engages the targets that mediate the 

clinical benefit.

To better test intervention effectiveness in community practice settings, NIMH will support research 

that employs the following Strategies:
NIMH Strategic Plan for Research 39

Goal 3

Strategy 3.3.A: Developing and testing approaches for adapting, combining, and sequencing 

interventions to achieve the greatest impact on people’s lives and functioning

Interest areas include:

1. Developing and testing approaches for implementing new indications and developing and 

testing adaptations or augmentations of evidence-based interventions when research suggests 

that a moderator or negative prognostic factor can be targeted to improve response 

substantially for a readily identifiable refractory subgroup.

2. Testing integrated and sequenced approaches to optimize effectiveness and safety, while 

minimizing unnecessary or off-label use of devices or psychotropic medications among children, 

adolescents, and adults.

3. Developing and testing broadly relevant preventive/early interventions that target shared 

modifiable risk and protective factors and/or key domains of functioning (e.g., emotion 

regulation, cognitive systems, social processes) and thereby change life trajectories and reduce 

risk for multiple mental illnesses.

4. Focusing on strategies that address the needs of individuals and populations at risk for 

relapse/recurrence and manage chronic disorders (e.g., post-acute phase interventions/service 

strategies that are matched to the stage of illness both in terms of the goals and approaches to 

maximize the chances of complete recovery and sustained remission).

5. Developing and testing approaches that employ mobile health (mHealth) and other emerging 

technologies to boost the effectiveness of evidence-based interventions and to monitor health. 

6. Examining when and how social determinants of health moderate intervention outcomes and 

identifying opportunities to implement interventions that target modifiable determinants. 

7. Using community-engaged research approaches to ensure that mental health interventions align 

with the needs of underserved, minoritized, and marginalized populations; that community 

stakeholders are involved in all phases of research; and, that community-based intervention 

studies employ rigorous designs to address health disparities questions. 

Strategy 3.3.B: Conducting efficient pragmatic trials that employ new tools to rapidly identify, 

engage, assess, and follow participants in the context of routine care and other settings

Interest areas include:

1. Conducting effectiveness trials that leverage practice-based research and other research 

investments to inform intervention development and increase the efficiency and relevance of 

effectiveness research, including identifying targets and optimal timing for intervention. 

2. Supporting refinement of preventive and treatment interventions for mental illnesses, while 

capitalizing on efficiencies to facilitate participant recruitment and data collection.

3. Supporting practice-based research aimed at refining and testing efficacious preventive 

interventions (including universal, selective, indicated, and tiered approaches), so that they are 

scalable and can be sustainably implemented in settings (e.g., primary care, schools, 

communities) where preventive services are delivered to youth.

4. Externally validating practice-based research across diverse populations and contexts to 

enhance the relevance and translation potential of trial results.
NIMH Strategic Plan for Research 40

Goal 3

Strategy 3.3.C: Enhancing the practical relevance of effectiveness research via deploymentfocused, hybrid effectiveness-implementation studies 

Interest areas include:

1. Encouraging deployment-focused intervention and service models and effectiveness testing that 

consider the perspective of relevant stakeholders and key characteristics of intended 

intervention settings, to increase the likelihood that the interventions/services are feasible and 

scalable, and the research results will have utility for end users. 

2. Emphasizing hybrid effectiveness-implementation research that goes beyond examining the 

effect of interventions on symptomatic or functional outcomes and designing studies to address 

questions regarding how client-, provider-, community-, and organizational-level factors impact 

clinical outcomes, implementation, and scalability of research-generated interventions.

3. Encouraging hybrid effectiveness-implementation trials across diverse settings to identify 

setting characteristics (e.g., workforce capacity, case mix) that impact intervention delivery and 

test strategies to sustain intervention effectiveness and quality of implementation in diverse 

settings. 

4. Examining novel applications of technology that can generalize across indications, target 

populations, and operating platforms to facilitate the delivery of interventions and enhance 

their reach and therapeutic value.
NIMH Strategic Plan for Research 41

Goal 4

Goal 4: Advance Mental Health Services to Strengthen Public Health 

Through mental health services research, investigators seek generalizable strategies for increasing 

access to and continuity with evidence-based interventions, fostering high quality equitable care, and 

improving clinical and recovery outcomes for millions of people with mental illnesses. To increase the 

public health impact of services studies, investigators test ways to develop or adapt, implement, scaleup, and sustain effective service delivery strategies and interventions for varied populations across 

multiple service and community settings in a cost-effective manner. This work requires new research 

designs, measures, and statistical approaches for evaluating system-wide interventions and measuring 

population-level effects. Increasingly, stakeholder input is sought to improve the reach and sustainability 

of evidence-based practices. New models of health care financing and delivery of care, along with 

evolving technologies such as electronic health records, health informatic systems, and multipurpose 

mobile computing devices, present unique opportunities for conducting deployment-focused services 

research in real-world settings. Such research may help to improve mental health care by determining 

the effectiveness of service strategies and optimizing the organization and sustained delivery of 

evidence-based preventive and treatment interventions; speeding the implementation of researchbased innovations in community settings; and, ultimately ensuring optimal outcomes for individuals at 

risk for and affected by mental illnesses, particularly those from underserved communities and 

underrepresented minoritized groups.

The following Objectives further define this Goal:

Objective 4.1: Improve the efficiency, effectiveness, and reach of mental health 

services through research

Practice-based research, conducted within primary, specialty, and non-traditional health care and other 

community settings, is uniquely suited to address questions concerning clinical epidemiology; access to 

care, quality, effectiveness, and continuity of services; and, clinical, functional, and societal outcomes 

associated with mental health interventions. Weaving systematic data collection into routine care is an 

efficient means for capturing information about clinical populations, provider behavior, system-level 

performance, and outcomes for key subgroups. In addition, NIMH recognizes a need for more research 

on the impact of various financing strategies to ensure care for all, especially children and adolescents at 

risk for and with developmental precursors of mental illnesses and people with serious mental illness,

neurodevelopmental conditions, and complex health needs.

To test approaches for improving the efficiency, effectiveness, and reach of mental health services, 

NIMH will support research that employs the following Strategies:
NIMH Strategic Plan for Research 42

Goal 4

Strategy 4.1.A: Employing assessment platforms within health care and other relevant systems 

to accurately assess the distribution and determinants of mental illnesses and to inform 

strategies for improved services 

Interest areas include:

1. Examining mental illness prevalence, service use, intervention response, and relapse events via 

data from large, diverse, and representative population samples or practice-based research 

networks, to identify new opportunities for individual-, provider-, organizational-, community-, 

or system-level interventions. 

2. Promoting data-driven approaches for improving screening and detection of low base-rate 

events (e.g., suicidal behavior, first episode psychosis); monitoring real-time trends in incidence, 

prevalence, and severity; and, identifying novel service delivery targets for preventive 

interventions or treatment engagement. 

Strategy 4.1.B: Optimizing real-world data collection systems to identify strategies for 

improving access, quality, effectiveness, and continuity of mental health services 

Interest areas include:

1. Developing pragmatic, valid, and reliable measures of engagement, intervention fidelity and 

quality, and outcomes that can be applied at the person, clinic, system, community, and/or 

population level to advance measurement-based care.

2. Comparing performance feedback methods and quality improvement processes for adoption 

across a range of systems and age groups to advance the principles of learning health care.

3. Applying computational modeling and data analytics to electronic health records, administrative 

claims data, and information from other sources to study mental health needs, social 

determinants, and services over time, and to identify mutable targets for improving service 

access, delivery, quality, and outcomes.

Strategy 4.1.C: Comparing alternative financing models to promote effective and efficient care 

for individuals with serious emotional disturbance and serious mental illness

Interest areas include:

1. Comparing alternative financing mechanisms that promote high quality, clinically effective, 

affordable, and efficient mental health care across settings and populations and discourage lowvalue services.

2. Optimizing public and commercial financing mechanisms that cover integrated care packages for 

individuals with complex needs (e.g., combination psychopharmacology, psychotherapy, 

rehabilitative therapy, care coordination interventions).

3. Studying the impact of national, state, provincial/county-level, or other health care system rules 

and regulations on participation in provider reimbursement and/or waiver programs.

4. Understanding the role of financing and economic factors on developing and supporting a 

mental health workforce qualified to deliver evidence-based mental health services.
NIMH Strategic Plan for Research 43

Goal 4

5. Understanding the impact of economic factors affecting patients’ access to and ability to seek 

high-quality mental health services on mental health outcomes.

Objective 4.2: Expedite adoption, sustained implementation, and continuous 

improvement of evidence-based mental health services

The delay between research findings and implementation in real-world settings is often lengthy, and 

delayed uptake of effective mental health interventions and services is widespread. NIMH recognizes 

the need for research to develop and test strategies that speed dissemination, adoption, and 

implementation of evidence-based interventions and sustain these practices over time. Strategies that 

reduce the lag between research discovery and science-driven practice could radically alter the quality 

and outcomes of care provided for all individuals with mental illnesses.

To accelerate deployment-focused intervention and services research, NIMH encourages strong 

partnerships among scientists, those who directly benefit from evidence-based approaches (e.g., service 

users, providers, caregivers), and other public and private stakeholders. Effective partnerships with and 

among these stakeholders are crucial for identifying salient services research questions, developing 

realistic interventions and services, and testing adoptable, scalable, and sustainable approaches that 

promote continuous improvement of mental health care. 

To speed adoption, implementation, and continuous improvement of evidence-based mental health 

services, NIMH will support studies that employ the following Strategies:

Strategy 4.2.A: Strengthening partnerships with key stakeholders to develop and validate 

strategies for implementing, sustaining, and continuously improving evidence-based practices

Interest areas include:

1. Conducting dissemination and implementation studies that reflect active partnerships between 

scientists and key stakeholders across all phases of the research process.

2. Investigating strategies that promote rapid incorporation of practice-based research findings 

into health and other system decision making, clinical practice guidelines, and reimbursement 

policies for mental health services. 

3. Addressing workforce issues related to implementation and sustainment of evidence-based 

approaches in health care and other settings (e.g., training providers in new treatment models 

and technologies; maintaining provider competence; involving paraprofessionals and peer 

providers; retaining qualified providers; managing staff turnover without compromising the 

quality of services; and, studying policies that impede or facilitate high quality care).

Strategy 4.2.B: Building models to scale-up evidence-based practices for use in public and 

private primary care, specialty care, and non-traditional settings

Interest areas include:
NIMH Strategic Plan for Research 44

Goal 4

1. Examining and monitoring client, caregiver, provider, organizational-level, and community 

factors, including social determinants of health, that affect the usability and transportability of 

interventions and services (i.e., the degree to which the evidence-informed intervention can be 

implemented with fidelity).

2. Adapting interventions and services with demonstrated effectiveness in one setting to 

determine fit for use in other contexts such as low-resource settings or non-specialty 

community/practice settings where mental health care is or could be delivered (e.g., primary 

care, schools, child and adult welfare, criminal and juvenile justice settings, long-term care 

facilities, geriatric service programs).

3. Employing hybrid effectiveness-implementation designs to enhance the delivery of evidencebased mental health practices and improve implementation outcomes (e.g., fidelity, 

acceptability, feasibility, appropriateness, penetration, and sustainability of services within a 

single study). 

Strategy 4.2.C: Developing decision-support tools and technologies that increase the 

effectiveness, implementation, and continuous improvement of mental health interventions in 

public and private primary care, specialty care, and other settings

Interest areas include:

1. Developing and validating novel tools, smart technologies, real-time analytics, and ecologically 

valid measures to monitor the engagement of intervention targets in services interventions.

2. Examining and adapting the attributes of evidence-based interventions (e.g., intensity, duration, 

frequency) and implementation (e.g., fidelity, feasibility, acceptability) that affect their 

generalizability to practice settings.

3. Developing and testing decision-support algorithms for matching services within a health system 

(e.g., pharmacotherapy, psychotherapy, rehabilitation, care coordination, transition planning) to 

clients’ needs over time, including stepped-care algorithms that span non-specialty and mental 

health specialty services.

4. Developing and testing strategies (e.g., shared decision making or behavioral economic 

approaches to behavior change) to enhance prevention and treatment engagement and 

adherence.

Objective 4.3: Develop innovative service delivery models to dramatically improve 

the outcomes of mental health services received in diverse communities and 

populations 

Service delivery models provide a framework for mental health care, which account for various settings, 

providers, and resources. Available data indicate that many current service delivery models are 

inadequate to meet the mental health service needs in the United States and around the globe. To 

provide high quality care to populations in need, researchers may need to adapt evidence-based models 

to account for moderators, including social determinants of health, known to impact intervention 
NIMH Strategic Plan for Research 45

Goal 4

effectiveness among underrepresented, underserved, vulnerable, and minoritized groups. Services 

research and implementation science strategies that test adaptations should be designed to determine 

whether the adapted strategy counteracts moderators that have been shown to impede effectiveness 

and clinical outcomes. 

NIMH is committed to supporting research that reduces disparities and advances equity in mental 

health services and outcomes. As such, we need innovative and sustainable service delivery models that 

address disparities that stem from historical, social, and economic inequities that disproportionately 

affect minoritized and marginalized populations and people with serious mental illness, to include 

people experiencing instability in housing, employment, income, and food. People with serious mental 

illness are among the first and most disproportionately affected by these social and economic 

insecurities. We must develop and test novel components of care across multiple settings where mental 

health services are needed and use developmentally and culturally appropriate tools to better reach 

populations in need and substantially improve the delivery of evidence-based mental health care. 

To improve the outcomes of individuals receiving mental health services and to ensure equity of 

outcomes in all populations, NIMH will support research to develop innovative services delivery models 

that employs the following Strategies:

Strategy 4.3.A: Adapting, validating, and scaling-up programs currently in use that improve 

mental health services for underserved populations

Interest areas include:

1. Testing innovative approaches for reducing empirically documented disparities in care access, 

quality, and outcomes for racial and ethnic minority groups; individuals limited by English 

language proficiency, educational, or cultural barriers; sexual and gender minorities; individuals 

living in rural areas; socioeconomically disadvantaged persons; and, other underserved groups.

2. Combining data from multiple sources of information (e.g., electronic health records, 

administrative claims data, epidemiologic surveys, census data, qualitative methods) to identify 

underserved groups and to explore novel approaches for coordinating health/community 

service resources and improving overall health outcomes.

3. Conducting research to better understand, predict, and reduce mental health workforce 

shortages across pediatric, adolescent, adult, and geriatric services; reduce the shortage of 

culturally and linguistically competent care providers for racial and ethnic minorities; reduce the 

workforce shortages in certain geographic areas (e.g., rural and underserved communities); and, 

promote care that is respectful and affirming of an individual’s sexual orientation and gender 

identity.

Strategy 4.3.B: Developing and validating service delivery models that provide evidence-based 

care for individuals throughout the course of mental illness

Interest areas include:
NIMH Strategic Plan for Research 46

Goal 4

1. Developing and testing innovative strategies to promote early identification and engagement in 

prevention and mental health services for children, adolescents, and adults, especially for those 

experiencing early symptoms of mental illness.

2. Characterizing care pathways to identify mutable barriers and facilitators to improving access to 

care across the lifespan, including children at risk for autism or mental illnesses, transition-age 

youth with autism or emerging mental illnesses, and adults with autism or mental illnesses.

3. Defining and testing the specific mechanism(s) of action (i.e., targets) in service delivery 

approaches purported to improve mental health outcomes across developmental stages. When 

paraprofessionals or peer providers are delivering services, the research should make clear the 

intended purpose for involving nontraditional staff (e.g., addressing workforce shortages, 

instilling hope and re-moralization, improving client engagement) and then test whether 

engagement of these targets mediates outcomes, with consideration for scalability of strategies 

that prove effective.

Strategy 4.3.C: Developing and validating systems-level strategies, using technology and other 

approaches, to identify, support, optimize, and monitor the effectiveness of evidence-based 

care throughout the course of illness

Interest areas include:

1. Using technology to improve prevention and early detection of mental illnesses, connect clients

across all ages to evidence-based care, increase reach of and engagement with services for 

underserved populations, and improve client-level outcomes.

2. Developing and testing clinician-facing “dashboards” or other system-level technologies that can 

be used to support providers in their use of measurement-based care, to facilitate and optimize 

system-level quality monitoring and improvement, and to improve clinical workflows.

3. Developing and testing implementation strategies for evidence-based practices (e.g., ensuring 

availability, accessibility, effectiveness, scalability, sustainability) in low-resource settings or nonspecialty settings where significant unmet need exists (e.g., the criminal and juvenile justice 

systems, employment settings, military or veteran organizations, schools, and the child welfare 

system).

4. Building novel service delivery models that capitalize on systems that are already engaging 

individuals with mental health needs (e.g., schools, social services, or other community-based 

settings, online/virtual communities).

Strategy 4.3.D: Developing and validating decision-making models that bridge mental health, 

medical, and other care settings to integrate the appropriate care for people with serious 

mental illness and comorbid medical conditions

Interest areas include:

1. Developing and testing service delivery models for people with comorbid conditions (e.g.,

medical comorbidities, co-occurring substance use disorder), such as care decision models that 

integrate treatment for mental illnesses and medical conditions, and service delivery 
NIMH Strategic Plan for Research 47

Goal 4

interventions to reduce modifiable health risks associated with premature mortality in people 

with serious mental illness. These innovative service delivery models should be feasible in a

wide range of settings, including low-resource settings, and acceptable to a wide variety of 

health disparity populations, since racial and ethnic minorities have greater prevalence of 

comorbidities.30 

2. Developing and validating decision-support tools to assess mental health and functional needs, 

medical risk factors, and mental health/medical treatment availability in non-specialty settings 

where children and adolescents are served, and to facilitate treatment planning. 

3. Using existing and developing novel technologies (e.g., mobile devices, information systems, 

artificial intelligence) to significantly improve access, engagement, quality, effectiveness, and 

efficiency of integrated mental health services, while making sure that these advances benefit 

people with a wide range of backgrounds, socioeconomic status, ethnicity, race, and 

geographical area of residence.

4. Investigating strategies for active symptom management that reduce the symptom burden in 

individuals with serious mental illness and multiple chronic conditions.
NIMH Strategic Plan for Research 48

Strategic Planning Process

Strategic Planning Process

The National Institute of Mental Health (NIMH) updates its Strategic Plan for Research every five years 

to keep pace with scientific advancements and the changing landscape of the mental health field. NIMH 

uses the Strategic Plan to communicate our priorities and help guide future mental health research 

efforts at the institute. The new 2020 plan retains core elements of previous NIMH Strategic Plans, and 

has been revised, updated, and expanded in response to the many discoveries and changes in the field 

over the past five years. 

We began by updating the institute’s four overarching Goals (referred to as Strategic Objectives in the 

2015 Strategic Plan for Research). To accomplish this, we sought input from NIMH leadership, subject 

matter experts, and other staff to identify knowledge gaps and opportunities for research advancement. 

The four Goals are intended to be broad and capture the diversity of topics the institute must focus on 

to achieve its mission. The Goals successively build in scale from basic neuroscience and behavioral 

science to research on delivery of mental health services. These four Goals are:

1. Define the Brain Mechanisms Underlying Complex Behaviors

2. Examine Mental Illness Trajectories Across the Lifespan

3. Strive for Prevention and Cures

4. Advance Mental Health Services to Strengthen Public Health

Updating the plan was an iterative process, with opportunities for NIMH staff, advisory boards, and the 

public to contribute. NIMH presented a framework for the 2020 plan to the Interdepartmental Serious 

Mental Illness Coordinating Committee (ISMICC), and cross-walked the institute’s priorities with ISMICC 

focus areas and recommendations. The framework was also presented to the National Advisory Mental 

Health Council (NAMHC) and a draft plan was reviewed by the NAMHC members. We incorporated their 

feedback and published a revised draft plan for public comment; members of the scientific community, 

professional societies, advocacy organizations, and the general public were invited to share feedback via 

a Request for Information (RFI) published in the NIH Guide and in the Federal Register. Comments were

submitted via a web-based RFI input tool, email, or mail from December 2, 2019 to January 15, 2020.

The institute received robust feedback from our many stakeholders, including researchers, mental 

health advocates, and individuals with lived experience. After reviewing comments and making 

numerous edits, the final plan was presented to the NAMHC and published on the NIMH website. 

The 2020 NIMH Strategic Plan for Research is the product of many authors. We would like to thank 

everyone who took the time to review and provide feedback and input on the many draft Plans. We look 

forward to your continued involvement as we support research to transform the understanding and 

treatment of mental illnesses to pave the way for prevention, recovery, and cure.
NIMH Strategic Plan for Research 49

Strategic Planning Process

Updates to the Plan

The NIMH Strategic Plan for Research is a living document, which means it is updated regularly to keep 

pace with ever-evolving scientific approaches and research priorities that can lead to new discovery. The 

most recent update was published in May 2023. Archived PDFs of the previous versions of the plan are 

available below.

• NIMH Strategic Plan for Research – 2022 Update – published June 2022 (PDF)

• NIMH Strategic Plan for Research – 2021 Update – published July 2021 (PDF)

• NIMH Strategic Plan for Research—published May 2020 (PDF) 

In addition, on the Progress pages included in the digital version of the Plan, we highlight key 

contributions of NIMH and NIMH-funded investigators in advancing research toward achieving the four 

Goals of the NIMH Strategic Plan for Research and the institute’s mission.
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NIMH STRATEGIC PLAN FOR RESEARCH

NIH Publication Number: 20-MH-8096

https://www.nimh.nih.gov/strategicplan

Published: May 2020

Updated: May 2023