Nimh Strategic Plan For Research 2024 Update

NATIONAL INSTITUTE OF MENTAL HEALTH
STRATEGIC PLAN FOR RESEARCH
Updated: May 2024

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 ...........................................................................................................................................8
Enhancing Risk Management ................................................................................................................................8
Improving Administrative Processes.....................................................................................................................8
Promoting Workforce Development and Diversity...............................................................................................8
Accomplishing the Mission ............................................................................................................................................9
Challenges and Opportunities .....................................................................................................................................10
Mental Health Equity ..............................................................................................................................................10
Coronavirus Disease 2019 (COVID-19) Pandemic ...................................................................................................11
Suicide Prevention...................................................................................................................................................11
Early Intervention in Psychosis ................................................................................................................................12
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
Comorbidities ..........................................................................................................................................................19
Translation ..............................................................................................................................................................19
NIMH Strategic Plan for Research i

Table of Contents
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 ii

Message from the Director

This year’s update to the strategic plan is bittersweet for me, as it is the last for which I am at the helm
of National Institute of Mental Health (NIMH), the lead federal agency charged with setting and
supporting the national agenda for mental health research. It has been an incredibly exciting and
rewarding time for me as Director of NIMH. 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 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 three of the first truly novel antidepressants in
decades—esketamine for treatment-resistant depression in addition to brexanolone and zuranolone 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. This NIMH Strategic Plan for Research aims 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 learning healthcare network
that will use data from community-based first episode psychosis clinics to enhance the delivery,
evaluation, and continual improvement of evidence-based care. With the vision of increasing the reach
of learning healthcare beyond psychosis, we have begun to encourage collaborations with more clinics,
including Certified Community Behavioral Health Clinics, to address the needs of communities reliant on
these public mental health care providers. 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,
NIMH Strategic Plan for Research 1

American Indian/Alaska Native, LGBTQ+, individuals with disabilities, and other minoritized and
marginalized communities, continue to experience greater challenges.
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 50 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 have been committed to dismantling structural racism and other structural
inequities 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 and equity-supporting 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

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 4,000 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 five scientific funding Divisions—the Division of Neuroscience and
Basic Behavioral Science, the Division of Translational Research, the Division of Services and Intervention
Research, the Division of AIDS Research, and the recently formed Division of Data Science and
Technology. Assisted by the Division of Extramural Activities, NIMH staff in these Divisions 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 causes, diagnosis, treatment, management, and prevention of
psychiatric disorders. NIMH IRP investigators utilize the unique resources of 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 more than 650 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
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:

Overview of NIMH
• 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 or condition (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 and traits across mental disorders and
recognizes that knowledge gained from studying one may inform understanding of and treatment for
others.

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 interested parties, including NIMH leadership and staff, the National Advisory
Mental Health Council and its workgroups, 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 NIH-Wide Strategic Plan for Research
on the Health of Women, 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,
the National HIV/AIDS Strategy, and the HHS Ending the HIV Epidemic initiative. 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 Research, Services, and Policy; 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
5
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 that sample sizes within
studies are appropriate so they are adequately powered for meaningful effect sizes; the statistical
analysis plans included in grant applications contain sufficient information for reviewers to properly
evaluate them; there exists appropriate expertise in review sections and program staff to properly
assess statistical methodologies; and, that there is sharing of data, software, tools, and other resources
that can enable third-party confirmation and mega-analyses which consolidate data from multiple
studies.
Fostering Resource and Data Sharing

NIMH encourages and supports open science by investing in resources and programs to enable Findable,
Assessable, Interoperable and Reusable (FAIR) data to foster the reuse of NIMH-funded data that is
critical for advancing equitable research. 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 NIMH-funded research on mental health and HIV. Finally, NIMH
encourages the sharing of software, tools, and other resources in alignment with the FAIR Principles for
Research Software (FAIR4RS Principles) to improve the transparency and reproducibility of NIH-
supported data.
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.

Stewardship
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.
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, with other
agencies within 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), and the Department of Energy (DOE)). NIMH also works
domestically and internationally with public, private, non-profit, and research partners, including those
in the biotech and pharmaceutical industries, and other international mental health research funders.
To broaden the dissemination and impact of research, NIMH works with interested parties—
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 and other structural inequities
within NIH and across the biomedical research community.

Stewardship
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
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

NIMH takes an active role in supporting and encouraging 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 while pursuing equity and inclusion.

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
interested parties 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.
9
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 illness. [1] Similar trends are observed globally, and the burden of mental illness
is predicted to rise worldwide in the coming decades. [2, 3] Mental illnesses are prevalent across all
groups, regardless of age, sex, race, ethnicity, sexual orientation, disability, geographic residence, 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, which 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 provisional rates for 2022
indicate an additional 2.6% increase. [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.
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. Racially and ethnically minoritized populations,
sexual and gender minorities, socioeconomically disadvantaged populations, individuals with disabilities,
and underserved rural populations experience striking disparities in the burden of mental illness, access
to and engagement in care, and recovery. Moreover, people from disadvantaged, 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). [14] In accordance with the 21st Century Cures Act, NIMH staff,
through coordination with the NIMH Office for Disparities Research and Workforce Diversity (ODWD),
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, disability, and social determinants of health
(e.g., education, economic stability, quality of housing, access to health care, experience of
discrimination). In addition, NIMH funds research that considers individuals’ intersectionality, a

framework that addresses the interlocking systems of inequality that individuals with multiple
dimensions of socially marginalized identities may experience. [15] 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 a range of backgrounds.
Coronavirus Disease 2019 (COVID-19) Pandemic

NIH continues to work on understanding and mitigating the impact of SARS-CoV-2 and the COVID-19
pandemic on health and well-being across various communities. 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 has also participated 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 NIH’s Community Engagement Alliance (CEAL). NIMH-supported
researchers continue to examine the effects of COVID-19 on mental health and are developing and
testing ways to understand and improve delivery of care and treatment of mental illnesses in the
context of a pandemic. As access to mental health services continues to be insufficient for the demand,
this work remains critical to meet the increased mental health needs for all who have been impacted by
the pandemic and to prepare for potential future public health outbreaks and service interruptions.
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). [12] Provisional
data released by the CDC for 2022 noted an increase of 2.6% in the number of deaths by suicide in the
United States. [13] This is, in part, due to rising rates among middle and older aged adults. NIMH’s
portfolio includes projects aimed at identifying individuals and populations most at risk for suicide,
understanding the contributors to suicide risk, developing suicide prevention interventions, and testing
the effectiveness and implementation 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. [16] 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. [17, 18] 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. [17] 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 thoughts and behaviors in adolescence and adulthood. NIMH
collaborates with other federal agencies like SAMHSA to study crisis response services. More specifically,
NIMH is interested in understanding which approaches are most effective in the emerging crisis
response landscape, as states and localities build, increase, and/or improve these systems. 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 thoughts and
behaviors across age, race, and ethnic groups. Understanding disparities in suicides among Black,
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 large-
scale 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, [19] variable adherence to treatment
guidelines, [20] and poor attention to comorbid medical conditions associated with premature mortality.
[21]
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. [22, 23, 24] Through collaborations with other
federal agencies, NIMH transformed these findings into real-world change. [25, 26] CSC is now the standard
of care for early psychosis, with more than 360 CSC programs across the country. CSC programs have
helped thousands of 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 currently supports eight regional scientific hubs and a national data coordinating
center that aims to standardize, collect, and aggregate data across more than 100 community clinics in
17 states 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,
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 in the AMP
SCZ Data Repository within 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.
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
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 supports 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
for advancing HIV prevention, treatment, and ultimately cure. NIMH seeks data science HIV research,
including artificial intelligence/machine learning approaches that are transformative, translational, and
transdisciplinary. NIMH also supports implementation science to enable researchers to bring evidence-
based interventions or strategies 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 health technology derived biomarkers and outcome
assessments for inclusion in clinical trials for monitoring responses to interventions. While the
technology frontier offers promising 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 and accessibility considerations 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, have 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 has also released a curated list of human
genes that include statistically significant variants associated with mental health traits or risk for
psychiatric illnesses based on published studies. This list is intended to aid basic, translational, or clinical
investigators who are interested in applying to NIMH for research grants involving particular genes
based on their disease association.
NIMH is focused on expanding the ancestral diversity of genetic cohorts and samples to increase our
understanding of the genetic determinants of serious mental illnesses, such as 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 obsessive-
compulsive 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

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 and neurodevelopment these
manipulations are most effective.

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 long-
term, 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, disability, 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, simulation modeling of alternative prevention strategies, and implementation research that
tests strategies that can be used to promote the adoption and sustained implementation of effective
preventive interventions in communities.

Global Mental Health

The interconnectedness of global societies calls for a concerted and collaborative effort, drawing upon
the resources and expertise of diverse cultures and regions, to comprehensively address mental illnesses
worldwide. NIMH's global mental health research programs aim to study diverse populations,
understand the prevalence and impacts of disorders, develop effective interventions, enhance mental
health services access and delivery, and explore the bidirectional relation between social determinants
of mental health and mental health outcomes.
Global mental health programs provide an opportunity to improve our understanding of the factors
impacting mental health across diverse cultures, socioeconomic statuses, and societal contexts. These
efforts facilitate the integration of genetics, cultural backgrounds, societal and familial structures, and
environmental factors into both basic and translational research on mental health. Such studies have
the potential to transform interventions by identifying new targets and approaches to address the
specific mental health needs of underserved populations, particularly those in low- and middle-income
countries (LMICs). Global partnerships may result in reciprocal learning, or the multidirectional
exchange, adaptation, and implementation of research advancements to improve outcomes for all.
NIMH's commitment extends to the implementation of cutting-edge tools and technologies aimed at
enhancing mental health screening, assessment, prediction, prevention, and treatment across diverse
systems of care. By leveraging these advancements, NIMH aims to strengthen sustainable research
capacity in LMICs and the reciprocal learning opportunities that foster a community dedicated to global
mental health research.
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 Development℠ Study (ABCD
Study®), which has enrolled nearly 12,000 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-

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 among 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 focuses on fundamental
psychological/biological systems (such as cognitive or sensorimotor processes) and integrates many
approaches and levels of information to understand function and dysfunction in 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. Beyond improving research sample
characterization using integrative, functionally based measures, this approach holds promise for
uncovering mechanisms of mental illnesses, identifying putative therapeutic targets, and paving the way
for novel, personalized preventive and treatment interventions. In keeping with its potential to promote
precision psychiatry, the RDoC framework served as the basis for a recent funding initiative to identify
new clinical signatures that can be used for individual-level prediction and clinical decision-making. This
initiative, called Individually Measured Phenotypes to Advance Computational Translation in Mental
Health (IMPACT-MH), encourages research that uses scalable behavioral measures and computational
methods, in addition to traditional clinical information, to help predict patient outcomes.
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.
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 across a variety of settings,
NIMH invests in studies that anticipate real-world implementation during intervention development.
Additionally, NIMH encourages engagement with decision makers and end users 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 data-
driven 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 of system dynamics may predict which patients might respond best to which of
the many existing treatments for depression, optimizing treatment selection, improving
implementation, and speeding recovery. These and other computational advances hold the promise of
objective, data-driven diagnosis and treatment recommendations for serious mental illnesses,
contributing to NIMH’s effort to bring precision psychiatry to patients. 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.
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 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. Use of novel data sources including social media
activity, geospatial data, and weather maps can help close the gap between the availability and demand
for mental health prevention and treatment services. 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, bioethicists, 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 and disciplines.
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 the NIMH 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
sciences, across areas of research funded by NIMH. Examples at the institutional level include NIMH’s
support for 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 a virtual listening session during which extramural researchers shared their
experiences navigating the NIH grant application process.

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 brain is composed of a vast number and variety of connected cells, which makes it challenging to
understand how they function during complex behavior. New single-cell multimodal analysis
technologies used by the BRAIN Initiative Cell Census Network and the BRAIN Initiative Cell Atlas
Network hold promise to overcome this challenge by creating a comprehensive census (“parts list”) of
neuronal and glial cell types involved in complex behaviors in mental health and in mental disorders.
Researchers are now mapping long-distance brain connections and looking at their variability in
unprecedented detail. 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. A complementary program, the BRAIN initiative Connectivity Across Scales program,
aims to generate brain wiring diagrams across multiple spaciotemporal scales and developmental
stages. The characterization of circuit function in the brain is augmented by the efforts of the BRAIN
Initiative Armamentarium program, whose goal is to apply the precision of molecular targeting to
generate tools to map, monitor, and manipulate specific neural circuits that underlie complex behavior.
The genomics revolution, fueled by technological advances, has revealed insights into the genetic
architecture of mental illnesses and neurodevelopmental disabilities. 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 locations in the genome where genetic
variation raises risk for psychiatric disorders. Because most participants in these studies have been of
European descent, more research is needed to determine whether the findings may 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.

Goal 1
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.
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 functional properties and dynamic interactions of neurons, glia, and immune
cells, and the effects of neuron-glia coupling on brain function and mental health-relevant
behaviors.
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
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 non-
neural components (e.g., immune system, microbiome, blood-brain barrier, vasculature).

Goal 1
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).
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
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

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,
(e.g., long-read Whole Genome Sequencing, single-cell multi-omic parallel sequencing, and other
emerging methodologies) 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
1. Performing large, well-powered, genome-wide multi-omic 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
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.

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
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
1. Increasing the power and reliability of genome-wide multi-omic studies in appropriate tissues.
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 phenome-
wide 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, novel neurotransmitter sensors, and novel microscopy
techniques to reconstruct brain 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

Goal 1
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
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
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 large-
scale samples) during cognitive function, emotional regulation, and social cognition at one or
more stage of development, from prenatal to late adulthood.
2. Investigating causal approaches for the manipulation of brain oscillatory rhythms associated
with optimal cognitive function, to understand their potential as treatment targets for cognitive
dysfunctions in mental disorders.
Strategy 1.3.C: Developing molecular, cellular, and circuit-level biomarkers of impaired neural
function in humans
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 multi-level 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.

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
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.

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

Many mental illnesses present in childhood, adolescence, and young and late 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 aging 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 and maturation 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, signaling when development or aging is going off course, and
producing the best individual outcomes for preventive and treatment interventions. 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 origins and progression of mental illnesses. Research to identify the earliest
markers or signs that distinguish typical from atypical brain and/or functional development and
maturation will be instrumental in predicting illness trajectories and outcomes later in life. NIMH
encourages deep characterization across multiple levels of investigation (e.g., molecules, cells, circuits,
networks, behavior) and integrative approaches to correlate their developmental patterns.
At the level of contextual factors, examining how 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 community-engaged
approaches to help identify 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
priorities and experiences of diverse populations participating in and impacted by 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 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.

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 diverse experiences. Yet, our understanding of how
different experiences interact with biology and psychological development interact to affect brain
development and maturation—and, ultimately, healthy and maladaptive behavioral 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 social 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, gender, or disability.
It is important to also consider the dynamic and non-linear nature of brain 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,
Strategy 2.1.A: Elucidating the mechanisms contributing to the trajectories of brain

development and behavior
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
hormonal changes in puberty, pregnancy, and menopause) and psychological mechanisms by
which experience, social determinants, and natural and built environment affect neural and
behavioral development.
3. Examining individual differences and the inter-relatedness of biological, behavioral, and
environmental (including natural and built, 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 neuroimaging, clinical, environmental, and other data types across
repeated assessments and across independent datasets.
5. Utilizing digital health technologies (e.g., biosensors, wearable devices, analysis of social media
use patterns, digital diaries or prompts) to measure behavior, mood, and physiology in real-
world environments, including social interactions and social networks.

Goal 2
6. Understanding the impact of widespread and complex syndemics (e.g., COVID-19, the youth
mental health crisis) on increasing risk for mental illness or exacerbating clinical symptoms and
poor outcomes for individuals with mental illnesses.
Strategy 2.1.B: Characterizing the emergence and progression of mental illnesses, and
identifying sensitive periods for optimal intervention
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 signs of alterations to subsequent impairment in these
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 and aging trajectories throughout life, including 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 and aging 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 and aging trajectories of neural circuits and associated behaviors, to prevent or
minimize illness 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; synaptic-
and 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 and aging processes.

Goal 2
To lay the foundation for predicting outcomes and optimizing preventive and treatment interventions,
Strategy 2.2.A: Determining early risk and protective factors, and related mechanisms, to serve
as novel intervention targets
1. Identifying early manifestations of core functional domains (see RDoC framework) particularly
during infancy, early childhood, adolescence, and other life periods of rapid change (e.g.,
menopause transition, aging) that predict the onset and course of mental illnesses.
2. Examining neurobehavioral 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
1. Identifying specific, clinically relevant, life stage appropriate, 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. Utilizing mobile and digital health technologies to capture dynamic changes in mood, behavior,
and physiology in real-world environments and identify and promptly address increased clinical
symptoms or risk for harm.
5. 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 social-
environmental factors.
6. 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.
7. 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.
8. 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.

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 are also potent risk factors that underlie mental
health 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 risk for 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 relevant to the condition in question, 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 functional impairment.

Goal 3
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
relationship, when appropriate. 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
often 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
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 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 therapeutic intervention strategies that target specific
molecular, cellular, neural circuit, psychological, intrapersonal, interpersonal, social, and other
upstream mechanisms driving core domains of cognitive, behavioral, and affective function that
are disrupted in 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 parameters (e.g., dose and
dosing regimen) needed to achieve functional impact.

Goal 3
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 mechanism-

based intervention development and testing
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, disability, 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.
8. Identifying appropriate study designs, methods, and measures for interventions that target
upstream (e.g., beyond the individual level) risk and/or protective factors for mental illness,
including mental health disparities.
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
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

Goal 3
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,

development, and diverse populations
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 therapeutic interventions previously found to be effective
in one population and applied to other, understudied populations, such as children, older adults,
minoritized populations, and 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
1. Developing and refining research methods that can be used to advance personalized
interventions, including computational algorithms for prescriptive approaches and innovative
trial designs.
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

Goal 3
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 outcomes relevant to
interested parties.
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:
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
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.

Goal 3
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
members 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
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.
Strategy 3.3.C: Enhancing the practical relevance of effectiveness research via deployment-
focused, hybrid effectiveness-implementation studies
1. Encouraging deployment-focused intervention and service models and effectiveness testing that
consider the perspective of relevant interested parties 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.

Goal 3
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.

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, scale-
up, 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, input from interested parties 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
research-based 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.
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. NIMH also supports the collection of data that measures
social determinants of health, such as socioeconomic status, education access and quality, and
neighborhood and built environment for reducing health disparities and improving health care
outcomes. 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,

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
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, as well as referral to
care, for 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
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 adults, older adults, and those with serious mental illness and youth with mental,
emotional, and behavioral disorders
1. Comparing alternative financing mechanisms that promote high quality, clinically effective,
affordable, and efficient mental health care across settings and populations and discourage low-
value 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,
regulations, and policies 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.

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 interested parties. Effective partnerships with
and among these individuals 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 end users and other interested parties to
develop and validate strategies for implementing, sustaining, and continuously improving
evidence-based practices
1. Conducting dissemination and implementation studies that reflect active partnerships between
scientists and key end users and other interested parties, such as service users, providers, and
payers, 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
and other 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

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 evidence-
based 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
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 groups who are underrepresented in mental health research and have
inequitable access to mental health care, researchers may need to adapt evidence-based models to
account for moderators, including social determinants of health, which are known to impact
intervention effectiveness. Services research and implementation science strategies that test

Goal 4
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
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 with disabilities; 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, gender
identity, and disability status.
Strategy 4.3.B: Developing and validating service delivery models that provide evidence-based
care for individuals throughout the course of mental illness
1. Developing and testing innovative strategies to promote early identification and engagement in
prevention and mental health or supportive services for children, adolescents, and adults,
especially for those experiencing early symptoms of mental illness.

Goal 4
2. Characterizing care pathways to identify mutable barriers, facilitators, and social and structural
determinants 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. Addressing workforce shortages, instilling hope and re-moralization, improving engagement
with care and reach of interventions using paraprofessionals, peer providers, and nontraditional
staff.
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
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 non-
specialty 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
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
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 and other health disparity
populations have greater prevalence of comorbidities. [27]
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.

Goal 4
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, disability, 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.

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 interested parties, 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.

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 2024. Archived PDFs of the previous versions of the plan are
available below.
• NIMH Strategic Plan for Research – 2023 Update – published May 2023 (PDF)
• 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.

References
References
[1] Substance Abuse and Mental Health Services Administration. Key Substance Use and Mental
Health Indicators in the United States: Results from the 2021 National Survey on Drug Use and
Health. Report No. HHS Publication No. PEP22-07-01-005, NSDUH Series H-57.
[2] Whiteford, H. A. et al. Global burden of disease attributable to mental and substance use
disorders: findings from the Global Burden of Disease Study 2010. Lancet 382, 1575-1586,
doi:10.1016/S0140-6736(13)61611-6 (2013).
[3] Collins, P. Y. et al. Grand challenges in global mental health. Nature 475, 27-30,
doi:10.1038/475027a (2011).
[4] Olfson, M., Gerhard, T., Huang, C., Crystal, S. & Stroup, T. S. Premature Mortality Among Adults
With Schizophrenia in the United States. JAMA Psychiatry 72, 1172-1181,
doi:10.1001/jamapsychiatry.2015.1737 (2015).
[5] Remien, R. H. et al. Mental health and HIV/AIDS: the need for an integrated response. AIDS 33,
1411-1420, doi:10.1097/QAD.0000000000002227 (2019).
[6] Arensen, M. C., B. Vol. 28 PTSD Research Quarterly (ed U.S. Department of Veteran's Affairs)
(National Center for PTSD, White River Junction, Vermont, 2017).
[7] Scherrer, J. F. et al. Association Between Clinically Meaningful Posttraumatic Stress Disorder
Improvement and Risk of Type 2 Diabetes. JAMA Psychiatry 76, 1159-1166,
[8] Fazel, S., Hayes, A. J., Bartellas, K., Clerici, M. & Trestman, R. Mental health of prisoners:
prevalence, adverse outcomes, and interventions. Lancet Psychiatry 3, 871-881,
doi:10.1016/S2215-0366(16)30142-0 (2016).
[9] Kessler, R. C. et al. Individual and societal effects of mental disorders on earnings in the United
States: results from the national comorbidity survey replication. Am J Psychiatry 165, 703-711,
doi:10.1176/appi.ajp.2008.08010126 (2008).
[10] Bloom, D. E. et al. The Global Economic Burden of Noncommunicable Diseases. (World Economic
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[11] World Health Organization. Investing in Mental Health. (Department of Mental Health and
Substance Dependence, Noncommunicable Diseases and Mental Health, World Health
Organization, Geneva, 2003).
[12] Prevention, C. f. D. C. a. Web-based Injury Statistics Query and Reporting System (WISQARS); Fatal
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(2023).
[13] Curtin S.C., G. M. F., Ahmad F.B. Provisional Estimates of Suicide by Demographic Characteristics:
United States, 2022. (2023).
[14] Shim, R. S. & Starks, S. M. COVID-19, Structural Racism, and Mental Health Inequities: Policy
Implications for an Emerging Syndemic. Psychiatr Serv, appips202000725,
doi:10.1176/appi.ps.202000725 (2021).
[15] Clauss-Ehlers, C. S., Chiriboga, D. A., Hunter, S. J., Roysircar, G. & Tummala-Narra, P. APA
Multicultural Guidelines executive summary: Ecological approach to context, identity, and
intersectionality. Am Psychol 74, 232-244, doi:10.1037/amp0000382 (2019).

References
[16] Ahmedani, B. K. et al. Health care contacts in the year before suicide death. J Gen Intern Med 29,
870-877, doi:10.1007/s11606-014-2767-3 (2014).
[17] Miller, I. W. et al. Suicide Prevention in an Emergency Department Population: The ED-SAFE Study.
JAMA Psychiatry 74, 563-570, doi:10.1001/jamapsychiatry.2017.0678 (2017).
[18] Ballard, E. D. et al. Identification of At-Risk Youth by Suicide Screening in a Pediatric Emergency
Department. Prev Sci 18, 174-182, doi:10.1007/s11121-016-0717-5 (2017).
[19] Addington, J. et al. Duration of Untreated Psychosis in Community Treatment Settings in the
United States. Psychiatr Serv 66, 753-756, doi:10.1176/appi.ps.201400124 (2015).
[20] Robinson, D. G. et al. Prescription practices in the treatment of first-episode schizophrenia
spectrum disorders: data from the national RAISE-ETP study. Am J Psychiatry 172, 237-248,
doi:10.1176/appi.ajp.2014.13101355 (2015).
[21] Correll, C. U. et al. Cardiometabolic risk in patients with first-episode schizophrenia spectrum
disorders: baseline results from the RAISE-ETP study. JAMA Psychiatry 71, 1350-1363,
[22] Kane, J. M. et al. Comprehensive Versus Usual Community Care for First-Episode Psychosis: 2-Year
Outcomes From the NIMH RAISE Early Treatment Program. Am J Psychiatry 173, 362-372,
doi:10.1176/appi.ajp.2015.15050632 (2016).
[23] Dixon, L. B. et al. Implementing Coordinated Specialty Care for Early Psychosis: The RAISE
Connection Program. Psychiatr Serv 66, 691-698, doi:10.1176/appi.ps.201400281 (2015).
[24] Rosenheck, R. et al. Cost-Effectiveness of Comprehensive, Integrated Care for First Episode
Psychosis in the NIMH RAISE Early Treatment Program. Schizophr Bull 42, 896-906,
doi:10.1093/schbul/sbv224 (2016).
[25] Centers for Medicare & Medicaid Services. (ed Department of Health and Human Services) (2015).
[26] Department of Veterans Affairs, V. H. A. (ed Department of Veterans Affairs) (2020).
[27] Akinyemiju, T., Jha, M., Moore, J. X. & Pisu, M. Disparities in the prevalence of comorbidities
among US adults by state Medicaid expansion status. Prev Med 88, 196-202,
doi:10.1016/j.ypmed.2016.04.009 (2016).

NIMH STRATEGIC PLAN FOR RESEARCH
NIH Publication Number: 20-MH-8096

https://www.nimh.nih.gov/strategicplan
Published: May 2020
Updated: May 2024
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NATIONAL INSTITUTE OF MENTAL HEALTH

STRATEGIC PLAN FOR RESEARCH

Updated: May 2024

NIMH Strategic Plan for Research i

NIMH Strategic Plan for Research ii

Message from the Director

NIMH Strategic Plan for Research 1

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

NIMH Strategic Plan for Research 2

NIMH Strategic Plan for Research 3

• Goal 1: Define the Brain Mechanisms Underlying Complex Behaviors

NIMH Strategic Plan for Research 4

Serving as an Efficient and Effective Steward of Public Resources

Setting Research Priorities

Monitoring and Measuring Programs

Emphasizing Rigor and Reproducibility

Fostering Resource and Data Sharing

Enhancing Oversight and Monitoring of Clinical Trials

NIMH Strategic Plan for Research 6

Creating and Strengthening Partnerships

Management and Accountability

Cultivating a Respectful and Inclusive Workplace at NIMH

NIMH Strategic Plan for Research 7

Enhancing Risk Management

Improving Administrative Processes

Promoting Workforce Development and Diversity

NIMH Strategic Plan for Research 8

Accomplishing the Mission

Challenges and Opportunities

Mental Health Equity

NIMH Strategic Plan for Research 10

Coronavirus Disease 2019 (COVID-19) Pandemic

NIMH Strategic Plan for Research 11

Early Intervention in Psychosis

NIMH Strategic Plan for Research 12

NIMH Strategic Plan for Research 13

Digital Health Technology

NIMH Strategic Plan for Research 14

NIMH Strategic Plan for Research 15

NIMH Strategic Plan for Research 16

Cross-Cutting Research Themes

A Comprehensive Research Agenda

NIMH Strategic Plan for Research 17

Global Mental Health

NIMH Strategic Plan for Research 18

NIMH Strategic Plan for Research 19

NIMH Strategic Plan for Research 20

Harnessing the Power of Data

NIMH Strategic Plan for Research 21

NIMH Strategic Plan for Research 22

Goal 1: Define the Brain Mechanisms Underlying Complex Behaviors

NIMH Strategic Plan for Research 23

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

NIMH Strategic Plan for Research 24

NIMH Strategic Plan for Research 25

NIMH Strategic Plan for Research 26

Objective 1.3: Identify and characterize the neural circuit mechanisms

NIMH Strategic Plan for Research 27

NIMH Strategic Plan for Research 28