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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 in mental health research. This section summarizes these major themes that, along with the challenges and opportunities facing the mental health field, motivated 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 that there is the potential to improve clinical care over the short, medium, and long term, study designs should use diverse 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. Studies should include both sexes and, depending on the research question, should consider how genetic background will advance the quality and interpretability of the outcomes. In addition, studies should include participants from diverse racial and ethnic backgrounds, and across gender identities, geographical context, socioeconomic status, neurotype, and age – offering the best possible representation, for the broadest number of individuals who may ultimately benefit from scientific advances.


NIMH has a developmentally focused, theory-based prevention research program that spans the life course from prenatal though adulthood, at different levels of intervention (e.g., universal, selective, indicated, tiered), and in different settings (e.g., families, schools, healthcare, 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, traumatic) are important opportunities for the implementation of prevention interventions at different developmental stages. NIMH supports research examining the efficacy and effectiveness of prevention interventions conducted in a variety of contexts and settings, and the implementation of effective interventions at scale in communities in a sustainable manner.

Global Mental Health

Mental illnesses are a global concern, presenting shared opportunities to advance science across international boundaries. NIMH investments in effectiveness and implementation research in low- and middle-income countries are producing innovative strategies for expanding access to mental health care and improving care quality and outcomes in a range of settings worldwide. At the same time, new global opportunities are emerging to advance our understanding of how genetics (or population genetics), cultural backgrounds, societal and familial structures, and environmental exposures can maximize the impact of basic and translational mental health research. Findings from this research will enhance our knowledge of mental health and illness; point to new targets for better preventive and treatment interventions; and, lead to novel approaches for addressing mental health needs worldwide, including those of currently underserved populations. NIMH also supports research on new and evolving technologies to improve mental health screening, assessment, prevention, treatment, systems of care, and the dissemination of cutting-edge science across the globe. International collaborations with researchers, providers, advocates, individuals living with mental illness and their families, and global health and development agencies are also improving NIMH’s ability to address mental illnesses here in the United States, especially for those from geographically, socioeconomically, and culturally diverse populations.

Environmental Influences

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 cultural milieu, family structure and interactions, poverty, neglect, and other social determinants of health. 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 now closer than ever to understanding how environmental factors affect brain development and shape behavior. For example, as part of the Adolescent Brain Cognitive Development (ABCD) study, which has enrolled over 10,000 children across the country, researchers are examining how biology and environment interact and relate to developmental outcomes, such as physical health and mental health. NIMH also continues to vigorously support efforts to study the biological and psychological impacts of trauma, mechanisms of prenatal risk, and numerous other environmental factors that may lead to mental illnesses.

Medical Comorbidities

Medical comorbidity is the co-occurrence of mental and/or other physical disorders, including substance use disorders. Comorbidities may affect both the development and clinical course of mental illnesses through their effects on basic biological processes. For example, in HIV, the infection and its treatments 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 other medical conditions will provide additional insight into the causes and facilitators of mental illnesses, as well as provide pathways to better outcomes for people with mental illnesses.


Exploring Novel Frameworks for Studying Mental Disorders. High rates of psychiatric comorbidity and heterogeneity of symptoms exist for patients when providers use the current diagnostic categories, which rely solely on self-reported or observable symptoms. NIMH’s evolving Research Domain Criteria (RDoC) framework integrates many levels of information (from cellular to behavioral) to advance our understanding of mental illnesses. Through the RDoC framework, NIMH encourages the identification of neurobehavioral mechanisms of specific domains of mental function, rather than creating models of discrete disorders. Beyond improving research sample characterization using objectively measurable factors rather than exclusively relying on self-report of symptoms, this approach holds promise for uncovering mechanisms of mental illnesses, identifying putative therapeutic targets, and paving the way for novel preventive and treatment interventions.

Advancing Interventions. Historically, novel prevention and treatment development has been slow, expensive, and high risk. To speed 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 and other settings, NIMH invests in studies that anticipate real-world implementation during intervention development. Additionally, NIMH takes an experimental approach to testing mechanisms of effective care delivery in real-world settings and engages stakeholders throughout the research process. 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 and prevention and treatment of mental illnesses. Computational approaches allow us to describe and test how complex, high-level phenomena emerge from interactions at smaller scale levels. For example, computational models can put into explicit mathematical terms testable hypotheses regarding how alterations in genes might affect circuit function. Similarly, computational models can test how circuit dysfunction impacts neural development and plasticity, and how that dysfunction manifests in behavior and leads to progressive, chronic disorders. In addition, computational approaches can help take advantage of large data sets, categorizing brain dysfunction in a way that has the potential to lead to better diagnoses, improved biomarkers, and tailored prevention and treatment interventions. Within clinical research, computational methods (e.g., data mining, machine learning, predictive analytics) may also be used to analyze electronic health records or other administrative data to identify modifiable risk factors and inform the optimal timing of interventions. NIMH is dedicated to supporting computational approaches that integrate knowledge gained at genetic, molecular, cellular, circuit, behavioral, and healthcare system levels.

Harnessing the Power of Data

Advances in data acquisition and the availability of aggregated, harmonized data sets, 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 optimal mental health care quality and effectiveness. Further, the development, validation, optimization, and expansion of digital mental health tools will improve our understanding of mental illnesses, help track the course of illness, and improve mental health care. Widespread data sharing and collaborations with experts in other areas of science, including ethicists, engineers, and computer scientists, add significant value to research and accelerate the pace of discovery.

Research Workforce

Training. Scientific advancement requires investment in future generations of mental health researchers. Supporting outstanding scientists who will advance the field to help people with mental illnesses is a priority for NIMH. NIMH supports multiple research training, education, and career development mechanisms to encourage the development of junior investigators across a range of scientific career stages, including supporting those in graduate school, residency, post-doctoral training, and those who are early stage faculty members. NIMH’s multidisciplinary training and career development mechanisms can support junior investigators at either the individual level or at the institutional level. One mechanism NIMH uses to support early investigators is the Biobehavioral Research Awards for Innovative New Scientists (BRAINS) program. Since 2009, the BRAINS program has helped extraordinary early stage investigators launch innovative research programs with the potential to transform mental health research. BRAINS awards support the person as well as the project; these awards afford an opportunity for early stage investigators to explore truly novel and potentially groundbreaking approaches, while providing a stable foundation from which to launch their independent research programs. In addition, NIMH is committed to the training and advancement of individuals from diverse backgrounds and at all academic stages. The Institute’s training, education, and career development mechanisms span all priority research areas described in NIMH’s Strategic Plan for Research.

Inclusion and Diversity. By prioritizing inclusion and diversity, NIMH maintains its commitment to improving recruitment, training, advancement, and retention of researchers from underrepresented groups, with diverse backgrounds, and whose experiences reflect varied perspectives and scientific specialties worldwide. For example, NIMH continues to support the NIH Blueprint Enhancing Neuroscience Diversity through Undergraduate Research Education Experiences (BP-ENDURE) program. BP-ENDURE offers opportunities in neuroscience research for individuals from underrepresented racial and ethnic groups, individuals with disabilities, and those at economic disadvantage.