# Challenges and Opportunities

The urgency of NIMH’s mission stems from the significant burden mental illnesses impose on individuals, their families, and society. In any given year, it is estimated that more than one in five U.S. adults live with a mental illness1 and the burden of mental illness is predicted to rise worldwide in coming decades.2,3 Mental illnesses cut across age, sex, race, ethnicity, and socioeconomic status. Mental illnesses occur more commonly in people with other chronic illnesses, such as heart disease, diabetes, cancer, and HIV.4,5 In fact, people with a mental illness may have an increased risk for chronic illnesses6 and effective treatment for mental illnesses can reduce that risk.7 Individuals with mental illnesses are also disproportionately represented among homeless and incarcerated populations.8 Furthermore, serious mental illnesses significantly impair one’s ability to function in daily life, are associated with personal loss of earnings,9 have a negative global financial impact,10 and are among the leading causes of poor health and early mortality worldwide.4,11 Tragically, suicide remains an urgent public health crisis in the United States.12 Although the national suicide rate declined between 2018 and 2020, the rate rose again in 2021 and is, at least in part, driven by disparities among certain minoritized groups.13 The burden of mental illnesses demands that we harness scientific knowledge and tools to achieve better understanding, prevention, and treatment of these disabling conditions. In this section, we outline our plans to leverage considerable research opportunities to address the many challenges of mental health and mental health research.

## Coronavirus Disease 2019 (COVID-19) Pandemic

To address the ongoing challenges that SARS-CoV-2 and the COVID-19 pandemic pose to our health and well-being, NIH is working urgently in unprecedented ways to understand and mitigate health threats. The NIH Strategic Plan for COVID-19 Research ** provides a framework for funding research across the scientific spectrum, primarily focusing on the direct testing, therapeutic, and preventive approaches needed to address SARS-CoV-2 and its long term consequences. As part of the strategic response to COVID-19, NIMH is actively engaged with the NIH Researching COVID to Enhance Recovery (RECOVER) ** initiative, which seeks to understand, prevent, and treat post-acute sequelae of SARS-CoV-2 infection. NIMH is also participating in multiple Rapid Acceleration of Diagnostics (RADx®) ** initiatives, including the RADx® Underserved Populations (RADx-UP) ** program, which aims to lay the foundation to reduce disparities for those underserved and vulnerable populations who are disproportionately affected by the COVID-19 pandemic. NIMH is also involved in several other NIH-wide efforts, including the Social, Behavioral, and Economic Impacts of COVID-19 ** and Maternal and Child Health ** workgroups. Emerging data indicate that people with serious mental illness have been hard hit by the pandemic. Individuals with schizophrenia or depression are more than seven times more likely to contract COVID-19 and are more than twice as likely to die from it if they do fall ill, compared with individuals who do not have a mental illness.14-16 NIMH-supported researchers are examining the effects of COVID-19 on mental health and developing and testing ways to improve delivery of care and treatment of mental illnesses in the context of a pandemic. This work is critical to meet the increased mental health needs for all who have been impacted by the pandemic, particularly as access to mental health services remain insufficient for the demand. In addition, NIMH staff continue to develop resources and share coping strategies to help people during the pandemic. More information about NIH’s response to the COVID-19 pandemic and guidance for researchers can be found on the NIH COVID-19 webpage **.

## Suicide Prevention

Given the troubling rise in the national suicide rate in the past decades, suicide prevention research remains an urgent priority for NIMH. From 1999 through 2018, U.S. suicide rates had shown small but consistent increases. The overall national suicide rate decreased ** between 2018 (14.2 per 100,000) and 2020 (13.5 per 100,000); however, the suicide rate rose again in 2021 ** (14.1 per 100,000). This is, in part, due to****rising rates among some racially and ethnically minoritized groups **, and explanations for these disparities are being explored.12,13 NIMH’s portfolio includes projects aimed at identifying individuals and populations most at risk for suicide, understanding the causes of suicide risk, developing suicide prevention interventions, and testing the effectiveness of these interventions and services in real-world settings. NIMH intramural and extramural research efforts have resulted in the development of screening tools and clinical pathways for implementation in real-world settings to identify those at risk for suicide. Our current collaborative efforts are testing the benefits of various strategies for risk detection and intervention. Because many suicide decedents in the United States have accessed health care services in the 12 months preceding death, health care systems can play a vital role in identifying individuals at risk and preventing suicide attempts.17 NIMH research has focused on emergency departments as a critical focal point, demonstrating that brief screening tools can improve providers’ ability to identify individuals at risk for suicidal behavior.18,19 Pairing this screening with a low-cost intervention, such as safety planning and follow-up phone calls, results in significant decreases in subsequent suicide attempts in the following year.18 NIMH-supported research has also led to the development of a computerized adaptive screener, which may make it easier for providers to screen more people and could help emergency departments quickly facilitate a connection with mental health services. NIMH continues to support research to identify how and why these screening and follow-up interventions work, and how these evidence-based tools can be scaled up for broader implementation to prevent suicide attempts and deaths. To more rapidly test and implement novel suicide risk reduction strategies, NIMH is supporting Practice-based Suicide Prevention Research Centers that will advance research, implementation, and training in specific content areas. Given that firearms account for over 50% of suicides annually in the United States, NIMH is funding research on preventing firearm injury and mortality. In addition, accumulating evidence suggests that various preventive interventions delivered early in life can change children’s mental health and substance use trajectories in a positive manner, including decreased risk for suicidal ideation and behaviors in adolescence and adulthood. NIMH continues to focus on understanding how disparities in suicide arise and can be addressed including among sexual and gender minority youth and adults who have elevated rates of suicide ideation and attempts across age, race, and ethnic groups. Understanding disparities in suicides among Black, 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,20 variable adherence to treatment guidelines,21 and poor attention to comorbid medical conditions associated with premature mortality.22 In addition, the RAISE studies demonstrated that early intervention improves clinical outcomes among youth and young adults with first episode psychosis, and that CSC is a feasible and cost-effective approach to early intervention in first episode psychosis.23,24,25 Through collaborations with other federal agencies, NIMH transformed these findings into real-world change **.26,27CSC is now the standard of care for early psychosis **, with more than 360 CSC programs ** across the country. In 2019 alone, CSC programs helped over 22,000 young people confronting the tremendous challenge of a first episode of psychosis by ensuring they had access to the best possible evidence-based care.

NIMH leveraged this expansion of CSC programs in the United States through the Early Psychosis Intervention Network (EPINET). The goal of EPINET is to accelerate advances in early psychosis care, recovery outcomes, and scientific discovery through a national early psychosis learning health care partnership. In this “learning health care system,” data that are routinely collected in CSC programs, as part of clinical practice, drive continuous improvement in client care and further scientific inquiry. Through EPINET, NIMH supports eight regional scientific hubs that include more than 100 CSC clinics in 17 states, as well as a national data coordinating center that standardize, collect, and aggregate data across community clinics and use computational methods to study CSC quality and treatment effectiveness. By studying large, nationally representative datasets, EPINET may offer crucial insights into how best to tailor early psychosis care for individuals and provide information to guide improvements in diagnosis and intervention.

NIMH has joined the Accelerating Medicines Partnership® (AMP®) to form a public-private partnership between the NIH, the U.S. Food and Drug Administration (FDA), the European Medicines Agency, and multiple public and private organizations to establish the AMP Schizophrenia (AMP SCZ) initiative. AMP is managed through the Foundation for the National Institutes of Health (FNIH) **. The goal of the initiative is to generate tools for future studies that will improve success in developing early stage pharmacologic interventions for people who are at risk of developing schizophrenia and other psychotic disorders. AMP SCZ ** has established a research network focused on identifying biological markers of disease progression, outcome measures and clinical endpoints. The initiative has also established a Data Processing, Analysis, and Coordinating Center to allow researchers to integrate and analyze data from new and key existing cohorts at clinical high risk for psychosis, with all data and analyses made publicly available through the NIMH Data Archive **. Findings from these studies may enable researchers to develop algorithms that predict the course of illness for individuals with clinical high risk for psychosis and allow clinical trials to test new pharmacologic interventions to prevent the onset of psychosis.

## Mental Health Equity

Mental health equity ** is the state in which all people have a fair and just opportunity to experience their highest level of mental health and emotional well-being. Racial and ethnic minorities, sexual and gender minorities, socioeconomically disadvantaged populations, and underserved rural populations experience striking disparities in burden of mental illness, access to and engagement in care, and recovery. Moreover, people from minoritized and marginalized communities are disproportionately affected by existing disparities that have been exacerbated by recent acts of racism and discrimination and converging public health crises (e.g., COVID-19, HIV, and opioid epidemics).28 In accordance with the 21st Century Cures Act, NIMH staff work closely with the National Institute on Minority Health and Health Disparities (NIMHD) **, the Office of Research on Women’s Health (ORWH) **, and other NIH institutes, centers, and offices to ensure activities take into account the health needs of minoritized individuals and women and are focused on reducing health disparities. In our efforts to achieve mental health equity, NIMH developed an Approach to Mental Health Disparities Research which outlines five priority research areas to address mental health disparities, and an NIMH Strategic Framework for Addressing Youth Mental Health Disparities. NIMH supports research that addresses the needs of individuals and communities across age, race, ethnicity, language, gender identity, sexual orientation, geography, and social determinants of health (e.g., education, economic stability, quality of housing, access to health care, experience of discrimination), as well as their intersectionality (a framework that addresses the multiple dimensions of individuals’ identity and social systems as they intersect with one another and relate to inequality).29 Of particular priority is research that identifies mechanisms contributing to the persistence of mental health disparities, and tests interventions aimed at reducing disparities, improving outcomes, and promoting equity. Further, to build a valid evidence base for effective prevention, treatment, and mental health services, NIMH strives to foster a culture of inclusion that values and fosters partnerships between study participants, communities, and researchers from all backgrounds.

## HIV Research

The prevalence of mental illnesses is higher in people with or at risk for HIV compared to the general population. Mental illnesses can be a barrier to HIV prevention, testing, linkage to treatment, treatment engagement, and retention in care. Mental illnesses are associated with poor health outcomes such as lower medication adherence, higher HIV incidence rates, and increased disease burden. There are also many co-occurring biological, psychosocial, and structural factors, as well as social determinants such as stigma, violence, and stress, that influence the development and course of mental illnesses and HIV. Mental health research is an integral component of HIV-related research across the lifespan. As such, NIMH supports a broad research portfolio in the United States and around the world to prevent HIV acquisition in high incidence populations and improve treatment and care among people with HIV, including those with comorbid mental and substance use disorders.

NIMH utilizes basic science to understand the pathogenic mechanisms of HIV-associated central nervous system (CNS) disorders, while translational research supports the development of therapeutic strategies to treat HIV-CNS comorbidities, including cognitive disorders and mental illnesses. In addition, NIMH supports efforts focused on eradicating the virus from the CNS, a prerequisite to finding a safe, effective, and complete cure for HIV. To complement efforts in basic and translational science, NIMH also advances behavioral and social science research to examine individual, interpersonal, community, institutional/health system, and environmental factors; peer and community-based strategies; structural and psychosocial determinants; and, data science, methodologies, and technological approaches critical in HIV prevention and treatment. NIMH supports implementation science to enable researchers to bring evidence-based interventions to the greatest number of people who may benefit, and develop innovative communication and dissemination approaches that facilitate trust and use of those interventions, particularly among people with HIV in resource-limited settings. NIMH also places a high priority on HIV research that can impact individuals from high-incidence populations across the lifespan, both domestically and globally, including racial and ethnic minorities, sexual and gender minorities, mobile populations, adolescents, women, and infants.

## Digital Health Technology

Recent advances in technology continue to evolve and create new opportunities to improve access, availability, utilization, and quality of mental health care services. The pace of research and clinical use of digital health approaches has been dramatically accelerated by the COVID-19 pandemic. The growth of digital health technologies, which blend mobile health and health information technology (such as smartphones, wearable sensors, electronic health records), gives the public, health care providers, and researchers new ways to access information and to measure and manage health and productivity. Ongoing NIMH-supported research leverages mobile and other emerging technologies to develop, test, and deliver targeted preventive and treatment interventions for disorders such as anxiety, insomnia, and depression. Approaches include just-in-time interventions that can be pushed out using smartphones or other technology based on information about the person’s current state and needs. Additional innovations employ patient- and clinician-facing digital monitoring devices, smartphones, and other applications or dashboards that facilitate monitoring and early detection of changes in patient status that might signal the need for additional or more intensive services to forestall relapse or hospitalizations. NIMH is also interested in digital biomarkers ** and outcome assessments for inclusion in clinical trials for monitoring responses to interventions. While the technology frontier offers promising opportunities for therapeutics (e.g., drug development **, brain stimulation, behavioral therapies) and mental health care, much work remains to address questions about efficacy and effectiveness, bias, regulation, privacy, and additional ethical considerations. As technology is increasingly utilized in mental health research and care, innovation is needed to bridge the digital divide and ensure that lower resourced settings are included.

## Genetics

Tremendous progress has been made in psychiatric genetics. Genome-wide association studies (GWAS) as well as rare variant association analyses, both of which required global-scale collaborations to assemble immense sample sizes, uncovered statistically rigorous and fully-replicated genetic links to schizophrenia, autism, depression, and other psychiatric disorders. In considering the complexity of the genetic landscape, the *Report of the National Advisory Mental Health Council Workgroup on Genomics***provided recommendations for the future of genomics research: 1) utilize statistically rigorous, unbiased, and well-powered studies; 2) harness innovative approaches that address both common and rare genetic variants; and, 3) leverage universal datasets that capture genetic and phenotypic variation across diverse human populations. NIMH is focused on expanding the ancestral diversity of genetic samples, and increasing our understanding of the genetic determinants of mental illnesses like obsessive-compulsive disorder, anorexia nervosa, and other disorders where additional work is needed. A significant goal is to better understand how molecular, neural, environmental, and psychosocial mechanisms interact with the genetic and epigenetic links that have been identified. Acquiring this new knowledge will likely cross levels of analysis, from genes to cells to circuits to behavior.

## Neural Circuits

Neuroscience has provided us with the tools to look deeply into the function of neural circuits, and directly test hypotheses about brain-behavior relationships using noninvasive brain stimulation technologies. Over the past decade, technologies—such as optogenetics, chemogenetics, viral tracing, and high-resolution optical imaging—aimed at measuring and modulating the activity of specific circuits, have facilitated the attainment of a vast knowledge base about the circuits that control behavior and mental processes. Noninvasive neuromodulation devices allow scientists to change function within circuits for therapeutic benefit, and this approach led to the U.S. Food and Drug Administration (FDA) approval of transcranial magnetic stimulation (TMS) for the treatment of depression and 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 these manipulations are most effective.

Updated:  May 2023