NAMHC Minutes of the 241st Meeting

May 29, 2015

Department of Health and Human Services
Public Health Service
National Institutes of Health
National Institute of Mental Health

Introduction

The National Advisory Mental Health Council (NAMHC) convened its 241^st meeting in closed session to review grant applications at 8:30 a.m. on May 29, 2015, at the Neuroscience Center in Rockville, Maryland,until adjournment at approximately 10:50 a.m. (see Appendix A: Review of Applications). Following a brief break, the NAMHC reconvened at the same location for the open policy session at 11:00 a.m. and adjourned at approximately 4:29 p.m. In accordance with Public Law 92-463, the policy session was open to the public.  Thomas Insel, M.D., Director of the National Institute of Mental Health (NIMH), chaired the meeting.

Council Members Present at the Grant Review and/or Open Sessions

(See Appendix B: Council Roster)

Chairperson

• Thomas R. Insel, M.D.

Executive Secretary

• Tracy Waldeck, Ph.D.

Council Members

• Patricia Areán, Ph.D. (by telephone)
• Deanna M. Barch, Ph.D.
• David A. Brent, M.D.
• B.J. Casey, Ph.D.
• Benjamin G. Druss, M.D., M.P.H.
• Hakon Heimer, M.S.
• Richard L. Huganir, Ph.D.
• Marsha M. Linehan, Ph.D.
• Maria A. Oquendo, M.D.
• Mary Jane Rotheram, Ph.D.
• Carol A. Tamminga, M.D.
• Hyong Un, M.D.

Ex Officio Members

• John W. Davison, M.B.A., Ph.D. Department of Defense (DoD)
• Theresa Gleason, Ph.D., Department of Veterans Affairs

Liaison Representative

• Gwen Littman, M.D., Center for Mental Health Services, Substance Abuse and Mental Health Services Administration (SAMSHA)

Others Present at the Open Policy Session

• Angela Banks, Otsuka Pharmaceutical
• Devin Breckenridge, NIH Interpreter
• Tyauna Brown, Synergy Enterprises
• Pearl Chiu, Salem VA Medical Center
• Nicola Croll, HSC Pediatric Center
• Robin Cunningham, Cure Alliance for Mental Illness
• Flavio Fröhlich, University of North Carolina
• Justin Harding, National Association of State Mental Health Program Directors
• Alan Kraut, Association for Psychological Science
• Juliana LeMaster, NIH Interpreter
• Nick Rooney, NIH Transcriber
• Nim Tottenham, Columbia University
• Lori Whitten, Science Writer
• TaRaena Yate, Synergy Enterprises

Open Policy Session Call to Order and Opening Remarks

NIMH Director Thomas Insel, M.D. called the open policy session to order and welcomed all in attendance.

Approval of Minutes of the Previous Council Meeting

Turning to the minutes of the February 2015 Council meeting, Dr. Insel asked whether Council members had any comments, revisions, or questions. Receiving none, the Council unanimously passed the motion to approve the minutes.

NIMH Director’s Report

Dr. Insel reviewed the agenda for the open policy session and provided an update on activities related to NIMH.

At the White House level, the Precision Medicine Initiative  is a major topic. President Barack Obama highlighted the Initiative at the State of the Union Address on January 20, 2015 and followed up with a speech at the East Wing on January 30. He called for $130 million in additional funding for the National Institutes of Health (NIH) to develop a 1 million person cohort (called the National Research Cohort). In addition, the President’s fiscal year (FY) 2016 budget calls for $70 million to the National Cancer Institute (NCI) for cancer precision medicine, $10 million to the Food and Drug Administration (FDA) for establishing databases to advance innovation, and $5 million to the Office of the National Coordinator for Health Information Technology to develop data standards and privacy measures. Currently, most medical treatments are designed for the average patient; precision medicine aims to personalize care to the individual. The Precision Medicine Initiative Working Group  of the Advisory Committee to the Director of NIH has been formed and is charged with developing a vision for how to harness the advances in technology, scientific understanding, and participant engagement to develop a platform for precision medicine research and move precision medicine into every day clinical practice. The Precision Medicine Initiative has a near-term focus on cancers and a longer-term aim to generate knowledge applicable to the whole range of health and disease. Read about the scientific justification of the Precision Medicine Initiative in a New England Journal of Medicine Perspective  by NIH Director Francis Collins, M.D., Ph.D., and former NCI director Harold Varmus, M.D.

NIMH has described its current vision for precision medicine in psychiatry (see PMID: 25931539 ). The National Research Cohort offers a potential platform for collecting information on symptom-based categories and linking that to integrated data—including genetic risk, brain activity, physiological measures, cognitive and behavioral processes, and life experiences—to develop more precise, data-driven categories (clusters) for choosing interventions or prognoses.

Dr. Insel noted that there is great Congressional interest in biomedical research issues. The 21st Century Cures Initiative , led by Representatives Fred Upton (R-MI) and Diana DeGette (D-CO) of the House Energy and Commerce Committee, would establish an Innovation Fund ($1.86 billion per year for 5 years) to support biomedical research. The funds would include support for early stage investigators, modernization of clinical trials for data sharing, and improvement of the regulatory process for Federal health agencies. The Act also calls for NIH to develop an agency-wide Strategic Plan. NIH will submit its Strategic Plan, which outlines how the agency sets priorities and ensures accountability, by December 2015. The NIH Strategic Plan will aggregate the plans of its component Institutes, Offices, and Centers.

On the Senate side, the Committee on Health, Education, Labor, and Pensions, led by Senators Lamar Alexander (R-TN) and Richard Burr (R-NC), released a report entitled, Innovation for Healthier Americans , which addresses regulatory issues and focuses on drug development and the need to support basic science and improve clinical trials. The driving force behind this report is the need to reduce the time and cost of developing medical products for American patients. Congress has expressed increasing recognition and support for NIMH’s work. The Helping Families in Mental Health Crisis Act , sponsored by Rep. Tim Murphy (R-PA), is the most far-reaching legislation on mental health policy in decades. It would establish an Assistant Secretary for Mental Health and Substance Abuse; focus on serious mental illness (SMI); and, address several policy challenges for people with SMI, such as bed shortages, the Medicaid “one doctor a day” rule, Health Insurance Portability and Accountability Act (HIPAA) restrictions, the need for secondary prevention, translation of research into practice, and integration of mental health and physical health.

Dr. Insel recently attended hearings for the Senate Committee on Appropriations’ Labor, Health and Human Services, Education, and Related Agencies  subcommittee, chaired by Roy Blunt (R-MO). Senators asked about the prevalence of mental disorders and expressed interest in bringing the funding for mental health disorders up to par with that of other conditions.

At the Department of Health and Human Services (HHS) level, the NIMH collaboration with the Substance Abuse and Mental Health Services Administration (SAMHSA) on the epidemiology of mental illness will develop and field-test a survey to assess mental disorders among youth and adults. This collaborative effort will conduct the survey with a nationally representative sample of more than 13,000 respondents (plus parents of youth respondents) in 2017, and obtain consent for follow up. The effort will also involve a clinical validation/calibration study on the mental illness and psychotic symptoms modules in the survey. Dr. Insel commented that NIMH staff members are excited to work with SAMHSA on this important effort.

At the NIH level, the Genotype-Tissue Expression (GTEx) project aims to increase our understanding of how changes in our genes contribute to common human diseases, in order to improve health care for future generations. Supported by the NIH Common Fund, and administered by the National Human Genome Research Institute, GTEx established a unique database (GTEx Portal) and a tissue bank with more than 30 tissue types from 900 donors that can be used by researchers around the world. The first results were recently published (see PMID: 25954003 ). Published pilot studies are useful for demonstrating how to handle data from this project. For psychiatry, GTEx will help elucidate which common genetic variants are related to changes in gene expression in different parts of the brain and which ones influence function.

The NIH Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is guided by Brain 2025: A Scientific Vision, the report the BRAIN Working Group released a year ago. The Initiative focuses on developing tools that measure circuits and networks to determine how they are connected to behavior. Much has happened since the report’s release. New FY 2015 initiatives include: Short Courses in Computational Neuroscience and Research Tools and Methods; New Concepts/Early Stage Research for Large-Scale Recording & Modulation; Next-Generation Invasive Devises for Recording and Modulation in the Human Central Nervous System; and Clinical Studies to Advance Next-Generation Invasive Devices for Recording and Modulation in the Human Central System.

Turning to upcoming meetings, the Partnerships for Developing and Integrating Innovative New Technologies for Human Brain Research (June 3–4, 2015) aims to encourage research using the latest-generation devices for central nervous system neuromodulation and interfacing with the brain in humans. The meeting will describe the proposed NIH framework for incentivizing new studies using these devices, discuss regulatory and intellectual property considerations, and solicit recommendations for data coordination and access. Dr. Insel noted that the meeting aims to engage the private sector, including small companies that are developing electrodes and devices. Although NIMH has had similar meetings to engage companies in drug development, it has not met with firms that develop devices. The June meeting is an attempt to start the process.

Dr. Insel remarked that this is a fantastic period of discovery for the BRAIN Initiative, and the first papers are now being published. Although it is impossible to discuss all the papers, Dr. Insel highlighted work by Lihong Wang, Ph.D. of Washington University that offers proof of principle for micro-imaging in animals. The photo-acoustic microscopy technique uses pressure waves to measure biological structures and functions. With this technique, brain tissue minimally scatters pressure waves, allowing for deep imaging penetration. It is non-invasive, targets defined subpopulations of neurons, and its deep penetration enables measurements of whole brain activity (see PMID: 25822799 ).

Other exciting discoveries from the BRAIN Initiative come from the DREADD (Designer Receptors Exclusively Activated by Designer Drugs) project. One might think of this work as chemogenetics—in which scientists use genomic engineering to create new receptors and then activate cells by providing ligands for those receptors. A recent publication from this project showed improved social behavior in an animal model of autism by increasing the activity of oxytocin-producing neurons using DREADD (see PMC: 4498455 ). Although the BRAIN Initiative is highly productive and continues to grow, one challenge is keeping its research activities in the limelight. The Initiative’s budget is already below the anticipated levels. Although the Precision Medicine Initiative is important, appropriate levels of support for the BRAIN Initiative must be sustained and further developed.

Turning to the NIMH Strategic Plan for Research, Dr. Insel reported that the document is final and referred Council members to their packets for a copy. He thanked Council members for their comments, which greatly improved the document. Now that NIMH has outlined its cross-cutting research themes and strategic objectives, the Institute must develop corresponding initiatives and determine how to implement its Strategic Plan. The afternoon discussion on concept clearances represents the beginning of that process.

NIMH has published a white paper that outlines its funding for mental disorders and HIV/AIDS and it is posted on the website. Dr. Insel presented a chart of funding by disorder during the past 5 years. Another graphic showed a regression analysis between disability-adjusted life years (DALYs) and NIH and NIMH funding for 40 disorders. Investments for mental illness research are clearly below what NIMH would like them to be. Dr. Insel cautioned that although such an analysis is not definitive, it is one factor for Council members to consider as they think about how to implement the NIMH Strategic Plan for Research.

Other important considerations include data sharing and management of investments. The NIMH Data Archive is a bioinformatics system that will store all data from clinical research funded by NIMH, and the Institute welcomes research data from other funding sources. Currently, four websites allow the community to access the Archive data repositories. The Archive contains research data from more than 100,000 human study participants, and this number will continue to grow. This resource will help focus the field and provide researchers with an opportunity to conduct important secondary analyses, as well as other ways to use these datasets. In addition to the Archive, the NIMH Repository and Genomics Resource offers more than 150,000 well-characterized, high-quality patient and control samples. This resource receives, processes, and stores biomaterials ready for analysis from primary sources submitted by NIMH grantees. It distributes biomaterials to approved investigators and creates and distributes computational and sample-selection tools that support analysis of the genomic and clinical data. Dr. Insel commented that these resources demonstrate a new era of data sharing and open science that has some challenges, including changing the culture in academia. NIMH would like Council members’ guidance on how to encourage open science among academic researchers.

The status of the budget has not changed since the February meeting. The NIMH FY 2015 appropriation is $1.4 billion, a $17 million increase over the NIMH FY 2014 appropriation. Funding for competing Research Project Grants is $228 million, and $25.2 million for NIMH BRAIN Initiative projects. Language in the Senate and House Appropriation bills continues to require SAMHSA to collaborate with NIMH to incorporate coordinated specialty care after a first episode of schizophrenia into block grants in all 50 states.

The President’s FY 2016 proposed budget requests $31.1 billion for NIH, which represents a $1 billion increase over FY 2015. The request for NIH includes specific increases for the Precision Medicine Initiative ($200 million) and the BRAIN Initiative ($70 million). The President’s Budget is a request to Congress, and appropriation depends on Congressional action. Unless there is an overall deal to loosen current statutory budget caps, sequestration, could potentially result in a 5 percent across-the-board cut for FY 2016 unless Congress acts to exempt NIH.

Dr. Insel next reported on NIMH staff updates. Jane Steinberg, Ph.D., Director of the Division of Extramural Activities, retired in April. Dr. Insel thanked Dr. Steinberg for her tremendous contributions to the Institute. Tracy Waldeck, Ph.D., is now Executive Secretary for the Council. Jean Noronha, Ph.D., is serving as the Acting Director of the Division of Extramural Activities during the search for a permanent replacement. Holly Lisanby, M.D., a national leader in non-invasive neuromodulation, will be joining NIMH as Director of the Division of Translational Research in fall 2015. . Until Dr. Lisanby joins, Philip Wang, M.D., Dr.P.H., will serve as Acting Director of the Division of Translational Research. NIMH staff has received many honors, and Dr. Insel highlighted that Joel Sherrill, Ph.D., of the Division of Services and Intervention Research received a Meritorious Research Service Commendation from the American Psychological Association.

Dr. Insel reviewed the meeting agenda and welcomed questions and discussion from Council members.

Discussion

Marsha M. Linehan, Ph.D., commented that the update was great, but wondered about NIMH research on behavior. It is known that changing behavior can alter the brain, and this is an area that requires more research. Dr. Insel responded that NIMH staff discusses the appropriate balance between biological and behavioral research a great deal. This particular overview focused on biological projects, but NIMH supports research in areas other than brain pathways. Cognitive science makes important contributions to deconstructing disorders, according to current research. Neuroimaging findings introduce complexity and suggest that researchers need to operationalize and standardize behavioral data. Dr. Insel commented that the NIMH Strategic Plan for Research is broader than genes and imaging. He asked for Council guidance on opportunities in important areas of cognitive, social, and behavioral research. Perhaps Council members could form a workgroup to identify the most exciting opportunities in behavioral and social science that are not currently represented in the NIMH research portfolio.

Patricia Areán, Ph.D., endorsed the idea of a Council workgroup to identify opportunities for NIMH in behavioral and social science research. She commented on the importance of research to refine behavioral assessment technology, including both cognitive and behavioral tests. Who will fund research on the use of smart devices to measure behaviors and other methodological work? Dr. Linehan added that computerized intervention is the future, so the workgroup will need to include people who are knowledgeable in that field. Dr. Insel added that Council members interested in this topic should identify obtainable goals that map onto the NIMH Strategic Plan for Research.

NIMH Biobehavioral Research Awards for Innovative New Scientists (BRAINS) Awardee Panel

Dr. Insel remarked that NIMH initiated the BRAINS Program to encourage early stage investigators to generate exciting, high-risk/high-reward ideas that are not in the mainstream. Dr. Insel thanked Kathleen Anderson, Ph.D. for her work on this effort, and he noted that this is a model that NIH wants to follow.

Dr. Anderson remarked that it is a pleasure to introduce these phenomenal investigators. The goals of the NIMH BRAINS Program are to: (1) solicit highly innovative, creative, and ambitious research applications from early stage investigators with the potential for transforming our understanding of the etiology, pathophysiology, and treatment of mental disorders; (2) support promising new investigators early in their careers so they can develop independent, high-risk/high-reward research programs that address the highest priorities for NIMH; and (3) reduce the age at which promising early stage investigators receive their first NIH/NIMH R01. To be eligible for an award, an investigator must address a critical knowledge gap identified in the NIMH Strategic Plan, hold a tenure-track position with no prior R01 support, and propose a highly innovative and high-impact project. The BRAINS Program offers five years of support, up to $1.6 million per award. During its 5-year history, NIMH has awarded 46 BRAINS grants and recommends 10 for this year. NIMH invited three of the awardees to share their research and experiences as a BRAINS awardee with Council.

Rational Design of Brain Stimulation: At the Intersection of Biology, Engineering, and Medicine

Flavio Fröhlich, M.D.
Assistant Professor, Departments of Psychiatry, Cell Biology and Physiology
Biomedical Engineering, and Neurology, University of North Carolina at Chapel

The goal of Dr. Fröhlich’s research is to revolutionize the treatment of psychiatric illnesses by developing novel, non-invasive brain stimulation paradigms using rational design. This work meaningfully blends neuroscience and clinical research and strives for the vertical integration of clinical trials, brain stimulation, animal research, and computer simulations. Rational design spans molecules, synapses, neurons and glial cells, networks, and brain areas. Dr. Fröhlich’s work targets brain network dynamics by stimulating non-invasively with transcranial alternating current stimulation (tACS) with very weak current and measuring changes with electroencephalography (EEG).

Using computer simulation, Dr. Fröhlich and his colleagues have achieved state switching using tACS (see PMC: 3812055 ). In other research, they are targeting alpha oscillations, the “offline” state involved in long-range functional connectivity and internal processes. Disrupted alpha oscillations are implicated in many mental disorders. The researchers are also studying alpha (offline) and gamma (awake) oscillations and non-REM sleep spindles in the thalamus and have observed state-dependent modulation of these in computer simulations. Using non-invasive brain stimulation to increase alpha oscillations during creative ideation has the potential to enhance creativity, and the researchers have found proof of principle in studies with volunteers. They are also interested in targeting sleep spindles to boost memory consolidation, have conducted a pilot study, and hope to expand this effort to a study with healthy volunteers. Dr. Fröhlich’s laboratory is also interested in tACS and neurodevelopment in animal models, the LP/pulvinar complex, and developing device technology. They are working on tACS clinical trials with various patient populations (people with schizophrenia, depressive disorder, and premenstrual dysphoric disorder) and expect results in about 2 years. Dr. Fröhlich added that tACS stimulation is considered safe for testing in healthy and patient populations.

In summary, Dr. Fröhlich remarked that targeted non-invasive brain stimulation (with tACS and other techniques) has the potential to revolutionize psychiatry by targeting neuronal network dynamics. Currently, the work is in early stages, with few randomized controlled trials, ad hoc stimulation paradigms, and no mechanistic basis. However, the work is headed for rational design by leveraging an emerging understanding of interaction dynamics between endogenous network activity and stimulation paradigms. Dr. Fröhlich added that he was trained as an electrical engineer, and the BRAINS award made the transition into psychiatry possible. The convergence of fields that have been traditionally separate is exciting.

Longitudinal Examination of Human Amygdala-vmPFC Development

Nim Tottenham, Ph.D.
Associate Professor, Department of Psychology, Columbia University

Dr. Tottenham commented that her research focuses on the link between early adversity and later socio-emotional outcomes, particularly examining the neurodevelopment of the amygdala, prefrontal cortex (PFC), ventromedial prefrontal cortex (vmPFC), and medial prefrontal cortex (mPFC). The amygdala detects threat in the environment and is involved in other aspects of fear. In humans, this brain structure takes a long time to develop and continues to mature throughout childhood and adolescence. The main idea of Project PACT (Parents and Children Coming Together) is to use neuroimaging and other measures to generate a developmental growth chart for the amygdala-PFC neural circuit. The project involves scanning 150 racially diverse children and adolescents every 2 years across 5 years. The participants have experienced both typical and early institutional care (orphanage followed by adoption into families in the United States).

Findings from children with typical care indicate that the amygdala produces a healthy response to fearful faces at age 4 years, but does not show adult-like connectivity with PFC despite the presence of other developed connections. The neural activity of the amygdala matches behavioral responses to fearful faces. Additionally, connectivity of this circuit predicts its connectivity 2 years later. Therefore, Dr. Tottenham and colleagues have observed stability in the neural signal and developmental prediction regarding connectivity. It is exciting to see that the amygdala can respond to emotional events under certain conditions in children. Childhood is a stage in which dynamic changes in the environment can shape neural and behavioral development. Humans have many years of caregiver attention, and it seems that parents provide major regulatory scaffolding for brain development during a time of neural immaturity.

A well-established research partnership with B. J. Casey, Ph.D., has shown that children from institutions who have experienced an absence of parental care (an extreme example of childhood neglect) and are later adopted are at significantly elevated risk for anxiety. After adoption, these children show a huge heterogeneity in outcomes, and initial evidence suggests that neural data might provide some predictive value for outcomes. This work showed that children who have experienced early deprivation display elevated amygdala reactivity, and these findings have been replicated. The findings are also consistent with animal research showing premature amygdala myelination, reactivity, fear retention, and adult fear regulation in response to parental deprivation. Dr. Tottenham noted that the research has not found any gender differences, but those might emerge with larger sample sizes. The amygdala seems to be a final common pathway for the impact of early adversity, and neural signals from this structure have predictive value regarding anxiety. Among typically developing adolescents, amygdala-mPFC connectivity is more mature. The development of this neural circuit in children who have been adopted from institutions looks more like that of adolescents. A current hypothesis is that the absence of parental care specifically accelerates the development of midbrain and limbic structures (including the amygdala-mPFC), which benefits the individual in the short term, but may underlie difficulties with fear regulation in the long term.

A key question is: Why are parents important for emotional development? Data from animal research is compelling and indicates that the presence of the mother dampens the reactivity of the amygdala (mediated by cortisol). The presence of a parent blocks fear learning in children, which is moderated by attachment security. Dr. Tottenham and colleagues aim to examine this phenomenon among children and develop a neurobiological model for why and how parental care is important for anxiety and mental health. The larger goal is to understand the emergence of mental health disorders during adolescence.

Dr. Tottenham remarked that a BRAINS award has changed her life, because it allows her to fulfill her dream of developing a growth chart for the amygdala-PFC circuit. The grant supports following families over a 5-year period, which is very important for her work. It has been great to establish collaborations with cohort colleagues. As part of the award, grantees meet with members of the BRAINS Program Advisory Board, which was great for discussing optimization, mechanisms, and clinical translation. Access to these experts is a great gift for a researcher, especially early career investigators. BRAINS awardees also have the opportunity to cultivate a relationship with NIMH, which is very important for career development. The grant has also boosted the yield, innovation, and confidence of students in the laboratory (13 trainees, with some who are obtaining their own funding).

Toward A Computational Psychiatry

Pearl Chiu, Ph.D.
Assistant Professor, Virginia Tech Carilion Research Institute and School of Medicine, Virginia Tech Department of Psychology

Dr. Chiu remarked that her research uses quantitative, model-based, and neuroscience approaches to understand and treat mental disorders. Her research seeks to clarify the functional neuroscience of human motivation and decision-making and identify clinically useful multidimensional phenotypes that are not accessible by brain or behavior alone. Her work takes computational-model‒based understandings about neuroscience and uses human mental disorders as model systems to address these issues. The work focuses on depression and substance dependence (e.g., smoking), seeing them as disorders of motivation and decision-making. A depressed person is unmotivated, whereas one who abuses substances is hyper-motivated for their drug of choice. By better understanding these disorders, the research may help develop new biologically informed interventions to change the neural and behavioral substrates of decision-making.

Dr. Chiu and colleagues use neuroimaging and decision-making tasks to understand the impact of various factors on learning and decision-making, including cognitive strategies, social influence, changing task statistics, and functional magnetic resonance imaging (fMRI)-guided neuro-feedback. By tracking the neural activity associated with normal learning in decision-making tasks, Dr. Chiu and colleagues can fit computational models of neural functioning to the data to understand where, when, how, and why the decision-making process breaks down. Dr. Chiu said she was particularly excited about the possibility of changing the neural and behavioral substrates of decision-making within the individual. For example, she and colleagues scanned the brains of people with depression before and after cognitive therapy. They found that depressed people show improvement over time in response to therapy and that individuals who are more sensitive on the loss prediction error parameter are less likely to respond to cognitive strategies. These data indicate new neuro-mechanistic targets in depression that may be changed though behavioral training.

Such fMRI-guided neuro-feedback allows people to see how their brains are responding in various situations and change this activity. Dr. Chiu and colleagues have shown that smokers craving cigarettes (a significant predictor of relapse) can be trained to shift brain activity towards a non-craving state. These results provide proof of principle that fMRI-guided neuro-feedback can change the brain activity of smokers and that these neural changes match the subjective experience of craving. Dr. Chiu and her colleagues are examining effect sizes, optimal dosing, and the duration of these changes.

Dr. Chiu spoke of her experience as a BRAINS awardee. The award launched her research and provided a mechanism (advisory committee mentors) to interact with world-class experts, which Dr. Chiu described as an incredible opportunity. The award and associated funding from a diversity supplement has helped her support superb trainees. The award has also provided opportunities to participate in multi-site, consortia, and center applications, which has increased interaction with more senior scientists and group efforts. The award also facilitated participating in study sections which has been eye-opening and rewarding. She stressed the importance of the BRAINS award for jump-starting data collection for new investigators and allowing researchers to pursue innovative, high-impact ideas, rather than play it safe. Dr. Chiu noted that a challenge for standing study sections may be how much to weigh innovation relative to the other metrics. To encourage significant innovative projects, relative weighting toward the investigator’s track record and qualifications, perhaps over approach details, could be helpful. Efforts to fund the investigator and continued funding opportunities like BRAINS are a promising step in this direction.

Discussion

Dr. Insel thanked the presenters and noted that NIMH hopes to expand the BRAINS Program to support more innovative work conducted by the next generation of researchers. He asked Council members for guidance on the potential mechanisms and changes to the process involved in funding the investigator.

Dr. Linehan thanked the BRAINS awardees for their wonderful work and recognized NIMH for supporting her own research. So many people help investigators along the way, and she suggested a model in which the Institute supports and develops the talent of creative people with great potential. One important area of support is feedback on grant writing. Dr. Insel added that NIMH has fabulous Program staff that can help both investigators who have not been funded by the Institute before, as well as those with active grants. Unfortunately, not enough investigators consult with Program to develop research concepts, despite NIMH encouraging scientists to do so.

Deanna M. Barch, Ph.D., commented on the importance of innovation in research on mental health. However, the requirement for pilot data in funding applications can hamper innovation. An investigator has to conduct a study to obtain pilot data to apply for funding, but how do they do this research without funding? The outcomes of the BRAINS Program should help determine whether funding people with good ideas but no pilot data is a successful mechanism.

Carol A. Tamminga, M.D., commented that NIH grant review committees need to involve BRAINS awardees. Their unique experience in this Program provides them with a good perspective on innovation in science and the opportunity to begin work in an area different from one’s training. Dr. Casey applauded the BRAINS Program, particularly for support of a broad spectrum of research topics.

Mary Jane Rotheram, Ph.D., offered kudos to NIMH for supporting such a fantastic program. She noted that the social networks of BRAINS Program investigators are enmeshed and cited a Science article indicating that that some of the best science is conducted at already well-funded schools. A challenge is: How does NIMH establish a system for developing early stage investigators that does not only fund well-supported universities? Researchers from smaller universities need a professional network and assistance or NIH may miss their talent. Reducing inequity is an area of great interest to many at the moment.

Hakon Heimer, M.S., stressed that scientific mentoring is critical. Perhaps it would be possible to bring top-class mentors to investigators at small universities. The Society for Neuroscience has a program based on this idea; perhaps NIMH might establish a similar program. Dr. Insel responded that NIMH has a mechanism to support low-resource environments and address these issues. Is that enough? He added that the system of science is built on lineage and mentors, but revolutionaries with great ideas who want to break the rules may not necessarily go into such a system or follow the traditional path.

Dr. Barch noted that the International Congress on Schizophrenia Research pairs early stage investigators with mentors. Mentorship is important because researchers often do not understand how the NIH system works. For example, researchers mistakenly believe that they are forbidden to contact NIMH Program officers to discuss potential projects. The field needs information about opportunities and access.

Dr. Tamminga remarked on the opportunities available for researchers to analyze information from NIMH databases. Data access is a great way for researchers with interesting ideas but not many resources to generate analyses. Dr. Insel added that the Human Connectome Project  will provide imaging data from 1,200 subjects, along with deep phenotyping. This is a great example of an opportunity for researchers to conduct analyses and test interesting ideas without needing to spend time collecting data. Researchers could use such analyses as pilot data to support their NIMH grant applications, and Dr. Insel welcomed feedback from the Council on the most effective scale for such a program.

Dr. Insel encouraged members of the Council and presenters to discuss ways to ensure that BRAINS awardees can continue to develop their research. Dr. Rotheram remarked that researchers in the social and behavioral sciences typically need four R01 grants to cover their salaries. People have been trying to figure out how a bigger percentage of these awards can be allocated to salary. Currently, there is a capped amount for salary in grants. Dr. Chiu remarked that researchers have different salary coverage requirements and that it can be expensive to hire good post-doctoral researchers, research assistants, and statistical consultants. Supporting students and retaining participants in long-term brain scan studies can also require resources. Dr. Chiu asked how the energy and mindset from the BRAINS Project might be transferred into study sections. Dr. Insel suggested that BRAINS awardees serve as study section reviewers.

Dr. Fröhlich suggested that NIMH might look for talented investigators across a broad range of disciplines, but must be sure to inform them about the challenges in psychiatry.

Dr. Tottenham remarked that a key issue was maximizing the yield from her laboratory’s longitudinal studies. A problem is that by the time all the data have been collected, the grant will end. Supporting the continued analysis of these data is important. There are also many challenges involved in working with children and families over the long term. Dr. Tottenham added that funding the investigator is an appealing idea for many reasons. NIH and NIMH should consider what innovation means. Many think of technological innovation, however, some ideas that do not involve cutting-edge technology are highly creative.

Hyong Un, M.D., suggested that NIMH draw lessons from innovation science and innovation tournaments used in business. The processes used by business to spur innovation might be instructive.

Dr. Tamminga remarked that an important issue is sustaining innovation over the course of a career path. There are lofty expectations for investigators who start at a high level, and she suggested that BRAINS awardees talk with their mentors about this issue. Dr. Insel thanked BRAINS awardees for their presentations and Dr. Anderson for her work on the program.

FY 2017 Concept Clearances

Dr. Insel remarked that the Concepts put forth today connect with the NIMH Strategic Plan for Research, in that they are part of developing initiatives to implement its strategic objectives. He thanked all who worked to develop the Concepts and noted that these ideas are at an early stage. Council members’ feedback will help shape the Concepts so staff can finalize them. The Concepts cover areas in which NIMH will solicit investigator applications to fill gaps in its research portfolio. Presentations will be brief to leave time for Council discussion. NIMH will post approved Concepts on the website for further feedback. In response to a question from Dr. Gleason about the funding associated with the Concepts, Dr. Insel commented that no amounts were linked because the Institute does not know its budget for next year.

First Generation Research Domain Criteria (RDoC) Measurement Elements

Bruce Cuthbert, Ph.D.
NIMH RDoC Unit

Dr. Cuthbert explained that the RDoC Project is a significant cross-cutting effort for the Institute in the 2015 Strategic Plan for Research. RDoC aims to support research that considers mental illnesses in terms of fundamental behavioral-neural systems (e.g., fear or working memory) rather than traditional diagnostic categories. The long-term goal is to develop a scientific foundation that can inform future neuroscience-based diagnostic systems for mental illnesses. RDoC aims to develop and implement an operational template for including standard data elements in RDoC-themed research. The initiative also aims to produce an initial, provisional set of recommended standard measures for each Domain and Construct within the RDoc matrix (5 Domains and 23 Constructs), with the goal of facilitating data sharing. Where standard measures do not currently exist, this initiative aims to support research to develop new measures. Ideally, this initiative will support the establishment of 2 to 4 paradigms and/or measures that are available for each RDoC construct. This will provide researchers with a choice among a group of vetted elements, while still maintaining a degree of standardization. RDoC will also contribute to precision medicine for psychiatry.

Dr. Cuthbert noted that Council approved an earlier iteration of this Concept in 2013. For the present RDoC Concept, the goal of the research is to convene consensus working groups to evaluate availability of measurement for each construct in three categories: (1) Tasks for research studies (laboratory, mobile apps); (2) symptom- or function-based measures for use as outcomes in clinical trials (e.g., mobile devices); and (3) screening measures for trials and other large studies. He remarked that NIMH is having discussions with the FDA about how to start one aspect of this process for developing outcome measures in clinical trials

The expected outcomes of the research include the availability of two to four measures in each of the three categories for each Construct. It is important for investigators to have a choice of tasks. Where no measures are available, NIMH will fund research for task or instrument development, and this represents a difference from the last iteration of the RDoC Concept. The research will attend to developmental issues and norms and establish standard measures to facilitate data sharing through the RDoCdb (RDoC Database). RDoC research will also involve periodic re-assessment of the standard tasks to maintain currency.

Discussion

Maria Oquendo, M.D. liked the Concept. One challenge is to determine how to measure constructs in the matrix and provide a menu of measurement options. Dr. Insel asked Dr. Barch whether current tools cover the measurement of these Constructs. Dr. Barch responded in the negative. The field has few valid measures, so researchers will need to develop those. Additionally, existing measures must be gathered together and organized. Researchers use various measures that have interesting differences and commonalities.

Dr. Barch suggested that NIMH start by asking currently funded RDoC researchers about their measures and then having an expert group curate these measures. Dr. Areán added that it is important to consult with RDoC researchers who are measuring constructs behaviorally. Dr. Linehan supported the plan to offer multiple measures for each construct, as the field will want flexibility. She recommended that these measures not require a great deal of training to administer.

Reducing the Burden of Suicide among American Indian and Alaska Native Youth

Catherine Roca, M.D.
Office for Research on Disparities & Global Mental Health

Dr. Roca noted that many Council members are already aware of the mental health care crisis related to high rates of suicide among Native youth. For example, there is an ongoing crisis at the Pine Ridge Indian Reservation There were 14.66 suicides per 100,000 people for American Indian/Alaska Natives (AI/AN) ages 10 to 24 of both sexes between 2009 and 2012. Native males in Alaska ages 10 to 24 have the highest rate of suicide among any demographic in the United States, with 109 suicides per 100,000 people. Within Alaska, there are regional differences in suicide rates, and not all communities are affected. Dr. Roca remarked that this shows the importance of local context and of exploring local pockets of resilience.

The state of the science of AI/AN youth suicide prevention research suggests some successes. Two recent reviews of the indigenous suicide prevention literature indicate that some gatekeeper and school-based programs have had success. However, there are few rigorously evaluated preventive interventions in this population. Recommendations from the National Action Alliance for Suicide Prevention’s AI/AN Task Force include the development of community capacity and collaboration on the design of local programs, understanding localized suicide rates in specific community contexts, and an emphasis on protective and resilience factors. The recommendations highlight the need to develop projects collaboratively with communities from the beginning. It is important to understand that many Native communities have a prohibition on talking about suicide and prefer a wellness or strengths-based approach to this issue. The proposed initiative aims to determine how to improve the adoption, fidelity, and sustainability of effective suicide prevention programs in AI/AN communities and to identify effective, feasible approaches to means reductions where possible. A final goal of the initiative is the implementation of research to identify appropriate applications of technology to extend mental health resources in remote rural settings.

By building research capacity, collaborating with end users, and generating knowledge through research, NIMH expects this initiative to have a public health impact—that is, save lives. Through collaborative hubs in tribal regions, the initiative is expected to develop effective, community-informed intervention research that can be brought to scale. NIMH expects that the research will produce sustainable suicide prevention programs and reduce AI/AN youth suicide rates. The initiative is timely, with the United States assuming Chairmanship of the Arctic Council  for 2015–2017. It also coincides with the emergence of the HHS Tribal Behavioral Health Agenda and the Prioritized Research Agenda for Suicide Prevention .

Discussion

David A. Brent, M.D., commented that this issue is very important. He noted that socioeconomic factors greatly influence suicide and wondered how to address this root problem. Dr. Roca replied that socioeconomic factors are just one component of suicide. For example, mapping of low levels of economic opportunity and suicide in Alaska indicates that they do not necessarily overlap.

Dr. Tamminga remarked on a program in a Native community in which grandmothers taught teen mothers parenting skills along with traditional practices. This program had a very positive impact and was an effective way to introduce social change. Dr. Roca highlighted the importance of sustainability in mental health efforts in Native communities (as well as in global communities). The person intervening may not be a mental health professional but people who have stature in the local community. This model may be helpful in suicide prevention.

Dr. Linehan added that Native communities often guide how interventions are implemented, for example, by modifying effective treatments in culturally appropriate ways. Dr. Brent commented on the need to recognize the historical, social, and economic context in these communities. Dr. Insel added that recognizing the context helps to manage expectations. Intervention can save lives. The United States assuming the Chairmanship of the Arctic Council in 2015 could have a public health impact. NIMH will work with SAMHSA on refining this Concept. Dr. Oquendo spoke about the need for community-based participatory research and listening to community concerns. Some communities may have negative reactions, so those involved with this initiative should be aware of all possible perceptions.

The Neural Mechanisms of Integrated Social and Emotional Representations

Janine Simmons, M.D., Ph.D.
Division of Neuroscience and Basic Behavioral Science

This initiative maps onto NIMH Strategic Objective 1: Define the Mechanisms of Complex Behavior. The initiative aims to stimulate and support research investigating the neural circuits and dynamic patterns of brain activity involved in the perception, interpretation, and representation of multi-dimensional social and emotional cues. Affective biases, deficiencies in interpreting social cues, and difficulties using social and emotional knowledge in context-appropriate ways are significant issues across mental disorders. In current research, emotional stimuli are one dimensional and static, despite the multi-dimensional nature of social and emotional cues and functional brain circuits. The initiative aims to fill the gap in this area of research and move the field from a modular view toward a multi-dimensional understanding of social and emotional representations.

The initiative’s goals are to: (1) examine the interactions across neural circuits required for processing of multi-dimensional social and emotional cues; (2) measure and model the neurophysiological temporal dynamics associated with the formation and utilization of social and emotional representations; (3) study changes in these networks with experience and across developmental trajectories; and (4) explore how dysfunction in these circuits relates to social and emotional dimensions of behavior in psychiatric populations.

The expected outcomes are to: (1) establish the dynamic circuit-level mechanisms through which processing of complex social and emotional stimuli occurs; (2) identify processes by which coherent multimodal percepts are maintained across a range of spatial and temporal scales; (3) translate these findings into dimensional studies of clinical populations; and (4) train a new generation of investigators in multi-dimensional concepts and techniques to elucidate the neurobiology of complex behaviors.

Discussion

Dr. Casey commented that this Concept nicely complements RDoC, as the Constructs are overlapping and interacting. This is a complex area, because early neurodevelopmental problems can lead to a cascade of issues dealt with in other systems. Dr. Huganir added that this research is complex but greatly needed. Dr. Simmons agreed that this is a complex topic, but NIMH wants to encourage research in this area.

Dr. Barch suggested supporting studies that examine the root causes of disorders across developmental stages, which will inform work on early intervention. Dr. Simmons noted that there is some ongoing research in this area: for example, work on multi-sensory integration among typically developing and autistic individuals. Dr. Tamminga remarked on striking findings on the CA2 area of the hippocampus, which has been linked with social cognition. This was a surprising finding with implications for many areas of research. She suggested that NIMH compile a collection of surprising findings so researchers can pursue them. Dr. Simmons noted that NIMH does have a grant on the CA2 area of the hippocampus. Dr. Insel explained that NIMH is trying to understand the interaction of neural networks (i.e., the network of networks). Dr. Simmons added that NIMH is supporting a range of complementary research techniques to identify cell types as well as neural networks. The field has some exciting new tools that will advance this research.

Adult Maturational Changes and Dysfunctions in Emotion Regulation

George Niederehe, Ph.D.
Division of Translational Research

This initiative implements Strategy 2.1 from the NIMH Strategic Plan for Research: “Characterize the developmental trajectories of brain maturation and dimensions of behavior to understand the roots of mental illnesses across diverse populations.” Age-related differences across the lifespan are a major aspect of diversity. The initiative aims to stimulate research in a major gap area ‒ changes in emotion processing over the adult life course and their relation to dysregulation in adult affective disorders. With this initiative, NIMH aims to promote mechanistically oriented studies and identify potential adult life-stage‒optimized targets for intervening in emotion dysregulation or preventively building resilience.

The MacArthur Midlife Survey indicates that for most adults, normal aging is associated with general trends toward improved emotion regulation. This includes increasing positive and decreasing negative affect, greater emotional stability, higher life satisfaction, and a “positivity” bias in information-processing. While attending to and remembering positive information, older adults recruit different neural networks, although the reasons are not clear. It is important to consider sex differences and control for medical comorbidity in this research.

The initiative will obtain information from many different fields of research, including cognitive and affective neuroscience, neuroimaging, neurophysiology, gene expression and epigenetics, and perhaps neuroendocrinology. Research questions of interest include emotion processing irregularities in later-life affective disorders, maturational shifts in emotion regulation among people with disorders, and divergent neurobiological and emotion processing trajectories. The initiative also will encourage research on the different brain circuits recruited during emotional challenge or task performance as a function of age, sex, and mental disorder and their ability to predict resilience or deteriorating clinical course.

Expected outcomes for the initiative include an improved understanding of change trajectories with age in adult emotion processing (healthy and in psychopathology) and clues to intervention or prevention strategies most appropriate to various stages of the adult life cycle. The initiative is also expected to result in a stronger and more mechanistic research field regarding emotion processing in later-life mental disorders and an expanded lifespan developmental component within the NIMH portfolio of psychopathology research.

Discussion

Dr. Brent commented on the great importance of research in this area. He asked about the delineation with research funded by the National Institute on Aging (NIA). Dr. Niederehe clarified that NIA supports research on affective processing in normal aging, but almost none of that work focuses on adult psychopathology. Dr. Insel added that although there is a huge amount of research on adult cognition, there is very little information on affective regulation.

Dr. Barch noted that many researchers who study emotional regulation focus on life changes and other factors, not necessarily the underlying neurobiology. She stressed the importance of research that combines neurobiology and environmental factors and an openness to work that does not necessarily tie directly to neural mechanisms. Dr. Areán agreed and suggested a broad focus on how environmental factors can shape neurobiology and emotion regulation. Dr. Insel commented that NIMH will look for partners, and potentially NIA, for this initiative.

Pragmatic Strategies for Assessing Psychotherapy Quality in Practice

Joel Sherrill, Ph.D.
Division of Services and Intervention Research

Psychosocial treatments are widely delivered. An estimated 16 million (6.6 percent) adults in the United States received these services during the past year. Among adults with a mental illness, approximately 24 percent received outpatient counseling or psychotherapy during the past year. However, it is unknown how much of this treatment is evidence based. There is no easy way to know whether treatment delivered in care is consistent with the intervention tested in a research study. This initiative is intended to support the development and testing of pragmatic tools and strategies for measuring the quality of psychotherapy delivered in practice settings. The initiative supports Strategy 4.4 of the NIMH Strategic Plan for Research (Develop valid and reliable measures of treatment quality and outcomes), as well as the Institute of Medicine’s (IOM) panel on “Developing Evidence-Based Standards for Psychosocial Interventions for Mental Disorders,” which emphasizes the importance of quality and outcome performance measures. The initiative also supports the Mental Health Parity and Addiction Equity Act of 2008 and the Patient Protection and Affordable Care Act of 2010, which compel increased attention to quality assessment and accountability.

Dr. Sherrill reviewed challenges and decision points related to the measurement of psychotherapy quality in practice. One is that the fidelity measures used in efficacy studies have limited utility for community practice. Various assessment parameters must be considered, such as: Who is the most appropriate information source? What should be measured? When should quality be assessed? How should measures be obtained? When assessing quality, it is critical to balance reliability/validity and feasibility/efficiency. Quality assessment needs to take into account the burden to providers and disruption in administrative and clinical routines.

Informed by the IOM recommendations, this initiative aims to support the initial development of quality metrics and assessment strategies. These metrics and assessments will incorporate end-user input to ensure feasibility and utility for informing practice and policy and that correlate strongly with patient outcomes. The initiative also aims to support research that prospectively examines the feasibility, reliability, and validity of the measures and determines their utility for assessing the quality of psychotherapy in practice settings.

Expected outcomes include a set of research-informed, pragmatic tools for assessing the delivery of psychotherapy across a variety of interventions and target populations. These tools could facilitate therapist training and supervision, quality monitoring and quality improvement initiatives, and research on effectiveness, implementation, and quality improvement. The initiative is expected to generate a body of generalizable knowledge regarding best practices for the assessment of psychotherapy in community practice settings. It is a concrete step toward realizing the IOM recommendations, addressing Strategy 4.4 of the NIMH Strategic Plan for Research, and ensuring the availability of high-quality psychosocial interventions.

Discussion

Dr. Un commented on the importance of this area of research. Excluding pharmacological costs, two-thirds of the cost of behavioral treatment goes to outpatient care. However, there are no practical and feasible measures despite increasing pressure for accountability. Measures must not be too time-consuming and difficult to use. If the field does not develop assessments, arbitrary ones will be imposed. This Concept should involve the private sector. Dr. Areán agreed and noted that particular organizations are already involved in similar efforts (e.g., the Department of Veterans Affairs [VA] and the Mental Health Research Network). Internationally, the United Kingdom has a program to increase access to evidence-based behavioral therapies. Important issues include measuring fidelity over time, as well as maintaining the quality of care. Swift release of a funding announcement would be desirable.

Dr. Gleason commented that she would put Dr. Sherrill in contact with the VA’s Services Research Group for consultations. This is a critical area of need, and perhaps there could be a bridge between NIMH and VA efforts. Dr. Insel noted that the VA’s efforts for cognitive-behavioral therapy could serve as a model. Dr. Gleason emphasized that the questions posed by this initiative are critical (e.g., about what to measure and when, as well as fidelity).

John W. Davison, Ph.D., M.B.A., of the Department of Defense (DOD), remarked that this initiative is very important for his organization, which provides direct care and purchased care. It is critical to move beyond credentialing. DOD has the means to collect information and outcomes through its behavioral health data portal. One future focus might be on person- or clinical-centered measurements. His organization would be willing to pilot test tools in their direct care and military treatment centers, and perhaps with other providers, if NIMH develops measures.

Dr. Un remarked that most U.S. health care organizations are open systems, and care varies among providers under contract in these networks. He added that it is not a good idea to use medical records to obtain this information, as it will not be feasible. Dr. Tamminga commented that the American Journal of Psychiatry and other journals are always looking for rigorous studies on this topic to publish. Dr. Brent suggested that NIMH consider alternative ways to assess quality and computer scoring to enhance efficiency.

Improving Outcomes Associated with Mental Health First Aid

Amy Goldstein, Ph.D.
Division of Services and Intervention Research

Dr. Goldstein explained that mental health first aid  is “…an 8-hour course that teaches you how to help someone who is developing a mental health problem or experiencing a mental health crisis. The training helps you identify, understand, and respond to signs of mental illness…” It has been thought of as a gatekeeper training program, a mental health literacy program, a preventive intervention, and a services/engagement intervention. A question of interest is: Can mental health first aid be an opportunity to facilitate early identification and access to care for a disorder such as schizophrenia, thereby reducing the duration of untreated psychosis?

A challenge is that there are not many studies on mental health first aid. A 2014 meta-analysis reported on 15 studies, and only 4 of those were randomized controlled trials. The research suggests that mental health first aid has an impact on knowledge, attitudes, and self-reported helping behavior. This intervention has no impact on the receipt of services, referral to services, or reduction of symptoms. Although mental health first aid has been widely disseminated, there is little data on its effectiveness. Most of the training in mental health first aid has taken place in open systems, so it is difficult to track whether those trained use it and, if they do, the impact of the intervention.

The initiative is relevant to Early Psychosis Prediction and Prevention (EP3) in that one aim is to fund studies to examine the impact of mental health first aid on reducing the duration of untreated psychosis. It supports of Strategy 3.3 of the NIMH Strategic Plan for Research (Test interventions for effectiveness in community practice settings). The initiative will fund a range of studies intended to enhance the effectiveness of mental health first aid for achieving the goals of accurate identification of youth with early mental illness symptoms and referral to the appropriate level of care. It also aims to increase the understanding of the mechanism of action for this intervention.

Potential research questions include: What is the impact of training school providers in mental health first aid on other NIMH high priority outcomes (e.g., reduction in duration of untreated psychosis and access to coordinated specialty care for first episode psychosis)? What is the effectiveness of mental health first aid as a preventive intervention in and of itself? What are feasible and sustainable approaches to measuring fidelity and meaningful outcomes of mental health first aid in various community settings where it is currently in use?

Discussion

Dr. Tamminga suggested studying the long-term impact of mental health first aid among deployed troops. Benjamin G. Druss, M.D., M.P.H., asked whether the goal is to improve downstream goals (e.g., increase early identification and reduce the duration of untreated psychosis). There are interesting implementation questions about how this intervention is being used globally. Dr. Goldstein noted that there are school-based trainings for mental health first aid, and community-based trainings are being announced. Dr. Insel asked whether current trainings could be adapted to reduce the duration of untreated psychosis from the current average of 72 weeks to the targeted goal of 2 weeks. Dr. Druss commented that it may be possible to develop mental health first aid into a more intensive and specific intervention for achieving these goals. Dr. Goldstein remarked that current mental health first aid training is very broad, so enhanced training would be required to address outcomes for specific disorders. Dr. Un added that trainers are already under pressure to reduce the training from 8 to 4 hours. He asked who would be responsible for developing modules for a more intensive intervention, and noted that mental health first aid is designed to be implemented by the general public.

Dr. Barch asked whether there was a similar initiative specifically designed for middle or high school students – that is, a type of mental health literacy program. Dr. Littman noted that SAMHSA has a program to train school providers in mental health first aid and has released an announcement for community-based training. Currently, these do not involve training youth. Dr. Goldstein remarked that there is a general “gatekeeper” program on youth mental health. Dr. Barch noted that students need mental health literacy. Dr. Brent added that the results of a large European randomized controlled trial suggested that mental health literacy (i.e., lessons in how to identify problems in yourself and others) was the only intervention tested that reduced the rate of suicide attempts.

Preventing Suicide in the Juvenile Justice System

Denise Juliano-Bult, M.S.W.
Division of Services and Interventions Research

Ms. Juliano-Bult noted that a number of studies show that justice-involved youth are at higher risk for suicide than youth in the general population. In fact, the adjusted risk for suicide in juvenile justice residential facilities is three times that of the general population of adolescents, and the risk for those in justice-related community settings is estimated to be greater. In addition, when at-risk youth leave the juvenile justice system, many are likely to remain at risk for suicide. These findings underscore the need for detection and ongoing suicide prevention treatments and services for this population. This Concept is complimentary to the Concept targeting AI/AN youth, another high risk population.

The goal of this initiative is to support research on how the structure and legal leverage of the juvenile justice system can be used to detect and prevent suicidality in youth who come in contact with that system. The initiative responds to the National Action Alliance for Suicide Prevention’s Prioritized Research Agenda for Suicide Prevention . The initiative also addresses the recommendations of the Action Alliance’s Youth in Contact with the Juvenile Justice System Task Force, which highlighted the critical need to develop effective suicide prevention strategies that can be implemented at each point of contact in the justice system, along with the need to improve collaboration between mental health and juvenile justice for sustainable delivery of such interventions. The initiative aligns with the NIMH Strategic Plan for Research Strategy 4.2 (Establish research-practice partnerships to improve dissemination, implementation, and continuous improvement of evidence-based mental health services) and 4.3 (Develop innovative service delivery models to improve dramatically the outcomes of mental health services received in diverse communities and populations).

Ms. Juliano-Bult added that effective strategies developed under this initiative will also enable identification of any untreated mental health problems, adding to the potential public health impact of the results. She indicated that a literature review did not identify any empirical studies on the effectiveness of preventive interventions in the juvenile justice system. High-impact research areas under this initiative include the development of effective, scalable strategies for routine, evidence-based screening and intervention in various juvenile settings, as well as effective strategies to engage youth in on-going treatment and services post-release to prevent future suicidality. The research will focus on understanding and intervening on critical, unique contributors to improve outcomes for justice-involved youth and systems-level interventions to ensure continuity and coordination of mental health care as youth move through multiple settings. Interventions that engage multiple types of staff and others (e.g., peer advocates) may contribute to continuously improving risk detection, screening, referral, and intervention.

Discussion

Dr. Casey emphasized the importance of this initiative. She participated in an IOM report on juvenile justice system reform and learned that the number of incarcerated youth with mental health issues is staggering. She stated that all individuals in this system could benefit from interventions to prevent chronic mental illness and justice system recidivism. Dr. Tamminga agreed and added that in her studies of the brains of adults and adolescents post-suicide, retrospective diagnoses indicated that most of the adults (85–90 percent) had depression or severe depression. In contrast, most of the adolescents had impulsive disorder. The dynamics seem to be different between these two groups.

Dr. Brent asked whether NIMH would collaborate with NIDA on the initiative, as this population has a high rate of comorbid drug abuse. Ms. Juliano-Bult commented that members of NIMH and NIDA staff have met twice to explore use of NIDA’s large juvenile justice research infrastructure as a platform for the initiative. It was noted that epidemiological studies suggest that approximately 60 percent of youth who complete suicide have mood disorders and appear to have had significant impulsive and aggressive symptoms.

Understanding and Addressing the Multi-Level Influences on the Use of HIV Prevention Strategies among Young Women in Sub-Saharan Africa

Pim Brouwers, Ph.D.
Division of AIDS Research

Dr. Brouwers acknowledged Susannah Allison, Ph.D., who is the lead staff member for this initiative. HIV incidence remains high among adolescent girls and young women in Sub-Saharan Africa (SSA), even within clinical trial settings. However, uptake and adherence to HIV prevention strategies (e.g., condoms, pre-exposure prophylaxis [PrEP], and microbicides) in this population is low. More than 7,000 new HIV infections occur every week among young women globally, the majority of them in SSA. There are multiple, complex interacting levels of factors that determine uptake and adherence ‒ including individual, partner, family, and society.

The goal of this initiative is to gain a greater understanding of the multi-level factors that influence the uptake and adherence to HIV prevention strategies among adolescent girls and young women in SSA. The initiative also aims to develop and test novel interventions to address these factors and enhance the uptake and adherence to HIV prevention strategies among adolescent girls and young women in SSA.

Currently, most research focuses on individual level factors, but this is not sufficient. The field needs research on factors beyond those at the individual level that influence uptake and adherence to HIV prevention strategies. Information is needed on how partners, peers, family, and community affect HIV prevention use and adherence among adolescent girls and young women. A major area that requires research is how to address barriers to uptake and adherence at multiple levels.

Research supported by this initiative has the potential to strengthen future biomedical HIV prevention interventions for adolescent girls and young women by addressing barriers to use and adherence. It may also enhance the delivery of President’s Emergency Plan for AIDS Relief programs and other services for adolescent girls and young women in SSA. Relevant research examples include studies to enhance our measurement of partner dynamics, behaviors, and social and cultural norms that influence HIV risk and product use. Other research may study the impact of mental health (depression in particular), substance use, and stigma on the uptake of HIV prevention strategies and interventions to address perceptions and misperceptions of low risk for HIV among adolescent girls and young women. Research might also focus on interventions to address partner-, family-, and community-level barriers and facilitators to uptake and adherence.

The initiative supports Strategic Objective 3 of the NIMH Strategic Plan for Research, Strive for Prevention and Cures, and is central to NIMH Division of AIDS Research because it advances combination prevention to key populations through behavioral and social research. It complements ongoing efforts at the National Institute of Allergy and Infectious Diseases (NIAID).

Improving the HIV Pre-Exposure Prophylaxis (PrEP) Cascade

Pim Brouwers, Ph.D.
Division of AIDS Research

Dr. Brouwers recognized the work of Michael Stirratt, Ph.D., who is the lead staff member for this initiative. The initiative aims to develop and test interventions to improve the screening, engagement, and retention of high-risk populations in HIV PrEP clinical care. It also aims to support both adherence to PrEP treatment regimens and persistence in PrEP treatment among persons at high-risk for HIV infection in the United States. PrEP medication confers up to 99 percent protection from HIV infection when taken with high adherence, and newly issued Center for Disease Control and Prevention clinical guidelines recommend PrEP for HIV-negative men and women at high risk for infection. However, scant research has tested how to engage and retain high-risk groups in PrEP or how to promote adherence and persistence to PrEP medication.

There is a need to improve the Cascade of HIV PrEP use, with points for intervention along the various steps: (1) At risk for HIV infection; (2) identified as PrEP candidate [Screening and Targeting Interventions]; (3) interested in PrEP; (4) linked to PrEP program [Engagement Interventions]; (5) initiated PrEP; (6) retained in PrEP [Retention Interventions]; and, (7) achieve adherence and persistence [Adherence/Persistence Interventions]. There has been low awareness of PrEP among high-risk populations to date, and PrEP uptake has been slow despite growing health insurance coverage. Early data indicate that some PrEP initiators do not stay persistent to daily oral PrEP regimens. Therefore, novel research is needed to target, engage, and retain high-risk individuals in PrEP care and support their adherence and persistence. Such research would strengthen the preventive impact of oral PrEP programs and provide platforms for future delivery of novel PrEP formulations (e.g., vaginal rings and long-acting injectables). Persistence (i.e., taking PrEP medication over time) is independent of adherence (i.e., taking medication every day).

The initiative would support studies that focus on outreach and communication strategies to promote PrEP awareness, engagement, and uptake in high-risk groups. Also of interest are studies on screening and decision tools that at-risk individuals can use to evaluate their HIV risk and PrEP appropriateness. The initiative would support work to develop and test interventions designed to improve linkage and retention of high-risk groups in PrEP programs as well as programs for PrEP adherence and persistence.

The initiative supports Strategic Objective 3 of the NIMH Strategic Plan for Research, Strive for Prevention and Cures, and is central to NIMH Division of AIDS Research because it advances combination prevention to key populations through behavioral and social research. It complements ongoing efforts of the NIAID Division of AIDS.

Discussion

Regarding the first HIV-related initiative, Dr. Casey asked the extent to which young SSA females’ perceived low risk for HIV infection maps onto coercion and the role of women in their societies. Dr. Brouwers commented that he did not think the differences in female roles between the various regions of SSA were that great. Dr. Casey added that older women act as role models for younger ones. Dr. Brouwers remarked that multilevel research should help address the impact of role models. He added that the risk for HIV among young women relates to some extent to economic disadvantage and to base rates of the infection.

Dr. Tamminga asked for more information on PrEP, particularly its side effects. Dr. Brouwers responded that PrEP’s side effects are relatively limited. Generally, most people do not complain of any side effects, and side effects are not the primary reason for people not using this medication. Other HIV medications have worse side effects than PrEP. Dr. Insel stressed that PrEP is up to 99 percent effective and needs to be taken only once daily. There is approximately 25 percent uptake among people who would benefit. He added that NIMH’s Division of AIDS Research is integrated with NIAID, so that these efforts are carefully coordinated between the two Institutes.

Dr. Insel remarked that Council members should vote on continuing with all of these initiatives if funds are available. NIMH uses Concepts to develop funding opportunity announcements to fill gaps in research. A motion to move forward with these Concepts was called for, seconded, and supported unanimously.

Public Comment

Dr. Insel invited members of the audience to make any comments to the Council. Hearing none, he thanked all who participated in the meeting. He recessed the open session meeting at approximately 4:29 p.m.

Appendix A

Summary of Primary MH Applications Reviewed

May 2015

Category	IRG Recommendation
	Scored #	Scored Direct Cost $	Not Scored (NRFC) #	Not Scored (NRFC) Direct Cost $	Other #	Other Direct Cost $	Total #	Total Direct Cost $
Research	605	$781,401,256.00	440	$475,206,760.00	11	$3,085,108.00	1056	$1,259,693,124.00
Research Training	1	$1,846,260.00	0	$0.00	0	$0.00	1	$1,846,260.00
Career	55	$37,535,402.00	26	$17,479,147.00	0	$0.00	81	$55,014,549.00
Other	0	$0.00	0	$0.00	0	$0.00	0	$0.00
Totals	661	$820,782,918.00	466	$492,685,907.00	11	$3,085,108.00	1138	$1,316,553,933.00

Appendix B

Department of Health and Human Services
National Institutes of Health
National Institute of Mental Health
National Advisory Mental Health Council

(Terms end 9/30 of designated year)

Chairperson

• Thomas R. Insel, M.D.
  Director
  National Institute of Mental Health
  Bethesda, MD

Executive Secretary

• Tracey Waldeck, Ph.D.
  Chief, Extramural Policy Branch
  Division of Extramural Activities
  National Institute of Mental Health
  Bethesda, MD

Members

• Patricia A. Areán, Ph.D. (16)
  Professor
  Director of Targeted Treatment Development
  University of Washington
  Department of Psychiatry and Behavioral Sciences
  Seattle, WA
• Deanna M. Barch, Ph.D. (16)
  Gregory B. Couch Professor of Psychiatry
  Department of Psychology, Psychiatry and Radiology
  Washington University
  St. Louis, MO
• David A. Brent, M.D. (17)
  Academic Chief
  Child & Adolescent Psychiatry
  Endowed Chair in Suicide Studies
  Professor of Psychiatry, Pediatrics and Epidemiology
  Director, Services for Teens at Risk
  University of Pittsburgh School of Medicine
  Pittsburgh, PA
• Randall L. Carpenter, M.D. (15)
  Co-Founder, President and Chief Executive Officer
  Seaside Therapeutics
  Cambridge, MA
• BJ Casey, Ph.D. (16)
  Sackler Professor
  Department of Psychiatry and Neuroscience
  Sackler Institute for Developmental Psychobiology
  Weill Medical College of Cornell University
  New York, NY
• Benjamin G. Druss, M.D., M.P.H. (18)
  Rosalynn Carter Chair in Mental Health and Professor
  Department of Health Policy and Management
  Rollins School of Public Health
  Emory University
  Atlanta, GA
• Lisa Greenman, J.D. (15)
  Attorney
  Federal Death Penalty Resource Counsel Project
  Washington, DC
• Hakon Heimer, M.S. (16)
  Founding Editor
  Schizophrenia Research Forum
  Brain and Behavior Research Foundation
  Providence, RI
• Michael F. Hogan, Ph.D. (18)
  Consultant and Advisor
  Hogan Health Solutions LLC
  Delmar, NY
• Richard L. Huganir, Ph.D. (17)
  Professor and Director
  Department of Neuroscience
  Investigator, Howard Hughes Medical Institute
  Co-Director, Brain Science Institute
  The Johns Hopkins University School of Medicine
  Baltimore, MD
• Steven E. Hyman, M.D. (15)
  Director, Stanley Center for Psychiatric Research
  Broad Institute
  Cambridge, MA
• Marsha M. Linehan, Ph.D. (17)
  Professor and Director
  Behavioral Research and Therapy Clinics
  Department of Psychology
  University of Washington
  Seattle, WA
• Maria A. Oquendo, M.D. (17)
  Vice Chair for Education
  Professor of Psychiatry
  Department of Psychiatry
  Columbia University
  New York State Psychiatric Institute
  New York, NY
• Gene E. Robinson, Ph.D. (16)
  Director, Institute for Genomic Biology
  Swanlund Chair
  Center for Advanced Study Professor in Entomology And Neuroscience
  University of Illinois at Urbana-Champaign
  Urbana, IL
• Mary Jane Rotheram, Ph.D. (16)
  Bat-Yaacov Professor of Child Psychiatry And Behavioral Sciences
  Director, Global Center for Children and Families
  Director, Center for HIV Identification Prevention And Treatment Services (CHIPTS)
  Semel Institute and the Department of Psychiatry, University of California, Los Angeles
  Los Angeles, CA
• J. David Sweatt, Ph.D. (16)
  Professor
  Evelyn F. McKnight Endowed Chair
  Department of Neurobiology
  Director, McKnight Brain Institute
  University of Alabama at Birmingham
  Birmingham, AL
• Carol A. Tamminga, M.D. (15)
  Professor and Chair
  Department of Psychiatry
  University of Texas
  Southwestern Medical Center
  Dallas, TX
• Hyong Un, M.D. (17)
  Head of EAP & Chief Psychiatric Officer
  AETNA
  Blue Bell, PA
• Professor
  Evelyn F. McKnight Endowed Chair
  Department of Neurobiology
  Director, McKnight Brain Institute
  University of Alabama at Birmingham
  Birmingham, AL

Ex Officio Members

Office of the Secretary, DHHS

• Sylvia M. Burwell
  Secretary
  Department of Health and Human Services
  Washington, DC

National Institutes of Health

• Francis Collins, M.D., Ph.D.
  Director
  National Institutes of Health
  Bethesda, MD

Department of Veterans Affairs

• Theresa Gleason, Ph.D.
  (Acting) Deputy, Chief Research & Development Officer
  Office of Research & Development
  Department of Veterans Affairs
  Washington DC

Department of Defense

• John W. Davison, M.B.A., Ph.D.
  Chief, Conditioned-Based Specialty Care Section
  Clinical Support Division
  Defense Health Agency
  Department of Defense
  Office of the Chief Medical Officer (OCMO)
  TRICARE Management Activity, OASD (HA)
  Falls Church, VA

Liaison Representative

• Paolo del Vecchio, M.S.W.
  Director
  Center for Mental Health Services
  Rockville, MD