NAMHC Minutes of the 256th Meeting
May 30, 2019
Department of Health and Human Services
Public Health Service
National Institutes of Health
National Advisory Mental Health Council
Introduction
The National Advisory Mental Health Council (NAMHC) held its 256th meeting at 9:00 am, May 30, 2019 at the Neuroscience Center in Rockville, Maryland. In accordance with Public Law 92-463, the session was open to the public until 12:30 pm, and closed thereafter from 2:30 pm for consideration of grant applications. Joshua Gordon, M.D., Ph.D., Director of the National Institute of Mental Health (NIMH), presided as Chair.
Council Members
(Appendix B, Council Roster)
Chairperson
Joshua Gordon, M.D., Ph.D.
Executive Secretary
Jean Noronha, Ph.D.
Council Members Present
- Laura Almasy, Ph.D.
- Tami Benton, M.D.
- Randy Blakely, Ph.D.
- Ian Gotlib, Ph.D.
- Alan Greenberg, M.D., M.P.H.
- David Henderson, M.D.
- Lisa Jaycox, Ph.D.
- Cheryl King, Ph.D.
- John Krystal, M.D.
- Gregory Miller, Ph.D.
- Neil Risch, Ph.D.
- Rhonda Robertson Beale, M.D.
- Elyn Saks, Ph.D.
- Brandon Staglin, M.S.
- Sophia Vinogradov, M.D.
Department of Veteran Affairs
- Amy Kilbourne, M.D., Ph.D.
Department of Defense (Ex Officio Member)
- Steven Pflanz, M.D.
Liaison Representative
- Anita Everett, M.D.
Others Present at the Open Policy Session
Open Policy Session Call to Order & Opening Remarks
Joshua Gordon, M.D., Ph.D.
NIMH Director, Dr. Joshua Gordon, opened the NAMHC meeting by welcoming Council Members and the public. Following introductions, the Council unanimously passed a motion approving the final Summary Minutes of the January 31, 2019 meeting.
NIMH Director’s Report
Joshua Gordon, M.D., Ph.D.
Legislative Updates
Dr. Gordon updated participants and attendees on recent NIMH congressional activities. He spoke about a Senate reception in April that celebrated the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative®. Dr. Gordon also described visits that he and other NIMH staff had made across the country, including a meeting with Representative Garret Graves (R-LA). Dr. Gordon described meetings with Representatives John Sarbanes (D-MD) and Paul Tonko (D-NY). He also noted that NIMH Deputy Director Dr. Shelli Avenevoli recently testified at a hearing on suicide prevention among veterans, where Dr. Avenevoli presented NIH-supported research aimed at reducing suicide rates among veterans.
NIMH Budget
Dr. Gordon spoke about two recent NIH appropriation hearings, which were attended by NIH Director Dr. Francis Collins and several NIH Institute Directors. The House Committee on Appropriations has passed a bill including an approximately $2 billion budget increase for NIH. If the bill becomes law, programs such as All of Us and the BRAIN Initiative will receive additional funding. Dr. Gordon explained that in 2019, the appropriations of about $1.8 billion will allow NIMH to fund 26 percent of grant applications.
Priorities
Dr. Gordon described recent Institute activities focused on autism. The latest full meeting of the Interagency Autism Coordinating Committee (IACC), held in April 2019, included discussion of data visualization tools, disability policy, and employment issues among people with autism. A recent IACC workshop addressed the mental health needs of people on the autism spectrum, highlighting research on anxiety, depression, suicide, and aggression. For Autism Awareness Month, NIMH hosted a panel of authors who spoke from their perspectives as women with autism.
Dr. Gordon shared exciting news that the U.S. Food and Drug Administration (FDA) approved two new depression medications that arose from NIMH-funded research. Dr. Gordon spoke about how these new medications, esketamine and brexanolone, are the result of hard work and innovations from NIH researchers, and he thanked the individuals who were involved in the development of these new drugs. He also noted the recent work of Steve Paul, M.D., who studied allopregnanolone, which is related to brexanolone, as an effective treatment for women who suffer from severe post-partum depression.
Staff and Leadership News and Awards
Several NIMH staff members have received recognition in recent months, including Robert Heinssen, Ph.D. (recipient of the 2019 Distinguished Service Award from the National Alliance on Mental Illness) and Jeymohan Joseph, Ph.D. (recipient of the Distinguished Service Award from the Society of Personalized Nanomedicine). Sue Swedo, M.D., retired at the end of March 2019 and was recognized by the NIH as a scientist emeritus. Judith Rumsey, Ph.D., is retiring from the NIMH Brain Circuitry and Dynamics program at the end of May 2019. Dr. Gordon recognized Dr. Steve Pflanz, who would be retiring the next day. Dr. Gordon thanked him for his participation as the Council’s representative from the Department of Defense.
At the NIH level, Noni Byrnes, Ph.D., is now permanent Director of the NIH Center for Scientific Review. Ned Sharpless, M.D., has been named Acting FDA Commissioner and Doug Lowy, M.D., has been named Acting National Cancer Institute Director. Finally, Debara Tucci, M.D., has been named as Director of the National Institute on Deafness and Other Communication Disorders.
Policies, Progress, and Initiatives
There have been a number of activities under the BRAIN Initiative . The BRAIN Investigators Meeting was the largest it has ever been with over 1,500 registrants. The BRAIN 2.0 Advisory Committee will provide revisions to the BRAIN Initiative Strategic Plan to the NIH Director. And, the neuroethics subgroup under the BRAIN Initiative is working on a companion volume describing a neuroethics roadmap.
The NIH has recently started the Helping to End Addiction Long-termSM or NIH HEAL Initiative as part of a government-wide effort to address the opioid epidemic. NIMH is a partner on several components of this initiative, including efforts to implement evidence-based treatments for mental health and addiction comorbidities in collaborative care. Relevant to the HEAL Initiative is the HEALthy Brain and Child Development Study , which plans to enroll mothers and their children who have been exposed to opiates in the womb. Researchers seek to understand the longitudinal impact of prenatal opioid exposure on brain development, behavioral function, and other outcomes.
The All of Us Research Program , an effort to develop whole-genome sequencing on 1 million Americans, is approaching 200,000 enrollees. NIMH is engaging with the initiative by collaborating to develop behavioral assessments for the All of Us program, which will be additionally important for NIMH’s computational psychiatry efforts.
Science Highlights
NIMH intramural researcher, Lisa Horowitz, Ph.D., MPH collaborated with NIMH extramural investigators to publish a study investigating the temporal relationship between the release of the Netflix series 13 Reasons Why and suicide rates among adolescents in the United States. The television show, which was sensationalized in the press, depicted the act and aftermath of a teenage suicide. Several studies suggest that the program increased awareness of suicide among teens, and many schools have since created activities and settings to start conversations about suicide. Unfortunately, evidence also suggests that the show’s release is associated with increased rates of youth suicides. Dr. Gordon explained that the release of this study received major press attention, and NIMH published an editorial piece in USA Today addressing the need for responsible depictions of suicide in the media.
NIMH also recently funded a study of the cerebellum in psychiatric disorders, most notably autism. Currently, the cerebellum is primarily understood as an area of the brain that controls motor behavior. To examine other potential functions of the cerebellum, Kamran Khodakhah, Ph.D., and his colleagues used optogenetics, a technique that allows modulation of specific neurons, to study the neural connections between the cerebellum and areas of the brain that regulate reward-related behaviors. They found a neural pathway indicating that the cerebellum may be involved in reward-seeking behaviors. The research team also used a mouse model to determine a neural connection between the cerebellum and the ventral tegmental area of the brain, which mediates the rewarding aspects of social interaction.
Another recent study, headed by Debjani Guha, Ph.D., and colleagues, has focused on the efforts to understand the implications of HIV infection in the brain. The research team investigated if individuals with HIV are more likely to have extracellular vesicles—small pockets of material produced by cells—in their cerebrospinal fluid than non-infected individuals. When certain cells produce a high number of vesicles, researchers can use these measurements to try to determine where the virus might be active in the brain. This study found that individuals with higher numbers of extracellular vesicles were more likely to experience HIV-related cognitive impairments, including dementia, suggesting that this cellular process plays an important role in neurocognitive degeneration. This is a promising path of discovery for the treatment and eradication of HIV/AIDS infections.
Discussion
Dr. Rhonda Robinson Beale asked if the 13 Reasons Why study picked up on an expected trajectory of a dramatic decrease and then increase in suicide incidents. Dr. Horowitz responded that the highest spike in suicides was in April 2017, soon after the show’s release in March 2017, not only within the study period, but across the last 19 years. She clarified that the increase in suicide rates is not only statistically significant in boys, but also in girls, when the 18- and 19-year-old age group is added to the analysis.
Council Workgroup on Drug Development
Dr. Gordon proposed a new Council working group to address drug development. He emphasized the importance of maintaining an experimental therapeutics approach to interventions. In 2010, a Council workgroup on interventions presented a report with recommendations to improve intervention development by identifying and engaging neural circuits, focusing on underlying biology, and funding mechanisms that support early stage studies. By 2014, the intervention component of the report had evolved into a modified experimental therapeutics framework that identified target engagement as a fundamental tenant. In order for NIMH to fund an early stage clinical trial, there needs to be evidence for that target engagement. The experimental therapeutics framework also encourages identifying specific dysfunctions and developing personalized treatment. NIMH has different funding mechanisms for early stage research in target engagement. In recent years, NIMH has moved away from funding confirmatory efficacy trials for drugs because these trials should be the domain of the drug companies, but NIMH still recognizes the need for and have continued to use confirmatory efficacy studies for psychosocial interventions.
Dr. Gordon noted that psychosocial target engagement should be defined in a way that allows for flexibility. There is a recognized need to define targets more broadly and mechanistically. New language for psychosocial interventions emphasizes molecular measurements, such as positron emission tomography (PET) scans, as a key criterion for a “go/no-go” decision to move forward with a new drug treatment. Dr. Gordon explained that there is an incorrect, widespread belief that program officers will reject all applications that do not use PET scans.
There have been efforts at NIMH to look at clinical trial applications and their success rates. Dr. Gordon reviewed internal preliminary data that suggests success rates are similar across applications that seek to study various types of interventions, including psychosocial, pharmacological, or device. It appears that psychosocial intervention applications have been slightly more successful than device or drug intervention applications. Dr. Gordon also pointed out a significant difference in the types of applications NIMH receives. From 2015 to 2018, NIMH received more than 400 applications to test psychosocial interventions, but only received 105 applications to test drugs or devices. He called for efforts that might increase the number of drug and device development applications.
Dr. Gordon also noted a few broad areas that he encourages the working group to explore: first, defining and evaluating target engagement, and second, working to encourage more drug development applications. He would like the working group to explore the results of the NIMH FAST Fail contracts and recommend if the program would still be a worthwhile investment.
Dr. Gordon explained that, although large-scale confirmatory efficacy studies should remain the domain of the drug industry, there are specific examples that the working group could explore. Some investigators have suggested that there are many off-patent medications that may benefit from small-scale confirmatory efficacy approaches that NIMH could consider.
He concluded by reviewing the four questions that a drug development working group could consider, including defining and evaluating target engagement; approaching special populations; assessing the value of FAST Fail contracts; and considering using confirmatory efficacy trials at NIMH. Next steps include soliciting volunteers to chair/co-chair the working group and to collaborate with these individuals to modify or narrow areas of interest to be addressed. Dr. Gordon hopes that the preliminary recommendations will be developed within 9 to 12 months, culminating in a written report for consideration by the Council.
Discussion
Dr. John Krystal expressed his support for the new work group and suggested that the new working group should consider the extensive workforce infrastructure needed to support these efforts. He pointed out that, although there are many promising new drugs on the market, institutional infrastructure often cannot support a principled, scientific investigation process.
Mr. Brandon Staglin mentioned that many patients, such as those with schizophrenia, may stop taking a drug because of undesirable side effects. He recognized that in the United States, first-line treatments for psychiatric illnesses are primarily medication-based because private insurance companies may see less profit in psychosocial treatments. He suggested that NIMH or the Substance Abuse and Mental Health Services Administration partner with other agencies to stimulate incentive to implement these opportunities for psychosocial treatments. Dr. Gordon said that although psychosocial interventions are not the focus of the working group, they would still like to address how to sustainably and effectively implement them in the real world.
Dr. Sophia Vinogradov suggested this could be a new era of drug treatment, but added that there is a challenging lack of resources, physician researchers, infrastructure, training, and support. She expressed interest in participating in the working group.
Dr. Rhonda Robinson Beale addressed Mr. Staglin’s comment. She said that from a billing perspective, it is relatively easy to receive reimbursement for psychosocial interventions because the billing codes are broad; however, these interventions tend to have low efficacy and high drop-out rates. She suggested that NIMH work to reduce the perception that studies conducted by pharmaceutical companies are invalid due to bias. Dr. Gordon added that it is important to consider the payment system when conducting these trials. He said that although NIMH is limited in its capacity to solve these problems, the working group could aim to address these questions from the experimental therapeutic perspective.
Dr. Elyn Saks brought to attention a recent lawsuit that successfully challenged failures in treatment parity.
NIMH Strategic Planning: 2020 and Beyond
Joshua Gordon, M.D., Ph.D. and Meredith Fox, Ph.D
Dr. Meredith Fox presented on the next iteration of the NIMH Strategic Plan for Research. The Strategic Plan for Research is updated every five years, and the Strategic Research Priorities are updated annually to allow for flexibility over the five-year period. She began by explaining that the 2020 Strategic Plan will be a refresh of the current 2015 plan rather than a full overhaul. The current Strategic Plan addresses critical questions such as balancing immediate mental health needs with long-term investments and linking advances in biology with environmental factors. To address these questions, the current Strategic Plan lays out four Strategic Objectives, including: 1) Define the mechanisms of complex behaviors; 2) Chart mental health illness trajectories to determine when, where, and how to intervene; 3) Strive for prevention and cures; and 4) Strengthen the public health impact of NIMH-supported research.
NIMH leadership has agreed that the 2020 Strategic Plan should remain a high-level document with the same four overarching goals. They also agreed to update the current document to keep pace with the science, rather than aiming for a full rewrite. The biggest changes to the new document will be related to the current Strategic Research Priorities. These priorities, which are currently very detailed and exist as a separate document, will be brought to a higher level and integrated into the main Strategic Plan. NIMH also wants grantees to have one-stop access to a digital, living plan with increased flexibility to update scientific innovations and provide valuable resources. Unlike the 2015 Plan, the 2020 Plan will be dynamically updated with new press releases and exciting findings as they emerge. The Plan will also be available for download in PDF format.
Dr. Fox explained that the new Strategic Plan will address requirements from the 21st Century Cures Act, including topics related to reducing mental health disparities among women and minorities. NIMH also aims to include measurable performance metrics, effective stewardship of public resources, and a description of the planning process. NIMH plans to include a section for opportunities and challenges, and cross-cutting research themes.
Council members will receive a draft of the new plan by early August. Feedback from the Council will be discussed at the September Council meeting. After integrating recommendations from the public and NIMH stakeholders received through a Request for Information, a near-final document will be presented to the Council at the winter meeting after which it will be published. Dr. Fox acknowledged the valuable input and effort from staff across the Institute to update the Strategic Plan.
Discussion
Dr. David Henderson wondered if there are any data on 2015 outcomes as they relate to the effectiveness of early Strategic Objectives. Dr. Fox responded that NIMH routinely collects this data. Some results have been shared with the public, for example in Director’s Messages. Other data is used for internal assessment. For example, every council round, each NIMH Office or Division that puts forward grants assesses the number of activities performed under each Strategic Objective. Dr. Gordon added that Congress also asked for outcome metrics and this is being built into the 2020 version.
Dr. Randy Blakely expressed support for the new online format and asked that the Council consider how this change might affect access for certain groups, such as elderly and multilingual populations. Dr. Blakely added that efforts should be centered on evidence-based therapeutics and an institutional approach to improve public education efforts. Dr. Tami Benton suggested looking into outreach targeted for multiple generations and to consider how best to engage younger people. Dr. Fox said they are planning to engage multiple generations and are considering outreach efforts in other media, such as video to reach a variety of audiences and stakeholders.
Dr. Robinson Beale echoed Dr. Blakely’s suggestion to ensure that NIMH provides information to the public about what works and what doesn’t. She recognized that there is a reluctance to make definitive statements, but noted that the information is still important for public safety. She asked about the definition of “public health burden” and suggested including medical cost of a given disease or condition as an additional priority. Dr. Robinson Beale noted the alarming trend of rising depression and anxiety in the Millennial generation, and she encouraged collaboration and cross-training initiatives among pharmaceutical researchers and psychosocial researchers.
Dr. Alan Greenberg asked if NIMH has considered a social media strategy to solicit input on the Strategic Plan and to disseminate information to the younger generation. Dr. Fox said that NIMH has one of the largest number of Twitter followers of all the HHS agencies, and they are working to develop new outreach methods to engage different populations of people, including youth. Dr. Gordon added that they also engage in Twitter chats and host Facebook Live sessions.
Dr. Amy Kilbourne asked if they have engaged with the Foundations for Evidence-Based Policymaking Act, a relatively new law requiring federal agencies to justify their funding, including an annually updated evidence-building plan. The law aims to ensure not only that policy is based on sound evidence, but that the processes themselves are evidence-based. Dr. Kilbourne suggested that this could be included in the Strategic Plan. Dr. Gordon said that this agenda has trickled down to the NIH level.
Mr. Staglin added to the comments about soliciting input via social media, suggesting that the priorities of the Strategic Plan should be set around implementation for wide adoption. He said that NIMH could benefit from input directly from actual users about the treatments that work best for them. Dr. Fox said there are some regulations about obtaining this kind of information from social media, and that instead they can seek this type of input via the Request for Information (RFI) and direct the public to provide feedback through that mechanism.
Dr. Cheryl King noted that the peer review process has remained the same for a long time, and she asked if there is a timeline for evaluating the peer review process every few years. Dr. Gordon replied that the last few years have seen several initiatives in this area. Some efforts at the Center for Scientific Review (CSR) have examined the relative quality of review by study section with specific metrics. CSR has also experimented with blind review. Others have focused on improving the process by identifying metrics and correlating application scores with resulting activities. NIMH has also begun reviewing NIMH grants for evidence of bias. For the most part NIMH has not identified biases, but the effort remains important, considering the number of grants funded. Overall, there is an ongoing effort to improve the process.
Dr. Krystal pointed out the challenges of blind review, and he said there is a need to determine what metrics should be used to evaluate the impact of blinding process. Dr. Gordon responded that blinding procedures for these experiments have been labor intensive and expensive. They are asking questions about potential race and gender biases, and studies have predicted lower success rates among women and minority investigators. Dr. Gordon said that blinding processes can help reduce these biases. Dr. Neil Risch said that including this as a program priority can address the problem, and Dr. Gordon said that there may be legal limits to consider.
Concept Clearences
Identification, Validation, and Manipulation of Neural Circuits Related to Mental Illness in Non-Human Primates
Doug Meinecke, Ph.D
Dr. Doug Meinecke explained that his research team is motivated by the recognition of highly successful preclinical work in rodent models, which have allowed them to manipulate, dissect, and analyze cell neuromechanisms that may be associated with cognitive function and other components of mental illness. They would like to use non-human primates to bridge the gap between rodent and human research efforts. This would necessitate a careful approach, with a key focus on a bidirectionality in which human research and non-human primate research inform each other. They aim to probe behaviors in humans and primates that confirm circuit homology among different species, and test techniques that are relevant to humans as a preclinical validation of concept.
Discussion
Dr. Vinogradov and Dr. Gregory Miller both expressed their enthusiasm for this research approach. Dr. Miller added that it is important to consider how to present this research to the public because it could easily be misinterpreted. He also suggested that Dr. Meinecke remove the word “underlying” as it unnecessarily narrows the scope of research. Dr. Gordon reiterated the imperative to ethically treat non-human primate subjects, and that NIMH promotes numerous efforts to ensure that non-human primates are used ethically and only when necessary.
Dr. Gordon called for a motion to approve the concept. A motion to approve was passed.
BRAIN Initiative: Non-Invasive Neuromodulation – New Tools and Techniques for Spatiotemporal Precision
David McMullen, M.D.
Dr. David McMullen presented an initiative to develop new tools and methods for brain stimulation. NIMH is currently funding 14 projects across various methodologies, including electrical, magnetic, ultrasound, nanoparticle, and optical technologies from the previous funding opportunity announcement. This concept encourages research to optimize existing stimulation methods and develop and test novel tools and methods of neuromodulation that go beyond the existing forms of neural stimulation.
Discussion
Dr. Vinogradov expressed enthusiasm about the application. Dr. Blakely asked if there are computational models built into the initiative towards understanding efficacy at the mechanistic level. Dr. McMullen answered that they were included. Dr. Anita Everett asked if there is a longitudinal aspect beyond addressing short-term outcomes, and Dr. McMullen answered that the clinical trials will assess the long-term outcomes. Dr. Gordon asked if this initiative would support clinical research for NIMH and Dr. McMullen responded that they would target the confirmatory efficacy and address implementation questions, and also include stakeholder perspectives to assess long-term impacts. He hopes that feedback from the Centers for Medicare and Medicaid Services and other private payers can inform these decisions. Dr. Robinson Beale asked how they can ensure they are addressing duration, frequency of administration, and sustainability metrics to understand efficacy. Dr. McMullen answered that this BRAIN Initiative represents early-stage tool development and does require information about dosing, length of dosing, and long-terms outcomes.
Dr. Gordon called for a motion to approve the concept. A motion to approve was passed.
Utilizing Invasive Recording and Stimulating Opportunities in Humans to Advance Neural Circuitry Understanding of Mental Health Disorders
David McMullen, M.D.
Dr. David McMullen reviewed the concept to understand neural circuits, an effort to explore neural recordings in humans beyond traditional non-invasive methods. The results could inform future treatments and may help to bridge the gap between animal and human trials. Dr. McMullen reviewed the current approaches to invasive neural circuit recording and how those methods have advanced neuroscientific fields, including language, motor skills, and memory. The current effort would shift the field towards questions specifically relevant to mental health. This initiative arises in the wake of two failed pivotal trials for deep brain stimulation, demonstrating a gap in circuit-level understanding. Dr. McMullen also explained that the initiative is facilitated by increasingly common use of stereo-EEGs to measure motor and language areas, which can be translated to answer mental health questions because mental health diseases are disorders of distributed networks.
Discussion
Dr. Vinogradov noted the similarities between Dr. McMullen’s and Dr. Meinecke’s goals of bridging non-human primate research and human research. She said that the explosion of digital technologies makes this a timely effort and an important translational bridge. She asked about developmental aspects and functioning under these tasks, including a lifespan focus. Dr. McMullen agreed about the lifespan as an important area of study. Dr. Miller asked if this funding would be used as an add-on to existing projects or if it would create entirely new projects that would not otherwise be funded. Dr. McMullen answered that the intention is to add additional tools and time for the researcher rather than create entirely new efforts.
Dr. Gordon called for a motion to approve the concept. A motion to approve was passed.
Autism Biomarkers of Clinical Trials
Ann Wagner, Ph.D.
Dr. Ann Wagner reviewed how the goal of this initiative is to encourage the next stages of development and validation of biomarkers for use in clinical trials for the treatment of core social deficits in autism spectrum disorders (ASD). Currently, there are no approved drugs for the treatment of ASD symptoms, so the identification of biomarkers for the use of objective measure of treatment response would greatly enhance drug development efforts. She explained that a 2012 biomarker working group identified EEG and eye tracking measures as prime candidates for this purpose. With co-funding from NINDS, NICHD, and the Simons Foundation, NIMH funded the Autism Biomarkers Consortium for Clinical Trials. Data has been collected from 280 children with ASD and 119 typically developing children ages 6 to 11 years old, and these data are being prepared for final analysis. Dr. Wagner said that a recent FDA acceptance letter has provided guidance about the scientific issues to be addressed by a biomarkers qualification package. She summarized their intended next steps for moving the most promising measures further towards biomarker qualification.
Discussion
Dr. Ian Gotlib said that a lot of this could come under existing R01 investigations. Dr. Wagner said they could, but not at the level and with the guidance of the FDA. Dr. Gotlib added that the longitudinal and integrative aspects of the effort were important. Dr. Lisa Jaycox noted that the efforts to capitalize on promising work will be helpful to the field. Dr. Gordon added that the goal of this initiative is not just discovery and translation; but more broadly aims to identify biomarkers that the FDA will approve and solidify as best practices for clinical trials, which will require adherence to strict criteria. Dr. Wagner said that the N170 marker is the first biomarker from the neuroscience committee that received a letter of acceptance into the Biomarkers Qualification Program, representing significant steps towards this goal. Dr. Blakely asked if this initiative was extended to underrepresented populations, including women with ASD. Dr. Wagner said that they did not explicitly list additional populations, but recognized their importance.
Dr. Gordon called for a motion to approve the concept. A motion to approve was passed.
Accelerating Treatment Development Research in Clinical High Risk for Psychosis
Robert Heinssen, Ph.D. APBB
Dr. Robert Heinssen said that the goal of this concept is to encourage collaborative research to advance understanding of the biology that underlies clinical risk for psychosis. The goal is to promote observational studies to identify and validate biomarkers, and to explore novel targets for pharmacologic intervention. There are already studies that have examined the changes in perception, thinking, and behavior that precede a first psychotic episode. Recently, scientists have streamlined these assessments into psychosis risk calculators that may be used prospectively to enrich samples in biomarker and intervention development studies. The leadership of the NIH Accelerating Medicines Partnership (AMP) program acknowledged these advances and encouraged NIMH to explore opportunities in risk prediction and pharmacological trials in early psychosis. Currently, they suggest mobilizing existing programs to pursue coordinated experimental medicine studies to address psychosis, cognitive problems, and mood symptoms in high-risk individuals. Major objectives for this research include extending biomarker approaches, using computational techniques, and pursuing pharmacologic interventions that address unmet needs.
Discussion
Drs. King and Vinogradov expressed enthusiastic support for this initiative. Dr. Vinogradov added that this effort would contribute to the foundation of clinical and translational sciences, as well as infrastructure for implementation. Mr. Staglin said that this effort is a good step towards capitalizing on research that has been funded by NIMH for the last 15 years, and that the initiative will help young people with newly-developing psychotic illness treat their symptoms and maintain their health. Dr. Everett expressed her excitement about this initiative and suggested that this partnership provides an opportunity to look into workforce development.
Dr. Gordon called for a motion to approve the concept. A motion to approve was passed.
Implementation Research in HRSA Ryan White Clinics: Screening and Treatment for Mental Illnesses to Further the National “End the HIV Epidemic” (EtHE) Goals
Dianne Rausch, Ph.D.
Dr. Dianne Rausch stated that this concept is a response to an initiative that was announced at last year’s the State of the Union address with the goal of ending the HIV/AIDS epidemic. Dr. Rausch explained that the goal is to reduce new infections by 75 percent in the next five years and 90 percent in the next decade. To that end, there is an aim to bring together the CDC, HRSA, SAMHSA, and NIH to target jurisdictions with the highest HIV rates. Currently, HRSA receives funding to increase service delivery and improve rates of retention and viral suppression, which is particularly valuable for underserved populations such as youth, transgender individuals, and racial/ethnic minorities. Previous research has suggested that longer depression can yield worse HIV outcomes, finding that a 25 percent increase in days of depression was associated with a 19 percent increase in mortality risk. This was also associated with a higher viral load and a high number of missed appointments, indicating that mental illness affects HIV outcomes. Dr. Rausch reviewed a model of screening and treatment that can improve these outcomes by treating depression, PTSD, stress, and anxiety. The goal of this effort is to use the task-shifting or peer model to provide stepped care, digital health technologies, and transdiagnostic approaches.
Discussion
Dr. Greenberg and Dr. Henderson expressed their support for this initiative. Dr. Greenberg pointed out that among a large NIH-support cohort in Washington, D.C., almost half of people with HIV have a psychiatric diagnosis, and there is a critical need to support this population. Dr. Henderson said that he has encountered a number of successful programs that can be translated to reduce comorbidities and address disparities in HIV care.
Dr. Krystal added a point about the biology of HIV, suggesting that new work on sorted white blood cells has examined the epigenetic interactive effects of HIV infection, depression, and substance use. They found that these factors do interact and modulate each other, signifying a need for crosstalk between services-oriented work and mechanisms-oriented work.
Dr. Tami Benton said that adolescents and LGBTQ+ youth have the lowest rate of viral suppression. There are challenges to providing HIV care for this population, and she suggested opportunities to collaborate with experts who can provide insight about treating adolescents with HIV.
Dr. Gordon called for a motion to approve the concept. A motion to approve was passed.
Adapting Immunotherapy Strategies for Targeting HIV/CNS Reservoirs: Potential Benefits and Risks
Jeymohan Joseph, Ph.D.
Dr. Jeymohan Joseph reviewed the goal and purpose of this concept, which is to adapt immunotherapy-based technologies for targeting viral reservoirs in the central nervous system, and to examine the potential health risks of applying these technologies. Currently, a number of approaches have targeted these viral reservoirs, but none are being optimized to specifically study central nervous system reservoirs in HIV. Some immunotherapy approaches have been used to target central nervous system disease in other fields, such as cancer and Alzheimer’s disease. This concept aims to refine and adapt these immune-therapy based approaches to target central nervous system reservoirs using in vitro and in vivo models, with an additional goal of examining the potential toxicity risks associated with this approach.
Discussion
Dr. Blakely asked why NIMH should find this work relevant when other agencies, such as NIAID, are already funding similar initiatives. Dr. Joseph responded that although NIAID is focused on viral reservoirs, they are not interested in the central nervous system, and there is a unique opportunity for NIMH to support research in this domain.
Dr. Krystal pointed out that other diseases are not always explicitly the focus of relevant agencies. Dr. Gordon added that this initiative will be funded by specific allocation given to NIMH for HIV and AIDS research, and it will not detract from resources that they would otherwise spend on mental illness research. He added that it would be beneficial if this research also provided guidance towards other, more traditionally funded NIMH research initiatives.
Dr. Blakely asked how much of this initiative will go towards human studies rather than in vitro and animal models. Dr. Joseph responded that this is early stage research.
Dr. Gordon called for a motion to approve the concept. A motion to approve was passed.
Dr. Gordon stated that the next presentations will be funding opportunity announcements from the BRAIN Initiative and other programs. Because these concepts had already been presented and vetted before the multi-council working group, current discussion was encouraged but not required. Dr. Gordon suggested that reviewers could submit their written comments for later consideration.
BRAIN Initiative: Marmosets for Neuroscience Research
Greg Farber, Ph.D.
Dr. Greg Farber explained that this concept was originally developed to improve access and availability of marmosets for neuroscience research. Marmosets are small, non-human primates that are useful for studies related to genetic and circuit-based technologies.
Discussion
Dr. Gotlib asked how the number of marmosets would be increased for research purposes. Dr. Gordon clarified that the purpose of the concept is to increase the number of marmosets, while a series of RFAs developed under this concept will address different issues. Dr. Farber explained that, although the marmoset is a pest in Brazil, government regulations prohibit exporting the monkeys internationally. They have developed a strategy to allow the small existing colonies in the United States to breed a higher number of animals that can be used for research. Dr. Gordon added that there will be measures to increase the genetic diversity by collaborating across data centers, as well as management and technological assistance to ensure the animals are being cared for appropriately.
BRAIN Initiative: Models of the Developing Human Nervous System
Dr. Gordon explained that the goal of this concept is to create models of the developing human nervous system. Dr. Gordon said that they aim to stimulate basic research, study human stem cells as they relate to human brain development and physiology, and validate new models by comparing them to existing data.
Renewal of the Silvio O. Conte Centers for Basic Neuroscience or Translational Mental health Research
Dr. Gordon reviewed the purpose of the Silvio O. Conte Centers, which is to provide opportunities to support collaborative efforts among interdisciplinary research teams. Direct funding for each center is approximately $2 million, a substantial increase over the last few years. Each project addresses a specific scientific question, which receives a one-year renewal period.
Renewal of the National Cooperative Drug/Device Discovery/Development Groups (NCDDG) for the Treatment of Mental or Substance Use Disorders or Alcohol Addiction
Dr. Gordon said that this initiative, with support from NIDA and NIAAA, is a multi-institute effort to aid discovery of pre-clinical development, early proof of concept testing in humans for new pharmacological approaches to treating mental disorders, including substance use disorders. These collaborative efforts have been successful in moving certain targets forwards into human testing, and they propose renewing this concept.
Renewal of the Development and Application of PET and SPECT Imaging Ligands as Biomarkers for Drug Discovery and for Pathological Studies of CNS Disorders
Dr. Gordon stated that the purpose of this concept is to encourage the development of novel radioligands for central nervous system disorders. They aim to ensure that these initiatives are focused on development and target engagement for drug discovery, disease progression, and treatment efficacy. Dr. Gordon explained that they have produced a set of requirements to be used in these applications.
Genetic Architecture of Mental Disorders in Ancestrally Diverse Populations
Dr. Gordon said that this initiative has produced genetic discovery platforms and large databases from individuals who have volunteered their genetic data for discovery and applications in mental disorders. Unfortunately, these efforts do not currently serve a diverse population, so there are ongoing efforts to fund diversity initiatives so that the data can apply to larger groups.
Discussion
Dr. Laura Almasy expressed her support for the Genetic Architecture concept. She asked them to consider expanding or deleting existing specifications for certain study designs, case control, parent trial trios, and nuclear families. She suggested that they might also be interested in encouraging ancestral diversity in studies related to biomarkers or risk factors, which also require increased diversity. Dr. Gordon responded that this initiative is specifically focused on genetics, although they have considered expanding the program to include biomarker-based studies. Dr. Risch echoed Dr. Almasy’s point that these challenges apply to all genetic study designs. Dr. Gordon agreed that they would need to look into expanding the study designs or eliminating them from the program altogether. Dr. Krystal wondered if NIMH could require all imaging studies to collect DNA and bank across all of the data from funded studies. Dr. Gordon said that NIMH has considered this, but think it may be outside the scope of this initiative. NIMH is waiting on results of existing studies before heavily investing in imaging genomics. There is hope that the larger funded studies, such as ABCD, will provide an example of how to build diversity initiatives into large-scale projects.
Dr. Gordon clarified that although the concept clearances cover a large range of issues, they do not represent the full diversity of the NIMH portfolio. They invite additional applications and projects that address a broader array of topics.
Dr. Gordon called for a motion to approve the six concepts. A motion to approve was passed.
Public Comment Period
There were no public comments.
Adjournment
The open session of the NAMHC meeting adjourned at 12:29 pm.
Closed Session
The grant application review portion of the meeting was closed to the public in accordance with provisions as set forth in Section 552b(c)(4) and 552b(c)6. Title 5, U.S. Code and Section 10(d) of the Federal Advisory Committee Act, as amended. The closed session was set to resume at 2:00 pm.
Appendix A
Summary of Primary MH Applications Reviewed
Council: May 2019
| IRG Recommendation | ||||||||
|---|---|---|---|---|---|---|---|---|
| Category | Scored # | Scored Direct Cost $ | Not Scored (NRFC) # | Not Scored (NRFC)
Direct Cost $ |
Other # | Other Direct Cost $ | Total # | Total Direct Cost $ |
| Research | 677 | $957,064,894 | 505 | $606,424,882 | 0 | 0 | 1182 | $1,563,489,776 |
| Research Training | 0 | 0 | 0 | 0 | 0 | |||
| Career | 86 | $65,144,129 | 37 | $28,853,096 | 0 | 0 | 123 | $93,997,225 |
| Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Totals | 763 | $1,022,209,023 | 542 | $635,277,978 | 0 | $0 | 1,105 | $1,657,487,001 |
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
- Joshua A. Gordon, M.D., Ph.D.
Director
National Institute of Mental Health
Bethesda, MD
Executive Secretary
- Jean Noronha, Ph.D.
Director
Division of Extramural Activities
National Institute of Mental Health
Bethesda, MD
Members
| Laura A. Almasy, Ph.D. (22)
Professor Department of Genetics Perelman School of Medicine University of Pennsylvania Philadelphia, PA |
Cheryl A. King, Ph.D. (21)
Director Mary A. Rackham Institute Professor, Department of Psychiatry and Psychology University of Michigan Rachel Upjohn Building Ann Arbor, MI |
| Marjorie L. Baldwin, Ph.D. (22)
Professor Department of Economics W. P. Carey School of Business Arizona State University Tempe, AZ |
John H. Krystal, M.D. (19)
Robert L. McNeil, Jr. Professor of Translational Research Chair, Professor of Neurobiology Chief of Psychiatry, Yale-New Haven Hospital Department of Psychiatry Yale University School of Medicine New Haven, CT |
| Tami D. Benton, M.D. (19)
Psychiatrist-in-Chief Department of Child and Adolescent Psychiatry And Behavioral Sciences Children’s Hospital of Philadelphia Philadelphia, PA |
Gregory A. Miller, Ph.D. (20)
Professor and Chair Department of Psychology University of California, Los Angeles Los Angeles, CA |
| Randy D. Blakely, Ph.D. (20)
Professor Department of Biomedical Sciences Charles E. Schmidt College of Medicine Florida Atlantic University Jupiter, FL |
Yael Niv, Ph.D. (21)
Professor Princeton Neuroscience Institute, Room 143 Department of Psychology Princeton University Princeton, NJ |
| Ian H. Gotlib, Ph.D. (20)
David Starr Jordan Professor and Chair Department of Psychology Stanford University Stanford, CA |
Neil J. Risch, Ph.D. (21)
Director Institute of Human Genetics Lamond Family Foundation Distinguished Professor In Human Genetics University of California, San Francisco 513 Parnassus Avenue San Francisco, CA |
| Alan E. Greenberg, M.D., M.P.H. (20)
Professor and Chair Department of Epidemiology and Biostatistics School of Public Health George Washington University Washington, DC |
Rhonda Robinson Beale, M.D. (19)
Senior Vice President and Chief Medical Officer Blue Cross of Idaho Meridian, ID |
| David C. Henderson, M.D. (20)
Chair Department of Psychiatry Boston University School of Medicine Boston, MA |
Elyn R. Saks, J.D., Ph.D. (20)
Orrin B. Evans Professor of Law Gould School of Law University of Southern California Los Angeles, CA |
| Lisa H. Jaycox, Ph.D. (20)
Senior Behavioral Scientist Health Program Rand Corporation Arlington, VA |
Brandon Staglin, M.S. (21)
Director Marketing and Communications One Mind Institute Rutherford, CA |
| Sophia Vinogradov, M.D. (22)
Donald W. Hastings Endowed Chair University of Minnesota Medical School Professor and Department Head Department of Psychiatry Minneapolis, MN |
Christopher A. Walsh, M.D., Ph.D. (19)
Chief, Division of Genetics and Genomics Boston Children’s Hospital Bullard Professor of Pediatrics and Neurology Harvard Medical School Boston, MA |
Ex Officio Members
Office of the Secretary, DHHS
- Alex Azar
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
- Amy M. Kilbourne, Ph.D., M.P.H.
Director
Quality Enhancement Research Initiative
Health Services Research & Development
Department of Veterans Affairs, Ann Arbor
Ann Arbor, MI
Department of Defense
- Steven E. Pflanz, M.D.
Air Force Director of Psychological Health
Mental Health Branch Chief
Air Force Medical Support Agency
Fall Church, VA
Liaison Representative
- Anita Everett, M.D., DFAPA
Acting Director, Center for Mental Health Services
Substance Abuse and Mental Services Administration
Rockville, MD
Others present
- Juliane Caron – FABBS
- Erin Cadwalader – Lewis-Burke Associates
- Jonelle Duke, Bizzell Group
- Yari Jamali, Transcriber
- John Karvatas, Transcriber
- Monica Mallampalli – Postpartum Support Int’l/The Reilly Group
- Marie Rowland, Science Writer
- A.J. Walker – National Association of State Mental Health Program Directors
- Phil Wang – American Psychological Association
- TaRaena Yates, Bizzell Group
NIMH Staff
|
Anji Addington
|
Greg Greenwood
|
David Panchision
|