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NAMHC Minutes of the 254th Meeting

September 20, 2018

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 254th meeting at 9:00 am, September 20,2018 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 grants applications. Joshua Gordon, M.D., Ph.D., Director of the National Institutes 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

  • Rhonda Robinson Beale, M.D.
  • Tami Benton, M.D.
  • Randy Blakely, Ph.D.
  • Benjamin Druss M.D., M.P.H.
  • Ian Gotlib, Ph.D.
  • Alan Greenberg, M.D., M.P.H.
  • David Henderson, M.D.
  • Michael Hogan, Ph.D.
  • Lisa Jaycox. Ph.D.
  • Cheryl King, Ph.D.
  • John Krystal, M.D.
  • Gregory Miller Ph.D.
  • Neil Risch, Ph.D.
  • Elyn Saks, J.D., Ph.D.
  • Brandon Staglin, M.S.

Department of Veteran Affairs

  • Amy Kilbourne, M.D., Ph.D.

Department of Defense

  • Steven Pflanz, M.D.

Liaison Representative

  • Paolo del Vecchio, MSW

Others Present at the Open Policy Session

  • Erin Cadwalader, Lewis-Burke Associates
  • Nancy Carlson, American Counseling Association
  • Kurt DeSoto, Association for Psychological Science
  • Florence Fee, No Health without Mental Health
  • Craig Fisher, American Psychological Association
  • Karen Gibson-Serrette, Longevity Consulting
  • Jennifer Grinnell, Everymind
  • Sheila Harley, Harley Business Group
  • Michael Knopp, NIH Transcriber
  • Preston Maclean, Guide Consulting Services
  • Oscar Morgan, Danya Institute
  • Jennifer Pacurari, Engility
  • Elizabeth Scherer, Science Writer
  • Karishma Sheth, Everymind
  • Anika Smith, Longevity Consulting
  • Andrew Sperling, National Alliance on Mental Illness
  • Kelly Taylor, University of California
  • Fuller Torrey, Stanley Medical Research Institute
  • Cheyanne Welch, American Association for Emergency Psychiatry

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 current NAMHC members (both present and online) as well as the public, also noting that the session was being broadcast broadly to the NIMH community and the public. Following introductions, and comments by Dr. Miller confirming that he had forwarded minor changes to the May minutes, the Council unanimously passed a motion approving the final Summary Minutes of the May 17, 2018 meeting.

NIMH Director’s Report

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

Federal Updates and Constituent Relations

Dr. Gordon opened his report noting the recent appointment of Dr. Kelvin Droegemeier as Director of the White House Office of Science and Technology Policy (OSTP) and said that OSTP has been a proponent of mental health issues. He also highlighted NIH Director Dr. Francis Collins’ testimony this past Summer, first to the House Committee on Energy and Commerce Subcommittee on Health around implementation of the 21st Century Cures Act, and second to update the Senate Committee on Health, Education, Labor, and Pensions about Prioritizing Cures, Science and Stewardship at NIH. Dr. Collins’ testimony highlighted NIH’s greater emphasis on current NIH funding programs to identify, grow, and retain new- and early-career investigators across critical career stages. He said that the Substance Abuse and Mental Health Services Administration’s (SAMHSA) Assistant Secretary Elinore McCance-Katz provided testimony to the House Committee on Energy and Commerce, Subcommittee on Health around SAMHSA’s activity around mental health needs under the auspices of the 21st Century Cures Act.

Dr. Gordon shared his congressional interactions with Sen. Bill Cassidy (R-LA), Sen. Angus King, (I-MA) and Sen. Heidi Heitkamp (D-ND), all of whom have voiced concerns about suicide and national suicide prevention efforts. NIMH Deputy Director, Dr. Shelli Avenevoli, also participated in Senator Heidi Heikampt’s (D-ND) Stop Suicide Summit geared toward addressing national suicide prevention strategies.

NIMH staff also participated in Congressional Briefings on a number of topics including autism spectrum disorder (ASD) (Rep. Chris Smith [R-NJ] and State Rep. Franklin Foil [R-LA]), mental health research and suicide (Rep. Bobby Rush [D-IL]), suicide prevention (Rep. Mark DeSaulnier [D-CA] and Rep. Bonnie Watson-Coleman [D-NJ]), and teen depression and youth mental health (Rep. Michael McCaul, [R-TX]). He emphasized the numerous interactions focused on autism as Congress writes the renewal of the Autism CARES Act. He added that there have also been numerous constituent outreach efforts including the Washington Post Live’s June 13 Mental Health and Wellbeing in America Summit, and the July Annual Outreach Partnership Program, as well as the development of key NIMH resources for the public such as a new borderline personality disorder publication, and suicide prevention research.

Leadership News

Several new NIH institute and center directors have been appointed, with Dr. Helene Langevin now leading the National Center for Complementary and Integrative Health, and Dr. Bruce Tromberg, who will assume the helm of the National Institute of Biomedical Imaging and Engineering in 2019. With Dr. Patricia Grady’s retirement from the National Institute of Nursing Research (NINR), Scientific and Acting Deputy Director Dr. Ann Cashion is currently serving as Acting Director.

Policy Updates & News

Dr. Gordon said that concerns had been raised with regard to the failure of a small but not inconsequential number of NIH-funded researchers to disclose funding from outside resources including foreign governments, intellectual property, and sharing of confidential information. These concerns prompted Dr. Collins to issue an August 23, 2018 statement highlighting NIH’s response, including the formation of a new working group to identify methods to protect the integrity of the Nation’s biomedical research.

Shifting to policy news, Dr. Gordon stated that NIH Office of Extramural Research released a scientific rigor perspective designed to help researchers develop better grant proposals, especially in the area of genetics research. Additionally, NIH is currently seeking public comment on a draft Behavioral and Social Clinical Trials Template to assist with Preparation of Phase 2/3 Investigational New Drug or Investigational Device Exemption trial protocols. Additionally, NIH is seeking public feedback through October 11 on human participants research reporting.

Dr. Gordon provided updates on four NIH-Wide initiatives, first noting that several components of NIH HEAL (Helping to End Addiction Long-term InitiativeSM) have been fast-tracked, including a component evaluating opioid use disorder/mental health disorders comorbidity. He said Dr. Collins has formed a 2.0 version of the initial NIH BRAIN (Brain Research through Advancing Innovative Neurotechnologies®) Initiative working group reevaluating how to best achieve broad-reaching goals in the context of neuroscience. The group first met in August and is holding several public workshops to explore the state of human neuroscience. The All of Us Research Program has launched a research hub awareness site, which is currently focused on member recruitment, and within a few years, on rolling out large-scale behavioral testing. Finally, the ABCD (Adolescent Brain Cognitive Development) Study is expected to complete recruitment shortly. With regard to ABCD, Dr. Gordon mentioned that recruitment has ‘outstripped’ initial targets and, that participant diversity is good. Initial studies will examine the prodromal psychosis adjunct to substance use disorders. Closing the section, Dr. Gordon highlighted activities of the BRAIN Initiative Cell Census Network (BICCN), including a series of public workshops. BICCN has released its first large dataset comprising molecular profiling data for greater than 1.3M individual cells from the mouse brain; the first manuscript demonstrates the presence of a specific cell type in the human brain.

NIMH Budget Update

NIMH has been receiving a steady number of applications and awarding an increasing number of research project grants (RPGs) over the past five years. The success rate is about 21%, and approximately 575 grants will be rewarded in FY18. Dr. Gordon said that there has been an increase in the dollar value of the awards, especially within the human research portfolio, with the expectation of adequately powered, more rigorous, reproducible scientific observations. Within the NIH Next Generation Researchers Initiative policy, NIMH will prioritize short-term research while applicants on resubmit applications and anticipates funding 80 early-stage investigators and more than 340 at-risk investigators. For FY19, House Appropriations Committee filed and passed a two-bill minibus appropriations funding that provides $39.1B for NIH, and $1.8M for NIMH, which is approximately $100M more than FY18.

Workgroups and Committees

Dr. Gordon updated Council members and meeting attendees on the Research Domain Criteria (RDoC) Matrix Workgroup changes, highlighting the addition of a sensorimotor domain for Council approval. He noted that RDoC is a living document and that there are future plans to make it more data-driven. Moving on to the Interagency Autism Coordinating Committee (IACC), he mentioned the upcoming September 27 public workshop comprising experts in health, epidemiology, patient-provider interactions, and comorbid conditions affecting individuals with autism spectrum disorder (ASD). The next full committee meeting is scheduled for October 17 and is open to the public.

NIMH News to Know

Awards

Dr. Gordon said that unprecedented numbers of NIMH staff received national awards in 2018. Director of NIMH Division of Services and Intervention Research, Dr. Robert Heinssen, received the American Psychological Association’s Michael S. Neale Award for his outstanding leadership in fostering and promoting evidence-based research for individuals with early serious mental illness. Dr. Michael Freed, Chief of the Services Research and Clinical Epidemiology Branch, Ms. Denise Juliano-Bult, Chief of Disparities in Mental Health Services Research Program, and Dr. Andrea Horvath-Marques, Chief of the Mental Health Disparities Program all received the 2018 Administrator’s Award for Collaboration Health Resources and Services Administration.

Staff Updates

Dr. Gordon welcomed Dr. Hugo Tjeda, who joined the NIMH Intramural Research Program in September as Chief of the Unit on Neuromodulation and Synaptic Integration. He also announced the recent passing of Dr. David Jacobowitz, former head of the Section on Histopharmacology in the NIMH Division of Intramural Research Programs for 30 years. Additionally. Dr. Gordon noted NIMH’s ongoing recruitment for program officers; interested parties should email NIMHsearch@mail.nih.gov.

NIMH Realignment

Dr. Gordon said while main divisions at NIMH are being maintained, the Institute is aligning genomics and global mental health research with Division portfolios. Not only will this help to prioritize health disparities research, but, it will also enhance intramural/extramural interactions, promote collaboration to Institute-wide priorities, and redefine offices as ‘thought leaders.’ In turn, this will allow teams to tackle long-term topics under the office leadership and the Office of the Director. Most of the changes will be reflected within grants coding, with the exception of the Office for Research on Disparities and Global Mental Health, which is seeking approval for a name change (Office of Disparities Research and Workforce Diversities). NIMH is seeking candidates who possess an expertise in modern approaches to disparities research for the Director of the Office of Disparities Research and Workforce Diversities. Dr. Gordon encourages Council members’ candidate recommendations.

Science Highlights.

Science highlights included: 1) the use of an electronic health records-based algorithm that can be used to identify patients at high-risk for suicide attempts and completion within 90 days, 2) translational research that uses transcranial magnetic stimulation to predict antidepressant efficacy, 3) multidimensional coding by basolateral amygdala neurons that provide further insight into circuit-level manipulation and outcomes; 4) NIMH’s Small Business Innovation Research, which is engaged in ongoing development of spatial light modulators technology that facilitate three-dimensional optogenetics imaging of neurocircuits, the ultimate goal of which is to enable researchers to interpret complex patterns of activity but also replicate them.

Discussion

Dr. Gotlib asked for a clarification of ‘at-risk’ investigators, to which Dr. Gordon replied that while an NIH-wide standardized definition has not yet been developed, NIMH is specifically looking out for investigators at risk for losing all NIH/NIMH funding if not awarded a grant within current fiscal year.

Dr. Robinson Beale congratulated Dr. Heinssen on his work and asked if there were pathways for moving public-applicable research into the public arena. Dr. Gordon noted continued success with SAMHSA around evidence-based practices in suicide and serious mental health issues, universal screening emergency rooms, and work with the Mental Health Research Network. Dr. Avenevoli added that NIMH continues to engage in ongoing global conversations to help move specific pathways forward. Dr. Robinson Beale said that she raised the question to highlight the need for payers to be at the table to ensure that research is billable or included in a value-based approach. Dr. Gordon agreed, noting the need to ensure that the research questions are being answered in ways that demonstrate cost-effectiveness and reimbursement.

Dr. Benton asked how increased funding for implementation science (specifically with regard to preventive interventions for suicide) might address better integration into the healthcare setting. Dr. Dr. Heinssen said that his division (DSIR) has asked researchers to partner with stakeholders that play a role in implementation including payers, policymakers), including that the ED-SAFE study (universal screening in emergency rooms.) This is an example of research in real-world treatment settings that achieved decision-maker buy-in/assurances. Dr. Heinssen also noted that NIMH is most assertive in areas where they have a strong evidence base such as Coordinated Specialty Care suite of depression services which is now being reimbursed by the Centers for Medicare and Medicaid Practices (CMS). Dr. Gordon said convincing private insurers to pay for mental illness is something that needs work.

Mr. Staglin then inquired how these programs affect young and even elderly patients within Medicare, and if there are things that NIMH could be doing alone or in coordination with SAMHSA to influence private insurers to cover Coordinated Specialty Care on a broader basis. Dr. Heinssen noted the distinction between Collaborative Care for depression and Coordinated Specialty Care for first episode psychosis. Collaborative Care for depression is offered in primary care settings and adopted by CMS while Coordinated Specialty Care for first episode psychosis was accepted by CMS as an evidence-based intervention in 2015, and was later expanded to over 250 services through a combination of Mental Health Block Grants, Medicaid waivers, and state general funds. He added that the National Alliance on Mental Illness (NAMI) is organizing stakeholders to develop a case for private insurers.

Dr. Saks commented that a former student had brought several class action suits challenging implementation of parity.

Dr. Robinson Beale added numerous organizations might be helpful in the effort including AHIP (trade organization for all health plans), ABHW (trade organization for behavioral health), and the Blue Cross Association. She emphasized that private insurers need to be at the table as strongly as public ones, and that one of the largest pushbacks originates at the employer level.

Shifting gears, Dr. Greenberg asked Dr. Gordon to comment more on the decision to align two NIMH Centers with Division portfolios. Dr. Gordon first explained that the wholesale integration of Global Mental Health and Division of AIDS research will reflect both the global research of the AIDS division that actually combines expertise, and the many global research hubs that currently operate alongside AID research investments. Similarly, the genomics portfolio is being integrated with the Division of Neuroscience and Basic Behavioral Science and the Division of Translational Research on a grant-by-grant basis, depending on where the scientific expertise is and where synergies can be found. The primary changes reflect a team-based approach to ensure the Institute-wide priorities create research opportunities that are spread across scientific areas of each of the divisions. He said that the overall financial commitment to these areas will not change, will be primarily driven by quality of the science, and that NIMH will continue to support existing programs.

RDoC Workgroup Update, Addition of the Sensorimotor Domain

Bruce Cuthbert, Ph.D.

Dr. Cuthbert briefly reviewed the RDoC Framework, noting that it was conceived to be flexible and evolving, with continual updates based on acquisition of new data in various fields. He explained that a Changes to the RDoC Matrix Council Workgroup (CMAT) was formed in 2015 by the NAMHC to develop a standard process for submitting proposed Matrix and Framework changes, and to evaluate these changes and subsequently make recommendations to the Council for approval. Dr. Cuthbert said that while the addition of a motor systems domain was initially conceived in 2011, recent influx of data demonstrating the importance of motor systems with respect to mental disorders such as psychotic spectrum with catatonia, ASD, and attention deficit hyperactivity disorder prompted an in-person workshop. During the workshop (held on November 3-4, 2016 with 21 experts in basic and translational research), participants were asked to identify and define the constructs for the domain, and list elements comprising various units of analysis. He explained that the time delay between the workshop and presentation of the motor domain constructs to the Council was due to the need to ensure that balance was maintained with respect to NIMH’s existing research portfolio in the area, and so as to not upset the balance between NIMH and the National Institute of Neurological Disorders and Stroke (NINDS) co-funding and shared interest.

Dr. Cuthbert said that the sensorimotor domain defines systems responsible for the control and execution of motor behaviors, and their refinement during learning and development. He added that development is extremely important, not only for childhood disorders like ASD, but also for looking at risk and early motor manifestations of psychopathology in adults. Dr. Cuthbert explained that the first construct. Motor action refers to processes engaged during planning and action of a motor action in a context-appropriate manner. It is comprised of five sub-constructs: 1) action, planning, and selection (e.g., selecting a particular method of conducting an action, e.g., cost-benefit calculations about the chosen action), 2) sensorimotor dynamics (interchanges between sensory, perceptual, and motor systems to produce smooth, effective movement), 3) initiation, 4) execution, 5) inhibition and termination. The second construct, agency and ownership, is the sense that one is initiating, executing, and in control of actions and sensory consequences; he explained that agency is lacking in addiction or OCD, leading to compelled behavior. The third construct is habit, i.e., overlearned motor sequences based on reinforced learning, which, he said, may overlap with positive or negative habit constructs within the respective Valence domains. The fourth construct is innate motor patterns, e.g., unlearned action plans triggered by internal or external stimuli, e.g., stereotyped expressions of affect, orientation to salience, or the startle reflex.

Dr. Cuthbert said future activity for CMAT involves negative valence revisions, as well as determining the proposal vetting and evaluating process, not just in terms of the systematic aspect but also transparency to the entire field and how to attain maximum input from the scientific community and the public. Additionally, CMAT is considering potential refinements to criteria for changes to the matrix and defining constructs.

Discussion

Mr. Staglin asked if any thought had been given to meta-analyzing how the sensory motor domain interacts with other RDoC domains, e.g., motor skill learning and effect on long-term mood to foster wellness in brain health conditions. Dr. Cuthbert said that while other research is examining this, that CMAT hopes that the addition of motor domain will raise the importance of motor systems for promotion of healthy mood changes. Dr. Gordon added that the question illustrates the importance of the RDoC approach as motor function might influence many different diagnoses through its impact on pursuit of joyful or stress-reducing activities.

Dr. Gordon thanked Dr. Cuthbert and seeing that there were no additional questions, asked for motion to approve the Report. A motion to approve was passed unanimously.

Before moving on to the Concept Clearances, Drs. Gordon and Cuthbert confirmed that there would be a guide notice posted when the sensory motor domain processes are published and added to the RDoC Framework in two-to-four weeks. Dr. Gordon said that the contact on the notice would be Dr. Janine Simmons from the Division of Neuroscience and Basic Behavioral Science (DNBBS). He reinforced that the need to ensure restricted interest in this area without interference with the outstanding work/expertise in other Institutes on the basic science of motor control and planning. He concluded the update by encouraging interested investigators to contact NIMH in advance at the earliest possible stages to ensure that the application is directed to the appropriate institution.

Concept Clearances

Dianne Rausch, Ph.D., Christopher Gordon, Ph.D., Eve Reider, Ph.D., Michael Freed, Ph.D., Alexander Arguello Ph.D., Michelle Freund Ph.D., Shelli Avenevoli, Ph.D.

Dr. Gordon briefly reviewed the framework and purpose for presenting Concept Clearances to the Council and public, highlighting their ‘potential’ nature, and the uncertainty with regard to their pursuance/reliance on sufficient funding. He stated that in addition to the six NIMH Concepts for potential notice, two additional Concepts would be presented on behalf of colleagues at the National Institute of Drug Abuse (NIDA). Dr. Gordon shared that two Council member commenters had been asked to review the Concept and lead each discussion.

Understanding the Mechanisms of Neuropsychiatric Side Effects and Neurological Toxicities of HIV Anti-Retroviral Therapy (ART).

Dianne Rausch, Ph.D.

Dr. Rausch reviewed the current state of antiretroviral therapy (ART), noting the primary goals of early diagnosis and care linkage, consistent adherence, and use of ART as pre-exposure prophylaxis (PrEP) to prevent HIV infection among and between high-risk groups. She emphasized the importance of maximizing adherence, noting the recent availability of agents that improved toxicity profiles and were longer acting, and efforts to develop new targets (including immune-based therapies). She said that despite advances, all of these agents have side effects, including neuropsychiatric events (e.g. depression, anxiety, headaches, suicidality, sleep disturbances), which have been documented in up to 30% of patients, and are most frequently reported with nucleoside, non-nucleoside reverse transcriptase inhibitors (especially efavirenz). Dr. Rausch pointed out that not only is it difficult to distinguish drug neurotoxicity from HIV’s direct central nervous system effect, but also, may result in treatment interruption requiring a change in regimen. While toxicities have been known for some time, emerging reports of neural tube defects among women taking the newest ART agent – dolutegravir – at time of conception, have renewed interest in innovative research to identify risk factors, mechanisms underlying neuropsychiatric side effects, and neurological toxicities associated with these treatments. Dr. Rausch said that the ultimate Concept goal was development of ways to identify/measure these ART-induced events so that interventions can be developed to prevent or overcome them.

Discussion
Dr. Alan Greenberg, Dr. David Henderson, Council Discussants

Dr. Greenberg said that given the wide array of neuropsychiatric side effects and toxicities associated with ART fall within the purview of NIMH, that the initiative was innovative, timely, and very important. However, he recommended that case definitions be included to ensure uniformity across studies, and that NIMH might consider engaging some of the larger HIV cohorts in order to update the prevalence of these conditions with current antiretroviral regimens. Additionally, he suggested that an expert panel be convened to help prioritize the focus of the request for applications (RFA) and raise visibility. Dr. Rausch agreed, stating that her group had just held a workshop with a group of experts familiar with both HIV and psychiatric conditions to explore the types of questions to be asked, targets, etc. Concurring with Dr. Greenberg’s points, Dr. Henderson said that as HIV had become a chronic disease, this was something that needed to be addressed in order to provide clinicians with information to drive appropriate treatment choice.

Dr. Krystal added two additional suggestions: 1) to understand the extent to which the toxicity is mechanism-specific versus an off-target action of the drug, and 2) if the toxicity is purely due to drug action, or the interaction of the drug and effects of the virus on the brain. Dr. Gordon concurred, noting that the second question might be addressed through research on people already taking ART prophylaxis. Following up. Dr. Benton said that researchers were also seeing early cognitive changes among younger adolescents with good CD4 counts and low viral loads not on treatment, thereby reinforcing the need to understand the mechanisms underlying the relationship. Dr. Risch emphasized that it would be important to focus on a PrEP cohort as they would be using medication for a long time and are representative of an uninfected group who might suffer the consequences of taking medications beyond what is currently known (e.g., higher STD risk).

Dr. Gordon then called for a motion to approve the Concept. A motion to approve was passed.

Implementation Research to Inform and Enhance President’s Emergency Plan for AIDS Relief (PEPFAR) Pre-exposure Prophylaxis (PrEP) Delivery

Christopher Gordon, Ph.D.

Dr. Chris Gordon stated that the Concept goal was to support NIH/NIMH collaborative implementation science research to help support President’s Emergency Plan for AIDS Relief (PEPFAR) PrEP delivery initiatives across low- to middle-income countries. He said that PEPFAR is running behind its current, albeit modest targets, and that it is unclear if the issue is operational, lack of demand, or difficulty identifying ideal PrEP candidates. Consequently, the goal is to issue a funding opportunity announcement (FOA) to fund supplements to NIMH grantees already positioned to partner with PEPFAR personnel to address individual uptake questions. Exemplar research foci range from evaluating PrEP adoption provider training and delivery models in varied settings, to examining characteristics of PrEP adopters and decliners, adherence, and alignment of use with risk, duration, and reasons for discontinuation.

Discussion
Dr. Alan Greenberg, Dr. John Krystal, Council Discussants

Dr. Greenberg said that the Concept is a ‘homerun,’ adding that it is highly innovative approach and one of significance because PrEP has become a cornerstone of HIV prevention, and treatment as prevention. Adding that Dr. Chris Gordon’s expertise in behavioral, biomedical, and HIV prevention interventions is nationally-recognized, he anticipates tremendous research interest and participation on the academic side. He cautioned that sites conducting the implementation research would need to have capacity and infrastructure to conduct the research. Dr. Krystal said that two additional issues might be considered: 1) specific groups where adherence might be difficult (e.g., women, teenagers), and, 2) how to manage risks/benefits of medications in these distinct subpopulations, adding that other issues include the influence on the overall landscape as medications other than Truveda become available, and related financial burdens in developing/developed countries. Dr. Jaycox inquired about the supplement version of the Concept clearance, to which Dr. Chris Gordon said that they will be competitive, and that early thinking was roughly $150K annually (facilitating funding of eight to 10). For clarification purposes, Dr. Gordon explained that NIMH funds administrative supplements provide additional avenues of pursuit and are judged by NIMH staff while competitive supplements are peer review and council approved. Dr. Miller asked if the supplements would be investigator-initiated. Dr. Chris Gordon responded that the strategy is to issue a FOA and put out a call for eligible investigators, reinforcing that collaboration between the research team and PEPFAR sites will be critical.

Dr. Gordon called for a motion to approve the Concept. A motion to approve was passed.

Secondary Data Analysis to Examine Long-Term and Cross-Over Effects of Prevention Interventions

Eve E. Reider, Ph.D.

Dr. Reider explained that the Concept goal was to encourage research that harmonizes and integrates existing early-life prevention intervention trials data sets to improve understanding of risk/protective factors, and their effect (e.g., cross-over, unexpected beneficial) on important mental health outcomes in childhood, adolescent, and young adulthood. She said that not only have data shown that early development interventions can positively affect outcomes like suicide ideation and related behaviors, but also, that there are emerging analytic approaches for integrating and harmonizing these data sets to provide larger sample sizes and increased statistical power for low base rate subgroup analyses. Dr. Reider added that this approach has the potential to address numerous scientific questions, e.g., does targeting common childhood conditions reduce risk for mental health disorders in adolescence or adulthood? Do preventive interventions that focus on decreasing or ameliorating known risk factors like child abuse and neglect, reduce later psychosis and suicide ideation behaviors? Or, do they improve mental health trajectories in racial/ethnic, and sexual gender minority populations? She closed by noting that information provided by this approach might also provide evidence for even earlier interventions targeted to proximal risk factors most likely to affect multiple mental health disorders later in life. Harmonized data sets would be submitted to the NIMH Repository to serve as a community resource.

Discussion
Dr. Cheryl King, Dr. Tami Benton, Council Discussants.

Dr. King expressed strong support for the overall concept but asked if the intended timing for early childhood intervention was too universal and limiting, also noting that important outcomes into young adulthood among higher risk groups such as sexual and gender minority or teens who have experienced sexual or physical trauma. Dr. Reider noted that it pertains to both childhood and adolescent interventions followed over time, and all intervention levels including universal, selected, indicated, and tiered.

Dr. Benton said that the methodology requires a higher degree of expertise, which might limit the investigator pool. In accordance with Dr. King, she thought that the methodology lent itself to universal interventions, stating that most psychopathology studies were shorter and that the FOA would need to include this focus. She also inquired if any consideration had been given to making this a two-pronged process, with the initial FOA focusing on the more complex harmonization. Dr. Reider said that there has been a lot of preparatory work already done in this area, including an NIH meeting focused on methodology and questions, but much more can be done. Still, she believes that the field is ready for these types of analyses, even though it will take a lot of work to harmonize data. Dr. Gordon said that this discussion should serve as a notice to the field that NIMH hopes to begin collaborating in the near future.

Dr. Robinson Beale added one additional modification; to include rural versus urban subsets. She said that data show a higher suicide rate among rural adolescents. Additionally, she asked if recruitment could be boosted by encouraging researchers to collaborate with organizations with built-in access to certain children and adolescent population. Dr. Reider replied that the research uses existing datasets and that no recruitment is involved, adding that there may be value in including these communities in terms of adding to the overall understanding of topic.

Dr. Hogan asked if there was any consideration to approach other Institutions such as National Institutes of Health Information Technology Acquisition and Assessment Center (NITAAC) or National Institute of Child Health and Human Development (NICHD) which are doing similar work. Dr. Reider said that she would be happy to approach them to look at mental health and comorbidities. Dr. Gordon added that NIMH typically seeks collaboration with other Institutes in the development of funding, agreeing that it would be pertinent in this case.

Dr. Gordon then called for a motion to approve the Concept. A motion to approve was passed.

Hybrid Effectiveness-Implementation Clinical Trials to Optimize the Collaborative Care Model for Patients with Opioid Use Disorders and Mental Health Conditions

Michael C. Freed, Ph.D., EMT-B

In April 2018, NIH launched the HEAL Initiative, an aggressive, trans-agency effort to expedite scientific solutions to the current national opioid health crisis. While millions of Americans struggle with opioid use disorders (OUD), and comorbidity with mental health disorders are high, only 20% receive treatment. Dr. Freed said that a large body of evidence supports the clinical and health services outcomes benefits of the collaborative care model, which entails screening for indicated conditions, use of a disease registry, measurement-based care, treat-to-target principals, and patient-provider decision making vis a vis care managers, behavioral health consultants, and other members of the care team. He emphasized that NIH’s interest lies in hybrid effectiveness-implementation research that will evaluate the clinical effectiveness of optimized collaborative care with medication-assisted treatment (MAT) versus standard care or active comparators (most specifically for OUDs, concomitant mental health disorders). Additionally, there is interest in understanding how to best sequence treatment, e.g., treat mental health disorders to determine OUD-related outcomes, and if adoption of these practices will translate into profitable, cost-neutral, or debt-incurring scenarios.

Discussion
Dr. Benjamin Druss, Dr. Michael Hogan, Council Discussants

Expressing his support for the FOA in general and the broader issue of inter-institute collaboration around opioid crisis-related issues, Dr. Druss asked if it would be possible to include inter-specialty mental health settings, primary care and emergency medicine as well as in the public sector where opioid users with serious mental health issues are disproportionately represented. Dr. Hogan agreed that the focus should extend beyond solo practice general practitioners, adding that he believes that an important limitation is that the robust funding package for collaborative care does not lie with Medicare, and that most OUD patients are not in Medicare plans. Dr. Druss noted that when it comes to change, most practitioners ‘adapt, not adopt,’ which is not equivocal to evidence, and wonders if any consideration has been made in that regard. Finally, he recommended research around suicide risk in OUD, noting that roughly one-third of OUD-related deaths are misclassified as ‘accidental’ due to lack of tangible evidence.

Dr. Kilbourne asked if there was interest in estimating cost in terms of the intervention itself and the implementation strategies. Dr. Freed replied that there was interest in getting buy-in from study sites since implementation is a huge factor.

Dr. Saks wondered if it would be useful to consider the concept of supportive decision-making, i.e., patients invite important people in their lives to assist with decisions, noting that not only does this increase numbers of people who are architects of their owns lives, but might hopefully lead to better decisions.

Dr. Robinson Beale noted that when approaching mental health interventions, she always returns to the question of measurement, particularly since it has not been adopted uniformly. She asked if there were any measures directed toward tracking and quantifying psychosocial interventions over time to move the field forward. Dr. Freed said that they were currently working with NITAAC on measuring various outcomes (e.g., real-time measurement of influence of face-time with the provider, or reductions in suicide rates, or abstinence).

Dr. Gordon then called for a motion to approve the Concept. A motion to approve was passed.

Computational Models for Integrative Analysis of Multi-omic and Single-cell Data to Elucidate Cell Type-specific Gene Regulatory Architecture for Mental Disorders

Alexander Arguello, Ph.D.

Dr. Arguello’s Concept focused on encouraging methods to integrate both existing and emerging data sets for molecular expression in the brain at both the tissue and single cells level. He said that historically, cells have been characterized through genes, and the ability to understand the nuances of gene expression has been limited by technology. Moreover, tissue analysis in the normal and abnormally developing brain is limited. Fortunately, advances in analysis of single-cell technologies are facilitating mapping of cellular diversity of the brain at single-cell resolution., e.g., hierarchical isolation and classification of individual cells/cell types into a visual cortex based on patterns of gene expression (Allen Institute). The Broad Institute is similarly measuring gene expression in single cells but using a snapshot approach that allows researchers to reconstruct cell trajectories through their development and as they pass specification decision points on the way to terminal fates and tissues. The BRAIN Initiative Cell Census Network and Human Cell Atlas are all likewise, building comprehensive maps of the body. Dr. Arguello explained that the strategy is to leverage existing and prior investments in tissue-level brain analyses and combine them with emerging single cell datasets, to encourage research methods to integrate data types with the development of computational and statistical tools. The end goal is to produce an aggregated set of resources for the community and then apply them to existing genetic data in order to elucidate the pathogenesis of psychiatric disorders at the cellular level.

Discussion
Dr. Neil Risch, Dr. Christopher Walsh, Council Discussants

Dr. Walsh opened the discussion, commenting on the importance of the work and enabling technology, also noting that RNA sequencing conducted in bulk has disadvantages but can be used to inform single cell analysis and visa versus. Dr. Risch added that this is the next step toward understanding genetic variation and functional genomics. He asked why the focus appeared to be on the computational side versus data acquisition, as there might be some purpose in merging disparate data types. Dr. Arguello said that the strategy was to support single cell analysis in post-mortem tissues, but that the focus was mostly on data analysis and integration; he also said that separate efforts are going toward data generation. Dr. Walsh added that he assumed that there are also efforts underway to supporting technology. Dr. Arguello concurred. Dr. Risch also asked if there were simply not enough people working on the computational side of this type of data and if more infusion was needed. Dr. Arguello said that there was a concerted effort to integrate across different types of datasets in a large-scale systematic manner. Dr. Gordon asked if the tools will be available for use by other researchers. Dr. Arguello said that the goal was to make them openly available as software.

Dr. Walsh then asked if the expression data sets would be sufficiently public in order to attract a broad investigator community. Dr. Arguello said that this was actively being worked on.

Mr. Staglin commented that in addition to all of the reasons stated for doing this, it leverages datasets thereby obviating the need for recruitment (and related time and expenses), resulting in getting results for helping patients faster.

Dr. Gordon then called for a motion to approve the Concept. A motion to approve was passed.

NIH NeuroBioBank

Michelle Freund, Ph.D.

Dr. Freund said that NIH’s NeuroBioBank has been in existence for five years; this Concept focuses on obtaining approval for re-competition/re-solicitation. The Bank comprises six academic settings that are supported through contracts rather than grants, which allows the sites to operate as a unified, centralized resource. Funded by NIMH, NINDS, NICHD, and most recently, by NIA, the sites have postmortem brain collection programs that facilitate collection of 100 brains per year per site representing diverse neurological, neuropsychiatric, and neurodevelopmental cases. Overall, there are currently 15,000 subjects in the database, the program has managed more than 1,200 requests since its inception, filling roughly 80% of them. Dr. Freund said that the Concept goal includes improved efficacy/efficiency, collection of greater numbers of samples, and centralization of certain program components, ultimately to bring all of the sites into the same funding cycle.

Discussion
Dr. Christopher Walsh, Dr. Randy Blakely, Council Discussants

Dr. Blakely said that it is impressive how many researchers use this resource to move into a more translational area, to test a hypothesis around circuitry or a molecule via animal models and then are able to access comparable human samples in the same brain region. He asked Dr. Freund to comment on the communication process between different units, gathering of information about best practices, and how this might impact the RFA. Dr. Freund replied that the six sites are expected to participate in monthly director meetings that are held by teleconference, adding that there is also annual in-person meeting which just took place. She said that there were a lot of growing pains around best practices and standardized protocols, many of these have been resolved. However, she emphasized that the process is not an RFA but an RFP (Request for Proposals and that the Statement of Work is similar to the original one but also reflects substantial changes based on five years of learnings. Dr. Blakely then asked if there has been a review of the collection relative to special populations across the country such as Native populations in the Northwest, that might not be well-represented, and will these be included in the RFP. Dr. Freund replied that there would likely be broad requirements in the Statement of Work, but that there is a breakdown of ages, gender, racial diversity and they have the ability to reach out to the Banks and ask them to make efforts. She also said that the geographical location of the site does not necessarily represent the origin of the brains. She added that they expect that existing contracts will continue but are also holding an open competition; the number of contracts that can be supported relies on the Institute’s contribution.

Dr. Walsh said that given his comments about single cell analysis in humans, the availability of appropriate tissue resources become bottlenecked, and consequently, he anticipates that the program will grow accordingly and exponentially. Dr. Freund replied that they would like to increase the collection yield to over 600 cases annually per site, especially since the collection is depleted in some of the more requested brain tissue types. Dr. Walsh concurred, noting that it will be important to go for volume.

As there were no additional comments or questions, Dr. Gordon called for a motion to approve the Concept. A motion to approve was passed.

Renewal of the Adolescent Brain Cognitive Development (ABCD) Study

Shelli Avenevoli, Ph.D.

Dr. Avenevoli provided a brief overview of the ABCD study, noting that it is a multi-institute, longitudinal study of roughly 12,000 children ages 9-10 followed through early adulthood (20 years) to evaluate factors that influence individual brain development trajectories that might also influence substance use and mental illness onset. Recruitment ends mid-October; most of the participants have arrived through a school-based strategy but there is a subsample of 860 twin pairs as well. She said that the sample represents a diverse population, there are 21 study sites across the country, and the objectives remain the same for continuation. ABCD is funded for five years through 2020 and the request for concept clearance is for renewal. She noted that one of NIMH’s contributions has been to house study data in its archives where interim data on the first 4,500 participants focus on basic demographics, in-depth, behavioral and diagnostic assessments ranging from physical/mental health to substance use and mental illness, and also biological sample collections, and brain images. Interim three- and six-month assessments continue data collection and ensure that participants are engaged.

Trans-NIH Baby Brain Cognitive Development (bBCD) Study

Shelli Avenevoli, Ph.D.

In the interest of time, Dr. Avenevoli transitioned immediately to the Trans-NIH Baby Brain Cognitive Development (bBCD) Concept proposal, which she said overlaps with ABCD. She added that the opportunity to take advantage of potential funding through NIH-HEAL initiative and focus on the long-term brain impacts of prenatal drug and adverse environmental exposures, including health outcomes like substance use and mental illness. She added that bBCD will study brain development from a much earlier age, and potentially, in utero. Additionally, the Concept was developed in the context of the ongoing opioid crisis, focusing on prenatal opioid exposure leading to neonatal opioid withdrawal syndrome at birth, and risk for poor mental health outcomes. Ultimately the goal is to establish a large cohort of pregnant women representative of regions across the nation significantly impacted by the opioid crisis, oversampling substance-using mothers as well as a cohort of non-exposed infants and tease out causality. She noted that the Concept is in its early stages, and that NIDA is hosing two meetings this Fall to obtain expert and stakeholder feedback.

Discussion
Dr. Ian Gotlib, Dr. Tami Benton, Council Discussants

Dr. Gotlib believes that this is a ‘slam-dunk.’ He asked if there had been any consideration to including developmentally-appropriate measures throughout the study’s continuum through late adolescence and early adulthood that might not be captured by ABCD, adding that in his own work on 10-year old daughters of mothers with depression, they have been looking at predictors such as brain function, brain connectivity, and endocrine function. Dr. Avenevoli responded that that was the intent. Dr. Gotlib said that the only thing that he might add for consideration is to incorporating animal offspring model exposure to opioids, noting that this might be useful to tease out early developmental trajectory of brain infants in infants. Dr. Avenevoli thought that was a great suggestion and wanted to assure the Council that there are numerous working groups for all of the assessment components grouped by annual or developmental stage follow up.

Dr. Benton commented that it would be exciting to see the ABCD data used to develop standards of norms that could be used by primary care physicians to identify children earlier who might have ‘fallen off the curve.’ Regarding the bBCD study, she said that she hoped that they take advantage of the opportunity to use advanced neuroimaging and other biological markers during the pre-partum period to study brain development.

As there were no additional comments or questions, Dr. Gordon called for a motion to approve the Concepts. A motion to approve was passed.

Public Comment Period

Dr. Gordon welcomed members of the public or anyone else who would like to speak to do so. Dr. Fuller Torrey had made a request to comment and was invited to the microphone.

Dr. Torrey inquired as to the responsibility of NIMH for drug development, in particular for schizophrenia and bipolar disorder “now that big pharma is pulling out.“ Noting that he had researched the issue and had forwarded a Treatment Advocacy Report to Dr. Gordon that demonstrated lack of activity and funding, and he asked if it was an appropriate consideration for members of the Council. Dr. Krystal said that he agreed with Dr. Torrey that it was a huge challenge, adding that determining the right targets, and getting the correct compounds into the hands of investigators would be a boon to the field. He added that NIMH is working on this. Dr. Gordon thanked Dr. Torrey and Dr. Krystal.

Adjournment

The open session of the NIMHAC meeting adjourned at 12:30 p.m.

As there were no additional comments or questions, Dr. Gordon called for a motion to approve the Concept. A motion to approve was passed.

Closed Session

The grant application review portion of the meeting was closed to the public in accordance with provisions 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 p.m.

Appendix A

Summary of Primary MH Applications Reviewed
Council: September (October) 2018

IRG Recommendation
Category Scored # Scored Direct Cost $ Not Scored (NRFC) # Not Scored (NRFC)
Direct Cost $
Other # Other Direct Cost $ Total # Total Direct Cost $
Research 500 $711,902,463 359 $435,939,102 0 0 859 $1,147,841,565
Research Training 0 0 0 0 0 0 0 0
Career 73 $54,702,396 26 $20,710,358 0 0 99 $75,412,754
Other 0 0 0 0 0 0 0 0
Totals 573 $766,604,859 385 $456,649,460 0 $0 958 $1,223,254,319

Appendix B

Department of Health and Human Services
National Institutes of Health
National Institutes of 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

  • 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
  • Randy D. Blakely, Ph.D. (20)
    Professor
    Department of Biomedical Sciences
    Charles E. Schmidt College of Medicine
    Florida Atlantic University
    Jupiter, FL
  • 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
  • Ian H. Gotlib, Ph.D. (20)
    David Starr Jordan Professor and Chair
    Department of Psychology
    Stanford University
    Stanford, 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
  • David C. Henderson, M.D. (20)
    Chair
    Department of Psychiatry
    Boston University School of Medicine
    Boston, MA
  • Michael F. Hogan, Ph.D. (18)
    Consultant and Advisor
    Hogan Health Solutions LLC
    Delmar, NY
  • Lisa H. Jaycox, Ph.D. (20)
    Senior Behavioral Scientist
    Health Program
    Rand Corporation
    Arlington, VA
  • Cheryl A. King, Ph.D. (21)
    Director
    Mary A. Rackham Institute
    Professor, Department of Psychiatry and Psychology
    University of Michigan
    Ann Arbor, MI
  • 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
  • Gregory A. Miller, Ph.D. (20)
    Professor and Chair
    Department of Psychology
    University of California, Los Angeles
    Los Angeles, CA
  • Yael Niv, Ph.D. (21)
    Associate Professor
    Princeton Neuroscience Institute
    Department of Psychology
    Princeton University
    Princeton, NJ
  • 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
  • Rhonda Robinson Beale, M.D. (19)
    Senior Vice President and Chief Medical Officer
    Blue Cross of Idaho
    Meridian, ID
  • Elyn R. Saks, J.D., Ph.D. Ad Hoc (20)
    Orrin B. Evans Professor of Law
    Gould School of Law
    University of Southern California
    Los Angeles, CA
  • Brandon Staglin (21)
    Director of Marketing and Communications
    One Mind Institute
    Rutherford, CA
  • Christopher A. Walsh, M.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

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

NIMH Staff

Anji Addington
Rajini Agarwal
Alexander Arguello
Ishmael Amarreh
Phyllis Ampofo
Kathy Anderson
Victoria Arango
Shelli Avenevoli
Frank Avenilla
Susan Azrin
Shaunna Bach
A. Beckel Mitchener
J. Borzan
Linda Brady
Alicia Caffi
Holly Campbell-Rosen
Monica Carter
Mindy Chai
Zieta Charles
Mark Chavez
Jay Churchill
Rebecca Claycamp
Claire Cole
Heather Coulter
Bruce Cuthbert
Roberto Delgado
Debra Dabney
Tara Dutka
Greg Farber
Michele Ferrante
Meredith Fox
Michael Freed
Michelle Freund
Julie Frost Bellgowan
Nick Gaiano
Marjorie Garvey
Lisa Gilotty
Miri Gitik
Nitin Gogtay
Chris Gordon
Anna Ordonez

Margaret Grabb
Greg Greenwood
Adam Haim
Wanda Harris-Lewis
Samantha Helfert
Robert Heinssen
Mi Hillefors
Meena Hiremath
Cathleen Hsu
Shuang-Bao Hu
Ann Huston
Terri Jarosik
Tamara Johnson
Andrew Jones
Jeymohan Joseph
Denise Juliano-Bult
Tamara Kees
Ashley Kennedy
Doug Kim
Darnetta King
Megan Kinnane
Susan Koester
Bo Yeon Lee
Thomas Lehner
Tamara Lewis Johnson
Sarah Lisanby
Thomas Lehner
Jane Lin
Amber Linde
Alan Lo
David McMillen
Julie Mason
Doug Meinecke
Enrique Michelotti
Becky Miller
Diana Morales
Sarah Morris
Eric Murphy
George Niederehe
Julia Zehr

Jenni Pacheco
David Panchision
Maryland Pao
Jane Pearson
Michele Pearson
Jonathan Pollock
William Potter
Janani Prabhakar
Beverly Pringle
Diane Rausch
Bruce Reed
Eve Reider
Christian Richardson
Melba Rojas
Mary Rooney
Andrew Rossi
Jamie Rotini
Judy Rumsey
Agnes Rupp
Chris Sarampote
Rachel Scheinert
Michael Schoenbaum
Aileen Schulte
Teri Senn
Pamela Shell
Erin Shannon
Gwen Shinko
Joel Sherrill
Janine Simmons
Dawn Smith
Michael Stirratt
David Stoff
Leandra Stubbs
Brooke Sydnor
Adam Thomas
Ashlee Van’t Veer
Aleksandra Vicentic
Ann Wagner
Abera Wouhib
Yong Yao