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NAMHC Minutes of the 232nd Meeting

National Advisory Mental Health Council Minutes of the 232nd Meeting
September 13, 2012

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

Introduction

The National Advisory Mental Health Council (NAMHC) convened its 232nd meeting in open policy session at 8:30 a.m. on September 13, 2012, in the Neuroscience Center in Rockville, Maryland, and adjourned at approximately 2:15 p.m. In accordance with Public Law 92-463, the policy session was open to the public. The NAMHC reconvened for a closed session to review grant applications at 2:30 p.m. on September 13, 2012, at the Neuroscience Center in Rockville, Maryland, until adjournment at approximately 5 p.m. (See Appendix A: Review of Applications). Thomas R. Insel, M.D., Director, National Institute of Mental Health (NIMH) chaired the meeting.

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

(See Appendix B: Council Roster)

Chairperson: Thomas R. Insel, M.D.

Executive Secretary: Jane A. Steinberg, Ph.D.

  • David Amaral, Ph.D.
  • Virginia Trotter Betts, M.S.N., J.D.
  • Randall L. Carpenter, M.D.
  • Ralph J. DiClemente, Ph.D.
  • Howard B. Eichenbaum, Ph.D.
  • Lisa Greenman, J.D.
  • Steven E. Hyman, M.D.
  • Portia E. Iversen
  • Roberto Lewis-Fernández, M.D.
  • Thomas H. McGlashan, M.D.
  • Steven M. Paul, M.D.
  • Rhonda Robinson Beale, M.D.
  • Carla Shatz, Ph.D.
  • Gregory E. Simon, M.P.H., M.D.

Liaison Representative at the Open Policy Session:

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

Others Present at the Open Policy Session:

  • Alison Bennett, International Neuroethics Society
  • Katie Bess, National Association for Rural Mental Health
  • Christine Cameron, Federation of Associations in Behavioral & Brain Sciences Foundation
  • Yoshie Davidson, American Academy of Child and Adolescent Psychiatry
  • Mark Egan, Alderson Court Reporting
  • Florence Fee, No Health without Mental Health
  • Lara Gregoria, National Eating Disorders Association
  • Ron Honberg, National Alliance on Mental Illness
  • Cecelia Johnson, American Academy of Child and Adolescent Psychiatry
  • Helen Mathas, Grant Group
  • Thomas Mellman, Howard University and the International Society of Traumatic Stress Studies
  • Nancy Moy Yuen, SRI International
  • Wendy Naus, Lewis-Burke Associates, LLC
  • Matthild Schneider, Treatment and Research Advancements Assoc. for Personality Disorder
  • Tanya Shuy, U.S. Department of Education
  • Paula Skedsvold, Federation of Associations for Brain and Behavioral Sciences Foundation
  • Karen Studwell, American Psychological Association
  • Paula Tarnapol Whitacre, Science Writer

Open Policy Session: Call to Order and Opening Remarks

NIMH Director Dr. Insel called the open policy session to order and welcomed everyone in attendance.

Approval of the Minutes of the Previous Council Meeting

Dr. Insel asked the Council members for comments on the minutes from the May 2012 Council Session. Receiving none, the motion to pass the minutes was unanimously approved.

NIMH Director’s Report

Dr. Insel provided an update of activities related to NIMH at the White House, the Department of Health and Human Services (HHS), the National Institutes of Health (NIH), and NIMH levels.

White House Update

In August 2012, the White House issued an Executive Order calling for “Improving Access to Mental Health Services for Veterans, Service Members, and Military Families.” The Administration directs key federal departments, including HHS, to expand suicide prevention strategies and take steps to meet the current and future demands for mental health and substance abuse treatment services for veterans, service members, and their families. Efforts are already underway to address the call for strengthening suicide prevention, enhancing access to mental health care, increasing the number of mental health providers, and promoting research on more effective treatments. The U.S. Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS ) is a joint research effort between the Department of the Army, NIMH, and several academic institutions to identify factors that both protect soldiers’ mental health and those that put a soldier’s mental health at risk. The ultimate goal of Army STARRS is to provide empirical evidence to help the Army develop targeted prevention and treatment strategies.

A future White House initiative from the Office of Technology and Science Policy (OSTP) is focused on neuroscience. Philip Rubin, Ph.D. has been named Assistant Director for Social, Behavioral, and Economic Sciences in OSTP and will lead the initiative and will increase cross-talk among agencies such as the National Science Foundation, NIH, and the Defense Advanced Research Projects Agency. The agencies have proposed the Brain Activity Map project—an initiative to increase our capacity to record from brain areas by three orders of magnitude over the next five years. Specifically, this initiative will encourage the development of new classes of multi-neuron sensors necessary for revealing the large-scale actions of neural processes. Dr. Insel expressed hope that this work could expand exponentially as a Grand Challenge Initiative integrating neurobiology and nanotechnology.

A future White House initiative from the Office of Technology and Science Policy (OSTP) is focused on neuroscience. Philip Rubin, Ph.D. has been named Assistant Director for Social, Behavioral, and Economic Sciences in OSTP and will lead the initiative and will increase cross-talk among agencies such as the National Science Foundation, NIH, and the Defense Advanced Research Projects Agency. The agencies have proposed the Brain Activity Map project—an initiative to increase our capacity to record from brain areas by three orders of magnitude over the next five years. Specifically, this initiative will encourage the development of new classes of multi-neuron sensors necessary for revealing the large-scale actions of neural processes. Dr. Insel expressed hope that this work could expand exponentially as a Grand Challenge Initiative integrating neurobiology and nanotechnology.

HHS Update

On September 10, 2012, the National Action Alliance for Suicide Prevention  released the revised National Strategy for Suicide Prevention. Many stakeholders are coming together to “bend the curve” and reduce the national suicide rate 20% by 2017 and 40% by 2024. NIMH will be deeply involved with the research task force called for in the national strategy. Modeled after the approach that has reduced the rates of homicide and traffic fatalities, the task force will aim to identify the highest-risk groups and develop more effective prevention strategies.

The Interagency Autism Coordinating Committee (IACC) held its first meeting under the Combating Autism Reauthorization Act in July 2012. The IACC discussed the status of autism research and began the planning process for updating the IACC Strategic Plan for Autism Spectrum Disorder Research for 2012.

NIH Update

Regarding the Common Fund, Dr. Insel said that two areas of research have been identified for fiscal year (FY) 2013 funding: expansion of the Undiagnosed Diseases Program  and the Extracellular RNA Communication Program . He reminded Council that Common Fund projects are not disease-specific. Rather, the focus is on tool development and to provide incubator space for a field that has promise, but may have barriers to overcome in order to realize its potential. NIMH serves as co-lead for three current Common Fund initiatives: the Genotype-Tissue Expression Project , the Single Cell Analysis Program , and the Health Care Systems Research Collaboratory Program . Institute directors are meeting to consider a final list of focus areas for FY 2014.

The Advisory Council to the NIH Director (ACD) has three work groups examining critical areas: the biomedical workforce , diversity of the biomedical workforce , and data and informatics  Dr. Insel suggested that these issues be put on the agenda of a future NAMHC meeting, and he briefly highlighted some of the findings related to the demographics of the workforce and career pathways for scientists as they leave postdoctoral training. Dr. Insel encouraged Council members to review reports from each of the working groups, available on the ACD website .

NIMH Update

Following up on Council’s request for a “big picture” view of the NIMH portfolio, Dr. Insel presented a series of slides assessing how NIMH’s funding patterns compare to NIH as a whole, delineating specific areas of research and funding. Slides depicted broad research topics based on algorithms of titles and abstracts of NIH’s entire funding portfolio and illustrated how NIMH research topics relate. Critical details include:

  • In FY 2011, training constituted approximately 3% of the total funds awarded by NIMH; approximately 7% supported research centers; approximately 12% supported the intramural research program; and, approximately 78% supported other extramural research. The percentages are comparable to NIH-wide values.
  • Approximately 12% of NIMH funding supported clinical trials, again in line with the NIH average.
  • Approximately 6.5% of NIMH funding supported health services research—higher than the NIH average of 3.8%.
  • Using the NIH Research Condition and Disease Categorization (RCDC)  coding, the topics that received the most NIMH funding in FY 2009-20011 included brain disorders, behavioral and social sciences, neuroscience, clinical research, pediatrics, genetics, depression, schizophrenia, and basic behavioral and social sciences.

Dr. Insel also discussed NIMH funding by division. The Division of Neuroscience and Basic Behavioral Science (DNBBS) represented 34% of total NIMH funding in FY 2011; the Division of Adult Translational Research and Treatment Development (DATR), 19%; the Division of AIDS Research (DAR) 13%; the Division of Services and Intervention Research (DSIR), 12%; the Division of Developmental Translational Research (DDTR), 11%; and the Division of Intramural Research Programs (DIRP), 11%.

Dr. Insel noted that in FY 2012, the NIMH budget had a 0.2% increase over FY 2011, which is below the rate of inflation. It is expected that NIMH will award about 565 new grants for FY 2012. This estimated number of new grants is consistent with the NIMH average for the past decade overall, and a recovery from the reduction of almost 20% last year. Effort is being made to project how many new grants can be funded, although funding levels for FY 2013 remain uncertain. The implications of managing in uncertain times include reducing out-year commitments and providing Special Council Review (SCR) for research project grants (RPGs) from Principal Investigators who already receive over $1M (direct costs) in NIH funding. Other measures include eliminating meeting support, constraining large and lengthy mechanisms, and maintaining careful stewardship of unobligated balances on funded projects. With flat budgets, nothing new can be added without halting current commitments. Dr. Insel requested Council advice on where the opportunities to grow and to cut might be.

Dr. Insel concluded his report by acknowledging the work of three NIMH scientists who have taken on new positions, and by making note of other staff moves. Jacqueline Crawley, Ph.D., is now at the MIND Institute at University of California Davis. Esther Sternberg, M.D., has joined the University of Arizona’s Center for Integrative Medicine as Director of Research. Alexei Morozov, Ph.D., has accepted a position as Assistant Professor at the Virginia Tech Carilion Research Institute and the School of Biomedical Engineering and Science. Dr. Insel announced that Stefano Bertuzzi, Ph.D., who has led the Office of Science Policy, Planning, and Communications (OSPPC) for the past year, will become the Executive Director of the American Society for Cell Biology in October 2012. Dr. Insel welcomed Susan Amara, Ph.D., who will become NIMH’s new DIRP Scientific Director beginning in January 2013. He noted that searches are underway for an Associate Director for Clinical Research and a Director for the Office of Autism Research Coordination.

Discussion

Steven Paul, M.D., acknowledged the importance of every disorder in the NIMH portfolio. Yet, given the advances in the treatment of HIV/AIDS, he questioned whether in such austere budget times HIV/AIDS should continue to have such a high priority in NIMH funding, or if that funding should perhaps rather go to disorders that have not seen as much progress in treatment.

Steven Hyman, M.D., noted that the Institute Director does not have discretion in the allocation of funds to HIV/AIDS1 National Institute of Allergy and Infectious Diseases (NIAID) has been the lead Institute for research on HIV/AIDS, focusing largely on vaccine and treatment development. NIMH has focused on behavioral aspects of treatment and prevention of HIV/AIDS. Dr. Hyman questioned whether NIAID should now consider supporting behavioral research associated with HIV/AIDS in addition to their current portfolio. He noted that NIMH does not fund behavioral interventions around smoking or other behavioral risk factors or conditions.

Roberto Lewis-Fernández, M.D., said that the issue is obtaining balance of the portfolio. One way to frame the issue, however, is to consider not only the effort behind developing vaccines and treatment, but to also consider the science that enables these discoveries to make a public health impact. In the case of HIV/AIDS, discrimination and social inequalities mean that treatments and behavioral interventions do not reach everybody who needs them in the same way. The question at hand is how much of the behavioral research for HIV/AIDS prevention should be supported by NIMH?

Dr. Paul stressed his point is not that behavioral research on HIV/AIDS is unimportant, but that it is also important to cut the suicide rate by 50%, and to fund other NIMH research priorities.

Dr. Insel said that NIAID Director Anthony Fauci, M.D., sees behavioral research as an essential component of HIV/AIDS research, as the epidemic and the science behind it have changed. He praised Diane Rausch, Ph.D., Director of DAR, and her team, who are working very closely with NIAID. The question now is whether it is time to make structural changes to move funding of behavioral components of HIV/AIDS research into NIAID. However, it should be noted that such a change does not mean that the money allocated within NIMH for HIV/AIDS research could be used for another disorder.

Dr. Paul reiterated he was not addressing the structure but the priority itself, given the current budget and fiscal realities. Science has advanced the treatment of HIV/AIDS to a degree that was not dreamed of 20 years ago, he said, in part because of the efforts of advocacy groups to drive research.

Dr. Insel said that perhaps the Council could assist in determining the future focus on HIV/AIDS program. Dr. Paul and Dr. Hyman both stressed their respect for the work of DAR. Dr. Hyman said he had no doubt the Division could handle the research very well, but instead whether research silos hamper integration of ideas and delay advances in public health.

Retiring Council Members

Dr. Insel thanked retiring Council members for their service and invited them to share their parting observations and comments.

David Amaral, Ph.D.
Dr. Amaral thanked Dr. Insel and other NIMH staff for the opportunity to serve on the Council and to observe the professionalism in ensuring fair processing of thousands of grant applications. Not all of the excellent science proposed can be funded, however, and he expressed hope that the campaign talk of nation-building will result in more funding for research and for adequate incentives for young scientists and clinicians to remain in the field.

He also made comments based on his interest in and advocacy for autism research. He said he has been increasingly impressed with research that indicates links between environmental factors, the immune system, and psychiatric disorders. He encouraged NIMH to foster additional interdisciplinary studies that bring together neuroscientists, immunologists, and even cancer researchers who have had a long history of studying inflammatory processes to establish which environmental factors, and through which mechanisms the environment is contributing to mental health problems. If immunology and neuroscience are brought together, this could have a rapid and profound impact on strategies for preventing and treating mental disorders.

He concluded by praising NIMH for its efforts in fostering scientific careers for young psychiatrists through its summer “boot camp.” He suggested expanding the program to bring basic scientists into the clinic, so that they meet people afflicted with the disorders they are studying.

Ralph J. DiClemente, Ph.D.
Dr. DiClemente said his experience on Council has been gratifying and illuminating, an experience he wished all investigators could have as a look behind the scenes. He said that while systems are important, he wanted to focus on the people, who are competent, committed, and dedicated. He praised Dr. Insel for assembling a talented group, as well as for his leadership and for setting a new agenda for the Institute. He underlined the importance of translational and services science research to ensure that innovations are disseminated. Dr. Insel noted that NIH has created the National Center for Advancing Translational Sciences (NCATS), and Dr. DiClemente said it should certainly be an area in which NIMH is engaged. New models are needed to move products, innovations, and interventions into the community.

Howard B. Eichenbaum, Ph.D.
Dr. Eichenbaum expressed his gratitude for his experience on Council and all who made it pleasant. He referred to a discussion at a previous Council meeting about funding research into the basic functions of the normal human brain. He stressed the importance of this research, noting that abnormalities can be very subtle alterations from normal. Returning processes and functions to normal requires understanding what normal looks like and will require targeted interventions rather than using a “sledgehammer” approach that affects the entire brain. He said he is optimistic about the next level of breakthroughs. He also praised the Research Domain Criteria (RDoC) approach to guide future clinical research.

Portia Iversen
Ms. Iversen said she would focus her parting words on advocacy and stakeholder involvement, as that has been her role on Council. She has been impressed by the level of expertise, knowledge, and capability of the NIMH staff. She emphasized the high level and quality of work program officers do behind the scenes. Recounting her own experience in developing a scientific review board for Cure Autism Now, she realized how little research was going on in the area of autism research. She related the struggles that the parent advocates endured for the first couple of years as they tried to interface with the scientific research community and convey the urgency of the discoveries and treatments needed for children with autism. She recounted how the board developed a two-tiered system of review based on the NIH/NIMH model. In addition, Ms. Iversen asked for Council to receive a more intensive orientation as well as periodic refreshers so that members can provide NIMH with the best possible advice.

Thomas McGlashan, M.D.
Dr. McGlashan said that serving on Council has been a rich and unique experience. Council members are able to use their tenure in science and experience of both success and failure to know quality in the conduct of science and ensure an objective and impartial review process. That said, council members are seldom close enough to an individual project and its original review to spot problems or deficiencies; thus, he stressed the importance of NIMH staff in bringing any deficiencies to the Council’s attention. He urged the staff to use Council liberally as the ultimate witness to the validity and objectivity of the review process.

Steven M. Paul, M.D.
Dr. Paul also expressed his gratitude for the opportunity to serve on Council. He noted his own experience as a fellow and researcher at NIMH, and he said the number one priority in his view is the next generation of scientists. He expressed great admiration for the staff in the divisions and their role in advancing science. He urged them not to lose sight of the purpose of the work—the people and their families afflicted with mental illness. NIMH may be the last best hope for many of them.

Recent Discoveries from the Neurodevelopmental Genomics Project

At Dr. Insel’s invitation, Raquel E. Gur, M.D., Ph.D., the Karl and Linda Rickels Professor in Psychiatry at the University of Pennsylvania, reported on recent discoveries of the Philadelphia Neurodevelopment Cohort, which received funding through the American Recovery and Reinvestment Act of 2009 (ARRA). Dr. Gur and Dr. Hakon Hakonarson are the two Principal Investigators of this collaborative R01 between Children’s Hospital of Philadelphia (CHOP) and the University of Pennsylvania.

The aims of the study are to: phenotype a cohort of 10,000 already genotyped youths ages 8 to 21 and assess behavioral dimensions that indicate vulnerability to major mental illnesses; perform neuroimaging on a subsample of 1,000 participants to establish neural substrates of behavioral phenotypic trajectories; establish gene networks underlying neuronal vulnerability leading to mental disorders; and establish a publicly accessible resource.

Data on sample selection and procedures were detailed in the presentation. Study participants were recruited from a large sample of youths genotyped at the Center for Applied Genetics (CAG), Children’s Hospital of Philadelphia, who met the study inclusion criteria. The investigators conducted a clinical assessment of psychopathology and a computerized neurocognitive battery developed at the University of Pennsylvania.

For psychiatric disorders, endorsement of symptoms associated with phobias, social anxiety, attention deficit, and some oppositional and conduct disorders were notable. The data have been analyzed and have been compared to the National Comorbidity Survey. To consider the relationship between medical and psychiatric disorders, which has not been assessed in epidemiological studies, the team divided the sample into four medical groups, based on their electronic medical records and updated information provided at the assessment. About half of the children are typically developing and are taking no medication on a routine basis; about 2,300 have mild medical disorders that required monitoring but did not affect normal functioning; about 1,700 have more serious chronic disorders; and about 450 have life-threatening illnesses such as cancer. Psychiatric disorders were examined in these four groups. Most notable is that groups with even mild medical disorders have high levels of general anxiety, whereas children who are now stable after a life-threatening illness report less psychopathology, even when compared to typically developing children. This effect may indicate greater mental resiliency after going through adversity.

The computerized neurocognitive battery measured speed and accuracy on domains that include executive function, memory, and social cognition. Dr. Gur presented findings of sex differences and age effects. For example, females outperformed males on measures of attention, memory, and social cognition. Males outperformed females on measures of spatial and motor ability. Regarding age, performance improved with age in all domains, especially in executive function and reasoning. Another component important in performance is within-individual variability. With brain maturation, there should be more evenness in performance, and the data generally confirm this.

Cognitive performance by the four medical groups described above indicated some differences, both in accuracy and speed. Independent of psychiatric condition, youth with significant medical conditions did have some cognitive deficits. However, those with mild medical conditions excelled in intellectual ability and in verbal and nonverbal reasoning, even compared to typically developing youths. This effect may reflect spending more time with adults. All groups with medical conditions showed impairment in social cognition and motor speed. These findings indicate that the psychological and cognitive wellbeing of a child are linked, and should not be overlooked when evaluating children.

Illustrating another finding, Dr. Gur stated that youths with at risk for psychosis who are not help-seeking in this population-based sample already show cognitive impairment, with a pattern similar to that of individuals with psychosis.

The neuroimaging protocol included structural, functional, and perfusion measures. Structural Magnetic resonance imaging (MRI) provides measures of gray matter, white matter, and cerebrospinal fluid; diffusion tensor imaging (DTI) shows white matter and connectivity; and arterial spin labeling provides an absolute measure of how much brain tissue is perfused per minute. Two tests associated with psychopathology were also performed during the functional MRI (fMRI) - emotion identification and the n-back task, a working memory task. Dr. Gur presented data demonstrating the effects of development on the brain, including decreases in gray matter, increases in white matter, and changes in patterns of brain activity. The ability of the individual to activate the appropriate brain circuitry, rather than age, seems to be the moderating variable that drives performance. In addition to the effects of development, sex differences are evident.

These multi-modal neuroimaging, neurocognitive and psychopathology data enable examination of brain maturation in typically developing youths and those with early indications of mental illness. By integrating this data with genomics, researchers can look at brain-behavior dimensions as envisioned by RDoC in hypothesis-driven studies.

The major effort now is in data analysis. Collaboration with intramural and extramural researchers has already begun. Among participants, those showing psychosis proneness are assessed longitudinally every two years.

Dr. Gur concluded by thanking NIMH, collaborators, and the children and families who participated.

Discussion
After thanking Dr. Gur, Dr. Insel referred to an earlier discussion Council had in the study’s infancy, saying that while it is still a work in progress, he wanted everyone to get a first glimpse of the early results. He noted that this is more than a research project; it is actually a rich resource with future opportunities for others to study the data.

Dr. Amaral praised the study and asked about the potential for diagnostic use of the data in the clinic in future years. Dr. Gur said that from the beginning, the study was organized with signed consent from the participants and parents for future contact. She said that they have been successful in maintaining this connection with the families. Dr. Gur said that the data will be available for other investigators, and that the study team welcomes collaboration.

Paolo del Vecchio, M.S.W., reported another recent study from Children’s Hospital in Philadelphia that shows a 62% increase in the use of antipsychotic medication among children receiving Medicaid, with 65% of the prescriptions for off-label use. The Substance Abuse and Mental Health Services Administration (SAMHSA) has been working with the Administration of Children, Youth and Families and the American Academy of Child and Adolescent Psychiatry to address potential overuse of antipsychotic medications in pediatric populations. Mr. del Vecchio also referred to a joint study with NIMH to look at U.S. prescription practices and encouraged more of these partnerships.

Dr. Paul remarked that the DTI data with respect to gender were particularly striking. He asked if these gender differences are also observed in adults. Dr. Gur noted that most studies have had relatively small samples, and that sex differences have not been examined in that way. Dr. Insel commented that the effect size of this study is truly remarkable (having made an earlier reference to the 10,000 electronic medical records that have been gathered for this study).

Ms. Iverson commended Dr. Gur, particularly on how the data will be shared, asserting that this study will potentiate discoveries and treatments at a much more rapid rate as a result. She noted the study seems congruous with RDoC in that there is a wealth of data to make diagnosis more scientific. She suggested the DTI could also be used for disorders such as autism as both a diagnostic tool and as a means for tracking any changes that occur with specific interventions. Dr. Gur indicated that they are doing a pilot study for the children with psychosis risk using a social cognition intervention to see what strategies might work.

Carla Schatz, Ph.D., expressed enthusiasm for the coordination of the genomics study. She also expressed the hope that comorbidity with a range of disorders, such as diabetes, would be included within the context of the general study.

Dr. Insel reflected on the size of the effects for gender and age with this study and applauded Dr. Gur for this level of analysis. Dr. Insel pointed to this study as an example of what ARRA has made possible in a very short time, reminding Council that this grant application was funded just three years ago, and that already a wealth of data has been established.

Dr. Hyman said these studies illustrate the importance of unbiased, technology-based searches. He conveyed the importance of moving beyond the constraints of narrow models for finding the right balance between unbiased tool-driven approaches with adequate sample sizes, which will then generate new hypotheses for more traditional approaches.

Division of Services and Intervention Research (DSIR): Portfolio and Priorities

Noting Council’s request for delving deeper into review of the divisions’ performance, Dr. Insel turned the discussion over to Robert Heinssen, Ph.D., A.B.P.P., the Director of DSIR. Dr. Heinssen provided an update on how the Division has put recent Council’s workgroup report recommendations into practice. Specifying that much of the science moving through the translational pipeline eventually comes to DSIR, he said the Division’s goal is to improve mental health at both individual and population levels. This goal is accomplished through research that enhances the effectiveness of day-to-day clinical practice and the quality of the overall care system. He further emphasized that DSIR-supported research seeks to improve the way treatment is conducted in the U.S., with the goal of better outcomes for all individuals who require mental health services. Representing about 12% of the NIMH budget, DSIR’s total amount of funding has remained stable over time, but distribution has shifted in response to Council’s workgroup reports. As the Institute has moved away from large practical clinical trials, funding in interventions research has lessened while funding in the services research has increased in response to the 2006 Council workgroup report, The Road Ahead.

The Adult Treatment and Preventive Intervention Research Branch focuses on studies that refine treatments of known efficacy in order to maximize their effectiveness in real world settings. Comprising 46% of DSIR’s research budget, the overall goal of this branch is to enhance the efficacy signal of promising interventions while adapting them for implementation in real world settings. Another 46% of the DSIR budget is devoted to the Services Research and Clinical Epidemiology Branch, which focuses on strategies for dissemination and broad implementation of evidence-based services, as well as sustainment of high quality interventions in service systems over time. The overriding goal of this branch is transformation of the current mental health service system into a learning health care system that continually aspires to improved outcomes. Complementing these two branches is the Clinical Trials Operations and Biostatistics Unit, which covers the remaining 8% of the DSIR budget. This branch provides expertise on the management of clinical trials to all divisions throughout NIMH in the areas of best practices for clinical trial operations, data and safety management, preparation of public use data sets, and distribution of archived data sets from completed trials.

Guidance from NAMHC, in the form of The Road Ahead report, has encouraged DSIR to focus research attention on significant public health problems such as suicide prevention, reducing medical comorbidities and early mortality among persons with serious mental illness, and preempting disability among adolescents and young adults experiencing a first episode of psychotic illness. The Road Ahead further encouraged DSIR staff to be proactive in engaging stakeholders at all levels - consumers, family members, clinicians, administrators, and the Institute’s federal partners – to identify research opportunities likely to inform both practice and policy decisions. In the subsequent 2010 From Discovery to Cure report, Council recommended a new approach to NIMH interventions research, with greater attention to early phase trials that emphasize target engagement, pathophysiological mechanisms, and experimental medicine methods. While suggesting that these changes require a reallocation of resources towards the earlier stages of intervention development, the Council recognized that under certain circumstances, effectiveness trials are necessary to address pressing questions regarding clinical practice. This guidance has stimulated decision rules to guide consideration of proposals that seek to optimize existing treatments. However, two broad follow-up questions remain: which studies are likely to produce significant public health impact, and what is the best mix of NIMH-requested versus investigator-initiated research for completing these studies?

To address these key questions, DSIR now examines the intersection of population characteristics, the effectiveness of existing interventions, and the needs and interests of key stakeholders. The Recovery After an Initial Schizophrenia Episode (RAISE) initiative illustrates how alignment of population, treatment, and stakeholder factors can inform the development of a potentially high impact, policy-relevant intervention research study. In the case of RAISE, the rationale for the comparative effectiveness trial is based on evidence that (1) duration of untreated psychosis is a modifiable risk factor for disability in schizophrenia; (2) persons experiencing a first episode of psychosis are quite responsive to available pharmacologic and recovery-oriented interventions; and, (3) multiple stakeholders and policymakers desire better long-term outcomes for persons with serious mental illness. The RAISE trial tests the feasibility, practical implementation, clinical impact, and cost-effectiveness of selective prevention approaches for improving functional outcomes in schizophrenia. This comparative effectiveness study involves 403 participants from 34 clinical sites across 22 states, and tests the overall impact of phase-specific specialty care versus standard treatment offered in typical community settings.

A number of partners have been involved in RAISE from the start – SAMHSA, the Social Security Administration and the Centers for Medicaid and Medicare Services (CMS) – who are interested in a variety of outcomes, such as recovery from psychosis, work entry and sustained employment, and opportunities to achieve better clinical outcomes and reduce the cost of care. The RAISE trial will take five years to complete, so keeping stakeholders engaged over time presents a challenge. Regular briefings to all three agencies about study progress, with updates on the scientific evidence supporting early and coordinated care for first episode psychosis, have been effective for maintaining stakeholders’ interest. Based on success with RAISE, DSIR is planning other high-impact initiatives in areas where population characteristics, intervention opportunities, and policy interests align around problems of public health significance. Examples include suicide prevention in emergency medicine settings and improving physical health and reducing mortality among people with serious mental illness.

In approaching these areas of study, the question is raised as to the best mix of NIMH-requested and investigator-initiated research. Looking at the various funding mechanisms reflecting different levels of programmatic involvement, in FY 2011 about 60% of the DSIR portfolio was comprised of investigator-initiated projects, 30% were grants that responded to NIMH-wide program announcements, and 10% were cooperative agreements or contracts. A possible rebalancing for the short term may be to allocate about one-third of DSIR investments to contract activities and cooperative agreements, one-third to research project grants that respond to DSIR-relevant program announcements, and one-third to an “incubator space” reserved for investigator-initiated ideas. Dr. Heinssen asked for Council’s feedback and guidance as to whether DSIR has met the mark in responding to the 2006 and 2010 Council reports, or if anything has been missed. Finally, he asked if DSIR staff should require that future proposals be justified in terms of public health significance and potential for population health impact.

Discussants
Gregory Simon, M.P.H., M.D., said he agreed that the scientific program staff should be more directive to make the best use of the investment. He suggested strategizing a balance between large, long-term studies of multi-component interventions, which are sometimes necessary, versus more targeted and focused studies addressing a specific question. The program staff has a key role to play in considering the public health impact and state of the science.

Dr. Simon said that science is moving into an era that is more about the heterogeneity of effects – spanning the range from neurobiology to sociology. He said there is interest in heterogeneity within individuals, across individuals, and between groups of individual, requiring a systematic view. He indicated that this systematic view involves clarity regarding the right methods for studying heterogeneity and clarity when considering how studies will be designed and the data analyzed. The targets and signals that can provide answers to patients, providers and health systems about whether a treatment is working are also critical for effectiveness, and are of importance even for health services researchers to consider. Pointing to the tendency, particularly in services intervention research, to favor studies that will generate successes, Dr. Simon stressed encouraging “instructive failure.” Some research projects might not work, but learning why they do not work generates knowledge.

Rhonda Robinson Beale, M.D., spoke from the perspective of a health plan and service administration that insures 43 million people in the United States and another 9 million worldwide. Her company’s clinical technology assessment committee uses a process to review new research and technologies to determine whether or not the evidence supports insurance coverage, as well as to develop level of care guidelines and medical policies and contracts with providers.

Health plans are looking at the changes that health care reform may bring about, such as ways to differentiate providers based on their performance. One way her company does this is to “tier the network.” A simple system for outpatient care is based on an algorithm that considers global distress, risk factors, and costs to develop ratings. The system increases referrals to those who have a higher rating.

Health care systems also examine how individual providers function within the system and issues of accountability. Dr. Robinson Beale said that her company is stimulating systems of care to combine and work together, so that once providers see a patient, they share in the accountability of what happens to him or her. Eventually, they hope to create “centers of excellence”, starting with eating disorders. These centers of excellence are organizations of care that can deliver the best outcomes in a way that is transparent both to providers and consumers.

Dr. Robinson Beale concluded with recommendations related to the DSIR portfolio and research priorities:

  • Conduct an annual forum to include health plans and health systems (including states), in order to receive feedback from the “real world” in terms of gaps, to disseminate relevant research findings and proven outcomes, and to communicate progress toward closing evidence gaps
  • Align directed research to address gaps in evidence so that technologies move to a level considered to be proven more quickly
  • Support overlapping research in areas of concern to achieve proven, consistent outcomes
  • Require standardization where it makes sense to address comparative effectiveness
  • Become the independent entity to conduct non-biased testing of devices to bring credibility and rigor to an area typically subject to scrutiny

General Discussion
Dr. Insel opened the floor to further discussion. Dr. Hyman said the issue of duplicative research versus what is necessary for replication has become very pressing, particularly where there have been failures to replicate published preclinical studies. He said it is important to think about this as policy and review issues, and to consider the decision rules for determining the need for replication studies. Dr. Insel said replication was the topic of a meeting sponsored by the National Cancer Institute (NCI). A point made at the meeting by those in the biotechnology sector is that reimbursement for diagnostics will trump the reimbursement for therapeutics, and we need to be thinking about how to confirm or show what is worth paying for in the diagnostic space.

As a topic for the next Council meeting, Virginia Trotter Betts, M.S.N., J.D., suggested a discussion of the trajectory of NIMH funding and whether the public health-focused research supported by DSIR receives sufficient funding. She also noted that the points made by Dr. Robinson Beale are the same issues that mental health commissioners are discussing with Medicaid commissioners and with the individuals who will be running the state health insurance exchanges under health care reform. A huge area of discussion among these groups involves the delivery of care to people who are often poor and disenfranchised. Service providers are often compromised by low reimbursement rates, making it difficult to attract people to these professions.

Briefing Update: Research to Improve Health and Longevity of People with Severe Mental Illness (SMI)

Dr. Lewis-Fernández co-chaired a recent trans-NIH meeting to address premature mortality in people with SMI, often caused by conditions for which proven interventions exist. Trans-Institute collaboration and the involvement of many stakeholders are needed to identify and bridge the gaps in research.

The meeting included presentations and discussions to review current knowledge of health interventions effective in the general population; to identify knowledge gaps in health interventions for people with SMI, including factors unique to racial, ethnic, and gender groups; to target strategies to reduce early mortality and the research needed to expedite widespread delivery of interventions; and to discuss platforms and context for future research.

Dr. Lewis-Fernández discussed the major pathways that lead to poor health outcomes among people of low socioeconomic status, and by extension most of those with SMI. These pathways include environmental resources and constraints that lead to differential access to services, psychological influences that relate to health behaviors, and allostatic load - the body’s ability to adapt to stressors such as poverty and discrimination.

The four types of common modifiable health risk considered at the meeting were: tobacco and other substance abuse; poor diet, lack of exercise, and obesity; metabolic syndrome and diabetes; and hypertension and high cholesterol. Many of the basic elements of interventions to reduce or eliminate these risks are known, such as reducing polypharmacy and considering treatments with fewer adverse metabolic side effects. Many interventions, when done singly, have modest effects. Determining the right combination of interventions, particularly for people with SMI, is difficult. Complicating this determination is the Limited data available on the impact of factors such as race, ethnicity, and gender on the successful implementation of interventions or elucidating biological mechanisms. The meeting participants also discussed effective yet practical delivery models and strategies for coordinating primary and mental health care.

For next steps, a multi-stakeholder approach is needed, including many NIH Institutes and other agencies, states, consumers, and families. This approach could take the form of a Common Fund initiative related to multiple comorbidities. Dr. Lewis-Fernández suggested that Council discuss whether this initiative would be a good way to move forward to address the public health crisis of early mortality for people with SMI. More generally, questions include how to elevate the priority of the problem and whether funds should be dedicated to this initiative. Another question raised was about focusing on targeted populations, such as consumers who are Medicare and Medicaid eligible and represent a high cost.

In terms of research, a two-track system was proposed: developing and testing new approaches with an eye toward clinical rather than statistical significance, and leveraging existing “natural experiments” already being carried out by states, insurers, and others. One discussion topic was the notion of a time-sensitive mechanism for grants to take advantage of these ongoing efforts. Other suggestions included a meta-analysis of existing data sets. Longer-term strategies were suggested to look at heterogeneity of outcomes and clinical significance of interventions to reduce common modifiable health risk factors.

Dr. Insel thanked Dr. Lewis-Fernández and introduced Susan Azrin, Ph.D., Chief of the Primary Care Research Program in DSIR. Dr. Azrin presented a concept for a potential future NIMH funding initiative.

Improving Health and Reducing Premature Mortality in People with Severe Mental Illness 
Dr. Azrin described the goal of this potential initiative as providing support for research on service interventions that demonstrably reduce the prevalence and magnitude of modifiable health risk factors related to shortened lifespan of people with SMI. The research generated would address how to adapt effective strategies to reduce risk factors for people with SMI; how to expand service delivery capacity to reach the largest number of people with SMI; and what strategies can best improve implementation of effective health interventions for people with SMI.

Discussion
Ms. Iversen noted that many people with SMI are isolated. She suggested a component about case management, tracking, and personal contact.

Dr. Paul asked whether demonstration projects were taking place to intensively treat and follow up with a subgroup of patients. Dr. Lewis-Fernández said that, based on what was presented at the meeting, the results have been modest, but the focus is often on statistical rather than clinical significance, so participants are not followed long enough to know the effect on mortality.

Dr. Insel said there is also interest in this topic in Scandinavia and the United Kingdom, but even with access to treatments, the comorbid conditions are difficult to treat. He noted NIMH is currently funding 27 studies related to SMI and and premature mortality, but the question from the meeting is whether there is a way to do more, and with more accountability, to close the gap.

Ms. Trotter Betts asked if representatives from CMS were at the meeting. As she noted, reducing mortality is cheap but reducing morbidity leading to mortality is expensive, and payers must be at the table, especially with the impact of the Affordable Care Act on states. Philip Wang, M.D., Dr. PH, NIMH Deputy Director and Acting Scientific Director, commented that CMS is looking at preventative services through their Innovation Center. Dr. Insel agreed with the importance of getting CMS involved. Mr. del Vecchio said SAMHSA has been working with CMS on a home health initiative that integrates care.

Priorities for Developing New Interventions

Dr. Insel introduced Bruce Cuthbert, Ph.D., Director of DATR. Dr. Cuthbert said his presentation was based on the work and thoughts of the NIMH leadership and many program staff colleagues on novel targets and how to evaluate them. His presentation also drew on a 2010 Council Workgroup report about how to foster more efficient drug development, as well as non-pharmacological treatments, for more personalized treatment for mental illness.

For heart disease, a combination of factors has resulted in a marked decrease in deaths since 1970. In contrast, treatment for mental illness tends to be trial and error and is not based on knowledge of mechanisms, with no cures or vaccines available. The bottom line is that neither the prevalence of mental disorders nor mortality associated them has decreased, despite some promising research. Moreover, investment in psychiatric drug development has decreased in the last several years.

Dr. Cuthbert explained the concept of a “fast-fail” paradigm, as developed by Dr. Paul and others. Traditional drug development has tended to follow preclinical to clinical pathway with an emphasis on trials with humans in relatively large phase II studies. Yet by phase III, there have been expensive and embarrassing failures. In contrast, a “quick-win, fast-fail” approach means more work in preclinical development (made possible through high throughput screening and other approaches) and early (phase I and IIa) trials in humans, to develop proofs of concept. More will fail at the onset, but when a drug does emerge from early clinical trials, it has a better probability of ultimate success.

Given this general approach, figuring out the objective of new treatments has been another part of the problem. A marketed psychiatric drug is efficacious, on average, in only about half the patients who take it; one reason, he posited, is because of artificial grouping of heterogeneous syndromes with different pathophysiological mechanisms into one disorder. The ultimate goal is for clinical trial design and patient segmentation to improve to the point of matching disease phenotypes to circuit-based deficits. The Research Domain Criteria (RDoC) matrix presents a way to improve precision medicine. He expressed hope that RDoC will provide better avenues to get more specific circuit-based measures to develop interventions through the “fast-fail” approach.

In the classic sense of pharmaceutical development, the term “target” refers to molecular targets, such as a receptor or an enzyme. Additional targets include functional targets - or a measurable change in a brain function - which may or may not be related to clinical outcomes. Clinical targets represent a change in measures of an actual clinically-relevant construct.

Targets are seen as relevant for all new treatments in all domains, and the ability to look at precise treatment targets is important across all areas of new treatment development. The core of this experimental approach is: given that most drugs and other treatments will not succeed, it is better to “fail fast and fail often” and to move on quickly, while also learning from the failure. Focusing on phases 0 through IIa, the first step is to demonstrate target engagement, rather than jumping forward immediately and hoping for efficacy.

Dr. Cuthbert said that implementing this approach first involves replicating key early findings. It would also place great emphasis on rational rescuing and repurposing of drugs, and NCATS now has a program in this area. Data-sharing is critical, including the failures from which to learn. Finally, there would be renewed emphasis on more efficient trials, especially those conducted at NIMH.

NIMH has issued a contract solicitation called Fast-Fail Trials or “FAST contracts.” Three announcements have been issued through FedBizOpps on autism spectrum (FAST-AS), psychotic disorder spectrum (FAST-PS), and mood and anxiety spectrum (FAST-MAS). He acknowledged the hard work not only of the program staff, but also of staff members who developed these new contracts. The contracts are under final review. One of the key aspects of the FAST initiative is to line up the research with RDoC to cut across traditional diagnostic categories.

As discussed at the May Council meeting, a Council workgroup will be convened to advise Council on how to identify the best targets and trial designs. The workgroup will be co-chaired by Dr. Paul and Dr. Hyman and coordinated by DATR Deputy Director Jill Heemskerk, Ph.D. The workgroup will include Council members, outside consultants, and principal investigators who receive FAST contracts.

Discussion
Dr. Hyman noted that he, Dr. Paul, and NIMH staff members have begun talking about the workgroup, but parallel efforts will also be needed. Pharmaceutical companies say that drug development is affected by a lack of validated targets, so the question is how to validate a target. Another issue is that animal models do not tend to predict efficacy. A third issue is the difficulty in conducting a proof of concept trial without biomarkers and with disorders of waxing and waning symptoms or symptoms that are context-dependent. He praised the RDoC approach.

Dr. Insel noted that NIH has launched a microphysiological systems program with DARPA and the Food and Drug Administration (FDA). The five-year effort brings together research experts, mostly engineers, to consider how to use microfluidics and other new systems to build human tissues in chips for high-throughput screening. Dr. Hyman stressed the importance of understanding molecular mechanisms, and not behaviors in rodents or other model animals that some theorize to resemble a human behavior.

Dr. McGlashan asked if deficit psychopathology is an RDoC domain, which he said is key, especially with psychosis. Dr. Cuthbert said deficit psychopathology is covered in the RDoC matrix in areas such as motivation, brain arousal systems, and approach motivation systems. The challenge is to think about basic brain circuits and what the brain has evolved to do normally, and then to figure out what goes wrong in these basic systems.

Ms. Iverson said it is destructive to place some of the best and cutting-edge science into the silos of descriptive categories, as has been done with some autism research.

Dr. Simon noted many people who live with chronic mental health conditions have taken a number of different medications and had variable experiences. He suggested looking at patterns of experience that are particularly informative or identifiable patterns of failure and success from which to learn. Dr. Hyman said it will be hard to find patterns until there are some real markers and a better diagnostic approach, which is why RDoC is so important.

Dr. Insel asked if other Council members would like to be part of the workgroup. Ms. Iverson, Dr. McGlashan, and Dr. Carpenter agreed to serve.

Concept Clearances

Building an Evidence-Based Response to Disaster and Mass Trauma Events
Dr. Insel introduced Farris Tuma, Sc.D., who also presented on behalf of Susan Borja, Ph.D., both from DATR. This initiative seeks to leverage the existing disaster response infrastructure and workforce to integrate evidence-based and promising interventions into current mental health response. Partnership between researchers and disaster response providers will enable individuals in the field to plan, in advance of large scale emergencies, rigorous intervention and services research studies to improve care for new and complex mental health needs in the wake of disasters. Major research and public health questions to be addressed by this initiative include: (1) whether a broader range of services can reduce severity and/or duration of common adjustment problems and better address needs of those with pre-existing conditions; and, (2) whether there are long-term benefits (health/mental health co-morbidity, occupational/economic functioning, family/parenting, etc.) of early assistance programs.

Leadership from the majority of federal and non-federal emergency response resources deployed following disasters have partnered to establish a work group to address this issue. The work group includes the U.S. Department of Health and Human Services’ Assistant Secretary for Preparedness Response, the Office of the Assistant Secretary for Health/Division of the Civilian Volunteer Medical Reserve Corps, the National Institutes of Health, the Federal Emergency Management Agency, the Administration for Children & Families, the Substance Abuse and Mental Health Administration, and the American Red Cross. Cooperation among the partner organizations provides an opportunity to learn about the utility of existing disaster mental health response programs in comparison to promising newer strategies for identifying and intervening with high risk survivors, and integrating standard evidence-based services into programs that currently fail to address clinical needs in the first few months after a disaster. The goal of this partnership would be to plan for and then systematically examine screening, counseling, referral, and care as usual; standard evidence-based treatments; emerging and promising early-intervention models; and technology-based approaches to screening, referral, and treatment.

Ascertaining Critical Transitions in Eating Disorders
Julia Zehr, Ph.D., from DDTR, presented on behalf of Mark Chavez, Ph.D., from DATR, and Marjorie Garvey, Ph.D., and Shelli Avenevoli, Ph.D., both from DDTR. The initiative aims to support research that will advance our understanding of the biological mechanisms underlying eating disorders by studying periods of transition.

Eating disorders are associated with high morbidity and mortality, as well as with frequent relapse after treatment. Clinical presentations of eating disorders are highly heterogeneous, and individuals diagnosed with eating disorders often have significant comorbid psychopathology (e.g., anxiety, depression, substance use, suicidality, and personality disorders), in combination with physiological, endocrine, and metabolic dysregulation. Research into eating disorders has identified disruptions in a variety of functional domains, including reward systems, cognitive function, and behavioral regulation. In particular, recent findings on neurobiological dysregulation of distinct circuits suggest that multi-dimensional approaches to measure brain-behavior relationships are timely and scientifically tractable ways to advance our understanding of biological mechanisms contributing to this group of disorders.

Transition periods are likely to provide unique insights into brain-behavior associations; may help separate state from trait measures of psychological and cognitive processes in disordered eating behaviors; and may help optimize the timing of intervention. For this potential initiative, transitions may include those during development (e.g., puberty, menopause); during clinical course (e.g., adaptive to maladaptive dieting, sub-threshold to threshold clinical symptoms); or over the course of treatment (e.g., illness to recovery, recovery to relapse). This initiative would encourage researchers to test integrative models and mechanisms incorporating biological, behavioral, and experiential factors during these transitions.

Cognitive Training Resource Exchange (CogTREx)
Dr. Insel introduced Ann Wagner, Ph.D., from DDTR, who represented a team of nine NIMH staff working on this concept. She referred to a previous Council presentation about a workshop on cognitive training (CT) interventions for mental disorders. The workshop highlighted some promising research, although most of this work is in the early development stages. A recurrent theme was the need to share information, tools, and resources among investigators.

This initiative aims to create an online site for the exchange of information and tools developed in collaboration with, and accessible to, researchers engaged in the development and testing of CT interventions. The site may include: a registry of studies, searchable on key study elements (e.g., age, diagnosis, domains of functioning, circuits targeted); assessment tools, forms, procedures, and associated data dictionaries; and publications and meeting abstracts resulting from studies, including negative results. CogTREx aims to facilitate the more rapid translation of emerging findings on the neuroscience of mental disorders into interventions targeting the neural impairments underlying mental disorders.

Discussion
Ms. Iverson said she hoped that the exchange could involve neuroimaging data, such as the data collected in the project reported by Dr. Gur. Dr. Robinson Beale said she hoped the structure could be applied to other areas, as a learning environment.

Emergency Department (ED) Suicide Prevention in Youth
Dr. Insel introduced Amy Goldstein, Ph.D., from DSIR, who spoke on behalf of collaborators Jane Pearson, Ph.D., Ben Vitiello, M.D., and Joel Sherrill, Ph.D., all also from DSIR. Suicide continues to be the third leading cause of death among youth aged 10-24 years old. Emergency Medicine Department practitioners are responsible for risk assessment, discharge, and referral of high risk suicidal individuals, yet no evidence-based standards exist for these practices. This initiative aims to support research to improve identification, evaluation, and appropriate referral by ED staff of youth at risk for suicide. This research will lay the foundation for future efforts to match appropriate interventions to at-risk youth, to increase intervention effectiveness, and to improve long-term clinical outcomes.

Discussion
Dr. Insel noted this concept falls into the broader strategy discussed earlier around suicide prevention. Dr. Lewis-Fernández expressed support for the importance of the topic, and underscored the need to recognize the strong racial-ethnic variations that exist in terms of suicide prevention and behavior. Dr. Goldstein replied that these issues would be considered. Ms. Trotter Betts cautioned that although an algorithm might be determined, implementing it in already overwhelmed hospital emergency rooms might not happen. Dr. Goldstein said the research would build on the Emergency Department Safety Assessment and Follow-Up Evaluation taking place with adults at eight hospitals. The emergency departments are asking if they can use the screening instruments for adolescents, so the interest exists. Dr. Insel added it is important to build in follow-up after the emergency room visit. Dr. Robinson Beale suggested involving health plans and organized managed health care organizations. Ms. Iverson pointed out that a screening tool would be useful for camps, schools, and other settings.

Leveraging American Recovery and Reinvestment Act (ARRA) Resources to Accelerate Research on Neurodevelopment
Dr. Insel introduced Shelli Avenevoli, Ph.D. from DDTR, who acknowledged the other five members of the NIMH team who worked on this concept, which involves two ARRA projects focused on neurodevelopmental genomics, including the one presented earlier by Dr. Gur. The goal of this concept would be to stimulate the broader research community to use the resources created under ARRA for secondary analyses to develop and test hypotheses; to establish associations among genetics, brain anatomy, and brain function; and to evaluate the combined and interactive influences of these factors on mental illness during development. The expected outcomes would include advanced knowledge in high-priority areas, broader dissemination, and advanced methodology to integrate across data modalities and levels of analysis. They would hope to foster collaboration between the original PIs and other investigators, including early-stage investigators.

Discussion
Dr. Shatz praised the idea and suggested reaching out to other major initiatives that are also gathering enormous amounts of data on normal development and on mental disorders. Dr. Insel asked for Council’s suggestions about who could be involved and how to build out the initiative.

Gut Microbiome-Brain Interactions in Mental Health: Implications for Mental Disorders
Dr. Insel introduced Nancy L. Desmond, Ph.D., DNBBS, who also spoke on behalf of Susan Koester, Ph.D., DNBBS, Roger Little, Ph.D., OSPPC, and Aleksandra Vicentic, Ph.D., DNBBS. Dr. Desmond said that this concept addresses microbes within the human body, which outnumber cells in the body by an estimated ten to one. What is known to date comes from the NIH Common Fund Human Microbiome Project  and similar studies in other countries, recently published papers, and the development of metagenomic tools. Recent studies from European labs suggest the gut microbiome affects brain development and behavior.

The goals are twofold: (1) to facilitate collaboration between microbiome scientists and neuroscientists to study microbiome-brain interactions relevant to NIMH’s mission, and (2) to stimulate investigator teams to explore mechanisms by which the microbiome influences brain structure, function, and behavior during pre- and post-natal brain development, including placental influences. The outcomes would begin with a workshop to discuss gaps, any low-hanging fruit, and priorities, and ultimately to figure out if and how the microbiome is modulating development and susceptibility to disorders.

Discussion
Dr. Insel noted that this concept fits in the category of an area not yet represented in the portfolio, but that it represents a new opportunity. Dr. Hyman said interest in this area is burgeoning, although it remains highly speculative. He observed the potential connection with the previous concept on eating disorders. Dr. Shatz said this is a far-off area now, but it could be one in which NIMH takes a lead. It is also interesting in terms of bringing together other Institutes and disciplines.

PsycENCODE: Exploring the Functions of Non-Coding Elements in the Brain
Dr. Insel introduced Patrick Bender, Ph.D. DNBBS who spoke on behalf of Andrea Beckel-Mitchener, Ph.D., DNBBS, and Thomas Lehner, Ph.D. Office of Genomics Research Coordination. This initiative aims to support studies on mental disorders based on new concepts of transcriptome complexity that assign functional roles to non-coding and potentially novel coding transcripts, exploring their potential as trans-regulators of gene transcription, mRNA splicing, mRNA stability, molecular transport, and influence on chromosome architecture.

Using Collaborative Care to Reduce Racial and Ethnic Disparities in Mental Health Care
Dr. Insel introduced Pamela Collins, M.D., M.P.H., to speak on behalf of a team that included Su Yeon Lee, Ph.D., and Robert Mays, Ph.D., both from the Office for Research on Disparities & Global Mental Health (ORDGMH), about a concept concerning evidence-based interventions to reduce ethnic and racial disparities in mental health care. The goal is to support innovative research on the implementation of a package of evidence-based interventions to reduce disparities in mental health among diverse racial and ethnic minorities in the U.S. Areas of interest include: research that identifies and studies the implementation of key components of collaborative care that can increase assess to, and engagement and retention in, mental health services for mood and anxiety disorders; and effectiveness studies on the implementation of evidence-based interventions that can increase the likelihood of improved clinical, functional, and economic outcomes for members of diverse groups.

Discussion
Dr. Insel noted that the Institute wants to take a more proactive stance on what is the huge public health issue of reducing racial and ethnic disparities in health care. Dr. Hyman noted this has been studied in the past and asked whether the research underlying the proposed interventions have the potential of reaching the next level. Dr. Collins said more data and studies exist that show particular elements of interventions to reduce disparities. They are thinking about how to bring different components of the evidence base together to see if coordinated implementation will make a difference. Dr. Insel suggested that this might be a discussion at the next Council meeting. Dr. Robinson Beale commented the issue is very important from a health care delivery perspective. It is something that will be measured with money attached to it, so people will be paying more attention to it than they have in the past.

Building the Next Generation of Global Mental Health Researchers
Dr. Insel introduced LeShawndra Price, Ph.D., from ORDGMH, who also spoke on behalf of Dr. Collins. She began by noting that collaborative global research activities permit innovation in high-income countries to be adapted in lower-income settings, and vice versa. A new cadre of researchers is needed to work collaboratively across disciplines and cultures to address priority global mental health challenges. To address this need, the goal of this concept is to create new and enhanced training opportunities for early career investigators interested in pursuing global mental health careers. Expected outcomes include an increase in the number of early career investigators interested in the field, development of a cadre of mental health researchers who can address global mental health concerns in multiple settings, and an increase in the number of early career investigators applying for and receiving RPG awards.

Discussion
Dr. Lewis-Fernández asked for clarification about how the goal of this initiative would be achieved. Dr. Price said that ideas include developing a curriculum and other resources, and perhaps offering an individual award. They are working with the NIMH training team and other NIMH staff on ideas. Dr. Lewis-Fernández was in support of a concerted effort. He mentors people who are interested in the field but do not see any funding to develop within this field.

Dr. Insel closed the session by noting that as these concepts develop, staff may bring more information forward to Council and that all concepts are pending budget decisions. Council concurrence through the presentations can allow staff to start developing the concepts further to create some exciting opportunities.

Public Comment
Dr. Insel invited members of the audience to make any comments to the Council.

Paula Skedsvold, Federation of Associations in Behavioral and Brain Sciences, asked whether the Council has discussed the impact of sequestration on NIMH-funded research. Ms. Skedsvold said it could be a significant cut that scientists need to be aware of. Dr. Shatz shared Ms. Skedsvold’s concern. Dr. Eichenbaum remarked that the Society of Neuroscience has coordinated a letter-writing campaign. Allison Bennett, from the International Neuroethics Society, described the new organization and invited Council members to participate.

Tanya Shuy, the parent of an adult child with mental illness, said she felt a sense of promise in what she heard about biomarkers and genomics. She also urged looking at the potential of artificial intelligence and gaming to study neural circuitry in the brain.

Dr. Insel thanked all who participated in the meeting. He recessed the open session meeting at approximately 2:15 p.m.

Thomas R. Insel, M.D., Chairperson

1 The website that describes the establishment of the OAR is here http://www.oar.nih.gov/about/history.asp. Specifically, Congress subsequently passed the NIH Revitalization Act of 1993, which significantly strengthened the OAR, providing it with the authority to plan, coordinate, and evaluate AIDS research, to set scientific priorities, and to determine the budgets for all NIH Institute and Center AIDS research. Please see http://www.oar.nih.gov/budget/ for more information on the congressional allocation of funds for HIV/AIDS research.

Appendix A

 Summary of Primary MH Applications Reviewed
May 2012
Category IRG Recommendation
Scored
#
Scored
Direct Cost $
Not Scored
(NRFC)
#
Not Scored
(NRFC)
Direct Cost $
Other
#
Other
Direct Cost $
Total
#
Total
Direct Cost $
Research 607 $636,502,068.00 580 $494,491,590.00 5 $5,168,389.00 1192 $1,136,162,047.00
Research Training 2 $2,362,214.00 0 $0.00 0 $0.00 2 $2,362,214.00
Career 46 $33,251,157.00 25 $17,554,649.00 0 $0.00 71 $50,805,806.00
Other 0 $0.00 0 $0.00 0 $0.00 0 $0.00
Totals 655 $672,115,439.00 605 $512,046,239.00 5 $5,168,389.00 1265 $1,189,330,067.00

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

(Terms end 9/30 of designated year)

Chairperson

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

Executive Secretary

Jane Steinberg, Ph.D.
Director
Division of Extramural Activities
National Institute of Mental Health
Bethesda, MD

Ex Officio Members

Office of the Secretary, DHHS
Kathleen Sebelius
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
Veterans Affairs
Ira Katz, M.D., Ph.D.
Department of Veterans Affairs
Office of Mental Health Services
Washington, DC

Liaison Representative

Paolo del Vecchio, MSW
Director, Center for Mental Health Services
Rockville, MD