May 28-29, 2009
U.S. Department of Health and Human Services
Public Health Service
National Institutes of Health
National Institute of Mental Health
The National Advisory Mental Health Council (NAMHC) convened its 221st meeting in closed session to review grant applications at 10:30 a.m. on May 28, 2009, at the Neuroscience Center in Rockville, Maryland, and adjourned at approximately 5 p.m. (see Appendix A: Review of Applications). The NAMHC reconvened for an open session on the following day, May 29, 2009, in Building 31C, National Institutes of Health, from 8:30 a.m. until adjournment at 12:30 p.m. In accordance with Public Law 92-463, the open policy session was open to the public. 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 G. Amaral, Ph.D.
Carl C. Bell, M.D.
Glorisa J. Canino, Ph.D.
Elizabeth Childs, M.D., M.P.A.
Ralph J. DiClemente, Ph.D.
Howard B. Eichenbaum, Ph.D.
Daniel H. Geschwind, M.D., Ph.D.
Portia E. lversen
Dilip V. Jeste, M.D.
Norwood Knight‑Richardson, M.D., M.B.A.
Pat R. Levitt, Ph.D.
David A. Lewis, M.D.
John S. March, M.D., M.P.H.
Thomas H, McGlashan, M.D.
Steven M. Paul, M.D.
Enola K. Proctor, Ph.D.
Ira Katz, M.D., Department of Veteran Affairs
John A. Ralph, Ph.D., Department of Defense
Liaison Representative Present at the Open Policy Session:
Anna Marsh, Ph.D., representing A. Kathryn Power, M.Ed., Center for Mental Health Services, (CMHS), Substance Abuse and Mental Health Services Administration (SAMHSA)
Carol Alter, Academy for Psychosomatic Medicine
Peggy Bailey, National Alliance to End Homelessness
Stephanie Bernstein, Institute for the Advancement of Social Work Research
Thomas Bryant, National Foundation for Mental Health
Pamela Collins, Columbia University
Frank Donovan, Transcriptionist, Executive Reporters
Mary Evans, Institute of Medicine
Blair Feldman, Council on Social Work Education
Michael Fitzpatrick, National Alliance on Mental Illness
Steve Foote, NIMH Contractor
Sarah Hutcheon, Society for Research in Child Development
Jenny Jones, Council on Social Work Education
Ann Michaels, National Foundation on Mental Health
Mary Ellen O’Connell, National Academy
Anand Pandya, National Alliance on Mental Illness
Amy Pollick, Association for Psychological Science
Bette Runck, Science Writer
David Shern, Mental Health America
Andrew Sperling, National Alliance on Mental Illness
Rita Webb, National Association of Social Workers
Jill Wetzel, Infinity Conference Group
Open Policy Session: Call to Order and Opening Remarks
NIMH Director Thomas R. Insel, M.D. called the open policy session to order, welcoming all in attendance.
Approval of the Minutes of the Previous Council Meeting
Turning to the minutes of the February 2009 Council session, Dr. Insel asked if Council members had revisions or comments on the minutes. Ms. Portia Iversen asked that the minutes be revised to include a clear statement of the data from the gender and minority report, which were presented at the meeting. With that revision, the minutes were unanimously approved.
NIMH Director's Report
Peer Review Update: The major change in peer review that will occur in the immediate future is the implementation of the 9-point scoring system. In brief, discussed applications will be assigned an overall impact/priority score ranging from 10 (best) to 90 (worst). Applications to be considered at the next Council meeting will have been reviewed under this new system, which is described on the Enhancing Peer Review Website . The NIH had conducted and continues to conduct extensive training with staff and the extramural community, and the Enhancing Peer Review Website is an excellent resource for additional information and training.
Financial Conflict of Interest: The NIH is seeking comments from the public on proposed changes to Federal regulations regarding the Responsibility of Applicants for Promoting Objectivity in Research for which Public Health Service (PHS) Funding Is Sought (42 C.F.R. Part 50, Subpart F) and Responsible Prospective Contractors (45 C.F.R. Part 94). The existing regulations issued in 1995 were designed to promote objectivity in research by establishing standards to ensure there is no reasonable expectation that the design, conduct, or reporting of research funded under PHS grants or cooperative agreements will be biased by any conflicting financial interest on the part of the researcher. The Advanced Notice of Proposed Rule Making (ANPRM) was published in the Federal Register (PDF file, 4 pages) on May 8, 2009, and comments may be submitted until July 7, 2009. Concern over the adequacy of the existing policy led to the ANPRM, which is expected to stimulate a national conversation on the issue, involving grantees and academic institutions, as well as the NIH.
Recovery Act Funding: As was discussed at the February Council meeting, the American Recovery and Reinvestment Act (ARRA) was signed into law on February 17, 2009. This stimulus package allocated $10.4 billion for the NIH, of which about $366 million is specifically targeted for NIMH. These funds will be used to promote economic recovery by creating and retaining biomedical jobs and supporting innovative projects that can serve as platforms for future, longer term efforts. Of the NIH funds, some $1.8 billion will be used for construction and infrastructure support, a step that will quickly create jobs. About half a billion dollars of those funds will be used for intramural construction, including completion of the Porter Neuroscience Research building, which will provide roughly 178,000 net square feet for neuroscience research on the NIH campus.
Some $8.2 billion will go to extramural scientific research. The NIH moved very quickly to distribute the ARRA funds to stimulate and accelerate scientific research. The law requires that the funds be obligated by September 30, 2010. The NIH approach was, first, to use existing mechanisms to fund additional meritorious R01s, R21s, and R03s grant applications that have been peer-reviewed and approved by NIH Institute and Center councils. At NIMH, projects that were aligned with Institute priorities and could be converted to 2-year projects were considered for ARRA funds. Another existing mechanism is the administrative supplement, and NIMH has received a huge response to the NIH-wide call for administrative supplements.
Other mechanisms being employed to distribute the ARRA funds are new. Some extend to the entire NIH and some are developed just for NIMH.
- The largest sum will go to the Challenge Grants in Health and Science Program, which are 2-year awards at $500,000 per year total cost. The NIH Office of the Director has committed about $200 million to these awards NIH-wide, and NIMH has committed an additional $90 million. The NIH specified 15 target areas that should be addressed, and NIMH created subtopics for many of those areas. Challenge Grant applications were due by the end of April; more than 21,000 were submitted, approximately 900 relevant to NIMH. The formidable task of reviewing and funding that many applications is now firmly underway at the NIH.
- The Research and Research Infrastructure “Grand Opportunities” grants program (GO grants) is to support high-impact ideas that lend themselves to short-term, non-renewable funding and may lay the foundation for new fields of investigation. The program will support large-scale research projects at U.S. institutions that accelerate critical breakthroughs, early and applied research on cutting-edge technologies, and new approaches to improve the synergy and interactions among multidisciplinary and interdisciplinary research teams. NIMH has set aside $67 million for GO grants and has suggested three topics that could be done quickly and would not have to be done again. The target areas are: genomic profiling of mental disorders, largely concerned with re-sequencing; neurodevelopmental genomics; and, a transcriptional map of the pattern of gene expression in the developing human brain, about which little is known at present.
- NIMH is the lead Institute on a $60 million multi-Institute request for applications to study the heterogeneity of autism spectrum disorders (ASD). The focus is on the short-term objectives of the Strategic Plan for ASD Research developed by the Interagency Autism Coordinating Committee (IACC).
- About $1.1 billion of the stimulus money is targeted to comparative effectiveness research; the NIH will receive approximately $400 million of that total, and the remainder will go to the Department of Health and Human Services (DHHS) Office of the Secretary and the Agency for Healthcare Research and Quality (AHRQ).
- Additional opportunities are also available. More information on the ARRA program can be found at the web site . The website explains the funding opportunities and provided details regarding the reporting requirements and the need for transparency.
Leadership changes: Philip Wang, M.D., Dr.P.H. has been appointed to the position of NIMH Deputy Director. Dr. Wang previously served as the Director of the Division of Services and Interventions Research (DSIR). Dr. Wang replaces Richard Nakamura, Ph.D., who was recently named Scientific Director, of the NIMH Intramural Research Program (IRP).
Pamela Collins, M.D., M.P.H., is coming to NIMH from Columbia University in July to head the Office of Special Populations (OSP). She brings her expertise in global mental health and health disparities; NIMH efforts in both subjects will be expanded under her leadership. Robert Mays, Ph.D. had been the Acting OSP Director for the previous 18 months.
Wayne Goodman, M.D., who has been the Director of the Division of Adult Translational Research and Treatment Development (DATR) for the last 2 years, is moving to Mt. Sinai School of Medicine, where he will be chair of the Department of Psychiatry.
William Riley, Ph.D., Deputy Director of NIMH's Division of AIDS and Health and Behavior Research (DAHBR), is moving to the National Heart, Lung, and Blood Institute (NHLBI) in June.
NIMH Budget: In addition to the ARRA funds, NIMH now has its FY09 budget, which is about 2.7 percent larger than the FY08 budget. The President's 2010 budget for the year beginning in October 2009 has been published. Although it will be modified by Congress, the proposed budget does indicate the President’s priorities: The increase for the NIH was 1.4 percent, the increase for cancer research was 5 percent, and the increase for autism research was almost 16 percent. There is also a strong interest in comparative effectiveness research, as evident in the ARRA funding, and it is apparent that the NIH will be asked to help in the process of health care reform.
Recent Breakthroughs: Dr. Insel called the Council’s attention to several recently published articles reporting research supported by NIMH. Given the large number of recently published articles, he limited his selection to only a few translational research articles published in Science, Nature, or Cell in the previous 3 weeks. He said that over the last few years, the number of articles relevant to NIMH’s purview in these journals had increased dramatically.
First, Dr. Insel highlighted a paper by Daniel Weinberger, M.D., and his IRP team published in Nature Medicine.1 The study has implicated cellular machinery that maintains the flow of potassium in cells as having a significant role in the development of schizophrenia, and thereby revealing a potential molecular target for new treatments. Expression of a previously unknown form of a key potassium channel was found to be 2.5 fold higher than normal in the hippocampus and prefrontal cortex—brain regions essential to memory formation—of people with schizophrenia. An extensive series of experiments suggest that selectively inhibiting the gene variant that encodes production of this particular form of potassium channel (known as KCNH2) could help correct disorganized brain activity in schizophrenia—without risk of cardiac side effects associated with some existing antipsychotic medications. Because the form of potassium channel under investigation is important to the higher mental functions disturbed in schizophrenia, the researchers propose that a treatment designed to inhibit just this form might spare any heart-related side effects associated with some existing antipsychotic medications while improving the disorganized neural firing characteristic of the brain in schizophrenia.
Dr. Insel then discussed a paper published in Nature by NIMH-funded researchers at Stanford University.2 They devised an innovative method for modulating distinct brain circuits in the cortex. Calling their method ‘optogenetics,’ the researchers genetically engineered mouse brain cells to be sensitive to fluorescent light in such a way that different colors of fluorescent light served as an on/off switch for the cells. The researchers were then able to expose the mouse cells to specific kinds of fluorescent light to selectively block or enhance parvalbumin interneuron activity. They found that when they blocked the activity of these interneurons, they eliminated a specific frequency range of circuit activity, whereas when they heightened activity of these interneurons, synchronized rhythm emerged. Furthermore, the combination of PV interneuron and synchronized rhythmic activities enhanced overall circuit function by boosting signal and reducing noise—i.e., rendering messages transmitted between cells loud and clear. The optogenetic approach presents a whole new and highly selective way of analyzing brain function, enabling researchers to determine the roles of different factors affecting brain performance and pathology.
In two additional papers published in Nature, investigators funded in part by NIMH, NINDS, NICHD, NIDCD and NCRR identified common and rare genetic factors that affect the risk of ASD. The first study provided strong confirmation of the association between ASD and two genes encoded on chromosome 5, called CDH9 and CDH10.3 Both genes encode cadherins—cell surface proteins that enable cells to adhere to each other. The second study searched for genes that were duplicated or deleted in individuals with ASD, and in the rare cases where those variations occurred, many tended to affect genes involved in cell adhesion.4 In the developing brain, cell adhesion proteins enable neurons to migrate to the correct places and to connect with other neurons. The results of these studies point to the importance of genes that are involved in forming and maintaining the connections between brain cells. Together, the studies suggest that genetic differences in cell-to-cell adhesion could influence susceptibility to ASD on a large scale.
The final paer Dr. Insel highlighted held considerable importance for translational science.5 In their article in Science, NIMH-funded researchers described a behavioral design in which a fear memory is destabilized and reinterpreted as safe in an animal model. This was accomplished by presenting an isolated memory retrieval trial before an extinction trial. The procedure appeared to attenuate the fear memory without the need for medication and might be relevant to human behavioral treatments, if the retrieval and extinction period can be appropriately timed. This investigation of memory consolidation and tuning provides an example of how conceptually driven animal research might be useful for guiding clinical practice. Clinicians may have the greatest opportunity to change fearful memories not during the initial learning but at some later time, when memory reconsolidation occurs.
The Human Connectome Project
Michael Huerta, Ph.D., NIMH Associate Director for Scientific Technology, outlined a plan for a 5-year research project, supported by the NIH Blueprint for Neuroscience Research, to develop and share knowledge about the structural and functional connectivity of the human brain.
Neural connectivity is a basic feature of brain organization and a major organizing principle of neuroscience knowledge. For human brains, however, no connectivity data exist in any comprehensive, systematic, or modern sense. In the past 5 years, several non-invasive imaging technologies have emerged that can acquire structural and functional connectivity data from human brains, in vivo. Researchers studying human brain function in health and illness have increasingly realized the importance of connectivity data to unravel the mystery of how the mind works.
The purpose of the Human Connectome Project (HCP) will be achieved through a range of research activities. The HCP will support the optimization and combination of already existing cutting-edge, non-invasive imaging technologies to acquire structural and functional in vivo data about axonal projections and neural connections, with the aim of collecting data from hundreds of healthy adults. HCP will also support the collection of demographic, sensory, motor, cognitive, emotional, and social function data from each participant. DNA samples will be collected from each participant, from which whole genome single nucleotide polymorphism (SNP) genotype data could be derived, as would blood for generating cell lines. Investigators funded through the HCP will develop data and analytic models to better understand and use these data and will link connectivity patterns to existing architectonic data. NIH will rapidly make data and models available to the research community via a user-friendly informatics framework to include tools to query, organize, visualize and analyze data and use the models. Outreach efforts will engage and educate the research community about the imaging tools, data, models, and the informatics platform.
The project’s major goals are to deliver by the end of 5 years: 1) a set of integrated, optimized, noninvasive tools and methods to collect human connectivity data in vivo; 2) high-quality, well-characterized, multi-modal, quantitative datasets of human connectivity data linked to genetic and behavioral data from hundreds of healthy adult subjects; and, 3) rapid, user-friendly dissemination of the data, models, and informatics tools developed in the project to the research community via outreach activities and a robust informatics platform.
Dr. Huerta said that in addition to providing an entire class of crucial data that is currently missing from human neuroscience, the project will improve the field’s ability to integrate different types of data and thereby transform our understanding of brain function and dysfunction. The HCP is intended to produce high-quality datasets that could, for example, serve as control data for other studies of brain disorders, of connectivity changes over the life span, or of connectivity across species. The data will also be useful in understanding normal biological variation. The new technologies and methods developed will be available for the entire research community, providing the means for investigators to further develop and contribute to the emerging field of human connectomics.
During the discussion that followed Dr. Huerta’s presentation, Daniel Geschwind, M.D., Ph.D., was particularly interested in the emphasis on dissemination and ensuring that the data produced by the project be accessible to the research community. Dr. Huerta noted that one of the three goals was focused on just this issue and that this project will be funded via a cooperative agreement, requiring the NIH to have significant involvement in the funded project to foster data sharing.
David Amaral, Ph.D., applauded the HCP effort but encouraged caution in the realm of the project’s potential to show connectivity at the micro level; Dr. Huerta agreed, as that is not the goal of the project. David Lewis, M.D., questioned the project’s ability to achieve a sufficient level of resolution by relying on noninvasive imaging. Dr. Insel suggested that one way to visualize the project is to think of it as a Google map. It will show the freeways but won’t tell who lives in each house. He pointed out that a parallel effort is underway in the mouse brain. It is at a more detailed level, and it will show all the roads in addition to the freeways.
John March, M.D., M.P.H., encouraged the collection of data on different age groups, including children and the elderly, since the brain changes with age. Pat Levitt, Ph.D., echoed that suggestion. He reminded the Council that experience changes brain architecture, which will not be interpretable without accompanying data on family and individual history. He also recommended that ethnicity data be collected. Dr. Huerta said that for the HCP to be supported by all 16 Institutes, Centers, and Offices associated with the NIH Blueprint for Neuroscience Research, it was conceived as a starting point—measuring connectivity at a time point in the development of healthy individuals that is of common interest to most participating Institutes. Once the technologies are optimized and integrated, different Institutes may fund studies focusing on subject populations of different ages and disorders, as well as perspectives relevant to those respective Institutes. This first-step intends to build a data, tools, and methodology infrastructure. Dr. Insel added that the project is building on cutting-edge technologies and techniques.
The Council voted unanimously to approve the concept.
Institute of Medicine Prevention Report: Preventing Mental, Emotional, and Behavioral Disorders Among Young People: Progress and Possibilities
Christopher Gordon, Ph.D., NIMH Associate Director for Prevention provided a brief introduction to the report on prevention published by the Institute of Medicine (IOM). Dr. Gordon highlighted several of the IOM recommendations, noting the consistency of these recommendations with the NIMH strategic plan:
- To know the true public health impact of illness and intervention, it will be necessary to improve the capacity to measure the incidence and prevalence of disorders and an assessment of the risk and protective factors involved in causing mental disorders.
- As targets for intervention, risk factors and risk indicators—biological, behavioral, and social—need to be identified long before the onset of symptoms.
- The report demonstrates that interventions that clearly work are available. NIMH can assist in the necessary next steps with advances in the science of implementation research and by strengthening relationships with the Institute’s community partners responsible for the implementation of the interventions.
- The synergy among neuroscience and behavioral and social sciences needs to be fostered. To that end, NIMH will sponsor a workshop to bring together basic and applied behavioral and social prevention scientists.
- NIMH will continue to encourage projects that test the utility of platforms that interest youth and to do a better job of reaching prevention providers.
- NIMH will continue to strengthen interactions with Federal partners, such as SAMHSA, National Institute on Drug Abuse, and National Institute on Alcohol Abuse and Alcoholism.
Carl Bell, M.D. highlighted the committee’s major objective to review the science and Federal efforts in prevention since the last report in 1994. He credited the entire IOM committee, noting their dedication and commitment to prevention science. Prevention research has exploded in the last 15 years, and it now appears possible to create a society that protects its members, cultivates resiliency, and prevents disorders. Nevertheless, the IOM report notes that between 14 and 20 percent of young people currently has a psychiatric disorder, with a total estimated cost of $247 billion annually.
Throughout his talk, Dr. Bell emphasized the need to begin prevention efforts early in people’s lives, given our understanding of mental disorders as developmental disorders. The 2000 Surgeon General’s report on youth mental health found that symptoms often appear 2-4 years before mental disorders are diagnosed. Three out of four adult disorders had an onset by age 24, one of two by age 14. Common risk factors include poverty, coercive processes in families, lack of self-regulation, and aggressive social behavior. Neuroscience and behavioral research have shown that self-regulation is critical for successful development. Because the cerebral cortex is not fully mature until the mid-twenties, children must be helped to develop the capacity to stop, think, and then act.
The new IOM prevention report includes recommendations for promoting mental health, not simply preventing mental illness. The science is now strong enough to help individuals achieve developmental competence; enhance self-esteem, mastery, well-being, and social inclusion; and, strengthen the ability to cope with adversity. Preventive interventions have several generic features, including reducing or minimizing toxic biological and psychological processes; richly reinforcing self-regulated, pro-social behavior; teaching pro-social skills and values; and fostering acceptance. Based on his past HIV and violence prevention efforts in this country and in Africa, Dr. Bell developed a model of field principles to cultivate resiliency and health behavior change. They include, for example, rebuilding the social fabric, enhancing connection among family members, minimizing the effect of trauma, and reestablishing the adult protective shield.
Dr. Bell said that the IOM committee was adamant that future efforts should be directed toward primary prevention rather than the preventive aspects of treatment (secondary prevention). Although Dr. Bell did not disparage the value of treatment, he insisted that focusing solely on preventing the recurrence of episodes tends to detract from primary prevention efforts.
The IOM prevention report is focused on primary prevention and cited evidence that some disorders can be prevented. Dr. Bell highlighted a few such studies, noting evidence for reduced incidence of adolescent depression, multi-year reductions in substance abuse, conduct disorders, antisocial aggression, and child maltreatment. One such program that has been shown to be effective is nurse-family partnerships involving single teenage mothers. They can reduce abuse and neglect, enhance child behavioral development, increase economic well-being, delay the birth of a subsequent child, and reduce drug use and arrests among children as they reach adolescence. Multiple randomized controlled trials in South Carolina have shown that a community-wide system of parental supports reduces maltreatment and out-of-home placements. School-based programs have also shown the potential for reduction of substance abuse, aggression, and violence. Social and emotional learning programs in the schools have shown promise in improving academic performance. Limited cost-effectiveness data are available as well.
With this research base demonstrating that prevention is possible, Dr. Bell and the IOM report are calling for more prevention implementation research and more effectiveness trials as well as community-research partnerships. Conducting implementation research is very complex, and there is a great need for community involvement in this type of research. To put knowledge into practice requires a joint effort from Federal agencies, stakeholders, and researchers to develop and promote mental, emotional, and behavioral health with the aims of preventing illness and behavioral problems in young people.
During the discussion following Dr. Bell’s presentation, Dilip Jeste, M.D., suggested that prevention efforts not be restricted to children. Several animal and human studies have shown that it is possible to prevent mental and physical disability and disease through the lifespan. Dr. Bell agreed. He said that in the next 10 years, much of the focus on health care will concern children and the elderly.
Dr. Levitt said he spends a fair amount of time with State legislators and businessmen and women, talking about the neuroscience of child and brain development and prevention. He said it is difficult to get policymakers to understand that prevention programs are a legitimate approach to improving mental and physical health. It is important to engage local and State legislators, who, regardless of party, have often proven to be amenable to understanding that there is a social responsibility that extends beyond the family. Dr. Bell agreed that past efforts have been stymied by those who are averse to governmental involvement in their families. He continued that the public should hear that science has advanced to the point where it is unethical to deny children effective interventions.
Dr. Geschwind commented on the lack of integration among different organizations that care for people throughout the life span. Again, Dr. Bell cited the need for leadership in forming a common shared vision about the interdependency of resources across care systems. For example, if the education system spends money on an intervention that results in fewer adolescents detained in correctional facilities, then that is a cost savings for the criminal justice system.
Elizabeth Childs, M.D., P.C., said that it may be prudent to identify individuals who are at critical risk, given the funding constraint and the reality that different populations have different prevention needs. Policymakers need a great deal of help in deciding where to expend effort. Disentangling interactions of biology and behavior is one issue where the research community could be helpful. Given limited budgets, administrators have to make choices between, for example, putting more police on the streets and investing in identifying hyper-vigilant school children who may be at risk for mental illness. Dr. Bell cited his own experience in Illinois when he and his colleagues were able to identify protective factors in the lives of at-risk children. With protective factors, traumatic incidents did not lead to symptoms of trauma. Dr. Bell encouraged an emphasis on protective factors rather than employing deficit models; examine people who are successful, despite being at-risk, to identify their strengths and protective factors.
Strategic Plan Implementation Process: Overview
Dr. Insel reviewed the four major objectives of the NIMH Strategic Plan, setting the stage for the presentations on the implementation efforts relevant to each of the four objectives:
- Objective 1: Promote Discovery in the Brain and Behavioral Sciences to Fuel Research on the Causes of Mental Disorders
- Objective 2: Chart Mental Illness Trajectories to Determine When, Where, and How to Intervene
- Objective 3: Develop New and Better Interventions that Incorporate the Diverse Needs and Circumstances of People will Mental Illnesses
- Objective 4: Strengthen the Public Health Impact of NIMH-Supported Research
Dr. Insel provided a brief overview of how the unexpected influx of ARRA funds has provided a jumpstart to the implementation plans for the four objectives. Since NIMH staff had already formed working groups that were deep into the implementation planning phase, NIMH was well poised for action. However, ARRA funds carry the constraint of funding only research that can be accomplished in 2 years. Dr. Insel reminded Council that ARRA funds are not the only source of funds for implementing the Strategic Plan and not all ARRA dollars will be committed to meeting the Plan’s objectives (e.g., AIDS, training, bioethics, intramural initiatives). He also reminded Council that the Strategic Plan did not cover AIDS research or training efforts, each of which has its own strategic plans.
Strategic Objective 1
Linda Brady, Ph.D., Director of the Division of Neuroscience and Basic Behavioral Science reported that in addition to the Strategic Plan, the working group for Strategic Objective 1 employed the recent Council workgroup reports Priorities for Basic and Behavioral Science Research at NIMH and Transformative Neurodevelopmental Research in Mental Illness to guide its recommendations.
Dr. Brady reminded Council that the ultimate goal of Strategic Objective 1 is to accelerate the pace of scientific discovery by fostering opportunities for serendipitous discoveries, novel approaches, broader scientific participation, and integration of high-value datasets to achieve a fuller understanding of the complex neurobiological architecture of the processes underlying mental illness. She described four sub-objectives: 1) develop an integrative approach to understanding the pathophysiology going from genes to circuits to behavior; 2) discover components of genomics and epigenomics that contribute to disease pathophysiology; 3) identify biological markers and behavioral measures that can serve as biosignatures indicating risk for disease, progression of disease, treatment response, and adverse effects; and 4) find new ways to characterize or classify dimensions of function that run across disorders.
The implementation of Strategic Objective 1 has been able to take full advantage of ARRA funding opportunities in the area of Challenge Grants, Grand Opportunity (GO) grants, the autism RFAs, as well as the opportunities available via administrative and competitive supplements. Dr. Brady then highlighted a few topic areas within each funding mechanism.
In addition to the foregoing ARRA mechanisms, several ongoing companion efforts are underway through base funding and other RFA initiatives. These efforts include exploratory studies for induced pluripotent stem (iPS) cells; comparative interdisciplinary studies of cerebral cortical development; mouse models containing human alleles, novel tools to look at brain function; and the Center for Genomic Studies of Mental Disorders, the genetics and phenotypic data repository.
Another ongoing activity is the Research Domain Criteria initiative (RDoC) that is exploring new ways to define disorders across domains of function (e.g., cognition, executive function, attention, arousal, and fear). Participants in the project include NIMH staff, former NIMH director Dr. Steven Hyman, members of the group revising the American Psychiatric Association’s Diagnostic and Statistical Manual (DSM), the World Health Organization, and the American Psychological Association. The project aims to develop a framework for classifying psychopathology based on the emerging evidence from clinical neuroscience and genomics. The new classification scheme would be used to guide investigators regarding the kinds of patient groups to be incorporated in clinical research studies funded by the Institute.
Steven Paul, M.D., asked whether NIMH has plans to collaborate or otherwise interact with the private sector, which could, for example, provide reagents or iPS cells. Dr. Paul said that NIMH could be a catalyst for making reagents and other materials available to the academic community quickly. Dr. Brady said she and her colleagues frequently explore public-private partnerships. Such collaborations have been ongoing in the psychiatric genomics consortium, for example.
Strategic Objective 2
Molly Oliveri, Ph.D., Director of the Division of Developmental Translational Research, reported that the implementation working group for Strategic Objective 2 employed both the Strategic Plan and the Council workgroup report Transformative Neurodevelopmental Research in Mental Illness to guide its recommendations and implementation plan. Dr. Oliveri reminded Council of the three sub-objectives within Objective 2: 1) to define the developmental trajectories of mental disorders; 2) to enhance understanding of how cultural diversity may influence those trajectories; and, 3) to develop tools that can better define and identify risk and protective factors for mental illness across the life span. The ultimate goal is to develop a comprehensive risk profile to help determine when to intervene to prevent the onset of a mental disorder or improve its trajectory.
The sub-objectives focus on the interactions between risk and protective factors, experiential factors, and genes, with a particular emphasis on timing. When do experiences occur (e.g., stressful experiences at certain levels of a child’s neural maturation)? When are particular genes expressed? Such knowledge is critical for defining developmental trajectories (first sub-objective) and, based on knowledge of trajectories, devising developmentally sensitive tools for risk assessment (third sub-objective). The focus is on early and mutable factors so that interventions can take place in time to prevent or preempt disorder. The second sub-objective focuses on the impact of cultural experience on trajectories; the idea is to disentangle cultural experience into its component processes that combine and interact with all of the other influences to shape trajectories. As Dr. Bell had pointed out earlier, these risk processes are embedded in cultural experience, along with the protective factors (e.g., cultural identity, sense of belonging, values, and beliefs).
Dr. Oliveri said her team used the term mental health developmental trajectory map to refer to the accumulation of knowledge across levels, both basic and applied, and how that knowledge might be put into practice. Variables that can be relevant to trajectories are at all levels of analysis, e.g., genotype, gene expression, neural maturation, working memory, social cognition, functional imaging, stressful events, peer relations, and immigration status, and they range across the life span from the prenatal period onward. The ultimate aim is to make a tool box available to practitioners as an aid in risk assessment and consideration of intervention options.
As with Strategic Objective 1, Strategic Objective 2 was also able to take full advantage of ARRA funding opportunities in the areas of Challenge Grants, GO grants, the autism RFAs, as well as the opportunities available via administrative and competitive supplements. Dr. Oliveri highlighted a few topic areas within each of these funding mechanisms.
Ongoing companion efforts include comparative interdisciplinary studies of cerebral cortical development; biobehavioral research awards for innovative new scientists (BRAINS); exploratory studies of iPS cells from healthy and mentally ill patient populations; novel interventions for neurodevelopmental disorders; and identification and characterization of sensitive periods for neurodevelopment of mental disorders.
Strategic Objective 3
Philip Wang, M.D., Dr.P.H., NIMH Deputy Director, described plans for implementing the third objective: to develop new and better interventions for mental disorders that incorporate the diverse needs and circumstances of people with mental illness. As an example of the guiding principles that were used to develop initiatives in this area, he discussed pathways to personalized medicine. Such pathways often start with identifying mediators and moderators of treatment outcomes, generally using existing clinical trial datasets and exploratory analyses. Based on what is found, the work can move into a second phase—stratifying subjects by these predictors in prospective treatment trials. Next would be assessments of the value and clinical benefits of such stratification schemes, followed by the dissemination and promotion of the use of these predictors through practice guidelines. This outcome is at the heart of NIMH’s mission.
Dr. Wang described the sub-objectives to Strategic Objective 3: 1) further developing innovative interventions and designs for intervention studies; 2) expanding and deepening the focus to personalized intervention research; 3) strengthening the application of mental health interventions in diverse care settings and populations by examining community and intervention delivery approaches and how they may affect intervention outcomes–the goal being to adapt and modify interventions to increase their reach into populations that might not otherwise be able to benefit from them; and 4) identifying and systematically studying elements of personalized mental health care. The ultimate goal is to improve existing approaches and devise new ones for the prevention, treatment, and cure of mental illness, thereby allowing those who suffer from these disorders to live full and productive lives. Efforts to implement this objective will involve all the ARRA mechanisms with the exception of the GO grants, and Dr. Wang described some of the topic areas within each funding mechanism.
Ongoing companion efforts that will also serve to jumpstart Strategic Objective 3 include the Collaborative Study of Suicidality and Mental Health in the U.S. Army. The initiative aims to identify risk and resiliency factors for suicidality and other adverse mental health outcomes, as well as rapidly develop new interventions for these conditions. Another effort is the Research on Biomarkers for Mental Disorders initiative, which is working to develop biomarkers and biosignatures of psychopathology, treatment response, and adverse effects to treatments. And a third effort is the Recovery after an Initial Schizophrenic Episode (RAISE) initiative to ameliorate disability in schizophrenia. By design, RAISE will also assist with the implementation of the fourth strategic objective.
Dr. Insel noted that whereas plans for implementing the first two strategic objectives were informed by Council workgroup reports, there was no such report to inform Strategic Objective 3. The suggestion that a workgroup be formed to consider the next generation of interventions was put forth at the last Council meeting. Dr. Insel noted that this is the area with the largest gap between the Institute’s priorities and the topics of investigator-initiated projects. Even those applications that score highly are not always innovative or likely to have the desired impact. He asked Drs. March and Lewis, who volunteered to co-chair the new workgroup, to share their ideas for refining the charge to this Council workgroup to inform interventions.
Dr. March said that the basic issues are how to understand the development of new interventions, how to understand the place for existing interventions, and how to understand the movement of these interventions into community practice. Applications that now are submitted, for the most part, are at the intersection of early-phase intervention work and later-phase intervention work. What is needed to optimize the early-phase intervention studies is to capitalize on the discoveries in translational neuroscience. The challenge becomes how to align the research being done in the field with the objectives outlined in the NIMH Strategic Plan. This “new interventions research” will look quite different and be more effective in improving public health than research done in the last two decades.
Dr. Insel commented that rarely has the Institute seen a grant application that takes a personalized, preemptive approach, such as that outlined in the Strategic Plan. It is clear that investigators need guidance about what is most likely to get funded. Dr. March added that the workgroup will also need to consider public-private partnerships and borrow from the experience of other Institutes in reconfiguring neuroscience medicine.
Dr. Lewis said that he is concerned that the interventions not be simply aimed at molecular targets, but also behavioral targets and the timing of interventions. The field needs to be motivated to think about improving the very early phases of deciding when, where, and how to approach interventions.
Enola Proctor, Ph.D., said the preceding comments underscore a change that will be needed in the teams doing this kind of research; this need is consistent with the recommendations in the Council’s training report. The teams should be trans-disciplinary and committed to translation. The more perspectives brought to the construction and the testing of interventions, the more readily they will move out into the real world and yet capitalize on all the basic science discoveries.
Dr. Levitt emphasized that the many references to biomarkers and biosignatures did not address the changes that take place biologically over time. The signatures that are assumed to be valuable for personalized strategies for intervention or prevention may not be, because the inability of a system to maintain homeostasis is really what needs to be measured. He said that scientists already know that biologically cross-sectional measures are not going to be meaningful. A change in gray matter thickness over time is very important. A change in cortisol levels is informative.
Dr. Insel pointed out that the emphasis on trajectories in the second strategic objective addresses this problem. Change across time will need to be accounted for to come up with predictors. This undertaking is transformative. Schizophrenia isn't solely psychosis, which is a late stage of the illness. These new efforts are aimed at defining much earlier stages in the same way that is being done in the rest of medicine. The question is how to intervene—cognitive remediation or family support. What will it take to intervene in stage 1 or maybe the beginning of stage 2, rather than waiting until the very end of stage 2 or stage 3, when a patient is already hearing voices? That is where the field should ideally be in 5 years.
Strategic Objective 4
David Chambers, D. Phil, Chief of the Services Research and Clinical Epidemiology Branch within the Division of Services and Intervention Research, reported on the implementation plans for Strategic Objective 4, strengthening the public health impact of NIMH-supported research. He outlined the sub-objectives: 1) to improve understanding of the factors affecting access to service, quality, and cost of services, and the means by which newly discovered effective mental health interventions are disseminated and implemented; 2) to improve the research and dissemination activities of the Institute through monitoring and evaluation; 3) to strengthen partnerships between NIMH and stakeholders groups around the country; and 4) to strengthen the Institute’s relationships with other Federal agencies that address mental health issues.
Dr. Chambers said that the implementation working group was well aware that the path from bench to bedside to practice must involve feedback. Knowledge gained in practice settings and in the community should inform future research. Improving public health will involve partnerships among the research enterprise, stakeholders, patient consumers, families, providers, and Federal agencies. He and Dr. Insel acknowledged the close relationship the Institute has with SAMHSA, represented at the meeting by Anna Marsh, Ph.D., Deputy Director of the Center for Mental Health Services. Dr. Chambers also emphasized that activities throughout NIMH, not only its research, are directed at improving public health.
As with Strategic Objective 3, implementing Strategic Objective 4 will gain traction via all of the ARRA mechanisms except the GO grants, and Dr. Chambers described some of the topic areas within each funding mechanism. In addition to the opportunities created by ARRA funds, NIMH has several companion efforts underway in the implementation of Strategic Objective 4. These include creating a pooled State administrative database, i.e., a natural laboratory, for policy-relevant services research; developing a longitudinal tracking system for mental disorders; leveraging existing health care networks to transform effectiveness research; and the RAISE initiative discussed briefly by Dr. Wang. The RAISE initiative embodies the idea that research will be done in concert with other agencies and stakeholders to achieve a public health impact. RAISE is intended to develop early interventions that have the promise of preventing clinical deterioration and functional disability. Applicants are required to have a partnership with end users, include the perspectives of the provider and the funding agency in the initial conception of an intervention, and spell out a dissemination plan if the intervention proves successful. The outcomes to be measured are not only confined to symptom improvements but also include broader functions, such as educational attainment and work status. There is significant NIMH staff involvement in this project to help guide the project over the award period.
Glorisa Canino, Ph.D., called attention to the Council’s workgroup report on services, The Road Ahead, which advocated ongoing evaluation of the extent to which the report’s recommendations were being implemented. One of those recommendations was to consider the effectiveness of treatments for different ethnic, racial, geographic, and age groups. She suggested that NIMH conduct a systematic evaluation of its research portfolio to look at the number of applications that address each of the strategic objectives. Dr. Canino opined that the Institute may not receive competitive applications for services research because it is not communicating to investigators that disparities and services research are priorities.
Dr. Levitt built on Dr. Canino’s comments by pointing out that better strategies are needed for communicating with stakeholders—i.e., health care professionals, community advocates, policymakers, and the public. Research can help policymakers decide where and when to invest in prevention and intervention programs. Social scientists have proven methods for learning how to frame messages so that health care professionals can implement knowledge discovered through research.
Dr. Marsh volunteered SAMHSA’s collaboration in those efforts. The splitting of the Alcohol, Drug Abuse, and Mental Health Administration into NIMH and SAMHSA created a schism in the research-to-services continuum. She said her agency receives large numbers of applications for services; some of those applicants may be prime candidates for collaborating with academic researchers. Dr. March agreed that it is important to break down the wall between SAMHSA and NIMH.
Dr. Childs suggested that in addition to addressing disparities in health care for different racial and ethnic groups, it is also necessary to consider health care disparities among individuals with severe mental illness. At present, people with severe mental illness have life spans that are about 25 years shorter than average. The field fails to give enough attention to understanding why mental illness is a precursor to cardiac disease, diabetes, and other diseases.
Dr. Insel concluded the session by noting the many suggestions that had been made about disparities, portfolio balance, communication issues, and the newly formed workgroup on interventions research. More discussion to refine these ideas is needed, he said, but certainly high priority must be given in the short term to strengthening the relationship with SAMHSA.
Advocacy Group Discussion
Dr. Insel introduced two representatives from mental health advocacy groups who had been invited to comment on the implementation of the NIMH Strategic Plan. The first to address the Council was Michael Fitzpatrick, M.S.W., Chief Executive Officer and Executive Director of the National Alliance on Mental Illness (NAMI).
Mr. Fitzpatrick described several aspects of the NIMH Strategic Plan that are of interest to NAMI. First, NAMI is particularly excited by the emphasis on translation and the importance of translating research into community practice. NAMI is also excited by the focus on mental illness across the life span and the interest in serving diverse communities. To date, research breakthroughs have been very slow to translate into better services within the community. Continued efforts to coordinate the work of Federal agencies, such as the NIH, SAMHSA, and the Centers for Medicare and Medicaid Services might have an enormous impact on the translation of research findings and community services. NAMI is intrigued by the RAISE study, which is extremely important because it targets resources at the early stages of schizophrenia, before the illness devastates the individual and his or her family. In addition, NAMI supports continued efforts with comparative effectiveness research as a basis for personalized medicine. It is especially important that it is of high quality and that it is not used to drive cost decisions in States or communities.
Mr. Fitzpatrick also mentioned NAMI’s concerns—primarily its disappointment in the President's budget, which provides only a 1.7 percent increase for NIMH whereas inflation is projected to be 3.5 to 4.5 percent. This allocation does not recognize the public health burden of serious mental illness or the scientific opportunities that could lose their momentum if not adequately funded. NAMI is also concerned about the short amount of time allotted for dispersing the stimulus funds.
NAMI shares many goals with NIMH, Mr. Fitzpatrick said. NAMI places great importance on the need for vastly improved treatments for people with serious mental illness. As an organization that represents persons with serious mental illness and their families, NAMI is disappointed with available medications and with the lack of research into effective treatments. Many current treatments are unavailable in some communities across the country. NAMI is interested in novel innovations, novel treatments, and novel medications and will cooperate with NIMH in implementing its Strategic Plan.
David Shern, Ph.D., President and Chief Executive Officer of Mental Health America (MHA) and a former NIMH grantee, began his comments by noting that this year is the 30th anniversary of NAMI and the 100th anniversary of MHA, formerly the National Mental Health Association and originally the National Committee on Mental Hygiene. He briefly reviewed the history of the mental health movement with its initial emphasis on mental hygiene. The movement began as an effort to improve treatment, but it also drew from the experience in other areas of public health. Just as germ theory led to improved sanitary conditions, the early visionaries saw science as a means to discover how to prevent mental illness. But they lacked the necessary technology. Today the science is available. Recent breakthroughs give hope that something akin to germ theory may emerge to aid in understanding developmental disorders, how the environment interacts with different vulnerabilities to create illness or health, and how interventions can help to ensure health.
Dr. Shern congratulated NIMH on the development of a well-crafted Strategic Plan to improve our understanding of the basic biology of normal development and then psychopathology as variations of normal development. MHA is very excited by the potential in the arena of genomics and gene-environment interaction. Dr. Shern also endorsed the RDoC initiative, noting that the field of mental disorders really needs a greater level of scientifically derived descriptive information about its disorders. Dr. Shern noted that he would like to see a greater emphasis on environmental influences in Strategic Objectives 1 and 2. The pathway from cells to circuits to behavior might be better characterized as cells to circuits to behavior to response to cells to circuits. That conceptualization might begin to capture the complex dynamic nature of determining phenotypes and would lessen the dualism between biology and the environment. Objectives 3 and 4 present exciting possibilities for early interventions and improving the treatment provided to all mentally ill individuals. The RAISE project is exemplary in having patients, advocacy groups, and the payers involved.
Dr. Shern suggested that Council form another workgroup with a "neurons to neighborhoods" perspective to follow up on the IOM prevention report. The IOM report cites research demonstrating the interaction between genetic endowment and the environment in neurodevelopment and neuroplasticity and the effects of traumatic or salutary experiences. Technologies to alter those influences have been shown to be effective in clinical trials. The challenge is to bring those interventions to the community.
Dr. Proctor thanked the guests for reminding Council to consider all four strategic objectives together. The RAISE research does just that and portends important features for intervention research. Both Dr. Shern and Mr. Fitzpatrick reiterated their enthusiasm for the RAISE project.
Amy Pollick, Ph.D., Director of Government Relations for the Association for Psychological Science (APS), told Council about a national initiative in the training of clinical researchers in psychology, the Psychological Clinical Science Accreditation System (PCSAS). It is an independent, nonprofit body designed to provide rigorous, objective, empirically based accreditation of Ph.D. programs in psychological clinical science. Much of the foundation for this system was laid by APS and the Academy for Psychological Clinical Science, which is a group of the top 50 or so clinical psychology programs in this country. NIMH leadership has been instrumental in establishing the accreditation system, she said.
The PCSAS board will begin accrediting programs in June. The APS is encouraging institutions with clinical psychology Ph.D. programs to apply. The PCSAS board has been in close touch with the Veterans Administration, the Department of Education, and the Council on Higher Education on Accreditation to make sure that the system conforms to the appropriate rules and regulations. Institutions interested in the new system's mission of advancing public health through the promotion of science-centered education and training in clinical psychology are now being invited to join the PCSAS founder's circle by contributing to the founder's fund. More information can be found at www.PCSAS.org.
A major article on this initiative, which will be published this fall in the Journal of Psychological Science in the Public Interest, will lay out the rationale and foundation for a new approach to clinical psychology training and will be widely disseminated.
Mary Ellen O’Connell, Study Director of the IOM prevention report discussed by Dr. Bell, reminded Council about the brief versions of the report for policymakers and researchers. She said that two additional briefs are expected to be published, one that focuses on the economic arguments in the report and another with parents as the target audience. Other dissemination efforts are also being contemplated, and she invited Council to share ideas on how to do that.
Dr. Insel reminded Council members that the next full Council meeting will be held on September 24-25, 2009, but that NIMH staff will be in touch to schedule some teleconferences over the summer to review applications received in response to ARRA funding announcements.
Dr. Insel adjourned the 221th meeting of the NAMHC at approximately 12:30 p.m. on May 29, 2009.
I hereby certify that, to the best of my knowledge, the foregoing minutes are accurate and complete.
Thomas R. Insel, M.D., Chairperson
1 Huffaker SJ, et al. Nature Medicine, 2009 May 3; 15(5): 509-518.
2 Sohal VS, et al. Nature. 2009 Jun 4;459(7247):698-702.
3 Wang K, et al. Nature. 2009 May 28;459(7246):528-33.
4 Glessner JT, et al. Nature. 2009 May 28;459(7246):569-73.
5 Monfils MH, et al. Science. 2009 May 15;324(5929):951-55.
Appendix A: Summary of Primary MH Applications Reviewed
Council: May 2009
|Scored #||Scored Direct Cost $||Not Scored (NRFC)#||Not Scored (NRFC) Direct Cost $||Other #||Other Direct Cost $||Total #||Total Direct Cost $|
Appendix B: Council Roster
(Terms end 9/30 of designated year)
|Thomas R. Insel, M.D.|
National Institute of Mental Health
|Jane A. Steinberg, Ph.D.|
Division of Extramural Activities
National Institute of Mental Health
David G. Amaral, Ph.D. (12)
Carl C. Bell, M.D. (11)
Glorisa J. Canino, Ph.D. (09)
Elizabeth Childs, M.D., M.P.A. (10)
Robert Desimone, Ph.D. (11)
Ralph J. DiClemente, Ph.D. (12)
Howard B. Eichenbaum, Ph.D. (12)
Daniel H. Geschwind, M.D., Ph.D. (11)
Portia E. Iversen (12)
Dilip V. Jeste, M.D. (10)
Norwood Knight-Richardson, M.D., M.B.A. (09)
Pat R. Levitt, Ph.D. (09)
David A. Lewis, M.D. (11)
John S. March, M.D., M.P.H. (10)
Thomas H. McGlashan, M.D. (12)
Steven M. Paul, M.D. (12)
Enola K. Proctor, Ph.D. (10)
Ex Officio Members
Office of the Secretary, DHHS
National Institutes of Health
Department of Defense
A. Kathryn Power, M.Ed.