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NAMHC Minutes of the 228th Meeting

National Advisory Mental Health Council Minutes of the 228th Meeting
May 5-6, 2011

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 228th meeting in closed session to review grant applications at 10:30 a.m. on May 5, 2011, at the Neuroscience Center in Rockville, Maryland, and adjourned at approximately 4 p.m. (see Appendix A: Review of Applications). Following a brief break, the NAMHC reconvened at the same location from 4:15 p.m. until 5:45 p.m. for an open policy session. The open policy session reconvened the open policy session the following day, May 6, 2011, in Building 31C on the National Institutes of Health (NIH) campus, from 8:30 a.m. until adjournment at 12:30 p.m. In accordance with Public Law 92-463, the 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.
  • Virginia Trotter Betts, M.S.N., J.D.
  • Robert Desimone, Ph.D.
  • Howard B. Eichenbaum, Ph.D. (via teleconference)
  • Daniel H. Geschwind, M.D., Ph.D.
  • Portia E. Iversen
  • David A. Lewis, M.D.
  • Roberto Lewis-Fernandez, 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.D., M.P.H.

Ad Hoc Members:

  • Eric D. Jarvis, Ph.D.
  • John W. Newcomer, M.D.

Ex Officio Member:

  • Ira Katz, M.D., Ph.D., Department of Veterans Affairs
  • John A. Ralph, Ph.D., Department of Defense

Liaison Representative at the Open Policy Session:

  • Crystal Blyler, Ph.D., Center for Mental Health Services, Substance Abuse and Mental Health Services Administration (SAMHSA)

Others Present at the Open Policy Session:

  • Michael Byer, M3 Information
  • Llewellyn Cornelius, Society for Social Work and Research
  • Damien Fair, Oregon Health and Science University
  • Vicki Fung, Kaiser Permanente
  • Wendy Greene, Executive Court Reporters
  • John Hsu, Harvard Medical School
  • Danielle Hunter, Dixon Group
  • Carla Jacobs, Council on Social Work Education
  • Alan Kraut, Association for Psychological Science
  • Anne Michaels, National Foundation on Mental Health
  • Marie Monfils, The University of Texas at Austin
  • Wendy Naus, Lewis-Burke Associates, LLC
  • Bette Runck, Science Writer
  • Angela Sharpe, Consortium of Social Science Association
  • Vikaas Singh Sohal, University of California, San Francisco
  • Anita Sostek, Autism Speaks
  • Andrew Sperling, National Alliance on Mental Health
  • Karen Studwell, American Psychological Association
  • Sheris Williams, Dixon Group
  • Nancy Yuan, SRI International

Open Policy Session: Call to Order and Opening Remarks

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

NIMH Services Research: Maximizing Rigor, Relevance and Impact

David Chambers, D. Phil., Division of Services and Interventions Research (DSIR), opened his presentation by defining services research and emphasizing its place in the NIMH Strategic Plan. The NIMH services research portfolio focuses on the goals of improving the understanding of factors affecting access to service, the quality and cost of services, and the means for disseminating and implementing effective new interventions. The NIMH services research portfolio focuses on research to respond to the demonstrated needs of the mentally ill. The services portfolio generally addresses Strategic Objectives 3 and 4 of the NIMH Strategic Plan and, in fiscal year 2010, services research accounted for approximately $106.6 million in funded research.

Four key dimensions are considered when selecting high priority research applications.

  • Relevance: The NIMH prioritizes studies within the actual service settings where patients and their families receive care with a focus on creating actionable information for consumers. In this context, the branch considers consumers to include patients, families, providers, practitioners and health systems, as well as purchasers and policy makers.
  • Impact: For services research, impact refers to meaningful outcomes in overall functioning, not simply responses on symptomatic scales. High priority studies should lead to actual behavior change in patients and providers, and to improvements in practices, programs, and policies. Many studies address the optimal dissemination of research findings and effective implementation of the practices that are known to have benefit. The goal of this research is transfer of knowledge and effective interventions to service agencies, policy agencies, the private sector and other health systems.
  • Rigor: Maintaining rigor in services research can be complex; the phenomena being studied require a range of methods of inquiry. Some studies are solely quantitative, while others use mixed methodologies. Studies address questions at multiple levels of analysis, from the individual up to systems. Some use existing data, whereas other projects collect the data for analysis. A major challenge is to balance external validity (generalizability) and internal validity (controlled experimental design) of the work.
  • Efficiency: NIMH is looking for platforms through which research can be done better, faster, and cheaper. The Mental Health Research Network (MHRN) is one example of a platform created to improve the efficiency of the research portfolio by making the best use of existing data, leveraging existing health care networks, conducting research within service systems, and narrowing the time it takes to apply a newly developed intervention within the community. NIMH has also been working with the Substance Abuse and Mental Health Services Administration (SAMHSA) and the Centers for Disease Control and Prevention (CDC) to improve longitudinal tracking of the population with mental disorders—i.e., how well their needs are being met and how services are delivered over time. The Institute is also seeking enhanced uses of health information technology to improve access to care and efficiency of data collection.

Dr. Chambers presented three initiatives as exemplars of the attempt to balance these dimensions of the services research portfolio. These include an initiative relevant to mental health policy, a second focused on dissemination implementation, and MHRN.

The emphasis on mental health policy grew directly from Council recommendations in 2005 and 2006. Council members asked: How does NIMH ensure that its research has an impact on policy? How does it facilitate policy research? How does policy at different levels affect individuals with mental disorders? In response, NIMH has worked to reduce the entrance barriers for researchers interested in doing this kind of policy research. Efforts included a contract to facilitate partnerships between state agencies and researchers interested in studying the impact of mental health policies, a request for applications (RFA) that resulted in five grants studying state policy awarded to researchers and their partners in 12 states, and a series of recent investigator-initiated studies of major policy issues and directives, such as parity, Medicare Part D, cost-sharing, disparities, and practice variation. These efforts correlate with a new NIH Common Fund initiative on Health Economics, co-led by NIMH, to address the science of health care reform.

The NAMHC report, The Road Ahead (presented in May 2006), highlighted the importance of the second initiative—to improve successful implementation of evidence-based interventions across service settings to diverse populations. NIMH has led 12 other Institutes and Centers (ICs) and the NIH Office of Behavioral and Social Science Research in a series of program announcements soliciting applications that drive significant improvements in the degree to which effective interventions are implemented. NIMH grantees are conducting highly ambitious and impactful studies. For example, a randomized controlled trial in 54 counties, 39 within California and 15 within Ohio, is developing and empirically testing a model for implementing mental health treatment for children in foster care, trying to improve the reach and quality with which evidence-based practices are delivered. Whereas a decade ago, most of the implementation research emphasized identifying barriers and facilitators, we are now moving to a greater emphasis on the comparative effectiveness of active implementation strategies.

The third initiative, the MHRN, arose from the challenge of conducting large-scale studies with limited funds. NIMH looked to leverage health care networks to improve the process through which researchers could identify, recruit, and enroll consumers, patients, providers, and systems within studies. A 2010 RFA, as well as targeted supplements via funds from the American Recovery and Reinvestment Act of 2009 (Recovery Act), allowed NIMH to improve data infrastructure within existing health care networks to incorporate mental health information. The MHRN is a 10-site cooperative agreement that includes health maintenance organizations in several states. The group is tasked with building the knowledge and experience base for conducting much more efficient, large-scale studies and analyzing existing data from these sites in pilot effectiveness trials to more rapidly identify, enroll, and randomize subjects. This melding of research and practice within the health care network has the potential to bring about a better understanding of the care process, no longer relying on what we think constitutes a good service outcome. While NIMH has been developing the MHRN, the NIH Common Fund has been working on the potential Health Maintenance Organization (HMO) collaboratory for all of health research; NIMH is co-leading this effort.

The principle that drives NIMH’s services research portfolio is that mental health must be seen in the context of all health. Beyond focusing on the gap between research and practice, we are developing an evidence base around what care should optimally be delivered, and how that compares to what is typically delivered. This is an opportunity to reduce and potentially eliminate disparities as well as improve quality of care.

Discussion

Roberto Lewis-Fernández, M.D. voiced the need for new therapeutics. However, he emphasized the desperate need to find ways to transmit existing therapeutics, which when used in appropriate ways produce favorable outcomes—that is, effective approaches that combine psychotherapy and medication, and that engage people in the process of getting their needs met. He asked how much effort should be devoted to creation of new technologies versus focusing on dissemination and implementation of existing technologies.

Referring to the earlier example of collaborative care for depression, Gregory Simon, M.D., M.P.H. called for less research on proven treatment models and more emphasis on dissemination and implementation, as well as policy work to encourage reimbursement for effective treatments. Virginia Trotter Betts, M.S.N., J.D. agreed and urged agencies under the guidance of the Department of Health and Human Services (HHS) to come to agreement about which treatment practices should be adopted and covered by insurance benefits. Rhonda Robinson Beale, M.D. applauded the work Dr. Chambers and his colleagues are doing. She stated that existing practice guidelines are not very informative, because they do not rank the evidence. She also expressed concern that some of the most popular psychiatric journals are not peer-reviewed, yet they are the ones that guide clinical decisions. She said what is needed is a clear mechanism for ranking the evidence, the result of which could be used to develop practice guidelines, and inform decisions about which ones to adopt. Another issue of concern is that patients often do not match the diagnoses for which evidence-based treatments are shown to be effective. Clinicians are faced with fashioning a treatment based on experience and what the patient presents. The best clinicians are those who are able to put these factors together and develop some quantitative way of measuring an outcome.

Dr. Chambers replied that an increasing number of investigators have been interested in collecting the right outcomes and testing the use of feedback systems to improve care. Some are actively testing the combination of effective treatment with outcomes management, and feeding back into supervision. Across the behavioral health field, a broader effort is also under way to ensure that the right kinds of outcomes are being collected in electronic health records.

New Direction for the NIH Office of Behavioral and Social Sciences Research

Dr. Insel introduced Robert Kaplan, Ph.D., NIH Associate Director for Behavioral and Social Sciences Research and Director of the Office of Behavioral and Social Sciences Research (OBSSR). Dr. Kaplan came to NIH in early 2011 from the University of California, Los Angeles (UCLA), where he was a distinguished professor in the Department of Health Services at the School of Public Health and the Department of Medicine, in the School of Medicine. There he served as principal investigator on prevention research and directed a services research training program at the UCLA RAND-CDC Prevention Research Center. Prior to his UCLA appointment, he was Professor and Chair of the Department of Preventive Medicine at the University of California, San Diego School of Medicine.

Dr. Kaplan described the substantial investment at NIH in social and behavioral sciences research and stated that among the ICs, NIMH is very high in that list. Expressing support of the goal to redevelop basic behavioral research in OBSSR, Dr. Kaplan said there is a sense that intervention research in the behavioral and social sciences is disconnected from the basic science underlying them. Within the current vision for OBSSR, one aim is to reintegrate studies of basic sensory processes, memory and cognition, and so forth, expanding the NIH investment in this vital area of bench to bedside research.

In line with the NIH’s strategic objectives, NIH Director Francis Collins, M.D., Ph.D. has declared five areas of focus: high-throughput technologies, translational medicine, health care reform, global health and reinvigorating the biomedical community. Stating his Office’s strong commitment, Dr. Kaplan outlined the activities OBSSR is involved in that support many of these aims.

High-throughput Technologies. OBSSR has begun collaborating with QualComm, a San Diego-based company, to study gene-environment interactions, with an emphasis on improving the technologies for measuring environmental exposures. The goal is to record exposures over time—to create an ‘exposome’. The exposures may include, for example, diet, physical activity, environmental factors, psychosocial stress, and addictive substances. Unlike genetic influences, the exposome develops over time; therefore its measurement is remarkably complex. The potential for real-time measurement of exposure is changing with the widespread availability and use of cell phones and other technologies. To take advantage of these advances it will be necessary to undertake several kinds of new collaborations, notably with engineering scientists. However, privacy and data analysis concerns remain to be addressed.

Translational Science. Dr. Kaplan said that NIH is involved in a new enterprise called the National Center for Advancing Translational Science (NCATS), a potential NIH center that focuses primarily on the translations of new molecules into product licenses (bench to bedside). Dr. Kaplan stressed the need to place greater emphasis on dissemination. Although he enthusiastically supports the discovery of new therapies, he said he is concerned about the relative lack of expenditure on dissemination; it is estimated that for every dollar spent on discovery, one penny is spent on dissemination.

Global Health. In addition to international health concerns regarding infectious diseases, there is growing concern about non-communicable diseases in the developing world. Dr. Kaplan showed a set of slides to illustrate the relative burden of HIV as well as non-communicable conditions in contrast to world population. Another comparison demonstrated disparities in the production of scientific publications, which are heavily concentrated in the northern hemisphere and Australia. NIH is beginning to invest more in international health with some grants in Africa. The primary focus has been on training, though there is strong interest in expanding the portfolio.

Discussion

Eric Jarvis, Ph.D. asked Dr. Kaplan to explain how he sees the social and behavioral sciences fitting into the five initiatives outlined by Dr. Collins. Dr. Kaplan said that NIH interests are quite broad, and the Institute as a whole supports a wide range of activities, from basic research to dissemination and implementation and community studies. He explained that psychologists and sociologists traditionally were most frequently found in the behavioral and social sciences, but this is expanding to include more anthropologists and engineers.

Steven Paul, M.D. commented on the relative contribution of medications on the morbidity and mortality from cardiovascular disease. He followed by asking why there has been no tangible impact on depression or suicide rates with the advent and introduction of antidepressants. He asked if we are simply not doing what has been done with other medical illnesses, such as hypertension, pointing out that blood pressure and cholesterol levels can now easily be measured and treated.

Philip Wang, M.D., Dr.P.H. said he thinks it has to do with the basic efficacy of the treatments. Even in a very refined efficacy setting, the effect size for antidepressants is quite small. Dr. Paul replied that decent responses of 50 percent cannot be sustained when compliance is low. Dr. Wang said one could debate low compliance versus efficacy, but that the minimal response rates underline the important question. How efficacious should something be before spending a lot of effort disseminating it?

Comparing the complexities involved in measuring and treating mental illness versus more straightforward health issues, Portia Iversen wondered if NIMH could support a continuously updated electronic database that would help clinicians and researchers keep up with changing evidence about best practices. For example, a family doctor in a small community could access information on the signs of depression and the recommended treatment for a given set of symptoms, with guidelines for administration based on patient response. It could also serve as a research tool for more involved study, and electronic alerts would notify users of updates.

Dr. Insel responded that although the Institute has an extensive dissemination effort, apparently it is not working well enough.

Thomas McGlashan, M.D. asked if some of these variables are easier to collect in countries with national health care systems. Dr. Kaplan said his office is trying to improve the uniform collection of information in primary care settings to address the inconsistencies formed by differing variables and types of measurement. In the last six months, three separate reports from The National Academies and the Institute of Medicine presented the same conclusion—that we need common data elements in electronic medical records and other data systems. NIH is involved in a coalition of agencies within HHS and elsewhere in government working to define common data elements for the electronic medical record. Illustrating the complexity of this endeavor, Dr. Kaplan gave the example of a simple query to determine how many primary care doctors there are in the US. The answer depends on which database is queried, with the number ranging from 180,000 to about 270,000. Even with Medicare records it is difficult. An examination of billing patterns reveals that specialists are identifying themselves as primary care physicians. When you go a step further and try to figure out what happens in psychiatry and clinical psychology, it becomes almost impossible.

Dr. Insel adjourned the meeting at approximately 5:45pm to be reconvened the following morning at approximately 8:30am.

May 6, 2011 Open Policy Session: Call to Order and Opening Remarks

The Council reconvened the following morning on the main campus of NIH in Bethesda, Maryland. Dr. Insel called the open policy meeting to order and welcomed all in attendance. He also welcomed Crystal Blyler, Ph.D. from SAMHSA, stepping in for Kathryn Power.

Approval of the Minutes of the Previous Council Meeting/

Turning to the minutes of the January 2011 Council meeting, Dr. Insel asked if Council members had any comments, revisions or questions about the minutes. Hearing none, the minutes were approved unanimously.

NIMH Director’s Report

Before reporting on the Institute’s budget, Dr. Insel commented that he spends a great deal of time talking to many different communities where he often hears interest expressed in the science being supported by NIMH but also frustration about the disconnect between the science and the discharge of services. Noting that it appears to have become more acute in the last year, Dr. Insel quoted a reported $2.2 billion decrease in services for people with mental illness across the country from state budgets. On top of that are the potential changes in Medicaid coverage and the real questions about what happens with health care reform. For NIMH, the question is not whether to support either basic or services research; it is determining the right balance between the two. That balance may be different for conditions such as AIDS, where the cause, effective treatments, and prevention measures are understood. Autism, on the other hand, has a different set of considerations. Unlike HIV/AIDS, the cause of autism is not known, no real preventive interventions exist and the field is still struggling with diagnosis. The incidence is increasing rapidly and available treatments are expensive, intensive and have only modest effects. Dr. Insel said it is the Council’s role to help guide the Institute in deciding the balance of its research portfolio.

Turning to the budget, Dr. Insel reminded Council that NIH has been operating for much of the fiscal year (FY) without a clear budget, and he reported a full year Continuing Resolution (CR) was ultimately passed on April 8, more than six months into the current FY. The NIMH FY 2011 CR budget is $1.477 billion. This is roughly a 1 percent decrease from FY 2010. While this is the first decrease in NIMH funding in the past three decades, it is considerably less than the cuts to many other agencies during this period of financial restraint. Following the productive two years of the Recovery Act, FY 2011 will feel like a period of austerity to the NIMH research community. The Institute expects to support 452 new and competing awards in FY 2011, which is nearly 20 percent below its average annual target of 550 new grants. This drop reflects not only the budget reduction, but also an increase in the cost of non-competing grants, amounting to an extra $30 million this year relative to recent years. With expectations that the budget will be flat or lower in FY 2012 and beyond, NIMH has been reviewing its funding strategy to ensure (a) a robust pool of R01s; (b) a continuing pipeline for new investigators; and, (c) a focus on innovation relevant to the NIMH Strategic Plan. The Institute is also looking at one year funding opportunities, such as projects from the Recovery Act that could use an additional year to move them further along.

Commenting that these kinds of situations prompt people to think about and do things that perhaps should have been done all along, Ms. Betts suggested that efficiency might be attained by reducing duplication in the research agendas and pooling resources of the substance abuse Institutes and NIMH, seeing as clinically, the conditions often co-exist.

Dr. Insel said the Neuroscience Blueprint does exactly that: it pools resources from the brain Institutes to create cross-cutting projects. He commented that with budgets tightening, there is more of a shift towards leveraging investments and creating efficiencies. The question is whether it could be done better. Could clinical trials be combined? Should the AIDS programs be combined? Should intramural programs be combined? This may be an opportunity for change, and Dr. Insel asked Council for input as these opportunities are explored.

John Newcomer, M.D. encouraged NIMH to take a close look at applications and funded grants to reduce the number of “me too” grants. He also encouraged cooperation among all the ICs in the use of common data repositories.

Dr. Insel said considerable time has been devoted to talks within the Institute about standardization, as well as the integration and sharing of data. He noted that it is expensive to develop standardization and requires an investment. Dr. Insel noted that some Recovery Act funds went into projects to create standards to begin to get everyone on the same page. He said it is going to require a culture change.

Carla Shatz, Ph.D. talked of sharing data and resources to increase efficiency and prevent duplication. She said she incentivizes people at her own institution to share their inventions and discoveries well before they are published. She criticized universities for continuous increases in salaries, with seemingly little consideration of how those expenditures cut into grant funds. She would like Council members and their respective institutions to think of ways that could provide more flexibility in resourcing funds for projects. She thinks that rather than being penalized, investigators could be given incentives to supplement their NIH-funded projects with private funding to create what she called true private/public partnerships.

Ms. Iversen affirmed the comments Dr. Shatz made about data sharing; she said it is incumbent on the investigators to truly make an effort to share data and make the most of these resources. She requested that the Council be updated about the status of this class of projects. Specifically, she wants to know more about the process for assuring that investigators are following through on their commitments to share data.

In response, Dr. Insel said that the topics of data sharing, standardization and integration of projects are of huge importance, especially now, and would be put on a future Council meeting agenda.

Concept Clearances

Astrocyte Heterogeneity, Development, and Function in Brain Regions Relevant to Mental Illness

David Panchision, Ph.D., Branch Chief within the Division of Neuroscience and Basic Behavioral Science (DNBBS) described a concept for a potential future initiative aimed at supporting discovery research on astrocyte diversity and function, adaptation of new technologies to astrocyte research, and the application of these technologies to the study of brain processes relevant to mental illness.

It is estimated that 50 percent of human brain mass is composed of astrocytes, a type of support cell in the brain, whose courses of development correlate with the trajectory of mental illnesses. There is increasing evidence linking astrocytes to mental illnesses, such as schizophrenia. However, most basic neuroscience funding and studies focus on neurons, while studies of astrocytes are relatively few in number. This gap has been due to the lack of tools to identify and target astrocytes robustly. However, a convergence of new astrocyte markers and genetic tools to study astrocyte function provide traction to address this gap, and to yield mechanisms or predictive measures of cell function relevant to mental illness.

Three research areas will be supported through this initiative: 1) defining the molecular basis of functional heterogeneity between astrocyte subtypes in the brain; 2) developing or utilizing new genetic tools for reporting or manipulating astrocyte development, subtype identity, or function; and, 3) using these novel tools or subtype properties to assay brain regions or domains of function relevant to mental illnesses.

This research is expected to yield new tools for reporting and manipulating diverse astrocyte subtypes in model systems; characterize novel combinatorial regulatory mechanisms of astrocyte development; identify mechanisms by which astrocytes regulate neural circuits serving cognition, emotion, or social function; distinguish the role of astrocytes in gene variants or gene-environment-development interactions relevant to mental illnesses; and, indicate new astrocyte activities that may be therapeutic targets for mental illnesses.

Discussion

Dr. Jarvis said he wholeheartedly supports the initiative. Noting that the three research areas focus on the cellular/molecular level, he recommended adding a research area that would invite investigations of whether astrocytes actually have an effect on mental functioning or disorder.

Dr. Shatz commented that microglia are important as well, as they are closely involved in the same processes for astrocytes described by Dr. Panchision.

Noting that astrocytes are incredibly important for epilepsy and Alzheimer's disease, Dr. Paul asked if this initiative could be undertaken with the other brain Institutes. Dr. Insel replied that there is a lot of activity in this area at the National Institute of Neurological Disorders and Stroke (NINDS) and that Dr. Panchision will pursue this possibility.

Neural Mechanisms Underlying Sex Differences in Risk and Resilience for Mental Illness

Janine Simmons, M.D., Ph.D., Branch Chief within DNBBS, described a concept for a potential future initiative to support basic and translational research on the neurobiology of sex differences in order to expand our understanding of the etiology and developmental trajectories of mental disorders in males and females, and to inform novel approaches to individualized interventions and treatment across the lifespan.

It is well established that an individual's sex can influence susceptibility, prevalence, and age of onset for mental disorders. Disorders that emerge early in development, such as autism spectrum disorder, attention deficit hyperactivity disorder, Tourette syndrome, and early-onset schizophrenia, tend to be more prevalent in males. Disorders with onset in adolescence or adulthood, such as major depression, anxiety, and eating disorders, are more prevalent in females. Despite these clear epidemiological trends, very little is known about the precise timing, neural circuitry, or mechanisms underlying the expression of sex differences in mental disorders. Analysis of the NIMH portfolio suggests that explicit testing for sex differences is rarely proposed, whether in basic or translational research, and that there are very few translational studies that compare the etiology of mental disorders between males and females. Particularly lacking are theoretical models of disease that attempt to explain how neurobiological sex differences at particular points in development interact with other biological or environmental factors to confer risk and resilience for mental disorders. Moreover, sex differences are likely to contribute significantly to individual differences in response to treatment and intervention. Research on sex differences in the developmental etiology of mental disorders may provide information fundamental to the development of personalized interventions.

Anticipated outcomes of this initiative include: 1) increased understanding of how interactions among sex chromosomes, steroid hormones, and environment shape sexually dimorphic neural pathways and behavior; 2) stimulation of research on neurodevelopmental sex differences that confer vulnerability or protection in individuals at familial/genetic risk for mental disorders; and, 3) identification of sexually dimorphic points of vulnerability and developmental divergence that influence the onset and symptoms of mental disorders.

Discussion

Dr. Jarvis agreed with the inclusion of both males and females in animal models, pointing out that it seems to be encouraged, but not necessarily enforced. He cautioned the Institute to be prepared for budgets to go up, because twice the work is sometimes required. Dr. Simmons said that a recent intramural workshop on the subject revealed that one of the major barriers to studying sex differences appears to be budget constraints.

Howard Eichenbaum, Ph.D. said in animal studies including females, the Institute may have to be quite selective. Adding females inflates the group size to allow for variances in cycling, with many groups at different points in the cycle. In certain cases, this can be an important factor.

Dr. Insel quoted Dr. Collins in saying there is an 18-fold difference in aggression based on one genetic change, the Y chromosome. It represents a big scientific opportunity—a chance to try to understand what it is about the Y chromosome that makes that difference. How do differences in the estrus cycle lead to such huge effects? Through the workshop that Dr. Simmons mentioned, it has become clear that the effect sizes of gender are much larger than the effects found in other comparisons.

Dr. Blyler suggested that this initiative may be a good place to address co-occurring disorders, because the flip side of depression in women is alcoholism and substance use in men. Collaborating with Institutes such as the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism to address these disorders would be appropriate.

Innovative Pilot Studies of Novel Mechanisms of Action Compounds

Lois Winsky, Ph.D., Branch Chief within DNBBS described a concept for a potential future initiative to support innovative Phase I and Phase IIa studies of compounds of potential neurobiological relevance with novel mechanisms of action. Phase I studies (first-in-human pharmacology experiments) will assess target engagement, pharmacological or physiological effect, safety, and tolerability of novel compounds in order to build a pipeline for initial Phase II testing or efficacy trials. Phase IIa proof-of-concept studies of novel compounds will use pharmacologically based dosing, with assessment of target engagement and impact on clinically relevant physiological systems. The initiative encourages a broad approach for exploring pharmacological and functional effects of compounds, in the context of standard outcome measures.

There is a critical need to accelerate the development and testing of novel treatments for mental disorders. This need is intensified by the poor success and approval rate of new drugs for central nervous system disorders, and the departure of pharmaceutical companies from psychiatric therapeutic development. This initiative will address this need by supporting experimental medicine-based Phase I and Phase IIa studies. The objective of the initiative is to facilitate Phase IIa and proof-of-concept studies, as well as rapid collection of data, in order to de-risk novel mechanism of action or combination treatments and thereby attract private funding for further clinical and commercial development.

Discussion

Dr. Paul said he strongly endorses this program. He recounted recent brainstorming sessions with a big pharmaceutical company that convinced him that industry will renew development of novel compounds if the NIMH-supported research justifies it. Dr. Paul said that doing Phase IIa studies in psychiatry is not easy, because they can produce difficult-to-interpret data, or placebo responses that are greater than drug effects. He advised the staff to be very careful doing Phase Ib or IIa proof-of-concept studies, and to be vigilant about detecting type-II errors and reducing placebo responses.

Dr. Insel said that a recent meeting at NIH with heads of many pharmaceutical companies and their lawyers was held to discuss rescuing the compounds that they have put on the shelf. This is an NIH-wide effort, and it will come under the purview of the new NCATS, once it is authorized and appropriated.

Dr. Robinson Beale said that in most of the failed trials, failure occurred while looking for a clinical effect; the initiative will go beyond that and assess the presumed biological mechanism.

Dr. Insel emphasized that this research is a new way of thinking about drug development. It uses true experimental medicine, moving quickly into humans. Projects are conducted on a small number of participants, but go much deeper. For example, PET imaging might be used to verify that the compound actually does get into the brain and has an effect. And if the drug failed, researchers will know it was not because it never got into the brain, but that it was the wrong compound.

Harnessing Advanced Health Technologies to Drive Mental Health Improvement

David Chambers, D.Phil., Branch Chief within DSIR, described a concept for a potential future initiative aimed at supporting research to test the effectiveness of existing health information technologies (IT) to improve access to and quality of mental health care significantly, and improve the collection and use of actionable mental health information.

Advances in health technologies continue at an exponential rate, drastically altering the way we communicate, seek information, and receive services. As these technologies grow increasingly powerful and mobile, they offer the potential to transform mental health care and enable care providers to assess biological processes, disease states, behaviors, attitudes, and the environment more rapidly and accurately. Advances in sensor technologies, virtual reality, mobile assessment, and gaming represent real opportunities to increase access, engagement, reach, and quality of care significantly.

A November 2010 NIMH workshop co-sponsored by the Agency for Health Research and Quality entitled, “Mental Health & Health IT Research: The Way Forward,” assembled experts in mental health interventions and services research together with technologists, providers, consumers, and industry representatives to discuss opportunities to leverage emerging technologies toward improved research and service delivery. Participants identified a number of significant gaps in knowledge, which were provided with a cross-walk with relevant ongoing analyses within the NIMH portfolio. This initiative would target studies to close these gaps.

Key topics for study under this concept include: 1) effectiveness of technology-supported service delivery models that allow for asynchronous assessment, service delivery, and monitoring; 2) effectiveness of mobile technologies (e.g., smart phones, texting services, social media) to increase use of mental health services and adherence to treatments; and 3) use of technologies (e.g., tablets, smartphones, sensing devices) to improve data capture, real-time assessment, and prediction of risk and acute service need.

Discussion

Dr. Simon strongly endorsed this initiative. He emphasized that “technology-enabled assessment” should not be construed as using a smart phone to administer the same self-report measures that have always been used. Instead, the research should consider direct interaction with core pathophysiological processes. Instead of asking people about how their brains are functioning, it may be possible to interact directly with how their brains are functioning and what their activity patterns are. This technique would bypass a lot of the problems with current measures. He also added that this could tie in with the Research Domain Criteria (RDoC) Project in pulling out the new raw material that is needed to understand and more correctly classify and diagnose mental health conditions.

Dr. Robinson Beale said there is much activity in this area, and she has seen a mismatch between providers and consumers in the types of content they are accessing. There are also standardization issues. She suggested that NIMH could help to define the dynamics involved and identify standard domains that need to be addressed. She suggested that the Institute’s role might be centered on evaluating the research currently being conducted more than merely funding new research.

Ms. Betts said a lot of work in suicide prevention for adolescents and on social networking has been done in Australia, because of its vast distances and partnerships with scientists in the United Kingdom. She recommended their work be consulted before embarking on a new initiative.

Advancing HIV Prevention through Transformative Behavioral and Social Science Research

Dianne Rausch, Ph.D., Deputy Director of the Center for Mental Health Research on AIDS, Division of AIDS Research, described a concept for a potential future trans-Institute initiative co-sponsored by the NIH Office of AIDS Research (OAR) and the National Institute of Allergy and Infectious Diseases (NIAID). This initiative aims to advance generalizable knowledge about HIV prevention through transformative behavioral and social science research. An underlying assumption for this initiative is that methods of and findings from social and behavioral studies can make essential contributions to research which utilizes biomedical modalities. In addition, biomedical perspective is essential for the advancement of social and behavioral HIV research on prevention.

In July 2010, the White House released the National HIV/AIDS Strategy. The Strategy presents a vision of the United States as a place where new HIV infections rarely occur, and where all persons have access to needed care. As one response to the Strategy, the OAR sponsored and convened the “Social and Behavioral HIV Prevention Research Think Tank” in September 2010. This meeting brought together experts from research and academic institutions, government agencies, and community constituency groups to exchange information on the state of HIV social and behavioral prevention research in the United States, to develop ideas for further research, and to determine opportunities for partnerships and collaborations. One of the outcomes of the meeting was a set of recommendations addressing research approaches and questions for consideration.

The objective of this research initiative is to expand the behavioral and social science knowledge-base, for the development or implementation of interventions with the potential to affect the prevention of HIV transmission or acquisition, and to result in decreases in HIV incidence at the population level. This initiative is specifically applicable to HIV in the United States.

Discussion

Dr. McGlashan asked which programs have been most effective to date.

Dr. Rausch said that circumcision was thought to be very effective in men internationally. It is difficult to look for incidence in this country, but there has been much effort to take the concept of circumcision and its effects and move it more broadly. One of the most recent successes has been the prophylactic use of antiretroviral medications, which has been very effective with gay men and men who have sex with men. That approach becomes more complex with women, who may become pregnant. More research is needed on how best to use pre-exposure prophylaxis; for example, for which populations would pre-exposure prophylaxis be most advantageous? Yet another strategy being discussed domestically and globally is testing and treatment linked to care. Treated, the HIV-positive person becomes less infectious and is less likely to pass on the virus. If people get linked to care and stay in care, they are less infectious and are healthier overall. There is a huge endeavor worldwide to find more effective ways to get people to test; unfortunately, there is a lot of resistance to it.

NIMH New Investigators

Dr. Insel welcomed the four presenters to the Council meeting, noting that one of the highest priorities for NIMH is promoting the next generation of scientific leaders. NIMH has invited four promising new investigators doing exciting work to give brief presentations on their areas of science and to talk about the challenges they face as junior investigators, particularly in the current fiscal climate.

Functional Developmental Trajectories in Youth with and without Mental Disorders

Damien Fair, PA-C, Ph.D., Assistant Professor, Behavioral Neuroscience at Oregon Health and Science University, explained the technique used: resting-state functional connectivity MRI (rs-fcMRI) combined with graph theory to study principles of typical and atypical brain development. With traditional task-based fMRI, subjects enter the scanner, and then repeatedly follow a pattern of doing a task interleaved with a control task (for example, finger-tapping and then resting). Statistical averaging makes it possible to identify the parts of the brain that are active during the task, relative to the resting portion. Because of what was once thought of as noise in the signal, numerous repetitions of the task were required. However, more recent research has found that the regions activated during a functional task are also spontaneously oscillating when they are at rest, suggesting this presumed noise was not noise at all. Dr. Fair focuses his research on this ‘resting-state’ connectivity.

The other technique being used is graph theory: the study of networks, where networks are sets of nodes that are linked by specific lines or edges. For their purposes, the nodes are the brain regions of interest, and edges or links are the spontaneous or correlated neural activity. Probably the most widely known discovery about networks is the so-called small world effect: the idea that any two people, no matter how far apart they are, can be connected by at least one link, though there are probably many short chains.

Researchers have quantified the structure of small networks using two parameters: path length (how quickly a node can reach another node in the system) and cluster coefficients (how many nodes are linked). Understanding what happens when going from a system that has a high cluster coefficient and high path lengths, to a system that has high cluster coefficients and short path lengths, is important for research into the developing brain.

Using these tools, Dr. Fair and his colleagues found in 2007 that if you look at connections that seem to get bigger or stronger with age—i.e., are bigger in adults than children—and that seem to be between regions that are more distant in space, you will find that there was an increase in these long-range connections over time. They also noticed that connections that seem to be bigger or stronger in children than in adults seemed to be between regions that are closer in space, that is, there seemed to be a decrease in these short-range connections over time. Dr. Fair said he was excited by this observation because it reminded him of what he had read about the development of the small world by Watts and Strogatz. Thus, he and his colleagues tested the idea and found that in adults, as expected, there are high cluster coefficients and short path lengths. Adult brains are organized as a small world. But they also saw the same thing in children, whose brains were also organized as a small world, in that they had high cluster coefficients and short path lengths.

The investigators learned from this observation that network maturation seems to follow the principle of “local to distributed trajectory” over time. In addition, they found that these small world metrics were surprisingly similar, suggesting a corresponding level of global efficiency within the network for children and adults. They were able to develop functional growth curves for brain development, similar to the pediatrician’s growth curves for height, weight, and head circumference. To be truly translational and clinically useful, however, the findings must prove to be robust across institutions, and sensitive enough to pick up disease processes. With the collaboration of New York University researchers and a world-wide consortium, Dr. Fair’s group generated a dataset across many institutions to start testing their ideas. They are preliminarily finding the same types of short- and long-range connections in subjects, even across institutions, and that information was enough to develop growth curves.

Their findings from a sample of individuals with ADHD revealed that: 1) many development-related changes in rs-fcMRI are robust to institutional variance; 2) underlying physiologic distinctions within ADHD can be discerned even in patients with substantially overlapping clinical symptoms; and 3) combined-type ADHD is associated with developmental immaturity, detectable in individual cases, opening the door for translational applications.

In closing, Dr. Fair mentioned the three factors that were instrumental in his development as a scientist. First was an excellent mentorship. His mentors Brad Schlaggar, Steve Petersen, and Joel Nigg have been pivotal in his growth as a scientist. Second, he was able to secure many small funding awards that helped him become more autonomous early on and allowed him to hire help so that he could use his time more efficiently. And, third, he had access to data, with multiple collaborators and data sharing within and between institutions, all of which has accelerated his progress significantly. Dr. Fair thanked NIMH for inviting him to speak and providing funding support for his research.

Discussion

Dr. Newcomer asked if the group conceptualizes the ADHD effect as an epiphenomenon of the children’s lack of learning, or if it is somehow causally related to their problems?

Dr. Fair said he believes it is probably not an epiphenomenon as a result of not learning in school, but that the pathology is actually leading to some of the problems that children might have in school. He said he and his colleagues are studying younger and younger children in some populations and will be able to test those possibilities.

Dr. McGlashan asked if they have looked at treating ADHD, and if they are addressing how the patterns reflect developmental trajectories.

Dr. Fair said that while in the scanner, the children are off their medications. Preliminary data on how stimulants affect these patterns suggest that they very quickly make these systems become more mature. The group is now examining this more specifically over time.

Medicare Drug Benefits and High Cost Medications: Antipsychotic Use under Part D

Vicki Fung, Ph.D., a health services researcher and health economist at the Kaiser Permanente Northern California, described her study of the impact of Medicare drug benefits on patients receiving antipsychotic drug therapy. Her research focuses on health care financing and, in particular, insurance coverage. Her goal is to try to understand how insurance benefits can be designed affordably in a way that improves access and quality of care for vulnerable populations, especially patients with mental illness.

Dr. Fung explained that the structure of the new Medicare Part D program can have important implications for whether patients with mental illness receive appropriate therapies and are able to stay on those therapies, and there is much to learn about how this program is affecting patients. Dr. Fung said that her study will examine the impact of Medicare drug coverage levels on three outcomes: 1) antipsychotic drug use, including adherence to therapy and choice of therapy; 2) major clinical events, including hospitalizations, emergency department visits and mortality; and 3) medical spending, including pharmacy spending, outpatient and hospital costs to explore the net impact on total costs. These represent sequential steps in a pathway, by which cost sharing can affect patients’ clinical and economic outcomes.

The introduction of Part D presents a natural experiment in which to examine some of these fundamental questions. A range of cost-sharing levels will be studied. Some patients are enrolled in the more basic Part D plans that have high cost sharing, including the “donut hole” or coverage gap, which occurs when patients lose coverage after their drug spending exceeds a certain level during the year. Some are enrolled in enhanced plans that have some supplemental coverage during this gap. And some receive subsidized coverage that fills in the gap completely, either through their former employers if they have retiree drug benefits, or through low-income subsidies provided by Medicare; that group includes most of the dual-eligible Medicaid/Medicare beneficiaries.

Dr. Fung said she and her colleagues will examine these questions using comprehensive electronic data from two large Medicare Advantage systems. The data will be used to study patients longitudinally, both before and after the introduction of Part D, and adjustments will be possible for potential confounders, including socioeconomic factors and comorbidity levels. With access to detailed diagnostic information, there is particular interest in potential variations in responses to cost sharing by diagnosis. This takes into account the appropriateness of the antipsychotic prescription across different diseases and the level of evidence that supports use of these drugs to treat a particular disease, as well as the availability of treatment alternatives. Having just recently been funded, Dr. Fung said she did not have any preliminary findings yet to share; however, an interdisciplinary team has been assembled to address the clinical, methodological and policy issues anticipated in the study.

Discussion

Dr. McGlashan applauded this work, as it is clinically sensitive and sorely needed.

Referring to Dr. Fung’s early comment about people with mental health problems being especially vulnerable to the unintended consequences of the Part D policy, Dr. Simon suggested building into the experiment some a priori possibilities about how people in varying situations would be expected to respond to different incentives and then use some of these data to observe that.

Dr. Fung said that even after years of study, researchers are still trying to figure out how the benefit works; therefore it is hard to imagine how a beneficiary can understand it. Several cost-sharing mechanisms exist within the plans, including tiered co-payments and fixed co-payments versus coinsurance. It is a prime opportunity to examine how patients respond to various types of cost sharing mechanisms throughout their continuum of spending.

Dr. Paul asked if the researchers are starting to model in concurrence with the implications of virtually all psychiatric medicines going generic within the next 12-16 months. By 2014, there may not be any patent-protected psychiatric drugs, except for one of the long-acting injectable antipsychotics.

Dr. Fung said she thought that during the study period at least one or two antipsychotics will go generic, giving the researchers a chance to examine how patients respond to these changes and how the drug use patterns vary along with these changes in the marketplace.

Fear Memory Attenuation: Testing Reconsolidation Extinction Boundaries

Marie Monfils, Ph.D., Assistant Professor of Psychology at the University of Texas at Austin said that most of her work focuses on fear memory, using fear conditioning as a paradigm. Dysregulation of the fear response occurs in many mental disorders. Progress in understanding the neural basis of fear learning has largely come from conditioning studies in which an initially neutral conditioned stimulus (e.g., a tone) is paired with an unconditioned stimulus (e.g., a foot-shock), such that at a later time, the tone alone comes to elicit a fear response. In her studies, Dr. Monfils said, she pairs an auditory tone as the neutral stimulus with a shock to produce an expression of fear, in a rodent model system.

Following initial learning, fear memory is consolidated, after which the memory is more resistant to modification. After consolidation, the memory can later be retrieved by presenting the conditioned stimulus. This process engages two seemingly opposing mechanisms: reconsolidation and extinction. Extinction of the fear expression occurs when a conditioned stimulus is presented repeatedly in the absence of a threat. Clinically, exposure therapies are based on this principle. Such therapies, however, even when facilitated pharmacologically, do not last forever. Extinction actually leads to the formation of a second fear memory that serves to inhibit or suppress the original fear response. The result is a susceptibility to the return of fear because of spontaneous recovery, reinstatement, or renewal, depending on the conditions in which the stimuli have been presented.

Another way of reducing fear memory, based on the principle of reconsolidation, is based on research suggesting that each time memory is retrieved, it becomes susceptible to updating. In rodents, if this retrieval is targeted and the reconsolidation process interfered with, then a drastic reduction in fear expression occurs. This approach may not be ideal, because the drugs used to target fear memories are generally toxic to humans.

A recently devised method uses a combination of extinction and reconsolidation principles to capitalize on the strengths of both approaches. The goal is to use extinction in a period during which the memory is destabilized—during reconsolidation. This technique allows for a more persistent attenuation of the fear via updating of the initial memory.

Discussion

Dr. Eichenbaum asked whether the exposure that would be within the reconsolidation window operates by a different mechanism than does the action of a drug which blocks cellular reconsolidation. What does this difference say about the original ideas about reconsolidation blockade? Will it reverse the plasticity process or do something else?

Dr. Monfils said that her intention is not to wipe out memories. Most likely, there is an additional adaptive basis for reconsolidation that allows for memories to be strengthened and/or updated.

New Approaches that Measure how Psychiatric Illness Alters Information Processing in Prefrontal Microcircuits

Vikaas Sohal, M.D., Ph.D., Assistant Professor, University of California, San Francisco, spoke about information processing in prefrontal microcircuits and its relevance to psychiatric disease. Dr. Sohal described the hypotheses that disruptions in parvalbumin (PV) interneurons and gamma oscillations — a form of synchronized neural activity — contribute to schizophrenia. Researchers have found deficits in PV interneurons in post mortem brain tissue from patients with schizophrenia, and PV interneurons are thought to generate gamma oscillations during cognitive tasks. Thus, PV interneuron hypofunction in schizophrenia may cause disruptions in gamma oscillations, resulting in disorders of information processing that contribute to cognitive deficits and other symptoms of schizophrenia.

Dr. Sohal has tested aspects of this hypothesis by studying the role that PV interneurons play in gamma oscillations, using an innovative method for modulating distinct brain circuits in the cortex developed in Karl Deisseroth’s laboratory. Calling their method ‘optogenetics’, the Deisseroth lab 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. These optogenetic tools, or light-activated proteins, include a protein that is activated by blue light, and a protein that is activated by yellow. When the blue-light sensitive protein is activated, brain cells fire, whereas when the yellow-light sensitive protein is activated, cells are inhibited from firing.

In the first set of experiments, Dr. Sohal and his colleagues recorded gamma oscillations in the prefrontal cortex of anesthetized mice. When they inhibited PV interneurons using the yellow light protein, they found, consistent with their expectations, that this suppressed gamma oscillations in the prefrontal cortex. In the second experiment, they did the opposite. They used the blue-light protein to activate PV interneurons in a way that mimicked feedback inhibition. This feedback inhibition dramatically increased the amount of gamma frequency power in these circuits, but it did not have much effect at other frequencies. These two findings were consistent with the idea that PV interneurons are not just involved or participating in gamma oscillations, but actually are playing a critical role in the genesis of these oscillations. Dr. Sohal next investigated the effect of gamma oscillations on neurons, using tools from math and physics. He and his colleagues confirmed that gamma oscillations can enhance the amount of information that individual neurons transmit. This observation is consistent with the idea that disruptions in PV interneurons may lead to disruptions in gamma oscillations that would impair information processing, possibly contributing to impaired cognition in diseases such as schizophrenia.

A second project focuses on dopamine and its effects on the prefrontal cortex in schizophrenia. Dr. Sohal’s team used drugs to activate dopamine D2 receptors in brain cells from the prefrontal cortex and found something that looks like noisy activity in one particular type of neuron. Dr. Sohal and his colleagues explored the idea that noisy activity contributed abnormal prefrontal functioning by observing mice exploring a novel social target while using blue-light protein activity to turn on neurons in the prefrontal cortex of these mice. They found that stimulating these brain cells in a way that might model “noisy” prefrontal activity dramatically impaired social behavior in these mice. Dr. Sohal said he hoped that these experiments illustrate new techniques that can be used to study how cellular and synaptic mechanisms might contribute to behaviors that are relevant to symptoms of mental illness. He hopes this work leads to a greater understanding of the pathways that produce these symptoms and could eventually be utilized to develop new treatments.

Regarding his experience as an early-stage investigator, Dr. Sohal said that residency training is a time when many young investigators who have completed M.D.-Ph.D. training stop doing research. Many who do continue feel that it is a relatively unproductive time in their careers. He suggested a grant mechanism that would support new residents with M.D.-Ph.D. training by stipulating a certain amount of time and the necessary resources for them to carry out their research. This would incentivize residency programs to protect time for research in a standardized way and would free residents from having to negotiate that time on their own. This would also hopefully be an incentive for the resident to convey what is being learned to their peers and others involved in the clinical enterprise.

Discussion

Dr. Jarvis asked about the experiments involving D2 receptors and commented that as a technicality it might be a better approach to think of it as activating the circuit as opposed to a specific cell type.

Dr. Sohal replied that these initial experiments were intended to set up an area where they could start to see an effect, but are now focusing on circuit consequences. Dr. Sohal said he thinks about these experiments in two ways: first looking at what one very simple manipulation does, then trying to control and understand all the parameters in the system.

David Lewis, M.D. asked about the role of PV interneurons in gamma oscillations, since there are at least three different classes of gamma neurons that express PV in the mouse cortex; he asked if Dr. Sohal had thoughts about ways to look at the relative contribution of each to the oscillation.

Dr. Sohal said he has struggled with this question. He said that although they do not have the tools to specifically target different subtypes of PV interneurons, an alternative is to use optogenetic tools to assay the connections to and from different subtypes of PV interneurons to determine circuit activity. A second approach is to causally identify how different subtypes contribute to disease by studying mice in which there are disruptions in PV interneuron development.

Dr. Insel noted that the field of inhibitory neurons is exploding now, and researchers who do functional assays are needed to dissect out the subclasses, which can be defined with molecular tools.

Dr. Paul said he was intrigued by the phencyclidine data and the connection Dr. Sohal made with L-type calcium channels. He wondered if it could be like a quick in vitro screen for new antipsychotics.

Dr. Sohal replied that through their study, they think phencyclidine may play a different role than the commonly thought of agonist receptor antagonist function; they are looking at some synaptic mechanisms that may be involved. While he is just getting his lab going and there is much work to be done, he is making an effort to put people on projects to study different antipsychotics.

General Discussion with Early-Stage Investigators
Summarizing the recommendations made by the presenters to improve the experience of early-stage investigators, Dr. Insel invited the Council to engage in conversation with the four investigators and Nancy Desmond, Ph.D., Director of the NIMH Office of Research Training and Career Development. This discussion produced the following observations:

  • Relatively small grants awarded to postdoctoral students can be very helpful in funding the students’ research, and these grants also provide the postdoctoral student with the needed autonomy to have an impact on the direction of their research.
  • Small grants from a junior investigator’s home institution can catalyze a project and can be used as a step toward getting an NIH grant, which provides a longer, more stable source of funding.
  • Among the factors that keep early investigators from getting discouraged and leaving the field is good initial mentorship. Being part of an established team with a senior investigator who serves as strong mentor is critical to getting to the point of obtaining one’s own funding.
  • Senior faculty members and deans can be influential in helping junior investigators protect their time, by helping junior investigators avoid unnecessary service on committees, for example.
  • Early investigators should be encouraged to take advantage of opportunities to network with others who have diverse opinions and expertise as a means to grow their science and collaborations.
  • It is important for junior investigators to get advice from more experienced researchers; however, junior investigators should also be encouraged to follow their own vision, rather than adhere too closely to the vision of a mentor.
  • Feedback from study sections provides invaluable learning as early-stage investigators are becoming familiar with the grant process.
  • Many potential scientists are fascinated with the brain, and there are a number of directions they can go within neuroscience. For those choosing clinical study in the mental health field, it is quite challenging, especially in cognitive and systems neuroscience, which involves heterogeneous and problematic patient populations. In clinical rotation, it is important that the scientific knowledge of M.D.-Ph.D. students is valued by the clinicians with whom they work. A supportive environment can tip the balance in favor of a scientific career in mental health.
  • The K99 Pathway to Independence Award has been a useful mechanism for transitioning the promising postgraduate student into a stable position in a laboratory. Since the grant mechanism was first offered several years ago, the vast majority of its recipients have successfully transitioned to faculty positions.

Dr. Insel thanked the four scientists for presenting to Council, saying that in the midst of tough budget talks, it is encouraging to hear about the exciting things happening in science. He commended them for finding a way forward despite any obstacles they met.

Public Comments

Llewellyn Cornelius, Ph.D. from the Society for Social Work and Research appreciated the comments from the Council about striking a balance in the NIMH portfolio. In particular, he thought the comments related to projects assessing cost effectiveness and high-impact research were timely; it is an important issue for all researchers within the academic community and in grant review panels. He also endorsed the idea of a guidance document that would help researchers understand where NIMH thinks the science should go. Scientists need to know not only the best subjects to pursue, but also what is fundable and which projects would have the most impact for NIMH.

Dr. Insel thanked everyone for their participation. He said the comments received about the concept clearances were extremely helpful, as well as the discussion about finding the right balance.

Adjournment

Dr. Insel adjourned the meeting at approximately 12:30 p.m.

I hereby certify that, to the best of my knowledge, the foregoing minutes are accurate and complete.

Thomas R. Insel, M.D., Chairperson

Appendix A

 Summary of Primary MH Applications Reviewed
May 2011
Category IRG Recommendation
Scored
#
Scored
Direct Cost $
Not Scored
(NRFC)
#
Not Scored
(NRFC)
Direct Cost $
Other
#
Other
Direct Cost $
Total
#
Total
Direct Cost $
Research 766 $885,265,654.00 662 $605,900,001.00 0 $0.00 1428 $1,491,165,655.00
Research Training 3 $4,920,475.00 0 $0.00 1 $125,640.00 4 $5,046,115.00
Career 3 $36,237,950.00 18 $11,722,025.00 0 $0.00 66 $47,959,975.00
Other 0 $0.00 0 $0.00 0 $0.00 0 $0.00
Totals 817 $926,424,079.00 680 $617,622,026.00 1 $125,640.00 1498 $1,544,171,745.00

Appendix B
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

Members

David G. Amaral, Ph.D. (12)
Professor
Department of Psychiatry
The M.I.N.D. Institute
University of California, Davis
Sacramento, California
Carl C. Bell, M.D. (11)
President and CEO
Community Mental Health Council and Foundation, Inc.
Chicago, Illinois
Robert Desimone, Ph.D. (11)
Director, McGovern Institute for Brain Research
Massachusetts Institute of Technology
Cambridge, Massachusetts
Ralph J. DiClemente, Ph.D. (12)
Candler Professor
Department of Behavioral Sciences and Health Education
Rollins School of Public Health
Emory University
Atlanta, Georgia
Howard B. Eichenbaum, Ph.D. (12)
Professor and Director
Center for Memory and Brain
Department of Psychology
Boston University
Boston, Massachusetts
Daniel H. Geschwind, M.D., Ph.D. (11)
Gordon & Virginia MacDonald
Distinguished Chair in Human Genetics
Professor of Neurology & Psychiatry
University of California, Los Angeles
Los Angeles, California
Portia E. Iversen (12)
Co-Founder
Cure Autism Now Foundation and Autism Genetic Resource Exchange
Los Angeles, California
Kay Redfield Jamison, Ph.D. (13)
The Dalio Family Professor in Mood Disorders
Professor of Psychiatry
Department of Psychiatry and Behavioral Sciences
The Johns Hopkins University School of Medicine
Baltimore, Maryland
Erich D. Jarvis, Ph.D. (Ad Hoc)
Associate Professor
Department of Neurobiology
Duke University Medical Center
Durham, North Carolina
David A. Lewis, M.D. (11)
Director, Translational Neuroscience Program
University of Pittsburgh
Pittsburgh, Pennsylvania
Roberto Lewis-Fernandez, M.D. (13)
Professor of Clinical Psychiatry
Columbia University Director
NYS Center of Excellence for Cultural Competence and Hispanic a Treatment Program
NY State Psychiatric Institute NYSPI
New York, New York
Thomas H. McGlashan, M.D. (12)
Professor
Department of Psychiatry
Yale University School of Medicine
New Haven, Connecticut
John W. Newcomer, M.D. (Ad Hoc)
Senior Associate Dean for Clinical Research
Leonard M. Miller Professor of Psychiatry and Behavioral Sciences
Leonard M. Miller School of Medicine
University of Miami
Miami, Florida
Steven M. Paul, M.D. (12)
Director
Appel Alzheimer’s Disease Research Institute
Professor of Neurology (Neuroscience) and Psychiatry
Weill Medical College of Cornell University
New York, New York
Rhonda Robinson Beale, M.D. (13)
Chief Medical Officer
Optum-Health Behavioral Solutions
Glendale, California
Carl Shatz, Ph.D. (13)
Director, Bio-X
Professor of Biology and Neurobiology
James H. Clark Center
Stanford, California
Gregory E. Simon, MPH, M.D. (14)
Senior Scientific Investigator
Center for Health Studies/Behavioral Health Service
Group Health Cooperative
Seattle, Washington

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, Maryland
Veterans Affairs
Ira Katz, M.D., Ph.D.
Department of Veterans Affairs
Office of Mental Health Services
Washington DC
Department of Defense
John A. Ralph, Ph.D.
Commander, U.S. Navy
National Naval Medical Center
Bethesda, Maryland

Liaison Representative

A. Kathryn Power, M.Ed.
Director, Center for Mental Health Services
Rockville, Maryland