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NAMHC Minutes of the 230th Meeting

National Advisory Mental Health Council Minutes of the 230th Meeting
January 20, 2012

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

Introduction

The National Advisory Mental Health Council (NAMHC) convened its 230th meeting in open policy session at 8:30 a.m. on January 20, 2012 at the Neuroscience Center in Rockville, Maryland, and adjourned at approximately 12:30 p.m. In accordance with Public Law 92-463, the policy session was open to the public. The NAMHC reconvened for a closed session to review grant applications at 1:15 p.m. on January 20, 2012, at the Neuroscience Center in Rockville, Maryland, until adjournment at approximately 5 p.m. (see Appendix A: Review of Applications). Thomas R. Insel, M.D., Director, National Institute of Mental Health (NIMH) chaired the meeting.

Council Members Present at the Grant Review and/or Open Policy Sessions
(See Appendix B: Council Roster)

Chairperson: Thomas R. Insel, M.D.

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

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

Ex Officio Members:

  • Ira Katz, M.D., Ph.D., Department of Veterans Affairs

Liaison Representative at the Open Policy Session:

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

Others Present at the Open Policy Session:

  • Erica Ahmed, Mental Health America
  • Andrea Baruchin, Foundation for the National Institutes of Health
  • Eric Caplan, Biopractices, LLC
  • Christina Carter, Society for Women’s Health Research
  • Jeffrey Charvat, National Association of School Psychologists
  • Yoshie Davidson, American Academy of Child and Adolescent Psychiatry
  • Florence Fee, No Health without Mental Health
  • Jo Anne Goodnight, ITECS Innovative
  • Ron Honberg, National Alliance on Mental Illness
  • Danielle Hunter, Dixon Group
  • Sarah Hutcheon, Society for Research in Child Development
  • Alan Kraut, Association for Psychological Science
  • E. James Morton, Treatment and Research Advancements Association for Personality Disorder
  • Anne Michaels, National Foundation for Mental Health
  • Josha Narotsky, Transcriber
  • Wendy Naus, Lewis-Burke Associates, LLC
  • Michelle Rodrigues, SEI International
  • Carl Schmid, The AIDS Institute
  • Matthild Schneider, Treatment and Research Advancements Association for Personality Disorder
  • Jerilyn Schweitzer, Science Writer
  • Angela Sharpe, Consortium of Social Science Association
  • Andrea Silva, American Academy of Child and Adolescent Psychiatry
  • Paula Skedsvold, Federation of Associations for Brain and Behavioral Sciences
  • Anita Sostek, Autism Speaks
  • Margot Walker, Research Council
  • LaTrese Wallace, Dixon Group

Open Policy Session: Call to Order and Opening Remarks

NIMH Director Dr. Insel called the open policy session to order and welcomed everyone in attendance. He introduced four new Council members:

  • Randall L. Carpenter, M.D., Founder, President, and CEO of Seaside Therapeutics;
  • Lisa Greenman, J.D., an attorney with the Federal Public Defender Organization;
  • Steven E. Hyman, M.D., Scholar-in-Residence with the Stanley Center for Psychiatric Research at the Broad Institute; and
  • Carol Tamminga, M.D., Chair and Professor in the Department of Psychiatry at the University of Texas, Southwestern Medical Center at Dallas

Dr. Insel specifically welcomed Paolo del Vecchio, M.S.W., Acting Director of the Center for Mental Health Services (CMHS), Substance Abuse and Mental Health Services Administration (SAMHSA).

Approval of the Minutes of the Previous Council Meeting

Dr. Insel asked Council members for comments on the minutes from the September 2011 Council Session. Jane Steinberg, Ph.D., NAMHC Executive Secretary noted one amendment to the minutes, which were subsequently approved unanimously.

NIMH Director’s Report

Dr. Insel reviewed several ongoing activities at the Department of Health and Human Services (HHS) and National Institutes of Health (NIH) levels since the September 2011 NAMHC meeting.

HHS and NIH-Wide Updates

Dr. Insel highlighted the reauthorization of the Combating Autism Act, which reestablished the Interagency Autism Coordinating Committee (IACC). The IACC is a Federal advisory committee that coordinates all efforts within HHS concerning autism spectrum disorder. Through its inclusion of both Federal and public members, the IACC helps to ensure that a wide range of ideas and perspectives are represented and discussed in a public forum. Related to autism research, the National Database for Autism Research (NDAR) received the HHS Innovates Award. NDAR is a model for creating a federated structure for a secure data repository. NDAR provides a rich source of genetic, imaging, and clinical data on autism from more than 20,000 research participants that can be shared with researchers around the globe.

Dr. Insel introduced a few new NIH Common Fund initiatives. One is the NIH Director’s Early Independence Award Program which funds independent research for exceptional new researchers in order to foster innovation and encourage early career scientists to omit the traditional post-doctoral training and move into independent research positions. Another program, the Single Cell Analysis Initiative, aims to increase the understanding of heterogeneity at the single cell level. In addition, there are several developments in the field of regulatory science, including a new partnership between NIH and the U.S. Food and Drug Administration including a project with the Defense Advanced Research Projects Agency (DARPA) to develop tissue on a chip to begin to miniaturize methods of predictive toxicology.

The top scientific breakthrough of the year, according to Science, came from the HIV Prevention Trials Network 052 Trial, a project of the National Institute of Allergy and Infectious Diseases (NIAID). This study produced the extraordinary finding that immediately treating both individuals of sero-discordant heterosexual couples with antiretroviral therapy, rather than employing the standard method of waiting to treat the HIV-negative individual, reduced the rate of infection by 96%.

Both the Small Business Innovation Research and the Small Business Technology Transfer Research Programs were reauthorized for 6 years as part of the National Defense Authorization Act for Fiscal Year 2012 (FY12). Dr. Insel noted key changes in the legislation that have increased flexibility in these programs. One change enables small businesses that are primarily owned by venture capital to participate in the program for the first time and gives NIMH flexibility in mixing Phase I and Phase II Awards. These changes represent real improvements in the programs and offer some real opportunities for new directions with these small business programs. The Small Business Administration will be responsible for enacting these changes, which will be announced broadly.

Dr. Insel spoke of the creation of the National Center for Advancing Translational Sciences (NCATS). Dr. Insel described NCATS as being formed through a reorganization of current programs into a new entity that advances translational science. NCATS’s mission is to catalyze the generation of innovative methods and technologies that will enhance the development, testing, and implementation of diagnostics and therapeutics across a wide range of human diseases and conditions. He said NCATS aims to address the issue of developing new therapeutics. In addition to small molecules and therapeutics, NCATS will address issues of target validation, the development of biomarkers, and preclinical toxicology. In addition, NCATS will be the home for Clinical and Translational Science Awards, previously maintained within the National Center for Research Resources. These large awards make up about 80% of the NCATS budget, or nearly $500M.

NIMH Updates

Turning to the budget, Dr. Insel described FY11 as a year of austerity. While the budget has been below inflation since 2003, 2011 is the first year NIH experienced an absolute budget decrease, leading to a substantial decrease in the funding of Research Project Grants (RPGs). In FY12, the budget rebounded and the number of RPGs will likely increase to 531 or higher (In FY11, 465 new projects were funded with the annual target hovering around 500 new projects). Dr. Insel noted a decrease in the number of applications received in the past few years, with the exception of FY11. He does not believe that the decrease represents a reduction in the pool of applicants or the number of applications being written, but rather some unidentified change in the applicant cohort. He added that another driver in the budgeting process has been a large increase in the average cost per grant. Dr. Insel noted that despite the FY11 budget, NIMH succeeded in funding about 100 new investigators, a number he hopes to increase in FY12. This support for new investigators fulfills NIMH’s goal of maintaining a successful pipeline for funding new scientists.

Just as FY11 could be termed a “year of austerity,” Dr. Insel stated it could also be known as a year of “scientific humility” and “complexity.” He said that last year scientists noted that the human brain is much more complex than previously thought, particularly with regard to ribonucleic acid (RNA). Dr. Insel cited two recent papers published in Nature that challenged the traditional fundamental understanding that the RNA profile of different organ systems stays consistent across the life span. The first paper (Nature 478, 483-489 (27 October 2011)) showed that RNA in the human brain varies not only across regions but also across time, perhaps most surprisingly during fetal development. He added that approximately 60% of genes are expressed in a drastically different way prior to birth, and that the variation is due to genes being spliced differently, not merely being turned on or off as had been thought previously. The importance of this finding may lie in an increased appreciation for the significance of genetic variations that have not looked functional in the past but may actually represent neurodevelopment disorders that are not expressed until later in life.

The second paper (Nature 479, 534-537 (24 November 2011)) presented the finding that deoxyribonucleic acid (DNA) sequences differ from each other in different parts of both the brain and the body. This was particularly evident in the hippocampus, where the most variations were found –around 14,000 – between the DNA there and the DNA in blood or other body cells. This finding suggests the existence of a process called retrotransposition, in which repetitive seemingly nonfunctional sequences move around and later cause changes in tissues that have already formed. Dr. Insel noted that this finding goes against widely held beliefs that once the brain has been formed it remains static. Although it is accepted that neurons do not change much postnatally, these findings suggest that somatic mutations may occur after prenatal development. Dr. Insel suggested the possibility of utilizing the genome of cancer cells as a model, for classifying individual lineages of the cells involved in mental disorders to identify the mutations that might be relevant for therapeutics.

Dr. Insel underscored how the research community is becoming increasingly aware that what is genomic is not necessarily inherited. He remarked that fully understanding many psychiatric disorders may depend on understanding their association with de novo changes – genomic changes that develop in offspring. He emphasized that this is a new frontier in our understanding of the universe of de novo single nucleotide variants and the need to do full genomic sequencing to find signals that might be associated with disease.

Addressing a broader view of future NIMH research priorities, Dr. Insel briefly touched on how the four strategic objectives identified in the 2008 Strategic Plan have guided many important NIMH decisions, in particular the research investments. He asked the Council for input into which direction the Institute should take next as the five-year plan draws to a close.

Discussion

Gregory Simon, M.D., M.P.H., asked whether there is any tension between large infrastructure activities such as the CTSAs and smaller scale efforts to support innovation such as the Early Independence Awards.

Dr. Insel replied that NIMH tries to strike a balance between supporting large-scale infrastructure and innovative smaller-scale efforts like the R01 Research Project Grant programs. He added that NCATS will do that at many different levels, as well as investing in databases that will make information widely available.

Carol Tamminga, M.D., asked how NCATS gets its portfolio and whether that process will be regulated.

Dr. Insel answered that NCATS will receive little new funding, rather it will oversee a group of activities that were formerly in the National Human Genome Research Institute as well as the CTSAs. The newer components will be an effort on testing organ tissue in partnership with DARPA, some projects around drug repurposing.

Referring to the issue of complexity and our early stage of understanding it, Roberto Lewis-Fernández, M.D., asked how much of the budget should be devoted to long-term efforts versus immediate public health issues.

Dr. Insel invited other Council members to reply, adding that this is a fundamental question.

Steven Hyman, M.D., agreed with Dr. Insel’s previous use of the word “humility,” saying that although we have made advances in science, efficacy for antidepressants and antipsychotic drugs plateaued a long time ago. As to the balance between big and small science, he noted that an effective large platform is successful only to the degree to which it enables the efficacy of smaller groups. As an example, he cited the Genome Project, which cost $3 billion but enabled smaller labs to avoid the difficult and inaccurate process of completing sequencing themselves. He added that despite the complexity, he is optimistic that we have found the first set of real clues, and that we can move forward by encouraging new partnerships and a different kind of risk-taking in translational science.

Carla Shatz, Ph.D., commented that the papers mentioned by Dr. Insel underscored the notion that many profound disorders may originate both in fetal development and from environmental effects. She suggested that we need to find new ways to study very early development, as early as in utero. She added that she finds the issue of the decreasing number of grant applications very troubling, and wondered whether the decrease might be a sign that small science – where most scientific breakthroughs arise – may be losing out to big science.

Dr. Insel replied that, at first, he had missed the downward trend because of his focus on the overall increase in FY11, but after a re-review of the numbers for NIH, he found the same downward trend in a number of other Institutes. He does not have a clear explanation of why this decrease occurred and also expressed concern about it.

Steven Paul, M.D., agreed that the paper Dr. Insel highlighted about somatic retrotransposition in the human brain has profound implications, if the findings can be validated. He asked whether that phenomenon can be modeled in animals. Dr. Paul indicated the need for new strategies to obtain such data.

Dr. Insel replied that although the original research on the topic came from plants, it is present throughout taxonomy, and there appears to be something special about the brain generating more retrotransposition than other tissues. He added that the phenomenon must be replicated, even though it is very difficult to do. Dr. Insel remarked that this kind of technique requires having a single cell population in order to look at granule cells.

National Action Alliance for Suicide Prevention

Dr. Insel introduced Jane Pearson, Ph.D., Chief, Preventive Interventions Program in the Division of Services and Intervention Research at NIMH and lead NIMH staff for the Research Task Force (RTF) of the National Action Alliance for Suicide Prevention (Action Alliance). Comprised of many HHS agencies and private entities, the Action Alliance’s RTF over the past 16 months has involved close to 20 NIMH staff and contractors.

Dr. Pearson provided a brief history of the Action Alliance. Established in September 2010 by HHS Secretary Kathleen Sebelius and Defense Secretary Robert Gates, the Action Alliance is a public-private partnership established to help implement the goals and objectives of the 2001 National Strategy for Suicide Prevention (NSSP). The Action Alliance is led by Public Sector Co-Chair, The Honorable John McHugh, Secretary of the Army and Private Sector Co-Chair, The Honorable Gordon H. Smith, President and CEO of the National Association of Broadcasters – a former Senator who lost his son to suicide.

The mission of the Action Alliance is to advance the NSSP in three ways:

  • To champion suicide prevention as a national priority;
  • To catalyze efforts to implement high priority objectives of the NSSP ; and
  • To cultivate the resources needed to sustain progress.

The Action Alliance organizational structure is comprised of public and private sector Co-Chairs (mentioned above), as well as an Executive Committee, 12 Task Forces, Advisory Groups, and a Secretariat, with representatives from 190 organizations. It aims to advance specific, high-priority objectives of the NSSP requiring leverage and coordination at the national level. The high-level leadership of the Action Alliance, representing a broad range of public- and private-sector organizations from across the country, makes this pioneering work possible.

The Co-Chairs and Executive Committee (EXCOM) members provide strategic leadership for the Action Alliance and represent diverse fields and perspectives needed to advance suicide prevention. The 12 Task Forces enhance national infrastructure and promote suicide prevention interventions among high-risk populations and in specific settings. Their work is collaborative and time-limited, aiming to achieve specific objectives of the NSSP. The Advisory Groups draw from suicide prevention organizations, professional associations, and ad hoc groups representing the interests of vulnerable populations and others that provide expertise and insight to the EXCOM and Task Forces. The Secretariat, a team drawn from the national Suicide Prevention Resource Center staff, supports the operations of the Action Alliance and communications among its members.

Working under the Executive Committee are three categories of task forces.

  • Three Infrastructure Task Forces launched in the fall of 2010 to develop infrastructure to support suicide prevention for all populations. These task forces are: Data and Surveillance, National Strategy for Suicide Prevention Revision, and Research Prioritization.
  • Three High-Risk Populations Task Forces launched in the winter of 2011 to address select populations that have increasing or disproportionately high rates of suicidal behaviors. These high-risk populations are: American Indian/Alaska Native; Lesbian, Gay, Bisexual, and Transgender Youth; and Military/Veterans.
  • Six Interventions Task Forces launched in the spring of 2011 to advance interventions in specific suicide prevention domains or settings. These task forces are: Clinical Care and Intervention, Clinical Workforce Preparedness, Faith Communities, Public Awareness and Education, Youth in Contact with the Juvenile Justice System, and Workplace.

The 2002 Institute of Medicine report, Reducing Suicide: A National Imperative, has served well as a research agenda, but because of the continued rise in rates, task force members decided that their goal had to include reducing the rate of suicide morbidity – or attempts – and mortality. The RTF considered a number of approaches for developing a research agenda. Cindy Claassen. Ph.D., then working for the Veteran’s Administration, had initiated a discussion on the need for a prioritized research agenda with both National Council on Suicide Prevention representatives and NIMH. The RTF consulted with experts who had developed research strategies in Australia and Canada. Ultimately, the task force came up with the specific goal of developing a research agenda that has the potential to reduce suicide morbidity and mortality by at least 20% over five years and 40% over ten. They developed a process to seek input from stakeholders; conduct a grant portfolio analysis; conduct a targeted literature review; develop a burden ‘map’ that identified high risk groups; publish a NIH Request for Information (RFI); and plan to engage experts in drafting an agenda that would identify short- and long-term research objectives. Dr. Pearson stated that efforts were underway to develop ‘logic models’ that would serve to summarize the information known about the proposed aspiration research goals, such as improved detection of imminent risk and improved continuity of care of suicide attempters. Location mapping of suicides and suicide attempts is also being conducted to identify populations that have not yet been reached.

Discussion

Dr. Shatz asked whether the literature and grant portfolio review was focused entirely on human clinical studies or whether there is room to look at animal models.

Dr. Pearson replied that because the task force has focused on the applied side of research, there has not yet been a focus on animal research. She added that through the stakeholder survey, they have received a request for better animal models. The RFI also offers an opportunity to suggest approaches that utilize animal models.

As a psychiatrist who has lost patients to suicide, Dr. Paul stated his belief that this is one of the most important areas NIMH has been addressing and should be addressed with vigor. He wondered why more medical models had not been adopted, adding that the notions of primary and secondary prevention could apply as easily to suicide prevention as to other illnesses. Noting that a previous suicide attempt makes another attempt likely, he questioned the types and timing of interventions.

Dr. Pearson replied that NIMH is currently funding an eight-site emergency department study that seeks to identify useful screening approaches and brief interventions to reduce repeat attempts among those seen in emergency departments.

Dr. Insel added that in terms of NIMH investments, the biggest project NIMH is involved in is the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). It is essentially a Framingham study involving well over 25,000 subjects being tracked over time. A major goal of the study is to identify very specific suicide predictors.

Paolo del Vecchio, M.S.W., thanked NIMH for its partnership with SAMHSA on the Action Alliance. He pointed out that economic conditions may well be playing a role in the increased suicide death rates recently confirmed by data from the Centers for Disease Control and Prevention (CDC). He added that white middle-aged males are one group showing a notable increase in suicide and noted that primary care settings might be a good avenue for interventions, as many people go to primary care before attempting suicide.

Dr. Insel commented that increasing numbers in suicide deaths contrast with the numbers of deaths by homicide, traffic fatalities, and other sources of mortality that have decreased dramatically.

Virginia Trotter Betts, M.S.N., J.D., suggested that the increase in suicide deaths may be due to improved reporting methods. She added that both mental health commissioners and emergency room nurses around the country are faced with suicidal patients but do not have anywhere to place them, such as when the patients are uninsured or the mental health system is full. She said this is a very complex problem that requires a focus on prevention as well as primary, secondary and tertiary care. Lastly, she noted that there are many opportunities for intervention and research. Practitioners and families might ask what can be done immediately to address this public mental health issue and the very serious delivery problem that is keeping people from getting treatment.

Dr. Insel commented that Ms. Betts had just defined the agenda for the Action Alliance, a major agenda item for the entire department.

Referring to the surveillance aspect of data collection, Dr. Simon noted a distinction between violent and non-violent means of suicide and asked whether the RTF has the capacity to distinguish between the two.

Dr. Pearson replied that the Action Alliance is aware of this distinction and that they have asked the CDC to map out those groups as separate populations.

Ira Katz, M.D., Ph.D., recognized Dr. Insel’s contributions to the Action Alliance in this area. He acknowledged the difficulties in national surveillance leading to the public’s lack of access to recent data, and contrasted these reports to the current, monthly reports available for suicide rates in the Department of Defense (DOD).

Dr. Pearson responded that the Surveillance Task Force of Action Alliance is looking at models of suicide surveillance programs used by other countries as well as the surveillance program used to track the flu in this country. She explained that national statistics are often hindered by just one or two states that delay verifying their data. The Action Alliance is working on new approaches to estimate the suicide rate which would enable quicker access to validated statistics.

AIDS Behavioral Science Research Updates

Dr. Insel introduced Phil Wang, M.D., Dr.P.H., NIMH Deputy Director, to discuss the efforts within the NIMH Division of AIDS Research (DAR). Dr. Wang was pinch-hitting for Dianne Rausch, Ph.D., Acting Director of DAR, who was called away on a family emergency.

Several recent studies using a biomedical intervention to prevent the spread of HIV have shown unanticipated success at significantly reducing transmission. These approaches have included the use of antiretroviral drugs administered to the uninfected partner to prevent the virus from establishing infection from an infected partner, and the use of antiretroviral drugs administered to the infected partner to significantly reduce the viral load to a point where the probability of transmission is approaching zero. These studies have generated enormous enthusiasm within the AIDS field as the possibility of eliminating the epidemic could actually become a reality.

That said, other studies with similar potential for positive outcomes have showed varying ranges of success. These varying outcomes reinforce the concept that while we have the tools to end the epidemic, it is clear that different circumstances, environments, populations, ethnic norms, social beliefs, as well as availability of resources will require a combination approach using all the tools at hand to effect a change.

When thinking about treatment as prevention, it is clear that this is a complex issue. It is widely understood from CDC and other data that while there is relatively good outreach to get people tested, there is drop-off in engagement at each stage of the “treatment cascade.” Only 79% of individuals that get tested go back for their diagnosis, 59% get linked to care, 39% are retained in care, and ultimately only 17% of individuals who are eligible and would benefit from care are actually engaged in care and have their illness well controlled.

Treatment as prophylaxis is also complicated and raises a number of issues. In order for individuals to agree to use treatment as prophylaxis, they must understand their risk. In addition, antiretroviral drugs are not without side effects, and they will likely not be used consistently, if the risk of illness and infection is not perceived. This raises the issue of the integration of behavioral science into the biomedical intervention. HIV prevention now has the tools to make transformative changes in HIV transmission and potentially end the epidemic. But behavioral components are critical to the successful prevention of new infections. This controlled approach defines the research agenda for DAR.

Under the guidance of Dr. Insel, DAR recently convened two summit/workshops to bring together a group of experts to look at the behavioral science research currently supported by DAR and discuss if the research funded was targeting the agenda defined by an expanded AIDS test-and-treat prevention agenda. With the overall goal of wide dissemination and highly effective biomedical and behavioral interventions, the summits created broad recommendations. These recommendations included increasing the efficacy and durability of interventions, personalizing and targeting high risk groups, and optimizing reach while avoiding redundancy. Some of the more specific recommendations include:

  • Develop a focused strategic plan
  • Encourage innovative approaches Continue targeting high-risk groups
  • Bring effective intervention to scale
  • Increase collaboration with other stakeholders
  • Develop principles for international research

The Division has begun implementing these recommendations by issuing a number of Requests for Applications (RFAs). To increase collaboration with other stakeholders, the Division is working closely with the CDC, NIAID, the Gates Foundation, and the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR).

Dr. Wang added that DAR is undergoing a structural reorganization to better meet these challenges. The new structure will contain an “incubator” space to encourage novel interventions as well as areas for rapid up-take and integration of effective behavioral interventions, capacity building, and engagement in partnering with other stakeholders.

Discussion

Dr. Lewis-Fernández commented that this agenda is very comprehensive and thoughtful. He said that the DAR research agenda has long been a model for other areas in mental health, which are still seeking effective treatments. He indicated that a possible goal for the other areas could be assessing where each disease lies along a continuum (i.e., finding treatments at one end and providing access to them, then disseminating them with fidelity and addressing issues of compliance at the other end). This strategy would enable more policy-wide agility in deciding where to invest funds.

Dr. Simon seconded this idea, saying that we are in very different places with regard to different conditions.

Dr. Tamminga said that the old smoking cessation campaign from 20 years ago did not start taking effect until movie stars became involved. She said that this model may provide some ideas for simple methods of achieving treatment compliance.

Dr. Hyman reminded the group that the behavioral community has been allied with the medical community for many diseases.

The Office of Science Policy, Planning, and Communications: Its Role for NIMH in a Rapidly Changing Landscape

Dr. Insel introduced Stefano Bertuzzi, Ph.D., M.P.H. as the new Director of the Office of Science Policy, Planning, and Communications (OSPPC). Dr. Bertuzzi gave a brief overview of how he sees the changing landscape of mental health research. Citing data from RAND Corporation, he showed the overall increase in the number of mental health publications worldwide, and a decreased share of U.S. publications in the field. He added that the productivity in the European Union and BRIC countries – Brazil, Russia, India, and China – is increasing. He concluded that the field has become much more complex from both a scientific and an organizational perspective, with many more public and private players and a consequent greater than ever need for leadership and coordination of efforts to avoid duplication and to create synergy.

Dr. Bertuzzi introduced staff members and defined the four branches that make up the OSPPC: Science Policy and Evaluation (SPE), Reports and Analysis (RA), Science Writing, Press and Dissemination (SWPD) and Electronic Communication (EC). SPE is responsible for providing transparency and accountability of NIMH investments to stakeholders such as Congress and other parts of the public and private sector, including NIH, the White House, the Office of Management and Budget, and the extramural research community. An important function of this branch is communicating the value and public health relevance of NIMH-supported research. This branch is also responsible for evaluating the office’s activities; one example of this function is the new initiative to monitor RFA progress with appropriate indicators.

Dr. Bertuzzi defined the RA Branch as the “vital statistics department” of the Institute. It is responsible for keeping an information system to analyze NIMH’s investments, coding the grants according to differing criteria and reporting them to programmatic divisions, the NIMH leadership, and to support SPE in their activities with stakeholders. RA is also tasked with gap analysis, by looking into what is not being funded by NIMH and mining other data resources to see what others in the research community are prioritizing, in order to capitalize on investments. Noting that many NIMH initiatives cut across NIH Institutes, Dr. Bertuzzi indicated that Roger Little, Ph.D., is responsible for representing NIMH in trans-NIH activities such as the Common Fund and the Neuroscience Blueprint.

Also intertwined with NIMH’s data and policies are SWPD Branch and the EC Branch. The staff in both SWPD and EC write and provide the information presented in brochures for the public and the content that goes on the NIMH website, NIMH’s biggest “megaphone.” The website receives a strikingly high number of hits, in particular those pages with information on specific diseases.

Dr. Bertuzzi remarked that many users access the NIMH website and, based on feedback received in focus groups, users generally view the NIMH web content, as authoritative and trustworthy. He noted the importance of keeping content on the website brief and to the point to avoid overloading viewers with too much information. He added that NIMH is doing very well in terms of social media; it has more Facebook “friends” than any other NIH Institute and follows behind only the NIH Central Twitter account in number of followers. NIMH also recently started a YouTube account that broadcasts videos of interviews with scientists and different stakeholders. Dr. Bertuzzi described the latest activity developed for use on the Internet, a service called GovDelivery that enables NIMH website viewers to sign up to receive pushed email messages on topics they selected.

With regard to other forms of communication, NIMH answered approximately 28,000 phone calls in 2011 and distributed close to 1.8 million publications – 14% of which were distributed by NIMH Outreach Partners. In addition, NIMH put out a number of press releases through EurekAlert!, an online service run by the American Association for the Advancement of Science.

Dr. Bertuzzi asserted that, in the current atmosphere of shrinking budgets, significant needs and a complex environment, OSPPC has a big role to play. With competing priorities in the federal budget, NIMH must be able to explain to the public what they are getting in return. He said it is important that the Office step in at the crossroads between the science, the policy, and the communications and play the role of an in-house mental health “think tank” for policy change and public awareness in order to analyze, understand, prioritize, initiate change and articulate what it is NIMH wants to do to improve the field of mental health.

Discussion

David Amaral, Ph.D., wondered if Dr. Bertuzzi planned to use new channels of social media to get advice directly from the public about which direction to take.

Dr. Bertuzzi responded that the government’s use of social media is a very recent phenomenon, and that the OSPPC is in the process of writing a policy on how to use social media responsibly to ensure the quality of information received and responded to.

Dr. Hyman asked why there’s such a great disconnect between the importance of mental disorders as a public health menace and the minimal resources invested in researching and treating them. He added that it is striking how economic data about the cost of mental illness is ignored around the world. He suggested there may be a cognitive reason for this disconnect, and wondered whether there is a role for NIMH and communications research to get the word out and to improve the effectiveness with which it is received.

Dr. Bertuzzi agreed that this is one of the fundamental questions. He suggested that with NIMH’s research, interventions and communications capabilities, it can develop a strategy to convey the message.

Dr. Insel agreed that this is a huge problem that we do not yet fully understand.

Dr. Katz mentioned that suicide has garnered people’s attention all over the world, including the department of defense.

Dr. Insel agreed that the military’s position towards mental health issues mirrors the way in which they took on civil rights and integration 20 years before the rest of the country. He added that a major part of this effort has resulted from General Peter Chiarelli, Vice Chief of Staff of the U.S. Army making mental health a priority for DOD. When General Chiarelli soon retires, it’s not clear whether this effort will outlast him or spread to the civil sector.

Dr. Lewis-Fernández said this is an area which calls for an interdisciplinary approach. He said it was a good opportunity to integrate the expertise of those who focus their careers on public health and social psychology with the more disease-focused approach at NIMH.

Mr. del Vecchio remarked that there are still attitudinal barriers to disclosing that one has a mental illness and wondered how we can make it safer for people to make this disclosure.

Dr. Tamminga said this issue is complicated by the fact that we do not even have one standard name for many mental illnesses, and that often the names used by the public differ from the names used by scientists. She added that we need to know the scientific basis of mental illness in order to have a public definition of it.

Dr. Insel concluded that the OSPPC presents an opportunity to use reverse engineering to discover which scientific approaches have been successful in the past. This information can be used to prioritize funding for the methods that are most likely to have the greatest impact in the future.

Division of Developmental Translational Research: Portfolio and Priorities

In his introduction, Dr. Insel remarked that in the past, Council members have expressed an interest in hearing more about scientific progress and results of NIMH funded research. To respond to this request, NAMHC will hear from each of the NIMH research divisions over the next several meetings. He introduced Molly Oliveri, Ph.D., Director of the Division of Developmental Translational Research (DDTR) at NIMH who will begin our conversation.

Dr. Oliveri explained that as one of the four non-AIDS funding divisions, DDTR lies in the middle of a continuum between basic and applied research. Its mission is to translate knowledge about the developmental origins of mental disorders from basic science to their prevention and cure. When research supported by the Division discovers promising new treatments, they are moved into the Division of Services and Intervention Research to undergo effectiveness trials, community-based trials, and mental health services research.

Next Dr. Oliveri outlined the three priority research areas within DDTR:

  1. Neurobehavioral mechanisms investigating mental illnesses at all levels, from neurobiological and genetic to experiential factors, seeking biologically based markers that can be used for clinical research.
  2. Developmental trajectories examining each mechanism over time, from conception to late adolescence/early adulthood. The goals of this area are to develop integrative longitudinal models that track risk and protection over time, to examine sensitive periods in development when the brain is maximally open to environmental influence, and to identify early signs in order to enact the earliest possible intervention.
  3. Novel interventions development both traditional efficacy trials of pharmacological and behavioral interventions as well as new, exploratory treatment studies, many of which are on the behavioral level for children. The primary emphasis of novel interventions is seeking treatments that are targeted to particular brain processes or functions. The end goal is early identification and early intervention, before the disorder becomes prominent.

In terms of budget, DDTR awarded 381 grants totaling nearly $150M in FY11. The largest proportion (63%) of grants awarded were Research Project Grants (RPGs), which received 75% of all research dollars and mainly fell into the R01 category. Dr. Oliveri noted that most grants within DDTR support human research, but the division also contains a small portfolio of animal research. Support for early stage investigators is a special priority.

Dr. Oliveri added that Mentored Career Awards, which received 20% of the total grants awarded, are of particular interest to the Division as they represent the future of research. She noted that these are awarded predominantly to Ph.D.’s, but that 37% were awarded to M.D.’s and M.D./Ph.D.’s. In FY 11, 70% of the Mentored Career Awards were awarded to women. She highlighted examples of the projects from several researchers who had received Mentored Career Awards, including Rebecca Santelli (Sex Differences in Early Brain Development), Shafali Jeste (Neural Predictors of Language Acquisition in Autism) and Damien Fair (Functional Circuits as an Endophenotype for ADHD).

The DDTR project-based Research Centers (P50 grants) received 10% of the grant dollars awarded and 3% of the total grants in the Division. Illustrating the investigators and the integrative nature of the projects, Dr. Oliveri listed the 11 Centers and highlighted several findings from B.J. Casey’s Interdisciplinary Developmental Science Center and Eric Courchesne’s Autism Center for Excellence.

An overview of illustrative findings from funded projects that comprise the translational continuum within DDTR were broken down into four categories of research on neurodevelopment: Identifying Mechanisms, Mapping Trajectories, Prediction, and Intervention. Dr. Oliveri described results from completed and ongoing studies in each of the categories. Next, she provided a survey of recent Funding Opportunity Announcements (FOAs) and grants DDTR was able to award through various RFAs that focused on sensitive periods for development of mental illness, epigenetic modifications during neurodevelopment, sex differences in mental illness, and the development of novel interventions for mental disorders. She noted in particular the Biobehavioral Research Awards for Innovative New Science (BRAINS), an initiative for early stage investigators that has funded grants for the past three years.

Discussion

Dr. Hyman remarked that there is a great deal of exploratory science supported in the Division. He wondered whether the Division ought to bring investigators from the scientific community together to set goals and priorities based on the greatest opportunity for translation.

Dr. Oliveri wondered whether he meant that in a top-down way, and he answered that he meant it in a collaborative way, e.g., by inviting the schizophrenia prevention community to suggest which conditions were most promising/ripe for intervention development.

Dr. Oliveri replied that the developmental translational field is still quite young and dependent on the methods and pharmacotherapy interventions from decades of past research with adults but not children. She added that the Division seeks input from a wide range of investigators within and outside of NIMH.

Dr. Hyman said that part of his motivation in asking the question was based on the pharmaceutical industry’s withdrawal from developing drugs for psychiatric disorders.

Dr. Insel then summarized the two questions being raised. First, in a tough budget economy, how much research should we direct and how much should we solicit people’s best ideas? Second, how do we develop a process to identify what an initiative should target? Dr. Insel noted that the institute is committed to continue to drive some areas of specific needs through RFAs, especially areas in which few unsolicited applications are submitted. He said that the role of NIMH has traditionally been that of a meeting “convener,” bringing together investigators and others in the community with a role to play in developing funding priorities.

Dr. Tamminga asked about autism spectrum disorder research, and Dr. Oliveri responded that most of the autism spectrum disorder research portfolio is supported in DDTR.

Concept Clearances

Development of Tools to Explore the Synaptome

Michelle Freund, Ph.D., Chief of Molecular Biotechnology and Neurotechnology Programs in the Division of Neuroscience and Basic Behavioral Science (DNBBS) at NIMH discussed an initiative to encourage applications to develop novel technologies and/or tools to facilitate the study of genes and proteins at the synapse on a large scale. Being able to characterize the synaptome at the level of hundreds to all genes/proteins would be a major advance for basic and translational research. The new tools should enable discovery science related to the synapse with substantially greater sensitivity, selectivity, and spatiotemporal resolution.

Over the previous decade, technological developments in the life sciences have led to a proliferation of “-omics” approaches, whose goals involve comprehensive discovery of entire classes of biochemical or genetic entities for a given tissue or cell type. The nervous system represents a challenge and also an opportunity for this type of approach, because of its unique cellular and subcellular compartmentalization. A variety of methods are now available (or in development) for isolating components from different neural cell types and subcellular domains.

Much evidence points to specific pathologies related to the synapse in a number of brain disorders, including autism spectrum disorder, schizophrenia, and other neurodevelopmental and neurodegenerative disorders. The complexity and molecular diversity of the synapse are vast. A cell's identity can be characterized in a number of ways including its lineage, molecular composition, epigenetic state, activity profile, morphology, and the nature of its connections (inputs and outputs). Specifically, the ratio of excitatory vs. inhibitory inputs, the specific location of synapses, as well as the strength and capacity for plasticity can provide useful information about potential function. Furthermore, the dynamic nature of synapses must be considered when attempting to understand their role in circuit function.

The addition of new tools to further our understanding of synaptic function as it relates to plasticity, cell type specificity, neurodevelopment, and dysfunction of brain circuitry are critically needed. Tools to interrogate the synapse could include chip-based approaches to characterize gene or protein expression, protein capture, or novel technologies for biochemical or genetic analysis. These technologies should provide resources relevant to many of the existing Blueprint programs, especially neuroplasticity, cognition, disease research, and therapeutic target discovery.

Discussion

Dr. Hyman asked how big the collaborations can be and whether there are collaborating mechanisms. He added that multi-site efforts might be very important.

Dr. Freund responded that this initiative is thought of as a means to stimulate the field with small scale projects to start and perhaps expanding this effort in a future.

New Experimental Medicine Studies: Fast-Fail Trials (FAST)

Bruce Cuthbert, Ph.D., Director of the Division of Adult Translational Research and Treatment Development discussed an initiative to expeditiously test and analyze novel pharmacological interventions and their molecular and/or clinical targets for treating clinical dimensions of psychopathology associated with traditional psychiatric disorders. Recent breakthroughs in basic science and in the understanding of complex disorders offer promising new opportunities for researchers to pursue and develop novel treatments for those living with mental illnesses. Now is a critical time to take advantage of new breakthroughs and tools, but the paths for treatment discoveries are not clearly marked. Despite the tremendous advances in basic neuroscience and behavioral science that drive our understanding of the mechanisms underlying complex disorders, there is a dearth of new therapeutics in the discovery pipeline.

The overall goal of this initiative is to implement an experimental medicine paradigm of “fast-fail” proof-of-clinical-mechanism and proof-of-concept trials in order to expeditiously test and analyze compounds (i.e., new chemical entities, re-purposed compounds) and their molecular and/or clinical targets for treating clinical dimensions of psychopathology (e.g., anhedonia, cognitive function, social engagement) associated with traditional psychiatric disorders. NIMH has a strong interest in strategies for ameliorating clinical dimensions of psychopathology embedded in diagnostic entities, but not typically identified as the primary target of current clinical therapeutics.

The initiative will focus on the analyses of novel molecular and clinical targets, engaged by both new and re-purposed compounds. Evaluating potential biomarkers, including receptor occupancy with positron emission tomography and engagement of relevant brain systems with functional magnetic resonance imaging, electroencephalogram, emotional reactivity, neurocognitive performance, etc., in early phase (Phases I and IIa) clinical trials to demonstrate biological effects could provide information critical to the decision as to whether to proceed further with a specific compound. These types of small trials could prove valuable in de-risking a compound or demonstrating a “fast-fail” for a new target.

Discussion

Dr. Tamminga asked whether the initiative would support nonpharmacologic trials in the future.

Dr. Cuthbert replied that nonpharmacologic trials had been included in an earlier initiative and may well be considered in the future, but pharmaceutical compounds are the focus of this initiative.

Dr. Shatz asked whether there is a pipeline of potential drugs and targets waiting to be tested.

Dr. Paul added that if you juxtapose this initiative with efforts to rescue and repurpose drugs, you will not need many new mechanisms to jump start the field. He cited the example of a drug that had been developed but failed to treat Alzheimer’s disease that works for schizophrenia.

Dr. Insel clarified that to some extent this is about getting compounds de-risked, but it is also about target validation, because you might gain information about the compound occupying the receptor and thus engaging the target.

Thomas McGlashan, M.D., wondered whether there is any evidence that the pharmaceutical industry is interested in this.

Dr. Cuthbert replied there is interest and that a number of companies have expressed an early interest in potentially getting their compounds tested for the treatment of depression.

Dr. Tamminga commented that many times when the pharmaceutical industry has used a fast-fail approach, they have done so because there has been too small of a drug effect. However, she noted that a small drug effect may actually be a significant drug effect in a subgroup of people.

Dr. Cuthbert agreed that this approach is focused on specific neural circuits rather than broad heterogeneous categories.

NCATS Drug Rescue Program

Linda Brady, Ph.D., Director of DNBBS, discussed an opportunity to advance therapeutics through the use of drugs that are not clinically in development – through drug rescue and repurposing drug candidates and compounds that are currently on the market. She added that this could be a valuable approach to provide novel therapeutic options for a wide range of human diseases, and would facilitate the development of diagnostics as well.

Earlier in 2011 at a roundtable discussion between NIH and industry to explore the uses for abandoned or neglected compounds and approved therapeutics, a number of opportunities and challenges were identified. Dr. Brady stated that the meeting resulted in a very positive outlook on the prospects and potential of this project to generate and de-risk new concepts for therapeutic indications across a wide variety of diseases. A resulting idea was that NCATS could serve as a clearinghouse for discontinued compounds and make them more broadly available for studies by facilitating interactions among the private sector, academic researchers and advocacy groups, possibly by establishing template partnership agreements to facilitate the transfer of compounds and biologics. A few challenges to this type of work are its resource intensity and patent implications for the collaborators from private industry.

The goal of the Drug Rescue Program would be to identify new therapeutic uses for proprietary drug candidates and biologics across a broad range of human diseases, particularly in areas of unmet medical need. The pilot initiative would match candidate agents from participating pharmaceutical companies with new indications from the biomedical research community and pair the top concepts with the compounds that would allow investigators to test their hypotheses. The program would create a synergy among the groups by providing pre-negotiated templates to facilitate partnership agreements. Plans to develop an initiative, review it, fund it, and provide coordinated oversight would be included. The pharmaceutical partners would provide compounds or biologics, in-kind support, expertise, assistance in developing protocols to test the hypotheses, and all relevant clinical data, including toxicology and safety data. The researchers would provide their knowledge of the biology of the diseases they have been studying, new concepts to be tested, and access to patients to participate in the pilot.

It is expected that this program would inform subsequent NCATS drug rescue and repurposing efforts by allowing NCATS to assess the efficiencies achieved through the use of template partnership agreements, the interest of pharmaceutical partners in joining future initiatives, and lessons learned in the process of discovering and de-risking these discontinued compounds or biologics.

Discussion

Dr. Simon remarked that explicit or implicit in all three concept clearances is the idea that the initiatives are about targets and mechanisms as opposed to conventional diagnostic categories. He asked how the initiatives fit together with each other and how NIMH’s Research Domain Criteria (RDoC) initiative informs all of them.

Dr. Brady agreed with Dr. Simon’s assessment of the initiatives and added that this is true for many initiatives, even beyond psychiatric disorders. She stated that in each case, the goal is to find the best biological questions and mechanisms based on our understanding of disease biology and to locate opportunities to test those novel mechanisms.

Dr. Insel commented that this issue is not specific to NIMH, and that although NIMH hopes to benefit from this process, the first real success was in the field of chronic lymphocytic leukemia in which a repurposed compound moved into clinical trials within 12 months of being repurposed. He added that this is an extraordinary way to move forward quickly because a lot of the work has already been done in an earlier effort.

Dr. Paul pointed out that although pharmaceutical companies are a likely place to locate appropriate compounds; there are other places to look as well, including biotech companies and academic groups. He suggested that although the government does not view itself as a profit-seeking entity, this program could become self-funded if a small royalty was charged.

Dr. Insel asked Dr. Paul what the strategy for that would look like.

Dr. Paul answered that much depends on whether there is an intellectual property (IP) and who owns it. He indicated that while most of the results of the studies will be negative, in the event of a positive result, it would be nice to have a small royalty stream for NCATS.

Dr. Shatz commented that if you could create template partnership agreements, with or without royalty streams, this could be extremely transformative in the way universities and pharmaceuticals come to agreements. She mentioned that the sophisticated IP and technology licensing organizations within universities may be a good source of experience and perspective for developing these agreements.

Dr. Insel added that the goal of this initiative is to create a model national resource with many players involved.

Dr. McGlashan asked how the initiative would identify and mobilize clinical samples to be used as targets of the treatments.

Dr. Insel replied that it is not clear how well NIMH will be able to compete against other important medical areas. He noted that this is a competitive process, and that if you could make currently unavailable compounds available to academic investigators, you would get back a number of proposals of which at least a few might be for mental illnesses or central nervous system disorders.

Dr. Paul concluded that it sounds as if the team is thinking ahead, and that having this infrastructure in place is going to be key to repurposing and testing these molecules.

Approval of Concepts

Dr. Steinberg proposed a motion to approve all three concepts, which were passed unanimously without further discussion.

Public Comment

Dr. Insel invited the public to the microphones to ask questions or make comments. No questions or comments were offered.

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
January 2012
Category IRG Recommendation
Scored
#
Scored
Direct Cost $
Not Scored
(NRFC)
#
Not Scored
(NRFC)
Direct Cost $
Other
#
Other
Direct Cost $
Total
#
Total
Direct Cost $
Research 588 $612,373,960.00 491 $454,270,063.00 2 $438,371.00 1081 $1,067,082,394.00
Research Training 27 $42,426,788.00 10 $13,214,521.00 0 $0.00 37 $55,641,309.00
Career 47 $35,280,801.00 22 $14,198,551.00 0 $0.00 69 $49,479,352.00
Other 1 $975,000.00 0 $0.00 0 $0.00 1 $975,000.00
Totals 663 $691,056,549.00 523 $481,683,135.00 2 $438,371.00 1188 $1,173,178,055.00

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

(Terms end 9/30 of designated year)

Chairperson

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

Executive Secretary

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

Members

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

Liaison Representative

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