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NAMHC Minutes of the 229th Meeting

National Advisory Mental Health Council Minutes of the 229th Meeting
September 23, 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 229th meeting in open policy session at 8:30 a.m. on September 23, 2011 in the Neuroscience Center in Rockville, Maryland, and adjourned at approximately 12:30 p.m. The NAMHC reconvened for a closed session to review grant applications at 1:15 p.m. on September 23, 2011, at the Neuroscience Center in Rockville, Maryland, until adjournment at approximately 5 p.m. (see Appendix A: Review of Applications). 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.
  • Daniel H. Geschwind, M.D., Ph.D.
  • Portia E. Iversen
  • David A. Lewis, M.D.
  • Roberto Lewis-Fernández, M.D.
  • Thomas H. McGlashan, M.D.
  • Steven M. Paul, M.D.
  • Rhonda Robinson Beale, M.D.
  • Gregory E. Simon, M.D., M.P.H.

Ex Officio Members:

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

Liaison Representative at the Open Policy Session:

  • Kathryn Power, M.Ed., Director, Center for Mental Health Services, Substance Abuse and Mental Health Services Administration (SAMHSA)

Others Present at the Open Policy Session:

  • Andrea Baruchin, Foundation for the National Institutes of Health
  • Jim Bernstein, American Society for Pharmacology and Experimental Therapeutics
  • Roberta Diaz Brinton, University of Southern California
  • Maja Bucan, University of Pennsylvania
  • BJ Casey, Weill Medical College of Cornell University
  • Yoshie Davison, American Academy of Child and Adolescent Psychiatry
  • Destiny Decker, Traditional Values Coalition
  • Florence Fee, No Health without Mental Health
  • Aaron Halleck, American Sign Language Interpreter
  • Ron Honberg, National Alliance on Mental Illness
  • Danielle Hunter, Dixon Group
  • Alan Kraut, Association for Psychological Science
  • Anne Michaels, National Foundation for Mental Health
  • Wendy Naus, Lewis-Burke Associates
  • Judith Orvos, Science Writer
  • James Pavle, Treatment Advocacy Center
  • Brian Rasmussen, American Association for Marriage and Family Therapy
  • Michelle Rodriguez, Social & Scientific Systems, Inc.
  • Jonathan Sack, One Mind for Research
  • J. David Sweatt, University of Alabama, Birmingham
  • Carol A. Tamminga, University of Texas
  • Margot Walker, Research Council UK
  • Sheris Williams, Dixon Group
  • Matthew A. Wilson, Massachusetts Institute of Technology

Open Policy Session: Call to Order and Opening Remarks

NIMH Director Dr. Insel called the open policy session to order and welcomed all in attendance. He indicated that much of the session would be devoted to discussion of the NIMH Division of Intramural Research Programs, and he welcomed the members of the Board of Scientific Counselors to the meeting.

Approval of the Minutes of the Previous Council Meeting

Turning to the minutes of the May 2011 Council meeting, Dr. Insel asked if Council members had revisions or comments on the minutes. Hearing none, the minutes were 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 as well as recent scientific advancements in mental health.

HHS and NIH-Wide Updates

Referring to the September 2011 Director’s Report, Dr. Insel touched upon new and ongoing initiatives at NIH and NIMH, including the impact of health care reform, new Common Fund initiatives and changes in the intramural program.

Dr. Insel stated that health care reform is the number one priority for 2011 and likely for 2012, with HHS as the major agency tasked with implementing the Patient Protection and Affordable Care Act of 2010 (ACA).

Dr. Insel noted that NIMH plays an important role in the Interagency Autism Coordinating Committee (IACC), which is chaired by the NIMH director. As the lead Institute on autism spectrum disorder (ASD) for the federal government, NIMH directs research on ASD and coordinates service-related issues. Dr. Insel indicated that discussion remained ongoing in the Senate regarding extending the Combating Autism Act of 2006, under which the IACC operates and which is set to expire on September 30, 2011. He said that if the Act was not reauthorized in the current Congressional session, it likely would be carried forward in a continuing resolution for another few months, and possibly could be reauthorized by the Senate in the future.

Another major effort involving NIMH is the National Action Alliance for Suicide Prevention (Action Alliance). Under the direction of the Secretary of HHS and the Secretary of the Army, many different stakeholders are being brought together to develop strategies for reducing the rate of suicide in the United States. Estimates based on data collected from 2008 by the Centers for Disease Control and Prevention (CDC) indicate that the number of deaths is climbing, now up to over 36,000, which is in marked contrast to the numbers for homicide, traffic fatalities, and other causes. SAMHSA is the lead agency on the Action Alliance, and NIMH continues to collaborate with SAMHSA on how to bend the curve on this statistic.

The “Common Rule” regulations for protection of human subjects in research (45 C.F.R. Part 46), which have been in place since 1991, have been revised in an attempt to streamline the regulatory burden in human subjects protection, and the interim final document  is available for public comment.

HHS has issued a final rule in the Federal Register that amends the Public Health Service (PHS) regulations on Responsibility of Applicants for Promoting Objectivity in Research for which PHS Funding is Sought (42 C.F.R. Part 50, Subpart F) and Responsible Prospective Contractors (45 C.F.R. Part 94). Since dissemination of the original regulations in 1995, questions have been raised about whether a more rigorous approach to investigator disclosure, institutional management of financial conflicts, and federal oversight is required. After considering all public comments, HHS developed the final rule resulting in major changes to the 1995 regulations. The 2011 Final Rule includes a de minimis threshold of $5,000 for disclosure; disclosure of all significant financial interests related to the investigator’s institutional responsibilities; and, an expanded definition of income excluded from the disclosure requirement. Additional information regarding the changes to the financial conflict of interest rules, including compliance dates and a comparison of the 1995 regulations, can be found in NIH Guide Notice NOT-OD-11-109 .

Next, Dr. Insel gave an overview of new NIH Common Fund  initiatives, including the National Center for Advancing Translational Sciences (NCATS), the Medical Education and Partnership Initiative (MEPI) and H3Africa , the Single Cell Biology project, and the Center for Regenerative Medicine.

Dr. Insel said there was hope that NCATS would launch at the start of the new fiscal year, but with delays in approval of the FY 2012 budget, it could be another few months. He stressed the importance of the NIH Scientific Management Review Board’s recommendation to develop a Center dedicated to catalyzing and accelerating treatment development and reengineering the entire discipline of translational science. He indicated there is enthusiastic support by the President and Senate for the Center, adding that the Senate Appropriations Committee had included additional NIH funds to fuel the creation of NCATS. The Center will be formed by uniting and realigning existing NIH programs that play key roles in translational science, including the National Center for Chemical Genomics, a part of the Molecular Libraries Program. Dr. Insel indicated that the goal is to create a national network to specially highlight first-in-man trials and Phase I and IIa trials using the Clinical Center and the Clinical Translational Science Awards at 60 different academic medical centers. A new partnership with the FDA and funding for the Cures Acceleration Network, which had been mentioned in the ACA, are ways of propelling this effort and re-engineering the pipeline.

NIMH is also involved in MEPI and H3Africa, a global health education effort led by the Fogarty International Center and the National Human Genome Research Institute, focused on creating research capacity in the greatly underserved region of sub-Saharan Africa. Representing a new model for international collaboration, awards are intended to strengthen local partnerships or build new ones between African medical institutes and U.S. partners to provide clinical education and research training opportunities to in-country faculty and students working on non-communicable diseases and other priority health areas, including maternal and child health and mental health, related to and beyond HIV/AIDS.

Coordinated by Andrea Beckel-Mitchener, Ph.D., NIMH is taking the lead in a partnership with the National Institute of Biomedical Imaging and Bioengineering on a new Common Fund program dedicated to single cell analysis supporting the development of innovative tools and technologies to tackle the problem of biological noise in population-level analysis. Many biological experiments are performed on groups of cells, under the assumption that all cells of a particular type are identical. However, recent evidence reveals that significant heterogeneity exists among individual cells within a population, and these differences have important consequences for the health and function of the entire population.

Another new effort under way is the NIH Intramural Center for Regenerative Medicine (NIH-CRM), an initiative to create a world-class center of excellence in stem cell technology on the NIH campus, including induced pluripotent stem cells (iPSC), which can have applications in many systems and organs of the body. Mahendra Rao, M.D., Ph.D., has been appointed as the director of NIH-CRM, which will be administered by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Rao is internationally known for his research involving human embryonic stem cells and other somatic stem cells. Acknowledging that similar efforts are going on in other arenas, Dr. Insel stated that the intramural program is setting up standards to be used nationally and testing out the various approaches.

Dr. Insel reviewed a recent paper published in Science (Ginther et al, 2011) that outlined the results of an NIH-funded study of the ethnic and racial diversity of NIH grantees between FY 2000 and FY 2006. The study, focused on Ph.D.s applying for R01 grants, found that 1.4 percent of more than 40,000 applicants self-identified as Black, 3.2 percent as Hispanic, 16.2 percent as Asian, and 69.9 percent as White. There were significant differences in award probability by race and ethnicity, with applications from Black investigators 13.2 percent less likely to be awarded. Controlling for the applicant’s educational background, university affiliation, country of origin, training, previous research awards, and publication record did not eliminate this disparity. Indeed, after controlling for these confounds, Black applicants remained 10 percentage points less likely to be funded. An essay by Larry Tabak, D.D.S., Ph.D. and Francis Collins, M.D., Ph.D., in the same issue of Science revealed how troubling the findings were despite concerted efforts by NIH to level the playing field. In this article, Dr. Collins expressed his determination to find a far better way. To this end, an early career reviewer program will bring minority scientists into review committees at an early stage to gain an understanding, as well as to influence the process. A new workgroup within the Advisory Committee of the Director of NIH, chaired by Shirley Tilghman, Ph.D. of Princeton University, will propose specific plans and policies to ensure the diversity of the biomedical workforce.

Turning to the NIMH budget, Dr. Insel noted that spending at NIMH for intramural research and for research management and support comprised 17 percent of NIMH’s overall budget for FY 2010. The other 83 percent of the budget was accounted for by extramural grants, which totaled $1.233 billion and provided support to more than 400 institutions. The FY 2011 budget was $1.477 billion, a reduction of $16.2 million over the previous year. The FY 2012 request for NIMH is $1.517 billion, an increase of $27.5 million, or 1.84 percent over the 2010 level and 2.64 percent over the FY 2011 level. The Budget Control Act, enacted on August 2, 2011, subsequently capped FY 2012 discretionary spending for non-security agencies at the FY 2011 enacted level, which is below the President’s FY 2012 budget request and nearly 1 percent below the FY 2010 budget. Dr. Insel noted that from a historical perspective, funding has not kept pace with inflation in recent years and the result is a loss of actual purchasing power for research, which is very worrisome. This is also reflected in the number of new grants funded by NIMH, which fell to 457 in 2011, below the target of 500; the estimate for 2012 is projected at 480 to 490.

Discussion

Steven M. Paul, M.D., asked whether Dr. Insel foresaw a further reduction in research awards beyond 2012.

Dr. Insel replied that NIMH’s traditional annual target is 550 grants, and the Institute has come close to meeting that goal every year since 2002. He noted, however, that the projection of 480 to 490 grants for 2012 may represent a “new normal.”

Thomas H. McGlashan, M.D., voiced a concern about how much of the NIMH budget is earmarked for research on treatment of established disorders versus prevention, and opined that more focus on prevention may be warranted.

In response, Dr. Insel remarked that NIMH has been in the forefront of research on the early intervention prodrome for schizophrenia. Investigation into robust markers of risk for mental illness is in the early stages, particularly compared with work that has already been done in areas such as cardiovascular disease and cancer. He added that the strategic plan lays out a shift in research focus to a much earlier trajectory in the development of disease.

Robert Desimone, Ph.D., said consideration should be given to balancing funding for new awards and continuing grants to ensure that grants from several years ago do not receive funding at the expense of more promising new applications.

Dr. Insel acknowledged the import of Dr. Desimone’s concern and noted that funding for a typical R01 grant is reduced an average of 18 percent during the five-year project period, with the result being that investigators are effectively being asked to complete five years of work with only four years of funding. He asked Council members to reflect on how NIMH should handle funding for non-competing grants in 2012 and beyond.

Rhonda Robinson Beale, M.D., expressed concern that the advent of health care reform might bring with it a “pay for performance” mentality that could have an impact on funding or defunding of research, based on the potential for the results to “move the needle” on patient populations. She also suggested that research focused on engagement of patients and provision of services be prioritized.

Dr. Insel acknowledged that engagement could become the metric by which health care is reimbursed and encouraged Council members to think carefully about how NIMH’s research is linked to outcomes.

Comments from Retiring Council Members

Dr. Insel again acknowledged the contributions of Council members whose tenure ends on October 1, 2011: Robert Desimone, Ph.D., Daniel H. Geschwind, M.D., Ph.D., and David A. Lewis, M.D. Dr. Insel invited the departing members to address the Council.

Dr. Desimone noted that with his retirement from Council, this will be the first time in more than 30 years that he has not been affiliated with NIMH, noting that the NIMH Division of Intramural Research Programs (DIRP) offers unique possibilities for principal investigators. One benefit is the flexibility to change direction on already funded research, whereas, in a university setting, that would only be possible if funding had come from a private source. He applauded the large number of high-quality presentations at the recent NIMH DIRP retreat.

Regarding extramural research, Dr. Desimone noted that R01 grants are the lifeblood for many investigators outside NIMH. He suggested that as a mental exercise, Council think through how the Institute would proceed in terms of budgeting, were Congress to mandate that the number of awards stay constant. He also called attention to the number of universities in recent years that have used funding from NIH to support infrastructure, and suggested that the dynamic may need to change to ensure that more money goes into salaries for researchers.

Finally, Dr. Desimone reflected on his recent visit to China, where a McGovern Institute is being established. He observed that the Chinese government is spending a great deal of money on medical research as an investment in the future. China does not, however, have a system for awarding grants and the Chinese are envious of NIH’s process for making such decisions, which is merit-based and divorced from personal relationships and political influences. He thanked the exceptional NIMH staff and his fellow Council members, and said it had been an honor being involved in the Council process and its decisions about mental health research.

Dr. Geschwind echoed Dr. Desimone’s comments about the quality of the DIRP. He remarked that this point in history represents an unprecedented opportunity to change the course of neuropsychiatric disease using genomics and urged that pharmaceutical companies remain involved in such research. Dr. Desimone also noted the enormous amount of data generated by clinical trials and brain imaging projects and the lack of a method for collecting and storing the data such that it can be reanalyzed once individual studies are completed. He cited the work done at Alzheimer’s disease centers as a model for the type of longitudinal research needed in neuropsychiatric illness and the opportunities for collection of health information inherent in development of electronic medical records.

Dr. Lewis noted that participating in Council gave him a new appreciation for the size, complexity, and scope of NIMH’s organization and the talent, dedication, and creativity of the team involved in NIMH’s research. He said the experience will help him to be more effective in explaining the mission and mechanisms of NIMH to the constituencies with whom he interacts. It also will make him more skilled in advising the young scientists in his organization and others with whom he interacts, about the importance of engaging with an NIH program officer as early as possible, listening intently and carefully to the advice offered, and cultivating a relationship with that program officer. Having been on Council, his upcoming participation in an initial review group will be a much richer experience.

Dr. Insel invited Richard Nakamura, Ph.D., departing Scientific Director of DIRP, to address the Council members.

Dr. Nakamura thanked the Council members and the NIMH Board of Scientific Counselors for the privilege of working with them, noting that he has been at NIMH since 1976. He underscored the value of his interactions with the staff, the scientists in the intramural program, and the Council members over the years. He also expressed his admiration and thanks to the Board of Scientific Counselors for their wonderful work in reviewing the DIRP, acknowledging their assistance in making significant changes and providing very valuable counsel and support. As he moves to the Center for Scientific Review, he takes from his experience at NIMH an appreciation of the Board of Scientific Counselors’ approach to evaluating research programs, which includes looking at not only what needs to be eliminated but what needs to be cultivated and advanced.

Dr. Insel thanked Dr. Nakamura for his 35 years of service to NIMH, his dedication and the example he has set in defining what public service is.

Progress Report from the Army Study to Assess Risk and Resilience in Service-members (Army STARRS)

Kevin Quinn, Ph.D., of the NIMH Division of Neuroscience and Basic Behavioral Science, gave an overview of Army STARRS , described the study components, and provided a perspective on the current status of the research. Army STARRS is a five-year study on suicide and suicidal behavior among soldiers, and the largest single study on the subject of suicide that NIMH has ever undertaken. The research comprises four components: the Historical Data Study; New Soldier Study; All Army Study; and, the Soldier Health Outcomes Study. In addition, there are a series of smaller specialized substudies. These components are designed to identify factors that protect a soldier’s mental health and those that put a soldier’s mental health at risk. The total cost for the five-year project period is estimated at $65 million, with $50 million in core funding provided by the Army and $15 million in supplemental funding from NIMH. Data collection and analysis are being done on a continuous basis, and the researchers are providing quarterly reports to the Secretary of the Army and the Vice Chief of Staff of the Army.

The Historical Data Study is focused on analysis of records from 38 Army and Department of Defense (DOD) databases which track active duty soldiers and suicide events between 2004 and 2009. The New Soldier Study is assessing the health, personal characteristics, and prior experiences of new soldiers in their first week of basic training. Soldiers across all phases of Army service are being assessed in the All Army Study. More than 11,000 soldiers are currently enrolled in the All Army Study, with a target of 35,000. Interviews of individuals who have attempted suicide, relatives of the deceased, and controls are part of the Soldier Health Outcomes Study A, which is taking place at five locations across the United States. The Soldier Outcomes Study B is a psychological autopsy of soldiers who have completed suicide, and involves phone interviews conducted by the University of Michigan with Army supervisors and next of kin of the deceased. Special Studies include a Clinical Calibration Study, a Pre/Post Deployment Study, and a Pre/Post Separation Study.

Researchers from Army STARRS examined data from the U.S. Army’s Total Army Injury and Health Outcomes Database (TAIHOD), which includes information from Regular Army soldiers and covers the period between 2004 and 2008, to identify potential predictors of risk for suicide among soldiers. In 2004, the Army noted a sharp increase in the rate of suicide among soldiers, and by 2008, the rate for soldiers exceeded that for civilians when adjusted for demographic factors. The trend was not explained by the increased rotation of soldiers into war zones, and the rise in suicides was seen even among soldiers who had never been deployed. Preliminary analyses of the TAIHOD data found that the suicide rate was highest among those currently deployed (18.3 deaths per 100,000) and dropped after deployment (15.9 per 100,000).

The suicide rate increased among women (from 5.1 to 15.2 per 100,000) more so than among men (from 14.8 to 21.1 per 100,000), when comparing soldiers who have never deployed to those currently deployed. Being married is associated with a lower risk of suicide during deployment (15 per 100,000 among those married versus 24.5 per 100,000 among those never married). Being married also may protect against accidental death, but only when not deployed (27.7 per 100,000 among those married, compared with 39.8 per 100,000 among those never married). In a war zone, the suicide rate for women is statistically indistinguishable from that of men.

So far the small number of socio-demographic variables considered, such as sex, age, education, marital status, and race, and career-related variables, such as rank, time in service, and deployment status, show a meaningful concentration of risk of suicide. Twenty-two percent of suicide deaths occur in the 5 percent of soldiers with the highest suicide risk profile, and the same basic pattern is found for accidental death, with 19 percent of deaths among the 5 percent of soldiers with the highest-risk profiles.

Further analyses of TAIHOD are under way to understand and validate the variables that may predict risk for suicide. The Army STARRS researchers are examining data from other Army and DOD databases that may include information beyond that in TAIHOD. Investigators are focusing on periods thought to be high-risk in a military career, such as deployment and periods immediately before and after deployment.

Discussion

Dr. Desimone asked if Army STARRS is examining suicide in the context of a variety of psychiatric problems including sleep.

Dr. Quinn indicated that a history of current and past sleep problems is part of the data being collected. The surveys used in the New Soldier and All Army studies are comprehensive assessments of psychopathologies, based on the World Health Organization’s Composite International Diagnostic Interview (CIDI). The questions include personal history, family history, history of stress, and medication use. Dr. Quinn noted that maximizing the environmental conditions for the interviews was a challenge, because every minute of a soldier’s life is programmed.

Noting that substance abuse disorders are a risk factor for suicide in the general population, Dr. Beale asked if they are being taken into consideration as a risk factor in the studies and whether issues related to military culture, such as “Don’t Ask, Don’t Tell,” are being factored into the research.

Dr. Quinn acknowledged that substance abuse is a sensitive subject for the investigators and the soldiers, and indicated that questions on past and current use of substances are included in the CIDI and in the Army STARRS interviews. The study is confidential and only aggregate data are shared with the Army for purposes of long-range tracking. The Army has committed to never asking for or receiving data on individual responses and the soldiers have been assured that their information is confidential. He noted that the Army is very sensitive to the stigma associated with reporting mental health problems and has gone to great lengths to make soldiers feel comfortable about participating in the study and disclosing their problems.

Ira Katz, M.D., Ph.D., asked if a cross-sequential analysis would be performed of Army STARRS data and data on suicide in veterans.

Dr. Quinn indicated that a longitudinal Pre/Post Separation study is being considered to track soldiers prior to entry into the military and after they leave the service.

Dr. Insel congratulated Dr. Quinn and the Army STARRS investigators on research into this urgent issue. He said the findings will have enormous implications for civilians as well as the Army and NIMH is proud to be a part of this initiative.

NIMH’s Intramural Program: Future Directions

Dr. Insel opened the discussion by providing an overview of recent changes in the NIMH DIRP. In addition to Dr. Nakamura’s departure, Daniel Weinberger, M.D., who had led the largest research program within the DIRP, left in August. Dr. Insel noted with sadness the passing of Howard Nash, M.D., Ph.D., a senior investigator in the NIMH Laboratory of Molecular Biology, who died in June. Philip Wang, M.D., Dr.P.H. is serving as Acting Scientific Director for the DIRP, with assistance from Rajesh Ranganathan, Ph.D., and an administrative team to help with the transition to new leadership. Dr. Insel acknowledged the presence of Drs. Ranganathan and Wang, as well as members of the NIMH Board of Scientific Counselors (BSC): Chair J. David Sweatt, Ph.D., and members Roberta Diaz Brinton, Ph.D., Maja Bucan, Ph.D., B.J. Casey, Ph.D., Carol A. Tamminga, M.D. and Matthew A. Wilson, Ph.D.

Offering a historical perspective on the DIRP, Dr. Insel noted that a Blue Ribbon Panel (BRP) of distinguished experts was convened in 2008 to review the general organization, operation, and administration of the DIRP. The panel was co-chaired by Solomon Snyder, M.D., Department of Neuroscience at Johns Hopkins School of Medicine and Dr. Tamminga. The BRP’s report acknowledged the value of the program, while identifying areas in which the DIRP had not realized its full potential. Among the recommendations from the BRP was to view NIMH DIRP as an incubator, an environment that fosters innovation and adaptability, in which scientists can participate in high-risk research and work with unique resources, such as the NIH Clinical Center. The BRP identified a need for the DIRP to become more innovative and adaptable in responding to emerging national needs, and to support exit strategies for investigators leaving the Division, to encourage the transition to the extramural research community.

One of the areas in which the DIRP has already demonstrated its unique value is imaging. The DIRP was the incubator for the actively shielded 7 Tesla imaging system, which is now in broad use, and it has one of the largest and best positron emission tomography (PET) development programs outside of industry. In the next few months, the Division will have an 11.8 Tesla magnet in clinical use, which is a first for the United States.

Aside from extraordinary capabilities in imaging, the DIRP is known for supporting cognitive science in both non-human primates and clinical populations, including research in neurophysiology, post-mortem studies, and work aimed at validating results from clinical neuroimaging. Dr. Insel noted that the NIH Clinical Center affords researchers the opportunity to study rare diseases, perform longitudinal studies, and carry out deep characterization of patient groups. He cited the work of Carlos A. Zarate, Jr., M.D. and Husseini Manji, M.D. in developing fast-acting antidepressants and identifying ways to predict which patients will respond. Such research, Dr. Insel said, could transform development of antidepressants and provide powerful tools for stratifying the patient population. In the area of genetics, he cited the work of Francis McMahon, M.D., in identifying common variants in bipolar disorder and major depressive disorder; a paper in Nature by tenure track investigator Heather A. Cameron, Ph.D., on neurogenesis; the cutting-edge research on how the cortex works being done by the computational laboratory of Dietmar Plenz, Ph.D.; and, the work of David Leopold, Ph.D., and his colleagues in bringing together imaging and neurophysiology to explore whether issues such as “blind sight” represent a cognitive or an imaging phenomenon. He also highlighted the groundbreaking work in modeling social deficits and other psychiatric symptoms in mice, and in identifying the best targets for medication development being done by Jackie Crawley, Ph.D., as well as Dr. Weinberger’s pioneering work in developmental neurobiology of disorders such as schizophrenia, and the research of tenure track investigator Kazu Nakazawa, M.D., Ph.D. on postnatal NMDA receptor ablation in corticolimbic interneurons.

Noting the extraordinary breadth of basic and clinical neuroscience within the DIRP, Dr. Insel explained that the Division has 873 employees out of the total 2,023 at NIMH. Among them are 47 principal investigators, a decrease of 35 percent over the past decade. Importantly, ten of the DIRP scientists are outstanding tenure track investigators who have arrived in the past decade; and while the faculty has declined by approximately 25 percent in recent years with a turnover rate of approximately 50 percent in the last 12 years, the budget for the DIRP has increased by an estimated 47 percent. The DIRP represents 11 percent of the NIMH budget, or $170M; the challenge, Dr. Insel said, is how to balance the budget, given that scientific research is in some ways more costly to perform at the DIRP than in the extramural world. It is anticipated that $3 million of the FY2012 budget will be earmarked for the Porter Neuroscience Center, which will provide 300,000 square feet of new space for neuroscience, 20,000 square feet of which will be used by NIMH.

Dr. Insel posed several questions for consideration by Council members:

  • What is special about the DIRP?
  • What kind of leadership should it have?
  • What does it mean to make the DIRP an incubator?
  • What should the DIRP be focusing on scientifically?
  • What is the future for the Clinical Center?

Dr. Insel then turned the discussion over to Dr. Sweatt, who is the outgoing Chair of the BSC, and to members of the BSC.

Dr. Sweatt provided an overview of a teleconference held by the BSC in August to generate discussion about the future of the DIRP, resulting in several recommendations. The BSC members agree upon and very seriously support a mission statement for the DIRP as a program that is unique, very innovative, and designed to have the highest scientific impact.

The top strategic priority for achieving that mission statement is the recruitment of a new Scientific Director, who must be of top intellectual, scientific and administrative caliber. Dr. Sweatt acknowledged that the Scientific Director’s position is very challenging and also offers an opportunity to leave a scientific legacy of enormous importance. The recruitment process for a new Scientific Director is under way and the Board indicated that the change in leadership represents new opportunities.

Board members also discussed the need for fulfilling the idea of exchange in the incubator model, with researchers moving between intramural and extramural, as a way to help highly successful researchers make the transition from the DIRP to the extramural program, and to help trainees make a similar transition. Referring to a slide in Dr. Insel’s presentation that showed decreases in the number of DIRP investigators, Dr. Sweatt noted that those statistics have translated into closure of one or two labs at every meeting of the BSC in the past 5 years. He underscored Dr. Insel’s comment on the importance and high degree of novel and innovative research that is coming out of the DIRP, particularly as it relates to human studies. Some of the best work in the world is being done through the DIRP in human studies, psychophysics imaging and direct translation-relevant studies.

Discussion

Dr. Wilson suggested that NIMH consider partnering with private research institutions, endowments, or individuals to obtain more funding for high-risk, high-reward research that is typically not considered for traditional extramural funding.

Dr. Casey underscored the importance of the presence of the DIRP in the Nation’s capital with regard to advancing the agenda of mental health research.  She noted that the DIRP has produced wonderful research and urged that NIMH do all it can to ensure that this continues, and also identify areas of the DIRP that are not cutting edge.

As a member of the BRP and the BSC, Dr. Tamminga commented on the importance of collaboration between laboratories in the intramural and extramural programs.  Such collaborations might increase appreciation of the DIRP’s research and resources while affording the DIRP access to the strengths of the extramural program.  She also underscored the high quality of the science emerging from the DIRP even as the faculty has been reformulated.

Dr. Bucan expressed the need for an extremely strong strategic plan for the DIRP and for identification of opportunities for interaction between the DIRP and the extramural program.

Dr. Brinton expressed that the DIRP is a unique and precious resource for the Nation and the world that needs to remain in the vanguard of discovery and translation.

Dr. Sweatt said he believes that development of a strategic plan for the DIRP will represent a challenge, and that the goal should be to prioritize scientific areas for investment, rather than address organizational issues.

Dr. Insel opened the floor to Council members for their comments.

David G. Amaral, M.D., complimented Dr. Insel’s presentation and echoed Dr. Sweatt’s sentiments that the focus should be on identifying unique areas of intramural scientific research in which NIMH should be investing, rather than attempting to replicate the high-impact research in mental health that is already going on at universities and institutions throughout the country.

Dr. Insel concurred that the DIRP cannot do everything and should target a small number of research initiatives with the goal of doing truly outstanding work in those areas. 

Regarding recruitment for a new Scientific Director, Dr. Amaral asked whether the DIRP can compete with the best universities and institutes in the United States in terms of compensation.

Dr. Sweatt acknowledged that is a difficult question, given NIH salary caps.  He suggested that the search committee emphasize the huge opportunity to make a scientific impact that is inherent in the position of Scientific Director and the opportunity to oversee a department with a $170 million annual budget.

Dr. Desimone suggested that the new Scientific Director convene meetings involving members of the DIRP, extramural scientists, and BSC members to discuss the strategic plan for the DIRP.

Gregory E. Simon, M.D., M.P.H., commented that the review process for DIRP needs to favor innovation.  He also suggested that the DIRP’s science be truly an open source to promote collaboration between intramural and extramural scientists.

Roberto Lewis-Fernández, M.D. urged that diversity of investigators be included in discussions about the strategic plan for the DIRP.

Dr. Paul acknowledged that the DIRP has been very important in setting an agenda in mental health research, and stated that one measure when evaluating the DIRP is whether the return on its $170 million annual investment is what the public and the field expect and deserve.

Dr. Robinson Beale suggested recruiting patients as partners in NIMH research over the long term, with the goal of providing stable populations for longitudinal studies.

In response to Dr. Beale’s comment, Dr. Insel noted that the DIRP affords a unique opportunity for longitudinal studies of rare diseases that cannot be accomplished anywhere else.

A recruiting strategy suggested by Dr. Geschwind would challenge investigators to find a solution to a particular problem in mental health and provide an environment in which they can commit to spending the next ten years on work aimed at meeting that challenge.

Dr. Insel noted that a similar approach was taken with the Genes, Cognition and Psychosis Project (GCAP), which was designed as a five-year project but ultimately took seven years to complete.  He said the challenges with such initiatives include keeping to a “sunset” date.

Dr. Paul suggested expanding NIMH’s guest researcher program to encourage extramural researchers to work on DIRP projects for a limited period of time.

Dr. Insel expressed interest in Dr. Paul’s suggestion, saying it could result in a more nimble intramural program and one that need not be confined to the facility in Bethesda.  He noted that the National Institute of Diabetes and Digestive and Kidney Diseases has an intramural program in Arizona, and the National Institute of Allergy and Infectious Diseases has one in Montana.

Ms. Betts asked what percentage of the budgets of other NIH Institutes is devoted to intramural research.

Dr. Insel responded that the percentage varies by Institute.  Overall, 9.2 percent of the NIH budget is spent on intramural research, versus 11.4 percent within NIMH.

As a member of the BSC, Dr. Tamminga said that the panel uses scientific excellence as its criterion, and she thought that a scientific strategic plan would be very valuable to the BSC’s work.

In response to the various suggestions about a strategic plan for the DIRP, Dr. Insel acknowledged that its investigators should be guided by core principles and values, while expressing concern that their efforts to innovate not be hampered.

Dr. Sweatt clarified that NIMH’s intention should be to identify scientific priority areas for the DIRP and hire stellar investigators without dictating the research they should be conducting in those areas.

Dr. Desimone suggested that the DIRP may need to reach out to other NIH intramural programs and to NINDS for advice on how to recruit junior investigators for scientific research in need areas.

Howard Eichenbaum, Ph.D. commented that the biggest challenge for the DIRP right now is scientific leadership, and recruitment of the Scientific Director is critically important.

Dr. Simon questioned whether NIMH should be doing clinical research with patients in earlier stages of disease rather than those individuals typically admitted to NIH’s inpatient units.

Dr. Insel clarified that not all of the clinical research done by the DIRP involves individuals admitted to NIH’s inpatient units.  He cited the example of a longitudinal study by Ellen Leibenluft, M.D., on childhood bipolar disorder conducted in an Amish community in Ohio.

Regarding the recruitment of a new Scientific Director, Dr. Insel indicated that the Council would be engaged in the process, as will the BSC and DIRP staff.  A series of town hall meetings and other types of conversations are envisioned.

Concept Clearances

Eradication of HIV-1 from CNS Reservoirs: Implications for Therapeutics

Jeymohan Joseph, Ph.D., Chief of the HIV Pathogenesis, Neuropsychiatry and Treatment Branch, Division of AIDS Research (DAR) discussed an initiative aimed at fostering discovery research to define and characterize the sources of HIV-1 persistence in the central nervous system (CNS) for people on suppressive anti-retroviral therapy, and fostering translational research to enable therapeutic eradication of HIV-1 from the brain.

Highly active anti-retroviral therapy (HAART) is able to suppress HIV-replication to low levels (1-50 viral copies per mL) without completely eliminating virus.  This limitation is due to latent sequestered virus found in cellular reservoirs, including memory T cells, monocyte-derived macrophages, hematopoietic cells, and cells within the gastrointestinal tract, genitourinary tract, and brain. The NIH has placed a high priority on the goal of eradicating HIV-1 from persistent reservoirs, and a number of eradication strategies are currently being tested.  However, many of the therapeutic strategies under consideration may not be optimal for targeting the HIV-1 cellular reservoirs within the CNS and could potentially have devastating consequences on the brain.

Additional research is needed to target viral reservoirs in the CNS sanctuary because of unique anatomic features in the brain, such as the blood-brain barrier and enclosure within the restricted skull cavity.  One of the challenges for eradication of CNS-specific HIV-1 reservoirs includes developing anti-HIV-1 therapeutics that can traverse the blood-brain barrier.  Another challenge is that the current eradication strategies being tested may have detrimental effects in the CNS, due to neuronal toxicity of reactivated virus and other inflammatory sequelae.  Discovery research is needed to focus solely on expanding the knowledge base about CNS HIV-1 latency and eradication strategies, tailored directly for the brain compartment.

Dr. Joseph said that the expected outcomes of the research are to increase understanding of how HIV-1 reservoirs are established in CNS-derived cells such as macrophages and astrocytes, and of the mechanisms by which HIV-1 persists in this compartment.  The researchers hope to develop CNS-based cell assay systems, screening approaches, and animal models to test HIV-1 eradication strategies, and to identify CNS-targeted therapeutic strategies to eradicate latent HIV-1 from the brain.

A National Neurobank

Roger Little, Ph.D., Senior Advisor in the Office of Science Policy, Planning, and Communications (OSPPC) discussed an initiative designed to create a centralized biorepository for the acquisition, receipt, storage, and dissemination of human brains, related biospecimens, and associated clinical data.  The goal is to increase the availability of, and access to, high-quality specimens for research on the neurological basis of disease, while also increasing efficiency and economy of scale.  Another goal is to increase tissue donation by increasing awareness of the value of these gifts for understanding brain disorders, via a concerted outreach effort to the disease advocacy community.

Dr. Little said that the NIH has historically funded brain banks through grants to individual or small groups of investigators with a particular disease focus.  Donor tissues are collected at these disease-specific banks, while other tissues of value to NIH Institutes are excluded from the collection.  Much of the tissue is often not fully utilized and is collected with protocols and quality metrics that vary from site to site.  Clinical and phenotype data generated from these samples, which is particularly important for psychiatric cases, are shared in an inconsistent manner, as are the samples themselves.

A trans-NIH workgroup was formed in September 2010 to evaluate current approaches and NIH investments in biobanking.  Based on consultation with experts both outside and within the NIH, the workgroup supported a coordinated approach to a neurobank.

Discussion

Dr. Amaral applauded the goals of the neurobank and said that such an effort is clearly needed.  As an alternative to a centralized repository, he suggested creating an integrated network of neurobanks with uniform standards for quality control and collection.  With such a geographically disbursed network and the opportunity for connections at the local level, next of kin might feel more comfortable donating a loved one’s brain tissue.

Dr. Little said the investigators recognized the value of local connections and that they have invested significant time in developing relationships with their local populations.  Nevertheless, it is up for debate whether it would make sense to build infrastructure for tissue storage in many locations versus in a single location.

Dr. Amaral emphasized that within the autism community, donations of brain tissue are lacking.  In his experience with these patients and their families, the families are more willing to contribute their child’s tissue to banks in their own state than to contribute to a bank that is far from where they reside.

Dr. Simon suggested that the researchers partner with large health systems that have providers who care for specific patient populations.  These systems would have established relationships with the providers and longitudinal data on the treatments patients are receiving.

Dr. Robinson Beale suggested partnering with health plans, advocacy groups, and community groups.

Dr. Paul suggested the Alzheimer’s Disease Cooperative Study (ADCS) as a model for the neurobank initiative and potential resource for brain tissue.

Dr. Insel noted that the ADCS has 30 centers across the country and has collected thousands of tissue samples, and therefore remains a good model of a standardized and coordinated approach to collection and banking.

Dr. Lewis emphasized the need to engage investigators in helping to design the ongoing collection process, such that the tissue samples collected are appropriate for addressing the scientific questions of interest.

Ms. Betts emphasized the importance of educating patients who are being treated for neurological disease about brain tissue donation, so that they can be empowered to make a real contribution beyond their lifetimes.

Dr. Little indicated that a public website is envisioned as a part of the neurobank initiative, and the NIMH communications office is actively involved in outreach to disease advocacy groups.

Public Comment

James Pavle, Executive Director of Treatment Advocacy Center, expressed his appreciation of the quality of the discourse during the meeting.

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
September 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 546 $528,979,556.00 486 $402,068,650.00 4 $755,519.00 1036 $931,803,725.00
Research Training 1 $852,003.00 1 $1,604,054.00 0 $0.00 2 $2,456,057.00
Career 62 $47,539,293.00 21 $15,636,465.00 0 $0.00 83 $63,175,758.00
Other 4 $4.00 0 $0.00 0 $0.00 4 $4.00
Totals 613 $577,370,856.00 508 $419,309,169.00 4 $755,519.00 1125 $997,435,544.00

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

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

Liaison Representative

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