NIMH held its sixth annual meeting of the Professional Coalition for Research Progress (The Coalition) on April 23, 2010 in Washington, D.C. This annual meeting serves as an opportunity for representatives from professional organizations with an interest in NIMH research to hear about advances in mental health research and current and new research directions and strategies for NIMH. Coalition members also network with colleagues and throughout the day engage in direct dialogue with the NIMH Director, Thomas Insel, M.D. and senior NIMH staff. This meeting of the Coalition featured invited speakers who provided information on new opportunities for behavioral and social science research at NIH, the Human Connectome Project, economic perspectives on mental health research, novel therapeutics and biomarkers of response for mood disorders, as well as the overall prospects for continued research support. This document provides a summary of the meeting highlights. See the attached agenda and participant roster for more information.
State of the NIMH
Dr. Insel welcomed Coalition members to the meeting and provided an update on activities at NIH and NIMH since the Coalition’s 2009 meeting. His State of the NIMH address included information on the five programmatic areas that the NIH Director, Francis Collins, M.D., Ph.D., has selected to direct future research at the agency; a status update on the success of the American Recovery and Reinvestment Act (ARRA) at NIH and NIMH; NIMH Intramural Research Program efforts to develop novel therapies for mental disorders; and, health care reform. Dr. Insel described Dr. Collins’s five areas of scientific opportunity and how the objectives of the NIMH Strategic Plan align with these areas: applying genomics and other high throughput technologies; translating basic science discoveries into new and better treatments; using science to enable health care reform; focusing on global health; and, reinvigorating the biomedical research community.
Dr. Insel told Coalition members how ARRA funds have helped the Institute to jumpstart the implementation of the NIMH Strategic Plan. He explained that NIMH has spent the $366 million it received through ARRA to expand the payline for research project grants; to support faculty hiring; supplement currently funded projects in specific areas of need; and, to begin work on NIMH signature projects, such as the Army Study to Assess Risk and Resilience in Service members (Army-STARRS), the Recovery After an Initial Schizophrenia Episode project (RAISE), research on the heterogeneity of autism spectrum disorders (ASD), and the Transcriptional Atlas of Human Brain Development. NIMH ARRA funds have also been used to support grants through a wide range of NIH-wide ARRA initiatives, including NIH Challenge Grants in Health and Science and Research and Research Infrastructure Grand Opportunities Grants . At the NIH level, over $5 billion in ARRA funds were awarded by the end of 2009 leading to the creation/retention of an estimated 50,000 jobs over two years. Dr. Insel discussed the current funding success rates for ARRA projects and concerns about what will happen in 2011, after ARRA ends—when funding returns to base levels. He also discussed future challenges related to drug development—specifically, the concern that the pharmaceutical and biotechnology industries are moving away from the development of medications targeting the central nervous system. Finally, he also talked about mental health-related requirements of the recently passed Patient Protection and Affordable Care Act (HR 3590)—the health care reform legislation—including the Cures Acceleration Network, comparative effectiveness research, post-partum depression research, the Centers of Excellence for Depression research; and conflict of interest.
New Opportunities for Behavioral and Social Science Research at NIH
Richard J. Hodes, M.D., Director of the National Institute on Aging, told Coalition members about two new opportunities for behavioral and social science research at NIH: the Basic Behavioral and Social Science Opportunity Network (OppNet ) and the Science of Behavior Change (SOBC ) Roadmap program. He explained that OppNet is a trans-NIH initiative to expand funding for basic behavioral and social science research (b-BSSR) with additional investments that complement NIH’s current research portfolio. OppNet b-BSSR research will be focused in three categories: behavioral and social processes, biopsychosocial research, and methodology and measurement. He discussed current strategic planning activities and noted that funding opportunity announcements (FOAs) for fiscal year (FY) 2011 will be released in summer 2010. Dr. Hodes also discussed the SOBC program, and how it will support research that integrates basic and translational science and cuts across disciplines of cognitive and affective neuroscience, neuroeconomics, behavioral genetics, and behavioral economics. His remarks emphasized the need to coalesce behavior change around issues related to economics, policy, genetics, and neuroscience, all of which affect behavioral change, as it emerges as a transdisciplinary science. Dr. Hodes highlighted the outcomes of the June 2009 SOBC meeting and outlined the similarities and differences between OppNet and SOBC.
Coalition members engaged Dr. Hodes in dialogue about OppNet and the SOBC initiatives. They were pleased to hear that NIH has placed increased emphasis on social science and behavior change research, and inquired about next steps for these initiatives, in particular information dissemination and implementation efforts. Dr. Hodes noted that there will be research on how best to disseminate findings to the field. With regard to next steps, he discussed OppNet and SOBC FY 2010 FOAs, and mentioned NIH’s commitment to continuous feedback and input from the public.
NIH Human Connectome Project
Mike Huerta, Ph.D., Program Lead for the Human Connectome Project (HCP) provided an overview of the project for Coalition members. Funded through the NIH Blueprint for Neuroscience Research , the HCP will use brain imaging to map the circuitry of the healthy adult human brain. Dr. Huerta described that there is currently a wealth of data available for the human brain at cellular and subcellular levels, but a virtual absence of connectivity data for any mammal, including humans. Because connectivity underlies brain function and dysfunction, it is crucial to fill this knowledge gap. Until recently, methods used to collect connectivity data were painstakingly slow and could not be used with humans. But now the landscape has changed: Dr. Huerta described new imaging technologies developed to allow non-invasive collection of data from humans. He described how the HCP will make available to the research community the connectivity data from hundreds of subjects, providing insight into human brain function, and opening up new lines of inquiry in human neuroscience.
Economic Perspectives on Mental Health Research
Michael Schoenbaum, Ph.D., Senior Advisor in the Division of Services and Intervention Research presented information on economics research as it relates to health impact and outcomes, as called for in the NIMH Strategic Plan. He told Coalition members that there are two primary challenges to improving health: 1) available care is not delivered well or in a manner that will improve health, and 2) the interventions that are delivered have limited efficacy in improving outcomes. To address these challenges, Dr. Schoenbaum suggested enhancing the effectiveness and efficacy of interventions through the use of screening and diagnostic procedures, and enhancing the fidelity of interventions to provide more precise treatments. 1 He discussed how more lives can be saved if the effect size is increased in basic and clinical research. With regard to fidelity, Dr. Schoenbaum discussed the use of effectiveness trials (such as CATIE, STAR*D, TADS, and STEP-BD), policy evaluations, training grants, and dissemination research. He also discussed the costs associated with improving health and the benefits of cost effectiveness research and the potential harm to society caused by the continued delivery of suboptimal interventions.
Novel Therapeutics and Biomarkers of Response in Mood Disorder
Carlos Zarate, M.D., Chief of Experimental Therapeutics in the NIMH Mood and Anxiety Disorders Intramural Research Program, told Coalition members about progress made in the treatment of severe mood disorders. He discussed the limitations of existing treatments for depression, and that it can take weeks to months and several different antidepressant trials to achieve remission. 2 Dr. Zarate mentioned that there have been no significant gains in the number of new molecular targets for the treatment of mood disorders in several years, and though there have been new insights, treatment for mood disorders lags far behind treatment for other medical illnesses, such as stroke or heart disease. He discussed research focusing on dysregulation of the glutamatergic system in the brain, and how a de-regulation of this system may occur in patients with mood disorders. Researchers can bring about a quicker response to therapeutics by targeting α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) and N-methyl- D -aspartic acid (NMDA), two glutamatergic receptors. Ketamine, an anesthetic agent used for many decades, modulates these glutamatergic receptors, and Dr. Zarate detailed research showing rapid response and remission rates with ketamine in patients with treatment-resistant depression. Significant response rates were seen within a few hours, and remission rates seen in one day, as compared to 10 to 14 weeks of standard antidepressant treatments. 3 Dr. Zarate also described the use of multi-modal imaging and other new technologies to identify biomarkers for predicting response to ketamine. He concluded by stating that two different studies with ketamine in two different mental disorders produced the same remission rates at an early time point (day 1) and with the same pre-treatment imaging biomarker strongly predicting response. These studies support the theory that directly targeting the AMPA and NMDA receptors in the anterior cingulate cortex region is essential to developing therapeutic medications that produce a rapid antidepressant response. Furthermore, early work with the imaging biomarkers indicates that neurobiological parameters may be valuable predictors of treatment response, possibly explaining more variation than common sub-diagnostic classifications can.
During the discussion period, Coalition members expressed interest in learning more about this new approach to treating depression with ketamine. They inquired if the drug development industry is aware of or is interested in the research. In response, Dr. Zarate noted that there is considerable interest in developing ketamine or ketamine-like drugs for the treatment of depression. However, ketamine produces dissociative side-effects, which limits its administration on an ongoing basis. He stated that there are efforts underway to develop ketamine-like compounds with a more favorable side-effect profile and to develop other methods for delivering ketamine, e.g., intranasally. He also mentioned research with other compounds to determine if the antidepressant effects can be maintained after an initial dosage of ketamine.
The Climate for Research Support
The Honorable John Porter, former Member of the U.S. Congress and current Chair of Research!America, talked to Coalition members about the federal funding cycle and the political climate for research support. He told the group that the efforts of Coalition and NIMH Alliance for Research Progress members were essential to securing the doubling of the NIH budget. He detailed the steps involved in developing the annual budget, starting from the development of the Presidential Budget Request, to the submission of the NIH Congressional Justification, to the budget resolution and appropriation. Mr. Porter said that the President has called for a three-year freeze on all non-defense, discretionary spending. The freeze, coupled with the fact that the budgets of most government agencies have remained flat, and the current state of the economy present a challenge for appropriators, as all agencies are now competing for increased funding. Mr. Porter discussed the importance of the development of targeted messaging that shows the impact of biomedical research on society and the potential outcomes that could be accomplished with increased support. He encouraged Coalition members and their constituents to get involved by volunteering to serve as science advisors for policy makers in all levels of government. He directed Coalition members to the resources on the Research!America website (http://www.researchamerica.org/).
The Honorable John E. Porter, J.D.,
Coalition Speakers (L to R) Richard J. Hodes, M.D., Michael Schoenbaum, Ph.D., Thomas Insel, M.D., Mike Huerta, Ph.D., Carlos Zarate, M.D.
1 Woolf SH, Johnson RE. The Break-Even Point: When Medical Advances are Less Important than Improving the Fidelity with Which they are Delivered. Ann Fam Med, Nov-Dec;3(6):545-52.
2 Sanacora G, Zarate CA, Krystal JH, Manji HK. Targeting the Glutamatergic System to Develop Novel, Improved Therapeutics for Mood Disorders. Nat Rev Drug Discov. 2008 May;7(5):426-37.
3 Zarate CA, Singh JB, Carlson PJ, Brutsche NE, Ameli r, Luckenbaugh DA, Charney DS, Manji HK. A Randomized Trial of N-methyl- D –aspartate Antagonist in Treatment-Resistant Major Depression. Arch Gen Psychiatry. 2006 Aug;63:856-864.