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Alliance for Research Progress - January 16, 2009 Meeting

Meeting Summary (Outreach)

Overview

The National Institute of Mental Health (NIMH) convened its tenth meeting of the Alliance for Research Progress (Alliance) on Friday, January 16, 2009 in Bethesda, Maryland. This document provides an overview of the proceedings. The meeting served as an opportunity for participants to hear about exciting new research and advances in the NIMH Intramural Research Program (IRP), to network with colleagues, and to interact directly with the NIMH director, Thomas Insel, M.D., and senior NIMH staff to discuss public health needs as seen from their constituents. Invitees included representatives from national voluntary organizations representing patients and their families. The overall theme for the meeting was the NIMH Division of Intramural Research Programs. Participants heard presentations from NIMH researchers on New Treatments for Depression; Developmental and Underlying Brain Changes in Children; and, the Physiological Basis of the Brain's Dynamic Mental Process. In addition, they toured the NIH campus and Clinical Research Center where they viewed brain scans in the functional Magnetic Resonance Imaging (fMRI) and Magnetoencephalography (MEG) facilities. Mr. Andrew Sperling, Director of Legislative Advocacy at the National Alliance on Mental Illness (NAMI), led a lunchtime discussion of the Paul Wellstone-Pete Domenici Mental Health Parity and Addiction Equity Act of 2008. For more information on the speakers, please see the attached agenda and participant list.

Major Themes

State of the NIMH
Dr. Insel focused on three key issues: transitions; the NIMH Strategic Plan; and, the new Research, Condition, and Disease Categorization (RCDC) system. He told Alliance members about transitions in the presidential administration, the Department of Health and Human Services, and Congress; and how these transitions and changes in policy may affect NIH research. Dr. Insel noted that NIH is operating under a continuing resolution and that without the supplemental funding received last year NIMH is currently operating with fewer funds than in FY08. He also discussed the "un-doubling" of the NIH budget and that approximately 54,000 jobs in research have been lost as a result of the flattening of the budget. He also talked about the economic stimulus package and a range of activities that could be accomplished with the funds.

Dr. Insel next discussed the development of the NIMH Strategic Plan, which is a vehicle for setting priorities, exploiting new scientific opportunities, and maximizing the public health impact of NIMH research. He detailed the importance of each of the four strategic objectives outlined in the plan and noted that the next step is implementation.

  1. Promote discovery in the brain and behavioral sciences to fuel research on the causes of mental disorders.  This objective will help us determine the mechanisms of disease circuitry and learn more about the fields of genomics and epigenomics.
  2. Chart mental illness trajectories to determine when, where, and how to intervene. This objective will assist us in finding biomarkers and longitudinal designs to define risks at different phases and individual risks.
  3. Develop new and better interventions that incorporate the diverse needs and circumstances of people with mental illnesses.  This objective will lead to better interventions by understanding the pathophysiology of mental illnesses to offer pre-emptive care.
  4. Strengthen the public health impact of NIMH-supported research.  This objective will measure how NIMH is affecting community and health disparities.

In the context of the Strategic Plan, Dr. Insel told Alliance members about "disruptive innovations in mental health," which are new ideas that have revolutionized research on mental illnesses.  These innovative ideas are: mental disorders are brain disorders; mental disorders are developmental disorders; mental disorders result from complex genetic risk plus experiential factors; and, current treatments may be necessary but at not sufficient for recovery.  A universal understanding of these innovations among Americans would also contribute to reducing discrimination against people with mental illnesses, while increasing knowledge about the need for more effective treatments.

Dr. Insel also told Alliance members about the launch of the RCDC system on January 15, 2009. The new system provides consistent and transparent information on NIH-funded research. He mentioned that the system categorized data for 215 disease areas and that some of the funding levels may appear to have increased or decreased due to the new categorization system. He encouraged Alliance members to view mental health data on the RCDC web page .

Intramural Research Program Overview
Richard Nakamura, Ph.D., Scientific Director of the NIMH IRP provided an overview of the IRP.  He told Alliance members that the IRP represents the Institute Director's way of instantiating the overarching plan for solving the problems of mental disorders. He mentioned that the IRP receives 11 percent of the NIMH budget and highlighted the formula used by the program to promote outstanding science in the service of public health by employing brilliant and dedicated scientists, renewing interests in science through vigorous training and active recruiting of researchers, providing strong administrative support, and working corporately towards a common goal. Dr. Nakamura also noted the unique process of the Board of Scientific Councilors, which helps the IRP to focus funding on the best science, concentrates the Program's emphasis on fostering innovation, and provides resources to researchers across their career in science.

In addition to highlighting the benefits of the IRP and its management of resources and personnel, Dr. Nakamura told Alliance members about the challenges the Program faces, including concerns that basic science is not integrated or consistently outstanding; clinical research training programs are losing many talented scientists to the pursuit of other career options due to funding struggles; researchers are accepting lucrative research positions overseas and in private industry; and, the reputation of the IRP is lagging behind its actual performance.  He stated that the public does not know about the good work done by the IRP.  Next steps include encouraging new trials of new treatment targets; enhancing basic science and neurodevelopment research; increasing the number of public-private partnerships; and, promoting the innovative research conducted by the NIMH IRP.

New Treatments for Depression
Carlos Zarate, M.D., Chief of the Mood and Anxiety Disorders Research Unit and Associate Clinical Director of the Laboratory of Molecular Pathophysiology, told Alliance members about progress made in the treatment of major depression. He discussed the limitations of existing treatments for depression and that it can take 10-14 weeks or longer for a person coping with depression to achieve remission. Dr. Zarate mentioned that there have been no significant gains in the number of new molecular targets for treatment of depression and schizophrenia in several years and though there have been new insights, treatment for depression lags far behind treatment for other illnesses like stroke, heart disease, or diabetes. "This was one of the reasons the NIMH Mood and Anxiety Disorders Program was developed." He discussed intramural research projects that address problems with plasticity and cellular resistance, as well as treatments targeting the glutamatergic system. He talked at length about promising responses to treatments using riluzole and ketamine, in terms of the rapid and lasting effects. Dr. Zarate told Alliance members that NIMH IRP research identifying new targets for treatment might re-ignite interest in depression in the pharmaceutical industry and set a new bar and a new standard for quick and effective treatments.

Developmental and Underlying Brain Changes in Children
Judith Rapoport, M.D., Chief of the NIMH Child Psychiatry Branch, discussed brain development of children and how the brain interacts in the case of disorders. She talked about how the advent of magnetic resonance imaging (MRI) enabled researchers to screen hundreds of children since then, and charting the development of the brain.  This work has contributed to a growing awareness of the neurodevelopmental basis of psychiatric disorders. She mentioned that research conducted from 1989-2009 provides unique data to answer questions concerning the environmental and genetic influences on brain development and, in some cases, identify anatomic abnormalities in the brain at baseline, when children enter research protocols. Dr. Rapoport also presented data about brain development and attention deficit hyperactivity disorder (ADHD) and childhood onset schizophrenia. She showed Alliance members a number of interactive videos that highlighted neurodevelopment and IQ (children with higher IQ often have brains that mature later) and that revealed subtle differences in cortical thickness between children with and without ADHD.  She also showed and discussed how the cerebellum may be the most plastic area of the brain in responding to and compensating for illness.1

Dr. Rapoport described research to answer the question of whether cortical development in ADHD parallels healthy development along with findings that showed a difference in the posterior parietal area (the posterior attention system) of the brain. She suggested that there ultimately might be unique training approaches to assist children with delayed development in this region on the brain. She also discussed the hypothesis that ADHD is an issue of delayed or deviant development. To this, Dr. Rapoport cited an important IRP study of cortical development that showed that the brains of children with ADHD, on average, reach a designated state of maturation 3 years after healthy controls. She noted that this delay in cortical development could help to explain why many youth eventually seem to improve with age.

Dr. Rapoport told the Alliance that a benefit of the IRP is its ability to enable such challenging studies of rare illnesses as schizophrenia in children.  She described a study of 105 children and families and noted significant findings. All children were severely ill. One third had unremarkable early development problems. Another third of the sample was found to have had autism spectrum disorders (ASD) as characterized by the lack of reciprocal social interaction in the years before psychosis. The remaining third was found to have developmental lags in walking and talking, or speech difficulties without diagnosis of ASD. She showed a video noting the changes in cortical development in this group and discussed chromosomal variations and the need for additional longitudinal study of children into adulthood.

Studying the Physiological Basis of the Brain's Dynamic Mental Process
David Leopold, Ph.D., Director of the Neurophysiology Imaging Facility and Chief of the Unit on Cognitive Neurophysiology and Imaging, talked to Alliance members about the use of neuroimaging in primate studies to understand the workings of the brain's unique dynamic mechanisms, as they relate to basic behaviors. He discussed the commonalities that exist between parts of the human brain and those of animals and how the study of primate brain structures and circuitry will increase knowledge of normal human brain function and will benefit mental health research. Dr. Leopold's presentation focused on a discussion of the endogenous activity patterns of the brain and effects on perception; differentiation between regions of the visual cortex and how these regions carry perceptual signals; and the relationship between functional magnetic resonance imaging (fMRI) and the electrophysiological measurements of perceptual activity.

Dr. Leopold used optical illusions as examples of how the brain activity patterns spontaneously fluctuate in response to visual stimulants. He detailed how the primary visual cortex interacts with the surrounding association cortex, and described primate experiments, using optical illusions, that assist in understanding this relationship. Dr. Leopold stressed that subjects are not harmed or mistreated in NIMH IRP protocols and that primates are trained to communicate what they perceive using technology, while a special primate fMRI machine measures brain activity. He briefly discussed research findings when a similar study was done on human subjects. By combining methods in the primate, his research was able to reproduce the human findings and further demonstrate the complex relationship linking fMRI signals to the behavior of neurons in the brain.2  In closing, Dr. Leopold emphasized the need to study the normal brain as a means to understand disease process and the benefits of animal studies in advancing neuroscience.

Discussion

The afternoon discussion periods were filled with active dialogue about the NIMH Strategic Plan and the morning IRP presentations. Dr. Insel engaged participants in a discussion of the benefits of the possible discovery of a "statin" for mental illnesses.  Statins (or HMG-CoA reductase inhibitors) are a class of drugs that lower cholesterol levels in people with or at risk of cardiovascular disease.  A similar drug for those at risk for mental illnesses could lower their risk of disease and prevent progression. Other discussion centered on post traumatic stress disorder and suicide prevention activities with the military; and knowledge gained from a recent visit from a North Korea delegation about how the North Korean stock market crash affected suicide in that country and what could be the lessons for the U.S. in this current economic crisis. Participants stressed the need for a communication plan to increase public awareness about mental health, brain disorders, and NIMH research. Alliance members suggested national events with the media to increase awareness as well as the need to quickly translate NIMH research and evidence-based practices to institutions of higher education. Participants also expressed approval and agreement with the revised NIMH Mission Statement. The meeting concluded with an interactive tour of the NIH campus and Clinical Center, and presentations by Maryland Pao, M.D., the NIMH Clinical Director, and scientists Sean Marrett, Ph.D., and Richard Coppola, Sc.D. from the NIMH Magnetic Resonance Imaging facility.

Photographs

NIMH Alliance for Research Progress - January 16, 2009
Photo of Speakers (L to R): Dr. Pao, Dr. Zarate, Dr. Nakamura, Dr. Rapoport, Dr. Leopold, Dr. Insel
Speakers (L to R): Dr. Pao, Dr. Zarate, Dr. Nakamura, Dr. Rapoport, Dr. Leopold, Dr. Insel
Photo of Mr. Sperling
Mr. Sperling
Photo of Alliance members
Alliance Members
Photo of Ms. Gorman leading  Alliance members on a campus tour
Ms. Gorman leads Alliance members on a campus tour
Photo of Alliance members touring the NIH Clinical Center
Alliance members touring the NIH Clinical Center

Footnotes

1 Thompson PM, Vidal C, Giedd JN, Gochman P, Blumenthal J, Nicolson R, Toga AW, Rapoport JL. Mapping Adolescent Brain Change Reveals Dynamic Wave of Accelerated Gray Matter Loss in Very Early-Onset Schizophrenia. Proc Natl Acad Sci USA, 2001 Sep 25;98(20):11650-5.

2 Maier A, Wilke M, Aura C, Zhu C, Ye FQ, Leopold DA. Divergence of fMRI and Neural Signal in V1 During Perceptual Suppression in the Awake Monkey. Nature Neuroscience, 2008 Oct;11(10):1193-1200.