A major reorganization and expansion of research on mood and anxiety disorders is at the forefront of changes underway in the National Institute of Mental Health, Division of Intramural Research Programs (DIRP). The improvements-including creation of new labs and outside recruitment of several senior investigators-were recommended a few years ago by a distinguished panel of outside experts convened to assess the quality of the Institute's intramural clinical science. They bring new areas of expertise to the Institute's in-house research program, the world's largest center for studying mental illness, which accounts for about 12 percent of the NIMH science budget.
"This infusion of fresh talent will help us translate advances in the science of emotion into better treatments-and maybe even preventive interventions-for mood and anxiety disorders," said NIMH Director Steven E. Hyman, M.D.
Although some of the planned new units and personnel are still being finalized, several newly recruited, tenured researchers are slated to begin work at the Institute's Bethesda, MD labs in the coming months:
Dennis S. Charney, M.D., has been appointed Director of a new DIRP Mood and Anxiety Disorders Program, inaugurated today, that will ultimately encompass 9 clinical branches, freestanding sections and basic laboratories, many of them new. Professor of psychiatry and director of psychiatric research at Yale University, he is known for studies on the neurobiology and drug treatment of depression, schizophrenia, panic disorder and post-traumatic stress disorder. Charney will also serve as Chief of a new Experimental Therapeutics and Pathophysiology Branch (ETP) within the new Program.
Daniel Pine, M.D., a child psychiatrist from Columbia University, will head a Section on Development and Affective Neuroscience within the ETP that will employ neuroimaging and neuroendocrine methodologies to study childhood depression and anxiety disorders. One of the questions to be addressed: whether childhood depression, like childhood onset diabetes, proves to be a fundamentally different disorder than the adult onset form.
Kathleen Merikangas, Ph.D., a leading psychiatric geneticist/epidemiologist from Yale, as chief of the ETP's Section on Developmental Genetic Epidemiology, will search for biological markers in children of families at risk for developing mood disorders. Identification of such a marker and underlying genes could lead to development of new preventive treatments.
Christian Grillon, Ph.D., a psychophysiologist from Yale, joining ETP as a tenure-track investigator, will conduct psychophysiological studies on startle reflex and fear conditioning in anxiety disorders.
Husseini Manji, M.D., returns to the DIRP after 6 years at Wayne State University's psychiatry department, to become Chief of a new Laboratory of Molecular Pathophysiology. He will follow up leads on abnormalities in nerve signal transduction in bipolar disorder and the therapeutic potential of the anti-cancer drug tamoxifen in treatment refractory mania.
Robert B. Innis, M.D., Ph.D., previously a Yale psychiatry professor and brain imaging expert, will serve as Chief of a new Molecular Imaging Branch (MIB). Known for pioneering positron emission tomography (PET) studies of neuronal receptors in psychiatric disorders, he will mount a major upgrade of the Institute's functional brain imaging and nuclear medicine capabilities, including the acquisition of two new PET scanners. Innis will be at NIMH only part-time for the first year.
Victor Pike, Ph.D., a leading radiochemist from Hammersmith Hospital in the U.K., as Chief, Section on PET Radiopharmaceutical Sciences within the MIB, will establish a new facility for developing radioactive tracers for use in PET scan studies of depression and anxiety disorders. These "ligands" will be made available to extramural researchers.
Wayne Drevets, M.D., a psychiatry and brain imaging researcher from the University of Pittsburgh, will be Chief of MIB's Section on Neuroimaging. He will use PET and magnetic resonance imaging (MRI), both structural and functional, to study depression and bipolar disorder. Preliminary evidence of neuron loss in depression will be followed up.
Also joining the Program in the coming months: new tenured recruitments to lead two new basic laboratories on neuroplasticity, and genes and behavior, and a tenure-track researcher on childhood bipolar disorder within the existing Pediatric and Developmental Neuropsychiatry Branch headed by Susan Swedo, M.D, also part of the Program.
The new units will complement four existing DIRP components also joining the Program: Biological Psychiatry Branch, Robert Post, M.D., Chief; Clinical Neuroendocrinology Branch, Philip Gold, M.D., Chief; Section on Biological Rhythms, Thomas Wehr, M.D., Chief; and Laboratory of Clinical Science, Dennis Murphy, Chief.
"We're bringing together a critical mass of expertise to forge what will be the strongest research group in the world focused on the pathophysiology and treatment of mood and anxiety disorders," said Program Director Charney. "We'll attack the problem from multiple perspectives: children and adults, basic and clinical, molecular biology to brain imaging, testing novel treatments in state of the art clinical trials. This requires a resource investment that no single university can make."
NIH intramural programs are unique in offering investigators the opportunity to pursue research fulltime, free from teaching responsibilities and the need to compete for grants. However, the NIMH Intramural Program has traditionally recruited only younger investigators-fellows, post-docs, etc.-on temporary appointments. After serving a research apprenticeship, most leave to take positions at universities; few ever attain tenure at NIMH. Over the years, the resultant insularity has taken its toll on the Intramural Program's scientific standing, according to the panel of outside experts. In l998, that Clinical Research Planning Panel recommended, among other things, that DIRP import seasoned investigators in the fields of cognitive science/neuroimaging, experimental therapeutics, and genetics. Following this advice, Robert Desimone, Ph.D., Director of the NIMH Intramural Program, initiated a major reprogramming of IRP resources to make the new programs possible. The new appointments represent the first time since its creation half a century ago that the NIMH Intramural Program has implemented a major recruitment of senior, tenured scientists, noted Desimone. Ultimately, the Mood and Anxiety Disorders Program will bring in about a dozen senior investigators and dozens of new support staff. "The new recruitments are already bringing a tremendous amount of energy and excitement to the Intramural Program, and our long-standing intramural investigators are seeing many new opportunities for collaboration," added Desimone.
In another "first," the Mood and Anxiety Disorders Program will collaborate with investigators at local universities to establish satellite outpatient research programs that will reach patient populations heretofore inaccessible to DIRP studies. "This will allow us to recruit larger samples of patients, sufficient to answer questions regarding the pathophysiology of mood and anxiety disorders, as well as to test the efficacy of novel treatments," said Charney. "It will also permit us to follow patients longitudinally."
A consolidated inpatient unit for studies of childhood mood, anxiety and psychotic disorders will be inaugurated this Fall. Additionally, NIMH's brain bank, which has focused on schizophrenia, will be expanded to include mood and anxiety disorders studies. Donations of post-mortem brain tissue of people who had bipolar disorder, for example, will be aggressively encouraged, said Charney.
The fiscal year 2000 budget for the NIMH DIRP is about $115 million. The new Mood and Anxiety Disorders Program component will start at well over $10 million per year in direct costs, and may total as much as $15-20 million once infrastructure costs are considered. The amount dedicated to the new Program is expected to grow as it becomes fully operational in the next few years. The total fiscal year 2000 NIMH budget including both intramural and extramural research is approximately $972 million.
In addition to establishing "departments" like the new Mood and Anxiety Disorders Program, the Panel of outside experts recommended that DIRP set up "core" facilities to be shared by multiple labs and branches. Over the past year, within the Office of the Clinical Director, a Clinical Core Team led by psychiatrist Catherine Roca, M.D., has centralized patient recruitment and assignment to studies, and managed patient informed consent and "customer care" issues that had previously been handled at the clinical branch level. Susanna Sung, M.S.W., a new social worker/outreach recruiter, has begun to aggressively "market" DIRP studies to potential patients and referring mental health professionals, taking out ads in newspapers, and developing and disseminating fliers, pamphlets and web notices.
Other core facilities under development include shared resources for neuroimaging and bioinformatics-development of computer tools for analysis of the imaging data, which will also be shared with the extramural community. Already operational is a state-of-the-art 3 tesla MRI scanner facility, headed by physicist Peter Bandettini, Ph.D. This scanner facility, run jointly with the National Institute of Neurological Disorders and Stroke (NINDS), is one of the first that can image brain activity, via functional MRI (fMRI), in real time. In collaboration with NINDS, NIMH is also in the process of acquiring a second 3 tesla MRI scanner to support the new Mood and Anxiety Disorders Program studies, and a larger 7 tesla scanner for MRI spectroscopy, which will permit visualization of specific molecules in the brain at unprecedented resolution. In a joint venture with NINDS and the National Eye Institute (NEI), NIMH will also purchase a vertical MRI scanner for studying brain activity in awake non-human primates. The MRI scanners' high spatial resolution will be complemented with the high temporal resolution of a new magneto encephalography (MEG) scanner, arriving next spring, which can capture brain activity in human subjects that lasts only milliseconds.
In collaboration with the National Human Genome Research Institute (NHGRI), NIMH will also be setting up a gene array core that will permit investigators to observe changes in the expression of large numbers of genes simultaneously, in both humans and mice. This will make it possible to study changes at the molecular level associated with pathology or various behavioral or genetic alterations.
The NIMH Intramural Program is also intimately involved in the planning for a new National Neuroscience Research Center laboratory building to be erected on the NIH Campus. It will be shared with NINDS and several other institutes, and promote cross-institute collaborations in translational research on the brain in neurological, perceptual, and psychiatric disorders.
The National Institute of Mental Health (NIMH) is part of the National Institutes of Health (NIH), the Federal Government's primary agency for biomedical and behavioral research. NIH is a component of the U.S. Department of Health and Human Services. For more information about NIMH and its research programs, visit the NIMH web site http://www.nimh.nih.gov.