$11 million grant boosts schizophrenia research

Neuroscientists at Washington University School of Medicine in St. Louis have received a five-year, $11.6 million grant to fund a Silvio O. Conte Center for the Neuroscience of Mental Disorders. Since 2001, the National Institute of Mental Health (NIMH) has funded a feasibility center at Washington University, but the new grant upgrades the center’s status, funding and number of research projects.

The Conte Center is one of 15 of its kind around the country and the only one in the Midwest. The centers were created in honor of former Massachusetts congressman Silvio O. Conte, a long-time advocate for scientific research.

Conte Centers focus on translational neuroscience research that applies basic neuroscience concepts to improve the understanding of a specific psychiatric disease. In this case, the researchers are focusing on schizophrenia.

“There is evidence that there are underlying biological causes of psychiatric problems, including schizophrenia,” says Charles F. Zorumski, M.D., the Samuel B. Guze Professor and head of the Department of Psychiatry and professor of anatomy and neurobiology at the School of Medicine. “The NIMH-funded Conte Centers emphasize the relationship between the biology of mental illness and the symptoms we see in the clinic. As this research makes it possible to connect those dots, we hope to develop better tools for diagnosis and treatment.”

Center director John G. Csernansky, M.D., the Gregory B. Couch Professor of Psychiatry at the School of Medicine, coordinates the efforts of neuroscience researchers at Washington University, as well as Yale University and The Johns Hopkins University. “By working together under the umbrella of the Conte Center, we should be able to translate our discoveries into clinically relevant findings more quickly,” Csernansky says.

Investigators at the Conte Center are supported by three research cores. Washington University houses the administrative and assessment core and the biostatistics and data management core. The center’s brain-mapping core is housed at Johns Hopkins.

Experiments conducted through the Conte Center are grouped into five research projects. In the first project, Csernansky, C. Robert Cloninger, M.D., the Wallace Renard Professor of Psychiatry, and Lei Wang, Ph.D., research assistant professor of psychiatry, are using high-resolution magnetic resonance imaging (MRI) to study brain structures in volunteers who are in the early stages of schizophrenia, the siblings of those volunteers and healthy controls who are the same age as the siblings. The second project, coordinated by Deanna Barch, Ph.D., associate professor of psychology in the College of Arts & Sciences at Washington University, uses functional MRI (fMRI) to study changes in the activity of the same brain structures.

The imaging studies take advantage of unique work done by a research group based at The Johns Hopkins University. Computer engineers there — led by Michael I. Miller, Ph.D., director of the Conte Center’s brain mapping core as well as director of the Center for Imaging Science, the Seder Professor of Biomedical Engineering and professor of electrical and computer engineering at Hopkins — have designed programs that can extract detailed information about brain structure and function from standard MRI images and fMRI images. In the case of the highly folded cortex, these programs can “flatten” out images to make comparisons easier.

“These brain mapping tools allow us to look for very small differences in the brain with an unprecedented degree of detail,” Csernansky says.

In addition to imaging studies of humans, the center’s third project also uses imaging tools to evaluate animal models. Researchers based at Yale University are using MRI scans to determine the sequence of changes in brain structures in Rhesus monkeys that have been exposed to very low levels of X-ray before birth. That project, which simulates the disruption of neurodevelopment thought to occur in patients with schizophrenia, is headed by Lynn D. Selemon, Ph.D., research scientist in neurobiology at Yale.

The fourth project is led by Lawrence H. Snyder, M.D., Ph.D., assistant professor of anatomy and neurobiology at Washington University. Snyder’s group is mapping the circuitry involved in working memory in the primate brain.

In the fifth project, James Cheverud, Ph.D., professor of anatomy and neurobiology and of genetics, and Hongxin Dong Ph.D., research instructor in psychiatry, will map mouse genes involved in forming key brain structures shown to be abnormal in schizophrenia, such as the hippocampus and thalamus. A key collaborator in that project is Robert W. Williams, Ph.D., the William and Dorothy Dunavant Professor of Excellence in Developmental Genetics and professor of pediatrics at the University of Tennessee Health Science Center in Memphis, who created the world’s largest database of genetically characterized mouse strains, called the Mouse Brain Library.

“In all of these projects, we’re working to find particular ways in which brain structure and function are different in patients with schizophrenia and their close relatives,” Csernansky says. “As we find that abnormalities run in families, those findings suggest the existence of genes that are in control of the formation of those structures, so we can go back to our animal models, look for those genes and then return to our patients to determine whether the genes actually increase the risk of schizophrenia.”

Csernansky hopes that, taken together, the Conte Center’s projects will lead to better understanding of schizophrenia and, in particular, to improvements in diagnosing and treating the disease early in its course.

Washington University School of Medicine’s full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked second in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.