Schizophrenia research receives boost

University neuroscientists have received a five-year, $11.6 million grant to fund a Silvio O. Conte Center for the Neuroscience of Mental Disorders.

Conte Centers focus on translational neuroscience research that applies basic concepts to improve the understanding of a specific psychiatric disease.

In this case, the researchers are focusing on schizophrenia.

Center Director John G. Csernansky, M.D., the Gregory B. Couch Professor of Psychiatry, coordinates the efforts of neuroscience researchers at Washington University, as well as Yale and Johns Hopkins universities.

“By working together under the umbrella of the Conte Center, we should be able to translate their discoveries into clinically relevant findings more quickly,” Csernansky said.

The experiments are grouped into several research projects.

In the first, 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.

Another project, coordinated by Deanna Barch, Ph.D., associate professor of psychology in Arts & Sciences, 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 Johns Hopkins.

Computer engineers there have designed programs that can extract detailed information about brain structure and function from standard MRI 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 said.

In addition to imaging studies of humans, the center 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-rays before birth. The project simulates the disruption of neurodevelopment thought to occur in patients with schizophrenia.

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

Finally, 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.

“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 said.

“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 risk.”