RESEARCH UPDATE 2004

Planning for the Future

This is a time of enormous excitement in brain research, a time in which new and powerful technologies of neuroimaging, molecular biology and computer analysis, applied in conjuction with the established fields of psychology, epidemiology, genetics and pharmacology, give promise that brain function in health and disease may finally be understood.

The work of the research community at McLean Hospital addresses the great needs of improving psychiatric diagnosis and treatment. Our mission is to perform the nations highest quality research in psychiatry. McLean will continue to keep its research enterprise productive and cutting edge by supporting new technologies, the best people and new research facilities and projects.

Bipolar Disorder and Schizophrenia

Managing weight is a challenge for many patients with severe and persistent mental illness, since many antipsychotic medications cause weight gain. Franca Centorrino, MD, and collaborating researchers in the Bipolar Disorder and Schizophrenia Program have developed a program in which almost every subject who completed the curriculum lost weight. The lifestyle interventions also resulted in overall health benefits, as participants lowered their resting heart rate, blood pressure, cholesterol and triglycerides by the end of the study. By designing a program specifically for the needs of subjects with psychiatric illnesses, these researchers have shown that weight gain, previously thought to be an almost unavoidable corollary to drug treatments of psychotic disorders, can be managed and controlled.

Directed by Francine Benes, MD, PhD, scientists in the Structural and Molecular Neuroscience Program are trying to determine whether there are normal changes that take place during adolescence that might trigger the onset of schizophrenia in susceptible individuals. One of these changes is an ingrowth of dopamine fibers from the base of the brain to GABA-using cells in the highest, cortical levels of the brain. If too many of these connections form, the GABA neurons function abnormally, which, in turn, may induce functional changes in the affected regions.

Led by Bruce Cohen, MD, PhD, scientists in the Molecular Pharmacology Laboratory have discovered that all-known antipsychotic drugs change the activity of cells which release the neurotransmitters GABA and dynorphin to signal other nerve cells. The results suggest that agents which work directly at receptors for GABA and dynorphin may be better, more effective treatments for disorders, such as schizophrenia.

Investigators in the Laboratory of Psychiatric and Molecular Neuroscience, directed by Joseph Coyle, MD, have discovered that an enzyme which regulates an important neurotransmitter, glutamate, is less active in critical brain regions of patients with schizophrenia. In clinical studies, patients have been given drugs, including D-serine and D-cycloserine, to enhance the glutamate system. Early results are encouraging, showing reduced symptoms and improved cognitive function.