March 27, 2000
Researchers at Johns Hopkins have discovered a phenomenon in the brains of individuals with schizophrenia and other mental illnesses that may help doctors develop better drugs.
According to the results of the study that appear in the March issue of Molecular Psychiatry, individuals with schizophrenia, bipolar disorder and major depression have lower than average levels of a certain brain protein and, thus, less "plastic" brains. By examining the cascade of events that lead to the formation of the protein, the researchers hope to improve current therapeutics. The discovery also supports a theory that retroviruses may be associated with some cases of mental illness.
"When designing treatments for these disorders, it is probably going to turn out to be very important to interfere with the cascade of interactions," says Nancy Johnston-Wilson, Ph.D., a research associate at the Stanley Neurovirology Laboratory at Hopkins and lead author of the study.
In an effort to more precisely identify the cascades associated with these disorders, Johnston-Wilson examined levels of some key proteins in autopsied brains from 24 schizophrenics, 23 individuals with bipolar disorder, 19 people with major depression and 23 individuals unaffected by the diseases.
The researchers discovered that the brains of those with the three mental illnesses had significantly lower levels of phosphorylated glial fibrillary acidic protein (GFAP) in comparison to the controls. GFAP usually forms filaments and is part of the structural network of cells that nourishes and detoxifies nerve cells. When GFAP becomes phosphorylated, however, these filaments fall apart, making membranes flexible and allowing for cell division. The researchers, therefore, conclude that individuals with these three mental illnesses have brains that are less plastic than the brains of individuals without the disorders. Plasticity is a normal aspect of the brain that allows it to adjust to inputs.
Next, the researchers plan to examine the series of biochemical events responsible for phosphorylating GFAP. Many biochemicals including neurotransmitters, growth factors and cytokines (proteins that regulate the intensity and duration of inflammatory response) can trigger phosphorylation.
"Identification of pathways which are altered in disease will give us a logical place to target for therapeutic interventions," says Johnston-Wilson. "Since the drugs currently used to treat schizophrenics take a couple of weeks to take effect, it's likely they are targeting the same pathways but in a more round about way. If we knew, more directly, what was altered, we could design better therapies."
The decrease in phosphorylated GFAP also supports a new theory that some mental illnesses are triggered by a virus, because cell cultures of viruses including HIV-1 also show a decrease in the protein. "If mental illness is due to viral involvement, we may be seeing the same thing," says Johnston-Wilson.
To learn more about viruses and their role in mental illness, travel to http://www.med.jhu.edu/stanleylab/. Other authors of the study include Robert Yolken from the Stanley Neurovirology Lab at Johns Hopkins School of Medicine; Andrew Shore from the Health Services Research and Development Center at Johns Hopkins School of Hygiene and Public Health; E. Fuller Torrey from the Stanley Foundation Research Programs, NAMI Research Institute in Bethesda, Md; and Christina D. Sims, Jean-Paul Hofmann and Leigh Anderson from Large Scale Biology Corporation in Rockville, Md.