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April 10, 2001
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Hopkins Researcher Finds Retroviral 'Footprint' In Brains Of People With Schizophrenia

A research team led by a Johns Hopkins Children's Center scientist has found the strongest evidence yet that a virus may contribute to some cases of schizophrenia.

In this week's Proceedings of the National Academy of Sciences, Children's Center neurovirologist Robert Yolken, M.D., and his colleagues report the molecular "footprint" of a retrovirus in the cerebrospinal fluid of about 30 percent of people with acute schizophrenia and about 7 percent of people with a chronic form of the disease. The footprint was absent in the brains and cerebrospinal fluid of all people who did not have schizophrenia.

"While a low level of retrovirus expression occurs in most human tissues, we found an unexpectedly high level of expression in the cerebrospinal fluids from individuals who'd had a recent onset of schizophrenia," says Yolken, director of the Stanley Division of Developmental Neurovirology and a principal investigator in the research. "A significant portion of the people with schizophrenia in our study population had active expression of the retrovirus, whereas individuals without schizophrenia lacked the footprint."

The footprint is actually retroviral RNA created by the active expression of an endogenous retrovirus in the "W" family of endogenous retroviruses (HERV-W). Previous research by Yolken and others suggests activation of the viruses and the onset of certain forms of schizophrenia are caused by both genetic and environmental factors. This recent report identifies the HERV-W-like retrovirus as a prime candidate for the environmental component of some schizophrenia cases.

The researchers also examined brain tissue obtained postmortem from individuals with schizophrenia and from individuals who were normal or had a disorder other than schizophrenia.

Unlike HIV and other retroviruses, endogenous retroviruses are a natural part of the human genome, having inserted themselves into the human genome millions of years ago, in some cases. Scientists are just beginning to understand how these retroviruses may be involved in human diseases, Yolken says.

"While our report doesn't explain why the retrovirus becomes active in the first place, it presents clues as to what may happen when it does become active," Yolken says. "Our ultimate hope is that we can interfere with the retrovirus by preventing it from become active. If we can do that, it may give doctors another method of treating schizophrenia."

Using molecular markers, the research team looked for retroviral footprints in the cerebrospinal fluid of 35 individuals diagnosed with schizophrenia and in a control group of 12 individuals who were healthy or had a neurological condition other than schizophrenia. Twenty-nine percent of patients diagnosed with acute schizophrenia and 7 percent of patients diagnosed as being in the chronic stage of the disease presented easily detectable levels of a retrovirus footprint from the HERV-W family. By contrast, the cerebrospinal fluid of individuals not diagnosed with schizophrenia contained undetectable levels of the retroviral footprint.

Yolken, whose work has focused on learning how mental disorders may be caused by microbial pathogens, genetic predisposition and environmental triggers, says that while "a lot of cases of schizophrenia probably aren't associated with retroviruses, we found a significant portion of people with schizophrenia for whom this is the case."

Schizophrenia is a neuropsychiatric disease that affects as many as one in 100 people in the United States, and results in the annual expenditure of $65 billion dollars in health care and related costs.

Håkan Karlsson, Ph.D., and Justin McArthur, Ph.D., of the Johns Hopkins School of Medicine, and Johannes Schröder, M.D., Silke Bachmann, M.D., of the University of Heidelberg, Germany, and E. Fuller Torrey, M.D., of the Stanley Medical Research Institute in Bethesda, Maryland, also contributed to the report. Support for the research was provided by a grant from the Stanley Foundation.

The Stanley Division of Developmental Neurovirology at Johns Hopkins Children's Center is devoted to the elucidation of the role of infection and immunity in the etiology of schizophrenia and bipolar disorders: http://www.stanleylab.org.


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