Virus Provides a Clue to the Cause of Schizophrenia

Medically Reviewed by Jacqueline Brooks, MBBCH, MRCPsych
From the WebMD Archives

April 9, 2001 -- Scientists have long believed schizophrenia to be a disease that lies dormant, waiting for the right set of circumstances to strike its teenage or young adult victims. Whether genetic, biological, or environmental -- or some complex mix -- the precise nature of the early defect remains largely undetermined, although the disease affects some 2 million Americans.

Now researchers believe that a viral remnant long ago incorporated into the genetic makeup of all humans -- like a footprint frozen in the winter snow -- is brought to life in some individuals, leading to a cascade of events that can result in schizophrenia, a mental illness that causes delusions and hallucinations.

And what may be responsible for activating that viral remnant is another infection, say researchers in a report that appears in this week's Proceedings of the National Academy of Sciences.

"Researchers everywhere are interested in the way genes and environmental factors interact in schizophrenia, and among the environmental factors we are interested in are infections," author Robert Yolken, MD, says. "Currently, we can't make recommendations for changes in therapy, but our findings may lead to new ways to treat or prevent schizophrenia."

Yolken, a professor of neurovirology at Johns Hopkins Children's Center in Baltimore, says the footprint they have found lies across what he calls the "borderland between genes and infection."

For the footprint is really a retrovirus -- a virus that carries genetic material found in all human cells. And the particular retrovirus they identified is believed to have infected humans so long ago that it became a part of the very genetic makeup of humans, a bit of dormant "junk" in the human genome.

Yet, when they looked at the fluid bathing the brains of patients with schizophrenia, they found something remarkable: evidence that the retrovirus had become active.

The activated retrovirus was found in 10 of 35 individuals with intense symptoms of schizophrenia. Yet, in 22 patients with other neurological diseases and 30 individuals with no disease at all, there was no evidence of activation.

While retroviruses can be found in normal human tissue, Yolken writes that "a significant portion of the people with schizophrenia in our study population had active ... retrovirus, whereas individuals without schizophrenia lacked the footprint."

Precisely when the retrovirus is activated, and the exact connection between activation and symptoms of schizophrenia is unknown, the authors say.

It may be activated when the fetus is in the womb by a winter flu or virus caught by a pregnant mother, causing an immediate infection at a critical time when brain cells are forming. Or the reactivated virus may lie in wait for a decade or more before it blooms in the presence of yet another infection in early adolescence or adulthood -- just the time when many patients with schizophrenia first experience symptoms.

"Many of us have become impressed with the realization that infectious agents can get in the central nervous system and sit there for 15 years before they can become active," another author E. Fuller Torrey, MD, tells WebMD. He is director of the Stanley Foundation Research Programs, which helped fund the study.

Both researchers are quick to point out that not all schizophrenia is caused by infection. "My feeling is that schizophrenia is a mixture of diseases, so it is extremely unlikely that either a virus or genes will explain all the cases," Yolken says. "We believe that perhaps 30% of cases may be related to infection."

But he says the findings suggest that doctors may someday be able to treat individuals who are at risk for schizophrenia -- based on their family history or early developmental signs -- with antiviral therapies to keep the retrovirus from becoming active.

Because herpes viruses are known to directly activate retroviruses, Yolken hopes to conduct studies using common antiherpes medications in acute patients to determine if they can improve symptoms of schizophrenia. If the drugs work, they could be used in at-risk patients to forestall retrovirus activation, and thereby prevent schizophrenia, he says.