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January 14, 2008 — Exposure to the mumps virus and cytomegalovirus during childhood is associated with later development of schizophrenia and nonaffective psychosis, according to a study in the January issue of the American Journal of Psychiatry.

Swedish researchers found that central nervous system (CNS) infection with the mumps virus was related to an almost 3-fold increased risk for nonaffective psychosis, while infection with cytomegalovirus increased the risk for such psychosis by a factor of more than 16.

"We think that this study supports that the window of vulnerability exists not only during fetal life but all through childhood," commented Christine Dalman, MD, PhD, from the EPI/Karolinska Institutet, in Stockholm, Sweden, who was lead author for the study. "This means that there are plenty of opportunities to prevent psychotic illness [and that] you are not predetermined from birth to become ill," she said in an email to Medscape Psychiatry.

One of First Studies of Exposure During Childhood

Although researchers have investigated infections during fetal life as a potential risk factor for future development of psychosis, this study is 1 of the few to look at exposure to infections in the CNS during childhood.

Using the Swedish National Inpatient Registry, Dr. Dalman and colleagues found that 2435 of the 1,187,553 children born in Sweden between 1973 and 1985 were hospitalized for bacterial infections and 6550 were hospitalized for viral infections before the age of 13 years. They also collected data on subsequent psychotic illnesses in these patients until December 31, 2002. Altogether, 2269 of the study subjects were diagnosed with a nonaffective psychosis. Among these, 23 (including 8 with schizophrenia and 4 with schizoaffective syndrome) were diagnosed with a CNS infection in childhood.

Their results showed that the risk for nonaffective psychosis was related to CNS infections by the mumps virus or cytomegalovirus.
Risk for Nonaffective Psychosis with Viral Exposure
Virus Risk Ratio 95% CI
Mumps virus 2.71.2 – 6.1
Cytomegalovirus 16.64.3 – 65.1

However, there was no association with bacterial infections. The researchers looked at various possible confounders and found that adding parental psychotic illness or living in an urban center to the analysis had no substantial influence on the results.

Although according to the authors, it might be expected that infections earlier in life might be more harmful than those occurring later, the age at the time of the viral exposure was evenly distributed during childhood and did not seem to matter substantially.

The most common age at onset of psychosis was between 18 and 26 years. The mean age of onset of psychosis did not differ between those exposed to viral infections and those who were not exposed.

Mumps Virus Highly Neurovirulent

While mumps and cytomegalovirus infections were associated with increased risk for psychosis, the authors stress that since the numbers are small, results concerning specific infections should be interpreted with caution. "Nevertheless, it is of interest to note that mumps before vaccination was the single most common cause of aseptic meningitis or mild encephalitis," they wrote. They also noted that mumps virus can be highly neurovirulent.

According to the authors, the virus probably invades the brain across the choroids plexus, from which it spreads through the ventricles followed by invasion of the brain parenchyma. "Certain viruses have the propensity to invade the brain" and affect it at either the intracellular or intercellular level, explained Dr. Dalman, adding that, unlike bacteria, viruses need the cells in the body to survive. "Maybe this invading strategy of the virus affects the expression of the genetic code," she speculated.
Interestingly, both viruses implicated by the study for increasing the risk for psychosis are prone to invade the brain. "Our finding that an elevated risk is associated with mumps virus and cytomegalovirus infections indicates that the risk relates to infectious agents with a propensity to invade the brain parenchyma rather than to CNS infections in general," the authors wrote.

Vaccinations To Prevent Psychosis?

The study results raise the question of whether increased vaccinations may have an impact on rates of psychosis. Dr. Dalman believes inoculations may present an opportunity to prevent such illnesses.
However, she said, rates of vaccinations seem to be dropping rather than increasing. The rate of vaccination for mumps, morbilli, and rubella, for example, has decreased in certain areas of Sweden in recent years, from 95% to 75%, "due to misleading information about risk for autism associated with the vaccination," she said.

But she also noted that exposure to a virus is not enough to cause psychosis. "There has to be some kind of vulnerability, presumably some genetic predisposition," she told Medscape Psychiatry.
Infection Hypothesis "Plausible and Testable"

An editorial in the same issue by Alan S. Brown, MD, from the New York Psychiatric Institute, noted the growing number of investigations recognizing that an infectious hypothesis for schizophrenia is "both biologically plausible and testable."

He calls this most recent article "enlightening" and comments that the researchers capitalized on state-of-the-art national Swedish registries containing data on childhood hospitalization for infections and on psychiatric hospitalizations of people in adulthood.
The authors report no relevant conflict of interest.

 

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