Questioning the theory that prenatal exposure to the flu virus might be a risk factor for schizophrenia, a new study finds no link between the flu pandemic of 1957 and later schizophrenia rates.

In an analysis of studies from Europe, Australia, Japan and the U.S., researchers found no higher-than-normal risk of schizophrenia among people born in the nine months after the 1957 flu pandemic.

The findings, reported in the Schizophrenia Bulletin, conflict with those from some earlier studies linking the same pandemic to a heightened schizophrenia rate.

While the exact causes of schizophrenia are not clear, it is considered a disorder of disrupted brain development, and researchers have long believed that schizophrenia arises from a combination of genetic susceptibility and environmental factors.

Among the suspected environmental factors is fetal exposure to a mother’s infection during pregnancy, with the influenza virus being one of the potential culprits.

The first evidence came from a 1988 Finnish study that found an increased rate of schizophrenia among people who were in the womb at the time of the 1957-58 Asian flu pandemic that killed about 2 million people worldwide.

Since then, studies have come to conflicting findings as to whether prenatal flu exposure might contribute to schizophrenia. However, some smaller studies that have used mothers’ blood samples to measure flu exposure during pregnancy have supported a link.

One theory is that inflammatory substances released in the mother’s blood in response to the infection may cross the placenta and affect fetal brain development in a way that makes the child more vulnerable to developing schizophrenia later in life.

These latest findings, however, “do not support this hypothesis,” report the researchers, led by Dr. Jean-Paul Selten of the University Medical Center Utrecht in the Netherlands.

The results are based on 11 international studies that compared rates of schizophrenia among people who were in the womb during the 1957-58 pandemic with those of people born within the few years before and after the outbreak.

The researchers also analyzed two studies that included women who were pregnant and reported having the flu during the pandemic.

Overall, Selten’s team found no increased schizophrenia risk among people who were in the womb during the flu pandemic, at any trimester of pregnancy.

According to the researchers, the original Finnish study that focused on the 1957 pandemic used an “inappropriate statistical method” to arrive at its conclusions. Their re-analysis of that data, they add, uncovered no increased risk of schizophrenia.

“We conclude that the evidence to support the maternal influenza hypothesis is insufficient,” the researchers write.

SOURCE: Schizophrenia Bulletin, online December 3, 2009.