Schizophrenia is a devastating brain disease affecting 1% of the population worldwide, and more than two million Americans in a given year. Symptoms include delusions (bizarre thoughts and perceptions that have no basis in reality), hallucinations (hearing voices, seeing things, and experiencing other illusory sensations related to touch, taste, and smell), and disordered thinking (resulting in fragmented, disconnected and sometimes nonsensical speech and behavior), as well as social withdrawal, extreme apathy, diminished motivation, and blunted emotional expression. Consequently, those who suffer from schizophrenia are more likely to be self-destructive, substance abusers, unemployed, homeless, and incarcerated. Additionally, one in ten persons with schizophrenia will commit suicide, while even more will make an attempt.

Though the exact cause is unknown, schizophrenia seems to result from a combination of genetic vulnerability (e.g. a child whose parent has schizophrenia has about a 10 percent chance of developing the disease) and various, poorly understood environmental factors present during a person's development. On average, schizophrenia appears sometime between the late teens and early thirties. In addition, problems during pregnancy such as inadequate nutrient supply to the fetus, viral infections that reach the womb, and complications during childbirth , are also associated with increased risk of schizophrenia.

In pursuit of an explanation, and in hopes of more effective treatment and possible prevention, scientists are studying genetic and environmental influences on the disease. A new study, reported in the August 2004 issue of the Archives of General Psychiatry , adds weight to existing evidence that prenatal exposure to the influenza virus increases schizophrenia risk.

About the Study

The main objective of the study was to determine if adults with schizophrenia were more likely to have had mothers exposed to influenza when they were in the womb than adults with schizophrenia.

The Prenatal Determinants of Schizophrenia (PDS) study, as it was called, enrolled the children (now adults) of women who had participated in a child development study in Alameda County, CA between 1959 to 1966. This former study had recruited nearly every pregnant woman who received care from the Kaiser Foundation Health Plan (KFHP) during this time period. Children recruited for the follow-up study- totaling 12,094- were those who were still active members of KFHP as adults- from 1981 to 1997- and thus had current as well as prenatal medical records available for analysis.

The PDS researchers determined if participants’ mothers had been exposed to influenza based on the presence of influenza antibodies in frozen blood samples taken during each trimester of their pregnancies.

Diagnosis of schizophrenia and other schizophrenia spectrum disorders (SSD) was determined through a rigorous process of medical record review and interviewing. Of the 71 cases diagnosed, 64 had blood samples available from their pregnant mothers and were entered into analysis.

The control group consisted of 125 adults without schizophrenia, but who were otherwise similar to the 64 cases in terms of their membership in KFPH, date of birth, sex, and number and timing of maternal blood samples. The researchers were also careful to consider the influence of other possibly relevant factors such as maternal age, paternal age, maternal education, and maternal ethnicity.

The Findings

Twenty-five percent (5 cases) of those participants with schizophrenia were influenza-exposed during the first trimester as compared to 11% (4 controls) of those participants without schizophrenia amounting to a seven-fold increase in risk from first-trimester exposure. However, since the number of cases and controls was so low, these results did not reach statistical significance (meaning researchers could not rule out chance as an explanation for them). Furthermore, there was no increase in risk associated with exposure during the second or third trimesters, which directly contradicts earlier research demonstrating increased risk specific to second trimester exposure.

Through a broader comparison, however, researchers revealed a stronger (statistically speaking) association: 21% (9) of schizophrenia cases, versus 9% (7) of controls were influenza-exposed during the first half of pregnancy (including the first trimester as well as part of the second trimester), amounting to a three-fold risk increase.

As an aside, the study found that besides prenatal exposure to influenza, both lower maternal education and increased paternal age slightly increased the risk of schizophrenia.

How Does This Affect You?

Researchers applied their study findings to the general population and concluded that 21% of schizophrenia cases may be attributed to influenza exposure during the first trimester of pregnancy, while 14% can be attributed to exposure during the first half of pregnancy. It important to note, however, that this study was not without its flaws. The researchers, for example, were unable to account for a family history of schizophrenia, since no such data was available). Larger studies that take genetics into consideration will need to duplicate these findings before we can conclude that influenza is truly a serious risk during pregnancy. Many questions remain. How does exposure to the influenza virus in the womb have such an adverse impact on the psychological development of a child into adulthood? Why would exposure during one trimester make so much more of an impact than exposure during another? Would different strains of the virus have different impacts?

While schizophrenia is very rare, influenza is very common- and so is its vaccine. If subsequent studies do confirm the findings of this one, routine vaccination of women of reproductive age could prevent a significant number of future schizophrenia cases.