Exposure To Influenza During Pregnancy May Increase Risk Of Schizophrenia In Offspring

Today's findings are part of a larger team study known as the Prenatal Determinants of Schizophrenia (PDS), which examines prenatal infection, nutrition, chemical exposure, paternal age, and a range of other prenatal factors that influence schizophrenia risk.

The study has shown for the first time that serologically documented prenatal exposure to influenza is associated with schizophrenia. The risk of schizophrenia was increased threefold when influenza occurred during the first half of pregnancy; however when influenza occurred during the second half of pregnancy, no increased risk was observed.

"It is an exciting time for research that combines serologic documentation of infectious diseases during pregnancy, long-term follow-up, and careful assessments for schizophrenia and other disease outcomes," said Alan Brown, MD, lead author and associate professor of clinical psychiatry and epidemiology at the New York State Psychiatric Institute and Mailman School of Public Health. "Because the individuals whom we are studying have only recently passed through the age of risk for schizophrenia, it has become possible only in the last few years to analyze archived prenatal serum specimens in order to address the question of whether schizophrenia is related to prenatal risk factors such as viruses, as well as nutritional factors and toxins, during pregnancy." The 40-year study of the CHDS was made possible by ongoing support from the National Institute of Child Health and Development.

"These findings represent the strongest evidence thus far that prenatal exposure to influenza plays a role in schizophrenia," said Ezra Susser, MD, DrPH, senior investigator of the PDS study, chair of the Department of Epidemiology at the Mailman School of Public Health and head of Epidemiology of Brain Disorders at the New York State Psychiatric Institute. "Although the findings may ultimately have implications for prevention, we strongly caution against making any public health policy recommendations until these links have been confirmed through further study."

The PDS, initiated by Dr. Susser together with Dr. Brown and Dr. Catherine Schaefer of Kaiser Permanente Division of Research, included a nested case-control study of the CHDS birth cohort, which was recruited from 1959-1967, and was followed up for psychiatric disorders 30-38 years later. During that time period, the CHDS, under the direction of Jacob Yerushalmy, University of California, Berkeley, recruited nearly every pregnant woman who received obstetric care from Kaiser Permanente in Alameda County, California. All of the children born were automatically enrolled in Kaiser Permanente. The PDS study cohort consisted of the sub-sample of 12,094 live births who were members of Kaiser Permanente from January 1, 1981 through December 31, 1997.

Dr. Brown and colleagues from the PDS team measured influenza antibody in archived serum samples derived from the blood of 64 pregnant women whose offspring later developed adult schizophrenia and from a comparison group of 125 pregnant women whose offspring did not develop schizophrenia. They found an association between the presence of elevated influenza antibody levels and schizophrenia in the adult offspring suggesting that prenatal exposure to influenza may increase the vulnerability for schizophrenia.

This study was funded by the National Institute of Mental Health, the National Alliance for Research on Schizophrenia and Depression, and the Lieber Center for Schizophrenia Research.

The PDS research is part of a number of "life course studies" being overseen by Dr. Susser at the Mailman School. In addition to the CHDS study, Dr. Susser and his team are looking at large birth cohorts from the U.S., Israel and Norway to observe the pathogenesis of chronic and acute diseases and their links to prenatal and postnatal exposure to environmental factors such as viruses and toxins.