Some, but not all, previous studies suggest that prenatal influenza
exposure increases the risk of schizophrenia. These studies used dates of
influenza epidemics and maternal recall of infection to define influenza exposure,
suggesting that discrepant findings may have resulted from exposure misclassification.
To examine whether serologically documented prenatal exposure to influenza
increases the risk of schizophrenia.
Nested case-control study of a large birth cohort, born from 1959 through
1966, and followed up for psychiatric disorders 30 to 38 years later.
Population-based birth cohort.
Cases were 64 birth cohort members diagnosed as having schizophrenia
spectrum disorders (mostly schizophrenia and schizoaffective disorder). Controls
were 125 members of the birth cohort, had not been diagnosed as having a schizophrenia
spectrum or major affective disorder, and were matched to cases on date of
birth, sex, length of time in the cohort, and availability of maternal serum.
Main Outcome Measures
Archived maternal serum was assayed for influenza antibody in pregnancies
giving rise to offspring with schizophrenia and matched control offspring.
The risk of schizophrenia was increased 7-fold for influenza exposure
during the first trimester. There was no increased risk of schizophrenia with
influenza during the second or third trimester. With the use of a broader
gestational period of influenza exposure—early to midpregnancy—the
risk of schizophrenia was increased 3-fold. The findings persisted after adjustment
for potential confounders.
These findings represent the first serologic evidence that prenatal
influenza plays a role in schizophrenia. If confirmed, the results may have
implications for the prevention of schizophrenia and for unraveling pathogenic
mechanisms of the disorder.