Serologic evidence of prenatal influenza in the etiology of schizophrenia

This is a 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. 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. 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.