Environmental and genetic factors contribute to the development of schizophrenia. For example, epidemiological evidence has linked infections during pregnancy with increased incidence of schizophrenia in the adult offspring. At the same time mutation to DISC1, a protein involved in neurone migration and synaptic plasticity, is an important genetic risk for the disorder. Accordingly, the aim of this project was to determine if these environmental and genetic influences converge along a common pathogenic pathway leading to schizophrenia. Using a model of prenatal infection by bacterial endotoxin in rodents, we demonstrated a 50% reduction in DISC1 protein expression in the hippocampus and cortex of juvenile offspring. In addition, we found a significant induction of prostaglandins (final mediators of the inflammatory process) in the fetal brain while many cytokines remained unaltered. Taken together our results identify prostaglandins as potential mediators of the teratogenic effects of prenatal infection and show that prenatal infection itself can affect systems related to genetic risk factors for schizophrenia, in this case DISC1.

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