We wish to highlight 3 potential implications of this work for future research and interventions. First, it is important to test the plausibility of this hypothesis and to identify pathogenic mechanisms by which these infections increase schizophrenia risk. This can be addressed by translational approaches, such as that noted above for influenza, and by clinical studies, which we have been conducting, that aim to relate prenatal infection to brain anomalies that have been observed in adult patients with schizophrenia.
Second, we believe that it is essential for future work to investigate interactions between prenatal infection and susceptibility genes. Given that the effect sizes observed have been moderate, it is likely that prenatal infection increases risk of schizophrenia only among subgroups of vulnerable individuals, including those who are genetically predisposed or who have been exposed to other environmental factors. This work could help to provide a more complete picture of disease causation and potentially aid in the identification of vulnerability genes.
Finally, studies of prenatal infection and schizophrenia may hold considerable promise for preventive efforts. Our data on influenza indicated that as many as 14% of schizophrenia cases would not have occurred if influenza infection during early to mid-gestation had been prevented.5
This may have important public health implications, given that there are many available preventive strategies for influenza and other infections, including vaccination, antibiotics, and simple hygienic measures.
In summary, our data thus far suggest that several prenatal infections and inflammatory biomarkers may contribute to the etiology of schizophrenia. It must be emphasized, however, that these findings require replication in independent samples before any specific public health measures are recommended. Nonetheless, the study of prenatal infection in schizophrenia promises to play an important role in revealing at least some of the biological underpinnings of this devastating disorder.