The neurodevelopmental impact of prenatal infections at different times of pregnancy: the earlier the worse?

Environmental insults taking place in early brain development may have long-lasting consequences for adult brain functioning. There is a large body of epidemiological data linking maternal infections during pregnancy to a higher incidence of psychiatric disorders with a presumed neurodevelopmental origin in the offspring, including schizophrenia and autism. Although specific gestational windows may be associated with a differing vulnerability to infection-mediated disturbances in normal brain development, it still remains debatable whether and/or why certain gestation periods may confer maximal risk for neurodevelopmental disturbances following the prenatal exposure to infectious events. In this review, the authors integrate both epidemiological and experimental findings supporting the hypothesis that infection-associated immunological events in early fetal life may have a stronger neurodevelopmental impact compared to late pregnancy infections. This is because infections in early gestation may not only interfere with fundamental neurodevelopmental events such as cell proliferation and differentiation, but it may also predispose the developing nervous system to additional failures in subsequent cell migration, target selection, and synapse maturation, eventually leading to multiple brain and behavioral abnormalities in the adult offspring. The temporal dependency of the epidemiological link between maternal infections during pregnancy and a higher risk for brain disorders in the offspring may thus be explained by specific spatiotemporal events in the course of fetal brain development.