Schizophrenia is caused by interaction of a combination of genetic and environmental factors. Of the latter, prenatal exposure to maternal stress is reportedly associated with elevated disease risk. The main orchestrators of inflammatory processes within the brain are microglia, and aberrant microglial activation/function has been proposed to contribute to the aetiology of schizophrenia. Here, we evaluate the epidemiological and preclinical evidence connecting prenatal stress to schizophrenia risk, and consider the possible mediating role of microglia in the prenatal stress-schizophrenia relationship. Epidemiological findings are rather consistent in supporting the association, albeit they are mitigated by effects of sex and gestational timing, while the evidence for microglial activation is more variable. Rodent models of prenatal stress generally report lasting effects on offspring neurobiology. However, many uncertainties remain as to the mechanisms underlying the influence of maternal stress on the developing foetal brain. Future studies should aim to characterise the exact processes mediating this aspect of schizophrenia risk, as well as focussing on how prenatal stress may interact with other risk factors.
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