Epigenetic Alterations to NR3C1 and HSD11B2 and the Developmental Origins of Mental Disease Risk

Abstract

Gestation is one of the most critical periods of human development where adverse exposures occurring during pregnancy can shape the health of the offspring over the life course and contribute to the intergenerational transmission of disease risk. Many psychiatric conditions are now thought to originate in part in utero. As such, a myriad of gestational exposures may contribute to the biological embedding of poor mental health for the next generation. Increasingly, researchers are examining epigenetic alterations as mechanisms linking prenatal exposures to offspring mental disease risk. Epigenetic alterations, which can functionally regulate gene expression and thus phenotype, are tremendously sensitive to intrauterine exposures. Epigenetic mechanisms related to neuroendocrine regulation may be the linking mechanisms between adverse in utero exposures and later life poor mental health. This chapter reviews the evidence linking (1) prenatal exposures to epigen-etic modifi cation of genes involved in the regulation of cortisol (NR3C1 and HSD11B2) and (2) how such epigenetic alterations can in turn lead to changes in offspring mental disease risk.