Genomic Risk for Schizophrenia, the Early Life Environment, and the Room Left for Developmental Epigenetic Plasticity

Most individuals with genomic risk for schizophrenia do not develop the disorder, suggesting that the path that goes from genetic susceptibility to disease is not linear. Research suggests that schizophrenia etiopathogenesis may rest in the altered functioning of the epigenetic machinery that regulates interactions with the environment since early life. Some of the genetic variants associated with schizophrenia play a role very early in placenta, interacting with severe complications during prenatal and early postnatal life, and with sex-biased gene expression. Risk genes appear to contribute to biological processes crucial for the physiology of the placenta, and its ability to adapt to environmental conditions in order to provide support to the embryo/fetus. In this scenario, the developing brain may be canalized toward altered paths that, if maintained, may lead to the onset of the disorder; however, such paths do not imply certainty of developing the disorder and are likely reversible, hence they can be rescued. Identifying the placental mediators of schizophrenia trajectories of risk may help defining strategies of prenatal prevention, aimed at improving placental health; further, it may enable us to identify high-risk individuals, who could benefit from specific postnatal prevention.