Discrete Placental Dysfunction: The Overlooked Player in Prenatal Roots of Neuropsychiatric Diseases?

Prenatal complications and damaging environmental influences during pregnancy are known to be connected to the risk for a variety of neuropsychiatric diseases such as schizophrenia, autism, and attention deficit hyperactivity disorder. However, uniform mechanisms of direct fetotoxic influences could not be shown so far. Recently, maternal preeclampsia has been found to be a risk factor for schizophrenia in the offspring. As preeclampsia is primarily a placental disease, this finding may serve as a starting point to consider discrete placental dysfunction in general as an important contribution to the etiopathogenesis of several neuropsychiatric diseases. Here, we briefly review the current knowledge concerning links between prenatal conditions, genetic factors, and disturbed placental development, as well as between prenatal conditions, genetic factors, and the etiopathogenesis of several neuropsychiatric diseases. Furthermore, interrelations between disturbed placental development and the etiopathogenesis of these neuropsychiatric diseases are discussed. It is shown that disturbed placental development and the etiopathogenesis of several neuropsychiatric diseases show a variety of amazing similarities and interrelations. Therefore, we hypothesize that disturbances of placental development and maturation form a crucial and overlooked link between genetic predisposition, damaging environmental influences during pregnancy and the etiopathogenesis of several neuropsychiatric diseases, ultimately due to discrete abnormalities of uteroplacental and/or fetoplacental blood flow. Prospects and limitations of testing this hypothesis in human beings and in animal models are discussed. It is suggested that confirmation of this hypothesis will establish a new basis for research on prenatal roots of several neuropsychiatric diseases, with new avenues to effective primary prevention of these diseases by therapeutic intervention already during pregnancy.