A compelling new study suggests that activity in the placenta could be the missing link connecting environmental factors with genetics in relation to the development of many behavioral disorders, including schizophrenia.

A large volume of recent research has been uncovering new insights into how disorders such as schizophrenia can arise. A variety of genetic variants have recently been revealed that predispose a person to developing schizophrenia and most prenatal research has focused directly on how fetal brain development can be negatively disrupted. This new research turns the spotlight squarely onto the placenta.

"For the first time, we have found an explanation for the connection between early life complications, genetic risk, and their impact on mental illness and it all converges on the placenta," says Daniel R. Weinberger, one of the lead researchers on the study.

While the presence of certain genetic variants seem to be key to the development of schizophrenia, a great deal of recent research has begun to hypothesize that the condition begins when a child's brain is developing during pregnancy. Previous studies have intriguingly found correlations between obstetric complications and an increased risk of schizophrenia, but any mechanism that could explain this link has remained a mystery.

This new research, led by the Lieber Institute for Brain Development, found that complications in pregnancy seem to "turn on" genes known to be associated with schizophrenia and this activity is seen specifically in the placenta. The more signs a placenta displayed of being under stress (inflammation, for example), the greater the expression was seen in these genes known to increase the risk of schizophrenia.

The research also found that a person's genetic risk of schizophrenia seemed to be strongly modulated by complications experienced during pregnancy. It was found that those with a high genetic risk of schizophrenia were five times more likely to develop the condition if they experienced obstetric complications, compared to those with no history of pregnancy stresses but an equally high genetic risk.

Another finding in the research revealed schizophrenia genes expressing more prominently in placentas from males rather than females. This may help explain the mystery of why schizophrenia (and a variety of other behavioral disorders) appear at rates two to four times more frequently in males than females. The study hypothesizes that the sex bias seen in these disorders could stem from the placenta's role in neurodevelopment.

This fascinating research excitingly bridges the classic nature/nurture debate, finding a clearly identifiable environmental experience that seems to strongly activate the expression of genes leading to schizophrenia. The role of the placenta in this developmental process is also important as it suggests a larger focus on placental health during a pregnancy could lessen a person's risk of developing a variety of neurodevelopmental disorders.

"The surprising results of this study make the placenta the centerpiece of a new realm of biological investigation related to how genes and the environment interact to alter the trajectory of human brain development," says Weinberger.

The study was published in the journal Nature Medicine.