Schizophrenia: The placenta may explain risk

New research finds a connection between genes and the birth complications that raise the risk of schizophrenia: the placenta. The findings might help to accurately predict who will develop the condition and reduce risk by improving the health of the placenta.

Scientists are hard at work trying to understand what causes schizophrenia. It is a debilitating mental health disorder that affects around 1 percent of the general population.

Researchers know, for example, that genes play a vital role. In fact, around 10 percent of people who have a relative with schizophrenia will develop the condition themselves.

Recent studies have put as much as 80 percent of schizophrenia risk down to genes. Others have shown that a specific risk gene for schizophrenia affects the brain's development prenatally, supporting the idea that the condition is neurodevelopmental.

On the other hand, researchers have observed that a viral infection in the mother can also raise the risk. For instance, some studies have shown that offspring of mothers with high levels of a pro-inflammatory protein called interleukin-8 were twice as likely to develop schizophrenia than controls.

So, genes, inflammation, and the mother-child bond all seem to play a role in the development of schizophrenia. But could there be one element that links all of these factors together?

New research suggests so. The missing link, explain the authors of a new study published in the journal Nature Medicine, is the placenta.

Daniel R. Weinberger, the chief executive officer of the Lieber Institute for Brain Development in Baltimore, MD, is the lead investigator of the new research.

Placenta contains schizophrenia risk genes

Weinberger and colleagues compared the genetic risk of developing schizophrenia in normal births with that in complicated deliveries — that is, births resulting from pregnancies with preeclampsia and intrauterine growth restriction.

Overall, the researchers investigated the obstetrical history and genetic makeup of more than 2,800 adults — 2,038 of whom had schizophrenia.

The scientists found that those who were genetically prone to schizophrenia and also had early life complications were five times more likely to develop the condition compared with people who, although they had the same genetic predisposition, did not have early life complications.

So, the researchers went on to analyze the genes in the placentas from the complicated births.

They found that the genes associated with schizophrenia were overwhelmingly expressed in these placentas, compared with those from normal births.

Furthermore, there was a direct link between the expression of these genes and the degree of inflammation in the placentas.

Another striking discovery was that the placentas from complicated births contained far more schizophrenia genes if the mother had given birth to a boy rather than a girl.

This may explain the sex differences in prevalence, symptoms, and how responsive people with schizophrenia are to treatment.

Weinberger comments on the findings, saying, "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."

"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."

Daniel R. Weinberger