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A new origin for schizophrenia may have come to light: the placenta. A poorly-working placenta while in the womb may affect brain development, making the condition more likely – particularly if a mother experiences complications during pregnancy or childbirth.

Schizophrenia involves hallucinations and delusions, and usually begins when people are teenagers or in their twenties. The cause is unknown, and environmental factors – such as issues during pregnancy and childhood trauma – seem to play a role.

However, genetics also seems influence schizophrenia, and several hundred genes have been implicated in the condition. In 2014 a identified 108 regions in our DNA that can slightly raise a person’s likelihood of developing the condition. As you’d expect, many of these regions contain genes that are active in the brain, but others do not.

of the Lieber Institute for Brain Development in Maryland and his team wondered if genetics might explain why only some people whose mothers have complications during pregnancy go on to develop schizophrenia. To investigate, they focussed on a group of complications that have been linked to the condition, including infections during pregnancy, pre-eclampsia, fetal growth restriction, and several specific problems during childbirth. Together, these factors affect up to a fifth of pregnancies, but only 1 per cent of people get schizophrenia.

Missing link

The team analysed data from nearly 2900 people, some of whom had schizophrenia, and some of whom were similar to these people in other ways but did not have the disorder.

The analysis revealed that the 108 genetic regions did seem to be associated with whether people who’d experienced complications in the womb and childbirth went on to develop schizophrenia. When the team looked at these regions, they found that about half of them appear to be involved in the function of the placenta, and contain genes that are particularly active during pre-eclampsia and fetal growth restriction.

“The placenta is the missing link between maternal risk and fetal brain development,” says Weinberger. “It has been hiding in plain sight for a long time.”

The findings are “unexpected but very plausible”, says of the University of Oxford. “If you have got a less efficient placenta you might not be taking on the nutrients or oxygen you need.”

Mini placentas

This restriction of nutrients and oxygen may affect brain development in ways that then predisposes a person to schizophrenia in later life – particularly if complications during pregnancy or childbirth exacerbate the problem.

Weinberger’s team is now investigating what the specific genes do by growing miniature placentas in the lab. These are just a few hundred micrometers in diameter, and generated from skin cells donated by people with schizophrenia.

They hope that if they can find out how schizophrenia-linked placentas behave differently from other placentas during complications, it could lead to treatments to mitigate any effects this may have on a fetus’ brain. “Maybe there’s a way to improve placental health during times of complications,” says Weinberger.