Schizophrenia-related genes in the placenta are predictive of the size of a baby’s brain at birth and the rate of cognitive development. In a complicated pregnancy, such genes could raise the risk of developing schizophrenia later in life, new research suggests.
“This is further evidence that early life matters in schizophrenia, and the placenta plays a bigger role than we imagined,” Daniel R. Weinberger, MD, director and CEO, Lieber Institute for Brain Development, and professor of neurology, psychiatry, and neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, said in a news release.
“The holy grail would be to identify, based by complicated pregnancies and placental risk scores, who is at maximum risk for schizophrenia from very early in life, and these individuals could be followed more carefully,” Weinberger told Medscape Medical News.
The study was published online February 8 in Proceedings of the National Academy of Sciences.
A Therapeutic Target?
As reported by Medscape Medical News, in 2018, the same group of researchers reported that genes associated with schizophrenia are activated in the placenta during a complicated pregnancy, increasing a child’s risk of developing schizophrenia later in life.
In this latest study, they further explored the biological interplay between placental health and neurodevelopment.
They found that a higher placental genomic risk score for schizophrenia, in conjunction with early-life complications during pregnancy, at labor/delivery, and early in neonatal life, is associated with changes in early brain growth and function, particularly in males.
“The higher the placental schizophrenia gene risk score, the smaller the brain size at birth, and this was associated with slower cognitive development over the first 2 years of life, particularly in the first year of life,” said Weinberger.
This research defines a “potentially reversible neurodevelopmental path of risk that may be unique to schizophrenia,” the researchers write.
Although most individuals on this altered neurodevelopmental path likely “canalize” back toward normal development, some may not be rescued and instead “decanalize” toward illness, they add.
To date, prevention of schizophrenia from early life has seemed “unapproachable if not unimaginable, but these new insights offer possibilities to change the paradigm,” Weinberger said in the news release.
“Measuring schizophrenia genetic scores in the placenta combined with studying the first two years of cognitive developmental patterns and early life complications could prove to be an important approach to identify those babies with increased risks,” he added.
Commenting on the study for Medscape Medical News, Christopher A. Ross, MD, PhD, professor of psychiatry and behavioral sciences, Johns Hopkins Medicine, Baltimore, Maryland, said that this is “an interesting and important paper that replicates and extends previous findings of the relationship of placenta genes to schizophrenia in adults.
“The hypothesis continues to be ― and they are continuing to support it ― that events in early development could set a person up for a risk of schizophrenia later in life,” said Ross.
This research, he added, also supports the concept that there are at least two broad classes of genetic risk for schizophrenia.
“One acts through genes that are expressed in the brain and doesn’t relate to early life events, and the other acts through genes expressed in the placenta in patients with these early life events,” said Ross.
The study had no specific funding. Weinberger and Ross have disclosed no relevant financial relationships.
Proc Natl Acad Sci. Published online February 8, 2021. Full text
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