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A link between schizophrenia and the placenta

Written by Charlotte Harrison, Science Writer.

The genetic risk of schizophrenia is believed to be linked largely to genetic variants that disrupt the development and function of the brain. But now, a study in Nature Communications shows that the placenta plays a greater role in schizophrenia risk than previously thought.

The transcriptomic study, led by researchers from Johns Hopkins University, identified more than 100 genes linked to the risk of schizophrenia because of their role in the placenta.

“While the results do not detract from the importance of gene expression in brain for schizophrenia risk, they reveal a wider stage, including placenta,” noted the study authors.

Candidate mechanisms

The analyses found 139 placenta and schizophrenia-specific risk genes. Some of the candidate mechanisms were common to male and female placentas, in particular the nutrient-sensing capabilities of the placenta and the invasive properties of the trophoblast cells that form the outer layer of an early-stage embryo.  

However, many risk genes were sex-biased. Male-specific genes had candidate mechanisms that were associated with inflammatory pathways, such as interleukin-15 signalling, while female-specific genes were related to insulin signalling.

Coronavirus risk factor?

Surprisingly, some schizophrenia-specific risk genes were related to coronavirus pathogenesis. This finding led the authors to investigate the expression of these genes in placentas from a small number of SARS-CoV-2-positive pregnancies; the results showed that a set of immune-relevant genes, such as heat shock proteins, NFKB, nuclear receptors and blood-brain barrier genes were upregulated.

This finding tentatively indicates that SARS-CoV-2 infection during pregnancy may be an environmental risk factor for schizophrenia. 

New opportunities

The study also identified several genes in the placenta linked to diabetes, bipolar disorder, depression, autism and attention deficit hyperactivity disorder. However, the placental transcriptome had a greater association with schizophrenia than the other disorders and traits. 

The authors highlight that knowledge of placental mechanisms of schizophrenia risk provides opportunities for preventing the disorder.  

“These new molecular insights into how genes related to disorders of the brain and other organs play out in the placenta offer new opportunities for improving prenatal health and preventing complications later in life,” said lead author Daniel Weinberger in a press release.