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Placenta Genes May Play a Significant Role in Schizophrenia Risk

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A study has highlighted that over 100 genes linked to the cognitive disorder schizophrenia may influence risk for the condition not because of how they act in the immature brain but because of their function in the placenta. The research was published in Nature Communications.

Schizophrenia’s gene links

Geneticists have long thought that the genetic risk component of schizophrenia primarily affects the brain. The new research reveals that genes' expression in the placenta may have a larger role than previously believed. Researchers sequenced the transcriptome – all the gene readouts produced from constituent cells – of 147 healthy placenta samples and compared them with similar data from brain tissue samples.

Dr. Daniel Weinberger, the paper’s senior author and director and CEO of the Lieber Institute for Brain Development, commented, “The secret of the genetics of schizophrenia has been hiding in plain sight – the placenta, the critical organ in supporting prenatal development, launches the developmental trajectory of risk. The commonly shared view on the causes of schizophrenia is that genetic and environmental risk factors play a role directly and only in the brain, but these latest results show that placenta health is also critical.”

Genes linked to the later risk of developing schizophrenia were found to alter how well the placenta was able to detect nutrients like oxygen, which are present in the mother’s bloodstream, and pass those on to the developing fetus based on the information received. The cells that influence this exchange are called trophoblasts. The study authors said that their findings suggest that lower levels of gene expression could inhibit how well the placenta is able to nurture the growing fetus.

Further gene associations in the placenta were identified – showing links to diabetes bipolar disorder, depression ADHD and autism. Nevertheless, the greatest number of links identified were connected to schizophrenia.

Heritability is the extent to which variation in a trait is affected by variations in genes passed down from previous generations. The study suggested that variation in placental genes may have a more significant impact on variation in schizophrenia presentation than variation in brain genes. The study also found that sex played a role in the gene associations identified. Males are more likely to be diagnosed with schizophrenia and male cases are identified earlier. The study found that inflammation-linked genes played a more significant role in the placenta from a male child.

Prevention potential

The major appeal of targeting genes that affect the placenta is the potential to alter risk for conditions at an incredibly early stage of development and improve the potential for prevention, said Dr. Gianluca Ursini the paper’s lead author and an investigator at the Lieber Institute. “Scientists could detect changes in placental risk genes decades before the possible onset of a disorder, possibly even in the mother’s bloodstream during pregnancy. If doctors knew which children were most at risk of developmental disorders, they could implement early interventions to keep them healthy.”

“In the modern era of molecular and genetic medicine, the standard treatment for a complicated pregnancy is still primarily bedrest,” said Weinberger. “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.”   

Reference: Ursini G, Di Carlo P, Mukherjee S, et al. Prioritization of potential causative genes for schizophrenia in placenta. Nat Commun. 2023;14(1):2613. doi:10.1038/s41467-023-38140-1

This article is a rework of a press release issued by the Lieber Institute for Brain Development. Material has been edited for length and content.