Summary: In a paradigm shift, researchers have identified more than 100 genes associated with schizophrenia risk primarily through their role in the plasma, not the developing brain.

The study underscores the importance of the placenta in the development of the disease, challenging the century-old assumption that schizophrenia risk genes primarily affect the brain.

The study also found that these risk genes affect the critical function of identifying and metabolizing substances in the mother’s circulation. The findings suggest that assessing the health of the placenta may be the key to early intervention and prevention of developmental disorders.

Key facts:

  1. The study found that more than 100 genes associated with schizophrenia function mainly through their roles in the placenta and not in the brain, challenging a long-held assumption in the field.
  2. These schizophrenia-risk genes significantly affect the placenta’s ability to perceive and metabolize nutrients from the mother’s blood, affecting the health of the developing fetus.
  3. The researchers identified genes in the plasma associated with diseases such as diabetes, bipolar disorder, depression, autism and ADHD, and found that schizophrenia has more genetic associations than these other conditions.

Source: Liber Institute for Mental Development

New research led by the Lieber Institute for Brain Development has found that more than 100 genes associated with schizophrenia risk appear to be caused by their role in the plasma, not in the developing brain.

For more than a century, scientists have assumed that schizophrenia-susceptible genes are primarily, if not exclusively, about the brain.

But recent research, just published in Natural relationshipsThey found that the placenta plays a greater role in the development of the disease than previously known.

“The secret of schizophrenia genetics is hiding in plain sight: the placenta, a critical component to support prenatal development, initiates the developmental trajectory of the risk,” said Daniel Weinberger, the paper’s senior author and director and CEO. Libertarian Institute for Mental Development on the Johns Hopkins Medical Campus in Baltimore.

Credit: Neuroscience News

“The conventional wisdom about the causes of schizophrenia is that genetic and environmental risk factors play a role directly and only in the brain, but these recent results show that the health of the placenta is also important.”

The researchers found that the schizophrenia genes affect the vital function of the plasma to sense nutrients, including oxygen, in the mother’s blood and exchange nutrients based on what it finds.

Schizophrenia risk genes are at low levels in placental cells, called trophoblasts, which are central to maternal-fetal nutrient exchange, negatively affecting the placenta’s role in nurturing the developing fetus.

The paper also identified several genes in plasma that are responsible for diabetes, bipolar disorder, depression, autism and attention deficit hyperactivity disorder, or ADHD.

However, the scientists found far more genetic links to the genes for schizophrenia than for these other disorders.

The researchers found that schizophrenia risk genes in the plasma had a relatively greater effect on heredity than genes in the brain.

“Targeting plasma biology is an important new potential approach to preventing this sacred organ of public health,” said Gianluca Ursini, MD, Ph.D., lead author of the paper and an investigator at the Lieber Institute.

“Scientists were able to identify changes in placental risk genes decades before the disorder began; Perhaps even in the mother’s blood during pregnancy. If doctors knew which children were most at risk for developmental disorders, they could implement early interventions to keep them healthy.

The scientists also found sex-dependent differences in placental risk genes. Different genes are associated with schizophrenia risk depending on whether the placenta is from a boy or a girl. During pregnancy with boys, inflammatory processes in the placenta seem to play a central role.

Previous studies have shown that men are more prone to prenatal stress than women. In general, developmental disorders such as schizophrenia are more common in boys and girls.

The researchers also revealed the pregnancy outcomes of Covid-19. The scientists studied a small sample of placentas from mothers with Covid-19 during pregnancy, and found that the plasma susceptibility genes for schizophrenia were significantly activated in these placentas.

The findings suggest that infection with Covid-19 during pregnancy may be a risk factor for schizophrenia because of how the infection affects the placenta. Lieber Institute scientists are pursuing this possibility with NIH-funded testing of covid-19 placentas to learn more.

Lieber Institute researchers hope that their ongoing research on plasma genes will one day lead to new medical and diagnostic tools, possibly revolutionizing the field of prenatal care.

“In the modern era of molecular and genetic medicine, the standard treatment for complicated pregnancies is still primarily bed rest,” Dr. Weinberger said. “These new molecular insights provide new opportunities to improve prenatal health and prevent complications later in life by understanding how genes associated with brain and other organ disorders play a role in plasma.”

So schizophrenia and genetics research news

Author: Kate Sargent
Source: Liber Institute for Mental Development
Contact: Katie Sargent – Libertarian Institute of Mental Development
Image: Image credited to Neuroscience News.

Preliminary study: Open Access.
Prioritization of potential schizophrenia-causing genes in plasma” by Daniel Weinberger et al Natural relationships


Prioritization of potential schizophrenia-causing genes in plasma

Our previous work has shown that genomic risk for schizophrenia is associated with early life complications and influences disease- and sex-specific neurodevelopmental trajectories.

Here, in plasma, we have identified specific genes and potential mechanisms that may mediate such effects.

We performed TWAS in healthy placentas (N= 147) to extract the candidate placental causal genes we confirmed with SMR; We performed a similar analysis on the fetal brain to look for placental and schizophrenia-specific associations (N= 166) and additional placental TWAS for other abnormalities/characteristics.

Analyzes in the total sample and stratified by sex ultimately highlighted 139 placental and schizophrenia-specific risk genes. The candidate molecular mechanisms are focused on nutrient sensing abilities of placenta and trophoblast invasiveness.

These genes encode the coronavirus-pathogenesis pathway and showed increased expression in plasma from SARS-CoV-2-positive pregnancy samples.

Screening for placental risk genes for schizophrenia may provide opportunities for prevention not suggested by brain research alone.

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