The secret genetic risk of schizophrenia uncovered

The secret of the genetic risk of schizophrenia has been hiding in plain sight — the placenta, says a groundbreaking study

A groundbreaking study led by the Lieber Institute for Brain Development has shed new light on the genetic risk of schizophrenia.

This goes against long-held beliefs that the genetic risk of schizophrenia is found in the brain.

In fact, researchers have discovered that more than 100 genes linked to schizophrenia risk exert their influence through the placenta.

The results, published in Nature Communications, suggest that the placenta plays a much larger role in schizophrenia than previously thought.

‘The secret of the genetics of schizophrenia has been hiding in plain sight’

Dr. Daniel Weinberger, senior author of the study and Director/CEO of the Lieber Institute for Brain Development, comments, “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’

“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.”

The researchers identified that the genetic risk of schizophrenia influences a crucial function of the placenta related to nutrient sensing in the mother’s bloodstream, including oxygen levels, and subsequently exchanging nutrients accordingly.

However, these risk genes were found to be expressed at lower levels in the placental cells responsible for this maternal-fetal nutrient exchange, called trophoblasts.

Consequently, the placenta’s ability to nourish the developing fetus is negatively impacted.

Several genes in the placenta are associated with other conditions

In studying schizophrenia, researchers found that other genes in the placenta are linked with other conditions, including:

• Diabetes
• Bipolar disorder
• Depression
• Autism
• Attention deficit hyperactivity disorder (ADHD)

However, genetic associations with schizophrenia outweighed those for the other disorders.

Additionally, the researchers noted that the risk genes for schizophrenia found in the placenta might have a relatively greater impact on heritability, or the likelihood of inheriting the illness from ancestors, compared to risk genes found in the brain.

Targeting placenta biology could offer a new method of prevention

Targeting placenta biology could offer a novel approach to prevention, representing a holy grail for public health.

Detecting changes in placental risk genes, potentially even in the mother’s bloodstream during pregnancy, could provide early indications of developmental disorders, enabling timely interventions to support the health of at-risk children.

Presence of sex-based differences

Another noteworthy finding was the presence of sex-based differences in placental risk genes.

The genes associated with the risk of schizophrenia differed depending on whether the placenta originated from a male or female child.

In pregnancies involving male children, inflammatory processes in the placenta appeared to play a central role.

Previous research has indicated that males are more susceptible to prenatal stress, and developmental disorders such as schizophrenia are more prevalent among males and boys.

Moreover, the study uncovered concerning results regarding pregnancies affected by COVID-19.

Analysis of a small sample of placentas from mothers who contracted COVID-19 during pregnancy revealed significant activation of schizophrenia risk genes in these placentas.

This suggests that COVID-19 infection during pregnancy may pose a risk factor for schizophrenia due to its impact on placental functioning.

The Lieber Institute scientists are further investigating this possibility through NIH-funded research on COVID-19-affected placentas.

Promising prospects for developing new treatment approaches and diagnostic tools

The ongoing study of placental genes by the Lieber Institute researchers holds promising prospects for developing new treatment approaches and diagnostic tools.

It has the potential to revolutionize the field of prenatal medicine, improving prenatal health and preventing complications that may arise later in life.

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

“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.”