Placenta Plays Crucial Role in Schizophrenia Risk

More than 100 genes associated with the risk of schizophrenia appear to contribute to illness due to their involvement in the placenta rather than the developing brain, states a recent study led by the Lieber Institute for Brain Development.

For over a century, scientists had generally assumed that genes linked to schizophrenia primarily pertained to the brain. However, the latest research, published in Nature Communications, reveals that the placenta plays a significantly greater role in the development of the illness than previously recognized.

Dr. Daniel Weinberger, the senior author of the paper and Director and CEO of the Lieber Institute for Brain Development at the Johns Hopkins medical campus in Baltimore, highlights that the genetic secrets of schizophrenia have been hiding in plain sight – the placenta, a crucial organ in supporting prenatal development, sets the trajectory for risk. He emphasizes that while the common perception is that genetic and environmental factors solely impact the brain, the study’s findings underscore the critical role of placental health.

The study demonstrates that genes associated with schizophrenia influence a vital placental function of sensing nutrients, including oxygen, in the mother’s bloodstream and facilitating nutrient exchange based on these findings. These schizophrenia risk genes show lower expression in the placental cells responsible for the core maternal-fetal nutrient exchange known as trophoblasts, thereby negatively impacting the placenta’s nurturing role in the developing fetus.

Furthermore, the paper identifies several placental genes that act as causative factors for diabetes, bipolar disorder, depression, autism, and attention deficit hyperactivity disorder (ADHD). However, the study reveals a far greater number of genetic associations between genes related to schizophrenia and the placenta compared to these other disorders.

The researchers also note that risk genes for schizophrenia found in the placenta may have a relatively stronger influence on heritability, referring to the likelihood of illness being inherited from ancestors, than risk genes identified in the brain.

Dr. Gianluca Ursini, the lead author of the paper and an investigator at the Lieber Institute, underscores the significance of targeting placental biology as a potential approach for prevention, which is a vital pursuit in public health. He suggests that monitoring changes in placental risk genes decades before the potential onset of a disorder, possibly even detectable in the mother’s bloodstream during pregnancy, could enable early interventions to maintain the health of at-risk children.

The study also reveals interesting sex-based distinctions in placental risk genes. Different genes are associated with schizophrenia risk depending on whether the placenta originates from a male or female child. In pregnancies with male children, inflammatory processes in the placenta appear to play a central role. Previous research has indicated that males are more susceptible to prenatal stress, and developmental disorders such as schizophrenia are generally more prevalent in males.

Additionally, concerning findings emerged regarding pregnancies affected by COVID-19. The study examined a small sample of placentas from mothers who contracted COVID-19 during pregnancy and found a significant activation of schizophrenia genes related to placental risk. This suggests that COVID-19 infection during pregnancy might be a risk factor for schizophrenia due to its impact on the placenta. The Lieber Institute scientists are further investigating this possibility through NIH-funded research focused on examining COVID-19 placentas.

The ongoing study of placental genes by the Lieber Institute researchers holds promise for the future development of new treatment and diagnostic tools, potentially revolutionizing the field of prenatal medicine.

Dr. Weinberger emphasizes that in the modern era of molecular and genetic medicine, the standard treatment for a complicated pregnancy still primarily involves bedrest. He underscores that these new molecular insights into the manifestation of genes related to brain and organ disorders in the placenta offer fresh opportunities for enhancing prenatal health and preventing complications later in life.

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