Newswise — BALTIMORE, Md. (May 15, 2023) – According to a recent study led by the Lieber Institute for Brain Development, it appears that over 100 genes associated with an increased risk of schizophrenia contribute to the development of the illness through their impact on the placenta rather than the developing brain. The study suggests that these genes play a role in the functioning of the placenta, which is an important organ during pregnancy, rather than directly affecting the development of the brain. This finding provides new insights into the mechanisms behind schizophrenia and highlights the significance of placental health in relation to the condition.
For more than a century, scientists had believed that genes associated with the risk of schizophrenia primarily affected the brain. However, the latest research, recently published in Nature Communications, reveals that the placenta plays a much more substantial role in the development of the illness than previously recognized. This discovery challenges the longstanding assumption and highlights the significant influence of the placenta in the development of schizophrenia.
According to Dr. Daniel Weinberger, the senior author of the study and Director/CEO of the Lieber Institute for Brain Development, the genetics of schizophrenia have been right in front of us all along, hidden in the placenta. The placenta, a crucial organ in supporting prenatal development, sets the course for the development of the illness. This challenges the conventional understanding that genetic and environmental factors only impact the brain directly in schizophrenia. These findings highlight the critical role of placental health in the development of the condition.
The study revealed that genes associated with schizophrenia have an impact on a crucial function of the placenta: sensing nutrients in the mother's bloodstream, such as oxygen, and facilitating the exchange of nutrients accordingly. These genes are expressed at lower levels in the specific placental cells responsible for this maternal-fetal nutrient exchange, known as trophoblasts. As a result, the placenta's ability to effectively nurture the developing fetus is negatively affected. This discovery provides insights into how these schizophrenia risk genes influence the functioning of the placenta and potentially contribute to the development of the illness.
In addition to schizophrenia, the study identifies several genes within the placenta that play a causal role in various other disorders, including diabetes, bipolar disorder, depression, autism, and attention deficit hyperactivity disorder (ADHD). However, the researchers observed a higher number of genetic associations with schizophrenia compared to these other disorders. This finding suggests that the genetic factors contributing to schizophrenia have a stronger influence within the placenta compared to the genetic factors associated with the other investigated disorders. It highlights the distinctive nature of the genetic mechanisms underlying schizophrenia in relation to these conditions.
Another notable finding from the research is that the risk genes for schizophrenia identified in the placenta may have a relatively higher impact on heritability, which refers to the likelihood of the illness being inherited from ancestors, compared to risk genes found in the brain. This suggests that the genetic factors associated with schizophrenia that are active in the placenta play a crucial role in the transmission of the illness across generations. Understanding this distinction provides valuable insights into the genetic basis of schizophrenia and its inheritance patterns.
According to Gianluca Ursini, the lead author of the paper and an investigator at the Lieber Institute, focusing on the biology of the placenta presents a critical and promising approach to prevention—a goal of utmost importance in public health. By targeting the placenta, scientists may have the opportunity to detect alterations in risk genes associated with developmental disorders, including schizophrenia, long before the potential onset of the disorder. This detection could even be possible by examining the mother's bloodstream during pregnancy. Identifying children at the highest risk for these disorders would enable doctors to implement early interventions and strategies to support their well-being and overall health. This highlights the potential for early detection and intervention through a placenta-centered approach to improve long-term outcomes for individuals at risk.
The study also uncovered intriguing sex-based distinctions in the risk genes within the placenta. The genes associated with schizophrenia risk differed depending on whether the placenta belonged to a male or female child. In pregnancies with male children, the researchers observed that inflammatory processes in the placenta appeared to have a central role. Prior research has indicated that males may be more susceptible to prenatal stress compared to females. It is worth noting that developmental disorders, including schizophrenia, tend to occur more frequently in males and boys in general. These findings shed light on the potential influence of sex-specific factors in placental biology and their association with the risk of schizophrenia and other developmental disorders.
The researchers also made a concerning discovery related to pregnancies affected by COVID-19. They examined a small sample of placentas from mothers who had contracted COVID-19 during pregnancy and found a significant activation of the schizophrenia risk genes in these placentas. This finding suggests that COVID-19 infection during pregnancy may serve as a risk factor for schizophrenia due to its impact on the placenta. In response to this finding, scientists at the Lieber Institute are further investigating this possibility through research funded by the National Institutes of Health (NIH). Specifically, they are examining placentas affected by COVID-19 to gain a deeper understanding of the relationship between the infection and its potential implications for the development of schizophrenia.
The researchers at the Lieber Institute hold the aspiration that their continued study of placental genes will eventually lead to the development of novel treatment and diagnostic tools. Their aim is to make significant advancements in the field of prenatal medicine, potentially revolutionizing the way prenatal conditions are detected, monitored, and treated. By gaining a deeper understanding of the genetic factors and mechanisms within the placenta, they envision the possibility of improving outcomes for both mothers and babies and offering new avenues for interventions and preventive measures.
Dr. Weinberger emphasizes that despite the advancements in molecular and genetic medicine, the conventional approach to managing a complex pregnancy is still largely limited to bedrest. However, the newfound understanding of how genes associated with brain disorders and other organ-related conditions manifest in the placenta opens up exciting possibilities for enhancing prenatal healthcare and averting potential complications later in life. By leveraging these molecular insights, there is potential for significant improvements in prenatal health outcomes and the implementation of preventive measures to promote lifelong well-being. This research offers promising avenues for advancing the field and transforming the standard of care in prenatal medicine.
About the Lieber Institute for Brain Development (LIBD)
The mission of the Lieber Institute for Brain Development and the Maltz Research Laboratories is to translate the understanding of basic genetic and molecular mechanisms of schizophrenia and related developmental brain disorders into clinical advances that change the lives of affected individuals. LIBD is an independent, not-for-profit 501(c)(3) organization and a Maryland tax-exempt medical research institute affiliated with the Johns Hopkins University School of Medicine. The Lieber Institute’s brain repository of more than 4,000 human brains is the largest collection of postmortem brains for the study of neuropsychiatric disorders in the world.
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