Baltimore, MD – February 8, 2021
Genetic scoring of genes associated with schizophrenia in the placenta can predict the size of a child’s brain at birth and the degree of brain development which, according to other factors, may lead to schizophrenia later in life according to a study published today in Proceedings of the National Academy of Sciences (PNAS). Researchers at the Lieber Institute for Brain Development (LIBD) and the University of North Carolina School of Medicine (UNC) used UNC MRI scans from newborns and brain development measures for the first two years of life to detect them. They noted that this was the most important.
“By identifying the specific genes activated in the placenta that appear to be specific for the risk of schizophrenia, we have entered a set of biological processes that can be targeted to improve placental health and reduce the risk of schizophrenia, “says Daniel R. Weinberger, MD, President & Director of the Lieber Institute.” To date, prevention from early life has seemed inaccessible if not unbelievable, but these new perspectives offer opportunities to change the paradigm. “
Weinberger notes that most children with a higher schizophrenia gene score do not develop schizophrenia placenta because other genetic and environmental factors compensate for these placental effects later in development. However, he says that, in principle, individuals with other genetic risk factors for schizophrenia and early life problems during pregnancy may not be able to compensate and develop the disease, especially if they are male .
The researchers also found that in adult individuals with schizophrenia, the same genetic scores that represent placental gene expression predict brain size measured on MRI scans, and the direction of the relationship the same as found in the neonates. This was not found in individuals who were routine controls in the study of adult subjects.
John H. Gilmore, MD, Distinguished Professor of Eure and Vice-Chair for Research in the Department of Psychology and UNC principal investigator of the study, said, “I read Dr. Weinberger’s classic paper outlining the idea- neurodevelopmental perception of schizophrenia during my psychiatric residency. encouraged me to create the UNC Early Brain Development Study to better understand early childhood brain development and its relationship to risk for schizophrenia. Thirty years later, it has been a career high to collaborate with Drs. Weinberger and his team on this study, one that will advance our understanding of the complex interactions of genetic and environmental risk factors in the earliest stages of human brain development. “
The study builds on more than 30 years of scientific evidence showing the risk for schizophrenia, a disorder commonly diagnosed in early adult life, starting much earlier in life, even in prenatal life. Many studies have shown that complications during pregnancy, such as infections and malnutrition, can increase the likelihood of schizophrenia. Recent genetic studies have shown that many of the genes identified as risk factors for schizophrenia are abundantly expressed in the brain before birth, adding to the circulating evidence that early life is important.
In 2018, scientists at the Lieber Institute reported that some of these genes were also activated or “mutated” in the placenta and that they were specifically translocated if the pregnancy was complete. -fold for example with conditions such as pre-eclampsia or intrauterine growth restriction (Nat Med 2018). Earlier findings suggested that placenta health may be a factor in the risk of schizophrenia, and in particular, if the children are male, the effects are greater. They also lead the researchers to further investigate the biological interaction between placental health and neurodevelopment.
In the current study, UNC and LIBD researchers were also looking for similar relationships in other neurodevelopmental disorders. Complex pregnancy increases the risk for autism, ADHD, and intellectual disorders, so scientists studied the link between brain size at birth and psychosis over the next two years and genetic scores. representation of risk genes for these and other developmental disorders and markers expressed in the placenta. None of these disorders showed similar associations with those detected with schizophrenia, suggesting that the effect of placental gene expression may be associated with the risk of schizophrenia with early brain development.
“This is further evidence that there are early life issues in schizophrenia and that the placenta has a larger role than we thought,” Dr. Weinberger said. “Measuring the genetic scores of schizophrenia in the placenta along with studying the first two years of cognitive development patterns and early life problems could be an important approach to raise these high-risk children. Understanding the pathways that lead to neurodevelopmental disorders is a major challenge, but one that is essential for designing prevention – oriented strategies. “
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About the Lieber Institute for Brain Development (LIBD)
The mission of the Lieber Institute for Brain Development and Maltz Research Laboratories is to translate an understanding of underlying genetic and molecular mechanisms of schizophrenia and related developmental brain disorders into clinical advances that alter the lives of individuals. LIBD is an independent, not-for-profit 501 (c) (3) and Maryland tax-free medical research institute affiliated with the Johns Hopkins University School of Medicine. The Lieber Institute brain deposit of more than 3,000 human brains is the largest collection of postmortem brains for the study of neuropsychiatric disorders in the world.
About the University of North Carolina School of Medicine
The UNC School of Medicine (SOM) is the largest medical school in the state, graduating approximately 180 new physicians each year. It is consistently ranked among the top medical schools in the U.S., ranking 1st overall for primary care by US News & World Report, and 6th for research among public universities. More than half of the school’s 1,700 faculty members were principal investigators for active research awards in 2020. Two UNC SOM faculty members have won Nobel Prize awards.
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