Schizophrenia is a mental disorder affects a person's perception of reality, and may impact many aspects of their life, including how they think and behave. This complex disease can manifest in different ways, and the causes are still poorly understood. Genetic, environmental, and biological factors such as the structure of the brain are thought to play a role in the development of the disease. Now researchers have found over 100 genes that are associated with the risk of schizophrenia, and these genes work through the placenta, not in the developing brain. The findings have been reported in Nature Communications.
While studies have found that genetic and environmental influences are involved in schizophrenia, this study has shown that the health of the placenta "is also critical," noted senior study author Daniel Weinberger, MD, Director and CEO of the Lieber Institute for Brain Development. "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 genes that were identified in this study appear to affect the ability of the placenta to detect nutrients in the maternal bloodstream and initiate exchanges based on that information. The genes are expressed at low levels in placental cells that are crucial to the maternal-fetal exchange of nutrients, which are cells called trophoblasts.
Many genes were also found that could be involved in the development of attention deficit hyperactivity disorder, autism, bipolar disorder, depression, and diabetes.
Lead study author Gianluca Ursini, MD, PhD, a Lieber Institute investigator, noted that it may be possible to prevent disease by targeting the placenta. If researchers and clinicians can assess placental risk gene expression before a disorder starts to develop, disease might be prevented in those who are at risk.
Developmental disorders tend to happen at higher rates in boys and men. This study showed that there are some sex-based difference in how placental risk genes are expressed, and risk genes differed depending on whether the placenta was linked to a male or female child. Inflammatory processes seem to be central to pregnancies with male children, the study suggested.
This study also assessed a small number of pregnancies in which the mother had COVID-19. The researchers determined that placental risk genes had been dramatically activated in these patients, and could explain why COVID-19 during pregnancy may be a schizophrenia risk factor. The investigators are following up on this finding.
This research may be one of the first steps toward changing how disease prevention is approached in the future.
"In the modern era of molecular and genetic medicine, the standard treatment for a complicated pregnancy is still primarily bedrest," noted Weinberger. "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."