Modifications in the placenta linked to psychiatric disorders

An international research team, led by the Immunogenetics Research Laboratory at the University of the Basque Country (UPV/EHU) and the Biobizkaia Health Research Institute, has identified associations between modifications in the placenta and the risk of developing schizophrenia, bipolar disorder and major depression disorder. The team’s findings, published in the journal Nature Communications, represent a significant advance in understanding the biological basis of neuropsychiatric disorders and open new lines of investigation for early detection, as well as for the development of more effective therapies.

Epigenetic modifications are chemical changes in DNA and its associated proteins that regulate gene activity without altering their sequence. One of the most studied modifications is DNA methylation, a process in which methyl groups — small molecules composed of one carbon and three hydrogen atoms — are added to specific regions of the DNA. This mechanism, essential for development, environmental adaptation and disease predisposition, is influenced by genetics and responds to factors such as diet, stress, and exposure to pollutants.

The study results indicate that schizophrenia, bipolar disorder and major depression disorder are the neuropsychiatric disorders most strongly linked to DNA methylation in the placenta, highlighting the placenta as a key element in neuropsychiatric development. Other conditions, such as attention deficit hyperactivity disorder (ADHD) or autism, show some potentially causal associations, although to a lesser extent, while no visible effects were found in other analysed pathologies.

“These findings reinforce the hypothesis that schizophrenia and other disorders have a neurodevelopmental origin and that the placenta plays a fundamental role in this process,” said study coordinator Dr Nora Fernandez-Jimenez, assistant professor at the UPV/EHU Faculty of Medicine and Nursing and a researcher at Biobizkaia.

The discovery that genetic risk may be linked to placental DNA methylation opens new avenues for preventing and treating psychiatric disorders. As noted by first author Dr Ariadna Cilleros-Portet, who completed her PhD at UPV/EHU, “If we could identify risk factors at the prenatal stage, we could intervene before symptoms appear, adjusting treatments or designing personalised preventive strategies.”

The study also underscores the importance of understanding where and when each genetic factor acts in pathology, since this could impact therapeutic decision-making. According to Fernandez-Jimenez, “Not all genes associated with a disorder should be treated directly; some may have acted in an earlier developmental stages and may not be actionable in adulthood.”

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