Summary: A new multicenter study highlights the placenta’s critical role in early neuropsychiatric development, showing that DNA methylation in placental tissue can influence the activity of genes linked to psychiatric disorders. The research identifies strong associations between placental DNA methylation and schizophrenia, bipolar disorder, and major depressive disorder, suggesting that some genetic risks may become active before birth.
The findings point to the placenta as a mediator of genetic and environmental influences on the developing brain. Understanding these prenatal epigenetic changes could enable earlier risk detection and the development of targeted preventive and personalized treatment strategies.
Key Facts:
- Placental influence: DNA methylation patterns in the placenta are associated with genes implicated in psychiatric disorders.
- Early detection and intervention: Prenatal identification of epigenetic risk markers may create opportunities for prevention and early therapeutic strategies.
- Neurodevelopmental origins: Evidence supports that conditions such as schizophrenia and related disorders have origins in prenatal development.
Source: University of the Basque Country
Study overview
A collaborative team of 28 researchers from 18 institutions across Europe and the United States examined how placental epigenetic modifications—chiefly DNA methylation—relate to risk for multiple neuropsychiatric disorders. Their analyses focused on how methylation at specific CpG sites in fetal placenta correlates with genetic variants and with gene expression in placental tissue, aiming to determine whether these epigenetic marks could mediate genetic risk.
Epigenetic modifications are chemical changes to DNA and associated proteins that regulate gene activity without altering the underlying DNA sequence. DNA methylation—addition of methyl groups to particular DNA regions—is a well-studied mechanism that affects development, responses to environment, and disease susceptibility. Methylation patterns are shaped by inherited genetic factors and by prenatal exposures such as maternal diet, stress, and environmental pollutants.
In this study, researchers found that placental DNA methylation shows the strongest associations with schizophrenia, bipolar disorder, and major depressive disorder. There were also indications of potentially causal links with attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders, though these associations were less pronounced. Other conditions analyzed in the study showed no clear connections to placental methylation patterns.
“These results support the hypothesis that schizophrenia and related disorders often have neurodevelopmental origins, and highlight the placenta as a central player in shaping risk during pregnancy,” explains Dr. Fernandez-Jimenez.
Implications for personalized medicine and prevention
Linking genetic risk to placental DNA methylation expands possibilities for early detection and intervention. If at-risk methylation profiles can be identified prenatally or in the newborn period, clinicians and researchers could develop interventions that reduce or modify risk before clinical symptoms emerge. Such strategies might include tailored maternal care, nutritional adjustments, or other prenatal and early-life measures designed to influence epigenetic trajectories.
“Detecting risk factors during pregnancy could allow us to intervene earlier, personalize prevention plans, and potentially alter disease trajectories,” says Cilleros-Portet, who completed her PhD at UPV/EHU and is now a postdoctoral researcher at Mount Sinai Hospital in New York.
The study also underscores that timing and tissue context matter: some genes linked to psychiatric disorders may exert their influence during prenatal development and therefore may not be direct therapeutic targets in adults. Knowing where and when genetic risk acts can guide more precise therapeutic decisions and research priorities.
“Not every gene associated with a disorder will be actionable in adulthood because its primary effects may have occurred in earlier developmental windows,” Fernandez-Jimenez adds.
This work represents a significant advance in mapping the biological pathways that connect genetics, placental epigenetics, and neuropsychiatric outcomes, and it opens new lines of investigation for early detection and the development of more effective, stage-appropriate therapies.
Additional information
The study was conducted by IRLab (UPV/EHU and Biobizkaia), a multidisciplinary group coordinated by Dr. José Ramón Bilbao, full professor at UPV/EHU and researcher at Biobizkaia. Dr. Fernandez-Jimenez has led research in epigenomics related to celiac disease and more recently placental epigenetics. Dr. Cilleros-Portet completed her doctoral thesis this summer on placental DNA methylation and its health implications under the supervision of Fernandez-Jimenez and Bilbao, and she is currently a postdoctoral researcher at the Icahn School of Medicine at Mount Sinai in New York.
Author: Arantza Beitia
Source: University of the Basque Country
Contact: Arantza Beitia – University of the Basque Country
Image: The image is credited to Neuroscience News
Original Research: Open access. “Potentially causal associations between placental DNA methylation and schizophrenia and other neuropsychiatric disorders” by Fernandez-Jimenez et al., published in Nature.
Abstract
Potentially causal associations between placental DNA methylation and schizophrenia and other neuropsychiatric disorders
Recent evidence emphasizes the placenta’s role in neurodevelopment and its influence on the risk of neuropsychiatric disorders. Using placental methylation quantitative trait loci (mQTL) and cell type– and gestational age–adjusted models, the study authors built a public cis-mQTL database with over 214,000 CpG sites measured in 368 fetal placenta samples. They integrated these data with genome-wide association study (GWAS) summary statistics for ten neuropsychiatric disorders using summary-based Mendelian randomization and colocalization analyses, and assessed the impact of methylation sites on placental gene expression in an independent cohort.
The analyses show that placental cis-mQTLs are enriched in placenta-specific active chromatin regions and indicate that part of the genetic risk for schizophrenia, bipolar disorder, and major depressive disorder operates through placental DNA methylation. Support for potential causality came from conditional analyses revealing secondary association signals, the involvement of cell type–specific imQTLs, and correlations between identified methylation sites and expression of relevant placental genes.