Summary: A new study highlights the placenta’s role in neuropsychiatric development, showing that DNA methylation influences gene expression tied to psychiatric disorders. Researchers found strong links between placental DNA methylation and conditions like schizophrenia, bipolar disorder, and major depression.
These findings suggest that genetic risk factors for psychiatric disorders may be active before birth. Understanding these early epigenetic changes could lead to targeted interventions and personalized prevention strategies.
Key Facts:
- Placental influence: DNA methylation in the placenta affects genes linked to psychiatric disorders.
- Early intervention potential: Identifying risks in prenatal stages may allow for prevention.
- Neurodevelopmental origins: Schizophrenia and other disorders may start before birth.
Source: University of the Basque Country
A study that involved 28 researchers from 18 institutions across Europe and the United States highlights the placenta as a key element in neuropsychiatric development.
The research has demonstrated that specific epigenetic modifications in the placenta, particularly DNA methylation, can influence the expression of genes associated with psychiatric disorders.
These findings suggest that genetic risk may already manifest during the prenatal stage.
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.
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 analyzed 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,” explains Dr. Fernandez-Jimenez.
Implications for Personalized Medicine and Prevention
The discovery that genetic risk may be linked to placental DNA methylation opens new avenues for preventing and treating psychiatric disorders.
“If we could identify risk factors at the prenatal stage, we could intervene before symptoms appear, adjusting treatments or designing personalized preventive strategies,” adds Cilleros-Portet, who completed her PhD at UPV/EHU last summer and is currently a postdoctoral researcher at Mount Sinai Hospital in New York.
The study also underscores the importance of understanding where and when each genetic factor acts in pathology, since this could impact therapeutic decision-making.
“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,” concludes Fernandez-Jimenez.
This research represents a significant advance in understanding the biological basis of neuropsychiatric disorders and opens new lines of investigation for early detection, as well as for the development of more effective therapies.
Additional Information
This study was conducted at IRLab (UPV/EHU and Biobizkaia). IRLab is a multidisciplinary research group coordinated by Dr. José Ramón Bilbao, full professor at UPV/EHU and researcher at Biobizkaia. Dr. Fernandez-Jimenez has been working in this laboratory for years, developing her own research lines in the epigenomics of celiac disease and, more recently, of the placenta.
This summer, Dr. Cilleros-Portet completed her doctoral thesis on placental DNA methylation and its impact on health in this laboratory, under the supervision of Fernandez-Jimenez and Bilbao. She is currently a postdoctoral researcher at the prestigious Icahn School of Medicine at Mount Sinai in New York.
About this genetics and schizophrenia research news
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. Nature
Abstract
Potentially causal associations between placental DNA methylation and schizophrenia and other neuropsychiatric disorders
Increasing evidence supports the role of the placenta in neurodevelopment and in the onset of neuropsychiatric disorders.
Recently, mQTL and iQTL maps have proven useful in understanding relationships between SNPs and GWAS that are not captured by eQTL. In this context, we propose that part of the genetic predisposition to complex neuropsychiatric disorders acts through placental DNA methylation.
We construct a public placental cis-mQTL database including 214,830 CpG sites calculated in 368 fetal placenta DNA samples from the INMA project, and run cell type-, gestational age- and sex-imQTL models.
We combine these data with summary statistics of GWAS on ten neuropsychiatric disorders using summary-based Mendelian randomization and colocalization. We also evaluate the influence of identified DNA methylation sites on placental gene expression in the RICHS cohort.
We find that placental cis-mQTLs are enriched in placenta-specific active chromatin regions, and establish that part of the genetic burden for schizophrenia, bipolar disorder, and major depressive disorder confers risk through placental DNA methylation.
The potential causality of several of the observed associations is reinforced by secondary association signals identified in conditional analyses, the involvement of cell type-imQTLs, and the correlation of identified DNA methylation sites with the expression levels of relevant genes in the placenta.
