Researchers identify DNA methylation markers linked to increased risk of schizophrenia in newborns

An international research team led by researchers from Virginia Commonwealth University has for the first time identified markers that can indicate early in life whether a person is predisposed to schizophrenia.

The ability to predict the risk of developing schizophrenia later in life can enable early detection and intervention, which researchers hope can reduce the impact of the disease on individuals, families and communities. Their results were published in Molecular Psychiatry.

Schizophrenia is a serious psychiatric disorder that is most often detected in young adults. It affects up to 1% of the world’s population and can cause debilitating effects such as a feeling of loss of touch with reality. According to the World Health Organization, people with this disorder are up to three times more likely to die prematurely and often face discrimination, social isolation and debilitating physical illnesses.

Although schizophrenia involves an inherited genetic component, there is strong evidence that environmental factors play a role in whether or not the disease develops. These environmental factors can trigger chemical changes in DNA that regulate genes on or off through a process called methylation.

Investigating possible genetic triggers for a disease like schizophrenia is complicated because methylation changes can be caused by the disease itself and related factors such as stress and the medications that usually accompany it.

Due to the effects of the disease on the methylome -; the term for all of nucleic acid methylation changes in the genome of an organism or in a particular cell -; ideally, samples should be obtained before illness occurs. But since schizophrenia is a brain disorder, that would be impossible.

To solve this problem the research team -; led by VCU School of Pharmacy professors Edwin van den Oord, Ph.D, and Karolina Aberg, Ph.D. -; devised a unique approach.

First, they looked at blood samples that had been taken shortly after birth from 333 infants in Sweden, tracking down 24 million methylation marks. The team used statistical analysis that allowed them to study methylation marks at a cell type-specific level.

Since the blood drawn was taken hours after birth, years before any symptoms of schizophrenia appeared, these results cannot be influenced by the illness itself or other postnatal factors. »

Karolina Aberg, Ph.D., study principal investigator and associate director of the Center for Biomarker Research and Precision Medicine at VCU

Next, the team validated any significant findings from the blood samples by comparing them to transcriptional data from 595 post-mortem brain samples from different people -; some with schizophrenia and others in a control group who did not have the disease. The brain samples were provided by researchers around the world, including Europe, North America and Australia.

The team also compared their results to methylation data from adult blood taken from schizophrenia cases and controls -; a total of 2,970 people.

The researchers concluded that certain methylation differences already present in newborns indicate an increased risk of developing schizophrenia.

“In other words, we could identify methylation differences between individuals who later in life would develop schizophrenia and controls that are unique to specific cell types in neonatal blood.“, said van den Oord, the first listed author of the article in Molecular psychiatry and Director of the Center for Biomarker Research and Precision Medicine. “Research will continue around these methylation differences to develop potential future clinical biomarkers that will enable early detection and intervention..”

This work was supported by a $2.3 million grant from the National Institute of Mental Health. Laboratory work and analyzes took place at VCU’s Center for Biomarker Research and Precision Medicine, which is affiliated with the VCU School of Pharmacy.