Schizophrenia, conceptual image

Ancient viral infections that occurred hundreds of thousands of years ago, so called “fossil viruses,” now found in thousands of human DNA sequences have been linked with major psychiatric disorders according to an international research collaboration led by investigators at King’s College London (KCL).

Roughly eight percent of the human genome is comprised of what are officially called Human Endogenous Retroviruses (HERVs) that resulted from these ancient infections. Until recently, these viruses were considered junk DNA, but recent genomic research advances have discovered where in human DNA these viruses are located, and some look to be contributing to the development of disorders such as schizophrenia, bipolar disorder, and depression. Findings of the research which was partly funded by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Center and the U.S. National Institutes of Health (NIH), are published in Nature Communications.

The finding is the first to show that a specific set of HERVs expressed in the human brain contribute to a susceptibility to psychiatric disorders and marks an important advance in better understanding the genetic components that contribute to their development.

“This study uses a novel and robust approach to assess how genetic susceptibility for psychiatric disorders imparts its effects on the expression of ancient viral sequences present in the modern human genome,” said  co-senior author Timothy Powell of KCL, PhD, a senior lecturer at KCL. “Our results suggest that these viral sequences probably play a more important role in the human brain than originally thought, with specific HERV expression profiles being associated with an increased susceptibility for some psychiatric disorders.”

The study drew upon data from large genetic studies that involved tens of thousands of people both with, and without, mental health conditions. The team also had access to information from autopsy brain samples from more than 800 people, which allowed the team find how DNA variations linked to psychiatric disorders affect the expression of HERVs.

Findings showed that most psychiatric risk variants impacted genes with well-known biological functions, but the researchers also found that some of the risk variants preferentially affected the expression of HERVs. From this data, the team identified five distinct HERV expression signatures associated with psychiatric disorders including two associated with schizophrenia, one with risk of developing bipolar disorder and schizophrenia, and one associated with risk of depression.

According to first author, Rodrigo Duarte, PhD, a research fellow at KCL, said that while there are known substantial genetic components to some psychiatric disorders involving many different parts of the genome, “we were able to investigate parts of the genome corresponding to HERVs, which led to the identification of five sequences that are relevant to psychiatric disorders. Whilst it is not clear yet how these HERVs affect brain cells to confer this increase in risk, our findings suggest that their expression regulation is important for brain function.”

This research opens up a new avenue of scientific inquiry to better understand the role of HERVs and their function—including more inquiry into those identified in the study. “We think that a better understanding of these ancient viruses, and the known genes implicated in psychiatric disorders, have the potential to revolutionize mental health research and lead to novel ways to treat or diagnose these conditions,” said Douglas Nixon, PhD, co-senior author and a researcher at the Feinstein Institutes for Medical Research at Northwell Health.

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