New study from King’s College London shows that numerous DNA sequences from ancient viral infections are active in the brain, and some of them play a role in making individuals more susceptible to psychiatric disorders like schizophrenia, bipolar disorder, and depression. The findings were published in Nature Communications.This project is partially funded by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre and the US National Institutes of Health (NIH).
Approximately eight percent of our genetic material consists of sequences known as Human Endogenous Retroviruses (HERVs), which are the result of ancient viral infections that took place hundreds of thousands of years ago. Previously, it was thought that these ‘fossil viruses’ were simply useless DNA, with no significant role in the body. However, thanks to advancements in genomics research, scientists have now identified the location of these fossil viruses within our DNA, allowing us to gain a better understanding of their function.
Dr. Timothy Powell, a Senior Lecturer at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London, and co-senior author of the study, stated that this new research is the first to demonstrate that specific HERVs expressed in the human brain play a role in susceptibility to psychiatric disorders. This marks a significant advancement in understanding the complex genetic factors that contribute to these conditions and builds on previous findings.
The study uses an innovative and strong method to examine the impact of genetic susceptibility on psychiatric disorders.The study focused on ancient viral sequences found in the modern human genome and their impact on the human brain, particularly in relation to psychiatric disorders. The research suggests that these viral sequences may have a greater influence on the brain than previously believed, and that specific expression profiles of HERVs are linked to an increased vulnerability to certain psychiatric conditions. The analysis included data from large genetic studies involving thousands of individuals with and without mental health issues, as well as information from brain samples of 800 individuals obtained during autopsies. The goal was to investigate how DNA variations associated with psychiatric disorders affect the expression of HERVs.Most genetic risk variants associated with psychiatric diagnoses affected genes with established biological functions. However, the researchers discovered that certain genetic risk variants specifically influenced the expression of HERVs. The researchers identified five distinct HERV expression signatures linked to psychiatric disorders, including two HERVs associated with schizophrenia risk, one associated with both bipolar disorder and schizophrenia risk, and one associated with depression risk.
Dr. Rodrigo Duarte, the lead author and Research Fellow at IoPPN, King’s College London, stated: “We are aware that psychiatric disorders have a genetic component, and our findings suggest that HERVs may play a role in these disorders.”There is a significant genetic element to psychiatric disorders, with various parts of the genome contributing to susceptibility. Our research focused on investigating specific parts of the genome related to HERVs, which resulted in the discovery of five sequences linked to psychiatric disorders. Although we do not yet understand how these HERVs impact brain cells to increase risk, our findings suggest that regulating their expression is crucial for brain function.”
Dr Douglas Nixon, co-senior author of the study and a researcher at the Feinstein Institutes for Medical Research at Northwell Health in the US, stated: “Additional research is needed to further investigate the role of these HERVs in psychiatric disorders.”The exact function of most HERVs, including those in our study, needs to be understood. We believe that gaining a better understanding of these ancient viruses and the genes linked to psychiatric disorders has the potential to revolutionize mental health research and lead to new methods for treating or diagnosing these conditions.”
