Introduction
A groundbreaking study published in Nature Communications has unveiled a startling connection between ancient viral DNA embedded in the human genome and major psychiatric disorders. This research, spearheaded by scientists at King's College London's Institute of Psychiatry, Psychology & Neuroscience (IoPPN), sheds new light on the genetic underpinnings of conditions such as schizophrenia, bipolar disorder, and depression.
The Viral DNA in Our Genes
The study reveals that about 8% of the human genome is composed of Human Endogenous Retroviruses (HERVs), which are remnants of ancient viral infections that occurred hundreds of thousands of years ago. Previously dismissed as "junk DNA," these sequences were not considered to play significant roles in human biology. However, advances in genomics have enabled researchers to pinpoint the locations of these viral sequences within our DNA, leading to a deeper understanding of their potential impact.
A Novel Approach to Psychiatric Disorders
The research team at IoPPN is the first to demonstrate that specific HERVs expressed in the human brain contribute to the susceptibility to psychiatric disorders. "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," explains Timothy Powell, co-senior author of the study and a senior lecturer at IoPPN. Their findings suggest that these viral sequences play a more significant role in the brain than previously thought, with certain HERV expression profiles linked to increased susceptibility to psychiatric conditions.
Methodology and Findings
The researchers analysed data from extensive genetic studies involving tens of thousands of individuals, both with and without mental health conditions, and autopsy brain samples from around 800 people. Utilizing data from the CommonMind Consortium, they explored how DNA variations associated with psychiatric disorders influenced HERV expression.
The study uncovered five distinct HERV expression signatures associated with psychiatric disorders:
- Two HERVs linked to schizophrenia risk
- One HERV connected to both bipolar disorder and schizophrenia
- One HERV associated with depression risk
These findings suggest that psychiatric disorders have a substantial genetic component, with various parts of the genome contributing incrementally to susceptibility. Rodrigo Duarte, the study's first author and research fellow at IoPPN, notes, "In our study, 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."
The Path Forward
While the exact mechanisms by which these HERVs affect brain cells and confer increased risk are not yet clear, the study emphasizes the importance of their expression regulation for brain function. The research team acknowledges the need for further exploration, particularly by incorporating data from additional brain areas, developmental stages, and tissues to gain a comprehensive understanding of HERVs' roles.
Douglas Nixon, co-senior study author and researcher at the Feinstein Institutes for Medical Research at Northwell Health, underscores the potential impact of this research: "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."
This study marks a significant step forward in unravelling the complex genetic factors contributing to psychiatric disorders, offering hope for more targeted and effective treatments in the future.
Reference
- Powell, T., Duarte, R., & Nixon, D. (2024). "Ancient Viral Sequences in the Human Genome Linked to Major Psychiatric Disorders," Nature Communications.
- King's College London Institute of Psychiatry, Psychology & Neuroscience (IoPPN).