Ancient viruses linked to schizophrenia, bipolar and depression

Ancient ‘fossil’ DNA in humans could leave people more susceptible to major psychiatric disorders such as schizophrenia, bipolar disorder and depression, a new study has found.

The results could pave the way for better diagnosis and treatment.

About 8% of the genome is made up of sequences called human endogenous retroviruses (HERVs) – products of ancient viral infections that occurred hundreds of thousands of years ago which made their way into human DNA.

It had been thought that these fossil viruses had no important function, and were simply ‘junk DNA’.

However, a study led by King’s College London has discovered where in our DNA these fossil viruses are hiding, helping them to understand what functions they may have.

The study is the first to show that a set of specific HERVs in the human brain contribute to psychiatric disorder susceptibility.

Co-senior author Dr Timothy Powell, from King’s College London, said: ‘This study uses a [new] 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.

‘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.’

Researchers looked at data from large studies involving tens of thousands of people, both with and without mental health conditions, as well as information from autopsy brain samples from 800 people.

Humans have two version of each gene, one dominant, which the body ‘expresses’, turning it into a function, and the other recessive.

The study found that some genes preferentially affected the expression of HERVs.

The researchers reported five robust HERV expression signatures associated with psychiatric disorders, including two that are associated with risk for schizophrenia, one associated with risk for both bipolar disorder and schizophrenia, and one associated with risk for depression.

First author Dr Rodrigo Duarte, a research fellow at King’s College London, said: ‘We know that psychiatric disorders have a substantial genetic component, with many parts of the genome incrementally contributing to susceptibility.

‘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.

‘While 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.’

Co-senior author Dr Douglas Nixon, from Feinstein Institutes for Medical Research at Northwell Health, US, said: ‘Further research is needed to understand the exact function of most HERVs, including those identified in our study.

‘We think that a better understanding of these ancient viruses, and the known genes implicated in psychiatric disorders, have the potential to revolutionise mental health research and lead to novel ways to treat or diagnose these conditions.’

The study is published in the journal Nature Communications.