New research from the University of Aberdeen has identified an area of DNA that plays a key role in controlling anxiety, ‘paving the way’ towards personalised anxiety medication.

In the study, the team uncovered crucial DNA ‘switches’ on key genes in parts of the brain that affect anxiety levels in mice.

The researchers say the findings between this part of the human genome and anxiety can help us better understand the condition affecting a quarter of 16–34-year-olds in Scotland.

Led by Professor Alasdair Mackenzie, the research comes as part of the team’s wider programme to understand genetic differences that influence disease risk and health outcomes.

The human genome contains key areas of DNA which ‘code for’ proteins directing our cells to form specific tissues, from muscles to nerve cells, that make up who we are.

An underexplored part of DNA, known as the ‘dark genome’, has received increased attention from researchers – and it is here where Professor Mackenzie says these key drivers of health conditions may be found:

“We already know that 95% of the genetic differences associated with disease are found outside of protein coding genes. This part of the genome, known as the “non-coding genome” has not been well explored because we previously lacked the tools to do so.  

“We also know that the non-coding genome contains information in the form of gene switches that tell genes where and when to be turned on.

“This is important as genes have to be switched on in the right cells and at the right times to ensure good health and when they are not turned on correctly can contribute to conditions like anxiety, depression and addiction. These areas of the non-coding genome are what we study in our lab.” 

Professor Mackenzie’s team say many of these switches have remained “virtually unchanged or conserved” for hundreds of millions of years and can be found in both humans and mice.

They then used the gene editing technology CRISPR to delete these switches from mice, to study their role in mood, food intake and preference for alcohol.

Researchers focused on an ‘enhancer’ called BE5.1 which sits within and helps control a neurological gene known to be essential for learning and memory.

By deleting this enhancer, researchers found that levels of anxiety increased in female mice.

Additionally, they found that the effects of this deletion on ‘anxiety-like behaviour’ in mice could be reversed by using the sedative and relaxant diazepam.

This suggests that BE5.1 is a vital part of the complex genome system underpinning how the brain helps alter levels of anxiety.

According to the Mental Health Foundation, anxiety has been on the increase since the pandemic, and a third of people on anti-anxiety medications do not experience ‘sustained’ relief from anxiety. 

Looking to an open-database of human genomes, the researchers found an association between variation in a part of this enhancer sequence with worry and anxious feelings in previously studied groups of people.

The researchers say that future research could unveil anxiety-specific drug targets that help modify or control anxiety levels via this switch.

However, while appearing connected, the team says further work is needed to fully understand the link and what it could mean for supporting people with anxiety.

Dr Andrew McEwan, the study’s first author, explained:

“To understand the basis of complex human diseases, that includes mental illness and other conditions such as obesity, depression, and addiction, it is as important to understand the mechanisms that ensure proper production of proteins in the right cells as it is to understand the proteins themselves.

“This will only be achieved if we better understand the non-coding genome in health and disease and the function and role of the thousands of enigmatic gene switches that lurk in its depths.” 

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