Researchers have discovered a gene that they believe could be driving anxiety symptoms, potentially opening up a new therapeutic avenue. When the team modified the gene, they managed to reduce anxiety levels in animal models, suggesting the gene could be closely tied to the complex condition. 

Anxiety disorders are a set of complex conditions involving interactions between genetics and the environment, with trauma playing a critical role in their onset in many cases. Approximately one in four adults will be diagnosed with an anxiety disorder in their lifetime, but treatment remains extremely limited. 

Anti-anxiety medications exist, but they are limited in efficacy and less than half of the people that take them will achieve remission. This is largely due to how poorly scientists currently understand the brain circuitry that leads to these events, making understanding them the number one priority in combatting anxiety.  

To this end, researchers from the Universities of Bristol and Exeter looked to identify the underlying mechanisms behind anxiety symptoms by inducing stress in animal models and analyzing molecular events that may underpin them. They focused on a group of small molecules called microRNAs (miRNAs), which are also found in humans and bind to messenger RNA (mRNA) to stop them from producing proteins. Such miRNAs have been found to control proteins integral to processes in the amygdala, which regulates our emotions and has been implicated in anxiety disorders. 

Mice were subjected to stress and then immediately after the researchers took samples from their amygdalae for analysis. These were then compared to a control group to identify any differences during stressful events compared to standard brain activity. 

Immediately after stress, the team found a miRNA molecule called miR483-5p was increased, which they then demonstrated subsequently suppressed a gene called Pgap2. This gene is thought to drive anxiety-linked behaviors and miR483-5p acts as a stopper on this gene, regulating the amygdala’s stress response. Together, the team believes this pathway could be directly involved in anxiety symptoms. 

The team now want to further explore this pathway as a potential anxiety treatment option, hoping to fill a much-needed gap in treatment. 

“miRNAs are strategically poised to control complex neuropsychiatric conditions such as anxiety. But the molecular and cellular mechanisms they use to regulate stress resilience and susceptibility were until now, largely unknown. The miR483-5p/Pgap2 pathway we identified in this study, activation of which exerts anxiety-reducing effects, offers a huge potential for the development of anti-anxiety therapies for complex psychiatric conditions in humans,” said Dr Valentina Mosienko, one of the study’s lead authors, in a statement. 

The research is published in Nature Communications.