First discovery of genetic brain pathway a relief for anxiety sufferers
UK researchers have, for the first time, identified a genetic pathway in the brain that plays a key role in controlling anxiety, opening the door to the development of more effective treatments in the future.
One in four people will be diagnosed with an anxiety disorder at least once in their lifetime, often presenting as repeated episodes of sudden feelings of intense anxiety, fear or terror that peak within minutes.
It’s known that severe psychological trauma triggers genetic, biochemical, and structural changes in a part of the brain called the amygdala, a complex structure that lies in the temporal lobe. It’s the region that processes fearful and threatening stimuli and is implicated in stress-induced anxiety, which can lead to anxiety disorders, including panic attacks and post-traumatic stress disorder (PTSD).
Current anti-anxiety drugs aren’t particularly effective, with more than half of people not achieving remission after treatment. Researchers from the Universities of Bristol and Exeter suggest that the reason why these drugs are ineffective is that there’s a lack of understanding about the brain circuitry and molecular interactions that underlie anxiety.
“Stress can trigger the onset of a number of neuropsychiatric conditions that have their roots in an adverse combination of genetic and environmental factors,” said Valentina Mosienko, corresponding author of the study. “While low levels of stress are counterbalanced by the natural capacity of the brain to adjust, severe or prolonged traumatic experiences can overcome the protective mechanism of stress resilience, leading to the development of pathological conditions such as depression or anxiety.”
The research team decided to investigate these molecular causes of anxiety, focusing on microRNAs (miRNAs), small, non-coding fragments of RNA that coordinate complex brain responses by regulating target genes.
Performing tests on mice, the researchers found that acute stress increased a particular miRNA, miR-483-5p, in the mice’s amygdala. miR-483-5p then suppressed the function of the gene Pgap2, which is responsible for changing the amygdala’s neurons and drives behavior associated with anxiety.
Put simply, the researchers found that miR-483-5p acts as a “molecular brake” for the Pgap2 gene, mitigating changes in the amygdala brought on by stress and resulting in a reduction in anxiety.
This is the first discovery of the miR-483-5p/Pgap2 pathway. The greater understanding of the mechanisms underpinning anxiety provided by the study could lead to the development of more effective treatments for this often debilitating condition.
“miRNAs are strategically poised to control complex neuropsychiatric conditions such as anxiety,” Mosienko said. “But the molecular and cellular mechanisms they use to regulate stress resilience and susceptibility were, until now, largely unknown. The miR-483-5p/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.”
The study was published in the journal Nature Communications.
Source: University of Bristol