Anxiety Relief in Sight: Scientists Identify Key Gene

An international group of researchers, led by scientists from the Universities of Bristol and Exeter, has made a significant breakthrough in anxiety research. They have identified and studied a particular gene in the brain that instigates symptoms of anxiety. Crucially, they have shown that alterations to this gene can notably reduce anxiety levels, thereby providing a hopeful direction for future anxiety treatment options. The pioneering findings of this study have been recently published in Nature Communications.

Anxiety disorders, which will affect 1 in 4 people at least once in their lives, are fairly prevalent. Profound psychological distress can trigger genetic, biochemical, and structural transformations in the amygdala neurons—areas of the brain closely linked to stress-induced anxiety. This can lead to the manifestation of various anxiety disorders, including panic attacks and post-traumatic stress disorder (PTSD).

Yet, the effectiveness of existing anti-anxiety medications remains unsatisfactory, with over half of the patients not attaining remission post-treatment. This limited success is attributed to our limited understanding of the neural circuits at play in anxiety and the molecular events that lead to stress-related neuropsychiatric states.

In this groundbreaking research, the team aimed to uncover the molecular events in the brain that are associated with anxiety. Their research focused on a set of molecules known as miRNAs in animal models, which are also present in the human brain. These molecules regulate several target proteins that control cellular processes in the amygdala.

The researchers discovered that following acute stress, there was an increase in a specific molecule, miR483-5p, in the amygdala of a mouse. The team demonstrated that this increase in miR483-5p suppressed the expression of another gene, Pgap2, which in turn drives changes to neuronal structure in the brain and behaviors connected to anxiety. The findings suggest that miR-483-5p serves as a molecular counterweight that mitigates stress-induced changes in the amygdala, promoting anxiety relief.

This new revelation about the amygdala miR483-5p/Pgap2 pathway—through which the brain regulates its stress response—is an initial step towards finding novel, more potent, and urgently required treatments for anxiety disorders that will enhance this pathway.

One of the lead authors of the study, Dr. Valentina Mosienko, an MRC Fellow and Lecturer in Neuroscience at Bristol’s School of Physiology, Pharmacology, and Neuroscience, commented on the study. She said, “Stress can be a trigger for several neuropsychiatric conditions, which originate from a negative combination of genetic and environmental factors. While the brain naturally adjusts to low levels of stress, severe or prolonged traumatic experiences can overcome these protective mechanisms, leading to pathological conditions such as depression or anxiety.”

Dr. Mosienko further stated, “miRNAs are strategically positioned to control complex neuropsychiatric conditions like anxiety. However, until now, the molecular and cellular mechanisms they employ to regulate stress resilience and susceptibility were largely unknown. The miR483-5p/Pgap2 pathway we identified in this study—which when activated exerts anxiety-reducing effects—offers vast potential for developing anti-anxiety therapies for complex psychiatric conditions in humans.”

This study was made possible through funding provided by several organizations, including the Medical Research Council, the Academy of Medical Sciences, the Leverhulme Trust, Marie Sklodowska-Curie, and the Polish National Science Centre.

Reference: “miR-483-5p offsets functional and behavioural effects of stress in male mice through synapse-targeted repression of Pgap2 in the basolateral amygdala” by Mariusz Mucha, et al., 25 April 2023, Nature Communications.
DOI: 10.1038/s41467-023-37688-2

Frequently Asked Questions (FAQs) about Anxiety-Driving Gene Discovery

More about Anxiety-Driving Gene Discovery

• Nature Communications
• Medical Research Council
• Academy of Medical Sciences
• Leverhulme Trust
• Marie Sklodowska-Curie
• Polish National Science Centre