Evolutionarily speaking, anxiety is an important mental state – but not so much when it gets out of hand, preventing you from leaving the house. Current anti-anxiety medication comes with some negative side effects, but researchers at the Max Planck Institute for Experimental Medicine have now identified a protein in the brain that may be the key to new, more targeted treatments.

The brain is an incredibly complex organ, so there's no single cause of anxiety, but the amygdala is believed to be one of the big players. As the part of the brain that processes feelings of fear and anxiety, overactivity of the amygdala has been linked to anxiety disorders.

Some existing anti-anxiety medications, like benzodiazepines, target the amygdala. Specifically, they do so by boosting inhibitory synapses that, as their name suggests, reduce the activity of nearby neurons. In this case, that includes fear- or anxiety-related neurons that may be firing too readily, so the drugs help calm them down.

Unfortunately, the medications don't discriminate and will affect many other inhibitory neurons as well, leading to side effects like sleepiness and reduced concentration. Developing new medications that are more targeted is a key priority.

To that end, the Max Planck researchers investigated a recently-discovered protein called IgSF9b. This protein has been found to build a kind of bridge across inhibitory synapses, which can cancel out the inhibiting effect. They suspected that blocking this protein might be a more targeted approach to treating anxiety disorders.

To test it out, the researchers engineered mice with pathological anxiety. These animals tend to cower in a corner of an empty chamber, rather than explore it. But when the team blocked the production of IgSF9b, they found that the symptoms disappeared, and the mice began to move around the chamber more naturally. Inspection of the animals' amygdalas confirmed that this behavior change was due to the inhibitory synapses functioning better.

"Blocking IgSF9b in pathologically anxious mice has an anxiolytic (anxiety-relieving) effect and normalizes anxiety behaviour in these animals," says Olga Babaev, an author of the study. "This protein could therefore be a target for pharmacological approaches to treating anxiety disorders."

The research was published in the journal Nature Communications.

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