In the last year, an estimated one-in-five adults living in the US will experience a form of anxiety, the effects of which can be debilitating for those who experience an anxiety attack characterized by sweaty palms, rapid breathing, trembling, and shaking that's then topped off by a surge of overwhelming panic.

For the half of anxiety sufferers who do not find relief in traditional treatments such as cognitive behavioral therapy and antidepressants, scientists have revealed a possible way to slow down an anxiety attack: safety signals. When life events trigger the crushing fear associated with an anxiety attack, turning to a symbol or sound not associated with adverse effects can relieve anxiety by activating a different brain network in both mice and human subjects.

“A safety signal could be a musical piece, a person, or even an item like a stuffed animal that represents the absence of threat,” said Paola Odriozola, a PhD candidate in psychology at Yale and co-first author, in a statement.

Study participants were shown a shape associated with a threatening outcome, followed by both the threatening shape and a secondary non-threatening shape (For mice, researchers used different tones). Brain imaging revealed that a different neural network was activated than in exposure therapy, a treatment that gradually exposes a patient to a perceived threat in order to lessen the level of associated anxiety. The second shape, or “safety signal”, suppressed the subject’s fear compared to the threatening shape. In particular, the Yale University researchers found that the ventral hippocampus, a part of the brain that responds to perceived threats, was activated and may be key to inhibiting fear response in animals.

Behavioral therapy gradually exposes patients to the source of their fear over time, eventually reteaching the brain to respond differently to once-perceived threats. For those who don’t respond to CBT, safety signals may be an effective method to reduce the threat response and prevent anxiety attacks in the future.

“Exposure-based therapy relies on fear extinction, and although a safety memory is formed during therapy, it is always competing with the previous threat memory,” explained Dylan Gee, assistant professor of psychology at Yale and co-senior author. “This competition makes current therapies subject to the relapse of fear – but there is never a threat memory associated with safety signals.”

Importantly, the study was conducted with individuals who do not have anxiety disorders, leaving much to be studied in terms of how safety signals function in adults and children diagnosed with anxiety disorders, added Gee. Furthermore, safety signals in daily life may be more complex than during an experiment and may interfere at times with treatment or serve as a “crutch”. 

"There is much more research needed to understand how, when, and for whom safety signals might be helpful, but we think that judiciously incorporating safety signals into treatment could be helpful for individuals who have not benefited sufficiently from existing interventions or at particular developmental stages," said Gee. 

Regardless, the researchers write in the journal Proceedings of the National Academy of Sciences that their work presents a potential solution to enhance current treatments for anxiety disorders by targeting neural circuits through safety signaling.