Dysregulation of fear response and fearful behavior in the absence of threat is a hallmark of anxiety and stress-related disorders such as posttraumatic stress disorder (PTSD). Approximately 5.2 million adults in the United States are affected by PTSD (Colvonen et al., 2019). Patients who suffer from the disorder express learned fear inappropriately in situations where they are actually safe. The ability to recognize and properly respond to perceived danger is critical to the prevention of chronic stress and anxiety disorders that burden large populations of people. Learning to associate distinguishable signals, such as images or sounds, with safety can reduce fear and anxiety by activating different circuits in the brain than in typical anxiety treatments. This pairing approach is therefore a promising neurodevelopmentally optimized approach to enhance treatment outcomes for anxious individuals.
Learned safety is a process of learning to regulate or inhibit fear responses by identifying periods of security, and a “safety signal” is a stimulus or cue that signals the absence of threat, mitigating against an aversive event. Safety learning is an important topic in psychology because the ability to differentiate safe from unsafe cues is vital for any organism to survive in their environment. Fear and safety learning processes give people the ability to pair new cues with danger, remember those cues when they present in new environments, and learn new cues when the danger is over. Trauma and threat cues play a role in modulating fear learning processes. For example, after a robbery, a person may learn to fear the cue “gun” in a dark alley. However, seeing the same cue, a gun, in the context of a shooting range would not bring about the same response.
Safety learning relies on the principles of classical conditioning. In classical conditioning, a person or animal learns to associate a neutral stimulus (the conditioned stimulus) with a stimulus that produces a behavior (unconditioned stimulus) that naturally produces a behavior (unconditioned response). Safety learning occurs when a neutral conditioned stimulus (CS+), such as a blue light, is repeatedly paired with an unconditioned stimulus (US), such as a shock. During learning trials, another neutral conditioned stimulus (CS-), such as a yellow light, is never paired with the unconditioned stimulus (the shock). As such, the yellow light (CS-) is the cue that signals safety and does not evoke an anxious response. The inability to inhibit the fear response when exposed to both safety and fear signals predicts the persistence of PTSD symptoms (Colvonen, 2019), and therefore must be monitored.
The standard treatment for people with anxiety disorders is exposure therapy, which involves repeatedly presenting a fear-provoking stimulus until an anxious person becomes accustomed to it. The goal of this therapy is to extinguish the person's fear response as she learns that what she fears will not occur. While exposure therapy is often an effective treatment for PTSD, a significant proportion of patients are non-responsive to the treatment. Through advancing our understanding of mechanisms that influence PTSD acquisition, maintenance, and treatment, we can help create more effective interventions to decrease the risk of PTSD, and its severity. Research suggests that safety signals activate different circuits in the brain than do typical therapies for anxiety, suggesting that this approach may serve as an alternative to current interventions and enhance treatments for patients with anxiety disorders (Colvonen, 2019).
Safety learning can have practical, everyday applications such as when integrated in PTSD treatment. A combat veteran with PTSD may experience increased fear in response to a previously learned cue, such as overcrowded grocery stores, even though they may be surrounded by many other cues that signal safety, such as storefronts and peaceful surroundings. Being able to differentiate between these safe and unsafe cues in the appropriate environments is essential to facilitate the extinction process of a generalized fear response. In the case of the combat veteran, the ability to scan local stores and restaurants and see no life threatening signals (CS) can decrease her anxious response (CR). The combat veteran must be able to differentiate safe and threatening cues, and use the safe cues to inhibit the fear response.
An example of incorporating safety learning clinically can be seen in a study conducted by Meyer et al. in 2019, in which mice and human participants were taught to associate safety with sounds and colored shapes. In the presence of a safety signal, both mice and humans experienced a reduction in the physiological and behavioral response that normally occurs when a threat is perceived. The reduction in fear response was immediate, in contrast with the lengthy training procedures required with exposure based therapies.
There are many possible applications for safety learning. For patients with anxiety disorders, safety cues are employed with the goal of reducing fear. In a laboratory setting, safety cues are studied as standardized stimuli such as shapes, sounds and odors. However, outside of the laboratory, safety cues can take on many forms such as objects, people, or actions. For example, an individual with social anxiety might typically only enter new situations in the presence of her partner. Someone with a panic disorder might always carry her anti-anxiety medication. Safety cues can be combined with exposure therapies to increase the effectiveness of the therapy.
Research has suggested that safety cues can assist in increasing an approach behavior, which is important for achieving effective exposure. Safety signals can act as encouragement for patients to get closer to a stimulus during exposure, or accelerate the rate at which they approach the stimulus. Studies that have examined treatment acceptability in relation to safety signals have shown that patients rate exposure to aversive events as more acceptable, and report higher levels of anticipated adherence to the treatment, when using safety signals (Odriozola, 2021).
There is still progress to be made in the field. Much of the research on fear extinction and safety learning has been focused on men, despite the rising prevalence of PTSD in women. Importantly, research suggests that fear discrimination in humans is more sensitive to trauma history in women than in men. While there is relatively limited research regarding sex differences in fear extinction, reserach exploring this area is proliferating. A study on sprague dawley rats, aimed to test circuitatry sex differences in fear extinction demonstrated that female rats show greater distinction between a feared CS+ and a safe CS-, as they were able to regulate fear to a safety signal faster than males (Folib et al, 2021).
In situations that are not dangerous, fear should be suppressed. With high proportions of the population suffering from anxiety disorders, continued research in safety learning and fear extinction will hopefully translate to clinical therapies for preventing onset and maintenance of treating these disorders.
References
Foilb, A. R., Sansaricq, G. N., Zona, E. E., Fernando, K., & Christianson, J. P. (2021). Neural correlates of safety learning. Behavioural Brain Research, 396, 112884. https://doi.org/10.1016/j.bbr.2020.112884
Colvonen, P. J., Straus, L. D., Acheson, D., & Gehrman, P. (2019). A Review of the Relationship Between Emotional Learning and Memory, Sleep, and PTSD. Current psychiatry reports, 21(1), 2. https://doi.org/10.1007/s11920-019-0987-2
Odriozola, P., & Gee, D. G. (2021). Learning About Safety: Conditioned Inhibition as a Novel Approach to Fear Reduction Targeting the Developing Brain. The American journal of psychiatry, 178(2), 136–155.
Meyer, H. C., Odriozola, P., Cohodes, E. M., Mandell, J. D., Li, A., Yang, R., Hall, B. S., Haberman, J. T., Zacharek, S. J., Liston, C., Lee, F. S., & Gee, D. G. (2019). Ventral hippocampus interacts with prelimbic cortex during inhibition of threat response via learned safety in both mice and humans. Proceedings of the National Academy of Sciences, 116(52), 26970–26979. https://doi.org/10.1073/pnas.1910481116