Where do fears come from? How can new knowledge improve treatment?

As a clinician and researcher, how do you define fear?

Fear is a person’s whole body response to a threat.

You are walking in the forest and you see a snake. Your body responds, “It’s dangerous!” Your mind-body response to the snake is usually a fear reaction. So you’re going to have the response you’ve labeled as fear, a mixed state of feelings, thoughts, behaviors, and physiological changes. Everyone experiences fear a little differently depending on how they integrate component responses.

It’s your whole response to the threatening situation, not just how you feel about it. Classically, your body prepares to face the threat with a “freeze, flight, or fight” response.

Frost: “Don’t notice me, please.” Escape: “I’m going to escape while I still can.” And fight, our last resort.

A rambling snake seems like an innate response. What about learned or conditioned fears?

So that’s the next step. When we talk about fear, we are essentially talking about a type of threat response. Things that threaten you are things that will harm you.

There are a lot of things in the world that can evoke a fear response that we don’t know exactly why. Some people are afraid of snakes even though they have never been harmed by them. This is called unconditioned fear.

Conditioned fears are different in that they are learned. For example, a car accident is a huge and potentially deadly event. Often people will learn to fear certain things that weren’t scary before the car accident. Like the steering wheel. Shuttlecocks usually don’t hurt people. But our car accident victim was focused on the steering wheel at the time of the accident. And so now, every time they see a shuttlecock, they have a meaningful life or death response. Flyers are now part of a new threat memory. The reaction to flying is a conditioned fear reaction.

So, taking conditioned fears into account, what are the different types of fear that you see in your work?

First, let’s be clear here and differentiate between the different threat response disorders:

  • Post-traumatic stress (PTSD). When you have an event, you have a distressing and disabling reaction to the experience of the trauma, including fear of the things you learned to fear during that traumatic event. It can be like the example of the car accident I mentioned, or the post-traumatic fear reactions experienced by soldiers in conflict zones.

  • Anxiety disorders. Anxiety disorders are a fear reaction to a threat you have not yet encountered or an anticipated threat. “I didn’t do well on this test,” for example.

  • Panic disorders. It’s like having a severe fear reaction out of the blue. For many, it can feel like a heart attack.

Basically, these illustrate different types of disorders where people have problems with their fear responses. Panic: reaction of fear without threat. Anxiety: Fear response to an anticipated threat. Post-traumatic stress: response to a memory of threat.

What is exposure therapy and has it always been the best treatment option for fear?

Exposure therapy is a highly effective and strongly evidence-based intervention originating from mid-20th century psychiatry.

Let’s say you’re afraid of heights. There’s this ladder, and you have to climb it to fix something. But you’re paralyzed by your fear. You just can’t climb that ladder. It’s just too scary for you to do that.

In general, therapy involves putting yourself in a position to do what you are afraid of while being in a safe environment. You learn that you are safe, and then retain that learned memory of safety. Security memory competes with the threat association to heights.

Our work has much broader implications for exposure therapy. Exposures are actually a technique that is an active ingredient in many therapies that target a threat association.

In PTSD, for example, indicated therapies may include trauma-focused cognitive behavioral therapy, narrative therapy, or eye movement desensitization and reprocessing. These are all very different types of therapies that, looking under the hood, you find have some sort of exposure element to target the threat association. They bring the individual closer to their feared threat memory, but they also reinforce the individual and provide them with memories of safety that rival threat memories in different ways.

Why did you and your team decide to research the improvement of exposure therapy?

It was really a fortuitous moment between chocolate and peanut butter. I was recruited to CU Anschutz to learn different mathematical models of the mind and how we can apply them to treatment.

Exposure therapy is usually super effective, but for 50% of people it’s not as effective and for many it doesn’t last long. This is because their fears may return over time. Without a lasting safety memory, a patient’s memories are tenacious and lead to recurring fear responses. A fear response may return if the person is threatened again or perhaps finds themselves triggered in a different context. Sometimes their symptoms are milder. Unfortunately, full-fledged symptoms may return.

My colleagues and I were in Matt Jones’ office talking. Matt is a prolific genius at rigorously mapping psychological processes to mathematics. He and Sam Paskewitz had worked on how stimuli compete to trigger memories. I had already studied the cerebral basis of memory threat/security competition in humans. The light bulbs were going out. So when I heard about their new experiment, I immediately asked them to apply it to threat learning. Later we asked Sarah Kennedy for help because she had a deep understanding of how fear learning theory can be applied to therapy and is one of the main experimental behavioral therapy experts on campus. That was just everything here at CU. The following year, the AB Nexus solidified our partnership.

We had to find a mathematical framework that explained all of this – what is observed in people and experiences. All this without exception. Once you have expressed it mathematically, that means you now have an accurate theory. It’s a hot topic, and people have been trying to figure out how we can map this for quite some time, mostly because the basic science is so good. Fortunately, we have ties between CU Boulder and CU Anschutz, and AB Nexus, both in the modeling and clinical health aspects. So to avoid taking a beating and to honor the work of my colleagues, they frankly integrated a deep body of work into a cohesive theory of processing fear, expressed in mathematics..

What is the result of your mathematics and your equations? How does it show a new model and paradigm for exposure therapy to make it more sustainable?

The big lesson was the potential of precision medicine in behavioral health, to use a popular expression.

What if instead of months of exposure therapy, we could tell you in a week or two if this is the right therapy? What if you’re in exposure therapy, highly invested, but struggling with threat learning? We can also tell you early.

Mathematically, this research is analogous to Newton’s equations in physics. They are simple and elegant equations that help describe motion and force. They’re not perfect, but they’re powerfully predictive for daily gross movements. You can land a person on the moon with them. More complex elaborations, such as relativity and quantum physics exist for narrow problems. We actually did some stress testing on models that were made for therapy, but found that they needed a bit more work.

We succeeded because we drew on a considerable body of experimental and mathematical work – translating and, in some places, revising the Rescorla-Wagner family of equations. This is specifically intended for use in measuring and predicting learning processes involving threat memories. By detailing a set of equations to measure and predict how people acquire and forget both safety and threat memories, we may be able to better help people who have trouble with their fear responses to threat memories. . It impacts a staggering percentage of people over their lifetime and is one of the leading causes of disability worldwide, accounting for all diseases.

Already, supported directly by the AB Nexus, we have preliminary evidence that we can use this family of equations to predict how well patients will respond to treatment based on what they learn during their treatment sessions.

Let’s say you’re in your therapist’s office: you associate your therapist and that office with security. It is really these security signals that help you prevent this threat response. And so, as soon as you walk out of your therapist’s office, if you don’t learn to generalize those memories of safety, your fear response may return. Unfortunately, experiments and models suggest that security memories are less stable than threat memories.

Because the equations sum up our whole theory in a compact form, it’s easy to see how precisely things are related. This is an exciting future for behavioral health research. There are actually many implications for the practice and prediction of individual responses for those who brave the article. It’s the start of an exciting new research program to test a theory that incorporates more than 50 years of work on learning about threats to patient care.

About Antoine L. Cassell

Check Also

IMU-838 treatment associated with low rate of confirmed disability worsening in relapsing MS

Recently reported interim data from the Phase 2 EMPhASIS trial (NCT03846219) of Immunic’s investigational agent, …