The rare disease that stops people from feeling fear

Feeling fear is an evolutionary survival tactic. A small number of people have a rare condition that means they’re not scared of anything. How do they live a life without fear?

Imagine jumping out of an aeroplane and feeling nothing. No rush of adrenaline, or quickening heartbeat.

That is the reality for Jordy Cernik, a British man who had his adrenal glands removed to reduce anxiety caused by Cushing’s syndrome – a rare disease which occurs when the adrenal glands produce too much cortisol, a stress hormone. 

The treatment worked a little too well. Jordy stopped feeling anxious – but something was wrong. On a 2012 trip to Disneyland, he went on a rollercoaster ride and realised that he felt no fear. He subsequently skydived out of a plane, zip-wired off the Tyne Bridge in Newcastle and abseiled down the Shard in London – all without feeling the smallest raised pulse. 

Cernik’s experience is rare, but not unique. It may sound familiar to anyone who lives with Urbach-Wiethe disease (also known as lipoid proteinosis), a genetic condition so rare that only about 400 people have ever been diagnosed with it.

One famous Urbach-Wieth patient, known as SM, has been the subject of scientific studies at the University of Iowa in the US since the mid 1980s.

In the early 2000s, Justin Feinstein was a graduate student when he joined the team, and began looking for ways to frighten SM.

“We showed her every single horror movie we could find,” says Feinstein, now a clinical neuropsychologist at the Float Research Collective, which promotes Floatation-Reduced Environmental Stimulation Therapy (Rest) as a treatment for pain, stress, anxiety and related conditions.

Yet neither the Blair Witch Project, Arachnophobia, The Shining, or Silence of the Lambs elicited any fear in her. Even a tour of Waverley Hills Sanatorium, a creepy haunted house, had no effect.

“We exposed her to real life threats like snakes and spiders. But not only did she show a pronounced lack of fear, she couldn’t help but approach them,” says Feinstein. “She had this almost overwhelming curiosity to want to touch and interact with the different creatures.”

Urbach-Wiethe disease is caused by a single mutation in the ECM1 gene, found on chromosome 1. ECM1 is one of many proteins crucial for maintaining the extracellular matrix (ECM), a supportive network that holds cells and tissues in place.

When ECM1 is damaged, calcium and collagen begin to build up, causing cell death. One part of the body that seems to be particularly vulnerable to this process is the amygdala, an almond-shaped region of the brain long thought to play a role in processing fear.

In SM’s case, she stopped feeling fear when Urbach-Wiethe disease destroyed her amygdala.

“What’s remarkable is that it is specific to fear – her ability to process other types of emotion are mostly intact, whether that be happiness or anger or sadness,” says Feinstein.

Different types of fear 

However, the story is actually more complicated than this. It turns out that the amygdala may play more of a role in certain types of fear than others.

For example, it seems to be crucial for fear conditioning. Experiments with rodents show that animals that experience an electric shock immediately after a noise learn to freeze when presented with the noise alone.

However, while SM knows not to touch a hot pan just out of the oven, she cannot be fear conditioned – that is, she doesn’t experience a racing heartbeat and surge of adrenalin when presented with a stimuli that has previously been associated with pain.

SM is also unable to recognise the fearful facial expressions of others, although she can pick out expressions of joy and sadness.

She is also extremely sociable and gregarious, but at the same time has difficulty recognising and avoiding dangerous situations, which has led to her being threatened at knife and gunpoint on more than one occasion.

“She tends to approach people that she should be avoiding, and she’s gotten herself in quite a bit of trouble as a consequence of her inability to sense the trustworthiness of individuals,” says Feinstein.

In one study, researchers asked a stranger to approach SM, who signalled the distance at which she felt most comfortable. Her preferred distance was 0.34m (1.1ft), which was almost half that of other volunteers, suggesting she is unusually comfortable with people being in her personal space. 

“In that situation, SM and other individuals with amygdala damage will go nose-to-nose with relatively unfamiliar experimenters, which is something that healthy control participants with an intact amygdala would essentially never do,” says Alexander Shackman, professor of psychology at the University of Maryland, US. 

The finding suggests that the amygdala may play a role in organising how we respond to the social world.

Nevertheless, there are some types of fear that seem to occur independently of the amygdala. In one experiment, Feinstein and colleagues asked SM to breathe in carbon dioxide, which triggers a feeling of fear and suffocation in some people.

Scientists expected her to react fearlessly, but to their surprise she panicked. Two other patients, also with damage to their amygdala, also experienced intense fear during the experiment. 

“In the case of SM, it triggered a full-blown panic attack,” says Feinstein. “It was the most intense fear that she had ever felt in her entire adult life.”

The finding set Feinstein on a decade-long search for the truth about the amygdala’s role in fear. It turns out that there are actually two different fear pathways in the brain, depending on whether the threat is external or internal.

When it comes to external threats, the amygdala acts like an orchestra conductor, directing the other parts of the brain and body to produce a response.

First it receives information from the brain areas that process vision, smell, taste and hearing. If the amygdala detects a threat, such as an approaching burglar, snake or bear, it then sends messages to the hypothalamus, a region just above the back of the neck.

The hypothalamus then communicates with the pituitary gland, which in turns gets the adrenal glands to release cortisol and adrenaline into the bloodstream.

“This will cause your heart rate to go up, blood pressure to rise, and all the classic sort of fight-or-flight symptoms of a typical fear response will be evoked,” says Feinstein.

However, when it comes to internal threats, such as detecting raised levels of CO2 in the blood, the brain manages things in a different way.

The body interprets the high CO2 as a sign of impending suffocation, as there aren’t any oxygen sensors in the brain. Feinstein’s research has shown that it is the brainstem, a region that regulates unconscious bodily functions such as breathing, that senses the rise in CO2 and initiates a sense of panic.

The amygdala puts the brakes on this response, preventing fear; hence why patients like SM, who are missing their amygdala, have such an exaggerated response. (Scientists still don’t know why, however, the amygdala behaves this way.)

“It’s a very significant scientific result, because what it’s teaching us is that the amygdala is not crucial for all flavours and forms of fear, anxiety and panic,” says Shackman. “It seems to be crucial for orchestrating fear in response to external threats, such as the mugger, the snake, the spider, the monsters jumping out of the haunted house, but it doesn’t seem to be responsible for triggering a very strong sense of panic in response to this more internal trigger.” 

The evolutionary importance of fear 

Of course, SM is just one person, and so scientific findings based on her experience won’t necessarily be true for everyone else. What is unique about her case is that her disease almost completely destroyed her amygdala while leaving other regions intact.

However, people can respond to the same type of brain injury in different ways. The age at which brain damage occurs can also play a role in how a person recovers.

Nevertheless, the remarkable story of SM highlights why we evolved fear in the first place. All vertebrates, including mammals, birds, reptiles, amphibians and fish, possess an amygdala, and it is clearly a huge aid to survival.