We are living in an era of crises worldwide, around one billion people are suffering from stress-related illnesses and that number is rising. The key to resilience is staying healthy even when faced with life’s great burdens. What keeps people mentally healthy in spite of serious crises while others break down? Resilience is a natural phenomenon that enables people to continue developing after they experience a catastrophe or traumatic event.
Leading researchers are trying to identify the secret to resilience. As resilience researchers, we aim to identify strategies that can help prevent people from developing mental illnesses. Can we learn to be resilient?
Georg Ballmann’s son Luca was killed here on a January evening. Luca’s mother Helen called the auther on a Saturday morning just after seven. She just said one thing: “Luca is dead”. After a birthday party at a club, Luca and his friend Freddy, both 16, got into an argument with another group of teenagers. They tried to calm things down.
But the situation escalated and ended with Freddy being pushed in front of an oncoming train. Luca was pulled along with him. It’s a tragedy that Georg Ballmann shares with Céline and Björn Wilke, Freddy’s parents. They all grieve for their two sons. In 2019, the police appeared at the Wilkes’ door early in the morning.
They said we should sit down. It was the worst sentence of author’s life, really just that one sentence: Your son died last night. And you’re sitting there at the table, you don’t want to believe it, but you don’t say “this can’t be happening”. It’s as if the earth is opening up and sucking your whole soul away.
That your whole world is collapsing. The day plays out like a bad movie and you don’t realize what’s happened. You call a few people and then you’re sitting at home. We were lucky that friends came to the auther very quickly and looked after them. The two families have an endlessly long and painful road ahead.
Stress and even crises are part of life. Nevertheless, many people stay mentally healthy. The question is how? The largest center for resilience research in Europe is in Mainz, Germany. Here, neuroscientist and brain researcher Professor Raffael Kalisch researches the mechanisms of mental resilience. What is mental health?
A schoolmate and close friend of her had a breakdown in the first year of his studies while she was having a wonderful time. To her it was all fascinating and great and new. And during that time, she watched her friend fall apart. And that made her ask herself: Why does it happen to some people and not to others? What are the risk factors for mental illness? The interesting thing is that it’s not just really big, extreme life events that can make people mentally ill.
It’s not just a serious accident, an act of violence, or the death of a loved one, but also minor stresses that can affect people if they occur frequently and over an extended period of time. What do those with resilience do differently? To find out, Kalisch is conducting a long-term study of healthy people who find themselves in a particularly difficult phase of their lives.
We take young people who are in this transitional phase from family and school to adult life, that are leaving a familiar environment. We see that in this phase of life, stress-related illnesses tend to emerge for the first time or, if they are pre-existing, become more severe. Every three months, the 200 participants in the study answer a questionnaire about their mental state.
To what extent have you felt more calm or tense in the past two weeks? Sitting on a packed train on my way home from work was a bit stressful. But in the mornings, I would occasionally just make myself a cup of tea and relax for ten minutes and then I was able to settle down. Because we do this every three months, we get a very good picture of stress levels over a long period of time.
So that we can see over that time how strongly they react psychologically to life’s challenges. Some are affected more, others affected less. And in the end, this gives us a picture of what mental resilience looks like when encountering stressors. At regular intervals, participants come to the institute for a thorough examination.
Kalisch and his team use MRI machines to look for indications of how mental stress is processed in the brain. And they examine how stress affects the body. To do this, they take blood and hair samples. We can measure the concentration of the stress hormone cortisol from a hair sample. One centimeter of hair typically corresponds to one month of hair growth, so the analysis of one centimeter, or in this case three centimeters, tells us something about the activity of the stress hormone system over the previous three months.
The results have been logged since the study began in 2016, so there is now a large database of information. Ultimately we want to understand what mechanisms people use to stay mentally healthy in the face of adversity. And once we know these mechanisms better, to utilize or strengthen them, especially in people who do not succeed in doing that.
The study in Mainz is due to be finished soon. Kalisch has already identified certain resilience factors one of which is how positively or negatively the participants themselves assess their stress levels. There seems to be a connection to optimism and the fact that people believe they can somehow cope, that it will probably work out somehow.
That seems to be connected to resilience, so someone who cultivates this kind of positive assessment style or develops it over time is less likely to be affected. So can we influence how resilient we are? Professor and Psychiatrist Marianne Müller is also conducting research at the resilience center in Mainz, investigating what makes some people particularly resilient.
I think this is promising in terms of better understanding psychiatric illnesses. For many decades, we’ve had only moderate success in trying to understand how psychiatric illnesses, for example stress-related illnesses such as clinical depression, develop. While psychiatric research focuses primarily on the clinical picture, the science of resilience is more concerned with healthy people.
Müller is first exploring the basics: What does resilient behavior even look like? With her colleague Ulrich Schmitz, she is investigating this in mice. Resilience can only be measured in the context of stress. That’s why they put small brown mice in the cage with a much larger and stronger white mouse. We take male mice, which, like all or almost all other male vertebrates, show territorial behavior.
This means that if you place a test mouse with a larger mouse in its home cage, the larger mouse won’t accept it and will try to scare or drive it away. This leads to social stress. The brown mouse is removed in order to prevent it from becoming injured. The experiment is repeated for 10 days. They want to know: What is the long-term effect of this permanent stress on the behavior of the stressed mice? After a day’s break, they undertake a second experiment: The brown mice are again exposed to the white aggressor mouse.
But this time the white mouse is in a cage. The researchers now observe the following: How do the previously stressed mice behave? Do they stay away fearfully? Are they brave enough to approach the white aggressor in the cage? We assumed that the mice were resilient if they always investigated the white mouse a lot, as if they had never experienced stress.
However, we thought this might not be resilience at all, but rather the result of a less than optimal learning process over time that the test mouse has not learned, has not understood that this white mouse strain is potentially dangerous. If that were the case, this mouse could not be described as resilient.
So is the intrepid mouse perhaps just too… dumb? The researchers investigate this question in a third experiment. Here, two large mice are placed behind bars in the cage: The aggressive white one and a brown one, with which the stressed little mouse has had no negative experiences so far. Our test mouse was allowed to freely explore the box, examine and visit the different social partners and interact with them.
And we were able to show there are mice that are able to distinguish between the white mouse, which comes from the aggressor strain, and the brown mouse, which is neutral and with whom it has not had any negative experiences. Is resilient behavior about being able to distinguish between threat and safety? We currently see a resilient mouse as a mouse that examines the brown mouse in a completely normal and unimpressed manner, but keeps its distance from the white mouse because it has learned that the white mouse is a potential threat.
We consider this a resilient behavioral phenotype. That means resilient behavior in mice doesn’t mean simply bravely confronting every impending danger but rather weighing up the situation and adapting behavior accordingly. This is directly transferable from mice to humans. There’s a lot of data showing that people who can distinguish between negative stimuli and neutral stimuli are better protected against stress and associated stress-related mental illness.
In this respect, we are also quite confident that we can use this to derive further neurobiological findings. Moving on. Finding her way back to life Céline Wilke tries to do this every day after the death of her son Freddy. I said goodbye for the last time on Friday evening, when he told me cheerfully. “Mom, I’m off.
I told him to have fun. That was our farewell. I can still see him in that moment. He was in a good mood, looking forward to the evening with his friends. And in retrospect, I’m glad that the last time we saw each other was really a pleasant moment and that we said goodbye to each other nicely without knowing that we’d never see each other again.
On the day of the funeral, the whole town mourned with the families. Luca and Freddy are buried together in the same grave. And then the whole congregation walked a good kilometer here from the church in a funeral procession. It was like being in a trance. And the burial itself, of course you noticed that there were a lot of people there,
but it passes you by and somehow you don’t really have any clear memory of the moment. And the funeral, it felt like this whole heaviness, this coffin with both of them.
Maybe there is a bit of religion in her after all. The physical part will be buried for now, but the emotional part, it will take a very long time before this wound is no longer quite so open. Munich. Here, at the Max Planck Institute of Psychiatry, neuroscientist Elisabeth Binder wants to find out: Why do some people remain mentally healthy despite severe stress, while others become ill under the same stress? One topic we researched was genetic predisposition.
Could it be that certain people are genetically predisposed to react more or less to stress and are therefore more or less at risk of negative effects later on, such as depression or post-traumatic stress disorder? Elisabeth Binder wants to know: Could it be a gene variant that alters our perception of stress? To find out, she is tracking down the hormone cortisol, an important hormone for our metabolism and immune system that’s also released when we’re under stress.
It’s regulated by something called the HPA Axis. When we experience stress, the brain is activated. This sets off a complex cascade of events. In the brain, stress signals are sent to the hypothalamus. This in turn releases hormones that make their way to the pituitary gland. The pituitary gland then releases its hormones to the adrenal cortex, which instructs our bodies to make extra cortisol to deal with the stress.
Cortisol allows all the cells in our body to flood with additional energy to aid the fight or flight response. Cortisol is our main stress hormone and it travels to all organs in the body. It’s very important that we are well prepared for a stressful event. Cortisol binds to receptors in our cells and that’s a good thing Because the receptors then report back to the brain: “Thank you! We have enough cortisol bound here now.
” The stress response is then switched off in the brain and we calm down again. At least when everything is functioning correctly. Many people are nervous at interviews, but normally, when the situation is over, our stress hormone levels should downregulate again. People with this particular genotype are not so good at this.
So for them, the stress hormone stays higher for longer. The question Binder asks is: Why is that? Why are some people not as good at calming down than others? And this is where genetics come into play. One of the genes responsible for our stress regulation is the FKBP5 gene. It is activated during stress and ensures that an important enzyme is released.
It has the same name as its corresponding gene – fkbp5 The problems start when too much of it is released Then the enzyme wedges its way between the stress receptor and the cortisol, and thus blocks the stress receptors’ message to the brain that there is enough cortisol. The brain is misinformed – it keeps firing and we can no longer calm down.
We think that stress causes too much of this fkbp5 to be released and that people simply release too much of the stress hormone after even the slightest stress. And we know that too much of this stress hormone in the long term is bad for many processes including in the brain, which also increases the risk of psychiatric illnesses.
The researchers have identified the FKBP5 gene as one of several important causes of our hormonal stress regulation. Variants in this gene could be partly responsible for why we react with more or less stress. The researchers are now looking for a way to block activity directly at the FKBP5 gene. And here at the institute, this has been investigated in mice that have been given this FKBP5 blocker whether they are more resilient to stress and are better able to cope with it to the extent that this can be measured in a mouse.
Psychotherapy is one of the most effective treatments anxiety disorders. What we don’t yet know is how it works in detail And based on our research findings, one possible mechanism could be working at the cell nucleus level Can we put these caps back on the stress genes with the help of psychotherapy? Domschke examines the blood of patients who are afraid of heights she climbs the tower of the Freiburg Cathedral with them every day for two weeks.
The patients did what we call exposure exercises, where they exposed themselves to their fear of heights So they went up the tower, had to look down and after the therapy we took blood samples again. And what we saw was that in patients with a successful response to psychotherapy, MAOA methylation had returned to the level of the healthy control subjects.
Domschke also obtained the same result in a study on psychotherapy. The number of test subjects is still too small to make a definitive statement, but the initial results are promising. So there are stress gene variants that we bring into the world with us, and yet we can have a major influence on our resilience if we manage to shape our environment consciously and well.
It allows him to stay active, and keep the memory of his son alive. At the Mainz resilience center, psychologist Michèle Wessa focuses her research on very practical help for people in crisis situations. She says that resilient behavior can only develop very gradually. It doesn’t work to develop training courses that somehow make people more resilient and more efficient within an hour and a half or even a day, which is perhaps what some people would like to see.
But what about the situations in life that we cannot change? I may not be able to change the actual situation that triggered the stress, but I can always change something about how I react to the stress. And I think it’s really important that I learn for myself that although I don’t always have control over the stressor, I do have some control over my reaction to it.
Remembering the successes, trying not to judge experiences too negatively, staying active despite adversity – these are key factors for resilience. We’ve learned a lot. I understand the term now, and know more about the topic of resilience.
We also learned how we feel and that we can influence what is happening inside of us: our fears and how we can fight against them. And yes, it was a great experience. We can equip ourselves mentally at an early age to cope better with crises later on, which we will all experience in one form or another. But to what extent does being resilient also mean social pressure to self-optimize to be ready to perform at all times? Resilience simply means finding ways to deal with stress.
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