Like every Israeli, Alon Chen had to do three years of military service, and was posted with the paratroopers to the middle of the war in Lebanon. “I lost a friend. When you go and you treat the person that is injured and is dying, and you cannot help him, it leaves its mark,” he recalls. From then on, he knew he wanted to dedicate the rest of his life to understanding what happens to a brain that suffers a traumatic experience.
The son of Moroccan Jews who emigrated to Israel in the 1950s, Chen is the first generation in his family to go to university. He received his PhD in neurobiology and spent time in the United States specializing in the effect of stress on the brain at the molecular level. He currently leads the Weizmann Institute of Science in Israel, one of the most prestigious research organizations in the world, as well as a center studying stress-related mental illnesses run jointly by the Weizmann and the Max Planck Institute in Germany.
Speaking ahead of a recent lecture at the Ramón Areces Foundation in Madrid, Chen asserted that society today exacerbates depression, anxiety, bulimia and other diseases that we do not understand properly. These conditions are treated with the same drugs as 50 years ago, which do not work on one of every three patients, he added, amounting to a modern mental health crisis.
Question. You study the effect of stress on our brains at almost a molecular level. You cannot get into people’s brains, so how do you approach your field of study?
Answer. The best model for humans is other humans, but unfortunately, we cannot take out [live] human brains. We can image the brain, we can do blood tests and learn a lot, and we can use post-mortem brains. Stress eventually causes and affects many, many pathologies, like depression and anxiety. We do have access from different brain banks, for people who [died by] suicide, for example, because of depression or some other reason. So we do have human brain samples, but first, we use animal models.
Q. Isn’t animal and human stress very different?
A. We think the same genes, the same proteins, the same brain circuit, the regulatory response to stress exists all the way from fish to humans.
Q. And what does that response look like?
A. It’s a survival response. You know, if I’m sitting with you here now and a lion enters the room, both of us perceive the lion as a challenge, as a stress, as a threat. The brain will activate what we call the central stress response. It’s a response which will activate the entire body, but also your brain, which will cause a cascade of events. You will have your heart rate increasing and your blood pressure, glucose level, your respiration. It doesn’t have to be a lion by the way. You can just now get a very, very upsetting phone call. Any psychological stress.
Q. And why does all that happen?
A. Your brain will prepare your body to escape, and that is the reason it’s increasing the glucose level because you need energy to escape, of course. But your cortisol level, your stress hormone will go high, and cortisol has many effects on the brain. Also within your brain there are a lot of changes. Your cognition will change. You will remember this event very well. You are going to have changes in your area of the brain which affect your attention, focus, your appetite. You don’t need to think about your lunch now and you don’t need to think about sex. Almost every major brain region will change its activity because of this lion. And collectively, all these systems will go out of balance, out of homeostasis. It’s a normal and healthy response because you want to survive this. However, if we activated all the systems and we survived the challenge or the lion just left, the system has to switch off. Part of the stress response is not only to activate. The response is to switch off, and the people who cannot control this may develop stress-related disorders.
Q. What are these disorders?
A. Not only psychiatric disorders, not only depression. We all know about depression and anxiety and post-trauma, and eating disorders, but also metabolic-related [disorders], you know, Type 2 diabetes and obesity. But the question is why? Why is someone who is exposed to chronic stress or the traumatic stress of a bomb blast, a rape, an accident, why do they develop trauma and not less importantly, why are other people resilient? In the last 50 or 100 years, scientists were mainly busy asking why someone is sick. However, the majority of the population are resilient. So what we try to do now is ask why?
Q. Do you know how they manage to stay resilient?
A. The mechanism of resilience is not the opposite of the mechanism of being susceptible or vulnerable, so if you have a gene that makes you more susceptible and this goes up, it doesn’t mean that if it goes down you’re more resilient. Resilient [people] also have a different mechanism, or a separate one, that if you can study them, we can mimic them, we can copy them and help people.
Q. Is the predisposition to become ill from stress genetic?
A. We know that these diseases and disorders have a genetic component. We see it in the family tree. This is what we call genetic predisposition. Most of us carry a genetic predisposition to something, for depression, Alzheimer’s, cancer. If I just look at mental health, you can see that schizophrenia has a much stronger genetic contribution, 70% or 80%. Depression is probably less: 40% or 50% genetics. So how come you develop a disease or not if it’s 50%? It’s the environment. The environment is everything you drink, you eat, you smoke, you breathe in. Stress is the most significant factor that affects it, which will eventually interact with your genetic predisposition and will determine whether you develop a disease.
Q. Could you provide an example?
A. If you have an identical twin from the same fertilized egg, meaning both of you inherit the same genetic predisposition, but you were separated at birth and you grow up in Madrid in nice neighborhoods and your brother grows up in a war zone, in a very stressful environment, the chance he will develop depression or post-trauma is significantly higher. You have the same genes, so genetics are important, but the environment is no less important. Your environment can come out at a different time of your life, so you can be exposed now as an adult to stress, as a teenager, as a young kid, as a baby and even as an embryo, meaning that your mother was the one who was exposed to stress and she transmitted some signals to you while you developed, and made you more or less susceptible to develop disease later in life.
Q. What happens when you suffer stress very early in life?
A. You can have a totally normal life. Normal childhood, teenager, high school, not a problem. And then suddenly you have a trigger. And this trigger could be anything. A trauma could be rape. Trauma could be, you know, you lost someone you love. It could be just an accident. Something you experience could be war. It can activate this embryonic signature and suddenly the disease is floating.
Q. Can you identify those genetic markers yet?
A. It’s what we call epigenetics. Epigenetics are chemical modifications on top of your DNA. And the environmental signature is in this domain, in this epigenetic mark. Today we can measure epigenetic markers, and we can sequence not only the DNA, we can also sequence your epigenome, not only your genes.
Q. Can you identify which people are most at risk for stress-related diseases?
A. We are not there yet. In other fields like cancer, for example, women that carry mutations to a gene called BRCA1, well we know the chances those women will develop breast cancer are significant. So this is a genetic predisposition to develop breast cancer, or depression, or anxiety, or schizophrenia. But this is exactly where research is being done now. Maybe in the future before we send soldiers [to war] they will screen their genome or even epigenome and tell them no, look, they are prone to develop trauma.
Q. You often say that today’s drugs for depression or anxiety are the same as they were 50 years ago?
A. The majority of the available drug treatment today is based on a very similar mechanism discovered more than 50 years ago, which is fine if they are working. The problem is the efficiency of SSRIs or selective serotonin reuptake inhibitors like Prozac and others: you still have 30% to 35% of patients not responding to anything. And when I give you the treatment, you need between five to eight weeks usually until the drug even starts to be effective. Some of them have major side effects, from migraine to sexual dysfunction, so people prefer not to get treatment. So we definitely need new solutions, and that will only come from understanding the brain.
Q. How close are we to being able to mimic these genetic mechanisms of stress resistance?
A. There has been major progress in the last decade. We still have a very long way to go because a disease that is composed of genetic predisposition is very complex, not from a single gene. It’s not a mutation that causes blindness or deafness, it’s many, many genes and interaction between those genes, and then the environment. Your depression and my depression could be totally different depressions. You may have the same symptoms, but the underlying mechanism for depression could be totally different. So we may end up having 100 different types of depression. So we first need to start with better diagnostics.
Q. How has the pandemic affected society’s stress levels and mental health?
A. We all talk about the physiological, clinical symptoms and how people are suffering from [Covid-19] infection and that’s very, very important. But when this pandemic ends, we won’t see those people anymore. But you know what will happen? We’re going to continue seeing people who develop trauma and depression and anxiety because of the pandemic. You go now to a psychiatric hospital, and they are loaded with people. They cannot cope with the pressure. The number of depressed kids, young adults suffering from trauma because of lost jobs, lost businesses. The impact of the pandemic on mental health is already huge, but people don’t talk about it enough and it’s going to stay with us for years after this pandemic.
Q. What does work against stress, besides medication?
A. Probably the most scientifically proven approach is exercise. Exercise is the best way to cope with depression and anxiety. You don’t need to run a marathon or be an Ironman, just any type of combination of aerobic and anaerobic activities. The majority of the population that suffers from depression can still do those things. They can go and do something that they feel is making them feel better. I have a very stressful work life but I like the sea, and I do sea kayaking. Three times a week I wake up at 5am and go to the sea. I do 10 kilometers, or I like to work in my garden. The pandemic taught us how critical this is, and we are very social organisms. We like to be with people, we like to kiss, we like to hug, we like to be with partners and therefore not having this is affecting you. Meditation is another scientifically proven practice. It doesn’t work for everybody, but it works for many.
Q. And how can you help those other people?
A. You always have to remember that we have that fraction of people who are very, very sick, and you know, you can take 10-year-old kids, even six sometimes and the only thing they want is to die. Right? Why does a six-year-old go into the playground slide and want to jump head down because she wants to die? This is something in the chemistry, the electricity in the brain that is not working, it’s a brain disease. We need to stop thinking about mental health. There is a soul, but this is your brain. I can put electrodes in your brain and I can make you more anxious or less anxious. It’s electricity and chemistry, and we need to understand this. And we need to educate the public that mental health is a disease like any other disease, it’s like cancer or Alzheimer’s. So we need to educate the public about this.
Q. Israel has been in conflict with its neighbors for most of its history. How has this affected citizens’ mental health?
A. In Israel, every few years we have tough periods with conflict and missiles and sirens. In a way, there is some resilience in the population. And I think this is one of the reasons Israel was very good at handling this pandemic. We were extremely organized. The system is organized for emergencies.
