Raül Andero, neuroscientist: “Mental health drugs are not very specific, like speeding up and slowing down at the same time” | Health and well-being

An accident, the loss of a loved one, or any serious extraordinary event leaves traces in the brain that can be permanent. Neuroscientist Raül Andero Galí, born 42 years ago in Mollet del Vallès (Barcelona) and member of the Catalan Institute for Research and Advanced Studies (ICREA), analyzes the consequences of acute exposure to strong stressful stimuli (traumatic stress), which can change the volume of some areas of the brain, hormones , including sexual (testosterone and estradiol), and the behavior of some genes or proteins. Understanding the long-term consequences of such a distressing event, which can even lead to changes in the memory or learning process, is the first step in developing a treatment. This is the goal of the research laboratory (Andero Lab), which received Leonardo support from the BBVA Foundation, awarded with up to 40,000 euros per project. Total support since the creation of the program in 2014 amounts to HRK 20 million.

Ask. What causes traumatic stress?

Answer. Exposure to situations that may threaten our lives or the lives of our loved ones: a traffic accident, for example, or war. The stress caused by going to work or traffic jams, which are stressful situations but not traumatic, would not be traumatic. The one we study is always generated by external circumstances, the environment and our interaction with it, events and actions that can have very serious consequences and put our lives in danger. It could be because of something we did wrong (such as using drugs and driving) or because of someone else.

P. What effects does it have?

R. There are countless of them, especially in the field of hormones. The body releases hormones due to exposure to traumatic stress (cortisol is the most well-known), but there are also changes in the neurochemical signals that neurons exchange. For example, the neurotransmitter glutamate is released in unusual ways and can change the way neurons communicate long-term, over months, years, or even permanently. There are also changes in the brain or in the regulation of the menstrual cycle. Even a decrease in the number of neurons in areas of the brain has been described. New changes in the brain caused by traumatic stress are being discovered every day.

P. Is it all a pity?

R. When we talk about traumatic stress, it is by definition negative. It should be noted that most people exposed to this trauma can usually resume a normal life after a few months. But there are people who never can. This is where we need new treatments to prevent those who have been exposed to traumatic events from experiencing these effects and being able to resume normal lives. It is not about forgetting the traumatic event, but about reducing its impact on mental health.

P. How do you research brain damage after traumatic stress?

R. We are working with animal models and also with human studies to try to understand how traumatic stress changes memory neural networks. When someone is in a car accident, the memory of the event is very strong: there are usually nightmares or nerves when getting back into the vehicle. This happens because this stress has changed the memories we associate with the car and the accident. What we want to investigate is how stress and memory interact and how to bring pathological levels of interaction back to normal.

Fear is necessary for the survival of mammals and has not changed much with the evolution of the species

P. How does an animal study translate to humans?

R. Our group is a pioneer in Spain in the study of markers that are found in animal models and also exist in humans. Obviously, a lab animal is not a person, but they are both mammals and there are many processes that work the same, such as fear memories associated with stress. We exploit this similarity to study generalities such as genes that act in similar ways in the brain or hormones. Fear is necessary for the survival of mammals and has not changed much with the evolution of the species. We can conclude this by studying behavior and doing more or less similar tests on people, combining the results and finding many similarities.

P. But don’t humans have a pre-traumatic stress biomolecular record to analyze the changes?

R. An ideal experiment would be to have many variables before and after the trauma to compare what is happening. With animal models, we try to solve this limitation and, in humans, we study patients who went to the emergency room after, for example, a car accident or a sexual assault. If volunteers come forward, we look at many variables. A few months ago, we discovered that the timing of a woman’s menstrual cycle at the time of trauma does not play a role in the development of post-traumatic stress disorder. It is very complicated to study and we were one of the first groups to point this out. One of our theories is that it doesn’t matter if there are spikes in estradiol during the menstrual cycle because traumatic stress is so brutal that it’s like a train going down a track, whether or not there’s a car on it.

P. Is the goal of scholarship research to manipulate and disrupt stress-affected elements?

R. The fundamental goal of this Leonardo scholarship is to understand molecular mechanisms. We will focus on an enzyme that is synthesized in both humans and animals by the Ppm1f gene, which we discovered and is associated with traumatic stress. What we do is we manipulate it, we delete that gene in adulthood and see if it prevents the effects of traumatic stress. We will also use MINISCOPES [visualización in vivo de corrientes de calcio con microscopios mimiaturizados] monitor, in the brains of laboratory animals, between 200 and 400 neurons. We can see live and direct how memories are created. This is fascinating because we can investigate what changes we can induce to reduce the effects of trauma and, understanding all this, we could transfer it to humans, since we work with this gene in mice, but it is also important in patients with post-traumatic stress disorder.

In laboratory animals, we eliminate the function of genes so that there are no consequences of traumatic stress or they are reduced. This could help find a cure

P. Manipulate the genome to avoid the effect of a traumatic event?

R. We do it on laboratory animals, of course. It is not ethical in humans and cannot be tolerated. But in laboratory animals, we disable the function of the gene so that the effects of traumatic stress are absent or reduced. This could help find treatments, drugs or therapies that affect the expression of this gene in humans. The way we see it, it’s about identifying which gene or receptors are important, and then other specialist groups can find therapeutic targets. We can direct you to where you can find appropriate therapies.

P. Could there be a post-traumatic stress pill?

R. The general idea would be to combine psychotherapy and pharmacology. Medications currently available in mental health for non-neurological psychiatric disorders are anxiolytics to treat anxiety and antidepressants. These drugs target receptors that are expressed almost everywhere in the brain. Sometimes they work, and sometimes it’s like driving a car and pressing the accelerator and the brake at the same time. The drug activates one area and inhibits another, because the receptors do different things in different areas. They are not very specific. This does not mean that you have to make changes in your treatments; You have to keep doing what your psychologist or psychiatrist tells you. What we want to develop are drugs that, for example, are more targeted at the neurons and areas of the brain that we want, rather than the whole brain, as is often the case with the drugs that are out there now.

P. Could there be specific treatments for different types of traumatic stress?

R. I think that’s a long way off. We still don’t have an effective treatment for treating traumatic stress. With finding something that is more efficient than what we already have, we would sign.

For everyday stress, I always recommend a very healthy diet, exercise, meditation and above all avoiding drugs

P. And for exact non-traumatic stress?

R. I am also very interested in this daily stress as it can have very detrimental effects on mental health. I always recommend a very healthy diet, exercise, meditation and above all avoiding drugs.

P. Why did you become interested in stress? Is it a disease of today’s world?

R. My interest in traumatic stress stems from the fact that it is the only psychiatric or psychological disorder that occurs as a result of a single event. Schizophrenia is not well known when it starts and there are people who do not know when their depression started. Instead, in PTSD, you know that the accident happened, the day and the date. I am interested in this because we have a great therapeutic possibility, treatments can be done.

P. Can stress be measured?

R. There is no one-size-fits-all method, nor is it worth measuring stress hormones alone. The most famous is cortisol, which prepares us for action. But there is no single stress hormone. Cortisol administration is being studied to prevent traumatic outcomes, but it will not be that simple because it is not the only factor; there are other genes, neurotransmitters and neurochemical signals.

P. A supply of stress hormones to combat it?

R. Yes, it is so paradoxical. One might expect it to generate more stress, but we already reported in 2018 that it reduces some of the harmful effects of trauma in animals. The mechanisms are still being studied.

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