Was macht Stress mit unserem Gehirn?

Good evening, ladies and gentlemen, we warmly welcome you to today's conference as part of the Studium Generale. My name is bankrupt or I am irritated by the physicist and I am pleased to present to the speaker today's lecture, a broader one, as you can see, it is about the human brain. And this is a topic that is now being investigated in many places with a great research effort. An example is a large research project in the European Union, the Human Brain Project, in which several hundred research groups work together with a budget of around one billion. euros and the objective is to discover how the brain works.

How a structure works, perhaps even approaches can be used for a new type of computing. New York computing, that is, computing based on or similar to how it is believed to work in the brain and in this way you have an alternative to current silicon-based computers. The basic functions of the research in which Prüssner has participated do not go in this direction, but they are no less important and, in reality, they affect each of us differently. In this case, each of us is exposed to

stress

. As a physicist, when I think of

stress

, I first think of it as mechanical stress or tension, but I think in your case the third head or brain is not caught between the two. pollutant but is exposed to psychological stress.

Mr. Brussels holds the chair of clinical neuropsychology at the University of Konstanz and has been here for a year. He is Professor Albert's successor because we may know something about you and we have already given a lecture. this semester with two representatives from Konstanz Freibad and Mrs. Holzinger and we will also have more lectures from various groups here at the university. We take advantage of this opportunity to show you only what is being done internationally, but above all what is being done. What has been done here at the University of Konstanz in terms of cutting-edge research brings me to Mr.

Christ's scientific career. He studied psychology in Trier and did his PhD there, then went to Canada to Montreal as a postdoc and had a lot of studies. Success there People loved him, so he was promoted from Rostock to assistant professor and, as I said, about a year ago he was transferred to Konstanz. As I said, he is the chair of clinical neuropsychology and is involved. in studies of the experience and behavior of the central nervous system. Today he will report on his concerns and extensive experiences. I look forward to his talk. It was a good afternoon for everyone. here today and to be able to tell you a little bit about my research topic on stress in the brain, which I said in the introduction.

I have been here at the University of Konstanz for a year, but I have not dealt with the topic of stress in the last 20 years and that is why I have tried to summarize a little what there is to say on the topic, the interesting thing is what maybe a little tense. I go into the depths of science, but I was told that I can find as varied an audience as possible here, so I try to convey the content as stress-free as possible and that everyone can follow me. In the end, I think we also have the opportunity to discuss it broadly.

So I hope we can. We will then discuss any questions that may arise. That is what I would like to address with you today. We will start with a definition of what stress is. How can it be classified and categorized? The biological effects of stress are particularly interesting to the researcher because they have a lot to do with what happens in the brain. I would like to observe the consequences and consequences of acute stress on the brain. the effects of memory names that I have treated and that I would like to tell you and on the other hand, the effects of activation of the different brain structures that react in a certain way to stress, these are the imaging studies that I have performed Especially in the Montreal topic and depending on how much time is left at the end, I would also like to address the chronic effects of stress on the brain.

There is the still very well-known toxicity hypothesis, of which I will speak a little critically. and finally with the development hypotheses. On the subject, it has already been said that stress is a term that originally comes from physics and mechanics. It's about how much stress you can put on a body before it breaks, but I find that to be the meaning. The term is relatively clear when it comes to stress in psychology, if we imagine that we are or are stressed under stress and we can break down under certain circumstances if this can lead to stress-related illnesses such as exhaustion, depression or chronic exhaustion. , which would be important to me, the connection is there.

We will immediately differentiate between stress and stressor so that we can then take home what the difference is and how it can be defined and then I would like to give you different examples so that you can then associate the terms of stress with things that we encounter in everyday life; on the one hand, I think that an acute threat like an attack by a wild animal or a person is certainly something that is full of stress, on the other hand. It is a test of what you have to do in school or university. There is something about passing that is perceived as chronic stress, but in comparison there are also things like constant time pressure because you are constantly chasing your deadlines or having an illness. that you suffer and that accompanies you constantly, but also things like grieving for the loss of a partner or a family member or the worry that something is going to happen, all of these are things that can cause us stress and put us in a state of stress. .

Now I would try to illustrate this a little with a small movie and make it clear to us that I hope that now our body's reaction to stress also works well. It's an ancient mechanism that has been powering our ancestors for over a million years. It was the basis for survival when threatened, so here is the example of the sharp attack of the mammoth, which then appears unexpectedly and puts you in a state of stress. I think the other thing that was important to her was the message. that our stress system is something that we basically bring with us from the beginning of human evolution, that it is one of the oldest systems that we have in our brain is still very rudimentarily anchored there and can immediately take over if we are in an acute state. of threat.

In the second clip, a little of the connection with the present and a small representation of what tends to stress us these days. We all face stress and it is often unavoidable. Stress arises when we do not feel well. Faced with life's challenges, the lack of support in the social environment, the pressure of deadlines at work, as well as financial and health problems, can cause excessive demands. The feeling of not being able to adequately meet the expectations placed on art arises. to the high level of responsibility, so I think that's what we can all do with something and the expectations of no longer meeting the demands that are placed on us is, I think, almost something that a lot of people can relate to when they say it. .

Disappointing someone, whether at work or in your private life, is something that creates tension in us, which we can definitely call stress. Now we can distinguish between stress and stressors. The stressor is the event in the environment or environment. organism, for example in the case of diseases, that is, now it is not something that comes from the outside, but something that occurs within the organism itself and that results in a response to stress and, in comparison, stress is the response not body specific. to face this stressful situation to face this stressful situation to face this stressful situation To be able to face the situation and to be able to adjust it At this point I would like to briefly explain to you the.

Rathaus and Volkmann's theory when a situation is actually considered stressful and because it can be categorized as something else and saved: this is the so-called stress appraisal theory that Lazarus and his followers presented in 1984, where it is said that with each When it arises a new situation, there is an immediate evaluation that we make that decides whether we classify it as stressful or not. In English, this evaluation is received as Tracy and is the decisive one. The elements in this theory of the street press are primary and secondary. present that takes place, that is, a first immediate evaluation of the event that flows towards us and then a second additional evaluation and this first immediate evaluation that is related to how I evaluate my own feelings, possibilities, resources and abilities to face this situation that is coming. towards me and that is really a comparison in which you say that if I believe that I have more skills and more resources than what this situation now requires of me, then I can handle it well, then I am not stressed and you can also show that the bodily reactions that can be observed under stress they do not occur, but if this comparison ends in such a way that you say yes, I cannot master it completely, so more is required of me than I can handle. capable of accomplishing, whether they are physical or psychological tasks that are presented to you, then the alarm system is activated and you say I can't do it and the body activates the stress systems.

There is already the transition to the biological system where we get there. for the moment but this primary evaluation leads us to see something as a threat or as a challenge threats when we don't have the resources challenge when we say yes, that can be exhausting but I can do it, it can be done and in that case, I can deal with that. I have to deal with how I do it and what steps are taken next. This comes in this second assessment step in this secondary presl where I then look at what resources, behavior and copying strategies I have available to me. willingness to face this situation.

Now I have already said that this will come later. This also results in biological processes and we will see them below, but now one last example of what stress is to transmit this again and transmit the. a whole range of stress possibilities for you, which is why there is an entire website about it that discusses nothing more than workplace hazards and how they can cause stress. Whoever is interested in it www stationary es bed dot com. He also gives other examples, but I also think it's understandable that then the person is certainly now in a stressful situation, his dress is now full of coffee, the work he tried to finish there and then maybe send it out has to be redone.

Maybe he spilled coffee on himself, maybe he hurt himself falling on the chair from behind, I think. This is clear if we now look at the biological effects of stress or ask what they are, then we can distinguish between effects on the brain. and in the body I think the most important body effect is actually the energy supply, so now it is immediately understandable when we say that this is a stress that the body has to deal with, then it makes sense that as an immediate consequence the body. It then activates your energy systems to provide more energy so you can cope with this stressful situation.

Adrenaline comes from escape behavior, no doubt something many of you have heard about. Cortisol is perhaps less known but is now also relatively widespread. the hormonal system, which is then supplied as a hormone through the adrenal cortex and has long-term metabolic effects that can also be understood primarily in relation to energy supply if we look at this hormonal system. If we take a closer look at cortisol production, the hypothalamus, pituitary, and adrenal axis, we can illustrate it with a diagram like this. At first, a stressor is something we perceive as a burden. in the central er system of the brain that we will now talk about repeatedly, so if it were there, it would be important to me that we convey it directly from the beginning.

That is, the hippocampus is a structure in the temporal lobe that has. a lot to do with memory. The contextualization of the location of the situation in space and time where this has ever happened to me, what memories, what other associations do I have with this situation and is it also part of the limbic system and does it play? an important role in the perception of stress and in this. Deciding whether something is considered stressful or not due to activation of the hippocampus leads to activation of the hypothalamus, which is our central switching point for mediating neural and endocrine effects in the body which sends more hormonal messages to the pituitary gland.

From there another hormone is sent that finally reaches the adrenal cortex through blood circulation and which, in addition to racing, is the one that then produces and releases cortisol and which is also interesting and important for our subsequent reading or understanding. Due to the effects of stress, cortisol is a steroid hormone that can return to the brain. Therefore, it can cross the blood-brain barrier and, unlike many other hormones, can find receptors directly in the central nervous system. The brain, where other effects are triggered in relation to the hormonal axis that we have described here is the e media effect.of cortisol in the brain, which causes it to shut down, so it acts on the hippocampus, hypothalamus and pituitary gland with a negative feedback loop to stimulate additional activity of these structures to reward and suppress so that no more cortisol is released from the adrenal cortex, very elegantly worked out by mother nature, the axis shuts down, so to speak, on top of that, that came from the escape behavior, the adrenaline system that comes from the adrenal gland, the adrenaline here at the right is our HP axis as we just saw in the diagram on the left just a rough overview of our autonomic nervous system with the sympathetic and parasympathetic nervous systems and the sympathetic nervous system is something that is directly affected when we are very stressed and then within seconds there is a strong release of adrenaline from the driving side and that is really interesting in the combination because the adrenaline system is immediate in seconds, while cortisol takes much longer, minutes up to 20 minutes, in reach maximum circulation in the body, which means they also relax a little.

We have that sharp energetic effect and then the. Cortisol delays the effect, which is briefly summarized in the clip to summarize these biological effects before continuing. In response to a stress impulse, the emotional center instructs the body to produce stress hormones. The adrenal cortex mainly releases adrenaline and cortisol, as a result, blood pressure and pulse increase, blood flows to the muscles of the arms and legs. Unnecessary energy consumers such as digestion are interrupted, pain sensitivity is reduced, all of this serves to overcome the threat. Whether fleeing or fighting, the body reacted with relaxation a long time ago.

The so-called hippocampus in the brain plays a central role, instructing the body to slow the flow of hormones. Now let's summarize the biological effects. I think that was also understandable, at least I hope so, and now we will look a little at how we can work with stress in research in the laboratory to better understand what stress does to our bodies and the first question that plays an important role . Its role is how we can actively work with stress, as we do, we can induce stress to then examine the effects of stress on the brain, but also on behavior and it was said that yes, I am originally from Trier and my father is a doctor there, Clemens Kirschbaum. , developed the so-called Trier social stress test together with the big hammer in 1993.

Well yes, I would say that it has become a leader in stress research, it has also been used in a large number of experiments around the world and It consists in five minutes of free speech in front of a committee followed by five minutes of mental arithmetic in front of this committee. It is not said that you usually still have to do mental calculations and the speech you have to stick to is typically something. For which you have very little time to prepare. 5 to 10 minutes in advance they tell you what topic this speech should be about.

This can be a fictitious job interview for an effective job advertisement. And he's usually not very well versed in it. the content of this position, so you quickly become embarrassed and can no longer present yourself very well, and that is something that is full of stress. Here's a little clip to illustrate it like this. Does it work once? service of science and that it was not entirely calm if she believes me in a few seconds Berlin Charité University Hospital in the heart of the stressed capital, I become part of a scientific experiment of exhaustion is a little different Presented what you want now .

In my sport I like to test saliva to detect the stress hormone, cortisol, and then we can see how much your body reacts to stress. The saliva goes to the test and I go to the so-called stress test. You want to get a salary increase there. There are the numbers you said. That's how compelling it is, it's disgusting. I don't want to do anything with a microphone in front of the camera and the panel extremely warm. Now I have to present my advantages and in the end I can. Don't think about anything relatively quickly Yes, that's pretty typical and representative of this test.

The committee sits stone-faced and gives no feedback on whether you are performing well or poorly and why you haven't prepared. For the topic, you usually lose your mind relatively quickly and then report this silence to the committee. You look at you, you look around, you don't know what to do next, at some point someone from the committee says you still have time, keep talking and of course that is often perceived as additional stress. There are now many studies that have strived to discover what is really stressful about this stress test, why it is something that our stress systems seem to react to.

Dickerson would never have contributed to this with such power and with such force and would have contributed to this and introduced the concept of socially motivated threats and in Principle he argues that a physical threat from a wild animal attacking us is just as important to our survival. as a threat to our survival. our social status and evolutionarily I think it can be understood that if we were part of a community, part of a group and the group was essential for the survival of the individual, the threat of exclusion from the group's editorial team can lead to our being at risk. survival and this threat to social status is something we still feel today when we are in any situation where we are psychologically social.

If we have to do something, we run the risk of looking bad in this evaluation of others. So if our performance in the group has something to do with the status we have then, it could lead us to come out worse in our status than we came in here and I think that has parallels that you can also imagine, for example, talking about. freely in front of a large crowd is something that normally leads to a very strong activation of the stress systems; it just happens because, of course, there is a danger that at some point you will lose a thread, I no longer know what I should say or you lose your voice and that, of course, would be perceived as extremely embarrassing because others would judge you socially poorly.

This fear of speaking freely is certainly something that is related to this and this test, which also works through the camera. recordings and the microphone is so robust that you can also make it virtual. There are now over ten studies that have shown that if you simply put a person in front of a virtual audience, the virtual audience is not real people but just a computer. generated panel that this stress response always occurs That is still there, that is, even though everyone knows that these are not real people who do not really evaluate you, this response still appears.

This is an image to illustrate, first of all, which one. Systems react and secondly, it is this social aspect that plays a role. Here you can see on the left side of the image the cortisol response over time in minutes in relation to the onset of stress. This gray bar here is stress and you can. See that with the onset of stress in the tsc the cortisol starts to rise and then about 15 minutes in the case after the stress starts it reaches its maximum and then slowly goes back down, that was the original tst with the committee from which You have to do your act.

If you compare that to a situation where people have to do the same thing but without a committee, that means you have to give a speech, you have to do mental calculations but there is no one there, you do it practically in an empty room, then you can see. that the cortisol stress response is almost gone and here the heart rate is significantly reduced, which could also just be something to do with it. Having to get up and get up alone is somewhat stressful for the cardiovascular system and compared to the third control group. , basically nothing has been done now, but these ten minutes of stress are just standing there without talking and without having done the calculations, you can still see a slight cardiac effect but there is absolutely no cortisol effect anymore, so I think That's really clear. indication that it is this social component that triggers stress, which we ourselves have examined in numerous studies.

Here is another image to show how this response occurs on all systems. On the one hand, here's cortisol with the stress response. Measured every four minutes after stress begins, it peaks and then drops again. Family as Another mark for the autonomic nervous system rises and peaks during the stress response and when the stress response ends, it rises immediately. down again In this area shown below you can see the heart rate variability or period as we have called it here. Then there is also a significant reduction in heart rate mobility. On the one hand, this is due to the fact that when the.

Heart rate increases, less variability in heart rate is possible. On the other hand, this is also related to a shutdown of the sympathetic system, which is also observed in relation to stress. I think I can illustrate it very well with this example. acute effects on energy systems, autonomic nervous system, sympathetic nervous system and green system, HPG axis with cortisone or HNA axis. Now let's look at what acute effects activating these systems has on memory and. There is a story that they can be positive or negative. Acute stress has effects that promote or harm memory. This depends, on the one hand, on the moment in which the stress occurred and, on the other hand, also. depending on the type The function of memory is where we will get to it in the second step.

Now, first, the question of time. There is the message that cortisol improves the storage and consolidation of information and then you can imagine this in experiments of this type. So if you do a memory task where you memorize something, there must be words or objects in the room or images that will then be retained better if they are constructed with stressful content, so if you send the person to this memory test social stress beforehand or the content itself is stressful, this will lead to better storage. Consolidation and retrieval of memory content occurs, then an increase in the ability to remember can be observed compared to a neutral or non-stressful situation filled with learning content. then you see a not so strong consolidation and then in retrieval you also see a lower memory performance, which was also the case.

It has been shown in a variety of experiments and that this has mainly to do with cortisone is illustrated, for example in this 2013 paper by Stapler and his colleagues were able to show that in their case delayed recall is associated with delayed retrieval of things previously learned. So the stress, then the stressful situation, is associated with better memory and the really crucial thing is that the amount of cortisol, the cortisol that we have that was released as a result of this stress correlates with memory performance with recovery of these memory contents, suggesting that actually, depending on the amount of cortisol, this content was also better retained.

Another study that I found very interesting in relation to the preparation for today's conference, so I wanted to present it briefly in relation to that. It is generally the case that when you are preparing for an exam, for example, you are not stressed while you are studying for the exam, but you are stressed when the exam takes place, which means that it is actually completely incorrect for you to say that stress should occur when In order to benefit from this effect, you learn that activating stress systems during enco has a positive effect and in fact there are studies that said what we can do and they put people on the treadmill while people had to learning vocabulary, swimming, walking, ringo käppele qualification improves golden globe memory and they were able to show that this. it actually leads to an improvement in learning content.

If you look here, it's the memory performance while they were on the treadmill and learned their vocabulary and on the right is the memory performance when they did it in a relaxed, stress-free state, so you can see that the performance is better here. and here again this connection between the individual release of cortisol and memory performance number of memories words positive praise here too, that is, the more cortisol was released when they worked very hard on this treadmill and then appropriately activated their stress system , then This would also lead to a significant increase in learning performance.

Therefore, it would be said that everyone who has to study for exams or has yet to prepare for exams now knows how they can improve their memory performance. home and place the book on top when you get it back. Now it seems to be exactly the other way around, if we put stress before the situation just before the actual test situation or the recovery situationreal memory, then you can see very reliably and with effects that are much stronger that the memory performance decreases, which means that then we are. In fact, that's why the advice is exactly wrong in normal life.

We should stress when we are learning and not when we have to. remember it, but we are usually not stressed when we are learning but rather bored and very stressed when we have to remember it. There are also many findings about this in the review, but here also the only example is a study by a former colleague of mine, Oliver Wolff, who is now in Bochum, where it could be seen that when cortisol is present, explicit memory performance is reduced. significantly reduces and also that the amount of cortisol is associated with the number of words recorded, that is, memory retrieval and now it is a negative praise that means that the higher the cortisol, the lower the memory performance.

The second point that he wanted to make and what he had promised now was the connection with certain forms of memory and the crucial thing. is that it is limited to one type of memory, that is, creative memory also has episodic and semantic distinctions, but that is crucial because it is mediated through the hippocampus. So this structure that also carries out stress regulation in the brain is also inhibited by incoming cortisol, meaning it only has something to do with reduced memory performance and other forms of memory in implicit conditioning. or skill recovery seems to be affected by it.

Being calm, stress has no measurable effect, so far, suggesting that it is actually closely related to this structure in the brain. This is also the transition to the activation studies that we have been working on, especially in Montreal, where our goal was to investigate what acute activation or deactivation. effects that we can see in the brain when we subject people to acute stress and the first difficulty was finding means to be able to do this in the imaging study, which is typically an imaging study in which the person disappears into the big machine where you can no longer see people, the person does not see anyone else, so the door closes and then the device turns on and there is a lot of noise where you have no possibility of putting a committee in front to seat the person or let the person people talk freely because then, especially in imaging studies, the person has to keep their head as still as possible.

Sometimes after that they're ready, so there's something they have to bite into for the head to actually do it. Don't move, that's what it means. What we normally care about stress is impossible, so we thought maybe we could use mental arithmetic to calculate stress, which also plays a role in the TSC in the social stress test, because you can also show it in computerized form, which It means you can get it through the computer screen. On the imaging device, the tasks you need to solve are then displayed. These tasks are usually associated with multiplication division and always have an answer between 0 and. 9 and then you can participate in a lottery on the scanner on the imaging device with a mouse.

Click left and right, select the correct answer and do mental calculations this way, so that's possible now, but you still need the social component. that is, what really makes stress stressful, to ensure that there is also a cortisol response, so we think about what we should do. So a social comparison says that we actually want to see what happens in the brain when you do mental calculations, but in order for us to then compare between people, we need to make sure that everyone does the same amount of mental calculation and is equally good. Here is the standard performance we have discovered over many attempts, what you and yours are capable of. performance must always be in accordance with standard performance.

What the person does not know is that this representation is that of mental arithmetic but it is manipulated by us, the computer calculates and observes how well and how quickly the person can calculate y. then, in the course of the experiment, you make the tasks a little harder and too fast, so that the person can no longer calculate well and then, very soon, their performance is significantly lower than what is called normal performance, we do . this for a few minutes until it has established itself and the person is significantly worse off, then we stop and the experimenter enters the scanner and asks the person how it happened that he is now significantly worse off than everyone else and that outside of the assistant and the Technicians are also scratching their heads and don't know how it happens that the experiment simply does not work for this person and that of course an hour of such a scanner is also quite expensive and that this scan can no longer be used if the person not on the next try, hopefully the calculations will be better and with these instructions you will leave them again knowing that everyone outside is now watching in fascination as the person continues to calculate and the person can then try as hard as they want because the manipulation is The algorithm adapts automatically to the performance of the person or test subject, it will not improve on subsequent attempts and that is actually a social component that then manages to generate stress there as well, which means that we also see a cortisol response in the city.

Findings in response to these extras from Montreal that Kenny Stw has mentioned and what is, of course, interesting is to see what brain structures change when a person experiences acute stress in this situation. So what's happening in the city? brain when you are very stressed the short answer is Exactly something different happened than what we really expected. So we expected to see a series of activations in the brain that can now be associated with acute stress, but that was dominant. we saw in many areas of the central nervous system and now, in the meantime, many studies have replicated a deactivation, meaning that specific centers in the central nervous system close down when faced with acute stress and this closure of specific structures leads to a stress reaction if, in addition to other areas, the hippocampus is also affected.

You may also see a significant increase in cortisol response in your activity and this is something you can then look at specifically using so-called region of interest analysis. , so only the hippocampus is removed and then the activation changes in each case. If you look at the deactivation and associate it with the release of cortisol, you can see that there are clear positive associations here the more the hippocampus is affected by this deactivation. the more the cortisol system seems to be affected and of course we have a lot of ideas about this about how this happens and what kind of explanation can be found so now you can find a reduction in activity and I think you can really understand this. has a connection with memory effects, namely that the reduction of the hippocampus as a result of exposure to stress leads to this.

This means that what caused you stress is better retained, so there is no longer any interference from the hippocampus's further processing of subsequent stimuli, but rather, the hippocampus takes a break after the stress has been complete and has arrived and is processed in the central nervous system. That's a bit in the revolutionary sense: you want to make sure that what's stressing you out is kept and stored so that you might be able to cope better in the future, prepare better, or think more about what coping strategies you can use. To not feel so stressed in the future, this would also partly explain the effects on memory. that if the stress is related to the memory task, then it will be easier to remember the stress and if the stress comes together during recovery, then you will have a hard time.

One situation is to recover what you were stressed about because the hippocampus is currently shutting down. and then you are no longer able to remember or save what you were originally stressed about, so here too I think it is a finding and an interesting result is something that was surprising, but if you think about it, it can make sense in relation to the task. What Stress Can Do to Memory In the last part of the previous day, I would like to now talk about the chronic effects of stress, which have also been particularly researched. They may have heard it too. which in part has a lot to do with stress then how toxic it is for our brain to what extent stress can damage our brain or certain areas of our brain and in that then there is a very interesting hypothesis that but I think that when In the case of people, it must be evaluated in a particularly differentiated way.

Here is also a short video to clarify how you can differentiate acute from chronic stress as a stimulus for stress along with fears and worries about the future. find an increase in appetite Stress hormones that are no longer broken down properly a sequence of nerve cells forms in the hippocampus of all places, relaxation begins, so that was now the version of the WDR in this of the SWR in this program In the stress odyssey, chronic stress was said to be high and then cause a reduction in volume in the hippocampus. In principle, this is exactly the hypothesis.

It has been at the forefront of stress research for many years, even decades. This is the European toxicity hypothesis and Robert Suchomski from Stanford in California is the researcher who made his career and became famous with this hypothesis and I don't know why always. I'm talking about this theory, there has to be a photo of him. I think it has something to do with the fact that I'm not, I'm in his hair. In any case, this theory has something to do with that. This negative feedback loop occurs when cortisol is released from the adrenal gland and then turned off in the hypothalamus and especially the hippocampus, so let's go back to this image which was initially where we saw this cascade from various central nervous structures.

The end of the adrenal cortex with cortisol and having negative feedback turns off again and Europa Polski was now able to show, especially in animal experiments, that if you stress the animals long enough to expose them to high doses of these corticosteroids for a period of time long enough that there is then a reduction in the volume of the hippocampus, which has to do with cell death, so that this excessive exposure to glucocorticoids leads to atrophy in the brain, especially in the hippocampus, but the hippocampus In negative feedback, this deterioration of the hippocampus would cause cortisol to no longer be able to disconnect the axis itself as well, so we would have even higher levels of cortisone. then it has an even more toxic effect on the brain, so it creates a vicious cycle where cortisol levels get higher and higher due to enough chronic stress and massive damage occurs to the brain because cortisol now has this toxic effect. . and this later became very well known as a very famous theory and there are many studies from the 80s and 90s here as an example 11 publications by roberta polski waste careers pet foil brain so also very catchy yes why stress is bad for your brain and I had given several examples here, all of which clearly depression is very often associated with increased exposure to cortisol and is often associated with increased expression of cortisol and the longer this depression lasts, the lower the volume per campus of Cushing's syndrome as a tumor.

On the part of the pituitary gland, a complete lack of control of the hormonal axis occurs with a maximum release of cortisol, because the system no longer functions or is not regulated at all. Also in this case, the greater the amount of cortisol released, the smaller the volume of the hippocampus and in case of stress. , i.e. stress related to war operations, post-traumatic stress disorders as a typical consequence: the longer the combat operation lasts, the smaller the volume of the hippocampal, so the results are apparently very clear and convincing. cell death, which can occur in the hippocampus if the stress is only strong and A colleague of mine from Montreal has been around for quite some time, so Sonja Libya also contributed her findings in 1998 in Nature Neuroscience, where she was able to show that when cortisol levels were high, hippocampus-dependent memory performance in delayed recall was affected, they remembered less well and also here the volume of the depot campaign seemed to be related to the amount of circulating cortisol, so also There is the idea that these two are firmly associated with each other to the mechanisms by which this should occur.

Programmed cell death in the body also turns into apoptosis. On the one hand, it was said to involve a suppression of growth factors, an institution of glucose transport and an enhancement of eccentric amino acids. acids, which together lead to theneuron overloads and then starts its own demise and I myself am in it over time. I also worked on it for a long time and tried to find out whether it can be believed or not, but in 2005 my colleagues from the Netherlands ab und biege and Lucassen finally buried this theory because they had the elegant idea to say what really happens to these Cushing's patients, that is, those who had peak cortisol levels due to a pituitary tumor after being successfully treated, can be treated relatively Well, the pituitary gland is removed and then the hormones have to be replaced, but because is relatively encapsulated, this tumor often does not spread or generally does not spread, so after hormone replacement people have a relatively good prognosis and may have a positive prognosis. relatively normal life and we both saw that in Cushing the volume of the hippocampus was significantly reduced in relation to the level of cortisol release.

There was and our colleagues were able to show that if we look again after a few years that we are now hired and we no longer have elevated levels of cortisol, then the volume of editorial work decreases and the hippocampus seems to grow again, so to speak, and it seems be recovering and the almost compelling argument is that if cortisol is so toxic then it should have a greater incidence. of dementia in old age because they suffered massively from this cortisol from a young age and the neurons have broken down massively, but that is true, Cushing's disease does not have a higher incidence of dementia in old age, which means that what you observe is acute and exposure to cortisol probably has nothing to do with pro- and apoptosis but rather a temporary contraction of the structures beneath.

This cortisol attack causes your dendrites to retract or perhaps become smaller in neuron volume, but this is temporary. They don't die and when. This attack ends because of the cortisol, they can grow back, extend their dendrites again and then resume their normal function. So there is the message that I think is very important is that cortisol is said to have a temporary impairment of the function of memory and the central nervous system, even in the case of chronic stress, this is something that happens when one relaxes and the impulses do not have to be permanent, but can reappear.

Now I just have to change briefly. Many of the findings that found this connection between cortisol and hippocampal volume or structures in the brain may have been found because stress has a different effect than originally assumed, and that's the case now. the last part of the lecture, which is about development or stress during critical periods of development, which is then called stress in early childhood or city life, and I think you can do that here, which takes to the argument that the effects are actually permanent and also seriously damaging and can be found in the brain and has something to do with stress, but the stress must have occurred while the person's body was in a critical phase of development.

What are the types of early childhood stress? pre-death or post-mortem events, for example, such as lack of oxygen during childbirth or dramatic events that happened to the mother or oneself before or after physical neglect, emotional abuse, or in the context of child care. parents emotional and physical care that is missing or On the other hand, this overproduction that helicopter parents have is also a very fashionable term at the moment, which can have negative consequences. This is a dramatic problem, which is also clearly present in Western civilization. As evident from many publications, here only as an example, Best Pizza Galley of 2011 has reconstructed that in 2007 alone, 22 percent of all children in the US came into contact with the welfare office due to one or several forms of abandonment and relief and the city or tranquility Stress is associated with 34 percent of all psychiatric disorders and even with 44 percent of all psychological disorders that begin in childhood - i.e. , when stress occurs during brain development - actually seems to have clear consequences: only partially called a psychiatric disorder.

The connection is depression, anxiety disorders, substance abuse and psychosis being one of the main ones, but eating disorders are also disorders that occur much more frequently when stress is recorded in early childhood. The idea here is that early childhood stress has a strong effect on brain development and we can see it right away. Which in turn has an effect on the regulation of stress systems and this regulation of stress systems. Being less able to deal with stress carries the risk of psychiatric illnesses. My Berlin colleague, now at the Charité, Christine Heim, in her time as a postdoc in Atlanta with Charles Nenner showed that early childhood stress was significant in live broadcasts. associated with a significant reduction of the hippocampus significantly on the left side and then tendentiously on the right side, so this structure in the central nervous system is reduced in volume and permanently reduced is when stress in the form of stress in early childhood It occurred during the critical years of development, the first 16 years of life or something like that, and we ourselves tried to understand this in several studies and we were able to see that early childhood stress here, in the form of tarantula care by parents, it seems to have an effect.

Growth affects the integrity of the hippocampus, so its final size in its final development depends on stress in early childhood, which then influences the cortisol response in adulthood. Thus, this original hypothesis is confirmed to a certain extent. It is significantly associated with the regulation of the stress system, but the hippocampus is not modified by chronic or acute stress in adulthood, but rather by stress during the critical phase of development and that is the level of its campus in its size is fixed and as a result the regulation of the stress system is fixed and that appears to be a programmatic effect which then leads to the stress response remaining permanently changed throughout life.

Now I have to go back again because I made a small mistake with the slides. , which means if we get down to it, I would summarize it like this: Stress is a physical reaction to a form of threat, a stressor that is perceived as such. The reaction in the body is mediated by energy systems. I have seen that the sympathetic system, adrenaline leaks and the android system, the hp axis, cortisol, stress has effects on memory. The effects depend on when the stress occurs, with the appearance of the materials to be learned, in hensing, so memory performance improves and in connection with withdrawal it worsens considerably, it has negative effects, chronic stress leads to a reduction in activity on campus, but this is reversible, meaning you actually see a contraction of the structure, but that seems to be the case with Breuer and when chronic stress goes away, this contraction goes away too.

Shrinkage returns again and the decisive factor in brain development is early childhood stress. What happens to us during critical development is what determines whether we are permanently associated with a modified stress system. I wanted to thank my colleagues who also contributed to this work, so my previous and current cooperation partners, especially Michael Meaney from Montreal, should batten down the hatches and now Christine Heim in Berlin, the page, the PhD students and postdocs who they did most of the work that I showed you is related to these results and now also my start of the new laboratory here in Konstanz, where I hope to be able to do many studies, so thank you very much and we have time for questions.