 Thank you everybody So the goal for the next 15 minutes from my side is convince you that depression as Nothing to do or at least is not just being said or said in it at all And I'm gonna start saying that in fact depression manifests itself as a sum of many different symptoms which Include or might not even include depression the first big type of symptoms that affect depressed patients is something that Has to do with moods which includes alteration of emotion and thoughts and because we know that the press patient very often suffer from alteration of their memory alteration in their thoughts anxiety Suicidality totes and also mood swings and sadness But that happens sometimes and sometimes cannot be there But this is not all of all of it depression also includes alteration in behavior, especially social behavior We know that the press patient tend to withdraw from their family from their friends and also from everyday life including work and everyday activity and Finally depression also affects the physical aspect of our patients the press patient in fact manifests normally lack of energy like lack of a proper sleep they have Changing their appetite and very often ends up in drug abuse situations for all these reasons Depression is now considered the leading cause of disability worldwide and is known to affect roughly four percent of the whole population And interesting the distribution between women and men that's not equal and we know that women are more prone to develop depression than men So despite this very clinical picture Depression is still one of those pathology that is not so uncommon to hear people replying to a depressed patient Oh, just stop being sad. I was sad yesterday as well Just snap out of it But depression as any any other pathology is not something you can snap out of it because as any other pathology is Characterized by a malfunctioning organ in your body when we talk about depression the malfunctioning organ That is not working properly in your body is the brain and we know that not only the brain of Patients is not responding normally as is expected to activities, but also in in a normal state It's not functioning as it's supposed to be On top of these big malfunctioning of the brain We know that during the depression course also other organs start to work not properly And these organs include many different for example the immune system That is the one that protects you from germs and your heart the metabolism Including the gut and the stomach and so on and your hormones in general So why these organs especially why does the brain stop working? So what's the trigger of depression? Well depression is a complex pathology and that means that it comes out of interaction of risk factors For depression we know two main risk factors the first one being the DNA as Also Lily mentioned the beginning of the day the DNA is what your genetic code that you narrate from your parents and As you might know the DNA is what determines all your body function and Importantly also every each on each one of us as a unique DNA We which means when we look inside your DNA We're gonna be able to find small differences between you and everybody else around the world And we know when we look at these small changes that some of them Increase your chance of develop depression and some decrease your chance of develop depression But this is not enough to explain you if someone gets Depressed and someone doesn't we know that a second factor plays a major role in this and this is what we call in the scientific terms environment with environment we refer to any Experiences you go through your life. So as DNA also these experiences can be good. So it can Improve your chances to stay healthy and this includes like the exercise or having support environment around you And some of them can be bad and increase your chances of develop depression like for example trauma or drugs We know that your DNA small changes Determine how you're gonna respond to what happens to you So there is an interaction between these two factors that at the same time Interact on a level of the brain and determine how your brain works And if you collect enough negative risk factors your brain and yourself might develop depression Throughout many years of studies we found out that especially one factor is particularly important somehow plays a major role And this is stress So it's a very negative impacting life experiences So when we talk about stress or a stressor we refer to any real or perceived Armour situation that can happen to you so that can be either physical or psychological And this is such an important event in your life That's something that you need to be able to survive for those reasons in your body You have a stress system that is able to allow you to survive and overcome the stress The stress system starts in your brain when you perceive a stress your brain activates sort of response that leads to activation of many other organs and Ultimately leads to the production of hormones, especially cortisol something you might have already heard of Cortisol and these hormones going your blood torrent and at the same time They act on many different organs change your their function allowing you to respond to the stress among these organs importantly, also the brain is one of the Organs that is somehow targeted from the cortisol and on the court on the brain also there We change this functionality for is for example, we know that we impact on memory and focus and the second response the very important one that from comes from the brain is The understanding that your stress response has been active and is now helping you out to overcome the stress So the stress that the brain now needs to tell the rest of the body that the stress has passed and you need to go back to normality So that's the other very important task of the brain is to shut down this response and these overall allows you to overcome any stress in your life and The proof that let's say a proof that this is a very important system Can be found in the fact that these system can be found in a very similar manner also in simpler animals like fish or mice and We know or at least we know we learned that However, the system can go rogue. What happens when you are of over exposed keep being exposed to stress Well, somehow something stopped working properly and your stress system keep being activated You keep have production of these hormones and somehow your brain doesn't shut down the response anymore And this is a situation that's very often observed in the press patient Their stress system keeps being activated their levels in the blood torrents are not as they are supposed to be of these hormones So this is a strong connection that we acquired throughout the years And we can also see it like more in ground numbers when we look at stress in everyday life or in Like people human studies. So we know that life stress that something can happen continuously in time So it becomes chronic. There are many different phase of life stress one of them that we can take as an example is bullying So we know that as I mentioned before Depression in the normal population are threat affect roughly between five to five and four percent of the population However, when we focus and look only at those people that got bullied throughout their life We know that the percentage of people that are affected by depression increases to 15 percent So being bullied chronically so for a long period in your life Increased your chance of develop depression of three times So these are very important studies. This is all the grounds of the press research came from However, if we now want to ask more complicated question keeping on with this study becomes a little bit complicated Why because any study that involves humans is also suffer from some limitation when we study for example pulling We know that all our patients actually went through many different experiences in the life So our samples will be very different. Also all our all our people Gonna have different DNA as I mentioned before and finally the main organ that is malfunctioning in the in the In the body of the press patient a brain is brain and we cannot really access directly to the brain of our patients So this is when research tries to look around for solution a way of to overcome this to his problems and one of the solution the research found was to turn himself to other Other system that might help to make some research that can be helpful also for human one of this system is the rodents or more specifically mice and rats because Using mice and rats allows us to overcome some of these disadvantages when we use mice arrest For example, we can define controlled experiments We know what our mice went through in matter of experiences and we know what their DNA look like Also, we can modify their DNA and finally we do have access to the organs of the mice So given the fact three very important things that the stress system is Similar between mice and humans that the DNA code is very similar between humans and mice and finally that somehow Their brain function can can be Reconnecting between the two system we can we learn that we can use mice Effectively for our questions. So how do we study the pressure in mice? Well, we don't wait Sorry, I just finished tell you that we use mice. Well, yes But also told you that depression is a mood disorders, which means when we diagnose depression We sit down with a patient. We ask him or her. How do you feel? What's your thoughts where you moods? We cannot really sit down with a mouse and ask it. How do you feel today is better than yesterday? But we can use the mice to study the mechanism that we think are behind depression How do we do that? Well in a kind of similar way that we do with humans So we know that humans have a well-being state. They enjoy specific stuff. They are social animals and They have a normal functioning body and we know that when a combination of DNA and environment applies They're doing their state can change and they develop a depressed state Which includes lack of enjoyment normally social withdrawal and a change in their body functioning Well, we can look at similar things in mice as well. We know that mice have a well-being state. They are Normally animals that enjoy specific stuff. For example, they love sugar They are very social animals as well as humans and they have normal body functioning In experimental settings, we can apply a combination of DNA and environment and when we talk about environment we normally talk about stress and We are able to observe an alteration in their behavior or in their state that we call depressive Like because we can never talk about depression and this usually includes lack of enjoyment For example, they're becoming different to sugar. They become social avoidance and their body function start to change So how this happened in real life? Well, we we have many different types of for example stress that we can apply One of the most used so far the most successful is called social chronic defeat Social chronic defeat is very often thought to be simile to what bullying situation is Chronic social defeat is based on the fact that mice are social animals, but are also very territorial So how does this work? Well, we take a mouse a big usually white mouse and we give it we give him it His own cage so this is going to become his own and his own Territory that he wants to protect and then we take our mouse of interest a small black guy And we put it inside the cage of the the other one What's going to happen is the big mouse is going to protect his own territory So it's going to attack our mouse of interest the black one It's going to defeat it and that's it because we are going to rescue the mouse at that point But we are going to make this happen multiple times across many days So once per day usually 10 21 days So what's happened to our small mouse that is being exposed to a physical and a psychological stress that they cannot avoid? And it keeps happening as bullying happens in real life to humans What we can see is that these mice after chronic social defeat do develop some of those Characteristic that we can observe in the press patient for example, they have depressive like symptoms So they if when they are put in presence of another mouse Normally mice live love seeing other mice they go interact because they are social these poor mice after so Chronic social defeat they start to be away from them and avoid it so they develop social avoidance They also tend to not like sugar anymore. So they become indifferent and any and many other different type of behavior like they become anxious and at the same time We can also see depressive like bodies because we know that the for example the stress system Malfunction and the level of the cortisol in their blood is always increased as we can see in the press patient And we know that their brain works differently from healthy controls Similar in the same regions that we can observe in humans But since now we are using mice we can start and go a little bit deeper and ask ourselves What else can we discover about the brain of these animals and that can help full in human research? Well, since we do have access to the brain of our mice We can ask ourselves. What's the structure underneath? Is it working properly or not? So you might know brain as any other organs is composed of brain of cells So brain cells which are very specific in this case. They have a very specific structure So we can ask ourselves is the brain now working properly because the cells underneath are now working properly when we look at the cells of the press of Normal mice, this is our brain cell look like in green So they have a very well structure. They have long branches. They are very wide They have many and these allows the cell to actually be healthy and to make the brain work So this is a structure that is necessary for the brain to work when we look at the cells of a defeat mouse That's what it looks like. So as you can see the cell is not as it's also supposed to be is smaller There are not as many branches. They are shorter And this is telling us that these cells cannot be working properly because it's not doesn't have the structure that is supposed to be So from this point, we can also ask further question like why are these cells different? Why is this the fact some are contributing to the behavioral changes that we see? Can we prevent it or fix it? So this is just an example of our mouse research is helping in an understanding of stress response and depression But mice are used in every day in many different labs trying to solve many different questions For example exactly how the brain changes with depression or chronic stress exposure How the brain cells are affecting in this process why women and men develop a depression with different ratio? Why antidepressant how they work because we currently don't know how antidepressant work even if they do and Can we actually improve the current treatments? So after this 15 minute talk I would like to go home and have like just few points in your mind That depression is a very common pathology that affects 300 million people worldwide That is a complex pathology made of interaction of complex symptoms that might or might not include the sadness And it comes out of interaction of the DNA and environments especially stress plays a role and that we can use mice to kind of start to understand some of these these alterations and Overall, I would like you that next time that the depression words come up to join and spread what you learn Just to help to reduce the stigma that still comes with mental health and depression that only improve quality of life For our patients. Thank you Thank you Elena. I think that you have touched very Interesting and also very important topic. So even before people stopped clapping. I already saw a Great many of hands. I think this mister in the second row would like to have the word first If you would like you can you can show say the question like that and I will repeat it for the audience So the question was why do you use mice and not monkeys? Depression research is also stress response. It's also done in monkey Of course using an animal comes with ethical implications, right? So monkeys are indeed more similar to humans, but they're also more similar to humans which means they come with a bigger ethical bargain and With a more complex system that is more difficult to be understood mice are simpler They are still have many thing in common with humans and they're way easier to handle from Technical point of view and from ethical point of view Because I mean what you spend for one mouse for one monkey you get hundred mice, right? You also need to have different training is it's completely different thing also monkeys does exist though the research I had to think of the planet of the apes at this question So any further ones I see one hand over there Thanks for the talk first and I have one question Does the female mice also has higher rate than male mice to get depression? Yes So again, we are not talking about depression in mice, but when we talk about being susceptible in to stress to chronic stress so changing your behavior after being exposed to chronic stress females tend to Change their behavior more easily However, and that's actually my phd topic disease Female mice are not studies. This is a big bias in neuroscience in general Neuroscience is based on male mice for many different reasons that we could discuss or not So females are very much underrepresented so far So that's also why the reason we don't really know why women in general are more prone to develop depression or why they are more Susceptible to stress, but their search is now getting back up to it. So it's a ongoing Topic, let's get one more question the guy behind a Christmas tree with the beard and glasses In the dark So thanks for the talk really nice I wanted to ask you what you think about the social stigma in humans that Goes into the numbers of depression between females and males Sorry, can you so do you think there's a difference because we have a genetic difference? Or do you think there's a difference between us? conception and like gender difference in General so is it because we see see males or males behave different because they think they should behave different or is it because of the genes But you mean what's the connection with the stigma? You mean the difference in the sexes. Sorry, we always talk about sexist biology. Yeah, so the difference in the sexes is Measured yeah, but because you have a perception of the sex I mean there's a sex and The but how much do you think is this our society doing to this because you also conceive yourself as male or female? Yeah, so That's maybe a good point a lot of the way in which depression is diagnosed is somehow by symptoms that are Probably less probable to be Shown by men because our society works So men's are less prone also to go and get diagnosed that's definitely true And also we are now discovering that symptoms are not equal between men and women men are for example more prone to get anger and Aggression whereas women are more prone to get said sadness for example So we do have a bias in how we diagnose depression and that's my and that's come from society of course So how we perceive the two sexes But we know by biologic bed basic biology that for example the stress system in women and Female mice and female rats is more Active so you have the same stress men and woman and the woman reacts more So we know that somehow there is an overreaction in the female. That's maybe you're already a lot of other stuff as well, but We know that's true We are not under percent sure how big is the sex biases in depression because we might have a diagnosis bias But that's still in ongoing So thank you for answering those questions