The video effectively dismantles the outdated "chemical imbalance" myth by focusing on neuroplasticity and structural repair, providing a much-needed scientific update for the public. It successfully explains the clinical delay of antidepressants through the lens of cellular growth rather than mere neurochemistry.
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Por que o Antidepressivo demora a funcionar? Serotonina não explica tudo #neurociencia #cienciaAdded:
As you can see here, the topic of our class is the neurobiology of depression. This is a lesson I prepared for you to help you gain a deeper understanding of depression within its environment, from a neurobiological perspective. For those who don't know me, welcome. I am Rafael Crage, a neuroscientist, PhD candidate in neuroscience, PhD candidate in psychology, and trainer of therapists. The idea behind today's lesson is to help you gain a deeper understanding of what depression is. It's important to reinforce a few concepts here before we move on. This lesson is not suitable for diagnosis. No, please don't ask in the chat or comments if so-and-so or you are depressed because you read or heard something. That's not our focus. You need a psychologist, a serious professional psychiatrist, who will attend to you, not just for a half-hour consultation or an hour-long live session, but who will attend to you with care, compassion, explain things to you, listen to you, and accompany you for a certain period of time. So, this diagnosis is a serious matter and shouldn't be treated lightly, okay?
Today's lesson is not a diagnosis, it does not serve as treatment, and its focus is purely educational. This is to help you and to give you a more in- depth understanding of this subject. And this is not a lesson for those who are, how can I say, scientists. It's a class for those who are curious, for those who are just starting out. This is a lesson for those who want to understand what's behind depression, and it's not about those theories of cause and effect, like "why it happened, it's the child, it's the father, and it's the mother."
No, here we're going to look at the biology of it, what's behind it associated with the brain, some neural networks, and talk a little bit about BDNF, which are strange acronyms that you don't need to worry about memorizing right now, but you'll get a slightly more in-depth view, especially if you're just starting out. So this isn't a class for complete beginners; it's a class that already has a certain level of depth. It's a class for those who know a little about the subject or have heard about it, but it's also not a class for scientists. So don't worry, you don't need to have a deep education to follow me here. And I'm also saying here that this isn't a class for scientists, because maybe there's a pharmacist here who will look at the content of the class, or a doctor who will look at the content of the class and say: "No, Rafael, but there are 10 things in this cascade that you didn't mention." Yes, because this is an open class for anyone who wants to understand the subject, and not a class for those who are already familiar with the subject and want to delve deeper into which ARMEC cascade they want to be associated with transmembrane anal BNF. That's not the idea, okay? This is to help people gain a deeper understanding of what lies behind or is associated with depression in its neurobiological aspect, and to open their eyes and ears so that we can have a more in-depth perspective. And of course, I'll also be talking about therapy throughout this lesson to help you get a more complete understanding of the subject, okay?
I always like to bring up a case, and I'm going to talk about Ivanir here. Ivanir is a gentleman, a 70-year-old man, 59 years old actually, a banker. And he was recently diagnosed with moderate depressive disorder. And here I'm going to talk a little bit about how people arrive at this diagnosis, and that it's not simply a matter of saying they're sad or tired. He's already tried medication, he's already tried therapy, and nothing has worked. So I'm going to take Ivanir's case here to help us gain a slightly deeper understanding of what's associated with what we call depression.
And the classic question that we're going to bring up, and I'm going to bring it up here for you, I want you to answer me in the chat, and answer me like this, without fear of being wrong, okay? What's going on in Ivanir's brain?
Could someone here who's participating please tell me, even if it's just a brief explanation, " Don't worry, I want to interact with you so you don't think I'm talking to myself on camera"?
What's going on inside Vanil's brain? So, if you think it's something from the prefrontal cortex, the hippocampus, the amygdala, dopamine, or serotonin, please tell me, while I take a sip of water, what you think is associated with this mammalian brain and with this picture and this diagnosis of depression.
I need to meet my goal here of a little over 2 liters of water. So don't be surprised, in class I'll grab this water jug to take a break, okay?
Ah, Andreia put it like this, E Alves, I don't know his name, put it like this, I have no idea. Great, that's a good start, don't worry, okay? Welcome, whether you're very welcome or very welcome (feminine), I don't know. Oh, and Alves, the last name is showing up here. And the important thing is that when we become aware that we don't know things, that's when knowledge emerges.
Knowledge arises when we realize that we don't know. If we knew everything, we wouldn't go looking for it.
So here's what Jordan puts it: neurotransmitter dysregulation, frontal lobe hypoperfusion, neurophysiological dysregulation.
Ah, it's impossible to know what's happening, there's no way to measure it.
Well, I appreciate all those responses, but none of them really showed any understanding of what's actually behind this neurobiology, okay? Yes, it is possible to know what is happening in the brain, because if we didn't know, if it were simply something completely random, we wouldn't have studies, we wouldn't have tests, we wouldn't have treatments.
for these things. So yes, it is possible to know what is happening in this brain. It's not simply a matter of neurotransmitters, it 's not simply a matter of hypofunctioning of a specific area or network.
And it's not simply that idea that there's a hypofunctional or hyperfunctional neurotransmitter, which I know many people still have, right?
Audre coloc is a response to stimuli.
Great, perfect. It will be a response to stimuli, but we need to delve a little deeper into this, okay?
Especially for therapists, to avoid being too general, it's important to understand this content here. And before I go any further, I just want to give a warning, so to speak, an important heads-up. And I would like you to write it down. If you 're there, you can take notes or write in the comments, that already helps to remember it, okay?
Everything we're discussing here regarding the human central nervous system in relation to depression, which is today's topic, doesn't necessarily mean it's the cause of depression.
So, let's imagine the following: a person, I'll give a silly example, a person salivated and ate brigadeiro. It 's not correct to say that saliva made the person gain weight or eat the brigadeiro, but saliva and brigadeiro are happening together, okay?
Correlation does not imply causation.
So, when we observe the nervous system of a human being, which is our focus here, but it could even be that of a mouse, for example, in my laboratory where we work with mice, when we look at the brain, the central nervous system of a living being, which in this case is exhibiting depressive behavior, it is not correct to say that it is what we are seeing in the brain that is causing the depression. It's not the cause, but something associated with it. Similarly, I know that someone smiled when I said that, because there will be people who say: "Oh, that's good! Because what caused the depression was childhood trauma." That 's wrong too.
Childhood trauma does not cause depression. Childhood traumas are associated. What is the difference between correlation and causation? I'll give you an example, another silly analogy. I have some kind of object here. If I drop this random object here on my desk, you might hear it fall. Somewhere in this city, someone tripped and, I don't know, tripped and fell to the ground. He wasn't hurt, he just tripped and fell to the ground.
This does not mean that when I dropped this object, it caused that person to fall. These are just two events happening at the same time, not the same space, but at the same time. This is a correlation.
Childhood trauma is associated with poor family care, socioeconomic vulnerability, and is also associated with difficulties in life progression and access to medication. So, it's not that childhood trauma makes a person sick today, but rather that a person who is in an adverse environment is more likely to remain in that adverse environment for a long time.
And the sum of these problems throughout life, associated with a genetic vulnerability that people usually ignore, will generate what people will call disorder X, Y, Z.
So, when we talk about science, we are never talking in a literal, direct, or harsh way, where an X generates a Y, because that is very difficult to observe. Those who like this idea of X causing Y to happen are usually not scientists, but rather popularizers, journalists, or poorly trained therapists. You, as my student, know how much I nag, how much I argue, how much I reject this idea of causation. Ah, X happened, so this will cause this problem. No, that's not true. It's impossible to know this.
Now, we can look at a correlation. Right now, if I take a picture and see neurotransmitter X and behavior Y, I have a correlation, but that doesn't mean that X generated Y. Is that clear? It's here. Did you understand that? This is something fundamental for you to understand. Please tell me if you understood this, yes or no. That 's great. Luciana even adds to that here. Very well, Luciana, thank you. Oh, depressive disorder is a disorder, not an illness. Therefore, there is no causality. Yes, correlation. Perfect, Luciano, thank you very much. But in the world of therapy, we see people loving that basic assumption that, oh, you, I don't know, your mom forgot you at school, so you were left alone and that's why you have depression today. I was like, what do you mean? What does one thing have to do with the other? But people like it because it seems to sell more, I don't know, sell more mentoring. People like doing these things, okay?
So what's going on in Ivanir's brain? Something. That might be the most appropriate answer, okay? What's going on in Ivaniro's brain? Something, [laughs] something happened there. We can talk about neurotransmitters, yes we can.
Can we talk about BNDF?
Can we talk about ketamine? It's possible, we could be talking about an apoptotic process, it's possible. Something is happening in Ivanir's brain, but we can't say for sure yet exactly what X is causing that disorder, that depression, as Lua commented very well just now, she added very well now, okay? And quickly, depression is not sadness. It's very common for people to have this idea, and unfortunately, I've even seen some news stories about singers, actors, and actresses who committed suicide. It 's very common for family members or someone to say, "Wow, but you can't tell that person was thinking, or they didn't seem sad, they were so happy, they were here talking to us, they were here laughing. And it's... you can't tell, you couldn't say they had depression." It's very common for people to associate depression with nedonia, which was one of the first ways to diagnose depression more than a century ago, associating nedonia, that lack of pleasure, with depression, which later began to be called depressive disorder, mood disorder, isn't that right?
And people have this belief that depression means sadness.
But depression, as we'll see shortly, involves many other signs and symptoms. And not necessarily two or three, four people diagnosed with depression will have the same signs and symptoms. They will have things in common, of course, but not necessarily the same signs and symptoms. And it's important for you, as a therapist, to understand this, not necessarily to want to diagnose, that's not what I'm trying to do.
Speaking, but so you can understand that sometimes people come to you and say, "I have depression." And if you don't have this deeper understanding, you'll look at them and say, "But that person isn't, they 're smiling."
If you believe that depression is sadness, you'll miss the chance to help that person, okay?
According to a study by Marx ET, which you can access later from 2023, there is an estimated 185 million people in the world with depression. Brazil, in fact, is the second country on the planet. The second or third, I don't remember exactly, if anyone knows, please write it down. It's the second or third country on the planet with the highest rate of people with depression. We're talking about this in percentage terms, not because Brazil has millions of inhabitants, okay?
But Brazil, you can see here, in orange, let me see if I can, oops, go back to the slide, you can see that Brazil is in this kind of orange color, which has a high prevalence rate. Some other countries also have... Quite a lot, although much smaller than in Brazil, but as I said, in percentage terms, and some other countries probably have underreporting, especially some more remote countries or those with low access to literature, low access to medication, and some other countries, as you can see, for example, Russia, which are very cold, very isolated regions.
So, there is also a high rate of depression related to other countries that don't have as much social isolation due to the climatic conditions of the place itself, okay? So, Brazil has a high rate of depression, and there is a tendency in the coming years for these values of 4-5%, which are the common values today, to increase or double in the coming years. This is because of social isolation, dietary issues, sedentary lifestyles, and many other problems that are also part of our routine or daily life today, okay?
And perhaps the most common medications you know, like fluoxetine, imipramine hydrochloride, which always have a tongue twister, are the most common and best-selling antidepressants on the planet.
That's all. There are two major problems, not only with these medications but also with other medications associated with the treatment of depression: latency, the delay in treatment before results begin to appear, which takes several weeks. It 's estimated that one-third of those who begin treatment don't achieve the desired results over the weeks or months of treatment. This is a fundamental problem. For years, treatment for depression has been sought through medication, through an understanding of neurobiology, which is becoming increasingly clear. I believe that in the coming years we will see a revolution in the use of pharmacotherapy for depression and anxiety, and for many other problems as well, but for depression and anxiety, I believe that in the coming years we will see some very incredible and revolutionary processes in treatment, improving quality of life. It will be something very beautiful that we in the scientific community are following some treatments that are under development, and the hopes and expectations are very good.
But the current problem, and in fact a recurring one for decades, is that pharmacotherapeutic treatment has not been giving... The intended result.
For those in therapy, or my students, for example, we talk a lot about implicit reintegration therapy, and for those who don't know it yet, stay with me until the very end because I'm going to talk a little more about it.
But we often observe people who spend years undergoing pharmacotherapy and don't achieve adequate results.
Because, whether we like it or not, there's a very strong dogma in this idea that any problem—and here I'm not talking about depression itself, okay?—but any problem you have, medication will solve. And let it be very clear that I am obviously not against medication. I am a neuroscientist, obviously I am not against medication, but what I see is an exaggeration in people believing that medication will help them with everything. An example, a silly analogy. Imagine a person who flosses and goes to the dentist properly, but they are exhausted, I don't know, eating hard pork rinds every day. No teeth can withstand that. So, if this person doesn't learn to deal with the things they do... In her daily life, it's no use spending money on the best available treatment if she doesn't learn to cope with things, if she doesn't learn to deal with what she sees, what she believes, what she feels. So, there are excellent studies showing that pharmacotherapy is fundamental in many cases, but if that person doesn't learn to deal with themselves, doesn't learn to deal with their experiences, doesn't learn to deal with what they feel, doesn't learn to deal sometimes with the pains and frustrations of the past that they carry, there is no medicine in the world that will help that person, okay? No matter how potent the medication that person has access to and availability of. And that's where therapy will be fundamental for a large part of people, including, okay? Major depressive disorder involves nine symptoms according to the DCM5TR today, okay? But it's not that the person needs to have all nine symptoms; they need to have at least five of these symptoms associated over at least two weeks, among these nine symptoms, for the professional to diagnose them with depressive disorder. Among these Symptoms: The nine symptoms described in the DSM-5TR include depressed mood, anhedonia ( the absence of pleasure that people usually associate with depression), changes in weight and appetite (which can increase or decrease, for example, a person may lose their appetite or be much hungrier than normal), sleep disturbances (they may experience increased insomnia or excessive sleep), [ __ ] agitation ( meaning they are very agitated or much slower in their movements), fatigue, feelings of guilt or worthlessness, difficulty concentrating, and suicidal ideation. Not everyone with depression will have suicidal ideation, and not necessarily a person with suicidal ideation will have depression.
This is what usually confuses people. Because people are used to, for example, the flu – you sneeze and your nose snot comes out, it's the flu. Or a cold. It's like a combination of factors. So, people have this belief that a person with a disorder will have that thing, that symptom, and if they have that symptom, they'll have that type of disorder. Not necessarily. It's a combination of factors, okay? So, looking at these nine main symptoms, if the patient comes, for example, to a psychiatrist and reports that in the last two weeks they've been feeling more tired, losing weight, unable to sleep, feeling very tired, and having a strange feeling of guilt or worthlessness with these five symptoms, one of which is either anhedonia or depressed mood, one of these two has to be present, either depressed mood or anhedonia. So, of these two plus one of the others, okay? So it could be depressed mood plus four, or anhedonia plus four, but it has to be one of the two, depressed mood or anhedonia plus four. So, let's say the person arrives there... Oh, I've lost the pleasure in things, I'm not feeling well, so Janedonia has already taken hold here, I'm feeling tired, I can't sleep properly, I'm overeating and I feel useless, I feel guilty about everything. For two weeks, the psychiatrist already has at least, of course it's not that simplified, the psychiatrist will ask other questions, will analyze life history, perhaps talk to family members, will check if there aren't other things that could also be causing it. For example, the person has just undergone bariatric surgery and they will feel these things. They may feel this, these things even due to the lack of absorption of nutrients. But of course, here I'm only speaking generically, as I said, this is just a lesson for clarification, it's not for diagnostic criteria, okay?
With these five symptoms, for two weeks, the psychiatrist already has what is necessary to then say whether or not the person fits the profile of depressive disorder.
And normally when the person has this, they already leave there. Like a prescription for medication that you get at the pharmacy, right? Of course, ideally you should seek out more than one professional.
Why? Because this also requires caution from the professional, knowing how to ask questions. Ideally, it shouldn't be done with just one consultation; you should seek out more professionals and have more consultations. And also learn to observe your life well. And that's why therapy will be fundamental in these cases, so the person can look, learn to look at themselves. It's very common for people not to know how to look at themselves with the craziness and rush of their daily lives, okay? And again, it's not just taking medication that will fix things in life if you do n't know what to do with your life.
And this whole hypothesis of this whole treatment process for depression with medication has a curious history, because normally in medicine, in science, these discoveries that change treatments happen randomly. In the 1950s, they were testing a medication called hyperoneside, which is no longer manufactured, right, but is no longer available due to its side effects, but in the 1960s... 50 of them were using hepronzide, which was an experimental treatment for people with tuberculosis. It was an experimental treatment, it didn't work for people with tuberculosis, but the people or patients reported an improvement in their mood, they felt lighter, happier.
And what happens there? It began to be noticed that a medication could help people's mood.
And the most important thing, the most impactful thing for you, mammal watching me here, is that this hepronzide, the hypothesis of the treatment or the result of hepronzide, was associated with an improvement in a neurotransmitter that you know called serotonin.
So this is where the serotonin hypothesis begins, which is the idea that serotonin is associated with mood, that it would be associated with depression.
I want you to pay attention to this. I'll repeat it. Let me see if you hear my campaign for you to pay attention. This is where the revolution in the use of drugs for the treatment of depression begins. And the initial hypothesis was the serotonin or monoamine hypothesis, but these are technical terms, I won't try to explain them. It might complicate things a lot for you, but the idea is that serotonin is associated with depression because people are taking medication that they believe influences serotonin levels.
And if this medication, which they believe increases serotonin, means that people whose mood improves, it's because they have more serotonin due to the medication, and therefore, a medication that increases serotonin improves depression. This serotonergic hypothesis persists to this day, but incredibly, it's an idea that has never been verified. There has never been, I repeat, never since the 1950s, a confirmation of this hypothesis. And why? Because it's not possible to verify it. And why?
Because there's no way to know what an adequate serotonin dosage is in a healthy brain.
Yes, my dear mammal, you'll see shortly, throughout the slides, that just a few years ago, and when I say just a few years ago, we've had studies since 2010, 2020 that are beginning to show that the effect of medication has never necessarily been due to monoamines, serotonin. Norepinephrine, dopamine, but also other factors.
And the most interesting thing is that even today there are many healthcare professionals who are not up-to-date. You who are listening to me know this, it wasn't your obligation, but a healthcare professional should know this inside and out. Because it's very common for people to go on podcasts, I've seen psychiatrists going on podcasts to say that drug X is important because of serotonin. This hypothesis has never been confirmed.
In fact, it's a hypothesis that is increasingly being observed to go down the drain, to hell, because there's no way to measure it. What is associated with the improvement of depression is another factor. These are factors that have been observed in the last 20 years, even less. And that's the general focus now. And that's why we say that in the next 10, 20 years there will be very important, impactful revolutions for the world of psychopathology treatments in general, with medication, with drugs. It's very interesting what we're going to see in the coming years, okay?
And the logic of the time That was exactly the idea, that depression was associated with low serotonin levels. If a person took medication, their serotonin levels would rise, and then they would improve, but it was never proven, it doesn't make sense. And you, those who have been my students for a long time, know how much I've nagged people about dopamine in ADHD, for example. Who has heard this thing about dopamine and ADHD?
Write it down. I was going to ask you to raise your hand, drink some water.
But, uh, you can't raise your hand, so write it down. Who here has heard those things like, "HDM is caused by low dopamine?" Who has heard that?
And then you have to do something to raise dopamine to improve concentration. Who has heard these things, write it down for me. Oh, because ADHD medication works because of dopamine. You take a cold shower to increase dopamine.
Dopamine fasting. Who has heard these things, please write it down, yes, I have. No, just so I know.
[clearing throat] Carlos Jadel, Carlos Jadel put something interesting. What's interesting, my dear?
Poliana, Poliana commented that, unfortunately, this is the majority, I think she's talking about the issue of psychiatrists here in 15 minutes of the prescription. Then Poliana says she's seen this in terms of health insurance and such. Unfortunately, it is, unfortunately this is very common, okay? It's not right, but unfortunately we know that this ends up happening. Poliana has already said it, she's heard it here many times, for sure. Gabriel also says yes.
Uh, it also applies to the issue of bipolar disorder. Edgar, Juda Nicola, on Instagram there are a lot of people talking about treating dysbiosis to increase serotonin. The other day I even made a React post talking about, refuting a doctor saying that depression starts in the gut because it's from the gut. The gut produces 90% of the body's serotonin and that makes me cringe because it's such a ridiculous idea.
First of all, serotonin is not the cause of... The serotonin problem isn't the problem that causes depression. It starts there. Secondly, serotonin from the gut doesn't go up to the brain; it doesn't go there.
The serotonin in the gut has a function in peristaltic movement and other processes within the intestine. It's just there, it stays there, it doesn't go up to the brain.
And it's very interesting, curious. I don't know how to define how a person who says they study something for 10, 15 years and don't know the basics of physiology, don't know the basics, the very basics. It's revolting. It's revolting. Sometimes I feel revolted seeing the bizarre things we see on the internet, okay? Because it puts people at risk.
So, some people say they've seen a lot of things about bathing. Laud also says here that's what she hears most.
I also hear these things that the gurus say all the time. It's crazy, okay? So, these hypotheses, the monoaminergic hypothesis, that a monoamine is... To attribute an illness, a problem, or a behavior to ADHD is nonsense.
It's wrong. Simply wrong. There's no physiological basis for it. A monoamine, for example, dopamine.
Dopamine cannot be held responsible for ADHD because dopamine has several functions, four functions in the central nervous system alone and other functions in the peripheral nervous system.
It's responsible for everything from moving your arm to grab something.
Parkinson's is associated with a problem in the dopaminergic system; that is, the person loses neurons in the dopaminergic system, which is why it's a neurodegenerative disease. And then, since they no longer have the neurons associated with the movement pathway, the nigrestriatal pathway, which dopamine is associated with, they experience difficulty in movement, so they start to have tremors. So, Hunton's disease, which I also study in my lab, is similar, in quotes, to Parkinson's, but it has another problem in another pathway, but it's also associated with... Dopamine and GABA, that is, it will generate a lot of problems in the person, not because of one molecule, but because of a system where that molecule is part of it. It's like saying you got a ticket because of a wheel bolt on your tire.
When you drive, you're not using your car's tire, okay? There's no bolt on the car's tire, okay? Were you speeding? Yes. Why? Because of the wheel bolt. No, man, the wheel bolt is there.
There are a lot of bolts still. There are more bolts on the tire than tire. But it's not the bolt that made you get the ticket.
But the bolt is there. You understand?
Dopamine is there, it's there in the process, poor thing. It's there in the middle, but it's not what makes you an idiot, rude, or silly with people. It's something else.
But it's there in the middle. [laughs] That's what sometimes's missing in the heads of the people who claim to study neuroscience. "Competence, doesn't understand that the nail and the heel, I don't know, are different things, even though they 're on the same foot, okay?" That's what you always need to understand.
And that is the very peculiar paradox regarding the timing of the issue here, concerning depression or pharmacotherapy treatment. Why?
It is known that a medication can even influence a very rapid peak in the release and production of dopamine, or, excuse me, serotonin, in the synaptic cleft. Why? Because it goes there and inhibits the reuptake of that serotonin.
Let's leave those technical terms for another lesson, okay? But serotonin becomes more available in the synaptic cleft, meaning there is more serotonin there in the cleft, in the space between neurons. Excellent. But why doesn't the person already feel this acute improvement in the same way that serotonin is present in the synaptic cleft?
Because serotonin isn't the person's problem, is it?
Why is it that some clinical improvements take weeks to start showing results? When will that happen? Remember, 1/3 of people don't achieve this improvement.
And depending on the person, depending on the patient, the person will spend several months trying various medications until they arrive at a dosage or a type of medication that will make them feel better. It could take months.
But why is there this mysterious thing here in the middle? Can anyone here give me an idea?
You, anyone watching me here, can you give me an idea? What is associated with this mysterious thing? What's behind this? Oh, if a person takes medication, within a few hours, or depending on the medication, within a few days, they already experience a peak of serotonin in the synaptic cleft within a few hours.
But it takes weeks for it to start having a positive effect. Why? What is associated with this space? Why does she have to keep taking it for weeks before she starts to notice an improvement?
Isabel asked here about learning to deal with the past. No, no, Isabel, no, the past generates depression, but I don't know, imagine that it's you and a person separated 10 years ago and to this day she, I don't know, can't talk to another person. It's no use her wanting to take medication to be happy if she can't talk to people, you understand? That's what I'm talking about. If she hasn't learned to deal with herself.
Hmm. Change in behavior. Excellent.
Alisson gave a good answer. Who else here agrees or disagrees with Alisson's statement? Alisson wrote: "Change in behavior". But why will the change in behavior cause this improvement here, this mystery of latency that's shown in the graph? What's associated with that?
Try answering me.
Could it be because the brain keeps getting more serotonin until it's expelled through the nose? It's something else, something else, I don't know, it's dopamine.
There is something in between that time period, and for decades no one knew exactly what it was, although there were some hypotheses.
Things are a little better these days.
And to help you better understand where we're going with this mysterious area of what's in this valley, this hidden valley of things, remember, if you're watching this lesson and have already liked it, please like this lesson.
We have 130 people, no, we have... No, we have quite a few people here, look.
But where are the likes? Crush that fun. There are 129 people watching.
Oh, that's great. Thanks for a Monday spent watching a lecture on the neurobiology of depression. When we decided on this topic, I thought: "Oh man, this is going to draw a handful of random people because, well, neurobiology of depression on a cold Monday, which is cold here in Florianópolis, I figured nobody's going to show up." That's great, there are 129 people participating here. Sending a hug to you all, and congratulations to all the mothers.
belated for Mother's Day. It was yesterday, May 10th. I brought some ribs for my mom, but the ribs were cold and I had to go out to buy some, [laughs] I had to go out to find the market open to buy lasagna.
[laughs] Some people posted this here.
Andrey mentioned behavior, Aum mentioned a lack in the receiver, Audrey talked about environment, time, placebo, and choices.
Marcelo Jesus gave an amazing lesson.
Thank you, Marcelo. I saw that you sent a WhatsApp message today, but I haven't been able to reply. I only saw that your name appeared there. Thanks. Change of environment. Adriana is talking about a really good class. Thanks. Anyone participating, feel free to take a screenshot, okay? Adriana is here participating. You can take a screenshot, you can post it on Instagram, or make a story. Does movement, serotonin, and excess cause anxiety? No. The therapist's acceptance has to do with privacy. Oh, very good, Adelmar. Adelmar here, congratulations. A round of applause, Adelmar!
Aemar even deserves a round of applause here because, truly, congratulations, it has to do with neural placidity. Did you hear clapping?
Did you hear clapping there? Write down if Aldemar heard applause because that will have something to do with this neural plasticity. And to talk about this mineral plasticity, there's no way to avoid explaining or telling you about this cascade of stressors, hypothalamus, pituitary and adrenal glands, the HPA axis, which some people also call HPA, although the term pituitary is already outdated in Brazil. So here we're going to talk about H, we're going to talk a little bit, I'll show you, I'll explain to you where these strange acronyms come from, okay? This cascade of stress will help us understand what is associated with this mood disorder that people call depression.
And that's why there's a real change in the person using pharmacotherapy treatment, as well as in the therapeutic process itself. What is associated with improvements in a person's life through medication or therapy, or medication combined with therapy, which is usually considered the gold standard in the world of science? But there is a cascade of stress that will involve this HA axis. And yes, you need to write this down, my dear mammal. Yes, you can take a screenshot. Students will later receive a PDF of these slides in the WhatsApp groups. So, the HPA axis originates from the hypothalamus, pituitary gland, and adrenal glands.
Ha.
I placed a threat or warning symbol here on the previous slide. This warning/threat symbol can be anything. It could be you waking up late, it could be your, I don't know, the bus is crowded, it could be someone arguing with you, it could be a pain you're feeling, you have a headache, you have the flu, you had surgery, it could be someone arguing with you, it could be you passing through the middle of a shootout, you're in a war zone, I don't know, it's something that bothers you. And here, my dear mammal, it's important that you pay attention to this, because cortisol is not a stress hormone, okay?
That's a lot, it's... I get very sad when I say this, it's very unfair to say that cortisol is the stress hormone. It's the same as saying that a knife is an instrument of death. No, you use a knife to spread butter on bread.
It's the same as saying that a cup causes trauma, or mental trauma, because you see someone throwing a cup at someone's head in the street. No, a mug for drinking coffee.
Cortisol is not the stress hormone.
Cortisol is a hormone released in our body, following an incredible neurophysiological cascade that makes you open your eyes to get out of bed, that makes you go to the gym, lift weights, that makes you excited to work, that makes you want to play with your child, with your dog, with your friends, play cards, I don't know. Cortisol is a hormone associated with survival. That 's not a bad thing.
Unfortunately, it is associated with the issue of stress because it is present in the midst of stress, but it is not the cause of stress and it is not generated by stress.
Continuous stress is associated with chronic cortisol activity.
But he, poor thing, doesn't do anything. It's the same, it's the same again, the wheel bolt on the tire. The guy drives 200 kilometers per hour and gets 20,000 fines. But it's not the tire bolt that causes the accident, which is what makes him get a fine. It's clear that if there's no screw in the tire, it won't drive a car, right? But no, it wasn't the screw that made the guy accelerate. That's what you need to understand. Cortisol is not to blame for anything. You need cortisol to get up and argue with your boss. But it's not cortisol's fault that you're arguing with your boss.
[laughs] That's what he's telling you to fight with the boss. It's not cortisol's fault that you're stuck in morning traffic. This is where you've decided to live.
Cortisol is released into the body during the day like this: "Okay, let's face this traffic." But every day you want to argue with your boss and face traffic, it's not the cortisol's fault, okay?
This is the point we need to understand when we talk about the neurobiology of color. So this cascade of symptoms begins with an aversive stimulus, or, if you want a more technical, nicer term, an aversive stimulus, which can be something external, it can be a noise outside, it can be a thought, it can be a memory. You wake up and think: "Today I'm going to have to face that damn boss again in my meeting, and I wasn't prepared, and I'm going to get fired, and I'm going to have to live on the street." Okay, cortisol is associated with that response to that stimulus. And then there's a whole cascade associated with it. Notice that this cascade doesn't start directly down there with the adrenal gland, which is down here above the insulins to generate cortisol. There's a whole cognitive process involved here as well, which is where therapy comes in, my dear.
My dear, I've already lived in Florianópolis, I'm already talking, my dear. This is where the cognitive process of therapy, of psychotherapy, begins.
Or, I don't know, if you also like philosophy, if you also like meditation, this cognitive process of rethinking metacognition, this process of self-analysis, this process of stopping, of giving yourself time, is part of this regulation process.
The hypothalamus is a region of our beloved brain that is associated with the hormonal regulation of everything we do. It is through the hypothalamus that we are able to survive and perform the basic functions of life. The hypothalamus doesn't decide to initiate this cascade on its own. The hypothalamus, again, will respond to the stimulus. Of course I understand, I understand it just like a screw, the screw on a car wheel. Your problem doesn't stem from the stimulus itself, but from the way you learned and are conditioned to deal with stimuli. Did you understand that? I 'll repeat it. It 's not the stimulus itself that's responsible for your problems, it's how you've learned to react to that stimulus. Let's imagine you 're so used to dealing with São Paulo's traffic that it does n't bother you anymore, you're already fine with it. You might even think it's normal to just chill for an hour stuck in traffic. You don't even care. I even found it funny, but for someone who isn't used to traffic, it could feel like the end of the world; that person could suffer a lot.
Therefore, often the same stimulus that may be aversive to one person may be neutral to another person. When someone swears, another person hears it and is completely astonished.
Wow, someone swore, and another person didn't even pay attention because they don't care about that at all. So, the hypothalamus is not the cause of your stress; it's part of a mechanism that involves a cognitive process and a set of responses conditioned by the group around you. All this I'm saying to help you piece together the puzzle in your head that therapy will be fundamental for a large number of people.
Why? Because people need to learn how to deal with the [ __ ] life they have, damn it. She doesn't know how to deal with this damn life. She keeps looking at Instagram and she thinks that everyone who swears is bad. She thinks that anyone who disagrees with her politics is bad. She needs to learn to deal with herself, because if she doesn't learn to deal with herself, it's no use putting ketamine up her nose, she won't get better.
And yes, I mentioned ketamine because today ketamine is an extremely promising medication that gives very rapid results in treating treatment-resistant depression.
What is that? Refractory depression occurs when a person has already taken two types of medication and has not obtained any results.
Of course, with a psychiatrist's guidance, okay?
And ketamine, when I say it gives very fast results, it's a matter of 2 hours. So, the person goes to a public healthcare facility ( SUS), goes to the hospital accompanied by a medical team, and they will receive a microdose of ketamine. Ketamine is extremely powerful; it gives a feeling of... it's called a psychomimetic drug. She will mimic a person who is experiencing psychosis, that is, hallucinations, detachment from the body, absence of the body. So, it's an extremely powerful drug. So, with microdosing under the supervision of a psychiatrist in a safe setting, the person can feel an improvement within a few hours, especially when they have a lot of suicidal thoughts within a refractory depression process, that is, people who are already at the breaking point. So, acetaminophen, a very promising drug for the coming years, is already being thoroughly analyzed and treated, with incredible results in just a few hours. And, of course, the person ends up in a long treatment, but I, for example, have already done a therapeutic process with a gentleman who used ketamine every week for years, well, not years, sorry, but for a very long time. And he himself said that he didn't want to get better because he liked feeling angry at the people who hurt him. I said, "So, why are you doing these things?" He says, "Ah, because it helps me remember the people who hurt me." I said, "Do you know you're spending money?"
But he was rich. So much so that he went to talk to her by helicopter. In other words, once again, it's the illusion people have that simply taking a pill will make them better, that it will cure them. No. You need to learn to deal with what you want, with what you have, and want to deal with what you have, okay? So, the hypothalamus is part of the cascade, it's not the cause of your problems. Just to make this very clear, I like to emphasize this. As someone who works in neuroscientists, I 'm astonished when I see people saying that the hypothalamus is the cause of their problem. It is not. That's it, it's the same as saying that your finger is responsible for you eating brigadeiro. No, you need your finger to eat brigadeiro, but it 's not the finger that makes you gain weight. A, the hypothalamus will send a signal to the pituitary gland, and the pituitary gland will release a hormone called ACTH into our bloodstream. Don't worry about that jumble of strange little names. Now, the important thing is for you to understand that in our beloved brain, something will trigger the hypothalamus, which will release a hormone. This hormone that you see here, where I'm hovering the mouse over the hypothalamus, this hormone will travel to the pituitary gland, which is located here in front and looks like these little boxing bags hanging down.
In the pituitary gland, another hormone will be released that will travel through the bloodstream to the adrenal gland. And in the adrenal gland, this hormone called cortisol will be released. And this cortisol is associated with you living, doing the things you have to do in life. The problem is that when the hypothalamus is constantly being activated by the stimulus you're experiencing, it will continue to generate cortisol that we'll call toxic, because, well, you should have solved the problem, but you didn't.
Think about it. You were supposed to resolve the issue, but you didn't. Every day you go there and face the same beast.
In nature, throughout all of evolution, throughout the entire evolutionary line of mammals, of humans, you never actually fought against a tiger 6 days a week, from 8 am to 6 pm, on a scale of 6. You would throw a rock at the lion, the lion would chase you, then you would hide, climb up, I don't know, I don't know if you can run from a lion, but that was the idea, you would run away from the lion. The lion gave up because he was tired, saying, "Ah, I'm not going to chase after that skinny guy." The lion was going to his den, you were going, you were going to yours too. That's it, it's over. The next day you wouldn't have to deal with the lion, you could just leave peacefully and do something else.
We, who are here in our den, working from 8 am to 6 pm, deal with the traffic, see, go, I don't know, do something else until 2 am, looking at our phones, watching TikTok, we spend the whole day fighting the lion. And the human brain wasn't made for that. The human brain was made for you to fight with some animal, to eat, and to sleep in your room, preferably alone—no, not alone, with company. We're the ones who keep messing things up.
Why are more and more people becoming depressed, despite improved diagnosis? It's because we're exhibiting increasingly harmful behaviors.
And here's a key word in this little blue square that I want you to pay close attention to, which is this: cell damage. And while you, while I drink water, I want you to comment, write in the comments: "Damage, cell phone". Please write it like this: "Dan celular". And remember to like this lesson so it reaches more people on YouTube and organically promotes our lesson here.
You can also invite more people by sending this and this live video to people via stories, or something like that, okay? But write the words "cellular damage" in the comments, like this: " cellular damage". Write to me, please, so I can get my water.
Let's see if I can reach my goal by the end of class.
From, cell phone.
Because if you take that word now, " mommy, son, giving the cell phone," you'll be able to truly understand what people have been trying to understand for decades—what's associated with depression, but couldn't.
Because today we're going to have a more in-depth and complete understanding of depression at a neurobiological level, okay? that depression is not caused by a monoamine issue like serotonin, but by a process of cellular damage. And of course, this cellular damage we're talking about here refers to the cells in our brain, okay? It's clear that other cells in the body will also be damaged. We could also talk about the gut-brain axis here, which is another axis entirely. We'll talk about this craziness another day, but today we're just talking about what's in our heads, okay? What is known today, what is understood today, is this: The thing is, this continuous stress, which we allow to happen, isn't in the body's nature, and it's going to generate this thing, this figure here in the middle, look, this figure here in the middle.
What do you observe when comparing the healthy figure to the restored figure? In the image on the left, where you see the healthy figure, you can understand that it's like, you know, the little broccoli, that cute little green broccoli, that has the stem, the little florets, and each floret has a little tree, each one of those very pretty things, think of that in a way similar to our brain with its neurons.
A healthy brain has a beautiful structure, a trunk, branches, and micro-branches, just like you see in this image on the left, the image of a healthy brain.
Chronic cortisol, and not only that, but other things will also be associated, but we're focusing on it here to make it a little easier for the class, will generate a process of removing this arborization.
He's going to prune those trees.
And what we're understanding today is that what's behind recovery from depression isn't simply a functional issue at the molecular level, at the serotonin level, I mean, but at the level of this regeneration, this restoration. This image here is beautiful. Let me see if I can do it. I can't just put her here because I think she's the one. Take a picture of her, she's so beautiful. Take a picture, take a photo. I'm going to stay here looking at her, look. Take a picture, take a screenshot. I'll take a look here. I'm going to count to three, okay. One two three. Strip. Because it's a very beautiful image that I prepared for you. This is what you need to understand, especially if you are a therapist, that what is associated with the improvement of a person with depression is not simply because they have more or less serotonin, it is because the dendritic arborization of this brain, the trees of these neurons, are connecting better to what is called neuroplasticity. This is clear. I'll teach another class someday. It 's not that exaggerated thing that people are making up, like, "Oh, I'm going to teach you neuroplasticity 3 neuroplasticity." That 's not how it works, is it? I know you've probably heard this before. Ah, because thought generates neuropathy, isn't that right? Ah, because repeating such a thing generates neuroticism. That's not how it works.
What you need to understand is that what is associated with the improvement of a person with depression is not simply serotonin, it is a combination of restored dendritic arborization.
The medication will be associated with that.
I mentioned ketamine a few minutes ago. Acetamine, she observes in a very, very, very powerful way this improvement of dendritic arborization in the prefrontal cortex, for example, so it's a very revolutionary and very recent drug, okay?
And of course, for this dendritic arborization to occur, fertile ground is necessary. So here I am talking to you now about something called neurotrophic theory.
And I'm no longer talking about the monoamine theory, which is the predominant theory to this day in the view that people had and still have of associating depression with serotonin, just as people associate ADHD with dopamine, which is wrong. Neurotrophic theory posits that what is associated with depression is this neuronal growth.
And one of the molecules associated here, in this case, is going to be this strange term, BDNF. I put BDNF like this, see. Can you see?
Brain-derived neurotropic factor or brain-derived neurotrophic factor. I'll try, don't worry too much about memorizing it, but don't just rely on your brain. Today, BDNF is perceived throughout virtually the entire body, but BDNF is a... how can I explain this in a simplified way?
It is the chemical support that will signal to your cell that it needs to grow. BDNF is like, you know, that stuff we put in fertilizer? BDF is the fertilizer that will tell your cell what to do. No, in this case, BDNF is the fertilizer that will tell your neuron, "Grow."
If BDNF says "grow," the neuron grows.
If BDNF says, "Don't grow, the neuron dies." Apoptosis, then, are relatively recent processes in the world of neuroscience.
BDNF is associated, for example, with physical activity, which is now considered the main preventive treatment, and also, when possible, because not everyone with depression can get out of bed to go to the gym, but preventively it is the best option.
When moderate to intense physical activity is possible, it is being observed as one of the main restorative factors in this brain development process, which will lead to an improvement in depression.
That's why physical activity is fundamental, and I know we tend to ignore it because of our busy lives, okay?
So, the neurotrophic theory goes beyond the idea that a person has depression because of serotonin and begins to understand that what is associated with this depression is cellular activity.
This cellular activity depends on a large cascade of events, and BDNF is the fertilizer that tells your brain cells to grow or not. And for that, he will need encouragement.
This stimulus, when we talk about food, sleep, physical activity, but also the absence of stress. Because if a person is in a stressful environment, the brain understands that it doesn't need to develop as much. The BDNF goes here, I put this little image here for you, let me put the BDNF here. This little image that I put here for you is associated with stimulating or binding to receptors, which will cause the postsynaptic neuron, that is, the one after the synapse, to have the command, the order to maintain better and stronger connections with the presynaptic cells. This BDNF is responsible for whether or not our dendritic tree structure grows. And here I put it that BDNF is a kind of neural fertilizer. It will promote the growth and survival of this synapse. A synapse, for those who have forgotten, is the space between two cells, two neurons. And it is in this space, in this synaptic cleft, that the entire biochemical process will take place, carrying information from neuron A to neuron B. And, eternally, the chronic stress that comes from the HPA axis will cause a drop in BDNF, leading to the death and atrophy of these neurons. And the antidepressant will work gradually on the development of these neural networks, because it will influence, in one way or another, the development and production of this natural fertilizer called BDNF.
And this is where we get the idea of depression as a multi- systemic process in our brain. When I said leave the HPA, pituitary gland and hypothalamus pituitary adrenal gland, we're only talking about one CD, only one cascade.
Today we know that depression acts directly on major centers of our brain, but not only, I repeat, not only the prefrontal cortex, hippocampus and amygdala.
The prefrontal cortex has a very interesting study that I presented in my doctoral thesis, which states that the prefrontal cortex is one of the main areas associated with people who have chronic depression, continuously for a long time. The neurons in the hyperfrontal cortex appear to wither, that is, they lose this dendritic arborization. The hippocampus is associated with memory. Media is associated with an immediate response to a stimulus. So, it's common for people with depression, especially chronic depression, to have more difficulty regulating their emotions, which is why the prefrontal cortex is important, in regulating what they're feeling. The hippocampus with its memory and the mygdala, its hyperreactivity. So, it's common for people with depression to have difficulty regulating their feelings, because the neural connections between these networks that you see here in yellow, the neural connections that you see in this network, in these yellow networks, in this triangle, are damaged. What happens when you lose this branching in this dendritic arborization? Do you lose speed?
Dendritic arborization. I'll give you a silly example here. You look here at the fingers of my hand. Let me take a look here. Here. Look at the fingers on my hand. Uh, imagine that this left hand of mine here, it's a neuron and it needs to carry information forward to another neuron that's here.
Here on my right hand, right here. See how I have five fingers on my left hand.
Yes, it's much easier for information from my left hand to reach my right hand because I have a thumb, an index finger, and a finger, meaning there are more ways to communicate.
For some reason, this neuron loses little fingers, and only the little pinky finger remains here, see? The information is more recalcitrant, it takes longer, it is not complete in carrying the neurochemical information from neuron A to neuron B. What will happen when a person undergoes a drug treatment process involving psychotherapy, for example? It will stimulate BDNF to produce new dendritic branches, more "little fingers" on the neuron, so that more "little fingers" connect to other neurons, facilitating the communication process.
In practice, when you observe this image that I put here, which is in yellow, blue, etc., when a person has or loses this connectivity between the hippocampus, midgut, and frontofrontal cortex, they are unable to cope with what they are feeling. She can't cope with the memories, she ca n't cope with the guilt, she can't cope with the feeling of pain, of failure, of loss, with the thoughts of suicide, of death, of failure, of misfortune, of catastrophe.
Therefore, there needs to be some kind of stimulus. If that person's brain isn't able to do that, they can't improve. And that's why sometimes a person can spend years in therapy and still not get better. Why? Because it's common for therapists [clearing their throat] to sometimes help the person understand what they're feeling, understand their pain, understand the memory, understand what happened, you know.
But her own brain, due to years of chronic stress, can no longer produce the neurochemicals necessary for that cell to control itself, to expand, to increase its arborization, its arborization. So, it is often necessary, in some cases, that people with a longer- lasting, more severe disorder do need medication. Why?
Because fertile soil is necessary for neurons to establish themselves.
And this fertile ground for the neuron to establish itself needs neurochemical support.
Even if the person knows, even if they want to, even if they are in therapy, if their own brain is not able to produce the necessary neurochemical substrate, the brain cannot recover.
Did you understand this? Why do I say this? Because there are a lot of people who blame themselves for needing medication and not being able to get it, and not taking it. I know a lot of people who spend their time tormenting themselves. Ah, because I go there and do therapy. Oh, I'm not going to take medicine. Damn, bro, take this. Ah, but I 'll take my medicine. I'm going to take some medicine. There will be side effects. There's nothing more damaging than being an annoying idiot who's messing things up. That 's not a sufficient side effect. What's wrong, man?
Pay attention.
Your life being this way isn't too much of a side effect anymore.
Take your medicine, bro. Stay calm and go to therapy if you need it too.
Can you understand this? That's how it is, which is why it's good for us to understand neuroscience, because it takes the weight off the blunders of those self-proclaimed gurus. Because the little kid will keep saying, "Oh, don't take medicine because medicine has side effects." But the guy's right there, and he can't even take a shower.
Damn, what's a bigger side effect than that?
Let the guy take his medicine.
Ah, but the long-term use of this medication will be harmful. And the guy thinking about suicide, it's not going to hurt him to keep thinking about suicide.
Oh, but that guy is whatever, damn it. The guy can't have good sex because of this bad feeling. That's not bad enough. Let the guy take his medicine.
We need to get rid of this silly prejudice that our great-grandmother and grandmother instilled in us, that boldo tea cures everything, man. And what good will solves it. It is not. It is not.
There are people who, due to their own biological factors or because life has dealt them many blows, have already given their brains what they had to give. If he doesn't have an external stimulus, he won't go anywhere, folks.
Go on, but don't go anywhere. Oh, therapy is therapy, man. Therapy will always be good for you to deal with your past, to deal with your pain, your anger, your frustration, your fear, with who you have learned to be.
But biology is unforgiving. There is no way to. You're going to get old, you're going to get wrinkles, your hair is going to fall out. It 's not therapy. Therapy won't make your hair grow back, wrinkles disappear, and you become young again. You'll have to use the substrate to help you. And everyone already does that. Toma Way, Toma Uses Botox, uh, Toma and the Pique, uh, what about those other more powerful things, retracted and monjaro, everyone's using that crap. Ah, but I'm not going to take medicine because medicine, medicine is chemicals. Oh there. And what's all that plowed stuff you stick up your ass? What is all this for, to look beautiful, to be healthy, to be happy? Not there. Not there. That's why my grandmother used to say that garlic tea improves everything.
Yeah.
So you have to take care. You, who are studying mammals, be careful with the exaggerations of those therapy gurus who think therapy solves everything because therapy is magic.
And also be careful with those self-proclaimed gurus who think that just taking medicine will make things work, because it wo n't. So you have to have a broad view of things. That's why I'm here teaching you, so you can have this broader perspective on things. That's why, as a neuroscientist, I'm going to tell you, you have to take medication, you want to take medication, you're getting good professional support, of course, go ahead and do therapy if you can manage it, okay? That's the ideal in both worlds. Of course, ideally you would be rich.
I don't know about you. Ideally, you should be rich.
Ideally, you'd be rich, not have to work at 7 am, and be able to go home and relax on Thursday.
Eh, eh, having someone who cleans your clothes, your house. Ideally, you should be rich and travel. Are you going to travel this weekend? Yes, I'm going to travel. Ideally, you should be rich. [laughs] If you're not rich, try going to bed earlier, okay? Of course, when you're rich you can also regulate these things a bit, but ideally that's the way it is. That's actually the little secret. Do you want to be happy?
Become rich. [laughs] Since it's not easy for a lot of people, what do you do? Take your medicine, go to therapy, try not to get too bothered by the annoying neighbor, try not to argue online with the crazy people there, try to get rid of this problem a little bit. Then when you get rich, then great, then you, you, you change your plan, okay? It's like flying in a helicopter there. Adriana said: "You used to travel by helicopter, but today you can't travel by helicopter?" Okay, so you'll have to take medicine.
[laughs] Are you taking a helicopter ride today? No. Then you'll need to take antidepressants. How much does a helicopter ride cost? When you're flying in a helicopter, then you won't worry so much, okay? More or less. Have more humility in your heart, my dear mammal. That's what I'm trying to tell you, okay? You won't be perfect, and you don't have to be perfect to be happy. Just live. And therapy, where does it fit into all of this? Of course, medication, as I said, in short, medication is responsible for neurosis today, according to the neurotrophic theory.
We understand that what is associated with the improvement of depression is not serotonin, as people used to believe and many still believe today, but rather an influence on the process of neuronal development. Look how beautiful, it's the brain adapting, the tiny neurons, the little fingers are being rescued. And therapy, where does that fit into the equation? Therapy, it's going to enter this mysterious latency period here, look. Let's say that since a person started taking medication, therapy will help them improve their chemical balance, generate new growth, and gain a deeper, more refined perspective. I'll say, imagine the person says, "And now she's undergone a weight-loss treatment, she's started using contraceptives, pills, and other weight-loss aids."
And she's happy because she finally lost weight, uh, she lost weight, man, that's great, she lost weight, congratulations. Now do this: start going to the gym, start distancing yourself from those annoying people who only think they'll be happy if they're drunk on the weekend. Then, things start to change. So, you see, it's not simply a matter of shoving something down your throat, swallowing something, and that's it. Now you have to learn to live life in a different way. That's where therapy comes in. So therapy is fundamental for you, as a mammal, to understand this neuroplasticity process, and therapy will also influence this neuroplasticity process, okay? Here I'm going to share not just these, but these are the most famous ones, so to speak. This one here, from 2006, is the Stard study, where he used data from over 4,000 patients, investigated and studied them, and concluded and observed that when a medication or treatment didn't work, a multi- pronged approach involving more than one thing was essential for these people.
In other words, instead of just taking medication X or undergoing therapy Y, when a person engaged in a multi-faceted approach, they achieved better results. And that's why you, as a therapist, always have to be updating yourself, refreshing your knowledge, and reviewing the content to stay sharp.
Another study, this one from 2015, relatively more recent, states that the combination of psychotherapy and pharmacotherapy in the treatment of depressed adults is significantly more effective than either therapy alone or pharmacotherapy alone.
And that's where therapy will be essential in this chemical terrain and in this process of planting new connections in the brain. Just a reminder that there are 185 million people in the world today, okay? It's not just in Brazil, Brazil has 200 million P's, think about it, man.
Brazil today has 200 million inhabitants.
There are 185 million people in the world diagnosed with depression, okay? Well, imagine all the other people who don't have a diagnosis due to financial difficulties, prejudice, etc. Imagine an entire Brazil, okay? That number represents an entire Brazil of people with depression. That's very sad.
And not all of these people will have access to good pharmacotherapy. Not all of these people will be a good fit for pharmacotherapy. Not all of these people will fit into therapy A or B.
And that's why I always like to talk about updating my knowledge, especially for you who are my students, especially for you who have already studied reintegration therapy with me, you know how much I prioritize, how much I encourage, how much I prioritize continuous study and improvement in my work, in my life, okay? And for those of you participating with me here, I want to invite you to participate in our in-person training in implied reintegration therapy, which will take place at the end of the year, in November. Once again, it's class 22, the 22nd class.
The 20th and 22nd in-person classes of implicit reintegration therapy will take place in Balneo and Camboriu. A training program that is constantly being updated. We had class 21 this past April in Banário and Camboriu as well.
The group that participated, Adri was there too, now much more in-depth, much more up-to-date, with new content, with a much more simplified approach to what can be simplified so you have more security and peace of mind, bringing a much more in- depth scientific framework than I gave in the last classes, three, four years ago, uh, about four years ago, I don't even remember anymore, which were the last classes we gave.
So, for those of you who need or want to delve deeper, and even if you're not yet a therapist, this training is also suitable for you, because our in- person training is part of the ongoing online training as well.
And the update, as Jodan put it there, is huge. So, for those who are more experienced students and need a refresher course, and I recommend that you come to this refresher course to delve deeper into these more refined details of neuroscience in therapy, I recommend that you come to our training program. And of course, always with a mother's heart, we have a very special promotion right now for those participating in this live stream, an offer that lasts until May 15th. Today is the 11th, so there are 11, 12, 13, 14, and 15. So, until Friday, if I'm not mistaken, that's it, right? Until Friday. Until Friday at midnight, a really cool 30% discount promotion for you, the student who wants to refresh your knowledge, or for you who are participating in this live event and always wanted to be a therapist but couldn't afford it, didn't want to go back to college. Come to this training program where you'll have the support of a neuroscientist; many of these people have been therapists for much longer and will be guiding you—they've been my students for a long time. Come and join this training. 7 days, Balneário Camboriú, an in-person immersion that also includes full support, all of our online components that you have access to after the training as well, okay? To learn more about the payment methods available, such as Pix, bank slip, and credit card (which can be a combination of bank slip and Pix payments), please contact us, Jordânia. Hey, what's the link for anyone who wants to talk, whoever wants to, what's the link, the QR code, or is it in the video description, what's the WhatsApp number for anyone who wants to talk?
Our website is also linked in the video description, in case you want to delve deeper and learn more about our goal. But for anyone who wants to join our training and send a WhatsApp message, or something like that, please write " Jordandi" in the comments, and I'll put the WhatsApp name on the screen for anyone who wants to see it, okay?
Adriana just participated in T21, oh, T22, T21 was absolutely incredible here, oh.
Aha.
The ClickS app. I do n't know if you've already... Oh, here I am. Oh, I'll leave WhatsApp on the screen. The WhatsApp icon on the screen looks like this one here. 47983070, okay? This is the WhatsApp number where you can speak directly with our team to start a conversation. Our company link is also in the video description; it's the website and we have a WhatsApp number so you can get in touch and learn more, okay? I would now like to take these last 5 minutes to answer questions, to chat a little more, since I won't be able to take all the time to answer questions, whether about implicit reintegration therapy or the training, or also to continue delving deeper into the content of the lesson presented here. What questions do you have that you need to talk to me about right now?
Oh, I left it turned off. Wait a minute. Okay, that's it now.
Adriana, the training is a gift, a generous offering filled with so much knowledge and so much transformation. Thanks.
Let me see if I can do it. Excellent.
Thank you, Bruna. The training was wonderful.
Transformer. Thank you, Bruninha.
Fábia, this promotion is simply wonderful. Water level indicator. Fabia, Fabia was in T21. Cool. Come to shift 22. Leandro Freitas will be on shift 22. Leandro, that's great. I'm very happy. Congratulations, therapist. Will it be saved so I can watch it again later?
Yes, it will be recorded and will end here.
It will be available here on YouTube soon, which is why I uploaded it directly to YouTube to make it easier for you to access it, okay?
I'll ask Jordana to send the PDF of the presentation to the groups later.
So, I'd like to answer some of your questions now about the topic of today's class, about depression, about any of these studies, or any other information you'd like to ask about.
Take advantage of these last few minutes here. I also want to thank all of today's participants. I was very happy, like I said, I didn't think there would be many people. I thought there would be about 10 people because it was Monday, because of the theme, but we ended up with 120, 130 people, so I was really happy. Camila, this training has only one problem, it only lasts 7 days, right?
In-person training is great, people participate, and you form a lot of friendships.
Regiane, I'm in training, I'll continue with the others. Thank you, Regi. You'll be very welcome, Regi.
Ah, Carlos asked: "At what stage of depression does cellular damage occur?" Ah, Carlos, great question. Carlos, depression itself is already seen as cellular damage, okay? It's not that depression will cause cellular damage; depression is already a result of cellular damage, okay?
Did you understand that? Ah, the order is reversed, okay?
Ah, Ana Cláudia commented: "What situations increase BDNF production, physical activity, diet?"
Physical activity is now considered the most important factor in stimulating the production of necessary proteins, okay? Physical activity, and diet as well—in this case, a diet that isn't so detrimental, meaning not constantly drinking alcohol. Drinking too much coffee, eating a lot of empty calories.
I'm not talking about a specific diet here.
In principle, it would be a diet where you try to avoid as much as possible any of those empty, ultra-processed foods, like Doritos and chocolate every day, all the time. Quo will eat your Doritos and chocolate, okay, fine, but don't make that your main meal. That's what I'm trying to say, okay? So, nutrition, sleep, and physical activity. Of course, in order to have good quality sleep, physical activity, and a good diet, you will also need to have a specific routine for that. So, things are kind of going hand in hand. To have good quality sleep and physical activity, you may already need to reduce your stress, and at the same time, physical activity and sleep will also reduce your stress. So, they are two sides of the same coin, okay?
It starts from one side to the other.
Reducing your stress and doing physical activity. The two things will reinforce each other over time.
Marcelo CN information. Thank you, Marcelo.
Katiara asks: "Can you talk about how BNF can be stimulated?" Oh, I just saw your question, but I already answered it. Physical activity can relieve or ward off stress, but physical activity is the best, and this is the most evident fact today, especially with mice. And we also make a translation to animals, to human animals with rats and mice and other mammals, we observe a recovery of neurons after physical activity. Yes, put them in the water to swim, put them on their little wheel. Neuronal recovery is superior for animals that undergo this type of moderate to intense physical activity compared to animals that do not undergo physical activity. We can't see this directly in humans, because no code of ethics accepts making people walk on a treadmill after having their heads opened for euthanasia. So we base our observations on animals, and there's a high probability that this also happens with human beings, because we observe it in practice with people. So, the person is there, starts doing physical activity, and begins to feel an improvement in well-being and overall quality of life. It's clear that for her to have that too, she's also making other changes in her life, so the two things go hand in hand. It's OK?
Thank you, Gabriel, for participating.
I'm very happy. Oh Regiane, thank you so much for the live stream. Thank you, Regiane, for following along.
Thank you, Neia. Excellent information.
Damia, thank you. Damião, I'm sorry, I really appreciate your help. This is great information, because many cases, many people, are in need of this excellent lesson.
Thank you, Damião. I'm glad I could help. Thank you, Alexandra. The class is great, and it's almost over, finishing the training. Thank you, Alexandre.
José Hítilton.
José asked: "A person who suffered a stroke... Let me just fix something here.
Uh-huh. Okay.
Here, José asked: "A person who suffered a stroke has depression, is it possible that neither medication nor therapy can help?" I've tried to help someone like that, therapy didn't have the desired effect. José Elton, that's right. It's possible that neither therapy nor medication can help a person. It's possible, okay? Not even in cases like that.
Why? A stroke causes neuronal damage.
So, it's possible that the neuronal damage the person suffered is already influencing their mood response, okay? Furthermore, José, depending on the after-effects or how the person is affected, they don't feel well, they have difficulties in their daily lives, then it involves financial issues, then the person has to take strong medication to deal with the after-effects. And this strong medication already has, as a side effect, symptoms associated with depression. So it becomes a cycle. Do you understand?
Perhaps normally older people who suffered a stroke, so I'm assuming it 's an older person. What did this patient you treated suffer? Their age, the resulting sequelae, the medication they're taking—all of this influences the depressive symptoms, okay? So it's a cycle you can't break simply by taking A or B or using technique X or Y, Z. The whole process is necessary and takes a long time.
André, good evening, Rafael. What's the online program like after the in-person training? Great question, André.
Thank you, André. The online classes, like these, are continuous classes.
You have access to some materials, you have access to some therapies, access to recorded therapies, and you also have access to our group where you can ask your questions.
And also the entire mentoring and continuous supervision process that we provide afterward, okay? So, André, don't worry, feel free. There's a link below; you can also send a WhatsApp message to the number I'll see if I can find it again here, 988300370.
You can send your questions, and then we'll send them to you. Okay, so the syllabus is good? And with the syllabus you can get more detail, a more in-depth look at the content.
Camila, and when a person goes to therapy, uses medication, but lives in a stressful environment, in that case, does the damage tend to continue happening? Camila, well, in principle, the damage will continue. Uh, let's try to give a silly analogy. Imagine you went there, you had back pain, you had treatment, the person put your spine back in place, but you get home and you sit crooked on your sofa, you're going to damage your spine again. Do you understand?
Because the brain reacts to the stimulus. If the stimulus you're getting is a stimulus that hurts you, it will hurt you.
Okay, Camila? So yes, it will be necessary to change the environment so that you continue to have improvement or have a superior improvement in your treatment.
Luciana asked, Rafael, I asked above if you've seen anything that explains why lithium, ketamine, even ECT, have such good results for persistent disorders, Disorder, bipolar disorder, schizophrenia, depression, acetamine. I don't have the slide here right now. Let me see if I can get the slide easily. But ketamine, it has a chemical process, okay? Ketamine will stimulate a receptor called the NMDA receptor. This receptor will be blocked by acetamine so that glutamate... here's the technical explanation, okay? I'll explain, you can watch the recorded class later.
[laughs] In our cells, we have two types of receptors, AMP receptors and NMDA receptors. Ketamine will block the AMP receptor, uh, NMDA. With the NMDA receptor blocked, glutamine won't enter.
And when glutamine doesn't enter, it won't activate the intracellular cascade responsible for causing the neuron to undergo apoptosis.
Since this cascade is blocked, what will happen is a stimulus from another neurochemical pathway that will cause the cell in the neuron to amplify the branching.
Dendritic. So it's a neurochemical process involving AMPA and NMDA receptors, blocking the NMDA receptor and activating intracellular cascades, activating the dendritic branch at the end. To give an example, imagine a radio signal you're receiving, and someone blocks one of the speakers.
When you block the speaker, it will activate a different beat in the other speaker. And that beat that activates in that other speaker will generate a different sound that the person wasn't hearing, simply because you put your hand on top of a speaker. That's all, okay?
And regarding the question you asked about ECT, why does ECT have such good and persistent results for bipolar disorders and depression? Because of the management the person is achieving in their affective regulation. And again, the management or this behavioral change will influence how that neuron expresses itself. And it's also because, most likely, people who already have bipolar disorder or schizophrenia are also using medication. So, both things... They will potentiate each other. So, the person is using the medication, they are receiving the stimulus for the neuron to be modified, and in the meantime, they are receiving support for emotional regulation, which helps them better cope with what they are feeling. So, the neuron is more flexible, so to speak, and someone is saying: "Hey, instead of fighting with daddy, come here and relax." So it causes the neuron to have regulation, to have a better pathway now for a new connection that will be better for the person. That's the neurobiological explanation of it, okay? It's not simply because the neuron changed, it's because, in addition to being better, in addition to changing, it now has better direction. That's where psychotherapy comes in. That's why psychotherapy combined with pharmacotherapy has better results, because in addition to influencing the neurobiological process, you're telling it: "Now come here and stay up here." Understand?
That's what happens.
Thank you, Neil. I'm glad to... Help.
Thank you, Edmaro, for your kindness. And Ana Cláudia, finally, the supposed elevation of serotonin helps the recovery of neuronal damage via BDNF. Serotonin may be associated with this neuroplastic process, but not with it in itself, it's not serotonin.
So what we observe today is that the problem with serotonin in depression is the result and not the cause. Why? When there is less dendritic arborization in neurons, less serotonin will be used.
Okay?
Jordania put it this way: "Guys, T22C, incredible, don't forget to participate."
Long-time students, come for the refresher course, I'm sure you'll benefit greatly from it. Thank you, Camila, for your kindness. Jan also saw the registration link in the WhatsApp groups. Melody, I'm glad you enjoyed the explanation. My dear friends, I want to thank you all for your kindness and affection in participating. I hope you found this lesson truly beneficial, a more in-depth lesson on neurobiology. Remember to attend the upcoming classes, sign up for our training here, and take advantage of this special price we're offering, especially for our long-time students, to refresh and continue improving their skills in implicit reintegration therapy. And if you've watched this recorded lesson up to this point, congratulations, I'm very happy. I hope you enjoy our content and that it helps you improve your perspective on the world, your understanding of others, and how you relate to them. And remember, if you have any questions, if you need anything, write to us here. We 'll be very happy to be able to help you as well. Have a great week, all the best, and see you in the next class.
Bye-bye.
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