Adolescent Brain and Eating Disorders (Part 1) - Dr. Spaulding-Barclay
Hello, and welcome to the Family Days Presentation on understanding the adolescent brain. I'm Michael Spaulding-Barclay. I'm an Adolescent Medicine Physician. Many of you won't know what I am and that's okay. I'll talk about that. I'm currently a Medical Director for Child and Adolescent Services. I realized I did not update my recent promotion, which is always fun, here at Eating Recovery Center in Denver. And I also function as an Adolescent Medicine Consultant over at ACUTE Center for Eating Disorders at Denver Health, which is an organization that treats the most severe eating disorders for adult patients, usually. And then they recently expanded down to teenagers and asked me to come aboard to help with some of that. So a little bit about me, now, there are three physicians here at ERC, Colorado in Denver. And so, I have about a third of the patients.
And so for those of you who your kids talk about Dr. Mike, that's me. I grew up in Indiana. I went to IU Bloomington. So I'm a Hoosier. And then I got married after college and started medical school at Indiana University right there in Indianapolis. I also did my pediatric residency there. I thought about going up to Chicago for that, but my wife had her teaching certificate and there was not reciprocity between the states. So we stayed here. Then my wife had been willing to marry me and stuck in graduate school for seven years of training with me. So I told her I'd go anywhere in the country. She wanted to go. So she got into graduate school in Boston. So we moved out there. I was a primary pediatrician out in Boston for about three years.
After that, we decided to move back to Indiana, originally, to be closer to our family. We wanted to start having kids of our own. And also I decided to do The Adolescent Medicine Fellowship there. And I chose Indiana University because it was one of seven sites that had a Maternal and Child Health Bureau grant to do a specific education called Leadership Education and Adolescent Health, which was a fantastic program for me to be involved in. There were only seven sites across the country that were allowed to do that. So that was great for me. I was also able to get a Master's Degree in Clinical Research during that time as well, and got to publish some of that... Or present some of that research. My first academic job was as the Medical Director of the Eating Disorder Center at the children's hospital in Kansas City, which is Children's Mercy Hospital. And that's affiliated with University of Missouri-Kansas City School of Medicine. I did that for five years.
And then in 2012, I came here to Denver and joined The Child and Adolescent Center here, and was made Associate Medical Director in 2014. And then in 2019, I became the Medical Director of our program here. So when I was at the children's hospital in Kansas City, I had much more academic time. And so, I was a member of an adolescent research working group for the National Institute of Health. I was able to be much more involved in the Society of Adolescent Health and Medicine. I was President of our Midwest Chapter. I was a National Committee member. I used to lecture for the American Academy of Pediatrics a lot, the Society of Adolescent Health and Medicine frequently. I was on two not for profit eating disorder boards, the Eating Disorders Task Force in Indiana, and then the Body Balance Coalition in Missouri.
And if you're familiar with USA Gymnastics, then Christy Henrich is a name you'll recognize. And she is very open that she had her eating disorder and she died from complications of her disease. And her family and her loved ones were from Missouri, and they set up that foundation. So I was a part of their board while I was there. And I've really cut down on a lot of that work since I've come to ERC because we believe in the docs in Denver being here full-time. And so I don't have a private practice. And pop in a day or two a week, I'm here full-time. So I've only kept up with, really, the Academy for Eating Disorders. Since then, I recently finished in May of 2019, my three year stint as the Co-Chair of the Medical Care Standards committee for that organization for both adults and children.
So I get a little break from the administrative hassle for a little bit and hope to rejoin that committee next year. From a personal standpoint, I've been married, again, as I said, to my wife since 1994. We've got two kids, a fifth grader and an eighth grader. Usually, I wear bow ties. I didn't dress up as fancy for today's lecture. So that's me. I just wanted to give you a little background, so that you know, I actually know what I'm talking about, which is good, because it can be hard to hear multiple perspectives from different people in different treatment centers and maybe not know what people's background and training is. So that's why I shared that with you today. Okay. So today what we're going to talk about is, really, this overarching question, right? Which is, what does optimal nutrition status and normal weight have to do with brain development and brain wellness.
And really, I separated those two, nutritional status and normal weight. Because technically, they're two separate things. And we're going to talk about that over time. And then they're linked to the brain development and why we care in eating disorders. So this slide was just to kind of orient you to... That's what a brain looks like. And of course that's a brain that's been preserved, because normally, they're very gelatinous and it would just kind of ooze over the table, but that's been a preserved brain. But really, we have that picture to kind of start us in recognizing how far the brain research has come. Not just in eating disorders, but even in adolescents. And so this allows us to realize and think about, in a very rudimentary way, we started with kind of looking at the brain.
And it actually started within the 1700s, if you had a slanted forehead, you were probably a criminal. And if you had a smooth forehead, you were probably an aristocrat, right? And we've come a long way from there. But that still let us, kind of step back and think about where we started because that'll help us see how far we've come. So a little bit about the brain, for some of you this takes you back to, maybe, biochemistry or neuroanatomy, and that might be rather frightening. So we'll keep it pretty straightforward. On this slide, you'll see a couple of pictures and I'll get to those in a second. But to start with, the main components of the brain are divided into three, really three specific things, gray matter, white matter, and then fluid. And I'll talk a little bit later about why they're called gray and white. But the gray matter is really the nerve bodies, neuronal nerve brain cell. All of those mean the same thing.
Neurophil which is dendrites and other cells that support of a function of the neuron cells or the nerve cells, and then capillaries or blood vessels that go through the brain. And then the white matter of the brain, are what are called myelinated axon tracks. And if you look at the upper right hand corner photo, you're going to see a black background and a white cell body. And then there all these kind of spicules that are spreading out from that cell body. And those are the white matter, the myelinated axon tracks. Now, you can also look at that. And if you think of the highway system for the United States, you'd see, "Okay, that's a city. And then there are highways that are leaving from that city and connecting to other cities along the way." And that's a great way of looking at how the brain functions.
Now, the lower right hand picture is of the myelinated axon tract. And so what you'll see is that, the middle part is labeled axon and that's the nerve kind of track, that's running through the brain and throughout the body. And then surrounding that... And you'll see, it's kind of trying to give you a three dimensional picture surrounding that, wrapping that axon is something called myelin, the myelin sheath. The myelin functions kind of the insulation around the wires. And the way we talk about that is of course that increases the efficiency of the transmission and the information. So for instance, if I could do an experiment where I could actually slow down the speed of light, obviously you can't do that, but if I could, I could set up two lamps and the first lamp would have a light switch that was connected with a plug to the wall that had insulated wire.
And so I would flip the switch and instantly the light would light up and it would light up very brightly. But if I had another lamp where I had a wire that was not insulated, number one, don't get shocked, so don't touch it, right? But I would flip on the light. And if we could actually see this, the light would turn on more slowly. And it would actually be a little bit dimmer because the speed of the electron flow across that wire would be slower than the insulated wire. And some of that energy would be lost or dissipated to the atmosphere. And so we would lose some of the efficiency of the transmission of that information. And so the myelinated axon tracks are how the information travels throughout our body on the nerve stream.
And so the reason we talk about that and the reason we care is that myelin... And you'll see on the picture that myelin is yellow. And yellow, historically, in Atlases of Neuroanatomy and Anatomy is the function of depicting fat. And so myelin is actually supremely made of fat. Many of you, obviously you're watching this, you have a loved one or your child who has an eating disorder and all eating disorders share the hallmark of malnutrition. It doesn't matter if it's a restricting anorexia nervosa or a binge/purge subtype of anorexia nervosa, bulimia nervosa, binge eating disorder. It doesn't matter. There's no nutrition in all of them. And so if there's loss of fat content in the diet, then we're going to see a decrease or a loss of the myelin surrounding those myelinated tracks.
Now, this slide you don't have to try to read it. It'll be very small on screen, but basically it says that high cholesterol level is essential for myelin membrane growth. And we highlighted the part and I'll read that sentence that says, "This shows that cholesterol is an indispensable component of myelin membranes and the cholesterol availability, oligodendrocytes is a rate limiting factor for brain maturation." So let's say that again, "Cholesterol availability is a rate limiting factor for brain maturation." Yet I just said, that you have a teenager who has an eating disorder, which means they're suffering from malnutrition. And so they've actually limited the brain's development. That's why we're so hardcore about our treatment approach in children and adolescents and why weight restoration is really starting to be called brain rescue.
That's also why... I'll back up. It's called brain rescue. Now, that's also why we think FBT or family-based treatment can be so helpful. If you've heard of family-based treatment before, that's basically... For those of you who are very familiar with it, I apologize. I'm going to dumb it down quite a bit. But it's basically putting the parents back in charge of feeding their child and supporting their child during this process. Because of course, as we just talked about, their brain has been limited. They have malnutrition, so they have less cholesterol. They have myelin damage. Their brain is not functioning efficiently. It is a rate limiting step in ongoing brain maturation. They can't do this work. So that's why we love FBT. Now, this is a funny slide in some ways.
Now, I love Time Magazine itself, because I think Time Magazine is the perfect combination of science and complete crap, right? Because you've got scientific articles which are great and well-researched, and very good. But then you've also got that annoying ad in the back. And for those of you who are women that carry a baby to term, you had that ad that always said, you're supposed to wear this necklace. And it has a jingly little charm and it bounces on your belly as you walk. And it stimulates the child's development of musical appreciation. And if you don't do that, you're a terrible mother to be, and if you do it for only 49.95 for three equal installments, you too can encourage your child's brain development. So that's the crap part of Time Magazine. But I love this because it was very simple and it had both, right? Eat butter, which is kind of a funny statement and we laugh, but in reality, butter is a fat source, right?
And we talked about, without cholesterol, without our fat, to be able to do the myelin sheath, we're limiting our brain's development. So that's why I love this. But I also like it because in the smaller print, it says, "Scientists labeled fat the enemy, and why they were wrong." And I also like this because it allows me to remember to be humble because in reality scientists were wrong, right? But also, sometimes scientists were lying and that's always something we've got to watch out for. It's a problem, and we realize that, and that's not great. But it's competing interests, and we live in currently, in the United States. We live in a capitalistic society that's having to look at this. So I think it keeps us humble in several ways. One, is that we can be wrong. And the other is that we have to watch out to make sure that people are really caring about what's most important.
Now, I said I'd talk about why we have gray matter and white matter. And in reality, I hope it will burst your bubble. But in some ways, as doctors, we're not that smart. Because on a MRI image or on the CAT scan image, sometimes, these look white and they look gray. And so this is a picture of three separate representations of what you can see in an MRI. And if we start on the right side of the screen, that is a depiction of a brain as if I was standing like this and you cut my brain in half like that. So you're looking from the side into the brain. The middle picture is actually lying down on the table and looking up. So I'd be lying like that, and you'd have cut me across that way. And the far left picture is looking directly out at you and having cut my face in this way.
And so, CAT scans and MRI scans can give multiple views and pictures, so you can traverse through the brain and see three dimensional structures that way. Now, I feel very limited ability to do kind of spatial recognition. And I really struggled. My wife says that I cannot find the right size Tupperware for the leftovers for the life of me. And I think that's absolutely accurate. But when you're a radiologist, you can do this very well. And so, you can actually see these pictures by looking at three dimensional or two dimensional cuts repeatedly. You can make, in your mind, a three dimensional picture. And so we can see structures within the brain. Now, obviously, if you're thinking of a brain tumor, that would be helpful, but also it can be very helpful for tracking the development of the brain. And we'll talk about that.
So this slide packs a lot into one slide. And so we'll stay on this slide for a little bit. What I want to start with is on the far left. And I'll read it to you because it might be hard to read on the screen. And it's a structural MRI to track changes in size and shape of neuroanatomical structures with development. Basically the original way that brain imaging was able to be used... Remember I had the picture of the brain that was outside and was being preserved, that was the lumpy bumpy brain in the forehead, and then we moved into brain imaging. And the first way we were able to image the brain was structurally. And so what you can see on the slide is that highlighted in red is a slightly inverted E-shape, and then maybe a long peanut or almond-shape that's near the center.
So the concept of this was you would have a surgeon who has a patient who suffered a gunshot wound or was in a car crash, and they came in and had an abnormality or a destruction of brain tissue in the areas that are highlighted. And that physician realized, "Oh, this patient cannot do the following processes." Can't do XYZ, right? And so they realized, "Well, XYZ must be controlled in the brain, in that area." Which is great, right? Because then they publish that. And then some surgeon halfway across the country or the world, but say, "I saw the same thing." And then maybe a stroke specialist would say, "I had a patient who had a stroke. And they had destruction in the same area. And they too could not do XYZ." And so that's when we realized you can find out what areas of the brain tasked with certain areas of function.
However, then even smarter people said, "Now, wait a minute. We know that inverted E and this long almond-shape are involved in doing this task. What does that area of the brain look like in an infant? What does it look like in a child? What does it look like in a teenager? What's it look like in adult or in a geriatric patient, because then you could track the brain's development over time, at least from a structural standpoint. And that can provide a lot of information and data, which is great." Now, obviously, not enough. And so that took us to the next phase. And the next phase is the middle picture. And the middle picture says, "Functional MRI imaging or FMRI, tracking changes in the brain and behavior with development." So in this instance, what this allows you to do, there are special MRIs where you can put someone in the scanner and you can have them do something like listen to music.
And the area of the brain that is involved in the process of hearing and processing auditory information becomes active. It's using energy. You can have them do a math problem, and the area of the brain that's involved in doing mathematics would light up because it becomes active and it's using energy. You can show them pictures of kittens and puppy dogs and flowers, and the vision center will light up. What's interesting is that some studies have shown when you put patients with anorexia nervosa in that scanner and you show them either a picture of themselves, or they see a reflection of themselves, the vision center actually goes dormant or is not used very much. The area of the brain that actually lights up as being active is a very rudimentary central part of our brain. It functions as the fear and rage center, the fight or flight center.
And that area of the brain lights up and it's processing the information. So we were really struck with that. We said, "Well, we always thought we knew you have distorted view of yourself..." Because a patient with anorexia nervosa, restricting type, might be appearing grossly underweight, right? Yet they see themselves as overweight. So we always knew they're clearly not seeing themselves appropriately, but we didn't really know what that meant. And then this brain imaging showed that they're not actually processing the information within the visual cortex. So in reality, it brings up the question of, do these patients even see? The old saying, "If a tree falls in the woods and no one is there to hear it, does it make a sound?" And of course, as a scientist, I'm like, "Of course it does. It causes vibrations in the air and that's how sound is transmitted." But it's an existential question, right? If no one's there to actually appreciate that that has happened or to hear it, it doesn't matter, right? So if patients aren't using the visual center of the brain to process the information, are they really seeing themselves? And we just don't know.
Now, the other piece, looking at this functional brain imaging is, what this allowed us to do is... In this example I gave of the person that had a stroke or had a car crash or a gunshot wound. And they couldn't a certain action, right? Or couldn't do a certain task. Functional brain imaging allowed us to then look at healthy people and say, "Well, what portion of that inverted E? Is it the entire portion of the inverted E? The entire long almond or peanut-shaped segment of that that's involved in... Well, no, we highlighted in yellow. It's really the tips of the E, and the tip of that peanut, or that almond-shape structure that are involved in actually doing that task. And so, again, with functional MRI, then you could look at that task being performed at different ages across the spectrum, and see the change and the development of the brain over time, which really opened up our understanding in the brain and development.
And actually, is one of the things that allowed us to realize that adolescence is a true period of development. It's actually not a social construct based off the bleeding heart liberals, right? Who wanted to stop people from having to be children and work. After the industrial revolution, and so they made up the construct of adolescents. Well, actually, no, it's not made up. There's a tremendous amount of adolescent brain development that does actually occur. And in the final, the right hand side of the screen is diffusion tensor imaging. And look, that's way above my pay grade. I am not a brain imager. I'm not a neuroscientist in that way. And so it's extremely complicated. But what it's looking at is actually, we've got these two areas, right? The inverted E and this almond-shape. And we know that really, it's just the tips of those two that are involved in these processes.
Well, how are they connected? Well, if you reflect back on the slide before, when I told you that imaging and brain scans is actually cuts of the brain. And it's only by putting each of those images together, that you get a three dimensional picture, you can realize that, "Well, the transmission of information from the E to the almond might actually be going in a three-dimensional path." And so, on the right hand side of the screen, you can see these almost look like wires, blue, red, and green wires, and they're traversing. And that's just in one cut, they're traversing back and forth. If we were able to pile all the cuts on top of each other, you would see that that's a true three-dimensional pathway or structure. So diffusion tensor imaging is able to look at the connections, basically, the connections between the brain and the areas of the brain.
And then again, you can look at the connection process and see, number one, is it different as the brain develops? And number two, how does that process develop? How do those connections start? When do they start? How strong are they? Did they become more stronger? Did they become less strong? And that's been a fascinating area of brain research. Again, way above my pay grade. And I can barely understand diffusion tensor imaging. But recognizing that it's allowing us to realize that it's the connections within the brain that are made that are actually important, really leads us into the next phase of our discussion. Now, this picture I love because... The first picture I had a gelatinous brain that was there and everybody thought, "Oh, that's the brain." Well, not really. The brain when we think about it, is the function of the brain. And I like this picture, because it's all of these wires, this massive millions and millions of wires, all passing and intertwined with each other into different areas, all of them connected. That lets you realize how complicated the brain is.
And it also allows you to realize how destructive a process that hurts the brain can be. Because even if that process is as simple, and this is not simple, but as simple as a foreign object coming through the brain, like a gunshot, or blunt trauma that occurs to the brain in a car crash, or brain tumor that grows in an area of the brain. It's not just hurting that brain tissue, anything that was coming through there as a wire is being destroyed. And so that could be impacting the brain all over the place. And that's the concern that we have because of course, malnutrition, which we talked about is present in every single one of your family members or loved ones or your children's illnesses is damaging brain tissue. It's starving the brain and in adolescence, it's stopping brain development.
Now, we're going to talk a little bit about the brain's development and we'll get down to kind of brass tacks here, right? So we're going to look at it in our outline here, we're going to look at the childhood process, and then adolescence. We're going to repeat the same ideas. We're going to use the idea of pruning, right? So proliferation or growth and then pruning or trimming away. And if you own any trees and bushes in your backyard, you know what this looks like, right? You actually have to cut some of the branches, destroying the tree. Cutting that branch, destroying that branch rather, to help the health of the tree or the bush overall. So you're actually doing good by pruning, even though you're destroying part of the tree at first, right? So that's the analogy or the metaphor rather, we're going to use to look at this.
We're also going to talk about the sequential process of the brain's development. And hopefully that will give you a little bit of insight into your teenager, wherever they are. And that might, hopefully, give you a little compassion for yourself on your frustration level with your team. Because it might explain that in reality, we're going to, hopefully, shift the paradigm from, teenagers are annoying and act in stupid ways all the time to shifting... To realizing that in fact teenagers are highly impressive because most of them are functioning at peak brain developmental capacity at all times. Fascinating, right? Teenagers for years have been described as making bad decisions and poorly thought out decisions and are so annoying, yet in reality, they may be functioning even better than we are at times. So it's a humbling experience to think about. Then we're going to talk about the hormones and the environment and those influence on the brain's development. And then finally, we're going to talk about what's really important to you of course, it's the relationship of all these things to eating disorders. And how we can provide a developmental, any sensitive approach to eating disorders. And we'll talk about that.
Now, let's look at childhood. So when does this start? So here's a pictorial representation of this process. And on the left side of the screen, you see a blue nerve cell, it's just in one nerve cell as an example. And then there are five surrounding orange cells, and there's a couple orange cells off on the left side of the screen. One on the top and one on the bottom that are not on there, but you can see the myelinated axon tracks have reached out like a hand. And this slide is to show the proliferation. Everybody's trying to touch each other. All the nerves as they're reaching out to make as many connections as they possibly can make. So there's all these little tiny red arrows that are touching and reaching out. That's proliferation, just growth and reach out, touch everything you can.
The process of pruning is shown on the right hand side of the slide. And there's two things I want you to notice. Number one, is there's little scissors on there. They cut out most of the connections. So the bottom two orange nerves have been cut off. Those aren't needed. Top two are cut-off, those aren't needed. The bottom one that was coming in from the off the screen has been cut-off. And so really, the pathway is from the upper left hand corner of the screen, coming in to connect to the blue nerve cell, going straight across and connecting to the orange nerve cell at the end of the screen. What you'll also notice is that, we're trying to represent that by the thickening of those connections. So the yellow highlighting the connection to the pathway and literally, the little red arrows have become big blue feet that are connected to that next nerve.
And so there's tons of proliferation and pruning, which may be weak connections, but they're everywhere possible. And then the pruning process cuts out what you don't need and strengthens what you have left. Now, back to a Time Magazine pictorial representation. And I love this because it's talking about how a child's brain develops. It was a great scientific article on brain development. And they have the little pictures in the brain of the child playing the violin. And again, in the back, you can buy the little dangly thing for 49.95 in three monthly installments. That makes you feel inadequate as a parent. But what I also like about this is it the bottom, and what it means for Child Care and Welfare Reform. Now, obviously, we're not going to talk about Child Care Welfare Reform. That's not the point, but it is the acknowledgement that even Time Magazine was able to realize that brain development of children is important and it starts in infancy. And we're going to talk about, and it actually starts before infancy.
When you look at brain development, humans actually achieve maximum neuronal density during pregnancy. So the second trimester of pregnancy, between the third and six months of development in the uterus, and that's that upper picture of nerve proliferation, dramatic growth within the brain. And during the last trimester pruning has already started, we're already cutting out. I love this slide too, because it says, "Non-essential brain cells." Which I always think is a little scary to say, and perhaps a little bit arrogant on scientist's part to say those are non-essential. But we're trimming out areas of the brain that we don't think we're going to need to be using, that's already happening. The baby hasn't even been born and the process of both proliferation and pruning is already occurring. Now, this also highlights something else that we know, which is, children that are born prematurely are removed from the uterus during that pruning phase.
And we do know that there are higher incidences of some developmental brain abnormalities that occur in children who were born severely prematurely and it may be because of part of that. So we already know this process happens and it's important, but it's fascinating that it happened before we're even out as a baby. Now, the second phase we look at, we're going to look at brain development from birth to age six. And this is where you need to cut us just a little bit of slack, and I'll guide you through the metaphor. But I'll explain why we chose this one later and you'll get it. But in the top of the slide, the first point, in early childhood, significant brain growth, so proliferation in the gray matter. So that actually, the 90 to 95% of our adult brain size is achieved by kindergarten. Now, that's partly why they call them toddlers, right? They're toddling about on their huge head for their tiny little body.
But in reality, if proliferation was where it was at, then we would be at our maximum smartness in kindergarten, and we're obviously not. So the second bullet part says, "Of course the size of the brain has been attained." But not the power of the brain. And the power of the brain is actually going to be achieved through the interconnectivity. So we're going to have some pruning that occurs, and then the connections that are made within the brain. Now, the second phase of childhood from about age six to age 12, again, this time period of significant proliferation. So really, we've got proliferation from birth to 12, but we wanted to show you it's brain size achievement, birth to six. And in six to 12, there are significant connections that are being made.
So proliferation could be put in quotations there, because it's not necessarily growing more brain cells, but it's thickening of this connectivity. So everything's coming together. And what's interesting is that this peaks slightly differently based on gender. So girls peak just a little bit earlier and that's done by about age 11 and for boys, it's done by about age 12 and a half, which is interesting because we know developmentally, girls develop both physically and also emotionally a little bit earlier than boys do. And they go through puberty a little bit earlier than boys do. So it's interesting that this occurs. And there are some correlates we'll talk about later.
Now, what happens during adolescents? Overwhelming, and most of your children are already in adolescence. So let's talk about that. So I love this quote though, and you'll have to indulge me. So I'll use my old man cranky voice. And I had a neighbor who had this old man cranky voice. And I never knew why until my brothers explained to me that it was... When I was six, I think I was six because I think, it was kindergarten. I had climbed onto a shed in the backyard and peeled off every single one of the shingles because it was hot Pennsylvania summer, and they just peeled off so easily. And I was fascinated by that.
But I'll use my cranky man voice because of that, because I too would have been angry at me. "Youth today loves luxury. They have bad manners, contempt for authority, no respect for older people or our elders. They talk nonsense when they should be working. They don't stand up when I walk in the room any more. They contradict their parents. They talk too much. They put their feet on the table. Ah, you dang kids get out of my yard." That's the classic explanation to that. So who wrote this? Was it my neighbor? I mean, it certainly could have been, in the seventies. Socrates. So we have teenagers for millennia, right? It's hilarious to think about this. So I love that this idea of teenagers have been a thorn in our backside forever, was there well before science was developed. Well before brain imaging was even thought of. Well before they knew the brain was anything important. So we've had that.
That's why this paradigm shift of looking at adolescent brain development and recognizing that there may be functioning at peak developmental capacity instead of always making dumb decisions, and always being a thorn in our side is so profound. Because the paradigm has always been that, "They're annoying and make terrible decisions." And for any of you out there who are teenagers and are watching this to learn my heartfelt apologies, because I actually believe you are developing at peak development or operating at peak developmental brain capacity. But this idea of you always annoying us has been around forever. So this classic idea of adolescent behavior being influenced by raging hormones, and underdeveloped cognitive controls led to immature behavior. So it was this idea of teenagers always have a lot of go, go, go, but they never have the, "Whoa, whoa, hold on a second. I want to think that through."
Well, part of that is influenced by hormones. Hormones, it turns out are incredibly active within the brain. When we look at hormones in general, we know hormones play a role throughout the body, particularly in the teenage years. And we know some of that. We have sexual characteristics that develop because of hormones. We also have some diseases that are very prominent or have spikes in change and their behavioral presentation during the adolescent years. So body composition, that's the difference between our muscle development and our growth. So for instance, my wife taught high school English, I said that prior, and the little freshmen would leave at the end of the school year, and they'd be like, "Bye Mrs. SB." And they'd walked down the hall. And then she said, sophomore year, she would start in the fall. And these giants would come thundering down the hall saying, "Hey, Mrs. SB, how was your summer?" And she was like, "Oh my gosh, what happened to little Timmy?" Well, he's body composition changed. He grew taller, his muscle mass shifted from fat mass, his voice deepened. All of these things that occur. And we know they're hormonally mediated.
And we also know there are certain diseases that either present or change during the adolescent years, acne is a great example. If you are a 40 year old person and you've always had clear skin and all of a sudden you develop significant facial acne, you need to go to your doctor, because you have a tumor until proven otherwise. Because that's not supposed to happen at that age range. But when teenagers came into my office and they had acne, my first thought was not, "Oh my goodness, they have a brain tumor, or kidney tumor or technically, an adrenal tumor." My thought was, "Yeah, they have acne. Welcome to adolescence. We're going to give you some creams that you feel like don't work that well. And you will be annoyed and won't want to use them, and we'll constantly be in this battle of trying to get you to use them."
But also there are certain cancers that are more active or become more diagnosed during the teenage years. A great example of that would be testicular cancer. It is a disease of young men. So I'm almost 50 I'm well out of the range of testicular cancer, I'm never going to get that. That's a teenager and mid-20s, early 30s disease. And then you're out of the woods. Certain types of epilepsy. Epilepsy is just a fancy word for seizure disorder. And so there are certain types of seizures or epilepsy that are prominent during the puberty years, or have a peak in development. Bipolar disorder, you can see that come on during late adolescence. Schizophrenia can present in the mid-20s, kind of the very end of adolescence, and it has to be during adulthood.
So we've always known that there were certain diseases that were seen during adolescence. We knew it must be some sort of developmental phase. It wasn't just a social construct. It was something real. And then as we learn more and more about these things, we thought hormones are probably involved and it turns out they certainly are. Now, looking within adolescence, in this idea of proliferation and pruning, let's go on to that again. So again, the same picture, right? There's proliferation. And we talked about that by about age 11 to 12, a significant amount of proliferation in brain, both the volume of the brain was achieved by about eight, six, but then an increase in all of this connectivity. So that was another way we use the word proliferation. And then adolescence happens, and adolescence is that period of pruning.
So again, the same slide we saw before, where you're cutting out connections to the brain that we don't think are important. So between the ages of 12 and the early twenties, almost a percent a year is cut away. So we lose about 15% of our gray matter. Now, this is a great example of when grandma's right. Grandmas usually are right. They may not always have the exact right thinking, but in general they're usually spot on. So use it or lose it. "If you stop taking your piano lessons now, you're going to regret it later." Yeah. Totally stopped taking my piano lessons. Totally regret it later. It's not impossible for me to learn to play piano now, but it's a lot harder, why? Well, you'll be happy to know because I'm caring for your child but I spend a lot more effort on science and math and thickening those connections.
But I lost some of the ability to make those connections very thick along the artistic pathway that way. My oldest brother, he continued on with his piano lessons and he can still accompany his kids today when they play. So grandma was right about that. Use it or lose it, but it's that combination. You're using it. So not only are you losing the parts you're not using, but you're using the parts that are left. And so you're thickening those connections. So that's continuing to be kind of perfected throughout this process. So I did that with science and math and got better and better at it. And I got less and less good at like learning a foreign language and learning music.
So, as the brain is becoming gradually more effective, trimming away areas we don't need, and thickening the connections of other areas, what we're realizing... The second bullet point is, this is at the expense of losing some of our ability to heal from injury to the brain. So for instance, if you look at a child who's two or three years old and they end up having a disease that impacts their brain as a stroke or brain tumor, and it impacts the area of learning to walk compared to me at 50, almost 50 years old, having the same thing happen to me, well, who is it going to be easier to train, to learn how to walk? Well, the two year old, because they were barely knowing how to do it anyway. And their brain is so plastic and they have so development ahead of them. They can find how to walk and learn and retrain their brain much easier than I can because I've already trimmed down most of that stuff that I didn't need anymore.
So we know some basic examples of that from, again, looking at things structurally. Structural damage to the brain and how our bodies recovered from it. But then we can also look more at function of the brain. And so what about things that impact the way our brain functions? It may not be a blood loss or a blunt trauma, but injuries to the brain like a seizure disorder that alters the electrical conduction within the brain? Well, if that happens during childhood or adolescence where the brain is developing, that impacts the brain differently than if it happens at my age. What about damage to the brain that's emotional? And whether that's witnessing violence, being a part of a violence, whether it's anxiety or depressive disorders, which we know when you have anxiety, your brain is releasing chemicals that are actually neurotoxins.
So your brain is anxious and you're releasing chemicals that actually are damaging your brain and making that worse. You're marinating in this sauce that's actually bad for your brain. It's impacting the way that develops. Again, very different than now for me, at almost age 50 when the brain development has been completed. Now, the good news is processing speed continues to increase till about age 25 or so though, and it's all downhill from there. So for most of you watching, sorry, we're on the bottom half, that's for sure. Now, just in case you're a pictorial person, or you learn visually, this is a picture of the brain and you'll notice on the left, it's labeled age five, then the bottom age eight, then up to age 12, down to 16, then back up to age 20. And you'll notice the color change, and the lighter colors, yellows, reds, oranges, and light greens are the very, very rudimentary or early phase of the brain that's not very developed.
And the later phase of the brain is the dark blues and the purples. And those are the developed part of the brain. And what you see is, you see that trajectory, during adolescence, the brain is becoming much more developed and still even at age 20, there's a lot of red and some yellow and some green in there. Despite the fact that in the United States, we've said at age 18, you're an adult and you can make your own decisions and you can vote and you can be drafted in the army. You can join the army. Meanwhile, that also means we could be taking 18 year olds, putting them truly, in true life or death situations, where they truly have to make split second decisions that are incredibly important all while following rules of engagement or guidelines that are created by people, my age, drinking coffee, and eating pizza sitting out until we hash out the rules of engagement.
My brain's fully developed and there's age 20 still not fully developed. Really makes us think about how we've made some decisions in our world. I'll read this, you don't have to read it on the slide. This is a quote from Jay Giedd, and he used to be the Chief of Brain Imaging through the National of Mental Health, which is one of the institutes within the National Institutes of Health. And this is why we chose proliferation and pruning. I think his is even more beautiful. He uses the idea of sculpting. And so I'll read this to you, "Right around the time of puberty and on into the adult years is a particularly critical time for brain sculpting to take place. Much like Michelangelo's David, that beautiful sculpture. You started with a huge block of granite. That's the brain at the peak of the pubertal years.
The art then is created by removing pieces of the granite. And that is how the brain is sculpting itself. Bigger isn't necessarily better, otherwise, the peak and brain function would actually occur at age 11 or 12 and a half. Rather the advances in brain function by taking away and pruning down some of those connections themselves." So you start with a block of granite and by destroying some of the granted you release the beauty that is underneath that. So now let's look, take a breath. Now let's say, go to the bathroom, get some coffee, put me on pause, whatever you do.
Now, we'll move into the sequential areas of the brain and how that maturational process occurs. I warn you, some of these slides have a lot of small print. You don't need to read it. If you can see it, that's great. I'll read the important parts to you, so no stress. But basically, we're going to talk about how the brain matures in a very sequential process. And it basically goes back to front. And so, let's look at some of those areas. So one of the first parts of the brain to develop is called the cerebellum. You'll see this list on the bottom right hand side of this screen, there's a large yellow area that's pointing at it. It's in the very back and the bottom of a brain. And in the small print that you probably can't read, basically, it talked about, initially, we thought the cerebellum was mostly involved within kind of physical coordination. And part of that was because they did studies on rat, where if they chopped off the cerebellum, they got all wonky and they couldn't control the limbs very well.
But it turns out, of course, we needed to be humble because, once again, with more study and elaborate thought, we realized that actually the cerebellum is very involved in higher processes of learning, particularly within supporting functions of mathematics, music and advanced social skills. Now it's interesting, you could make the argument that some of the social skills may actually be through the recognition and interpretation of body language, and that's a movement-based process. So there is some possibility that would really make sense. And that we were a little foolish to think at first it was mostly just movement. What's also of interest about the cerebellum is that the cerebellum is really sensitive to the environment and even more so than specifically to our genes or the heredity. So it's taking input from the environment, is very sensitive to that. Talk about more about that in a second.
Now, we're going to move back to front. It's kind of detouring. We're going into the deep part of the brain, but just go with it on me. And this is the amygdala, the yellow arrow pointing to it on the screen. The amygdala is the emotional center of the brain. That's the fear and rage center that I talked about before in a functional MRI scanning that lights up like a Christmas tree when patients with anorexia nervosa see themselves. It's not the vision center of the brain. It's this fear and rage center, this emotional center of the brain. What's important though, I just talked about the first part to develop as a cerebellum. The second is the emotional center of the brain. So of course, teenagers are functioning and reacting out of an emotional context. Makes total sense, it's the next thing to develop.
Next we move on to the basal ganglia, which is an area of the brain. It's interesting. It's a little bit larger in females than male. So again, a different hormonal structure of set up there, which is interesting to think about. And basically the basal ganglia is trying to act as kind of the administrative assistant and the secretary that's kind of helping you to organize and prioritize some of this information. But again, isn't it interesting that you're starting to develop your emotional response system well before you have anything that organizes or prioritizes any of that. Which is why we get those beautiful times when we ask our kids, "Oh my gosh, what were you thinking? Ah!" And they say, "[inaudible 00:43:01]." And we're like, we want to pull our hair out. Maybe I already did pull my hair out. When in reality, now nobody talks like this, but wouldn't it be fascinating, if we went to visit our child and get them out of the jail because they'd been locked up and we let them sit overnight and we go there in the morning and we say, "Oh my gosh, son, daughter, what were you thinking?"
And they say, "Mother, father allow me to explain. I was walking along the sidewalk with my peers, cajoling and prodding me forward. And I saw that brick on the ground and it's beautiful, perfectly rectangular shape, and has this hole drilled through it. So I knew it would really fly through the air with less friction and resistance. I've learned that in math recently, and I saw that plate glass window and I knew, Oh, those two were destined to join one another. And in fact, yes, father, I did actually see the police car across the street out of my peripheral vision, which I took note of. But also, I was recognizing my peers behind me laughing and building me up and saying that I wasn't brave enough. And my gosh, I'm going to show them. So I picked up that brick and I threw it with all my force and I made sure when I threw it, that I looked over my shoulder to make sure that the person I was interested in the most was taking notice of me. And I threw with all my might. And oh, father, mother, if you could have been there and heard the crash that it made and the stimulation to my brain and the sensory sensation, that's why I did that father. And it was totally worth it."
That would be great. No one talks like that. It would still be terrible and it would be dumb and they still would have been arrested, but it would make a lot more sense for us. And then if they stopped to say even further, "Mother, I did that because I have a biological drive to provide my brain the input it needs to perform its brain development. And without getting this input and without developing, I'll be stunted forever. So I knew this was in best interest to pursue this incredibly emotionally engaging experience. That's why I did it." Although we don't like necessarily what it said, we like that a lot more than, "I don't know." Right? "Why did you do that?" "Oh, I don't know." Because they're annoyed and frustrated and feel they're so stupid, acting so dumb. When in reality, they're acting at peak developmental capacity and encouraging their ongoing brain development, which we'll hear about later is essential to mental health.
Now, the corpus callosum is the next area of the brain that we talk about that develops, it's really... That's the connection between the two hemispheres of the brain. And it's really... Again, initially they just thought that wasn't that important. And it's incredibly important in processing brain information, particularly in the efficiency and the speed with which we can process that information. And then finally, the last part of the brain that develops is the prefrontal cortex. Now, the prefrontal cortex on this slide is described as the CEO of the brain or the area of sober second thought. Teenagers have tons of hormones that go, go, go the emotional center of the brain that go, go, go. The prefrontal cortex is our, whoa. "I saw the beauty of the brick and the plate glass window, and I wanted them to meet, but I realized not the best idea with a cop sitting over there. So I don't think I'm going to do that today." And the whoa, is the last thing to develop. And we know brain development isn't complete until nearly 25, maybe a little earlier in girls, 23, right?
That's why teenagers are engaging in what we've call stupid behaviors. So again, it's from back to front, but we can also look at this differently, we can look at the back of the brain or posterior, in other words for back, don't worry about that. But the back of the brain, those areas of the brain development really mediate direct communication with the environment. So the area that involves vision or visual cortex is in the back of the brain, the auditory cortex. Some of the hearing or some of the touch and spatial processing are in the back of the brain. So the areas that are... It makes sense. They're involved in input of information from the environment and having to make decisions. And it also makes sense that it's very rudimentary, because any rudimentary animal knows, "Oh, all of a sudden it got dark, that could be a shadow. I got cold, I should move into the sun." So it's mediating contact with the environment and that's what the brain is functioning from.
The mid point area of the brain, the midbrain that we talk about that functions next is really the input of coordinating that sensory input. It's the start of emotions and attaching value to some of these things that are coming. And so, "Oh, I really like that sound, or I really like that view." Artists that are can identify things that are aesthetically pleasing to them from a visual cortex standpoint. And they can start prioritizing that and making decisions based on the emotions surrounding those issues. And then finally the front or the anterior, or the front portion of the brain, which again, is the prefrontal cortex, the area of sober thought, putting all of that together, weighing the costs and benefits, the consequences to our behaviors.
So go, go, go, at first, the whoa comes later. A finer a way of looking at this as the kind of trying brain way of looking. So reptiles share with us the reptilian brain or the internal structures of the back of the brain structures, mediating contact with the environment. Mammals, the limbic system. Limbic system is just another area for our emotional system. And then finally we say the Neo-mammalian or the humans are the only ones that develop a neocortex that allows us to think brilliantly and have this sober second thought. So big, deep breath. We'll summarize this very briefly. Again, we talked about this concept of proliferation and pruning. There's proliferation that occurs from birth to age six and then proliferation, again, that goes from age six to 12, which is the increasing, strengthening connectivity that's happening in the brain.
And then fine tuning or the pruning process is what occurs during adolescents. The cutting away is what actually is that allowing the brain to fully come on line. But that it does so in a very sequential process, so that, it's the last thing to come on line is the thing we all wish they had first, which is the ability to weigh the consequences to their actions. But that actually comes later. And if you, that has a child, that's making these dumb decisions. Well, gosh, any of you that have a child or a loved one that has a disease that seems irrational, perfect explanation of eating disorders. They seem completely irrational. And in some ways it makes sense that there's a peak of onset of eating disorders during the adolescent time frame. Now, it doesn't just mean that maturation will make it all get better, but it's definitely interesting that occurs during this period of brain development.
And finally, like I mentioned before, full brain maturation, isn't complete until about age 25. So now let's shift gears a little bit and let's talk about the hormonal and environmental influences on brain development. Now, I love this slide because we're going to... I highlighted a few things. But these are the steroid hormones. So we all know hormones like testosterone and estrogen. We've heard about those. Those are listed on the lower right hand side of the screen. Testosterone and estradiol is just a fancy name for estrogen. That's listed under the gonadal hormones. The gonads are our sex hormones. So the testes and the ovaries are what create those. But in reality, you'll see there's a bunch of arrows and there's these precursors. So estrone is what turns into estradiol and you can follow the arrows back and you'll end at cholesterol.
And if you look at the bottom of the screen... We don't have time to talk about these today, very much, but also aldosterone and cortisol are adrenal steroids. Adrenal gland, is a different area of the body. And these create aldosterone and cortisol, which are very actually involved in the regulation of excitability and some impacts on mood and anxiety. However, we don't have time to talk about those. But those also come from cholesterol. So in reality, cholesterol is the building block for steroids. So we're always thinking of sex steroids as sexual characteristics, right? Breast tissue development, body, hair, body odor, all of that stuff, muscle mass changes. But in reality, these are involved in processes all over our body. All of them coming from the same fundamental building block of cholesterol, yet, your kids and loved ones have a disease that is marked by malnutrition, right? Malnutrition. Eat butter, joking aside, we'll move on.
So let's look at the hormone influences on the brain. Again, the peak of brain proliferation is kind of correlated with that onset of puberty. The brain gets its peak at about 11 for girls, about 12 and a half for boys, that's about when puberty starts. So they're obviously linked. However, we also know there's variation in the timing of puberty. So there are kids who are late bloomers. There are kids who are early bloomers. And we know that, although these processes, brain development and sexual characteristics with hormones are linked, they're not a hundred percent tightly linked. So the process that occurs in the brain is going to occur, even if secondary sexual characteristics haven't yet developed. So if you have a late physical developer, you'll notice that their voice is still high. They don't have a lot of muscle development. They complain about being flat chested or whatever it is.
Yet you know, that intellectually, socially, developmentally, they're still as advanced as their age match peers, right? And vice versa. If they're really early pubertal developers from a physical characteristic standpoint, their brain did not go faster. So in reality, they may look like a 16 year old girl or a 17 or 18 year old boy, but they're still functioning like the age they are, 11 or 12 year old, maybe 12 or 13 year old, if you're lucky. But you can imagine if you look like an older teenager, people are going to expect certain behavior on a view that you may not be developmentally ready to do, which also might put you in peril. There may be times that you're an early developer and you find yourself in a pseudo dating situation that catches you totally off guard because you didn't catch the cues that everybody else was leaving and you should leave too. And then you find yourself in the basement with an older boy or girl that you don't know. And so you can see where that might get kids into situations that are difficult to navigate for them.
We also know that hormones, whether they're gonadal hormones or adrenal hormones, and again, we're not going to talk much about adrenal hormones, are very involved in all the organs developments throughout the entire body. So of course, they're involved in the brain. And where are these hormones involved? All over the body and all over the brain, but particularly in areas of the brain that regulate mood and excitability. Now on the screen, you'll see that it's talking about serotonin. There are several other neurotransmitters, norepinephrine, dopamine, all of them can be involved in this. Serotonin is just a very well known one that people have heard of, but they're involved in the mood and excitability pathway, which makes sense during adolescence, is the time period of high stimulation of the mood and anxiety standpoint, mood and anxiety center of the brain, of the emotional center of the brain it's being stimulated like gangbusters. So it makes sense that would be those where those receptors for hormones would be located.
Now really, the next few slides are just if you're really a visual person, or if you happen to be a neuroanatomist out there, you'll recognize all of these areas of the brain. We're not going to go into them. But it's just showing that all of these areas are involved in hormone receptor interactions and influence brain development. Now, this slide is actually looking on the left hand side of the screen. What it's supposed to look like is kind of a tree branch, and that's a nerve and there's little spicules, right? Like those hands that we're reaching out to make connections with other nerves. And the right side of the brain is a slide that's supposed to represent a brain tissue that was just dipped in estrogen. And what it's supposed to see, if it shows up nicely on the screen like it does for my screen is that there's a lot more of these little spicules or thorns on the bush. Lots more hands reaching out to make connection just by dunking it in estrogen, fascinating process.
Other areas of the brain, these are kind of central or limbic systems of the brain that are being looked at, obviously, anywhere in the brain that we look, it's been influenced by hormones, which is fascinating. So we know that sex hormones are especially active in this limbic center or this emotional center of the brain. And so partly, that's why it's creating this tinderbox of emotions. A lot of go, go, go, and very little of the whoa, that goes along with it. So adolescents are actively looking for experiences to create these intense feelings. So again, referring back to my parody of what the child should say, "Well, so father, mother, I was driven to have these experiences to create my further brain developmental process." Maddening and necessary.
Now, let's look at the environment and how the environment affects the brain. Now, I share these slide sets with Dr. Ovidio Bermudez, who hopefully you get to hear one of his talks as well. He's a brilliant scientist. He's an incredible clinician and a wonderful man. And I don't know exactly how he came up with this slide, but I like to think it was this, because this a way of coming up with a definition for environment. And so the world we live in, our habitat, which kind of implies kind of home or where we want to be a little bit more or where we function, which shows that, well, maybe our environment can influence us. We might function better in different environments. And also may imply that we can be in different environments and still function even if they're not great for us. And then finally this, the world in which we feel comfortable.
And again, I haven't run this by him, exactly, but I know him well enough to know that this could very well be plausible. So this is attributed to Nathan who was probably some dude who sat in seat 4C on this Southwest flight that Dr. B was on back in 2012. Again, I don't know if that's true, but I could totally see this. Dr. Bermudez is the amazing person that, you can all of the socially acceptable signs up while you're traveling that say, "Do not talk to me." And you know what these are, right? You're already sitting down, you've already got your seat belt on. You got your book open. You have your ear pods in, even if they're not plugged in, you have them. Everything is saying, "Don't talk to me" If Dr. Bermudez sits down beside you, he's going to start talking to you. And by, gosh, you're going to close the book. You're going to take out the headphones and you're going to find yourself, "Oh, it's time to descend into our landing city." And you're going to realize, where did the time go? I just had this amazingly stimulating conversation with this doctor from Denver.
And so I can easily see this guy, Nathan and Dr. B, getting into this conversation about, "Well, how do we really define our environment and how it impacts us as kind of humans on the planet on a very existential standpoint? And Nathan saying, "What's the room which we feel comfortable?" And Dr. B being wise enough to latch onto that and realize, "That's the perfect definition." Because where we feel comfortable, we're going to gravitate to being in that environment. We're going to try and control that environment. It's going to influence us and we're going to influence it. So I love that definition. It really shows how the environment is incredibly impactful on all of us.
Now, another way of looking at how the environment can impact us is looking at twins studies, right? And I tell you, twin studies are fascinating and I've gone down that rabbit hole before. And it is truly amazing because you can basically find a twin study that looks at anything and all of them, right? The twins that are identical twins that were raised by the same family. Fraternal twins, they're not identical, but they're fraternal twins. They were raised by the same family. Identical twins that were separated at birth and raised by different families who didn't know them. You can find it all. What's maddening about twin studies? Is that it shows how complex this is to study. Because in reality, many times you run up with, "Yeah, we're not sure."
And one of the things that it'll say is in fact, "Sometimes, it is the unique experiences that twins have that actually shaped them or change them more than shared experiences do. However, even defining unique from shared experiences can be very difficult." Dr. B used to tell a story about, let's imagine two twins, identical, coming home from the library at night on campus. And somebody jumps out of the bushes and grabs both their purses and takes off. So they got mugged, or their wallets or whatever. It's a gender neutral story, I don't care. One twin whips out their cell phone from the back of their phone, clicks a selfie, puts it on Facebook or Instagram, or whatever kids use these days, and says, "Dude, just got mugged. Whoa."
The other twin doesn't do that. They walk home together. It's a day later, the second twin couldn't go to class that day. The first twin's getting nervous. The second twin actually didn't leave the room, too scared. First twin calls their parents, parents come down to college, take the second twin, take them home, maybe enroll them in treatment program for severe anxiety because they've haven't even leave the home. They've been crippled with anxiety from that. A shared experience and identical twins, completely experienced differently. So in reality, I think the environment is incredibly difficult to evaluate how that's impacting us. Yet, we'll continue to try. But it brings up the question, to what extent may environmental and pathophysiological influences, hormones, malnutrition, brain tumor, all of that, negatively impact the brain if they occur during adolescence, because it's a period of development? So not only is it impacting the brain, but it's impacting the brain while the brain is attempting to become maximal in its power.
So for instance, if these are brain exposures, like being exposed to repeated traumas, exposed to repeated violence, we know that's bad. That's why it's in every movie known to man. They'll have the montage flashback scene where the child hears themselves told that they're stupid and they're bad over and over and over again. And we're instantly able to say, "Oh, I get it." Right? Right. It's a device they'll use in a two hour movie, I realized that. But we immediately get it, "Yeah. That's inherently bad." So we know that. But what about when that happens during a period of adolescence and there's also malnutrition occurring. So their brain is telling them these things, how many of you have talked to your child and they've talked about the eating disorder voice? It's not psychotic, right? It's a well known kind of way of looking at the eating disorder and depersonalizing it.
But a lot of them will experience it as this voice telling you things. And I got to tell you, it's almost never like, "Great job today. You've done enough. You're really good." It's not that. It's always negative, terrible things. So I was told to explain it to parents by saying, "Think of the worst possible thing you could hear that you never wanted people to know about you, and saying it over and over, and everybody's saying it." So you walk into work and your boss says, "Hey, you're a terrible father. You're a horrible provider. You can't support your wife very well." "By the way, Mike, you're the worst younger brother ever. And you're a terrible son." "You're a horrible doctor. And everybody at work is undermined by you." All the things I don't want to hear, over and over and over again. With depression, anxiety, we already know that it's causing a marinate, that's destructive to the brain tissue itself. And then on top of that, they're seeing the world through this depressed lens, which is dark and hopeless. Not seeing any way out, not wanting to do anything fun anymore because it doesn't have any joy or value in it anymore. Anxious and worried, retreating, isolating, protecting themselves as best they can. Obviously that makes things so much worse.