- Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. Victor Karian. Dr. Victor Karian is a professor and the vice chair of psychiatry and behavioral sciences at Stanford University School of Medicine.

He is one of the world's foremost experts on post-traumatic stress disorder, in particular, the treatment of post-traumatic stress disorder in children and adolescents. Although his knowledge and today's discussion certainly extends to adult PTSD as well. Dr. Karian is also the director of the Stanford Early Life Stress and Resilience Program.

And today's discussion focuses on the psychological and the neurobiological underpinnings of PTSD, and which treatments are most effective for PTSD. We focus heavily on a particular therapy called Q-centered therapy that was developed by Dr. Karian and colleagues, that has been shown to offset the triggering by words or events or memories that often are the precursors to PTSD episodes.

And this has been shown to be effective in both children and adults. Today's discussion explores the difference between anxiety, stress, and trauma. We talk about how those things of course are related, but how they can be separated out to better understand if indeed somebody has trauma and how to best approach the treatment of that trauma.

As you'll soon see what makes Dr. Karian's work so unique is that it combines the psychological, the neurobiological, but also practical tools, such as mindfulness. It relates mindfulness and cognitive behavioral therapy to the underlying biology and what's known about the psychiatry and psychology of PTSD at its different stages, depending on the trauma, the age of the person, et cetera.

Today, Dr. Karian clearly explains all of that so that by the end of today's conversation, you'll really understand what PTSD is and is not. And of course, the best ways to treat it. Before you begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford.

It is however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is Eight Sleep. Eight Sleep makes smart mattress covers with cooling, heating, and sleep tracking capacity.

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Again, that's wakingup.com/huberman to access a free 30-day trial. And now for my discussion with Dr. Victor Carreon. Dr. Victor Carreon, welcome. - Thank you. Thank you so much for having me. - I'd like to talk today about PTSD, post-traumatic stress disorder, in particular in young people, but also in adults.

But before we do that, can you educate us on the definition of stress and maybe distinguish between short-term stress and long-term stress? And then perhaps we can segue into PTSD. - That's a very good way of starting because in reality, my main interest was the role of stress and the role of stressors and how stressors really would activate the gene makeup and make us vulnerable to things that we might be vulnerable.

But at the time when I was training, everything psychiatry as a field was very diagnosis-based. So you needed an anchor. And hence, I used PTSD to communicate what I was really referring to. But the reality is that the experience of stress, as we now know, is a spectrum from beneficial to not beneficial to traumatic.

So it really, stress operates in our lives as an inverted U-shaped curve. The more stress we have, the better we perform, the better we do. If we don't care about that exam that we're gonna have tomorrow, we'll probably fail. So it's good to be somewhat stressed, right? Vaccines are a stress in the system.

So we'll talk about this, I hope, but I'm very concerned also about the overprotection of kids to protect them from any type of stress because it is through this experience of early stress that of us develop our problem-solving abilities. And we become aware of our coping mechanisms. We become aware of our support system.

How can I manage that stress? And we can, we can manage stress because in the same way that through the process of homeostasis, we process, we have a range of temperatures, right, in which we can live, the same thing with stress. We can actually cope up to a certain point.

After a certain point, it's not homeostasis anymore, and it turns into what we call allostasis, when it really starts having a physiological cost to the body. So in that inverted U-shaped curve, there's that optimal point where your health, your happiness, your performance, everything is better because of the stress you've been having.

But after that optimal point, all of those outcomes, health, performance, start to decline. Happiness starts to decline. And it is in that second part of the curve where we find traumatic stress. Traumatic stress being a type of stress that is not only something you have to cope with, but it actually puts your physical integrity in jeopardy.

It's a threat, and you have to manage that. And when you experience traumatic stress, many outcomes are possible. One is that you're resilient, and we'll talk a little bit about that as well, I hope. But another one is that you may develop symptoms of post-traumatic stress disorder. And the reason that I didn't anchor on the diagnosis right away from the outset, and I was interested in studying stressors, is because many kids, we were seeing many kids that had symptoms of PTSD without having the diagnosis that were demonstrating functional impairment.

So they were not doing well in school, they were not doing well with their relationships, they were experiencing distress, right? So their function was affected, yet they didn't have the diagnosis. So the diagnosis is good in that it's there, and it is a behavioral definition that we can anchor in, but there's more nuance to that.

So then that shows the whole spectrum. And of course, we can come out of PTSD, and we can go back to that optimal point. So we don't want to get rid of stress, but we just want to return to that optimal point. And treatment is available, and people can recover from PTSD, and especially kids can recover from PTSD.

But there's one thing that really gets in the way, and that's something that in my team we call, we have a phrase that we say, "PTSD feeds on avoidance." If we pretend that something didn't happen, if we pretend that it will go away, if we pretend that treatment is not necessary, then that's when it gets complicated.

And it gets complicated with substance abuse, it gets complicated with self-injurious behaviors, and then at that point, it becomes harder to treat. - Is it also possible that PTSD gets worse if we tend to look at it over and over again, ruminate on it in the absence of any structured clinical support?

Meaning if people perseverate on their traumas, can the negative impact of those traumas actually root deeper into us? - It's interesting that you use the word perseverate, because one of the characteristics of trauma when it affects children is that it robs them from play. Play is something that's essential in development, it's how we grow socially, emotionally, physically.

But when play becomes traumatic play, it becomes non-joyful, but it becomes perseverant and repetitive. This is the attempt of the individual to try to make sense of what happened. And the reason why it's not good to be alone with it and kind of perseverate on it by oneself is that we're probably not looking at the right insult.

So in our experience, usually PTSD doesn't result from that one traumatic event. We all carry a backpack, and we can all carry all the stressors that have come our way, like we were saying before. But if you're five, six, seven years old, and that backpack gets really heavy, you can fall backwards.

And when you fall backwards, that's because you don't have the tools, really, to carry that. But what I'm saying is that it is the accumulation of stressors, some of which may be traumatic, that cause the symptoms of PTSD. So for example, some of us went to Haiti after an earthquake, right?

And I was starting my program at that time, I was very young, all ready to talk about earthquakes and know everything about earthquakes. It was the last thing they wanted to talk about. They saw the earthquake as an opportunity to talk about the violence they had been experiencing, the poverty, the lack of education.

So they were talking to me about everything they were carrying that led some of them to develop symptoms of PTSD. - I see. As you describe these other aspects of one's life that can have negative impact, poverty, violence, et cetera, I get the impression that PTSD can be caused by a single event or trauma, but that there's a cumulative aspect to it.

So is it the case that in children, because their brain is far more plastic, we know this, I mean, brain circuits are modified even by passive experience in childhood, whereas in adulthood it requires focused attention in order to learn, unless it's a negative event, for better or worse, that in kids it takes far fewer or less intense negative experiences in order to create PTSD because the brain is so plastic?

Or is there a similarity between youth and adult PTSD? - Epidemiological studies confirm your assertion. Children, we think, we usually, you know, one line that I really don't like is children are resilient, because children are really not. They're more vulnerable. They have the opportunity to become resilient if we help them and we tell them what tools to use and how to develop and all of that, but they are more vulnerable to PTSD, and part of it might be that neuroplasticity, and this is why we care for them, right?

This is why we protect them and give them safety, because they are vulnerable. By the same token, that neuroplasticity can work both ways, because if PTSD is teaching us that the environment can have an impact on biology, that's the only lesson, right? Environment can have an impact on biology.

In PTSD, it's a negative impact because of a negative stress or accumulation of stressors, but that also means that if the impact is positive, as in a good supportive system or as in psychotherapy, that recovery can actually happen in an easier way. - Before we talk about therapeutic interventions, I'm curious about genetic predisposition, and a topic that comes up a lot anytime the letters PTSD are stated in that order is transgenerational trauma.

I can imagine at least two forms of transgenerational trauma. One is a generation of what are now grandparents or great-grandparents or parents are impacted by some trauma, either in the family or maybe in culture or even broader scale. And then discussions about that pass through generations, impact the children, and therefore their adult life.

I could also imagine, and I think this is normally what people are referring to when they talk about transgenerational trauma, this idea that somehow the genome is modified by the trauma such that even if kids are raised by parents that adopted them or they have no contact with the grandparents or great-grandparents that experienced the trauma, that somehow they are more vulnerable to, or in some cases, the idea has been put forward, carry that trauma, put in air quotes, such that their life is more difficult, even though they never had a direct experience of that trauma.

What are your thoughts about transgenerational passage of trauma, both forms, both the narrative passage, as well as the potential for epigenomic or genomic passage of transgenerational trauma? - No, this is a very interesting subject. The jury is still out if genomic changes that result as a consequence of stress can be passed from one generation to the other.

But certainly the genes that made one generation vulnerable are being passed to the next generation as well, that we know. So it can be passed that way. But what happens is that there's also this impact of learning. And I have treated kids that come to me with all of the symptoms of PTSD, and there's no trauma.

I cannot find the trauma, and the parent cannot find the trauma, and the kid doesn't report a trauma. But when I'm talking with the parent, the trauma becomes evident in the history of the parent. So the parent has developed PTSD and behaves in a way that has been learned by the new generation, ways like avoidance, or re-experience, or hyper-vigilance, or lack of trust, things like that.

So certainly, there are pathways in which it can go from one generation to the other. And we know that the battle between nature and nurture is pretty much over, right? We know that they both influence vulnerability and that they both interact. And I imagine that's what's happening in some of these situations.

- In terms of stress, I always think of stress as both a response within the brain and a response within the body. And I'm not alone in that belief, I think. We know that adrenaline, epinephrine, is released from the adrenals, but also from areas of the brain like locus coeruleus, so that there's this parallel effect of elevated states of mind, more alert, more focused on narrow locations in space and time.

And the body is also prepared for action. I think this is what underlies the increased heart rate, the, you know, shaking in some cases, sweating. It's essentially a preparation for action. With PTSD, I often hear that some of the symptoms are more of the opposite end of the spectrum in terms of autonomic arousal, right?

Things like dissociation, fatigue, kind of checking out, which I realize is dissociation. But things that are more akin to kind of parasympathetic, right? For those that don't know, the sympathetic/parasympathetic represents the continuum of autonomic interaction. Sympathetic having nothing to do with emotional sympathy. It's all about fight or flight type responses.

Although at lower levels, it's what's responsible for us being alert here, but not in fight or flight. And parasympathetic being more of the rest and digest, even leading into sleep type responses. - So, you know, if somebody experiences a big stressor, a trauma, or chronic stress to the point where it becomes PTSD, is there a tendency for them to be more hypervigilant and have a, you know, a startle response, to have their head on a swivel all the time, looking for danger, or to be more dissociative, or can both sets of phenotypes exist in the same person?

- Yeah. No, this is very interesting. While we're talking about the letters, let me say that a lot of people call post-traumatic stress disorder post-traumatic stress injury. Not considering it a disorder, but considering it something that where our fight or flight mechanism, the autonomic nervous system, has been desensitized, and we need to regulate it again.

And it's gonna hurt. It's gonna be painful. It's just like when you break your arm and go to the emergency room, and it hurts to be placed back in place, but it's the cure, is what cures it. So a lot of people visualize, and sometimes I do, as an injury, rather than a disorder.

- Post-traumatic stress injury. - Injury. - Interesting. - And so what happens? So this autonomic system gets activated. We have our fight or flight reaction. But what happens to a young kid? Because they're very little, and they cannot fight. They're also very dependent, and they cannot flight. So they're stuck.

They're stuck there. So they freeze. They freeze, and that's dissociation. It's actually, during development, a healthy defense mechanism. But very much like a white blood cell, that's very helpful, if you have too much of it, you develop a leukemia. You can develop dissociative disorders if that's the only thing you have.

But it does help children cope with some of these situations, pretending this is not real, or this is not happening to me. It's the only thing they have left. And because this arousal system is so key in the development of these children, I thought that we should look at the hormone cortisol in the kids.

And when I started, when I was a fellow doing my child psychiatry fellowship, I was seeing all types of kids with all kinds of issues. Some had ADHD, some had OCD, some had PTSD symptoms. But I was getting a lot of kids with notes from school saying, "This kid has ADHD.

"Please place on Ritalin," right? A stimulant medication. And I'm like, "Wow, the diagnosis has been made. "There's already a treatment plan. "What am I training here for?" (laughs) But in some instances, they were right. The kids had ADHD. But in most cases, what happened is that that hypervigilance that you're talking about was being misinterpreted as hyperactivity.

And the dissociation was being misinterpreted as inattentiveness. So the kids were getting a diagnosis that was not correct. Of course, there are other very complex cases where you have both ADHD and PTSD. Also, ADHD can put you at risk to develop PTSD 'cause you're not as attentive as to what's happening in your environment.

But there are definitely two different conditions. And it was that clinical observation that made me think, well, people don't know enough about PTSD. And certainly they don't know enough about PTSD in children. And we were having some research in adults around that time in terms of cortisol levels. David Spiegel, who you've had here, Rachel Yehuda at the Bronx VA, looking at PTSD in adults.

But I said, "But how does PTSD look early on? "What's happening in the hypothalamic "pituitary adrenal axis that is responsible "for secreting cortisol and regulate cortisol "when these children are young?" Because this is a new axis. Is it already not working or is it working right? And so we did a number of studies that demonstrated that the normal circadian rhythmicity of cortisol was there.

It was higher early in the morning, which we need to jump out of bed. And as the day progresses, it decreases. Very helpful, it goes up when we are stressed, like when we have lunch. After we have lunch, cortisol goes up, right? So that we can help manage the insult of digestion or whatever.

And these kids were having those levels. But something was happening in a number of studies. And we noted that the pre-bedtime level was higher. We were measuring it at different times. In the morning, pre-breakfast, pre-lunch, pre-dinner, pre-bedtime. But it was the pre-bedtime level that wouldn't come as low as the healthy controls.

It would remain high. And this was also important clinically because many of the symptoms these kids were having were happening at night. Aneurysis, right? Bedwetting, nightmares, not sleeping deep enough, not sleeping long enough, fears. At that point, I felt, well, we don't know anything other than the cortisol pre-bedtime is elevated, right?

Maybe they need it to be. Who knows? But I was concerned about the work by Sapolsky, right? And Bruce McEwen, his mentor, demonstrating the neurotoxicity that glucocorticoids can have in key areas of the brain. Areas in the limbic system and the cortical system. Which, interestingly enough, have a lot of glucocorticoid receptors.

So then we decided to look at brain structure and brain function in youth with PTSD symptoms and see how this cortisol would relate to that or not. And we did that through MRI, magnetic resonance imaging. - Let's talk about cortisol for a moment. It's a topic that has not received enough attention in previous episodes of the podcast.

I'm just going to summarize a little bit of what you said and you'll tell me where I'm wrong. Cortisol starts to rise just before we wake up in the morning, assuming a good night's sleep. And peaks maybe, I don't know, 30 to 90 minutes after waking. For you slow risers like me, probably a little delayed.

By the way, the height of that peak and I would say the steepness of the curve can be increased by viewing morning sunlight. We know this. Bright light increases that cortisol peak. It'll make you a better early riser. But in any case, typically the pattern then is that it rises through mid morning and into the early afternoon and then starts to taper off to lower levels.

And as you mentioned, we'll see bumps in cortisol post meal. If there's a stressor, we get a disturbing text, we get a bump in cortisol, but these aren't huge peaks unless it's a big stressor, correct? And then by evening cortisol levels in healthy individuals are typically low and that allows for transition into sleep, among other things allow for transition into sleep.

But you said in these kids with PTSD, cortisol doesn't come down to low levels as much as it does in healthy individuals in the evening and nighttime. And that I imagine would lead to perseverating on stressors from the day. This kid was mean, I have a test tomorrow. Maybe any stressor becomes more intense in our mind and body, as it were, and that perhaps could lead to issues with quality or duration of sleep, which then could perpetuate the cycle.

Do I have that correct? - Correct. - Okay, so has the direct intervention of just trying to suppress evening cortisol ever been done? I mean, certainly there are drugs that will do this. Has that approach ever been taken? - I thought about that when I had those high levels, but I felt that we needed to understand better.

I think yes, that there were some attempts with some medications, and I don't think that led to anything in terms of helping those kids, or just helping individuals in general that had high levels of cortisol because of traumatic stress. But nighttime, you're right. It is a time when basically we fall asleep because we let it go.

And this kid's hyperarousability does not allow them to let it go. So if these levels are high, as I was finding, what impact are they having in brain development? And usually the younger you are, the more universally distributed receptors are. So glucocorticoid receptors could be anywhere at that point, but as we age, they become more localized.

And the glucocorticoid receptors, and cortisol is a type of glucocorticoid, are more common in areas like the hippocampus and the prefrontal cortex, which I also found interesting because these areas relate to the symptoms, right, that many individuals with PTSD have. - Memory, anticipation of the future, problem-solving, context-dependent problem-solving, so on.

- And even those attention issues that make them overlap with kids that have ADHD as well. So this frontal limbic pathway, the prefrontal cortex communicating with these emotional areas of the brain, including the amygdala, which is very close to the hippocampus, needed to be investigated in pediatric PTSD. And what I sometimes call pediatric PTSS because post-traumatic stress symptoms.

Because, as I mentioned, there's a group of kids that have post-traumatic symptoms, do not fulfill criteria for DSM-5 PTSD, but their function continues to be impaired. Sometimes that's because of comorbidity. There's a high incidence of comorbidity with anxiety and depression. So most of our studies that have looked at PTSD symptoms also look at the impact of the interventions that we're doing in anxiety and depression as well.

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If you'd like to try AG1, you can go to drinkag1.com/huberman to claim a special offer. Right now, they're giving away five free travel packs and a year's supply of vitamin D3K2. Again, that's drinkag1.com/huberman to claim that special offer. - I definitely wanna get into some of those interventions, including some of the ones that you've developed that are very novel and are being used to great success.

I want to just circle back for a moment on this relationship between PTSD and, in some cases, inappropriate diagnosis of ADHD. As you mentioned, these two things can coexist in the same person. So we don't want anyone who has been told that they have ADHD and PTSD, or even just ADHD, to immediately assume that that diagnosis is wrong based on what we're gonna talk about.

But it is possible that the ADHD that a child is told they have is reflective of PTSD. And I imagine that if that PTSD arises through something in the family structure or dynamic, it would be even harder to unmask because the parent perhaps would be less motivated to try and understand that if they played some sort of role in it.

So I realize this is a complex problem with a lot of layers. But if you were to just throw out a number based on your experience, what percentage of pure ADHD diagnosis would you like to see explored for the possibility of a PTSD influence? Let's just keep it kind of diplomatic that way.

As opposed to saying what percentage of ADHD do you think is actually PTSD? - I firmly believe that ADHD does exist. I'm gonna say two facts that we know in the field. One, are kids getting over-medicated? The answer is a clear yes. They're getting more medications that they need.

- For ADHD. - For anything in general, kids. Now, in ADHD, they're getting under-medicated. So that's the second fact. So the first one is that if we look at kids overall in the field of mental health, those that manage to receive treatment, which access is something else we should talk about 'cause like 50% of them do not get access to mental health services.

Those that manage to get it may end up with the appropriate treatment, right? A medication or a psychotherapy. But there's another subset of them that will be medicated no matter what they present with because they need to be seen fast or it's a fast solution. So there's many reasons for that.

But are kids getting over-medicated? Yes. But within those kids, those that truly have attention deficit hyperactivity disorder are getting under-medicated. And that's because of that access issue because most of them were not identifying. And that's a pity because the first line of intervention for ADHD is stimulant treatment. It does work.

And it works very well for children that have the correct diagnosis. But the first line of intervention for children that have a history of PTSD, be it acute or chronic, is psychosocial. It's a psychosocial intervention. So if you give a kid that has PTSD and no ADHD a stimulant medication, not only is not taking care of ADHD 'cause they don't have it but it adds to that hyperarousability that is manifested there from before.

By the way, there are clinical ways of separating hyperactivity from this hyperarousability and hypervigilance. Hyperactivity, if you see a kid that is not medicated and has ADHD and they have the hyperactive symptoms and the hyperactive type, they're gonna be hyperactive for most of the time that you're with them.

The kid that has hyperarousability, it will be more of an on and off phenomenon. The hypervigilance and hyperarousability comes more when they're presented with a cue that consciously or unconsciously reminds their body of the traumatic event or the traumatic experiences. What happens though is that usually we don't know what those cues are, right?

So we just see a kid that sporadically becomes hypervigilant or hyperaroused. And then the other thing is, is hypervigilance something that needs to be treated? You know, I learned this from a mother early in my career. She's like, I was giving some talk in the community and she came to me afterwards and she said, "Listen, we live in a street that's very dark "and it's very dangerous.

"And my kid has to pass through that every day. "I want him to be hypervigilant. "And if he has developed this trait of hypervigilance, "this is something that could be helpful to him." And I said, "You're right." I said, "You're right, it's not only to him, "to a lot of people, it could become very helpful "to be hypervigilant to assess the environment "in which they are in." So the problem is not the hypervigilance.

The problem is knowing when to turn it on and when to turn it off. Having the cognitive flexibility, right? To be able to say, yes, this is a dangerous situation and I better respond this way. If I can give you an example of a kid, right? A kid that experiences domestic violence and has associated that with noise in the house, learns that running and getting into the room is a safe thing for them because they're out of the picture, right?

And they protect themselves in the room. But a year later, they're in the classroom and for some reason the classroom gets this level of noise. The body, without him knowing, right? The body reacts by the response that was helpful. This is classical conditioning, right? So he runs out of the classroom.

But he's missing the context. The teacher is missing the context. When the teacher sends him to the principal's office, the principal doesn't have the context, right? That this response was actually adaptive at one point and helpful at one point and the body has had a hard time letting it go.

To ask that kid to give us the only response that he has is not the way to help him. We need to help him develop new competitive responses so that the experience of the other responses then extinguishes that response that was adaptive at one point but now is maladaptive.

By the way, if they are in a traumatic situation, again, we still want them to use it, right? We still want them to run and get out of there. It's part of that hypervigilance that's protecting them in a way. - It's so interesting. You said, if I understood correctly, that in kids with genuine ADHD, the hyperactivity is fairly persistent across environments and with different people, et cetera.

- I'm sorry to interrupt, but if I could add, the inattention comes and goes because we all know kids that have ADHD that if you give them the right video game, all of a sudden they become attentive, right? - This is a very important point. When I did the solo episode on ADHD, I was frankly shocked to learn, but it was validated by the literature and certainly by the responses from the audience that kids with ADHD and adults with ADHD, for that matter, absolutely have the ability to sharply attend to something if it's something that's very engaging to them, really exciting, something that they typically enjoy.

But their ability to direct and maintain attention in other environments that are required for normal life progression, school, work, relationships, et cetera, is very diminished compared to those without ADHD. So what I have in my mind is a step function, meaning an increase in a steady state of hyperactivity in a kid with ADHD, but then a jagged line beneath that of attention.

This is, I believe, the picture we're painting here, but that in PTSD, the hyperactivity is a jagged line and it really needs a cue, as you said, a loud noise, or maybe it's the presence of a particular voice. I once attended a trauma, it wasn't trauma release as much as it was genuine trauma treatment center out in Florida.

A friend of mine runs the center and I was out there learning about the practices they use in order to inform potential experiments for intervention in my lab back at Stanford. And he said something really interesting. He said, you know, when you bring people in to this sort of environment and they've all had trauma, you see a pretty rich array of responses to even just the same conversation.

And then at one point, perhaps because he said that, I noted that a woman raised her hand and she said that particular timbres of voices in the room were really activating her. You know, this was important. It wasn't just what was being said. It wasn't that people were yelling at each other or even the volume of the voices, but that even just the frequency, the lowness or the highness of the voice, as it were, was triggering something in her brain that was giving her these bodily sensations.

And it was a very important insight for her to be able to then start to direct interventions. So I guess we all hear the kind of now stereotypical example of, you know, the veteran who experiences combat comes back and hears a car backfire and then they hide. That's kind of, we read about this and hear about this, but it seems like it's much more subtle than that, that sometimes the cues for this hyperactivity, this hypervigilance is very much linked to something that sometimes even the person with PTSD doesn't recognize until they start to be put into that environment again and again, and then they can pinpoint it.

My question now is if they can pinpoint what the cue is, do they stand a better chance of recovery as opposed to somebody that just like, feels like I'm hyperactive, then I'm exhausted, I'm wired and tired. And now I also imagine that in kids, they don't have necessarily the verbal proficiency to be able to express what's going on for them.

And in fact, many adults don't really know because we don't have a great language for expressing this body-mind thing. In any event, a lot of questions there, but what are your thoughts about the requirement for being able to understand what the cues, what the triggers are in order for a child and or adult to be able to start to make inroads into their PTSD?

- First, a word on the Vietnam veteran, because there's a very important study that was published years ago that demonstrated that those veterans that had a history of child maltreatment and went to war had PTSD at higher prevalence than the ones that did not have a history of child maltreatment.

So-- - Child maltreatment. - Yeah. - I see. So they were traumatized before they went to combat. And maybe they did not develop PTSD, but once again, that point of the accumulation, right, of the stressors at different times. And I'm just mentioning that because you may have a veteran and you're waiting to look at the classical cues, where in fact, it might be more like a voice, like the example that you were giving that triggers them.

What triggers an individual is very personal. So cues are usually neutral. And they're usually related to our senses. And I know you like senses a lot. So what we see, what we hear, all of these things. The senses are really the window to the central nervous system, right? This is how we get information the first time.

So in this state of hyperarousability, when something traumatizing is happening, our senses are really acutely aware of what's going on. And they are making sense of the insult, but they also are registering everything that's related to that. So these cues usually are neutral. So they're not like a gun, for example, because a gun is not a cue, it's a threat, right?

But it's usually a color. So there was a red car parked near where they were, so the color red may be a cue, may be a trigger. It was raining the day that that happened, so rain may be a cue, may be a trigger. And to answer your question, identifying those cues are important because they let you know when your symptoms are coming.

They let you know that they're not coming out of nowhere. They let you know that you're not a problem or that you're crazy or that you're bad, which is sometimes the messages that kids get when they go to that principal's office, okay? But they let you know that they learn themselves, this is a normal response, right?

I've learned through my psychosocial intervention, I've learned that this is a cue that triggers a response from me, triggers a response that was helpful at one time. And through classical conditioning, and we do teach classical conditioning to the kids, those responses then become present, become conditioned, right? When the cue is there, when the trigger is there.

So yes, to answer your question, it is important to know the cues. Now, what happens? Are we gonna know all the cues to everything, to all of our behaviors and this shift in mood that sometimes we have during the day and we don't know why, right? No, the answer is no, we're not gonna know all the cues.

But the beauty of this is that if we can just learn about one or two or three cues, what our response is, there's more of a forgiveness to ourselves in that when we respond inappropriately, we can think, well, maybe I was exposed to a cue, right? Because I've learned all of this about cues and classical conditioning, maybe that's what's happening here.

- Yeah, I'm thinking again about post-traumatic stress injury. The reason I like that term, even though I realize I'm using it non-clinically, is that if we understand that the autonomic nervous system, this seesawing back and forth, or this push-pull between the sympathetic, fight or flight, and parasympathetic, rest and digest, loosely speaking, systems are always at play in us.

When we sleep, more parasympathetic. When we're alert and calm, more sympathetic. And when we're stressed or having a panic attack, extremely sympathetic. If we understand that as a biological system, which it is, that deploys hormones and shapes our patterns of thinking and what's available to us in our memory, et cetera, then PTSI, post-traumatic stress injury, I feel like it liberates us a bit to understand that, yeah, this autonomic system has been disrupted in a way.

And if I think about the autonomic system as a seesaw, which I often do, I think about the seesaw having a pivot point with a hinge. It's almost like the post-traumatic stress injury is to create the tendency for that hinge to be too tight. And sometimes that makes it more dissociative and we're exhausted and kind of checked out.

And maybe it creates the hinge to be too tight such that we're more on the sympathetic, excuse me, sympathetic the way I, for those listening, I'm using my hands, but you don't have to see it to understand that the alertness system is locked in place. It's hard to get out of that.

And I almost feel like the injury that is post-traumatic stress injury is a tightening down of the hinge with the seesaw tilted too much to one or the other side. And I, as a biologist, I just wish that we understood what that dysregulation was or is. Chances are it's not one location in the brain or body, it's gonna be a network phenomenon.

But I feel like the word disorder, the D in PTSD is so critical because it highlights the importance and the pervasiveness of this thing, but that the I in post-traumatic stress injury hopefully will give people, it certainly is giving me some sense of relief or liberty and understanding that these are nervous system injuries that need treatment and that there isn't something wrong or crazy with us because of the fact that we, you know, suddenly feel like we're having a panic attack.

You know, I've had people I know close to me in my life say, "I'm having a panic attack." I'm like, "What do you mean? What happened?" They're like, "Nothing happened. That's the point." "Well, how'd you sleep?" "Well, it's okay." You know, and you start doing the curbside diagnosis that neither of us is qualified to do, right?

But this is what we do as caretakers for each other in our lives. And it very well could be that their autonomic system just got, that hinge is just locked in place for whatever reason. Maybe it's one sip too much of coffee. Maybe it's one sip too little. It's probably something or a bunch of things.

I realize I'm getting outside my expertise here because I'm not a clinician, but I feel like this PTSI thing is sticky and important for people to hear about it. Certainly changing the way that I think about PTSD. - Yes, no, and I like the visualization of your seesaw and the example of the hinge because it reminds me of that cognitive flexibility, right?

It's not there. It's kind of stuck. It's kind of tight, too tight. And in some individuals, they just experience the dissociation. They're like stuck on the bottom, right? Sitting on the bottom on the seesaw. Whereas for the other individuals, they're hyperaroused all the time. Then you have everything in between.

But no, that's a very good representation of it. - And I feel like a good night's sleep allows some recalibration of the tightness of that hinge. Put differently, anytime we don't sleep well or long enough, we're not good psychologically. A good night's sleep is good for everything. - We're finally at the point in history where everyone seems to accept that.

I really have to tip my hat to Dr. Matthew Walker from UC Berkeley for writing the book, "Why We Sleep." You know, it was only a few years ago that book came out and he deserves such a token of praise for that because prior to that, there was this, oh, I'll sleep when I'm dead mentality.

I think people knew sleep was important, but they didn't really understand. And he had to come out as kind of the downer message, like, listen, this is serious stuff. - You better sleep. - You better sleep. But I think we're there now. I think in 2024, we're there. I think people understand.

- And I think people have their own experiences with sleep, right? We've all felt that cold that's coming. And if we really sleep those eight hours, we may be able to fight it 'cause we've strengthened our immune system. If we don't, we will get sick. - Yeah, absolutely. Let's talk about some of the treatments that you use and have developed for PTSD in young people.

And maybe we should define young people. Are we talking about the 18 and under just because that's typically what we think about? - So in pediatric psychiatry, we have three different populations. We have the preschoolers, we have the school age, and we have the teenagers. And they're all very different.

They all have responses and defenses that are very different. The projects that I'm describing happen mostly with the school age children. - So preschoolers are gonna be essentially, I think of kindergarten starting at five. So you're talking about zero more to more or less five or six years old as the preschoolers, kindergartners, and then transition point.

- Correct. - And then for the kids we're about to talk about, we're really talking about what, six years old until about end of adolescence? - Yeah, 15 and then, yeah, then the teenagers later on. - Okay, great. - So I work mostly with the school age kids. And like I said, when we started doing magnetic resonance imaging to look at the impact of cortisol, we have a number of studies really demonstrating that those kids with higher levels of cortisol had less volume of the hippocampus.

The first study that we did in that was cross-sectional and there was no difference. And it gave me a lot of hope that there would be a window of opportunity there where we could intervene. Because what we were seeing in chronic PTSD in adults was that there was smaller volumes of the hippocampus which help us process memories and have strong connections with the emotional center of the brain, the amygdala, and also with the prefrontal cortex.

And what we found was that cross-sectionally there was not this difference, but we also follow a small sample longitudinally. And there we saw a correlation between that higher pre-bedtime cortisol and the smaller hippocampal volume. More impactful was a functional imaging study, as many of your audience members know, with magnetic resonance imaging we not only can look at the structure, but we can also give tasks of memory, for example, or of executive function and different tasks that tap at the areas that we are interested in looking.

So when we look, when we give a memory task and we looked at how children with post-traumatic stress symptoms were behaving compared to kids that do not have symptoms or other psychiatry diagnosis, we were seeing that the healthy kids were activating a lot of more voxels or units of the imaging of the hippocampus.

So there was concern here that yes, that plasticity that you talked at the beginning was really affecting the development of the brain of the kids. And then with the prefrontal cortex we saw something similar in the ventromedial area of the prefrontal cortex. So, but with other tasks, right? With tasks of executive function or tasks of emotion, looking at faces, for example, emotional faces.

All of this to say that they probably have a malfunctioning frontostriatal pathway and frontolimbic. So, frontolimbic, I'm sorry. So if we think of the amygdala, for example, in close proximity to the hippocampus, being involved in this hypervigilance and we have some data to show that the amygdala becomes active very quickly when you present emotional faces to young kids.

And that that hyperactive amygdala needs a break of some sort. That break comes from the prefrontal cortex. But if you have a prefrontal cortex that's not working that well either, then your break is not working, right? So then the issue came here. Well, this is important information to know what we need to target with treatment.

And can we target this with psychosocial interventions and the way that we provide treatment? And we decided to begin with what we discussed earlier, with the cues, right? And teaching and having kids understand what cues are, what classical conditioning is, talking to them about the impact of trauma, talking to them about the impact of treatment and how recovery is possible, right?

So an educational piece. And something that I never thought I would end up doing was developing a treatment, right? I felt I'm here to investigate and use the treatments that we have. But it became very clear to me that there were a population of kids that still needed a form of treatment that was not out there.

So most treatments out there for trauma were targeting one traumatic event and not targeting that backpack, that allostatic load. Also, and rightfully so, most treatments were requiring that the parents were involved in treatment as well. - I could see where that might be problematic when the parents perhaps were the source of the trauma.

- And also when there's avoidance, right? And also when there's practicalities that if they lose one day from work they're gonna get fired. So sometimes the parents are just not available and the kids are totally ready to begin and do the work. So I wanted them to be able to do so.

So how can we devise a treatment that is hybrid, and by that I mean multi-modal, that is not only cognitive behavioral therapy but that it brings other elements that are important like self-efficacy, empowerment, insight-oriented work, and give it a structure that can be tested. And that's how we created Q-Center, Q being C-U-E, Q-Center Therapy for kids that have PTSD.

And we've had a number of trials with them and it helps decrease symptoms of anxiety, symptoms of depression, and symptoms of PTSD. And not only as scored by the student but also scored by observers, by the parents. And in one of the trials where we measure actually how the parents were doing, parents that were not participating in treatment, their own anxiety was decreasing as well.

And that's easy to understand, right? If your kid is doing better, you're gonna do better as well. So that was very, very good to see. But then we wanted to see that plasticity too. Is this doing something to the activation of the brain? And that's when we brought functional near-infrared spectroscopy into the picture because it's cheaper than MRI and it's more portable and it's easier to do.

It only gives you cortical information. It doesn't get into those interesting limbic structures. - So it's, just to highlight for a second, the fMRI, functional magnetic resonance imaging is wonderful because it allows a lot of imaging both on the superficial outer parts of the brain but also deep into the brain.

My understanding is that, and perhaps this has changed in recent years, that the spatial resolution can be very good. You can pinpoint very small areas if you have a powerful enough machine, magnet. The temporal resolution, the ability to see changes in the neural circuit activation and deactivation over time at one point was somewhat limited, but now some of those limitations have been overcome.

But then what you're talking about, near-infrared spectroscopy is excellent because it can be taken to a school, right? You don't have to, you couldn't bring an fMRI machine to a school unless it's a medical school where there's the machine. It's much less expensive. The downside is, oh, excuse me.

And my understanding is that the spatial resolution isn't quite as high as MRI, but the temporal resolution is very high, which is a huge advantage. And then there's this one disadvantage that you can only really image the outer portions of the brain, but nonetheless, there's a lot of information there, right?

So a little technical lesson. - And these outside areas of the brain, the cortical area and the prefrontal area, we're helping predict which kids would do better, only for those kids that were having Q-center therapy and another gold standard treatment called trauma-focused cognitive behavioral therapy, when they were both compared to treatment as usual.

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If you'd like to try Function, go to functionhealth.com/huberman. Function currently has a wait list of over 250,000 people, but they're offering early access to Huberman Lab listeners. Again, that's functionhealth.com/huberman to get early access to Function. I want to get into the Q-centered therapy versus cognitive behavioral, versus the no therapy conditions you just described.

But before we do that, I just want to have a brief discussion about some of the neuroscience you mentioned, because I think people will find this very interesting and certainly not just a listing off of names of structures. You said that the frontolimbic pathway is important here, the limbic pathway, including the amygdala, but other structures as well.

And my understanding, and I think the generally accepted understanding about these limbic pathways, is that they create a response state, a state of alertness, a state of relaxation, that they translate certain information that impinges on them into a level of reactivity, either low, medium, or very high. When I say reactivity, a tendency to move toward or away from something or stay still, put in broadly speaking.

Now, the fronto piece, the feeding in of information from the frontal cortex, where context-dependent decision-making, and as you said, executive function takes place, is so critical for all of us as we mature. Even as a, I would say, if you look at a puppy, everything's a stimulus. And then over time, they're not going to pick up everything in the room.

That's without question, largely due to the development of these frontolimbic pathways. And in children and in humans, that is, it's the same. I can imagine that the signals coming from the frontal pathway to the limbic system are going to be somewhat cryptic to people that aren't familiar with psychiatry and neuroscience.

So maybe we could just throw a few of those out there. Here's an example, tell me if I'm wrong. But the way I think about this is, okay, a kid is in a room and they're hyperactive. And, or maybe something set them off and they're particularly vigilant and stressed.

They're in the stress response. The frontal cortex is the pathway by which an internal dialogue could be delivered to quiet that limbic pathway. The message that would perhaps trigger that would be the kid recognizing because they learned, this is okay, I've had this happen before, it passes. Or I'm supported, there's Dr.

Carrion, there's my mom, there's my dad, there's my teacher, there's my friend, I'm supported because we know social support is important. Or it's normal to feel stress every once in a while. So these kinds of thoughts or these internal dialogues that we're told that we should do for ourselves when we're stressed, I think we can be pretty certain that that's the kind of information that would trigger this frontal to limbic suppression.

- And can I comment on that dialogue because all of those are examples of positive thoughts, right? Positive thoughts that are good, but they're not automatic thoughts. They are thoughts that need to be practiced, right? Negative thoughts, unfortunately, that reside in our reptile brain are automatic. So that hyper response, I'm in danger type of situation, when we evolved, right, is responsible for our survival.

So we learn the negative thoughts very well. I'm in danger, I have to run, I have to get on top of this tree, the lion might come, whatever. So only 50 million years ago, when we developed the frontal cortex more, positive thoughts came into the picture. And they're very helpful for all the reasons you're mentioning, but they're not automatic like the negative ones are.

Hopefully they will become. So what I tell the kids is if they don't play guitar, if I give you a guitar right now, would you be able to play me a song? - Absolutely not. I have absolutely zero minus one musical ability, but I love music. - But if I gave you a guitar with guitar lessons and you practice, you probably will be able to play a song a year from now.

- Well, me with some degree of proficiency, but not much. - With a lot of help. - But everybody else, yes. - A support system. - A support system, that's right. And with enough practice hours and enough focus and determination, I'm convinced I could become at least proficient even at 49 years of age.

- So we have a slogan in my team, which is practice positive thoughts. All the thoughts you were mentioning are good ones and we have to practice them, right? This is what I'm learning. No, I'm not bad. This is happening because of the cue. - Even when the limbic system is not active, do you encourage your patients to practice positive thinking?

- All the time. - Even when they're not in the stress response? - All the time. - Interesting. - It's like, it's learning a tool. So in this Q-Center therapy, one of the lessons is that they have an empty toolbox and this toolbox gets filled with tools that they learn.

I'm practicing positive thoughts, deep breathing, mindfulness, all of this muscle relaxations are tools that we teach them, but they decide and here's where the empowerment comes in. They decide what the cues are. They decide what tools they're gonna put into their toolbox or they're not going to put in the toolbox.

And by far, whatever tools they develop that have not been taught by me or anybody else work better when they develop it themselves. - Interesting. - And you know, I had this case once and it got illustrated really well. When I was in one of the sessions, you teach them breathing exercises, muscle relaxation, things that we know help and I'll talk a little bit more about how we know that they help.

And then they have like a week to practice and then they come the next week and we see where they are and what's in the toolbox and things like that. And the next week when she came, she was much, much better, you know? And I said, I was very proud.

I'm like, oh, you've been practicing the tools, right? That we discussed last week. And she's like, no, I actually don't remember anything you said last time. But I came up with this thing that when I feel bad, I'm drinking a glass of orange juice every time. And at that moment, I knew I could go both ways.

I could go, no, no, you must practice my tools. Or I could say, how wonderful. You've identified a tool that helps you to drink a glass of orange juice, which obviously is what I did. And then she was able to have that in her toolbox. And we have multiple examples like this.

- So she would drink a glass of orange juice in order to quell her anxiety? - Yeah, if she felt bad. - And is this something that she would do even when she wasn't feeling stressed? I mean, it's kind of interesting, but it suggests and it completely squares with everything I understand about prefrontal cortical limbic pathways, which is that they're highly subject to contextual learning, right?

If anything, the frontal cortex is this incredible feat of evolution that allows us to link essentially any stimulus with any non-learned response in the body, right? I mean, this is what allows soldiers to learn to overcome their fear of bomb blasts and run toward them if necessary. I mean, it can come both ways, of course.

- But for me, and this still needs to be tested, is nothing necessarily about the glass or even the orange or the vitamin C or anything like that. It's about the fact that she has this message. She has sent a message to herself. I can take care of myself because the best tool that I have is me, is my own body.

Whatever these kids go in the future, there's something that's always gonna be there with them, which is themselves. So they, as themselves, is the best tool they can have. You know, their body, the way they think, all of these things. - Do you think this is why we hear the kind of classic anecdote about the patient who has anxiety attacks whose psychiatrist gives them a couple of pills of medication that can help reduce anxiety, and they decide to keep those pills in their pocket should they have an anxiety attack.

And knowing they have those pills in their pocket allows them to control their anxiety. - Yes, because it gives them a sense of control, right? And they have control over this. And some people may choose to leave them in the fridge, and some people may choose to put them elsewhere, but it's what they decide.

It's that decision they're making that gives them a sense of control. That's important. - It's so interesting, the sense of agency and control over the non-negotiable stress response. You know, I sometimes, unfortunately, get, in my opinion, incorrectly attached to ice baths. We've talked about cold water exposure on this podcast.

Our colleague Craig Heller at Stanford Department of Biology, phenomenal scientist, was on this podcast. We talked about some of the beneficial uses of deliberate cold exposure. There are a lot of arguments. Does it increase metabolism? Doesn't seem like it does very much. Is it useful for inflammation? Perhaps, but the one thing that everyone agrees is that being in uncomfortably cold water makes you breathe faster, excuse me, and stress a bit.

In other words, it kind of sucks. It's uncomfortable. And I think one non-negotiable fact about deliberate cold exposure is that it gives people an opportunity to explore their own stress response if they're going to do it safely, right? You take a cold shower, you have some control. You can get out immediately, obviously.

You don't want it so cold that you give yourself cardiac arrest. You know, you have to be careful with deliberate cold exposure. But the adrenaline response to uncomfortable cold is non-negotiable. And I believe that whether or not somebody decides to recite the alphabet or think about how cold it is or whatever it is, what they're doing is they are practicing this frontal control over the limbic pathways.

It's just sort of a general exercise for controlling the limbic system through thought. But as our colleague David Spiegel has said to me many times, he says, you know, it's not just the state that you're in. Here, we're talking about stress as the state. It's how you got there.

And in particular, did you have any control over how you got there and whether or not you can get out? And I think that the kind of stress that you're talking about in post-traumatic stress disorder or in post-traumatic stress injury is typically of the sort that people didn't have a choice.

Certainly, these kids didn't have a choice about the initial exposure to the trauma or stressors, but that also the stress is showing up when they would least want it to appear or when it's very inconvenient to appear. - So this narrative is an important part of recovery, but we feel that it needs to come after the education piece and after learning a toolbox, having defenses, because sometimes it can get very charged when you go through the narrative and you want to assess many things during the narrative.

You want to assess gaps of memory. You want to assess potential cues. You want to assess the emotions that are present. So, and the narrative should be one that covers not only negative events, but also neutral ones and also positive events. And it sounds like a lot, right? But when you're talking about kids that have 10, 11, 12 years, it is doable.

You know, you can really manage it. By the way, with the cold showers, I think you're getting to the hinge of that see-saw. I think the cold shower probably does, not the cold shower, what do you call it? - Deliberate cold. It could be from a cold shower. I always say that because oftentimes people think, oh, you know, they're just trying to sell cold plunges.

And the truth is you don't need that. I mean, the fact of the matter is it's independent of income. Actually, a cold shower will save you money on your heating bill. I'm not saying everyone should take a cold shower. I love a nice warm or hot shower. I sometimes use the cold shower as a stimulus and I hate it every time, but I always learn something each time.

By the way, it feels great when you get out. So that's nice. And it does for many hours, especially if you end it with some warm water. But the learning I believe is in recognizing just how destabilized our patterns of thinking get when we have adrenaline in our body, which is what uncomfortable cold does.

And it deploys that adrenaline in the brain and body. And it also is a great learning in seeing the return to a baseline, just seeing how that affects our psychology. And to my mind, I can think of no other zero cost or even negative cost, meaning saves money, approach that works the first time in every time, that is safe enough, right?

I mean, I'm not interested in anything that has to do with snakes, for instance. I don't mind spiders. I'll pick them up with my hands as long as it's not a black widow or a particularly large spider and I'll put it outside. But I don't like snakes. I don't like thinking about them.

I don't like being near them. So, you know, there are other stressors that one could use, but it's so individual. Whereas cold water seems to be pretty uncomfortable for everybody. - I think you need some exposure of snakes when you're cold. (laughing) - No interest. It's so interesting. You know, these things get so firmly rooted, but I'd love to talk about this toolbox because first of all, it's according to your work, and this has been done repeatedly, it's very effective.

And I love the idea that it can be customized. So the words that come to mind is a customized toolbox for combating stress and PTSD. And the fact that it can be customized and maybe even covert, like we can have these tools inside us. We don't need to share them with anybody if we don't want to, but that they are very effective.

I think that those are very compelling reasons for exploring the toolbox approach a bit more here. So you mentioned one way to go about this is to think about or to have in mind some negative, some neutral and some positive experiences. And then to think about the different tools that one would deploy under those different conditions.

- Correct. So the exercise of the events is a lifeline that we do separate from the toolbox. We actually work on the toolbox first to identify coping mechanisms and coping tools that help. - So what would that look like? Let's say I'm a nine-year-old, I come into your clinic and I meet the criteria for PTSI or PTSD.

What sorts of questions would you ask? - Yes, so the first thing I would say, when you're feeling a certain way, whatever way we're talking about, right? - Anxious. - Agitated, anxious. - Nervous. - Is there anything that makes you feel better? Because the experience of having something and they bringing something is important too.

And sometimes they do, they say, I listen to music or I play the guitar or I go to play or-- - My friends. - Or my friends or my teammates mostly, actually. - They say teammates? - Teammates is pretty popular. - I love that. - Yeah, there's something about sports.

And sports is something that comes up a lot when we do the toolbox. People put in their sports they're doing or talking to their coach or talking to their teammates or learning a new sport. Sports are big, so that's an example that they give. Talking to friends, planning a sleepover, listening to music, different things like this.

- Are there any particular tools for when kids are stuck in a stress response? - Yes. - Because I, myself, am familiar with the toolkits that I use, certainly teammates is one of them. And I have others, including long exhale breathing, physiological size, these things will be familiar to some of the listeners.

But certainly there are times when we're stressed about something and we don't want to be and we have a hard time pulling our thoughts and our emotions and the stress response out. - So the ones I just mentioned are some ideas that the kids bring with them. What we always try to do is we teach them exercises of relaxation.

We have to be very careful with this because, like you say, it's good to be personalized, right? It's good that it's adapted to the kid. And that's why we don't tell them put this in your toolbox. We tell them learn it and if it helps you, you decide if you put it in the toolbox or not.

So when I talk about the treatment being not so much about the what, because there's many components here like education, narrative, that are common, right? Exposure, we can talk about. It's not so much about the what, but it's about the how. It's about empowering kids to identify those cues, to say if a tool works or doesn't work, to develop their own tools.

So, but sometimes they're very stuck, right? And they need a little bit of help. So we teach them breathing exercises and we have a script for that. We teach them muscle relaxation and we have something for that. We teach them the positive thinking, for example. So that's a cognitive type of tool.

And we teach them mindfulness because of our other work in prevention that we can talk about later in which mindfulness has been helpful. And also yoga, very simple yoga exercises. So nothing too complicated. Things like the mountain pose, for example, can be quite helpful for some kids. If anything, it helps them reassess the moment and stop.

And if we're gonna think about it in cognitive behavioral terms, kind of break that chain of negative thoughts that happen one after the other, which can lead to a panic attack, right? That's many times how a panic attack can start. - Well, what's so interesting to me about the stress response is that while it's quick to start, it's slow to shut off for logical reasons related to our evolutionary trajectory, right?

Wouldn't it be wonderful if you could stress when needed and then it would turn off when needed? But what we're really talking about here is intervening in the stress response either before or as it's happening, but then also making sure that the tail of that stress response isn't too long.

- We're also talking about eradicating stress that causes discomfort, right? And this causes distress, not necessarily to live a life without stress or to get rid completely of stress 'cause that would be impossible. - In certain cultures, there are accepted practices that adults use to deal with stress, things like worry beads.

And a few years back, there were those, what are those, what were the little spinner things that kids had? When those were popular, maybe they're still popular, did you observe any reductions in stress? You know, kids have a lot of energy. Like sometimes I think we confuse energy and stress.

Wouldn't we all love to have the kind of energy that we had in childhood? I was observing this the other day. You'll see a kid sitting cross-legged, listening in class, and then all of a sudden it's time to move across the room and they'll just pop up and move across the room.

Like when was the last time any of us like popped up out of our chairs unless we were particularly excited or scared as adults? Just that immediacy to action implies that there's a lot of energy in the system. So I could imagine that having some ways to siphon off some of that energy through, as far as I can tell, you know, things like worry beads or fidgets or whatever those are called.

I mean, they might irritate some adults around, but really they're pretty innocuous when you think about it. - I like that you're not calling it nervous energy because it is just what you said, it's just energy. It's extra energy that needs to be placed somewhere and they're trying to find out where to place it.

- I mean, we have colleagues that, not all of them, this is not a requirement for being a professor at Stanford, but I've got colleagues that work 80 hours a week. You could argue that's healthy or unhealthy depending on the context and their agreements with others, but, you know, that requires a lot of energy and I know they are not particularly happy working less.

So, you know, I think sometimes we are dismissive or kind of pejorative about physical energy and shaking and moving. But, you know, I see, I know someone in my life who bounces her knee while she works and it kind of makes me a little bit nervous, but boy, does she have a lot of focus and energy.

You know, so, I mean, I think it's wonderful, in other words. - Yeah, and some of us, you know, choose to have meetings while walking rather than being in an office. - That's certainly my preference. - You know, I go for a walk sometimes when I have a meeting.

So, yes, so there is increased energy, but there's increased energy that of, I feel like I need to do something and there's increased energy that causes a lot of discomfort. So, for this kid, kids that experience discomfort, then they can look at their toolbox and say, "Which one I'm gonna use?" And that gives them also a choice, which goes back to that sense of control again.

- Earlier, meaning off microphone, we were talking about the fact that some people, indeed some kids, have a different tendency to anchor towards thinking or feeling or action when under stress. And you were describing the four quadrant system. Could you share with us this four quadrant system? Because I think it's both extremely valuable to children and to adults.

It's certainly something that I plan to incorporate into my life. - Yes, so we have to be careful with structured interventions because sometimes structured interventions can break a little bit the fluidity of the relationship that a therapist and a child may have or a therapist and a patient. So, it's better to be semi-structured and to really be attentive to the temperament that the kid brings into that relationship or into that session.

And certainly, with the toolbox, as you mentioned, we see an example of that. We also add that in Q-Center therapy by dissecting and examining a response. So, for example, a child that breaks windows or a child that screams or a child that leaves the classroom running, we try to understand what's happening at that moment.

And the way that we do that is by looking at a square. And a square is composed of four corners. And the four corners are what you're thinking, so it's a cognitive side to it, what you're feeling emotionally, what you're feeling physically, and what you're actually doing, what the action is.

And this is your classical triangle of cognitive behavioral therapy in terms of what you're thinking, what you're doing, and how you're feeling. But we felt it was important to add that somatic physiological component because for many children, they don't have the vocabulary to talk about all of this. They just tell you, "I have a headache," or, "I have a stomachache," and there's no other medical reason that explains it, right?

So, depending on the kid that comes, you're gonna start examining their response through one of those corners. So, if the kid is really brainy and likes to think about the things they think or don't think, you start in the cognitive corner. Other kids are very attentive to their body and they say, "I feel my heart racing when I engage in this behavior or in this response," and you start with that corner.

The beauty of this is that most of the time, you don't have to work in all of the corners. By just working in one corner, all the other corners change and a new response develops. Okay, so if I'm thinking that I'm not in danger, maybe I don't need to leave running.

Maybe I can just tell the teacher I'm distressed by the amount of noise. All of a sudden, the kid has created a new square. That's another square. So, hopefully we take that one response as a square and build a cube, right, of many potential responses so that when the cube happens, now there's an armamentarium of responses and if I'm too distressed to think what response to do, I can bring myself there by using my toolbox.

So, it all kinds of starts tying together and then as I have more responses, as I understand cues, I can begin talking about this narrative that I have where I will fix some cognitive distortions, hopefully, like it was my fault I made it happen to things like, no, it wasn't my fault.

Somebody else was responsible and I'm just a survivor, right, I'm not a victim. I'm a survivor. That's another cognitive distortion that can be fixed. So, all of that, we've included all of this in a manual for therapists, right? So, we have a manual for therapists that is called Cue Center Therapy for Youth with Post-Traumatic Symptoms published by Oxford.

But I believe that adults that want to re-examine their childhood or their history or want to think about their kids or are interested in trauma can get a lot from actually examining this manual and studying this manual and in fact, I believe in so, so strongly that we are beginning the first steps of adapting it not only for youth, but also for adults.

- In this four-corner system, and forgive me because I called it a four-quadrant system, but in this four corners of the square system, you said there's thinking, which is cognitive, there are emotions, then there's feelings, which are somatic, physical, and then actions. So, actions are straightforward. Thinking would be, for instance, if I understand correctly, I'm in danger.

Emotions would be, I'm scared. So, it's a verbal label. I'm depressed, I'm scared, I'm sad, I'm-- - Yeah, in a way, it's cognitive too, right? But it carries an emotion with it. And then, in terms of the physical feeling, it's of the body, but it could include of the head too.

Like, I have a headache, or my heart is racing, or I'm, you know, or something of that sort. And then, actions, of course, is the action that they-- - And action is a really fun one because you can imagine there are some kids that are not psychologically minded at all, and they don't even want to engage in this with me.

And they are like, okay, what is it that I'm doing? I'll do something different. So, they'll immediately develop the next square. So, they cannot talk too much about their emotions or how they're feeling physically or look at the negative thought. But they say, oh, is the problem that I'm running out of the classroom?

Well, what if I don't? And they give you another action. And so, some kids start with that corner. So, you can really start with any of the corners. - Yeah, I love that earlier, you were talking about practicing positive thinking even when, perhaps especially when, one is not in the stress response or trauma response, but also, of course, when one is in the trauma response.

I think that's just so vitally important for people to hear, certainly for me to hear. I'm not claiming to have PTSD, but as a novel concept that I've not heard raised before around these topics. The other is this four-corner system, which immediately occurs to me as so powerful because it breaks down the kind of reflex arc of the stress response into its component parts, right?

What's of the body, what's of the thinking, what's of the thinking that's emotional, and then what's the action? And you said as soon as one identifies one of these corners and starts to kind of look at it differently and consider some of the optionality that exists, an alternative, that all these other options cascade from that.

And I believe that in doing that, you've described what for thousands of years, really, but recently we've heard a lot about in the kind of mindfulness arena as creating space, right? Like this notion of creating space, not outer space, but creating space within us to choose better options is something that I think until right now, as you've described this, has remained unfortunately very mysterious.

You know, people talk about, okay, you know, you want to be reactive, excuse me, you want to be responsive, not reactive. Responsive implies some optionality to your responses. Reactive implies kind of a reflex arc of just whatever the default was. But this notion of space is like too squishy for me as a biologist to really be able to latch onto.

And I would argue, given the prevalence of PTSD and stress, it's probably too squishy for most people. It hasn't really led anywhere specific. But I think what you're describing is the ability to become responsive as opposed to reactive, assuming that the word responsive includes like some options within it.

And so this four corner system to me is genius because it gives us an anchor point to start from. So could you say that if a child or adult is uncomfortably stressed, maybe about a trauma, but just is caught in the stress response, that actually pulling out a pen or pencil or crayon as it were, and drawing a square, and just really like, what am I thinking?

Like, maybe it's just like, this is terrible. I don't like it. Writing down, I'm embarrassed. Like, I'm not with my friends. Like, I'm like not, you know, I'm flush. You know, my cheeks are flushing, whatever. I'm feeling like just weighed down or something. And then thinking, well, what are the actions?

I wanna remove myself from the situation. At that point is the suggestion that one find, what is the point of entry that feels most accessible? And to start there? - Yes, with one caveat. We usually use Wagner's emotional thermometer to measure where the kid is at. And it goes from like zero to 10 or one to 10 with different levels of stress.

And it's good to use something concrete because sometimes we think they're at 10 and they're at five or vice versa. - Yeah, we're very poor at assessing others' internal states. - We are. - As our colleague, Karl Deisseroth, who's also been a guest on this podcast, I heard him once say this in a very large lecture.

He said, you know, we're terrible, absolutely dreadful at assessing other people's emotions. In fact, most of the time, we don't even know how we feel. - Yeah, he always says that. And it's true. - It's so true. - And it's true. But I would say if the kid is at 10 at that moment, the best thing is to use a tool from the toolbox and not to engage on the square at that moment until they come down a little bit and they can pay attention and they can listen to you.

Because then they will be letting the information come in. They're so emotionally charged right at the moment that that may not be the right time. Which also, by the way, is the same thing as when you need to talk to kids about traumas that are happening in our society, right?

Sometimes you just wanna let them know that the door is open for communication. You may wanna talk about it at the moment where the kid may not be ready. But you can let them know, well, when you're ready, we can talk about it. Here, the same. When you're ready, let's go over the square exercise or the example if the kid is already familiar with it.

Or I have something to show you, right? And pick his curiosity that way. But I would say use the thermometer to see if that's a good time, right? If it's 10, nine, eight, probably not. Wait 'til it's like five, four, three. And then engage in that. - So the toolbox should be used essentially under any conditions.

And the kid should generate their own tools to add to the toolbox, customize the tools. And then the square can be used when they are at a slightly lower level of stress because it requires a certain level of cognitive intervention. They need to be able to think about and express their own state.

- Correct. - And is this something that you suggest kids only do with their therapist or is this something that they can do on their own as well, assuming that they're old enough to write and to think about it? - Yeah, well, our hope is that after a kid goes through Q-Center therapy, that they can internalize a lot of these activities and exercises and, like I said, become their own tool.

Take those for life and continue to use them. - Yeah, I'm certain that many, many adults, not just children, can benefit from these tools. I mean, I would argue that most of the bad things that happen in the world are the consequence of dysregulated autonomic function, put kind of bluntly.

- Yeah, by directional, right? Kind of making things worse. Once they happen, they impact the system even further. - Yeah, I mean, I think most homicides are homicides of jealous rage. From what I have read, I don't know if that's still true. And, of course, then that is probably also true for all the things that are not as severe as homicide, but still dreadfully bad, like assault and things like that.

- And it's interesting that you bring that up because I often think about, we've been talking about how we experience trauma as individuals, right? But we experience trauma in our civilization. We experience trauma in our history. We experience trauma in our nation and how does a nation heal? How does a system heal?

Well, the steps are not that different. - Perhaps this is the appropriate time to give you the opportunity to editorialize a little bit about social media and online behavior, setting aside really aggressive online behavior, bullying and things like that, which of course exists and is really serious. Do you see the behavior of kids and adults online, this sort of just maybe even the addiction to online, commenting and reading of comments and the kind of battling of issues back and forth, that clearly isn't going anywhere.

Some of it goes someplace functional, but most of it, I would argue, especially among the adults, is going nowhere. It's just very circular. It's my side versus your side, my side versus your side. And emotions get really stirred on there. Do you think that is reflective of a lack of tools for self-regulation?

Do you think like what we're seeing is the manifestation of just a lot of challenges in the world and/or an outlet for people to just vent without the need to address their own internal state and what's underlying the venting? I know many very, very intelligent adults who eventually just had to quit social media in order to have any level of functionality in their life.

- It comes down to that space you were talking about and building that space and creating that mindfulness, time that you need, which is also gonna be personalized. It's gonna be different for different people. This spring, I was in Morocco and I visited the Medina. I was staying at the Medina.

And I was overstimulated, as you can be, and enjoying it. But I imagine this is the state that teenagers are in all the time when they are with social media, bringing them information and different tidbits and different things that are happening all over the place. And very much like I found it restful to go to my hotel for a couple of hours before dinner, people need to build that space.

People need to create that space. What I tell parents is that it's important to remember that this was also a very helpful tool for us when we were in the pandemic, right? The kids were interacting socially, academics, school was happening through technology. So how can something so good be at times so harmful?

And I remind them about when they brought hammers to their house, right? And they had little kids. They had to teach them how to use them. This is a very important tool when you need to nail something or when you need to take a nail out. This can be dangerous, right?

You don't run with scissors. You have all these rules around other tools. We have to have these rules around social media as well. And I think that's what the Surgeon General is getting at when he talks about we need some regulations around it. But at the family level, I think parents need to say there are certain boundaries that we are going to have.

So at dinner time, for example, in this baskets, all the phones go into the basket. And that's what we're gonna do from now on. But it is very difficult because when you establish rules like that, kids watch you like a hawk. So you have to model the behavior you are expecting, right?

The moment that you as a parent decide, oh no, I need to go to the basket during dinner 'cause I need to check this thing out, then it breaks. So that's what I think. I think it can be quite helpful. And I think that it can be dangerous. We've seen examples of that.

And it is a tool like any other, like a knife, that we need to learn how to use it. - I think what you're describing to my mind is a situation where the tool has become the terrain. It's like social media has become the landscape in which many people live as opposed to the real world.

I mean, my original understanding of social media is that one would experience and do things in the real world and then bring those to social media. That's certainly what I do. I teach on social media and I do the learning for that teaching, the drawing in some cases, the preparation in the quote-unquote real world, and then bring it to social media.

But I feel like it's almost like the hammer has become the landscape. - The house. - Yeah, or something like that. The hammer has become the house. Yes, that's a much more eloquent and appropriate. Yeah, I feel like with social media, the tool of social media has become the terrain in which people are living in.

So that just feels like a closed loop. Use sort of an engineering example. So it's like, it doesn't go anywhere. Like you can never actually get the relief that you're seeking. And I think we default to descriptions about dopamine and dopamine hits. And there's some truth to that. But the more I look at the literature on brain activation during social media use, it doesn't really speak to dopamine and reward prediction error as much as it does, just sort of a mindless compulsion and kind of just passive overuse as opposed to like rewards, like, oh, this is so cool and that's so cool.

I mean, it can be. I mean, I've been watching some of the track and field races of the Olympics and there's a, I mean, I was cheering out loud for a few of them, but it's usually something quite different. - Yeah, I think if you live in a virtual world all the time, then you're not living, right?

You're not in the real world. So it's like, how can you use the virtual? Are there ways that the virtual world can help you live the current world in a better way? Yes, so that's why I think it's helpful. But if you replace your life with a virtual life, then that's a pity.

That's very sad. - I see that in a lot of adults as well as kids. Let's talk about risk. You know, up until now we've been envisioning a treatment situation or a study that you're running where a kid and perhaps parents as well are brought into the laboratory or clinic at Stanford and you're talking to them, assessing them.

They're developing a custom toolbox and that's a wonderful opportunity for kids who sadly have PTSD or PTSI to be assessed and to develop tools that can really help them. That's been proven by the work you and others have done. But what about the many, many millions of kids and adults who are at risk either because of lack of access, it could be due to finances, geography, poverty, any number of different things, or they simply don't even know what PTSD and PTSI are.

Their parents don't know. What are some of the tools and interventions that you think could be implemented at the level of schools, families, or even individuals that might help them? - So here we were in my program, we had created Q-Center Therapy, right? We developed a training program for it.

We have a Q-Center Therapy training program. And I became increasingly concerned about my own staff and my own team because this is a team, as you can imagine, that are seeing trauma every day and are seeing trauma in kids. I was worried about vicarious trauma and the impact that this would have in their health.

So I remember that when I was doing my residency, I took a course in hypnosis and I was really struck by how much control one has during hypnosis. So it's nothing like anyone is doing to anybody else. It's really kind of having the control to relax yourself. - Self-directed hypnosis.

- Self-directed type of hypnosis. And I said, "I would like to bring something like that." And I met a PhD, John Rutger, that was a yoga instructor and also a mindfulness instructor, and I brought him to the team. And he had other things to do, but one of the main goals was to take care of the team.

And we started regularly practicing yoga and practicing mindfulness, as we were seeing all these cases and working with trauma and so forth. And I was able to see firsthand how helpful it was for me personally and for my team. At the time, we were doing some work in Ispalo Alto in some of the schools.

We were doing some pro bono counseling because this is another problem. Many of the schools have no counselors, right? So, but this was a while back, it's like 10 years ago. - Yeah, the Ispalo Alto School District, for those that don't know, Palo Alto, I guess it could be called West Palo Alto, is a separate city and county from Ispalo Alto.

Palo Alto is not exclusively, but is known for, at least nowadays, let's just be frank, fairly tremendous affluence relative to most places in the world, put bluntly. Ispalo Alto, a separate county, different school district, police system, has for as long as I can remember, having grown up in Palo Alto, has always been stricken with far fewer resources.

And while there've been tremendous efforts to improve the situation there, it is still at a steep disadvantage financially. But of course, many amazing people working there and living there, and growing up, there was some exchange across that Ispalo Alto, West Palo Alto border, as it were, in the school district, but they're pretty separate domains when it comes to resources.

- And it is not now, but many years ago, it was the number one murder capital in the US. It's also the place where Facebook is now. So, and IKEA, and there's people that bring some employment to the area, but also bring some other problems. - Yeah, that area where IKEA is used to be called, do you remember it was called Whiskey Gulch?

- Didn't know that. - For years, kind of terrible name, right? But it was a stark contrast, right as you literally crossed the train tracks heading towards Highway 101. In that case, that portion of Palo Alto, Crescent Park, an extreme of wealth to an extreme of poverty. - Yes.

- In literally a distance of 10 meters. - And of course, there are wonderful families there. - Of course. - That support the kids. There's a Ravenswood, which is also the other name for Ispalo Alto Family Health Center, that really provides a lot of good resources to the area.

And there's a good school district, but at this time, it was missing counselors. So we had some presence there. We decided to bring some of the things that we were learning in terms of yoga and in terms of mindfulness to two of the classrooms. At the end of about three months, I get called to the principal's office.

I have to go to the principal's office, because the principal was interested in finding out what was going on in there, because none of those kids in those classrooms had gone to her office in all that time. - They hadn't gotten in trouble. - They had not gotten in trouble.

So I explained what it was, and we decided to do a bigger scale study. And eventually, we partner with a group called Pure Power, purepowerinc.org, developing a yoga and mindfulness curriculum for students at schools. At that time, we started bringing yoga instructors into the classroom, but we very quickly learned that the best approach to this would be to teach the teachers and have the teachers teach the students, because the yoga instructors had no training on how to control a classroom, and the teachers did.

And some of these poses were so elemental that it was okay if they were not a yoga instructor. So anyway, we tested this curriculum, and there was a piece about it in the "NewsHour." I think it might still be there. And I get this wonderful phone call by this family in New York that wants to see how they can help me spread this further into not only the classrooms that I was working, but into the whole school or the school district.

And I knew at that point that two things were important, not only that they wanted and I wanted, but that the school district should want it, and also that at this time, we would need to do a very in-depth study to see what our intervention was and what the curriculum was, because mindfulness can be the name that you give to many different things.

So we wanted to make sure that our intervention of yoga and mindfulness exercises that now Pure Power carries is really what we're being tested. So they were very, very helpful in helping sponsor not only the dissemination of this curriculum through the school district, but a randomized controlled trial where we actually had a whole other district that would also be trained, but only after the study was over.

It was a demographically comparison school in San Jose, in the city of San Jose. Near enough for us to conduct the study, but far enough that where there wouldn't be too much dissemination from one district to the other. And it was good that we did a district-wide control, because if we would have done it by classroom or by school, it wouldn't have worked, because there was so much diffusion of what the kids were learning into their friends and their family and the other classes and the other people in the community that was beautiful to see, but it would have ruined a control study.

- So you needed literally physical and demographic separation. So you went with what used to be called the peninsula, the South Bay, East Palo Alto, and then San Jose, far enough apart that the kids weren't talking enough to blur the treatment groups. - Exactly. So we demonstrated feasibility. You know, we were able to do it.

We demonstrated acceptability. The kids liked it. The kids would do it. Some schools actually had a room specifically for them to go and do it, even if the teachers were not doing it in the classroom. And it ranged. It was like twice to three times a week for 15 or 50 minutes of this curriculum in the classrooms.

- Can I, sorry to interrupt, but could I ask you a little bit more about the curriculum? You said five, you said, or 15 to 50, five zero minutes, two to three times per week. And did the kids have to like change over to their yoga clothes? The reason I ask is that I could think of a number of real world barriers to getting something like this implemented.

I feel like going jogging, usually you get a little sweaty, you need running shoes, you know, there are other forms of exercise that require that less. But these days they're, as far as I know, not every school requires physical education. When I was growing up and through high school, you had to literally suit up.

You had to go in the locker room and put on your PE clothes as it were, and then you'd run or play volleyball, whatever the PE teacher told you to do, you had to do, if you wanted to get a decent grade. Is the yoga being done, I mean, you said it could be in the classroom or at a separate location, but are the kids basically getting up out of their chairs and just right in their school clothes, doing this for 15 to 50 minutes?

- So they stay with the same clothes, but we had mats. They had mats, every student had a mat. Then it's interesting that you mentioned PE because the first suggestion was let's do it during PE class. And I'm like, no, that's, you know, rowing from Paul to get to Peter.

Until I learned that PE, like you said, was not happening. - So sad. - Which I couldn't believe. And if anything, I think the study has helped for them to bring PE back. And the classes, which are these lessons and yoga movements and mindfulness, were really taking place in the classroom that whatever teacher learned it.

So if it was the math teacher, she was taking 10 minutes aside to do it. If it was the PE and PE was not happening there, they may dedicate the 50 minutes to do the yoga and the mindfulness. So we have a number of assessments that we did. And like I mentioned, yes, it was acceptable and it improved mood and all of that.

But I think the biggest finding that we published from that study was that it increased 73 minutes of sleep. - 73? - 73 minutes of sleep. - That's extraordinarily high. - On average for the students. And it increased the depth of sleep. So something that we did in this study was that we also did portable polysomnography.

And it was not in a sleep center, it was in their own house. So collaborating with Ruth O'Hara from the department, we were able to assess their sleep. And deep sleep is very important. That's where you process the events of the day. So these kids were increasing REM, total sleep, deep sleep, doing much better.

And then another thing because of our previous studies that we've talked about in terms of brain function, this hasn't been published, but we have some preliminary data demonstrating that those kids that went through the intervention before and after the intervention were able to decrease the activity of their amygdala, which was very powerful and also very helpful.

So many of these kids adapted this into their daily practices. After this study was over, we went to our control group and we taught those lessons there. And now it has served to identify even more tools that we can put in the toolbox of CCT. So we utilize some of the things there and here.

So Pure Power and our program have been collaborating a lot because it covers the risk group and the treatment group. So sometimes when we go to schools and we do trainings, we partner with them so that we have the yoga and the mindfulness and the cue center therapy. And I by no means mean these are the two things that everybody should be using.

I'm saying these are two more tools. In fact, I think we need more development, more development of interventions, both for treatment and for intervention. And how do we identify who needs what and how is where we're moving next. - Wow, what spectacular results. I mean, 73 minutes more of sleep is like, I mean, talk about effective medicine.

You know, I mean, we agreed at the outset that sleep is the foundation of mental health and physical health and all forms of cognitive and physical performance. I mean, when we know this, the study done at Stanford, albeit a small one of having athletes just get a bit more sleep or even just stay in bed a bit longer and no, not on their phones, but just lying quietly with eyes closed and resting or sleeping more improved shot accuracy in basketball players.

This has been shown in so many domains of cognitive and physical. It's like not even worth spooling off all the examples, but that is spectacular. It also makes me think I should start doing some yoga because I do get enough sleep, but that's significant. What do you think are the barriers to having this sort of thing implemented at national scale?

Now, I always think about this, you know, okay, so the results are in, maybe it's one study, maybe it's two, but you're talking about a basically harmless intervention and actually it's a very therapeutic intervention. Sure, there are some people that won't be able to do all the poses, et cetera, but there's always something that somebody can do.

Even people that are immobilized, there are certain forms of, believe it or not, cognitive yoga and that friend of mine who works with people who are quadriplegic, they can do certain things to keep nervous system function online. But, you know, essentially anyone can do this. What are the barriers from taking it from this East Palo Alto school to a study, to another study, okay, San Jose school, now let's say you get all of Santa Clara or, you know, neighboring counties, you know, what does it take to get something implemented at national scale so that the work can really ripple out and benefit all these kids who are, of course, are going to become adults?

- Well, we need to prioritize it, right? We need to prioritize education for starters, right? We were talking about classes not even having physical education or arts, for example. And we need to prioritize mental health and it needs to start early. And I think when we work our national budget, it needs to be, there needs to be earmarks for these two areas that should go to the Department of Education.

The Department of Education should make this a priority. Teachers are really, really overworked. They are under-resourced and, like, pediatricians many times are responsible for doing somebody else's work, right? Everybody tells them, oh, this will only take a minute or this will only take two minutes or if you make this assessment, you know, you can do that.

But the time is finite, right? And the space is finite. So they need more space, they need more time, they need more support, teachers. And then this needs to be a priority from districts to really implement programs like this. - So parents and even non-parents talk to the teachers in the school, talk to the principals in the school.

And I've been learning about the power of the telephone for lobbying. This has been around some things I've been involved with with the veterans community. I mean, the ability to look up and call your congressman or congresswoman and tell them that you are really concerned about or excited about a particular program does have impact.

I mean, at first I didn't think this was true, but I realized that when they start getting 50, 100, 1,000 messages about a particular topic that people are passionate about, they pay attention. Maybe it's because they just want to get reelected. Maybe it's because they are genuinely concerned about helping people.

I like to think it's the latter. But regardless of which, they run those messages up the flagpole when they bring issues. - So let me tell you what we just started doing in Puerto Rico. I'm from Puerto Rico. But Puerto Rico and Puerto Rican students have gone through a number of natural disasters that started with Hurricane Maria and continue with other hurricanes and also with earthquakes and this has led to violence and there's interpersonal violence.

So some of the kids in Puerto Rico have gone through a lot. But also, the whole island of Puerto Rico is one of the largest school districts in the U.S. The whole island is one district, meaning that if you do something, like a program like the one we're talking about, you can implement it island wide.

Currently, we are launching a project in Puerto Rico where all the teachers will be trained in the yoga and mindfulness curriculum and all of the counselors will be trained in Q-Center therapy. The kids are being assessed at baseline. Then they go through their yoga and curriculum and at time two, when they get assessed to see how they're doing after that, we also screen those that have PTSS, post-traumatic stress symptoms that cause impairment.

And then those go through the trained counselors and then they get assessed again in the latter part. So the goal is for us to, although we've talked about the two treatments, we've never really had both of them happen simultaneously and we want to do it in a large scale like this because if this works, if it's sustainable, if it's feasible, we can actually then bring it to other large school districts like New York, like LA, for example, and start disseminating this.

- I'd love your thoughts on something. I'm so impressed that you were able to bring this from a study or set of studies to a much larger scale in Puerto Rico. I could be wrong here, but I feel like in the United States, we have such a culture of fame and popularity and reward around people who are extreme performers.

You know, we hear about these NBA stars and right now we're seeing a lot about these incredible track stars and where we have these tech innovators that found huge companies. They used to be called unicorn companies, but all these incredible successes. And I wonder sometimes if the hyper-emphasis on these extreme performers has led to the conclusion in young people that unless you're going to be Michael Jordan or LeBron James or Mark Zuckerberg or Elon Musk or win an Olympic gold medal, that the practices that feed up to becoming those sorts of people, like mindfulness meditation or becoming a yogi for that matter, you know, I feel like there's been a push towards hyper-specialization and performance to the point where people are writing off the incredible utility of physical activity, mindfulness, you know, learning math, science, literature, and the arts.

You know, you're talking about the arts. - Humanities studies. - Yeah, music, right? Even for people like me, you know, I mean, sure. They always gave me the triangle 'cause I could manage that one and I don't want to insult the triangle players. I'm sure it's much more complicated than I'm giving the impression it is.

But the point is that I feel like there's been a not so gradual disintegration of the idea that there is utility. Indeed, there's great benefit to doing things, not with the intention of becoming a high performer, but just doing them for sake of how it enriches us in a number of different ways, including our mental health.

And I wonder whether or not the lack of PE is sort of a, well, if you're not going to run track and try and medal or something, you know, or go to championship meets, then like, what's the point? But I don't, I certainly don't subscribe to that. I'm curious what your thoughts are.

- Well, I think we need to redefine success and what it means to be successful. I think that we're currently describing it with the examples that you just gave, which probably was not the way that we were describing it in the '60s or the '70s. But it is harming individuals, which is most of us, that cannot attain that level of proficiency in an area.

And in fact, the individuals that are choosing to have a broader belonging, in a way, are more protected. I worry about those other individuals, too, that have that very personalized, not personalized, but very individualized, unique component in their life where they dedicate everything to that one thing. - Trust me, they often suffer in one or more of their other domains of life.

Some don't, but I would argue most do. - But the idea of belonging, right, is that you have, you belong to many different facets of life. You are a sports person, you're a community person, you're a student, you're a father, you're an aunt, you're different things. When you're only one thing and that fails, your whole identity is gone.

It doesn't even have to fail. You have to perceive that it has failed, and that's enough to throw you off course. And so with the current definition of success, we're not doing a service for those that attain that definition and those that do not attain that definition. I think it needs to be broader.

I think belonging needs to be included. I think the way that we care, not only for ourselves, but for the rest of our citizens needs to be included. Citizenship is important. So it is dynamic. So far it has been dynamic, how we define success, and hopefully it will change again.

- All right, I agree wholeheartedly. Let's talk about resilience. Earlier you said, you know, kids are not resilient, but you also implied, maybe you even stated it outright, that they can become resilient. What is resilience and what are some of the paths to resilience? - Resilience is a physical term, right?

It means you bounce, the coil bounces back to where it was originally. I like to think of the word adaptation because it means not only you bounce back, but you bounce back to a better place. Like I like to think that we adapted during the experience of the pandemic other than we were resilient of it.

Yes, we were resilient because we survived it. Some of us did, not all, right? Some of us have to deal with the grief of what happened during that time. But adaptation means that not only we go back to where we were before the pandemic, but that now we've learned from that experience to be in a better place.

Now, we know very little about resilience and we definitely know very little biology about resilience. We know that having a sense of humor is good. We know that perseverance is good. We know that the presence of an adult in a child's life that was there to give them opportunity or to talk to them about things they were going through, that's probably the best known resilient factor.

But what if it's not the presence of that adult, but there's something in that child that makes them seek and maintain that type of relationship, right? So I feel that we need to start looking at the biology of resilience. And one way that we've done that in my program is through a collaboration with Alex Urban from our department and from genetics, and Caroling Pertman, who's in his lab and one of his postdocs.

They work with organoids, and I don't know if you've mentioned organoids before to your audience. - I have not, but one of my good friends and colleagues at Stanford, Sergio Pasca, is one of the world leaders in organoids, and we hope to host him on this podcast soon. But please educate us on organoids.

They are oh so cool and oh so science fictiony, but they are oh so real as well. - So we have stem cells that can be converted to any type of cell under the appropriate nutrients and environments that we want to examine. So for a psychiatrist, of course, the interest is to turn them into neurons.

And not only they can grow in a Petri dish, but they grow suspended, so it's almost like a 3D. And Sergio uses the term asembloid for when he actually assembles them further to build more organ-specific-- - Mini brains. - Mini brains is the term that I like, yes. So these mini brains are these neurons that are growing in a circle like the brain, and they communicate with each other, and they are active with each other, and we can study.

So in conversations with Alex, and now that you all know my previous work with cortisol and all that, I was telling him and Carolyn, well, why would happen if we expose some of these organoids to cortisol? And of course, we needed to come up with, oh, what would be the right amount that would mimic trauma?

So we also involved Robert Zabolsky to help us come up with a concentration that would be trauma mimetic. And so we exposed a number of organoids to different levels of cortisol. For some of them, it was a trauma. For others, they were not exposed. Then half of that amount, or much less of that amount, was a trigger, the cue, right?

So some had the trauma and the cue. Some had no exposure. Some only had the cue. And then we compare what was associated with really, well, the first thing that they needed to do was identify that these neurons actually had these glucocorticoid receptors and that they were active. And they did have them, and they were active.

So we looked through epigenetic analysis, I should say, we is the royal we, right? It's more Alex and Carolyn. They look at the genes that were changed, that their activity changed because of this cortisol exposure. And through epigenetic analysis, which is this space between DNA and RNA, and there's like methylation patterns and all that, and some genes activity changes.

Some turn on, some turn off. So interestingly, the majority of the genes that we found there were genes that have been addressed in the literature as potentially being related to post-traumatic stress disorder. Things like the glucocorticoid receptor genes and things that you would think of. But there was another subset of genes that we identified that were novel.

And I was very interested in those because of my interest in accelerated aging because of stress. And those were genes that are related to collagen formation. And we know that atherosclerosis has been related to stress, for example. And we know that accelerated aging, not only in PTSD, but in mental health conditions overall, individuals that suffer from severe mental illness chronically in their life end up dying 25 years younger than the rest of the population.

That's very significant. And so stress and accelerated aging, interesting. Okay, so these are interesting findings in organoids. But when you have those, what you do is you move on to a population study. So these kids in Puerto Rico that are going through these interventions, besides me checking on their PTSD, their anxiety, their depression, they're giving me a vocal swap.

And in the vocal swap, those epithelial cells, we can actually take them through epigenetic analysis and see those kids at time one that even though they've gone through all this trauma, may not be faring that much worse as their counterparts and compare them. And not only that, we can actually also look at response, treatment response for the intervention, for the yoga and mindfulness preventive intervention, and for the treatment, for the cue center therapy.

So that's the plan. That's the plan in trying to bring more light into what is the biology of resilience and how can we understand resilience better. - What a spectacular study, goodness. And if any of you missed some of the underlying mechanics, I'll just quickly recap. These organoids are little brains in a dish that came to be by virtue of taking fibroblasts or other cells, so skin cells essentially, put into dishes, provided for what are called transcription factors.

These are the four transcription factors that Yamanaka won the Nobel prize for identifying that reverts those cells into stem cells. And then a few other goodies, molecular goodies, that then allow them to become neurons in particular. Then they grow into little mini brains. And then as Dr. Carrion was explaining, are exposed to cortisol at appropriate concentrations to mimic cortisol exposure in the whole person.

And then from that, the genomes of those cells and the epigenomes are analyzed to identify potential targets. The results are brought back to these kids in Puerto Rico, such that the genomes of all these kids experiencing different levels of stress and yoga, mindfulness interventions, or not, maybe they're in the control group.

The outcomes can be assessed and then one can address, hey, what are the genes that are protective against stress? AKA, what are the genes that are protective against high levels of cortisol? And a bunch of other, surely to be very transformative and important facts about how stress impacts the young brain to either give rise to PTSD or not.

I must say, as you described that study, I had three thoughts. One, wow, how awesome is this? That you can bridge across so many different levels of analysis. I mean, because you're talking about molecular genetics all the way up to yoga in school children in Puerto Rico. And PTSD, you know, it's just a complex disorder.

I was also thinking to myself, wow, what an incredible place Stanford is that such a collaboration is possible, right? Makes me delight in the fact that colleagues like you exist and Sergio and forgive me the names of the other colleagues, I'm not familiar. - Alex Urban and Carolyn Perlman.

- Thank you. And the third thing is how important it is to bridge across these different levels of analysis. I think this is the first time on this podcast where somebody has discussed an experiment that bridges across so many levels of analysis, literally from fibroblasts, skin cells in a dish, all the way to a complex psychiatric condition and in an attempt, excuse me, to create novel therapeutics.

So it's just truly spectacular. So if people are sensing a even further surge in my energy, this is the kind of thing that gets me so excited because in the landscape of science, we often see a study or we hear about organoids or we hear about a yoga intervention.

And these things tend to exist in silos, in isolation, but the ability to bridge across these levels of analysis, I believe is critical. And so, yeah, kudos to you for being a part of this incredible collaboration. - And collaborations are key, right? Because the world is so complex now that there's no way that a single lab could have all these expertise.

So you're right, a place like Stanford allows for these communications to happen, for these collaborations to happen. In 28 years that I've been there, I have never heard, no, I'm not interested in that. - I always say it, at Stanford especially, if two scientists meet for more than 30 minutes, what comes out of that is a collaboration.

As a final question, I'm gonna ask you to limit it to one answer, but I'm sure that there are many. The question is, if you had a magic wand and you could get any message out to the whole world about PTSD and PTSI, in particular in kids, in young people, but also in adults, what is that message?

What do you want people to know about post-traumatic stress disorder, stress and post-traumatic stress injury? - The first thing that comes to mind is the importance of listening and listening to what kids and adults have to say about their experiencing, and really creating a space for them where they or us don't feel isolated, that they feel supported, and that they feel that they can identify their own strengths and their own capabilities of making themselves better.

Everyone knows or has heard about psychiatrists and everybody thinks, "Oh, what would your psychiatry say?" And psychiatrists have these smart things to say to people that help them with their life, but the best psychiatrists that I know actually say very little. They listen. So I would say that listening to the experience that people have is key.

- Well, thank you so much for that. And Dr. Karyon Victor, thank you so, so much for the work you do. - Thank you for having me here. - It's spectacular work at so many levels. It's also very bold and brave work to tackle such a big problem with such focus and to really give people agency, this notion of a custom toolbox, I think, is profound, to give kids and adults, as it were, agency over their own interventions in an effort to really help themselves.

I appreciate you coming here today. More than I can express, I know the listeners and viewers of this podcast appreciate it as well. You are involved with Stanford Clinically, you're involved running studies, clinical studies that have great importance. So for you to take time to educate us with these tools is absolutely spectacular and is really appreciated.

Please keep us updated on your progress and please come back and tell us more about that progress when the time is right. - Thank you so much. - Thank you for joining me for today's discussion about post-traumatic stress disorder and its treatments with Dr. Victor Karyon. To learn more about Dr.

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