YouSaid · the spoken record

Karl Deisseroth

lines on the record: 178
first: 2022-04-07
most recent: 2022-04-07
sittings or episodes: 1
sources: podcast

Every line below is reproduced as it was said and linked to the record it came from. Nothing here is summarised or generated. Directory · Search · Corrections

“Human beings exist on a spectrum of how socially we can be. And this is pretty interesting actually scientifically, but also very important clinically. There are hypersocial states where people are almost too social. There are chromosomal deletion states where people have instant affinity and bonding and rich, deep seeming connections with people very verbal. On the other end, People with autism spectrum disorder are Not able to keep up with social interactions. And it's a spectrum. Some old to moderate difficulties. They may have inability to understand what the next thing to do in a social situation is, but may have perfectly good language abilities.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“Yeah, so in his case, not knowing that, it could have been simply that, let's say he had an internal psychic pain state, and it was in sort of a compensated mode for much of his life, able to generate enough joy from his comedy and his social interactions. But eventually later in life, you know, those things drop away, the balance shifts. You get tired of fighting the pain for that long. And then, so you've got this time-dependent non-stationarity that happens. And then the same symptom becomes no longer tolerable in the end.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“Louis Bonnie Dementia. This is a very interesting neurological disorder where among other things there's neuron death indeed, so you've got Frank neuron loss. It's not just a matter of some longstanding psychic pain, but you've got a progressive loss. And so clearly you've got a situation where he could have finally reached a point where the balance that he'd worked out between negativity and positivity was disrupted due to loss. The wrong cells died, the wrong projections were cut by the Louy body dementia. Certainly dopamine neurons die in Louis body dementia. Those are neurons that give rise to much of the feelings of reward and pleasure that we experience, among other roles. So clearly in his case there could have been a very concrete cellular neurological issue that was progressive and pushed him to that point.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“And so, I don't know to go back to your example of Robin Williams. I don't know what was going on inside him. I don't know the nature of his internal state. Was it active psychic pain that”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“You're very right about that. So my negativity, I have this, I never think I've done enough is sort of where my negativity comes from inside. I never think that I've Met the potential of the moment. I haven't done, I haven't, you know, Made the most of the opportunities that are available still early. I haven't progressed as far as I should. And exactly as you're saying, that works for a while. But then what happens as you get later in life and there's less runway to fix that? And then maybe then that negative voice is a problem.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“The way you phrase it, I think you're using it. I could be wrong, but if you phrased it in this semi-humorous way about your habenula, it seems to me that you're using that to good effect. But one never really knows what someone else's internal state is. As I look at you, I don't know the depths of what's going on. And it's possible that it's a much harder situation in there. Yes.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“Moments of unexpected pain. Habenula is there, it seems, it's active to report on internal negativity with its action. And so you could imagine strategies to target this brain structure that might have the effect of reducing psychic pain, reducing the negativity of internal states. That is a very concrete hope. It's precise. It's anatomical. Optogenetics has given us all the firm foundation we need to go after that question. So I think there is hope. If you look at the individual causes, the individual symptoms relating to suicide.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“Individual causes then if someone is anhedonic, if there is no joy in life, that very likely is addressable by optogenetics. We know how to turn that dial very robustly in animals. Motivation to overcome challenges that Have some hope of understanding. Psychic pain, internal, negative states. We have actually a handle on that as well. There's a structure in the brain called the Habenula and some links structures around it that seems to generate this negative internal state. It's active when a state of acute disappointment, acute outcomes that go wrong not as expected.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“And yet, we're very bad at understanding it, and we're relatively poor at predicting it, and our tools are not very powerful. We can put people in a locked unit, we can give them care, therapy for a while at some point. We release them, and there's only so much we can do. It's one of the most frustrating things of the suffering that is linked to suicidality.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“What do we do? Well, there's a whole range of options was it a suicidal gesture in the sense of not intending death or was it was the intent death and if it was the intent was death what were the reasons or the reasons transient? Are they gone now? What's the probability that it'll be repeated? So we do all these things to decide what sort of treatment should be carried out. But nowhere is there a deep understanding of the biology of the cells and circuits and activity patterns that underlie the action to end the self. It's a very It's this frustrating thing. It's so timely. It's so common. It shows up in veterans. It shows up in kids. It shows up in people at every stage of life.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“Has this concept of this is myself? The situation is not tolerable, therefore I will end the self. To our knowledge this is not something that can be studied in other animals. So it remains this. Very poorly understood action. And in predicting it, so what do we do as psychiatrists? We have this challenge. People come to the emergency room, they say they're suicidal, or their friends say they're suicidal, or they've taken some action that didn't lead to death.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“So that's a great question, actually. And there are other related questions. Some people may have the thought of suicide. Because there seems no point, there's no joy in life. That's one reason that some people can put forward. Sometimes there's not just the absence of joy. There's an active pain, an active psychic pain in some people. And that the inescapability of that. Enough to drive the thoughts of suicide. And then there are interpersonal and cultural reasons as well that can show up. But the act this act of ending of the self is in all these cases, there's no real way to study this in animals, no other animal as far as we know that we can study.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“I think the action of suicide is not well understood. It doesn't always, although often is correlated with depression, there are cases of suicide where there is not clear depression, that that's in the minority.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“You don't want to be out of control of those emotions. You want to identify them. You want to know where they come from, and you want to head them off as a civilized human being living on this earth, trying to get along with other people. You want to understand those moments.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“I've definitely those skills that have come from therapy, I found them useful. If I notice that we've all been through experiences where we wonder, oh, I got really mad in that interaction. Why did I get that mad? Yeah, sure. Maybe I could have been irritated, but man, why did I... And then thinking about it and realizing, okay, back up here, think about the broader context. Think about how that relates to prior events in my life. Okay, yeah. So this is a thing for me something of this class happens. Then it triggers me. So going forward, I'm going to be aware of that. And I've definitely used that because it's...”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“This is a really interesting question. I think everybody knows, and I can say this, that psychiatrists can be a little unusual. We think about ourselves, right? We think about our brains. May be one reason why we become psychiatrists is we think, oh, that's interesting going on in there. What's that about? So a little introspective, a little introverted maybe. And that's what can make us good when we're good. But also that. May select for people who have some unusual aspects, but you don't have to have all of them. There's a lot that can go wrong in the psychiatric realm. I think having Some of it, but not all of it, is enough. You get to see how low things can get. You can get a... Get empathy from that, even if the symptoms are not the same.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“I am fortunate that that has not come to my mind, and I have not seen it even in the distance. And in some ways I've wondered if that's made me, am I less effective psychiatrist because of that? I've been. I felt everything stripped away. I've been at the lowest of the low, and yet.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“Well, that's pretty hard. That was probably the lowest moment. And you learn a lot about yourself in those moments. What's left? And then what are the... The roots out from there, and that's that can be powerful to see in yourself”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“I had moments I was effectively a single dad for a while, a number of years, and these came at probably the hardest also professional lifetimes for me too, the absolute hardest days of late medical school, internship, taking call, you know, getting up at 3 a.m., you know, surgery. Medicine rounds unforgiving environments, and then all the while personal life, you know, stripped down to the bear. And these were low moments. And then I was hit particularly hard by. Experiences on the clinical ward connecting to deeply with patients like a child with a brain tumor and feeling it too strongly. And those things When you get down to those lowest of the low moments, when everything is stripped away and there's only this raw.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“Well, this is one of the terrifying things about writing the book was I do open up a little bit about my own personal life, my own personal challenges. And that was a considered decision because I could have done the patient work and the science work and the history of the human family work and tied it all together. But it wasn't. In an early draft, it was like that, but it wasn't real yet. Wasn't something that everybody could connect with. And I said, then I realized look, if I'm going to do this, I've got to open up myself and then people can connect with me and see what I'm really saying. And so I did. And that was not something that I'd gone in planning to do. In retrospect, I learned a lot about myself. It was actually really, I think, a good thing that I did, but it was scary.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“A lot is brought up there that you're right. There has to be some emotion in the therapist to care enough to keep going, to keep probing, to open up as he's doing so, right? He revealed a lot about himself, his own vulnerabilities, but that gave him authenticity. He had to open himself up so that the kid would see the authenticity and open himself up in return. So, how do you do that as a psychiatrist, as a therapist? You have to be careful. You don't want to do too much, but opening up a little bit does help. It does create a chance. You're offering up something and that helps the patient come back in return. It gives you that believability and authenticity.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“Frustration in you, or even in extreme cases, anger. The best thing for the therapist to do in that case is to recognize it and to realize that's probably being stirred by other people in the patient's life, and that could be the source of a lot of problems. And so instead of trying to wall it off and say, oh, I shouldn't be feeling that, I better be a better therapist instead and recognize it and use it. Help the patient that way. And so you've got to be a human being. You've got to be a person who feels. You've got to be open.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“So there's a balance. And actually, you do need some of it because let's say this person is having. Challenges, interpersonal challenges in their life. Best way to notice what those are. And to identify them and to work with them, If you can elicit some of those problems in the office, in the therapeutic interaction. And this is really powerful. As long as you're alert to it, aware of it, and you don't let it go out of hand, this transference we call it, is when You transfer Between the current therapeutic relationship and external relationships of the patient may have had with others. And so, if the therapist starts to feel An inner feeling like anger, let's say. So let's say you have a patient who is stirring.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“I think you've hit on the key thing there, which is the depth of the connection. There's too powerful a connection. That can impair therapy because it could impair open communication. If someone, if a patient has sees the relationship in a particular way, like in a friendly way, or like a parental child type way. Can cause problems because then what they choose to share, what they choose to bring up is selected to be appropriate for that view of the relationship. And so I and many other talk therapists actually prefer not to let things get, not let the connection get that deep. You want to have trust. You want to have a therapeutic alliance we sometimes call it. But it's got to be enough of a blank slate that the patient Not consciously or unconsciously constrained in what they choose to share. Great movie, great actors”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“Comparing cognitive behavioral therapy with interpersonal therapy, for example. And they both can work. And actually, in some studies, they look comparable. So there's, to your point, conversation and insights that come from conversation, if done well, if done artfully, can be as powerful.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“There are forms of talk therapy that are essentially conversational or they much more approach pure conversation. There's a befriending therapy. There's interpersonal therapy. These are approaches that are purely talk therapy, but they're not as structured as cognitive behavioral therapy. Cognitive behavioral therapy, they're manuals, there are guidelines. You can almost go through it in a very cookbooky way. There's homework that you get done. In its fullest form, it's very different from these more conversational strategies. But what's interesting is sometimes people compare them, and so you'll see almost like randomized controlled studies.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“In terms of actual treatment of actual therapeutic effects, data not as supportive as for cognitive behavioral therapy. But it's still interesting for insight. A lot of people still do it to gain insight into themselves. And in general, it's a good sort of conversation starter. Those methods, you know, they're good for getting things out. We don't focus on dreams typically these days in psychiatry, but they're great conversation starters. They're great ways to get things out if people have. And so we like to use those methods just to get the ball rolling sometimes, get people to open up a little bit. But the actual treatment tends not to involve these psychoanalytic approaches where you are really probing the unconscious mind and its manifestation through dreams, for example, as the goal. That's not the goal. Modern talk therapy, we're really...”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“Their neighbors' psychoanalysis is relatively, it's not nearly done as much as the talk therapy, like the cognitive behavioral therapy I mentioned. The psychoanalysis is a little more niche now, and partly because it's not data isn't”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“outweigh these negative forces that are present out there. And that makes a lot of sense. And all animals that have been studied in one form or another show this. Even the worm that I mentioned earlier, sea elegans with three hundred and two neurons, it can effectively give up in challenging situations. We've done this with zebrafish, tiny little transparent fish. You can give them a challenging situation and they will give up. But then if you stimulate a couple very specific brain regions in particular ways, you can motivate them to overcome the challenge. And if you inhibit those regions, they give up much more easily than they would otherwise. You can do this in mice. You can do this in rats. This is an ancestral conserved pattern to detect Things are pretty bad out there. And to conserve energy, to hunker down, to wait out the storm.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“But then it raises a question why are we built this way? It seems like it doesn't make sense, right? And here's where some of this thinking about where we came from. As the human family is kind of interesting, it doesn't make sense that somewhere on that spectrum It's good to detect that there's an array of adverse forces out there in the world right now at this moment and to withdraw. Hunker down to not fight, not strive, not try to meet the challenge, and”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“Very structured, very organized. Do you work hard? It requires insight and motivation, and you have to be motivated. But if you are, then you can identify these triggers that send you down particular pathways and work to intercept them. And that is amazingly very effective in mild to moderate cases.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“Exercise is extremely important in mood maintenance. Regulation of sleep and getting sufficient and regular enough sleep is very important. And talk therapy can be helpful in those mild or moderate cases. Just looking at cognitions, looking at patterns of thought that people may have fallen into, where they catastrophize, where they spiral from small things into big things. Little bit of talk therapy ten twelve sessions can help people identify those patterns they may have in themselves that are taking occasional negative thoughts which everybody has and magnifying those into more persistent negative states. Once you, if you work at this, it's kind of like homework. This is what we call cognitive behavioral therapy.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“Of the incredibly frustrating things about depression is the very nature of it. Makes it hard for the people who suffer to. Treatment because they're hopeless, so they don't think treatment will help. They have low energy, so they're not motivated to participate in treatment in many cases. Sometimes they're actively suicidal. That certainly doesn't help. They have all these things that Seem to prevent treatment from being effective. So the loved ones, that's where the loved ones are so important is helping them overcome these barriers to treatment, the motivation, the safety, and the insight. That's critical, and particularly for the severe cases. For the mild cases where people still have some insight and motivation and energy to get something done. Are many things you can do?”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“It's a big part of what we do. Every good psychiatrist should be a pretty adept in these verbal communications and talk therapy as part of what they do. I give medications, I deliver brain stimulation treatments, but a big, big part of everything I do with every patient is talk therapy because it works so well together with these other modalities, even alone, it can help people with moderate or mild depression by itself. People with severe depression, people with other psychiatric illnesses that are severe, you don't want to do talk therapy alone. It's not going to do it, but it still is crucial together with the others. And it's critical because It's part of how you reshape cognitions, complex activity patterns, and you won't get to that with a medication or a brain stimulation treatment.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“The theory of everything, and we don't even need the unifying principle to help people with insights that come from optogenetics.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“Yeah. Well, that I have some thoughts on too. But to this specific question, I don't think we need a theory of everything. I think there will be unifying principles we can get to. But even shy of that, if we can treat symptoms, and that's a big step. And as you say, different unhappy families are different. Different unhappy people are different. If we have somebody who comes to the clinic and I see someone with a profound Anhedonia as one of their main symptoms, inability to enjoy things, and if I know based on optogenetics work and animal work, that a particular medication can treat anhedonia even if it doesn't fix major depression in everybody. If I treat that one symptom in that one person, that's a good thing, and so we don't need...”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“Seemed totally unrelated can be completely understood because there's an altered pump action of the heart. That's what we are hoping for in psychiatry and in the study of depression or any disease. These different symptoms, the inability to enjoy things, the hopelessness, What's the unifying principle?”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“We can turn up or down social interaction. All these individual features of depression, individual symptoms we now can point to exact projections and cells that are causal in mediating these. But we don't know is why all these different symptoms show up together in major depression, in the human disease syndrome. And that's the mystery. In other fields of medicine, you know, someone with congestive heart failure who comes into the clinic, they have very different symptoms. They have shortness of breath, and they have swollen feet. Couldn't be two more different across the body sets of symptoms. Neither one obviously related to the heart, but they're both happening because the heart is not working as a pump. And now, thankfully, in cardiology, Understand these disparate symptoms”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“So I think the answer is there are many things involved, and all these different symptoms that I've mentioned. Those we can study and those we can fix, the individual symptoms, and we can do this in animals, to be clear. So in a mouse, for example, we can instantaneously and precisely turn up or down the motivation of an animal to overcome a challenge, we can turn up or down its ability to be motivated by or we think experience reward from situations or actions. Can increase its apparent energy level, its drive to meet challenges.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“Distinguish them from other possible causes. And then what do we do? Well, we have a range of treatments. We have medications that can help people, do help people, but not everybody. And if they don't work, then we can go to brain stimulation methods. We can do things even like electroconvulsive therapy, which is a very effective, but it's sort of the final thing we go to in the end. And so we have treatments, they work for some people, they don't do everything we'd like. But here's the problem is at a very deep level we don't understand really what's going on in the brain. We don't have a physical interpretation of the problem. Of all these symptoms, but we can't yet point to a set of cells or a set of circuits or an activity pattern that is causing major depression this disease state per se in human beings.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“And although you can have depression without anything terrible going on in your life, the symptoms can be made worse by stressors, by trauma. At a very deep level, there's nothing we can measure in a person objectively, so we don't have, there's not a known chemical, not a known structure that's different, not a known brain activity pattern that we can pick up with EEG. A lot of people are exploring this, but right now we have no objective measures. All we do is talk to people and we elicit these symptoms. We explore them.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“Discounting of the value of their own action, anything they can imagine themselves doing seems worthless or they are unable to enjoy things. We call this Anhedonia. There's no reward, no pleasure, not in food, social interaction, movies, books, anything that they would enjoy, positivity gone. They can have a profound negative internal state, psychic pain. And these things can seem, and in the severe cases, are inescapable. So, what is going on? Why is this state part of human existence? It's got a strong biological, genetic link, we know that. It's been linked to certain genes, certain regions of the chromosome, and twin studies. There's a clear genetic link. Explain everything, but it's a big part of it, and genetics are a strong contributor.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“This is my clinical specialty. I see patients in my outpatient clinical work with treatment-resistant depression, so very hard to treat, severe illness where medications haven't been working. I also see patients with autism spectrum disorders. These are my two clinical focal areas. But then I do emergency room work as well. The depression Why do I focus on that? It's so One feels tantalizingly close to helping these people who are suffering so deeply. And that's why I focused on it is these are people who there may not even be anything situational that's difficult or challenging in their life. You can have people who seem to have everything that you would want, every objective measure of the life is fine, and yet they can be... Just hit with this. Unstoppable Hopelessness, an inability to see into the future.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“Unleash this religiosity. But you see that in other realms of psychiatry, too, OCD can manifest as religiosity also. You can take people who never really had a... Religion never played a powerful role in their life. But then when their obsessive compulsive symptoms become severe, they can manifest in this.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“And nobody in his family either. So no family history, no personal history of any psychiatric illness. And he had never been religious particularly before either. Certainly no passionate type of religion. But he, not through any psychedelic or drug, he had a stressful experience, actually a post-9-11 change in how he was thinking, and he was pushed into a mania, a manic state, revealing that he had bipolar, never before known in this case, in this person. And his mania, his elevated state and bipolar included this profound religiosity, which he had never had before. And he was preaching in a... Elevated vigorous way to his family. And so this state can be created in people even late in life who had no predisposition for it and even without a neurochemical. So the causality of that is very interesting to explore. How did the manic state?”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“And so, and these things can happen People who had no predisposition, people who are as agnostic or atheistic as you'd like, they can have these, they can feel connected to God in these states. To be clear, I'm not advocating these. We don't know what's safe in human beings, but we definitely got. Not yet, but we definitely can do these experiments in mice, and that was already very productive in understanding dissociation. So we can already imagine making headway on these methods. And then I had a, and this does map on to the non-psychedelic human experience. I had a patient who's actually described in the book projections. This was the patient that's in the mania chapter, the bipolar chapter. Here was a guy who had never had a psychiatric illness or symptom in his life. He was a retirement age gentleman.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“Players in all this just by recording the activity. But then what we found is that optogenetics providing a causal pattern of activity guided by what you see can let you test hypotheses. And we saw this rhythm with ketamine and PCP for dissociation. And then we said, okay, let's test what's causal. We came in and provided that rhythm. We tried a few different things, but only one of the causal tests we tried actually caused the behavioral dissociation. And so that's how we home in on what actually matters.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“Here's where optogenetics is so useful because anytime you give an agent like an agent like ketamine or PCP, which we used for our dissociation experiments that I was mentioning, or you have a psychedelic LSD or DMT for this altered perceptual state, if you give either of those, these change everything across the brain. So just the fact that you maybe give them to a mouse, let's say, or eventually to a human. You won't know yet which sells to home in on as the causal.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“You mentioned psychedelics, you know, DMT and five MEO, DMT. These create this religious experience, this connection. People describe them as a strong connection to God. In theory, these are accessible with modern methods. Now that we have these rich recording methods, we can explore what are that precise millisecond resolution, cellular resolution, brainwide manifestations of these altered states.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source
“Self to our body, and how can that become separated? These are actually, believe it or not, now accessible and rigorously and quantitatively so. We did an experiment with optogenetics where we provided this abnormal rhythm. This particular part of the mouse brain, and we saw this separation of Detection of a stimulus and caring about it.”
2022-04-07 · Lex Fridman Podcast · #274 – Karl Deisseroth: Depression, Schizophrenia, and Psychiatry · IDENTIFIED FROM THE TRANSCRIPT · source