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Speaker A: 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 Doctor Karen Parker. Doctor Karen Parker directs the Social Neurosciences resea... |
Speaker B: Thank you. It's great to be here. |
Speaker A: This is going to be perhaps one of the longer conversations that we've been able to have over the years, in part because whenever I see you on campus, we're headed in our respective directions. But I'm very excited because the topic of autism is one that is on a lot of people's minds. And I think the first q... |
Speaker B: Well, I think it's a multifactorial answer, so we're getting better at detecting autism. In the past, we were diagnosing kids at nine or ten years of age. Clinicians are able to reliably diagnose kids at two to three years of age. Right. So there's more people. There are, pediatricians have autism screeners ... |
Speaker A: One in 36. Wow. I feel like it was just yesterday when it was one in 80. But is one in 36 the average across boys and girls? Does it skew differently if you look at just male births versus female births? |
Speaker B: Yeah, that's a great question. So autism is male biased and prevalence. So you have, and again, the studies vary. I mean, it's worth noting that autism is a highly clinically heterogeneous disorder, which means that if you've met one kid with autism, you've met one kid with autism. Right. So we have to bear ... |
Speaker A: So if physicians are able to detect autism early, say, in a two year old or a three year old, to imagine that they're working off of tests that don't rely heavily on language, because even though you can get some verbose two and three year olds, most two and three year olds don't have a very extensive vocabu... |
Speaker B: So autism is a behavioral diagnosis, unlike other areas of medicine where you might be able to take a blood test or there's other sort of tools, it's all a behavioral diagnosis by an expert. So usually a psychiatrist or a psychologist, they look for two core features. So this is based on the DSM five. And th... |
Speaker A: We're going to talk a lot today about interventions, but how early are some of the behavioral interventions, and I should just say any interventions introduced nowadays, if someone brings their child to the pediatrician and they take one of these tests and that child is deemed as having autism, will the one ... |
Speaker B: Well, so usually you need to have the diagnosis of autism, and then there are behavioral interventions or a variety of different ones that are used. There are some studies where, because autism is highly heritable, you can have one child with autism, and then if you have subsequent children, you're at an inc... |
Speaker A: I've heard before that parents in which one or typically both parents are, say, of the engineering, mathy physics, quote unquote hard science type are more likely to have autistic children. Is that true? I mean, did that bear out in the data? If you look at profession or I or undergraduate major, does any of... |
Speaker B: Yeah. Well, what I can say is that there's been some studies. So what we know is that autistic traits are continuously distributed across the general population. And there was a study and there's a couple different instruments that are used to be able to measure these autistic traits. So there's something ca... |
Speaker A: Okay, so that leads me to wonder whether or not this whole business of a spectrum is actually multiple spectrims. Is it spectrums or spectri? Someone will put it in the comments on YouTube. We know that for sure. Please let me know. I would like to know what is the plural of spectrum spectrums? Because when ... |
Speaker B: Yeah, I mean, I think this is where understanding the biological basis of behavior would then allow us to be able to say, here's these different dimensions, but not understanding the biology you're left with. Okay, are we lumpers or splitters? How do we think about this? Because autism is highly heritable. S... |
Speaker A: Has there been any specific neural network that we can point to and say, ah, that's the neural network that seems to be different in people who are on the autism spectrum? I saw a study published recently that seemed to point to the idea that the genes that are altered in autism at least include a large numb... |
Speaker B: I think that's a great question. Right. And there may be people talk about autism, right? And so when you think about where the major player is, you know, we're at the infancy of thinking about this, right? And so maybe for some people it's more of a brain based disorder. Maybe for some people it's, you know... |
Speaker A: Yeah, it's such a key point. And for those that have not heard of preclinical models, preclinical models are non human models. So it could be mouse, could be non human primate, could be flies or worms, for that matter. But we're going to talk a lot about non human primate preclinical models and the work that... |
Speaker B: The other primate. |
Speaker A: The other primate, right, exactly. Remind people that we're primates, old world primates. So thank you for doing that. So you've been talking about the genetic influences on autism, and of course, genes in the environment interact, right? It's never nature or nurture, it's always an interaction. And that isn... |
Speaker B: Right. So, I mean, there are, again, in lots of different epidemiological studies, so advanced parental age, prematurity, severe prematurity is a risk factor for autism, maternal illness during pregnancy. So there's a bunch of different things that have been associated with an increased. |
Speaker A: Risk for autism in terms of environmental influences and how they can intersect with biology. One of the things that I was really struck by in the early two thousands that, at least by my read of the literature, hasn't really gone anywhere, was this idea that was proposed by Pashko Rakesh, who used to run th... |
Speaker B: Yeah. I mean, it's a really spectacularly good question. I think the tricky part about it is that every single person that comes into a trial has a different genetic background. Right. And so until we can have these a priori stratified trials where you could, then, you know, as a good scientist, you would on... |
Speaker A: Got it. So you mentioned fragile x, which we know presents with autism like symptoms in some cases. And then I think of another disease like Timothy syndrome, a mutation in an l type calcium channel, which, for those of you that don't know what these l type calcium channels are, they're not just important fo... |
Speaker B: I mean, I think that that's the $64,000 question. Right. And again, in other areas of medicine. So if you think about, let's think about cancer biology, right? Like decades ago, somebody would come in with cancer and you would hit them with radiation, chemotherapy, and that was the best that we could do, rig... |
Speaker A: I'd like to take a quick break and acknowledge one of our sponsors, athletic greens. Athletic greens, now called ag one, is a vitamin mineral probiotic drink that covers all of your foundational nutritional needs. I've been taking athletic greens since 2012, so I'm delighted that they're sponsoring the podca... |
Speaker B: Okay so they're these small little peptides. They're nine amino acids long. So very tiny they only differ by two amino acids. And they're these ancient peptides that are hundreds of millions of years old. And in almost any species studied, whether it's the current version you might have vasatocin or other me... |
Speaker A: So house cats make vasopressin and oxytocin. Humans obviously make vasopressin and oxytocin and pretty much every other species that has to interact with and connect with other. |
Speaker B: Members of its species, especially mammals. Right. So oxytocin and vasopressin are pervasive. |
Speaker A: And mammalian species do the different species tend to make oxytocin and vasopressin in similar brain areas and tissues? |
Speaker B: Yes, but not completely overlapping. But I think the thing that, the beautiful mystery about these and the infuriating piece of them is that because they're so structurally similar they can have similar effects and there's four receptors that they bind to. So if you think about a hormone or a neurotransmitte... |
Speaker A: Oh, so oxytocin, vasopressin are chemically similar. |
Speaker B: Yes. |
Speaker A: Interesting. |
Speaker B: Yes. |
Speaker A: And where would you say lies their greatest output? Divergence, which is just nerdspeak for. Is there an example of something that oxytocin does that vasopressin doesn't and vice versa? |
Speaker B: Yeah. Okay. So what's really fascinating is these two neurotransmitters, or hormones, were discovered for their peripheral effects, which basically means not in their brain, but somewhere in their body. And so oxytocin's involved in uterine contractions and milk let down, and so was during lactation. So peop... |
Speaker A: Can I just briefly interrupt you, because I find this so interesting, and I know it's interesting to everyone listening as well, because. Yes, and thank you for making it clear that oxydocin has many different roles. But this role of mother love and bonding to infant has me needing to ask whether or not the ... |
Speaker B: Yeah. I mean, it's very species specific. Right. So I think that. And you need to think about, like, the evolutionary history of the species. Right. So if you think about sheep or goats, the early studies that were done, are you. The passage through the vaginal canal was what, you know, so you activated oxyt... |
Speaker A: So literally, the passage of the baby out of the vaginal canal triggers the oxytocin pathway, the release of oxytocin. |
Speaker B: Right. And lactation does too. |
Speaker A: Nature is so beautiful because if you had to pick one of to trigger the release of oxytocin, if oxytocin's role is to create bonding with offspring, that would be the event, because that's a tough one to mistake. |
Speaker B: But what I will say, because I think you will, to avoid you getting attacked on Twitter or wherever you might get. |
Speaker A: I'm going to get attacked anyway. If not for this discussion, then another one. But I'm tougher than I look. |
Speaker B: But it's really species specific. If you think about our species and a lot of primate species, we live in these extended family groups, and that's how we evolved. And so, unlike a goat or a sheep that might live in a herd where there's a lot of non relatives, we lived in a community of relatives, right. And ... |
Speaker A: Vein thrombosis. |
Speaker B: Yeah. And it was sort of like, welcome to motherhood. And I was in the ICU and had to get a filter put in an inferior vena cava filter to stop me from dying because I had scatter shot clots all over my lungs. And so I didn't really, you know, I didn't do a vaginal delivery. I had a c section, and I wasn't re... |
Speaker A: Anxiety disorder in terms of when and how oxytocin is released. You mentioned mother infant bonding, I think you said. Yes, that the infant is also releasing oxytocin. We think so. It's bi directional, we think. |
Speaker B: I think most of the work has been done in mom would be. And again, this has not been really done well in primates. So we're extrapolating this information from species that have different evolutionary histories than us. Right? So it's goats, sheeps, prairie voles, mice, rats. |
Speaker A: So what do we know about the role of oxytocin in humans? I mean, we know it's there. We presume, based on the animal models, that it's involved in mother infant bonding and presumably romantic partner bonding. At least you hear that a lot. It was unfortunately nicknamed the love hormone. And the reason it's ... |
Speaker B: But again, there's a lot of specificity. And I think if you're thinking about disorders, you would then have to study those specific subpopulations. Right. And you need, you know, a lot of this work has been done. So you have to think about how do we study it? Right. So the best way to study it would be to h... |
Speaker A: And those were data in humans. That's right. It reminds me that there was this brief moment where oxytocin wasn't just being discussed as the love hormone, it was being discussed as the trust hormone. |
Speaker B: Correct. |
Speaker A: Right. Also far too simple heuristic. But again, I think it's cool that the press picks up on these things and at least tells people about what's being discovered. And we just always have to be careful to not have it lead to the assumption that that's the only role of a given hormone. So it can reduce, appar... |
Speaker B: I hear you. I'm that way, too. |
Speaker A: Right. So how do we think about this? |
Speaker B: Okay, well, I would say the social features of autism are interesting, right? And so you might have. There was an attempt a long time ago, like 1979, there was a woman named Lorna Wing who tried to subtype the social features of autism, right? And so there could be people that are socially avoidant and reall... |
Speaker A: Sounds like junior high school. |
Speaker B: Yeah, exactly. And that's often why I. Some autistic kids do better with adults. Right. Because adults know how to sort of channel discussions with somebody who might be a little socially awkward. Right. But there's different phenotypes. I mean, people having a disinterest in social interactions could be tha... |
Speaker A: Something that, fortunately is changing. |
Speaker B: Yes. |
Speaker A: Thanks to a mandate by the. By the NIH. Correct. I had to just kind of smile, raise my eyebrows a little bit at the idea that the assumption that oxytocin administered to males. Yes. One can see why it wouldn't cause milk letdown or uterine contractions. But, of course, there could be other peripheral effect... |
Speaker B: So, intranasal, one dose. Correct. And for reasons that I don't understand, it's 24 international units. And I think maybe somebody did the first study using it, and this is how science happens. Right. And it worked. And so then everyone uses that protocol. And so then there's been a lot of studies looking a... |
Speaker A: And is oxytocin available over the counter? Does it require a prescription? I mean, you see sites that are selling it, but that doesn't mean anything these days, right? Yeah, there's gray market. There's all sorts of stuff going on. But I know people that have used oxytocin there's actually a market for. And... |
Speaker B: No. So it would need to be written like, the prescription would need to be written by a physician, and it's not on the market. Right. So there's one thing we should say is there's only two drugs that are approved by the FDA to treat autism, and they're both antipsychotics, which they treat associated feature... |
Speaker A: Interesting and unfortunate, and hopefully that will change in the not too distant future. Do we know that children with autism, people with autism. Cause I'm gonna just sort of assume that autism is stable over the lifespan. Like, if a child is diagnosed with autism, are they going to be an adolescent and a... |
Speaker B: So I would say that in a lot of cases, autism has lifelong impact, but there are people who outgrow their diagnosis. There are people who respond well to behavioral therapy. I mean, obviously it's not the cure all for everybody. There's lots of people who go through intensive behavioral therapy and probably ... |
Speaker A: Is it known whether or not people with autism, assuming they meet the criteria for being autistic at that moment, have lower natural circulating or active levels of oxygen? Because it's one thing for a nasal spray of oxytocin to improve social functioning, it's another to know that the effect is addressing a... |
Speaker B: Yeah, it's such a great question. Okay, so we should unpack that because there's been a lot of work in this area. So the first question is, where are we measuring the oxytocin? Right. So we mentioned oxytocin has all kinds of effects in the body as well as the brain, and it's released into the blood, but it'... |
Speaker A: Humans. |
Speaker B: Humans. And that maybe those are the individuals who could, who stand to benefit the most from treatment. And so we were the first group to ask, you know, across this range of individuals who showed up, and we did in all the trials that we'll talk about today. These are done with my colleague Antonia Hardin ... |
Speaker A: One intervention, one nasal spread. |
Speaker B: This was four weeks. Sorry, I should have clarified, this is four weeks of treatment being administered oxytocin twice a day. |
Speaker A: Okay. |
Speaker B: And so we saw effectiveness there. |
Speaker A: May I? Sorry to interrupt so much, but just male and female subjects. |
Speaker B: We did. But again, because autism is male biased and prevalence, even if you make this heroic effort to over recruit, try to get more girls in. In the study, we usually try to aim for the prevalence rate because it's difficult to get girls just because there's fewer of them. |
Speaker A: Got it. Okay. But boys and girls were included. They're taking oxytocin over the period of several weeks. And if they started off with lower baseline levels of oxytocin, you observed a benefit of the oxytocin treatment in those individuals. What about the individuals who had normal to high levels? |
Speaker B: They didn't see much benefit. Right. And so that was a cue to me to think that there may be a subset of individuals that, you know, for whatever reason, they have lower oxytocin, and they may stand to benefit more from treatment. And none of the prior had looked at blood oxytocin levels. And so what we had t... |
Speaker A: Were they looking to see who started off with low levels of oxytocin pre treatment? |
Speaker B: So what was interesting about that study, and there were a lot of issues with it, was that oxytocin is something where you, if you look at it, it degrades. That's kind of what I joke about. Right? So you need to take it. When we go in, we have, like, these really intense protocols, right? So you go in and we... |
Speaker A: So a lot of technical gymnastics, and. |
Speaker B: Then we make sure we spin it in a centrifuge cold, and then we pipe head it onto dry ice. So we have very many minimal loss of the signal. And so if you don't adhere to those rigid protocols, which is very difficult to do across multiple sites, it can be very difficult to get an accurate read of oxytocin. An... |
Speaker A: Well, it will be important for that work to be done eventually. Hopefully, the field will return to it, despite whatever trends might be happening. Now, I think it's important to know, for the parents of autistic children, whether or not there were any negative effects, effects of oxytocin administration, in... |
Speaker B: Right. It's a great question. And I know that I'm a parent of three children, and I know this sense of, like, you would do anything to help your child. Right. And so I think the tricky part is that one thing I will say is that all of the studies, and there's been many of them, have shown that oxytocin is rel... |
Speaker A: Well, we are definitely going to talk about vasopressin in detail. I mean, the reason I mentioned that hypothetical scenario is just the sense of urgency and in some cases, desperation that parents feel, and time's ticking. And if oxytocin's safe, then I guess I'll put in my vote that parents should at least... |
Speaker B: Right. It's a really great point. And there might be subsets of kids. Right. There might be kids where there would be a medication that would target other pathways, but that potently releases oxytocin. Right. But there might be kids that have an oxytocin deficiency. Right. That. That circles back to your poi... |
Speaker A: Paper and put it in the show notes. |
Speaker B: But, you know, so it could be, to your point about neuroplasticity, that oxytocin may be maximally beneficial in younger ages. Right. And if these studies are these hodgepodges across ages and across sort of different social phenotypes, finding that signal is really important. Right. And maybe age is a drive... |
Speaker A: Yeah. That's also a vote, in my opinion, for early examination of kids. Parents really need to get autism screening. And perhaps, maybe the most important thing is to make autism screening as available and as inexpensive as possible for everyone because of the importance of early intervention. Even if it's p... |
Speaker B: But the clinic wait times are really long. Right. So you have to have a specialist who's capable to diagnose autism. And so you could have a clinic where you're showing troublesome features and a parent wants to get their kid into a clinic. And you could have a twelve month or 18 month wait time. Right. And ... |
Speaker A: Well, you wouldn't want false positives, but I would think that a 32nd video clip, provided it's of something useful, is going to be more valuable than nothing. Given the time sensitivity, what are some of the barriers to getting this behavioral testing to be not just more prominent but pervasive? Like, it s... |
Speaker B: Yeah. It's not scalable. Right. So these interviews with parents and the tests that you do can take hours. Right. And any given clinician, even if they're working really long hours, there just aren't that many people that have the extensive training needed to make these expert diagnoses. Right. And so I thin... |
Speaker A: Does it have to be a physician? Sorry to interrupt. Or could a well trained technician do this? |
Speaker B: Yeah. Well, I mean, I think technically it's a DSM diagnosis, right. So it's usually somebody who has a clinical degree. So it would be a clinical psychologist. It could be a behavioral pediatrician. It could be a child psychiatrist or child neurologist. But again, that requires years and years of training. ... |
Speaker A: Are there human trials exploring MDMA, methylene dioximethetamine, also referred to as ecstasy and or psilocybin, for treatment of autism. |
Speaker B: So I was aware that maps had an MDMA trial in autism. I don't know what's happened with that. |
Speaker A: Yeah, perhaps it's still ongoing. I'll check the map site. I'm in communication with them from time to time. I mean, the reason for asking it, of course, you know, but maybe in case some of the listeners don't, is that MDMA causes these massive increases in serotonin. That seems to be the major source of the... |
Speaker B: Right. I mean, I think the tricky part, especially in children, is there's going to be a reluctance to potentially give them psychedelics. Right. And so is there a way to modify the chemical compound to, you know, be something that parents might be more willing to give to their children? Right, right. |
Speaker A: And I totally agree with that, I guess, to play devil's advocate, not against you, but. Well, I'll just state it very directly and then I'll take the heat as necessary. I mean, I've done two episodes about the drugs that tens of millions, if not hundreds of millions of parents are already giving their kids f... |
Speaker B: Yes. |
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