The Causes & Treatments for Autism | Dr. Karen Parker

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. Karen Parker. Dr. Karen Parker directs the Social Neurosciences Research program at the Stanford University School of Medicine. The goal of her laboratory's research is to understand the biological basis of social functioning at every every stage of the lifespan. So this includes the bonds that form between infant and parent or parents, as well as the bonds that occur between children as they grow up, which of course form the template for social functioning when we become adults. Dr. Parker's research is heavily focused on autism and indeed on all forms of autism spectrum disorders. Today we discuss autism. We talk about the prominent theories and current understanding of the biological basis for autism, as well as what still remains mysterious and unresolved about the causes of autism. You may have heard that the incidence, or perhaps just the diagnosis of autism has dramatically increased in the last 10 to 15 years. And today we discuss why it is in fact that the incidence, not just the diagnosis, but the incidence, of autism, has so dramatically increased. And Perhaps most excitingly, Dr. Parker shares with us brand new research findings from her laboratory that point to a new understanding of what causes autism as well as a novel treatment for autism. Before we 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. I've spoken many times before on this podcast about the fact that sleep is the foundation of mental health, physical health and performance.

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Dr. Karen Parker, welcome.

Thank you. It's great to be here.

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 head 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 question that always comes up, it seems, is whether or not the frequency of autism is indeed increasing or whether or not the field of medicine is getting better at detecting what was always there over time. Do we have any clear answers to that?

Well, I think it's a multifactorial answer. So we're getting better at detecting autism. Right. So in the past, we were diagnosing kids at 9 or 10 years of age. Right. And now clinicians are able to reliably diagnose kids at 2 to 3 years of age. Right. So there's more people. There are pediatricians have autism screeners now. So when you bring in your baby and over the first couple years of life, you're filling out screeners that are looking for autism symptoms. Right. So there's just a lot more awareness around autism. But the rates have increased to now 1 in 36 US children have a diagnosis of autism, which is over two years ago it was 1 in 44.

So 1 in 36, wow. I feel like it was just yesterday when it was 1 in 80. But is 1 in 36 the average across boys and girls? Does it skew differently if you look at just male births versus female births?

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 that in mind as we have this conversation. But, you know, different studies show that about for every one girl, there's three to four boys that are impacted by autism. So there's, you know, differences in the prevalence rate. And also there's different monitoring sites. So the way in the US that these data are generated is the CDC has 11 monitoring sites across the country, and so they follow children and then that's where the prevalence rates come from, and they release new prevalence rates every few years.

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 2 and 3 year olds, most 2 and 3 year olds don't have a very extensive vocabulary. And I'm guessing that they're also relying on things like visual gaze, among other things. We've already made clear that this is not a discussion to allow people to diagnose themselves or others. But with that said, what are some of the diagnostic tools that people use? You know, is it language? Is it vision? Does it present as, you know, abnormal auditory processing? Maybe you could give us a sampling.

So autism is a behavioral diagnosis. Right. So 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. And they look for two core features. So this is based on the DSM 5, and the two core features are pervasive social interaction challenges and the presence of restricted repetitive behavior. But there are a lot of people with autism who have anxiety. There are a lot of people with sensory challenges. There are a lot of people with seizure disorders, sleep disorders. So again, each person with autism has this sort of unique collection of traits and, you know, that's how they get diagnosed.

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? So 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 year old or the two year old immediately go into behavioral interventions?

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 increased risk of having subsequent children with autism. And these are called baby sibling studies. So what you're doing is enriching the population, population of infants that you follow prospectively who are more likely to receive an autism diagnosis. And there are studies where some of those children are enrolled in behavioral studies even when they're, quote, unquote, at risk.

I've heard before that parents in which one or typically both parents are say, of the engineering, math, physics, 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 undergraduate major, does any of that correlate with the probability of having an autistic child?

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 called the Social Responsiveness Scale, and then that's a US based instrument. And there's an autism quotient that's a similar measure that was designed in England. And what we know from work with the AQ is that individuals that are in intense STEM fields like engineering, physics and math have a greater burden of autistic traits, even if they don't have an autism diagnosis.

Okay, so that leads me to wonder whether or not this whole business of a spectrum is actually multiple spectra. Spectrums. Is it spectrums or spectra? Someone will put it in the. 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, you know, because when we hear the word spectrum, we think, okay, there's a spectrum of severity. In fact, I have some experience with severe autism, not in my family, but where I went to undergraduate university, UC Santa Barbara. Down the way from that school was the Devereaux School, which was a school which has been there for a long time, that parents would send their kids if they were, quote, unquote, severely autistic. It was actually where Dustin Hoffman went to study for his role in Rain Man. And the kids who were really delightful, they used to come into town every once in a while to the coffee shop where I'd study. And they would also continue on from there to Kmart, which is why the Dustin Hoffman character would say, gotta go to Kmart. Gotta go to Kmart. He would do that. Repetition, right. That Kmart was down the road from our, you know, our college housing and the Devereaux School. Those kids were literally in a away from home facility full time. And I spoke to some of the parents at one point, and they were at that facility, meaning the parents had sent them, their children away to live there full time. Of course, they'd get visits, and they'd get visits home because they were, I suppose we could say, at the far end of some spectrum that made it, at least to the parents idea, impossible for them to be at home. Okay. Now, at the other end of the spectrum, if one is just simply thinking in terms of severity, I know people who have self identified as autistic. That's how they've referred to it. So I feel comfortable saying that they've said, I am autistic. And they seem pretty high functioning, meaning they have driver's licenses, drive cars, are in healthy relationships, and manage life, apparently. Well, they have some traits that, yes, I would agree, are a little bit different. Right. So this is where we get into neurodivergence. But I guess the point is, should we think about autism as on a spectrum or given the fact that there are these kind of collections of different traits, could there be a spectrum of severity, also a spectrum of more stereotype behaviors, another spectrum that intersects with that, that has to do with obsession with a particular topic. You could imagine that there are 50 or 60 different spectra or spectrums. I still don't know which one to say. And that when we talk about the spectrum, we're really talking about something that's in multiple dimensions and not just one line that goes from severe to mild. Does that make sense?

Yeah, I mean, I think this is where understanding the biological basis of behavior would then allow us to be able to say, you're like, here's these different dimensions. Right. But not understanding the biology, you're left with, okay, are we lumpers or splitters? Like, how do we think about this? Because autism is highly heritable. So there's about 40 to 80% of autism is, is genetic. Right. So these vary wildly. Right. But that the common thinking is that the majority, about 50% of autism is, is associated with common genetic variants. And so the way that we've always thought about this is that there is this, you know, autism is largely an inherited polygenic condition. And but what I mean by that is that you have a lot of common variants that are additive. And so if you think about this collection of common genetic variants underlie this spectrum. Right. So if you have less of a dosing of some of these common variants, you might see somebody who's a lot more, who's higher functioning, like you said. And if you end up with one of these single gene, highly penetrant disorders, you might see severe intellectual disability and sort of lower functioning on the other end of the spectrum. But I think that there is a lot that we don't know. And what you're bringing up, I think underlines sort of an issue with autism, which is common for many brain disorders, which is like, if you don't understand the underlying biological basis, it also gets very difficult to diagnose and treat. Right. And that's where we are with a lot of different, you know, psychiatric and neurodevelopmental disorders.

To date, 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. And 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 number of genes that are altered or the proteins that are the consequence of those genes are altered and exist at the synapse, at the connections between neurons. And I'm asking it that way because some years ago I was at a talk on autism at Stanford and Someone raised their hand and says, do we even know that autism is a brain issue, Right. Couldn't it be an issue of the immune system or the cardiovascular system? Which at the time seemed like, okay, gosh, of course it's. But wait, then you stop and you think, that's a really good question. How do we know it's a challenge of the brain, right?

I think that's a great question. Right. And there may be. People talk about autisms, 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, the connection with the gut and the brain, right. I think what's also really tricky, right? So one thing that you have to ask is what are the barriers to progress in understanding autism, right? And so the way I think about this is that, let's just take for a moment that this is a brain disorder. How do you study it in people? Right? So, you know, it's very difficult to get access to either cerebral spinal fluid, which is a fluid that bathes the brain, brain tissue, biopsies. It's very hard to get people, especially children that are really impacted into a brain scanner, right? Cause they can't sit still, they may have sensory issues, they don't wanna go into a scanner, right. So a lot of the tools that neuroscientists or psychiatrists have to think about looking at the brain are limited, right? And then, and then the other part is how do you model? So the other way we might think about getting access or thinking about model systems. What we need to do is think about the control animals and we need to make sure that the species that we're modeling them in has features of control humans, if you will. So we need to have complex cognitive abilities, we need to have complex social skills, we need to have an organism that has vision as its primary sensory modality, right. Potentially sleep consolidating. So we need to think about all of those. And the tricky part, I think until fairly recently was that we were doing all of this work in mouse models. And, you know, the control mice just fundamentally lack many of the characteristics that are needed to model, you know, autism with fidelity. Right? And I think that's, you know, when we look at drug development pipelines, about 50% of preclinical failures. So that would be something that's tested in an animal that work and then fails in a human clinical drug trial. 50% of those failures can be attributed to poorly selected animal models. And so I think part of where we will be getting traction is picking, you know, developing sophisticated models as a sort of point of entry into being able to understand some of these things that are really difficult to study in people.

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 you've been doing. And of course, also the work that you've been doing in humans. The other animal.

The other primate.

The other primate, Right, exactly. I love to 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't just about the epigenome. It's also just about the fact that nature impacts the genome and our genome impacts the way that we interact with the environment, et cetera. So what is the role of the environment in autism? Both the frequency and the presentation of autism.

Right. So, I mean, there are, again, 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.

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 2000s, that, at least by my read of the literature, hasn't really gone anywhere, was this idea that was proposed by Pashko Rakish, who used to run the neurobiology department at Yale, expert in brain neuroanatomy and non human primates, and in humans, embryology, really a luminary of our field. And he had a series of papers exploring how the migration of neurons during early development, you know, as you and I both know, but most people out there probably don't know because we haven't covered this in the podcast. It's not typical dinner table conversation. You know, when you. When an embryo, when a human embryo is developing, the neurons are born at one location and they migrate out some distance to their final resting place, where then they grow out their connections and connect with one another. And that process of neuronal migration is oh, so critical for the eventual wiring of the brain. And Rakish had this idea that perhaps, and I really want to emphasize perhaps, that the more frequent incidence of autism might be correlated with the increase in early prenatal ultrasound. And he had these papers published in a number of really high profile journals, including Proceedings of National Academy and Science and elsewhere, showing that in a mouse model, if you do ultrasound with each successive ultrasound, you got more migration errors. Right. So to me, it was an interesting example of the environment, frequency of ultrasound and cell migration having some sort of interaction with. But it seemed like it never went anywhere, it never got tacked to. Okay, you should keep in mind the number of ultrasounds that you're getting for your child. And of course, ultrasounds are critical for pregnant women to get because they can stave off a number of developmental issues and they're super important. But we've heard about ultrasound within the scientific literature and then occasionally we'll hear other theories about, okay, it's having two parents who are both engineers. And then we'll hear, oh, you know, it's, you know, toxicity in the food environment. We've heard, you know, hypotheses about vaccines or the adjuvants that the vaccines are contained in. You know, in that large cloud of theories, has anything really emerged from them? It's like, okay, there really seems to be at least one major risk factor, environmental risk factor. Because I feel like all those theories come up, get some popular press, bunch of papers are published, sometimes those papers are retracted, like in the case of the vaccines, and then the theory kind of dies. So is there any specific environmental influence on autism that we can say? Yes, there really seems to be something there.

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 only manipulate maybe one, two variables at. But when you're doing these large epidemiological studies, because you can't, it's very difficult to do experimental studies. Right. Especially with developing children. I think that's an incredibly difficult study to do. Right. So there's been an interest in this field of there's these neurogenetic syndromes that have high penetrance for autism, which basically means that you could have a disorder or, you know, another genetic condition. Let's say it doesn't have to be a single gene, but that a lot of those kids tend, tend to also get an autism diagnosis. And so there's been work in like. So, for instance, Fragile X is a good example where because autism is so diverse in terms of clinical presentation that let's say you have a medication that could work for a handful of kids in the trial, you may not be statistically powered to see it. Right. So, you know, the way I think about the autism world is there's so little we don't know. So think about being in a dark room and you have a flashlight and you only see where you shine the light. Right. And so if you think about a very heterogeneous, genetically heterogeneous study, it's going to be very difficult to tease out these pieces because an environmental risk factor might be a driver for one kid, but not another. Right. And so I think what we need to do is to have these genetically defined subgroups of individuals and then be able to test the gene by environment interactions or in this genetically defined group of individuals, can we test this certain medication to see if. If it's beneficial for this subgroup of children?

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 for the function of neurons in the brain. They're really important for the function of neurons and other. Other tissues, including heart tissue. Right. So kids with Timothy syndrome have cardiac issues and they have autism. So I think it's important for us to kind of explore this a bit, because in most people's minds, kids with autism have autism, and occasionally they'll have other issues, gut issues or heart issues or musculoskeletal issues. But we often think that that's the consequence of the autism, but oftentimes that they have multiple things going on, and the autism actually could be secondary or independent of the other thing that's going on. So this is what leads me back to this idea of a spectrum. Is it possible that what we call autism is actually like 50 different disorders or 50 different conditions, depending on what one wants to call them? I mean, what is autism really? I mean, is it. What does it really center around? And I think here maybe it's useful to go like, do we go to the diagnostic criteria, like, how do we decide if a child has autism if they also have a bunch of Other things that are challenging them.

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, right? But with the invention of a lot of molecular, you can remove a tumor and you can do molecular profiling and even, you know, have personalized medications made, right, to attack that tumor. And so you know what's really tricky? When you have a behavioral diagnosis that's not biologically defined, you see a lot of heterogeneity. So it's incredibly difficult, I think, to answer this question because we don't know how many kinds of autisms there are, right? Like there will be people who say if you have a disorder like Fragile X or Prader Willi syndrome or Timothy syndrome or a variety of these other conditions, there will be people, I've heard clinicians say, well, that's not really autism, right? That's a piece of Fragile X, right? But if it's a behavioral diagnosis and they meet behavioral criteria, it becomes this weird circular argument, right? So, like, until we really understand what autism is, I think that it's going to be very tricky to start, you know, sub defining different aspects of the condition.

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Well, this is probably a good time for us to think about the work that you've done in terms of, of trying to tack the biology of social communication and behavior. Those things interact, not just language, but also behavior, to autism in humans, using non human primate models. And then of course, to also discuss some of the work that you've been doing in humans. And we can't have that discussion without first having a discussion about two neuropeptides that I think most people have heard of at least one of them them. And I think there's a lot of misunderstanding about, but you're going to clarify that for us, which are oxytocin and vasopressin. So before we dive into the important work that you've been doing on vasopressin in particular, but also oxytocin and autism, what are oxytocin and vasopressin really?

Okay, so they're these small little peptide, 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 vasotocin or other misotocin, which are sort of precursor forms in other species. But they're highly evolutionarily conserved and they're involved in social behavior in pretty much any. It could be egg laying, it could be, you know, but reproduction in social behavior across the phylogenetic taxes.

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.

Members of its species, especially mammals. Right. So oxytocin and vasopressin are pervasive in mammalian species.

Do the different species tend to make oxytocin and vasopressin in similar brain areas and tissues?

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 neurotransmitter, so oxytocin, vasopressin, if you think about them like a key and a receptor like a lock, and you have to put them together to open a door, open behavior, they can bind to these four receptors. So it can be very difficult to disentangle which one is acting and at which receptor and where in the brain.

Oh, so oxytocin and vasopressin are chemically similar. Yes, Interesting.

Yes.

And where would you say lies their greatest output divergence, which is just nerd speak for, is there an example of something that oxytocin does that vasopressin doesn't and vice versa?

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 letdown, and so was during lactation. So people sort of always thought of it as the female hormone. And then vasopressin has, at least in the peripheral system, has been involved in urine regulate, like, urinary output regulation, blood pressure. And so. So we only knew about their physiological roles as sort of classic hormones for decades. And what was interesting is these, like, naming conventions are fascinating in medicine. Right. So you could name a virus after where it was first found. Right. Or it could be named after somebody who discovered the disease. Like Alzheimer's, for instance, is a good example. And what was interesting, oxytocin was only named once. Vasopressin was named twice. So it's either called arginine, vasopressin, or antitrust diuretic hormone. And so it had two different names. And so as you can imagine, sometimes genes are named twice. And so somebody in cancer is studying one gene and somebody in autism is studying another. And they're not even communicating because they don't even realize that they've. At least historically, now we have all kinds of gene annotation sites, so it's less likely to happen now. But what was fascinating is they were. These hormones were named. Oxytocin is Greek for quick birth. So for decades, people only appreciated their physiological roles. But there are neuroanatomists saying, hey, so these are. Are both made. They're made in a lot of different places, but the action sort of happens in the hypothalamus where they're made. And there were anatomists that said, wait, these sort of project back into the brain what are these doing in the brain? And one of my favorite historical stories was I had a mentor, a colleague who I didn't train with, but he was a real source of wisdom to me for many years. And his name is Cort Peterson. And he told me this wonderful story about this Duke zoologist named Peter Kloepfer. Peter was studying ungulates, so sheep and goats. And he wrote a story, a paper in 1971 called Mother Love. What turns it On? And, you know, one thing about science is I love going back and seeing where do the pearls of wisdom come from. And so he wrote this and said, you know, oxytocin is orchestrating all these events of motherhood. And there are sheep and goats in particular that have offspring that are precocious, meaning they're basically born ready, you know, within an hour. They can run with the herd, unlike our species, which is altricial, meaning we have very helpless infants. And mom needs to bond really quickly with that baby if it's going to be running around. And you only, you know, from an evolutionary perspective, you want to be investing in the baby that's yours, not somebody else's. Right. And he hypothesized that it was oxytocin that was being co released into the brain and during milk let down. That was what turned mother love on. And that was really the beginning of this whole field of thinking. And so that opened up thinking about oxytocin in rodent maternal care and a variety of other instances.

Can I just briefly interrupt you? Cause I find this so interesting, and I know it's interesting to everyone listening as well, because, you know. Yes, and thank you for making it clear that oxydocin has many different roles. But this role, role of mother love and bonding to infant has me needing to ask whether or not the idea was that oxytocin is released in the mother when she interacts with her own baby. And that leads me to the question, is oxytocin also released in the baby in reaction to the mother, and how long is that effect lasting? Because in order to have a pervasive bond with that baby and not just some other baby, and of course, we still have visual cues and we know our baby versus another baby in most instances. There are rare exceptions, or perhaps not so rare exceptions. But leaving those aside, the mechanism that would allow for mother infant bonding and infant mother bonding by way of oxytocin, presumably is something that is literally changing their brains. Saying, you are the center of my life. Right. And the baby, of course, is saying, well, you are my life because you are the source of life.

Right.

Certainly for the early part. Early part of life. And nowadays it seems that that can extend well into the teens and twenties for some people. But how is oxytocin working? Is it working over the course of minutes, hours? Is there some specificity of this baby and this mom that links them in some more pervasive way? I mean, how is oxytocin doing this magic of bonding?

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 had activated oxytocin receptors that way. But if you gave an oxytocin antagonist, meaning you would get give into the brain, something that blocked the oxytocin receptors. So if the oxytocin is being released into the brain, but you have a pharmacological agent blocking its ability to bind to its receptors. These sheep and goats wouldn't bond to their baby, for instance.

So literally, the passage of the baby out of the vaginal canal triggers the oxytocin pathway, the release of oxytocin.

Right. As in L lactation does too.

Nature is so beautiful because if you had to pick one of them event 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. Right, right.

But. But what I will say, because I think you will, you know, to avoid you getting attacked on Twitter or wherever you might get.

I'm getting attacked anyway. If not, if not for this discussion, then another one.

But I'm tougher than I look, so. But it's really species specific. Right. So 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 so we, and we do all kinds of care of extended relatives. And so you wouldn't necessarily expect in a primate species where you have this long rearing history, where help from the family and biparental care, where sort of everybody sort of of like it takes a village to raise the baby we readily adopt in our. In primate societies. Right. And so, you know, like I had a C section, I Mean, I'll tell you something personal. I had a C section and had, I had a lot of postpartum complications. And so lactation didn't work out that well for me. One of my friends would say I had massive dvts and pulmonary emboli. And so I almost died after my son was born the first time. And so I didn't have a vaginal delivery. I couldn't.

Vein thrombosis.

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 scattershot clots all over my lungs. And so I didn't really, you know, I didn't, I didn't do a vaginal delivery. I had a C section and I wasn't really able to lactate. And man, I love that baby. Right. So, you know, I can give. You know, what I will say is it's really different in primates and we don't really understand how bonding occurs. But what I will say is that bonding between a mother. You really need to think about the evolutionary selective pressures. So I was an evolutionary biologist before I found neuroscience. Right. And so I really. Everything I do I think about from an evolutionary perspective, but it is. Many people go into the oxytocin vasopressin field because they have a lot of questions about social interactions. Right. Like I think if you think about us is being social is actually one of the, one of the core characteristics of our species. Right. So social interactions are rewarding from infancy. They keep us alive, as you mentioned. Right. And so I think it's not an accident that the way we think about disorder in our species is many disorders are disorders because of lack of social connectedness. Right. So it could be something like autism, where, where there's these pervasive social interaction impairments. It could be something like drug abuse where a risk factor for drug abuse is feeling socially disconnected and alone. Right. Social isolation or loss of a loved one is a very strong predictor of the onset of a stress related depressive.

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 bidirectional, we think.

I think most of the work has been done in mom would be. And again, this has not been really done well in primates. Right. So we're extrapolating this information from species that have different evolutionary histories than us. Right. So it's goats, sheep, sheeps, prairie voles, mice, rats.

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 unfortunate it was, is, is that while that might cue attention to oxytocin, and I'm a big fan of people paying attention to biological phenomena, it discards the other and many roles of oxytocin. But what can we say about oxytocin in humans, if anything, do we know that it does? So we're assuming based on the animal models that it does something. I mean, this is very different than dopamine, where there's tons of animal model data, but we know. But there brain imaging, where we know where dopamine is expressed and do we even know where oxytocin receptors are expressed in the human brain? Presumably that information is out there recently.

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 have radio tracers where you could then, which we do have for dopamine and other compounds, where you would then go and see where after somebody's performed a task, do we see activation or uptake? There are some imaging studies. They're usually done giving intranasal oxytocin. And then you basically ask questions about, okay, we give you oxytocin intranasally, which presumably enters the brain. We could talk about reasons why we think that. And then we have you perform on some task. Right. And so, you know, there's evidence if you give oxytocin, it diminishes the amygdala's response, response to fearful stimuli. Right. So that it might have this sort of pro social effect. And it was actually data like that that caused people to start thinking initially about oxytocin.

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.

Correct.

Right. Also far too simple a heuristic. But. 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, apparently it can reduce the output of the amygdala in some way, this brain area associated with threat detection. And so you could imagine how they that would bias the person toward being more pro social. Have there been studies exploring the role of oxytocin in making autistic children more pro social? And behind that question, I suppose, is the assumption you can verify or not that autistic children are less pro social than other children? Is that true? Or is it that autistic kids are just maybe more pro social with the one friend they really, really like? I happen to know some kids with autism, or however you want to phrase it, and they have close friends and they seem to really like those specific friends a lot. Like they seem very happy when they show up at the door and like all, all the hallmarks of healthy social mind. But it is true that they are uncomfortable in groups and where there's a lot of noise, a busy birthday party is overwhelming for them. But see them playing with one or two friends and like you could see all that and assume, okay, it's just kind of an introverted kid.

Actually, it kind of reminds me of.

Me, you know, I mean, I don't have a problem with crowds, but I much prefer to be with a small group of friends or one close friend.

Yeah, so I hear you. I'm that way too.

Right. So, you know, how do we think about this?

Okay, Well, I would say the social features of autism are interesting. Right. And so you might have. There were. 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 really just don't wanna have social interactions. There could be kids that are active but odd, which means that they have an interest in being social, but maybe they don't read social cues. Right. And they interact in ways that other kids don't understand or make. Could cause bullying. Right.

Sounds like junior high school.

Yeah, exactly. And that's often why 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 that they're highly socially anxious. Right. That making eye contact makes them anxious. Again, that's another caveat. There have been some studies administering oxytocin to individuals with autism. And again, these are these single dose studies. So the first studies that were done were looking at single dose oxytocin in males because some of the. And we can talk a little bit about why oxytocin versus vasopressin, which vasopressin actually would have been my choice based on the animal literature. And we can talk about that. But vasoxytocin was given to males partly because it wouldn't. The idea would be that the off target effects in the peripheral nervous system, that is milk let down uterine contractions, are not going to happen in males. Right. And so it was deemed that they might be safer subjects. Males are often also the go to for research studies, as you may have talked about on your podcast before too.

Something that fortunately is changing thanks to Amanda by the nih.

Correct.

I had to just kind of smile, slash, 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 let down or uterine contractions. But of course there could be other peripheral effects of oxytocin in males, but they had to pick one, so they went with males. Okay. And there is this higher incidence of autism in males, so it's not a terrible place to start. You just would hope that they would also do the experiment on fetal females. So they're doing this by nasal spray.

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 you know, 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 at, you know, there's one reading the mind and the eyes. So can you look at pictures of somebody's eyes and then ask what is the emotion that they're feeling right.

After receiving this information?

Oxytocin or placebo, where's your eye gaze going in a picture? Right. So one of the theories is that people with autism may, at least a subset of them, lack social motivation. So maybe they're not looking in the places like eyes where you receive a lot of social cues that are relevant to social communication. And so some of these early studies showed that a single dose of oxytocin in people that were had high functioning autism. So they were verbal like you said they could come in for studies and that it looked like it had some potential effectiveness. And so there bec a really strong interest in the field to think about oxytocin potentially as a therapy for autism.

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 by the way, folks, I'm not suggesting this, but someone the other day told me that they've been regularly taking oxytocin ketamine nasal inhalations as part of their work with their licensed therapist on PTSD type stuff relating to, let's just call it relational trauma. So that's happening. But let's just think about oxytocin alone for the moment. Are parents of autistic kids able to buy oxytocin nasal spray? No.

So, 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 features like irritability and they have off target effects like weight gain. And so we don't have any medications that are currently approved in the US or anywhere else for that matter to treat the core features of autism.

Interesting and unfortunate and hopefully that will change in the not too distant future. Do we know that children with autism, people with autism? Because I'm going to 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 adult with autism?