Simon Baron-Cohen: Autism and the male brain

so thank you very much and it's a pleasure for me to be here Thank You Sven and Kristian for this invitation I'm going to talk a little bit about this controversial hypothesis which tries to link autism with with our our sex or gender before I start I'm going to acknowledge my collaborators the work you're going to hear about involves teams and we have many names up here at the top we've got psychologists and also people working with imaging MRI and at the bottom scientists working at the level of biology particularly hormones spend mentioned testosterone and you'll hear a bit later in the lecture about our research in that area and also genetics so by way of background and this is just to remind you about the diagnosis of autism spectrum conditions that the diagnosis rests on the presence of two features the first are social and communication difficulties and the second these rather unusual narrow interests sometimes called obsessions although I think the term is a little pejorative but the person becomes very focused on a single topic and goes into it very deeply and also that the the individual likes routines and becomes very distressed or stressed by unpredictability instead wanting strong routines in their life and when these two features interfere with the person's functioning they might need a diagnosis on the autistic spectrum and at the moment we recognize two subgroups so classical autism and Asperger's syndrome I say at the moment because some of you may know that the plans for DSM either next year or the year after Sven and I were just discussing this over coffee is to add delete this second subgroup so that there's a single a single category called autism spectrum conditions but currently we recognize at least these two major subgroups and they differ in terms of language and in terms of IQ so in Asperger's syndrome when you take developmental history the child spoke on time language was developing at the typical rate and in Asperger's syndrome the individual has at least average IQ intelligence or even above whereas in classic autism invariably the child was late to talk when you take a history they didn't have single words by two years old and their IQ could be anywhere on the scale including in the range for learning difficulties so that's how they differ but they both share the same diagnostic features and you see in brackets here the sex ratio which is the impetus for this research question that in classic autism it's for boys for every one girl Asperger's syndrome as many as nine boys for every one girl get the diagnosis this could reflect a diagnostic practice and I could reflect our difficulties in making accurate diagnoses particularly in females but it could also be telling us something about the underlying biology particularly sex linked biology as part of the the cause of autism spectrum and you can see that these days we recognize about 1% of the population have autism spectrum condition so let me move now to the topic of sex differences because for a long time this topic was taboo within psychology researchers tried to avoid the topic and if sex differences came up at all they were dismissed as being purely the result of culture purely the result of of postnatal experience so I'm going to start the topic of sex differences by looking at the brain rather than behavior and then move to behavior in a minute so this first slide is simply showing differences first of all in brain volume between typical boys and girls so boys in blue and girls in red and this is simply showing that on average there are differences in total brain volume but the other thing you can see here is differences in the rate of growth of the typical male and female brain that in the females in girls and the brain is reaching its peak and volume at an earlier age two boys it's about a one year difference so we can see differences in total size but also in rate of growth if you take apart those differences in total brain volume you can see the differences in both gray and white matter differences in total volume but again we see the same pattern that in girls they're reaching their peak slightly earlier than boys so girls are developing faster total size may not be particularly important but rate of growth may be very important in terms of understanding developmental disabilities and if we look lobe by lobe just show you here the frontal lobe and here the temporal lobe we see the same pattern so you have to look at each lobe differently because the rate and the size is different load by lobe but we see the same pattern that girls are developing faster when it comes to to brain development so this is really just my way of fare of structural brain differences between the sexes and many of you don't need any persuasion that there are differences between males and females but I thought I'd start at the level of the brain to go gently into sex differences into psychology still at the level of the brain you can look at individual structures so not just lobes but particular structures and find sex differences these are just two by illustration in females they're Planum temporarily involved with language is larger on average than in males and the amygdala shows the opposite pattern being larger in males at least in childhood so these are showing that regions that are associated with specific functions the amygdala of course been quite complex but associated with emotion processing and as we'll see later with recognizing emotions and others seems to show a sex difference some researchers as you may know have used functional MRI to look at sex differences and found even within the amygdala there are sex differences of them showing laterality effects so for example and when subjects are asked to remember emotional stimuli women show more activity in the left and d'leh and and men show more in the right this is the work of Larry Cahill and colleagues from several years ago so there are differences in both brain structure and brain function in terms of average sex differences a final example of of neural sexual dimorphism comes from looking at neurotransmitters and I thought this slide was really quite dramatic in showing that males produce much more serotonin than females these are studies using pet positron emission tomography where you deplete the brain of serotonin and then look at the rate of synthesis of this set of this neurotransmitter so I think the idea that there are differences in the brain between males and females should no longer be a topic of controversy and the question really is what is its importance its significance and how does it come about so now I move to the level of behavior because this is where it's been much more controversial many of you know that one way to study sex differences in behavior has been to look at children during play and particularly to use this paradigm called spontaneous toy choice so this is where you put toys out on the carpet and you videotape the children and later code the videotapes to see how often the child spontaneously chose to play with one kind of toy or another and there are literally hundreds of studies of these of this kind conducted in different cultures and I'm going to summarize by saying that most studies show that boys and on average show a stronger preference to play with this cluster of toys toy vehicles like toy cars toy trains and other vehicles or constructional toys like Lego or building blocks the studies range from about one year of age through to five years of age showing consistent sex difference on average and girls on average are shown a different spontaneous preference which is to play with dolls not just playing with them but creating social stories often with emotional content on the right of this slide you can see one example from Melissa Hines who was in London at City University she's recently moved to Cambridge and what this is showing is that when you look at the masculine type toys like the toy car it's not that one sex plays with it and the other one doesn't we simply see differences on average so males spend more time relative to females and playing with these masculine type toys and so these are just differences on average and with the feminine type toys like the toy doll we see the opposite profile and it's important just to underline what I guess is obvious namely that these differences just apply on average you can always find individual boys and girls that are typical for their sex so all we're seeing is differences on average Melissa Hines use that same spontaneous toy choice method to look at sex differences outside of human the human species to look at other primates here and vervet monkeys and what you can see in this photo is a snapshot but from her group studies showing that male monkeys spend more time playing with the toy car and female monkeys spend more time on average playing with the doll suggesting that whatever the role of culture and and experience in the human case there might be some element of biology as independent of culture contributes to these sex differences in in behavior back to humans another way to look at sex differences in to is in terms of sex ratios in occupations here I'm getting into territory which is even more controversial so I'm going to try and go carefully and but if we look at the the ratios in many cultures I'd be interested to know how it is in Sweden there are there's a cluster of occupations which are more likely to be filled by men than women so this is this includes mathematics computer science physics engineering tool making if we take just the first of those in many cultures where it's been looked at the sex ratio is at least three-quarters male to a quarter female so an engineering is got a very similar sex ratio and my own experience working in a university that that prioritizes mathematics and physics and engineering is that the admissions policies are very much striving towards encouraging more women into these these disciplines as academic subjects but also professions but that despite the effort to attract more women these sex ratios remain skewed there's another cluster of occupations which shows the opposite profile more women than men end up in these occupations that includes primary school teaching and counseling if we look just at this data here this comes from the SAT math test from the US the test that's the entrance examination into university and what it's showing is year by year from 1972 to 1997 males and females and what we don't see here are the standard deviations but there's a significant between males and females on this particular subtest just for mathematics despite fluctuations year by year so it looks like it's not just toys of occupation but also performance on some tests aptitude tests showing these sex differences I want to just mention caveat to this this this kind of data which is that we know that whatever occupation you end up in is not simply the result of spontaneous choice so unlike the child play date that we looked at earlier where we can talk about spontaneous choice obviously with adult occupations there are many factors that will influence the field you end up in but it's tempting to look at these child and heat and adult profiles sex ratios and suggests that maybe what we're seeing is that in in males attention is more easily attracted by systems of one kind or another mechanical systems constructional systems and in females on average attention is more easily attracted by people and particularly the emotional lives of other people and that we may be seeing that same contrast between what's then earlier mentioned as an interesting systems being stronger on average in males and an interest in people and particularly the emotional lives of other people being stronger on average in females I guess Sven is doing something systematic here and okay thank you so you you were worrying about the battery life of the computer thank you very much and so I'm going to in the next part of the lecture expects lourdes hypothesis looking at sex differences in these two psychological processes empathy and systemising so asking the question are there sex differences in favor of females in empathy and in favor of males in terms of systemizing and at this hypothesis that maybe people with autism have an extreme of the typical male profile we can ask our people with autism showing this particular profile on these psychological tests first of all in terms of definitions empathy is a word we use all the time my definition of it is recognizes two components that first is the recognition element being able to identify another person's thoughts and feelings so I would see that as synonymous with what's also called theory of mind or mind reading being able to imagine someone else's thoughts and feelings the second element is the response element having an appropriate emotional response to somebody else's thoughts and feelings so empathy is an umbrella concept with at least two components and probably more systemising is a very different kind of process I've defined it as the drive to analyze or build a system any kind of system and you can see I've listed some of the more common types of systems that are around us in the environment mechanical systems like this computer abstract systems like mathematics natural systems like the weather collectible systems like a library the thing about systems is that they follow rules and when your systemising you're trying to identify the rules that govern the system so you can predict how the system works so back to autism one possibility is that some aspects of the symptoms we see in autism may be the result of below average empathy and particularly and this might apply to the social and communication difficulties and the difficulties taking other people's perspectives and the other side of autism may be the result of intact or even above-average systemizing and this may particularly apply to why they develop very narrow interests in systems why they have a preference for predictability and routine and because when you systemize and you're trying to understand a predictable system not a lawful system and why they might resist change because when you systemize we need to hold everything constant and just vary one thing at a time in order to understand the system so what's the evidence so I'm starting here with one of our psychological tests of empathy many of you will have seen it before it's called the eyes test it's in this version designed for adults in the general population where you look at the photograph of someone else's eyes and you're asked to pick which of these four words best describes what the person in the photo is thinking or feeling here the correct answer is dispirited which is a little bit sad and if you've got the answer correct you did this on the basis of really quite minimal information about emotional expression just from the eye region of the face the task was designed to be deliberately challenging in order to that test for sex differences that might be quite subtle what we see here is that men and women in the general population on average his the mean and the standard deviation show small but statistically significant sex differences so on this test they were 25 such photographs both sexes were doing well performing above chance in this quite challenging test but women were scoring slightly but statistically significantly higher than men here's a group of adults with Asperger's syndrome who were scoring significantly lower than the other two groups and part of what I want to draw attention to is this pattern that we see a sex difference on the psychological test and we see that people on the autistic spectrum despite good IQ and the fact that these are adults who've had the opportunity to learn are showing an extreme of the typical male profile another way to measure empathy is in terms of questionnaires this is the empathy quotient the EQ and so it's a different methodology but it reveals a similar similar pattern of results here you read each statement and you say whether you agree or disagree with each statement as a description of you so all of the items are to do with social sensitivity how easily you can pick up on other people's thoughts and feelings or judge what is socially appropriate in different situations once again what we see is that women in the adult population females are scoring higher than males and people with Asperger's syndrome according to self-report these are questioners that adults can fill in for themselves but people on the autistic spectrum are scoring significantly lower than the other two groups I've included here and just some data from about 4,000 people who took this online so we have the opportunity to get large samples and you can see it produces a relatively normal which is a new idea that empathy is on a spectrum just like many traits and that most of us are just average in terms of empathy but some people might be above average and others very low in empathy and there are sex differences in this too let's quickly switch to systemising to see the other side of the other psychological process here we've got a test and where it you're asked to understand or predict how a mechanical system works the items for this test was selected for from an entrance examination into engineering for adults in the general population let me just quickly show you that on this item the wheel rotates anti-clockwise and you're asked what will happen to this point P and the correct answer is C it's a multiple-choice that it will go back and forth some of you saw the answer very quickly and what we see here is that when tests like this are given to men and women in the general population men score higher than women on average there's the mean and in brackets the standard deviation and up here we've got some data from children with Asperger's syndrome and a control group who don't have the diagnosis and what you can see is that the group with Asperger's syndrome scored higher than those without the diagnosis this is a striking result when I tell you that the group with the diagnosis were chronologically younger than the group without so here these children with Asperger's syndrome were aged 7 to 11 years old taking a physics test and in mechanics and using material that they hadn't been taught at school the control group were teenagers in my home city of Cambridge who were aged 12 to 16 years old there were 20 items in this test and you can see that the typical teenagers were struggling with this test so it's reminding us about something that's becoming more familiar that here autism or Asperger's syndrome is a disability when it comes to understanding the social world but isn't always a disability when it comes to understanding the physical world and can even lead to precocious ability or eyelets of ability or talents questionnaires can also be used to look at systemising so now the format is the same but all the items in the questionnaire gauge how strong your interests are in different systems we've got one about a mechanical system another about an electrical system and it's self-report in the adult version we have other versions of this where parents can fill it in about their child but I'm just showing you the adult versions where now men score higher than women in the general population and I hope that was a deliberate decision to turn out the lights and and here we see adults with Asperger's syndrome scoring even higher than men and women in the general population questionnaires of course have their limitations there might be and some some some differences between the genders in terms of how they respond to questionnaires but in conjunction with the performance tests we seem to be seeing a pattern where people with Asperger's syndrome or autism are showing an extreme of the male profile some people have argued that systemising may be secondary to attention to detail that when you're trying to understand a system whether it's mathematics or a mechanical system will just ignore the the electrical lighting system what you have to do is pay attention to all the small details so here we've got a test which is been used by psychologists for over half a century it's called the embedded figures test where you have to find the target shape as quickly as you can in the overall design and what you see is that men in the population on average are faster finding this cube hidden in the overall design as the front of the cube and there it's receding into 3d this is the average number of seconds it takes to find the shape that men are taking about 46 seconds women about 66 seconds on average and people with Asperger's syndrome are even faster and more accurate on this test of attention to detail taking on average only 30 seconds 32 seconds so and the important point here is that again we're seeing this pattern of females being greater than males in terms of duration in this case and people with Asperger's syndrome being even quicker than typical males so sometimes the results are the opposite but still showing the same pattern and and this is a pattern that we can look at at both in terms of psychological tests and also at the level of the brain I don't think this is me pushing the buttons but we can continue it's fine good we'll just try to ignore their their stroboscope effects so what I've put up here is a model just to take a take a moment of summary that we were talking about two different dimensions empathy along one dimension systemising along another dimension and what we're finding is that on average more females are scoring in this light blue area where empathy is at a higher level than systemizing on average more males are scoring in this light pink area where they're systemizing is at a higher level than their empathy obviously there are many people who score in the middle area this white area where their empathy and their systemizing are at an equivalent level showing no discrepancy equally good or equally bad on these tests but people with autism seem to be falling down here where their empathy is below average if we imagine zero means average for the population and minus 1 minus 2 minus 3 increasingly below average but there systemising could be anywhere from average through to superior so when we when we model these two dimensions in this way the idea is we all fall somewhere in this space but people with autism may be an extreme along this dimension this diagonal of sex differences well that's the model here we can look at it in terms of actual data where we've asked people to take both questionnaires the EQ for empathy and the SQ for systemising in red are women in the population in blue are men in the population and in green are people with Asperger's syndrome or on with a diagnosis on the autistic spectrum and the data is not as clean as the model but I think you might be able to see that the red dots cluster more up here the blue down here and the green are clustering here the important point from this slide is the variability and the individual dip the individual differences just to guard against stereotyping so you can always find individual men who are as empathic as women and similarly individual women who are as systemizing as men and the conclusion from this kind of scatterplot is that you can't predict anything about an individual based on their gender nevertheless if we look at the group statistics we can see this trend coming out so here we can do a count of all those dots and if we look at different profiles empathy greater than systemising for example we find more women than men show that profile 44 percent versus 17 percent the opposite profile systemising at a higher level than empathy now we see more men than women 54 percent versus 17 and if we take this extreme where empathy is below average and systemising is at least intact if not above average this is where we see the majority of people on the autistic spectrum so and the the data is in the direction predicted by the model quickly jumping to imaging if we're looking for this pattern where people with autism are showing an extreme of the typical male pattern on the eyes test using fMRI we see that women show more activity bilaterally in this area of inferior frontal gyrus but particularly on the left side and people with autism show even less activity in that same region here the brain is switched over so that right is left but we're seeing that same pattern in terms of brain activity whilst they're taking an empathy test in terms of the embedded figures test that test of attention to detail again we see that pattern females showing more activity than males in parietal cortex it's at the back of the brain posterior piratical parietal cortex whilst they're searching for the target shape hidden in the overall design and people with autism show even less activity in that same region despite having better performance on the task so the fMRI data are also showing that pattern of autism being an extreme of the male brain and some people have looked at resting state data in terms of fMRI the so called default mode network and particularly looking at this network connected whilst you're doing nothing with your eyes closed and many of the same regions involved in understanding other minds are also activated when you're simply and instructed to do nothing but there's a sex difference in this resting state Network females showing more activity than males and people with autism shown even less activity in that network of regions so all of this talk about sex differences does raise the old question about how much of this could be attributed to postnatal experience and culture and it for us to address this question we decided to conduct a study of newborn babies we wanted to set to test whether any of these psychological sex differences were evident at birth and if we found any then whatever the role of postnatal experience we would be pushed to conclude that prenatal biology was also important so here we tested over 100 babies aged 24 hours old we asked the mothers for their consent and so the babies had just arrived and the babies were filmed awake whilst they were either looking at a human face or as a mechanical mobile and each stimulus was presented for one minute and then later the videotapes were coded for how long the baby looked at each object and what we're presenting here are the percentage of babies that looked longer at one kind of stimulus or another so if I jumped straight to the results what we see is more boys than girls 43% versus 17% looked longer at the mechanical mobile and in girls more girls than boys 36% versus 25% looked longer at the human face the fact that this was aged 24 hours old suggests that this might reflect prenatal and factors prenatal biological factors some of the critics of this experiment have said well you waited 24 hours that's plenty of time for postnatal experience to shape these sex differences and that is of course technically true but and it was the best we could do the the obstetrician is where we conducted this study asked us if we would wait for one day whilst the baby and the mother recovered from the birth and it seemed only reasonable but and some people may be persuaded that the fact that this sex difference is appearing so early in development may reflect prenatal biology so Sven mentioned earlier that our group have been looking at fetal testosterone as a candidate biological factor shaping sex differences and maybe playing a role in autism why have we selected fetal testosterone well and this the hormone produced by the fetus sometimes people think of it as as produced by males but actually both sexes produce the hormone it's just that males produce at least twice as much the interest for me is not so much the sex difference as simply the variability in the population that we see individual differences even within males that are twenty fold and the question is why and why do people produce such varying amounts and does it have any functional and structural impact on brain development and behavior and from the animal research and testosterone has been thought to have so called organizational effects on brain development organizational is another word for permanent and we know this from and from animal work where you can manipulate fetal testosterone for example in rats and look at the structure of the brain and also at behavior long-term postnatally what's found is the diffusion dect testosterone into the neonate or into and the amniotic fluid surrounding the fetus and then later look at the structure of the of the female rat brain you find it's been masculinized it resembles more a typical male brain male rat brain and in terms of behavior you also see this masculinization so obviously this would be unethical to do in humans but in animal research it's considered acceptable to manipulate hormone levels prenatally on or perinatally and look at these effects on behavior in rats male rats tend to run through mazes more quickly than female rats but the treated female reps have had extra testosterone on average are as fast as their male counterparts so the hormone seems to be changing both brain and behavior as you know the testosterone the hormone is produced by the testes in males in females it's produced by the adrenal glands it's produced by the fetus as I said it's carried by the blood and crosses the blood-brain barrier and the way that testosterone has its effects is by binding to androgen receptors testosterone is an androgen androgen receptors are found all over the body but also in the brain particularly in those parts of the brain that show the clearest sex differences in terms of structure and once it's bound to these receptors it's thought to have the effect on brain development by modulating neurotransmitters like serotonin and gaba and also preventing selective cell death or apoptosis so there are lots of good reasons to expect that this hormone might be affecting brain development and behavior in humans we have been conducting this research in humans in what we think is the most ethical way which is to take advantage of women who are having amniocentesis during pregnancy so it would be unacceptable to manipulate hormones it would also be unacceptable to measure the hormones in the amniotic fluid produced by the fetus in a random population but women who are opting to have this clinical procedure where a needle is put into that fluid they're having it because their doctor has advised them to do this and where it's part of a screening program for Down syndrome we're asking these women for their consent to also analyze testosterone in that fluid so this happens in pregnancy we then wait till after the baby's born and we can look at aspects of behavior in the child and look to see if there's any relationship between prenatal testosterone and later development so this just shows you first of all that we've succeeded in measuring the hormone this is boys so male fetuses and female foetuses and as I mentioned boys are producing more than girls but I also mentioned this huge variability there are some boys who are producing so little testosterone that they're in the female range equally there are some girls who are very high in testosterone so they're in the male range and the question that this next series of experiments addresses is if we ignore somebody's sex and just look at their hormone levels what does this predict about their postnatal behavior at the other side of this slide you can see a graph that comes from Melissa Hines book but which which really reflects a principal in neuroendocrinology namely that at birth and there's very low levels of testosterone being produced but if we go backwards into fetal life there's a surge in production of testosterone around the end of the first trimester of pregnancy you can see there's another small one postnatally at about 2 or 3 months old and if we continued this timeline through to puberty we would see a third one and the the puberty one we understand its function to do with timing of onset of puberty but the real question is why is the fetus producing so much testosterone prenatally and is this is the function of this to do with masculinization of the brain so here are just some of the data from this longitudinal study we saw the children at at their first birthday 12 months old and we looked at them in terms of how much eye contact they produced so these are typical children they're only in the study because their mothers had amniocentesis and what you see is they're filmed whilst they're playing and we code how often they look up at their mother's face girls produce more eye contact than boys in this 10-minute play session and when we relate this to the prenatal testosterone levels here we have hormone levels here eye contact in red we've got girls and in blue we have boys but there's a negative correlation so the higher the child's prenatal testosterone the less eye contact they make at their first birthday we also saw them at their second birthday but this time we asked the parents to complete a checklist of vocabulary how how many words does your child know and produce so again we see a very clear sex difference in language development but girls on average have a larger vocabulary than boys this is a finding that's been known about for a long time that girls talk earlier than boys here we have an opportunity to look at mechanisms that might give rise to this because we've got testosterone along the x-axis and again the lime sloped downward so it's a negative correlation the higher the child's fetal testosterone the smaller their vocabulary at two years old and when they jump now to looking at these children aged eight we're following these children through their childhood and here we've asked the children to take an empathy test the eyes test but adapted for children so the vocabulary and where you have to pick which word best describes what the person in the photo is thinking or feeling it's been adapted for a typical eight-year-old child and here the correct answer is he's interested in something but once again we see this negative correlation that the higher the child's fetal testosterone the more difficulty they're having in reading faces to decode facial expression for underlying emotions or mental states and when we've asked the parents to complete the EQ the empathy equation to their child I should have said earlier that the hormone data is analyzed by the biochemists completely independently to the psychological data so effectively and the parents and filling in the in the questionnaire are completely blind to their child's prenatal hormone data but what we see is that and there's a downward correlation again a negative correlation so the child the higher the child's fetal testosterone the lower the child is being scored in terms of empathy eight years later on this parent report questionnaire what about systemising now we're seeing the opposite pattern so the line is going upwards a positive correlation that the higher the child's fetal testosterone the more that the parent is rating the child as having stronger interests in systems of one kind or another for example collecting the whole set of something and systematically or taking an interest in the small details between different makes of vehicles on the embedded figures test that test of attention to detail where I told you earlier that there's a sex difference in favor of males here we're seeing that even if you're ignoring a person sex and just looking at their hormone status there's a positive correlation that the higher the child's fetal testosterone the faster and more accurate they are at the test of attention to detail and I should also have said that these results are seen both when you look at both sexes together but also when you look just within one sex so it's suggesting that this is not just circular it's not just read ascribing sex but it's actually a hormone effect getting closer to the question of interest is whether there's any relationship between fetal testosterone and autistic traits so remember that these are children who are typically developing each dot is a child happily running around Cambridge and there are about 235 children in this study because autism is only 1% of the population it means that a sample of 235 is much too small to look at whether there's any relationship between testosterone and diagnosed autism you'd need very large samples to do that there may be one or two children in here who have autism so instead we can just look at whether there's any relationship between fetal testosterone and autistic traits we do this using a questionnaire called the aq the autism spectrum quotient simply because it's a dimensional measure you can see up here that the aq which is in this case a parent report questionnaire but there's also an adult self-report version it produces a relatively normal distribution in the general population so everybody is scoring somewhere on this measure of autistic traits people with a diagnosis score more extreme so they're shifted over to the right and so in this sample of typically developing children were seeing a positive correlation that the higher the child's fetal testosterone that the more autistic traits the child is showing eight years later when the parents are filling it out I just going to mention that we have a collaboration with the bio bank in Copenhagen in Denmark because we're very interested to look at whether there's any relationship between fetal testosterone and actual diagnosis and the reason for the collaboration is that in Copenhagen they've been storing amniotic fluid from women who've had amniocentesis since 1980 and in their freezer they have 90,000 some of amniotic fluid so the other thing about Denmark many of you will know is that they have a National Register for psychiatric diagnosis so every new case that's diagnosed is entered into a national register and so our collaboration is identifying who has autism in the population looking back to see if their amniotic fluid is in the freezer and then doing this analysis for the the hormone levels and on that basis we've been able to identify 400 cases of autism and as many controls as we would would need were taking twice as many controls and we'll be reporting on that data later this year this last slide in terms of fetal testosterone is just showing that when you look at fetal testosterone at an even earlier point in development in terms of autistic traits using a parent questionnaire called the Q chat the quantitative checklist for autism in toddlers again we get this positive correlation that the higher the child's fetal testosterone the more autistic traits children show now that these children are old enough to tolerate MRI they're eight years old we've asked them to climb into the scanner and we're looking at brain structure and this is the first time it's been studied in humans and that we've taken the corpus callosum the connective tissue between the two hemispheres and look to see if there's any relationship between different segments of the corpus callosum and testosterone and you can see a positive correlation with lightwood asymmetry in just one segment which is region 4 on the corpus callosum this is an area where you see sex differences in the general population that females have a larger and corpus callosum in this section than males and he was seeing a correlation with with asymmetry in that region so it's sound confirming what we know from animal research that this hormone has an effect on brain development there are some other clues that hormones may be important in autism I'm not going to go into detail in this slide it's simply to show you from a range of other approaches we've been looking at fetal testosterone but you can also look from other sources of evidence so for example the timing of puberty in autism appears atypical that boys are more likely to go into pubic with autism are more likely to go into puberty slightly early and girls are more likely to start puberty slightly late and since the onset of puberty is very much linked to testosterone levels this suggests that there may be continuing hormonal dysregulation not just at the fetal stage but also in terms of current hormones we've looked at women with Asperger's syndrome in terms of testosterone related medical conditions for example PCAST polycystic ovary syndrome where individuals have irregular menstrual cycles and they have a late onset of puberty and they have hirsutism or access bodily hair so it's quite a common medical condition about 10% of the population of female population have this but this is more common in women with autism or Asperger's syndrome and it's known to be that caused by high testosterone levels we've also looked at testosterone related characteristics like tomboy ism so the likelihood that as a child girls were playing with male typical toys and again found this is much more common in girls with autism many of you know about this measure their digit ratio where and you look at the ratio between the second and fourth fingers the ring finger versus the index finger and the ratio is lower in typical males it's even lower in people with autism and this this digit ratio is correlates with fetal testosterone so it's often used as a proxy for your hormone levels in the womb I can see some of you looking at your fingers I should tell you that this and the way you have to measure it is putting your hand on a scanner or a photocopier because it's a very small and subtle difference although if you're an extreme case you may be able to see it with the naked eye finally people have looked at current testosterone either in saliva or in serum or looking at precursors of testosterone such as Andrew steamed iron finding elevated levels of these sex steroid hormones in people with autism and just in the last few minutes I'll just mention something about the sex steroid genes because we know that your how much testosterone you produce is a function of many genes there are at least 25 genes involved in either the production of testosterone or the transport or the receptors for testosterone and you can see a number of different studies have now started looking at these genes in autism finding associations and I'm just going to pick out the androgen receptor gene over here and here a whole set of genes that our group has looked at which either associate either show association with a formal diagnosis of Asperger's syndrome or with the aq or EQ so increasingly there's interest in whether these genes are some of the risk genes for autism and I should point out because I don't want and this kind of data to be misinterpreted that both the hormonal data and the genetic data may just simply be at one part of the causal pathway in autism I'm certainly not suggesting that hormones are the only factor but it may be it but this data is suggesting that they're part of the story so I'm going to finish by drawing some conclusions I've shown you lots of evidence I think that there are sex differences on average both in the brain and in the mind in humans particularly when it comes to the mind in areas like language development social development and particularly empathy and on the non social side attention to detail and an interest in systems and some clues that in autism we may be seeing an extreme of a typical male brain I think this is really intended as a hypothesis to generate research because there's still a lot more that needs to be done for example there have been very few large scale studies comparing males and females in autism and that would be a very straightforward study to do looking both at structural MRI DTI like tractography and also functional MRI to be able to test whether females with autism show masculinization of the brain at these different levels finally we've seen some evidence that fetal testosterone is associated with typical sex differences in the population and I'm hoping that next time I come back I can tell you about the results of our our large collaborative study with Denmark to see whether this hormone is also involved in the development of autism so I'd like to invite you to visit our website if you want any more information about these studies and knowledge the the what they're funding from our sponsors that enable this research thank you you

Channel: PsychiatryLectures

Views: 102,619

Keywords: Simon, Baron-Cohen, autism, testosterone, brain, child, mind, psychiatry, stockholm, lecture, lectures, talk, Karolinska, Institutet, 2011, Borat, attention, fetal, development, asperger, DSM, cambridge, professor, sven, bölte, university, mental, health, ethiology, causes, speaks, hormone, sex, gender, University, zero, degrees, of, empathy, student, Testosterone, debate

Id: PjE_yaJjXE8

Length: 60min 50sec (3650 seconds)

Published: Thu Sep 29 2011

Reddit Comments

[u/arex1337]

A Stockholm Psychiatry Lecture held by Professor Simon Baron-Cohen: "Is Autism an extreme of the male brain?". Lecture held at Karolinska Institutet, Stockholm Sept 26 2011.

[u/petemc123]

I thought this was some new shit from Borat