Men, Women and Spatial Intelligence

Do men and women differ in their cognitive capacities? It's been a popular topic of conversation since as far back as we have records of what people were talking about.

While it's now (almost) generally accepted that men and women are at most only very slightly different in average IQ, there are still a couple of lines of evidence in favor of a gender difference.

First, there's the idea that men are more variable in their intelligence, so there are more very smart men, and also more very stupid ones. This averages out so the mean is the same.

Second, there's the theory that men are on average better at some things, notably "spatial" stuff involving the ability to mentally process shapes, patterns and images, while women are better at social, emotional and perhaps verbal tasks. Again, this averages out overall.

According to proponents, these differences explain why men continue to dominate the upper echelons of things like mathematics, physics, and chess. These all tap spatial processing and since men are more variable, there'll be more extremely high achievers - Nobel Prizes, grandmasters. (There are also presumably more men who are rubbish at these things, but we don't notice them.)

The male spatial advantage has been reported in many parts of the world, but is it "innate", something to do with the male brain? A new PNAS study says - probably not, it's to do with culture. But I'm not convinced.

The authors went to India and studied two tribes, the Khasi and the Karbi. Both live right next to other in the hills of Northeastern India and genetically, they're closely related. Culturally though, the Karbi are patrilineal - property and status is passed down from father to son, with women owning no land of their own. The Khasi are matrilineal, with men forbidden to own land. Moreover, Khasi women also get just as much education as the men, while Karbi ones get much less.

The authors took about 1200 people from 8 villages - 4 per culture - and got them to do a jigsaw puzzle. The quicker you do it, the better your spatial ability. Here were the results. I added the gender-stereotypical colours.

In the patrilineal group, women did substantially worse on average (remember that more time means worse). In the matrilineal society, they performed as well as men. Well, a tiny bit worse, but it wasn't significant. Differences in education explained some of the effect, but only a small part of it.

OK.

This was a large study, and the results are statistically very strong. However, there's a curious result that the authors don't discuss in the paper - the matrilineal group just did much better overall. Looking at the men, they were 10 seconds faster in the matrilineal culture. That's nearly as big as the gender difference in the patrilineal group (15 seconds)!

The individual variability was also much higher in the patrilineal society, for both genders.

Now, maybe, this is a real effect. Maybe being in a patrilineal society makes everyone less spatially aware, not just women; that seems a bit of a stretch, though.

There's also the problem that this study essentially only has two datapoints. One society is matrilineal and has low gender difference in visuospatial processing. One is patrilineal and has a high difference. But that's just not enough data to conclude that there's a correlation between the two things, let alone a causal relationship; you would need to study lots of societies to do that.

Personally, I have no idea what drives the difference, but this study is a reminder of how difficult the question is.

Hoffman M, Gneezy U, List JA (2011). Nurture affects gender differences in spatial abilities. Proceedings of the National Academy of Sciences of the United States of America PMID: 21876159

Men, Women and Spatial Intelligence

Do men and women differ in their cognitive capacities? It's been a popular topic of conversation since as far back as we have records of what people were talking about.

While it's now (almost) generally accepted that men and women are at most only very slightly different in average IQ, there are still a couple of lines of evidence in favor of a gender difference.

First, there's the idea that men are more variable in their intelligence, so there are more very smart men, and also more very stupid ones. This averages out so the mean is the same.

Second, there's the theory that men are on average better at some things, notably "spatial" stuff involving the ability to mentally process shapes, patterns and images, while women are better at social, emotional and perhaps verbal tasks. Again, this averages out overall.

According to proponents, these differences explain why men continue to dominate the upper echelons of things like mathematics, physics, and chess. These all tap spatial processing and since men are more variable, there'll be more extremely high achievers - Nobel Prizes, grandmasters. (There are also presumably more men who are rubbish at these things, but we don't notice them.)

The male spatial advantage has been reported in many parts of the world, but is it "innate", something to do with the male brain? A new PNAS study says - probably not, it's to do with culture. But I'm not convinced.

The authors went to India and studied two tribes, the Khasi and the Karbi. Both live right next to other in the hills of Northeastern India and genetically, they're closely related. Culturally though, the Karbi are patrilineal - property and status is passed down from father to son, with women owning no land of their own. The Khasi are matrilineal, with men forbidden to own land. Moreover, Khasi women also get just as much education as the men, while Karbi ones get much less.

The authors took about 1200 people from 8 villages - 4 per culture - and got them to do a jigsaw puzzle. The quicker you do it, the better your spatial ability. Here were the results. I added the gender-stereotypical colours.

In the patrilineal group, women did substantially worse on average (remember that more time means worse). In the matrilineal society, they performed as well as men. Well, a tiny bit worse, but it wasn't significant. Differences in education explained some of the effect, but only a small part of it.

OK.

This was a large study, and the results are statistically very strong. However, there's a curious result that the authors don't discuss in the paper - the matrilineal group just did much better overall. Looking at the men, they were 10 seconds faster in the matrilineal culture. That's nearly as big as the gender difference in the patrilineal group (15 seconds)!

The individual variability was also much higher in the patrilineal society, for both genders.

Now, maybe, this is a real effect. Maybe being in a patrilineal society makes everyone less spatially aware, not just women; that seems a bit of a stretch, though.

There's also the problem that this study essentially only has two datapoints. One society is matrilineal and has low gender difference in visuospatial processing. One is patrilineal and has a high difference. But that's just not enough data to conclude that there's a correlation between the two things, let alone a causal relationship; you would need to study lots of societies to do that.

Personally, I have no idea what drives the difference, but this study is a reminder of how difficult the question is.

Hoffman M, Gneezy U, List JA (2011). Nurture affects gender differences in spatial abilities. Proceedings of the National Academy of Sciences of the United States of America PMID: 21876159

New Mutations - New Eugenics?

True or false: you inherit your genes from your parents.





Mostly true, but not quite. In theory, you do indeed get half of your DNA from your mother and half from your father; but in practice, there's sometimes a third parent as well, random chance. Genes don't always get transmitted as they should: mutations occur.



As a result, it's not true that "genetic" always implies "inherited". A disease, for example, could be entirely genetic, and almost never inherited. Down's syndrome is the textbook example, but it's something of a special case and until recently, it was widely assumed that most disease risk genes were inherited.



Yet recent evidence suggests that many cases of neurological and psychiatric disorders are caused by uninherited, de novo mutation events. Here are two papers from the last few weeks about schizophrenia(1,2) - but the story looks similar for autism, intellectual disabilities, some forms of epilepsy, ADHD, and others. Indeed they're often the same mutations.



Biologically, a given mutation is what it is, whether it's de novo or inherited. But on a social and a psychological level, I think there are crucial differences, and in particular I think that if it turns out that de novo mutations are important in disease, we're going to see attempts to take these variants out of circulation - far more so than in the case of the very same genes, were they inherited.



The old eugenics movement was based on the idea that if we stop people with bad genes from breeding - by sterilization, voluntary or otherwise, say - we'll be able to eliminate diseases and other undesirable traits. This idea is now generally regarded as extremely unethical, but many of its opponents have shared with the eugenicists the belief that it could work.



But if de novo mutations are what cause the majority of disease, then this approach would be pointless. Sterilizing certain people, or encouraging the healthy ones to have more children, would never be able to eliminate the 'bad genes' because new ones are being created every generation, pretty much at random.



So the de novo paradigm ought to be welcomed by opponents of eugenics. It wasn't just morally wrong - it was biologically misguided too.



But hang on. This is the 21st century. We have in vitro fertilization (IVF), and you can analyze the genes of an IVF embryo before you decide to make it into a child. In the near future, we might be able to routinely sequence the genome of any unborn child shortly after conception.



From there, it would be a small step to allowing parents to decide not to have children with de novo mutations.



This would be, in its effects, a form of eugenics - in the sense that it would produce the effect that the old eugenicists wanted. No more 'bad' genes, or not nearly as many. Opinions will differ as to whether it's morally different. But I would have said that politically, it's a lot more likely to happen.



I can't see forced sterilization returning any time soon. But if you were expecting a baby and you knew that it was not just carrying your and your partner's DNA, but had also suffered a mutation - might you not want to avoid that?



Psychologically, it matters that it did not inherit the gene. It would be a big step to decide that your child should not inherit one of your own genes. Of course, some genes are obviously harmful, like one that raises the risk of cancer, but think about the grey areas - a gene for social anxiety, mild autistic symptoms, obesity, a personality trait.



You might well feel that carrying that gene is what makes you, you; and so it would be natural for your child to have it. You might decide that if it was good enough for you (and all your ancestors), it's good enough for your children. You might well resent the very idea that it's a 'bad' gene at all, as an attack on your own self-worth.



But none of that applies if it's a de novo mutation. Indeed, quite the opposite - all those same considerations would probably lead you to want your children to carry as close as possible to a carbon copy of your DNA, with no random changes. It was good enough for you.



My point is that I think there will be much more support for the idea of genetic screening against de novo mutations than against inherited genes. More people will want it, it will be more socially acceptable, and more widely used. I'm not saying this would be a good or a bad thing, just making a prediction. In the future, diseases and traits that are primarily caused by de novo mutations will increasingly selected against.

New Mutations - New Eugenics?

True or false: you inherit your genes from your parents.





Mostly true, but not quite. In theory, you do indeed get half of your DNA from your mother and half from your father; but in practice, there's sometimes a third parent as well, random chance. Genes don't always get transmitted as they should: mutations occur.



As a result, it's not true that "genetic" always implies "inherited". A disease, for example, could be entirely genetic, and almost never inherited. Down's syndrome is the textbook example, but it's something of a special case and until recently, it was widely assumed that most disease risk genes were inherited.



Yet recent evidence suggests that many cases of neurological and psychiatric disorders are caused by uninherited, de novo mutation events. Here are two papers from the last few weeks about schizophrenia(1,2) - but the story looks similar for autism, intellectual disabilities, some forms of epilepsy, ADHD, and others. Indeed they're often the same mutations.



Biologically, a given mutation is what it is, whether it's de novo or inherited. But on a social and a psychological level, I think there are crucial differences, and in particular I think that if it turns out that de novo mutations are important in disease, we're going to see attempts to take these variants out of circulation - far more so than in the case of the very same genes, were they inherited.



The old eugenics movement was based on the idea that if we stop people with bad genes from breeding - by sterilization, voluntary or otherwise, say - we'll be able to eliminate diseases and other undesirable traits. This idea is now generally regarded as extremely unethical, but many of its opponents have shared with the eugenicists the belief that it could work.



But if de novo mutations are what cause the majority of disease, then this approach would be pointless. Sterilizing certain people, or encouraging the healthy ones to have more children, would never be able to eliminate the 'bad genes' because new ones are being created every generation, pretty much at random.



So the de novo paradigm ought to be welcomed by opponents of eugenics. It wasn't just morally wrong - it was biologically misguided too.



But hang on. This is the 21st century. We have in vitro fertilization (IVF), and you can analyze the genes of an IVF embryo before you decide to make it into a child. In the near future, we might be able to routinely sequence the genome of any unborn child shortly after conception.



From there, it would be a small step to allowing parents to decide not to have children with de novo mutations.



This would be, in its effects, a form of eugenics - in the sense that it would produce the effect that the old eugenicists wanted. No more 'bad' genes, or not nearly as many. Opinions will differ as to whether it's morally different. But I would have said that politically, it's a lot more likely to happen.



I can't see forced sterilization returning any time soon. But if you were expecting a baby and you knew that it was not just carrying your and your partner's DNA, but had also suffered a mutation - might you not want to avoid that?



Psychologically, it matters that it did not inherit the gene. It would be a big step to decide that your child should not inherit one of your own genes. Of course, some genes are obviously harmful, like one that raises the risk of cancer, but think about the grey areas - a gene for social anxiety, mild autistic symptoms, obesity, a personality trait.



You might well feel that carrying that gene is what makes you, you; and so it would be natural for your child to have it. You might decide that if it was good enough for you (and all your ancestors), it's good enough for your children. You might well resent the very idea that it's a 'bad' gene at all, as an attack on your own self-worth.



But none of that applies if it's a de novo mutation. Indeed, quite the opposite - all those same considerations would probably lead you to want your children to carry as close as possible to a carbon copy of your DNA, with no random changes. It was good enough for you.



My point is that I think there will be much more support for the idea of genetic screening against de novo mutations than against inherited genes. More people will want it, it will be more socially acceptable, and more widely used. I'm not saying this would be a good or a bad thing, just making a prediction. In the future, diseases and traits that are primarily caused by de novo mutations will increasingly selected against.

Brain-Modifying Drugs

What if there was a drug that didn't just affect the levels of chemicals in your brain, it turned off genes in your brain? That possibility - either exciting or sinister depending on how you look at it - could be remarkably close, according to a report just out from a Spanish group.

The authors took an antidepressant, sertraline, and chemically welded it to a small interfering RNA (siRNA). A siRNA is kind of like a pair of genetic handcuffs. It selectively blocks the expression of a particular gene, by binding to and interfering with RNA messengers. In this case, the target was the serotonin 5HT1A receptor.

The authors injected their molecule into the brains of some mice. The sertraline was there to target the siRNA at specific cell types. Sertraline works by binding to and blocking the serotonin transporter (SERT), and this is only expressed on cells that release serotonin; so only these cells were subject to the 5HT1A silencing.

The idea is that this receptor acts as a kind of automatic off-switch for these cells, making them reduce their firing in response to their own output, to keep them from firing too fast. There's a theory that this feedback can be a bad thing, because it stops antidepressants from being able to boost serotonin levels very much, although this is debated.

Anyway, it worked. The treated mice showed a strong and selective reduction in the density of the 5HT1A receptor in the target area (the Raphe nuclei containing serotonin cells), but not in the rest of the brain.

Note that this isn't genetic modification as such. The gene wasn't deleted, it was just silenced, temporarily one hopes; the effect persisted for at least 3 days, but they didn't investigate just how long it lasted.

That's remarkable enough, but what's more, it also worked when they administered the drug via the intranasal route. In many siRNA experiments, the payload is injected directly into the brain. That's fine for lab mice, but not very practical for humans. Intranasal administration, however, is popular and easy.

So siRNA-sertraline, and who knows what other drugs built along these lines, may be closer to being ready for human consumption than anyone would have predicted. However... the mouse's brain is a lot closer to its nose than the human brain is, so it might not go quite as smoothly.

The mind boggles at the potential. If you could selectively alter the gene expression of selective neurons, you could do things to the brain that are currently impossible. Existing drugs hit the whole brain, yet there are many reasons why you'd prefer to only affect certain areas. And editing gene expression would allow much more detailed control over those cells than is currently possible.

Currently available drugs are shotguns and sledgehammers. These approaches could provide sniper rifles and scalpels. But whether it will prove to be safe remains to be seen. I certainly wouldn't want to be first one to snort this particular drug.

Bortolozzi, A., Castañé, A., Semakova, J., Santana, N., Alvarado, G., Cortés, R., Ferrés-Coy, A., Fernández, G., Carmona, M., Toth, M., Perales, J., Montefeltro, A., & Artigas, F. (2011). Selective siRNA-mediated suppression of 5-HT1A autoreceptors evokes strong anti-depressant-like effects Molecular Psychiatry DOI: 10.1038/mp.2011.92

Brain-Modifying Drugs

What if there was a drug that didn't just affect the levels of chemicals in your brain, it turned off genes in your brain? That possibility - either exciting or sinister depending on how you look at it - could be remarkably close, according to a report just out from a Spanish group.

The authors took an antidepressant, sertraline, and chemically welded it to a small interfering RNA (siRNA). A siRNA is kind of like a pair of genetic handcuffs. It selectively blocks the expression of a particular gene, by binding to and interfering with RNA messengers. In this case, the target was the serotonin 5HT1A receptor.

The authors injected their molecule into the brains of some mice. The sertraline was there to target the siRNA at specific cell types. Sertraline works by binding to and blocking the serotonin transporter (SERT), and this is only expressed on cells that release serotonin; so only these cells were subject to the 5HT1A silencing.

The idea is that this receptor acts as a kind of automatic off-switch for these cells, making them reduce their firing in response to their own output, to keep them from firing too fast. There's a theory that this feedback can be a bad thing, because it stops antidepressants from being able to boost serotonin levels very much, although this is debated.

Anyway, it worked. The treated mice showed a strong and selective reduction in the density of the 5HT1A receptor in the target area (the Raphe nuclei containing serotonin cells), but not in the rest of the brain.

Note that this isn't genetic modification as such. The gene wasn't deleted, it was just silenced, temporarily one hopes; the effect persisted for at least 3 days, but they didn't investigate just how long it lasted.

That's remarkable enough, but what's more, it also worked when they administered the drug via the intranasal route. In many siRNA experiments, the payload is injected directly into the brain. That's fine for lab mice, but not very practical for humans. Intranasal administration, however, is popular and easy.

So siRNA-sertraline, and who knows what other drugs built along these lines, may be closer to being ready for human consumption than anyone would have predicted. However... the mouse's brain is a lot closer to its nose than the human brain is, so it might not go quite as smoothly.

The mind boggles at the potential. If you could selectively alter the gene expression of selective neurons, you could do things to the brain that are currently impossible. Existing drugs hit the whole brain, yet there are many reasons why you'd prefer to only affect certain areas. And editing gene expression would allow much more detailed control over those cells than is currently possible.

Currently available drugs are shotguns and sledgehammers. These approaches could provide sniper rifles and scalpels. But whether it will prove to be safe remains to be seen. I certainly wouldn't want to be first one to snort this particular drug.

Bortolozzi, A., Castañé, A., Semakova, J., Santana, N., Alvarado, G., Cortés, R., Ferrés-Coy, A., Fernández, G., Carmona, M., Toth, M., Perales, J., Montefeltro, A., & Artigas, F. (2011). Selective siRNA-mediated suppression of 5-HT1A autoreceptors evokes strong anti-depressant-like effects Molecular Psychiatry DOI: 10.1038/mp.2011.92

What Big Eyes You Have

According to the BBC, a new study has found that northern peoples have bigger eyes - and bigger brains.


Actually, the paper in question talked about eyes but didn't make much of the brain finding, which is confined to the Supplement. Nonetheless, they did find an effect on brain size too. Peoples living further from the equator have larger eye sockets and also larger total cranial capacity (brain volume), apparantly. The authors include Robin Dunbar of "Dunbar's Number" fame.

Their idea is that humans evolved larger eyes because further from the equator, there's on average less light, so you need bigger eyes to collect more light and see well.

They looked at 19th century skulls stored in museum collections, and measured the size of the eye sockets (orbits). They did this by filling them with a bunch of little glass balls and counting how many balls fit. They had a total of 73 "healthy adult" skulls from 12 different places, ranging from Scandinavia to Kenya.

Latitude essentially meant northern-ness because only one population (Australian Aborigines) were from far south of the equator.

Total brain size also increased with latitude, but eye size increased even faster, so the eye:brain ratio increased. They don't really discuss the brain size finding, except to suggest that it might be accounted for by increased visual cortex (though there's no direct evidence of that), but here it is, showing latitude vs. cranial capacity in ml.

The idea that northern peoples are brainier unfortunately has a long history. For example, it's been suggested that the coldness of northern climes meant that life was harder, so people evolved to be smarter to survive.

The heat of the Sahara was easy living compared to the deadly horrors of an English winter, in other words. Hmm.

The idea that higher latitudes are darker, so you'd need bigger eyes, and then a bigger brain (at least the visual parts of the brain) to process what you see, is certainly more plausible than that theory. However, the data in this paper seem pretty scanty.

Measuring skulls by filling them with little balls was cutting edge neuroscience in the 19th century. However, nowadays, we have MRI scanners. Although usually intended to image the brain, many MRI scans of the head also give an excellent image of the skull and eyes. Millions of people of all races get MRI scans every year.

Nowadays, people have medical records, so we can tell exactly how healthy people are. The people who became these skulls in a museum were said to be healthy, but how healthy a 19th century Indian or Kenyan could hope to be, by modern standards, I'm not sure. Certainly there's an excellent chance that they were malnourished and I suspect this would make your eyes and skull smaller.

Pearce, E., & Dunbar, R. (2011). Latitudinal variation in light levels drives human visual system size Biology Letters DOI: 10.1098/rsbl.2011.0570

What Big Eyes You Have

According to the BBC, a new study has found that northern peoples have bigger eyes - and bigger brains.


Actually, the paper in question talked about eyes but didn't make much of the brain finding, which is confined to the Supplement. Nonetheless, they did find an effect on brain size too. Peoples living further from the equator have larger eye sockets and also larger total cranial capacity (brain volume), apparantly. The authors include Robin Dunbar of "Dunbar's Number" fame.

Their idea is that humans evolved larger eyes because further from the equator, there's on average less light, so you need bigger eyes to collect more light and see well.

They looked at 19th century skulls stored in museum collections, and measured the size of the eye sockets (orbits). They did this by filling them with a bunch of little glass balls and counting how many balls fit. They had a total of 73 "healthy adult" skulls from 12 different places, ranging from Scandinavia to Kenya.

Latitude essentially meant northern-ness because only one population (Australian Aborigines) were from far south of the equator.

Total brain size also increased with latitude, but eye size increased even faster, so the eye:brain ratio increased. They don't really discuss the brain size finding, except to suggest that it might be accounted for by increased visual cortex (though there's no direct evidence of that), but here it is, showing latitude vs. cranial capacity in ml.

The idea that northern peoples are brainier unfortunately has a long history. For example, it's been suggested that the coldness of northern climes meant that life was harder, so people evolved to be smarter to survive.

The heat of the Sahara was easy living compared to the deadly horrors of an English winter, in other words. Hmm.

The idea that higher latitudes are darker, so you'd need bigger eyes, and then a bigger brain (at least the visual parts of the brain) to process what you see, is certainly more plausible than that theory. However, the data in this paper seem pretty scanty.

Measuring skulls by filling them with little balls was cutting edge neuroscience in the 19th century. However, nowadays, we have MRI scanners. Although usually intended to image the brain, many MRI scans of the head also give an excellent image of the skull and eyes. Millions of people of all races get MRI scans every year.

Nowadays, people have medical records, so we can tell exactly how healthy people are. The people who became these skulls in a museum were said to be healthy, but how healthy a 19th century Indian or Kenyan could hope to be, by modern standards, I'm not sure. Certainly there's an excellent chance that they were malnourished and I suspect this would make your eyes and skull smaller.

Pearce, E., & Dunbar, R. (2011). Latitudinal variation in light levels drives human visual system size Biology Letters DOI: 10.1098/rsbl.2011.0570

Autism Isn't Very Genetic...Or Is It?

The environment is more important than genetics in setting the risk for autism, according to a new study that's got the media in a tizzy.

The paper, which is free, is here: Genetic Heritability and Shared Environmental Factors Among Twin Pairs With Autism

It's a twin study, and like all such research, it aims to estimate heritability, the proportion of the variability in autism risk caused by straightforward genetic effects. A heritability of 0% means no genetics and 100% means purely genetic. Note, however, that complex interactions between genes, epigenetics, and gene-environment interactions would throw the whole thing off.

Twin studies rely on the fact that there are two kinds of twins. Identical, or monozygotic (MZ), pairs have identical DNA, while dizygotic (DZ) twins are no more alike than any other brothers or sisters, genetically. So MZ twins ought to be more alike than DZ twins (have a higher "concordance"), and the size of the MZ-DZ difference is a measure of heritability.

There have been several previous twin studies of autism, and they've tended to find a heritability of around 90%, with high MZ concordance and very low DZ. However, these tended to be small and used outdated methods of diagnosis.

The new study used California records to find all twin pairs, born in the state between 1987 and 2004, where at least one of the twins had a diagnosis of autism on the DDS register of people receiving state services for developmental disorders.

They found 1156 twin pairs. Of these, they managed to recruit and get full data from 202 pairs. They gave all these 404 kids full autism diagnostic assessments. This is not a great response rate. Parents of responders tended to be slightly better educated and more likely to be white than the non-responders.

Here's the key data: concordance was higher in MZ twins, but not by nearly as much as previous studies would predict. Putting these data into a statistical model, assuming a baseline rate of autism of 1% in boys and 0.3% in girls, found that the most likely explanation was a heritability of about 35-40% and an effect of "shared environment", i.e. family factors, of 55-60%.

So. Autism's not very genetic?

Maybe. This is certainly a major study and all autism researchers need to take note. But there's some caveats.

My major concern is that the DZ concordance might be too high, because a kid might be more likely to get diagnosed with autism if their twin already had a diagnosis. Suppose you're a parent and one of your twins is diagnosed - of course you're going to worry about the other one, and start thinking, are they really so different?

Although all the people in this study were (re)assessed for study purposes, the diagnostic instruments are hardly immune to the effects of prior diagnosis. The ADI interview is based on parental report of early childhood behaviour. Parents know whether the other twin has autism. The other interview, the ADOS, is based on direct observation of the patient, so it might avoid this - but you have to score on the ADI to get a diagnosis.

This, by itself, wouldn't explain the discrepency between these data and older twin studies. But we also know that diagnoses of autism in general has skyrocketed recently. People seem to be becoming more willing to accept that diagnosis, and more aware of the symptoms. So it's quite possible that some of the "unaffected" twins from older studies would get a diagnosis today if they were to have the kind of modern, formal assessment done in this study.

This doesn't mean that the new study is wrong. If this explanation is true, then the study is quite right - there is a strong shared environmental influence on autism diagnosis. But not necessarily on autism.

One reason to suspect that this is going on - and this is purely a hunch - is that the estimates of shared environmental influence, i.e family environment, was 55%. This is exceptionally high, because almost every other human disorder or trait for which twin studies have been done, have reported low shared environmental effects, and high individual environmental effects (smoking, alcoholism, anxiety, depression). In fact people have written books about this.

Maybe autism's different. Yet I'm more willing to accept that autism diagnosis is different.

A related, but seperate, point: it's very likely that some autism is more genetic than others. In particular we know that some cases are caused by single genetic variants, and these tend to be severe with associated low IQ and sometimes other abnormalities; this is sometimes called "syndromic" autism.

It's always easier to spot a severe case than a mild one. So it's quite possible that older studies had a higher proportion of these cases, because the diagnostic system was only able to pick up those ones. Maybe in more recent times, as diagnosis has expanded, "autism" is coming to cover a "less genetic" set of things.

The good thing about these data is that they span births from 1987 to 2004. So it would be possible to check this theory by looking to see whether the early data i.e. the older twins, have a higher heritability.

Finally, Michelle Dawson pointed out on Twitter that there's another large twin study from Wisconsin, as yet unpublished but presented at a conference. They found broadly comparable results.

Joachim Hallmayer, et al. (2011). Genetic Heritability and Shared Environmental Factors Among Twin Pairs With Autism Archives of General Psychiatry

Autism Isn't Very Genetic...Or Is It?

The environment is more important than genetics in setting the risk for autism, according to a new study that's got the media in a tizzy.

The paper, which is free, is here: Genetic Heritability and Shared Environmental Factors Among Twin Pairs With Autism

It's a twin study, and like all such research, it aims to estimate heritability, the proportion of the variability in autism risk caused by straightforward genetic effects. A heritability of 0% means no genetics and 100% means purely genetic. Note, however, that complex interactions between genes, epigenetics, and gene-environment interactions would throw the whole thing off.

Twin studies rely on the fact that there are two kinds of twins. Identical, or monozygotic (MZ), pairs have identical DNA, while dizygotic (DZ) twins are no more alike than any other brothers or sisters, genetically. So MZ twins ought to be more alike than DZ twins (have a higher "concordance"), and the size of the MZ-DZ difference is a measure of heritability.

There have been several previous twin studies of autism, and they've tended to find a heritability of around 90%, with high MZ concordance and very low DZ. However, these tended to be small and used outdated methods of diagnosis.

The new study used California records to find all twin pairs, born in the state between 1987 and 2004, where at least one of the twins had a diagnosis of autism on the DDS register of people receiving state services for developmental disorders.

They found 1156 twin pairs. Of these, they managed to recruit and get full data from 202 pairs. They gave all these 404 kids full autism diagnostic assessments. This is not a great response rate. Parents of responders tended to be slightly better educated and more likely to be white than the non-responders.

Here's the key data: concordance was higher in MZ twins, but not by nearly as much as previous studies would predict. Putting these data into a statistical model, assuming a baseline rate of autism of 1% in boys and 0.3% in girls, found that the most likely explanation was a heritability of about 35-40% and an effect of "shared environment", i.e. family factors, of 55-60%.

So. Autism's not very genetic?

Maybe. This is certainly a major study and all autism researchers need to take note. But there's some caveats.

My major concern is that the DZ concordance might be too high, because a kid might be more likely to get diagnosed with autism if their twin already had a diagnosis. Suppose you're a parent and one of your twins is diagnosed - of course you're going to worry about the other one, and start thinking, are they really so different?

Although all the people in this study were (re)assessed for study purposes, the diagnostic instruments are hardly immune to the effects of prior diagnosis. The ADI interview is based on parental report of early childhood behaviour. Parents know whether the other twin has autism. The other interview, the ADOS, is based on direct observation of the patient, so it might avoid this - but you have to score on the ADI to get a diagnosis.

This, by itself, wouldn't explain the discrepency between these data and older twin studies. But we also know that diagnoses of autism in general has skyrocketed recently. People seem to be becoming more willing to accept that diagnosis, and more aware of the symptoms. So it's quite possible that some of the "unaffected" twins from older studies would get a diagnosis today if they were to have the kind of modern, formal assessment done in this study.

This doesn't mean that the new study is wrong. If this explanation is true, then the study is quite right - there is a strong shared environmental influence on autism diagnosis. But not necessarily on autism.

One reason to suspect that this is going on - and this is purely a hunch - is that the estimates of shared environmental influence, i.e family environment, was 55%. This is exceptionally high, because almost every other human disorder or trait for which twin studies have been done, have reported low shared environmental effects, and high individual environmental effects (smoking, alcoholism, anxiety, depression). In fact people have written books about this.

Maybe autism's different. Yet I'm more willing to accept that autism diagnosis is different.

A related, but seperate, point: it's very likely that some autism is more genetic than others. In particular we know that some cases are caused by single genetic variants, and these tend to be severe with associated low IQ and sometimes other abnormalities; this is sometimes called "syndromic" autism.

It's always easier to spot a severe case than a mild one. So it's quite possible that older studies had a higher proportion of these cases, because the diagnostic system was only able to pick up those ones. Maybe in more recent times, as diagnosis has expanded, "autism" is coming to cover a "less genetic" set of things.

The good thing about these data is that they span births from 1987 to 2004. So it would be possible to check this theory by looking to see whether the early data i.e. the older twins, have a higher heritability.

Finally, Michelle Dawson pointed out on Twitter that there's another large twin study from Wisconsin, as yet unpublished but presented at a conference. They found broadly comparable results.

Joachim Hallmayer, et al. (2011). Genetic Heritability and Shared Environmental Factors Among Twin Pairs With Autism Archives of General Psychiatry

Autism In The I.T. Crowd

Is autism more common in Silicon Valley?


A new study from Simon Baron-Cohen and colleagues asked pretty much this question, although rather than California, they looked at Eindhoven in Holland. Eindhoven is the tech hub of the Netherlands:

This region contains the Eindhoven University of Technology, as well as the High Tech Campus Eindhoven, where IT and technology companies such as Philips, ASML, IBM and ATOS Origin are based... 30% of jobs in Eindhoven are now in technology or ICT, in Haarlem and Utrecht this is, respectively, 16 and 17%

The authors found that official rates of diagnosed autism amongst children enrolled in Eindhoven schools were more than twice as high as those in kids from the comparison cities of Haarlem and Utrecht. In Eindhoven, rates of any autism spectrum disorder were 2.3%, far higher than rates elsewhere (0.6-0.8%).

Narrowly defined "classical autism" was also higher. However, two control disorders, dyspraxia and ADHD, were no different.

A diagnosed autism prevalence of 2.3% is extremely high. Some recent studies have found similar figures when you actually go out and attempt to find undiagnosed cases and diagnose them. But for 2.3% of kids to already have a diagnosis, is remarkable.

Unfortunately, there's a big problem here, which is that this study has a sample size is 3. There were lots of data from each city: in total, 369 schools took part, with over 60,000 kids. But there were only three independent cities.

So while these data convincingly show that Eindhoven has higher rates of autism than the other two regions, this might just mean, say, that half of Dutch cities have local educational systems that promote diagnosis, and Eindhoven happens to be one of them.

To really answer the question of whether I.T. folk have more autism, you'd need to look at Silicon Valleys around the world, to increase your sample size.

I'd be surprised if there weren't a link. Autism is highly heritable and we know that the children of people with autism, or mild autistic traits, have a higher rate. I don't think it's too controversial to say that the average programmer has above-average autistic traits, and it's quite possible that a little autism is a positive advantage in IT professions.

This is certainly Baron-Cohen's hypothesis, as he's long argued that people with autism have a tendency to be strong "systematizers":

This striking difference in the prevalence of ASC is in line with the hyper-systemizing theory, and will require the phase two study using diagnostic assessments and screening methods, to determine the exact nature of regional differences in population prevalence. Future research should test if this higher prevalence in a high tech region is found in other cultures (e.g., in Silicon Valley, California)...

Roelfsema MT, Hoekstra RA, Allison C, Wheelwright S, Brayne C, Matthews FE, & Baron-Cohen S (2011). Are Autism Spectrum Conditions More Prevalent in an Information-Technology Region? A School-Based Study of Three Regions in the Netherlands. Journal of autism and developmental disorders PMID: 21681590

Autism In The I.T. Crowd

Is autism more common in Silicon Valley?


A new study from Simon Baron-Cohen and colleagues asked pretty much this question, although rather than California, they looked at Eindhoven in Holland. Eindhoven is the tech hub of the Netherlands:

This region contains the Eindhoven University of Technology, as well as the High Tech Campus Eindhoven, where IT and technology companies such as Philips, ASML, IBM and ATOS Origin are based... 30% of jobs in Eindhoven are now in technology or ICT, in Haarlem and Utrecht this is, respectively, 16 and 17%

The authors found that official rates of diagnosed autism amongst children enrolled in Eindhoven schools were more than twice as high as those in kids from the comparison cities of Haarlem and Utrecht. In Eindhoven, rates of any autism spectrum disorder were 2.3%, far higher than rates elsewhere (0.6-0.8%).

Narrowly defined "classical autism" was also higher. However, two control disorders, dyspraxia and ADHD, were no different.

A diagnosed autism prevalence of 2.3% is extremely high. Some recent studies have found similar figures when you actually go out and attempt to find undiagnosed cases and diagnose them. But for 2.3% of kids to already have a diagnosis, is remarkable.

Unfortunately, there's a big problem here, which is that this study has a sample size is 3. There were lots of data from each city: in total, 369 schools took part, with over 60,000 kids. But there were only three independent cities.

So while these data convincingly show that Eindhoven has higher rates of autism than the other two regions, this might just mean, say, that half of Dutch cities have local educational systems that promote diagnosis, and Eindhoven happens to be one of them.

To really answer the question of whether I.T. folk have more autism, you'd need to look at Silicon Valleys around the world, to increase your sample size.

I'd be surprised if there weren't a link. Autism is highly heritable and we know that the children of people with autism, or mild autistic traits, have a higher rate. I don't think it's too controversial to say that the average programmer has above-average autistic traits, and it's quite possible that a little autism is a positive advantage in IT professions.

This is certainly Baron-Cohen's hypothesis, as he's long argued that people with autism have a tendency to be strong "systematizers":

This striking difference in the prevalence of ASC is in line with the hyper-systemizing theory, and will require the phase two study using diagnostic assessments and screening methods, to determine the exact nature of regional differences in population prevalence. Future research should test if this higher prevalence in a high tech region is found in other cultures (e.g., in Silicon Valley, California)...

Roelfsema MT, Hoekstra RA, Allison C, Wheelwright S, Brayne C, Matthews FE, & Baron-Cohen S (2011). Are Autism Spectrum Conditions More Prevalent in an Information-Technology Region? A School-Based Study of Three Regions in the Netherlands. Journal of autism and developmental disorders PMID: 21681590

Do Pigs Get Autism?

What happens to a pig if it has a gene for autism?

There has been lots of research on mice who carry the same genes associated with autism in humans. Rats and recently monkeys have been studied as well. But the possibility of autistic pigs has been strangely neglected by science.

A new paper might just change that: Characterization of porcine autism susceptibility candidate 2 as a candidate gene for the number of corpora lutea in pigs. The authors found that, in female pigs, variation in a certain gene affects the function of the ovaries.

The corpus luteum is a little yellow blob (technically speaking) in the ovary. Its job is to secrete progesterone. Women's ovaries grow a new one during every menstrual cycle, and it normally breaks down and disappears before the period. However, if you get pregnant, the corpus luteum sticks around and continues producing that hormone.

Pigs, like many animals, can have more than one of these per ovary and it turns out that one of the genes controlling the number is a homolog of the human gene AUTS2. AUTS2 mutations are linked to autism (hence the name), smoking and mental retardation. The authors of this paper found several variants in this gene in domestic pig populations, and they show that it's expressed in the pig ovary.

It's quite a long leap from porcine lady bits to autism, I would say, but this actually does make sense, if you accept the Extreme Male Brain theory of autism. Boys are at least four times more likely to have autism than girls, and some say that masculinizing hormone testosterone may be the reason. This study fits with that, given that progesterone is a female hormone. Maybe mutations in AUTS2 gene alter sex hormone production?

On the other hand, it might be a coincidence. AUTS2 is strongly expressed in the brain, as well as the ovaries. Maybe it's just required for cell function, and if it's mutated, cells stop working normally: whether they be in the brain, or the corpus luteum.

Either way, it would be interesting to see whether AUTS2 affects pig behaviour... but I'm not sure what an autistic pig would look like.

Sato S, Hayashi T, & Kobayashi E (2011). Characterization of porcine autism susceptibility candidate 2 as a candidate gene for the number of corpora lutea in pigs. Animal reproduction science PMID: 21641132

Do Pigs Get Autism?

What happens to a pig if it has a gene for autism?

There has been lots of research on mice who carry the same genes associated with autism in humans. Rats and recently monkeys have been studied as well. But the possibility of autistic pigs has been strangely neglected by science.

A new paper might just change that: Characterization of porcine autism susceptibility candidate 2 as a candidate gene for the number of corpora lutea in pigs. The authors found that, in female pigs, variation in a certain gene affects the function of the ovaries.

The corpus luteum is a little yellow blob (technically speaking) in the ovary. Its job is to secrete progesterone. Women's ovaries grow a new one during every menstrual cycle, and it normally breaks down and disappears before the period. However, if you get pregnant, the corpus luteum sticks around and continues producing that hormone.

Pigs, like many animals, can have more than one of these per ovary and it turns out that one of the genes controlling the number is a homolog of the human gene AUTS2. AUTS2 mutations are linked to autism (hence the name), smoking and mental retardation. The authors of this paper found several variants in this gene in domestic pig populations, and they show that it's expressed in the pig ovary.

It's quite a long leap from porcine lady bits to autism, I would say, but this actually does make sense, if you accept the Extreme Male Brain theory of autism. Boys are at least four times more likely to have autism than girls, and some say that masculinizing hormone testosterone may be the reason. This study fits with that, given that progesterone is a female hormone. Maybe mutations in AUTS2 gene alter sex hormone production?

On the other hand, it might be a coincidence. AUTS2 is strongly expressed in the brain, as well as the ovaries. Maybe it's just required for cell function, and if it's mutated, cells stop working normally: whether they be in the brain, or the corpus luteum.

Either way, it would be interesting to see whether AUTS2 affects pig behaviour... but I'm not sure what an autistic pig would look like.

Sato S, Hayashi T, & Kobayashi E (2011). Characterization of porcine autism susceptibility candidate 2 as a candidate gene for the number of corpora lutea in pigs. Animal reproduction science PMID: 21641132

Autistic Brains 'Genes Differ'

The BBC say:

The brains of people with autism are chemically different to those without autism, according to researchers. A study, published in the journal Nature, showed the unique characters of the frontal and temporal lobes had disappeared.

It's not a bad summary, although it doesn't explain quite how interesting the new results are. Here's the paper, from a joint US/British team: Transcriptomic analysis of autistic brain reveals convergent molecular pathology

The authors took 19 brains from people with autism and 17 healthy ones. These came from people who donated their brains to science and then died. The study involved taking samples from three areas of the brain, the superior temporal gyrus, the prefrontal cortex, and the cerebellum. These are regions that have been implicated in autism, although to be honest, so has everywhere else in the brain.

They then looked at gene expression: mRNA levels. This measures the degree to which different genes are "activated" and being used to make proteins. Bear in mind that a gene itself could be completely normal, and yet be abnormally expressed: this was not a study of DNA mutations. So the BBC's headline is a bit misleading. The genes themselves were not the focus of this study.

Anyway, comparing the autistic and control brains, they found 444 genes that were statistically significantly either over- or under-expressed in the cerebral cortex samples from the autistic group. However, in the cerebellum, there were just 2 differences: so the cerebellum was ruled out from further analysis.

They then replicated the study in a different cortical area in 6 new cases and 5 new controls. They found extremely strong overlap with the original cohort, with the same genes being altered in the same direction in almost all cases. This makes me confident that there is something going on here. This scatterplot shows that almost all of the genes that were significantly different in the first batch were also different in same direction in the second one (although not always significantly, as you'd expect.)

However, the authors didn't stop there, and this is where it gets interesting. First, they used a pattern classification algorithm to try to distinguish patients and controls on the basis of gene expression. This is very much like the paper from last year showing that pattern classification could predict autism on the basis of brain structure.

Interestingly, the algorithm correctly " diagnosed" a case of autism who turned out to have a 15q duplication mutation. 15q duplication is a genetic disorder which causes autism, amongst other things, and it may explain up to 1% of cases of autism. This is only one case but it's important because it suggests that "15q autism" is not all that different to other kinds of autism on the neural level.

The authors then looked at what the over- and under- expressed genes actually were. They found that the "up" genes tended to be genes relating to immune and glial function, while the "down" genes tended to be involved in the formation and function of synapses between cells.

Very interestingly, one of the major clusters of genes , "M12", showed strong overlap with genes previously known to be expressed in a type of cell called PV+ GABA interneurons. In mouse models of autism, these are known to be deficient. M12 was underexpressed in autism, and it contains many genes which have previously been found to be mutated in some people with autism, such as CNTNAP2.

Another cluster, "M16", was overexpressed; it contains genes involved in immune and microglial function (microglia are specialized immune system cells inside the brain). However, M16 did not contain overrepresentation of suspected asd genes.

So this all points to something like this: autism is caused by disruption to the function of certain gene networks in the brain involved in synaptic function. This network is a delicate balance and it can be thrown off course by many different mutations and/or environmental factors.

There's no one gene for autism, but all of the genes for autism might be related, or rather, they might form a team that works together. If you want to look at it this way, you could say that autism is a bit like blindness. People can go blind for lots of different reasons: it could be damage to the surface of the eye, or the retina, or the optic nerve which carries information to the brain, or the brain itself. All of these parts depend on all the others to work, and if one of them goes wrong, the whole system suffers.

Also, whatever the abnormality in autism is, it seems to trigger a secondary change in the brain which is immune and/or glial related. By "secondary" I don't mean that it's less important. It might be what causes the symptoms of autism. But it's not the root cause (because if it were, mutations in this network would cause autism, and they don't seem to.)

This study raises many more questions than it answers, but in a good way. It certainly doesn't explain autism, but it's pointed the way towards more focussed research in the future - gene cluster M12.

Voineagu I, Wang X, Johnston P, Lowe JK, Tian Y, Horvath S, Mill J, Cantor RM, Blencowe BJ, & Geschwind DH (2011). Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Nature PMID: 21614001