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.

Susan Greenfield Causes Autism

British neuroscientist Susan Greenfield has caused a storm with her suggestion that the recent rise in the use of the internet and social media may be related to the recent rise in autism.

I point to the increase in autism and I point to internet use. That's all. Establishing a causal relationship is very hard but there are trends out there that we must think about.

This has led to fellow Oxford neuroscientist Dorothy Bishop of BishopBlog writing an Open Letter asking her to "please, please, stop talking about autism". Twitter has been enlivened by #greenfieldism's such as "I point to the rise of Rebecca Black and the Greek sovereign debt crisis, that is all."



However, in a Neuroskeptic exclusive, I can reveal that the situation is far worse than anyone feared. Greenfield is not merely spreading unwarranted speculations about the recent rise in autism diagnoses.



She caused that rise.



The graph above shows the total number of scientific citations for Susan Greenfield's papers, over time. This is as good a measure as any of the influence Greenfield has had over our culture.



The trend is obvious, the growth is dramatic, and the correlation with the modern autism epidemic is undeniable.

Susan Greenfield Causes Autism

British neuroscientist Susan Greenfield has caused a storm with her suggestion that the recent rise in the use of the internet and social media may be related to the recent rise in autism.

I point to the increase in autism and I point to internet use. That's all. Establishing a causal relationship is very hard but there are trends out there that we must think about.

This has led to fellow Oxford neuroscientist Dorothy Bishop of BishopBlog writing an Open Letter asking her to "please, please, stop talking about autism". Twitter has been enlivened by #greenfieldism's such as "I point to the rise of Rebecca Black and the Greek sovereign debt crisis, that is all."



However, in a Neuroskeptic exclusive, I can reveal that the situation is far worse than anyone feared. Greenfield is not merely spreading unwarranted speculations about the recent rise in autism diagnoses.



She caused that rise.



The graph above shows the total number of scientific citations for Susan Greenfield's papers, over time. This is as good a measure as any of the influence Greenfield has had over our culture.



The trend is obvious, the growth is dramatic, and the correlation with the modern autism epidemic is undeniable.

Brain Connectivity, Or Head Movement?

"It's pretty painless. Basically you just need to lie there and make sure you don't move your head".


This is what I say to all the girls... who are taking part in my fMRI studies. Head movement is a big problem in fMRI. If your head moves, your brain moves and all fMRI analysis assumes that the brain is perfectly still. Although head movement correction is now a standard part of any analysis software, it's not perfect.

It may be a particular problem in functional connectivity studies, which attempt to measure the degree to which different parts of the brain are "talking" to each other, in terms of correlated neural activity over time. These are extremely popular nowadays. It's even been claimed that this data may help us understand consciousness itself (although we've heard that before).

A new paper offers some important words of caution. It shows that head motion affects estimates of functional connectivity. The more motion, the weaker the measured connectivity in long-range networks, while shorter range connections were stronger. Also, men tended to move more than women.

The effect was small - head movement can't explain more than a small fraction of the variability in connectivity.


The authors looked at 1,000 scans from healthy volunteers. They just had to lie in the scanner at rest. They looked at functional connectivity, using standard "motion correction" methods, and correlated it with head movement (which you can measure very accurately from the MRI images themselves.) Men tended to move more than women. Could this explain why women tend to have higher functional connectivity?

Disconcertingly, head movement was associated with low long range / high short range connections, which is exactly what's been proposed to happen in autism (although in fairness, not all the evidence for this comes from fMRI).

This clearly doesn't prove that the autism studies are all dodgy, but it's an issue. People with autism, and people with almost any mental or physical disorder, on average tend to move more than healthy controls.

One caveat. Could it be that brain activity causes head movement, rather than the reverse? The authors don't consider this. Head movement must come from the brain, of course. Probably from the motor cortex. The fact that motor cortex functional connectivity was positively associated with movement does suggest a possible link.

However, this paper still ought to make anyone who's using functional connectivity worry - at least a little.

Head motion is a particularly insidious confound. It is insidious because it biases between-group studies often in the direction of the hypothesized difference....even though there is considerable variation that is not due to head motion, in any given instance, a between-group difference could be entirely due to motion.

Van Dijk, K., Sabuncu, M., & Buckner, R. (2011). The Influence of Head Motion on Intrinsic Functional Connectivity MRI NeuroImage DOI: 10.1016/j.neuroimage.2011.07.044

Brain Connectivity, Or Head Movement?

"It's pretty painless. Basically you just need to lie there and make sure you don't move your head".


This is what I say to all the girls... who are taking part in my fMRI studies. Head movement is a big problem in fMRI. If your head moves, your brain moves and all fMRI analysis assumes that the brain is perfectly still. Although head movement correction is now a standard part of any analysis software, it's not perfect.

It may be a particular problem in functional connectivity studies, which attempt to measure the degree to which different parts of the brain are "talking" to each other, in terms of correlated neural activity over time. These are extremely popular nowadays. It's even been claimed that this data may help us understand consciousness itself (although we've heard that before).

A new paper offers some important words of caution. It shows that head motion affects estimates of functional connectivity. The more motion, the weaker the measured connectivity in long-range networks, while shorter range connections were stronger. Also, men tended to move more than women.

The effect was small - head movement can't explain more than a small fraction of the variability in connectivity.


The authors looked at 1,000 scans from healthy volunteers. They just had to lie in the scanner at rest. They looked at functional connectivity, using standard "motion correction" methods, and correlated it with head movement (which you can measure very accurately from the MRI images themselves.) Men tended to move more than women. Could this explain why women tend to have higher functional connectivity?

Disconcertingly, head movement was associated with low long range / high short range connections, which is exactly what's been proposed to happen in autism (although in fairness, not all the evidence for this comes from fMRI).

This clearly doesn't prove that the autism studies are all dodgy, but it's an issue. People with autism, and people with almost any mental or physical disorder, on average tend to move more than healthy controls.

One caveat. Could it be that brain activity causes head movement, rather than the reverse? The authors don't consider this. Head movement must come from the brain, of course. Probably from the motor cortex. The fact that motor cortex functional connectivity was positively associated with movement does suggest a possible link.

However, this paper still ought to make anyone who's using functional connectivity worry - at least a little.

Head motion is a particularly insidious confound. It is insidious because it biases between-group studies often in the direction of the hypothesized difference....even though there is considerable variation that is not due to head motion, in any given instance, a between-group difference could be entirely due to motion.

Van Dijk, K., Sabuncu, M., & Buckner, R. (2011). The Influence of Head Motion on Intrinsic Functional Connectivity MRI NeuroImage DOI: 10.1016/j.neuroimage.2011.07.044

The Brain Is Not Made of DNA

A new paper claims to have found A novel functional brain imaging endophenotype of autism.
They used fMRI to show that the brains of teenagers with autism showed no activation differences to looking at smiling happy faces, or afraid faces, compared to unemotional ones. In teens without autism, there was strong activation in many emotional and face-related brain regions. The unaffected brothers and sisters of the autistic people showed intermediate effects.

This is a fine study. The finding that siblings of people with autism have weakened neural responses to emotional faces is quite important as it suggests that this finding correlates (to some degree) with your position on the autism "spectrum".

The abstract of the paper actually downplays this, and says "The response in unaffected siblings did not differ significantly from the response in autism". However, there was a significant linear trend of group, and looking at the graphs, it's clear the siblings were In The Middle, like Malcolm.


There's plenty more nice things you could do with these results, which is an unusally large and rich dataset (120 people - 40 in each group). You could see, for example, whether siblings tend to be similar in terms of neural response. You could see whether the siblings who are most alike in brain response, are closest in symptoms. Or just look a the structural data on brain size and shape to see if there are characteristic differences between siblings that make one of the autistic and the other not.

There are a few problems. Most of the analyses are subject to the non-independence problem, because they defined their regions of interest based on the areas that showed a significant happy vs neutral face effect in the control group. So it's no surprise that when they generated graphs from these areas, the control group showed the strongest effect. However, they also do whole-brain analyses which avoid this problem and I don't think it undermines the main results.

So it's a decent study. But is this a "biomarker", or "endophenotype", as the title of the paper has it?

These are both hot topics in neuroscience at the moment. As the authors put it (emphasis mine):

An endophenotype is a heritable feature associated with a condition, present in affected individuals regardless of whether their condition is manifested, which co-segregates with the condition in families and which is present in unaffected family members at a higher rate than in the general population.

In such family members, endophenotypes represent instances in which genes associated with a particular condition exert measurable effects in individuals in whom they are insufficient to cause the condition itself...

The promise of characterizing endophenotypes lies in their hypothesized intermediate position between genotype and phenotype... the etiology of the endophenotype is likely to be correspondingly simpler: it can be said to be ‘closer to the level of gene action’.

The idea, in other words, is that if we can find a difference in the brains of people with autism, and their unaffected relatives who (presumably) share some of the same genes, we might have found a mechanism by which the genes ultimately cause the symptoms.

It might be easier, then, to find the genes for brain-not-lighting-up-to-happy-faces, than it will be to find genes for autism. Then once we've found those, we can use them to better understand autism.

My concern is that, while in theory endophenotypes seem "closer to the genetics" because they're "biological" rather than "behavioural", this is just a philosophical illusion based on the idea that the mind is not the brain.

We actually have no idea whether brain-not-lighting-up-to-happy-faces is closer to genetics than autistic behaviour. I'd say that our default assumption should be that everything is exactly the same "distance" from DNA, that is to say, everything is the product of complex interactions between genes and environment.

Some things are under the more or less exclusive control of a small number of genes, and these are called "genetic", but it's important not to assume that just because something's "in the brain", it's probably "more genetic" in this sense. The brain is a product of the environment as well.

If you scanned my brain while playing an audio recording of Urda love poetry, not much would happen. I don't know Urdu. In someone who did speak Urdu, all kinds of language and emotional areas would light up. That doesn't mean Urdu-brain-response is genetic. It's exactly as genetic as speaking-Urdu, which isn't genetic.

Spencer, M., Holt, R., Chura, L., Suckling, J., Calder, A., Bullmore, E., & Baron-Cohen, S. (2011). A novel functional brain imaging endophenotype of autism: the neural response to facial expression of emotion Translational Psychiatry, 1 (7) DOI: 10.1038/tp.2011.18

The Brain Is Not Made of DNA

A new paper claims to have found A novel functional brain imaging endophenotype of autism.
They used fMRI to show that the brains of teenagers with autism showed no activation differences to looking at smiling happy faces, or afraid faces, compared to unemotional ones. In teens without autism, there was strong activation in many emotional and face-related brain regions. The unaffected brothers and sisters of the autistic people showed intermediate effects.

This is a fine study. The finding that siblings of people with autism have weakened neural responses to emotional faces is quite important as it suggests that this finding correlates (to some degree) with your position on the autism "spectrum".

The abstract of the paper actually downplays this, and says "The response in unaffected siblings did not differ significantly from the response in autism". However, there was a significant linear trend of group, and looking at the graphs, it's clear the siblings were In The Middle, like Malcolm.


There's plenty more nice things you could do with these results, which is an unusally large and rich dataset (120 people - 40 in each group). You could see, for example, whether siblings tend to be similar in terms of neural response. You could see whether the siblings who are most alike in brain response, are closest in symptoms. Or just look a the structural data on brain size and shape to see if there are characteristic differences between siblings that make one of the autistic and the other not.

There are a few problems. Most of the analyses are subject to the non-independence problem, because they defined their regions of interest based on the areas that showed a significant happy vs neutral face effect in the control group. So it's no surprise that when they generated graphs from these areas, the control group showed the strongest effect. However, they also do whole-brain analyses which avoid this problem and I don't think it undermines the main results.

So it's a decent study. But is this a "biomarker", or "endophenotype", as the title of the paper has it?

These are both hot topics in neuroscience at the moment. As the authors put it (emphasis mine):

An endophenotype is a heritable feature associated with a condition, present in affected individuals regardless of whether their condition is manifested, which co-segregates with the condition in families and which is present in unaffected family members at a higher rate than in the general population.

In such family members, endophenotypes represent instances in which genes associated with a particular condition exert measurable effects in individuals in whom they are insufficient to cause the condition itself...

The promise of characterizing endophenotypes lies in their hypothesized intermediate position between genotype and phenotype... the etiology of the endophenotype is likely to be correspondingly simpler: it can be said to be ‘closer to the level of gene action’.

The idea, in other words, is that if we can find a difference in the brains of people with autism, and their unaffected relatives who (presumably) share some of the same genes, we might have found a mechanism by which the genes ultimately cause the symptoms.

It might be easier, then, to find the genes for brain-not-lighting-up-to-happy-faces, than it will be to find genes for autism. Then once we've found those, we can use them to better understand autism.

My concern is that, while in theory endophenotypes seem "closer to the genetics" because they're "biological" rather than "behavioural", this is just a philosophical illusion based on the idea that the mind is not the brain.

We actually have no idea whether brain-not-lighting-up-to-happy-faces is closer to genetics than autistic behaviour. I'd say that our default assumption should be that everything is exactly the same "distance" from DNA, that is to say, everything is the product of complex interactions between genes and environment.

Some things are under the more or less exclusive control of a small number of genes, and these are called "genetic", but it's important not to assume that just because something's "in the brain", it's probably "more genetic" in this sense. The brain is a product of the environment as well.

If you scanned my brain while playing an audio recording of Urda love poetry, not much would happen. I don't know Urdu. In someone who did speak Urdu, all kinds of language and emotional areas would light up. That doesn't mean Urdu-brain-response is genetic. It's exactly as genetic as speaking-Urdu, which isn't genetic.

Spencer, M., Holt, R., Chura, L., Suckling, J., Calder, A., Bullmore, E., & Baron-Cohen, S. (2011). A novel functional brain imaging endophenotype of autism: the neural response to facial expression of emotion Translational Psychiatry, 1 (7) DOI: 10.1038/tp.2011.18

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

Gamma Waves: The Brain's Clock, Or Neural Noise?

Gamma waves are very hot at the moment.


Gamma band activity is a term for electrical oscillations recorded from the brain that have a frequency of over 25 Hz. In most brains, a peak frequency of about 40 Hz is seen. This makes gamma waves the fastest brain waves.

If you believe some recent claims, gamma waves are the answer to all the mysteries of life and the universe. They're said to underlie the symptoms of schizophrenia and autism, and they've been invoked to answer deep questions such as the binding problem and maybe conciousness itself. You can even buy a Nintendo game that promises to boost them.

A new paper from Burns et al casts doubt on all of these grand claims. Gamma-based theories of brain function all assume that gamma waves act a bit like a clock, with a consistent rhythm of about 40 Hz. Activity of about 40 Hz is indeed observed in brain recordings but is that just because the brain is randomly generating all kinds of signals, and only the 40 Hz ones "get through"?

To put it another way, imagine that you got a letter in the mail at 9 am every morning. That could be because someone is sending you one letter each day like clockwork. But it could also be that loads of people are sending you letters at random times, and your mailman only has room in his sack to deliver one each morning.

Here's the key data, recorded using electrodes implanted into the brains of two male macaque monkeys:


This shows that the monkey data closely resemble what you'd expect if gamma activity were filtered noise, and are not what you'd see if it were a more meaningful "clock". The "triangle" on the graph shows the number of bursts of a given frequency and duration.
The data also show that the phase of the gamma activity isn't consistent, which it would be if it were clocklike. In fact, the phases change entirely randomly.

So if gamma is just "filtered noise", what's the "filter"? Why 40 Hz, not 80 or 4000? Probably because this is just the maximum frequency at which neurons can fire. It takes a certain finite amount of time for cells to communicate with each other: a silicon chip can get a clock speed of many billions of hertz, but a cell just physically can't.

There's a catch, though. These monkeys were asleep, anaesthetized with the powerful opiate sufentanil. This is a good choice of drug: unlike most other sedatives and anaesthetics, you wouldn't expect an opiate to directly affect gamma oscillations. But still. If you believe that coherent gamma waves are the key to high-level concious experience, as many do, you might not expect to see much of that in the primary visual cortex in asleep animals.

However, this is clearly a very important issue, and it's not the first gamma-skeptic paper. In 2008, Yuval-Greenberg et al reported that many attempts to measure gamma activity using EEG were contaminated by electrical activity from scalp muscles. Rather than coming from the brain, the "gamma" activity reflected nothing more than tiny eye movements. The implications are still being debated.

This paper attacks the gamma hypothesis from a completely different angle, saying that even the "real" gamma in the brain, may be nothing more interesting than filtered noise.

Burns SP, Xing D, & Shapley RM (2011). Is gamma-band activity in the local field potential of v1 cortex a "clock" or filtered noise? The Journal of neuroscience : the official journal of the Society for Neuroscience, 31 (26), 9658-64 PMID: 21715631

Gamma Waves: The Brain's Clock, Or Neural Noise?

Gamma waves are very hot at the moment.


Gamma band activity is a term for electrical oscillations recorded from the brain that have a frequency of over 25 Hz. In most brains, a peak frequency of about 40 Hz is seen. This makes gamma waves the fastest brain waves.

If you believe some recent claims, gamma waves are the answer to all the mysteries of life and the universe. They're said to underlie the symptoms of schizophrenia and autism, and they've been invoked to answer deep questions such as the binding problem and maybe conciousness itself. You can even buy a Nintendo game that promises to boost them.

A new paper from Burns et al casts doubt on all of these grand claims. Gamma-based theories of brain function all assume that gamma waves act a bit like a clock, with a consistent rhythm of about 40 Hz. Activity of about 40 Hz is indeed observed in brain recordings but is that just because the brain is randomly generating all kinds of signals, and only the 40 Hz ones "get through"?

To put it another way, imagine that you got a letter in the mail at 9 am every morning. That could be because someone is sending you one letter each day like clockwork. But it could also be that loads of people are sending you letters at random times, and your mailman only has room in his sack to deliver one each morning.

Here's the key data, recorded using electrodes implanted into the brains of two male macaque monkeys:


This shows that the monkey data closely resemble what you'd expect if gamma activity were filtered noise, and are not what you'd see if it were a more meaningful "clock". The "triangle" on the graph shows the number of bursts of a given frequency and duration.
The data also show that the phase of the gamma activity isn't consistent, which it would be if it were clocklike. In fact, the phases change entirely randomly.

So if gamma is just "filtered noise", what's the "filter"? Why 40 Hz, not 80 or 4000? Probably because this is just the maximum frequency at which neurons can fire. It takes a certain finite amount of time for cells to communicate with each other: a silicon chip can get a clock speed of many billions of hertz, but a cell just physically can't.

There's a catch, though. These monkeys were asleep, anaesthetized with the powerful opiate sufentanil. This is a good choice of drug: unlike most other sedatives and anaesthetics, you wouldn't expect an opiate to directly affect gamma oscillations. But still. If you believe that coherent gamma waves are the key to high-level concious experience, as many do, you might not expect to see much of that in the primary visual cortex in asleep animals.

However, this is clearly a very important issue, and it's not the first gamma-skeptic paper. In 2008, Yuval-Greenberg et al reported that many attempts to measure gamma activity using EEG were contaminated by electrical activity from scalp muscles. Rather than coming from the brain, the "gamma" activity reflected nothing more than tiny eye movements. The implications are still being debated.

This paper attacks the gamma hypothesis from a completely different angle, saying that even the "real" gamma in the brain, may be nothing more interesting than filtered noise.

Burns SP, Xing D, & Shapley RM (2011). Is gamma-band activity in the local field potential of v1 cortex a "clock" or filtered noise? The Journal of neuroscience : the official journal of the Society for Neuroscience, 31 (26), 9658-64 PMID: 21715631

Eagle-Eyed Autism? No.

An interesting and refreshing paper from Simon Baron-Cohen's autism group from Cambridge. The results themselves are pretty boring - they found that people with autism have normal visual acuity.


But the story behind it is rather spicy.

Back in 2009, a Cambridge group - different authors, but led by "SBC", published a report claiming that people with autism have exceptionally acute vision. Their average visual acuity was claimed to be 2.8

On this scale, 1.0 is defined as normal, and a sharp-eyed young adult with excellent eyesight would get about 1.5. 2.8 means nearly three times as good. Which is, literally, superhuman - a bird of prey would be happy with that. The paper was titled "Eagle-Eyed Visual Acuity In Autism".

However, what followed was straight out of the Book of Obadiah - "Though you soar like the eagle ... from there I will bring you down, sayeth the Lord". Or in this case, sayeth two experts in visual acuity research, Bach and Dakin, whose qualifications included the fact that they wrote the software used in the original study, which is online here.

They wrote a knock-down critique, arguing that the results were a result of using the wrong settings, which meant that the task was extremely easy. In fact, even perfect performance would only correspond to an acuity of less than 1.

You could never make a test so hard that it would require an acuity of 3.0 on a standard computer. Pixels are just too big. A single pixel is easy to spot, for someone of normal-ish vision. The only way to make it harder would be to use a special, extremely high-res monitor, or to get people to sit a long way from the screen.

So how did a result of nearly 3.0 come out? Because they also turned on data extrapolation, basically saying that if you really aced the easy task, you'd probably do quite well on a harder one. This might be sensible in some situations, but it breaks down when the task was so easy. The autistics seemed to have super vision because they got, say, 99% right, as opposed to 98%.

Yet the present paper represents a happy ending as it's written by a combined team of Cambridge people, and Bach and Dakin as well, although the lead authors of the original weren't on it. This time, they used appropriate methods - they got people to sit 4 meters from the screen. To be extra sure, they also gave everyone an eye exam before testing.

And they found no difference at all. The present paper is heartening - rather than grimly sticking to their guns, they admitted their error.


This story should however serve as a cautionary tale; I previously wrote about the fact that in science, a little mistake can cause a lot of problems. This is one of those cases, although arguably there were two seperate mistakes, but one, the extrapolation, was only a problem because of the main mistake, the big pixels.

Tavassoli T, Latham K, Bach M, Dakin SC, & Baron-Cohen S (2011). Psychophysical measures of visual acuity in autism spectrum conditions. Vision research PMID: 21704058

Eagle-Eyed Autism? No.

An interesting and refreshing paper from Simon Baron-Cohen's autism group from Cambridge. The results themselves are pretty boring - they found that people with autism have normal visual acuity.


But the story behind it is rather spicy.

Back in 2009, a Cambridge group - different authors, but led by "SBC", published a report claiming that people with autism have exceptionally acute vision. Their average visual acuity was claimed to be 2.8

On this scale, 1.0 is defined as normal, and a sharp-eyed young adult with excellent eyesight would get about 1.5. 2.8 means nearly three times as good. Which is, literally, superhuman - a bird of prey would be happy with that. The paper was titled "Eagle-Eyed Visual Acuity In Autism".

However, what followed was straight out of the Book of Obadiah - "Though you soar like the eagle ... from there I will bring you down, sayeth the Lord". Or in this case, sayeth two experts in visual acuity research, Bach and Dakin, whose qualifications included the fact that they wrote the software used in the original study, which is online here.

They wrote a knock-down critique, arguing that the results were a result of using the wrong settings, which meant that the task was extremely easy. In fact, even perfect performance would only correspond to an acuity of less than 1.

You could never make a test so hard that it would require an acuity of 3.0 on a standard computer. Pixels are just too big. A single pixel is easy to spot, for someone of normal-ish vision. The only way to make it harder would be to use a special, extremely high-res monitor, or to get people to sit a long way from the screen.

So how did a result of nearly 3.0 come out? Because they also turned on data extrapolation, basically saying that if you really aced the easy task, you'd probably do quite well on a harder one. This might be sensible in some situations, but it breaks down when the task was so easy. The autistics seemed to have super vision because they got, say, 99% right, as opposed to 98%.

Yet the present paper represents a happy ending as it's written by a combined team of Cambridge people, and Bach and Dakin as well, although the lead authors of the original weren't on it. This time, they used appropriate methods - they got people to sit 4 meters from the screen. To be extra sure, they also gave everyone an eye exam before testing.

And they found no difference at all. The present paper is heartening - rather than grimly sticking to their guns, they admitted their error.


This story should however serve as a cautionary tale; I previously wrote about the fact that in science, a little mistake can cause a lot of problems. This is one of those cases, although arguably there were two seperate mistakes, but one, the extrapolation, was only a problem because of the main mistake, the big pixels.

Tavassoli T, Latham K, Bach M, Dakin SC, & Baron-Cohen S (2011). Psychophysical measures of visual acuity in autism spectrum conditions. Vision research PMID: 21704058

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