Autism, Testosterone and Eugenics

The media's all too often shabby treatment of neuroscience and psychology research doesn't just propagate bad science - it means that the really interesting and important bits go unreported. This is what's just happened with the controversy surrounding a paper from the Autism Research Center (ARC) at Cambridge University - Bonnie Aeyeung et. al.'s Fetal Testosterone and Autistic Traits. For research published in a journal with an impact factor of 1.538 (i.e. not good), it's certainly attracted plenty of attention - but for all the wrong reasons.


The Autism Research Center is headed by the dashing Simon Baron-Cohen, also one of the authors on the paper. He's probably the world's best-known autism researcher, and the author of some excellent books on the subject including the classic Mindblindness and The Essential Difference. Mindblindness, in particular, probably deserves a lot of the credit for interesting a generation of psychologists in autism. A big cheese, in other words. Surely his greatest achievement, however, is being Borat's cousin.

Baron-Cohen is famous for his theory that the characteristic features of autism are exaggerated versions of the allegedly characteristic features of male, as opposed to female, cognition. Namely, autistic people have difficulties understanding the emotions and behaviour of other people ("empathizing"), but may show excellent rote memory and understanding of abstract, mathematical or mechanical systems ("systematizing"). He and his colleagues have also hypothesised that an excess of the well-known masculinizing hormone testosterone, could be responsible for the hyper-male brains of autistics, just as testosterone is responsible for the development of masculine traits in boys. Amongst other things this would explain why rates of diagnosed autistic spectrum disorders are several times higher in boys than in girls.

Now, this is one of those wide-ranging theories which serves to drive research, rather than strictly following from the evidence. It's a bold idea, but there is, at the moment, not enough data to confirm or reject this idea. The simple view that testosterone = maleness = autism is almost certainly wrong, but it's a neat theory, there's clearly something to it, and, as one of the commentators on the paper puts it

To date, no theory of autism has provided such a connecting thread linking etiology, neuropsychology and neural bases of autism.

Anyway, the paper reports on an association between testosterone levels in the womb and later "autistic traits" in childhood. 235 healthy children were studied; for all of these kids, the levels of testosterone in the womb during pregnancy were known, because their mothers had had amniocentesis, collecting a sample of fluid from the womb. Amniocentesis is not risk-free and it can't be done for research purposes, but the mothers here got amniocentesis for medical reasons and then agreed to take part in research as well. Testosterone levels in the amniotic fluid were measured; notably, this probably represents testosterone produced by the fetus itself, rather than the mother.

The headline finding was that fetal testosterone (fT) levels were correlated with later "autistic traits", as judged by the mothers, who filled out questionaires about their kid's behaviour at the age of about 8. Here's a nice plot showing the correlation. The vertical axis, "AQ-child total", is the parent's total reported score on the "Autism Quotient" questionaire. Higher scores are meant to indicate autism-like traits (although see below). You'll also notice that fT levels are much higher in the boy fetuses than in the girl fetuses - not surprisingly. That's it - a statistically significant association, but there is still a lot of scatter on the plot. The correlation was still significant if the very high-scoring children were ignored. A similar pattern emerged using a different autism rating scale, but was less significant - probably because many scores were very low.
So, this was a perfectly decent study with an interesting result, but it's only a correlation, and not an especially strong one. How did this get written up? New research brings autism screening closer to reality puffed the Guardian's front page! They suggested that measuring fetal testosterone levels might be a way of testing for autism pre-natally, thus sparking off an entirely formulaic debate about the ethics of selective abortion, the usual denunciations of "eugenics", etc. Long story short - Catholics are against it, the National Autistic Society say it's a dilemma, while a family doctor on Comment is Free is unsure about the "test" because she can't read the article: she doesn't have access to the journal.

Lest it be said that the ethical debate is important in itself, even if the details of the testosterone-based screening test might be inaccurate, bear in mind that "testing for autism" is likely to raise unique issues. Are we talking about a test which could distinguish "low-functioning autism" - which can leave children unable to lead anything like a normal life - from "high-functioning autism", sometimes associated with incredible intellectual achievement? Would the test distinguish classical high-functioning autism from Asperger's? When and if a test is developed, these will be crucial questions. You cannot simply speculate about "a test for autism" in the abstract.

Anyway, after a few days of this nonsense Baron-Cohen rightly protested that the paper had nothing to do with prenatal testing, and that such testing isn't on the horizon yet.

The new research was not about autism screening; the new research has not discovered that a high level of testosterone in prenatal tests is an indicator of autism; autism spectrum disorder has not been linked to high levels of testosterone in the womb; and tests (of autism) in the womb do not allow termination of pregnancies.

Most importantly, there were no autistic kids in the study - all of the children were "normal", although some were rated highly on the autism measures. Moreover, as the plot above shows, any testosterone-based screening test would be very inaccurate. Which is why no experts proposed one.

Just like last time. Back in 2007 the Observer (the Sunday version of the Guardian) ran a front-page article about Simon Baron-Cohen's work on the epidemiology of autism. They said that he'd found that autism rates in Britain were "surging"; they probably aren't, and Baron-Cohen's data didn't show that they were, but despite this the Observer took weeks to clarify the issue (for details of the saga, see Bad Science.) In both cases, some important research about autism from Cambridge ended up on the front page of the newspaper, but the debate which followed completely missed the real point. It would have been better for all concerned if the research had never caught the attention of journalists at all.

The actual study in this case is very interesting, as are the three academic commentaries and a response from the authors published alongside it. I can't cover all of the nuances of the debate, but some of the points of interest include: the question of whether the Autism Quotient (AQ) questionaire actually measures autistic behaviours, or just male behaviours; the point that it may be testosterone present in baby boys shortly after birth, not in the womb, which is most important; and the interesting case of children suffering from Congenital Adrenal Hyperplasia, a genetic disorder leading to excessive testosterone levels; Baron-Cohen et. al. suggest that girls with this disorder show some autism-like traits, but this is controversial. Clearly, this is a crucial point.

Overall, while it's too soon to pass judgement on the extreme male brain theory or the testosterone hypothesis, both must be taken seriously. As for autism prenatal testing, I suspect that this will only come when more of the genetic causes of autism are identified. There is no single "gene for autism"; currently a couple of genes responsible for a small % of autism cases are known: CNTNAP2, for example.

Once we have a good understanding of the many genes which can lead to the many different forms of autistic-spectrum disorders, genetic testing for autism will be possible; I doubt that testosterone levels or anything else will serve as a non-genetic marker, because autism almost certainly has many different causes, and many different associated biochemical abnormalities. Maybe I'm wrong, but even so, if you're worried about hypothetical people aborting hypothetical autistic fetuses, you don't have to worry quite yet. Actual children are dying in Zimbabwe - worry about them.

[BPSDB]

Bonnie Auyeung, Simon Baron-Cohen, Emma Ashwin, Rebecca Knickmeyer, Kevin Taylor, Gerald Hackett (2009). Fetal testosterone and autistic traits British Journal of Psychology, 100 (1), 1-22 DOI: 10.1348/000712608X311731

Autism, Testosterone and Eugenics

The media's all too often shabby treatment of neuroscience and psychology research doesn't just propagate bad science - it means that the really interesting and important bits go unreported. This is what's just happened with the controversy surrounding a paper from the Autism Research Center (ARC) at Cambridge University - Bonnie Aeyeung et. al.'s Fetal Testosterone and Autistic Traits. For research published in a journal with an impact factor of 1.538 (i.e. not good), it's certainly attracted plenty of attention - but for all the wrong reasons.


The Autism Research Center is headed by the dashing Simon Baron-Cohen, also one of the authors on the paper. He's probably the world's best-known autism researcher, and the author of some excellent books on the subject including the classic Mindblindness and The Essential Difference. Mindblindness, in particular, probably deserves a lot of the credit for interesting a generation of psychologists in autism. A big cheese, in other words. Surely his greatest achievement, however, is being Borat's cousin.

Baron-Cohen is famous for his theory that the characteristic features of autism are exaggerated versions of the allegedly characteristic features of male, as opposed to female, cognition. Namely, autistic people have difficulties understanding the emotions and behaviour of other people ("empathizing"), but may show excellent rote memory and understanding of abstract, mathematical or mechanical systems ("systematizing"). He and his colleagues have also hypothesised that an excess of the well-known masculinizing hormone testosterone, could be responsible for the hyper-male brains of autistics, just as testosterone is responsible for the development of masculine traits in boys. Amongst other things this would explain why rates of diagnosed autistic spectrum disorders are several times higher in boys than in girls.

Now, this is one of those wide-ranging theories which serves to drive research, rather than strictly following from the evidence. It's a bold idea, but there is, at the moment, not enough data to confirm or reject this idea. The simple view that testosterone = maleness = autism is almost certainly wrong, but it's a neat theory, there's clearly something to it, and, as one of the commentators on the paper puts it

To date, no theory of autism has provided such a connecting thread linking etiology, neuropsychology and neural bases of autism.

Anyway, the paper reports on an association between testosterone levels in the womb and later "autistic traits" in childhood. 235 healthy children were studied; for all of these kids, the levels of testosterone in the womb during pregnancy were known, because their mothers had had amniocentesis, collecting a sample of fluid from the womb. Amniocentesis is not risk-free and it can't be done for research purposes, but the mothers here got amniocentesis for medical reasons and then agreed to take part in research as well. Testosterone levels in the amniotic fluid were measured; notably, this probably represents testosterone produced by the fetus itself, rather than the mother.

The headline finding was that fetal testosterone (fT) levels were correlated with later "autistic traits", as judged by the mothers, who filled out questionaires about their kid's behaviour at the age of about 8. Here's a nice plot showing the correlation. The vertical axis, "AQ-child total", is the parent's total reported score on the "Autism Quotient" questionaire. Higher scores are meant to indicate autism-like traits (although see below). You'll also notice that fT levels are much higher in the boy fetuses than in the girl fetuses - not surprisingly. That's it - a statistically significant association, but there is still a lot of scatter on the plot. The correlation was still significant if the very high-scoring children were ignored. A similar pattern emerged using a different autism rating scale, but was less significant - probably because many scores were very low.
So, this was a perfectly decent study with an interesting result, but it's only a correlation, and not an especially strong one. How did this get written up? New research brings autism screening closer to reality puffed the Guardian's front page! They suggested that measuring fetal testosterone levels might be a way of testing for autism pre-natally, thus sparking off an entirely formulaic debate about the ethics of selective abortion, the usual denunciations of "eugenics", etc. Long story short - Catholics are against it, the National Autistic Society say it's a dilemma, while a family doctor on Comment is Free is unsure about the "test" because she can't read the article: she doesn't have access to the journal.

Lest it be said that the ethical debate is important in itself, even if the details of the testosterone-based screening test might be inaccurate, bear in mind that "testing for autism" is likely to raise unique issues. Are we talking about a test which could distinguish "low-functioning autism" - which can leave children unable to lead anything like a normal life - from "high-functioning autism", sometimes associated with incredible intellectual achievement? Would the test distinguish classical high-functioning autism from Asperger's? When and if a test is developed, these will be crucial questions. You cannot simply speculate about "a test for autism" in the abstract.

Anyway, after a few days of this nonsense Baron-Cohen rightly protested that the paper had nothing to do with prenatal testing, and that such testing isn't on the horizon yet.

The new research was not about autism screening; the new research has not discovered that a high level of testosterone in prenatal tests is an indicator of autism; autism spectrum disorder has not been linked to high levels of testosterone in the womb; and tests (of autism) in the womb do not allow termination of pregnancies.

Most importantly, there were no autistic kids in the study - all of the children were "normal", although some were rated highly on the autism measures. Moreover, as the plot above shows, any testosterone-based screening test would be very inaccurate. Which is why no experts proposed one.

Just like last time. Back in 2007 the Observer (the Sunday version of the Guardian) ran a front-page article about Simon Baron-Cohen's work on the epidemiology of autism. They said that he'd found that autism rates in Britain were "surging"; they probably aren't, and Baron-Cohen's data didn't show that they were, but despite this the Observer took weeks to clarify the issue (for details of the saga, see Bad Science.) In both cases, some important research about autism from Cambridge ended up on the front page of the newspaper, but the debate which followed completely missed the real point. It would have been better for all concerned if the research had never caught the attention of journalists at all.

The actual study in this case is very interesting, as are the three academic commentaries and a response from the authors published alongside it. I can't cover all of the nuances of the debate, but some of the points of interest include: the question of whether the Autism Quotient (AQ) questionaire actually measures autistic behaviours, or just male behaviours; the point that it may be testosterone present in baby boys shortly after birth, not in the womb, which is most important; and the interesting case of children suffering from Congenital Adrenal Hyperplasia, a genetic disorder leading to excessive testosterone levels; Baron-Cohen et. al. suggest that girls with this disorder show some autism-like traits, but this is controversial. Clearly, this is a crucial point.

Overall, while it's too soon to pass judgement on the extreme male brain theory or the testosterone hypothesis, both must be taken seriously. As for autism prenatal testing, I suspect that this will only come when more of the genetic causes of autism are identified. There is no single "gene for autism"; currently a couple of genes responsible for a small % of autism cases are known: CNTNAP2, for example.

Once we have a good understanding of the many genes which can lead to the many different forms of autistic-spectrum disorders, genetic testing for autism will be possible; I doubt that testosterone levels or anything else will serve as a non-genetic marker, because autism almost certainly has many different causes, and many different associated biochemical abnormalities. Maybe I'm wrong, but even so, if you're worried about hypothetical people aborting hypothetical autistic fetuses, you don't have to worry quite yet. Actual children are dying in Zimbabwe - worry about them.

[BPSDB]

Bonnie Auyeung, Simon Baron-Cohen, Emma Ashwin, Rebecca Knickmeyer, Kevin Taylor, Gerald Hackett (2009). Fetal testosterone and autistic traits British Journal of Psychology, 100 (1), 1-22 DOI: 10.1348/000712608X311731

Prozac and Old Mice

A while back, I wrote about an important paper which cast doubt on the "neurogenesis hypothesis" of antidepressant drug action, which I summarized as

...the proposal that antidepressants work by promoting the survival and proliferation of new neurones in certain areas of the brain - the "neurogenesis hypothesis". Neurogenesis, the birth of new cells from stem cells, occurs in a couple of very specific regions of the adult brain, including the elaborately named subgranular zone (SGZ) of the dentate gyrus (DG) of the hippocampus. Many experiments on animals have shown that chronic stress, and injections of the "stress hormone" corticosterone, can suppress neurogenesis, while a wide range of antidepressants block this effect of stress and promote neurogenesis. (Other evidence shows that antidepressants probably do this by inducing the expression of neurotrophic signalling proteins, like BDNF.)

It's a popular theory at the moment, not least because it's the only real alternative to the older, much-maligned and certainly incomplete monoamine hypothesis of antidepressants. But the neurogenesis hypothesis has problems of its own. A new paper claims to add to what seems like a growing list of counter-examples: Ageing abolishes the effects of fluoxetine on neurogenesis.

The researchers, Couillard-Despres et. al. from the University of Regensburg in Germany, found that fluoxetine (Prozac) enhances hippocampal neurogenesis in mice - as expected - but found in addition that this only holds true in young mice. In middle-aged and older mice, there was no such effect. That's a new finding, and a very important one.

More specifically, the (male) mice were given injections of Prozac for two weeks each. Compared to mice given placebo injections, the mice on Prozac showed

increased survival and the frequency of neuronal marker expression in newly generated cells of the hippocampus in the young adult group (that is 100 days of age) only. No significant effects on neurogenesis could be detected in fluoxetine-treated adult and elderly mice (200 and over 400 days of age).

For mice, 100 days old corresponds to a human age of about 20 years; 200 days is 35 and 400 days is 65 years. The graph here shows the number of BrdU-labelled cells in the dentate gyrus, a measure of neural progenitor cell survival. As you can see, although Prozac robustly increased BrdU+ cell counts in the 100 day old mice, this effect was much less prominent (although perhaps still present a bit?) in the older mice.

It's already well known that hippocampal neurogenesis is age dependent. Young animals (and people) have lots of new neurones being generated, but the rate progressively and inevitably declines with age. This has always been a problem for the simple hypothesis that reduced neurogenesis causes depression, because if that were the case, we'd all be paralyzed by despair by the age of 50. Despite this, it remained plausible that antidepressants worked by increasing neurogenesis, but this new evidence suggests otherwise.

Or does it? What if it turns out that fluoxetine has no antidepressant-like effects in old rodents? In that case, the neurogenesis hypothesis would be supported, not weakened, by this evidence. The author's of the paper don't even consider this possibility, which is a little odd. They do note that antidepressants are effective in older people with depression, but given that this is a paper about mice that's not the same thing. Someone needs to find out whether Prozac has anti-depressant-like effects in the same kind of old mice as those used in this study. If so, the neurogenesis hypothesis will be looking pretty fragile.

This should also serve as a reminder that lab mice are animals, not research robots. They get old, like the rest of us, and research done only on young mice, or male mice, or a certain breed of mice, may not be applicable to others. I have two cats: if you stroke the grey one on the belly, she'll purr contentedly. But if you foolishly assume that the tabby one is the same, you'll get bitten pretty quickly...

S Couillard-Despres, C Wuertinger, M Kandasamy, M Caioni, K Stadler, R Aigner, U Bogdahn, L Aigner (2009). Ageing abolishes the effects of fluoxetine on neurogenesis Molecular Psychiatry DOI: 10.1038/mp.2008.147

Prozac and Old Mice

A while back, I wrote about an important paper which cast doubt on the "neurogenesis hypothesis" of antidepressant drug action, which I summarized as

...the proposal that antidepressants work by promoting the survival and proliferation of new neurones in certain areas of the brain - the "neurogenesis hypothesis". Neurogenesis, the birth of new cells from stem cells, occurs in a couple of very specific regions of the adult brain, including the elaborately named subgranular zone (SGZ) of the dentate gyrus (DG) of the hippocampus. Many experiments on animals have shown that chronic stress, and injections of the "stress hormone" corticosterone, can suppress neurogenesis, while a wide range of antidepressants block this effect of stress and promote neurogenesis. (Other evidence shows that antidepressants probably do this by inducing the expression of neurotrophic signalling proteins, like BDNF.)

It's a popular theory at the moment, not least because it's the only real alternative to the older, much-maligned and certainly incomplete monoamine hypothesis of antidepressants. But the neurogenesis hypothesis has problems of its own. A new paper claims to add to what seems like a growing list of counter-examples: Ageing abolishes the effects of fluoxetine on neurogenesis.

The researchers, Couillard-Despres et. al. from the University of Regensburg in Germany, found that fluoxetine (Prozac) enhances hippocampal neurogenesis in mice - as expected - but found in addition that this only holds true in young mice. In middle-aged and older mice, there was no such effect. That's a new finding, and a very important one.

More specifically, the (male) mice were given injections of Prozac for two weeks each. Compared to mice given placebo injections, the mice on Prozac showed

increased survival and the frequency of neuronal marker expression in newly generated cells of the hippocampus in the young adult group (that is 100 days of age) only. No significant effects on neurogenesis could be detected in fluoxetine-treated adult and elderly mice (200 and over 400 days of age).

For mice, 100 days old corresponds to a human age of about 20 years; 200 days is 35 and 400 days is 65 years. The graph here shows the number of BrdU-labelled cells in the dentate gyrus, a measure of neural progenitor cell survival. As you can see, although Prozac robustly increased BrdU+ cell counts in the 100 day old mice, this effect was much less prominent (although perhaps still present a bit?) in the older mice.

It's already well known that hippocampal neurogenesis is age dependent. Young animals (and people) have lots of new neurones being generated, but the rate progressively and inevitably declines with age. This has always been a problem for the simple hypothesis that reduced neurogenesis causes depression, because if that were the case, we'd all be paralyzed by despair by the age of 50. Despite this, it remained plausible that antidepressants worked by increasing neurogenesis, but this new evidence suggests otherwise.

Or does it? What if it turns out that fluoxetine has no antidepressant-like effects in old rodents? In that case, the neurogenesis hypothesis would be supported, not weakened, by this evidence. The author's of the paper don't even consider this possibility, which is a little odd. They do note that antidepressants are effective in older people with depression, but given that this is a paper about mice that's not the same thing. Someone needs to find out whether Prozac has anti-depressant-like effects in the same kind of old mice as those used in this study. If so, the neurogenesis hypothesis will be looking pretty fragile.

This should also serve as a reminder that lab mice are animals, not research robots. They get old, like the rest of us, and research done only on young mice, or male mice, or a certain breed of mice, may not be applicable to others. I have two cats: if you stroke the grey one on the belly, she'll purr contentedly. But if you foolishly assume that the tabby one is the same, you'll get bitten pretty quickly...

S Couillard-Despres, C Wuertinger, M Kandasamy, M Caioni, K Stadler, R Aigner, U Bogdahn, L Aigner (2009). Ageing abolishes the effects of fluoxetine on neurogenesis Molecular Psychiatry DOI: 10.1038/mp.2008.147

Biases, Fallacies and other Distractions

One of the pitfalls of debate is the temptation to indulge in tearing down an opponent's arguments. It's fun, if you're stuck behind a keyboard but still feeling the primal urge to bash something's head in with a rock. Yet if you're interested in the truth about something, the only thing that should concern you is the facts, not the arguments that happen to be made about them.

Plenty has been written about arguments and how they can be bad: sins against good sense are called "fallacies" and there are many lists of them. Some of the more popular fallacies have become household names - ad hominem attacks, the appeal to authority, and everyone's favorite the straw man argument.

Likewise, cognitive psychologists have done much to name and catalogue the various ways in which our minds can decieve us. Under the blanket name of "biases" many of these are well known - there's confirmation bias, cognitive dissonance, rationalization, and so on.

There's a reason why so much has been said about fallacies and biases. They're out there, and they're a problem. When you set your mind to it, you can find them almost anywhere - no matter who you are. This, for example, is written by someone who believes that HIV does not cause AIDS. By most standards, this makes him a kook. And he probably is a kook, about AIDS, but he’s not stupid. He makes some perfectly sensible points about cognitive dissonance and the psychology of science. And here, he offers further words of wisdom:

I have no satisfactory answer to offer, unfortunately, for how AIDStruthers could be brought to useful mutual discussion.
...
Here’s a criterion for whether a discussion is genuinely substantive or not, directed at clarification and increased understanding: no personal comments adorn the to-and-fro. If B appears not to understand what A is saying, then A looks for other ways of presenting the case, A doesn’t simply keep repeating the same assertions spiced with “Why can’t you…?”, and the like. [Added 28 December: Another hallmark of the non-substantive comments is that the commentator not only keeps harping on the same thing but does so by return e-mail, leaving no time to consider what s/he is replying to; see Burun's admission of suffering from that failing.]
...
One lesson from experience is that the aim of Rethinkers cannot be to convince the AIDStruthers. It soon becomes a sheer waste of time to attempt to argue substance with them; a waste of time because you can’t learn anything from them, and they are incapable of learning anything from you. Rethinkers and Skeptics should address the bystanders, onlookers, the unengaged “silent majority”. There seem always to be with us some people who cheerfully continue to believe that the Earth is only about 6,000-10,000 years old, and many other things that most of us judge to be utterly disproved by factual evidence.

That could have come straight from the pen of such pillars of scientific respectability as Carl Sagan or Orac - until you remember that by "Rethinkers" and "Skeptics" he means people who don't believe that HIV causes AIDS, while "AIDStruthers" is his term for those who do, that is, almost every medical and scientific professional.

The lesson here is that you don't have to be right in order to notice that people who disagree with you are irrational, or that much of the opposition to your belief is dogmatic. The sad fact is that stubborness and a tendency to dogmatism are a part of human nature and it's very hard to escape from them; likewise, it's very hard to make a complex argument without saying something at least technically fallacious (that witty aside? Ad hominem attack!)

The point is that none of this matters. If something is true, then it's true even if everyone who believes it is a dogmatic maniac. So it's certainly true even if the only people you know who believe it are idiots. What's the chance that you've argued with the smartest Christian ever, or the best informed opponent of homeopathy? In which case - the fallacies and biases of the people you have argued with certainly don't matter. In an argument, the only thing of importance is what the facts are, and the way to find out is to look at the evidence.

If you're taking the time to name and shame the fallacies in someone's reasoning or to diagnose their biases, then you're not talking about the evidence - you're talking about your opponent(s). Why are you so fascinated by him...? To spend time lamenting the irrationality of your opponents is unhealthy. The only people who have a reason to care about other people’s fallacies and biases are psychologists. Daniel Kahneman got half a Nobel Prize for his work on cognitive biases - it's his thing. But if your thing is HIV/AIDS, or evolution, or vaccines and autism, or whatever, then it's far from clear that you have any legitimate interest in your opponent's flaws. In all likelihood, they are no more flawed than anyone else - or even if they are, their real problem is not that they're making ad hominem attacks (or whatever), but that they're wrong.

So when barely-coherent columnist Peter Hitchens writes in the Daily Mail about wind farms

If visitors from another galaxy really are going round destroying wind turbines, then it is the proof we have been waiting for that aliens are more intelligent than we are.

The swivel-eyed, intolerant cult, which endlessly shrieks – without proof – that global warming is man-made, has produced many sad effects.

The point is not that people who believe that global warming is man made are not a cult. They're not, but even if they were, it wouldn't matter. The swiveliness of their eyes or the pitch of their voice is not obviously relevant either.

Of course, if you're out to have fun bashing heads, or writing columns for the Daily Mail, then go ahead. Learn the names of as many fallacies and biases as you can (including the Latin names if possible - that's always extra impressive) and go nuts. But if you're serious about establishing or discussing the truth about something, then there is only one set of biases and fallacies you ought to care about – your own.

[BPSDB]

Biases, Fallacies and other Distractions

One of the pitfalls of debate is the temptation to indulge in tearing down an opponent's arguments. It's fun, if you're stuck behind a keyboard but still feeling the primal urge to bash something's head in with a rock. Yet if you're interested in the truth about something, the only thing that should concern you is the facts, not the arguments that happen to be made about them.

Plenty has been written about arguments and how they can be bad: sins against good sense are called "fallacies" and there are many lists of them. Some of the more popular fallacies have become household names - ad hominem attacks, the appeal to authority, and everyone's favorite the straw man argument.

Likewise, cognitive psychologists have done much to name and catalogue the various ways in which our minds can decieve us. Under the blanket name of "biases" many of these are well known - there's confirmation bias, cognitive dissonance, rationalization, and so on.

There's a reason why so much has been said about fallacies and biases. They're out there, and they're a problem. When you set your mind to it, you can find them almost anywhere - no matter who you are. This, for example, is written by someone who believes that HIV does not cause AIDS. By most standards, this makes him a kook. And he probably is a kook, about AIDS, but he’s not stupid. He makes some perfectly sensible points about cognitive dissonance and the psychology of science. And here, he offers further words of wisdom:

I have no satisfactory answer to offer, unfortunately, for how AIDStruthers could be brought to useful mutual discussion.
...
Here’s a criterion for whether a discussion is genuinely substantive or not, directed at clarification and increased understanding: no personal comments adorn the to-and-fro. If B appears not to understand what A is saying, then A looks for other ways of presenting the case, A doesn’t simply keep repeating the same assertions spiced with “Why can’t you…?”, and the like. [Added 28 December: Another hallmark of the non-substantive comments is that the commentator not only keeps harping on the same thing but does so by return e-mail, leaving no time to consider what s/he is replying to; see Burun's admission of suffering from that failing.]
...
One lesson from experience is that the aim of Rethinkers cannot be to convince the AIDStruthers. It soon becomes a sheer waste of time to attempt to argue substance with them; a waste of time because you can’t learn anything from them, and they are incapable of learning anything from you. Rethinkers and Skeptics should address the bystanders, onlookers, the unengaged “silent majority”. There seem always to be with us some people who cheerfully continue to believe that the Earth is only about 6,000-10,000 years old, and many other things that most of us judge to be utterly disproved by factual evidence.

That could have come straight from the pen of such pillars of scientific respectability as Carl Sagan or Orac - until you remember that by "Rethinkers" and "Skeptics" he means people who don't believe that HIV causes AIDS, while "AIDStruthers" is his term for those who do, that is, almost every medical and scientific professional.

The lesson here is that you don't have to be right in order to notice that people who disagree with you are irrational, or that much of the opposition to your belief is dogmatic. The sad fact is that stubborness and a tendency to dogmatism are a part of human nature and it's very hard to escape from them; likewise, it's very hard to make a complex argument without saying something at least technically fallacious (that witty aside? Ad hominem attack!)

The point is that none of this matters. If something is true, then it's true even if everyone who believes it is a dogmatic maniac. So it's certainly true even if the only people you know who believe it are idiots. What's the chance that you've argued with the smartest Christian ever, or the best informed opponent of homeopathy? In which case - the fallacies and biases of the people you have argued with certainly don't matter. In an argument, the only thing of importance is what the facts are, and the way to find out is to look at the evidence.

If you're taking the time to name and shame the fallacies in someone's reasoning or to diagnose their biases, then you're not talking about the evidence - you're talking about your opponent(s). Why are you so fascinated by him...? To spend time lamenting the irrationality of your opponents is unhealthy. The only people who have a reason to care about other people’s fallacies and biases are psychologists. Daniel Kahneman got half a Nobel Prize for his work on cognitive biases - it's his thing. But if your thing is HIV/AIDS, or evolution, or vaccines and autism, or whatever, then it's far from clear that you have any legitimate interest in your opponent's flaws. In all likelihood, they are no more flawed than anyone else - or even if they are, their real problem is not that they're making ad hominem attacks (or whatever), but that they're wrong.

So when barely-coherent columnist Peter Hitchens writes in the Daily Mail about wind farms

If visitors from another galaxy really are going round destroying wind turbines, then it is the proof we have been waiting for that aliens are more intelligent than we are.

The swivel-eyed, intolerant cult, which endlessly shrieks – without proof – that global warming is man-made, has produced many sad effects.

The point is not that people who believe that global warming is man made are not a cult. They're not, but even if they were, it wouldn't matter. The swiveliness of their eyes or the pitch of their voice is not obviously relevant either.

Of course, if you're out to have fun bashing heads, or writing columns for the Daily Mail, then go ahead. Learn the names of as many fallacies and biases as you can (including the Latin names if possible - that's always extra impressive) and go nuts. But if you're serious about establishing or discussing the truth about something, then there is only one set of biases and fallacies you ought to care about – your own.

[BPSDB]

NOS1 - An Impulsivity Gene?

Neuroskeptic has warned before of the pitfalls of candidate gene association studies. With small sample sizes and multiple comparisons, false positive results are all too common, especially in behavioural genetics. Yet it's not all bad. The renowned Klaus-Peter Lesch and colleagues have just produced a paper which is a cut above the rest. They report on an association between a promoter region polymorphism in the gene NOS1 and "impulsive" traits.

NOS1 codes for the enzyme nitric oxide synthase 1, which is expressed in neurones and makes nitric oxide (Nitrogen monoxide, NO). NO is a small molecule with various roles in animals, most famously the ability to induce erections - Viagra works by enhancing this effect. NO is also known to act as a neurotransmitter, with widespread but poorly understood functions in the brain. It's therefore plausible that altered nitric oxide synthase function could affect behaviour, and several animal studies suggest that indeed it does.

The new paper, published in the Archives of General Psychiatry, reports on the characterization of a functional variant in the human NOS1 gene, and its association with behaviour in several large human samples. The polymorphism, which Lesch et. al. previously discovered and called NOS1 Ex1f VNTR, is a Variable Number Tandem Repeat in a promoter region of DNA. It can be either "short" (S) or "long" (L) (although note that these are arbitrary categories, since the length of the region varies along a range.)

The authors first established that Ex1f is a functional (biologically meaningful) variant, by showing that shorter forms of the Ex1f promoter are less active than the longer forms in vitro (see graphs). They then examined human brain tissue from post-mortem samples and found that the short/long polymorphism was associated with significant differences in the expression of a large number of proteins. Although most of the proteins in question were nothing to do with NO, this shows that the polymorphism does something, which is a start (many don't).

They then report on the association between the short form of the gene and what they call "impulsivity". Here's the exciting bit:

In two separate control samples of normal German adults (most of whom) were screened to exclude psychiatric disorders (n=640 and 1314), 21 and 20% carried two copies of the short allele (SS). I've helpfully highlighted that in green above. Then, in samples of German people who displayed various forms of impulsive behaviour, the SS genotype was more common: in 383 adults with ADHD (28% SS), 189 adults who had attempted suicide (25% SS), and adults with "Cluster B" personality disorders 26% SS, but not those with "Cluster C" disorders representing anxious traits. Also, in a sample of 182 criminals referred to a forensic psychiatry unit, those who had been assessed as "violent" were more likely to carry the SS genotype than those not (p=0.04). In a nutshell, SS is bad. There was a negative result in a family-wise association study in childhood ADHD, however.

As if that weren't enough data, in 1099 healthy volunteers, those carrying the S allele scored lower on the "Conscientiousness" factor of the NEO personality questionnaire than LL people, although the difference was only significant in women. Low conscientiousness could be seen as impulsiveness - although note that there are 5 personality factors on the NEO and the authors presumably checked for a genetic effect on all 5, so that's at least 5 comparisons.

Finally, they managed to work a bit of neuroimaging into the paper in the form of an EEG study in which SS subjects showed a greater posteriorization of the "no-go" centroid during a continuous performance task. The no-go centroid is an electrical signal which occurs in the brain during inhibition of an action; the authors claim that the fact that this signal occurred further back in the brain in SS subjects points "toward impaired function of the medial prefrontal cortex in these subjects, which probably underlies an improper cognitive control of initiated responses resulting in impulsive behaviors", but to be honest, that's very optimistic. What, if anything, this finding means is unclear.

Still, despite a couple of dodgy bits, the paper as a whole offers pretty good evidence that the NOS1 Ex1f variant is functional and influences personality. This is the first report linking NOS1 to behaviour in humans, although since the paper includes data from a number of different samples, it's more than just preliminary evidence. On the other hand, nothing in this field should be considered a fact until the exact effect in question has been replicated by independent researchers - at least, that's my rule of thumb.

The nature of the effect (the associated phenotype) is also unclear. The authors interpret it as increased "impulsivity", but that's a vague concept. Impulsivity in all situations? Only in social situations? Only when stressed? We don't know. Also, the authors seem to have only looked for associations with impulsive conditions. Were someone to look for an association with, say, depression, or schizophrenia, they might well find one, in which case this might be best seen as a resilience gene rather than an impulsivity one. No doubt someone will be doing such a study as we speak, so hopefully, we'll know soon.

History note: Klaus-Peter Lesch first attained fame as the lead author on the first paper associating the 5HTTLPR variant with personality. In the 12 years since this polymorphism has attracted more attention than any other in the field of behavioural genetics with several hundred papers at last count. So if that's anything to go by, we'll be hearing a lot more about NOS1. Stay tuned.

Andreas Reif, MD; Christian P. Jacob, MD; Dan Rujescu, MD; Sabine Herterich, PhD; Sebastian Lang, MD;, Lise Gutknecht, PhD; Christina G. Baehne, Dipl-Psych; Alexander Strobel, PhD; Christine M. Freitag, MD;, Ina Giegling, MD; Marcel Romanos, MD; Annette Hartmann, MD; Michael Rösler, MD; Tobias J. Renner, MD;, Andreas J. Fallgatter, MD; Wolfgang Retz, MD; Ann-Christine Ehlis, PhD; Klaus-Peter Lesch, MD (2009). Influence of Functional Variant of Neuronal Nitric Oxide Synthase on Impulsive Behaviors in Humans Archives of General Psychiatry, 66 (1), 41-50