Autism involves early brain overgrowth and dysfunction, which is most strongly evident in the prefrontal cortex. As assessed on pathological analysis, an excess of neurons in the prefrontal cortex among children with autism signals a disturbance in prenatal development and may be concomitant with abnormal cell type and laminar development.
Methods
To systematically examine neocortical architecture during the early years after the onset of autism, we used RNA in situ hybridization with a panel of layer- and cell-type–specific molecular markers to phenotype cortical microstructure. We assayed markers for neurons and glia, along with genes that have been implicated in the risk of autism, in prefrontal, temporal, and occipital neocortical tissue from postmortem samples obtained from children with autism and unaffected children between the ages of 2 and 15 years.
Results
We observed focal patches of abnormal laminar cytoarchitecture and cortical disorganization of neurons, but not glia, in prefrontal and temporal cortical tissue from 10 of 11 children with autism and from 1 of 11 unaffected children. We observed heterogeneity between cases with respect to cell types that were most abnormal in the patches and the layers that were most affected by the pathological features. No cortical layer was uniformly spared, with the clearest signs of abnormal expression in layers 4 and 5. Three-dimensional reconstruction of layer markers confirmed the focal geometry and size of patches.
Conclusions
In this small, explorative study, we found focal disruption of cortical laminar architecture in the cortexes of a majority of young children with autism. Our data support a probable dysregulation of layer formation and layer-specific neuronal differentiation at prenatal developmental stages. (Funded by the Simons Foundation and others.)
Thank you for posting that! I am not exposed to current research on autism, but I want to know what is happening.
Does that mean that autism can be an evolutionary symptom of trying to balance maximum intelligence (which I assume requires, in layman's terms, a ton of neurons) with robust brain organization and overall brain health?
And do we know if any other species experience autism?
It's not really interesting that a condition which is with you from birth might begin in the womb. The others I listed are also known to be... phrased conservatively... strongly influenced by something in the womb, but at least they all exhibit late-life onset and could conceivably begin at some later point.
The headline is really just a teaser in this case. The meat of the article is more about how autism begins, and how some of the critical developmental steps that lead to autism occur in the womb.
The other conditions (prostate cancer, for example) are much more significantly influenced by events that take place well after birth.
Prostate cancer is one of the poster children for the theory "the death rate from cancer is increasing because people have stopped dying of other things before they inevitably get cancer". Far and away the most significant influence on whether you have prostate cancer is whether you have a prostate gland; this is determined in the womb. In the depressing words of my mom's medical school professor, having a prostate gland is sufficient to develop prostate cancer; the prevalence is 100% (of males). The question (assuming what you're really worried about is mortality) is not "do I have prostate cancer?" -- you do. The question is "how badly is my prostate cancer growing?"
Given the amount of coverage bullshit theories about autism and it's causes got a few years ago don't you think it's worth promoting valid research about it (particularly where it directly contradicts the bullshit)?
Well, for one thing, it doesn't. Assuming the antivaxxers take this research to heart, which there is no particular reason to expect (how have they viewed other research?), watch for the message to become "save your grandchildren from autism by not vaccinating your children".
On the general question of "if one bad idea gets press, should we devote a bunch of extra attention to refuting it?"...
Daryl Bem managed to conduct some studies showing a "statistically significant" effect of ESP. He got those published in a respectable journal, which felt duty-bound to print them because Bem had followed all the formalities of the scientific method, and That Is The Process Of Science.
Obviously, ESP is not real, and this attracted several replication efforts. When they duly failed to replicate, they couldn't get published. Are you arguing that after publishing Bem's paper, the journal should have wasted further space publishing the inevitable refutations? Their position was that a paper demonstrating that ESP is not real has no scientific value, and they're completely correct about that (we already know!). So they opted to publish papers that might have something more worthwhile to say.
neolefty points out that the article's content has little to do with the title, and that's fair criticism of my complaint. But the title is so incredibly inane that it immediately sold me on the idea that reading the article would be nothing but a waste of time.
I'd like to say I don't care what anti-vaxxers think but sadly I have to as their children don't deserve to be lumbered with their irresponsible idiocy and the overall impact on herd immunity means that they're causing significant problems even outside their families.
There are two things here:
1) What's covered in the scientific literature
2) What's reported in the mainstream press
In the former you're absolutely right, in the later I don't think so (and the original link is the the BBC, not the NEJM).
Most people don't have the skills, time or subscriptions to go and view medical papers. When Wakefield got coverage for his bullshit for most people there was no "this is obviously wrong" because they had no evidence to suggest Wakefield was wrong. As a result his position became commonly and widely accepted.
When that happens I think the papers should spend time covering the refutations and trying to inform the public when real research - even if dull or obvious research - shows something which will slowly help the public adjust their incorrect viewpoint.
I'd love to think that the MMR/Autism thing has run it's course and we shouldn't have to do this any more (and hell, with even Jenny McCarthy backing down some we are getting there) but sadly I think we still have some way to go.
And in that vein, long live the promotion of tedious (but factual) research.
I mostly agree with what you're saying here; I'm not sure about this one:
> When Wakefield got coverage for his bullshit for most people there was no "this is obviously wrong" because they had no evidence to suggest Wakefield was wrong. As a result his position became commonly and widely accepted.
My gut says that isn't responsible for the acceptance. Antivaccine beliefs crop up from time to time, apparently independently, all across the world. They are generally cultural phenomena; e.g. the polio vaccine was rejected as being part of a Western conspiracy to do nefarious things to the people getting it. I'd be more inclined to blame the fact that getting injections makes some people pretty uncomfortable.
I'm not actually sure how widely accepted antivaxxers are; they're certainly vocal about their (deserved) persecution by saner people. As you mention, they're a problem more because even small concentrated groups of antivaxxers can cause big problems to everyone around them than because there are so many; UFO junkies aren't exactly accepted by the mainstream, but there are a lot of them in an absolute numbers sense and they're harmless.
I can't tell you how shocked I was when my sister's best friend, a graduate of UC Berkeley, came into our house and started telling us about the evils of wheat. Among other preposterous claims, apparently the wheat we eat today has been genetically engineered to be nefariously addictive, and has all kinds of ill effects on your bodily health. I was able to trace most of her ideas back to this guy, the natural culmination of the gluten-free food fad:
but, as is always the case, her ideas were garbled, and attributed even more evil to wheat, compared to what is presented in that awful, scaremongering book.
You can't stop completely crazy ideas from springing up in the most unlikely places, and skills, time, and access are much less protective than you might hope.
When Brazil had its antivax scare at the turn of the 20th century, the government showed up in full military force and vaccinated everyone anyway. That's the sensible way to handle antivaxx beliefs.
This has been a long, rambling comment. Let me try to sum up:
- Antivaxxers aren't doing it because they're convinced by any research. They're doing it as a weird cultural phenomenon, like many, many other crackpot quasireligious groups (UFOs / astrology / cryptozoology / 9/11 truthers / vegans / what have you). As with other quasireligious believers, they're not going to be convinced by argument or evidence. What makes them different is not that people weren't around to defend reality when they formed, it's that their beliefs and practices are quite harmful to everyone around them.
- Given the long and distinguished history of antivax movements, it doesn't make sense to me to blame this one on Andrew Wakefield and a failure to publish counterpapers in a timely manner. It makes more sense to view it as another antivax movement, fueled by whatever keeps causing and sustaining them, where the trigger is basically just a coincidence.
edit-addendum:
> Most people don't have the skills [...] to go and view medical papers
This is no less true now than it was in 1998. For all of those people, they have no evidence now to suggest that Wakefield was wrong. The publication of research discrediting him further and further can never help; by assumption, those people cannot understand medical papers. They don't understand Wakefield's paper either (which is what I'm getting at when I say "Antivaxxers aren't doing it because they're convinced by any research").
Summary: paper shows that presenting research explaining that vaccines do not cause autism does lower belief that vaccines cause autism, while simultaneously also lowering willingness to vaccinate children.
I think efforts to talk to antivaxxers are wasted efforts.
13 comments
[ 3.2 ms ] story [ 25.2 ms ] threadhttp://www.nejm.org/doi/full/10.1056/NEJMoa1307491
doi://10.1056/NEJMoa1307491
Background
Autism involves early brain overgrowth and dysfunction, which is most strongly evident in the prefrontal cortex. As assessed on pathological analysis, an excess of neurons in the prefrontal cortex among children with autism signals a disturbance in prenatal development and may be concomitant with abnormal cell type and laminar development. Methods
To systematically examine neocortical architecture during the early years after the onset of autism, we used RNA in situ hybridization with a panel of layer- and cell-type–specific molecular markers to phenotype cortical microstructure. We assayed markers for neurons and glia, along with genes that have been implicated in the risk of autism, in prefrontal, temporal, and occipital neocortical tissue from postmortem samples obtained from children with autism and unaffected children between the ages of 2 and 15 years. Results
We observed focal patches of abnormal laminar cytoarchitecture and cortical disorganization of neurons, but not glia, in prefrontal and temporal cortical tissue from 10 of 11 children with autism and from 1 of 11 unaffected children. We observed heterogeneity between cases with respect to cell types that were most abnormal in the patches and the layers that were most affected by the pathological features. No cortical layer was uniformly spared, with the clearest signs of abnormal expression in layers 4 and 5. Three-dimensional reconstruction of layer markers confirmed the focal geometry and size of patches. Conclusions
In this small, explorative study, we found focal disruption of cortical laminar architecture in the cortexes of a majority of young children with autism. Our data support a probable dysregulation of layer formation and layer-specific neuronal differentiation at prenatal developmental stages. (Funded by the Simons Foundation and others.)
Does that mean that autism can be an evolutionary symptom of trying to balance maximum intelligence (which I assume requires, in layman's terms, a ton of neurons) with robust brain organization and overall brain health?
And do we know if any other species experience autism?
new evidence that prostate cancer begins in the womb.
new evidence that schizophrenia begins in the womb.
new evidence that Alzheimer's begins in the womb.
The other conditions (prostate cancer, for example) are much more significantly influenced by events that take place well after birth.
On the general question of "if one bad idea gets press, should we devote a bunch of extra attention to refuting it?"...
Daryl Bem managed to conduct some studies showing a "statistically significant" effect of ESP. He got those published in a respectable journal, which felt duty-bound to print them because Bem had followed all the formalities of the scientific method, and That Is The Process Of Science.
Obviously, ESP is not real, and this attracted several replication efforts. When they duly failed to replicate, they couldn't get published. Are you arguing that after publishing Bem's paper, the journal should have wasted further space publishing the inevitable refutations? Their position was that a paper demonstrating that ESP is not real has no scientific value, and they're completely correct about that (we already know!). So they opted to publish papers that might have something more worthwhile to say.
neolefty points out that the article's content has little to do with the title, and that's fair criticism of my complaint. But the title is so incredibly inane that it immediately sold me on the idea that reading the article would be nothing but a waste of time.
There are two things here:
1) What's covered in the scientific literature
2) What's reported in the mainstream press
In the former you're absolutely right, in the later I don't think so (and the original link is the the BBC, not the NEJM).
Most people don't have the skills, time or subscriptions to go and view medical papers. When Wakefield got coverage for his bullshit for most people there was no "this is obviously wrong" because they had no evidence to suggest Wakefield was wrong. As a result his position became commonly and widely accepted.
When that happens I think the papers should spend time covering the refutations and trying to inform the public when real research - even if dull or obvious research - shows something which will slowly help the public adjust their incorrect viewpoint.
I'd love to think that the MMR/Autism thing has run it's course and we shouldn't have to do this any more (and hell, with even Jenny McCarthy backing down some we are getting there) but sadly I think we still have some way to go.
And in that vein, long live the promotion of tedious (but factual) research.
> When Wakefield got coverage for his bullshit for most people there was no "this is obviously wrong" because they had no evidence to suggest Wakefield was wrong. As a result his position became commonly and widely accepted.
My gut says that isn't responsible for the acceptance. Antivaccine beliefs crop up from time to time, apparently independently, all across the world. They are generally cultural phenomena; e.g. the polio vaccine was rejected as being part of a Western conspiracy to do nefarious things to the people getting it. I'd be more inclined to blame the fact that getting injections makes some people pretty uncomfortable.
I'm not actually sure how widely accepted antivaxxers are; they're certainly vocal about their (deserved) persecution by saner people. As you mention, they're a problem more because even small concentrated groups of antivaxxers can cause big problems to everyone around them than because there are so many; UFO junkies aren't exactly accepted by the mainstream, but there are a lot of them in an absolute numbers sense and they're harmless.
I can't tell you how shocked I was when my sister's best friend, a graduate of UC Berkeley, came into our house and started telling us about the evils of wheat. Among other preposterous claims, apparently the wheat we eat today has been genetically engineered to be nefariously addictive, and has all kinds of ill effects on your bodily health. I was able to trace most of her ideas back to this guy, the natural culmination of the gluten-free food fad:
http://www.wheatbellyblog.com/
but, as is always the case, her ideas were garbled, and attributed even more evil to wheat, compared to what is presented in that awful, scaremongering book.
You can't stop completely crazy ideas from springing up in the most unlikely places, and skills, time, and access are much less protective than you might hope.
When Brazil had its antivax scare at the turn of the 20th century, the government showed up in full military force and vaccinated everyone anyway. That's the sensible way to handle antivaxx beliefs.
This has been a long, rambling comment. Let me try to sum up:
- Antivaxxers aren't doing it because they're convinced by any research. They're doing it as a weird cultural phenomenon, like many, many other crackpot quasireligious groups (UFOs / astrology / cryptozoology / 9/11 truthers / vegans / what have you). As with other quasireligious believers, they're not going to be convinced by argument or evidence. What makes them different is not that people weren't around to defend reality when they formed, it's that their beliefs and practices are quite harmful to everyone around them.
- Given the long and distinguished history of antivax movements, it doesn't make sense to me to blame this one on Andrew Wakefield and a failure to publish counterpapers in a timely manner. It makes more sense to view it as another antivax movement, fueled by whatever keeps causing and sustaining them, where the trigger is basically just a coincidence.
edit-addendum:
> Most people don't have the skills [...] to go and view medical papers
This is no less true now than it was in 1998. For all of those people, they have no evidence now to suggest that Wakefield was wrong. The publication of research discrediting him further and further can never help; by assumption, those people cannot understand medical papers. They don't understand Wakefield's paper either (which is what I'm getting at when I say "Antivaxxers aren't doing it because they're convinced by any research").
coverage in mother jones: http://www.motherjones.com/environment/2014/02/vaccine-denia...
Summary: paper shows that presenting research explaining that vaccines do not cause autism does lower belief that vaccines cause autism, while simultaneously also lowering willingness to vaccinate children.
I think efforts to talk to antivaxxers are wasted efforts.