An Immune Disorder at the Root of Autism
nytimes.com
nytimes.com
It also bears repeating that what we call "severe autism" is really "some amount of autism comorbid with very low IQ". Autism is routinely overdiagnosed in preference to a more accurate diagnosis of intellectual disability because parents prefer it, again because it offers more hope, largely due to the popular trope of the autistic savant.
Parents of severely disabled children naturally hold out for any source of hope and I don't judge them for that in any way, but we can't let that get in the way of the science that really is their child's best hope. There is no evidence for the hygiene hypothesis.
I haven't done any research on this, but at the same time virtually every other chronic illness is caused, causes, and/or is exacerbated by chronic inflammation, so if inflammation during pregnancy doesn't have any effect on neurological development it would be extremely surprising.
If it's genetic, as you assert, then what hope is there?
I believe you're correct, but ...
> because parents prefer it, again because it offers more hope
This sort of thinking is popular because it offers hope and having that hope present offers a higher quality of life for the family.
Recognizing what their specific problems actually are, there is significant variation in the strength of the particular difficulties individual autistics face.
Teaching autistics to work around their disabilities; there has been significant progress on this approach for recognizing and dealing with other peoples emotions, for example.
Getting them the support they need for problems they cannot work around.
Drugs which target the specific pathways triggered by the gene.
Um... plenty? Tons of genetic diseases are treatable. This is where Genzyme, for example, makes most of its money. Cerezyme for Gaucher's disease or Fabrazyme for Fabry disease to name two.
On the contrary, there is copious evidence for the hygiene hypothesis:
http://en.wikipedia.org/wiki/Hygiene_hypothesis#Supporting_e...
PubMed: Epidemiological and immunological evidence for the hygiene hypothesis:
http://www.ncbi.nlm.nih.gov/pubmed/17544829
A quote: "...several epidemiological studies were conducted supporting this concept and generating novel ideas for the underlying mechanisms that were then followed up by use of well-defined animal models and human studies."
Your statement is, simply put, absolutely false.
EDIT: replaced "no evidence" with "inadequate evidence", as lutusp noted, the article is claiming a correlation, which is at least weak evidence.
The article shows a correlation between the hygiene hypothesis and autism. A correlation, by itself, could mean anything or nothing, but it is certainly evidence.
Are you using "evidence" as a synonym for "proof", as in law? I ask because science doesn't work that way.
This correlation may simply evaporate with further work, or reveal some connection not now apparent, but saying there's no evidence for the correlation is simply false.
> There is inadequate evidence of a link between the hygiene hypothesis and autism
Inadequate for what? The author isn't claiming more than is there, and it's a simple correlation at this point, one that merits further examination.
It isn't as though scientific theories are ever proven true. That's not how science works. And this correlation is far from even being a theory.
> the article is claiming a correlation, which is at least weak evidence.
No -- a correlation is not weak evidence of a cause-effect relationship, in fact it's not cause-effect evidence at all.
http://en.wikipedia.org/wiki/Correlation_does_not_imply_caus...
To understand why this is true, consider rain and puddles. A naive alien, seeing a correlation between rain and puddles, might conclude that the puddles caused the rain, or the reverse, or both rain and puddles are caused by an unevaluated third cause.
Because A might cause B, or B cause A, or A and B be caused by C, and without researching the true cause-effect relationships, the observed correlation means precisely nothing. No. Thing. It is not weak evidence, it is not evidence at all.
And "hearsay and anecdotes" are not any kind of evidence of interest to a scientist. The plural of anecdote is not data.
Of course he is. Here's a quote from the post to which I replied:
> There is inadequate evidence of a link between the hygiene hypothesis and autism ... the article is claiming a correlation, which is at least weak evidence.
But the above is false. A correlation is not "weak evidence" for a cause-effect relationship, or a "link", as the poster put it. We need to be perfectly clear that a "link" suggests a cause-effect relationship, but without specifying which way cause and effect run.
A correlation is an observation that can only lead to further work, and it is never, in and of itself, evidence of a cause-effect relationship, absent discovery of a mechanism.
This reminds me of one of my pet peeves about science journalism -- use of the word "link" to describe a correlation. It's tendentious and misleading. There are lots of studies that find "links" between utterly unrelated things, by simple data mining (searching for coincidental correlations devoid of meaning). Such meaningless correlations are often published as though they mean something, and they're nearly always described with the word "link" or another tendentious word.
Intentionally humorous examples:
http://www.businessweek.com/magazine/correlation-or-causatio...
Apophenia (seeing meaningful patterns or connections in random or meaningless data):
You link to a wikipedia article.
> There is some evidence that autism may be caused by an immune disease; One publication speculated that the lack of early childhood exposure could be a cause of autism.
The hygiene hypothesis has wider use than just autism - that a bunch of allergy and auto-immune stuff is caused by excessive cleanliness. There is strong evidence that might be true. But the link between autism and excessive cleanliness is, to quote one link that you provided, "speculative".
The abstract of the other study doesn't mention ASD; maybe I'm missing something?
(Just to be clear, because sometimes I'm not: The hygiene hypothesis is strong and important when talking about allergy and maybe auto-immune diseases; I need convincing that there's any link to ASD.)
Yes -- but my remark is about the hygiene hypothesis, not about autism. Read the post to which I replied. The poster said "There is no evidence for the hygiene hypothesis." I replied to that specific remark.
> The hygiene hypothesis has wider use than just autism ...
What? The evidence for the hygiene hypothesis is strong in many areas, but as to autism, it's mere speculation.
> But the link between autism and excessive cleanliness is, to quote one link that you provided, "speculative".
Yes -- and on what basis do you think I have taken any other position?
> The hygiene hypothesis is strong and important when talking about allergy and maybe auto-immune diseases; I need convincing that there's any link to ASD.
So does everyone else. There's no basis for this assumption in present evidence.
The comment you responded to was clearly talking about the hygiene hypothesis and autism. I'm not sure how you read it otherwise.
Since the post you responded to was saying that there is no evidence for the hygiene hypothesis (as a cause for autism) and you then replied to say that there was strong evidence for the hygiene hypothesis it's a reasonable assumption that you're still talking about causes of autism.
Worth noting is that the connection between inflammation, intelligence and health could be more related to the heritable trait of how stable or robust your phenotype is to noise (mutations and stochastic alike).
What I also find interesting is that the fear for a disease being genetic will likely flip in the next 2 decades. Genetic diseases will be more easily corrected than diseases that will evolve a slip right under your nose.
Foolish unless true. We just don't know, and it's too soon to be abandoning theories. Science doesn't proceed by categorically denying possibilities before they've been fully investigated.
> Genetic diseases will be more easily corrected than diseases that will evolve a slip right under your nose.
On the contrary, genetic diseases will with rare exception remain incurable.
2.) This is a testable hypothesis and will be known in time. I believe that we will have a good enough understanding and control over genetics such that effective therapies even for adults will be possible in the stated time frame. Also notice I used the word correct not cure, not a mere play in semantics but a subtle change that strongly alters meaning.
Wait -- if resolution requires the simple passage of time, then it's not testable, indeed it's not really a test. A "testable hypothesis" means a notion that's subject to practical test in the present. Waiting for a future yea/nay outcome isn't, strictly speaking, a test. More of a waiting game.
> I believe that we will have a good enough understanding and control over genetics such that effective therapies even for adults will be possible in the stated time frame.
Gene therapies have a pretty terrible track record to date. Nevertheless, if your "time frame" is 100 years, then I would have to agree it's likely, based on Clarke's First Law:
http://en.wikipedia.org/wiki/Clarkes_three_laws
Quote: "When a distinguished but elderly scientist states that something is possible, he is almost certainly right. When he states that something is impossible, he is very probably wrong."
> Also notice I used the word correct not cure, not a mere play in semantics but a subtle change that strongly alters meaning.
Yes, agreed, and if this era arrives, treatment recipients will have to be told that their improved condition by no means implies that their offspring won't be similarly afflicted.
I ask because I have a son with autism, and I have met leading immunologists in famous medical schools who subscribe to this hypothesis. That doesn't make the hypothesis right, but it is taken far more seriously than your comment would imply.
Second, "severe autism is really some amount of autism with very low IQ" part is also wrong in my opinion. Autism can be so severe that it makes IQ irrelevant (even in cases where it can be demonstrated to be high). The analogy here is with other mental illnesses like schizophrenia - when it is severe enough, it masks every other trait of that person, including IQ. That does not mean "severe schizophrenia is really some amount of schizophrenia combined with very low IQ". There are many severely autistic individuals who also demonstrate high IQ in specific areas (but still cannot lead anything close to a normal life), directly contradicting your statement.
I expect a little more thoughtfulness on a top comment in HN.
Of course, it may be false, but so could anything people say, even when backed up by "sources"; however, I really do feel the need to point out that it isn't false only because there are exceptions, as the word "overdiagnosed" only implies "more often than is warranted" and doesn't in any way leave out the possibility that it is sometimes correct, or even that there aren't "many" cases: just that the number of people who are diagnosed is larger, and possibly still much larger (even with "many" real cases), than the number of people who truly have the issue and should be diagnosed.
(To be very explicit: nothing I have said here relies on specific information about autism, nor can it, as I know absolutely nothing about that disorder.)
I am probably going to get downvoted for being realistic about it, but if you don't have autism you really don't know what its like. I wouldn't wish this on my worst enemy, and I would do anything for a possible cure, but I can't allow myself to be filled with a false hope that someday I can live a normal life.
As regards autism and IQ, your analogy to schizophrenia is completely inaccurate. Someone with high IQ can develop strategies to ameliorate essentially every aspect of their autistic symptoms - learning social and communication skills, structuring their life to deal with overstimulation, participating in behavioural therapy to minimise repetitive and autostimulative behaviours etc. Schizophrenics are by definition unaware that their delusional beliefs are delusional, whereas any intelligent autistic can be made aware of their social deficits and behavioural quirks and can learn to adapt around them.
As you said, some autistic people have high IQ in some areas but are still unable to live a normal life, but this is because their cognitive problems render them unable to overcome their autism symptoms. A specific cognitive impairment is still a cognitive impairment - strong arms do not nullify paraplegia.
While it may be the case that there are some individuals that have high IQ but severe levels of impairment, they are very much outliers. There is no generally-accepted classification for the severity of autism symptoms, but it is worth noting that those systems which simply use IQ are not obviously less useful than more complex schemes; IQ correlates as strongly with functional impairment as any other factor.
delusions are not necessary for a schizophrenia diagnosis
also, during periods of convalescence, on hallucinations: "they may learn to ignore them, or treat them as benign accompaniments of everyday living" --http://www.schizophrenia.com/family/delusions.html
While schizophrenia can have many very strong symptoms and is obviously not 'psychogenic' (e.g. in a Freudian sense), schizophrenics can and do learn skills to help them feel better and pass better and intelligence is an asset there.
I will agree that autism seems MUCH vaguer than schizophrenia as a diagnostic category, but that is also true of most other psychological disorders...
--- There are severely depressed people with very high IQ and they are fully intellectually aware of their depression, they try hard to compensate for it, doing all the types of things you mention in the context of autism. Tragically, for at least some of them, nothing seems to work.
My point is that it is more complicated than what you are asserting.
Why?
Ah, that... actually explains a lot. I've worked with several people with Autism diagnoses, and yeah, they were nerdy... really nerdy and socially inept, but also smart, productive individuals able to lead independent lives; People I'd be happy to call friend. Yeah, I have to go out of my way to figure out how to effectively communicate with them, but it's worth it. If I had a kid that grew up to be like them, I'd be proud.
I hear people talking about autism like it's this terrible thing, and I don't really understand, Your kids could very easily turn out a lot worse than the Autistic people I know.
Of course, if any of these people were low-IQ, or really, anywhere near average, they'd have a difficult time indeed.
The article is advertisement for the author's book, and I can't find any indication that the author has an educational background in biology. Based on his book's Amazon page, he's a journalist.
Thank you for asking that essential follow-up question for most submissions on HN. Some of the references that turn up in a Google Scholar search
http://scholar.google.com/scholar?as_ylo=2008&q=autism+a...
include free full-text download links, so we can follow up on this.
The author has a long history of advocating a link between parasite load and auto-immune disease
Yes, I also checked out the author as I submitted this article. He has postgraduate training in science writing, has worked for The Christian Science Monitor (a dodgy publication for medical reporting), and has been published in other professionally edited publications for his freelance science reporting. I thought the submitted article had enough caution of statement and names of actual researchers to be worth discussing here. The article is certainly far from the last word on the subject, but may point to a line of research that will be helpful in SOME (but certainly not all) efforts to reduce the incidence of autism in the future and to help children after they develop autism.
AFTER EDIT:
Some readers here may be interested in looking at the original case report by Leo Kanner that first described autism.
http://www.neurodiversity.com/library_kanner_1943.html
An author who I think provides a helpful intercultural perspective on autism and its diagnosis is Roy Grinker,
http://www.pbs.org/newshour/bb/health/jan-june11/grinkerext_...
who has studied autism in cultural contexts outside the United States.
You called this piece into question in part because of a past affiliation with the CSM. The CSM is a credible journalism venue; it's not fair to attribute fundamentalist Christian Science beliefs on people who happened to have worked there.
Anyways, my point is simple: fundamentalist Christian Science devotees might lack credibility in medical debates. But people who have merely at some point in their careers affiliated with the CSM do not.
http://www.economist.com/node/21560523
A long term antibiotics prescription messed up my gut bacteria, leading to problems with drowsiness and yeast infections. Strong priobiotics (100B+ cells daily) reverse these probems, which return within days when I stop the priobiotics. I can't speak for autism, but I can tell you first hand that gut bacteria do play a role in our health.
http://www.sciencedaily.com/releases/2012/07/120717141010.ht... http://media.caltech.edu/press_releases/13534
* Asthma
* Autism
* Allergies
* Immune system dysfunctions
All these conditions are now "linked" to the "hygiene hypothesis," the idea that we're not doing ourselves any favors by creating near-sterile living environments. A quote from the article:
"Scientists have repeatedly observed that people living in environments that resemble our evolutionary past, full of microbes and parasites, don’t suffer from inflammatory diseases as frequently as we do."
I emphasize about the linked article that it represents a correlation, not a cause-effect relationship. We won't be able to say with any certainly what causes autism until we can trace its evolution step by step, from a specific environmental stimulus to a biological mechanism, with all the steps fully described. We're not yet close to that goal.
This totally validates my need to go play in the mud and eat sketchy food from carts on the street.
I'm not sure I buy the "hygiene is harmful" argument or that we've gone overboard with it. I think a lot of other factors that have changed in the past 60 years might factor in, including a misguided government/agribusiness lead food pyramid that is way out of balance with our pre-civilization diets, as well as the introduction of highly processed and sweetened food that for many of us forms the majority of our diets.
You can be hygienic and still cultivate behaviors that increase your exposure to safe levels of microbes. For instance, I always wash my hands after using the toilet but I’m less concerned than most about the use-by dates on food products and prefer to make decisions based on my sense of smell and taste. Not sure if that’s a good example.
Indeed, hygiene is not harmful, but we have gone overboard with it. As with most things in life, going to the extremes is bad for your health.
Oddly off-topic and yet on-topic for HN, I'm working on a startup idea to assist families with special needs. I've been trying to go it alone, but not having a partner is tough. No one to speak with, no one to work with. If anyone is interested, even if it's just to chat, email me (found in my profile). I'm bad at asking for help. =/
My mom had a serious liver infection during her second trimester while carrying my older brother. He turned out autistic. After years of dressing down people about vaccines and other snake-oil causes of autism, she forwarded this article to me with one line, "This must be the reason." FWIW.
Anyway, I came two years later without complications. I also exhibited many odd behaviors that worried my parents at first, but wound up not being autistic.
Hang in there and keep your chin up. Your younger son might be fine.
He is fine. I know that's not what you mean, but regardless of the diagnosis, he is a wonderful child, and I would not have him any other way. My worry isn't for my children, but for the way society treats those with autism.
It's hard to explain. Thanks though. =)
I.e., suppose 50% of people suffer headaches, 50% suffer nausea, and 50% suffer aching back. Further, suppose 12.5% (= 50% x 50% x 50%) of people suffer all three symptoms - in this case, the three symptoms put together are NOT a syndrome.
On the other hand, suppose 40% of people suffered headaches, nausea and aching back together. In that case the three symptoms together are a syndrome.
A syndrome is probabilistic evidence that there is an underlying cause of multiple co-occurring symptoms.
Sorry, I wrote that up fast, if you are interested you can write a reply, I'll try answering tomorrow, it's late for me now.
It could be that men with some medical condition are both likely to father an autistic child and to postpone child-rearing for health reasons. Heck, the autism itself in a very mild form might be such condition - a mildly autistic man could be likely to pass more severe autism to his children, and have problems finding a mate.
It worked. He has now gone a year and a half without medication, and is in massively better shape than he was on the (expensive and only marginally effective) medications.
I suffer from psoriasis and psoriatic arthritis. For the most part the psoriasis is not a big deal, it's disfiguring, but only on my legs, and it itches to the point that I'm perfectly capable of scratching long past the point that I'm bleeding. The psoriatic arthritis is another matter, untreated I live somewhere between 5-7 on the pain scale, shaking hands is nerve-wracking (please, no bone crusher handshakes - I do suffer from hand squeezy death) and I can barely walk.
On meds I'm basically fine. I use Humira which if I understand correctly is a human monoclonal antibody glued to a receptor that interferes with something to do with T-cells. I.e. it causes a specific immune suppression that massively reduces the process that causes the psoriasis and arthritis symptoms - oh and I'm 100x more likely to get skin cancer.
I've been off meds for over 6 months now with very limited impact on my life. All I did was cut out refined sugars and grain from my diet.
I discovered this by accident (too lazy to refill my prescription, then realized that I hadn't refilled in ages and yet wasn't in pain)
I think that there's a huge load we don't understand in the relationship between inflammation and autoimmune conditions; there are many things that are involved
Just my 2¢, I love science so please disregard my anecdotal ramblings
The comments do not inspire much confidence either. To be honest I'm disappointed in Radiolab for being clearer, and addressing some of the crazy there.
Montefiore representin'! (Too bad they failed to mention the names of any of the people involved at Montefiore/Einstein so I could walk over to their lab and look at their posters or talk to them.)
What exactly will that do? Unless it is fragile-X or something that can be proven using genetic testing, it won't help at all.
Eradication seems an odd goal. Treatment and support are more realistic and less creepy-eugenics.
Think about this in everyday terms -- consider the financial advantage, the scientific prestige, that would accrue to someone who located such a link. Wealth, fame, the unrequited love of women. But even though this issue has been studied repeatedly, no one has been able to show a scientific correlation between vaccines and autism.
Andrew Wakefield pretended to show a link, but his motives are now obvious -- he received thousands of dollars in consulting fees from a group of lawyers trying cases related to this issue, and he sought a patent on a vaccine of his own design, a vaccine that would have enriched him if there was such a link. These facts call his objectivity into question. And examination of his "scientific" work shows a repeated pattern of fraud and deception.
I suggest that you think like a scientist. Scientists don't say what you have, in essence: "if it hasn't been disproven, that's an argument in its favor." Scientists only count positive evidence as support for a hypothesis, and there is none for this issue. Indeed all the studies come to the same conclusion -- there is no link between vaccines and autism.
There is the narrow possibility, which may well have been looked at but hasn't been discussed, that vaccines could make autism worse only when it is significant to begin with, so nothing is crossing the threshold between not-quite-autism to autism, but I don't think we have any more evidence cause us to expect that relative to the simpler hypothesis that vaccines have roughly the same impact at any degree of autism: none.
As for the bio-marker there are a number of things that could be looked at: flue/bascterial infection during pregnancy, age of father, anti bodies in mother, rheumatoid arthritis genetic markers in mother, asthma markers.
I have to disagree that it is a narrow possibility. So much of the future of a child is determined during the formative years. Intentionally aggravating an at-risk child's immune system over and over again is something that needs to be very closely researched. To not do so at this point given all that we know seems very unethical.
We call it "downvoting". It's something we do when people are wrong. Stop being wrong and we'll stop downvoting you.
http://www.cdc.gov/vaccinesafety/concerns/autism/index.html
http://www.nap.edu/catalog.php?record_id=10997
http://www.vaccinesafety.edu/cc-mmr.htm
http://briandeer.com/mmr/lancet-summary.htm
http://scienceblogs.com/insolence/2012/08/04/andrew-wakefiel...
http://www.sciencebasedmedicine.org/index.php/jenny-mccarthy...
http://www.sciencebasedmedicine.org/index.php/dr-google-and-...
http://www.sciencebasedmedicine.org/index.php/an-antivaccine...
It's so scary to see how many people refuse to open their minds to possibilities outside their preconceived notions. The responses in this thread are a prime example.
That possibility has been studied very extensively, and the science is in -- there is no link.
> It's so scary to see how many people refuse to open their minds to possibilities outside their preconceived notions.
Yes, true, but it's not too late for you to do just that -- read the science, and stop posting uninformed opinions.
Here is a good video about skepticism and minds, closed and open. Highly recommended!
In fact, the "hygiene hypothesis" is almost the diametric opposite; vaccines, by challenging our immune systems, would reduce the risk of autism. Not that it does that either, studies have repeatedly found no correlation between vaccination and autism.
See also: http://www.jennymccarthybodycount.com
No, that is false. That theory has been demolished by the many studies designed to compare outcomes between those who do, and do not, receive modern vaccinations:
http://www.autismsciencefoundation.org/autismandvaccines.htm...
The one study that claimed a link has been exposed as a fraud and its author has been sanctioned:
http://www.huffingtonpost.com/glenn-d-braunstein-md/andrew-w...
A quote: "In early January, the British Medical Journal called the 1998 study by Andrew Wakefield, which proposed a link between the measles, mumps and rubella (MMR) vaccine, gastrointestinal problems and autism, 'an elaborate fraud.' According to Fiona Godlee, the journal's editor-in-chief, 'It's one thing to have a bad study... In this case we have a very different picture of what seems to be a deliberate attempt to create an impression that there was a link by falsifying the data.'"
I ask you to educate yourself on this issue before posting discredited claims in a public forum.
Everyone is entitled to opinion, but when discussing articles like this it's fact and science that matter.
Comments like your cost lives.
We're already seeing increase in measles rates in the UK from the fallout of the MMR scare mongering around 10 years ago.
Please understand that parents who perceive any risk to their children will always err on the side of caution. When that perceived risk is based on lies and assumptions you stand the chance of exposing that child to other known and proven risks.
Please think before you post.
But, I think it's a range of epigenetic factors that trigger an auto-immune response to have autism expressed according to some genetic program. Vaccines with their adjuvants are but one trigger - and it should be patently obvious that this might well be the case from the article.
That's not how vaccines work, though. They create immunity through controlled exposure to the virus. If they were contributing to the "super clean" environment, then they would be preventing exposure.
The woman that is responsible for promoting actions (lack of actions) that killed lots of children?
http://www.jennymccarthybodycount.com/Jenny_McCarthy_Body_Co...