February 3, 2009

Two Causes Of Autism

Ah, finally, a post about science only, that doesn't offend anyone.

Whoops, sorry, that's my other blog.  In this blog, I write about how the parents cause autism.


First, let's get this out of the way: that was a joke, ok?  I do not think autism is caused by the parents.  Science has already disproven that link. Science shows it caused by rain.

Before any science is discussed here, take a minute and examine your prejudices, which run so deeply that I can't write a blog about narcissism without getting accused of writing too much about narcissism.

Why, when I wrote that autism was caused by the parents, did you think that was so offensively preposterous as to merit rebuttal in ALL CAPS?  Yet when I said it is rain, you were... intrigued?  

Not that you actually believed it was rain, of course, you figured that was a proxy for something else; but you did not allow that "parents" might be a proxy for something else.  Linking parenting to, well, anything, is so loaded with connotation that it is safely beyond consideration; yet a moment's reflection reveals that of course that's the best proxy.

Science in psychiatry, or in any field that pretends to examine behavior, is a false god.  It's not just the results that are biased; the way questions are asked, the questions that are asked, that can be asked-- and the ones that none dare ask-- safely protect even the sexy calf of the truth from ever being revealed.  

Take a break, Diogenes, it's going to be a long wait.


Well, what about all that rain nonsense?

In general, autism rates are higher in the norther U.S. than in the southern.

Looking at three states, Washington, California and Oregon, a study found the counties with the highest precipitation in the 1990s lead to the highest autism rates in 2005.  Additionally, kids under three who experienced higher than normal rainfall relative to other years had higher rates of autism.

What's nearly incomprehensible about this article is the next sentence:

There are a number of possibilities concerning what such an environmental trigger might be.

It goes on to list their top four explanations, but in case you don't see it, I'll spell it out: this environmental trigger is one that occurs to the child after he is born, not before, or to the parents.

They cite: rain means more TV watching; Vitamin D deficiency; household cleaners or some other indoor toxin; or the rain brings an atmospheric or ground toxin into play.

The obvious problems with the study are myriad, but

Because we do not provide direct clinical evidence of an environmental trigger for autism among genetically vulnerable children that is positively associated with precipitation, our results are clearly not definitive evidence in favor of the hypothesis. But the results are consistent with the hypothesis, and, therefore, further research focused on establishing whether such a trigger exists and on identifying it is warranted.
No one on the planet is going to misinterpret this study as actually saying rain causes autism.  What they will do, however, is hear your bias that it is something that happens to the child that leads to autism.

Which is exactly what you wanted, isn't it?


Fortunately, there's an editorial, "Do These Results Warrant Publication?"  in the same issue that critiques the study (e.g. reporting bias, etc) and then argues

that the authors' analysis and the editor's decision to publish it are to be lauded, despite the uncertain ultimate contribution of this work and the possibility (likelihood?) that nonprofessionals are going to misinterpret and misuse it.

You can say a study should be published despite misinterpretation, but why would you say it should be lauded if it is likely to be misinterpreted?

Not only was [cites numerous flaws in the study.] Nonetheless, I would argue, so what? The primary audience for the article of Waldman et al is not the practicing pediatrician, and certainly, it is not a member of the public at large. These individuals cannot take away any practical message from it.

Because people are idiots?

Of course, if a study's findings are no more than tentative ones... responsible authors will stress this, just in case members of the lay public are "eavesdropping" on the exchange of information between scientists.

He doesn't get it, at all.  Or maybe he does?  Repeatedly saying that the results are tentative, stressing the problems with the methodology, this masks and reinforces the ideological bias-- that autism is caused post-natally.

I believe that Waldman et al have indeed reported their results responsibly. They have made it clear that the message the public should take from their data regarding precipitation and autism is the same one suggested by an editorialist commenting on a recently observed modest association between prenatal exposure to cell phone use and behavior problems in childhood: "No call for alarm, stay tuned."


"Are you saying there can't be a component to autism that occurs after birth?"

How do I know?  I have no idea.  More importantly, they don't have any idea, either.  I have the very same evidence available that they do; the question is simply impossible to answer so far.

I am aware, however, that there are plenty of possibilities, both post-natally and pre-natally. This study doesn't test the existence of "environmental triggers" because it could easily be explained by completely genetic factors: for example, that parents who are predisposed to having autistic kids choose to live in Oregon.  (What, is that so insane?)

If his concern is misinterpretation and misapplication of a single study, then he should be aware enough to spot how it will be misinterpreted.

So it isn't misinterpretation that rain causes autism, but that this study has anything to tell us about environmental triggers at all.

The worry about the eavesdropping public isn't that they will read this study and hear, "rain might be involved somehow" but that they become convinced that there is an environmental trigger.

The study will adds to the study pool labeled "Evidence For Environmental Causes" and it simply isn't that.  But when those studies are stacked up on top of each other, it looks like that.


We can now reverse this discussion entirely.

There is considerable evidence that advanced paternal age, but not maternal age, increases the risk for certain psychiatric conditions but not others (e.g. schizophrenia yes, depression no) and increases massively the risk of autism.

I want you to take three seconds and come up with a plausible explanation for why that is.

You picked: defective sperm.  Me, too.

However-- and this is the point-- you must recognize that there is nothing in the epidemiological evidence that allows you to jump to that conclusion.  It is your bias that older father= defective sperm, i.e. that the older father is actually a proxy for a pre-conception risk factor, and NOT that he's too tired to play with the kid; or that any man who had to wait until later to have kids is semi-autistic himself, etc.  All of those are prejudices, biases, unfounded in science, but they are exactly the same as believing it has to do with defective sperm.

There is circumstantial evidence, e.g. with mice, that older fathers produce progeny with various "problems": decreased exploratory activity, worse performance on avoidance tasks, etc, but nothing that would hold up in court.

Advanced paternal age could just as well be a post-natal risk factor as it could a pre-natal one; just as rain could just as well be a pre-natal risk factor as it could a post-natal one.

However, both camps have chosen a side and fail to consider the other side.  They're already firm about when the problem started, or what kind of problem to look for.  Dialogue is therefore impossible.


There is an additional twist to this story: the kind of autism (or schizophrenia) that is associated with advanced paternal age may be a different kind of autism or schizophrenia then the heritable kind.

To illustrate this, consider the happy discovery that in monozygotic twins (identical) have a 50% concordance for schizophrenia.  Dizygotic twins (fraternal, non identical) have much less-- 10%-- the same as any other first degree relative. (For autism it's 60% MZ, 0% DZ.) This can easily be taken to mean, "it's genetic."  End of debate.

Well, it really depends on what "genetic" means.  You're going to want to sit down for this:

When MZ twins are divided between monochorionic (one placenta for both fetuses) vs. dichorionic (each MZ twin gets it's own placenta) you find slightly different concordances: 60% for the same placenta twins, and 10% for the separate placenta twins.

Remember, even though they have different placentas, their DNA is still completely identical.  If schizophrenia was really mostly about DNA, then the placenta shouldn't matter.  But it appears that placenta matters more than DNA.

The average reader will find this quite fascinating, but for me, the truly fascinating, jaw dropping part of it all is this: the article cited, above, was written in 1995.  Since that time, no one has furthered this line of inquiry.

Not because the study was debunked-- no one tried to debunk it.  It's simply too hard to study twins in this way, and since it is to hard, we pretend that it isn't important.  The only analogy that comes to mind is a political one: it's way too hard to track down loose Russian nukes, so instead we'll continue to work on disarming ours.

 Autism is a spectrum; schizophrenia is a spectrum, and not only are multiple factors involved, but likely specific factors are involved in specific subtypes only that we currently lump all together.

Add to that everyone's camping out in different corners of the nature/nurture octagon, and if you're wondering why over 40 years of research into the causes of both disorders we're still at the level of "rain," well, that's why.


It is my personal bias (emphasis mine and bold and underlined) that advanced paternal age is a proxy for both/either "defective sperm" or some diathesis of... developmental disorder... in the father.  Either or both may be relevant for different cases.  If someone wanted to do a second study, take the rain study and cross it against paternal age.  Do older fathers live in Oregon?

So where is the real money in genetic research in autism and schizophrenia?  More generally: where are we most likely to find "genetic" explanations for complex behavioral traits that defy simple "gene model" explanations?

Start by looking at the possible explanations for the genetic effects of advanced paternal age:

There are three main lines of thought.

1.  Older sperm has longer time to suffer point mutations.  Men's sperm is constantly (24 times a year) undergoing cell division, each time brings opportunity for mutation.

2.  Expanding trinucleotide repeats. 

3.  Imprinting.

I believe with no hesitation that the money is in imprinting.  Let me explain.

Part 3 In one week