Archive for the ‘autism’ Category

I’ll be done with grad school in about two weeks and able to start posting more frequently – hooray!  Today’s entry is a response I wrote for a friend who asked why the thimerosol-in-vaccine-causes-autism movement doesn’t go after thimerosol in household products to anywhere the same degree as in vaccines (especially in vaccines that no longer contain thimerosol).  This entry contains speculation, although it’s speculation based in existing cognitive science, primarily in cognitive anthropology work on what cognitive faculties make some beliefs catchier than other beliefs.  In the field this work gets called “epidemiology of beliefs”: what characteristics of human minds some beliefs compelling in a way that others are not?

The anti-vaccine movement comes in part from anecdotes of kids regressing at about the time they get the MMR vaccine. That’s actually accurate; when I was taking a cognitive development graduate class, the percentage estimated to regress in that way was about 25%. There was some speculation at the time that it’s due to kids’ brains undergoing a major reorganization at (coincidentally) about the same time they get the MMR.

(Kids make a bunch of neuronal connections, then prune out the less useful ones, and the speculation was that the children who lost language and social skills had not pruned as extensively. There was some research on head circumference at the time looking at whether kids with autism had greater head circumference – kind of a crude measure if you ask me but it did seem to be panning out.)

My own impression is that the anecdotes about regression after vaccine (but not anecdotes about regression before vaccine) kick off contamination fears in some people. In the literal “we have a mental faculty that’s highly alert to dangerous contamination by non-visible substances” sense. Which then kicks off a search for an essentialized underlying substance that will explain/justify their intuitions (also an extremely common thing for people to do).

What I’m getting at is that thimerosol isn’t a trigger for concerns, thimerosol-in-vaccines is an explanation for them. It’s the endpoint of a search. Why doesn’t it generalize from there? My speculation is that vaccines are required by authority and contact lens solution etc is not, and stories about having dangerous things forced on you are much more mentally catchy and conducive to righteous indignation and fear than are stories about stuff you can voluntarily avoid. So a lot of people don’t know about it, and it’s not that their lack of concern comes from lack of knowledge, but that their lack of knowledge comes from fears of thimerosol-in-household-products never taking root strongly enough to become widespread.

I looked up celiac disease and autism on pubmed the other day.  My mother’s secretary has a daughter recently diagnosed with autism, and diagnosed several years with celiac disease.  So we were sitting in the dining room and I’m snacking and looking up stuff on pubmed.

“There’s not much research, but the two studies I’ve found on autism and celiac did not find a link, except for this one quack guy,” I say, meaning Andrew Wakefield.

“Okay,” my mom says.  “So they haven’t done the research confirming it yet.”

“No,” I say.  “There are two existing studies that have looked, and they did not find evidence of a link.  I’m looking on pubmed, so if there were more studies they would very likely be there.”

“Ah,” my mom says. “So all we’ve got now to go on is anecdotal evidence.”

“No,” I say again.  “Studies looked.  They looked for a link, and they didn’t find a link, suggesting there’s not a link.”

I think at that point we detected mutually incompatible approaches to uncovering truth, and dropped the conversation.

——–

It’s a normal human thing to figure out what you believe is true (often by assuming anecdotes are representative of overall reality), and then seek out social back-up to help convince others of it.  In this approach to truth (which drives scientists up the wall), if science is used, it is used to support one’s own truth claims to others.  If someone is not trying to make truth claims to others, then there is no need for science; it doesn’t tell you anything you don’t already know.

In contrast, the role of science as-generally-agreed-upon is to test what we believe to be true to see whether it really is true. In this approach to science, science can disconfirm anecdotes, and its role is to drive what people believe, not just to back what they already do believe.  So it’s much less useful for normal human goals.

Frustrating, that.   Also frustrating that we don’t have much research on a lot of things.  It could be true that the two studies on autism and celiac disease didn’t pick up on an actual connection…but the point is, two studies that show no connection are a lot more meaningful than no studies that show no connection.

A lot of kids diagnosed with autism would previously have been diagnosed with general mental retardation.  Now genetic testing is finding that some kids with autism diagnoses have specific genetic deletions/duplications.  Does that mean that they’re not really autistic and “autism” was a misdiagnosis? Or that “autistic” will turn out to be a useful umbrella term for a bunch of different things?  My vote is for the latter…

Searching for similar diagnoses through DNA testing

The article stresses both the relief families find at meeting other families with similarly affected kids, and the distress they experience at seeing the degree of impairment that older children with the same problems (still) have. And there’s a demonstration of the way gender roles play in to who can back out of their responsibilities and who can’t – note the one father who decided to pick up and leave a week after a conference for families with affected kids, leaving the mom to raise their affected daughter alone.

The actual headline is “Fever can unlock autism’s grip“, which is catchier but inaccurate.  Autism is not some external thing that has ahold of of a child or adult; it’s a developmental disorder that causes autistic kids’ brains to develop in ways that differ from how normal kids’ brains develop.  Consequently, they show features of autism like impaired social skills and upset in response to change.

I don’t know what to make of this overall.  They say fever “restores” nerve communication in the brain, enabling autistic kids to act like normal kids.  Without real clear evidence that kids with autism initially have normal nerve communication, then they don’t, then they get a fever and they do, I’d vote for “alters” nerve communication.

In the same way that brains of people with mental disorders are not normal brains minus adequate practice, brains of autistic children (as far as we know at this point) are not normal brains with autism added on.

Be pretty intriguing if that turned out to be wrong, though.

I’m not sure what to make of this.

I do know that similarity in symptoms doesn’t necessarily mean similarity in etiology (in what causes a disorder).   For example, you can have a thyroid problem that looks like a mood disorder, but we know they’re not the same disorders because many people with mood disorders don’t have thyroid problems.  And brain damage can mimic psychiatric disorders.  Kind of like if you have a bucket chain to put out a fire – the house might burn down because there wasn’t any water, or it might burn down because the people started getting smoke inhalation problems and stopped.  Totally different causes, same end result.

I’ve wondered about that with ADD when it occurs in bipolar disorder versus when it does not.  Since ADD is so very common in bipolar disorder, maybe it’s a set of symptoms caused by something in the mood/energy brokenness, but caused by something else when there isn’t bipolar disorder.  Who knows?  I poked through PubMed a little but couldn’t find any speculations on the reason for the comorbidity (in bipolar or in anything else).

Several summers ago I spent six weeks in another country, doing research in collaboration with autism researchers there.  We traveled around by subway, train, and cab, visiting multiple schools with autistic children.  Some were regular schools that had an autism unit; others were boarding schools for special-needs children or for children with autism specifically.  We worked with the higher-functioning kids with autism (who had at least some language) and with younger mental-age-matched kids without autism (because mental retardation is very common in autistic kids – up to 74% although I read something non-peer-reviewed on the Internet that claims as low as 50% – to compare autistic and non-autistic kids on cognitive stuff you need to equate them on mental age, not chronological age).

We did a variety of tasks with the kids, involving stuff like sorting cards, or hearing stories and answering questions, or pushing buttons in response to pictures of faces on a computer screen.  One of the weirder tasks, which was something for our collaborators, not for me and my prof, involved measuring kids’ heads with a measuring tape.  I thought it seemed kind of an odd approach at the time – most of what I was involved in was heavily cognitive.  And so I’ve been surprised to see that line of research actually panning out.

Here’s a recent instance of it (citation below).  Researchers found that, very clearly, children with autism had larger head circumferences.  What I thought was interesting was that head circumference above the 75th percentile was  “associated with more impaired adaptive behaviors and with less impairment in IQ measures and motor and verbal language development.”

So something strongly associated with autism was also associated with less mental retardation (but mental retardation is strongly associated with autism).  There’s some interesting stuff in there…  I’m tempted to hypothesize beyond the data, but I’m not going to.

Larger head circumference was also associated with allergy/immune disorders in the kids and their first-degree relatives.  The researchers speculate that this relates to immune dysfunctions that themselves cause or are associated with increased cell cycle progression (cannot dredge what that means up out of my brain) and/or decreased apoptosis (deliberate, clean cell death).

At the time of my first couple years in grad school, it was being speculated that for the quarter or so of autistic kids who have a noticeable period of skill loss (coincidentally around the time of the MMR shot, which has led to a whole lot of bad crap) lose their skills around the time that the brain undergoes a major reorganization in which unnecessarily neuronal connections are “pruned” or cut back.

So: Maybe immune dysfunction leads to lack of cell death in pruning and maybe outside of it too, and thus autism and larger head circumference?

That and a dollar will get you one-quarter of a latte, or almost a small iced tea, or a tiny little bit of the funding necessary to gain actual knowledge, or a fair bit of annoyance from someone more educated who already knows why you’re wrong.   Speculation is tasty and rampant, but actual knowledge comes from eliminating the untrue theories with evidence, and hammering on the true ones until we decide there’s not much point in continuing to do so.

Sacco, R., et al. (2007) Clinical, Morphological, and Biochemical Correlates of Head Circumference in Autism. Biol Psychiatry.

Autism Diva has extensive hypotheses about variation in autism rates within Southern California. This is a good example of how you can start to explain cultural variation: you say could it be this, could it be this, could it be this, and then you move on to asking how to test each of those hypotheses.

Columbia University researchers have created a visualization of disease comorbidity using health records from 1.5 million people (article and full-text paper). There’s a lot they’ll be able to do with this – look for genetic links, look to see if some conditions protect from other conditions, look for potential environmental triggers like bacterial or viral infections.

This sounds awesome in general – people can process complex information about associations much faster when represented visually than when they see a bunch of numeric correlations. (Way to go, information usability!)
They find that bipolar, autism, and schizophrenia are associated (quotes from the paper):

We estimate that {approx}20–60% of autism-predisposing variations also predispose the bearer to bipolar disorder, and 20–75% of autism-predisposing variations also predispose the bearer to schizophrenia. It is therefore extremely likely that there is a three-way positive correlation among autism, bipolar disorder, and schizophrenia, a correlation that probably arises from a genetic variation that predisposes to all three disorders.

If so that’s extremely interesting, although I wonder how much of a link between autism and schizophrenia is due to the two being mistaken for each other (or perhaps the overlap in predisposing genes is why the two are mistaken for each other – our diagnostic categories are attempting to clearly delineate fuzzy categories).

Also, everything under the sun is associated with autism, apparently (I wonder whether there’s a causal relationship, and if so which way, or whether it’s third variables, or all of the above):

[A]utism, which typically manifests before the affected child is 3 years old, has a strong positive correlation with a number of neurological disorders, some of which have a late-age onset…: attention deficit, epilepsy, cerebral palsy, depression, schizophrenia, bipolar disorder, neurofibromatosis, Parkinson’s disease, and migraine. Our estimated significant overlap between autism and tuberculosis may indicate that both diseases are associated with genetic changes weakening the immune system.

They also mention associations between allergies/autoimmune disorders and autism, schizophrenia, and bipolar disorder. And here’s something totally new: female breast cancer is negatively associated with schizophrenia and bipolar disorder. They proposed an explanation involving schizophrenia and bipolar being associated with increased probability of abnormal cell death in some tissues, and breast cancer being associated with an increased probability of abnormal cell proliferation. And they mention that tamoxifen (a breast cancer treatment drug) can help treat bipolar disorder – I’ll try to follow up on that in a future post.

And the credits go to: Andrew Rzhetsky, David Wajngurt, Naeun Park, and Tian Zheng of the University of Columbia. And any unnamed undergraduate or graduate assistants.

(For anyone who’s requested an entry on a specific topic: I haven’t forgotten you, I’ve just been too busy to do background research because of moving this weekend, and have been doing stuff I could sit down and type out instead. Entries on schizoaffective disorder, kindling, worries about personality change on meds, and lots of stuff on culture coming up, among other things.)

The online magazine Spiked has an issue just out on MMR and autism, with a lot of articles which are both detailed and reasonable.

A meta-analysis of 55 published research studies found that social skills programs for autistic kids were poor overall, though better if the programs were held in the normal classroom setting rather than a pull-out one. They were more likely to use and to maintain the new skills, and more likely to use them in other settings. The researchers recommend greater amounts of programming, targeting programs towards kids’ skill deficits, and checking to see whether the program was actually carried out as designed.

No commentary on this one – just general surprise that they were found so solidly poor.