Archive for January 2010
Hello friends –
This post really ought to be Chapter 1, but since I wrote the other post first, and sort of liked the title, so we’ll just pretend; these posts are all about make believe in any case, right?
There is only one valid reason not to vigorously pursue environmental causes of autism; you need to believe that our observation of an increased rate of autism, one hundred percent of it, is an artifact of the four horsemen of the imaginary increase:
- Diagnostic Substitution
- Greater Awareness
- Increased Accessibility to Diagnosis
- Widening of Diagnostic Criteria
Lets start off with a couple of honest admissions and the reason they don’t make a whit of difference if our goal is to expose the notion of a static rate of autism as a fairytale, and a dangerous one at that.
- I have read very few papers regarding prevalence fully. In fact, I can’t think of the title of a single one. In the context of a precautionary principle, however, the methods and discussion for this type of study don’t really matter much; because the brush strokes used to craft the results are so necessarily broad and imprecise that they are admitted as meaningless even by people who believe in the fairytale. Think about it. The only way we have a static rate of autism is if all of our previous studies utilized methods of such poor quality that they missed ##-## per 100,000 cases of autism, where you get to replace ##-## with any set of numbers lower than 100 as you move backwards in time. The conclusions in our previous prevalence studies are so discordant over time that the flaws in their methodology are the super strings of the fairytale; responsible for all of our observations of increased autism rates while having natural physical properties that render them impossible to elucidate on completely. Given that even the proponents of the fairytale don’t give the methods of previous studies any currency, why should anyone?
- I cannot provide meaningful estimates on what percentage of the observed increase in rates is real versus artifact. Again, however, in the prism of a precautionary principle, it doesn’t matter, because any amount of real increase is alarming, and the only possible unalarming possibility is a zero percent increase. Here is a little thought exercise to illustrate this; imagine you are on a debate team and the topic is; “Autism rates have risen by X percent, health crisis or not?” and your team has drawn the ‘not a crisis’ side. Insert any number greater than zero for X, and then try to construct debate points to make this argument to a crowd of skeptics. This argument is implied whenever the fairytale is invoked, sometimes with the assertion that any real increase is “minor”, but one surefire way to get a storyteller to dissolve from a discussion is to try to get a value more concrete than “minor” for X. Autism is a disability, and while there are arguments to be made that it is also a ‘difference’, it isn’t a difference like having red hair or being left handed anymore than dyslexia is a different way of reading; any true increase has broad implications for us all.
- I have no doubt that the four factors listed above are, indeed, responsible to one degree or another towards what we are observing in autism rates. Unfortunately, unless we are able to explain our ever rising rates of autism completely with these explanations, we still must contend with ramifications of a true increase.
Even with the above caveats, a compelling case can be made that what we are observing is comprised of an actual increase in behaviors consistent with an autism diagnosis, and the argument that autism rates are static is long on faith and very low on the lifeblood of science; reliable data.
Neat looking study: Plasma cytokine profiles in Fragile X subjects: Is there a role for cytokines in the pathogenesis?
Posted January 29, 2010on:
I have yet to get my hands on a copy of Plasma cytokine profiles in Fragile X subjects: Is there a role for cytokines in the pathogenesis?, but plan on doing so relatively soon. Even still, the abstract looks pretty good:
BACKGROUND: Fragile X syndrome (FXS) is a single-gene disorder with a broad spectrum of involvement and a strong association with autism. Altered immune responses have been described in autism and there is potential that in children with FXS and autism, an abnormal immune response may play a role. OBJECTIVES: To delineate specific patterns of cytokine/chemokine profiles in individuals with FXS with and without autism and to compare them with typical developing controls. METHODS: Age matched male subjects were recruited through the M.I.N.D. Institute and included: 19 typically developing controls, 64 subjects with FXS without autism and 40 subjects with FXS and autism. Autism diagnosis was confirmed with ADOS, ADI-R and DSM IV criteria. Plasma was isolated and cytokine and chemokine production was assessed by Luminex multiplex analysis. RESULTS: Preliminary observations indicate significant differences in plasma protein levels of a number of cytokines, including IL-1alpha, and the chemokines; RANTES and IP-10, between the FXS group and the typical developing controls (p<0.01). In addition, significant differences were observed between the FXS group with autism and the FXS without autism for IL-6, Eotaxin, MCP-1 (p<0.04). CONCLUSIONS: In this study, the first of its kind, we report a significantly altered cytokine profile in FXS. The characterization of an immunological profile in FXS with and without autism may help to elucidate if an abnormal immune response may play a role and help to identify mechanisms important in the etiology of autism both with and without FXS.
I love the MIND guys. Anyways, the quick glance gives me some ideas:
- The big one here would seem to be that we seem to have additional evidence that immune dysregulation has very specific ties to autism; a pattern not just of immune dysregulation, but indeed, the beginings of an immunological signature, one so precise that given nothing but blood samples, we could beat Vegas odds in selecting which child has Fragile-X, and which child has Fragile-X and autism. This is also more evidence that an abberant immunological response might be playing a causative role in autistic behavior genesis; just having Fragile-X isn’t enough for you to have this profile, you also have to have autism.
- Some of the players there we know about already; IL-6 was found in increased levels in the CNS by Vargas, and Li , and was found to be generated at higher levels in several studies including Ashwood, Enstrom , Jyonouchi, and Jyonouchi. It also has great deal of support for a place in seizure generation. MCP-1 was also found in Vargas, Eotaxin is also chemotaxic, though I haven’t read anything about it yet.
That’s the abstract view, the whole paper should get here soon.
My original intention on starting this blog was to try to create more comprehensive, wide ranging screeds on autism than you might usually see in the blogosphere. Alas, this has seemed more difficult and time consuming that I was hoping it might, and my posts have been small. It was suggested to me by Kev at Left Brain / Right Brain that I ‘get my own blog’ if I didn’t like what he was interested in. While I’m not exactly taking his advice, it did occur to me that the post I intended to write back in response to a couple of posts there was lengthy enough and had thoughts I wanted to have stored more accessible that I could go ahead and double post it.
The thread on LBRB is here, wherein I mentioned that familial commonalities may not necessarily be the result of genetics per se, and was consequently challenged by dueling interpretations of the twin study fallacy. Here was my response:
Hello friends –
I’m not here to deny a genetic component to autism, but the lightning fast gunslinging of twin studies hinges on the notion that there is only one way to get to a particular developmental endpoint – genes. If we accept that there are other ways to achieve a particular developmental endpoint, a reliance on twin studies shows itself as a fallacy. You can have genetic and environmental mechanisms affecting neurodevelopment if we allow ourselves to believe that autism rates are increasing, but you can’t have the opposite; to believe that autism rates are stable, completely stable, we can’t allow any intrusion of changes to our environment to be affecting neurodevelopment.
Of course, when pressed, say with studies involving something like valporic acid, as mentioned by Socrates, and a whopping increased risk, you can get the acknowledgement that there are some things that can cause autism that aren’t genes, quickly followed by the impossible to substantiate claim that the amount of increase is very minor.
Unfortunately, we need to start ignoring mounting reams of clinical evidence from a galaxy of sythentic chemicals for this to make any sense.
Take the study I posted above, Prenatal Exposure to Organohalogens, Including Brominated Flame Retardants, Influences Motor, Cognitive, and Behavioral Performance at School Age, which, curiously, got left out of any discussions so that we could discuss twin studies. To illucidate briefly the frailty of an argument exhonnerating our influx of chemicals into the environment, lets examine one of the proposed mechanisms by which organohalogens are believed to affect neurodevelopment; affecting thyroid metabolism.
OHCs are known to exert their neurotoxic influence by affecting thyroid hormone homeostasis. It is hypothesized that OHCs affect thyroid hormone homeostasis by interfering with thyroid hormone signaling in the developing brain, by changing intracellular thyroid hormone availability, and by interacting directly at the level of the thyroid hormone receptors. On the one hand, OHCs have a high affinity for thyroid hormone receptors and lead to a decrease in thyroid hormone levels, whereas levels of TSH increase through hormonal feedback mechanisms. Previous studies on pregnant women and their infants found that PCBs are associated with higher levels of TSH and lower levels of T4 (Koopman-Esseboom et al. 1994). We found that PCP correlated with lower levels of thyroid hormone but brominated flame retardants correlated with higher levels of thyroid hormone. It is unknown whether the underlying mechanism by which PCBs affect thyroid hormones is the same for these OHCs. Our study disclosed consistent relations between thyroid hormones and outcome. We found that TSH correlated with worse neuropsychological functions. Thyroid hormones (T3 and T4), by contrast, correlated with better outcome. These findings, together with the negative correlations between OHCs and development, seem to confirm the hypothesis that thyroid hormone homeostasis may be involved.
Having thyroid metabolism interferred with during pregnancy is associated with a variety of bad outcomes, inclding, Pervasive developmental disorders, autism, reduced cognitive abilities , ADHD and many, many other condtions.
Unsurprizingly, when we look for associations between levels of these chemicals and development outcomes, we find results that should surprise no one, such as the study I linked to above, or another, here.
The facts on the ground are that these chemicals are completely novel to our planet in the past few decade and many have reached environmental ubiquity. We have a growing understanding of the mechanism(s) by which these chemicals can affect developing brains, and association studies that indicate that our clinical observations have merit for a variety of conditions, including autism. Finally, we seem to be observing an explosion of ever increasing behavior patterns that no one can really explain without necessarily invoking an the ever hopeful idea of progressing decrease in uncertainty of our diagnostic as rates continue to go in a single direction. The fact that twins have autism more frequently does absolutely nothing to change any of this if we allow ourselves to believe our observances of increase are not completely an artifact; but the inverse does not hold true. We must find a reason to believe that all of these studies, and many, many others are all wrong in exactly the same way for our environmental engineering to be without consequence.