Study Watch : IL-6 is increased in the cerebellum of the autistic brain and alters neural cell adhesion, migration and synapse formation

If you ever wondered how a dysregulated immune system could lead to the symptoms of autism, here is one possible answer for you.  A new study has added to the evidence that interleukin 6, a chemical messenger produced by and used by the immune system, can be abnormally high in the brains of some people with autism. More importantly, it showed that it is possible that these high levels of IL-6 can modify the physical functioning of the brain.

Or at least it can alter the physical properties of bits of mouse brains in petri dishes.  Replication of this exact study in human brains will have to wait until someone allows some researchers to play mad scientist with their brains...

Sorry, couldn't resist the bad joke.  But seriously, this is an interesting study and if you are interested in the immune system and how it could impact the functioning of the brain, it is worth reading.  The study is open access, so the entire text is freely available here.


IL-6 is increased in the cerebellum of the autistic brain and alters neural cell adhesion, migration and synapse formation.

Wei H, Zou H, Sheikh A, Malik M, Dobkin C, Brown T, Li X.

Background: Although the cellular mechanisms responsible for the pathogenesis of autism are not understood, a growing number of studies have suggested that localized inflammation of the central nervous system (CNS) may contribute to the development of autism. Recent evidence shows that IL-6 has a crucial role in the development and plasticity of CNS.

Methods: Immunohistochemistry studies were employed to detect the IL-6 expression in the cerebellum of study subjects. In vitro adenoviral gene delivery approach was used to over-express IL-6 in cultured cerebellar granule cells. Cell adhesion and migration assays, DiI labeling, TO-PRO-3 staining and Immunofluorescence were used to examine cell adhesion and migration, dendritic spine morphology, cell apoptosis and synaptic protein expression respectively.

Results: In this study, we found that IL-6 was significantly increased in the cerebellum of autistic subjects. We investigated how IL-6 affects neural cell development and function by transfecting cultured mouse cerebellar granule cells with an IL-6 viral expression vector. We demonstrated that IL-6 over-expression in granule cells caused impairments in granule cell adhesion and migration but had little effect on the formation of dendritic spines or granule cell apoptosis. However, IL-6 over-expression stimulated the formation of granule cell excitatory synapses, without affecting inhibitory synapses.

Conclusions: Our results provide further evidence that aberrant IL-6 may be associated with autism. In addition, our results suggest that the elevated IL-6 in the autistic brain could alter neural cell adhesion, migration and also cause an imbalance of excitatory and inhibitory circuits. Thus, increased IL-6 expression may be partially responsible for the pathogenesis of autism.

PMID: 21595886
DOI: 10.1186/1742-2094-8-52

Study Watch : Trends in the Prevalence of Developmental Disabilities in US Children, 1997–2008

According to a new study due to be published in the June issue of Pediatrics, the number of children and teenagers diagnosed with a developmental disability has increased 17 percent since the late 1990s.

Trends in the Prevalence of Developmental Disabilities in US Children, 1997–2008

Objective: To fill gaps in crucial data needed for health and educational planning, we determined the prevalence of developmental disabilities in US children and in selected populations for a recent 12-year period.

Participants and Methods: We used data on children aged 3 to 17 years from the 1997–2008 National Health Interview Surveys, which are ongoing nationally representative samples of US households. Parent-reported diagnoses of the following were included: attention deficit hyperactivity disorder; intellectual disability; cerebral palsy; autism; seizures; stuttering or stammering; moderate to profound hearing loss; blindness; learning disorders; and/or other developmental delays.

Results: Boys had a higher prevalence overall and for a number of select disabilities compared with girls. Hispanic children had the lowest prevalence for a number of disabilities compared with non-Hispanic white and black children. Low income and public health insurance were associated with a higher prevalence of many disabilities. Prevalence of any developmental disability increased from 12.84% to 15.04% over 12 years. Autism, attention deficit hyperactivity disorder, and other developmental delays increased, whereas hearing loss showed a significant decline. These trends were found in all of the sociodemographic subgroups, except for autism in non-Hispanic black children.

Conclusions: Developmental disabilities are common and were reported in ~1 in 6 children in the United States in 2006–2008. The number of children with select developmental disabilities (autism, attention deficit hyperactivity disorder, and other developmental delays) has increased, requiring more health and education services. Additional study of the influence of risk-factor shifts, changes in acceptance, and benefits of early services is needed.

Study Watch : In Search of Cellular Immunophenotypes in the Blood of Children with Autism

I ran across this study the other day and found it to be interesting.  It is open access so the full text of the study is freely available.  If you are interested in the possible relation between the immune system and autism, I suggest that you go read at least the discussion section of the paper, it will be worth your time.

The abstract for the study follows -

In search of cellular immunophenotypes in the blood of children with autism.
Ashwood P, Corbett BA, Kantor A, Schulman H, Van de Water J, Amaral DG.
Department of Medical Microbiology and Immunology, University of California Davis, Davis, California, United States of America

Background: Autism is a neurodevelopmental disorder characterized by impairments in social behavior, communication difficulties and the occurrence of repetitive or stereotyped behaviors. There has been substantial evidence for dysregulation of the immune system in autism.

Methods: We evaluated differences in the number and phenotype of circulating blood cells in young children with autism (n = 70) compared with age-matched controls (n = 35). Children with a confirmed diagnosis of autism (4-6 years of age) were further subdivided into low (IQ<68, n = 35) or high functioning (IQ≥68, n = 35) groups. Age- and gender-matched typically developing children constituted the control group. Six hundred and forty four primary and secondary variables, including cell counts and the abundance of cell surface antigens, were assessed using microvolume laser scanning cytometry.

Results: There were multiple differences in immune cell populations between the autism and control groups. The absolute number of B cells per volume of blood was over 20% higher for children with autism and the absolute number of NK cells was about 40% higher. Neither of these variables showed significant difference between the low and high functioning autism groups. While the absolute number of T cells was not different across groups, a number of cellular activation markers, including HLA-DR and CD26 on T cells, and CD38 on B cells, were significantly higher in the autism group compared to controls.

Conclusions: These results support previous findings that immune dysfunction may occur in some children with autism. Further evaluation of the nature of the dysfunction and how it may play a role in the etiology of autism or in facets of autism neuropathology and/or behavior are needed.

PMID: 21573236

Jabberwocky of the Day : Don't Comment Where I Said It

So, if you were responding to something that I wrote, where would you leave the comment? Would you leave a comment on the post where I wrote it? Or would you pick another post on a related subject and leave it there? Or perhaps you should start reading all of the posts from that point forward and choose one that says something kinda like what you want to say.

It might just be me, but I think that online etiquette strongly suggests that you leave your comments on the post where the issues was raised.

Confused yet? Go read one of the latest posts on Countering... (look flowers!).

Apparently Minority wasn't allowed to comment on the post that contained the offending text. According to the Ms Wombles, that was an "interesting choice", an attempt "bury it where no one will likely see it", and wasn't an "attempt at honest communication".

Really?

I just had an exchange with two people on an older post from last year.  Should I say that the commenters were attempting to "bury" their comments where only I can see them?  Should I be hostile to them because they disagreed with with I said?  Or maybe I should write a big long rant about how they are unfortunate people who have been "misled by the atrocious misinformation".

Of course the answer to all of these questions is a resounding no.  These people were simply expressing their views about what I wrote in the place that I wrote it.  And there is absolutely no need to treat other people badly simply because they don't happen to agree with me.  Nor is there a need to imply that they are "wrong" and I am "right" or that they have "misinformation" while I have some sort of monopoly on the correct information.

In fact, I actually welcome comments from people who don't agree with me.  I find that I can sometimes learn more from talking to people who disagree with me than with people who agree with me.

If I had to guess at Ms Wombles's intentions in writing what she did, I would say that she was attempting to intimidate Minority by pulling out a comment from an older thread and placing it front and center on her blog.  I'm guessing that she is trying an old teaching trick - public shame.

So Kim, here is your little bit of shame in return.

Minority called you on your statement - in the appropriate place - and you responded with public ridicule because you didn't care for what they said.  It really isn't nice to try to bully people into being quiet.  Don't you think you should apologize for being such a meanie?

On a slightly more serious note, one of the comments on the shameful piece suggested that the recent attacks on the Ms Wombles have just been personal name-calling attacks that don't address the underlying issues.  But I'm going to go out on a limb here and disagree.

(Well, I guess I can't disagree with the name-calling part since I did do a little bit of that - lets just call it "venting" instead, shall we?)

What I disagree with is that my quarrel with Ms Wombles isn't about the issues.  This debate is certainly about an issue and the issue is character.  The autism world is chalk full of people like Ms Wombles who spend their time attacking and demeaning anyone who dares disagree with them and I for one have had enough of them.

(Although, to be honest, there are far worse people out there than Ms Wombles.  One of them actually challenged me to a "duel" because of something that I wrote here.  Unfortunately, I didn't have a sword and they lived in France, so I had to decline.)

But I digress.  As I was saying, the issue is character. The issue is whether it is acceptable to stand on the sidelines when one member of the community tries to bully another.  As Ms Wombles so nicely put it, the issue is accountability after all.

I think it is long past time that the autism community holds its members accountable for their actions.

P.S. Kim, fourteen blogs, really?  Where do you find the time?

Study Watch : Early Diagnoses of Autism Spectrum Disorders in Massachusetts Birth Cohorts, 2001–2005

A new study in Pediatrics covers the the number of children receiving early intervention services for autism in Massachusetts.  I am sure will be writing about this one in more depth in the near future but  The main point here is that children receiving early intervention services for autism increased significantly for children born between 2001 and 2005.

One statistic that jumped out at me while I was skimming the study -

Among boys, early ASD diagnoses increased more than 70%, from 88 per 10,000 children for the 2001 birth cohort to 151 per 10,000 for the 2005 cohort.

That implies that the rate of autism in boys born in 2005 in Massachusetts is about 1.5%.  I feel more aware already...

The abstract is below -

Early Diagnoses of Autism Spectrum Disorders in Massachusetts Birth Cohorts, 2001-2005.

Manning SE, Davin CA, Barfield WD, Kotelchuck M, Clements K, Diop H, Osbahr T, Smith LA.
Bureau of Family Health and Nutrition, Massachusetts Department of Public Health, Boston, Massachusetts;

Objective: We examined trends in autism spectrum disorder diagnoses by age 36 months (early diagnoses) and identified characteristics associated with early diagnoses.

Methods: Massachusetts birth certificate and early-intervention program data were linked to identify infants born between 2001 and 2005 who were enrolled in early intervention and receiving autism-related services before age 36 months (through December 31, 2008). Trends in early autism spectrum disorders were examined using Cochran-Armitage trend tests. X(2) Statistics were used to compare distributions of selected characteristics for children with and without autism spectrum disorders. Multivariate logistic regression analyses were conducted to identify independent predictors of early diagnoses.

Results: A total of 3013 children (77.5 per 10 000 study population births) were enrolled in early intervention for autism spectrum disorder by age 36 months. Autism spectrum disorder incidence increased from 56 per 10,000 infants among the 2001 birth cohort to 93 per 10,000 infants in 2005. Infants of mothers younger than 24 years of age, whose primary language was not English or who were foreign-born had lower odds of an early autism spectrum disorder diagnosis. Maternal age older than 30 years was associated with increased odds of an early autism spectrum disorder diagnosis. Odds of early autism spectrum disorders were 4.5 (95% confidence interval: 4.1-5.0) times higher for boys than girls.

Conclusions: Early autism spectrum disorder diagnoses are increasing in Massachusetts, reflecting the national trend observed among older children. Linkage of early-intervention program data with population-based vital statistics is valuable for monitoring autism spectrum disorder trends and planning developmental and educational service needs.

DOI : 10.1542/peds.2010-2943

Dr. Offit on the Definition of Autism

In a recent Medscape article, Dr Paul Offit is quoted as putting forth the following idea on autism -

Dr. Offit said the study authors reach erroneous conclusions due to an erroneous definition of autism. A child with measles encephalopathy, he said, may have severe cognitive deficits that fall into the autism spectrum, but such symptoms themselves do not necessarily translate into a diagnosis of autism. 

The good doctor is of course talking about the recent paper that purports to show that autism might be more common in children compensated by the the so-called vaccine court than in the general population.  While I don't yet have much of an opinion on the paper, I do know that Dr. Offit's statement is just plain wrong.

First and foremost, a diagnosis of autism is based solely on the presence or absence of behaviors.  If you have enough of the behaviors of autism then you have autism, if you don't then you don't.  There is absolutely nothing in the definition that says anything about the underlying causes of the behaviors.  It is factually inaccurate to say that "severe cognitive deficits that fall into the autism spectrum" aren't autism.  Autism is autism - regardless of the cause.

Second, the authors in the paper actually used a validated autism screening test called the Social Communication Questionnaire (SCQ) with twenty-two of the children that they found.  While the test cannot definitively show that a person has a diagnosis of autism, it is certainly not an "erroneous definition of autism".  As a matter of fact, there are a quite a few research studies that have used the SCQ to help identify cases of autism

The problem is that Dr Offit has painted himself into a corner in regards to autism and vaccines.  He regularly says things such as "This hypothesis has been tested thoroughly. The question has been asked and answered.", as he did in this story.  He has written several books on the subject, all of which basically say the same thing - no relation between autism and vaccines.

I don't think he is now able to admit, either to himself or publicly, that he might have been wrong.  Instead he has to come up with non-autistic forms of autism and spends his time "defending" his idea against anyone who questions it.

This is precisely the reason why there is no such thing as an "asked and answered" question in science.  Once you have decided that you already have the answer you stop listening to what everybody else is saying.

Jabberwocky of the Day : The Qwibbler on Honor and Decency

quibble, quibble, quibble

I think I might have mentioned this before but I really dislike hypocrisy.  You either stand by what you say and demonstrate it through your actions - or you don't.  There are many people who say that they are one thing but through their actions and words show that they are another.  In my opinion, self-proclaim "community builder" and lady of science Kim Wombles is one of those people.

Consider her recent responses in the Bonnie "Sullivan" Offit incident.  For those of you who aren't familiar with the story, here is the short version.

J.B. Handley accused the then anonymous "Sullivan" of secretly being Bonnie Offit, wife of the ever-so popular Paul Offit.  Mr. Handley was so convinced that he was right (or that Sullivan would never out himself) that he makes two promises if he was wrong - never to publicly write about or utter the name Paul Offit again and to turn over the pauloffit.com domain to the Offits.

Much hilarity ensues from the right-wing of the autism world but the blogger known as Sullivan does not reveal his identity.  A few months later, Sullivan is "outed" by former members of the autism hub blogs and Handley is called on his promises.  Handley responds and says that he will make good on his promises.

Interestingly enough, a few days after he is "outed", Sullivan writes an apology to J.B. Handley saying that "I doubted that Mr. Handley would make good on his commitments, even going so far as to write that I didn’t think he had the integrity to do so. For those comments I offer a sincere apology. I was wrong." (Although he may have since retracted his apology).

All of that takes us up to about three weeks ago and since then people seemed to be losing interest in the affair.  That is until Liz Ditz decided to stir up trouble and call J.B. Handley "forsworn" for not keeping his promises.  Specifically she has a problem because the pauloffit.com domain name has not been transferred to the Offits and the then current content on the site was hostile to Paul Offit.

Here are a few facts that I can establish.  As of May 9th, 2011 at 04:19:54 GMT, google has a cache of the pauloffit.com domain that just has a single picture of the character of Sullivan from the movie Monster's Inc on it.  Liz Ditz published her piece on May 11th, 2011 at 4:45 PM EST (give or take).  I cannot find any record of what the pauloffit.com site looked like at that point but from the screen shot's included in Ms. Ditz's post, it appears that the site consisted of old news stories about Paul Offit.

I am not going to judge whether putting those stories on the site was a violation of Handley's promise, assuming that he actually was the one who modified the page.  There is the letter of the promise and then the spirit of it.  I will say that if Mr Handley was the one who put up the page then one of these things might have been broken.

Moving along, in jumps St. Wombles into the fray with a piece entitled "Handley Backs Out of Agreement Regarding Offit Website".  She says it is "despicable behavior from an often vile group of people" and that Handleys (alleged) behavior "should not be surprise to anyone", thus showing that she really does care about building community.  I mean, nothing builds community and shows tolerance for difference of opinion like calling someone "despicable "or labeling an entire section of autism parents an "often vile group of people".

Ahem.

The thing that I also found interesting is that it doesn't appear that the lady of science ever attempted to contact J.B. Handley to see what he was doing in regards to transferring the domain.  If you wanted to be strictly accurate, there was no evidence that J.B. Handley wasn't working to keep his promise.  As anyone who has tried to transfer a domain name from one party to another could tell you, it can sometimes take a little while for the transfer to happen.  Especially if the two parties to the transfer aren't on the best of terms as is clearly the case here.

So putting up a piece asserting that Handley backed out of his agreement without first actually establishing that that was indeed the case would be, what's the term, a little bit of "woo"?

Well, that brings us to earlier today when J.B. Handley explains on the Age of Autism site what the problem was.  Basically he says that the initial transfer attempt was made on May 3rd - less than a week after the initial "outing".  An e-mail was sent, presumably to Paul Offit, telling him that he could arrange to transfer the domain to be under his name.  Handley asserts that he followed up with the person who was co-ordinating the transfer twice in the next week and a half.

Which brings us back to another point of fact.  The pauloffit.com domain name was transferred on May 15th and Bonnie Offit is now listed as the contact on the domain.  The content of the site is now favorable to Paul Offit.  Presumably, the site is now in his hands.

At this point, Liz Ditz writes another post on the matter saying that "Mr. Handley has finally done the honorable thing."  Sullivan wrote a response to the matter on Left Brain Right Brain giving his take on the matter, suggesting it was a "tempest in a teapot".

So, what do you think the Qwibbler does?  I know a rational person would either just drop the matter or post a brief note that the transfer was done and leave it at that.  But the Qwibbler, she doesn't strike me as the most rational person around.

Instead of letting the matter drop, she instead launches yet another attack again Handley saying that he "shows himself to be without honor, without decency, and without facts".  She takes him to task for "breaking his promise" and for publicly talking about Offit while he was explaining the facts what was happening with the transfer.  Because, you know,  it is so easy to explain how you were attempting to communicate with someone without ever mentioning their name.

I guess she is right, technically Handley did break his promise while he was attempting to explain how he was keeping his promise.  Way to stand up for evidence and community Qwibbler.

Dumbass.

Screening for Autism with the ASSQ

I want to talk about the recent study that estimated that the prevalence of autism in South Korea was 2.6 percent because I think that is a very interesting result.  But to set the state for that discussion, I think I first need to talk about screening tests for autism and the Autism Spectrum Screening Questionnaire (ASSQ) that was used in the study.

In general, the purpose of a screening test is separate out which individuals in a group of people are likely to have a condition from those that are not.  In a perfect world, a screening test would only select those individuals that have a condition while not selecting those individuals who do not have a condition.

These concepts are formally called sensitivity and specificity.  The sensitivity of a test tells you have good of a job the test does at finding the people who have the condition while the specificity tells you how good of a job the the test does at telling you which people don't have the condition.

In an ideal world, you would want a test to identify every person that has a condition (sensitivity of 100%) and exclude every person who doesn't (specificity of 100%).  But, in the real world, tests are never that accurate and we have to make do with what we can get.

What normally happens is that the people who develop the screening test take the time to test it against a real population.  They will give the screen to a (hopefully) large group of people and see what the scores look like for those that have the condition compared to those that don't.  They will use that data to come up with what is known as a cut-off score.  This score is just a magic number were the sensitivity and specificity of a test have been maximized.

Or in simple terms, the cut-off score is where the test picks up the higher number of people with the condition while excluding the most people without it.  I think it is worth noting that even below the cut-off score it is still possible to have the condition.

A secondary point, one that is often overlooked, is that a screening test should filter out individuals who have other, similar conditions.  This concept is tied up in the idea of sensitivity and specificity but is often not tested directly.

For example, if you look at the literature for the Autism Quotient (AQ), you will find that it has somewhat decent properties.  However, if you you give the AQ to people with schizophrenia - a population that was not necessarily included in the initial validity studies - you would see that the AQ has a hard time telling whether a person has schizophrenia or autism.  Hence, while the AQ might be decent at finding people with autism, it is also good at finding people with schizophrenia.

That might seem like a small point but if you have conditions where one is much more common than the others, it can make all of of the difference in the world in what your screening test picks up.

With that in mind, lets look at the Autism Spectrum Screening Questionnaire (ASSQ).  I want to cover the properties of this test because it was the screening test used in the South Korea study.

The ASSQ is a 27 question test meant to detect "autistic disorders" in "high-functioning" children, particularly Asperger syndrome.  Eleven of the questions have to do with social interactive, six cover communication problems, while 5 deal with restricted and repetitive behaviors.  Each question has three possible answers - No, Somewhat, and Yes - and each question has a score from 0 to 2 - 0 indicates "normality", 1 is "some abnormality", and 2 is "definite abnormality".  So the range of possible total scores is from 0 to 54.

If you want to see the actual questions on the test you can see them here, starting on page 11 in the document.  I don't want to comment on the test questions, but really, are the questions "is old-fashioned or precocious" and "is regarded as an eccentric professor by the other children" indicative of autism?  Anyways.

The real question, problems with the questions aside, is how good of a job that this screening test does.  It is one thing to question the questions (pun intended) but it another to talk about how good the test is.

Unfortunately, the answer is somewhat mixed.  The ASSQ is designated to be given to both parents and teachers and the results for the different groups are different.

If you look at the initial study for the screen (total of 109 people in the study), you would see that the a parental cut-off scope of 15 would yield a "true positive rate" of 76% and a "false positive rate" of 19%.  A teacher cut-off of 11 would yield a "true positive rate" of 90% and a "false positive rate" of 42%.

Or, in other words, assuming that you had a group of 1,000 children and 1% of the them had autism (10 out of 1,000), the parent test with a cut-off of 15 would correctly identify 8 of the 10 while misidentifying 188.  The teacher test would find 9 of the 10 while misidentifying 415.

Later studies in larger groups of children found somewhat different results.  In one (4,408 children), the authors found that a combined parental and teacher cut-off score of 30 or a teacher score of 22 is best, saying that -

 A valid cut-off for parents' single score could not been estimated. The clinicians are reminded that the ASSQ is a screening instrument, not a diagnosing instrument. The importance of using both parents' and teachers' ratings for screening in clinical settings is underlined.

While in another study (9,430 children), the authors suggested that a combined parent and teacher score of 17 or greater lead to a sensitivity of 0.91 and specificity of 0.86.  Using the above assumptions, that would mean that the test would find 9 of the ten people with autism while saying that 139 had autism who didn't.

The take away here is that with the ASSQ, using somewhat typical cut-off scores, a "positive" screen on the test translates into roughly a 5% chance of actually having autism and a 10% chance of missing someone who actually does have autism.  As the cut-off score gets lower, the change of missing someone with autism is decreased (better sensitivity) while the chance of including people who don't autism increases (worse sensitivity).

However, as I mentioned above, you have to watch out for other conditions that are also going to screen as "positive" on the test.  One such condition that the ASSQ has trouble with is ADD/ADHD.  This condition was included in the initial study plus a few other ones that I found.

In the initial study, the ADD group had a mean parental score of about 10 and a mean teacher score of about 12.  The autism group had a mean of about 22 on the parent score and 25 on the teacher report.  So if the respective cut-offs are placed high enough, the test should be able to distinguish between autism and ADD.

However, over results suggest that the difference between the two groups might not be as pronounced. One result suggested that only the social part of the ASSQ was different in autism and ADHD -

The ASSQ scores of the PDD group and the ADHD group were significantly higher than the control group. Furthermore, the PDD group scored higher than the ADHD group. Both groups also showed higher scores than the control group in all three domains, that is, restricted and repetitive behavior, social interaction, and communication problem. The PDD and the ADHD group showed no significant difference in the domains of communication problem, and restricted and repetitive behavior. The PDD group had a higher score than the ADHD group only in the social interaction domain.

Another result also showed that the mean scores of a modified ASSQ  for children with ADHD was 24 while the PDD group was 31.  Scaling those values back to the original test ranges would yield a mean of 16 and 21, respectively.

So an open question for me is how well the ASSQ can tell the difference between ADD/ADHD and autism, especially at lower cut-off scores.  You will see why this is important next time.

References

Ehlers, S, C Gillberg, and L Wing. 1999. “A screening questionnaire for Asperger syndrome and other high-functioning autism spectrum disorders in school age children.” Journal of autism and developmental disorders 29:129-41. Pubmed PMID: 10382133

Mattila, Marja-Leena et al. 2009. “When does the Autism Spectrum Screening Questionnaire (ASSQ) predict autism spectrum disorders in primary school-aged children?” European child & adolescent psychiatry 18:499-509. Pubmed PMID: 19597920

Posserud, Maj-Britt, Astri J Lundervold, and Christopher Gillberg. 2009. “Validation of the autism spectrum screening questionnaire in a total population sample.” Journal of autism and developmental disorders 39:126-34. Pubmed PMID: 18592364

Fujibayashi, Hiromi, Shinji Kitayama, and Masafumi Matsuo. 2010. “Score of inattention subscale of ADHD rating scale-IV is significantly higher for AD/HD than PDD.” The Kobe journal of medical sciences 56:E12-7. Pubmed PMID:  21063141

Hattori, Junri et al. 2006. “Are pervasive developmental disorders and attention-deficit/hyperactivity disorder distinct disorders?” Brain & development 28:371-4. Pubmed PMID: 16504439

Study Watch : Autism Prevalence in Israel

Via pubmed -

Time Trends in Reported Autism Spectrum Disorders in Israel, 1986-2005.

Reports indicate sharp increase in prevalence of autism spectrum disorders (ASD). We aimed to assess the time trend in prevalence of ASD in Israel and describe demographic characteristics of the registered cases. We reviewed the autism registry of the Israeli Ministry of Social Affairs which includes 4,709 cases and identified 4,138 cases born between the years 1986 and 2005. Registered cases were mainly males (84.4%) and Jewish (96.6%). Prevalence data indicated an increase from 1.2 per 1,000 in those born in 1986 to 3.6 per 1,000 in 2003. Greater increase was seen in males, reaching a peak of 5.7 per 1,000, compared to 1.2 per 1,000 in females. Increased ASD prevalence was observed among Israeli children born in 1986-2005.

It is interesting how the 1986 and 2003 numbers are close to what the numbers were thought to be in the US during both of those times.  The standard disclaimers about changes in the definition of autism, how autism is measured, and the dangers of assuming that one number is representative of the entire population of autism apply.

And of course, if we are talking about current times, the rate of autism should be closer to 10 per 1,000, like it is now in the US.

References

Gal, Gilad, Lili Abiri, Abraham Reichenberg, Lidia Gabis, and Raz Gross. 2011. “Time Trends in Reported Autism Spectrum Disorders in Israel, 1986-2005.” Journal of autism and developmental disorders.
PMID : 21567257

Autism Jabberwocky Notes

Just a few semi-random notes about the blog.

First, due to the recent Blogger issues, about four or five comments were lost.  If you commented on something since Wednesday, you might want to go back and see if your comment is still there.  If it isn't, feel free to re-add it.  Or, if you don't have your original comment, feel free to drop me a line and I will re-add your comment as an anonymous user.

Which brings me to my second note.  Due to some feedback that several people have given me, I have changed the comment settings on the site so that people can leave anonymous comments.  I had initially prevented anonymous comments because of the spam that they brought, but since Blogger has added spam filtering I think it is safe to relax this.  Hopefully people who had trouble commenting in the past will be able to comment now.

Third, I am going to try an experiment with a company called clickochet and while I am doing this you may see some ads on the the right side of the site.  Let me just say that I am not trying to make any money from this site nor will I receive any money if anyone happens to click on the ads.  The only thing that I will receive in return is a chance to run ads of my own - which I would use exclusively to promote this site.  If this system works the way that it sounds like it should, I may keep it around.  Otherwise, the ads will disappear.  I suspect it is going to be the latter and the ads will quickly disappear,

If you are interested, Robert Cringely has a good write-up of how the system works.  But again, I will not be making any money from these ads nor am I trying to turn a profit from this site.  So click if you want, don't if you don't.  Or if you think I am being silly, tell me that too.

Finally, I think I am going to slightly change what I am posting here.  I want to write more than I do but, frankly, I don't have the time to devote to it right now.  Who knew that three children - with or without autism - plus a full-time job and the rest of life could take up so much time.  So what I think I am going to do is post more frequent shorter posts, such as the one earlier today on asthma, while still doing the longer ones as I have the time (I have three or so in the queue that I am working on right now).

Hopefully this system will work so there aren't stretches of weeks and weeks without anything appearing here.  Because there is a lot of interesting information about autism that I come across everyday that I don't have the time to go into detail about.  If you don't think that the newer style is worthwhile, please let me know.

Anyways, thanks for reading and I hope you enjoy where Jabberwocky is headed.

Asthma Becoming More Common

According to a new report from the CDC, asthma became much more common in the US between 2001 and 2009 -

During 2001--2009, the proportion of persons of all ages with asthma in the United States increased significantly (12.3%), from 7.3% (20.3 million persons) to 8.2% (24.6 million persons). A rising trend in asthma prevalence was observed across all demographic groups studied (Figure 1). Prevalence increased significantly during 2001--2009 for children (8.7% to 9.6%), adults (6.9% to 7.7%), males (6.3% to 7.1%), females (8.3% to 9.2%), whites (7.2% to 7.8%), blacks (8.4% to 10.8%), and Hispanics (5.8% to 6.4%). 

... 

In 2009, asthma prevalence was greater among children than adults (9.6% versus 7.7%), and was especially high among boys (11.3%) and non-Hispanic black children (17.0%). Prevalence among adults was greatest for women (9.7%) and adults who were poor (10.6%) (Table 1).

Of course, the reason the for the increase is unclear (I broke the text below into paragraphs to make it more readable) -

The prevalence and number of persons with asthma have increased since 2001, and demographic differences among population subgroups persist despite improvements in outdoor air quality and decreases in cigarette smoking and secondhand smoke exposure (11--13). Although probable causes for the increase in asthma are unclear, CDC's top priority is getting people to manage their asthma better.

Asthma has been more prevalent among children than adults, women than men, and blacks than whites since 2001. Similar to findings in previous studies (3--6), in 2009, asthma was more prevalent among children, women, non-Hispanic blacks, the poor, and in the Northeast and Midwest. 

The cause of this variation remains unclear and might be the result of characteristics associated with asthma development and disease duration that were not examined in this study, including genetic predisposition, history of atopy (a genetic tendency to develop an allergic reaction), health risk factors (e.g., smoking, obesity), earlier diagnosis, socioeconomic status (e.g., education or occupation), and exposure to environmental allergens or irritants (e.g., mold, tobacco smoke, secondhand smoke exposure, pet dander, outdoor air pollution, and any upper respiratory infection, such as influenza or common cold) (1--3,5,6). In particular, obesity and exposure to tobacco smoke each have been associated with increased asthma severity (14,15).

More detailed analytic investigation of these risk factors might help characterize subpopulations and identify those in greatest need of targeted prevention efforts.

I think I might actually fall over if an organization like the CDC ever identified a definitive "cause" of something like asthma.  It is slightly bothersome when you have an (estimated) 4 million more people effected by a condition like asthma over an eight year period and the best the CDC can come up with is a "our top priority is getting people to manage their asthma better".  Don't get me wrong, it is critically important to teach people how to manage their asthma - their lives just might depend on it - but don't you think the top priority should be figuring out why more people are developing asthma?

OK, that really isn't really a fair criticism because conditions like asthma are complex and may have many different possible causes.  But when you have a group of condition that keep getting more common - such as asthma, childhood obesity, diabetes, ADD/ADHD, and autism - and your explanation and response to each is the almost the same, then maybe it is time to try a new approach.

BMJ Editor on Big Pharma

Over at Nature's newsblog there is a short article quoting Fiona Godlee, editor in chief of the BMJ group, on the conflicts of interest in the publishing industry.  I don't really want to just copy the whole thing, so here are some of the interesting quotes -

Fiona Godlee, editor in chief of the BMJ group, told a select committee of the UK Parliament that “We have to acknowledge that the publishing industry has a number of different revenue streams, one of which is the pharmaceutical industry.”

... 

“It has been said that journals are the marking arm of the pharma industry and that is not untrue; to a large extent that is true,” Godlee told the Science and Technology Select Committee.

The BMJ is, of course, the same journal that had a little bit of a "whoops" regarding their recent take down of the de-doctored Wakefield.  Since the first step to recovery is admitting that you have a problem, I think it is good that an editor-in-chief of a large organization like the BMJ is openly talking about the conflicts of interest in the journal industry.

Go read the rest of the article here.

Jabberwocky of the Day : Reality Distortion

There are many other interesting things happening right now in the autism world that I should be writing about instead of this.  Things that are much more relevant such as the recent Korean prevalence study.  But, this is just so utterly ridiculous that I can't let it past.

First the background.  Apparently there is going to be an announcement later this morning about an investigation into autism and vaccines.  What the announcement is supposed to say is that autism is more than three times more common among the group of children compensated by the so-called vaccine court than it is the general population.  I am going to wait to see what the announcement actually says and what the data shows before jumping to any conclusions.

But, Left Brain Right Brain already has their reality distortion field in full-effect claiming that what is supposed to be a report in a "New York law school journal" is a  "legal battle" -

A news conference today will confirm that autism/anti-vaccine groups have lost the scientific battle for the idea that vaccines cause autism as they turn to the legal battle instead.

Never mind the fact that the recent US Supreme Court decision effectively closed down all legal avenues.  Even if the claims were exactly as stated there is no legal way to make the challenge. So I don't know what possible "legal battle" could be mounted.

But then it gets even stranger when LBRB claims that the so-called vaccine court would never distort the relationship between vaccines and autism and that autism isn't defined by its behaviors -

The report – at least in this news story – doesn’t seem to mention how many children were compensated for having autism. As we all kow ‘autism like symptoms’ or ‘symptoms and behavior consistent with autism.’ might be just that – but they are not autism. If they were I’m sure the court would’ve reported it.

Both of the claims are just straight up wrong.

There have been at least 3 cases where the vaccine court compensated children for their autism and went out of their way to avoid saying what they were compensating for was autism.  Perhaps the most notable was the case of Bailey Banks where the court basically invented a new medical condition, non-autistic pdd-nos, to avoid making the link.  From the decision -

These facts likewise satisfy the Althen test set forth above. Petitioner’s theory of PDD caused by vaccine-related ADEM causally connects the vaccination and the ultimate injury, and does so by explaining a logical sequence of cause and effect showing that the vaccination was the ultimate reason for the injury.

PDD is always autism yet the title of the ruling is "Non-autistic developmental delay".  If that isn't an attempt to avoid calling something autism, I don't know what it is.

Then there is the idea that "behavior consistent with autism" isn't autism.  Yet autism is defined solely on the basis of behaviors.  If you have the enough of the behaviors of autism then, BY DEFINITION, you have autism.  If you don't have enough, then you don't have it.  There is absolutely nothing in the clinical definition of autism that makes cases whether autism was caused by genetics, environment, vaccines, or little green men from mars.

I have to wonder how LBRB can champion the the idea that there is no "autism epidemic" because "autistic traits" are present, yet unrecognized, in the general population and then turn around and claim this set of "autistic traits" aren't autism because a vaccine might have caused them.

The cognitive dissonance that they experience over there must be stunning.

Jabberwocky of the Day : Fun With Words Edition

Flickr photo by madmolecule

From the "I want to be like former President Clinton" department, we have Left Brain/Right Brain bringing us the fun with word edition of Jabberwocky of the Day.

First up we have the we have to ask ourselves, what does the word "escalating" mean to you?  LBRB presents a new paper on autism in the elderly and using is to push the idea that there is no "autism epidemic".  They say (in part) -

You see, nobody working the field of geriatric psychology has any doubt that there is a large population of autistic people within the geriatric population

Lets ignore the use of the word "nobody" because one review published in one journal can't possibly have polled the entire field of geriatric psychology and established that not a single person in the field doubts the existence of a "large population of autistic people".  The entire statement is absurd on its face, even by LBRB standards.

Nor is there any support for the idea that there is a "large population" of adults with autism.  What LBRB quotes to support their statement is -

At present, one of the major challenges is that the majority of the currently older individuals with ASD has not received a formal diagnosis of ASD, and this would be diffcult to establish using the currently recommended diagnostic assessments, because for many of them, neurodevelopmental history would be hard to obtain. 

The idea is that most of the older individuals with autism don't have a formal diagnosis, not that there is a large group of adults without a diagnosis.  These are two different concepts.

What I think the point is this follow up statement -

As also published recently, it is becoming clearer that there is in fact, no ‘autism epidemic’ and that, in point of fact, research shows...

They are referring to another study, but we will come back to this study in a minute.  Focus on the idea that there is "no autism epidemic".  Now go read the results section of abstract of the first study -

With escalating numbers of ASD individuals with disability reaching old age, provision of care is the paramount issue that is only beginning to be addressed in a few European communities and in the USA. How ageing affects cognition in such individuals as they reach an age no longer consistent with parental care is unknown, lacking any published evidence, and there is a clear need to design cognitive and behavioural assessment tools appropriate to ageing in ASD individuals with disability, as was the case with respect to dementia as a whole. Although there is a growing body of evidence on pathological, imaging, neuropharmacological and other key brain abnormalities in ASD, these are, to date, confined to children and young (only rarely to middle aged) adults.

I read this paragraph to mean that there in an increasing number of elderly people with autism and that there is currently a complete lack of understanding of what is going to be needed to deal with the problem.

But see the first sentence?  Let me highlight the interesting part "With escalating numbers of ASD individuals with disability reaching old age".  You wouldn't typically see the word "escalating" used to a condition that is stable.  Last time I checked, the word "escalating" implies that something is increasing.

But even if you took a more literal reading of the sentence and assumed that the authors meant that more individuals are "reaching" (think surviving)  to older age that still doesn't tell us that there are a large number of them already there.  If anything, more people with autism surviving to older age has to mean that the number is increasing.

So no matter how you read it, if a condition like autism is "escalating" that says that there are more cases - not a stable level of them.  And if there are more cases, doesn't that mean that the increase of cases might be approaching an epidemic?

But no, according to LBRB, the word "escalating" now means a stable level of adults with autism,  therefore "vaccines haven’t caused an epidemic of autism because an epidemic of autism does not in fact exist."

Wait, were did the rate of autism in children and any data on vaccines come from?

Lets go back to that other study showing a stable level of autism in adults.  I haven't had a chance to get the study text yet but it looks like the same data that was put out over a year and a half ago.  I talked about it quite extensively back then and the long and short of it is that the result is somewhat flawed.  The data shows 19 adults who might have autism out of 7,461 (0.25 percent) and extrapolates that one percent of the population - a four fold increase.  Yet when you look carefully at how the extrapolation was done, I am not quite sure that it is valid.  I am sure that I will be writing about it in the future after I read the "new" research.

The funny part here is that LBRB presents this as some sort of new data.  I guess if you stare at the same thing over and over again, everything old becomes new again and the old new becomes "clearer".

Moving along, LBRB attempts to split hairs in the war against the evil "anti-vaccine" fringe.  Consider the following two statements -

vaccines can cause encephalopathy that causes autism

and

The government has never compensated, nor has it ever been ordered to  compensate, any case based on a determination that autism was actually caused by  vaccines. We have compensated cases in which children exhibited an  encephalopathy, or general brain disease. Encephalopathy may be accompanied by a medical progression of an array of symptoms including autistic behavior, autism, or seizures.

Some children who have been compensated for vaccine injuries may have shown signs of autism before the decision to compensate, or may ultimately end up with autism or autistic symptoms, but we do not track cases on this basis.

To me, these statements are more or less equivalent.  The second may be much more nuanced and full of weasel words, but the theme is the same -

1. A vaccine caused encephalopathy (brain damage).
2. Encephalopathy is "accompanied by" autism.

In this context, "accompanied" has a very specific meaning, mainly -

Be present or occur at the same time as (something else).
- the illness is often accompanied by nausea

Most rational people would conclude that if brain damage is "accompanied by" a neurological condition like autism that there might just be a connection there.  I mean, after all, how much of a leap is it if there is damage to the brain and a condition that can be caused by abnormalities in the brain that there just might be a connection?

It isn't like you would say that one condition is "accompanied by" a second condition to mean that the second condition just appeared out of the blue and has no relation to the first.

Yet LBRB insists that that the "can cause" and "may be accompanied by" are quite different -

Well, no, no its not. Lets look closley at the ‘offending’ paragraph:

We have compensated cases in which children exhibited an encephalopathy, or general brain disease. Encephalopathy may be accompanied by a medical progression of an array of symptoms including autistic behavior, autism, or seizures.

Quite clearly Bowman is saying that Encephalopathy may be accompanied by etc. A fact he goes on to clarify further in his next paragraph. How much clearer does it need to be?

Ginger Taylor and David Kirby really have got to stop misrepresenting people in this way. It does their beliefs no justice.

So remember, the next time that you have the flu "accompanied by" nausea, there is no relation between the flu and the nausea.  The flu appeared and then out of the blue the nausea appeared.

Yeah, right.

As for misrepresenting people, I couldn't have said it better. LBRB's continued instance on playing word games does their cause no good.  It is hard to take anyone seriously who tries to redefine the English language to make their case.

Although, former President Clinton would be proud.