Again, I would like to take the time to thank our guest blogger, Schwartz, for his time and effort in taking down Novella's shameful display of ignorance. Schwartz, I do hope to see more of your writing here. Thank you again! -MySocratesNote
In Part I of this series, we examined an interaction between Dr. Novella, and Mr. JB Handley regarding a new study on Autism. You can re-read the exchange here, here and here
The study being discussed is A Prospective Study of the Emergence of Early Behavioral Signs of Autism.
In the first segment we went through Dr. Novella’s last post and examined in detail his arguments. A close examination reveals almost all of them to be light in evidence and logic, and heavy in biased or erroneous opinion.
In this second segment, we’re going to drill in a lot deeper into the cornerstone of Novella’s primary argument and the unsupported assumptions his arguments all hinge on.
Let’s start with looking back at Novella’s key point in his final conclusion:
In the end, all that matters is the science, which clearly shows that there is no association between vaccines and autism. This one study has minimal implications for an alleged connection, except that it clears the most often implicated vaccine – MMR. It also supports other evidence that the onset of autism is earlier than many parents observe and much earlier than formal diagnosis, which calls into question any casual observations about the timing of onset to any potential triggers.
All of these conclusions rest primarily on one key assumption which is repeated by Novella throughout his opinion pieces.
As we now know, from multiple studies, true clinical onset (biological onset is likely earlier) is between 6 and 12 months.
I noted in the first segment that this assertion was unreferenced by Novella. This is certainly true in the second segment of the series which we looked at. When we look through the whole series, Novella’s hypothesis changes a bit over time and he discusses it in more detail in prior postings. Let’s review some segments from his first piece:
Retrospective studies, largely involving review of home movies, have suggested that autism can be diagnosed as early as 6-12 months,…
But what these results indicate is that clear signs of autism emerge between 6 and 12 months of age.
In this segment, he provides some references which we’ll go through a bit later.
Prior studies using home movies have shown that signs of autism can be detected between 8-12 months. A study looking at head circumference found statistical differences prior to 12 months. And one study looking at movements found differences between 4-6 months. So it seems the consensus of current evidence is that objective and detectable signs of autism emerge between 6-12 months. This study does not support detection prior to 6 months, but other studies do suggest this might be possible.
The true onset of autism in most ASD children likely began a year or two prior to the vaccines that are blamed as the cause.
The current study adds nicely to the growing consensus that the true clinical onset of ASD is between 6 and 12 months of age.
This shows an interesting progression:
* He starts out with suggesting that autism can be diagnosed as early as 6 months.
* Then we have clear signs emerging between 6-12 months.
* a couple more studies later (which we’ll examine in more detail later) and suddenly we have a consensus that detectable signs of Autism emerge between 6-12 months
* all of a sudden true clinical onset is most likely in the first year of life
* now we have a growing consensus that the true clinical onset is between 6-12 months
In the second segment we see:
As we now know, from multiple studies, true clinical onset (biological onset is likely earlier) is between 6 and 12 months.
Now we know the age of clinical onset is between 6 and 12 months…
He has now progressed to definitive onset being known without any further evidence: “The true clinical onset is known to be between 6-12 months.”
I’m going to point out and list the assumptions inherent in Novella’s assertion. Our astute readers will already realize Novella’s assertion is really a hypothesis, and infers the following assumptions:
1. There is a consensus about the age of the clinical onset of Autism
2. The “consensus” has changed from some earlier consensus or lack of consensus
3. The clinical onset of autism is consistent within a narrow range of 6-12 months
4. The onset is early and uniform, consistent with genetic causes
Keep these in mind as we review the evidence that Novella is using and ignoring to form his opinion.
After the current study under question, Novella’s first reference is his own opinion piece here.
Once you stop laughing, I’ve done the work for everyone and linked and summarized a couple of the studies his older opinion piece references.
Rate of Head Circumference Growth as a Function of Autism Diagnosis and History of Autistic Regression.
Summary of study findings:
* retrospective study of 28 boys with ASD and 8 with developmental delay
* measured the rate of growth of head circumference and compared to reference population data published by CDC
* in 60% of the autistic boys, they had accelerated growth prior to the onset of the symptoms of autism (7-10 months old)
* in the children who’s parents reported regression the results were similar – unknown if the sample size here was large enough to allow those results to be considered significant
This small study noted that in children that were ultimately diagnosed with ASD, there were biological differences from the general population at 7-10 months of age. However, these differences were not coincident with the onset of Autism as described by the studies authors in the conclusion:
Findings from this study suggest that the aberrant growth is present in the first year of life and precedes the onset and diagnosis in children with autism spectrum disorder with and without a history of autistic regression.
Summary of conclusions:
* identifies possible predictors of future onset of ASD
* does not suggest the onset of autism is coincident with accelerated head growth
* does not suggest an onset of Autism prior to 12 months of age
* suggests that head growth is similar in regressive vs non-regressive Autism
* despite significant differences, the results were not overly consistent or homogenous (60% with a small sample size)
Novella is implying that observed correlation of increased head circumference growth is coincident with the onset of Autism and thus it supports his assertion that the “true onset” of Autism is earlier than the reported onset of actual ASD symptoms. This study in no way suggests that increased head circumference growth causes or is equivalent to the onset of Autism.
Novella refers to some studies that looked at home videos and found some possible signs of autism as early as 12 months, but the link is broken. At any rate from his own description, these do not support a “true onset” from between 6-12 months of age.
The next study is from Philip Teitelbaum:
Movement analysis in infancy may be useful for early diagnosis of autism
Summary of study findings:
* retrospective study of 17 children diagnosed with Autism
* they found detectable movement disorders in all of the children including some issues visible at birth
* a wide range of different movement issues occurring at different ages were discussed
* based on 17 cases, the authors suggest that their diagnostics procedures could be used to provide an earlier diagnosis of autism
This is a very interesting study as they research a number of infant movements is explicit detail and find problems in each of their test cases and in some of the cases, very early ages. Here as well, we find a leap of assumption by the study authors similar to that of Novella:
Furthermore, because these movement disorders always could be detected with our methods as early as 4–6 months of age and sometimes as early as the first few days after birth, we suggest that the study of movement disorders in infancy may serve as an earlier indicator than presently available methods for diagnosing autism in children.
That wording is pretty bold as they state it can be used to diagnose Autism at such a young age. However, when we read on, it is tempered by a later discussion (emphasis mine):
The fact that such early diagnosis is possible now highlights the need for the development of earlier therapies that will be effective in the treatment of potentially autistic children. Because diagnosis was not generally possible so early, no systematic methods are currently available for the treatment of infants at risk for autism. Our findings should provide the impetus for systematic search for such treatment methods.
Yet another quote:
By combining movement analysis in infancy with MRI analysis, it may be possible eventually to diagnose differential areas of brain involvement in different subtypes of autism.
Novella has clearly focused on the text that supports what he seems to desperately want to believe: biological onset of autism occurs in the first months of life and pre-determined by genetics. Although Teitelbaum suggests this in one section, the bulk of the discussion appropriately limits the scope of his conclusions.
This study was published in 1998 and there was a single follow-up in 2004:
Eshkol-Wachman movement notation in diagnosis: The early detection of Asperger’s syndrome.
In this study, they find similar results as the first.
In the present article, using Eshkol–Wachman movement notation, we present evidence that abnormal movement patterns can be detected in AS in infancy. This finding suggests that AS can be diagnosed very early, independent of the presence of language. As shown earlier by us, almost all of the movement disturbances in autism can be interpreted as infantile reflexes “gone astray”; i.e., some reflexes are not inhibited at the appropriate age in development, whereas others fail to appear when they should. This phenomenon appears to apply to AS as well. Based on preliminary results, a simple test using one such reflex is proposed for the early detection of a subgroup of children with AS or autism.
Again, we get some strong but ultimately conflicting language. A few more observations come to mind here. This research is quite old, and yet, there has been no follow-up to validate these findings in a prospective, or larger study. I’ll also note that these studies were published in PNAS. Although it is peer-reviewed, they allow member authors to select their own referees and manage the referee process. This may explain the conflicting and sometimes overreaching statements. I also found it interesting to note that the members of second study group were recruited personally by the authors at conferences, the internet, and through advertisements.
* the authors find a correlation between autistic children and detectable movement disorders in some cases at an early age
* sample size is very small – 17 children
* the results do not support a uniform or consistent onset of symptoms
* the use of these finding as a diagnostic tool is untested despite the results being quite old
Unfortunately, the sample size is very small, so leaping to any conclusions regarding the “true onset” of autism is clearly premature.
In this opinion piece Novella makes the following statement based on the first two studies we just looked at:
Taken together there is copious evidence that autism is a primarily genetic disorder that is present at birth, with subtle but increasing signs that separate ASD children from non-ASD children as they age.
I’ll just note quickly, that in the comments on Novellas blog we see a familiar pattern: Novella hasn’t even read the original study. In fact, he doesn’t even link to it, he just links a press release. I’m curious how anyone – let alone a scientist – can consider two retrospective investigations of a total of 45 children copious amounts of evidence of anything.
(A side note: it is not lost on me that the original Wakefield Lancet study was a retrospective case study with a small number of cases and a key criticism is that the cases were recruited by the doctors…)
I’m also unclear what evidence is presented here to indicate that Autism is genetic in nature or that the onset actually occurs when some of these early signs are present. The only way to draw a genetic conclusion based on these studies is to assume that the early biological signs and movement disorders found in the first months of life are caused primarily by genetic defects. His assumption of early onset of Autism implies that the biological cause of autism is present and also causing the early signs observed in these two studies.
There is no evidence in either of these studies to support that hypothesis as they are only noting a correlation in a very small retrospective sample. Without a prospective study of a larger size, that conclusion is a giant leap of faith, unless you assume that the cause is genetic. Of course in that case, Novellas argument now looks circular because he uses these assumptions to state that the “true onset” of Autism is uniform and in the early years of life consistent with genetic disorders.
Early and fairly uniform onset is consistent with genetic causes of ASD, rather than environmental causes.
These studies do not provide any evidence of uniformity in timing or signs and symptoms.
Let’s get back to the study that started the whole series.
A Prospective Study of the Emergence of Early Behavioral Signs of Autism
In an editorial in the same journal (Journal of the American Academy of Child & Adolescent Psychiatry), Tony Charman, PhD discusses the study:
To date, less than a handful of studies have reported in terms of early signs that predict autism outcomes. The study by Ozonoff and colleagues  is the first to do so on a sample as large as 25 siblings who went on to receive an autism spectrum (ASD) diagnosis at 36 months.
On one side we’ve got Novella throwing around “copious” amounts of evidence and from the expert we have a handful of small retrospective studies.
From the study itself (Ozonoff et al) we see they talk about conflicting evidence from different patterns of the onset of autism:
Recently, the adequacy of a dichotomous classification of onset has been questioned,17 based on emerging results from studies that provide evidence of other onset patterns. Some parents report that their child displayed neither early signs of autism nor regression, a phenomenon that has been called developmental plateau17,18 or stagnation.19 Other studies have found evidence of both early signs of ASD and regression simultaneously present in the retrospective histories of children with ASD.9,11,12,20
The introduction of this study discusses the various onset patterns in autism and references no less than 20 different studies. Apparently Novella must have skipped or missed this part of the study because it’s pretty clear right from the introduction that there is no consensus on the question of onset of Autism(s), let alone “true clinical onset”. In fact, many of the different Autisms are classified by the differing timings of actual onset. There is certainly no evidence of uniformity. The authors confirm this in the discussion section and even diverge from the traditional classifications of the Autisms:
The present findings suggest that existing definitions of onset patterns will need to undergo further development. One possibility is that we need to expand the number of categories used to describe onset. For example, perhaps there are four rather than two categories of onset, including groups characterized by developmental plateaus and by mixed features of early symptoms plus later regression, as we have suggested elsewhere. 17 The prospective data acquired in the present investigation suggest another possibility, however. We hypothesize that symptom emergence may better be considered dimensionally, as a continuum characterized by the amount and timing of regression.
They are not describing consensus at all. In fact there is little consensus in the prevailing classifications and these authors are suggesting yet another point of view. However, this point of view is not consistent with Novella’s assumption of uniformity of onset. That is clear in the following quote:
In this conceptualization, at one end of the continuum lie children who display loss of social interest so early that the regression is difficult to see and symptoms appear to have always been present. At the other end of the continuum lie children who experience losses of social interest and communication skills so late that the regression appears quite dramatic.
So this study has already torpedoed two of Novella’s key assumptions, let’s tackle the “true clinical onset” at 6-12 months assumption. Looking at the abstract we see the following in the results:
Group differences were significant by 12 months of age on most variables.
The fact that significant differences were noticed at 12 months does not imply uniformity and is not evidence that the “true clinical onset” is uniform and occurs between 6 and 12 months. Reading the conclusions from the abstract:
These results suggest that behavioral signs of autism are not present at birth, as once suggested by Kanner, but emerge over time through a process of diminishment of key social communication behaviors.
The authors specifically avoid listing a timeline and that is consistent with the discussion we reviewed above. It appears that Novella might have gotten one assumption right: that the old consensus – genetic disorder present at birth as per Kanner – is no longer considered valid. If we go back to Tony Charman we see he also makes another important note when it comes to old preconceptions:
Ozonoff et al. suggest that regression might be the norm and not the exception in autism. A similar suggestion was recently made by Pickles et al.8 based on retrospective parental report. They found not only that regression was very specific to autism, as it was almost never found in children with language impairment without autism, but also a strong association between age of first words and likelihood of undergoing regression. That is, frank loss of language skills was associated with switching from the most advanced early language to being among the slowest (in terms of eventual onset of phrase speech).
He implies that Autism is unique compared to other developmental disorders involving language impairment. At first blush, that doesn’t seem consistent with uniform genetic disorders. He goes on:
We do not know what the nature and causes are of the neurodevelopmental perturbations that underlie regression but the existence of such “high-risk” prospective studies offers an opportunity to investigate these questions.
This pretty much puts the nail in the coffin of Novellas hypothesis masquerading as fact. Without knowing the causes or the nature of the neurodevelopment signs we’re seeing at a young age in some children, we can’t know whether they are genetically caused or whether they’re predictive of an autism diagnosis later in life.
Dr. Charman closes with this statement:
Ten years ago, the prospective study of the emergence of early or even prodromal signs of autism would not have been considered possible or practicable. These two studies exemplify the new science of “autism in infancy.”
The real Autism scientists are talking about small new groundbreaking Autism science in it’s “infancy” and the “scientist” Novella is spewing opinion about copious amounts of evidence and a conclusive understanding of the “true” clinical onset from genetic causes.
In this segment, we investigate in detail the cornerstone of Novella’s argument against vaccine causation and for the genetic causation of Autism. Not surprisingly, we find it completely unsupported by the evidence he provides. Even worse, most of his implicit assumptions contradict the evidence he references.
Walking through his arguments which move from a “suggestion of early signs” to a conclusive statement of “true clinical onset” of autism reveals that his interpretation of the evidence and application of logical arguments is seriously compromised. It is bordering on nonsensical. It appears he makes his definitive statements based on a few select lines from study abstracts and press releases. From this “selective hearing” – my apologies to Alan Golding and his video about Brian Deer – he makes giant leaps of assumption and produces what he and Gorski consider “scientific reference” material for doctors.
It certainly doesn’t take a degree in Neurology to understand the scope of these small case studies. If Novella makes so many errors of interpretation and leaps of assumption in these simple cases, it makes me question what he and Gorski are doing when they look into the far more complex epidemiology studies that form the basis of his vaccine safety arguments.
I can’t decide which of his bias’ he is so desperately trying to protect: the quickly dying idea that Autism is purely genetic or the idea that vaccines have no part in the autistic regression of many children. Perhaps if he declared his conflicts of interest, we would gain some insight into the true source of his bias?
I found a lot of details that have interesting implications when reading these studies. They point to a large variance in onset and early signs and symptoms which leads us farther away from a pure genetic cause and explains why there is a growing consensus that environmental influences have a key role to play in the causation of Autism. This new information certainly does not exonerate vaccines or MMR.
Perhaps I’ll write a third segment pointing some of my observations of the science.
Potential Conflicts of Interest: None