Archive | October, 2012

Application of DSM-5 Criteria for Autism Spectrum Disorder to Three Samples of Children With DSM-IV Diagnoses of Pervasive Developmental Disorders

3 Oct

With much attention focused on the change from DSM-IV to DSM-5 criteria for diagnosing autism, it is good to see more data coming out. As noted only a yesterday (Brief Report: Comparability of DSM-IV and DSM-5 ASD Research Samples) a large number of papers on the effect of the change have been published in 2012.

Add another to the list today: Application of DSM-5 Criteria for Autism Spectrum Disorder to Three Samples of Children With DSM-IV Diagnoses of Pervasive Developmental Disorders. This paper includes Catherine Lord as one of the authors and includes a large number of individuals (both autistic and non-autistic), with ” 4,453 children with DSM-IV clinical PDD diagnoses and 690 with non-PDD diagnoses (e.g., language disorder)”. In addition, the full paper is available online.

This may be the largest study so far, especially in that it uses recent DSM-5 criteria (earlier studies have used earlier versions).

The current study claims that the “proposed DSM-5 criteria identified 91% of children with clinical DSM-IV PDD diagnoses”. In other words, the large majority of children who are or would be diagnosed autistic under the DSM-IV would be diagnosed autistic under the DSM-5.

I am still unaware of any studies applying the DSM-5 to adults.

Here is the conclusion paragraph:

To our knowledge, this study is the most comprehensive assessment to date of the newly proposed DSM-5 ASD criteria. Based on symptom extraction from previously collected data, our findings indicate that the majority of children with DSM-IV PDD diagnoses would continue to be eligible for an ASD diagnosis under DSM-5. Additionally, these results further suggest that the revisions to the criteria, when applied to records of children with non-PDD diagnoses, yield fewer misclassifications. Our findings also contribute to literature that supports the use of both parent report and clinical observation for optimal classification accuracy.

Here is the abstract:

Objective Substantial revisions to the DSM-IV criteria for autism spectrum disorders (ASDs) have been proposed in efforts to increase diagnostic sensitivity and specificity. This study evaluated the proposed DSM-5 criteria for the single diagnostic category of autism spectrum disorder in children with DSM-IV diagnoses of pervasive developmental disorders (PDDs) and non-PDD diagnoses.

Method Three data sets included 4,453 children with DSM-IV clinical PDD diagnoses and 690 with non-PDD diagnoses (e.g., language disorder). Items from a parent report measure of ASD symptoms (Autism Diagnostic Interview–Revised) and clinical observation instrument (Autism Diagnostic Observation Schedule) were matched to DSM-5 criteria and used to evaluate the sensitivity and specificity of the proposed DSM-5 criteria and current DSM-IV criteria when compared with clinical diagnoses.

Results Based on just parent data, the proposed DSM-5 criteria identified 91% of children with clinical DSM-IV PDD diagnoses. Sensitivity remained high in specific subgroups, including girls and children under 4. The specificity of DSM-5 ASD was 0.53 overall, while the specificity of DSM-IV ranged from 0.24, for clinically diagnosed PDD not otherwise specified (PDD-NOS), to 0.53, for autistic disorder. When data were required from both parent and clinical observation, the specificity of the DSM-5 criteria increased to 0.63.

Conclusions These results suggest that most children with DSM-IV PDD diagnoses would remain eligible for an ASD diagnosis under the proposed DSM-5 criteria. Compared with the DSM-IV criteria for Asperger’s disorder and PDD-NOS, the DSM-5 ASD criteria have greater specificity, particularly when abnormalities are evident from both parents and clinical observation.

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By Matt Carey

Andrew Wakefield tries to make himself relevant again

2 Oct

Andrew Wakefield is the former research surgeon who championed the idea that the MMR vaccine causes autism. Multiple researchers have told me that even at the time of Mr. Wakefield’s first research announcements, Mr. Wakefield’s idea was a stretch in terms of biological feasibility. For a few years at least, Andrew Wakefield was relevant in the autism research community. People worked to replicate his findings and otherwise answer the questions he posed. That was years ago. The result is we now know his ideas of persistent measles infection and a leaky gut causing autism were not valid and that, at best, Mr. Wakefield was a mediocre scientist who took this poorly conceived hypothesis and ran with it. Running as in a “running with scissors”, ignoring safety. As has been demonstrated since, he was also ignoring ethical concerns as well. But this is all old news.

In 2004, yes 8 years ago, Brian Deer exposed many of the ethical lapses in Mr. Wakefield’s autism career. Since then we’ve heard a lot of words from Mr. Wakefield about how it is all about the children, but seen a lot of his actions more akin to it being all about himself. He sued Mr. Deer over those 2004 reports (how is that helping autistics?). Mr. Wakefield abandoned his suit (how is that helping autistics?). Mr. Wakefield asked that the GMC look into the possible charges stemming from the reported actions (OK, that helps autistics a little by exposing Mr. Wakefield’s ethical and scientific deficiencies better, but that wasn’t exactly his intention). Mr. Wakefield attended the GMC hearings even though he sayed he didn’t need his medical license (registration) any more. This provided a great deal of drama (again, how does this help anyone but Mr. Wakefield?) but not much advancement. Mr. Wakefield was struck off the register (which could be argued helps autistics in a small way). Mr. Wakefield appealed and then dropped his appeal of the GMC decision. When Mr. Deer wrote more articles, this time for the BMJ, Mr Wakefield filed a complaint with the PCC (press complaints commission) in the UK, but he appears to be not pursuing that. Just letting it exist as a complaint (again, benefit?). Then, this year, he chose to sue Brian Deer, the editor of the BMJ and the BMJ itself this year for defamation over another set of articles and public statements (again, to what benefit to autistics?).

Mr. Wakefield’s latest day in court was short, but likely expensive. A judge in Texas ruled that Mr. Wakefield doesn’t have the standing to bring that case to trial.

Recently Mr. Wakefield appealed. Which, frankly, was enough of a non event in my view that with Respectful Insolence covering the discussion I felt no need to.

In the past eight years we can point to no advances in autism research championed by Mr. Wakefield, but we can (and just have) point to numerous occasions of Mr. Wakefield use procedural methods to keep himself in the news.

Mr. Wakefield claims essentially that calling him a fraud is defamatory. Which brings up the part of recent events that I did find interesting. Again at Respectful Insolence, in Time to rally the troops against the antivaccine movement, Orac calls on people to, well, rally. I’ll stand apart from Orac on this one. Frankly, making this appear to be a controversy, adding drama, is not helping matters.

One might rightly ask, why write about this at all? Why spend time on a topic which has obviously become irrelevant? In setting up his press conference Mr. Wakefield (through his team) made a bit of a poor move.

Mr. Wakefield’s approach to the discovery of his ethical and scientific failings has been to deny even the most clear facts. For example, when presented with direct evidence that he had major financial interests in creating a viable court case out of the MMR/autism hypothesis (being a paid expert witness, creating test kits with the idea that litigation-driven profits will be millions per year, etc.), Mr. Wakefield tells us it is all about the children, and he made all his financial ties public in advance (which he didn’t). When it was discussed on TV that he had a patent application in place covering an alternative measles patent–one whose commercial viability hinged directly on the confidence level of the current vaccine–he told us that it was all misdirection on the part of Mr. Deer. Later it became public that Mr. Wakefield had business plans in place to develop the invention as a potential vaccine.

Essentially, after being caught with his hand in the cookie jar, Mr. Wakefield tells us he was never in the kitchen and, besides, he was only getting the cookie for the children.

From a public relations standpoint (and let’s not forget that Mr. Wakefield had a PR representative since before Brian Deer entered the scene) Mr. Wakefield has played his hand somewhat well. He plays the role of a man who remains polite even in the face of this alleged adversity we are to believe has been put upon him. Mr. Deer, on the other hand, is (I believe in his own words), mercurial and has made statements which are easy to use against him.

Mr. Wakefield is portrayed as the guy you’d love to sit down to a glass of beer (or more likely wine) with while Mr. Deer is someone you’d best not provoke (I believe the term “reptilian” has recently been used by his detractors). I’m not so motivated by the opportunity to sit down to a glass of wine with unethical people, but let’s move on.

In an article on the Age of Autism blog, Ed Arranga writes about Mr. Deer being brought out to the U.S. to give talks to some academics and how Mr. Wakefield will hold a press conference. As one would expect from the Age of Autism, the approach is strongly negative. Here’s how it starts out:

Brian Deer – a liar, fraud, and former reporter for The Sunday Times of London – is coming to the University of Wisconsin-La Crosse October 4 and 5 to lecture you about Dr. Andrew…

Mr. Arranga is doing the attack here, allowing Mr. Wakefield to retain his polite persona. But with a multi-million dollar lawsuit ongoing, is this really enough distance for Mr. Wakefield? How will the above statements play out should Mr. Wakefield win the chance to sue?

Mr. Arranga runs AutismOne, whose convention presents Mr. Wakefield as a prime draw. In other words, Mr. Arranga has a financial interest in Mr. Wakefield’s reputation. A small conflict of interest which, while obvious to most of his readers, should have been made clear in Mr. Arranga’s article. Mr. Arranga also serves on the “Strategic Autism Initiative”, a charity formed after Mr. Wakefield’s ouster from Thoughtful House. [Correction: Mrs. Arranga serves on the SAI board, but Mr. Arranga is not listed in the available tax document]. Most importantly to this discussion, Mr. Arranga is also on the “executive staff” of the “Dr. Wakefield Justice Fund“.

So someone intimately involved with Mr. Wakefield’s career and defense is calling Mr. Deer a “fraud” and a “liar” and, in general, attacking Mr. Deer. Consider that Mr. Wakefield’s case is based at least in part on the idea that using terms such as “fraud” is defamatory. Mr. Wakefield’s original court filing states that defamation occurred: “Based on Defendants’ purported “reanalysis,” Defendants made and continue to make assertions that Plaintiff Dr. Wakefield committed fraud and is “a fraudster.”” Again, one should ask, did Mr. Wakefield blunder in allowing this personal attack on Mr. Deer? How will a judge or jury view a man who sets his team to attack others while claiming that the very same terms are defamatory? It’s not enough to cost him the case, but it was not a wise move.

The sad thing is that this is as close to relevance and Mr. Wakefield can currently attain in the autism communities. Holding a press conference in response to lectures by Brian Deer, who is discussing events that happened 15 years ago. Attacking Mr. Deer through surrogates. Putting time, money and effort into the latest in a string of procedural maneuvers which, even if he were right, hold no benefit for the communities.

As far as cost/benefit calculations go, Mr. Wakefield is a simple case. Costs to the autism communities in time and resources wasted chasing the ideas he championed. Costs to the public at large in terms of health scares and increased infectious disease. All this weighed against a complete lack of benefit brought to the communities by Mr. Wakefield. I guess we should put this in terms of a benefit/cost ratio to avoid dividing by zero.

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By Matt Carey

Molecular Characterisation of Gastrointestinal Microbiota of Children With Autism (With and Without Gastrointestinal Dysfunction) and Their Neurotypical Siblings.

2 Oct

The possibility that gastrointestinal problems are linked–either causally or a comorbid condition–with autism is a topic of much discussion. Some of this focus results from the failed “leaky-gut” theory of autism causation and the also failed idea that the MMR vaccine causes the “leaky-gut”. Recently groups have started to look at the bacteria in the feces or intestines of autistics. From Wikipedia:

The human body, consisting of about 10 trillion cells, carries about ten times as many microorganisms in the intestines. The metabolic activities performed by these bacteria resemble those of an organ, leading some to liken gut bacteria to a “forgotten” organ. It is estimated that these gut flora have around 100 times as many genes in aggregate as there are in the human genome.

One recent study claimed to find a difference in intestinal bacteria between autistics and non-autistics with gastrointestinal disease. In specific, they claimed that

These findings elevate this little-recognized bacterium to the forefront by demonstrating that Sutterella is a major component of the microbiota in over half of children with autism and gastrointestinal dysfunction (AUT-GI) and is absent in children with only gastrointestinal dysfunction (Control-GI) evaluated in this study.

The authors were careful in their conclusions, mentioning that this finding might shed light on the “extent to which Sutterella may contribute to the pathogenesis of GI disturbances in children with autism”. Note this is different than saying that this sheds light on the origins of autism. This point was missed in some discussions of the study, I’ll point out.

It is odd in that study that Sutterella was not found in the non-autistics in that it has been found in non-autistics previously.

As happens too frequently, one study is followed by another which seems to claim the opposite. The study out recently, Molecular Characterisation of Gastrointestinal Microbiota of Children With Autism (With and Without Gastrointestinal Dysfunction) and Their Neurotypical Siblings, doesn’t find differences between autistics and non-autistics with GI complaints. In this study, the controls were neurotypical siblings of the same autistics. This is good choice as the siblings “share a similar environment”. Here is the abstract:

Many children with autism spectrum disorders (ASDs) suffer from gastrointestinal problems such as diarrhoea, constipation and abdominal pain. This has stimulated investigations into possible abnormalities of intestinal microbiota in autistic patients. Therefore, we designed this study to identify differences (and/or similarities) in the microbiota of children with autism (without gastrointestinal dysfunction: n = 23; with gastrointestinal dysfunction: n = 28) and their neurotypical siblings (n = 53) who share a similar environment using bacterial tag-encoded FLX amplicon pyrosequencing. Regardless of the diagnosis and sociodemographic characteristics, overall, Firmicutes (70%), Bacteroidetes (20%) and Proteobacteria (4%) were the most dominant phyla in samples. Results did not indicate clinically meaningful differences between groups. The data do not support the hypothesis that the gastrointestinal microbiota of children with ASD plays a role in the symptomatology of ASD. Other explanations for the gastrointestinal dysfunction in this population should be considered including elevated anxiety and self-restricted diets.

Emphasis added.

Note that this study claims to discuss the role of microbiota in the symptomology of ASD, not just GI disease in autistics.

There are multiple reasons why a direct comparison of the two studies is not precise, but the general idea is the there, especially to the lay public: one study says there autistics have a specific gut bacteria profile, another says there isn’t. And, so, we will see more studies.

In case you are wondering–do either of these studies have anything to do with Andrew Wakefield’s ideas of measles virus being involved with autism? The answer is clearly no. Unfortunately, many who promote the vaccine-causation link will jump on any study of the digestive system as somehow related to Mr. Wakefield’s hypotheses. Sad, but true.

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By Matt Carey

Brief Report: Comparability of DSM-IV and DSM-5 ASD Research Samples

1 Oct

Probably the most hotly debated topic in autism diagnosis and research this year has involved what changes may occur when the DMS-IV gives way to the DSM-5. The DSM is the Diagnostic and Statistical Manual of Mental Disorders and is used as a basis for determining diagnoses such as autism. There have been discussions (both online and elsewhere) claiming that the DSM is not only going to reduce the fraction of the population diagnosed autistic, but that it is designed to do so. People from many parts of the autism communities are concerned including autistics, parents and professionals.

A few studies have already been published, but more data are needed and welcome. This study focuses on “high functioning ” autistics. I need to get the paper to check the age ranges of the individuals in the study. So far there has been little or no data on autistic adults. That said, this study presents the result that of 498 autistics who currently meet the diagnosis criteria for autism (for research purposes), 93% of them will meet the criteria under the DSM-5.

Such a study can not explore how many who did not get a diagnosis under DSM-IV would get one with DSM-5.

Brief Report: Comparability of DSM-IV and DSM-5 ASD Research Samples

Diagnostic and Statistical Manual (DSM-5) criteria for ASD have been criticized for being too restrictive, especially for more cognitively-able individuals. It is unclear, however, if high-functioning individuals deemed eligible for research via standardized diagnostic assessments would meet DSM-5 criteria. This study investigated the impact of DSM-5 on the diagnostic status of 498 high-functioning participants with ASD research diagnoses. The percent of participants satisfying all DSM-5-requirements varied significantly with reliance on data from the Autism Diagnostic Observation Schedule (ADOS; 33 %) versus Autism Diagnostic Interview-Revised (ADI-R; 83 %), highlighting the impact of diagnostic methodology on ability to document DSM-5 symptoms. Utilizing combined ADOS/ADI-R data, 93 % of participants met DSM-5 criteria, which suggests likely continuity between DSM-IV and DSM-5 research samples characterized with these instruments in combination.

Below is a list of papers listed in pubmed on the DSM-5 and autism. I’ve highlighted some of the abstracts (or parts of abstracts) which show the sorts of results which are causing concern within the communities.

What the DSM-5 Portends for Research, Diagnosis, and Treatment of Autism Spectrum Disorders.

Editorial Perspective: Autism Spectrum Disorders in DSM-5 – An historical perspective and the need for change.

A comparison of diagnostic criteria on the Autism Spectrum Disorder Observation for Children (ASD-OC).
“Conclusion: Many children who are currently diagnosed with ASD may no longer be diagnosed, despite having significant impairments roughly equal to those who meet DSM-5 criteria.”

Postponing the Proposed Changes in DSM 5 for Autistic Spectrum Disorder Until New Scientific Evidence Adequately Supports Them.

Exploring the Proposed DSM-5 Criteria in a Clinical Sample.

The proposed DSM-5 criteria for Autism Spectrum Disorder (ASD) depart substantially from the previous DSM-IV criteria. In this file review study of 131 children aged 2-12, previously diagnosed with either Autistic Disorder or Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS), 63 % met the new DSM-5 ASD criteria, including 81 % previously diagnosed with Autistic Disorder and only 17 % of those with PDD-NOS. The proportion of children meeting DSM-5 differed by IQ grouping as well, with higher rates in lower IQ groups. Children who did meet criteria for ASD had significantly lower levels of cognitive and adaptive skills and greater autism severity but were similar in age. These findings raise concerns that the new DSM-5 criteria may miss a number of children who would currently receive a diagnosis.

Loss of autism in DSM-5.

How does relaxing the algorithm for autism affect DSM-V prevalence rates?

Although it is still unclear what causes autism spectrum disorders (ASDs), over time researchers and clinicians have become more precise with detecting and diagnosing ASD. Many diagnoses, however, are based on the criteria established within the Diagnostic and Statistical Manual of Mental Disorders (DSM); thus, any change in these diagnostic criteria can have a great effect upon children with ASD and their families. It is predicted that the prevalence of ASD diagnoses will dramatically decrease with the adoption of the proposed DSM-5 criteria in 2013. The aim of this current study was to inspect the changes in prevalence first using a diagnostic criteria set which was modified slightly from the DSM-5 criteria (Modified-1 criteria) and again using a set of criteria which was relaxed even a bit more (Modified-2 criteria). Modified-1 resulted in 33.77 % fewer toddlers being diagnosed with ASD compared to the DSM-IV, while Modified-2 resulted in only a 17.98 % decrease in ASD diagnoses. Children diagnosed with the DSM-5 criteria exhibited the greatest levels of autism symptomatology, but the Mod-1, Mod-2, and DSM-IV groups still demonstrated significant impairments. Implications of these findings are discussed.

Brief report: an exploratory study comparing diagnostic outcomes for autism spectrum disorders under DSM-IV-TR with the proposed DSM-5 revision.

DSM-IV vs DSM-5 diagnostic criteria for toddlers with autism.

CONCLUSION:
The proposed DSM-5 will result in far fewer persons being diagnosed with ASD. These results replicate findings from two previous studies, with older children/adolescents and adults. As a result of these new criteria, far fewer people will qualify for needed autism services.

Annual research review: re-thinking the classification of autism spectrum disorders.

Sensitivity and specificity of proposed DSM-5 diagnostic criteria for autism spectrum disorder.

CONCLUSIONS:
Proposed DSM-5 criteria could substantially alter the composition of the autism spectrum. Revised criteria improve specificity but exclude a substantial portion of cognitively able individuals and those with ASDs other than autistic disorder. A more stringent diagnostic rubric holds significant public health ramifications regarding service eligibility and compatibility of historical and future research.

Proposed criteria for autism spectrum disorder in the DSM-5.

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By Matt Carey

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