Early Autism and Developmental Disabilities Monitoring says autism prevalence is still rising...

"The overall ASD [autism spectrum disorder] prevalence was 13.4 per 1,000 children aged 4 years in 2010, 15.3 in 2012, and 17.0 in 2014 for Early ADDM [Autism and Developmental Disabilities Monitoring] sites with data for the specific years."

So said the surveillance summary published by Deborah Christensen and colleagues [1]. Those of you who follow the US ADDM initiative (see here) will already know about the aims of this "group of programs funded by the CDC" looking at the (estimated) autism numbers, changes to the numbers and the impact of the numbers on various communities. Through initiatives like the ADDM, we already know that the estimated prevalence of autism in 8-year olds living in the United States is round about 1 in 59 (see here) and that the estimate continues to grow for pretty much every surveillance year examined. We are also starting to find out about how the change to DSM-5 from DSM-IV is likely to/not to impact on future figures (see here). And hopefully, at some point, we might have some further data on what happens to autism past childhood (see here) from such an initiative.

The Christensen paper adds another tier to the knowledge being acquired as per their analysis of the (estimated) prevalence rate of autism in 4 year olds "whose parents or guardians lived within designated sites." Those sites were: Arizona, Colorado, Missouri, New Jersey, North Carolina, Utah, and Wisconsin. The Early ADDM initiative does not cover the same area as its big brother/sister ADDM but "is conducted in two phases using the same methods and project staff members as the ADDM Network." Those phases include first "reviewing and abstracting data from children’s records, including comprehensive evaluations performed by community professionals" and then a second phase involving "a review of the abstracted evaluations by trained clinicians using a standardized case definition and method." DSM-IV criteria covers most of the time points examined but: "For 2014 only, prevalence estimates based on surveillance case definitions according to DSM-IV-TR and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) were compared."

Results: as per the opening sentence of this post, the overall (estimated) autism prevalence across all sites for autism in 4 year olds was on the increase between 2010 and 2014. That's not to say that there weren't differences between the various sites - New Jersey, a favourite autism prevalence site (see here) showed the highest prevalence: 19.7, 22.1, and 28.4 per 1,000 for 2010, 2012 and 2014 respectively - but overall the prevalence rate was increasing not decreasing.

There were a number of other important points raised in the Christensen findings. So: "Among four sites with ≥60% data on cognitive test scores (Arizona, New Jersey, North Carolina, and Utah), the frequency of co-occurring intellectual disabilities was significantly higher among children aged 4 years than among those aged 8 years for each site in each surveillance year except Arizona in 2010." I don't think I need to say much more about that. Also: "The overall prevalence estimate using a DSM-IV-TR case definition was approximately 20% higher than the prevalence estimate based on DSM-5 criteria." Again, I don't think too much more discussion is needed on this point aside from saying that for 4-year olds, the switch to DSM-5 might have made more of a difference than for 8-year olds. Indeed in comparison to the Wiggins data [2] based on 8-year olds where "46.0% children met both DSM-IV-TR and DSM-5 surveillance status, 44.0% met neither the DSM-IV-TR nor DSM-5 surveillance status, 4.0% met DSM-IV-TR status, but not DSM-5 status, and 6.0% met DSM-5 status, but not DSM-IV-TR status of ASD" the Christensen data showed something a little different: "Among 1,237 children who met the surveillance case definition for either DSM-IV-TR or DSM-5, 974 (78.7%) met both case definitions, 234 (18.9%) met the DSM-IV-TR but not the DSM-5 case definition, and 29 (2.3%) met the DSM-5 but not the DSM-IV-TR case definition." Perhaps more study is required on the diagnostic changes?

What's more to say? Well, one of the authors - Walter Zahorodny - kinda said it all in a media comment: "There’s no letup. I really don’t understand why the rate is going up in this way." So maybe the next question, a question that really should have been examined a long, long time ago, needs to be 'Why?' rather than just a continual chain of studies saying autism prevalence is increasing...

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[1] Christensen DL. et al. Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 4 Years - Early Autism and Developmental Disabilities Monitoring Network, Seven Sites, United States, 2010, 2012, and 2014. MMWR Surveill Summ. 2019 Apr 12;68(2):1-19.

[2] Wiggins L. et al. Comparison of autism spectrum disorder surveillance status based on two different diagnostic schemes: Findings from the Metropolitan Atlanta Developmental Disabilities Surveillance Program, 2012. PLoS ONE. 2018; 13(11): e0208079.

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DSM-IV vs DSM-5 criteria for autism continued

It's another 'DSM-5 autism' post (see here) from me today as the findings reported by W. Jason Peters & Johnny Matson [1] caught my attention on a topic that has been and remains pretty important: what happened to the rates of diagnosed autism when clinicians switched from the DSM-IV to DSM-5?

DSM-IV and DSM-5 represent versions of the Diagnostic and Statistical Manual of Mental Disorders, one of two manuals containing standardised criteria for diagnosing various behavioural and psychiatric labels. Autism is included in the DSM (and has been for a while). As with various other labels, the refinements to the diagnosis of autism that came with the introduction of the DSM-5 have the been the source of some speculation as to the potential impact on the rates of diagnosed autism.

The data produced so far have been a little bit mixed as to whether more, less or the same number of people would reach diagnostic cut-off points under DSM-5 compared with the application of the DSM-IV criteria (see here and see here) but perhaps with a slight inclination towards DSM-5 being more restrictive (also including a separate catch-all category called social (pragmatic) communication disorder (SCD) (see here)).

And so it was with the Peters/Matson findings, as we are told that: "Fewer individuals met criteria according to DSM-5" based on their cohort of infants and toddlers. The caveat? Well: "individuals with higher levels of symptoms were more likely to meet criteria for both versions [DSM-IV-TR and DSM-5] as compared to either alone" which kinda stands to reason. Indeed other papers recently published [2] pretty much said the same. The conclusion: "results suggest that there are meaningful differences in how DSM criteria may apply to individuals with an ASD [autism spectrum disorder]."

And, since I'm on the topic of what the DSM-5 did or did not do to autism diagnoses, a timely systematic review and meta-analysis from Kulage and colleagues [3] also adds something to the conversation: "Findings suggest smaller decreases in ASD diagnoses compared to earlier reviews."

End of line.

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[1] Peters WJ. & Matson JL. Comparing Rates of Diagnosis Using DSM-IV-TR Versus DSM-5 Criteria for Autism Spectrum Disorder. J Autism Dev Disord. 2019. Feb 27.

[2] Wiggins LD. et al. DSM-5 criteria for autism spectrum disorder maximizes diagnostic sensitivity and specificity in preschool children. Soc Psychiatry Psychiatr Epidemiol. 2019 Mar 8.

[3] Kulage KM. et al. How has DSM-5 Affected Autism Diagnosis? A 5-Year Follow-Up Systematic Literature Review and Meta-analysis. J Autism Dev Disord. 2019 Mar 9.

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DSM-5 autism is "largely comparable to" to DSM-IV-TR autism

"Merry New Year". Welcome back to Questioning Answers in 2019. So let's continue.

The quote heading this post comes from the findings reported by Lisa Wiggins and colleagues [1] and their research aiming to "replicate agreement between surveillance status based on DSM-IV-TR criteria and DSM-5 criteria for ASD [autism spectrum disorder]." This authorship group have some interest in the description of autism across the DSMs (Diagnostic and Statistical Manual of Mental Disorders) as a function of their involvement with the United States CDC and their other, quite recent publication, talking about the national US autism prevalence estimates in 8-year olds for 2014 (see here).

As well as arriving at the conclusion that 1 in 59 children aged 8-year old in the United States *might* have autism [2] (still potentially an underestimate according to other recent figures), their latest prevalence paper also, for the first time, introduced the DSM-5 to the Autism and Developmental Disabilities Monitoring (ADDM) Network. Previously, the DSM-IV was top (diagnostic) dog, but with the publication of the DSM-5 (see here) there was a new sheriff in town. And as the DSM-5 started to be utilised more and more widely in diagnostic circles, so the CDC autism estimating teams had to start taking this into account in their musings...

Wiggins et al relied on data for "8-year-old children who had health and education records reviewed for ASD surveillance in metropolitan Atlanta, GA in the 2012 surveillance year as a part of the Metropolitan Atlanta Developmental Disabilities Surveillance Program (MADDSP)." As per the aims and objectives of the MADDSP - "estimates the number of children with selected developmental disabilities in metropolitan Atlanta" - autism is one of the diagnoses included in the surveillance program. DSM-IV-TR criteria for autism were applied to the health and education records of a cohort of children to see if diagnostic thresholds were met. Importantly too we are told that: "a previous ASD diagnosis was not sufficient evidence to confirm DSM-IV-TR surveillance case status." Alongside: "A DSM-5 coding scheme for ASD surveillance was developed by an independent body of ADDM-affiliated experts and then adapted and refined by a CDC-led clinical workgroup." Application of this DSM-5 coding scheme was similarly used on those education and health records data and results were collected and compared.

"Similar to ADDM data reported for the 2014 surveillance period, we found substantial agreement between DSM-IV-TR and DSM-5 surveillance status of ASD in a sample of records reviewed for the 2012 surveillance period." The figures in a little more detail: "46.0% children met both DSM-IV-TR and DSM-5 surveillance status, 44.0% met neither the DSM-IV-TR nor DSM-5 surveillance status, 4.0% met DSM-IV-TR status, but not DSM-5 status, and 6.0% met DSM-5 status, but not DSM-IV-TR status of ASD." The importance of this data is what the quote heading this post talked about: DSM-5 autism is "largely comparable to" to DSM-IV-TR autism. So when the ADDM eventually makes the transition over to DSM-5 derived autism data only, it means that all those years of DSM-IV diagnosed autism are still very much relevant (and can be used as a comparator) in a historical context.

But... the authors do mention about how some other studies have observed that: "fewer children meet DSM-5 criteria for ASD than DSM-IV-TR criteria for ASD in similar service settings" (see here and see here). This requires quite a bit more investigation; in particular how "record-review surveillance [such as that utilised by Wiggins et al] relies on information contained in surveillance records and does not include an in-person evaluation of the child." As I've indicated in my very critical musings on armchair diagnosis of historical persons (see here for an extreme example), there is absolutely no substitute for talking to and directly observing a person who has been referred for a diagnostic assessment. None. I've also previously suggested that another related label that crops up near to the DSM-5 description of autism - social (pragmatic) communication disorder (SCD) - might also need some research attention too. Indeed, I wonder if the ADDM might eventually start reporting on autism and SCD separately...

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[1] Wiggins L. et al. Comparison of autism spectrum disorder surveillance status based on two different diagnostic schemes: Findings from the Metropolitan Atlanta Developmental Disabilities Surveillance Program, 2012. PLoS ONE. 2018; 13(11): e0208079.

[2] Baio J. et al. Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years — Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2014. Morbidity and Mortality Weekly Report (MMWR). 2018; 67(6): 1-23.

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Unrecognised autism in epilepsy

"All children with epilepsy, particularly those with IQ ≤ [less than or equal to] 50, irrespective of age of onset of epilepsy, seizure type, frequency of seizures, or intractability of epilepsy, should be screened for ASD [autism spectrum disorder]."

So said the findings reported by Monica Juneja and colleagues [1] continuing an important research theme on how autism and epilepsy seem to be very, very closely linked (see here and see here).

Researchers "randomly selected" over 100 children with epilepsy "(defined as two or more epileptic seizures unprovoked by any immediate identifiable cause...)" who were first screened for using Social Communication Questionnaire (SCQ) for autism and then for some, given a more detailed diagnostic work-up. They reported that about 8% of their cohort (9/106) 'screened positive' on the SCQ - "had [a] SCQ score of ≥15" - and 8 of those 9 subsequently went on to meet the criteria for an ASD based on the DSM-IV. They conclude that: "The prevalence of unrecognized ASD was 7.5/100."

This is important work. It adds to an increasing body of peer-reviewed research literature that sees both autism as a risk factor for epilepsy (see here) and epilepsy as a risk factor for autism. The authors also make reference in their findings that they: "add to the growing body of evidence that epilepsy, autism, and ID [intellectual disability] are different clinical manifestations of neurological damage that disrupts the normal neuronal pathways in the developing brain." Accepting that 'neurological damage' is perhaps rather too sweeping a term to apply to the entire autism spectrum (see here), I do think such a conclusion by Juneja et al is worthy of further investigation. I say that from the point of view that the term 'epileptogenic brain lesions' is no stranger to the research literature [2] and that the use of the term 'comorbidity' referencing epilepsy appearing alongside autism, might not always be entirely accurate (see here)...

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[1] Juneja M. et al. Prevalence of Unrecognized Autism Spectrum Disorders in Epilepsy: A Clinic-Based Study. Journal of Pediatric Neurosciences. 2018;13(3):308-312.

[2] Kreilkamp BAK. et al. Neuroradiological findings in patients with "non-lesional" focal epilepsy revealed by research protocol. Clin Radiol. 2018 Sep 28. pii: S0009-9260(18)30519-1.

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Lower autism rate under DSM-5 (yet again)

So: "Results indicate that individuals diagnosed with PDD [pervasive developmental disorder] by DSM-IV-TR criteria may not be diagnosed using DSM-5 criteria."

That was the conclusion reached by Ferhat Yaylaci & Suha Miral [1] following their study of 150 children (3-15 years old) diagnosed with PDD "by DSM-IV-TR" whose symptoms/presentation were "reviewed through psychiatric assessment based on DSM-IV-TR and DSM-5 criteria." The percentage figure they arrived at (19.3%) indicated that about a fifth of participants might not reach diagnostic thresholds based on the DSM-5 criteria for autism spectrum disorder (ASD). PDD in DSM-IV by the way, refers to the autism spectrum.

As per the title of this post, I'm not surprised by this data as previous independent studies have similarly shown a drop in numbers of those 'fitting' the revised diagnostic thresholds included in the latest version of the DSM (see here and see here and see here). Combined with data indicating that the new diagnostic category termed 'social (pragmatic) communication disorder (SCD)' in DSM-5 is likely to fill up rather quickly (see here) to accommodate those not reaching the ASD diagnostic thresholds, the question on everyone's lips is: what will it mean to be diagnosed with SCD in terms of function of the diagnosis, services offered and public perception?

The short answer: we don't yet know.

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[1] Yaylaci F. & Miral S. A Comparison of DSM-IV-TR and DSM-5 Diagnostic Classifications in the Clinical Diagnosis of Autistic Spectrum Disorder. J Autism Dev Disorders. 2016. Oct 17.

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Yaylaci, F., & Miral, S. (2016). A Comparison of DSM-IV-TR and DSM-5 Diagnostic Classifications in the Clinical Diagnosis of Autistic Spectrum Disorder Journal of Autism and Developmental Disorders DOI: 10.1007/s10803-016-2937-8

Lower autism rate under DSM-5

"[The] Rate of autism spectrum disorder diagnosis was significantly lower under the recently implemented DSM-5 criteria."

The results reported by Michelle Hartley-McAndrew and colleagues [1] won't be a surprise to many of those who've been following the literature on transitioning from DSM-IV to DSM-5 criteria with autism diagnosis in mind. Indeed, I've covered the topic a few times on this blog (see here) and specifically the idea that "between 50 and 75% of individuals will maintain diagnoses" but that "the greatest decreases [were] among high-functioning populations with IQs over 70 and/or previous diagnoses of PDD-NOS or Asperger's disorder" as reported by Smith and colleagues [2] (their words not mine).

Hartley-McAndrew et al report results based on a chart review of participants attending an autism spectrum disorder (ASD) clinic. Looking at participants diagnosed with an ASD between 2010 - May 2013 using DSM-IV criteria and those diagnosed between June 2013 - June 2015 using DSM-5 criteria the authors report that "the 2013 to 2015 rate of autism spectrum disorder diagnosis (39%) was significantly lower (p<0.01) than the 2010- May 2013 sample years rate (50%)." So, unless something really dramatic has happened to the presentation of autism over those years, the stricter DSM-5 criteria employed is indeed impacting on the autism (prevalence) rate.

Following on from data (with appropriate caveats) suggesting that the rate of autism in parts of the world might be nearing 1 in 45 children (see here), the full extent of any effects from the DSM-5 change-over are not likely to be seen for some time as word continues to spread about DSM-5 (and bearing in mind that DSM is not the only diagnostic schedule around). With the cold dispassionate science spectacles on, one might see an interesting experiment emerging from the DSM transition as to the extent that the expanded diagnostic criteria of DSM-IV is represented in the autism rate as DSM-5 continues to become mainstream. I might also add that analysis of diagnostic movement to the category social communication disorder (SCD) - the unspoken 'catch-all' diagnostic category also included in DSM-5 - is likely to aid studies into how at least part of the quite massive increase in cases of autism was due to the way the condition was defined.

But then there are the questions: what if the autism prevalence rate more generally continues to rise? And what also will happen to rates of conditions such as attention-deficit hyperactivity disorder (ADHD) under DSM-5 (see here) in light of the increasing appreciation of such comorbidity quite frequently appearing when it comes to autism (see here)? I have a few hunches but let's see how this plays out.

And since we're on the topic of DSM-5 and autism, I'll point you in the direction of the 'Concise history of Asperger syndrome' review by Barahona-Corrêa & Filipe [3] (open-access) for some additional reading.

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[1] Hartley-McAndrew M. et al. Rates of Autism Spectrum Disorder Diagnosis under the DSM-5 criteria compared to DSM-IV-TR criteria in a Hospital Based Clinic. Pediatric Neurology. 2016. Jan 18.

[2] Smith IC. et al. The Effects of DSM-5 Criteria on Number of Individuals Diagnosed with Autism Spectrum Disorder: A Systematic Review. J Autism Dev Disord. 2015 Aug;45(8):2541-52.

[3] Barahona-Corrêa JB. & Filipe CN. A Concise History of Asperger Syndrome: The Short Reign of a Troublesome Diagnosis. Front Psychol. 2016 Jan 25;6:2024.

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Hartley-McAndrew, M., Mertz, J., Hoffman, M., & Crawford, D. (2016). Rates of Autism Spectrum Disorder Diagnosis under the DSM-5 criteria compared to DSM-IV-TR criteria in a Hospital Based Clinic Pediatric Neurology DOI: 10.1016/j.pediatrneurol.2016.01.012

An extremely low prevalence of autism in Quito, Ecuador

The title of this post is taken from the paper by Laura Dekkers and colleagues [1] (open-access) who sought to "get an estimate of ASD [autism spectrum disorder] diagnoses in children and adolescents aged between of five and fifteen at regular schools in Quito."

So, the starting point: "Ecuador has more than 14 million inhabitants... of which over 1.6 million are estimated to live in the capital city of Quito." As part of the "law requiring inclusive education", the authors decided to survey for "cases of ASD in regular schools" in Quito. Said schools were identified via the databanks of the Ministry of Education, of which 161 schools were eventually selected for analysis including just over 51,000 pupils aged 5-15 years. Cases of ASD within that population were "identified by the school administration" and included both autism spectrum diagnoses via DSM-III and DSM-IV criteria.

Results: 33 schools (~20%) reported having at least one pupil officially diagnosed on the autism spectrum. Interestingly the authors report that there was a possible relationship between school reporting one or more pupils on the autism spectrum and the size of the school - "the probability of reporting at least one pupil with an ASD diagnosis decreasing with the size of the school."

"Of the total number of pupils within all schools (N = 51,453) only 57 pupils had an official diagnosis of ASD. This brings the prevalence of ASD in Quito, as reported by schools for regular education, to 11.07 out of 10,000, which is 0.11 %." Most of those diagnosed were so with the label 'PDD-NOS' (Pervasive Developmental Disorder - Not Otherwise Specified). Bearing in mind the small numbers detected, the male: female ratio came in with a familiar statistic - "4.7 times more boys than girls" and mean age at diagnosis was a very poor 7-8 years of age.

Then another statistic: "Out of the 161 schools, 59 schools (36.6 %) mentioned that they thought that at their school there was at least one pupil who did not have an ASD diagnosis, but should have been diagnosed with ASD." In total there were 108 pupils falling into this 'maybe' category. And finally: "Out of all schools (N = 161), 14 schools (8.7 %) reported that they had at least once refused a boy or girl with ASD to their school, because of his or her behavior."

There are a few points to make about the Dekkers findings, some of which the authors already make themselves. First is the quite low prevalence rate estimated from their research. To quote (again): "We propose that the found percentage of 0.11 % reflects the current probability of receiving a diagnosis of ASD in Quito, Ecuador, rather than the proportion of the population that has ASD." Indeed, the authors provide a list of various factors that might have been contributory to the low prevalence rate estimated for autism in Ecuador including issues with accessibility to diagnostic services, the general lack of awareness of autism in the country and the stigma that still surrounds the label ("Autism is often not recognized as such and considered a punishment of God, leaving the family in shame hiding their child with problem behavior"). One might also entertain the notion that autism may not be as prevalent in Ecuador as other countries for genetic / biological or environmental reasons too; perhaps even learning some lessons from other labels (see here).

Second, we can expect more data from this group on this topic. "The ASD prevalence in special education was the second part of phase 1 of the PAE [Prevalence of Autism in Ecuador] project, including 11 special schools and centers, and a total of 1195 pupils; publication of the results is in preparation. We can expect a higher prevalence at these schools, because there is a trend for higher and increasing prevalence of autism in special education in areas with low prevalence of autism." I believe we have a few clues there as to what they found.

Finally, what is missing from the Dekkers data is information about the children themselves outside of just diagnosis and age. Things like whether comorbidity such as ADHD [attention-deficit hyperactivity disorder] is part of the clinical picture in light of what is known about a possible relationship (see here). Indeed, whether part of the low autism prevalence estimate suggested might also part of a wider trend in child psychiatry in Ecuador, and whether we can expect to see increasing rates as per other data from other countries [2]?

Music to close: Sash! - Ecuador.

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[1] Dekkers LMS. et al. Prevalence of Autism Spectrum Disorders in Ecuador: A Pilot Study in Quito. Journal of Autism and Developmental Disorders. 2015. Aug 30.

[2] van Bakel MME. et al. Low but Increasing Prevalence of Autism Spectrum Disorders in a French Area from Register-Based Data. JADD. 2015; 45: 3255-3261.

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Dekkers, L., Groot, N., Díaz Mosquera, E., Andrade Zúñiga, I., & Delfos, M. (2015). Prevalence of Autism Spectrum Disorders in Ecuador: A Pilot Study in Quito Journal of Autism and Developmental Disorders DOI: 10.1007/s10803-015-2559-6

DSM-5 impacting on autism numbers

"Consistent with previous reviews, the majority of included studies indicated between 50 and 75 % of individuals will maintain diagnoses."

That was one of the conclusions reached by Isaac Smith and colleagues [1] following their systematic review of studies comparing DSM-IV and DSM-5 criteria for autism spectrum disorder (ASD) and what the changes mean for eligibility for the label.

Authors further reported that: "the greatest decreases [were] among high-functioning populations with IQs over 70 and/or previous diagnoses of PDD-NOS or Asperger's disorder" when it came to those not fitting the latest autism description in DSM.

I've got little more to say on this topic over what has been discussed previously on this blog with DSM-5 in mind (see here). The newly appointed catch-all category of social communication disorder (SCD) remains a label to watch, not just with respect to how many people will be diagnosed and what level of services/support will be offered, but also with the idea that the broader autism phenotype (BAP) might also gain some clinical recognition.

Music: Nirvana - Drain You.

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[1] Smith IC. et al. The Effects of DSM-5 Criteria on Number of Individuals Diagnosed with Autism Spectrum Disorder: A Systematic Review. J Autism Dev Disord. 2015 Mar 22.

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Smith IC, Reichow B, & Volkmar FR (2015). The Effects of DSM-5 Criteria on Number of Individuals Diagnosed with Autism Spectrum Disorder: A Systematic Review. Journal of autism and developmental disorders PMID: 25796195

(Partly) explaining the increase in the prevalence of autism

"Changes in reporting practices can account for most (60%) of the increase in the observed prevalence of ASDs [autism spectrum disorders] in children born from 1980 through 1991 in Denmark."

Prince of Denmark @ Wikipedia 

That was the headline conclusion reported by Stefan Nygaard Hansen and colleagues [1] based on an analysis of births in Denmark between 1st January 1980 and 31st December 1991 (N=677,915) followed up until 31st December 2011 (or "until ASD diagnosis, death, emigration"). The suggestion being that an update to the ICD (International Classification of Diseases) criteria in 1994 - ICD-8 replaced by ICD-10 - played a significant role alongside "the inclusion of outpatient contacts" and voilà: "the apparent increase in ASDs in recent years is in large part attributable to changes in reporting practices". Some associated media coverage of this study can be found here.

This is certainly interesting data which again taps into those oh-so valuable Scandinavian health registries which are producing all-manner of interesting correlations and results (see here for another example). The question of what factor(s) might be driving the quite astounding increase in cases of autism worldwide (see here) has been a constant source of discussion and argument in certain circles. I have covered some of those debates before on this blog (see here).

Changes to the various diagnostic schedules as being a factor behind the alterations to the autism prevalence rate is by no means a new idea as per discussions about the the rival DSM (Diagnostic and Statistical Manual of Mental Disorders) criteria down the years. Indeed, looking at how the DSM-IV revision (which also came into play in 1994) might have influenced the autism numbers compared against the previous DSM-III criteria tells a similar tale (see here). The most recent DSM-5 revision also looks like it will be playing its own part on the epidemiology of autism at some point (see here) but we wait to see how that eventually pans out.

As per the press release for the Hansen study, there is still a question about the remaining percentage (~40%) of cases of autism not readily attributed to the changes in reporting practices.  A quick trawl through some of the other peer-reviewed work produced by Erik Parner, one of the co-authors on the Hansen paper, provides a few clues as to where researchers have been looking. I've covered some of these variables previously including: shifts in age at diagnosis (see here), the sibling recurrence rate (see here), maternal infection requiring hospitalisation (see here), etc. I might add that this list is not exhaustive as the words 'better autism awareness' are also likely to be banded around (see here for some recent interesting data on this).

I note also one sentence in the press release: "Environmental factors like using certain medications during pregnancy might also contribute, but more research is required to quantify the contribution of hypothesized risk factors" which I suspect ties into some work looking, for example, at prenatal valproate exposure and offspring neurodevelopmental outcomes [2]. Again, this is a topic which has been covered on this blog on more than one occasion (see here and see here) with no medical advice given or intended. I might add that valporate is not the only pharmaceutic which has come under the research spotlight (see here).

The Hansen results make a valuable contribution to the discussions about what might have been driving the increase in autism cases at least in Denmark [3]. Given their focus on participants with birth dates between 1980 and 1991 and the reporting changes included between 1994 and 1995, I'd be interested to see how future work from this group following up subsequent birth cohorts goes, assuming no significant changes in diagnostic schedules or other important adjustments to reporting procedures. I'd also rather hope to see a little more data about possible tie-ins with comorbidity for example, given the input of another Scandinavian team on the ESSENCE of autism...

To close: given that today is 'Remember, remember the 5th of November', I'm inclined to provide you yet again with a link to the rousing speech by 'V' from a favourite film of mine bearing in mind I'm not advocating such revolution. Oh, and please do be careful this Bonfire night...

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[1] Hansen SM. et al. Explaining the Increase in the Prevalence of Autism Spectrum Disorders. JAMA Pediatr. 2014. November 3.

[2] Christensen J. et al. Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA. 2013 Apr 24;309(16):1696-703.

[3] Parner ET. et al. A comparison of autism prevalence trends in Denmark and Western Australia. J Autism Dev Disord. 2011 Dec;41(12):1601-8.

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Hansen, S., Schendel, D., & Parner, E. (2014). Explaining the Increase in the Prevalence of Autism Spectrum Disorders JAMA Pediatrics DOI: 10.1001/jamapediatrics.2014.1893

The stability of an Asperger syndrome diagnosis

"Asperger Syndrome, when considered as an ASD/PDD [autism spectrum disorder/pervasive developmental disorder] diagnosis, was fairly stable into adulthood, but there was a significant increase over time in cases no longer meeting criteria for an ASD diagnosis according to the DSM-IV, or AS according to the Gillberg criteria".

The night is darkest just before the dawn.

That was one of the primary conclusions made in the paper by Adam Helles and colleagues [1] who prospectively followed a group of males diagnosed with Asperger syndrome (AS) in childhood into adulthood covering a period of some 20 years. I believe the starting point of this study has been seen before in the peer-reviewed literature in the paper by Cederlund & Gillberg [2] (open-access here) (a paper which takes me back to my own PhD days with it's important influence to some of my work). Other follow-ups have also been reported [3].

Looking at the diagnostic stability of AS, Helles et al noted that compared with baseline where all participants fulfilled diagnostic criteria, at follow-up (two follow-ups actually) there was a "significant decrease in the rate of cases fulfilling any PDD diagnosis according to the DSM-IV, from 91% at T1 [time 1] to 76% at T2 [time 2] in the 47 cases followed up twice". The decline in cases according to the Gillberg criteria was even more stark (82% at T1 and 44% at T2).

Researchers also noted a few other potentially important points in their findings such that: "Severity of autism spectrum symptoms at T1 was the main predictor of diagnostic stability at T2" and a fifth of those who met criteria for DSM-IV criteria for a PDD diagnosis "did not meet DSM-5 ASD criteria although they had marked difficulties in everyday life". This last point has been mentioned by other authors (see here).

There are a few ways one could take the Helles findings. One could see it as further evidence of the fluidity of presented symptoms when it comes to the autism spectrum as per other discussions in this area (see here). You might even view it as an extension of all that chatter on something like differing developmental trajectories along the autism spectrum (see here) or 'optimal outcome' and autism (see here) albeit without the focus on early intervention as potentially being involved (see here) as far as we know. Indeed, one has to wonder whether for those not meeting the diagnostic criteria as they age and mature, this may in part be because of the various strategies learned over a lifetime to overcome some of the barriers posed by the diagnosis?

But I can also see how for some people such research might be less well-received particularly when added to the 'disappearance' of the term Asperger syndrome from the latest revision of DSM (DSM-V). The paper by Spillers and colleagues [4] described concerns about "identity, community, the cure movement, and services" following the DSM-5 changes when talking to people on the autism spectrum. I wonder how the Helles findings on 'falling out of the spectrum' diagnostically speaking for some, might have similar tones if and when discussed.

Accepting that the Helles findings were eventually based on quite a small participant group and their insinuation that not reaching the diagnostic thresholds for something like Asperger syndrome does not imply a life free of some of the more 'disabling' aspects on and around the diagnosis (yes, including various comorbidity), I do think there is more to see in this area. The realisation that we know so little about the autism spectrum in the long-term [5] and how behaviours ebb and flow, that our systems of diagnosis might not necessarily be as robust as we want them to be (see here) and the continued alliance between diagnosis and service receipt excluding many at the diagnostic periphery all come into play. With all the research data collected down the years, one suspects that with a little bit of organisation and willingness to plough some financial and other resources into this issue, further insight into exactly how stable an autism diagnosis might be and for who should be fairly readily available...

Music to close, and having enjoyed the impressive tones of Sheryl Crow last evening, a song most parents will have a heard a few times: Real Gone.

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[1] Helles A. et al. Asperger syndrome in males over two decades: stability and predictors of diagnosis. Journal of Child Psychology and Psychiatry. 2014. 3 October.

[2] Cederlund M. & Gillberg C. One hundred males with Asperger syndrome: a clinical study of background and associated factors. Dev Med Child Neurol. 2004 Oct;46(10):652-60.

[3] Cederlund M. et al. Asperger syndrome and autism: a comparative longitudinal follow-up study more than 5 years after original diagnosis. J Autism Dev Disord. 2008 Jan;38(1):72-85.

[4] Spillers JL. et al. Concerns about identity and services among people with autism and Asperger's regarding DSM-5 changes. J Soc Work Disabil Rehabil. 2014;13(3):247-60.

[5] Howlin P. et al. Cognitive and language skills in adults with autism: a 40-year follow-up. J Child Psychol Psychiatry. 2014 Jan;55(1):49-58.

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Adam Helles, Carina I. Gillberg, Christopher Gillberg, & Eva Billstedt (2014). sperger syndrome in males over two decades: stability and predictors of diagnosis Journal of Child Psychology and Psychiatry : doi: 10.1111/jcpp.12334

Autism across DSM-IV and DSM-5 descriptions

The paper/poster(?) by Harker & Stone [1] kinda says it all when it comes to the question: what changed in the description of autism between the DSM-IV-TR and DSM-5? The added bonus of comparing the US IDEA (Individuals with Disabilities Education Act) description of autism with DSM-5 will, I assume, also be important to quite a few people not least when it comes to any further research which uses the datasets on numbers of cases for example (see here).

I have little more to say aside from reiterating what already appears to be happening when it comes to the use of the revised descriptions of autism - autism spectrum disorder - in DSM-5 on numbers being diagnosed (see here). That and the requirement for quite a bit more investigation on the social communication disorder (SCD) category [2] including what a diagnosis of SCD actually translates into in terms of services and provisions offered compared to a DSM-5 diagnosis of ASD...

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[1] Harker CM. & Stone WL. Comparison of the Diagnostic Criteria for Autism Spectrum Disorder Across DSM-5, DSM-IV-TR, and the Individuals with Disabilities Act (IDEA)3 Definition of Autism.

[2] Norbury CF. Practitioner review: Social (pragmatic) communication disorder conceptualization, evidence and clinical implications. J Child Psychol Psychiatry. 2014 Mar;55(3):204-16.

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Nearly 13% of children with a DSM-IV diagnosis?

I had tweeted about the paper by Sandra Petresco and colleagues [1] (open-access here) a while back as being the source of the sentence: "Nearly 13 % of the children presented a psychiatric diagnosis according to DSM-IV" based on their analysis of the Pelotas Birth Cohort [2] in Brazil.

Aleijadinho: Angel of the Passion @ Wikipedia 

The crux of the Petresco paper was that by looking at all the children, or at least the majority of children, born during 2004 in the city of Pelotas in Brazil and following them up when aged 6 years using the Developmental and Wellbeing Assessment (DAWBA) schedule [3], the rates of various developmental and/or psychiatric conditions according to ICD-10 and DSM-IV criteria were estimated.

The results (bearing in mind the paper is open-access)...

• Out of 4231 live births, 3,585 children were available for investigation at the age of 6. Trained interviewers delivered the DAWBA to parents, mostly in the clinical setting but about a fifth delivered in the family home. Data was analysed taking into account demographic information such as gender and socioeconomic status and various diagnoses assessed.
• Results: "It was found that 13.2% (N=475) and 12.8% (N=458) of the children fulfilled criteria for at least one diagnosis of psychiatric disorder according to DSM-IV and ICD-10, respectively". Boys were more likely to present with "any diagnosis". Top of the diagnostic pops was "any anxiety disorder" reported in nearly 9% of both boys and girls across both DSM and ICD definitions and then other diagnoses like ADHD (attention deficit hyperactivity disorder) and conduct disorder figured less frequently (both hovering around the 2-3% mark) which is interesting. Children from lower income families also seemed to have more risk of diagnosis.
• Another interesting figure here: autism was only picked up in 0.3% (n=10, 8 boys and 2 girls) of cases for both DSM-IV and ICD-10 criteria. Certainly spot on the mark for the 4:1 sex ratio but frequency-wise, quite a lot less than has been quoted in other parts of the world accepting some differences in the numbers included for study. That being said the authors do note that they only administered the screening questions from the "developmental section" of the DAWBA so might not have caught every case of autism. Other studies looking at DAWBA as a screening instrument for autism have also tended to suggest under-diagnosis as potentially being an issue [4].
• When it came to presenting with symptoms reflective of more than one condition, about 16-17% of children fitted this bill across the diagnostic schedules. An ADHD / conduct disorder came out as the most common combination (29%). More than two comorbid conditions was a rare event (n=3) but when present, all were boys.

I'm sure you'll agree that there is some rather interesting data to be had there. I can't help but wonder if similar cohorts using the same DAWBA tool and screening method sited at other areas of the globe would provide a rather interesting comparison to the Brazil data. Not least covering any relationship between different ethnicities in different environments and the frequency of reported DSM-IV and ICD-10 diagnoses?

That headline figure of 13% of children fitting some kind of diagnostic bill when it comes to DSM-IV and ICD-10 also merits a lot more examination. Again, with my head full of wonder, I'd be asking about whether further genetic / biochemical / other inspection might be revealing for this cohort, particularly when one takes into account the discussions about ESSENCE (see here) and the introduction of RDoC (see here) to research proceedings. How this figure might ebb and flow would also be a good idea for future study, bearing in mind the changing diagnostic times that we live in (see here).

Music to close. Grenade by Bruno Mars.

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[1] Petresco S. et al. Prevalence and comorbidity of psychiatric disorders among 6-year-old children: 2004 Pelotas Birth Cohort. Soc Psychiatry Psychiatr Epidemiol. 2014 Feb 1.

[2] Santos IS. et al. Cohort profile: the 2004 Pelotas (Brazil) birth cohort study. Int J Epidemiol. 2011 Dec;40(6):1461-8.

[3] Goodman R. et al. The Development and Well-Being Assessment: description and initial validation of an integrated assessment of child and adolescent psychopathology. J Child Psychol Psychiatry. 2000 Jul;41(5):645-55.

[4] Posserud M. et al. The prevalence of autism spectrum disorders: impact of diagnostic instrument and non-response bias. Soc Psychiatry Psychiatr Epidemiol. 2010 Mar;45(3):319-27.

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Petresco S, Anselmi L, Santos IS, Barros AJ, Fleitlich-Bilyk B, Barros FC, & Matijasevich A (2014). Prevalence and comorbidity of psychiatric disorders among 6-year-old children: 2004 Pelotas Birth Cohort. Social psychiatry and psychiatric epidemiology PMID: 24488152

Pain predicting sleep problems in autism

Not so long ago I talked about the paper from Smith and colleagues [1] on autism and obstacles to medical [comorbidity] diagnosis and treatment (see here). Aside from the need for professionals to overcome the issue of "a lack of expressive speech" as an impediment to undertaking a thorough medical work-up when presented with a person with autism, an important theme of that paper was the requirement to see beyond autism as being the 'reason' for every single behaviour or issue that affects a person. It's not.

Indeed, the paper by Megan Tudor and colleagues [2] which makes up the material for today's post, adds to that message with their report on pain as being a predictor of sleep problems for some children/young adults with autism. Once again, my thanks go to Natasa for providing the full-text version of the paper for my blogging consumption (yum!).

The long-and-short of the Tudor paper was as follows:

• Take two issues which have cropped up in the autism research literature more than once - sleeping issues and pain - and aim to examine "pain-related behaviors as a predictor of sleep problems in youth with parent-reported ASD using standardized parent-report measurement of both variables".
• Mothers of a sample of 62 children/young adults drawn from a larger study [3] [note to authors, your date is wrong for this reference] were questioned using several measures including the NCCPC-R (see here) and the CSHQ [4] (open-access) looking at pain and sleep respectively. I should also note that questionnaires were completed on-line and participants received a financial incentive to complete [a large chunk of] questionnaires.
• Results: parent-reported participant pain levels according to NCCPC-R scores "was high compared to normative information for this measure". Sleep issues were similarly elevated in the sample, particularly parasomnias. The discussion notes that pain scores were gathered across a slightly different timespan to the normative data (1 week retrospective report for the study vs. 2-hour observation period for the normative data) so one perhaps need to be a little cautious about this.
• Some regression analysis for scores on the two instruments revealed some potentially important results. So higher pain scores "predicted higher scores on CSHQ Total Sleep Disturbance" although with an R-squared value of 0.22 this is not necessarily a straight-forward connection. 
• Specific sleep problems including sleep duration, parasomnias and sleep-disorder breathing were also reported as being accompanied by a previous weeks pain-related behaviours and may well have had some very individual behaviours linked to them e.g. "problems with sleep duration were predicted by social communication of pain, such as comfort-seeking and being difficult to pacify" and "Parasomnias were predicted by facial communication of pain, such as grimacing or brow furrowing".
• The authors conclude that whilst there is more to do in this area of investigation (including the important use of control groups) their results should serve as a marker for healthcare professionals when dealing with children with autism who also present with sleeping issues. To quote: "how pain and sleep problems relate to one another and may affect children's daytime functioning...". This may have some far-reaching effects in terms of how sleep issues are traditionally managed when it comes to autism and other developmental disorders.

Going back to the my starting paragraph about autism not being to blame for every single behavioural manifestation noted among cases, I can't help but ask the question: why were parent-reported indicators of pain-related behaviours seemingly elevated in this sample? As far as I know - and I am just an outsider looking in - autism is not necessarily defined as a painful condition. Indeed, even the authors point to the possibility of a "high threshold for pain" [5] described in the DSM-IV TR diagnostic schedule for autism. Certainly if it was shown that autism 'is a painful condition', it would perhaps change some of the dialogue noted in Dr Insel's Four Kingdoms of Autism.

I do have a few theories about this notion of pain and autism however so bear with me. Tudor and colleagues allude to one of them insofar as discussions about "ongoing mild digestive discomfort" and "severe inflammatory bowel disease" with both issues having cropped up before on this blog previously. Thinking back to the paper by Kushak and colleagues [6] discussed in this post on lactase enzymes and autism, there is the suggestion that lactose intolerance (related to the sugar found in milk and dairy produce) "may contribute to abdominal discomfort, pain and observed aberrant behavior". With autism and inflammatory bowel disease in mind, the Walker paper [7] published a while back (discussed in this post) springs to mind.

Of course, I don't claim that every expression of pain noted in autism is necessarily one of being related to gastrointestinal (GI) function or dysfunction but one could certainly look to rule these issues out if one were being assiduous. As per some other potentially important issues, I might also refer you to a post I wrote a while back on self-injurious behaviour (see here) and other areas that one might look at when it comes to pain being potentially present in cases of autism.

The final angle that is perhaps worthy of exploration has already been touched upon in the additional reference by Allely [5] (see here again) in relation to how one of the core aspects of autism might itself have the ability to induce pain: sensory sensitivity. I say core aspect but am referring to the recent inclusion of sensory issues into DSM-V noting that not everywhere in the world has made the shift over the DSM-5. So, things like over sensitivity to sound for example, I assume may register on someone's behaviour and manner, just as issues with the visual modality might also have the ability to induce something like pain (see here). Indeed, migraine might be something else to look at with pain and autism in mind [8] and not just with the head in mind either [9]. As per previous statements, it all depends on how far one is willing to look into the issue of pain and the potential reasons for its presence...

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[1] Smith MD. et al. Autism and Obstacles to Medical Diagnosis and Treatment. Focus Autism Other Dev Disabl 2012; 27: 189-195.

[2] Tudor ME. et al. Pain as a predictor of sleep problems in youth with autism spectrum disorders. Autism. 2014 Feb 4. [Epub ahead of print]

[3] Walsh CE. et al. Predictors of parent stress in a sample of children with ASD: Pain, problem behavior, and parental coping. Res Autism Spec Disorder. 2013; 7: 256-264.

[4] Owens JA. et al. The Children's Sleep Habits Questionnaire (CSHQ): psychometric properties of a survey instrument for school-aged children. Sleep. 2000 Dec 15;23(8):1043-51.

[5] Allely CS. Pain Sensitivity and Observer Perception of Pain in Individuals with Autistic Spectrum Disorder. ScientificWorldJournal. 2013; 2013: 916178.

[6] Kushak RI. et al. Intestinal disaccharidase activity in patients with autism: effect of age, gender, and intestinal inflammation. Autism. 2011 May;15(3):285-94.

[7] Walker S. et al. Identification of unique gene expression profile in children with regressive autism spectrum disorder (ASD) and ileocolitis. PLoS ONE. 2013; 8: e58058.

[8] Fors S. & Fors MF. Is autism linked to migraine aura? Epidemiology. 2013 May;24(3):472-3.

[9] Casanova MF. The minicolumnopathy of autism: A link between migraine and gastrointestinal symptoms. Med Hypotheses. 2008;70(1):73-80.

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Tudor ME, Walsh CE, Mulder EC, & Lerner MD (2014). Pain as a predictor of sleep problems in youth with autism spectrum disorders. Autism : the international journal of research and practice PMID: 24497628

The potential impact of DSM-V on autism numbers

I don't really want to get too bogged down with the various discussions which have passed to-and-fro when it came to the expected impact of the introduction of DSM-V on autism prevalence estimates. I couldn't however let the publication of the paper by Matthew Maenner and colleagues* pass by without making some comment on it (or at least directing readers the various comments being made about it: see here and see here).

To summarise the new study: retrospectively apply the new DSM-V criteria for receiving a diagnosis of autism (sorry, autism spectrum disorder) to data pertaining to a cohort of children previously diagnosed with DSM-IV autism and see how much overlap there is. I think back to similar study when it came to comparing even earlier versions of DSM on autism prevalence estimates (see here) and the interesting effects that seemed to have.

The good news from the Maenner study: 81% of those DSM-IV classified as having autism were also DSM-V classified as having autism. Interestingly, also that those with comorbid intellectual disability or with a history of developmental regression were slightly more likely to meet the DSM-V criteria for autism. The not-so-good news: er, what happens to those children who didn't quite reach the DSM-V diagnostic thresholds..? Social communication disorder (SCD)? Well, we don't know yet because SCD wasn't looked at in the current study, and as far as I can ascertain, SCD is still wanting in terms of research into the diagnosis and indeed, outcomes. Just as an aside, I wonder if it might however also cover some of those unusual ICD codes relevant to autism?

Of course, as the various media on this paper point out, this was a study based on case notes or rather "clinician review of coded behaviors documented in children’s medical and educational evaluations" so one has to be a little bit cautious of making too many judgements. According to the Autism Speaks website there is further work coming to publication soon looking at more "in-person diagnostic evaluations" across both DSM-IV and DSM-V (see here). Perhaps some more concrete answers might emerge from that data; hopefully slightly more optimistic than the results from Wilson and colleagues**.

I'm gonna finish with a link to an interesting blog post by Allen Frances, who was previously Chair of the DSM-IV taskforce, titled: "Will the DSM-5 Reduce Rates of Autism?". According to the Maenner results, Dr Frances is correct in his assertion "Yes, by a lot" (or at least by about 20%). The arguments will no doubt rumble on about DSM-V (and don't even mention RDoC).

Update: 27 January 2014. And then came the paper by Kim and colleagues*** and some chatter about their findings. It seems that the SCD diagnostic coding would serve as a catch-all after all, for most of those not fulfilling the DSM-V criteria for ASD. All well and good I suppose but the questions about SCD remain in terms of what a diagnosis will actually mean for access to services and required provisions.

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* Maenner MJ. et al. Potential Impact of DSM-5 Criteria on Autism Spectrum Disorder Prevalence Estimates. JAMA Psychiatry. January 22, 2014. doi:10.1001/jamapsychiatry.2013.3893

** Wilson CE. et al. Comparison of ICD-10R, DSM-IV-TR and DSM-5 in an adult autism spectrum disorder diagnostic clinic. J Autism Dev Disord. 2013 Nov;43(11):2515-25.

*** Kim YS. et al. A Comparison of DSM-IV PDD and DSM-5 ASD Prevalence in an Epidemiologic Sample. Journal of the American Academy of Child & Adolescent Psychiatry. 2014. 23 Jan.

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Matthew J. Maenner, Catherine E. Rice, Carrie L. Arneson, Christopher Cunniff, Laura A. Schieve, Laura A. Carpenter, Kim Van Naarden Braun, Russell S. Kirby, Amanda V. Bakian, & Maureen S. Durkin (2014). Potential Impact of DSM-5 Criteria on Autism Spectrum Disorder Prevalence Estimates JAMA Psychiatry : 10.1001/jamapsychiatry.2013.3893

Darth DSM-5 and autism

Blue Harvest @ Wikipedia @ Family Guy

I need to create a suitable atmosphere for this post, so try this music for size and think Blue Harvest...

Right. The wait is over. The discussions / arguments / objections / agreements are all confined to history. Drum roll, spotlight centre-stage... enter DSM-5 and into unknown territory we all go, particularly with autism, sorry.. autism spectrum disorders (ASDs) in mind.

As you can see from the link above to the new diagnostic guidelines from the American Psychiatric Association (APA) the diagnosis of autism has, as was widely anticipated, changed somewhat to encompass quite a few adaptations (see this previous post).

I'm not saying too much more on this at the present time, bearing in mind 'spectrum' is a word which seems to get more of a mention in this revision of the DSM; and not just with autism in mind (see here and here*).

Obviously things aren't going to just change overnight with DSM-5 as it is eventally rolled out. Clinicians will need to learn some new diagnostic brushstrokes. Remember too that DSM is only one part of the diagnostic manuals currently in use (although even ICD is subject to revision in coming years already mentioning something called Social Reciprocity Disorder?). That being said, the implications of DSM-5 on issues like the autism numbers game - same as what happened across previous versions - are probably going to be subject to some pretty intense scrutiny over the coming years.

Don't also be under any disillusion that the new changes are going to herald any giant leaps forward in autism research anytime soon. Interestingly, Dr Tom Insel, head of the US National Institute of Mental Health (NIMH) was recently quoted as saying that "NIMH will be re-orienting its research away from DSM categories", reported also by other authors** (open-access). In other words, even with the fresh smell of new DSM in the air, a new 'nosology' is already planned.

To close, Peter 'Han Solo' Griffin on TIE fighters... dan-dan-da-dan, da-da-dan-dan-dan...

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* Adam D. Mental health: on the spectrum. Nature. 2013; 496: 416-418.

** Lai M-C. et al. Subgrouping the autism “spectrum": reflections on DSM-5. PLoS Biol. 2013; 11: e1001544.

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Lai M-C, Lombardo MV, Chakrabarti B, & Baron-Cohen S (2013). Subgrouping the Autism “Spectrum": Reflections on DSM-5 PLoS Biology