"NMDAR-antibody encephalitis might best be described as a mixed mood-psychosis syndrome"

Every once in a while a paper comes along with the potential to 'really shift opinions'. I'm gonna place the publication by Adam Al-Diwani and colleagues [1] in that category, and their (pre-registered) systematic review around the topic of N-methyl-D-aspartate receptor (NMDAR)-antibody encephalitis.

NMDAR-antibody encephalitis reflects a condition characterised by the immune system failing to identify self as self. For whatever reason, the immune system starts treating specific cells of the body as 'enemy' and mounts an immune attack against them. This results in the formation of specific antibodies - "against the NR1 subunit of the NMDA receptor" [2] - also typically resulting in "psychiatric features before progressing to seizures, a complex movement disorder, autonomic dysfunction, and hypoventilation." The book and film 'Brain on Fire' is about as good an education as you might need on the personal costs and effects of NMDAR-antibody encephalitis.

As Al-Diwani et al mention, things are getting rather interesting for NMDAR-antibody encephalitis in psychiatric circles. Awareness of the condition is growing, albeit with further 'flesh on the bones' required in terms of clinical features to look out for which could accompany the biological testing for the condition. Researchers sought to do just that: "the psychopathology of NMDAR-antibody encephalitis needs to be clearly defined to encourage accurate clinical identification and prompt treatment."

They trawled the peer-reviewed scientific literature looking for mention of NMDAR-antibody encephalitis, and eventually settled on over 300 records describing 1100 people in total. Over 460 of those people were identified with "definite NMDAR-antibody encephalitis according to consensus criteria" and their psychiatric features were examined. "The authors extracted 50 lower-level psychiatric features reported in these 464 patients, defined their frequency, and grouped them into eight higher-level features." Further comparisons were made leading to them assessing "whether individual patients were best described by one or by several psychiatric diagnoses" used as comparators.

Various features were potentially important: "The most common higher-level features were behaviour (316 [68%]), psychosis (310 [67%]), mood (219 [47%]), catatonia (137 [30%]), and sleep disturbance (97 [21%]), and these features frequently coexisted in individual patients." Various interesting graphs and figures are presented by the authors to illustrate their findings. The end result was the description of NMDAR-antibody encephalitis as "polymorphic and not to respect traditional psychiatric classifications." That being said, the notion of a "mixed mood-psychosis syndrome" represents as good a description as any based on the Al-Diwani findings.

Other details? "Overall, the age and sex distribution centred around young women, and the frequency of cases was greatly reduced after 40 years of age." Important information there about a potentially vulnerable group. Also: "139 (30%) of 464 cases were associated with ovarian teratoma, seven (2%) with previous herpes simplex virus encephalitis, and 24 (5%) with pregnancy." Ovarian teratoma is described as a rare cancer categorised as a 'germ cell tumour'. The *link* between ovarian teratoma and NMDAR-antibody encephalitis is something that has been of interest for a few years [3] and perhaps provides a clue for further investigation.

I do stand by my 'game-changer' type comment of the Al-Diwani paper. There is of course more to do in this area (including examining a curious link between NMDAR-antibody encephalitis and 'an autistic-like regression' in some children which is becoming all the more prominent in the research literature [4]). Putting all the various features identified by the authors into a useful set of diagnostic criteria is also a next step...

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[1] Al-Diwani A. et al. he psychopathology of NMDAR-antibody encephalitis in adults: a systematic review and phenotypic analysis of individual patient data. The Lancet Psychiatry. 2019. Feb 11.

[2] Finke C. A transdiagnostic pattern of psychiatric symptoms in autoimmune encephalitis. The Lancet Psychiatry. 2019. Feb 11.

[3] Acién P. et al. Ovarian teratoma-associated anti-NMDAR encephalitis: a systematic review of reported cases. Orphanet J Rare Dis. 2014;9:157.

[4] Khundakji Y. et al. Anti-NMDA receptor encephalitis in a toddler: A diagnostic challenge. International Journal of Pediatrics and Adolescent Medicine. 2018; 5: 75-77.

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Sex differences in autism presentation continued

The paper by Ligia Antezana and colleagues [1] provides the brief blogging fodder today and some further focus on potential sex/gender differences when it comes to the presentation of autism (see here).

The aim of the study was a relatively simple one: "to identify whether specific RRBI [restricted and repetitive behaviors and interests] (i.e., stereotyped, self-injurious, compulsive, insistence on sameness, ritualistic, and restricted), as measured by item-level data on the Repetitive Behavior Scale-Revised (RBS-R), can distinguish girls from boys with ASD [autism spectrum disorder]." The sample was a pretty good size - "615 individuals with ASD (507 boys; 82.4%)" - and the findings were rather interesting...

So: "Items that best-discriminated gender were heightened stereotyped behaviors and restricted interests items in boys and compulsive, sameness, restricted, and self-injurious behavior items in girls." The authors add that: "This study is the first to find that girls with ASD may have increased compulsive, sameness, and restricted RRBI compared to boys."

Bearing in mind the care required when talking about sweeping generalisations about 'boy autism' and 'girl autism', the Antezana results do point to a need for further study in this area. Not least because the authors rightly mention how: "Future research should disentangle whether elevated rates of RRBI in girls are central to the presentation of ASD in girls or an epiphenomenon of the high rates of co-occurring disorders (e.g., anxiety) noted in girls." This based on the idea that autism rarely exists in some sort of diagnostic vacuum (see here) and some of that *comorbidity* (if that is the right word to use) could very well be part and parcel of such clinical observations.

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[1] Antezana L. et al. Gender differences in restricted and repetitive behaviors and interests in youth with autism. Autism Res. 2018 Dec 17.

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Big data does... the extreme male brain theory of autism and the Empathizing–Systemizing theory

"Two long-standing psychological theories – the empathising-systemising theory of sex differences and the extreme male brain theory of autism – have been confirmed by our new study, the largest of its kind to date."

That was the opening sentence to a write-up (see here) of a recent research paper published by David Greenberg and colleagues [1] which sought to "test 10 predictions from the Empathizing–Systemizing (E-S) theory of sex differences and the Extreme Male Brain (EMB) theory of autism." The 'big data' words included in the title of this post refer to the collection of data from hundreds of thousands of people as part of a TV documentary that aired here in Blighty called 'Are you autistic?' whose data were included for study. This follows a similar format from some of the co-authors on the Greenberg paper on previous research occasions (see here).

Minus any charges of plagiarism, a few descriptors might be useful. First: "The first theory, known as the empathising-systemising theory of typical sex differences, posits that, on average, females will score higher on tests of empathy than males, and that, on average, males will score higher on tests of systemising than females." Second: "The second theory, known as the extreme male brain theory of autism, extends the empathising-systemising theory. It posits that autistic people will, on average, show a shift towards “masculinised” scores on measures of empathy and systemising." Researchers also talked about something called a 'd score': "the difference between each person’s score on the systemising and empathy tests" in their research, alongside mention of the words 'brain type'.

As part of the interactivity of that TV documentary, some 670,000 people "who indicated they were males or females" completed various measures: "the Autism Spectrum Quotient-10 (AQ-10)... the Empathy Quotient (EQ)..., Systemizing Quotient-Revised (SQ-R)..., and the Sensory Perception Quotient (SPQ)" via an on-line questionnaire portal. About 36,000 people who took part "indicated that they had been diagnosed with an “Autism Spectrum Condition”." Data from responses to the questionnaires were crunched pertinent to those 10 predictions from both theories (said predictions concerned sex differences based on responses to the questionnaires, those various 'brain types' and how responses might look with reference to the presentation of autistic traits). For good measure, researchers also describe carrying out an 'independent replication' of their findings on a separate cohort of adults ("14,354 participants (226 autistic individuals, and 14,119 controls)"). Although there were some minor differences from the larger main trial, to all intents and purposes the same procedures were employed "for calculating brain types and performing statistical analysis."

Results: well "all 10 predictions from the E-S and EMB theories" were confirmed. So for example, men taking part in the study "had a shift towards a high d score" suggestive of being more likely to be systemisers than empathisers, whilst "typical females had a shift towards a low d score" (i.e. more likely to empathetic than systemiser). The previous STEM (science, technology, engineering, and mathematics) findings [2] were also supported, in that: "STEM professionals on average scored significantly higher on the AQ" suggesting a link between the choice of STEM career and autistic traits. And for those reporting a diagnosis of autism or autism spectrum disorder (ASD): "autistic people, regardless of their sex, had a shift towards an even higher d score than typical males" (systemisers) but "were not more likely to work in STEM occupations, compared with controls."

There is a lot to take in from the Greenberg research and related commentary. The study has a number of things going for it insofar as the huge participant size and the use of an independent replication set to confirm findings. These factors should not be underestimated. The limitations? Well, self-report is still one of them, and the fact that at least one of the questionnaires used is probably picking up a lot more than just 'autistic traits' (see here). I'm also inclined to point out once again that the *correlation* between autistic traits and STEM career choice did not seemingly extend to those with autism being "more likely to work in STEM occupations, compared with controls." Going back to that 'what is being tested' issue, the AQ for example, might also be picking up something linked to "loneliness, social anxiety, depression, and anxiety" [3] or even something approaching the schizophrenia spectrum (see here) or personality disorder (see here). Indeed, one might have to entertain the idea that the definition 'autistic traits' may not tell the whole story in this study.

I have to admit to being still a little sceptical of big psychological theories such as the EMB or the E-S theory of sex differences. The reason? Whilst attractive in their compartmentalising nature, real life is often far from being so clear-cut and linear. The fact also that an important part of the evidence behind such theories remains a little 'fluffy' (see here for example) cannot be readily brushed under the scientific carpet. As for the use of the term 'brain types', well, I can see what the authors were getting at, but I'm not convinced such terminology is particularly useful. 'Brain types' kinda sits in the same category as 'neurotypical' (see here). I was also drawn to the fact that the authors have to explicitly say that their results don't mean that "autistic people lack empathy" and that "autistic people are not hyper-male in general." It kinda tells you how some of the history behind these theories shows that they have not exactly been received with open arms by many.

But even with all that, the Greenberg results cannot be just discounted, and more research on this topic is indicated.

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[1] Greenberg DM. et al. Testing the Empathizing-Systemizing theory of sex differences and the Extreme Male Brain theory of autism in half a million people. Proc Natl Acad Sci U S A. 2018 Nov 12. pii: 201811032.

[2] Ruzich E. et al. Sex and STEM Occupation Predict Autism-Spectrum Quotient (AQ) Scores in Half a Million People. PLoS One. 2015 Oct 21;10(10):e0141229.

[3] Reed P. et al. Loneliness and Social Anxiety Mediate the Relationship between Autism Quotient and Quality of Life in University Students. Journal of Developmental and Physical Disabilities. 2016; 28: 723-733.

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The Scotland Census 2011 and autism again: focus on children and young adults

Consider this post an extension of some previous chatter on this blog (see here). That previous chatter was based on the work published by Ewelina Rydzewska and colleagues [1] talking about how (a) Scotland seems to be pretty unique insofar as 'asking about autism' in their population Census, and (b) how examination of such a query, alongside asking a few other questions, represents an important research resource particularly pertinent to the idea that autism rarely appears in some sort of diagnostic vacuum (see here).

Now there's more from Rydzewska and colleagues [2] and their analysis of the Scotland 2011 Census. This time the specific focus was on under 25 year olds (their previous research was dedicated to looking at "the prevalence of comorbid mental health conditions and physical disabilities in a whole country population of adults aged 25+ with and without reported autism").

Researchers report that 1.6% of their population (25,063/1,548,819) were reported to have (or someone on their behalf) ticked the box to the question 'have any of the following conditions' that was labelled 'Developmental disorder (for example, Autistic Spectrum Disorder or Asperger's Syndrome)'. This was quite a bit higher than the 0.2% of adults (over 25 years old) that was previously reported on. They also reported that the traditional 4:1 male:female ratio regarding autism was intact as other recent population (estimated) prevalence studies have also indicated (see here and see here).

Then to the main event: "Autism had an odds ratio of 5.4 (5.1–5.6) for predicting deafness/partial hearing loss, odds ratio of 8.9 (8.1–9.7) for blindness/partial sight loss, odds ratio of 49.7 (38.1–64.9) for intellectual disabilities, odds ratio of 15.7 (13.4–18.5) for mental health conditions, odds ratio of 15.8 (14.1–17.8) for physical disability and odds ratio of 3.9 (3.8–4.0) for other conditions."

It's worthwhile reiterating some of those observations made by Rydzewska et al: the chances (odds ratio) of intellectual or learning disability appearing alongside autism in under 25 year olds was about 50 times more likely than in those not ticking that 'Developmental disorder' option. In terms of specific percentage frequencies, the figures for learning disability in the age groups 0-15 years (children) and 16-24 years (young adults) where autism was mentioned were 13-14% and 18% respectively. This was contrasted against percentages of 0.3% and 0.4% in similar non-autistic age groupings. I'm also minded to include the observation that girls with autism across both age groups seemed to be at some elevated risk of learning disability when compared to boys. The next highest risk values came in for the presence of a mental health condition where again girls with autism seemed to shoulder the highest risk (a divide that seemingly grew as children aged into young adults). The conclusion yet again is that for quite a few people, autism is not a stand-alone condition/label and that such "conditions are disabling and have a significant impact on long-term quality of life; their coexistence with autism adds extra complexity."

On the last blogging occasion when the first research paper from Rydzewska using the Scotland Census 2011 data was discussed, I held back from commenting too much on the adult prevalence figure picked up by authors. This time I'm not going to, because the difference between children/young adults with autism (or a developmental disorder) (1.6%) and autistic adults (0.2%) is too stark not to mention. I appreciate that there may be many variables/factors contributory to such figures, and that such figures are perhaps prone to some degree of error (bearing in mind the legal requirements behind completing a Census), but the disparity between them cannot be just brushed under the scientific carpet. They show that for the year 2011 in Scotland, autism - all forms of autism - was quite significantly over-represented in children and young adults compared with autism in over 25 year old adults. They show that arguments about the prevalence of adult autism potentially being on a par with childhood autism were/are wrong. They show that autism is disproportionately affecting children/young adults and by inference, the trend in autism being diagnosed is an upward one primarily stemming from childhood/young adulthood diagnoses and not from the late diagnosis of adults.

By saying that I'm not ruling out the idea that there may be adults in Scotland in 2011 who had slipped through the diagnostic net with autism in mind. I'm not saying that some 7 years later, things haven't moved on with regards to autism awareness and the like. But I do find it extremely unlikely that there were literally thousands and thousands of 'hidden' people 'undiagnosed' in Scotland in 2011 however much some people have inferred, and continue to infer, that this is true. The peer-reviewed evidence for this phenomenon is just not there, and certainly nowhere near there when it comes to those with 'very visible' autism who for example, require significant day-to-day social and health care support (see here and see here for examples).

I am hoping that when the next Scottish Census (2021) results eventually come in we might see more from this fabulous research opportunity with autism in mind. Even better would be for other countries to follow the Scottish lead in their questioning of their nation and perhaps provide a more accurate picture of the rates of autism across the age groupings.

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[1] Rydzewska E. et al. Prevalence of long-term health conditions in adults with autism: observational study of a whole country population. BMJ Open. 2018 Sep 1;8(8):e023945.

[2] Rydzewska E. et al. Prevalence of sensory impairments, physical and intellectual disabilities, and mental health in children and young people with self/proxy-reported autism: Observational study of a whole country population. Autism. 2018 Oct 17:1362361318791279.

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"the friendships and social experiences of autistic girls are similar to those of neurotypical girls"

The quote heading this post - "the friendships and social experiences of autistic girls are similar to those of neurotypical girls" - comes from the findings reported by Felicity Sedgewick and colleagues [1] (open-access available here) continuing a growing research theme looking at the presentation of autism across the sexes/genders. The results however perhaps challenge the idea that "being autistic ‘overrides’ being female in some way."

OK, first things first, by mentioning the word 'neurotypical' the authors refer to a not-autistic control group. As I've said on many, many occasions, the word 'neurotypical' from a research/clinical point of view is however meaningless (see here): there is no way for a living brain, with all its complex structures, connections and functions, some of which are changing second to second, to ever be described as 'typical'. And autism research in particular really shouldn't be using such a misnomer, no matter how [social media] fashionable it might seem.

Rant over. Despite using the term, the Sedgewick paper covers an important real-world part of the whole 'gender differences in autism' area looking at "gender differences in the friendships and conflict experiences of autistic girls and boys relative to their neurotypical [non-autistic] peers." Over 100 adolescents (aged 11-18 years) were included for study; about half diagnosed with autism with an "independent clinical diagnosis of an autism spectrum condition." Said autism diagnoses were also complemented by assessment via the gold-standard ADOS which actually revealed that: "Two boys and four girls failed to meet the ADOS-2 threshold (score = 7) for autism." Data from these children were still included in the study given the "pre-existing clinical diagnosis" and other supporting information. I'm wondering however if perhaps some of these children were examples that an autism diagnosis (or reaching the cut-off points on one of the gold standard autism assessment instruments) is not necessarily for life (see here)? Further, all participants "completed the Friendship Qualities Scale, the Revised Peer Experiences Questionnaire and were interviewed about their friendships" and results were analysed...

Results: "Autistic and non-autistic girls’ conflict and friendships were more like each other than autistic and non-autistic boys, and vice versa." The authors frame this in the context that their findings "provide compelling support for the possibility that gender may be more important than diagnosis in determining young autistic people’s social experiences." That's not to say that there weren't some important group differences in relation to social challenges, conflict and conflict resolution - "autistic girls described an ‘all-or-nothing’ approach, either taking sole responsibility for what had happened... or ending the friendship entirely, seeing the other person as the wrong-doer..., or feeling it could not be resolved" - just that there was more to align girls than to divide them when it came to comparisons with non-autistic peers.

Authors also report results from their interviews with adolescents which again revealed that gender over a diagnosis of autism seemed to a key aspect. So: "Having a few good friends was key, with all girls talking about having a small number of close friends that they considered to be ‘best’ friends. These close friends were those who they spent the most time with and talked to most." Also: "Both autistic and neurotypical girls emphasised that friends supported them." And finally: "Both autistic and neurotypical girls alluded to wanting to fit in, but in different ways." It should also be noted that Sedgewick et al mention how 'camouflaging' (a term being increasingly used in autism circles) is not a specific strategy reserved for autism: "Few girls reporting having boyfriends, but most said people dated to fit in with the popular crowd. These behaviours could be seen as a form of ‘camouflaging’, as teenagers described seeking peer acceptance, even if they were not personally motivated to date."

As to the boys of this particular cohort, well again, there didn't appear to be any really prominent stand-out separation points between autism and not-autism. As the authors report: "autistic and non-autistic adolescent boys reported their friendship and conflict experiences as highly similar – activity-focused, practically supportive friendships combined with a laissez-faire attitude to conflict. The exception to this pattern was that neurotypical boys described more intimate friendship experiences than their autistic male counterparts."

Cumulatively the Sedgewick findings reinforce the idea that there may be some subtle but important differences between boys and girls, women and men diagnosed with autism (see here). In this light, the suggestion that "autistic girls (and possibly women) need different strategies and supports to understand and effectively navigate the social expectations placed upon them" is correct when compared to males diagnosed with autism. The results suggesting however, little significant differences in friendships and social experiences between autistic girls and non-autistic girls (and autistic boys and non-autistic boys) kinda grates against some of the narratives that have emerged in recent years. It implies that rather than viewing someone as an 'autistic girl' one should perhaps first focus on that person as a girl when it comes to social experiences and friendships rather than subscribing to the idea that autism is wholly 'behind' any issues as some 'identity' discussions have intimated. The findings also imply that camouflaging and masking are not necessarily exclusive features of autism but, perhaps in some contexts, are rather more representative of a general effect specifically across gender.

I would like to see a lot more research done in this area. I'd like to see more longitudinal work done looking at friendships and social experiences into adulthood with autism in mind, where other environments replace the school playground (including the online and social media environments). I'd like to know about how friendships develop, persist or 'fall to one side' and whether other 'comorbidity' (see here), that more likely than not will 'follow' a diagnosis of autism (see here), play any role in such social experiences. I'd also like to see further work on societal inclusion (see here) in the context of the Sedgewick research too. There is a scheme of work to do.

And let us also not forget that learning the intricacies of things like friendships and social experiences or challenges such as conflict are also influenced by other important variables, such as a role for siblings [2] (for better or for worse)...

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[1] Sedgewick F. et al. 'It's different for girls': Gender differences in the friendships and conflict of autistic and neurotypical adolescents. Autism. 2018 Oct 3:1362361318794930.

[2] Ben-Itzchak E. et al. Having Siblings is Associated with Better Social Functioning in Autism Spectrum Disorder. J Abnorm Child Psychol. 2018 Oct 3.

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Male and female autism might not be so dissimilar?

I read with some interest the paper by Joanna Mussey and colleagues [1] concluding that "either very small or no gender differences in age at diagnosis, intelligence quotient, cognitive profiles, or autism spectrum disorder symptom severity" were detected in their cohort of males (N=566) and females (N=113) diagnosed with an autism spectrum disorder (ASD).

Interest because, in these days of talk about a possible specific female autism phenotype emerging (see here) in light of potential sex differences in the presentation of autism (see here), one has to be quite careful not to over-generalise too much. In much the same way that terms such as 'male brains' and 'female brains' don't really do justice to the complexity of brain structure and function (see here), so one perhaps has to ensure that female autism and male autism presentation aren't offered in an 'either or' fashion despite the possibility of subtle differences in either the expression of symptoms or for example, differences in the presentation of things like over-represented comorbidity between the sexes/genders (see here).

Mussey et al reported that previous studies talking about autism 'hitting harder' when it comes to females in relation to the presence of intellectual (learning) disability and "more severe impairments" might not necessarily tell the full story. Based on the use of various instruments to to ascertain autistic traits and beyond, the authors noted some differences between the genders on measures of autism signs and symptoms but the precise significance was, in the most part, deemed "of minimal clinical significance." Such findings have also been noted in other recent research [2]. Another important message from the Mussey study results was that at least some of the instruments used to assess for autism or ASD might need some further investigation with sex/gender in mind.

Having said all that I do think there are still important issues that need to be further investigated when it comes to sex differences in autism presentation. The idea for example, of a 'female camouflage effect' (see here) still looms large in this area; where for example, verbal and non-verbal communication skills might serve to *mask* other important diagnostic features. I'm also [carefully] inclined to inquire whether gender identity over biological sex might play something of an important role in the male and female presentation of autism for some, in light of other important research (see here). There is a further scheme of work to be completed minus sweeping generalisations.

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[1] Mussey JL. et al. Are males and females with autism spectrum disorder more similar than we thought? Autism. 2017 Aug;21(6):733-737.

[2] Fulton AA. et al. Gender comparisons in children with ASD entering early intervention. Research in Developmental Disabilities. 2017. 68: 27-34.

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Sex and age might affect comorbidity profiles in autism

The paper by Supekar and colleagues [1] provides some food for thought today specifically with the idea that comorbidity profiles accompanying autism might be influenced by age and gender in mind.

To quote: "These results highlight crucial differences between cross-sectional comorbidity patterns and their interactions with sex and age, which may aid in the development of effective sex- and age-specific diagnostic/treatment strategies for ASD [autism spectrum disorder] and comorbid conditions."

From a starting point assuming that the diagnosis of autism rarely exists in some sort of diagnostic vacuum (see here), researchers set about looking at comorbidity patterns for quite a few conditions/labels "using cross-sectional data from 4790 individuals with ASD and 1,842,575 individuals without ASD." The sorts of things that looked for were not uncommon to discussions about comorbidity accompanying autism on this blog (epilepsy, attention-deficit hyperactivity disorder (ADHD) and "bowel disorders" for example). The variables of sex (gender) and age were also included in the research mix.

Bearing in mind that sweeping generalisations about autism comorbidity profiles are not required, the authors highlighted a couple of important points. First: "Epilepsy, ADHD, and CNS/cranial anomalies showed exceptionally large proportions in both male (>19%) and female (>15%), children/adolescents with ASD. Notably, these prevalence rates decreased drastically with age in both males and females." This is interesting. With a rather large research gap quite visible when it comes to the concept of ageing and autism (see here), the author's data seems to be suggesting that the burden of comorbidity (some comorbidity) might decline as people diagnosed on the autism spectrum get older. Yes, the words "cross-sectional comorbidity" are important (more longitudinal study is required where people are 'followed' as they age) and there is no doubt that intervention to manage diagnoses such as epilepsy (and/or seizure disorder) probably plays a hand in presentation, but more investigation is certainly required.

Next: "the prevalence of schizophrenia increased with age affecting a disproportionately large number of older (≥35 year) adult males (25%), compared to females (7.7%), with ASD." Two points are made here: (a) rates of schizophrenia might be affected by sex, and (b) age might play a role in the presentation of schizophrenia in the context of autism. This follows a theme re-emerging over these past few years suggesting that the autism and schizophrenia spectrums might not be as separate and independent as many might believe (see here and see here). Quite a lot of [research] focus has been directed at some of the signs and symptoms of schizophrenia with [some] autism in mind (see here for example) and perhaps queries whether history was 'too quick' to try and distance the two labels from each other (were Mildred Creak and colleagues correct?). Given the significant issues potentially linked to a diagnosis of schizophrenia (see here) in terms of health inequality and the like (something also sadly not unfamiliar to autism too), the onus should surely be to screen (and keep screening) for schizophrenia when autism is present into adulthood? Said screening could be preferentially driven by the Supekar findings taking into account that caveat about not over-generalising findings.

I'm gonna stop there with discussing these results so as not to over-analyse the findings. The important take-away point is that autism is generally not a 'stand-alone' condition and that age and gender might have some important roles to play when it comes to at least some comorbidity.

Music: something lively I think so increase the volume please...

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[1] Supekar K. et al. The influence of sex and age on prevalence rates of comorbid conditions in autism. Autism Res. 2017 Feb 11.

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Supekar K, Iyer T, & Menon V (2017). The influence of sex and age on prevalence rates of comorbid conditions in autism. Autism research : official journal of the International Society for Autism Research PMID: 28188687

Gender dysphoria and autistic traits?

"Gender dysphoria is a condition where a person experiences discomfort or distress because there is a mismatch between their biological sex and gender identity."

That's how NHS Choices describe gender dysphoria illustrating how biological sex and gender identity are not always one and the same for everyone. I might add that science is also coming around to the idea that the dichotomy of two biological sexes (male and female) might also not be as accurate as we've all been led to believe.

With that short introduction in mind, I'm turning to the paper by Daniel Shumer and colleagues [1] today and their findings "consistent with growing evidence supporting increased prevalence of ASD [autism spectrum disorder] in gender dysphoric children." Based on the retrospective analysis of a small group of children and young adults presenting at a gender clinic, results using the "Asperger Syndrome Diagnostic Scale (ASDS)" suggested that "possible, likely, or very likely Asperger syndrome" might be a feature of almost a quarter of those presenting with gender dysphoria (9/39). Further: "routine assessment of ASD is recommended in youth presenting for gender dysphoria."

The issue of gender dysphoria and/or gender identity issues and autism has been popping up now and again in the peer-reviewed autism research literature for some years. The case report by Landén & Rasmussen [2] represents one of the earliest documentations of gender dysphoria alongside a diagnosis of autism and included the idea that there may be a "predisposition to gender dysphoria in autism." Whilst the small participant number included in the Shumer study and the introduction of 'possible' or 'likely' to a diagnosis of Asperger syndrome were perhaps contributory to the impressive 'correlation' posed between the label and gender dysphoria, other more controlled study has also hinted that autism or autistic traits may be over-represented among this group. de Vries and colleagues [3] for example, utilised the DISCO (Diagnostic Interview for Social and Communication Disorders) among children and adults attending a gender identity clinic and reported that ~8% of their total sample group (N=208) reached ASD thresholds. As they pointed out in their paper, the rate of ASD found in their sample: "confirms the clinical impression that ASD occurs more frequently in gender dysphoric individuals than expected by chance."

The idea that autism or autistic traits might show some link to gender dysphoria also taps into an interesting area of autism research based on the suggestion of sex hormones and cognitive styles exemplified in discussions about the 'extreme male brain theory' for example (see here for further discussions). Jones and colleagues [4] reported that Autism Spectrum Quotient (AQ) scores showed some interesting patterns particularly among transmen "(female-to-male transsexual people)" when compared to other groupings (transwomen, typical males, typical females and those with Asperger syndrome). They concluded that: "Transmen have more autistic traits and may have had difficulty socializing with female peers and thus found it easier to identify with male peer groups." Bearing in mind some words of caution about what the AQ is actually measuring (see here) and how we [structurally] define 'male' and 'female brains (see here) the results are perhaps consistent with some of the notions detailed in the extreme male brain theory.

There remains however, quite a bit more research to do looking at gender dysphoria and autism or autistic traits. That developmental processes may be part and parcel of any association has been suggested [5] and as always, I remind you that autism does not generally exist in a diagnostic vacuum (see here). Indeed, one might see some intriguing links taking into account suggestions about gender dysphoria and schizophrenia for example [6] in light of the bridges built (and destroyed) down the years potentially linking cases of autism and cases of schizophrenia (see here). That also the presence of another quite common comorbidity appearing alongside autism - ADHD (attention-deficit hyperactivity disorder) - might also play a role [7] further exemplifies just how complicated the relationships / connections might actually be.

Perhaps also we need to talk about sex and gender quite a bit more when it comes to autism...

A video and some music to close, and because its that time of year when resolutions are made to 'get fit'...

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[1] Shumer DE. et al. Evaluation of Asperger Syndrome in Youth Presenting to a Gender Dysphoria Clinic. LGBT Health. 2015 Dec 1.

[2] Landén M. & Rasmussen P. Gender identity disorder in a girl with autism--a case report. Eur Child Adolesc Psychiatry. 1997 Sep;6(3):170-3.

[3] de Vries AL. et al. Autism spectrum disorders in gender dysphoric children and adolescents. J Autism Dev Disord. 2010 Aug;40(8):930-6.

[4] Jones RM. et al. Brief report: female-to-male transsexual people and autistic traits. J Autism Dev Disord. 2012 Feb;42(2):301-6.

[5] VanderLaan DP. et al. Autism spectrum disorder risk factors and autistic traits in gender dysphoric children. J Autism Dev Disord. 2015 Jun;45(6):1742-50.

[6] Rajkumar RP. Gender identity disorder and schizophrenia: neurodevelopmental disorders with common causal mechanisms? Schizophr Res Treatment. 2014;2014:463757.

[7] Strang JF. et al. Increased gender variance in autism spectrum disorders and attention deficit hyperactivity disorder. Arch Sex Behav. 2014 Nov;43(8):1525-33.

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Shumer DE, Reisner SL, Edwards-Leeper L, & Tishelman A (2015). Evaluation of Asperger Syndrome in Youth Presenting to a Gender Dysphoria Clinic. LGBT health PMID: 26651183

Sex, STEM careers and the 'big data' of the Autism-Spectrum Quotient (AQ)

I'm a fan of 'big data' on this blog (see here) and the particular idea that large participant numbers can offer up some really important results or patterns of results relevant to our knowledge of labels like autism.  I do also believe there is a balance to be struck between big data and somewhat smaller data - specifically the value of the N=1 when it comes to a heterogeneous condition like autism - but big data is a nice way of introducing or confirming more general trends and/or correlations.

When I therefore came across the paper by Emily Ruzich and colleagues [1] (open-access available here) talking about "Autism-Spectrum Quotient (AQ) scores in a 'big data' sample" it was music to my ears. Describing how researchers tapped into data connected to a medical TV show - "Embarrassing Bodies: Live from the Clinic" - specifically AQ scores and other data for over 450,000 people living in the UK, results are presented on the value of the AQ with autistic traits in mind and the idea that sex and occupation type might influence such self-reported characteristics.

I've been particularly interested in the AQ on this blog and its various research uses down the years. Ranging from autistic traits in those adults diagnosed with epilepsy (see here) through to autistic traits in older adults diagnosed with depressive disorders (see here), this simple to use self-report instrument is proving to be a research choice for many. I still have some reservations about the instrument; specifically, it's discriminating power when it comes to autism and schizophrenia (see here) for example, but as a rough-and-ready 'screening' instrument we have little else currently on offer and importantly, the instrument is open-access to all.

Ruzich et al reported results examining "correlations between the AQ and age, sex, occupation, and UK geographic region" as a function of the airing of a particular episode of the Embarrassing Bodies program "that included a brief TV segment following an individual with Asperger Syndrome." I hasten to add that the program title in no way describes Asperger syndrome or any other part of the autism spectrum as being 'embarrassing', merely reflecting the program content that at other times can be rather 'personal' in nature. Researchers reported that whilst age and geographic area of AQ completers did not seem to correlate with total AQ scores, there was something statistically to see when it came to scores across the sexes/genders and when taking into account the career option selected by participants. So: "[A] Career in a STEM [science, technology, engineering, and mathematics] area of work is associated in an increase in AQ scores in both genders" and "on average, males (m = 21.55, SD = 8.82) scored higher than females (m = 18.95; SD = 8.52)."

The authors interpret this data as further evidence "that traits commonly associated with autism are strongly linked to traits associated with being male and with STEM occupations, regardless of other factors." Those with some appreciation of the research literature in this area might know about the discussions on how parental career choice might tie into offspring outcomes specifically with autism in mind [2]. Indeed, how concepts such as 'hyper-systemising' [3] have been suggested to represent a core cognitive style in relation to autism.

These are interesting data allowing for the fact that various caveats are included in the Ruzich paper when it comes to the data collected and the participant group included. Investigations remain about how such results might generalise to the autism spectrum in terms of career paths (see here) and performance data (see here) and indeed, whether one might consider the wider schizophrenia spectrum as potentially being relevant also to the current results (see here) as part of any comorbidity.

I do think we also need to exercise a little caution in how the results are presented; the generalised idea for example, that 'extreme maleness' might be somehow connected to a career in STEM and what that might mean for the issue of women in science and specifically recruiting more women into such career paths needs to be handled with due care and respect. I'd also suggest that media headlines like: 'Are you on the autistic spectrum? Take the test' related to the Ruzich results need to be taken with a pinch of salt in light of the difference between a self-report screening instrument and a detailed assessment for autism (I'll be posting about this soon enough...)

Music: Portishead - Wandering Star.

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[1] Ruzich E. et al. Sex and STEM Occupation Predict Autism-Spectrum Quotient (AQ) Scores in Half a Million People. PLoS One. 2015 Oct 21;10(10):e0141229.

[2] Wheelwright S. & Baron-Cohen S. The link between autism and skills such as engineering, maths, physics and computing: a reply to Jarrold and Routh. Autism. 2001 Jun;5(2):223-7.

[3] Baron-Cohen S. The extreme male brain theory of autism. Trends Cogn Sci. 2002 Jun 1;6(6):248-254.

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Ruzich E, Allison C, Chakrabarti B, Smith P, Musto H, Ring H, & Baron-Cohen S (2015). Sex and STEM Occupation Predict Autism-Spectrum Quotient (AQ) Scores in Half a Million People. PloS one, 10 (10) PMID: 26488477

Gender differences in chronic fatigue syndrome

The title of this post matches the title of the paper published by Monica Faro and colleagues [1] (open-access here) and some potentially important data on "whether there are gender-related differences in CFS [Chronic Fatigue Syndrome], and to define a clinical phenotype in men."

Starting with the idea that the prevalence of CFS - a generic term covering a spectrum of conditions characterised by severe and debilitating fatigue among several other things - may have a gender skew towards females over males [2], Faro and colleagues set about looking at whether the presentation of CFS might also differ between males and females. I should perhaps back-up a little and highlight how the sex differences in CFS frequency might be somewhat clouded by the fact that quite a few diagnostic criteria systems are currently around for CFS (also called myalgic encephalomyelitis, ME) and that under-diagnosis of men cannot yet be discounted as contributing to any gender differences. Think autism and the perceived gender skew there as an example of potential under-diagnosis in action with another label in mind.

Based on the analysis of over 1300 patients formally diagnosed with CFS (using the Fukuda 1994 definition), 119 (9%) of the cohort were described as male. Following the administration of a clinical interview "conducted by 2 specialized internists in the diagnosis of the disease" among other things, researchers reported a few interesting details. First, men in general seemed to be diagnosed slightly earlier than women. It wasn't a stark difference measured in decades for example, but a difference of on average, 4-5 years. Further: "Widespread pain, muscle spasms, dizziness, sexual dysfunction, Raynaud's phenomenon, morning stiffness, migratory arthralgias, drug and metals allergy, and facial oedema were less frequent in men." Fibromyalgia as "defined by the criteria of the ACR" was also reported to be less frequent in men than women (29% vs 58% respectively). Also of interest was the suggestion that: "The most common triggering factor was an infection" where men were more likely than women to relate their symptoms to such a factor.

These are interesting findings that add an extra dimension to discussions about CFS with a view to a possible role for gender differences. Obviously one has to be a little guarded about making too many sweeping generalisations that for example, CFS is a 'different condition' for men and women because we don't really have a great deal of evidence to back up such a claim. Insofar as the possibility that men are diagnosed earlier than women, this could point to a number of things. Either this is reflective of an earlier onset of the illness in men or that women find it more difficult to get diagnosed with CFS. I'd be interested to see how this variable pans out as and when more research in this area is forthcoming.

Music: The Calling - Wherever You Will Go.

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[1] Faro M. et al. Gender differences in chronic fatigue syndrome. Reumatol Clin. 2015 Jul 16. pii: S1699-258X(15)00081-9.

[2] Líndal E. et al. The prevalence of chronic fatigue syndrome in Iceland - a national comparison by gender drawing on four different criteria. Nord J Psychiatry. 2002;56(4):273-7.

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Faro M, Sàez-Francás N, Castro-Marrero J, Aliste L, Fernández de Sevilla T, & Alegre J (2015). Gender differences in chronic fatigue syndrome. Reumatologia clinica PMID: 26190206

Early sex differences are not autism-specific

The title of this post mirrors the title of the paper published by Daniel Messinger and colleagues [1] (open-access available here) that reported on "younger sibling sex differences and proband sex differences on the odds of ASD [autism spectrum disorder] in a large sample of prospectively followed high-risk siblings."

Researchers found that alongside "a three-to-one male:female odds ratio in ASD recurrence... the emergence of ASD symptoms in high-risk siblings—both with and without eventual ASD outcomes—occurs in the context of naturally occurring sex-related variability." Further that their results cast "doubt on a female protective effect among high-risk ASD siblings."

Based on participant data derived from the Baby Siblings Research Consortium (BSRC) [2], a collaborative initiative focused on identifying the earliest signs and symptoms of autism, researchers assessed cognitive functioning and autism symptom severity in over 1800 infants, over 1200 of whom were categorised as 'high risk' insofar as being a "younger sibling of a proband with an ASD diagnosis." Of those 1241 high-risk siblings "252 had ASD outcomes" on the basis of a clinical best estimate diagnosis derived from the various data sources available for each participant.

Results: well, there were quite a few of them as previously discussed but I'm going to pick out a few highlights:

• "The male rate of ASD recurrence in the high-risk siblings was approximately 1 in 4 (26.7 %) while the female rate was 1 in 10 (10.3 %)." Further: "The overall—combined male and female—ASD recurrence rate of 19.5 % yielded an ASD outcome for approximately one in five high-risk siblings." This is an important addition to the previous research done on sibling recurrence rates (see here) bearing in mind the potential effect of variables such as reproductive stoppage and multiplex status.
• "Challenging accounts of greater female affectedness, there was no evidence that girls exhibited lower levels of cognitive functioning or higher levels of symptom severity than boys." The idea that there may be a female phenotype of autism has gained significant research traction in recent times (see here) partially based on the idea that it may take 'more genetic issues to trigger autism in girls than boys'. Alongside the idea that females may somehow possess greater protection against autism is the suggestion that autism when it does appear in females, may show differences in terms of severity perhaps as a function of that larger genetic load required. Messinger et al however, report that things might not be so simple.
• "Boys across all groups exhibited slower growth trajectories and lower levels of cognitive performance than girls in fine motor, visual reception, receptive and expressive language functioning." Harking back to some previous musings on the 'fragile male' (see here) Messinger et al showed small but notable difference across the sexes and across ages suggesting female superiority of somewhere between "1.06 to 3.3 months on age-equivalent scores" compared to males. That's not to say males did not develop - everyone developed - rather that girls seemed to develop skills at a faster rate.
• "With respect to the ASD symptom severity indices, males exhibited higher levels of repetitive behaviors than females, but there were no sex differences in social affect severity scores." This finding tallies with other research in this area (see here). The indication being that aspects such as stereotyped language, hand and finger mannerisms or complex mannerisms may be quite a bit more prevalent in 'boy autism' compared to 'girl autism'. More than that however, such repetitive behaviours might be more present in boys over girls (taking out the variable of autism diagnosis) "consistent with a male focus on regularity in the behavior of non-social objects and events." 'Boys and their toys' is a phrase that springs to mind.

The authors conclude that their results "suggest that male:female ASD differences are not ASD-specific but instead reflect more general sex differences reflected through a prism of autism-linked symptoms."

These are interesting results that gain some scientific traction as a function of the large participant numbers included for study and the prospective nature of the study initiative. The authors have made quite a bit of the fact that their results provide "no overall evidence of a female protective effect" in their high-risk siblings group but acknowledge the need for further investigations in this area specifically where female autism is present and how "female probands in multiplex families (two or more female siblings) [may] confer greater risk for ASD in successive offspring." I wonder if this might include some further thought on how sex differences in brain plasticity [3] might potentially be linked to autism?

Once again, autism reveals just how complicated a condition it is...

Music: The Slits - Typical Girls.

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[1] Messinger DS. et al. Early sex differences are not autism-specific: A Baby Siblings Research Consortium (BSRC) study. Mol Autism. 2015 Jun 4;6:32.

[2] Messinger D. et al. Beyond autism: a baby siblings research consortium study of high-risk children at three years of age. J Am Acad Child Adolesc Psychiatry. 2013 Mar;52(3):300-308.

[3] Mottron L. et al. Sex differences in brain plasticity: a new hypothesis for sex ratio bias in autism. Molecular Autism. 2015. 6; 33.

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Messinger DS, Young GS, Webb SJ, Ozonoff S, Bryson SE, Carter A, Carver L, Charman T, Chawarska K, Curtin S, Dobkins K, Hertz-Picciotto I, Hutman T, Iverson JM, Landa R, Nelson CA, Stone WL, Tager-Flusberg H, & Zwaigenbaum L (2015). Early sex differences are not autism-specific: A Baby Siblings Research Consortium (BSRC) study. Molecular autism, 6 PMID: 26045943

Infant sleep duration a risk factor for autism spectrum behaviours in girls?

To quote from the study results published by Janet Saenz and colleagues [1] (open-access available here): "less sleep duration in infant girls across a period of 5 days was predictive of higher ASD [autism spectrum disorder] scores on the BITSEA [Brief Infant-Toddler Social and Emotional Assessment] in toddlerhood."

Based on a sample of 47 children - 29 males and 18 females - researchers initially studied sleep patterns for participants at 3-4 months of age using actigraphs to ascertain sleep duration and efficiency and determine whether there was any connection to later BITSEA scores at 18-24 months of age. They reported various results in the most part not significant across genders, sleeping patterns and the subsequent effect on scores of social-emotional problems. In the detail however, they did find a suggestion that "sleep duration was a significant predictor of autism spectrum behaviors" specifically in girls and "after controlling for sleep efficiency, a 1-min decrease in sleep duration resulted in a 0.01 point predicted increase in a child’s autism spectrum behaviors score." This, bearing in mind, that BITSEA scores for autism spectrum behaviours range between 0-17.

I'm not wildly enthusiastic about the results reported by Saenz et al given the relatively small sample size and the snap analysis of two variables (sleep and reported behaviour) separated by over a years worth of development. Correlation is not necessarily causation and all that jazz. Indeed, even the authors concede that their use of a "non-clinical sample" limits the applicability of their results to "the low severity end of the diagnostic spectrums."

That being said, I do wonder if these findings invite quite a bit more investigation specifically when it comes to all those resources being put into the early detection of autism as exemplified in the recent paper by Sacrey and colleagues [2]. Sleep and autism is a research topic not unfamiliar to this blog (see here) and the idea that there may be small but measurable differences in sleep parameters in cases of already diagnosed autism. I'm not aware of too much in the way of experimental research reporting on early sleep patterns as being a 'risk' factor for autism outside of results such as those reported by Humphreys et al [3]. The idea that sleep issues might become more present as a child develops is a theme explored by Sivertsen et al [4] and the behavioural 'issue' link has also been mentioned by others [5].

Finally, it is worth reiterating the focus on female autism spectrum behaviours reported by Saenz et al. As per other work by the authors [6] and findings supporting: "the hypothesis that early infancy may be another critical period for the development of gender-linked behavior" based on their examination of infancy salivary testosterone levels and toddler BITSEA ratings, there may be some important lessons to be learned. Sex differences in behavioural presentation when it comes to autism (see here) is a big talking point at the moment in light of discussions about how the gender ratios for diagnosis might be skewed by either a female autism phenotype or just plain old dogma about autism being a male-dominated label. Again, I've not come across much in the way of peer-reviewed research where sleep has been examined from the perspective of risk of autism or autism linked behaviours taking into account gender differences. Hence, another potential research project presents itself and perhaps even more intriguing: could 'alteration' of early sleep patterns offset the future risk of autism?

Music: Kelis - Caught Out There.

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[1] Saenz J. et al. Sleep in infancy predicts gender specific social-emotional problems in toddlers. Front Pediatr. 2015 May 11;3:42.

[2] Sacrey LA. et al. Can parents' concerns predict autism spectrum disorder? A prospective study of high-risk siblings from 6 to 36 months of age. J Am Acad Child Adolesc Psychiatry. 2015 Jun;54(6):470-8.

[3] Humphreys JS. et al. Sleep patterns in children with autistic spectrum disorders: a prospective cohort study. Arch Dis Child. 2014 Feb;99(2):114-8.

[4] Sivertsen B. et al. Sleep problems in children with autism spectrum problems: a longitudinal population-based study. Autism. 2012 Mar;16(2):139-50.

[5] Schwichtenberg AJ. et al. Behavior and sleep problems in children with a family history of autism. Autism Res. 2013 Jun;6(3):169-76.

[6] Saenz J. & Alexander GM. Postnatal testosterone levels and disorder relevant behavior in the second year of life. Biol Psychol. 2013 Sep;94(1):152-9.

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Saenz J, Yaugher A, & Alexander GM (2015). Sleep in infancy predicts gender specific social-emotional problems in toddlers. Frontiers in pediatrics, 3 PMID: 26029685

Trends in the diagnosis of autism in Australia

"The frequency of ASD [autism spectrum disorder] diagnoses in Australia has increased substantially from previously published estimates."

That was one of the conclusions reached in the study by Catherine Bent and colleagues [1] (open-access here) who aimed to "investigate the frequency and age at diagnosis of autism spectrum disorder (ASD) in children aged under 7 years living in Australia."

Drawing on "de-identified data" extracted from Helping Children with Autism Package (HCWAP) - an Australian Government initiative - covering the period 1 July 2010 and 30 June 2012, researchers examined various variables including: age at diagnosis, frequency of an ASD diagnosis and how particular child characteristics might have influenced both age and frequency of diagnosis.

Some 15,000 children under 7 years of age were reported to be in receipt of an ASD diagnosis over the study period. The blanket ASD description included the labels of classical autism (autistic disorder), Asperger syndrome and Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS). Autistic disorder took the lion's share of diagnoses, with over two-thirds of the cohort in receipt of this label.

"The average age at diagnosis of ASD in children registered with the HCWAP is currently 49 months, with the most frequently reported age being 71 months." There were however some interesting differences noted in terms of age at diagnosis as a function of label under the ASD umbrella. Those diagnosed with autistic disorder showing a pretty clear advantage in mean age at diagnosis (46.5 months) compared with those with Asperger syndrome (mean age: 59.5 months) and PDD-NOS (mean age: 51.1 months). Taken as a whole, the cohort tended to be diagnosed between 25-72 months of age with the peak age for diagnosis falling between 37-48 months of age. Compared with previous prevalence/incidence estimates for ASD in Australia, the data from Bent et al also "suggests that the incidence of ASD in Australia has increased substantially from previous estimates" with 0.74% of under-7 year olds diagnosed with ASD between 2010 and 2012.

These are interesting findings. I've briefly touched upon some of the research behind the epidemiology of autism (autism spectrum disorder) in Australia before on this blog (see here) and how parts of Oz seemed to be lagging behind other estimated population rates of autism [2]. Accepting that there may be various factors affecting the estimates of autism prevalence across different countries and even different regions of countries, the figures from Bent (0.74%) start to become more comparable with the Danish estimates reported some 4 years ago.

The idea that individual diagnoses covered under the umbrella term ASD might also translate into differences in age at diagnosis is also interesting if not new news. I recently covered some of the issues around the diagnosis of autism (see here) and in particular, some of the factors that seem to have some bearing on age at diagnosis (see here). Thinking back to some of my own research in this area [3] I remember detecting some differences in age of symptom onset/diagnosis according to diagnostic grouping albeit not significant in that particular cohort. The larger numbers from Bent and colleagues add to that sentiment and how, outside of sex differences in presentation, the differences between the various labels might affect the diagnostic journey.

"Given that research suggests a reliable and accurate diagnosis is possible for many children with ASD at 24 months... finding[s] represents a possible average delay of 2 years (and common delays of up to 4 years)." Accepting that in amongst the various 'autisms' there may be cases where onset is not normally present before 2 years of age, even potentially confounded by other behaviours/comorbidity, the onus seems to be very much on improved screening and detection of autism and quite a few more resources put into investigating "barriers that delay the diagnosis of ASD." Said barriers might also focus on healthcare providers as well as other factors [4] (see here for my take on this paper).

Music: Portishead - Sour Times.

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[1] Bent CA. et al. Mapping the diagnosis of autism spectrum disorders in children aged under 7 years in Australia, 2010-2012. Med J Aust. 2015 Apr 6;202(6):317-20.

[2] 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.

[3] Whiteley P. Developmental, behavioural and somatic factors in pervasive developmental disorders: preliminary analysis. Child Care Health Dev. 2004 Jan;30(1):5-11.

[4] Zuckerman KE. et al. Parental Concerns, Provider Response, and Timeliness of Autism Spectrum Disorder Diagnosis. Journal of Pediatrics. 2015. 14 April.

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Bent CA, Dissanayake C, & Barbaro J (2015). Mapping the diagnosis of autism spectrum disorders in children aged under 7 years in Australia, 2010-2012. The Medical journal of Australia, 202 (6), 317-20 PMID: 25832158