The ICD-11 diagnostic criteria for autism: criteria that actually gets it right?

I'd love to say that this post represents me getting back into autism research blogging but alas, I'm not sure I'd be able to stick to any sort of routine or plan. Work, family, karate, so many Star Wars spin-offs to watch, you know what it's like. Suffice to say that something important brought me back to making this entry: the ICD-11 criteria for autism (see here). 

So why blog about it? Well simply because I reckon that this latest version of one of the major ways that autism or autism spectrum disorder (ASD) is diagnosed is basically as good as we've ever got at defining autism and the various nuances around an autism diagnosis. 

Why? Lots of reasons, and I would invite as many people as possible to survey the criteria which is free for all to read. For me, it's as follows:

1. Autism, the catch-all diagnosis, is now not just singular autism, it's more. Much more. The criteria still consists of the timeless social communication issues (social affect as it was once called) and "persistent restricted, repetitive, and inflexible patterns of behaviour, interests, or activities." It's still talks about early onset (although the 'before 3 years of age' bit is long gone as in previous versions). Importantly it still talks about symptoms resulting in "significant impairment in personal, family, social, educational, occupational or other important areas of functioning." This last point is often not as well remembered as it should be, particularly in certain social media circles. But more than all that we now have separate diagnostic sub-codings for things like the presence of intellectual (learning) disability and functional language impairment in a sort of pick-and-mix matrices combination. The DSM-5 also tried this with their 'levels of support' or, dare I say it 'severity levels' (see here). Allied to all that is another sub-coding: loss of previously acquired skills. Y'know, all those reports of regression or plateau in skills that parents and caregivers talked about? They've been taken seriously and at last, now feature as part of the diagnostic work-up. Minus any 'I told you so' sentiments, we've already published on this a few years back (see here). The road has been long. Wow.

2. Alongside the core clinical features are quite a few other headings covering other types of behaviour that one may see accompanying autism. Anxiety, seizures and here's one: self-injurious behaviours (SIB). No it doesn't make for great reading (SIB can be absolutely devastating to the person concerned and their family) but at last, acknowledgement that it's an issue for some. There's also talk about other comorbidities / multi-morbidities (that's comorbidity not co-occurrence) to look out for. Some psychiatric, some behavioural and some somatic. Get ready for another 'I told you so' moment (see here). 

3. Standby for something really important included in the ICD-11 criteria: a list of some 18 other conditions where autistic signs and symptoms can significantly present is also provided. This is new. The list ranges from things like ADHD (attention-deficit hyperactivity disorder) to schizophrenia to personality disorder(s). Developmental coordination disorder (DCD) aka dyspraxia is also in there and acknowledges something that even the great Leo Kanner talked about. This will help clinicians (yes, the people who conduct formal autism assessments) no end. It means that they should also be on the look out for various other conditions when they make their assessments (indeed, if any of those listed overlapping conditions are also present in clinic, it might mean looking for autism too). I'll also, at this point, add in the almost forgotten issue of social (pragmatic) communication disorder (SCD) from the DSM-5 too. I'm also interested in that list of overlapping conditions because they seem to becoming more and more important to autism. Take schizophrenia for example. Did you know that an estimated 1 in 10 people with autism might be at risk of transitioning over to schizophrenia over a 10 year period according to this study from 'big data Taiwan'? And more recently we've seen research all about ADHD 'transitioning' into ASD as a primary diagnosis (see here); prodromal period anyone? Oh, and I should also mention that the word 'encephalitis' figures in those boundary conditions. I'd like to think this would trigger a lot more discussion and study on how immune system / inflammatory conditions *might* play a role in at least some autism. I say this on the back of our recent-ish review of autoimmune encephalitis and autism (see here) and my continuing interest in such things.

So there you have it citizens (hat-tip to the late great Christopher Plummer!), the ICD-11 diagnostic criteria for autism. Obviously we'll have to see where it all goes, but certainly, as the criteria beds in, diagnostic reports will get more and more detailed which has to be a boon for things like EHCPs (Education, Health and Care Plans) and getting things right for people (particularly children) when diagnosed. As for research, well, that will benefit too, given the more detailed diagnostic starting point other than just 'autism vs. non-autistic controls'. I reckon we're going to be seeing more and more objective biological markers in the coming years. One more thing: you've no doubt heard about the term 'profound autism'? Well, it looks like ICD-11, like DSM-5, is going to forward this concept a lot more in times to come. 

Peace be with you.

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Hsu TW, Chu CS, Tsai SJ, Hsu JW, Huang KL, Cheng CM, Su TP, Chen TJ, Bai YM, Liang CS, Chen MH. Diagnostic progression to schizophrenia: A nationwide cohort study of 11 170 adolescents and young adults with autism spectrum disorder. Psychiatry Clin Neurosci. 2022 Dec;76(12):644-651. doi: 10.1111/pcn.13468. Epub 2022 Sep 27. PMID: 36057134.

Kopp S, Asztély KS, Landberg S, Waern M, Bergman S, Gillberg C. Girls With Social and/or Attention Deficit Re-Examined in Young Adulthood: Prospective Study of Diagnostic Stability, Daily Life Functioning and Social Situation. J Atten Disord. 2023 Mar 13:10870547231158751. doi: 10.1177/10870547231158751. Epub ahead of print. PMID: 36915033.

Sala R, Amet L, Blagojevic-Stokic N, Shattock P, Whiteley P. Bridging the Gap Between Physical Health and Autism Spectrum Disorder. Neuropsychiatr Dis Treat. 2020 Jun 30;16:1605-1618. doi: 10.2147/NDT.S251394. PMID: 32636630; PMCID: PMC7335278.

Whiteley P, Carr K, Shattock P. Is Autism Inborn And Lifelong For Everyone? Neuropsychiatr Dis Treat. 2019 Oct 7;15:2885-2891. doi: 10.2147/NDT.S221901. PMID: 31632036; PMCID: PMC6789180.

Whiteley P, Marlow B, Kapoor RR, Blagojevic-Stokic N, Sala R. Autoimmune Encephalitis and Autism Spectrum Disorder. Front Psychiatry. 2021 Dec 17;12:775017. doi: 10.3389/fpsyt.2021.775017. PMID: 34975576; PMCID: PMC8718789.

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Autistic traits in schizophrenia: meta-analysed

"Current findings support that individuals with schizophrenia spectrum disorders have higher autistic symptoms than healthy controls."

So said the meta-analysis findings reported by Franco De Crescenzo and colleagues [1] and their study which "systematically reviews and quantitatively synthetizes the current evidence on the presence of autistic symptoms in individuals with schizophrenia spectrum disorders." I might quibble (again) with the use of the term 'healthy controls' but the findings reiterate something quite important: autistic signs and symptoms are not necessarily exclusively linked to a diagnosis of autism (see here and see here).

The De Crescenzo paper represents a 'let's boil down the existing peer-reviewed science literature into a coherent statement' kinda study; as 13 studies including nearly 2000 participants were included for review and meta-analysis. The primary outcome "was the Autism Spectrum Quotient (AQ)" and its use on those diagnosed with schizophrenia or schizophrenia spectrum disorder (SSD) vs. those with autism or vs. those asymptomatic controls as a total score or scores on the various sub-domains. The results went something along the lines of "individuals with SSDs have significantly higher autistic symptoms than healthy controls and lower autistic symptoms than individuals with autism." That finding followed for the total AQ score and most of the sub-domain scores.

What else is there to say? Well, the De Crescenzo results relied on the AQ for their measurement of autistic signs and symptoms. I've mentioned more than once on this blog how the AQ might show an important connection to autism but is not necessarily the premier (exclusive) autism screener (see here and see here). Applying such logic to the current meta-analysis findings and one has to be a little bit careful about what is being measured by such a scale and whether such overlap is there on the basis of just autistic signs and symptoms.

That all being said I have talked about overlap between scores on the AQ in autism and schizophrenia before on this blog (see here) and the notion of potential 'fuzzy boundaries' between the two labels. Indeed, it makes you wonder whether science and clinical practice were too quick to dismiss the important findings from Mildred Creak and colleagues [2] and the seeming desire to move autism as far away from schizophrenia as possible...

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[1] De Crescenzo F. et al. Autistic Symptoms in Schizophrenia Spectrum Disorders: A Systematic Review and Meta-Analysis. Front Psychiatry. 2019;10:78.

[2] Evans B. How autism became autism: The radical transformation of a central concept of child development in Britain. Hist Human Sci. 2013;26(3):3-31.

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Colliding spectrums again: autism and schizophrenia meta-analysed (again)

"The systematic review and meta-analysis showed a significant association between schizophrenia and ASD [autism spectrum disorder]."

That was the conclusion made by Zhen Zheng and colleagues [1] following their trawl through the peer-reviewed science literature with a view to examining "the association between schizophrenia and ASD."

This is not the first time that Zheng et al have featured in the autism meta-analysis arena (see here and see here and see here) so one could perhaps see them as seasoned professionals when it comes to this type of science. It's also not the first time that the relationship between autism and schizophrenia has been subjected to such analyses either (see here) continuing quite a long relationship between the labels and/or spectrums [2] (see here also).

So: "The meta-analysis of the prevalence of schizophrenia in individuals with ASD encompassed 1,950,113 participants and 14,945 individuals with ASD." From such numbers/data, authors were quite confidently able to determine that schizophrenia was more frequent in cases of autism than in control participants. Indeed, this was described as a 'robust' finding and the magnitude of the risk was not to be sniffed at: "odds ratio = 3.55, 95% confidence interval: 2.08-6.05, P < .001."

In relation to the "prevalence of ASD in individuals with schizophrenia", the authors relied on a smaller number of participants but concluded that: "The prevalence of ASD in individuals with schizophrenia ranged from 3.4 to 52%." Ergo, schizophrenia occurring alongside autism and autism occurring alongside schizophrenia both show over-representation.

As I mentioned on a previous blogging occasion when these labels were discussed in an overlapping sense, there are many implications from such findings. There are implications related to the preferential screening for schizophrenia and/or autism (also including other related issues too) when one or other label is diagnosed and for timely and appropriate intervention for such issues when detected (see here). There are implications for the idea that, biologically-speaking, there may be some shared mechanisms at work covering both (heterogeneous) labels (see here and see here for examples). There are also implications in relation to the social impact of such an association; bearing in mind the often very negative image portrayed of schizophrenia in certain quarters of the media and the rise and rise of 'autistic identity' in other circles. There is lots to think about.

And finally and quite timely, the paper from Giacomo Deste and colleagues [3] talking about the PANSS Autism Severity Score (PAUSS) as a "simple, fast and reliable tool for the identification of autistic features in adult patients with schizophrenia" looks rather interesting...

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[1] Zheng Z. et al. Association Between Schizophrenia and Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. Autism Res. 2018 Oct 3.

[2] Evans B. How autism became autism: The radical transformation of a central concept of child development in Britain. History of the human sciences. 2013;26(3):3-31.

[3] Deste G. et al. Looking through autistic features in schizophrenia using the PANSS autism severity score (PAUSS). Psychiatry Research. 2018. Oct 29.

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Selective mutism and autism

The findings reported by Hanna Steffenburg and colleagues [1] make for potentially important reading reporting: "In this study of a clinical group of children who were diagnosed with SM [selective mutism] and assessed at a center for neurodevelopmental disorders, 63% also met criteria for ASD [autism spectrum disorder]."

Selective mutism (SM) refers to an anxiety disorder typically manifesting during early childhood that affects the use of spoken language in certain social situations such as at school. 'Literally being unable to speak' is a phrase that follows SM in certain contexts, where speech and language skills are not typically affected when and where family or close friends are around. It's not surprising that there is 'overlap' between SM and autism given the characterisation of SM in terms of being "nervous, uneasy or socially awkward" and "stiff, tense or poorly co-ordinated" (minus any sweeping generalisations). And just before you question it, 'poorly-coordinated' is perhaps an under-rated aspect for many people diagnosed as being on the autism spectrum (see here).

Steffenburg and colleagues - including the notable ESSENCE-related name of Christopher Gillberg - sought to examine the possible 'overlap' of SM and autism on the basis that various diagnoses/labels can occur alongside SM; quite a few of them also recognised in relation to autism (see here). Approaching 100 children/young adults diagnosed with selective mutism were assessed at the premier 'autism spectrum conditions' clinic in Gothenberg, Sweden. The clinical assessment undertaken of course covered the diagnosis of autism but also various cognitive functions too.

Almost two-thirds of those with SM who were assessed also met criteria for an autism spectrum disorder (ASD). Added to that: "A further 20% (n=19) had autistic features that were “subclinical”, but, nevertheless, sufficiently marked to have an impact on everyday life." Only 17% were described as having no ASD symptoms. Those are pretty interesting percentages.

Authors also mention how: "The level of cognitive function was average in more than half of the study group but more than one-third of the study group had a borderline IQ or an ID [intellectual disability]." They use such a finding in the context of the ESSENCE term - Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations - where overlapping diagnoses/labels is the rule not the exception.

The implications? Well, screen and keep a continual eye open for autism in cases of SM seems to be an important first implication. That also includes keeping in mind those 'subclinical' signs and symptoms, which could be relevant to discussions about the broader autism phenotype (BAP) (see here) and also that curious DSM-5 diagnostic category known as social communication disorder (SCD) (see here). The focus on 'anxiety' in relation to SM might also be important given the pretty well-established connection between autism and anxiety (see here for example) following in the footsteps of some often forgotten autism research history (take a bow Mildred Creak and colleagues for including the term "acute, excessive and seemingly illogical anxiety"). I'm also minded to mention that given the pretty high rate of autism described in SM by Steffenburg and other researchers, further investigations perhaps need to be directed towards shared biology/genetics as well as shared behavioural presentation? Y'know, along the lines of whether 'comorbidity' might be something more 'core' (see here)?

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[1] Steffenburg H. et al. Children with autism spectrum disorders and selective mutism. Neuropsychiatr Dis Treat. 2018 May 7;14:1163-1169.

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"Due to the definitions of ME and CFS, “ME/CFS” does not exist..."

Today, May 12th, is ME/CFS and Fibromyalgia International Awareness Day, a day to designed to "bring awareness to ME/CFS patients, families, caregivers, and researchers." Keep that terminology in mind...

The quote heading the title of this post - "Due to the definitions of ME and CFS, “ME/CFS” does not exist..." - comes from the viewpoint paper published by Frank Twisk [1]. The report covers an important topic in the realms of chronic fatigue syndrome (CFS) also known as myalgic encephalomyelitis (ME) also known as systemic exertion intolerance disease (SEID) in terms of whether it is appropriate to use such terms of defining the illness in a mixed or interchangeable fashion. Indeed, whether the connections between all those 'also known as' words I just used are actually accurately reflective of current diagnostic descriptions...

It's no secret that science and clinical practice is still coming to grips with some of the fundamentals of CFS, ME and SEID (see here and see here for examples) in terms of what to call it, how to define it and how to test for some of the fundamental diagnostic characteristics (see here). It's also still dealing with things like the definition of recovery (see here), which might seem like common sense (a complete and sustained remission of symptoms) but hasn't been particularly straightforward in this area for quite a few reasons.

Twisk takes the reader through some of the history of the terminology used and, how, whilst there is overlap in the way that ME, CFS and SEID are defined (chronic and long-lasting weakness or fatigue is a commonality), there are also some important differences. Take for example the authors description of the Ramsay criteria for ME and specifically onset: "Illness commonly initiated by respiratory and/or gastrointestinal infection, but an insidious or more dramatic onset following neurological, cardiac, or endocrine disability occurs." This contrasts with the onset criteria for CFS and SEID which basically says little about how symptoms start or come about.

Twisk concludes that: "ME is a neuromuscular disease" and should typically not to be viewed as 'equivalent' to CFS. CFS, he argues, tends to rely heavily on a single mandatory 'chronic fatigue' symptom, something that might intersect with ME but does not go far enough to evoke a full diagnosis of ME. As for SEID, well, trumpeted as being the solution to all the diagnostic confusion, SEID has it's own issues according to Twisk. Not least that it can't serve both masters (ME and CFS) in diagnostic terms. Also important: "SEID case criteria are also applicable to subsets of people with other diseases, for example, Multiple Sclerosis (MS) and lupus; and psychological conditions, for example, major depression." There is the propensity for diagnostic confusion.

I do think that Twisk is on to something with his observations. I know quite a few people who don't like the confusion caused by combination terminology like 'ME/CFS'; often seeing it as conflating two (or even more!) quite different conditions. Add in yet another potentially important variable to such an argument - the addition of chronic disabling fatigue (CDF) as "a proxy for clinically diagnosed CFS/ME" as some authors have (see here) - and things get even more muddled. I daresay a lot of this confusion might also intersect with discussions/debates/arguments as to how far something like the biopsychosical (BPS) model should or rather shouldn't be applied to such fatigue related conditions (see here)...

You want to do something for ME/CFS and Fibromyalgia International Awareness Day? Well, first thing you could do is watch 'Unrest', then follow the #millionsmissing hashtag and then push for more research, biological research...

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[1] Twisk FNM. Myalgic Encephalomyelitis, Chronic Fatigue Syndrome, and Systemic Exertion Intolerance Disease: Three Distinct Clinical Entities. Challenges. 2018; 9(1): 19.

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Autistic traits in adult schizophrenia

"Results of this study indicate the existence, in a sample of patients with a diagnosis of schizophrenia, of a distinct group of subjects with ASD [autism spectrum disorder] features, characterized by specific symptomatological and cognitive profile."

So said the findings reported by Stefano Barlati and colleagues [1] continuing a research theme from this group [2] looking at the potential overlap between autism spectrum disorder and schizophrenia.

Reiterating my interest in how the autism and schizophrenia spectrums can and do collide (see here) both at a condition and trait level, the Barlati findings provide some pretty in-depth analysis of what autism *might* look like in the context of schizophrenia. They report evaluation of their cohort - "Seventy-five schizophrenia patients (20 females, mean age 42 ± 12)" - with two of the gold-standard autism assessment instruments: the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R) alongside other "clinical, neuropsychological, and psychosocial functioning measures."

It's important to say that, in these days of pluralisation of behavioural and/or psychiatric labels (see here and see here), quite a few participants (47/75) assessed as part of the Barlati study turned up "negative to all the autism scales administered." This tells us that it's not necessarily a straight-forward nor universal relationship when it comes to autism and schizophrenia (and vice-versa). More likely is the possibility that there either may be subgroups within the diagnosis of schizophrenia that present with significant autistic traits or possibly even that the timing or severity or grading of schizophrenia and its symptoms may predispose to autistic traits being more or less likely to be presented. That last point relies on the idea that various traits or characteristics of labels like schizophrenia and autism might not be as immutable as many people believe...

For however the participants diagnosed with schizophrenia who turned up clinically significant autistic traits in one or other or total domains/scores using the ADOS and ADI, further research is indicated. Further research on what this phenotype might look like longitudinally, how frequent it might manifest, and whether there may be unique challenges associated with it. It also might have some implications for intervention too (see here).

And yet again, such findings provide more fodder for the idea that autistic traits are not exclusively just part and parcel of a diagnosis of autism (see here), and the pressing need for formal, professional assessment when autism is suspected...

Oh, and then there's more...

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[1] Barlati S. et al. Autistic traits in a sample of adult patients with schizophrenia: prevalence and correlates. Psychol Med. 2018 Mar 20:1-9.

[2] Barlati S. et al. Autism Spectrum Disorder and Schizophrenia: Do They Overlap? International Journal of Emergency Mental Health and Human Resilience. 2016; 18: 760-763.

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"adult patients with CFS report few autistic traits in the self-report instrument, the AQ"

The findings reported by Indre Bilevicute-Ljunger and colleagues [1] tap into something of a developing interest I have on this blog: whether there is 'clinical overlap' between the diagnosis of chronic fatigue syndrome (CFS) (also known as ME or myalgic encephalomyelitis) and the diagnosis of autism or autism spectrum disorder (ASD) (see here).

Just before anyone gets the wrong end of the stick here, I'm not at all insinuating that CFS/ME and autism are one and the same. They are not. As per a previous research foray into the diagnostic borderlands of CFS/ME [2] I have however long been struck by how there may be some 'shared' symptoms relevant to both labels; particularly with reference to the presence of perceptual and motor issues ("auditory hyperacuity", "problems of balance", "walking problems"). Added also to a number of anecdotal reports suggesting that a diagnosis of autism is seemingly not protective against receipt of a diagnosis of CFS/ME, and it strikes me that there could be more investigations required in this area. At the time of writing however, there is very little in the peer-reviewed research domain examining any such 'overlap'.

Bilevicute-Ljunger et al - including the notable name of Susanne Bejerot on the authorship list (see here) - set out to examine any potential 'relationship' between autism and CFS by means of assessing three participant groups with everyone's favourite 'are you autistic?' self-report measure, the Autism-Spectrum Quotient (AQ). Said groups included those diagnosed with CFS (n=59) , those diagnosed with autism (n=50) and a group headed under the rather uninformative label of 'healthy controls' (HC) (n=53). The presented results showed that those diagnosed with ASD "scored significantly higher on the AQ than the CFS group and the HC group" and that: "No differences in AQ scores were found between the CFS and HC groups." Authors therefore concluded that: "Despite clinical observations of symptom overlap between ASD and CFS, adult patients with CFS report few autistic traits in the self-report instrument, the AQ."

Sounds pretty straight-forward eh? Well, hold on just a moment...

"The choice of instrument to assess autistic traits may influence the results." That was another line included in the Bilevicute-Ljunger paper, in conjunction with the idea that the AQ may very well be 'testing for' something in the context of autism, but that doesn't mean it is without issues in terms of things like specificity for autism (see here and see here). Indeed, I'll also take you back to a recent blog post (see here) which kinda said everything that needed to be said in terms of the [general] current state of adult questionnaires and screening measures for autism [3] including the AQ: "Evidence suggests some utility of diagnostic measures in identifying autism spectrum disorder among clinic referrals, although specificity for diagnosis was relatively low." Ergo, it is not completely unlikely that scoring high on the AQ and various other instruments *might* not necessarily mean just autism is present. I'll be coming back to the issue of AQ yet again on this blog quite soon.

Without trying to sound like someone who has a bee in their bonnet about the AQ not being a particularly great 'autism-specific' measure, I would like to see some further work done looking at any overlap between symptom presentation in CFS/ME and the same with regards to autism. I'd perhaps be minded to suggest that science starts to look at CFS/ME symptoms in autism rather than the other way around first and foremost. This would provide a baseline to see how prevalent CFS/ME in diagnosis or traits might be when an autism diagnosis is in the frame, particularly extending into adulthood. It might also provide some 'clues' as to whether shared or overlapping genetics / biology / physiology could be further investigated (hint: immune functions such as autoimmunity, oxidative stress, gut microbiota, etc. might be places to look) minus the psychobabble that both conditions have had to endure over the years. I'd similarly be interested in the idea that the sex ratios are seemingly opposing when it comes to ME/CFS and autism, and what that might mean for ensuring that screening for autism or autistic traits in relation to ME/CFS takes account of the chatter about sex/gender *potentially* influencing symptoms profiles (see here) and things like the female camouflage effect (see here)...

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[1] Bilevicute-Ljunger, I. et al. Patients with chronic fatigue syndrome do not score higher on the Autism-apectrum quotient than healthy controls: comparison with autism spectrum disorder. Scandinavian Journal of Psychology. 2018.  May 8.

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Colliding spectrums: autism and schizophrenia (meta-analysed)

Consider this post talking about the findings reported by Jorge Lugo Marín and colleagues [1] an extension of previous chatter on this blog about the possibility of overlapping spectrums when it comes to autism and schizophrenia (see here).

I appreciate that there is some 'history' when it comes to moves to separate autism and schizophrenia [2] but the evidence being produced more recently perhaps questions whether the historical 'eagerness' to compartmentalise the labels as separate and independent was more of a socio-political thing over and above a true reflection of the state of any relationship (see here and see here for examples). Indeed, when [peer-reviewed] science for example, starts talking about a possible 'subtype of autism linked to psychosis' (see here) you know that the connections are perhaps not to be under-estimated...

Lugo Marín et al report results following a meta-analysis of the relevant peer-reviewed science done on this topic. Ten papers fulfilled their inclusion criteria. They report that: "The pooled prevalence of SSD [schizophrenia spectrum disorder] in the total ASD [autism spectrum disorder] sample was close to 6%, pointing to a high co-occurrence of the two conditions." Further, that more research is required about the specific hows-and-whys of SSD or symptoms of SSD appearing alongside [some] autism (and vice-versa) and onward, the possibility of preferential screening and intervention.

I've thought about the relationship between autism and schizophrenia quite a bit over the years. Not only because in my own area of research interest - gluten- and casein-free diets and autism - there is history linking autism and schizophrenia (see here) but also because the relationship down the years seemingly plays into the stigmatisation of a label i.e. move autism 'away' from schizophrenia because of the perceived 'dangerousness' connotations attached to schizophrenia for example (see here for a more recent example of this in action [3]). On that point, the evidence is getting clearer that whilst the diagnosis of schizophrenia (plus other factors) is by no means preventative of 'dangerous' acts being committed, people diagnosed with the condition are seemingly far more likely to be victims of something like crime than perpetrators (see here). Sounds familiar doesn't it?

Then also there is the 'identity' perspective to consider when talking about autism and schizophrenia in the same breath. Schizophrenia is considered to be a mental health issue; autism by contrast is primarily viewed as a developmental condition, which, although increasing the risk of developing a mental health issue (see here for example), is not itself described as such per se. I say this acknowledging that support for schizophrenia as being a 'neurodevelopmental disorder' is also growing [4] as words like 'prodrome' become more frequently discussed. Also important in this context, are the possible effects of certain comorbidity being 'over-represented' in cases of autism potentially also impacting on the subsequent risk of a diagnosis of schizophrenia (see here).

Keeping the theme of 'identity' going when discussing autism and schizophrenia, there is another angle to consider in terms of 'ownership' of the labels and perceptions around such a concept. I speak of the movement towards use of terms like 'autistic person' over 'person with autism' preferentially considered by some (see here) and how such a move is seemingly at odds with identity in terms of schizophrenia. The term 'schizophrenic' is considered unsuitable in this day and age (see here - "A person is not the sum total of the symptoms") alongside other 'label-first' terms such as 'manic depressive' and 'psychotic' for example. You can perhaps see how labelling someone as 'autistic' whilst at the same time labelling them has 'having schizophrenia' under circumstances where the two spectrums collide, presents a quandary when it comes to language and identity and perhaps serves to reiterate the gulf between the labels/conditions in terms of perceived stigma for example.

What we can say on the back of the Lugo Marín findings is that, in these days of ESSENCE (see here) and RDoC (see here) the possible reunification of the autism and schizophrenia spectrums in specific cases, should not be seen as something detrimental to either label and could provide some important insights into the genetic and biological nature of both spectrums (see here). I have my views about where the two spectrums might meet on a biological level [5] but no doubt there will be lots of other intersections too. Indeed, once again harking back to the [sadly forgotten] writings of Mildred Creak and colleagues and their "9 key features of ‘schizophrenic syndrome in childhood’", their description is uncannily pertinent to large parts of the autism spectrum when taking into account inclusion of diagnostic items such as "abnormal perceptual experience", "distortion in motility patterns" and "acute, excessive and seemingly illogical anxiety" and the often pronounced effects that such symptoms can have on quality of life.



To close, a picture relevant to today...

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[1] Lugo Marín J. et al. Prevalence of Schizophrenia Spectrum Disorders in Average-IQ Adults with Autism Spectrum Disorders: A Meta-analysis. J Autism Dev Disord. 2017 Oct 4.

[2] Evans B. How autism became autism: The radical transformation of a central concept of child development in Britain. Hist Human Sci. 2013 Jul;26(3):3-31.

[3] Sasson NJ. & Morrison KE. First impressions of adults with autism improve with diagnostic disclosure and increased autism knowledge of peers. Autism. 2017 Oct 1:1362361317729526.

[4] Owen MJ. et al. Neurodevelopmental hypothesis of schizophrenia. The British Journal of Psychiatry. 2011;198(3):173-175.

[5] Prata J. et al. Bridging Autism Spectrum Disorders and Schizophrenia through inflammation and biomarkers - pre-clinical and clinical investigations. J Neuroinflammation. 2017 Sep 4;14(1):179.

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Completing the set: features of ADHD in childhood epilepsy

'Completing the set' used in the title of this post refers to the idea that a diagnosis of epilepsy rarely(?) seems to exist in some sort of diagnostic vacuum as per previous discussions whereby features of autism (see here) and dyspraxia / developmental coordination disorder (DCD) (see here) seem to be over-represented in cases of epilepsy.

This time around the focus was on attention-deficit hyperactivity disorder (ADHD) and the findings reported by Isabell Brikell and colleagues [1] suggesting that: "Individuals with epilepsy had a statistically significant increased risk of ADHD." Researchers arrived at their conclusions on the basis of examining some of those wonderful Scandinavian population registries that are providing all-manner of interesting details on possible trends and patterns in various areas: "We identified 1,899,654 individuals born between 1987 and 2006 via national Swedish registers..." Said data were actually used to look at "the familial coaggregation of epilepsy and ADHD and to estimate the contribution of genetic and environmental risk factors to their co-occurrence" but also served the purpose of looking at ADHD prevalence alongside epilepsy. Indeed it was also interesting to note the authors' conclusions about familial liability to the "cross-disorder overlap": "The genetic correlation was 0.21 (95% CI = 0.02-0.40) and explained 40% of the phenotypic correlation between epilepsy and ADHD, with the remaining variance largely explained by nonshared environmental factors." Mmm...

Such research - although requiring quite a bit more independent investigation [2] - follows an important trend in recent times observing how stand-alone developmental and/or psychiatric diagnoses often 'clump together' in seemingly at-risk patient groups. I've for example, talked about the important concept of ESSENCE - Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations [3] on this blog and how "co-existence with other conditions was the rule" (see here) rather than the minority perspective in the area of childhood psychiatry. Now we seem to be able to add ADHD to the list of comorbidity potentially over-represented alongside a diagnosis of epilepsy (bearing in mind that epilepsy covers quite a lot of diagnostic ground).

Mechanisms? Well, far be it from me to speculate too much, but an important starting point is the nature of epilepsy and how it affects brain function. It's not inconceivable that particular alterations to the functioning of the brain as a result of epilepsy (or even during some prodromal phase) might be enough to *induce* other behaviours/symptoms to be pronounced. Equally, one might subscribe to the the idea that changes to brain function due to other events or factors that may be connected to conditions such as autism or ADHD or DCD could be enough to induce the onset of epilepsy (this hypothesis draws support from the onset patterns typically seen in cases of autism and epilepsy). I don't doubt that relationships are likely to be complicated.

Much more needs to be done on this topic, not least in ensuring appropriate screening services when cases of epilepsy are diagnosed, particularly in childhood. With no medical or clinical advice given or intended (don't mess with epilepsy), I do wonder whether some of the peer-reviewed data talking about dietary changes being used to manage certain types of epilepsy also potentially impacting on presented symptoms of *some* other labels (see here) might also provide some clues as to potential shared mechanisms between epilepsy and other developmental/psychiatric labels?

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[1] Brikell I. et al. Familial Liability to Epilepsy and Attention-Deficit/Hyperactivity Disorder: A Nationwide Cohort Study. Biol Psychiatry. 2017 Aug 12. pii: S0006-3223(17)31858-9.

[2] Caplan R. ADHD in Pediatric Epilepsy: Fact or Fiction? Epilepsy Curr. 2017 Mar-Apr;17(2):93-95.

[3] Gillberg C. The ESSENCE in child psychiatry: Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations. Res Dev Disabil. 2010 Nov-Dec;31(6):1543-51.

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The strengthening relationship between eating disorders and ADHD

The results from Loretta Sala and colleagues [1] confirms a recent trend in research circles observing a potentially important relationship between various types of eating disorder and the presence of traits/behaviours consistent with a diagnosis of attention-deficit hyperactivity disorder (ADHD).

It's something that has been covered on this blog previously (see here) and represents an extension to the idea that the presentation of autistic traits might not be the only relevant comorbidity when it comes to eating disorders (ED) (see here).

Sala et al report results based on a sample of some 70 female inpatients "all with longstanding histories of eating disorder (ED)." Various scales and instruments were used to assess both ED and ADHD traits/symptoms including the "presence of a diagnosis of ADHD." Accepting the rather nebulous term ED, participants were divided up into specific groups based on the type of eating disorder present: anorexia nervosa restricting type (AN-R), anorexia nervosa binge-eating/purging type (AN-BP) and bulimia nervosa (BN).

Results suggested that ADHD comorbidity is not necessarily an uncommon feature among quite a few cases of ED: "13 patients reported comorbidity with ADHD; three in the AN-R subtype, nine in the AN-BP and one in the BN." Findings also suggested that further research efforts might need to be directed into how ADHD traits/symptoms correlates with other features in cases of ED; specifically in relation to scores on the EAT-40 and the presence of anxiety as measured by the Hamilton scales for Anxiety (HAM-A).

It can only be a good thing that science and clinical practice is beginning to understand that various behavioural/psychiatric labels are rarely observed in isolation to other comorbidity. Not only does this offer potential new avenues for screening/prevention/treatment (see here for one example) but could also provide some much-needed clues as to why conditions such as ED might come about and indeed, who might be particularly at risk for such conditions.

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[1] Sala L. et al. Attention-deficit/hyperactivity disorder symptoms and psychological comorbidity in eating disorder patients. Eat Weight Disord. 2017 May 22.

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Sala L, Martinotti G, Carenti ML, Romo L, Oumaya M, Pham-Scottez A, Rouillon F, Gorwood P, & Janiri L (2017). Attention-deficit/hyperactivity disorder symptoms and psychological comorbidity in eating disorder patients. Eating and weight disorders : EWD PMID: 28534123

Autism symptoms in children with ADHD

"Children with ADHD [attention-deficit hyperactivity disorder] had more ASD [autism spectrum disorder] symptoms than non-ADHD controls."

So said the findings from Jessica Leigh Green and colleagues [1] following their investigation of over 300 6-10 year olds looking at the prevalence of autistic symptoms "in a community-based sample of children with attention-deficit/hyperactivity disorder (ADHD) and non-ADHD controls." Conners 3 and the DISC-IV represented the analytical starting point pertinent to a diagnosis of ADHD, with autistic symptoms assessed via the Social Communication Questionnaire (SCQ).

As per the starting sentence, those diagnosed with ADHD (n=164) tended to present with quite a few more autistic traits than those without ADHD (n=198) and, importantly: "Greater ADHD symptom severity was associated with greater ASD symptom severity." Boys with ADHD also tended to fare worse than girls with ADHD when it came to the presentation of autistic symptoms. Ergo, yet again (see here) there seems to be something of an important 'connection' between autism and ADHD.

I don't think many people with some knowledge and interest in the intersection between autism and ADHD will be surprised by the Green results added to other recent findings [2]. As per the Gillberg concept of ESSENCE (see here) the fuzziness of child behaviour when it comes to identifiying psychopathology almost implies that there will be overlap in the presentation of specific labels. That specific interventions put forward for some autism might also be affecting ADHD-type symptoms more strongly than core autistic traits (see here) offers even more evidence for a connection between diagnoses/symptoms.

More research is of course implied in such findings, including that into what other symptoms might overlap the conditions [3] (yes, I'm talking about you motor issues) and the hows and whys of ASD + ADHD translating into a greater risk for future adverse outcomes as per other research in this area (see here). Whether too other factors such as poverty might also affect an autism-ADHD combination type (see here) also requires further study. Realisation that autism nor ADHD seemingly exist in a diagnostic vacuum is an important point raised from this and related work as we move further into the idea of comorbidity clusters (see here).

Music: Foxes - Holding onto Heaven.

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[1] Green JL. et al. Autism spectrum disorder symptoms in children with ADHD: A community-based study. Res Dev Disabil. 2015 Sep 30;47:175-184.

[2] Miodovnik A. et al. Timing of the Diagnosis of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder. Pediatrics. 2015 Oct;136(4):e830-7.

[3] Biscaldi M. et al. Identification of neuromotor deficits common to autism spectrum disorder and attention deficit/hyperactivity disorder, and imitation deficits specific to autism spectrum disorder. Eur Child Adolesc Psychiatry. 2015 Aug 2.

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Green JL, Rinehart N, Anderson V, Nicholson JM, Jongeling B, & Sciberras E (2015). Autism spectrum disorder symptoms in children with ADHD: A community-based study. Research in developmental disabilities, 47, 175-184 PMID: 26433184

Tics are common in adults with autism

The title of this post comes from a quote included in the paper by Ursula Kahl and colleagues [1] based on their study of the "phenomenology and characteristics" of tics in adults diagnosed with an autism spectrum disorder (ASD) compared with a small control group of adults with Gilles de la Tourette syndrome (GTS). A tic by the way, is a "sudden, fast, repeated movement or sound."

This is not the first time that tics have been examined with the autism spectrum in mind. The paper from Canitano & Vivanti [2] for example, looking at tics and GTS in cases of autism (N=105) concluded that nearly a quarter of children/young adults with autism presented with a tic disorder and about 1 in 10 with GTS. This followed previous research that came to similar conclusions [3].

The hows and whys of an association between tics and [some] autism is still a little up in the air. The presentation of tics has quite a strong genetic influence insofar as the data on familial linkage [4] and their frequency alongside other symptoms such as attention-deficit hyperactivity disorder (ADHD) and/or obsessive compulsive disorder (OCD). With the figures on ADHD comorbidity with autism in mind (see here), one shouldn't perhaps be surprised that tics might be present in some cases of autism. Indeed, my musings on the paper from Chen and colleagues [5] (see here) pretty much said as much.

"Tic awareness is limited in ASD" was the conclusion from Kahl et al.  I'd agree that tics aren't the first thing to come to mind when one talks about autism. That being said, with the increasing moves towards autism or autistic traits co-existing with a variety of other symptoms/diagnoses we shouldn't really be so surprised that tics might be part and parcel of presentation for some on the autism spectrum. As to the issue of management, well, I'd be minded to suggest that a case-by-case approach be taken [6] with something of an open mind to possible correlates bearing in mind no medical advice is given or intended...

Music: Spiritualized - Electricity.

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[1] Kahl U. et al. Tic Phenomenology and Tic Awareness in Adults With Autism. Movement Disorders Clinical Practice. 2015. March 30.

[2] Canitano R. & Vivanti G. Tics and Tourette syndrome in autism spectrum disorders. Autism. 2007 Jan;11(1):19-28.

[3] Ringman JM. & Jankovic J. Occurrence of tics in Asperger's syndrome and autistic disorder. J Child Neurol. 2000 Jun;15(6):394-400.

[4] O'Rourke JA. et al. The Genetics of Tourette Syndrome: A review. J Psychosom Res. 2009 Dec; 67(6): 533–545.

[5] Chen M-H. et al. Autistic spectrum disorder, attention deficit hyperactivity disorder, and psychiatric comorbidities: A nationwide study. Research in Autism Spectrum Disorders. 2015; 10: 1-6.

[6] Shprecher D. & Kurlan R. The management of tics. Mov Disord. 2009 Jan 15;24(1):15-24.

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Kahl, U., Schunke, O., Schöttle, D., David, N., Brandt, V., Bäumer, T., Roessner, V., Münchau, A., & Ganos, C. (2015). Tic Phenomenology and Tic Awareness in Adults With Autism Movement Disorders Clinical Practice DOI: 10.1002/mdc3.12154

Autistic traits in adult-onset psychiatric disorders?

"To conclude, the presentation of ALTs [autistic-like traits/symptoms] at the sub-threshold or threshold level may be closely associated with BPD [bipolar disorder] and SZ [schizophrenia]."

That was the conclusion reached in the paper by Junko Matsuo and colleagues [1] (open-access here) based on their analysis of nearly 300 adults aged between 25-59 years including those diagnosed with "MDD [major depressive disorder], n=125; bipolar disorder, n=56; schizophrenia, [and] n=44; healthy controls, n=65." The 'healthy controls' definition is that of the authors not mine.

"Autistic-like traits/symptoms were measured using the Social Responsiveness Scale for Adults [SRS-A]" we are told. Bearing in mind quite a bit of variation in the SRS-A scores across various diagnoses (including remitted and unremitted subgroupings too) there was a tendency towards "significantly higher total and social communication and autistic mannerisms subscale scores on the SRS-A compared to the HC [healthy controls] group."

Further: "Almost half of the clinical subjects, except those with remitted MDD, fell into the mild-to-severe range for ALTs, which is typical for sub-threshold or threshold ASD [autism spectrum disorder]." This effect seemed to be independent of symptom severity in those with BPD or SZ. However: "ALTs in subjects with MDD were associated with the depressive symptom severity in our study; in other words, although subjects with severe depressive symptoms tended to exhibit high ALTs, subjects with less severe depressive symptoms did not differ from healthy controls with regard to the proportion or degree of high ALTs."

Acknowledging the requirement for further investigation and the fact that authors "did not conduct a thorough and comprehensive evaluation of ASD" in their participant cohort, these are interesting findings. Regular readers might already have noted that I'm coming around to the idea that there may be some important links between the presentation of [some] autism and a variety of psychiatric diagnoses. I know this might take some people into some uncomfortable territory and muddy the waters when it comes to what exactly is being examined when it comes to autism research (see here for example) but to me this is really quite important science. Not least when it comes to the idea that a diagnosis of autism might elevate the risk of certain other labels being diagnosed (see here) and what that means for diagnostic vigilance and screening save any further health inequalities becoming apparent.

The detail about autistic-like traits/symptoms being 'associated' with depressive symptoms is something particularly interesting. As per some recent discussions on this blog on depression and autism potentially being interlinked (see here) and some flesh being put on the scientific bones when it comes to what facets of depression might be linked to autism (see here), I think there is quite a lot more to see in this area. We're not yet in a position to talk about what [definite] mechanisms might be influencing any correlation between autistic traits and depressive symptoms although I'm minded to suggest that there may be some possible research avenues based on the peer-reviewed literature as it stands. Take for example the idea that vitamin D might be implicated in both cases of autism and depression (see here and see here respectively). Even more 'out there', I'd like to pose another question: could studies of gluten also provide some research leads (see here and see here)? Either way, the application of the spectrum of autistic traits is growing and getting ever more complicated [2].

Music: The Strokes - Reptilia.

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[1] Matsuo J. et al. Autistic-Like Traits in Adult Patients with Mood Disorders and Schizophrenia. PLoS One. 2015 Apr 2;10(4):e0122711.

[2] Koolschijn PC. et al. Are Autistic Traits in the General Population Related to Global and Regional Brain Differences? J Autism Dev Disorders. 2015. April 7.

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Matsuo J, Kamio Y, Takahashi H, Ota M, Teraishi T, Hori H, Nagashima A, Takei R, Higuchi T, Motohashi N, & Kunugi H (2015). Autistic-Like Traits in Adult Patients with Mood Disorders and Schizophrenia. PloS one, 10 (4) PMID: 25838109

Systemic Integral Disorder: linking autism and schizophrenia?

Martial arts gradings call for my brood today (and well they should) so I'm gonna be fairly brief and introduce the paper by Haoran George Wang and colleagues [1] for your reading pleasure today alongside the concept of 'Systemic Integral Disorder' (SID) as a potential bridge between the diagnoses of autism and schizophrenia.

I'm always a bit wary of grand over-arching theories or universal conceptual 'break-throughs' when it comes to autism simply because the inevitable hype which follows such descriptions almost always misses some important points concerning heterogeneity (plurality) and the impact of accompanying comorbidity which seem to occur quite frequently for people on the autism spectrum. Carrying such preconceptions, I was therefore a little guarded in accepting the Wang findings outright.

Acknowledging that there is some history when it comes to autism and schizophrenia (see here) and how views and opinions change over time (see here), I am coming around to the idea that autism research might have been a little hasty in burning all the bridges connecting autism and schizophrenia. As per my discussions on the Lugnegård findings [2] (see here), work from the likes of Mildred Creak and colleagues [3] has been an unfortunate casualty of the division between the conditions and the terminology used at the time. The idea that a diagnosis of autism may not be protective against future development of schizophrenia or conditions linked to schizophrenia (see here) is also gaining momentum. This has some potentially very important implications for things like screening for example (see here).

The focus on structural genetics potentially also linking the labels autism and schizophrenia by Wang et al is interesting if a little insular in terms of things like the growing evidence base potentially linking shared epigenetic mechanism for example, to the conditions (see here). That also the idea of SID might very well overlap with something like the RDoC initiative is something else to consider.

Music: Overload by the Sugababes.

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[1] Wang HG. et al. Genetic and Developmental Perspective of Language Abnormality in Autism and Schizophrenia: One Disease Occurring at Different Ages in Humans? Neuroscientist. 2015 Feb 16. pii: 1073858415572078.

[2] Lugnegård T. et al. Asperger syndrome and schizophrenia: Overlap of self-reported autistic traits using the Autism-spectrum Quotient (AQ). Nord J Psychiatry. 2014 Nov 12:1-7.

[3] Evans B. How autism became autism: The radical transformation of a central concept of child development in Britain. Hist Human Sci. 2013 Jul;26(3):3-31.

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Wang HG, Jeffries JJ, & Wang TF (2015). Genetic and Developmental Perspective of Language Abnormality in Autism and Schizophrenia: One Disease Occurring at Different Ages in Humans? The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry PMID: 25686622

Late, delayed and mis-diagnosis of autism

It's inevitable that with all the mountains of autism research published on a daily basis, certain themes will occur at certain times. My post today is reflective of one of those themes and how, on occasion, the autism diagnostic process does not run as smoothly as we would all like to think.

I start this post with a link to an article discussing some forthcoming research to be published titled: 'The autistic pupils ‘traumatised’ by delayed diagnosis'. Describing the results of a survey of parents included as part of a scheme of work (see here) where experiences of the diagnostic process were gauged, researchers reported that over half of parents were "unhappy with the diagnostic process" for their children. The observation that children were waiting an average of 3.5 years from initial contact with healthcare professionals to final receipt of a diagnosis is a pretty eye-watering statistic too, albeit a step up from previous research in this area [1].

Next up is the paper from Davidovitch and colleagues [2] reporting that: "Subsequent late diagnosis of ASD [autism spectrum disorder] after an initial ASD-negative comprehensive assessment is a common clinical experience." Based on an: "Extensive chart review of patients' electronic medical records" from "a representative population-based registry of patients seen during 2004 to 2011" researchers reported that over 200 children were diagnosed with an ASD after their 6th birthday "although their initial comprehensive developmental evaluations before the age of 6 were negative for ASD." The authors discuss possible reasons for the reversal of diagnosis including "evolving diagnosis as well as missed and overdiagnosed cases of ASD."

Finally, is the paper from Aggarwal & Angus [3] with the conclusion: "ASDs can go undetected during childhood and these clients can sometimes present during adolescence to mental health services for a psychiatric comorbidity." This followed their experiences of a diagnosis of autism being potentially missed or masked during childhood, only to be picked up during adolescence when a referral was made "for a psychiatric comorbidity."

Taken as a collection, these articles/features reiterate that the diagnosis and diagnostic process of autism is often a very complicated thing even before one starts to talk about politics, the availability of resources to undertake such a task and on occasion, actually getting someone to take notice of the need for a referral (see here). I've talked before on this blog about the various factors than can influence the age of autism diagnosis (see here) stressing for example, the fluidity in behavioural expression particularly during the early years (see here) and even into adulthood (see here). Outside of the idea that there may be a number of diverse developmental trajectories when it comes to autism (see here) impacting on presentation, including the idea of regression potentially being present for some (see here), even the most seasoned autism professionals are not error-free when it comes to something like autism screening and diagnosis (see here).

Insofar as the Aggarwal/Angus results, and the idea that the label of autism may only come to diagnostic attention when other psychiatric comorbidity lead, this is something discussed previously on this blog (see here and see here). The overlap between the autism and for example, the schizophrenia spectrums (see here) is an area crying out for further research attention and how intersecting with the idea of ESSENCE in autism (lots of different labels/symptoms potentially following a diagnosis of autism), symptom masking can be a real issues (see here). That also goes for the potential appearance of autism in other conditions such as Down's syndrome for example (see here).

With the growing tide of research suggesting that early (sometimes very early) intervention may be able to make a real impact on the course of autism for some (see here and see here), late, delayed or even mis-diagnosis should be viewed not only as a source of significant stress for those on the autism spectrum and their loved ones, but also as an area of vital importance to autism research on the ways and means of minimising such issues.

[Update: 25 March 2015: The paper from Crane and colleagues [4] has been published. The full-text is available here.]

Music then. I've probably linked to this before but here is Blondie and One Way Or Another.

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[1] Howlin P. & Asgharian A. The diagnosis of autism and Asperger syndrome: findings from a survey of 770 families. Dev Med Child Neurol. 1999 Dec;41(12):834-9.

[2] Davidovitch M. et al. Late Diagnosis of Autism Spectrum Disorder After Initial Negative Assessment by a Multidisciplinary Team. J Dev Behav Pediatr. 2015 Feb 2.

[3] Aggarwal S. & Angus B. Misdiagnosis versus missed diagnosis: diagnosing autism spectrum disorder in adolescents. Australas Psychiatry. 2015 Feb 4. pii: 1039856214568214.

[4] Crane L. et al. Experiences of autism diagnosis: A survey of over 1000 parents in the United Kingdom. Autism. 2015. March 25.

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Davidovitch M, Levit-Binnun N, Golan D, & Manning-Courtney P (2015). Late Diagnosis of Autism Spectrum Disorder After Initial Negative Assessment by a Multidisciplinary Team. Journal of developmental and behavioral pediatrics : JDBP PMID: 25651066



Aggarwal S, & Angus B (2015). Misdiagnosis versus missed diagnosis: diagnosing autism spectrum disorder in adolescents. Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists PMID: 25653302