Monday, 24 July 2017

On DSM-5, Asperger syndrome and 'level of support'

It wasn't so much the findings reported by Garrido and colleagues [1] that took my attention, but rather their use of a particular sentence: "We have equated diagnosis of Asperger syndrome with ASD-level 1 of support" in the context of the DSM-5 guidance for diagnosing an autism spectrum disorder.

For those who might not know, the two main documents for diagnosing autism or autism spectrum disorder (ASD) are the ICD and DSM schedules. Both are currently under/have recently been the subject of revision (ICD-11 and DSM-5 respectively) and both have played a significant role in relation to various aspects around autism (see here for example).

The quite recently revised DSM-5 description of autism (see here) has been the source of quite a lot of discussion. Not only that the latest description might have some quite important effects on the numbers of people potentially being diagnosed with autism or ASD (see here) but also that this revision did away with the diagnostic sub-categories included in previous DSM versions; notably the diagnosis of Asperger syndrome. There were mechanisms built into the DSM-5 such that those already diagnosed with Asperger syndrome (AS) would not lose out in terms of 'identity' but as the DSM-5 becomes more readily used (and also assuming ICD-11 allies with DSM-5 as anticipated), the specific diagnosis of AS is likely to be consumed by the broader ASD label in the longer term. Other authors have talked about the hows-and-whys of this issue in more informed detail than I ever could (see here although I think the authors needs to spellcheck 'Asperger' in some places).

With that rather long introduction in mind, I want to go back to that 'ASD-level 1 support' labelling of AS in the Garrido paper. DSM-5 criteria for autism, sorry ASD, does provide the diagnosing team with an option to place the recipient of a diagnosis on a scale of severity ranging from 'requiring support' to 'requiring very substantial support' shown as levels 1-3 respectively. The assumption is that money and resources will be attached at varying degrees based on the support level indicated. The level 1 support option applied to AS presumes that the dyad of symptoms - social affect and restricted, repetitive behaviours - does impact on day-to-day functioning but issues such as the consistent and complex use of language as a communicative strategy for example, puts their support requirements below say those with 'marked' or 'severe' deficits in verbal and nonverbal social communication skills. Fair enough. When however it comes to the repetitive behaviour side of things in terms of severity, level 1 support basically acknowledges that inflexible behaviour "causes significant interference with functioning in one or more contexts" but importantly, does not use words like 'distress' as it does in level 2 and 3 descriptions.

I may just be focusing too much on details here, but it strikes me that the sweeping assumption made by Garrido et al reveals a broader issue with level of support shown in DSM-5. Although there is not a great deal of peer-reviewed research out there on the severity/support level components to the DSM-5 ASD diagnosis, the work that is there tends to suggest a degree of 'fuzziness' both in the pattern of skills/deficits displayed in relation to autism and onward how clinicians might define decisions on support level [2]. What seems to be inferred with the level of support criteria offered in DSM-5 is that those with a current diagnosis of AS as a group - this diagnosis then changing to ASD - will seemingly never hit criteria for levels 2 or 3 on the basis of the language and communicative skills they possess. I say this with the understanding that I'm not precisely sure whether the individual components of the dyad - social affect and restricted, repetitive behaviours - are separately graded in terms of level of support needed in DSM-5 or just condensed into one severity level for all the diagnostic components combined. Garrido and colleagues imply that one severity level is likely going to be the rule.

There is another issue that needs comment, on whether at least some cases of AS actually meet the operational criteria of DSM-5 ASD over and above the new categorisation of social (pragmatic) communication disorder (SCD) (see here). I can see this being a contentious point. SCD as the name suggests, focuses on 'the social use of verbal and nonverbal communication' and how 'deficits result in functional limitations in effective communication, social participation, social relationships, academic achievement, or occupational performance, individually or in combination'. Previous data has suggested that something approaching 10% of cases of AS - redefined as ASD in DSM-5 - might not actually meet DSM-5 criteria for ASD but might hit diagnostic thresholds for SCD [3]. As I've asked before on this blog, what level of support are those with SCD likely to get? and what are the implications for 'membership' of the autism spectrum for those diagnosed with SCD? are questions that still need answering.

I have been a little pedantic in this post but do want to convey the message that even with the redefinition of AS into ASD, the DSM-5 severity/level of support descriptions are in need of a lot more experimental study to see how they work in real-life [4]. Indeed, further longitudinal studies on how DSM-5 diagnosis and severity 'grading' translate into money, resources and services offered and received and onward outcomes for those diagnosed, should really be in the planning stages as we speak...


[1] Garrido D. et al. Communicative and social-adaptive profile in children with autism spectrum disorder: a new approach based on the DSM-5 criteria. Rev Neurol. 2017 Jul 16;65(2):49-56.

[2] Weitlauf AS. et al. Brief Report: DSM-5 “Levels of Support:” A Comment on Discrepant Conceptualizations of Severity in ASD. Journal of autism and developmental disorders. 2014;44(2):471-476.

[3] Kim YS. et al. A comparison of DSM-IV pervasive developmental disorder and DSM-5 autism spectrum disorder prevalence in an epidemiologic sample. J Am Acad Child Adolesc Psychiatry. 2014 May;53(5):500-8.

[4] Burns CO. & Matson JL. An evaluation of the clinical application of the DSM-5 for the diagnosis of Autism Spectrum Disorder. Expert Rev Neurother. 2017 Jul 5.


Saturday, 22 July 2017

"medical disorders in children with ASD and ADHD appear to be widespread"

The quote titling this brief post is taken from the results of the systematic review undertaken by Jet Muskens and colleagues [1] (open-access) who surveyed the peer-reviewed science literature "on medical comorbidity in the two major developmental disorders autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD)."

Continuing an important theme (see here), the authors concluded that various categories of conditions - "immunology, neurology and gastroenterology" - are over-represented in relation to autism and ADHD and that "future studies should not only focus on psychiatric symptoms, but provide a broader evaluation of medical disorders" when it comes to those labels.

Minus too much chatter, I was impressed to see that many of the research articles covered on this blog down the years had made it into the Muskens review. So, the likes of Harumi Jyonouchi gets a well-deserved mention (see here and see here) and the focus on how the immune system might be doing so much more than just protecting us from the odd pathogen or two. The authors also bring in some of the very convincing scientific evidence that various gastrointestinal (GI) issues are over-represented in relation to autism (see here). There's even mention of how useful that Taiwanese research database has been down the years to autism and ADHD research (see here).

What's more to say? Well, preferential screening for various medical conditions in the context of an autism diagnosis yet again, receives more support. As does the idea that when a medical diagnosis is received by a person diagnosed on the autism spectrum, that medical diagnosis deserves the same healthcare management and/or treatment as it does in the context of not-autism save any further health inequalities potentially appearing (see here). The days for example of 'blaming autism' for every single physical complaint are also to be consigned to the historical dustbin. And with it, recognition that concepts such as ESSENCE or 'autism plus' (see here and see here) really need to include the somatic as well as the behavioural/psychiatric...

Whilst welcoming the Muskens review, it's important to note that others have already 'primed' for the importance of medical comorbidity in relation to a diagnosis of autism...


[1] Muskens JB. et al. Medical comorbidities in children and adolescents with autism spectrum disorders and attention deficit hyperactivity disorders: a systematic review. European Child & Adolescent Psychiatry. 2017. July 3.


Friday, 21 July 2017

Antidepressants during pregnancy and autism in offspring (with care)

There are a few topic areas in the quite vast autism research landscape that consistently seem to keep cropping up. The possibility of some kind of *association* between pregnancy antidepressant use and risk of offspring autism is one of those areas (see here) as the results published by Dheeraj Rai and colleagues [1] (open-access) are presented for your attention. I would also draw your attention to an accompanying editorial discussing the Rai findings (see here).

So: "To help to improve the understanding of the association between antidepressant use during pregnancy and autism in offspring, we applied a range of... causal analytical methods on data from a large total population cohort in Stockholm County" was the starting point, as once again one of those very useful Scandinavian registries provided the source study material (indeed, Rai et al are seemingly experts in their analysis of such resources). The added bonus to the Rai study was their attempt to 'unravel' any association between gestational antidepressant exposure and autism from the reason why such medication was being taken in the first place: maternal psychiatric health issues (and whether this variable may in fact account, at least in part, for any association that has previously been identified).

From a starting population approaching three-quarters of a million people, researchers eventually settled on looking at over 250,000 children under 17 years of age (but over 4 years of age "in whom a diagnosis of autism might be less reliable") who were born to over 150,000 mothers. The vast majority of children (239,943 of 254,610) had no history of exposure to antidepressants during pregnancy. The remaining participants were divided up into two groups: one where there was documentation leading to the assumption of exposure to pregnancy antidepressants (n=3342) and one where there was an indication for such exposure ("mothers with a psychiatric disorder") but no recorded use of antidepressants during pregnancy (n=12,325). Researchers summed up how many children were diagnosed with an autism spectrum disorder (ASD) in each group and applied some statistical modelling.

Results: I think it's important to first highlight a statistic that seems to have been missed by many covering the Rai findings: "Of the 238 943 cohort children for whom there was no record of maternal history of psychiatric disorder or antidepressant use during pregnancy, 4889 had autism (2.1%)." That's 2.1% with a diagnosis of autism or ASD; quite a far cry from the 1% [estimate] statistic from just a few years back (at least here in Blighty).

Then: "Exposure to antidepressants during pregnancy was associated with a higher odds of a diagnosis of autism in offspring than exposure to a maternal psychiatric disorder without antidepressants." The authors caution that: "the absolute risk was small, and 4.1% of children exposed to antidepressants in utero had autism compared with 2.9% of those with a maternal history of psychiatric disorder." Further when looking at those children diagnosed with ASD in the groups, authors observed that "autism without intellectual disability" seemed to be over-represented; something also picked up in previous findings from authors on this current paper [2].

Alongside various opinions on these findings (see here for example), the authors caution about the possible meaning of their results. One obviously has to be quite careful when discussing such data to ensure that an important class of medicines is not unduly vilified. No medicine is however without potential side-effects and appropriate clinical decisions and good medicines management [2] is key, particularly when pregnancy is included as variable. The authors talk, for example, about how "if a causal link were robustly established, and if no pregnant women took antidepressants during pregnancy, only 2% of autism cases in this population would be prevented." Alongside they [importantly] mention that antidepressant use during pregnancy is not typically just a 'choice' but rather being clinically indicated: depression does not simply disappear when a woman is pregnant. Interestingly too, they mention about how their data "suggest that there is an increased background risk of autism in children of women with psychiatric conditions, regardless of antidepressant treatment." This follows a trend in other areas of psychiatry (see here for example).

Yet again, the call is further research in this area and, quite a few more investigations into the possible hows-and-whys of any association (with medication use and/or maternal psychiatric presentation) is made. I might also suggest that taking into account other childhood conditions such as attention-deficit hyperactivity disorder (ADHD), potentially over-represented when it comes to a diagnosis of autism or ASD, could be another important step forward in light of other preliminary *associations* being made with pregnancy medication history in mind (see here). This also includes looking at any issues associated with timing of potential exposure and/or dose ("Because of small numbers, we were not able to assess trimester specific or dose response effects.").

Insofar as the suggestion that autism without intellectual (learning) disability might be an important phenotype when it comes to any association, subsequent research in this area seemingly fits in well with increasingly vocal calls [4] to stop using the generic label of autism as a research starting point (see here). Allied to suggestions for more 'bottom-up' research with autism in mind (see here), also coincidentally mentioning "maternal SSRI use during pregnancy" in the context of autism [5], a future research agenda is seemingly emerging. I might also point out that certain sensitivities need to be kept in mind on the basis of suggestions that an 'environmental exposure' might, in whole or part, be *associated* with a particular type(s) of autism.

All such work - present and future - however needs to be done/presented with care, understanding and minus scaremongering, so as not to unduly alarm pregnant mothers, their families or indeed, the physicians providing their care at such a critical time...


[1] Rai D. et al. Antidepressants during pregnancy and autism in offspring: population based cohort study. BMJ. 2017; 358: j2811.

[2] Rai D. et al. Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study. BMJ. 2013 Apr 19;346:f2059.

[3] Angelotta C. & Wisner KL. Treating Depression during Pregnancy: Are We Asking the Right Questions? Birth Defects Res. 2017 Jul 17;109(12):879-887.

[4] Waterhouse L. et al. The ASD diagnosis has blocked the discovery of valid biological variation in neurodevelopmental social impairment. Autism Res. 2017 Jul;10(7):1182.

[5] Unwin LM. et al. A "bottom-up" approach to aetiological research in autism spectrum disorders. Front Hum Neurosci. 2013 Sep 19;7:606.


Thursday, 20 July 2017

Is gluten avoidance linked to a lower risk for depression?

I've talked a few times on this blog about how avoiding dietary gluten both within (see here) and outside of (see here) the context of coeliac (celiac) disease, the archetypal 'gluten is baddie' autoimmune condition, might have some pretty interesting effects on some aspects of a person's psychology. Today's post reflects yet more peer-reviewed science suggesting that there may indeed be something to see in this potentially important area; particularly pertinent to the presentation of depression or depressive symptoms.

So, the findings reported by Haley Zylberberg and colleagues [1] based on data from some 22,000 participants taking part in the US 2009-2014 National Health and Nutrition Examination Survey are the source material today. Some background material related to this cohort can be found here. They specifically looked at the "prevalence of depression, insomnia, quality-of-life variables, and psychotropic medication use in CD [coeliac disease] participants and PWAGs [people who avoid gluten] to controls." People who avoid gluten - PWAG - represent a group who don't have a diagnosis of CD but nonetheless similar to those who were diagnosed with CD, reported avoiding dietary gluten.

Results: "Depression was present in 8.2% of controls compared with 3.9% of participants with CD... and 2.9% of PWAGs." Even after adjustment for various confounding variables ("age, sex, race, income, and access to healthcare") those gluten avoiders (without CD) less frequently presented with depression compared with data from controls.

Added to the previous occasions where gluten consumption seems either to be linked to [some] depression or removal of gluten seems to positively impact on depressive symptoms at least for some, this is interesting work. Yes, quite a few more controlled trials are required to examine such relationships between food and mood. Although we can speculate on possible mechanisms [2] we don't really know why there may be an effect from gluten removal, but this is an emerging area of science; particularly in the context of how disruptive/disabling/damaging depression can be to someone.

Bearing in mind the caveats of this blog - no medical or clinical advice is given or intended - please don't assume that I'm advocating gluten removal for anything (unless clinically indicated) on the basis of this or other posts. If in doubt, consult your medical physician.


[1] Zylberberg HM. et al. Depression and insomnia among individuals with celiac disease or on a gluten-free diet in the USA: results from a national survey. Eur J Gastroenterol Hepatol. 2017 Jun 27.

[2] Pruimboom L. & de Punder K. The opioid effects of gluten exorphins: asymptomatic celiac disease. J Health Popul Nutr. 2015 Nov 24;33:24.


Wednesday, 19 July 2017

"Medical history was associated with increased risk of CFS/ME"

The paper by Berit Feiring and colleagues [1] (open-access) is the source blogging material today covering an area that I was previously unaware of: "to study the association between HPV [human papillomavirus] vaccination and risk of CFS/ME [chronic fatigue syndrome/myalgic encephalomyelitis] among girls eligible for HPV vaccination in the national immunisation programme in Norway."

A quick trawl of PubMed to look-see whether there was any previous peer-reviewed science in this area revealed some inklings about a possible *association* between use of the HPV vaccine and some symptoms that may follow a diagnosis of ME/CFS [2] but not much to say that risk of an actual diagnosis of CFS/ME was significantly heightened [3] following HPV immunisation. On the topic of postural tachycardia syndrome (PoTS) and HPV vaccination, I had been aware of some, limited peer-reviewed discussions (see here).

As it happens, Feiring et al did not observe any population-wide links between HPV vaccination and increased risk of CFS/ME based on their analysis of "176,453 girls born 1997–2002 [who] were eligible for HPV vaccination." They tempered their conclusions slightly given that they "did not have access to patient records for verification of the CFS/ME diagnoses" derived from the Norwegian Patient Registry (NPR) but for all intents and purposes, their data is compelling based on sample size and how well Scandinavian countries tend to treat their population data.

A few other, rather interesting aspects to the Feiring data are also apparent: "we observed an increase in the incidence of CFS/ME among adolescents aged 10–17 in Norway, during 2009–2014" and: "Medical history was associated with both increased risk of CFS/ME and lower uptake of HPV vaccine." The idea that numbers of cases of CFS/ME is on the up in Norway is an interesting one and perhaps contrasts with other data from here in Blighty for example (see here) bearing in mind the age groups analysed. I was however specifically drawn to the idea that: "The risk of CFS/ME increased with increasing number of previous hospital contacts."

Looking at hazard ratios (HRs) for a diagnosis of CFS/ME based on how many times a girl had had hospital contact, a rather interesting dose-dependent pattern emerged. So, examining the entire follow-up period, the (adjusted) HR for CFS/ME diagnosis for those with only one hospital contact was 1.64 (1.22–2.19). For those with seven or more hospital contacts, the HR jumped to 5.23 (3.66–7.49). Also potentially important were the possible reason(s) for hospital contact and risk of CFS/ME: "According to ICD-10 diagnoses, the highest risk of CFS/ME was found among girls with diagnoses in chapters I00-I99 (Diseases of the circulatory system)..., A00-B99 (Certain infectious and parasitic diseases)... and R00-R99 (Symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified)."

Other discussions on data also from Norway (indeed, from some of the same authors) has talked about medical history around CFS/ME and what conditions seem to be 'over-represented' (see here). On that research occasion [3] they concluded that: "Children with CFS/ME were frequently diagnosed with infections, supporting the hypothesis that infections may be involved in the causal pathway." Said previous findings are not so dissimilar from the current ones reported by Feiring and colleagues.

Insofar as the next steps on from the Feiring data, well one might - assuming independent replication and the like - see a way forward where a potential early warning system for possible CFS/ME screening might be put in place on the basis of patterns of hospital visits and the types/patterns of diagnosis that are given. I appreciate that there is quite a lot of heterogeneity when it comes to CFS/ME (possibly even another label ripe for pluralisation or spectrum-ing?) so I don't want to get too ahead of myself here but there is potential. Whilst HPV vaccination did not seem to be connected to later CFS/ME diagnosis in the Feiring cohort, the question about what factors could be driving the increase in cases remains open: "The reasons for the increase in CFS/ME in Norway are unknown."


[1] Feiring B. et al. HPV vaccination and risk of chronic fatigue syndrome/myalgic encephalomyelitis: A nationwide register-based study from Norway. Vaccine. 2017. June 23.

[2] Brinth LS. et al. Orthostatic intolerance and postural tachycardia syndrome as suspected adverse effects of vaccination against human papilloma virus. Vaccine. 2015 May 21;33(22):2602-5.

[3] Donegan K. et al. Bivalent human papillomavirus vaccine and the risk of fatigue syndromes in girls in the UK. Vaccine. 2013 Oct 9;31(43):4961-7.

[4] Bakken IJ. et al. Comorbidities treated in primary care in children with chronic fatigue syndrome / myalgic encephalomyelitis: A nationwide registry linkage study from Norway. BMC Family Practice. 2016; 17: 128.


Tuesday, 18 July 2017

Anxiety disorder is rife in 'high-functioning' autism

"Lifetime prevalence rates of 53.5% for depressive disorder 73.5% for anxiety disorders and 37.5% for ADHD [attention-deficit hyperactivity disorder] were found."

Those were the figures arrived at by Alexandru Gaman and colleagues [1] who set about investigating the "prevalence rates of psychiatric co-morbidities" among other things in a cohort of over a hundred adults diagnosed with "high-functioning" autism via the quite recently revised DSM-5 criteria. I've stressed the words 'high-functioning' to denote this being the authors' words not mine (personally, I'm not so sure that general level of functioning is all that good as a descriptor).

Various other observations were made by authors such as the finding that: "Subjects with psychotic co-morbid symptoms had a more severe social deficit" which might tap into some other discussions being had on how some of the screening instruments talked about with autism in mind are seemingly not adverse from potentially picking up other labels with a psychosis element to them (see here). I say that also with the understanding that at least for some, autism and psychosis are not diagnostically unstrange bedfellows (see here).

I've zoomed in on the anxiety disorder(s) bit to the Gaman findings because of their very high lifetime prevalence and because, day-to-day, anxiety disorders can be absolutely disabling for many people on the autism spectrum (see here). Indeed, with all the very positive talk about things like employment and further education opportunities [slowly] increasing for autistic young people and adults, one of the details that does not seem to be talked about as much is how issues like anxiety can significantly hinder not only efforts to get a job/student place but also keeping that job/student place in the longer term (see here). Talent is being outshone by crushing anxiety in some cases.

Gaman and colleagues concluded by talking about how identification of something like anxiety disorder is "a crucial clinical issue." I would very definitely agree with this viewpoint but more than that, efforts now need to go into what can be done about treating/managing such anxiety to make people's lives easier (see here); accepting that we still have some distance to go in this process [2]. I'd also like to see some kind of research parity being arrived at specifically with regards to the question: how prevalent and what effects does anxiety have for those NOT described as having 'high-functioning' autism?

To close, having recently been party to some interesting debate on social media about the ins-and-outs, rights-and-wrongs and positives-and-negatives of [exclusive] self-diagnosis with autism in mind, I'd like to link to a paper by Ashwood and colleagues [3] on how one of the premier 'are you autistic?' self-report schedules is not necessarily fit for purpose when it comes to a self-diagnosis of autism. Indeed pertinent to today's post, how "generalized anxiety disorder may ‘mimic’ ASD [autism spectrum disorder] and inflate AQ [Autism-Spectrum Quotient] scores, leading to false positives" echos a viewpoint that I championed: identity, emotions and politics aside, there is no substitute for a thorough professional assessment when autism is suspected. Outside of such an assessment being potentially pertinent to the idea that autism rarely appears in some sort of diagnostic vacuum (see here), it is perhaps even more important as the DSM-5 criteria for ASD and SCD [social (pragmatic) communication disorder] start to become even more mainstream and what it means/will mean to the concept of autistic identity too...


[1] Gaman A. et al. Psychiatric co-morbidities in a French cohort of adults with high-functioning autism (HFA). European Psychiatry. 2017; 41: S136.

[2] Lorenc T. et al. Support for adults with autism spectrum disorder without intellectual impairment: Systematic review. Autism. 2017 Jun 1:1362361317698939.

[3] Ashwood KL. et al. Predicting the diagnosis of autism in adults using the Autism-Spectrum Quotient (AQ) questionnaire. Psychological Medicine. 2016;46(12):2595-2604.


Monday, 17 July 2017

Second seizure risk and "idiopathic autism"

Idiopathic autism refers to instances where autism is the primary diagnosis and not something secondary to another - usually genetic - condition. The paper by Asad Qadir and colleagues [1] reviewed the files of some 150 people diagnosed with an autism spectrum disorder (ASD), idiopathic ASD, and a history of at least one seizure in connection to an important issue: recurrence risk of seizure. They concluded that the average age of first seizure in their cohort was around about 7 years old and many, over 90% of participants included for review, were at serious risk of a second seizure on average just over 6 months later.

This is an important finding. We already know that epilepsy and seizure disorder(s) are not uncommon bedfellows to parts of the autism spectrum (see here) (indeed, many parts of the autism spectrum seem to be prone to unusual EEG - electroencephalographic or electroencephalogram - findings). We know that non-febrile seizures (seizures not attached to fever) are quite a bit more common in relation to autism when compared with non-autistic siblings for example (see here). And on top of all that, we know that seizures can in some instances be life-threatening (see here).

The Qadir data highlights the "short time to second seizure" as a window to appropriate management of seizure when coincidental to autism. The data suggest that even after one seemingly isolated incidence of seizure, clinicians might consider being proactive in (i) screening for signs of EEG anomalies for example, and (b) be pretty assured that initiation of appropriate treatment/management of seizure is very likely applicable insofar as the risk of recurrence in those diagnosed with an ASD. I say all that with my blogging caveat of no medical or clinical advice given or intended, in full working order.

I'd also like to think that as our knowledge about the autism spectrum increases, in particular the idea that there may be many different routes to many different types of autism (see here) so science will start to put some further flesh on the bones that what we call idiopathic autism with epilepsy at the moment, does not necessarily mean things will stay 'idiopathic' in future times. Then, other questions need answering, such as whether certain 'epileptic encephalopathy syndromes' might actually be the cause of some autism [2]...

As I've said many times before on this blog, don't mess with seizures and/or epilepsy...


[1] Qadir AA. et al. Risk of Second Seizure in Pediatric Patients With Idiopathic Autism. J Child Neurol. 2017 Jan 1:883073817713906.

[2] Srivastava S. & Sahin M. Autism spectrum disorder and epileptic encephalopathy: common causes, many questions. J Neurodev Disord. 2017 Jun 23;9:23.