What's potentially behind self-injury coincidental to autism?

"Alexithymia, depression, anxiety and sensory differences may place some autistic individuals at especial risk of self-injury."

Those were some of the conclusions reached in the paper published by Rachel Moseley and colleagues [1] (open-access) following their investigation of an important topic - non-suicidal self-injury (NSSI) - in relation to autism "without intellectual disability." Self-injurious behaviour (SIB) is not a pleasant topic to talk about, but is important to quite a few people diagnosed as being on the autism spectrum (see here and see here).

Drawing on data provided by over one hundred adults with autism (autistic adults if you prefer), half of whom were categorised as 'current self-harmers', a quarter of whom were 'historic self-harmers' and a quarter of whom were 'non self-harmers', researchers set to work "to examine alexithymia, mentalising impairments, autistic traits and sensory differences" as possible important variables for NSSI. Alexithymia by the way, is described as "the subclinical inability to identify and describe emotions in the self." Researchers utilised several different questionnaires including a tool specifically designed to test for NSSI: The Non-Suicidal Self-Injury Assessment Tool (NSSI-AT), a "comprehensive instrument [that] documents the nature and bodily location of any self-injurious behaviours; their functional utility; their recency, frequency and likelihood of reoccurrence; the age of onset of self-injury; the severity of injuries" among other things. Results were collated and analysed.

Alongside the headline finding that was included in the opening sentence to this post, other interesting details also emerged from the data. So: "Of the 76 current and historic self-harmers, 60 could recall the onset of self-injury at an average age of 15.1 years." Bearing in mind that 15.1 years was an average age of onset, such a finding potentially provides a developmental window when self-harming could maybe be screened for and interventions put in place. Indeed, from what I understand, this is a fairly typical time of onset for self-injury in the general population minus any sweeping generalisations.

Also: "The most common function of NSSI was the regulation of low-energy affective states (depression, dissociation), followed by the regulation of high-energy states such as anger and anxiety." There's an important word in that last sentence - regulation - that needs a lot more inquiry. It implies that self-injury is not just mindless violence against self but might actually serve some sort of purpose. Indeed, other recent papers have also mentioned regulation in the context of self-injury [2] too. Allied to other research suggesting that 'challenging behvaiours' might for example, under some circumstances, also serve a purpose (see here) and how self-injury could present in a variety of ways (see here), and there are leads to follow. Indeed, it could imply that teaching regulatory processes such as those linked to exercise (see here) or the use of meditative techniques (see here) could be worthwhile for some at least.

And just before I leave this topic, I'm minded to bring in another issue that could be investigated in the context of self-injury: interoception and body awareness in the context of autism (see here). Minus any psychobabble, interoception represents "the sense of the physiological condition of the body." It strikes me as possible that a reduced capacity for interoception in relation to autism, as has been talked about in other independent study [3], could be another important variable in the cycle of self-injury and another point of intervention...

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[1] Moseley RL. et al. A ‘choice’, an ‘addiction’, a way ‘out of the lost’: exploring self-injury in autistic people without intellectual disability. Molecular Autism. 2019; 10: 18.

[2] Weiner L. et al. A case study of suicidality presenting as a restricted interest in autism spectrum disorder. BMC Psychiatry. 2019; 19: 126.

[3] Fiene L. & Brownlow C. Investigating interoception and body awareness in adults with and without autism spectrum disorder. Autism Res. 2015 Dec;8(6):709-16.

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"to [try and] advance the understanding of potential mechanisms underlying insomnia in adults with ASD"

The paper by Vanessa Hohn and colleagues [1] (open-access available here) provides the blogging fodder today and their findings in relation to the presence of insomnia as a "common source of distress in adults with autism spectrum disorder (ASD)."

Insomnia is essentially a regular problem in getting to sleep. It has a myriad of 'causes' ranging from uncomfortable sleeping conditions (bed, noise, temperature) to the influence of things like stress, depression and anxiety. Insomnia is no joke. Outside of the potential wide-ranging effects on physical and mental health [2] it puts a person at some heightened risk of all-manner of adverse outcomes [3].

As part of a suite of sleeping-related problems, insomnia is also no stranger to diagnostic labels like autism. With autism in mind, sleep problems that begin in childhood are pretty likely to carry over to adulthood. Nobody knows the precise reason(s) why those on the autism spectrum are more likely to experience sleep problems including insomnia. Some have speculated that the presence of autistic traits may be a risk factor for such sleeping issues (see here) but there is currently little detail regarding the bridge from core autism features to sleep problems. Others have observed an *association* between the presence of other somatic issues occurring alongside autism and sleep problems (see here and see here) but again, further clarity is needed on the hows-and-whys of any relationship and, importantly, what can be done to alleviate such issues.

Hohn et al started with the premise that: "Two characteristics of ASD could be relevant to insomnia complaints by hampering the entrainment of a circadian sleep-wake rhythm." They specifically talk about examining the link between sensory responsiveness and social skills in the context of insomnia in adults with ASD.

"Data were obtained from the Netherlands Autism Register (NAR), which is a longitudinal register including approximately 2000 individuals with ASD." Some 630 participants with autism were included for study, where "individual responses given to three measures of interest during an online survey in 2015 were analyzed." Those 'measures' were the Insomnia Severity Index (ISI), the Sensory Perception Quotient and the Autism Spectrum Quotient-28. The combined data were analysed.

Results: bearing in mind that this was a study exclusively including self-report from participants with autism - with no non-autistic control group - and one that relied on a single temporal snapshot of insomnia symptoms, one has to be a little careful with the findings. So: "The mean ISI score in the present sample was 9.50 (SD = 6.01), which is indicative of subthreshold insomnia and higher than means reported for the general population ranging between 1 and 7... but lower than values obtained from insomnia patients ranging between 17 and 20." Further, about half of participants scored in the "absence of insomnia" category with only around 20% of the group recording either moderate or severe insomnia. This tells us that, again according to self-report (and not using actigraphy for example), insomnia was not necessarily a widespread issue in this cohort but present in a not-significant number: about 1 in 5 people.

Next: "Primary analyses revealed that each of the covariates had a significant impact on the ISI total score." What this means is that biological sex, gender and medication use potentially played a role in insomnia. Women participating in the study tended to score higher on the ISI than men, and those aged 45-65 also seemingly showed more of a tendency towards insomnia. I don't think anyone would be really surprised with the idea that age and insomnia might be connected [4].

Some further statistical analysis of their results led researchers to opine on: "positive associations of insomnia severity with general and visual sensory hyper-reactivity and with impairment of social skills." I'm not too au fait with the specifics of the statistical modelling technique used by the authors - hierarchical multiple linear regression analyses (HMLR) - but can see what they did and how they did it, including "controlling for confounding effects of covariates" such as "medication, biological sex, intelligence, and age" (as previously mentioned). That being said, I'll draw your attention to some other conclusions reached by the authors: "The rather small effect sizes reported in the present study suggest that other factors not assessed in this study contribute to the emergence and persistence of sleep problems in adults with ASD."

The Hohn study does add something to the literature on sleep difficulties being experienced by quite a few people (children and adults) on the autism spectrum. I'm not overly convinced that they've stumbled upon evidence that core autistic features such as social skills problems and sensory issues are necessarily central to insomnia in their cohort but am willing to concede that they might play a role. Personally, I'd be inclined to go back to that data on 'comorbid' issues like gastrointestinal (GI) problems (see here) or breathing issues like apnoea (see here) as being something to explore further; also with the assumption that such issues are potentially 'treatable' and could have an important knock-on effect for something like insomnia and other sleep issues with autism in mind...

Oh, and don't forget the molecular handyperson that is melatonin and it's potential role in all of this (see here and see here). That and other potential avenues of research/clinical interest (see here)...

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[1] Hohn VD. et al. Insomnia Severity in Adults with Autism Spectrum Disorder is Associated with sensory Hyper-Reactivity and Social Skill Impairment. J Autism Dev Disord. 2019 Feb 9.

[2] Fernandez-Mendoza J. & Vgontzas AN. Insomnia and its impact on physical and mental health. Curr Psychiatry Rep. 2013;15(12):418.

[3] Garbarino S. et al. Insomnia is associated with road accidents. Further evidence from a study on truck drivers. PLoS One. 2017;12(10):e0187256.

[4] Foley DJ. et al. Sleep complaints among elderly persons: an epidemiologic study of three communities. Sleep. 1995 Jul;18(6):425-32.

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Are early "movement and sensory differences" prodromal signs of autism?

"These results highlight the importance of early surveillance of children who are at elevated risk for ASD [autism spectrum disorder], and early initiatives should focus on early signs of the phenotype, including both movement and sensory differences (prodromal signs) prior to the emergence of diagnostic characteristics."

It was that sentence from the findings reported by Lori-Ann Sacrey and colleagues [1] (open-access available here) that caught my eye, and the idea, once again, that movement 'issues' should perhaps be considered a core feature of autism (see here) or at least more of a core feature than they currently are. I might add that I've covered other important findings from Sacrey et al on this blog previously (see here).

Although open-access, a few details might be useful: "Infants were selected at random to comprise three groups of equal size: (1) 10 non-sibling controls (LR [low risk]-control; 7 boys); (2) 10 HR [high-risk] siblings without an ASD diagnosis (i.e., with an older sibling with ASD but did not receive an ASD diagnosis themselves at 36 months; HR-N; 3 boys); and (3) 10 HR siblings with an ASD diagnosis (i.e., with an older sibling with ASD and also received an ASD diagnosis at 36 months; HR-ASD; 6 boys)." As you can see the participant numbers were fairly small but to balance this, authors did report results based on testing "for differences in reaching-to-grasp" across quite a long period (6-36 months) and utilised quite an array of psychometric testing tools pertinent to their population and study aims.

Researchers found that: "Children who were later diagnosed with ASD showed higher (worse) total scores on the reach-to-grasp movement, as well as higher scores on the components of Orient, Lift, and Pronate compared to children in the LR and HR-N groups." They concluded that: "results suggest that such movement mechanics are relevant to monitoring motor development in children at risk for or diagnosed with ASD." Ergo, there may be quite a bit to see when it comes to early surveillance for autism in respect of movement and/or sensory differences.

Just before you leave I'll also bring the findings reported by Emilia Biffi and colleagues [2] to your attention. Theirs wasn't so much a study of the possible early 'prodromal' signs of autism with a focus on movement patterns but rather another finding suggesting that such movement issues may be persistent in relation to autism and can be readily tested for. Utilising some pretty nifty movement capture technology - "an immersive virtual environment using a 3-D motion analysis system with a dual-belt, instrumented treadmill" - Biffi et al reported that their findings "depicted gait peculiarities in children with ASD, including both kinetic and kinematic features." Movement and gait issues it seems, may very well be a vitally important part of autism...

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[1] Sacrey LR. et al. The reach-to-grasp movement in infants later diagnosed with autism spectrum disorder: a high-risk sibling cohort study. J Neurodev Disord. 2018 Dec 27;10(1):41.

[2] Biffi E. et al. Gait Pattern and Motor Performance During Discrete Gait Perturbation in Children With Autism Spectrum Disorders. Front Psychol. 2018;9:2530.

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Hyperemesis gravidarum exposure as a risk factor for autism?

Hyperemesis gravidarum mentioned in the title of this post refers to "prolonged and severe nausea and vomiting" during pregnancy alongside other symptoms. It's thought to affect only a relatively small percentage of pregnant women despite vomiting and nausea being pretty common throughout many pregnancies. Indeed, hyperemesis gravidarum (HG) is much more than just nausea and vomiting.

The findings reported by Marlena Fejzo and colleagues [1] looked at the "neurodevelopmental outcomes of 267 children delivered by 177 mothers with HG were compared to neurodevelopmental outcomes from 93 children delivered by 60 unaffected mothers." The study was undertaken on the basis that previous published research from this study group [2] had identified "neurodevelopmental delay" as a possible *correlate* tied to HG exposure during pregnancy. That being said, on that last occasion researchers also described finding "no evidence for increased risk of 13 emotional, behavioral, and learning disorders, including autism, intellectual impairment, and obsessive-compulsive disorder" in their cohort.

This time around: "Similar to at age 8, the children (now 12) exposed in utero to HG had over 3-fold increase in odds of neurodevelopmental disorders including attention, anxiety, sensory, sleep difficulty, and social development delay/social anxiety." With a longer follow-up period, researchers also reversed their 'no evidence for increased risk' sentiments with regards to a diagnosis of autism in their cohort. So: "there was also a significant increase in Autism Spectrum Disorder (ASD), reported in 22/267 (8%) of children exposed to HG in utero and no unexposed children."

Let me be clear on this: these latest results on their own don't necessarily mean that HG *causes* offspring autism. Although 8% of the HG exposed group reporting autism or ASD seems quite high, it has to be seen in light of an increasing (estimated) prevalence of autism more generally (see here and see here). I'd also suggest that as with many other pregnancy/gestational factors put forward as potentially influencing offspring autism risk, one needs to be mindful of the issues involved in teasing out which is the important variable from potentially many (see here and see here).

But... further investigation is indicated in this area. Indeed, I hark back to the findings reported by Andrew Whitehouse and colleagues [3] who observed a "strong, positive association between increasing frequency and severity of NVP [nausea and vomiting during pregnancy] and ASD severity in offspring." No, not necessarily HG, but an implication that some of the overt features of HG might hold some *connection* to offspring autism risk for whatever reasons...

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[1] Fejzo M. et al. Analysis of neurodevelopmental delay in children exposed in utero to hyperemesis gravidarum reveals increased reporting of autism spectrum disorder. Reprod Toxicol. 2018 Dec 27. pii: S0890-6238(18)30558-6.

[2] Fejzo MS. et al. Neurodevelopmental delay in children exposed in utero to hyperemesis gravidarum. Eur J Obstet Gynecol Reprod Biol. 2015 Jun;189:79-84.

[3] Whitehouse AJO. et al. Symptom severity in autism spectrum disorder is related to the frequency and severity of nausea and vomiting during pregnancy: a retrospective case-control study. Mol Autism. 2018 Jun 19;9:37.

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"The Importance of Adolescent Self-Report in Autism"

The findings reported by Jessica Keith and colleagues [1] provide the blogging fodder today and a rather important message about the value of self-report in the context of autism, but also with one or two caveats too.

The name of the research game was to investigate the "consistency of adolescent and parent reports of anxiety and auditory sensitivity in individuals with ASD [autism spectrum disorder]" as well as examine "their validity via comparisons with sympathetic arousal at baseline and in response to an auditory challenge." This, on the basis that anxiety is not an uncommon diagnostic bedfellow when it comes to autism (see here for example) and alongside, auditory sensitivity also having quite a long established relationship with some autism (see here).

As per the title of this post taken from the Keith paper - "The Importance of Adolescent Self-Report in Autism" - an important focus of the study was to look-see whether parental reports of anxiety and auditory sensitivity 'matched up' with self-reports from adolescents with autism themselves. Authors reported that they did to a degree, but that also self-report might also provide some greater depth: "demonstrating greater self-reported (than parent-reported) anxiety and sensory symptoms." Indeed authors concluded: "adolescents with ASD have a unique perspective on their internal experience, which can complement parent reports and provide a more comprehensive assessment of symptoms in research and clinical settings."

I don't think anyone should be too surprised that asking adolescents about their own experiences of anxiety, sensory issues or anything else is probably going to yield far more accurate results than proxy reporting or second-hand accounts alone. Indeed, in these days where more and more people diagnosed as being on the autism spectrum are offering up their own first-hand accounts of their experience of autism, this represents a good thing in terms of 'getting it right' when it comes to diagnosing and managing important and often life-affecting symptoms or clinical diagnoses such as anxiety.

Caveats? Well, yes. I'm all in favour of people self-reporting and providing valuable insight into their own experiences. What is slightly less appealing however is that such self-reporting is not a luxury shared by all on the autism spectrum. The lack of self-report coming say, from some under-represented parts of the autism spectrum (see here) can sometimes mean that 'autistic experiences' are skewed towards more 'able' (or should that be 'vocal') parts of the autism spectrum; this despite the oft-used phrase: if you've met one autistic person, you've met one person with autism (or words to that effects). A solution? How about devoting more research and clinical resources to 'enabling' those traditionally not thought to have the capacity for complicated self-report to do so? Indeed, a participatory solution would perhaps be the best step forward I think (see here).

Oh, and also bear in mind that it needn't be self-report versus parent-report when it comes to something like anxiety in the context of autism. Both viewpoints can provide something important [2] on the basis that individuals know themselves but parents also have quite a unique viewpoint of their children and their behaviour across their formative years...

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[1] Keith JM. et al. The Importance of Adolescent Self-Report in Autism Spectrum Disorder: Integration of Questionnaire and Autonomic Measures. J Abnorm Child Psychol. 2018 Aug 2.

[2] Adams D. et al. Parent descriptions of the presentation and management of anxiousness in children on the autism spectrum. Autism. 2018 Aug 16:1362361318794031.

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"ASD characteristics in adulthood are differently perceived across age, sex, and informants"

The research tag-team that is Anne Lever and Hilde Geurts have provided peer-reviewed fodder for this blog before (see here and see here). Without wishing to cajole their research interests into a specific box, quite a bit of their time seems to be taken up by looking at autism in the context of ageing, alongside how the label of autism does not seem to have a monopoly on the presentation of certain autistic traits.

A recent paper published by this team [1] provides yet more blogging material, specifically focused on testing "the association between age and ASD [autism spectrum disorder] characteristics, including empathy and sensory sensitivity, in adults aged 19–79 years." A scientific hat-tip is offered to other research in this area [2] that previously observed that: "older age was associated with higher ratings of ASD traits and better cognitive performance."

Drawing on data derived from a participant group numbering above 400 (N=237 with autism and N=198 without autism) spanning the age ranges, a variety of self-report and informant-report (family members, friends, other significant others) were utilised. I should point out that the autism participant group seemed to be represented by the 'more able' part of the autism spectrum (I don't use the term 'functioning') insofar as most either being diagnosed with Asperger syndrome or PDD-NOS (pervasive developmental disorder - not otherwise specified), being predominantly independent or living with a partner or housemate in residential status terms and also with that reliance on self-report used throughout the study kept in mind. This is worth knowing given other discussions on under-represented groups when it comes to scientific study (see here) and how representative autism research may or may not be to the entire spectrum.

Among the measures included for analysis we have an old favourite - the Autism-Spectrum Quotient (AQ) - as well as the Interpersonal Reactivity Index (IRI) (measuring various aspects of empathy) and the Sensory Sensitivity Questionnaire (SSQ) (examining sensory hyper- or hyposensitivity). Obtained results were collated and subjected to quite a few statistical analyses.

Results: noted as a 'group difference' findings were reported observing that: "Adults with ASD reported higher scores on the SSQ and on all subscales of the AQ than adults without ASD." This is pretty much what would be expected, despite any qualms I might have about what the AQ actually measures (see here for more of them). Sensory issues being reported as being greater in those with a diagnosis of autism also ties in well with their inclusion in the DSM-5 schedule for diagnosing autism or ASD (see here).

Then: "Within the ASD group, age-related differences were observed in self-reported ASD traits and sensory sensitivity, with a peak among middle-aged adults." Alongside that previously 'hat-tipped' study, the authors conclude that "ASD characteristics are more heavily experienced in middle adulthood than in younger or older adults." This is interesting from quite a few perspectives; bearing in mind that such findings say nothing about the expression of autism in childhood and early adulthood. Appreciating that the self-report of autism or sensory traits may not be the same as everyday autism expression, such findings *might* have some relevance to various issues such as the rise and rise of adult autism diagnoses being given and indeed, how a diagnosis of autism for some (a few?) might not be a 'lifelong' issue (see here). I know that last point raises blood pressure in some quarters as words like 'masking' are banded around (with the need for far greater study), but there is good reason to think that like many other conditions/labels, autistic behaviours and/or traits ebb and flow according to environment and perhaps other factors, such as the presentation of comorbidity for example (as per the author's other work [3] already mentioned). In short, the presentation of autism is probably dynamic and fluidic, rather than just a static thing.

Onward: "we replicated earlier findings that females with ASD had more sensory issues and reported more ASD characteristics than males... whereas females without ASD manifested fewer ASD traits than non-ASD males.". Females with ASD (74 females vs. 163 males) 'reported more ASD characteristics than males'? Intriguing - "ASD females reported higher scores than ASD males on the AQ total score" - to say the least in light of other [childhood] findings [4] but not without cautions. I go back once again the question of what the AQ is actually measuring and whether for example, the typically higher rate of mood disorders generally noted in females could be a potential confounder when it comes to AQ scores in the context of that previous reference [3] from the authors. This area requires further investigation.

Finally: "Overall, the current results show poor to fair agreement between self- and other-reports of well-known proxies, even though the agreement of the overall group was similar to those previously reported for social responsiveness." Again, some potentially important lessons to be learned here insofar as the 'meaning of autism' to a person and those around them. Indeed I note the authors' offer one explanation: "the self may be more accurate about traits that describe unobservable thoughts and feelings due to privileged access (e.g. feelings of empathy and sensory sensitivity), whereas an informant would be more accurate about observable behavior (e.g., ASD traits)." Again, jumping back into 'hot potato' territory, such a finding may have implications for the whole 'self-diagnosed vs. formal diagnosis' debate that still continues at a pace (see here).

There is quite a bit more to take in from this latest paper from Lever & Geurts and definitely some food for thought. I'll leave you however with one final quote from the authors that is perhaps one of the more important take-away points from their study: "it is important to repeatedly assess self-reported ASD characteristics during adulthood." Who would argue with that in terms of getting wants, wishes, needs and requirements accurate and up-to-date?

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[1] Lever AG. & Geurts HM. Is Older Age Associated with Higher Self- and Other-Rated ASD Characteristics? Journal of Autism & Developmental Disorders. 2018. Jan 18.

[2] Happé FG. et al. Demographic and Cognitive Profile of Individuals Seeking a Diagnosis of Autism Spectrum Disorder in Adulthood. J Autism Dev Disord. 2016 Nov;46(11):3469-3480.

[3] Geurts HM. et al. Autism Characteristics in Older Adults with Depressive Disorders. The American Journal of Geriatric Psychiatry. 2016; 24: 164-169.

[4] Øien RA. et al. Sex-Differences in Children Referred for Assessment: An Exploratory Analysis of the Autism Mental Status Exam (AMSE). J Autism Dev Disord. 2018. Feb 8.

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Food neophobia and autistic traits (or at least AQ defined autistic traits)

I was rather interested in the findings reported by Lorenzo Stafford and colleagues [1] suggesting "a positive association between food neophobia and the magnitude of autistic traits." Food neophobia is a fear of eating new or unfamiliar foods, and is something that most parents will have encountered at some point in their child/children's lives. With autism in mind, this type of issue is seemingly not uncommon in amongst various other food-related symptoms that can also be present.

Looking at the "broader aspects of autistic traits" and specifically whether a non-autistic (not diagnosed with autism) population showed any connection between their scores on the Autism Spectrum Quotient (AQ) and their scores on the Food Neophobia Scale (FNS), authors set about their study. They also examined whether olfactory sensitivity - "an olfactory threshold test for a food related odour" - might also show an effect in any relationship.

As per the opening paragraph to this entry, authors reported something of a relationship between AQ scores and FNS scores. Importantly, olfactory sensitivity did not seem to link in with AQ scores, suggesting that the link with food neophobia was not necessarily because of enhanced food odour perception for example. At least in this cohort.

This is potentially important work. Bearing in mind the quite small participant group (N=50), the reliance on "student participants" (not always the most representative of groups) as a non-clinical group and the assumption that AQ is actually measuring just the traits of autism (see here), the findings carry some interest. If there is indeed a connection between autistic traits and food neophobia, one could quite sensibly ask whether intervention(s) to ameliorate or reduce certain autistic traits might have some important knock-on effects for aspects of problematic food-related behaviours in relation to autism. Y'know, similar to the idea offered by other independent studies suggesting for example, that anxiety in the context of autism might be influenced by core traits (such as RRBs [restricted and repetitive behaviours]) and the implications thereof. Further investigations are implied.

And for those who might not fully understand just what food-related issues can mean in the context of autism...

Music to close: Harder, Better, Faster, Stronger.

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[1] Stafford KD. et al. Autistic traits associated with food neophobia but not olfactory sensitivity. Appetite. 2017. June 3.

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Sensory issues in adult ADHD controlling for autistic symptoms...

I was intrigued to read the paper by Bijlenga and colleagues [1] reporting on "the prevalence of sensory hyper- and hyposensitivity among adults with ADHD [attention-deficit hyperactivity disorder], controlling for autistic symptoms."

The authors concluded that among their cohort of over 100 adults diagnosed with ADHD, both sensory hyper- and hyposensitivity symptoms as described by response to the Adolescent/Adult Sensory Profile-NL (AASP-NL), were over-represented compared with population norm data. Interestingly, authors also took a snapshot of 'autistic symptoms' based on responses to the Autism-spectrum Quotient (AQ) and reported that: "Adults with ADHD had more autistic symptoms" but: "Sensory hypo- and hypersensitivity were both related to an increased ADHD score, even showing a dose-response relationship, but not to any autistic symptom or comorbid disorder."

My intrigue stems from a few implications of such findings, with the requirement for much more study. First is the quite important overlap between autism and ADHD (see here) confirmed symptom-wise in the Bijlenga paper. Second is the idea that, within this cohort at least, adults with ADHD may variably present with sensory issues. Third, assuming that the AQ 'does what it says on the tin' with regards to screening for autistic symptoms (see here), the lack of a notable connection between autistic symptoms and sensory sensitivities in the context of adult ADHD might have some important implications related to my first point when autism and ADHD appear simultaneously. Indeed it poses the question: are sensory issues, now noted in specific relation to autism via at least one diagnostic schedule (see here) actually 'a core part of all autism' or perhaps a feature of something else for some?

Reiterating that more research is required (not least more formal screening for autism over and above the use of AQ or related screening schedules) that last point/question might actually make more sense than many people might first realise. If, for example, we take the view that autism rarely exists in some sort of diagnostic vacuum (see here and see here) and that science and clinical practice really needs to be more proactive when it comes to an autism diagnosis being a starting point not the finishing line (see here), it's not beyond the realms of possibility that sensory issues for some might have been spuriously linked to autism when in fact other comorbid labels/symptoms better account for their presentation. This not only has implications for screening/diagnosis but also management of said sensory symptoms, as per other reports talking about the use of stimulant medication indicated for ADHD 'affecting' aspects of odour sensitivities for example [2]. By saying that I'm not making any sweeping judgements about pharmacotherapy for ADHD treating sensory issues present alongside autism, merely that new avenues might open up.

A final quick glance at some of the other peer-reviewed literature on the topic of sensory issues and ADHD reveals that there is some history in this area [3]. Said sensory issues have also been *linked* to some of the other behavioural facets noted in cases of ADHD [4]. Perhaps, in light of such data, it is time for ADHD - whether in symptoms or in label - to be taken into account when sensory issues are discussed in the context of autism in the science literature and in clinical practice?

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[1] Bijlenga D. et al. Atypical sensory profiles as core features of adult ADHD, irrespective of autistic symptoms. Eur Psychiatry. 2017 Feb 21;43:51-57.

[2] Romanos M. et al. Improved odor sensitivity in attention-deficit/hyperactivity disorder. Biol Psychiatry. 2008 Dec 1;64(11):938-40.

[3] Clince M. et al. Comparing and Exploring the Sensory Processing Patterns of Higher Education Students With Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder. Am J Occup Ther. 2016 Mar-Apr;70(2):7002250010p1-9.

[4] Shimizu VT. et al. Sensory processing abilities of children with ADHD. Braz J Phys Ther. 2014 Jul-Aug;18(4):343-52.

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Bijlenga D, Tjon-Ka-Jie JY, Schuijers F, & Kooij JJ (2017). Atypical sensory profiles as core features of adult ADHD, irrespective of autistic symptoms. European psychiatry : the journal of the Association of European Psychiatrists, 43, 51-57 PMID: 28371743

Sensory subtypes and anxiety and autism

"This is the first study to identify the existence of sensory subtypes among older children and adolescents with ASD [autism spectrum disorder] and explore their association with anxiety levels."

Far be it from me to question the above quote provided in the paper by Mirko Uljarević and colleagues [1] but I'm inclined to suggest that there has already been some research published on the link between sensory issues and anxiety in the context of the autism spectrum before (see here and see here). Indeed, I do wonder whether the assertions put forward by Mazurek and colleagues [2] on how gastrointestinal (GI) issues (yes, they are over-represented) might be an important part of any sensory/anxiety mix in autism could be something that is further looked at by Uljarević in their cohort?

Anyhow, the Uljarević paper is an interesting one given the idea that within the vast heterogeneity that is autism (or even the autisms) sensory issues as measured by "the short sensory profile" are not
uniform in their presentation (a shocker, I know). The finding that anxiety scores, as measured by the Spence anxiety scales, were potentially a little different according to sensory subtype (sensory adaptive, sensory moderate, sensory severe) particularly when it came to the sensory adaptive grouping - "Children and adolescents from the adaptive subtype had significantly lower anxiety scores when compared with other two subtypes" - is important. The implication being that with various other variables not differing (chronological age, expressive language, or severity of autism diagnostic features) sensory issues might be one important driver of the presentation of anxiety when it comes to autism.

As I've mentioned quite a few times on this blog, the topic of anxiety and autism is an important one (see here for example). There are a few different 'types' of anxiety (or anxiety diagnoses) that might be more applicable to autism alongside some discussion about how to measure anxiety when it comes to autism (see here). But the primary messages are: (i) anxiety is pretty rife in terms of accompanying a diagnosis of autism and (ii) the effects of anxiety can be absolutely, utterly disabling. Set in this light, if there are things that can be done to overcome anxiety over and above what might be traditionally offered (see here) by for example, 'affecting' those sensory issues, many people potentially stand to benefit.

Next question: how does one go about 'intervening' when sensory issues are present alongside autism? Well, the science is still a little sparse here outside of the odd case report on something like bumetanide showing a potential effect [3] for example. I might draw your attention to some preliminary work on how visual sensory issues might be a target for other interventions (see here) but there is still some way to go in that area too and one needs to be mindful of how ophthalmologic disorder(s) may also contribute (see here). Going back to the Mazurek paper and the 'triad' of sensory issues, anxiety and bowel problems hinted at with at least some autism in mind, one could speculate that treating said bowel issues *might* have further positive effects on sensory and anxiety issues too. Indeed, in the more general context of how anxiety and another important label - depression - may well have a functional bowel issue link (see here), there is plenty of research fodder to draw on hinting at a 'gut-brain' link in some cases. No doubt there are other ways and means to tackle sensory issues as and when they impact on quality of life and by the sounds of other research [4] sensory issues in autism as described by the DSM-5 are going to be pretty widespread.

To close, it's 'Remember, remember the 5th of November, gunpowder, treason and plot..' day here in the UK today. So here's V and his revolutionary chatter again and please, be careful this Bonfire night.

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[1] Uljarević M. et al. Sensory subtypes and anxiety in older children and adolescents with autism spectrum disorder. Autism Res. 2016 Oct;9(10):1073-1078.

[2] Mazurek MO. et al. Anxiety, sensory over-responsivity, and gastrointestinal problems in children with autism spectrum disorders. J Abnorm Child Psychol. 2013 Jan;41(1):165-76.

[3] Grandgeorge M. et al. The effect of bumetanide treatment on the sensory behaviours of a young girl with Asperger syndrome. BMJ Case Rep. 2014 Jan 31;2014. pii: bcr2013202092

[4] Green D. et al. Brief Report: DSM-5 Sensory Behaviours in Children With and Without an Autism Spectrum Disorder. J Autism Dev Disord. 2016 Nov;46(11):3597-3606.

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Uljarević M, Lane A, Kelly A, & Leekam S (2016). Sensory subtypes and anxiety in older children and adolescents with autism spectrum disorder. Autism research : official journal of the International Society for Autism Research, 9 (10), 1073-1078 PMID: 26765165

Sensory processing issues are present throughout the autism spectrum

I want to make an initial point about the paper by Corentin Gonthier and colleagues [1] and their research findings titled: 'Sensory Processing in Low-Functioning Adults with Autism Spectrum Disorder: Distinct Sensory Profiles and Their Relationships with Behavioral Dysfunction', I'm not a great fan of the use of the term 'functioning' when it comes to autism.

Yes, I know what message it's trying to convey in terms of 'severity' of autism and/or accompanying learning (intellectual) disability and/or the level of day-to-day adaptive skills a person possesses with the aim of providing some indication of how 'able' or 'disabled' they are. My issue, and indeed I'm not the only one with a bee in their bonnet about this, are that the terms 'low functioning' and 'high functioning' rarely provide an accurate portrayal of the cumulative aspects of a person. One example of this can be seen in the quite depressing statistics when it comes to employment and autism, and how even those 'high-functioning' people on the spectrum, sometimes with above average intellect, are much less likely to be employed than their peers. High-functioning does not always mean 'can-function' in real life (even those with seemingly impressive skills) and importantly, tends to take little account of how comorbid issues such as anxiety can be so utterly disabling for a person.

I digress. The Gonthier study set about asking an important question about an important group: do the various sensory processing issues quite commonly reported in those on the more able side of the autism spectrum also extend to those peoples with more profound difficulties? Based on data "collected for a representative sample of inpatients in autism care centers (N = 148) and a non-clinical control group" researchers concluded that yes, sensory dysfunction is "highly prevalent in low-functioning adults with ASD [autism spectrum disorder]" but no, there is no 'one-size-fits-all' profile for this population. Indeed, that lack of a universal profile in the cohort studied pretty much mirrors what has been noted in  the 'more able' autism phenotype.

One other detail mentioned in the Gonthier findings also caught my eye in that sensory dysfunction "predicts specific patterns of behavioral disorders" at least in this cohort. This is an intriguing suggestion that potentially amongst the myriad of issues falling under the heading of 'challenging behaviours' for example, there may be a role for sensory processing issues too. It does kinda make sense that sensory issues could invoke some of those so-called challenging behaviours allied to other research looking, for example, at how pain might manifest among some of those on the autism spectrum (see here). It also makes for an even stronger case that screening for the presence of ophthalmic issues as one potential source/complication of those sensory issues should be more widely indicated irrespective of where someone lies on the autism spectrum (see here) (and whatever description you use of their place on the spectrum).

But a lot more research is required on the topic of sensory processing issues, and indeed, covering the entire autism spectrum in line with other writings [2] ...

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[1] Gonthier C. et al. Sensory Processing in Low-Functioning Adults with Autism Spectrum Disorder: Distinct Sensory Profiles and Their Relationships with Behavioral Dysfunction. J Autism Dev Disord. 2016 Jun 30.

[2] Tager-Flusberg H. et al. Conducting research with minimally verbal participants with autism spectrum disorder. Autism. 2016 Jun 26. pii: 1362361316654605.

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Gonthier C, Longuépée L, & Bouvard M (2016). Sensory Processing in Low-Functioning Adults with Autism Spectrum Disorder: Distinct Sensory Profiles and Their Relationships with Behavioral Dysfunction. Journal of autism and developmental disorders PMID: 27364513

Autism: visual stress and coloured overlays?

The small study from Amanda Ludlow & Arnold Wilkins [1] is introduced for your reading pleasure today and the idea that "atypical sensory behaviours and symptoms of visual stress" were not uncommon features when it came to a diagnosis of autism and/or Tourette's syndrome (TS). As per that opening sentence, this was a small study - 12 children with autism, 12 children with TS and 12 controls - but that doesn't mean that the results might not be important...

So far you might be slightly underwhelmed by the idea that sensory issues (and onwards linked behaviours) might be over-represented when it comes to autism given what has already been talked about for quite a few years. But... following the introduction of a colour overlay (a coloured plastic sheet placed over text) supposedly thought to reduce visual stress, for at least for some children with autism there seemed to be some potential effects noted: "Four of the 12 children with ASD [autism spectrum disorder] and none of the control children read over 15% more quickly with an overlay." The test by the way, used to assess reading performance was the Wilkins Rate of Reading Test designed by one of the authors.

I'm interested in these findings. In one of the earliest posts on this blog, I discussed the idea that visual perceptual issues accompanying a diagnosis of autism might, to some extent, be 'countered' via the use of coloured overlays or tinted glasses (sometimes called Irlen lenses) (see here). Alongside a few quite well-known people on the autism spectrum using such visual aids, there is quite an appetite for this type of approach here in Blighty as for example, per the writings and practice of people such as Ian Jordan. Accepting that the plural of anecdote is not data, I've seen Ian talk about his work, and some of the case studies are really rather interesting including the possibility of a link between vision and coordination.

A quick scan of the other peer-reviewed literature in this area suggests that Ludlow & Arnold are no strangers to this potentially important area of autism research although quite a bit more needs to be done with regards to effectiveness and perhaps identify those potential 'best responders' to this type of approach. I might also suggest that said investigations might also benefit from some good old-fashioned ophthalmic inquiry too given what is starting to be understood about eye pathology and autism (see here).

I appreciate that talk of Irlen lenses and coloured overlays may not be everyone's cup of tea in light of the various 'discussions' these interventions have had when it comes to the diagnosis of dyslexia down the years. Yes, science definitely needs to come before any big claims are made or marketed. But the idea that sensory issues might be a rather common occurrence in relation to autism and that vision in particular might be an important source of those sensory issues reported perhaps means that this research avenue should be more thoroughly explored given that there may be something that can be done to alleviate visual stress as and when it does occur.

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[1] Ludlow AK. & Wilkins AJ. Atypical Sensory behaviours in children with Tourette's Syndrome and in children with Autism Spectrum Disorders. Res Dev Disabil. 2016 Jun 7;56:108-116.

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Ludlow AK, & Wilkins AJ (2016). Atypical Sensory behaviours in children with Tourette's Syndrome and in children with Autism Spectrum Disorders. Research in developmental disabilities, 56, 108-116 PMID: 27286465

Measuring anxiety comorbid to autism

Anxiety, whether reaching clinical thresholds or manifesting as something rather more subtle, is a common theme in autism research and practice these days. I've talked about it enough times on this blog (see here and see here for example) reflective of the growth in this peer-reviewed research area that has continued unabated.

Recognition of just how 'disabling' anxiety can be for someone on the autism spectrum is fairly widely noted these days. Problems however, still remain in terms of (i) how we measure anxiety when comorbid to autism and (ii) which strategies are most appropriate to tackle such issues, bearing in mind their wide impact on at least some of the 'autisms' (see here).

The paper by Jacqui Rodgers and colleagues [1] perhaps brings us one step closer to solving the first issue with the introduction of the "Anxiety Scale for Children - ASD, Parent and Child versions (ASC-ASD)." Readers can find out a little more on this scale from an accompanying website (see here).

Describing how existing anxiety measures "may require adaptation to accommodate characteristics of those with ASD [autism spectrum disorder]" the authors set about doing just that. So: "An adapted version of the RCADS [Revised Child Anxiety and Depression Scale] was created based on empirical evidence of anxiety phenomenology in ASD, which included additional items related to sensory anxiety, intolerance of uncertainty, and phobias." After taking into account the modifications suggested "during focus groups with parents" of children with autism among other things, researchers came up with a new 24-item scale with some good statistics in terms of reliability and validity.

There is still quite a way to go in terms of seeing how the ASC-ASD (various versions) copes with the various demands of autism research and practice but I'm kinda hopeful that we might see some productive results coming from its use. Whether anxiety is more or less likely among various groups on the autism spectrum is perhaps one of the first hurdles posed for the instrument in light of other data on another important comorbidity: depression (see here). I might also suggest that examining correlations between anxiety levels and other more somatic features discussed in the context of autism might also provide some important data too (see here). Please, don't get scared by the suggestion that gastrointestinal issues - now quite well-known to be associated with cases of autism (see here) - might be able to affect or be affected by psychology and behaviour...

That also the concept of 'intolerance of uncertainty' (see here) is included in the anxiety 'mix' is an important addition to the ASC-ASD given the rise and rise of this term with autism in mind [2]. The same goes for the focus on 'sensory anxiety' too, which might accord with an element included in the the latest DSM-5 criteria for autism (see here).

We wait to see what becomes of the ASC-ASD with fingers crossed...

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[1] Rodgers J. et al. Development of the anxiety scale for children with autism spectrum disorder (ASC-ASD). Autism Res. 2016 Feb 17.

[2] Hodgson AR. et al. Facing the Unknown: Intolerance of Uncertainty in Children with Autism Spectrum Disorder. J Appl Res Intellect Disabil. 2016 Feb 12.

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Rodgers J, Wigham S, McConachie H, Freeston M, Honey E, & Parr JR (2016). Development of the anxiety scale for children with autism spectrum disorder (ASC-ASD). Autism research : official journal of the International Society for Autism Research PMID: 26887910

Anxiety and sensory over-responsivity linked to gut issues in autism

"The name's Lonnegan! Doyle Lonnegan!"

Consider this micropost an extension of some previous discussions on this blog about how gastrointestinal (GI) issues present in cases of autism might show some connection to the presence of anxiety and sensory issues (see here). Today I'm discussing further research by Micah Mazurek and colleagues [1] which follows a previous publication by this author [2] on this topic.

In the latest paper, Dr Mazurek and colleagues describe the course of abdominal pain in 225 children diagnosed with an autism spectrum disorder (ASD). Of the quarter of participants who presented with "chronic abdominal pain at baseline", the majority (over 80%) still had the same GI issue at 1-year follow-up. Indeed, a further 25% of those who did not present with abdominal pain at the start of the study finished the study with such an issue. The authors conclude: "Abdominal pain appears to be common and persistent among children with ASD". Further, anxiety and sensory over-responsivity also seemed to correlate with bowel features which is probably not unexpected.

Yes, you might indeed say that this study was based on "the parent-reported GI Symptom Inventory Questionnaire" among other things and so one has to be slightly cautious about inferring states. But as I've mentioned before on this blog, parents/primary caregivers tend to be pretty good at picking up when such issues are present in their children (see here) if not precise to all the technical details [3].

Perhaps the most important detail about the Mazurek study is their mention of the word 'pain' and how so many of their cohort seemed to be enduring quite a bit of it for such a long period of time. You wouldn't think that there was guidance on identifying and managing these issues [4] would you? And whilst we are on the topic of GI issues and autism, I might as well bring your attention to the potentially important question asked by Heitzer and colleagues [5]: Should clinical trial research of psychotropic medication in autism control for gastrointestinal symptoms? Answers on a postcard please (although I will blogging about this paper in times to come).

So then, how about William Shatner singing Pulp to close. Replacing a Sheffield accent with a Montreal one... mmm, maybe he needs a little Henderson's Relish with that cheese?

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[1] Mazurek MO. et al. One-year course and predictors of abdominal pain in children with autism spectrum disorders: The role of anxiety and sensory over-responsivity. Research in Autism Spectrum Disorders. 2014; 8: 1508-1515.

[2] Mazurek MO. et al. Anxiety, sensory over-responsivity, and gastrointestinal problems in children with autism spectrum disorders. J Abnorm Child Psychol. 2013 Jan;41(1):165-76.

[3] Gorrindo P. et al. Gastrointestinal dysfunction in autism: parental report, clinical evaluation, and associated factors. Autism Res. 2012 Apr;5(2):101-8.

[4] Buie T. et al. Evaluation, Diagnosis, and Treatment of Gastrointestinal Disorders in Individuals With ASDs: A Consensus Report. Pediatrics. 2010; 125: S1-S18.

[5] Heitzer AM. et al. Should clinical trial research of psychotropic medication in autism control for gastrointestinal symptoms? J Clinical Pharmacology. 2014. 6 May.

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Mazurek, M., Keefer, A., Shui, A., & Vasa, R. (2014). One-year course and predictors of abdominal pain in children with autism spectrum disorders: The role of anxiety and sensory over-responsivity Research in Autism Spectrum Disorders, 8 (11), 1508-1515 DOI: 10.1016/j.rasd.2014.07.018

Scurvy, vitamin C and autism

I'd been thinking about writing this post on scurvy, vitamin C and autism for quite a while. The paper by Kitcharoensakkul and colleagues [1] really made the decision for me, following their discussions on three young children with walking difficulties who were eventually diagnosed with scurvy, one of whom was diagnosed with autism. The authors concluded: "These clinical manifestations and radiologic findings highlight the importance for rheumatologists to have a higher index of suspicion for scurvy in nonambulatory children". Nonambulatory by the way, means not able to walk about (independently). "Interestingly, all patients had concomitant vitamin D deficiency" was another important point made in the Kitcharoensakkul study which is something I'm always a little interested in on this blog (see here).

Limes... @ Fludkov @ Wikipedia 

Scurvy, as some people might already know, is a condition characterised by a lack of sufficient vitamin C (ascorbic acid). It can manifest in a variety of ways including fatigue, lack of appetite, irritability alongside various functional gastrointestinal (GI) symptoms. Gingival swelling or bleeding (the gums) is perhaps one of the best known [oral] signs of the disease. Nowadays it is quite a rare condition.

In other blog entries I've referred to myself as a Limey reflective of a slang phrase for someone from these hallowed Isles called Great Britain (Britain, Britain, Britain..), which seems to derive from the practice of giving lime juice to British sailors way back when, to prevent scurvy.

Suffice to say however that the Kitcharoensakkul paper is not the first time that scurvy has appeared alongside the word autism or words autism spectrum disorder (ASD) as I'll attempt to show you...

• Case studies describing scurvy concurrent to a diagnosis of autism can be found in the peer-reviewed research literature [2]. The description by Mawson [3] is typical although some symptoms reported in that particular case as being perhaps complicated by "treatment with indomethacin, which lowers vitamin C levels" is an important addition. I do think it is important to raise the point that some medicines can interfere with the availability of things like vitamins and minerals similar to such nutraceuticals affecting some medicines.
• Cole and colleagues [4] talked about the continued presence of scurvy "among susceptible populations" which includes "certain unique populations-particularly the elderly subjects, patients with neurodevelopmental disabilities or psychiatric illnesses, or others with unusual dietary habits" in their report on a "10-year-old autistic child". 'Unusual' dietary patterns are no stranger to autism [5] (open-access here) over and above any special dietary regimes being implemented (see here).
• Congidi and colleagues [6] described another case of scurvy in "an autistic child with food-avoidant behavior". They also described MRI findings for their patient. Indeed, this is something also described in the report by Tetsu and colleagues [7] who reported that the: "imaging findings of the thigh showed diffuse signal abnormality in the bone marrow, periosteum, and the femoral muscle". Further: "A biopsy specimen of the femur showed hematoma, proliferative fibroblasts, and few collagen fibers, which suggested a deficiency of vitamin C".
• Slightly outside of the issue of scurvy is the study presented by Dolske and colleagues [8] "exploring the effectiveness of ascorbic acid (8g/70kg/day) as a supplemental pharmacological treatment for autistic children in residential treatment". Although this was a small trial in terms of participant numbers, it was a "double-blind, placebo-controlled trial" lasting 30 weeks. The authors reported "a reduction in symptom severity associated with the ascorbic acid treatment" making specific mention of "sensory motor scores". Obviously I'm not making any recommendations about these findings (no medical or clinical advice given or intended) but do find them to be interesting and perhaps overlapping with other research where vitamin C supplementation has been included. So, think back to the Jim Adams trial data (see here) based on some older research [9]. As to the hows and whys, well, unlike the chatter about vitamin C therapy potentially impacting on Epstein-Barr antibodies no biological measure was used in the Dolske study so we are left speculating...

As you've probably realised, most of the research evidence surrounding the presence of scurvy in cases of autism is based on individual case reports. I can't for example, provide you with any population estimates of how prevalent scurvy might be in cases of autism because no-one has really looked at this issue with any great assiduity. I can point you in the direction of other work talking again about cases of scurvy appearing alongside schizophrenia for example [10] but will only say that a poor diet lacking in sources of vitamin C is as much to blame in those examples as it probably is where cases of autism are discussed.

Just before I go, there are a few other things to note about vitamin C and autism which may also be pertinent to other issues. I've talked about iron before on this blog and how there is some data suggesting issues with iron for some on the autism spectrum (although certainly not all). It's quite long been recognised that vitamin C also plays a role in the absorption of iron [11] particularly non-heme iron sources and a deficiency in vitamin C is probably not going to be conducive to 'optimal' function. Quite a while back I also talked about autism and oxalates (see here) but will say no more than re-iterating the study by Chai and colleagues [12] with the requirement for lots more investigation in this area.

To close, I was saddened to hear of the death of Prof. Paul Patterson this week, a real research pioneer who's studies on autism and schizophrenia were frequently discussed on this blog (see here and see here). One of his final research contributions was the very important study fronted by Elaine Hsiao supporting a "gut-microbiome-brain connection in a mouse model of ASD". My condolences go to his family and those who knew him.

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[1] Kitcharoensakkul M. et al. Scurvy revealed by difficulty walking: three cases in young children. J Clin Rheumatol. 2014 Jun;20(4):224-8.

[2] Monks G. et al. A case of scurvy in an autistic boy. J Drugs Dermatol. 2002 Jul;1(1):67-9.

[3] Mawson AR. Bone pain, growth failure, and skin rash after an upper respiratory illness in a boy with autism: possible association with altered retinoid metabolism. Clin Pediatr (Phila). 2009 Jan;48(1):21-5.

[4] Cole JA. et al. Scurvy in a 10-year-old boy. Pediatr Dermatol. 2011 Jul-Aug;28(4):444-6

[5] Bandini LG. et al. Food selectivity in children with autism spectrum disorders and typically developing children. J Pediatr. 2010 Aug;157(2):259-64.

[6] Gongidi P. et al. Scurvy in an autistic child: MRI findings. Pediatr Radiol. 2013 Oct;43(10):1396-9.

[7] Tetsu N. et al. curvy in a Child With Autism: Magnetic Resonance Imaging and Pathological Findings. Journal of Pediatric Hematology/Oncology. 2012; 34: 484-487.

[8] Dolske MC. et al. A preliminary trial of ascorbic acid as supplemental therapy for autism. Prog Neuropsychopharmacol Biol Psychiatry. 1993 Sep;17(5):765-74.

[9] Adams JB. & Holloway C. Pilot study of a moderate dose multivitamin/mineral supplement for children with autistic spectrum disorder. J Altern Complement Med. 2004 Dec;10(6):1033-9.

[10] Dubé M. Scurvy in a man with schizophrenia. CMAJ. Aug 9, 2011; 183(11): E760.

[11] Hallberg L. et al. The role of vitamin C in iron absorption. Int J Vitam Nutr Res Suppl. 1989;30:103-8.

[12] Chai W. et al. Oxalate absorption and endogenous oxalate synthesis from ascorbate in calcium oxalate stone formers and non-stone formers. AJKD. 2004; 44: 1060-1069.

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Kitcharoensakkul M, Schulz CG, Kassel R, Khanna G, Liang S, Ngwube A, Baszis KW, Hunstad DA, & White AJ (2014). Scurvy revealed by difficulty walking: three cases in young children. Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, 20 (4), 224-8 PMID: 24847751