Pain predicting sleep problems in autism

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Cry baby

The little angelic face looks up at you. The lip starts to wobble.. the eyes start to water... and then the tears start to flow. Anyone who has regular contact with young children will know all about crying. Whether it be crying at 3am to indicate feeding time or crying because of a wet nappy or just crying for the sake of getting some all important attention from mum or dad (perhaps because your older sibling has taken your favourite toy..), crying serves an important communicative function to the young infant and beyond.

Believe it or not there are said to be different types of crying in infants* (*not an endorsement) modified by things like age. Because crying is one of the first communicative tools of the young infant - probably the only aside from what comes out the other end, (ahem!) - it has also been the topic of some interest in various attempts at early screening / diagnosis for a variety of things including hearing loss and sudden infant death syndrome (SIDS). Cri du chat syndrome is perhaps the most famous condition associated with crying; whereby the distinctive 'cry of the cat' provides some clue to the presence of this rare genetic condition (which has been reported to be co-morbid to autism in rare cases).

I have been brought to the topic of crying because of this study which recently appeared suggesting that there may be some subtle differences in the presentation of crying and related indications of distress in young children with autism compared to control participants. It's not the first time that crying has been studied in relation to autism. The previous studies however have been focused more on things like what happens when the opiate antagonist naltrexone is used in autism (the effect being slightly bi-directional depending on the study you look at) and other facets such as crying during sleep. I remember publishing a study a while back now where infantile colic was reported in some cases of autism, particularly Asperger syndrome. Knowing what I know about colic, I would perhaps imagine that this might also be a contributor to infant crying in, and outside of autism.

Back to the study in question. At least two of the authors on this paper have been looking at crying in relation to autism before. Their previous study suggested that episodes of crying from children with autism have a higher fundamental frequency (sound) than either typically developing or developmentally disordered children. They suggested that because of this higher frequency, the cry from a child with autism was perceived with more 'unease' to listeners. The recent study adds to these initial findings in that children with autism presented with more severe 'distress' cues in their posture and facial expressions alongside their crying patterns. The collected findings suggest that crying and distress in young children with autism might be both different compared to non-autism controls and also considered more distressful. Higher fundamental frequencies of crying have cropped up in the literature before, not least when it comes to looking at pain and crying. This study of crying after the Guthrie test for PKU suggested a similar pattern. Whether the two examples necessarily have the same reason is not known.

Whilst I think it is important to step back from these findings and bear in mind the relatively small numbers of participants involved in these studies, I find myself intrigued by the suggestion of differences in crying according to autism diagnosis or not. If we are to assume that crying is one of the beginnings of communicative language as some have suggested, there may indeed be some merit in looking more closely at crying as a possible early diagnostic aid. The added bonus being that such analysis is non-invasive, objective (insofar as the various sound technologies doing the work) and I would assume fairly quick and easy to undertake.

And now in order to test your mettle... a song accompanying the adventures of Hazel, Fiver and Bigwig.