"a Brief Parent-Report Screen for Common Gastrointestinal Disorders in Autism"

I wanted to bring the findings reported by Kara Margolis and colleagues [1] to your attention today. Their observations pertinent to the "development of a brief, parent-report screen that relies minimally upon the child’s ability to report or localize pain for identifying children with ASD [autism spectrum disorder] at risk for one of three common gastrointestinal disorders (functional constipation, functional diarrhea, and gastroesophageal reflux disease)" represent something that 'fills a gap' in autism research and practice. Their authorship group including some of the great and the good looking gastrointestinal (GI) issues being over-represented in autism (see here and see here) was also an attraction to blogging about these results.

So, GI or gut problems are no stranger to autism. I don't think anyone (anymore) would seriously question such a finding given the multitude of times it has been recorded in the peer-reviewed science domain and beyond. Indeed, it's now even becoming more readily accepted that outside of functional bowel issues such as constipation and diarrhoea being over-represented in autism (see here), so other more pathological bowel states are also present for some too (see here and see here). And be in no doubt that such issues can be truly life-altering in their effects (see here and see here)...

It should also be acknowledged that when it came to starting the conversation about bowel issues and autism, it was parents and caregivers that led the way with their very astute observations of their nearest and dearest. Yes, there have always been 'professionals' who've shown an interest (and concern) in such observations, but parents and caregivers were there first. And despite many parents not (initially) being 'gastrointestinal experts', their observations, in the most part, were/are typically considered pretty accurate ones (see here).

So, Margolis et al talk about how the development of a screening instrument is the next logical step to ensure that parent reports of their children with autism potentially presenting with bowel issues are accurately recorded, onward to eventually leading to more specialised screening, evaluation and hopefully, appropriate intervention. Over 130 parents of children diagnosed with autism registered with the Autism Treatment Network (ATN) initiative agreed to take part in the study. Initially, parents were given a 35-item questionnaire looking at 3 particular functional bowel issues: "functional constipation, functional diarrhea, and gastroesophageal reflux disease" and asked to respond on behalf of their children. Gastroenterologists were also asked to evaluate the children; said professional were blinded to the parental responses to the questionnaire. When looking at these combined data sources, researchers were able to whittle down the 35-item questionnaire to 17 questions that seemed most important to the lay identification of potential bowel issues. Some further nifty statistics led authors to conclude that: "this 17-item screen identified children having one or more of these disorders with a sensitivity of 84%, specificity of 43%, and a positive predictive value of 67%." Ergo, the authors have 'the makings of' a potentially important parent/caregiver-based questionnaire to assess for the possible presence of bowel issues in autism. The makings of...

Obviously more work is required in this area. This instrument is labelled a 'screen' for such bowel issues so there is still the requirement for professional involvement when it comes to diagnosis and intervention. But one should never forget the very important perspective that parents/caregivers can have with regards to the presence of bowel issues in their children...

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[1] Margolis KG. et al. Development of a Brief Parent-Report Screen for Common Gastrointestinal Disorders in Autism Spectrum Disorder. J Autism Dev Disord. 2018. Oct 22.

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Bowel issues over-represented in autism (and perhaps linked to some behaviours)

"Make it so Mr WORF"

Once again(!) more evidence emerges from the peer-reviewed science domain highlighting how functional gastrointestinal (GI) issues such as constipation and diarrhoea are very much over-represented when it comes to a diagnosis of autism (see here). The study providing the data this time was by Zhu and colleagues [1] and was carried out in China; thus illustrating how such bowel issues cross countries and ethnicity when it comes to autism.

There's little novelty in their findings that all-manner of functional bowel condition were more frequently present in their cohort of over 320 children diagnosed with an autism spectrum disorder (ASD) compared with some 200 not-autism controls. The authors' observation that almost 50% of their sample of children diagnosed with autism presented with at least one bowel issue is not as surprising in research-terms as it perhaps once might have been.

What is perhaps interesting is the growing focus on how such bowel issues may *correlate* with behaviour noted in children with autism, as per the results of other independent findings (see here). To quote from Zhu et al: "Compared with ASD children without GID [gastrointestinal disorders] (n=166), the ASD children with GID (n=162) got higher scores in the "Body and Object Use" of ABC [Autism Behavior Checklist] scale... and had more emotional problems. Moreover, the score of behavior problems questionnaire was higher in the ASD children with GID." This is not necessarily new news to many people (particularly to parents and caregivers) but should be a topic that is given more research and clinical consideration among professionals.

More needs to be done in this area, not least on:

• improving the ways of detecting and reporting on functional bowel issues in the context of autism (see here),
• ensuring that questions about bowel function are asked during autism assessments and exams,
• moving away from over-simple 'psychological' assumptions/explanations to potentially account for bowel issues in relation to autism (see here) without appropriate gastroenterological referral (also including ridding ourselves of the old-saying 'it's part of their autism'),
• ensuring that appropriate gastroenterological resources are available and timely referral is present (particularly for paediatric resources),
• following guidance that is out there in the peer-reviewed domain on screening and treating bowel issues in the context of autism (see here),
• not being afraid to look for signs of more serious bowel pathology as and when functional bowel symptoms are present (see here) and,
• embracing the idea that gut and brain might not be completely separate and independent in the context of autism and beyond (see here). 

'Nuff said I think.

But just before you go, some other study results [2] for you to mull over with regards to the question: what is the 'normal range' of bowel movements? Answer: anything from 3 a day to 3 a week apparently.

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[1] Zhu J. et al. Association between behavioral problems and gastrointestinal disorders among children with autism spectrum disorder. Zhonghua Er Ke Za Zhi. 2017 Dec 2;55(12):905-910.

[2] Mitsuhashi S. et al. Characterizing Normal Bowel Frequency and Consistency in a Representative Sample of Adults in the United States (NHANES). Am J Gastroenterol. 2018 Jan;113(1):115-123.

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Guess what? Gastrointestinal symptoms are prevalent in autism

The paper by Calliope Holingue and colleagues [1] provides brief blogging fodder today and a topic that has finally found its way into accepted peer-reviewed science when it comes to autism spectrum disorders (ASD): gastrointestinal (GI) issues are an often over-represented comorbidity when it comes to ASD.

Reviewing the peer-reviewed research literature on this topic, the authors concluded that there are some quite wide and sometimes disparate findings on the frequency of functional GI symptoms in the context of autism. Part of the reason for this is the lack of a standardised tool for looking at GI symptoms in relation to the label.

But: "The prevalence range for constipation was 4.3-45.5% (median 22%), for diarrhea was 2.3-75.6% (median 13.0%), and for any or more than one symptom was 4.2-96.8% (median 46.8%)." Median by the way, refers to the middle number (or in this case middle percentage) from the collected datasets and stresses that approaching half of all people on the autism spectrum may present with 'any or more than one' GI symptom of clinical relevance.

I've said it before and will say it again, there is guidance out there for the screening, diagnosis and management of bowel symptoms as and when they occur alongside a diagnosis of ASD [2]. We can um-and-ah about the cause(s) of such issues (stressing that the physiological is likely just as important as any psychological explanations) but at the end of the day, those diagnosed with autism and accompanying bowel issues - both functional and/or pathological - should receive the same care and management for their bowel issues as anyone else, save any further tragedies. Indeed, given the links being made between something like slow intestinal transit and autism for example (see here), preferential screening should perhaps be the order of the day before severe endpoints are reached (see here)...

To close, and not to make light of GI issues in relation to autism, a cautionary tale against 'throwing your poo(p) out of the window because it would not flush'???

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[1] Holingue C. et al. Gastrointestinal symptoms in autism spectrum disorder: A review of the literature on ascertainment and prevalence. Autism Res. 2017 Aug 30.

[2] Buie T. et al. Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics. 2010 Jan;125 Suppl 1:S1-18.

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Anxiety and depression linked to functional bowel issues: lessons for [some] autism?

Pablo Picasso (1905) @ Wikipedia

IMFAR (International Meeting For Autism Research) 2015 kicks off in earnest today (see here) so in order to keep tabs on the various discussions over the web (#IMFAR2015) alongside the usual workload I'm offering a relatively short blog entry.

The paper served up today is by Maria Ines Pinto-Sánchez and colleagues [1] who reported that: "The prevalence of both anxiety and depression is influenced by gender, presence of organic diseases, and FGIDs [functional gastrointestinal disorders], and it increases with the number of coexistent FGIDs and frequency and severity of GI [gastrointestinal] symptoms."

Based on a participant number in the thousands, outpatients completed "questionnaires evaluating FGIDs and anxiety and depression (Hospital Anxiety and Depression scale)." Responses were analysed focused on those actually meeting "Rome III criteria for FGIDs" and authors came to a few conclusions. "Compared with patients not meeting the criteria, prevalence of anxiety... or depression... was increased in patients with FGIDs." Further: "The prevalence of anxiety and depression increased in a stepwise manner with the number of co-existing FGIDs and frequency and/or severity of gastrointestinal (GI) symptoms."

It's probably not a startlingly new idea that suffering with a FGID can in itself bring about certain psychological/behavioural symptoms. The pain and discomfort that such GI issues can entail is probably a big factor in that relationship although I say that mindful that anxiety and depression are complicated states with lots of potential 'pathways' behind them. More than that however, I'm interested in how these findings might overlay with other labels in mind. Say for example, one looks at the pretty extensive research literature talking about functional bowel disorders being present and over-represented in cases of autism (see here and see here) and all that 'gut-brain' axis chatter that you see these days?

Perhaps also relevant to the autism spectrum disorders (ASDs) is the growing recognition that psychiatric comorbidity/presentation such as anxiety and depression can also be a significant 'disabling' feature for many people on the spectrum (see here and see here respectively). Put these findings together with those described by Pinto-Sánchez et al and I'm hopefully not getting too ahead of myself saying that there may be a possible connection to be had.

Indeed, the possibility of a link between bowel issues and psychological issues such as anxiety with autism in mind is something that has already cropped up in the peer-reviewed literature as per the work from Micah Mazurek and colleagues [2] previously covered on this blog (see here and see here). Without trying to simplify any relationship and again keeping in mind that there may be many reasons for the presentation of anxiety in autism [3], the idea that functional bowel issues might be a key part of anxiety for at least some on the autism spectrum, offers some potentially important lessons including about how one might be able to 'intervene' to improve both physical and psychological health. The focus being on tackling GI symptoms in cases of autism. Y'know, the kinda thing that Tim Buie et al [4] talked about quite a few years back...

Music to close: Florence + The Machine - Ship To Wreck.

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[1] Pinto-Sánchez MI. et al. Anxiety and Depression Increase in a Stepwise Manner in Parallel With Multiple FGIDs and Symptom Severity and Frequency. The American Journal of Gastroenterology. 2015. May 12.

[2] 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.

[3] Weiss JA. et al. Bullying Victimization, Parenting Stress, and Anxiety among Adolescents and Young Adults with Autism Spectrum Disorder. Autism Res. 2015 May 11.

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

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Pinto-Sanchez, M., Ford, A., Avila, C., Verdu, E., Collins, S., Morgan, D., Moayyedi, P., & Bercik, P. (2015). Anxiety and Depression Increase in a Stepwise Manner in Parallel With Multiple FGIDs and Symptom Severity and Frequency The American Journal of Gastroenterology DOI: 10.1038/ajg.2015.128

MoBa does bowel issues in autism

'MoBa' in the title of this post, refers to the Norwegian Mother and Child Cohort Study and a handy resource which has already impacted on autism research (see here for example).

Now MoBa has turned its epidemiological clout to an issue which less and less is encountering scientific resistance: are gastrointestinal (GI) symptoms over-represented when it comes to a diagnosis of autism? Further, when do such bowel issues start to present?

The answer, shown in the paper by Michaeline Bresnaha and colleagues [1] is yes, functional bowel symptoms are seemingly more frequently reported when it comes to autism as per the results of quite a few other studies. To quote from the authors: "maternally reported GI symptoms are more common and more often persistent during the first 3 years of life in children with ASD [autism spectrum disorder] than in children with TD [typical development] or DD [developmental delay]." Said symptoms also seemed to present pretty early on; quite a bit before many children are diagnosed with autism. Some further coverage of these findings can be seen here and here.

Including a couple of giants in research terms on the authorship list - Mady Hornig and Ian Lipkin - who also continue to push the research boundaries in relation to another diagnosis which crops up on this blog (CFS/ME or SEID as it may well be eventually known) - MoBa was put to use.

Authors "defined 3 groups of children: children with ASD (n = 195), children with DD and delayed language and/or motor development (n = 4636), and children with TD (n = 40 295)." Maternal reports garnered prospectively covering various GI symptoms including "constipation, diarrhea, and food allergy/intolerance" were analysed across the groups covering children at 6, 18 and 36 months of age.

The results suggested that constipation and food allergy/intolerance were more likely to be reported in children with autism during the 6-18 month old age range compared with typically developing controls. Diarrhoea and food allergy/intolerance were also more likely to be reported in children with autism in the 18-36 month age range again, compared with TD controls. Children with autism/ASD were also more likely to present with "1 or more GI symptom in either the 6- to 18-month or the 18- to 36-month-old age period and more than twice as likely to report at least 1 GI symptom in both age periods compared with mothers of children with TD or DD." Some might quibble about the use of maternal report in discussing the presentation of bowel issues in children but I'm not one of them (see here) as the Gorrindo findings [2] drift back into my consciousness.

The press release attached to this study also contains an intriguing quote from Mady Hornig: "Although the connection of GI disturbances to autism remains unclear, the presence of GI symptoms in early life may not only help to identify a subset of children with autism who require clinical input for their GI issues, it may also open new avenues for determining the underlying nature of the disorder in that subgroup." The implication being that (a) GI symptoms, early GI symptoms, are not a universal (or exclusive) feature of autism, but are present in quite a few infants, and (b) among the increasingly pluralised view of autism (see here), the idea that said GI symptoms might represent something quite fundamental to some cases of autism offers something of an opportunity to perhaps intervene and treat/manage both bowel symptoms and potentially impact on behavioural features linked to autism. On this point I'm drawn back to some of the research from Micah Mazurek and colleagues talking about sensory issues and anxiety completing a triad with bowel issues with autism in mind (see here).

I'm probably repeating myself here but quite a bit more research is required on the relationship between autism and the presentation of GI issues. I'd be inclined to suggest that a few research areas might be useful to explore: (a) the link between functional bowel issues and more pathological bowel states (see here), (b) the link between inflammation / inflammatory markers and bowel issues (see here) taking into account the work of people like Harumi Jyonouchi for example (see here), (c) the possibility that bowel issues might have some connection back to the gut microbiota as per other work by Hornig/Lipkin (see here), and (d) how said GI issues might impact on issues such as pharmacotherapy in terms of drug availability and absorption issues (see here). This isn't an exhaustive list, just a few ideas to play around with.

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[1] Bresnahan M. et al. Association of Maternal Report of Infant and Toddler Gastrointestinal Symptoms With Autism Evidence From a Prospective Birth Cohort. JAMA Psychiatry. 2015. March 25.

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

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Bresnahan, M., Hornig, M., Schultz, A., Gunnes, N., Hirtz, D., Lie, K., Magnus, P., Reichborn-Kjennerud, T., Roth, C., Schjølberg, S., Stoltenberg, C., Surén, P., Susser, E., & Lipkin, W. (2015). Association of Maternal Report of Infant and Toddler Gastrointestinal Symptoms With Autism JAMA Psychiatry DOI: 10.1001/jamapsychiatry.2014.3034

Autism diagnosis as a predictor of slow colonic transit

Slow colonic transit is all about issues with the speed of gastrointestinal (GI) motility and how as well as deriving nourishment from our food/drink, the other important task which our gut undertakes is the removal of waste, which it generally does pretty well. The paper by Zainab Ridha and colleagues [1] suggested that a diagnosis of autism might be over-represented when it came to their review of children referred for "nuclear transit studies", that is measuring bowel transit by means of using a radiotracer. Indeed the authors note: "Neuropsychiatric disorders, in particular autism, are useful predictors of STC [slow transit constipation] and FFR [functional fecal retention] in children". I think we might have previously seen snippets of these results in another publication too [2].

You might feel a sharp scratch...

It's not new news that functional bowel disorders such as constipation and diarrhoea tend to be quite frequent issues accompanying quite a few cases of autism. I've covered some of the research on this topic before on this blog (see here). I might in particular, draw your attention to the meta-analysis by Barbara McElhanon and colleagues [3] (open-access) that concluded: "Children with ASD [autism spectrum disorder] experience significantly more general GI symptoms than comparison groups".

Although there is now pretty widespread acceptance that bowel issues can and often do accompany autism, there is still a degree of reticence to talk about what might be causing such issues and what *might* be done about them [4], specifically when approached in the context of more serious underlying bowel disorders potentially being linked to said functional bowel issues (see here). I hark back to one of my first ramblings on this topic which was titled: 'Should I mention gastrointestinal symptoms in autism?' as an example of how delicate an area of investigation this was/is.

I'd like to think that the paper from Ridha et al might however continue to open this research area up and highlight how the so-called gut-brain axis is growing in both acceptance and understanding. The additionally interesting data from the authors suggesting that: "15.8 % of patients with constipation were obese, compared to 6.4 % in the general Australian paediatric population" whilst not necessarily autism-exclusive might also stimulate further interest in light of the analysis of weight and activity with autism in mind too (see here). Oh, and that nutritional deficiency and a higher body mass index (BMI) might also be another curious combination for some on the autism spectrum [5].

I'm going to chance my [speculating] luck and say that among the many factors potentially involved in these combined factors, a role for those trillions of wee beasties that call us home (the gut microbiome) might also show some involvement...

Music: Joe Cocker - With A Little Help From My Friends (RIP).

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[1] Ridha Z. et al. Predictors of slow colonic transit in children. Pediatr Surg Int. 2014 Dec 31.

[2] Croaker D. et al. PO-0110 Predictors Of Slow Colonic Transit In Children. Arch Dis Child 2014; 99: A285.

[3] McElhanon BO. et al. Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis. Pediatrics. 2014 May;133(5):872-83.

[4] Coccolrullo P. et al. Lactobacillus reuteri (DSM 17938) in Infants with Functional Chronic Constipation: A Double-Blind, Randomized, Placebo-Controlled Study. J Peds. 2010; 157: 598-602.

[5] Shmaya Y. et al. Nutritional deficiencies and overweight prevalence among children with autism spectrum disorder. Res Dev Disabil. 2014 Dec 19;38C:1-6.

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Ridha Z, Quinn R, & Croaker GD (2014). Predictors of slow colonic transit in children. Pediatric surgery international PMID: 25549892

Functional GI issues and autism: not just an accumulation of case reports?

I've taken my time in posting this entry specifically dedicated to the paper by Virginia Chaidez and colleagues* which "puts to rest the idea that gastrointestinal problems among children with autism spectrum disorder are just an accumulation of case reports" according to one of the paper authors (see here). It's not that I don't see these findings to be absolutely fascinating, but rather that I wanted the research dust to settle a little before I added my [inflation adjusted] 10 pence worth of commentary.

Connecting the dots? @ Wikipedia  

Whilst receiving some media exposure at the time of publication, the Chaidez paper was slightly over-shadowed by another potentially interesting autism development published at a similar time by Warren and Klin (briefly discussed in a previous post) looking at eye gaze in young infants.

I suppose it's to be expected that chatter about [potential] novel early markers for autism will garner more headlines that the mundane task of scientific replication. Indeed, replication is once again the name of the game when it comes to the Chaidez paper, building on quite a bit of previous research suggesting that functional gastrointestinal (GI) issues can and do appear alongside quite a few cases of autism.

The details of the Chaidez paper are pretty straight-forward insofar as asking parents of children involved in the CHARGE study (beincharge!) to report on their children's behaviour and bowel activity via a couple of questionnaires (the Aberrant Behavior Checklist and the CHARGE Gastrointestinal History Questionnaire (GIH)). According to the study press release, the CHARGE GIH questionnaire "measures such disorders as abdominal pain, diarrhea, constipation and difficulty swallowing" but as yet I've not been able to find out too much about it's content validity and reliability within the peer-reviewed domain. Since I've mentioned CHARGE, I'll also draw your attention to some interesting research on air pollution and autism which I'll be posting about fairly soon.

Anyhow, based on responses from just shy of 1000 participants spread across categories of autism spectrum disorder (ASD) diagnosed, developmental delay (DD) diagnosed and typically-developing (TD), the results corroborate quite a lot of previous research undertaken in this area: "Compared to TD children, those with ASD [aOR 7.92 (4.89-12.85)] and DD [aOR 4.55 (2.51-8.24)] were more likely to have at least one frequent GI symptom". Functional bowel issues do seem to be more commonly reported in cases of ASD (and DD) compared with asymptomatic controls. A shocker, I know. Oh and just in case I have to say it again, parental reports of offspring GI complaints in relation to autism are actually quite sensitive as per the findings by Gorrindo and colleagues**.

There are some other very interesting details also discussed in the Chaidez paper and commentary which are worthy of comment. A long quote for you: "The researchers said that the study suggests that a chronic GI symptom, which can cause pain, discomfort and anxiety, could contribute to increased irritability and social withdrawal, particularly in children with deficits in social and communication skills. For children with autism, hyperactivity and repetitive behaviors may represent coping mechanisms for physical discomfort".

It's not rocket science to understand that having a functional bowel issue, or perhaps even something more pathological, which may impinge on a persons quality of life and may even cause some significant amount of physical and psychological distress, is probably going to [variably] show on a person's day-to-day behaviour. I think back to the paper by Kushak and colleagues*** (which was discussed in this post) on lactose intolerance in cases of autism and their quote: "Lactase deficiency not associated with intestinal inflammation or injury is common in autistic children and may contribute to abdominal discomfort, pain and observed aberrant behavior". I've used food as the example to highlight this issue but am not as yet, making any connection with those issues identified by Chaidez et al. Indeed, in a similar vein, I'm also brought back to the findings of Micah Mazurek and colleagues which talked about gut issues being potentially linked to anxiety and sensory issues in relation to autism as further evidence for that gut-brain or rather gut-behaviour relationship. The important mention that autism is rarely, in ESSENCE, a stand-alone condition is also worthwhile reiterating here.

You can probably tell that I'm pretty much sold on the idea that digestive issues can and do appear with greater frequency alongside cases of autism. This finding now being replicated quite a few times in the peer-reviewed arena and across different geographical boundaries. I hold off from saying this is a universal issue across all autism because the data don't point to that, and universals tend to be few and far between when it comes to the autisms. Perhaps GI issues form a part of one or more particular 'types' of autism?

As per yet another quote about the Chaidez paper: "The researchers did not address the reasons why the children with autism and developmental delay experienced more GI difficulties in this study. They noted that their findings suggest that the subject warrants additional inquiry". To me this then represents the important next step in this area of investigation. We know for example, that children with autism are more likely to experience problem issues in relation to food and feeding habits (see here and here). Research is also starting to appreciate that physical activity levels are also an important area of further investigation in relation to autism (see here) which might also impact on such GI issues.

After that it starts to get a little bit more 'interesting'. Are such issues a manifestation of problems with specific food groups? Gluten, casein or something more general like carbohydrates and their metabolism (see here)? Are there other factors which might be implicated in the presentation of such GI issues, bearing in mind this could be genetic factors and possibly even more environmentally-based factors? With all the quite detailed information available to the various research groups about cohorts such as those involved in CHARGE, the possible answers are already locked in the available data.

Without giving any medical or clinical advice, if readers need any further information about this topic, you are directed to your healthcare provider and the various evidence-based guidance on the subject**** (open-access). The commentary from Dr Tim Buie on the Chaidez study also contains some nuggets of information which readers might find useful (see here). And if readers are so inclined, another big name in GI issues and autism - Prof. Simon Murch - is talking at the NAS 2014 Professional Conference here in the UK (see here). One to see I'd say.

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* Chaidez V. et al. Gastrointestinal Problems in Children with Autism, Developmental Delays or Typical Development. J Autism Dev Disord. 2013 Nov 6. [Epub ahead of print]

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

*** 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.

**** Buie T. et al. Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics. 2010 Jan;125 Suppl 1:S1-18.

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Chaidez V, Hansen RL, & Hertz-Picciotto I (2013). Gastrointestinal Problems in Children with Autism, Developmental Delays or Typical Development. Journal of autism and developmental disorders PMID: 24193577

Are gut problems in autism linked to anxiety and sensory issues?

I'd been waiting to get hold of the recent article by Dr Micah Mazurek and colleagues titled: Anxiety, sensory over-responsivity, and gastrointestinal problems in children with autism spectrum disorders* (abstract here) for quite a few days before posting about it.

This paper was always going to catch my eye given the focus on gastrointestinal (GI) problems comorbid to cases of autism. That and the authors connecting issues with anxiety and sensory issues to the presence of such functional GI problems in cases of autism, which really neatly falls within the remit of my interest in our second brain and how it might do some much more than just digest food. Don't get me wrong, I know all about the difference between correlation and causation - as in one does not necessarily mean the other - and tread carefully when discussing Dr Mazurek's findings.

Perhaps a few study details first:

• Quite a large sample of children aged between 2-17 years old (N=2973) diagnosed with an autism spectrum disorder were included for study derived from the Autism Treatment Network (ATN). This means that we can reliably assume that (a) participants were diagnosed with autism, and (b) diagnosis was confirmed by gold-standard instruments such as ADOS.
• Parent report data was collected on various features pertinent to the current study including a subset of items derived from the Short Sensory Profile (SSP), the Anxiety Problem T-score from the Child Behaviour Checklist (CBCL) and a GI Symptom Inventory Questionnaire to measure GI health related to five chronic functional GI symptoms. Cognitive functioning was also assessed.
• The results: about a quarter of the participants studied presented with at least one chronic GI problem - that is a GI problem "within the past 3 months, duration of 3 or more months"; most frequently constipation. Children with chronic GI issues (n=733) scored higher on the CBCL Anxiety Problem scale than those (n=2239) without. Children with a chronic GI problem also presented with greater sensory over-responsivity (SOS) than those without such issues. SOS included features such as tactile sensitivity, taste-smell sensitivity (see here), movement sensitivity and visual-auditory sensitivity (see here). 
• Finally, logistic regression analyses seemed to indicate that both anxiety and SOS "significantly contribute to the prediction of chronic constipation, chronic abdominal pain, chronic bloating and chronic nausea".

To my mind, these findings make for some very persuasive reading. One could argue about whether parent report is the most accurate way of collecting such data. I would however highlight two studies in the autism research field which suggest that parent reporting might not be totally off the mark as per developmental history recall (here) and that very important study by Phillip Gorrindo and colleagues** on parent reporting of GI issues in autism.

What more to say that has not already been said. The possibility that functional GI issues might be over-represented in cases of autism is to my mind a point which requires little more research in light of research like this and this and this. Obviously not everyone with autism presents with such bowel problems and not everyone with such bowel problems presents with autism. Science still needs to determine whether there might be a specific autism phenotype where bowel issues are a primary somatic symptom as per the findings on lactose intolerance from Tim Buie and colleagues. But for those who, for whatever reason, would once argue that comorbid bowel features are merely a fluke finding to autism, some autism... show me your evidence.

Such bowel issues if present are more than likely going to affect people with autism at least to the same extent as they do to those with not-autism particular when in the paediatric population. I think back to the Autism Now series aired April 2011 and vaguely recall some description of a child with autism also with bowel problems and the way their behaviour seemed to manifest such issues. It certainly is not outside the realms of possibility that a person with autism with a comorbid bowel issue like constipation for example, might well have some accompanying stress and anxiety over going to the toilet for a number two with the expectation of the discomfort that this might well bring. In terms of more chronic generalised anxiety, well the research literature suggests that functional bowel problems and anxiety might already share the same bed as per studies like this one from Waters and colleagues***.

An important implication from the Mazurek findings is that if there is a connection between functional GI issues, anxiety and sensory issues, one would expect that attempts to resolve the GI issues may very well impact on the other symptom areas too and vice-versa. The authors talk about the use of cognitive behavioural therapy (CBT) as one potential avenue of intervention for these overlapping issues. Personally I'm not a great fan of CBT as being particularly useful to "treat" bowel problems in autism either directly or periperhally; to coin a phrase from a good friend of mine, bowel problems are probably not present as a result of some unconscious desire to obsessively collect bus tickets or anything like that. Rather better looking at a more physical - somatic causation is likely to yield more productive, long-term positive effects.

I've talked previously about how those trillion or so bacteria which make up our gut microbiota might very well have the ability to influence our behaviour - or at least in animal models. A friend of mine (thanks Dr Mark Wetherell) also put another interesting recent article my way by Dinan & Cryan**** which talks about the stress response potentially being affected by aspects of the gut microbiota. If we assume that the functional bowel issues noted in cases of autism might very well be partially present as a result of some bacterial issues - such as those here and here, it's not too difficult to suggest some tentative connection.

I hope I'm not getting too speculative when I also bring to your attention studies like this one from Messaoudi and colleagues***** and the use of probiotic formulations to reduce stress and anxiety responses in both animals and human volunteers. OK, no mention is specifically made about functional bowel problems in the Messaoudi paper, although similar probiotic formulations have been suggested to also affect bowel issues like constipation****** (full-text).

I do also wonder about the more traditional pharmacotherapies used to treat constipation and diarrhoea or indeed more serious underlying issues such as inflammatory bowel diseases and whether there could be potential positive effects from those also in cases of autism. This paper makes mention of the "symptomatic improvement in their behavior and general well-being after bowel clearance before colonoscopy" noted in cases of autism. I've often wondered whether interventions like the gluten- and casein-free diet which seem also to impact on bowel issues in cases of autism might be another case in point.

More research needed on the gut-brain axis in autism perhaps?

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* Mazurek M. et al. Anxiety, sensory over-responsivity, and gastrointestinal problems in children with autism spectrum disorders. Journal of Abnormal Child Psychology. August 2012.

** Gorrindo P. et al. Gastrointestinal dysfunction in autism: parental report, clinical evaluation, and associated factors. Autism Research. 2012; 5: 101-108.

*** Waters AM. et al. Functional gastrointestinal symptoms in children with anxiety disorders. Journal of Abnormal Child Psychology. July 2012.

**** Dinan TG. & Cryan JF. Regulation of the stress response by the gut microbiota: Implications for psychoneuroendocrinology. Psychoneuroendocrinology. 2012; 37: 1369-1378.

***** Messaoudi M. et al. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. British Journal of Nutrition. 2011; 105: 755-764.

****** Guerra PV. et al. Pediatric functional constipation treatment with Bifidobacterium-containing yogurt: a crossover, double-blind, controlled trial. World Journal of Gastroenterology. 2011; 17: 3916-3921.

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Mazurek MO, Vasa RA, Kalb LG, Kanne SM, Rosenberg D, Keefer A, Murray DS, Freedman B, & Lowery LA (2012). Anxiety, Sensory Over-Responsivity, and Gastrointestinal Problems in Children with Autism Spectrum Disorders. Journal of abnormal child psychology PMID: 22850932

Brain and gut in autism: a historical perspective

History was always something of interest to me at school, particularly British history throughout the Industrial Revolution. I don't know why, but listening to the life and times of people like Richard Arkwright and inventions like the Spinning Jenny, stirred something in me, combined also with having a very enthusiastic teacher.  It is with history in mind that I offer this entry.

Whilst the primary aim of this blog is to look at the various contemporary research produced on autism, I also intend to go back thorugh the archives occasionally and look at some of the older research done, just to see if there is anything we can learn. In this post, I want to cover this paper* by Goodwin and colleagues first published in 1971; one of the first papers I've found that talks about the gut-brain connection in relation to autism. The paper was published in the Journal of Autism and Childhood Schizophrenia which has evolved to become the Journal of Autism and Developmental Disorders. Indeed, it was one of the very first papers to be published in the journal.

Nowadays there is quite a lot of discussion about the gut-brain axis in relation to autism and lots of other things. Neurotransmitters such as serotonin (5-HT to us Brits) are for example, found in both gut and brain. There is, therefore some good reason to suspect that what effects the brain may also affect the gut and vice-versa.

The Goodwin paper basically followed up a previous piece of research published by the same authors (Goodwin & Goodwin, 1969) where autism was found coincidental to coeliac disease. The aim of the follow-up research was to compare and contrast various parameters pertinent to the gut-brain relationship in children with autism (n=15) (and their siblings, n=14) compared to asymptomatic children (n=25) and adults (n=300) and adults with schizophrenia (n=200) and non-specific 'mental disorders' (n=6).

There are a few really interesting details to arise from this paper including:

• They make mention of the work of the late Curt Dohan and his research on schizophrenia and cereal grains.
• Several participants diagnosed with autism had siblings also diagnosed with autism.
• Several somatic co-morbidities were noted in the autism group including anaemia (crescent cell which I think is better known as sickle-cell anaemia these days), eczema, asthma and hyperthyroidism.
• There were quite a few cases of persistent co-morbid functional bowel problems noted in the autism group (6/15), as well as individual cases of coeliac disease and episodes of gastroenteritis.
• Signs of early food intolerance (colic, milk intolerance, diarrhoea) were 'reported for all autistic subjects'.
• A case of autism and co-morbid coeliac disease is described: 'A normal diet, ordered in error, produced a brief relapse with exacerbation of autistic symptoms' (corrected by reinstitution of a gluten-free diet). 
• The authors note a novel way of introducing gliadin (gluten) and placebo to participants via a drink.
• Gliadin introduction decreased cortisol levels and affected circadian rhythms.
• The authors state that their results suggest childhood autism may be caused by a 'fundamental neurological dysfunction' but correlated with 'malabsorption and sensitivity to food'.
• Finally, the authors suggest that there is as much a need for further investigations, as there is 'a need for meticulous medical care, correction of sensory and gastrointestinal defects, and sustained observation of the autistic child in an environment conducive to learning and growth'.

Bearing in mind that this was research conducted almost a decade before autism came into the mainstream psyche (as represented by Wing and Gould's seminal 1979 paper), I find myself most interested in the reported findings. Not only were functional bowel problems being reported and discussed as co-morbidities to autism, the early food intolerance signs follow a similar path to those initially reported by Kanner in 1943. The somatic co-morbidities are also of interest, and in particular, the case study on coeliac disease and autistic symptoms which mirrors that of the most recent findings by Genuis.

I highlighted the gliadin and placebo drink because one of the main problems with the research looking at gluten- (and casein-) free diets for autism is the lack of double-blind, placebo-controlled trials. Whilst some research has been done on looking at developing GFCF and placebo test foods for such a trial, Goodwin and colleagues offer an extremely easy alternative: put your gluten (and casein) into a drink! It just goes to show that not seeing the wood for the trees is not an exclusively 'autistic' trait.

The last point highlighted is perhaps something we need to work on: providing meticulous medical care for people with autism and in particular the GI problems that a proportion present with. I don't want to do any finger-pointing but certainly there is some indication that some people with autism are not receiving the care they should be in this and other areas, despite all the relevant guidance and documentation being available.

To finish, a song released in 1971 from someone who has already been mentioned in previous posts.

* Goodwin MS. et al. (1971) Malabsorption and cerebral dysfunction: a multivariate and comparative study of autistic children. Journal of Autism and Childhood Schizophrenia. 1: 48-62.

Functional bowel problems and autism

It is perhaps one of the more widely discussed body parts related to autism spectrum conditions - the gastrointestinal (GI) tract. I say discussed, but this is at times perhaps too 'polite' a word to use given the various debates there have been on gut problems and autism, linked to all sorts of issues including: how prevalent they are, what causes them, whether they are linked to autism symptom onset and presentation and what can be done about them.

I should perhaps make a distinction at this initial point between the two types of GI involvement postulated in autism. On the one hand we have a potential association between some cases of autism and GI disease - things like variants of inflammatory bowel disease, coeliac disease, etc. On the other hand we have the association with functional bowel problems - things like constipation, diarrhea, bloating. Both types of GI disorder are linked to each other and both have been linked to autism to varying degrees, generating a considerable body of research literature in the process. I have touched upon GI disease co-morbidity in a few posts (most notably here and here). For this post I am focusing on the functional bowel patterns and symptoms in light of this recently published study following other independent research.

Before proceeding I will provide you with some information on constipation (prevalence: 5-30%) and diarrhea (prevalence: ???) with particular reference to the pediatric population. The prevalence figures for constipation should be the standard that should be borne in mind when looking at the data subsequently presented in this post. OK. The study in question is from the MIND Institute by Wang and colleagues, and looked at the prevalence of functional bowel problems in autism. The details: the parents/primary caregivers of 589 people with autism were interviewed and medical history data extracted. Data for 163 siblings (unaffected by autism) were also captured. Compared with siblings, parent reports detailed significantly more functional GI problems in the autism group (42% vs. 12%) (p<0.001). Constipation and diarrhea were the most commonly cited problems and having more severe autism was associated with a higher risk of presenting with GI problems.

Bearing in mind that this study was based on retrospective recall and relied on non-specialist testimony, there was a degree of overlap from the findings and other work in this area (a sample of which is here and here) although balanced with some disparity also (here and here). There are a few points we can draw from this collected information.

• Allowing for differences in the way that such functional bowel problems are described and reported (by who, using what criteria, compared against who, etc), a diagnosis of autism does not seem to confer any protection against co-morbid functional bowel problems, at least to the same extent that they occur in age-matched populations. Whether there is any effect from gender remains to be seen.  
• There is some evidence for functional bowel problems to be present more frequently in some cases of autism over others also being moderated by autism severity. At the present time however there are additional co-morbidities attached to autism (such as learning disability) that could at least partially account for results. 
• In amongst the various investigations on functional bowel problems, there are only a small number of studies looking at the various reasons why such functional bowel problems could be present. I tend to cite this study by Afzal and colleagues quite a bit, simply because they suggested that milk consumption was the strongest predictor of constipation in their group. Are there other factors such as quality of diet, water intake, medication or other environmental effects which could also affect presentation? 

Before I end this post, I would briefly like to touch upon the thorny issue of treatment for functional bowel problems co-occurring in autism. I say this is a thorny issue because quite a few people I have talked to down the years have not had a great experience when trying to get theirs or their child's functional bowel symptoms examined and treated properly despite some formal guidance being in place.

I am not assigning any blame and do not wish to offend anyone involved in such treatments, who do sterling work. The problem of treatment seems to exist for many reasons: low numbers of suitably qualified professionals (particularly pediatric gastroenterologists), a continued state of 'not-knowing' when it comes to autism and functional bowel issues (despite available guidance) and also perhaps other factors.

I would like to think that here in the UK, with the commencement of the NICE guidelines on autism, we will see some credit given to functional bowel problems as a potential co-morbidity to autism. Also hopefully not too far behind, some authoritative research on strategies for alleviating such problems specifically with autism in mind, and recognition of the pain and suffering that they can potentially cause.