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