"... and now believe their pet has canine autism"

A recent tweet from the account of one of the most popular TV breakfast shows here in Blighty made some waves (international waves no less) for a couple of reasons. Leaving aside the insinuation that vaccination *might* correlate with certain behavioural changes in domestic pets, the idea that autism might not be something exclusive to humans was also implied from said tweet.

Needless to say that quite a few people took exception to the idea of 'canine autism'; even the British Veterinary Association (BVA) insisted that "there is currently no scientific evidence to suggest autism in dogs." But is that actually scientifically accurate? And more widely, is it possible for a non-human to have autism or present with significant autistic features?

Before progressing through the evidence around this question, I think it's worthwhile getting a few things straight. First, I appreciate that whilst autism is a label or diagnosis denoting a set of behavioural characteristics that 'significantly impact on day-to-day life' according to current diagnostic schedules, it's also a label of identity for some people. One therefore needs to be sensitive to the effect that discussions about animals also potentially 'having that label' would have to those who associate with an autistic identity. Second, there is a long, very long, history in peer-reviewed research circles, where animals have been used to model aspects of autism. Take for example, the increasingly important research emerging on a role for prenatal valproate exposure as a route to potentially increasing the risk of autism and other neurodevelopmental conditions being diagnosed (see here); an area that has also included discussions of a valproate-treated rodent model of autism (see here) being used in research. Of course, one needs to be aware that modelling autistic features in animals is not the same as autism and all its complexity presenting in humans (including the idea that autism rarely appears in some sort of diagnostic vacuum) and the resulting 'logical fallacies' that can arise (see here). But the assumption is that elements of certain core features of autism can potentially present in non-humans too, and could provide important clues as to the underlying nature of autism.

Going back to that 'no scientific evidence' statement made by the BVA in the lay press, you might be surprised to hear that actually, dogs have been the topic of some research interest in relation to their presenting with some of the features of autism. In an article titled: 'Can Dogs Have Autism?' some of that research was discussed. Starting from an article published way back in 1966 [1] observing behaviour in a dog "resembling human infantile autism" up to more recent peer-reviewed studies [2], several commentators have speculated on facets of autism being present in certain dogs and perhaps being more readily presented in certain breeds of dog. I've actually covered this topic previously in another post on this blog (see here) based on other research [3] reporting on shared biochemical parameters noted in some children and some canines: "tail-chasing Bull Terriers." This, on the basis that from a behavioural and biological point of view, humans are not a million miles away from canines and vice-verse. In short, there is a small scientific evidence base pursuing the notion that facets of autism may present in non-humans too.

Minus too many deep, philosophical musings about our relationship with animals and any evolutionary *connections* between human and animal behaviours, this topic did get me thinking about quite a few other things. It got me wondering whether there may be other behaviours and/or behaviourally-defined conditions / labels that are readily diagnosed in humans but that might also present in non-humans too. I also started to wonder about the myriad of animal-assisted 'interventions' that have been mentioned with autism in mind down the years (see here) and whether other possible research connections could be made as a result. Are we being too presumptuous by saying that the essence of autism is a uniquely human state?

And without trying to trivialise or make light of what autism means to many, many people, there is a long history of speculation when it comes to cats and autism...

----------

[1] Fox MW. A syndrome in the dog resembling human infantile autism. J Am Vet Med Assoc. 1966 Jun 1;148(11):1387-90.

[2] Zamzow RM. et al. Characterizing autism-relevant social behavior in poodles (Canis familiaris) via owner report. J Comp Psychol. 2017 May;131(2):139-149.

[3] Tsilioni I. et al. Elevated serum neurotensin and CRH levels in children with autistic spectrum disorders and tail-chasing Bull Terriers with a phenotype similar to autism. Transl Psychiatry. 2014 Oct 14;4:e466.

----------

Neurotensin, autism and tail-chasing Bull Terrriers?

I'm not kidding.

The paper by Tsilioni and colleagues [1] (open-access) did indeed look at serum levels of neurotensin and corticotropin-releasing hormone (CRH) in a cohort of children diagnosed with an autism spectrum disorder (ASD) alongside levels in tail-chasing Bull Terrier dogs as compared to unaffected [non tail-chasing] Bull Terriers (BTs) and Labrador Retriever dogs. You may well smirk or even laugh at such research but, as per the recent [preliminary] broccoli chemical - autism study (see here), unusual research may yet offer some interesting insights into some of the biology of at least some of the autism spectrum.

Meg's gravy is famous.

Mention of neurotensin and autism really can only mean the involvement of one researcher: Prof. Theoharis Theoharides and his continuing interest in this area [2]. Indeed, the only thing seemingly missing from the Tsilioni paper is some analysis of another of Prof. Theoharides' interests: mast cells and autism (see here); although I do note that the authors mention how: "NT [neurotensin] is a vasoactive peptide isolated from the brain and is implicated in immunity. It is increased in the skin following acute stress, triggers skin mast cells (MCs) and increases skin vascular permeability in rodents through MC activation".

The Tsilioni paper is open-access but a few pointers might be in order:

• Greek children diagnosed with an ASD (N=40) fulfilling quite a few inclusion criteria provided a fasting blood sample. Similar samples were also provided by "normotypic" controls (I assume this means asymptomatic for ASD).
• "Serum from unaffected (n=18) and affected BTs (n=14) and unaffected Labrador retriever dogs (n=6) was collected at various facilities accessible to the owners and was sent to the senior Author’s laboratory on dry ice". Apparently a behavioural survey was used to classify Bull Terriers into affected and unaffected groups.
• Analysis for NT and CRH levels was completed on samples based on ELISA preceded by some clean-up steps. Results were presented to also include: "whether there is any relationship between the number of ASD children with GI [gastrointestinal] symptoms and high serum NT levels and whether it is more than expected by chance".
• So: group serum NT levels were significantly elevated in the cohort of children with ASD compared to controls (see here). As per the scatterplot shown in that last link however, this elevation was not noted for every child with autism; by my count about 11 children in the ASD group showed results above the upper 95% confidence interval (CI) for that particular group. The presence of GI symptoms also seemed to moderate this relationship: "There is a strong correlation between the number of ASD children with GI symptoms and high serum NT levels".
• Group serum CRH levels were also elevated for the ASD group compared to controls (see here) (12 of which seemed to show a similar pattern to that previously described).
• Bull Terriers affected by that tail-chasing behaviour - "reminiscent of stereotypic spinning exhibited by autistic children" - also showed group elevations in the levels of serum NT and CRH when compared to control dogs. The authors suggest that this: "supports the premise that these dogs could represent at least an autism endophenotype" from an animal model point of view (see this table for further information).

Outside of trying to model autism or more precisely behaviours associated with autism in another animal model other than rodents (see here) or monkeys (see here), the authors provide other clues for their report of a [potential] canine model: "This dog breed may be useful in the investigation of the diagnosis, pathogenesis and treatment of ASD. NTR and/or CRHR-1 antagonists, as well as MC blockers, could provide possible therapeutic approaches for stress-induced ASD. For instance, the natural flavonoid luteolin is known to inhibit mast cell-mediated allergic inflammation, and a dietary supplement containing luteolin was recently reported to significantly benefit children with ASD". That last sentence on luteolin as a potential intervention option for autism comes from other work published by the authors [3] in need of further, controlled study.

The evidence is starting to stack up suggesting that there may be more to see when it comes to NT and CRH levels in relation to at least some cases of autism (the autisms?). That GI symptoms (which are becoming much more readily accepted as being elevated in frequency when it comes to autism) might be a moderating variable of the presence of those peptide hormones is another potentially important feature in terms of how such pathology seems to interplay with behavioural symptoms (see here). I would like to see a little more focus on how other behavioural signs and symptoms (autism+) might also be affecting NT and/or CRH levels when it comes to cases of autism, and indeed, how this work overlaps with other reports of NT for example, in other conditions [4] potentially acting as "an endogenous antipsychotic drug" and more [5]

Music then. The Sound of Silence by S & G.

----------

[1] Tsilioni I. et al. Elevated serum neurotensin and CRH levels in children with autistic spectrum disorders and tail-chasing Bull Terriers with a phenotype similar to autism. Transl Psychiatry. 2014 Oct 14;4:e466.

[2] Angelidou A. et al. Neurotensin is increased in serum of young children with autistic disorder. J Neuroinflammation. 2010 Aug 23;7:48.

[3] Theoharides TC. et al. A case series of a luteolin formulation (NeuroProtek®) in children with autism spectrum disorders. Int J Immunopathol Pharmacol. 2012 Apr-Jun;25(2):317-23.

[4] Boules M. et al. Diverse roles of neurotensin agonists in the central nervous system. Front Endocrinol (Lausanne). 2013 Mar 22;4:36.

[5] Boules MM. et al. Elucidating the Role of Neurotensin in the Pathophysiology and Management of Major Mental Disorders. Behav. Sci. 2014; 4: 125-153.

----------

Tsilioni I, Dodman N, Petra AI, Taliou A, Francis K, Moon-Fanelli A, Shuster L, & Theoharides TC (2014). Elevated serum neurotensin and CRH levels in children with autistic spectrum disorders and tail-chasing Bull Terriers with a phenotype similar to autism. Translational psychiatry, 4 PMID: 25313509

Dog poo bacteria in the air

I apologise for the somewhat childish title to this post. It refers to a piece of research which most definitely fits into my 'other musings' category.

Here in the UK we are known as a nation of dog lovers. We do of course host the annual Crufts competition so as to celebrate our devoted four-legged friends. Whilst being man's best friend, there is some unpleasantness attached to dog ownership; things like cleaning up after their, ahem.. mess.

A new study by Robert Bowers and colleagues* published in the journal Applied & Environmental Microbiology suggests that such mess whilst not exactly great for the local pavement (US = sidewalk) might also be bad news for the local air quality at particular times of the year also. The study has received some coverage (here).

OK, apologies to any residents of Cleveland and Detroit, but apparently bacteria most likely derived from dog feces constitutes the dominant source of airborne bacteria in the Winter months in such places. Deep breath, mouth firmly closed (not that this will do much good).

I, like most people, never thought that bacteria in dog dirt on the ground might have the ability to become airborne. Indeed, bacteria are generally thought as being something present on floors, walls, doors and other surfaces rather than something we breathe in. Not so though as this report highlighted. As if to reiterate the point have a look at a report of a study on the fecal transport system here in the UK, including my locality; hence the age-old phrase 'now wash your hands'.

Of course the authors point out that much more research is needed to confirm the pooch as primary perpetrator and any onward effects to human health from such exposures. Whilst not wishing to force any connection to autism or anything else, I do find it interesting that our seasonal environment from a bacterial point of view might be quite fluid, and how this might perhaps tie into differing exposures and differing risk.


* Bowers RM. et al. Sources of bacteria in outdoor air across cities in the Midwestern United States. Applied & Environmental Microbiology. August 2011.