Autism, stress and cortisol

Stress is something that everyone, young and old, faces on a daily basis. Partnered with anxiety, stress has become part and parcel of the dictionary of modern day living despite the fact that even in times gone by, I'm pretty sure stress and anxiety were just as rife as they are today, if only under a different set of circumstances.

The stress Father @ Wikipedia 

My own personal view of stress is that it can be a double-edged sword. Particularly in these austere times that we all find ourselves living through, stress has generally taken on the most negative of connotations despite the fact that stress can often have a more productive side when linked to things like motivation and indeed in evolutionary terms, the 'fight-or-flight' response; I believe it falls under the term 'eustress'. Indeed some quite recent research suggests that it is the control factor of stress that might be important over the amount of stress and the concept of behavioural immunisation (UK-spelling) against future stress.

In trying to define stress as something tangible, physiological and measurable, one of the more widespread markers is that of cortisol, a primary stress hormone released in response to stress but also tied into our circadian rhythms. Issues with the cortisol response to stress are often associated with disruption of the hypothalamic-pituitary-adrenal (HPA) axis.

Measuring cortisol with autism in mind, has produced some interesting results so far. The earliest paper that I've found which looked at cortisol and autism is surprisingly one that has already been covered on this blog from Mary Goodwin and colleagues* and their introduction to the gut-brain axis as potentially being important in at least some cases of autism. I'm sorry that I can't link to the full-text of the Goodwin paper (which I recently mentioned in another piece on leaky gut and autism) but suffice to say that their initial measurement of plasma cortisol levels in autism vs. siblings was nothing to write home about. That being said, they did report some interesting findings based on supplementation with 1g of gliadin which "markedly decreased blood cortisol levels and abolished the normal circadian cortisol rhythm" in children with autism and their siblings. Food for thought bearing in mind that whole opioid-food-autism research and what opiates might do to cortisol levels.

Other research has reported other results when comparing autism with not-autism (and not siblings of children with autism either) as per papers like this one from Corbett and colleagues** (open-access) and this one from Kidd and colleagues***. These and other results suggesting that the usual patterns of cortisol were perhaps not followed in some cases of autism, alongside a heightened cortisol response as a reaction to novel stressor situations compared to not-autism.

Keeping in line with the autism-cortisol relationship I want to talk a little bit more about that paper from Kidd and colleagues as well as another paper published by Spratt and colleagues**** (open-access). A brief summary of both first:

Kidd paper:

• Comparing 26 children (mean age = 45 months) diagnosed with autism and confirmed by ADOS and ADI with 26 asymptomatic children  (mean age = 39 months), salivary cortisol and alpha-amylase (sAA) were measured 3 times a day over 2 consecutive days at three testing points (baseline, 3 and 6 months).
• Looking at both cortisol and sAA across the day (waking, midday, bedtime), mean levels were higher in the autism group than controls across each period although not significantly so.
• When participants with autism were divided into groups based on 'functional IQ status', those categorised as extremely low functioning children (authors words not mine) consistently presented with an elevated cortisol response across the day (although again, not significantly different from other functioning groupings). 

Spratt paper:

• Comparing 20 children with autism (mean age = 84 months) with 28 asymptomatic controls (mean age = 66 months), various measures of cortisol were analysed based on collection in urine, saliva and plasma (the blood draw for plasma cortisol analysis also serving as a stressor event too).
• Results: first production morning urine samples analysed for cortisol revealed no significant mean difference between the groups, although urinary cortisol levels were higher in the autism group taken as whole.
• Serum concentrations of cortisol were however significantly different between the groups (p=0.014). 
• Salivary cortisol showed some interesting trends in that, although presenting with a higher initial mean level of cortisol, the autism group did not differ significantly from controls at first testing prior to the blood draw stressor. That all changed following the next salivary cortisol test period 20 minutes after the blood draw, where the autism group registered a significantly elevated cortisol reading compared with controls. Indeed with the final salivary cortisol reading taken 40 minutes after the blood draw, the control group had already dipped below their baseline measurement, whereas the autism group as a whole remained elevated compared with their original baseline.
• Gender nor other items based on specific psychometric measures showed any significant correlation to  cortisol levels although there were some suggestions of links between the various testing medium (saliva, plasma, urine) at various periods of testing.

Based on these papers, one could surmise a few things:
(a) children with autism may present with an overall increase in cortisol levels, although not necessarily significantly outside the range seen in asymptomatic children,
(b) the effect of a novel stressor (novel insofar as children don't generally take part in blood draws everyday) seemed to correlate with a greater elevation in cortisol levels in cases of autism, and
(c) the regulation of stress, as in the stressor has passed and so cortisol levels should drop, seems to be affected in cases of autism, leaving a persistence of the stress state as per the findings of another study***** (open-access). Issues with habituation? I dunno.

Such important findings reported on cortisol and autism might potentially [and partially] explain some of the more debilitating aspects to the condition such as issues with responses to new and novel situations outside of those expected (the so-called repetitive behaviours domain) and maybe even the rates of anxiety that often accompany a diagnosis of autism. The implications resulting from an unusual pattern of production of glucocorticoids like cortisol noted in autism might also have some interesting links back to things like immune function too. Dare I even suggest a potential tie-in with findings related to things like hypertension too? How about something similar to that noted in depression with stress affecting neurogenesis?

Assuming some role for stress and the cortisol response to cases of autism, the final question should really be what can be done to mitigate its effects? Many parents and professionals have talked about routines and the various ways of planning for events and functions which might take a person with autism outside of their comfort zone as per things like trips to the doctors or even dentists. There's even been some speculation that dog ownership might positively affect the stress response in cases of autism, highlighting yet another effect from the pets win (prosocial) prizes potentially also following the Jedi massage route. It might also sound a little out of left field but I'm taken back to the work  by Julia Rucklidge and colleagues on micronutrients and stress (after earthquake) and whether or not similar mechanisms and modes of action might also pertain to autism? How about looking to control our bacterial masters too?

To conclude, it is rather quiet here, how about something a little big band from Iceland?

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* Goodwin MS. et al. Malabsorption and cerebral dysfunction: a multivariate and comparative study of autistic children. J Autism Child Schizophr. 1971; 1: 48-62.

** Corbett BA. et al. Variable cortisol circadian rhythms in children with autism and anticipatory stress. J Psychiatry Neurosci. 2008; 33: 227–234.

*** Kidd SA. et al. Daytime secretion of salivary cortisol and alpha-amylase in preschool-aged children with autism and typically developing children. J Autism Dev Disord. April 2012.

**** Spratt EG. et al. Enhanced cortisol response to stress in children in autism. J Autism Dev Disord. 2012; 42: 75-81.

****** Corbett BA. et al. Comparing biobehavioral profiles across two social stress paradigms in children with and without autism spectrum disorders. Mol Autism. 2012; 3: 13.

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Spratt EG, Nicholas JS, Brady KT, Carpenter LA, Hatcher CR, Meekins KA, Furlanetto RW, & Charles JM (2012). Enhanced cortisol response to stress in children in autism. Journal of autism and developmental disorders, 42 (1), 75-81 PMID: 21424864