Epidermal Growth Factor and autism

Stanley Cohen @ NIH

I'm sure that regular readers of this blog are getting pretty used to (replace with 'sick and tired of') me talking about cytokines in relation to autism and other research areas.

Cytokines are those little chemical messengers which are able to stimulate both arms of the immune system (innate and adaptive) having various effects for example, in mediating inflammation. Yes sirree, these little critters perform some pretty critical tasks related to our health and wellbeing.

Although there is still some debate with regards to terminology, cytokines - some cytokines - represent a very particular type of growth factor in that they are potentially "capable of stimulating cellular growth, proliferation and cellular differentiation".

It is with this 'growth factor' description in mind that I turn my attention to an interesting paper by Charity Onore and colleagues* (open-access) and some observations related to plasma levels of epidermal growth factor (EGF) in cases of autism. The picture accompanying this post by the way is of Stanley Cohen who received the Nobel Prize in Physiology and Medicine in 1986 for the discovery of EGF.

You might recognise the authorship group for this latest  paper as being linked to the MIND Institute and their seemingly endless supply of pretty interesting findings related to autism including a recent entry I made on their work on immune cell adhesion. I know some people (rightly) question some of the work coming out of the MIND Institute in terms of generalisability to all autism and the old correlation-causation conundrum. I myself, believe that there is a plethora of extremely valuable information being published in their repertoire of papers ripe for further investigation and replication including important work on endophenotypes. Just my opinion.

Anyhow, back to the Onore paper and a few factoids about EGF and the paper for your attention:

• Epidermal growth factor, or EGF to its friends, is one of a number of important growth factors. As far as I can ascertain, it is involved in quite a few important processes which include: (a) the growth and proliferation of neurons and glia (stimulating DNA synthesis), (b) aspects of wound healing, and (c) moderating gastric acid secretions. I would also draw your attention to an interesting paper on how EGF might also abate some of the more detrimental effects of testosterone on gastric ulceration just in case you were interested in that area of research.
• As part of the Autism Phenome Project, plasma levels of EGF and another growth factor, hepatocyte growth factor (HGF) were investigated in 49 children with autism (ages: 2-4 years old) and 31 asymptomatic control children. ELISA was the name of the testing game, and all samples were analysed in duplicate.
• Results: plasma levels of EGF were significantly lower in the autism group compared to controls (p=0.003). Plasma levels of HGF were marginally lower from a group point of view in the autism cohort but not significantly so.

As with many aspects of contemporary autism research, this is not the first time that reduced plasma EGF levels have been reported in cases of autism. Suzuki and colleagues** reported lower levels of EGF in their small participant group comprised of adults with 'high-functioning' autism. 

But before you get too carried with 'this technological terror you've created' the literature on EGF and autism is not all one way. Işeri and colleagues*** reported on increased serum levels of EGF in their cohort of children with autism. Indeed, this is not the only occasion that elevations in EGF been noted as per this study by Tobiasova and colleagues**** who further noted that the effects of the antipsychotic drug risperidone seemingly did little to affect EGF levels.

So what does it all mean? A good question and at the moment, I don't have a good answer. The various differences in levels of EGF noted among the studies indicate that EGF is probably not universally 'abberrant' in cases of autism, allowing for differences in age, ethnicity, comorbidity, etc. among the various cohorts studied. I'm not immediately surprised by that fact given that there is a growing appreciation that autism is more likely to be autisms (plural) and at the moment universal constants to describe the condition (outside of symptom classification) are few and far between.

The authors do talk about the possibility of a gastrointestinal element to their findings based on preliminary investigations which showed that "EGF levels are associated with increased bloating in children with ASD". When one considers the volume of work suggestive of both functional and more pathological gastrointestinal (GI)-related conditions being correlated with cases of autism (see here and here respectively), this suggestion takes on an interesting meaning. As far as I can see however, none of the other studies on EGF levels in autism reported on any potential somatic correlates like GI factors, so we can't readily verify this suggestion at the moment.

Drawing however on other research 'around' growth factors, I did stumble on this paper by Russo and colleagues***** (open-access) which seemed to indicate that decreased HGF in cases of autism might correlate with the presence of GI dysfunction in the form of an inflammatory bowel-like disease. Interestingly Russo et al also tied this back to another old friend, MET gene function - discussed here - and its important role in cortical development and gastrointestinal repair. Whether or not this might also tie into EGF is not immediately clear.

EGF and the other growth factors represent an interesting area for further study for autism research. Keeping in mind the other states and conditions also associated with issues with EGF levels like foetal growth (see here), aplastic anaemia (see here) and even cognitive decline in Parkinson's disease (see here), one can perhaps envisage some potential role for EGF in specific endophenotypes of autism. The trick is to find out what that endophenotype might be composed of...

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* Onore C. et al. Decreased levels of EGF in plasma of children with autism spectrum disorder. Autism Research & Treatment. 2012; 205362.

** Suzuki K. et al. Decreased serum levels of epidermal growth factor in adult subjects with high-functioning autism. Biological Psychiatry. 2007; 62: 267-269.

*** Işeri E. et al. Increased serum levels of epidermal growth factor in children with autism. JADD. 2011; 41: 237-241.

**** Tobiasova Z. et al. Risperidone-related improvement of irritability in children with autism is not associated with changes in serum of epidermal growth factor and interleukin-13. Journal of Child & Adolescent Psychopharmacology. 2011; 21: 555-564.

***** Russo AJ. et al. Decreased serum hepatocyte growth factor (HGF) in autistic children with severe gastrointestinal disease. Biomarker Insights. 2009; 4: 181-190.

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Onore C, Van de Water J, & Ashwood P (2012). Decreased levels of EGF in plasma of children with autism spectrum disorder. Autism research and treatment, 2012 PMID: 22937258