Friday, 17 October 2014

Altered ghrelin levels in boys with autism

"Honey, it's the '90s, remember?"
Saudi Arabia and autism research? It must be at least one author from the research tag-team that is Mostafa and Al-Ayadhi.

Indeed, in today's post it is Laila Al-Ayadhi featured on the paper by Felwah S. Al-Zaid and colleagues [1] (open-access) who concluded on: "a potential role for the hormone ghrelin in the pathogenesis of autism".

Ghrelin, by the way, is often called the 'hunger hormone' as a result of its effects in relation to energy homoeostasis. Alongside another hormone called leptin (which has also been implicated in cases of autism) the long-and-short of food intake regulation seem to be covered by these hormones [2].

The Al-Zaid paper is open-access but I'll direct you to a few important points...

  • A case-control study, authors looked at various measures for 31 boys diagnosed with autism compared with 28 age- and sex-matched controls.
  • Alongside various anthropometric measures, plasma and serum levels of "acyl ghrelin (AG), des-acyl ghrelin (DG), total testosterone (TT), free testosterone (FT), leptin and growth hormone (GH)" were measured. These were single spot measures with samples taken "after an overnight fast". 
  • Results: the autism group were on average heavier than controls but aside from that, no other physical measure was significantly different (mean height was greater in the autism group but just escaped significance). Both acyl ghrelin and des-acyl ghrelin levels were significantly lower in the autism group. By contrast, leptin levels were higher in the autism group (as per other independent findings) and free and total testosterone levels were significantly elevated compared to controls. Taking into account the effect of weight and it's link to adiposity, authors also showed that an analysis of a smaller subgroup (autism, n=27; controls, n=28) where mean weight was controlled for, found a similar trend in hormone levels (see this link to Table 3 of the paper) bearing in mind how body fat can influence the parameters.
  • Various correlational analyses were completed on the data but given the relatively small participant groups and the use of spot samples I'm not particularly minded to read too much into these findings at this time.
  • The authors conclude that their study: "contributes significantly to the understanding of hormonal dysregulation in the pathophysiology of autism, as it provides baseline data regarding hormonal profiles in autism and substantiates potential clinical interventions".

Small participants numbers and a "lack of female subjects with autism" kinda prohibit me from reading too much into these findings as they stand. I've already made mention of the research trend when it comes to elevated leptin levels and autism (see the paper from Rodrigues and colleagues [3] as one example). Likewise, testosterone levels and autism have received quite a bit of autism research attention down the years (see here). Indeed, elevations in testosterone levels not described in-utero with some potential relationship to foetal programming, has been the stuff of controversy in autism research circles [4].

Going back to the primary ghrelin findings and the observations of lower levels detected in their autism group, the authors speculate on some of the hows and whys of their findings. Gastrointestinal (GI) issues get a call-out and how some of the variety of GI issues noted in cases of autism "could affect the gastric mucosa and interfere with the normal function of ghrelin-secreting cells". although no particulars about GI issues are included in their descriptions of their cohort. One additional issue that I would perhaps add to the whole inflammation, dysbiosis et al discussions would be how ghrelin seems to play some role in GI motility [5] too. That being said, 'wide-ranging' is perhaps the best way to describe what biological processes ghrelin might impact on [6].

I was a touch surprised that the more usual role for ghrelin in terms of hunger and energy homoeostasis was not given more prominence in the Al-Zaid article on autism. Food and feeding patterns are important topics when it comes to autism as per discussions on the extremes sometimes noted in cases of autism (see here) and the increasingly important issue of weight (see here) (which also seemed to be picked up in the authors' findings). One might speculate that hunger and signals linked to hunger might be similarly tied into at least some of the feeding issues reported in autism?

As I seem to do in many discussions these days, I'll reiterate that there is quite a bit more to see and do in research terms on the relationship between ghrelin and related hormones and autism. The additional suggestion from Ghanizadeh [7] about the ghrelin being a "promising therapeutic target for co-occurring autism and epilepsy" might also be worthy of greater inspection.

Music to close. Iggy Pop and Lust for Life.

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[1] Al-Zaid FS. et al. Altered ghrelin levels in boys with autism: a novel finding associated with hormonal dysregulation. Sci Rep. 2014 Sep 26;4:6478.

[2] Klok MD. et al. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev. 2007 Jan;8(1):21-34.

[3] Rodrigues DH. et al. Changes in Adipokine Levels in Autism Spectrum Disorders. Neuropsychobiology 2014;69:6-10

[4] Geier DA. & Geier MR. A prospective assessment of androgen levels in patients with autistic spectrum disorders: biochemical underpinnings and suggested therapies. Neuro Endocrinol Lett. 2007 Oct;28(5):565-73.

[5] Greenwood-Van Meerveld B. et al. Ghrelin as a target for gastrointestinal motility disorders. Peptides. 2011 Nov;32(11):2352-6.

[6] Delporte C. Structure and physiological actions of ghrelin. Scientifica (Cairo). 2013;2013:518909.

[7] Ghanizadeh A. Ghrelin as a promising therapeutic target for co-occurring autism and epilepsy. Epilepsy Behav. 2011 Feb;20(2):420-1.

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ResearchBlogging.org Al-Zaid FS, Alhader AA, & Al-Ayadhi LY (2014). Altered ghrelin levels in boys with autism: a novel finding associated with hormonal dysregulation. Scientific reports, 4 PMID: 25257829