Tuesday, 5 February 2013

Insulin-like growth factor and autism

I admit to being a tiny bit sceptical/skeptical whenever I read a press release about hypothesis-only papers. Don't get me wrong, I'm all for people airing their ideas and opinions in the peer-reviewed domain, in fact in any domain including the blogosphere, as long as they are backed up by some kind of evidence (which need not just be of the double-blind, placebo-controlled variety). But I still feel a little bit cheated when there are no new findings or data included in a paper which is judged worthy to have the the fanfare of entering my Google News stream.
Hypotheses and speculations @ Wikipedia   

When I therefore came across a press release titled: Researcher uncovers potential cause, biomarker for autism and proposes study to investigate theory you can perhaps imagine my initial thoughts as the study by Steinman & Mankuta* was quite loudly proclaimed, very aptly appearing in the journal Medical Hypotheses.

So let's briefly go through what the hypothesis is and some background, bearing in mind my considerable non-expertise in this area:

  • The focus of the hypothesis is insulin-like growth factor-1 (IGF-1), sorry "sulphation factor", and how "depressed levels of this protein in the blood of newborns could potentially serve as a biomarker for the later development of autism". The focus on the prenatal and neonatal periods seems to be following recent research trends.
  • IGF-1 has lots of potential uses and links to body functions outside of its myelination duties including those related to apoptosis (programmed cell death) and also related to growth. There may even be some more aesthetic links to the protein (see here) highlighting its wide ranging uses and applications.
  • One has to go back quite a few years to see the golden age of IGF-1 - autism research as per papers like this one from Vanhala and colleagues** and this one from Riikonen and colleagues*** who eagle-eyed readers will note are one and the same research group. Both papers noted a decrease in IGF-1 levels in cerebrospinal fluid samples from participants with autism compared to controls.
  • Measuring IGF-1 levels in other biological fluids such as urine have also revealed some interesting findings potentially related to autism as per the paper by Anlar and colleagues****.
  • But don't be under any impression that the research literature is all one way on this issue. I note for example that Mills and colleagues***** reported elevations in IGF-1 and other growth-related compounds in their cohort, bearing in mind their chosen analytical medium and those all important issues of heterogenetity and comorbidity.

OK, like just about every other potential biomarker put forward for autism, things are not entirely cut-and-dried and the old chestnut that is heterogeneity comes into play. The big questions remain as to why IGF-1 might be aberrant in potential cases of autism and whether one could feasibly assume that supplementation with "Prozac®, Copaxone®, Increlex®, and recombinant human IGF" are safe enough to be indicated during the "early postnatal period of newborns" to affect IGF-1 levels. This particularly in light of both IGF-1 administration being linked to things like hypoglycemia (low blood sugar levels) and at least one of those meds being suggested to prop up IGF-1 levels potentially show some connection to autism offspring risk. The breast milk - IGF-1 angle does sound like the better alternative at the moment, bearing in mind what's already been done on 'bitty' and autism and other relationships in other developmental conditions such as ADHD.

A little reading outside of the IGF-1 - autism story also asks some interesting questions. I might be simplifying things here but quite a lot of the IGF-1 deficiency literature seems to circle the issue of growth impediment as per the research body on Laron syndrome. In those cases, and bearing in mind the related issue of growth hormone, "IGF-1 deficiency throughout childhood causes dwarfism". With such a connection in mind, does autism also manifest as growth impediment during childhood? Er, probably not, in fact just the opposite****** if I were to generalise.

But that's not to say that there may be something interesting with regards to IGF-1 and at least some cases of autism. Whilst trawling the literature for example, I stumbled across a paper by a favourite researcher on this blog, Paul Patterson******* and some work on how maternal immune activation might bring into play the pro-inflammatory cytokine, IL-6 (see this post) which could potentially impact on "the growth hormone-insulin-like growth factor (GH-IGF) axis". You can read some more about this proposed link in this paper (open-access).

As per the accompanying press release, the authors have drawn up a sort of routemap as to how they would like to see the IGF-1 - autism possible link looked at in a more scientific fashion. Quite a bit of the discussion focuses on looking at aminotic fluid or umbilical cord blood for measures of IGF-1. Neonatal blood spots are also mentioned (which have already been utilised in autism research circles). Indeed, I'd be tempted to suggest that if this is an area of potential investigation, rather than looking at bloodspots in a prospective study, assuming some stability of IGF-1, could not one begin by looking retrospectively based on a blood spot library for this potential biomarker?

----------

* Steinman G. & Mankuta D. Insulin-like growth factor and the etiology of autism. Medical Hypotheses. January 2013.

** Vanhala R. et al. Low levels of insulin-like growth factor-I in cerebrospinal fluid in children with autism. Dev Med Child Neurol. 2001; 43: 614-616.

*** Riikonen R. et al. Cerebrospinal fluid insulin-like growth factors IGF-1 and IGF-2 in infantile autism. Dev Med Child Neurol. 2006; 48: 751-755.

**** Anlar B. et al. Urinary epidermal and insulin-like growth factor excretion in autistic children. Neuropediatrics. 2007; 38: 151-153.

***** Mills JL. et al. Elevated levels of growth-related hormones in autism and autism spectrum disorder. Clin Endocrinol (Oxf). 2007; 67: 230-237.

****** Dissanayake C. et al. Growth in stature and head circumference in high-functioning autism and Asperger disorder during the first 3 years of life. Dev Psychopathol. 2006; 18: 381-393.

******* Hsiao EY. & Patterson PH. Activation of the maternal immune system induces endocrine changes in the placenta via IL-6. Brain Behav Immun. 2011; 25: 604-615.

----------

ResearchBlogging.org Steinman, G., & Mankuta, D. (2013). Insulin-like growth factor and the etiology of autism Medical Hypotheses DOI: 10.1016/j.mehy.2013.01.010