Monday, 16 June 2014

Blocking FRAAs and thyroid function in autism

FRAAs - folate receptor alpha autoantibodies - may correlate with reduced thyroid function in cases of autism is the primary finding from the paper by Richard Frye and colleagues [1] (open-access). And immediately my attention is piqued at the possibility of a link...

FRAAs have been mentioned before on this blog (see here) based on a really interesting paper by the autism research tag team that is Frye and Rossignol [2] who continue to give when it comes to peer-reviewed research on autism. On that occasion, they reported: "serum FRA [folate receptor α autoantibodies] concentrations were measured in 93 children with ASD [autism spectrum disorder] and a high prevalence (75.3%) of FRAs was found". The net result was that there may be issues with the availability of folate, and as in the condition cerebral folate deficiency (CFD), there may be some use in looking at folinic acid (leucovorin) to normalise levels of 5-methyltetrahydrofolate. But please note I'm advocating nothing on this blog just describing findings.

In their most recent paper, Dr Frye and colleagues took things one stage further:

  • Levels of blocking and binding FRAAs were measured from serum samples donated by 32 children diagnosed with an autism spectrum disorder (ASD). Based on participants' medical records, levels of thyroid stimulating hormone (TSH) were "abstracted" and correlated with FRAAs measures.
  • Results: bearing in mind this was a 'let's see' study with no control groups and TSH values derived from medical records, the authors reported: "No significant relationship was found between the binding FRAA and TSH. However, a higher blocking FRAA titer was significantly related to a higher TSH concentration". The correlation (r) came out at 0.36, which is OK but not necessarily what one might call a strong relationship.
  • They add: "Patients who were positive for the blocking FRAA were found to have a significantly higher TSH concentration as compared to patients who were negative for the blocking FRAA". 

There are a few other points to comment on in this paper. First is the focus on thyroid function and autism. I've talked a few times about maternal thyroid levels and how they may correlate to some extent with autism risk (see here and see here). The research literature on thyroid levels in people with autism is slightly more scant (see here), and bearing in mind that there are various other thyroid measures that might be relevant, the focus on TSH alone rather limits the conclusions one can draw about thyroid function in this study. Indeed, none of the participants in this sample had "an abnormally low TSH" result and only a few had "abnormally elevated TSH".

Allied to thyroid function, and mentioned by Frye et al is the issue of iodine deficiency, which again, has been mentioned on this blog with autism in mind (see here). Iodine plays an important role in the production of thyroid hormones. Unfortunately the current study did not assay for iodine levels so we are to some extent left in the dark about any role.

There's little more for me to say about this trial outside of the need for studies looking at rather more direct measures, and a few more of them particularly pertinent to the functions of the thyroid in an autism group. I might also add that in view of the suggestion that a milk-free diet "downregulates folate receptor autoimmunity" as per the work by Ramaekers and colleagues [3] (open-access) looking at CFD, future research might also assess any effect this might have on any thyroid link too. Got milk (opioid peptides)?


[1] Frye RE. et al. Folate receptor alpha autoantibodies modulate thyroid function in autism spectrum disorder. NAJMS 2014; 7: 53-56.

[2] Frye RE. et al. Cerebral folate receptor autoantibodies in autism spectrum disorder. Mol Psychiatry. 2013; 18: 369-381.

[3] Ramaekers VT. et al. A milk-free diet downregulates folate receptor autoimmunity in cerebral folate deficiency syndrome. Dev Med Child Neurol. May 2008; 50(5): 346–352.

---------- Richard E. Frye, Jeffrey M Sequeira, Edward Quadros, & Daniel A. Rossignol (2014). Folate receptor alpha autoantibodies modulate thyroid function in autism spectrum disorder N A J Med Sci. , 7 (2), 53-56 : 10.7156/najms.2014.0702053