Maternal prenatal male hormones associated with autism

 

This was originally noticed as a change in the ratio between the length of the 2nd and 4th fingers.  In prenatal androgen excess there is a change, with the 4th finger being relatively longer than in normal cases.

 

The research was done to see if other signs of raised male hormones might be found in autistic children.

 

There appeared to be psychological indications that autistic children were exposed to high levels of testosterone before birth and that amniotic fluid levels of the hormones could predict the behaviour of the child.

 

This has been followed up particularly by Baron-Cohen’s group to great effect, but, probably because the subject is covered so well by them, few other researchers have followed it. 

 

See testosteronism  and VIP below.

 

 

 

 

 

 

The 2D:4D ratio of significance in understanding prenatal hormones

 

 

Testosteronism:

this is the suggestion that the mothers of autistic children have more androgenic hormones in their blood while incubating the foetus or the hypothesis that autistic traits are increased following prenatal exposure to abnormally high levels of testosterone caused by congenital adrenal hyperplasia

 

Ingudomnukul E, Baron-Cohen S, Wheelwright S, Knickmeyer R. Elevated rates of testosterone-related disorders in women with autism spectrum conditions. Horm Behav. 2007 May;51(5):597-604. (they simply asked the mothers for signs of this: hirsuitism, tomboyism i.e. not specific. They found an excess of them in the mothers of the autistic children as compared to controls)

 

Knickmeyer RC, Baron-Cohen S. Fetal testosterone and sex differences in typical social development and in autism. J Child Neurol. 2006 Oct;21(10):825-45.  )They have followed this one up a lot but the proof is very difficult to come by). 

 

Baron-Cohen S, Knickmeyer RC, Belmonte MK. Sex differences in the brain: implications for explaining autism. Science. 2005 Nov 4;310(5749):819-23.  They have done quite a lot of work on the finger sizes (which vary according to pre-natal androgens) of autistic children.

 

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 (Morning blood samples collected following an overnight fast, compared to the pertinent reference means, showed significantly increased relative mean levels for: serum testosterone (158%), serum free testosterone (214%), percent free testosterone (121%), DHEA (192%), and androstenedione (173%). By contrast, compared to the pertinent reference mean, the relative mean level of FSH (51%) was significantly decreased. Additionally, at least one of the androgen attributes examined exceeded its recognized laboratory age- and sex-specific reference range in 81.4% (57 of 70) of the patients examined.  – All this shows that the increased androgen compounds were associated with a fall in FSH as you would expect if the androgens were being over-produced rather than the FSH being over excreted by the pituitary.  Beware, there is a tendency in autism to over interpret high or low levels when often the levels are within normal ranges even if they are higher than usual.  These authors recommend routine clinical measurement of androgens as a result of their findings

 

Tordjman S, Anderson GM, McBride PA, Hertzig ME, Snow ME, Hall LM, Ferrari P, Cohen DJ. Plasma androgens in autism.  J Autism Dev Disord. 1995 Jun;25(3):295-304.  (they measured slightly different and they were the same in the ausitic patients and controls).

 

Howard JM. This could be due to maternal testosterone... Arch Dis Child. 2006 Jul;91(7):622; author reply 622.

 

Knickmeyer RC, Baron-Cohen S, Auyeung B, Ashwin E. How to Test the Extreme Male Brain Theory of Autism in Terms of Foetal Androgens? J Autism Dev Disord. 2008 Mar 8 

 

Baron-Cohen S, Knickmeyer RC, Belmonte MK. Sex differences in the brain: implications for explaining autism. Science. 2005 Nov 4;310(5749):819-23. Review.  They put over the brain and personality changes that are associated with excess male changes.

 

Falter CM, Plaisted KC, Davis G. Male Brains, Androgen, and the Cognitive Profile in Autism: Convergent Evidence from 2D:4D and Congenital Adrenal Hyperplasia. J Autism Dev Disord. 2008 Mar 7

 

Manning JT, Baron-Cohen S, Wheelwright S, Sanders G. The 2nd to 4th digit ratio and autism. Dev Med Child Neurol. 2001 Mar;43(3):160-4. Children with autism had lower than expected 2D:4D ratios and children with AS higher ratios than expected in relation to their fathers' 2D:4D ratio. It was concluded that 2D:4D ratio may be a possible marker for autism which could implicate prenatal testosterone in its aetiology.

Fetal testosterone predicts sexually differentiated childhood behavior in girls and in boys. Auyeung B, Baron-Cohen S, Ashwin E, Knickmeyer R, Taylor K, Hackett G, Hines M. Psychol Sci. 2009 Feb;20(2):144-8. They report that fetal testosterone measured from amniotic fluid relates positively to male-typical scores on a standardized questionnaire measure of sex-typical play in both boys and girls.

Prenatal stress and risk for autism. Kinney DK, Munir KM, Crowley DJ, Miller AM.  Neurosci Biobehav Rev. 2008 Oct;32(8):1519-32.   This is to a large degree the discussion of the subject rather than statistics of known cases. 

How to test the extreme male brain theory of autism in terms of foetal androgens? Knickmeyer RC, Baron-Cohen S, Auyeung B, Ashwin E. J Autism Dev Disord. 2008 May;38(5):995-6; author reply 997-8. No abstract available.

Fetal testosterone and autistic traits. Auyeung B, Baron-Cohen S, Ashwin E, Knickmeyer R, Taylor K, Hackett G. Br J Psychol. 2009 Feb;100(Pt 1):1-22.  This is an excellent review article in which they look at the data associating amniotic testosterone levels  with many aspects of autism.  Studies of amniotic testosterone in humans suggest that fetal testosterone (fT) is related to specific (but not all) sexually dimorphic aspects of cognition and behaviour. It has also been suggested that autism may be an extreme manifestation of some male-typical traits, both in terms of cognition and neuroanatomy.  These findings are consistent with the hypothesis that prenatal androgen exposure is related to children exhibiting more autistic traits.

Gene expression profiling of lymphoblasts from autistic and nonaffected sib pairs: altered pathways in neuronal development and steroid biosynthesis. Hu VW, Nguyen A, Kim KS, Steinberg ME, Sarachana T, Scully MA, Soldin SJ, Luu T, Lee NH. PLoS One. 2009 Jun 3;4(6):e5775.  The way this is done is to look and see which genes on the lymphocytic population of autistic children are expressed as proteins, and compare this with the ones in a control group.   They found several genes being used involve 1.  Steroid biochemical formation pathway (including testerone and female hormones), 2  cholesterol importation into the cell (SCARB1 and SRD5A1 genes),  plus a list more.  What does not come out is a gene that is a reliable diagnostic, but it does give an insight into the reasons why other biochemical changes are seen in the body and brain.  They are going particularly into the effect of the genes, the proteins, and hence the formation of hormones that is involved.  This is a complex article. 

Prenatal VIP in mother’s blood

Regardless of genotype, offspring of VIP-deficient female mice exhibit developmental delays and deficits in social behavior.  Lim MA, Stack CM, Cuasay K, Stone MM, McFarlane HG, Waschek JA, Hill JM.  Int J Dev Neurosci. 2008 Aug;26(5):423-34. An interesting finding in that it is clear that the gene in the mother had an effect on the offspring’s ongoing brain construction.

Deficits in social behavior and reversal learning are more prevalent in male offspring of VIP deficient female mice. Stack CM, Lim MA, Cuasay K, Stone MM, Seibert KM, Spivak-Pohis I, Crawley JN, Waschek JA, Hill JM. Exp Neurol. 2008 May;211(1):67-84.

 

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