Big data does... the extreme male brain theory of autism and the Empathizing–Systemizing theory

"Two long-standing psychological theories – the empathising-systemising theory of sex differences and the extreme male brain theory of autism – have been confirmed by our new study, the largest of its kind to date."

That was the opening sentence to a write-up (see here) of a recent research paper published by David Greenberg and colleagues [1] which sought to "test 10 predictions from the Empathizing–Systemizing (E-S) theory of sex differences and the Extreme Male Brain (EMB) theory of autism." The 'big data' words included in the title of this post refer to the collection of data from hundreds of thousands of people as part of a TV documentary that aired here in Blighty called 'Are you autistic?' whose data were included for study. This follows a similar format from some of the co-authors on the Greenberg paper on previous research occasions (see here).

Minus any charges of plagiarism, a few descriptors might be useful. First: "The first theory, known as the empathising-systemising theory of typical sex differences, posits that, on average, females will score higher on tests of empathy than males, and that, on average, males will score higher on tests of systemising than females." Second: "The second theory, known as the extreme male brain theory of autism, extends the empathising-systemising theory. It posits that autistic people will, on average, show a shift towards “masculinised” scores on measures of empathy and systemising." Researchers also talked about something called a 'd score': "the difference between each person’s score on the systemising and empathy tests" in their research, alongside mention of the words 'brain type'.

As part of the interactivity of that TV documentary, some 670,000 people "who indicated they were males or females" completed various measures: "the Autism Spectrum Quotient-10 (AQ-10)... the Empathy Quotient (EQ)..., Systemizing Quotient-Revised (SQ-R)..., and the Sensory Perception Quotient (SPQ)" via an on-line questionnaire portal. About 36,000 people who took part "indicated that they had been diagnosed with an “Autism Spectrum Condition”." Data from responses to the questionnaires were crunched pertinent to those 10 predictions from both theories (said predictions concerned sex differences based on responses to the questionnaires, those various 'brain types' and how responses might look with reference to the presentation of autistic traits). For good measure, researchers also describe carrying out an 'independent replication' of their findings on a separate cohort of adults ("14,354 participants (226 autistic individuals, and 14,119 controls)"). Although there were some minor differences from the larger main trial, to all intents and purposes the same procedures were employed "for calculating brain types and performing statistical analysis."

Results: well "all 10 predictions from the E-S and EMB theories" were confirmed. So for example, men taking part in the study "had a shift towards a high d score" suggestive of being more likely to be systemisers than empathisers, whilst "typical females had a shift towards a low d score" (i.e. more likely to empathetic than systemiser). The previous STEM (science, technology, engineering, and mathematics) findings [2] were also supported, in that: "STEM professionals on average scored significantly higher on the AQ" suggesting a link between the choice of STEM career and autistic traits. And for those reporting a diagnosis of autism or autism spectrum disorder (ASD): "autistic people, regardless of their sex, had a shift towards an even higher d score than typical males" (systemisers) but "were not more likely to work in STEM occupations, compared with controls."

There is a lot to take in from the Greenberg research and related commentary. The study has a number of things going for it insofar as the huge participant size and the use of an independent replication set to confirm findings. These factors should not be underestimated. The limitations? Well, self-report is still one of them, and the fact that at least one of the questionnaires used is probably picking up a lot more than just 'autistic traits' (see here). I'm also inclined to point out once again that the *correlation* between autistic traits and STEM career choice did not seemingly extend to those with autism being "more likely to work in STEM occupations, compared with controls." Going back to that 'what is being tested' issue, the AQ for example, might also be picking up something linked to "loneliness, social anxiety, depression, and anxiety" [3] or even something approaching the schizophrenia spectrum (see here) or personality disorder (see here). Indeed, one might have to entertain the idea that the definition 'autistic traits' may not tell the whole story in this study.

I have to admit to being still a little sceptical of big psychological theories such as the EMB or the E-S theory of sex differences. The reason? Whilst attractive in their compartmentalising nature, real life is often far from being so clear-cut and linear. The fact also that an important part of the evidence behind such theories remains a little 'fluffy' (see here for example) cannot be readily brushed under the scientific carpet. As for the use of the term 'brain types', well, I can see what the authors were getting at, but I'm not convinced such terminology is particularly useful. 'Brain types' kinda sits in the same category as 'neurotypical' (see here). I was also drawn to the fact that the authors have to explicitly say that their results don't mean that "autistic people lack empathy" and that "autistic people are not hyper-male in general." It kinda tells you how some of the history behind these theories shows that they have not exactly been received with open arms by many.

But even with all that, the Greenberg results cannot be just discounted, and more research on this topic is indicated.

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[1] Greenberg DM. et al. Testing the Empathizing-Systemizing theory of sex differences and the Extreme Male Brain theory of autism in half a million people. Proc Natl Acad Sci U S A. 2018 Nov 12. pii: 201811032.

[2] Ruzich E. et al. Sex and STEM Occupation Predict Autism-Spectrum Quotient (AQ) Scores in Half a Million People. PLoS One. 2015 Oct 21;10(10):e0141229.

[3] Reed P. et al. Loneliness and Social Anxiety Mediate the Relationship between Autism Quotient and Quality of Life in University Students. Journal of Developmental and Physical Disabilities. 2016; 28: 723-733.

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"Androgens were not associated with autistic traits at 12 months of age"

EARLI - the Early Autism Risk Longitudinal Investigation study - has been mentioned on this blog before (see here) with the aim of the initiative to "examine possible environmental risk factors for autism and study whether there is any interplay between environmental factors and genetic susceptibility."

In this post I'm bringing the paper by Bo Park and colleagues [1] (open-access) to your attention and the observation(s) that umbilical cord blood levels of testosterone and other related androgens were seemingly not associated with autistic traits at 12 and 36 months of age in their cohort. Such findings represent yet another biological research blow (see here) to facets of the Extreme Male Brain (EMB) theory of autism and the suggestion that "ASD [autism spectrum disorder] is an extreme presentation of a typical male cognitive profile where the drive to “systemize” is stronger than the drive to empathize."

So, looking at cord blood samples from 137 children recruited on to EARLI - "a high autism-risk cohort following pregnant mothers with an older child diagnosed with an ASD (autistic disorder, Asperger syndrome, or pervasive developmental disorder not otherwise specified)" - researchers looked at whether measures of various androgens might correlate with scores on the Autism Observation Scales for Infants (AOSI) and Social Responsiveness Scale (SRS). Said schedules were administered at 12 months and 36 months respectively and various potentially confounding variables were taken into account when it came to looking at any associations. It's also worth pointing out that the technology of choice when it came to those measures of cord blood levels of androgens was an old favourite of this blog: liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Results: well as per the title of this post, and after adjustment for potentially confounding variables - "maternal age, gestational age, and cesarean delivery" - there wasn't a great deal to see in terms of levels of androgens and the presence of autistic traits. Indeed, the title of this post only tells half the story as testosterone was also found not to be associated with the SRS scores at 36 months too. The authors do note that: "Male infants (n=75) showed significantly higher umbilical cord testosterone levels and greater social deficits at 36 months of age" than females, but after adjustment for confounders this observation was left wanting. They also talk about some interesting observations about when a child had an older female sibling diagnosed with autism - "androgen levels and autistic traits may depend on sex of the older affected sibling" - but I'm not so sure about the strength of such findings and whether other mechanisms might also be at work. I might reiterate that autistic traits were the name of the research game in this study not a diagnosis of autism.

As mentioned, the Park findings represent another setback for the generalisability of the role of androgens (prenatal and beyond) in relation to autism and/or autistic traits. I guess that in these days of the plural 'autisms' (see here) it's perhaps not entirely unexpected that grand theories of autism seem doomed to fail when put up to scientific scrutiny. Indeed someone recently has talked about this [2]. I still however remain interested in the discussions around the EMB theory of autism, and although this and other research has not been entirely kind to the hypothesis, it is still perhaps deserving of further study in order to see who it may be most relevant to in these days of plural autisms and subgroupings...

To close, isn't this why Twitter was invented?

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[1] Park BY. et al. Umbilical cord blood androgen levels and ASD-related phenotypes at 12 and 36 months in an enriched risk cohort study. Molecular Autism. 2017; 8: 3.

[2] Müller R-A. & Amaral DG. Editorial: Time to give up on Autism Spectrum Disorder? Autism Res. 2017. Jan 27.

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Park, B., Lee, B., Burstyn, I., Tabb, L., Keelan, J., Whitehouse, A., Croen, L., Fallin, M., Hertz-Picciotto, I., Montgomery, O., & Newschaffer, C. (2017). Umbilical cord blood androgen levels and ASD-related phenotypes at 12 and 36 months in an enriched risk cohort study Molecular Autism, 8 (1) DOI: 10.1186/s13229-017-0118-z

"Are we expecting too much from the extreme male brain theory of autism?"

The title of this post reflects the commentary published by Andrew Whitehouse [1] (open-access) discussing the meaning of the findings reported by Kung and colleagues [2] who quite categorically stated that there was: "No relationship between prenatal androgen exposure and autistic traits" in their study.

OK, androgen exposure and psychology basically refers to the extreme male brain theory and autism which suggests that the so-called over-representation of autism in males is potentially down to hormone exposure (testosterone). The theory implies that androgen exposure at critical points in early development are skewing brain development towards a more 'male brain'. The definition of a male brain: well, apparently men are better systemisers than empathisers (better engineers that priests, I assume). The extreme male brain (EMB) hypothesis is an extension of the 'Theory of Mind' (ToM) stuff, which quite a few years back suggested that those diagnosed as being on the autism spectrum have greater difficulties in decoding mental states such as intents and desires. Grand psychological theories at their very finest you might say.

The problem is that whilst ToM and the EMB theory made great psychological textbook reading (certainly in their heyday between the mid-1980s up to the late 1990s) and have spawned a whole industry around testing and teaching ToM for example, the scientific evidence for these concepts being exclusively and universally attributable to the great heterogeneity that is autism is not actually all that great. A shocker I know; and don't even ask about how comorbidity around autism might also be pretty important to such psychological concepts (see here and see here for example).

Whitehouse - who himself has done some research in this area - talks quite a bit about the hows and whys of quite a few negative findings when it comes to the EMB theory (yes, there are quite a few) and what perhaps needs to be done to "advance beyond this stalemate" in relation to the EMB theory and autism.  His suggestion: "future research must first understand how the prenatal hormone environment relates to individual behavioural dimensions, and then incorporate this knowledge into the investigation of links with the more aetiologically and phenotypically complex profile of ASD [autism spectrum disorder]."

These are wise words indeed but I'd suggest this perhaps applies to any 'theory' in relation to autism, psychological, biological or genetic. Indeed, I believe that other authors (see here) have already staked their claim on how using the word 'autism' as a starting point for anything other than a descriptive label probably isn't going to move autism research along any time soon; autisms people, autisms. The challenge is also one of moving away from generalisations; so talking about male and female brains is probably about as useful as talking about left and right-sided brains. Indeed, I'll refer you to some discussions about 'gender brains' between the main proponent of the EMB theory and a psychologist a few years back (see here and see here) that kicked up some scientific dust.

I personally do think there is something in the findings looking at androgen levels and cognitive styles in the same way that there is something in most (replicated) peer-reviewed research when it comes to autism. But as Prof. Whitehouse indicates, it's probably going to be more relevant to some on the autism spectrum than others, and even then, disentangling the 'cognitive' structure of autism is going to be important [3]. The days of grand over-arching psychological theories about autism do seem to be riding off into the scientific sunset as the huge diversity and 'burden' of over-represented comorbidity start to come into plain sight. And certainly I don't think it's too rude to end with the words 'about time too'.

To close, I hark back to simpler days or should that be to a simpler future when Buck Rogers showed the 25th Century how to boogie. Tell him what you think Twiki.

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[1] Whitehouse AJO. Commentary: Are we expecting too much from the extreme male brain theory of autism? A reflection on Kung et al. (2016). J Child Psychol Psychiatry. 2016 Dec;57(12):1463-1464.

[2] Kung KT. et al. No relationship between prenatal androgen exposure and autistic traits: convergent evidence from studies of children with congenital adrenal hyperplasia and of amniotic testosterone concentrations in typically developing children. J Child Psychol Psychiatry. 2016 Dec;57(12):1455-1462.

[3] Happé F. et al. Time to give up on a single explanation for autism. Nat Neurosci. 2006 Oct;9(10):1218-20.

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Whitehouse AJ (2016). Commentary: Are we expecting too much from the extreme male brain theory of autism? A reflection on Kung et al. (2016). Journal of child psychology and psychiatry, and allied disciplines, 57 (12), 1463-1464 PMID: 27859346

The digit ratio and autism: ALSPAC says no

"In this population-based study, there was no strong evidence of an association between 2D:4D [second-to-fourth digit ratio] and ASD [autism spectrum disorder] diagnosis or traits, although the CIs [confidence intervals] were wide. These results are not consistent with the extreme male brain theory."

So said the study results from Anna Louise Guyatt and colleagues [1] (open-access) who investigated the 2D:4D ratio as part of the ALSPAC (Avon Longitudinal Study of Parents and Children) initiative. The 2D:4D ratio in case you didn't know, is the idea that the subtle difference in the length of the index finger and ring finger might be a marker for androgen exposure during the nine months that made you/us.

"The index to ring finger ratio (second-to-fourth digit ratio, 2D:4D) has been widely used as a proxy for fetal testosterone exposure in autism research" is the link back to autism and onwards the idea that testosterone exposure might be part and parcel of the extreme male brain (EMB) hypothesis ("that children with ASD exhibit an exaggerated form of the male cognitive profile... and proposes that prenatal androgens are plausible biological candidates.")

ALSPAC data was used to "examine the association between 2D:4D and ASD and various autistic trait measures in a population-based cohort in the UK." Further: "The primary hypothesis being tested was that lower 2D:4D would be associated with ASDs and ASD traits."

Analysis of the 2D:4D ratio was undertaken in 56 ASD cases, 616 "high risk trait group" participants and some 5300 other children who were part of ALSPAC. Aside from an autism diagnosis (or not) and various other measures looking at ASD traits, other data were also collected on things like socio-economic status (SES) as possible confounders. An IQ measure was also included for "44/56 of included participants with ASDs."

As per the opening statement, the results were not exactly convincing that the 2D:4D is associated with an increased risk for ASD. There was some weak evidence that 2D:4D ratios might be linked to autistic traits but, and it is an important point: "These associations were mostly directionally discordant with the extreme male theory of autism, and given the number of comparisons made, and the lack of consistent association between ASD diagnosis and 2D:4D in this study, we consider that they were due to chance."

ALSPAC as an initiative, carries some significant methodological strengths insofar of the hows and whys of data collected. I've mentioned previous results from the cohort on this blog before (see here and see here for example). Obviously ALSPAC is not perfect (no cohort ever is) and pertinent to the Guyatt results, the authors acknowledge that there may have been a bias towards the applicability of their results "being weighted towards Asperger syndrome and other high-functioning ASD cases" in light of their participant group.

That being said, I do think these results add to other research suggesting that once again, we should be guarded against making too many sweeping generalisations when it comes to the autism spectrum. In a previous post on the finger length ratio (see here) some of the other 'correlates' of the 2D:4D ratio were mentioned, excluding the 'specificity' of any findings to just autism. Other research on cord blood testosterone levels and autistic traits (see here) has been similarly critical of the EMB hypothesis.

But that might not mean that is all bunk though [2]...

Music: Phats & Small - Turn Around.

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[1] Guyatt AL. et al. Digit ratio and autism spectrum disorders in the Avon Longitudinal Study of Parents and Children: a birth cohort study. BMJ Open. 2015; 5: e007433.

[2] Baron-Cohen S. et al. The “Reading the Mind in the Eyes” Test: Complete Absence of Typical Sex Difference in ~400 Men and Women with Autism. PLoS ONE. 2015; 10(8): e0136521.

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Guyatt, A., Heron, J., Knight, B., Golding, J., & Rai, D. (2015). Digit ratio and autism spectrum disorders in the Avon Longitudinal Study of Parents and Children: a birth cohort study BMJ Open, 5 (8) DOI: 10.1136/bmjopen-2014-007433

Cord blood testosterone and autistic-like traits: no link?

Prof. Andrew Whitehouse has featured quite a bit on this blog. The most recent occasion (aside from this post) was a piece of research on maternal vitamin D status and early adult offspring scores on the Autism Spectrum Quotient (AQ) which concluded no overall link despite some interesting details. Indeed quite a bit of his work derived from the Raine study focuses on recording factors during pregnancy and the very earliest days in the big, wide world and seeing how they might relate to results like those derived from the AQ some years later. Not wholly dissimilar from the ethos behind looking at archive dried blood spots it has to be said.

Cord clamping @ Wikipedia  

In a similar vein, I want to talk about another of his papers* (open-access), this time on perinatal testosterone exposure and once again, early adult offspring AQ scores. And in particular a lack of association between the two variables and some potentially important implications for one of the more widely cited theories of how autism might come about.

I've kinda covered testosterone and autism before on this blog with reference to the finger length ratio (2D:4D), apparently quite an interesting correlate of how much testosterone we might have been swimming around in in-utero, and also more speculatively on a post on PCOS.

Most people thinking testosterone and autism are brought back to the theory posited by Prof. Simon Baron-Cohen - see one of the papers here** - extending the so-called extreme male brain (EMB) theory of autism*** itself extending the systemising/empathising sex differences**** again extending good old Theory of Mind (ToM). It's quite a logical train of thought I must admit, and probably why so many people truly do believe testosterone may show some primary connection to cases.

That being said, regular readers perhaps know that I'm not really one for sweeping generalisations when it comes to autism (see pages 949-951), no matter how much the science of psychology loves to try and compartmentalise conditions like autism. And take my word for it, psychology has been pretty fanatical about compartmentalising autism, its core cognitive features, down the years, almost it seems searching for some kind of scientific closure.

Anyhow, the paper in question is open-access but here are a few bullet points:

• The study is part of the Raine initiative again, whereby out of 861 children where BioT (free testosterone & albumin-bound testosterone) taken from umbilical cord blood at delivery was available, 707 provided diagnostic data at any of the specified follow-up points through infancy and early adulthood.
• Testosterone analysis was made by mass spectrometry, so one can't really fault accuracy, and DNA analysis from a small sample of the cohort ensured that cord blood samples were not contaminated by maternal blood so as to rule out reading maternal testosterone levels over offspring.
• Five of those 707 offspring were eventually diagnosed with an autism spectrum disorder (ASD).
• Results: "no significant correlations between TT levels and scores on any AQ scale among males (rho range: -.01 to .06) or females (rho value range: -.07 to .01)". TT = total testosterone.
• Indeed, "no significant association between BioT or TT concentrations and AQ scores among males (rho value range: -.07 to .08) or females (rho value range: -.06 to .12)".
• When looking at those 5 who were diagnosed with ASD, four "had TT and BioT levels lower than the sex-specific BioT means of the broader cohort, and all cases were within one standard deviation of these means".
• Not surprisingly the authors conclude that "testosterone concentrations from umbilical cord blood are unrelated to autistic-like traits in the general population".

There have been a few murmurs about this study in cyberspace, its results and implications for the EMB theory; partly genuine scientific interest, partly prejudice it has to be said. I'm going to try and remain objective. Assuming there was no significant sample degradation given that cord samples were taken at parturition and then thawed out apparently some years later for analysis, there are a few other factors to take into account which might have more general implications of the EMB-autism work.

Fair-do to Prof. Whitehouse for not totally poo-pooing the other research literature built up on testosterone and autism based on his findings. Indeed an even more recent study again by Bonnie Auyeung and colleagues***** (including Prof. Baron-Cohen) looking at amniotic fluid foetal testosterone and Q-CHAT results in 18-24 months old found a more positive relationship; bearing in mind a much smaller sample size and the focus on infancy not adulthood.

Back to the Whitehouse study: he for example talks about concentrations of cord testosterone not necessarily being the sole factor of any relationship but rather "individual differences in biological sensitivity to testosterone". That and the fact that the AQ is not a comprehensive autism assessment but rather a screen, and quite a subjective screen by all accounts. Other authors have talked about testosterone within a wider context of other biological markers as per this study by Geier and Geier****** who bring in words like glutathione, cysteine and homocysteine. I think you can see where I'm going with this; similar to the increasingly distant prospect of an autism gene, so an individual biomarker for autism is also looking less and less likely. Then there's heterogeneity (autisms not autism), comorbidity, etc. Indeed comorbidity is something that really needs a lot more study with testosterone-autism in mind.

Finally, I was interested to see that poverty might have been an influence on the AQ scores reported in the recent trial, to quote: "Total AQ scores were significantly higher for those adults whose mother was 
living below the poverty line during pregnancy". Assuming that you share the same enthusiasm for epigenetics and things like the Barker hypothesis as I do, you can perhaps see that this might be an area ripe for some further investigation.

To finish, a bad moon rising... oh yeah, I see it now.

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* Whitehouse AJ. et al. Perinatal testosterone exposure and autistic-like traits in the general population: a longitudinal pregnancy-cohort study. J Neurodev Disord. 2012; 4: 25.

** Auyeung B. et al. Fetal testosterone and autistic traits. Br J Psychol. 2009; 100: 1-22.

*** Baron-Cohen S. The extreme male brain theory of autism. Trends Cogn Sci. 2002; 6: 248-254.

**** Baron-Cohen S. et al.  Is there a link between engineering and autism? Autism. 1997; 1: 101-109.

***** Auyeung B. et al. Prenatal versus postnatal sex steroid hormone effects on autistic traits in children at 18 to 24 months of age. Molecular Autism. 2012; 3: 17.

****** Geier DA. & Geier MR. A clinical and laboratory evaluation of methionine cycle-transsulfuration and androgen pathway markers in children with autistic disorders. Horm Res. 2006; 66: 182-188.

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Whitehouse AJ, Mattes E, Maybery MT, Dissanayake C, Sawyer M, Jones RM, Pennell CE, Keelan JA, & Hickey M (2012). Perinatal testosterone exposure and autistic-like traits in the general population: a longitudinal pregnancy-cohort study. Journal of neurodevelopmental disorders, 4 (1) PMID: 23110806

The technological phenotype

On the question of cognitive styles possibly linked to autism, I have previously touched upon some of the various theories put forward. Ranging from problems with theory of mind, through to weak central coherence through to executive dysfunction, quite a bit of research has been devoted to this topic down the years providing psychologists in particular with plenty of experimental fodder to digest.

Perhaps the most interesting candidate in recent years has been the systemising-empathising hypothesis as expounded by Prof. Simon Baron-Cohen and colleagues. The basic tenets of the theory are relatively simple: according to Prof. SBC, the triad of 'deficits' linked to autism (social, communication, perspective-taking) are all in areas of empathising, whilst the various 'strengths' linked to autism (obsession with systems, repetitive behaviours, islets of ability) are all in areas of systemising. I touched upon this theory in a recent post. Gender has also been suggested to have a hand in the hypothesis (males = better systemisers; females = better empathisers) running alongside the gender ratios noted for autism, but for the purposes of brevity, I would direct you to this paper for a more comprehensive overview.

A recent paper reported here and also discussed here has caused a little bit of a stir in relation to the empathising-systemising (E-S) hypothesis of autism. The suggestion was that differing prevalence rates of autism might be accounted for by the level of technological expertise present in that particular geographical location. When I say technological expertise, I am not talking about those who are just 'internet-savvy'; no, here we are talking about people who are involved in highly technical (systemised) careers like engineers, IT and software, and maths and statistics, on the basis of some older research from SBC, that such techhy people are at the extreme of the E-S disparity and hence systemisers might be more likely to have a child with autism.

The current study in question looked at different regions in the Netherlands and based on quite a large sample suggested that the relative population density of such systemisers could be a potential pointer towards a higher prevalence of autism. Similar suggestions have been raised in previous times to, for example, account for the quite extraordinary rise in autism prevalence in places like California - California being HQ to quite a few tech companies, as well as being home to Silicon Valley. It all is suggested to tie into the theory of assortative mating also proposed by SBC.

There are a few interesting things to take from such research. Primary is that prevalence rates of autism are most likely not going to be uniform geographically potentially as a result of this, and lots of other factors, both genetic and environmental. I am happy to see that from this latest paper there have been suggestions that the results could be also be in part due to the fact that a more technologically focused area is liable to have a lot more disposable money and as a result better services for things like diagnosing autism compared to a less techhy place; not even taking into account possible people differences in knowledge and awareness of autism. The post on SES and autism dealt with this in more detail.

As with all the cognitive theories put forward for autism, the E-S theory 'might' be applicable in some cases: more systemised parental career choices could be a 'risk' factor for transferring the cognitive style attributed to autism. I say cognitive style, because more and more we realise that autism is probably not genetically transmitted, but there might be some transmission of the 'spirit' of the traits described a la evidence from the broader phenotype. Having said that, I can't envisage a universality for the theory for quite a few reasons; not least that autism is an extremely heterogeneous condition and as far as I am aware covers the entire population demographic in terms of familial composition and parental career patterns. The recent debates between SBC and Cordelia Fine, which have filled many pages of the Psychologist in recent months perhaps also should be brought into this post also. As always such research makes no reference to anything but autism, so co-morbidities whether behavioural or physical and their potential impact, don't get a look in unfortunately.

To end, did you know that video killed the radio star...

The finger length ratio

Apparently 2012 has been forecast to be quite a year for us humans. Depending on what you read (and believe), we are either destined for total annihilation or some population-wide transformation. For those of you who saw the recent Hollywood blockbuster 2012, it might be a good idea to book that space vacation fairly soon. Or maybe not...

I have to say that I have never really been one for the various methods suggested to predict our future. With my science hat on, the notion that we can 'see beyond' has never really excited me despite my openness to things like precognition (see the recent study from Daryl Bem for a more science-y take on this). Indeed, even if anyone were to be able to provide some experimental evidence for such an ability (and it is a big 'if'), I would have thought the first thing they would have done is pick the winning lottery numbers or failing that at least make some money on predicting things like the winner of the Eurovision Song Contest (now that would be some feat). If that person didn't personally want to financially benefit from the proceedings, they could always give the money to charity; in the current economic climate, there is most definitely a need.

One area in the whole 'future-reading' game has however been of perhaps slightly more interest to me: the idea that our hands may provide some clues to our future, at least our future health. I say all of this because of this study recently published, and picked up here, which suggests that finger length (ratio) may correlate with a form of motor neuron disease (amyotrophic lateral sclerosis, ALS). The study is an interesting one, in that researchers found that a low index finger to ring finger (2D:4D) ratio was significantly associated with ALS compared to controls (p=0.007). They further go on to link the findings back to an old friend, testosterone, and more specifically high prenatal testosterone exposure.

I have touched upon testosterone in relation to autism a while a back but did not go in to the detail. Testosterone and autism have been in the news of late following some focus on the use of the 'lupron protocol'. I will say no more on this particular issue. The basic theory is that autism is an example of an 'extreme male brain', whereby people with autism are hyper-systemisers, as opposed to empathisers. Systemisers are great at things like computers, engineering and map-reading abilities but not exactly great material for being a Priest / Vicar. Likewise I wouldn't necessarily put that great empathiser in charge of building your new skyscraper.

The reason put forward for such a male brain: elevated testosterone levels in-utero.

How do you measure such exposure? Well the digit ratio among other things has been put forward as quite a good correlate. What are the findings in relation to autism I hear you say? There is some evidence that autism follows the trend of low 2D:4D finger ratio potentially indicative of elevated prenatal testosterone exposure. I can see why the whole theory is so attractive. It is quite a simple theory (testosterone exposure = different way of thinking) and importantly, easily testable. The evidence base is quite large; and in terms of autism, bridges the gap between listed psychological/behavioural symptoms, physiological findings and even providing some information about possible transmission of autistic symptoms.

Having said that, there are a few issues with the theory which perhaps merit some discussion. First and perhaps foremost is the 'universality' of the theory to 'all' cases of autism. I think most researchers who set out to research/investigate/examine autism start in the same naive way that I did. You read the various research papers and textbooks which more often that not give you this impression that autism is autism (one condition with a few diagnostic variants) and from that you organise your research studies to look at autism as some kind of singular entity, comparing autism for example against not-autism controls (even this has issues), and if you are lucky a group like learning disability. The reality however as you progress through your career and wisdom starts to seep in, is that autism is very much not a singular autism, but rather autisms; and accompanying those autisms are as wide a variety of co-morbidities as you would expect to find in the not-autism population.

I started this post talking about finger ratio and risk of ALS. Wait a minute, low finger ratio and ALS, low finger ratio and autism. Does this mean that people with autism are at greater risk of motor neuron disease? Or on the flip-side, people with motor neuron disease for autism? There might be a familial possibility but I am pretty sure that ALS is not a significant co-morbidity to autism unless you perhaps factor in environmental exposure. Aside from the various papers suggestive of a relationship between (female) sexuality and finger ratio, finger ratio has also been linked to stock trading, athletic ability and risk of arthritis (the osteo- variety). Quite out of the blue, I also found this paper suggesting that latent toxoplasma infection might also show some involvement following on from my previous posts on T gondii and its potential 'mind controlling' effects (at least in the rat model).

I don't want to seem to negative on the whole finger ratio hypothesis. I am not saying that the 2D:4D ratio might not represent some effect in some cases of autism. The primary problems I have is when such effects are generalised to an entire population and potentially at the expense of an effect outside of the core condition.

Horoscope anyone?