ResearchBlogging.orgSiblings of those diagnosed with autism are more than 20 times as likely as members of the general population to also have autism. Some of these siblings also show evidence of autism-like but less marked cognitive and social communication problems. This suggests that autism has either an environmental cause typically found in all siblings during development or childhood or a strong heritable component, but there is not a known genetic link or a well established biological marker. A biological marker other than observed behavioral deficits would be a neurological phenotype such as might be seen in brain imaging.

Spencer et al, working from various units of Cambridge University seem to have identified such a marker.

… we show, for the first time, that the neural response to facial expression of emotion differs between unaffected siblings and healthy controls with no family history of autism. Strikingly, the functional magnetic resonance imaging (fMRI) response to happy versus neutral faces was significantly reduced in unaffected siblings compared with controls within a number of brain areas implicated in empathy and face processing. The response in unaffected siblings did not differ significantly from the response in autism. Furthermore, investigation of the response to faces versus fixation crosses suggested that, within the context of this study, an atypical response specifically to happy faces, rather than to faces in general, accounts for the observed sibling versus controls difference and is a clear biomarker of familial risk.

Autism is associated with limited reactions to emotional states of others. This study seems to identify the neurological component of that phenomenon, and sees it in individuals who are not otherwise diagnosed as autistic. This could suggest that the neural phenotype seen in this fMRI study is the root cause of the condition of autism, though of course that would have to be confirmed somehow with developmental studies.

The study included 40 adolescents between 12 and 18 years of age who were diagnosed with autism spectrum disorder, specifically with either autism or Asperger syndrome, as well as 40 unaffected siblings of those affected and 40 controls who did not seem to have autism of any kind. They were then given a task of observing faces displaying different emotional states while their brains were being scanned. The results are rather stunning. The control group showed differences in brain response when comparing happy vs. neutral faces, while both the sibling and autism groups simply did not. When comparing fearful and neutral faces, the control group and sibling group showed similar responses, but the autism group showed no change.

The lack of brain response to facial stimuli in autistic subjects was expected and has been demonstrated in previous studies. What was not expected, apparently, is the similarity between non-autism spectrum disorder siblings and the autism-diagnosed individuals. Various methods were used to ensure that the observed pattern had to do with emotional aspects of the faces being observed rather than the overall ability to parse what was being seen.

Press reports of this study emphasize that finding a biomarker in siblings proves that autism is genetic (and not, for instance, caused by vaccines). This is in fact what attracted me to the paper to begin with. However, this is simply not demonstrated by the paper. Merely having a set of observations inside the head, which seems somehow more deeply biological, does not make the observation more about genes than when the same phenomenon was only observed outside the head!

Putting it another way, The Brain Is Not Made of DNA! (That’s a post by Neuroskeptic on the same paper.)

It is important, however, that autism may include a feature that exists in non-diagnosed individuals and apparently not in the population at large, though this should be confirmed with a larger sample. If siblings of autistic individuals show this neurological “endophenotype” then there must be people out there who have the endophenotype but no close relatives with autism. If so, then the reason that some individuals express diagnosable autism could be investigated. This study thus both broadens the potential expression of an important phenotype and provides an avenue for research in figuring out what it is that causes it, and may encourage a closer look at sibs with and without diagnosed autism.

Spencer, M., Holt, R., Chura, L., Suckling, J., Calder, A., Bullmore, E., & Baron-Cohen, S. (2011). A novel functional brain imaging endophenotype of autism: the neural response to facial expression of emotion Translational Psychiatry, 1 (7) DOI: 10.1038/tp.2011.18

Comments

  1. #1 daedalus2u
    July 13, 2011

    Yes, nothing about this adds any confirmatory weight to the hypothesis that autism is solely genetic.

    This is actually quite expected. Autism is characterized by reduced ability to recognize facial features and expressions, that would have to be manifest in differential activation of different brain regions.

  2. #2 Stevarious
    July 13, 2011

    “Press reports of this study emphasize that finding a biomarker in siblings proves that autism is genetic (and not, for instance, caused by vaccines). This is in fact what attracted me to the paper to begin with. However, this is simply not demonstrated by the paper.”

    But why not? Doesn’t this study confirm – or at least, strongly infer – that vaccines do not cause autism? I mean, it’s not like siblings of autistic children are 20 times more likely to be vaccinated – thanks to the whole anti-vax movement I would imagine siblings of autistic children would actually be LESS likely to be vaccinated. What am I missing? Is it really just ‘correlation not causation’? That doesn’t seem to fit the circumstances.

  3. #3 Greg Laden
    July 13, 2011

    Stevarious, no, I don’t think so. That is quite a strong inference: That the sibling on an autistic kid was not vaccinated because of the anti-vax movement. In fact, that would actually be evidence in favor of vaccines playing a role (“See? The one we vaccinated got the autisim, the one we didn’t, despite having the gene for it, did not!!!”).

  4. #4 daedalus2u
    July 13, 2011

    Stevarious, there are other environmental effects besides vaccines. Casting ever increasing doubt on the vaccine hypothesis does not imply genetic causation.

    It is absolutely known that there are some environmental causes of autism. Thalidomide causes autism, as does valproate and some other anti-epileptic meds when exposed to them in utero. Maternal stress in utero causes autism.

    Autism is a property of a phenotype, not a property of a genotype.

    A lot of the neuroanatomy differences observed in autism are fixed in utero. The number of minicolumns is fixed at ~8 weeks gestation in utero. A larger number of minicolumns is one of the strongest characteristics associated with autism. That number is not something that vaccines can change.

  5. #5 Vince whirlwind
    July 13, 2011

    Parents want to blame something for autism. Some blame vaccines. Some might mis-read this study and blame genes.

    A neurological process more likely to be present in siblings could be genetic, but it also could be a product of their shared environment.

    This study does nothing to indicate which of the two is more likely, but as other studies have failed to find the genetic marker, there is surely a strong case made stronger by this study for blaming the environment.

    Has anybody studied the difference in parenting styles between the autism-affected and non-autism-affected families?

  6. #6 daedalus2u
    July 13, 2011

    Vince, the differences occur in utero. Parenting style is not the cause.

  7. #7 Neuroskeptic
    July 14, 2011

    Good post. See also my post on this paper, and the nice discussion in the comments about just what an “endophenotype” is: http://neuroskeptic.blogspot.com/2011/07/brain-is-not-made-of-dna.html

  8. #8 Greg Laden
    July 14, 2011

    Neuroskeptic! Thanks for that link. I had seen your post but while writing mine could not remember where. Now I will revise and include.

  9. #9 Harold L Doherty
    July 14, 2011

    “Parents want to blame something for autism.”

    Really? As the parent of an autistic son I would like to know what caused his autism. Does that mean I want to find something to blame?

    Is your comment based on any rigorous studies that have been done which establish that parents want to blame something for autism or is it just your personal belief?

  10. #10 Greg Laden
    July 14, 2011

    Harold, not to speak for Vince, but … I think a lot of people believe that parents want to blame bad things that happen to their kids on something as a version of wanting to explain it, and in the case of autism, we have the very loud and misguided anti-vax movement which “blames” autism on big pharma, science, and gummit.

    I think the ‘blame’ – ‘knowledge’ conflation is common but I agree with you that it is incorrect. Finding out what happened and why something happened and what people ultimately mean when they refer to “blame” are pretty different.

    I’ve written a bit about blame and about blame and vaccination, before: http://scienceblogs.com/gregladen/blame/

  11. #11 khan
    July 14, 2011

    Totally anecdotal: Am on spectrum (can’t read expression or emotion for shit); seem to have inherited it from Father.

  12. #12 june conway beeby
    July 16, 2011

    I’m always pleased to find scientific research on mental illnesses. My sense(personal)is that they are all somehow related to genetics. Case in point: Three of my offspring suffer from mental illnesses i.e., a)schizophrenia,(who killed himself when he was 20-years-old)and b)severe manic depression and c)autism. I also have aunts who suffered from mental illnesses, and a sibling who was ill as well but diagnoses were not easy to come by back then. And people were not aware that they were medical illness of the brain that could run in families.

    I look forward to science uncovering the causes and cures for serious mental illnesses to rid my descendants of the awful fear we now must live with.

    Thank you for the work you do.

  13. #13 magster2
    July 19, 2011

    In my family we have what I call “the curse of the firstborn”, a pattern which appears to be in its third generation. Two children are born, the first child has issues ranging from anxiety (including OCD) to ADHD to depression (including bipolar) to socialization difficulties to pervasive developmental disorder, and the second child is fine (in fact, often very successful by most people’s standards). (The pattern has only been broken once, sadly by a child who died of a heart defect.) deadalus2u, I’d love to hear more about the correlation with maternal stress in utero and/or any correlations with birth order.

  14. #14 that lung
    October 14, 2011

    “One of the known symptoms of Autism is for those with the disorder to have difficulty reading facial expressions of other people. A recent study has suggested, however that siblings of those with Autism show a similar lack of activity in the area of the brain that controls empathy. Researchers suggest that this may be a helpful biomarker for identifying the cause of Autism.

    Just this month, Science Daily published an article about this study. Dr. Michael Spencer led this study and says: “The findings provide a springboard to investigate what specific genes are associated with this biomarker. The brain’s response to facial emotion could be a fundamental building block in causing autism and its associated difficulties.”

    Previously, studies have shown that the brains of children with Autism process facial expressions differently than the ‘normal’ brain. This study was the first time that the connection between Autistic children and their siblings. Both show a lack of activity when reading others’ facial expressions. The siblings had no signs of Autism or Asperger’s Syndrome, however they had a lower activity in the areas of the brain that enables us to read facial expressions and controls empathy than those who had no familial connection to Autism.

    The only control that differed in the study was whether the non-Autism sibling had a sibling with Autism, it can possibly indicate that the differences can be due to the gene that causes the child to be at a genetic risk for Autism. How is it though, that only one sibling has Autism and the other doesn’t? It is known that in a family that has one child with Autism, the likelihood of having another child with Autism is 20x higher. However what about these families’ differed to where one child did not develop Autism?”

  15. #15 HFA person
    May 20, 2013

    That’s very familiar. I’m on the ASD spectrum too. When I look at people’s faces, I don’t mirror their expressions but neurotypicals tend to do it. It’s not that I can’t see but rather I just don’t feel it so I won’t mirror it.

    We can’t conclude that ASD is entirely genetic. It’s quite likely that siblings share the same environmental risk factors too.

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