Nature: Special issue on neuroscience: The autism enigma

5 Nov

The journal Nature has a special focus issue this week on autism. They introduce the issue in: Special issue on neuroscience: The autism enigma with the subtitle “Diagnoses and research funding are rising, but much about autism remains a puzzle. Nature seeks some truths.”

Articles in the issue include:

The mind’s tangled web (“Efforts to elucidate how genes and the environment shape the development of autism, although making progress, still fall far short of their goal.”)

The prevalence puzzle: Autism counts (“Shifting diagnoses and heightened awareness explain only part of the apparent rise in autism. Scientists are struggling to explain the rest.”)

Scientists and autism: When geeks meet (“Psychologist Simon Baron-Cohen thinks scientists and engineers could be more likely to have a child with autism. Some researchers say the proof isn’t there.”)

Changing perceptions: The power of autism (“Recent data — and personal experience — suggest that autism can be an advantage in some spheres, including science, says Laurent Mottron.”)

and:

Autism’s fight for facts: A voice for science (“Convinced by the evidence that vaccines do not cause autism, Alison Singer started a research foundation that pledges to put science first.”)

With a link to Nature’s autism page: www.nature.com/autism.

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16 Responses to “Nature: Special issue on neuroscience: The autism enigma”

  1. Nightstorm November 5, 2011 at 22:59 #

    I have no idea how I feel about this.

  2. daedalus2u November 6, 2011 at 04:25 #

    I think this is positive. Anything that brings the conceptualization of autism closer to a reality based view is positive.

  3. Shannon November 6, 2011 at 20:55 #

    So scientist DO believe in an epidemic, or at least that there are more and more people with autism than ever before???

  4. RAJ November 10, 2011 at 10:56 #

    Francesca Happe recently gave an invited lecture on accepting a well deserved women in science award. Happe is part of Robet Plomin’s group in the UK which has been studying and have published numerous articles based on all twins born born in the UK and Wales, The Twins Early Developmental Study (TEDS)and includes thousands of twin pairs born between 1994 and 1996.

    http://royalsociety.tv/rsPlayer.aspx?presentationid=1007

    Her lecture echoes the special issue in Nature on the progress in autism research. She states that there are no ‘genes’ that cause autism and there is no specific brain lesion unique to autism and there is no single mediating ’cause’ of autism and autism is not associated with ‘genius’.

    Happe is a behavioral geneticist as are all the members of Plomin’s group. The key concept of behavioral genetics is unravelling which is that auitsm is a genetic heritable condition whose outcome is predetermind at conception and is unalterable. Sir Michael Rutter has gone so far as to state the the behavioral geneticists are on their way to extinction

    The model of genetic determinasm never made sense since it assumes that human beings are the only organism in nature that is exempt from any environmental influences.

    It is an interesting lecture by Happe that echoes th papers published in the special issue on the puzzle of autism in the special issue in Nature’.

  5. Chris November 10, 2011 at 17:46 #

    And in recent news: http://www.medpagetoday.com/Neurology/Autism/29531

    Children with autism appear to have bigger brains with more neurons than normal for their age, a small preliminary study affirmed.

  6. brian November 10, 2011 at 23:05 #

    @Chris

    Eric Courchesne, the first author of the study that you mentioned above, made some interesting remarks in his keynote address at the last IMFAR and in the meeting’s press conference. Chourchesne, who described this premature acceleration of brain growth in 2003, said that the huge excess of neurons seen in the ASD-related brain overgrowth “that has been replicated by a number of independent research laboratories from around the world” clearly implicates prenatal events. He also stated that the evidence

    points strongly to dysregulation of functions that govern [brain development] in the second trimester . . . to very early events that are driving the failure of the normal organization of the brain . . . All these things are being driven by events that are prenatal . . . because there are no known mechanisms for producing such a gigantic difference in neuron numbers postnatally in the human brain.

    A companion paper on gene expression in the postmortem samples from some individuals with ASD should emerge soon. (An associated methods paper was recently published in BMC Genomics.) At IMFAR, Courchesne provided a preview of those results that he believes are related to prenatal overproliferation of neurons:

    What we found is dysregulation of pathways that govern cell numbers, and the functional integrity of cells. To be exact, what we found were pathways that showed dysregulation of the genesis of neurons, dysregulation of the way the cycling of cells that produces more and more neurons operates. Most importantly, we found down-regulation of DNA damage responses, and down-regulation of [programmed cell death].

    Down regulation of DNA damage responses is extremely interesting, because what it suggests is that in the process of cell cycling, not only are too many neurons being generated, but there’s the possibility that neurons that have defective DNA are not detected, and the DNA defect is not corrected — or if it can’t be corrected, it’s sent down a pathway of naturally occurring cell death. In the absence of that process, it’s possible that neurons are being generated that gather DNA defects, and that those defects and those cells are not gotten rid of but are retained, with their DNA defects, and that those DNA defects in turn are generating still more pathology . . . [and] we found down-regulation of a number of genes that regulate the normal neural patterning of the brain.

    David Amaral said at the same meeting that recent work at UC Davis

    confirmed what Dr. Courchesne has been saying for a number of years, that there is this precocious brain growth . . . but in our cohort, which is about 200 children that we analyzed, [precocious brain growth] is most prominently associated with children that have a regressive form of autism; these are the kids that seem to highlight the vaccine issue, because these children have normal development to 12 to 18 months and then lose social ability and lose language function and regress back into autism. But, again, the interesting thing is that even though the precocious brain growth is most associated with these kids who have a regressive form of autism . . . we see that the changes started around 4 to 6 months of life . . . So that despite the fact that the regression, the behavioral regression, takes place at 18 months or 24 months, the brain changes actually started taking place at 4 to 6 months, so it actually casts doubt on the idea that a vaccine, an MMR vaccine, for example, that’s taken at 12 to 18 months would be actually the precipitating factor, because things were starting much, much earlier than that.

  7. brian November 10, 2011 at 23:08 #

    The paragraph in my post above that begins with “Down regulation of DNA damage” was also intended to be a blockquote. That’s also from Courchesne’s keynote speech.

    • Sullivan November 10, 2011 at 23:40 #

      Brian,

      thanks. I think I’ve got it edited correctly now.

  8. passionlessDrone November 11, 2011 at 02:48 #

    Hello friends –

    Nice set of quotes, brian, thank you.

    I haven’t read this one yet, or the complimentary paper(s) but brian seems pretty up to speed on this area, and maybe others lurking are too. So here are a couple of things I was wondering about. Does anyone know if they have been been spoken towards, or speculated towards in this paper / other papers?

    The big one to me is the seeming time dependency of the dysreglation of growth cycle; it has been well documented that accelerated head growth is associated with autism. But it doesn’t seem to keep on increasing past infancy or childhood; wouldn’t we expect to see some rather dramatic differences in head sizes of adults with autism if the rate of overgrowth stayed constant throughout the lifetime with associated physical phenotypes that would have struck out at us a long time ago?

    Secondly, if this type of finding were replicated and found to have a strong predictive value for autism, or regressive autism, or whatever phenotype of autism, this type of expression study might be useful to us in understanding the big question, prevalance. If we could cull similar biomarkers from stored tissue in infants, children and adults from decades past, we might be able to start using useful data on historical rates. There are a lot of hurdles, but that is an exciting thought, IMO.

    Is there any discussion in the papers on the possibility that impaired synaptic pruning could contribute to the increased number of neurons?

    Most importantly, we found down-regulation of DNA damage responses

    Heh. Not a surprise, but nice to see documented here.

    Finally, it was very recently that we determined that new neurons could be born into the adult brain at all, for decades the mantra was that there was no new generation of brain cells in adulthood. The fact that there is currently ‘no known way’ of creaating this large of an excess of neurons after gestation is technically true, but maybe a little caution is warranted if we are going to admit just how little we know about this whole thing. Similarly, while the prenatal environment is no doubt critical, there is no sacred line at the passage from gestation that negates the ability of the environment to affect these very same processes.

    Anyways, I guess I’ll just try to get a copy of the paper, but would be interested in anyones thoughts.

    – pD

  9. brian November 11, 2011 at 03:29 #

    pD,

    Courchesne discussed many of those issues at IMFAR. If you choose to join INSAR you can access an official transcript of his address; however, an unoffical transcript (but free) is available here:

    http://thinkingautismguide.blogspot.com/2011/05/imfar-2011-dr-eric-courchesne-on.html#idc-container

    Courchesne is careful to indicate that there are no known mechanisms to substantial increase (nearly double) the number of cortical neurons postnatally. His paper, of course, reveals the results of his study of the number of cortical neurons, as opposed, say, to those in the hippocampus. Courchesne wrote in this recent paper: “Because cortical neurons are not generated in postnatal life, this pathological increase in neuron numbers in autistic children indicates prenatal causes.”

  10. passionlessDrone November 11, 2011 at 04:03 #

    Hi brian –

    Thanks for the link. Very nicely done by the TPGTA.

    – pD

  11. passionlessDrone November 12, 2011 at 01:58 #

    Hello friends –

    Regarding our knowledge of the ability to increase neuron number in the prefrontal cortex postnatally, this paper,

    Corridors of migrating neurons in the human brain and their decline during infancy

    was published last week. Here is the abstract:

    The subventricular zone of many adult non-human mammals generates large numbers of new neurons destined for the olfactory bulb. Along the walls of the lateral ventricles, immature neuronal progeny migrate in tangentially oriented chains that coalesce into a rostral migratory stream (RMS) connecting the subventricular zone to the olfactory bulb. The adult human subventricular zone, in contrast, contains a hypocellular gap layer separating the ependymal lining from a periventricular ribbon of astrocytes. Some of these subventricular zone astrocytes can function as neural stem cells in vitro, but their function in vivo remains controversial. An initial report found few subventricular zone proliferating cells and rare migrating immature neurons in the RMS of adult humans. In contrast, a subsequent study indicated robust proliferation and migration in the human subventricular zone and RMS. Here we find that the infant human subventricular zone and RMS contain an extensive corridor of migrating immature neurons before 18 months of age but, contrary to previous reports, this germinal activity subsides in older children and is nearly extinct by adulthood. Surprisingly, during this limited window of neurogenesis, not all new neurons in the human subventricular zone are destined for the olfactory bulb–we describe a major migratory pathway that targets the prefrontal cortex in humans. Together, these findings reveal robust streams of tangentially migrating immature neurons in human early postnatal subventricular zone and cortex. These pathways represent potential targets of neurological injuries affecting neonates. (my emphasis)

    Cautious approach to the limits of our knowledge win!

    – pD

  12. RAJ November 12, 2011 at 14:14 #

    One has to careful in interpreting the Courchesne paper on increased number of neurons in the brain. The seven brains studied all were associated with the most severe cases of auitsm. None of the seven cases had been diagnosed with PDD/NOS or Asperger Syndrome.

    Large head size (megalencephaly) has been consistently demonstrated in 20% of cases and around 20% of cases demonstrate small head size (microencephaly). Sixty percent of autistic children have head size in the normal range.

    Furthermore it isn’t clear how large head size is associated with autism. Ghazzudian et al examined headsize in recruiting twenty children diagnosed with autism and 20 childen diagnosed with ADHD. Four of the twenty children with autism demonstrated large head size which is 20% consistent with most reports of large head size in the literature. Five of the twenty children diagnosed with ADHD demonstrated large head size which is 25% of the ADHD group. All four of the autistic group with large head size were hyperactive and impulsive suggesting that large head size in autistic children may be associated not with autism but rather with co-occurring ADHD:

    http://www.ncbi.nlm.nih.gov/pubmed/10466865

  13. brian November 12, 2011 at 16:46 #

    Some may be interested in this PowerPoint presentation of work from Courchesne’s group, including the material that will by published by Chow, Pramparo, et al. on the gene expression and tissue development studies of the same post-mortem brain samples that were studied in Courchesne’s most recent article.

    http://autismus-kongress.de/media/Vortraege_2011/Attentional%20processing%20at%20the%20cellular_Courchesne.pdf

    The abnormal growth trajectory discussed here has apparently resulted in mixed results, since the brain size varies with the age distribution of the sample. Courchesne addressed this issue several years ago:

    http://www.ncbi.nlm.nih.gov/pubmed/15935993

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