Proton Magnetic Resonance Spectroscopy and MRI Reveal No Evidence for Brain Mitochondrial Dysfunction in Children with Autism Spectrum Disorder.

16 Mar

A study published today looks for mitochondrial dysfunction in autistic children. In specific, the researchers are looking directly at the brains of autistic children. The team, from the University of Washington, used both MRI (Magnetic Resonance Imaging) and proton magnetic resonance spectroscropic imaging (HRMS). MRI gives structural information on soft tissues. HMRS is a “spectroscopic” techinque: it gives chemical information on
Here’s a good reference with a discussion of HMRS on brain tissue (as a spectroscopy, not an imaging technique): Quantitative neuropathology by high resolution magic angle spinning proton magnetic resonance spectroscopy

With that background in hand, here is the abstract from the recent study on autism:

Proton Magnetic Resonance Spectroscopy and MRI Reveal No Evidence for Brain Mitochondrial Dysfunction in Children with Autism Spectrum Disorder.

Corrigan NM, Shaw DW, Richards TL, Estes AM, Friedman SD, Petropoulos H, Artru AA, Dager SR.

Department of Radiology, University of Washington, Seattle, WA, USA.
Abstract

Brain mitochondrial dysfunction has been proposed as an etiologic factor in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopic imaging ((1)HMRS) and MRI were used to assess for evidence of brain mitochondrial dysfunction in longitudinal samples of children with ASD or developmental delay (DD), and cross-sectionally in typically developing (TD) children at 3-4, 6-7 and 9-10 years-of-age. A total of 239 studies from 130 unique participants (54ASD, 22DD, 54TD) were acquired. (1)HMRS and MRI revealed no evidence for brain mitochondrial dysfunction in the children with ASD. Findings do not support a substantive role for brain mitochondrial abnormalities in the etiology or symptom expression of ASD, nor the widespread use of hyperbaric oxygen treatment that has been advocated on the basis of this proposed relationship.

Does this mean that mitochondrial dysfunction never occurs in autistics? No. But it makes it very unlikely that more than a fraction of autistics have mitochondrial dysfunction in their brains.

Beyond that, the use of spectroscopic imaging is very impressive to me. MRI structural data is quite valuable on its own, but adding chemical information is very powerful.

15 Responses to “Proton Magnetic Resonance Spectroscopy and MRI Reveal No Evidence for Brain Mitochondrial Dysfunction in Children with Autism Spectrum Disorder.”

  1. sharon March 17, 2011 at 07:10 #

    This is interesting and continues on the pattern of studies raising more questions than answers. I wonder if anyone knows when these studies are undertaken do they differentiate children born ASD from those with the regressive type?

  2. Neuroskeptic March 17, 2011 at 16:04 #

    Hmm…I’m having trouble accessing the full text (has anyone managed to?) and from the abstract it’s not clear what they actually did. What is an MRI or MRS measure of mitochondrial dysfunction? How sensitive is it? Does it reliably detect mitochondrial dysfunction in people who verifiably do have it?

    Until we know that, it’s hard to interpret this.

  3. daedalus2u March 17, 2011 at 18:50 #

    I haven’t seen the full text either, but MRS is magnetic resonance spectroscopy is used to measure the specific chemical environment of specific protons and so can tell how much of which type are present. What is important in mitochondrial disorders is what the ATP level is. That can be measured with MRS by looking at the protons that are on the phosphates of ATP. You can also measure pH.

    If the ATP levels in the brains of people with ASDs are “the same” as in the brains of people who are NT, that is very good evidence that the mitochondria in both are behaving “the same” and that there are no mitochondrial disorders.

    If there were mitochondrial disorders in ASDs, then you would expect to see reductions in ATP levels.

    MRI is magnetic resonance imaging and looks (mostly) at the distribution of the mobility of protons, are the protons attached to something, or are they free to move and if they move, in what directions and how fast. That can look at structures that hold moving fluids, like blood vessels, and also axons which have a large aspect ratio (long but not wide) so the diffusion inside them is anisotropic. CSF in the spaces between the different parts of the brain has pretty much isotropic diffusion so it shows up pretty easily. MRI looks at the contrast between those things and that contrast shows up as outlining the physical structures of the brain.

  4. Catherina March 17, 2011 at 18:57 #

    if you want to email me at catherinajtv at gmail dot com I have the full text.

  5. Catherina March 17, 2011 at 19:12 #

    whoops, strike that, I don’t have that paper (had clicked on the older paper link) – could not edit post.

  6. Science Mom March 17, 2011 at 19:34 #

    This was an e-pub ahead of print and is not in the April issue so perhaps next issue.

    • Sullivan March 18, 2011 at 02:16 #

      I should have waited for the paper to come out before blogging. There isn’t enough in the abstract to say if this is a good or bad study. But the technique really intrigues me.

      • Sullivan March 18, 2011 at 02:17 #

        I should go on. Anyone familar with NMR itself would see it as a spectroscopic method. But I have to admit I wasn’t aware of the method of spectroscopic imaging. I am clearly showing ignorance here, I know. But this is very cool.

  7. David N. Brown March 18, 2011 at 07:21 #

    The name for the equipment sounds like something out of a science fiction story- and, given that the mitochondrial issue only seems to have come up because of one case, taking a howitzer to a fly. And that got me thinking, by free association, of a scene in one of my “exotroopers” stories, in which three of the guys manhandle an energy weapon up a flight of stairs. Best gag:
    “What happens if this thing overheats?”
    “You tell me, you read the manual!”

  8. RAJ March 18, 2011 at 13:06 #

    Caution has to be exercised in considering interpretations of MRI,fMRI or proton magnetic resonance spectroscropic imaging. There is an emerging consesus that autism involves a disruption of pre-programmed neuronal migration and the establishment of aberrant synaptic connectivity.

    Aberrant synaptic connectivity is a microscopic anomoly and MRI,fMRI and proton magnetic resonance spectroscropic imaging is not capable of examining microscopic anomolies. It can observe, at a higher level, brain structure but it can only infer underlying microscopic anomolies.

    Studying post mortem brain tissues under the electron microscope is the only method that can detect microscopic anomolies and this especially so with respect to examining microscopic synaptic connectivity.

    Examining brain tissue under the electron microscope has identified an association between mitochondrial electron transport chain (ETC) complexes in the brain in autism subjects.

    http://www.ncbi.nlm.nih.gov/pubmed/21250997

  9. daedalus2u March 19, 2011 at 22:46 #

    I found this good article on neuroimaging in mitochondrial disorders. It discusses both MRI and MRS.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2600593/?tool=pubmed

    It would be pretty easy to tell if there were major mitochondrial difficulties in autistic individuals.

    RAJ, this article was about mitochondrial disorders, not synapse formation disorders. Not too long ago, there was a hysterical meme that all autism was mitochondrial in nature and that vaccines caused the mitochondrial disorder. The article shows that there is no detectable level of mitochondrial disorders in this set of autistic individuals.

  10. Catherina March 20, 2011 at 00:26 #

    wrote to the author who says he does not have the pdf yet himself…

  11. passionlessDrone March 21, 2011 at 14:00 #

    Hello friends –

    I read the paper that daedulus2u posted, at least the parts of it that I understood. It occurs to me that what we might be witnessing regarding the seeming different findings between this and Chauhan is the difficult to define difference between mitochondrial disease and mitochondrial disorder.

    Most of the patients and conditions described in the spectroscopy study could be characterized as degenerative; something you generally don’t use to descibe autism. The paper did describe the ability to recognize electron chain transport problems, though I’m not clear if the levels of impariment (40-60% depending on patient and chain in Chauhan), could be detected by the spectroscopic method defined. (?)

    I think that the findings from Brain region-specific deficit in mitochondrial electron transport chain complexes in children with autism may hint towards the difference; the regional specificity of electron chain transport problems observed in autism speak against global failure (at least in the CNS), and thus, against maternally inherited genetic problems, and more towards environmentally induced problems. The specific regions that Chauhan reported ECT problems have also been areas with immune activation observed in the autism cohort; perhaps the ongoing immune response, and correspoding ROS is playing a part in the region specific findings in Chauhan.

    Did anyone understand enough of the paper that daedulus2u posted to tell us if the processes in use could detect regional problems in electron chain transport?

    – pD

  12. daedalus2u March 21, 2011 at 16:37 #

    pd, the Chauhan study is very small, there were 5 subjects in their group A. Why the subjects were divided into two groups when the total population is so small is not clear from the abstract. I would have to see the whole study to be able to comment in depth, but I am concerned with the number of comparisons being made and whether the subjects were divided into two groups before, or after looking at the data. If they were looked at as one group, the results would not be significant.

    I would not expect mitochondrial difficulties to get better with age, they should get worse from everything we know about mitochondria. The different complexes do different things. Changes in different complexes imply different mechanisms.

    I don’t think that inferences can be made from this paper as to a role of mitochondria in autism.

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