December 10, 2010 2 Comments
Mitochondria are the powerhouses of the cell, the biology teachers will tell you. These organelles also happen to be likely former bacteria that once were independently living cells, capable of dividing on their own to make new mitochondria. Indeed, they continue to divide by a kind of binary fission as our cells divide, ensuring that a double dose is available for partitioning into the two new cells that result from cell division.
To achieve these feats, mitochondria have their own DNA, their own proteins, and their own protein-making machinery. That means that they also have the potential to undergo genetic mutations that affect the sequence of the proteins their genes encode. Because most of the proteins in mitochondria are mission critical and must function exactly right, the persistence of such mutations is relatively rare. But they do happen, causing disease. One question that has arisen in the study of the causes of autism is whether or not such changes might underlie at least a portion of the cases of this developmental difference.
The high-profile Hannah Poling case
Certainly lending a high profile to this question was the case of Hannah Poling, whose mitochondrial disorder appeared to be linked to her autism symptoms and may have interacted with a bolus of vaccine doses she received, followed by a high fever. Fevers can tax our cellular powerhouses, and if mitochondrial function is already compromised, the high temperatures and extra burden may result in chronic negative outcomes.
Poling’s case brought to the forefront the question of whether or not people with autism might have mitochondrial dysfunction at greater rates. A recent study in the Journal of the American Medical Association (which steadfastly keeps its articles unavailable behind a paywall) has sought to address that question by measuring markers of mitochondrial dysfunction in children with autism and comparing these endpoints with outcomes in children without autism.
Study specifics: “Full-syndrome autism”
The autistic group in the study had what the researchers called “full syndrome autism,” which I take to mean intense symptoms of autism. They used the Autism Diagnostic Inventory-Revised
(ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) to confirm this diagnosis and to ensure as uniform a population among their autistic group as possible. Ultimately, the study included 10 children in this group, recruited consecutively in the clinic based on their fulfillment of the selection criteria. This study was essentially case control, meaning that the control group consisted of 10 non-autistic children, selected to match as closely as possible the demographic characteristics of the autistic group.
The authors report that while only one child among the 10 who were autistic fulfilled the definitive criteria for a mitochondrial respiratory chain disorder, the children with autism were more likely to have indicators of mitochondrial dysfunction.
A problem with pyruvate dehydrogenase (break out your Krebs notes, folks)
Specifically, six out of ten showed lowered levels of activity for one parameter, while eight out of ten showed higher levels than controls for another metabolic endpoint, and two of ten showed higher levels than controls of a third metabolic endpoint. Overall, the results indicated low activity of a mitochondria-specific enzyme, pyruvate dehydrogenase, which is involved in one of the first steps of carbohydrate metabolism that takes place in the mitochondria. Reduced activity of an enzyme anywhere in this process will result in changes in the enzyme’s own products and products further down the pathway and throw off mitochondrial function. Further, half of the autistic group exhibited higher levels of DNA replication, an indicator of cellular stress, more frequently than controls and also had more deletions in their DNA than controls. Statistical analysis suggested that all of these differences were significant.
What does it mean for autism?
Do these findings mean that all or most people with autism have mitochondrial dysfunction? No. The study results do not support that conclusion. Further, the authors themselves list six limitations of the study. These include the possibility that some findings of statistical significance could be in error because of sample size or confounders within the sample and that there were changes in some of the endpoints in the autistic group in both directions. In other words, some autistic children had much higher values than controls, while some had lower values, muddying the meaning of the statistics. The authors note that a study like this one does not allow anyone to draw conclusions about a cause-and-effect association between autism and mitochondria, and they urge caution with regard to generalizing the findings to a larger population.
If there is an association, questions arise from that conclusion. Does mitochondrial dysfunction underlie autism, producing autistic-like symptoms, as some argued in the Hannah Poling case? Or, do autistic manifestations such as anxiety or high stress or some other autism-related factor influence the mitochondria?
Chickens, eggs, MRI, mitochondria, autism
As interesting as both of these recent autism-related studies are, we still have the “Which came first” question to deal with. Did autism cause the brain or mitochondrial differences, or did the brain or mitochondrial differences trigger the autism? Right now, these chicken-and-egg questions may not matter as much as the findings do for helping to identify autism more specifically and addressing some of its negative aspects. Regardless of your stance on neurodiversity or vaccine or acceptance or cure or the in-betweens where most of us fall, it would be difficult to argue that a mitochondrial dysfunction shouldn’t be identified and ameliorated or that an awareness of brain structure differences won’t lead to useful information about what drives autism behaviors.