View Full Version : Possible link between mtDNA and autism

05-12-10, 19:18
Autism is one of the most common and yet one of the least understood psychological disorders. Genetic inheritance, testosterone levels in the womb, environmental factors, brain damage, and even measles vaccinations have all been implicated, but none is sufficient alone to cause autism. Here is another clue from mitochondrial DNA that may explain some cases of autism.

Explaining autism - Energy drain : The cause of autism may be faulty mitochondria (http://www.economist.com/node/17626864?story_id=17626864&fsrc=rss)

One suggestion that does pop up from time to time is that the process which leads to autism involves faulty mitochondria. The mitochondria are a cell’s powerpacks. They disassemble sugar molecules and turn the energy thus liberated into a form that biochemical machinery can use. Mitochondrial faults could be caused by broken genes, by environmental effects, or by a combination of the two.
Dr Giulivi found that mitochondria from children with autism consumed far less oxygen than those from the control group. That is a sign of lower activity. One important set of enzymes—NADH oxidases—used, on average, only a third as much oxygen in autistic children as they did in non-autists, and eight of the autistic children had significantly lower NADH-oxidase activity than is normal.

The mitochondria of the autistic children also leaked damaging oxygen-rich chemicals such as hydrogen peroxide. These are a normal by-product of mitochondrial activity, but are usually mopped up by special enzymes before they can escape and cause harm—for instance, by damaging a cell’s DNA. The level of hydrogen peroxide in the cells of autistic children was twice that found in non-autists. Such high levels suggest the brains of autistic children are exposed to a lot of oxidative stress, something that would probably cause cumulative damage.

And here is the original article from the Journal of the American Medical Association Mitochondrial Dysfunction in Autism (http://jama.ama-assn.org/content/304/21/2389.abstract)

The mutations involved are unfortunately not mentioned in the abstract.

08-12-10, 16:06
One of the many risk factors I would say...I wonder if the so-called arctic and mtdna's harboring mutations affecting OXPHOS/ATP production for heat production would be over represented in ASD cases?
"mtDNA Mutations May Permit Adaptation to Changes in Diet and Climate. mtDNA variation would be the ideal method to foster adaptation to different environments. Mitochondrial oxidative phosphorylation (OXPHOS) uses dietary calories to generate ATP to do work and heat to maintain body temperature. The balance between these two functions is determined by the efficiency of coupling the mitochondrial inner membrane electrochemical gradient to synthesize ATP through the ATP synthase. Variants that reduce the coupling efficiency would reduce ATP production, but increase heat production. Such variants would be advantageous in the subarctic and arctic where survival of cold stress would be a major factor in survival. Partial uncoupling of the mitochondria would increase the basal metabolic rate of the individual and hence would require a higher caloric intake, such as that provided by a high-fat diet. Thus, mtDNA ATP6 variants that reduce coupling might partially account for the increased basal metabolic rate that has been observed in indigenous, circumpolar, human populations (29)."
All this heat production comes at a cost though:
"...efficiency of OXPHOS ATP production and thus exacerbate the energy defects of mildly deleterious new mutations."
They list the mtdna's by climate:
L0–L3 tropical and subtropical zones
H, V, U, J, T, I, X, N1b, and W temperate zones
A, C, D, G, Z, Y, and X arctic and subarctic
J and U5a have mutations that affect ATP production and make them susceptible to quicker disease progression, such as HIV:
The AIDS progression article gives some interesting implications for uncoupled (arctic, J, U5a) vs. highly coupled (H3 and H4, H5, and H6) groups. Makes me wonder if other mutations of the mtdna such as the deletions and insertions in your article could be made worse by certain haplogroups propensity to be uncoupled?
Me and my J1c3 cousin both have a son with ASD...????

19-07-12, 09:05
Here is another study (http://www.ncbi.nlm.nih.gov/pubmed/14722523) linking mtDNA defects to autism. It mentions A3243G, a mutation not listed in any known mtDNA haplogroup or subclade (http://www.phylotree.org/tree/main.htm) to date.

24-10-12, 06:29
You know, I have been diagnosed with Autism as well as most of my Biological cousins, my older half Brothers have been diagnosed with Autism as well and my Biological Dad and uncles have Bipolar. My Direct maternal side has Depression going back to five generations, is there some sort of trigger when two depression genes meet? Do other people with Autism have a similar family medical history? I have a feeling that there is more to it than the X chromosome.

02-03-14, 13:18
New evidence that dietary supplementation with vitamin D could help treat autism.Genetic research has shown that vitamin D hormone activates a gene which produces an enzyme leading to higher levels of serotonin (Patrick & Ames, 2014).
You can read more on http://www.spring.org.uk/2014/03/autism-vital-link-found-between-vitamin-d-and-serotonin-production.php

02-03-14, 19:46
Interesting to say the least. Can't wait for their deeper research and final conclusions.

06-04-14, 05:34
Okay, my mtdna is J1c7a. I know that I have plenty cousins on my paternal side with Autism so there must be a different gene.