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Differences in White Matter Fiber Tract Development Present From 6 to 24 Months in Infants With Autism

Posted Feb 23 2012 1:00am

If you watch for autism related news stories you likely have seen multiple stories on a paper out Friday in the American Journal of Psychiatry: Differences in White Matter Fiber Tract Development Present From 6 to 24 Months in Infants With Autism (full paper available online). The researchers studied brain structure in children and compared those who went on to be diagnosed with autism to those who did not. They found differences in white matter between the two groups. In particular fiber tracks were different.

Here’s figure 1 ( click to enlarge ) from the paper to give you an idea of what they mean by fiber tracks. Check the brain cartoons on the right. Then check the actual data in the graphs. These are “significantly different” trajectories for these measurements. They are not clear differences that could lead to a diagnostic tool.

Here is the abstract:


Evidence from prospective studies of high-risk infants suggests that early symptoms of autism usually emerge late in the first or early in the second year of life after a period of relatively typical development. The authors prospectively examined white matter fiber tract organization from 6 to 24 months in high-risk infants who developed autism spectrum disorders (ASDs) by 24 months.

The participants were 92 high-risk infant siblings from an ongoing imaging study of autism. All participants had diffusion tensor imaging at 6 months and behavioral assessments at 24 months; a majority contributed additional imaging data at 12 and/or 24 months. At 24 months, 28 infants met criteria for ASDs and 64 infants did not. Microstructural properties of white matter fiber tracts reported to be associated with ASDs or related behaviors were characterized by fractional anisotropy and radial and axial diffusivity.

The fractional anisotropy trajectories for 12 of 15 fiber tracts differed significantly between the infants who developed ASDs and those who did not. Development for most fiber tracts in the infants with ASDs was characterized by higher fractional anisotropy values at 6 months followed by slower change over time relative to infants without ASDs. Thus, by 24 months of age, those with ASDs had lower values.

These results suggest that aberrant development of white matter pathways may precede the manifestation of autistic symptoms in the first year of life. Longitudinal data are critical to characterizing the dynamic age-related brain and behavior changes underlying this neurodevelopmental disorder.

If the idea of differences in fiber tracks seems somewhat famiiliar, last year Eric Courchesne at UCSD reported at IMFAR about
Abnormally Accelerated Development of Higher-Order Long-Distance Cerebral Tracts In ASD Infants and Toddlers . The paper was highlighted at the IMFAR press conference (and discussed here at Left Brain/Right Brain .

At the press conference David Amaral mentioned similar work at the IMFAR press conference last year.

At 51:20 in the video above, Prof. Amaral speaks on the work that precocious brain growth at 4-6 months of age in infants and is most prominently present in children with regression.

“..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 a doubt on the idea that a vaccine, the 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.”

The talk that Prof. Amaral was speaking about was Total Cerebral Volume Is Associated with Onset Status In Preschool Age Children with Autism.

C. W. Nordahl1, A. Lee1, M. D. Shen1, T. J. Simon1, S. J. Rogers1, S. Ozonoff2 and D. G. Amaral1, (1)Psychiatry and Behavioral Sciences, UC Davis M.I.N.D. Institute, Sacramento, CA, (2)Psychiatry and Behavioral Sciences, M.I.N.D. Institute, UC Davis, Sacramento, CA
Background: Autism is a heterogeneous disorder, and multiple behavioral and biological phenotypes likely exist. One well-characterized behavioral phenotype is onset status. While some children with autism exhibit symptoms very early in life, others experience a regression or loss of previously acquired skills. There is currently very little known about the neural substrates associated with these two different behavioral trajectories in autism.

Objectives: We examined the relationship between total brain volume and onset status in a large sample of 2-4 year old children with autism spectrum disorder (ASD) (n = 48, early onset, n = 58, regression) and a comparison group of age-matched typically developing children (TD) (n = 55).

Methods: Diagnoses and autism severity were based on ADOS and ADI-R scores and clinical judgment by trained, experienced psychologists. Developmental quotients (DQ), verbal quotients (VQ) and nonverbal quotients (NVQ) were based on the Mullen Scales. Onset status was categorized based on parent reports from related ADI-R questions. Total cerebral volume was compared between autism onset groups as well as relative to age-matched typically developing controls. Autism severity and DQ were also evaluated in relation to brain volume and onset status.

Results: Children who exhibited regression had significantly larger total brain volumes than children with early onset autism (p = .004). Total brain volume in the early onset ASD group did not differ from the TD group, whereas total brain volume was significantly larger in the children with regression. Moreover, children with regression had significantly lower VQ (p = .03) and higher (i.e. more severe) ADOS social and communication scores (p = .02). Total brain enlargement remained significant even after controlling for these variables. There were no significant correlations between total brain volume and VQ or ADOS scores.

Conclusions: Total brain enlargement has been reported in children with autism under the age of five. However, behavioral associations with abnormal brain enlargement have not been fully explored. Our findings suggest that abnormal brain enlargement in autism is associated with a parent-reported regressive pattern of onset and more severe symptoms involving both developmental impairment and ASD severity.

The idea that autism, even regressive autism, has signs as early as 6 months is challenging to some groups on two levels. First the idea that autism involves physical differences in the brain. Second that these differences are present well before regression, or well before vaccines which are sometimes proposed as precipitating events.

The study itself has limitations, one being generalizability. It makes a lot of sense to monitor siblings of autistics since the recurrence risk is high and the chances of collecting data on autistics is higher than in the general populaiton. However, this leaves us with the question: are the types of autism found in siblings (familial autism) representative of all forms of autism?

  1. Harold L Doherty:
    "Second that these differences are present well before regression, or well before vaccines which are sometimes proposed as precipitating events." Really? Aren't vaccines administered to pregnant women? Do some vaccine ingredients cross the placental barrier?
  2. MikeMa:
    Next up: The vaccine that travels back in time! Interesting addition to the already huge and growing pile of evidence pointing away from vaccines as a cause for autism.
  3. Autism Blog – Differences in White Matter Fiber Tract Development … | My Autism Site | All About Autism:
    [...] Read more from the original source: Autism Blog – Differences in White Matter Fiber Tract Development … [...]
  4. Natasa:
    If confirmed/replicated etc findings like these would confirm my suspicion that the main insult in most cases happens very early in life. Prenatal infection and placental pathology seem to be crucial. Placental infection and/or inflammation is already highly suspect as behind autism (and has been partially confirmed - raised cytokines and other markers have been found in kids who later regressed). Very promising area of research imo, especially in terms of prevention and early treatment. Amniotic fluid inflammatory cytokines: Potential markers of immunologic dysfunction in autism spectrum disorders Exposure to prenatal inflammation is a known risk factor for long term neurobehavioral disorders including cerebral palsy, schizophrenia, and autism. Models of systemic inflammation during pregnancy have demonstrated an association with an immune response an adverse neurobehavioral outcomes for the exposed fetus. Yet, the most common route for an inflammatory exposure to a fetus is from intrauterine inflammation as occurs with chorioamnionitis... Interesting case study was published recently - mum had active CMV infection during pregnancy – only one of the triplets got infected and later developed autism. The placenta and amniotic fluid of that child showed clear pathology and presence of CMV, which was absent in other two placentas. It would also tie in neatly with further regressions kids go through vaccination, natural infections, exposure to allergens etc. This is because prenatal immune insult (either as direct infection or through maternal immune activation) dysregulates the immature immune system and makes it less able to fight off infections and more prone to inflammatory 'over-reaction' later on. Perfect fit to what we see in autism.
  5. Natasa:
    P.S. imo no need for the dualistic 'either-or' attitude here, as both early insult/signs of autism AND later regression following vaccination are perfectly compatible! Early immune/inflammatory insult can easily lead to brain findings such as above, while it would at the same time leave the immune system in a proinflammatory/overreactive state, but less able to fight and permissive to chronic infections. Triggers such as vaccines would lead to more circulating cytokines etc (not to mention the permissiveness ofimmune system to 'weakened' viruses) leading to more microglial reactivity, neurotransmitter imbalances etc ==== more symptoms of autism.

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