Autism Studies and Related Medical Conditions, January 2009 - TACA

and folate-dependent methionine synthase. Methionine synthase activity is
required for dopamine-stimulated phospholipid methylation, a unique membranedelimited
signaling process mediated by the D4 dopamine receptor that
promotes neuronal synchronization and attention, and synchrony is impaired in
autism. Genetic polymorphisms adversely affecting sulfur metabolism,
methylation, detoxification, dopamine signaling and the formation of neuronal
networks occur more frequently in autistic subjects. On the basis of these
observations, a "redox/methylation hypothesis of autism" is described, in which
oxidative stress, initiated by environment factors in genetically vulnerable
individuals, leads to impaired methylation and neurological deficits secondary to
reductions in the capacity for synchronizing neural networks.
Dolske, M. C., J. Spollen, et al. (1993). "A preliminary trial of ascorbic acid as
supplemental therapy for autism." Prog Neuropsychopharmacol Biol Psychiatry 17(5):
765-74.
1. This study presents the results of a 30-week double-blind, placebo-controlled
trial exploring the effectiveness of ascorbic acid (8g/70kg/day) as a supplemental
pharmacological treatment for autistic children in residential treatment. 2.
Residential school children (N = 18) were randomly assigned to either ascorbateascorbate-placebo
treatment order group or ascorbate-placebo-ascorbate
treatment order group. Each treatment phase lasted 10 weeks and behaviors
were rated weekly using the Ritvo-Freeman scale. 3. Significant group by phase
interactions were found for total scores and also sensory motor scores indicating
a reduction in symptom severity associated with the ascorbic acid treatment. 4.
These results were consistent with a hypothesized dopaminergic mechanism of
action of ascorbic acid.
Evans, T. A., S. L. Siedlak, et al. (2008). "The autistic phenotype exhibits a remarkably
localized modification of brain protein by products of free radical-induced lipid oxidation
" American Journal of Biochemistry and Biotechnology 4(2): 61-72.
Oxidative damage has been documented in the peripheral tissues of autism
patients. In this study, we sought evidence of oxidative injury in autistic brain.
Carboxyethyl pyrrole (CEP) and iso[4]levuglandin (iso[4]LG)E2-protein adducts,
that are uniquely generated through peroxidation of docosahexaenoate and
arachidonate-containing lipids respectively, and heme oxygenase-1 were
detected immunocytochemically in cortical brain tissues and by ELISA in blood
plasma. Significant immunoreactivity toward all three of these markers of
oxidative damage in the white matter and often extending well into the grey
matter of axons was found in every case of autism examined. This striking
threadlike pattern appears to be a hallmark of the autistic brain as it was not
seen in any control brain, young or aged, used as controls for the oxidative
assays. Western blot and immunoprecipitation analysis confirmed neurofilament
heavy chain to be a major target of CEP-modification. In contrast, in plasma
from 27 autism spectrum disorder patients and 11 age-matched healthy controls
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