A Hypothesis to Explain Regressive Autism, by Lord, PhD (Metametrix)

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A Hypothesis to Explain Regressive Autism

Tuesday, 12 October 2010 11:07 by Lord RSS Feed

What is autism?

Many years ago I sat at lunch with three of the foremost practitioners and

researchers in the emerging field of biomedical interventions to cure autism. I

asked them " What is autism? " After a pause of unbelief that I could be so naive,

one of them started to recite the standard string of symptoms. I interrupted her

and said, " I know the ICD9 codes. " I pointed with both index fingers to my

temples and asked again, " What is autism? "

We still don't know the answer to such a simple question about such complex

disorder. But I still think about it, and I have some hunch about certain

aspects of what goes on in the brain of a 12 to 16 month old child that might

lead to the CNS malfunction that is expressed as one of the several version of

what we call " autism. " In order to grasp the molecular level changes, I started

to probe the neurological sciences, and, in a nutshell, here is what I came up

with.

Brain Development

At about one year old, there is a critical stage in brain development that

requires the formation of myelinated neurons. Only then can the speed of

processing incoming sensory signals start to allow the amalgamation of neuron

firings into perception. As perception abilities mature then the full outcome of

awareness is possible. So the bright yellow blob hanging above the cradle

becomes a star that has a shiny surface, and the complex set of colors and

textures that has been appearing regularly becomes mom’s (or dad’s) face.

O.K., so myelination is important. And girls form myelin sheaths far faster than

boys, so they are faster learners than boys in the early going (boys manage to

catch up months later). Now, if something interrupts the myelination process,

then we could have a problem with awareness of the type that appears in the kind

of regressive autism that I will call “typical.†So, what could produce such

an interruption?

Think now of how inflammation affects the brain. The inflammatory cascade causes

the release of interferon gamma, that powerfully stimulates various cells in the

brain to produce quinolinic acid via the kynurenin pathway from tryptophan. Now,

what does quinolinate do?

Quinolinate powerfully agonizes NMDA receptors. Those are in the main neuronal

pathway of the brain, the glutamatergic system. In the extreme scenario of AIDS,

quinolinate goes so high that massive glutamate toxicity is produced causing

neuronal death that ultimately can be the cause of losing the patient. If there

were a sufficiently strong acute inflammatory event in the developing brain of a

12 month old child, then the disruption could be so great as to set up

simultaneous severe oxidative stress and interruption of the neuroplastic

processes working to form new synaptic connections. The disruption probably most

severely affects GABA and dopamine synapse formation. Those are very critical

for those processes of perception and awareness.

Individual Susceptibility

So, the hypothesis entails a specific sequence of events that could answer the

question, “What is (regressive) autism?†But what kind of events would

initiate such disruptions? Before that, however, I must introduce one more

parameter: individual susceptibility. By this, I mean that all children are not

nutritionally or genetically the same. There are subtle genetic factors that

predispose all of us to have above average optimal intakes for one or more

nutrients. Add to that the fact that human nutrition has been going downhill for

the past three generations with regard to:

1. omega-3 fatty acids,

2. trace elements, and

3. intestinal microbial mass diversity to name a few of the obvious

candidates.

And to this class of factors we must add that of toxicant exposures that have

been on the steady increase for a few generations. These factors may be present

singly or in multiples to set the stage for susceptibility to the neuronal

perturbations.

Now the hypothesis can be restated as: regressive autism is produced by an acute

inflammatory event that is unfortunately timed in the neuronal development of a

child who already has predisposition factors of nutrient limitations and

toxicant effects. So what would we guess the inflammatory events might be?

One of two common occurrences can fill in the blank to complete the etiologic

picture. First there is the common viral infection that can hit during the few

months interval critical to brain development. If that does not occur, then

there is the possibility of very strong reaction to vaccination. About 20% of

vaccinated children experience a severe, acute febrile episode that coincides

with the peak of the inflammatory cytokine cascade that is the intended

consequence of immunization. There are many descriptions of such childhood

events that have led directly to the sudden regression to autism.

Now that I have logical conclusion of the sequence of events, remember about the

difference between girls and boys described above? Autism affects far more boys

than girls. The hypothesis answers: of course; their synaptic disruption tends

to be much greater because of the lack of myelination and the correspondingly

greater oxidative stress.

Testing the Hypothesis

There is one immediately obvious way for testing the hypothesis: gather urine

specimens from a large group of children 10 days after they receive immunization

injections. Assay for kynurenin pathway intermediates xanthurenic, kynurenic,

quinolinic and picolinic acids and track the children for the occurrence of

regressive autism. Determine the statistical prediction for the disorder based

on levels of the intermediates. The hypothesis predicts that the incidence will

be higher in the children with upper range quinolinic acid when they are

compared with those with lower levels. An affirmative outcome would raise the

question of which factors most strongly predispose the children to display

elevated quinolinic acid and the autistic regression response. Much of the

current evidence about effects of toxicants, oxidative stress, methylation

pathway disruption and glutathione status may be shown to have importance in

this regard. ~ S. Lord, Ph.D.