Features of autism

29 Mar

I was planning on writing something about this for the 1 year anniversary of when the Department of Justice concession to Hannah Poling was leaked.

Why wait until now? Because it was basically impossible to discuss this last year. Immediately after the leak, the phrase “features of autism” was made into a running joke. The vaccines-cause-autism people all made great fun of how the government coined the phrase, presumably to avoid using the simple word, autism.

Anyone want to go back and look at the document now? Search for the word “features”.

First hit:

Dr. Zimmerman observed that [Hannah Poling] watched the fluorescent lights repeatedly during the examination and would not make eye contact. Id. He diagnosed [Hannah Poling] with “regressive encephalopathy with features consistent with an autistic spectrum disorder, following normal development.”

Note that that’s in quotes: “features consistent with an autistic spectrum disorder”. That’s right, Andrew Zimmerman, Hannah Poling’s own neurologist used the phrase “features of autism” about her, long before the Department of Justice ever did.

This is the same Andrew Zimmerman who submitted an expert report on Hannah Poling. This is the same Andrew Zimmerman who wrote an expert report, for the government side, in the Autism Omnibus Proceeding.

Not the only place “features” is mentioned in the Rule 4(c) report, either:

Second Hit:

[Hannah Poling] was evaluated by Alice Kau and Kelley Duff, on May 16, 2001, at CARDS. Pet. Ex. 25 at 17. The clinicians concluded that [Hannah Poling] was developmentally delayed and demonstrated features of autistic disorder.

So, why is it surprising that the Department of Justice would write:

In sum, DVIC has concluded that the facts of this case meet the statutory criteria for demonstrating that the vaccinations [Hannah Poling] received on July 19, 2000, significantly aggravated an underlying mitochondrial disorder, which predisposed her to deficits in cellular energy metabolism, and manifested as a regressive encephalopathy with features of autism spectrum disorder.

That’s the third place that “features” is used in the concession document. But, hey, it isn’t funny to talk about Hannah Poling’s own specialists describing her as having “features” of an autistic spectrum disorder.

It is very easy to make more out of this than is warranted by the scant information we have available. We don’t know what is in the rest of the documents that were provided as part of the case. What we do know is that the U.S. government did not create the phrase “features of autism” to describe Hannah Poling.

66 Responses to “Features of autism”

  1. Sullivan April 8, 2009 at 05:03 #

    But the larger point is, there are a great number of studies on having an activated immune system in the brain outside of what Pardo and Zimmerman have authored.

    1) I understood your point

    but

    2) You act as though Pardo and Zimmerman are unaware of the information you are providing. Sounds like a bad assumption.

    All of these studies post date the Pardo paper by several years.

    Not a good measure, is it? Why not compare to the date that the Pardo letter was written? May 13, 2008.

    Let’s see–you cite what appears to be a review paper by someone in Ukraine from 2008. Likely not new information that Pardo wouldn’t have known.

    You cite a paper from 2007. Obviously, Pardo had access to this.

    Then you cite a paper from 2008, which doesn’t really make a clear case that the neuroinflamation observed by Pardo and Zimmerman is damaging or causative in autism.

    What you are doing is demonstrating the exact thought process that leads to much harm in the autism community. You are connecting dots with very qualitative reasoning, but not admitting that your conclusions are merely hypotheses (at best). Hypotheses are OK–right up to the point that people start treating people based on the hypotheses. Also, when people go beyond hypotheses into the realm of being just plain wrong in order to support the idea that vaccines cause autism, the pseudo-logic is quite damaging.

    Pardo made a couple of very clear statements which are very damaging to the idea that vaccines cause autism–the neuroinflamation is not caused by toxicity nor is it caused by an infectious agent.

  2. Joseph April 8, 2009 at 19:55 #

    Out of curiosity, in these studies of pro-inflammatory cytokines, has psychological stress been controlled for? It looks like psychological stress tends to increase levels of TNF-?, IL-6, etc. See, for example, this.

  3. passionlessDrone April 8, 2009 at 20:15 #

    Hi Joseph –

    As far as I know, pyschological stress was not controlled for in any of these. It would seem to be relatively straightforward to concurrently measure cortisol, atch, or crh. It seems possible that the lack of such controls is the result of what Prometheus says, the first step is figuring out how common is actually is; then trying to descrambe the cause(s).

    Indeed, it wouldn’t suprize me to find that increased levels of stress could be a component in many cases. If LoftMatt were around, I’m sure that he could give us a voluminous source of references regarding the effect of psychological stress and it’s capacities to generate a wide range of physiological findings in autism.

    Here is a great one he pointed out to me on another site:

    Glutathione Depletion, Lipid Peroxidation and Mitochondrial Dysfunction Are Induced by Chronic Stress in Rat Brain

    I’d say that pretty much hits some sweet spots for autism!

    There are bunches, bunches more, but it will take me a while to dig them up.

    – pD

  4. dr treg April 8, 2009 at 21:27 #

    As well as affecting cytokine levels stress also affects the structure of dendrite spines i.e. the length and density of dendrite spines.
    http://www.sciencedaily.com/releases/2008/03/080311182434.htm

  5. Loftmatt April 9, 2009 at 04:23 #

    pD, I am out here. Just time deprived. Below is some text I have consolidated from a good article named Stress, Inflammation, and Hypertension on the acute phase response. I will add cites tomorrow on my favorite topic.

    Not surprisingly, most of the research on the effects of stress on blood pressure and cardiovascular disease has focused on the sympathetic nervous system, but there is another component of the stress response that may be relevant. This is the inflammatory or acute-phase response, which is switched on more gradually than the sympathetic nervous system and the HPA axis, but which is also partly under the control of the central nervous system. The function of this response may be to aid the healing of wounds inflicted during the fight and flight response by activating both the blood clotting cascade and the inflammatory response. It also serves as a defense against what the body regards as intruders, such as bacteria.

    The acute-phase response is mediated by cytokines (chemical messengers of the immune system), which are proteins and peptides produced in cells throughout the body, including in the liver, endothelium, fat cells, and brain. The cytokine that has attracted the most interest in the study of cardiovascular disease is C-reactive protein (CRP). Produced in the liver, CRP is a major player in the acute-phase response. While CRP levels increase during acute inflammatory responses such as with infections, the finding of slightly high levels in patients with cardiovascular disease, and its predictive value for events, was the trigger for the surge of interest in this field. The main inducer of the response, however, is another important pro-inflammatory cytokine, interleukin 6 (IL-6). When subcutaneously administered to humans, IL-6 provokes an acute-phase response, which is associated with an increase in CRP level. Thus, the levels of CRP and IL-6 are closely correlated, whereas other cytokines are not. IL-6 largely comes from macrophages, which, when activated, not only release IL-6, but also other cytokines such as IL-1 and tumor necrosis factor ? (TNF-?), both of which also stimulate CRP release. Evidence for a causal role of IL-6 comes from the observation that IL-6 knockout mice are unable to generate a normal acute-phase response.

    The acute-phase response is also an integral part of the response to external sources of stress that is mediated by the central nervous system. There is extensive evidence that during the acute stress response, cortisol, catecholamines, angiotensin, and other stress hormones, which are part of the central nervous system response, induce the liver and abdominal fat tissue to release cytokines and other inflammatory mediators, including IL-6. In general, the sympathetic nervous system increases cytokine secretion, while cortisol suppresses it. The relationship with cortisol is a 2-way street, however, since IL-6 acts on the hypothalamus to increase cortisol release. This sympathetically mediated secretion of IL-6 comes predominantly from adipocytes. Exercise is another potent activator of the sympathetic nervous system, and it also increases IL-6: in one study, a positive correlation was observed between peak plasma adrenaline or noradrenaline and IL-6 levels after 15 minutes of aerobic exercise.

    The acute-phase response includes the release of other proteins besides CRP, including serum amyloid A and fibrinogen. These cytokines may contribute to the development of metabolic syndrome. Serum amyloid A lowers high-density lipoprotein cholesterol levels, and TNF-? and IL-6 both have effects that lead to insulin resistance. Furthermore, circulating IL-6 stimulates the HPA axis, activation of which is associated with central obesity, hypertension, and insulin resistance. Adipocytes are an important source of IL-6 and other cytokines, and the blood levels of IL-6, CRP, TNF-? and fibrinogen are all correlated with visceral obesity. About 25% of circulating IL-6 comes from fat cells, and visceral fat releases 2 to 3 times more IL-6 than other fat cells. The acute-phase response leads to increased fibrinogen levels; IL-1 and TNF-? increase platelet number and activity. These considerations have led Yudkin and colleagues to propose that IL-6 is a central mediator of the relationship between chronic stress, inflammation, obesity, and coronary heart disease.

  6. dr treg April 9, 2009 at 14:14 #

    Perhaps though in autism, CSF TNF-alpha might be a better measurement of neuro-inflammation than CRP as this quote from Medscape shows:
    “Michael Chez, MD, a pediatric neurologist at Hawthorne Health Center, Libertyville, Illinois, and colleagues[4] measured the titers of TNF-alpha, a proinflammatory cytokine, in 8 boys who developed autistic regression between 15 and 24 months of age. At the time of the CSF measurement, their ages ranged from 2.1 to 9.5 years. All 8 patients had elevated TNF-alpha levels in CSF compared with in serum (P = .049). The 4 patients who had not been treated with immunosuppressants had the highest CSF:serum TNF-alpha ratios (33:1) compared with ratios for the 4 patients who had received immunosuppressant therapy (6:1). Values of other CSF components, such as cell count, glucose, protein, immunoglobulin production, myelin basic protein, oligoclonal bands, and lactic acid levels were unremarkable. Dr. Chez observed, “Larger studies with a control group are needed to examine predictive markers of autism that may also be useful as indicators of response to treatment. Early intervention against heightened TNF-alpha in the CSF may prove to be protective.”

  7. passionlessDrone April 9, 2009 at 14:50 #

    Hi Sullivan –

    Not a good measure, is it? Why not compare to the date that the Pardo letter was written? May 13, 2008.

    Sure. But the Pardo letter wasn’t meant to provide an overview of the science, just to refute what he felt were specific problems with interpretations of his particular paper. As far as thimerosal goes, I’d actually be inclined to agree with him.

    Then you cite a paper from 2008, which doesn’t really make a clear case that the neuroinflamation observed by Pardo and Zimmerman is damaging or causative in autism.

    Again, however, here we need a reason that excess glutamate release isn’t bad for autism, and is bad for every other condition. I’m not making the case that what Pardo or Zimmerman observed is damaging or causative in autism. Instead, I’m making the case that common byproducts of neuroinflammation are damaging for any condition. Excessive generation of ROS is bad for anyone; if you happen to have impairments in systems responsible for cleaning up this type of byproduct, then it is even worse. Excessive generation of glutamate is bad for anyone; if you happen to have genetic impairments in glutamate processing and/or compensatory calming neurotransmitters (i.e., GABA), then this is even worse. Likewise for tnf alpha; and if you’ve been shown to create more tnf alpha than ‘normal’ people to similar stimulating factors, then that’s even worse. If you are more likely to produce less anti inflammatory cytokines than others, the implications are again, worse. We have evidence for all of these things in the autism world.

    What you are doing is demonstrating the exact thought process that leads to much harm in the autism community. You are connecting dots with very qualitative reasoning, but not admitting that your conclusions are merely hypotheses (at best). Hypotheses are OK—right up to the point that people start treating people based on the hypotheses.

    Well, we’ve got several different things happening here, at least that what’s I’m getting from the above sentence.

    1) It does not appear to be a hypothesis that the results of excessive immune activation in the brain are capable of generating a suite of chemicals that are deliterious in a vareity of ways. If this is common to autism, we’ve addressed, as a maybe, though our available evidence indicates it is. As if this is causative of autism is much more difficult to detangle; at this point I have no problem admitting a lack of evidence that such immune activation causes autism, but that does nothing to mitigate the body of knowledge that the by products of immune activation have been shown again and again to be injurious by a vareity of mechanisms.

    2) A possible association to vaccines.

    3) I’ll freely admit that I’m thinking out loud, hypothesizing, theorizing, and/or participating in ‘idle speculation’ in terms of whether or not neuroinflammation is causitive of autism.

    I make no recommendations as to possible treatment options as a result of my thoughts. As towards whether or not my thought process leads to much harm in the autism community is based in very personal interpretations, and we are unlikely to resolve.

    Also, when people go beyond hypotheses into the realm of being just plain wrong in order to support the idea that vaccines cause autism, the pseudo-logic is quite damaging.

    I am saddened by how rapidly I have gone from qualitative reasoning to psuedo logic. 😦

    My position is not necessarily that vaccines can cause autism, but rather, they may be able to cause some of the physiological effects associated with autism, and in parallel, we haven’t really studied vaccines very efficiently; as vaccines are far more varied than just thimerosal and the MMR. I’m generally much more concerned about the potential effects our actions are having in children at ages far earlier than generally described in the existing court cases; where an unmistakable, drastic change in behavior occurred. Just because we don’t have parents reporting that their children’s behavior changed after their two month appointments doesn’t mean we might not be affecting a small subset of children; espeically those that have some particular qualities in terms of responding to, and resolving inflammatory immune responses that have been observed in autism. Please note that our picture gets lots fuzzier, and harder to descramble if instead of looking for a ’cause’ of autism, we go looking for increasing risk factors for specific components consistent with autism physiology. From my perspective, it seems like the biological components of autism seem to include lots of little things going wrong, as opposed to one big thing, and as such, an approach evaluating how some of these little things might be caused seems warranted. You may feel otherwise.

    I’ll freely acknowledge my concerns are speculatory; unfortunately, I’m not sure how we resolve our apparent differences as towards whether or not such out loud speculation is damaging or not. (?)

    Pardo made a couple of very clear statements which are very damaging to the idea that vaccines cause autism—the neuroinflamation is not caused by toxicity nor is it caused by an infectious agent

    I’d say that Pardo made a couple of clear statements that are damaging to the idea that thimerosal, or persistent infection via vaccination can cause autism. You have quietly substituted in that these two components are the only mechanisms by which vaccination could cause the observed immune activation. While these may be the only things put forth by claimants and some very vocal groups, this does not mean the list is necessarily comprehensive.

    Of particular importance here, to my speculative mind, is what Pardo failed to find; signs of ongoing infection. And yet, we have this observed imbalance; so what is causing it? There are many possibilities, as mentioned by Pardo:

    . . . immature pattern of development from an earlier age, or results from abnormal regulation of brain cells (neurons or astroglia) or a genetic abnormality affecting the immune system, among other possibilities.

    (my emphasis)

    I’d agree; there are probably lots of ways to get to this point. And, further, I’d bet that in any given individual, you could have many of these pathways involved; in lots of cases it might be immature patterns of development, genetic risk, and other things all working in concert.

    But why did I emphasize immature pattern of development? Because we have animal models showing that an immune response, and an immune response only is capable of creating long term behavioral and physiological changes that mimic some of what is observed in autism. I have referenced several of those studies above. In other words, immune challenges and/or seizures during specific timeframes seem to have the ability to permenantly alter the neuroimmune system of animals; so that in essence, animals without any sign of ongoing infection none the less display an activated immune response in the brain, increased succeptibility to seizures, and behavioral changes into adulthood. In many instances, the driving factor seems to be an increase in tnf alpha, a proinflammatory cytokine that people with autism just happen to generate at highly exaggerated rates when compared to people without that diagnosis. Concurrent administration of inflammatory inhibitors is sufficient to make control and treatment groups undiscernable. Other groups are evaluating the for long term, subtle changes from a variety of bacterial exposures in neonates. Somehow along the way, thimerosal and MMR have become synonomous with vaccination in whole; you might be surprized to find that I honestly hope this has been a benign juxtaposition.

    You can accuse me of stringing pearls, engaging in speculation, or psuedo logic all you want. I will openly acknowlege the problems of jumping from rodent models to humans. But when the rubber meets the road, you cannot show me a study wherein the fundamental function of vaccination; initiation of an immune response in infants, has been evaluated beyond MMR based studies. For all the bluster, this doesn’t seem to be an acknowledgement I ever read; and in fact, is usually ignored, as if this means the that their cannot be a problem. None of this would seem important to me if we haven’t established that children with autism have dramatically different immune systems than their non diagnosed peers.

    – pD

  8. passionlessDrone April 9, 2009 at 14:58 #

    Hi Dr. Treg –

    Perhaps though in autism, CSF TNF-alpha might be a better measurement of neuro-inflammation than CRP

    Indeed it may. In the Chez paper, he went to describe extremely high CSF to serum ratios of tnf alpha when compared to a variety of other neurological conditions such as Alzheimers and Parkinsons.

    The ratio of the cerebrospinal fluid levels to serum levels averaged 53.7:1. This ratio is significantly higher than the elevations reported for other pathological states for which cerebrospinal fluid and serum tumor necrosis factor-alpha levels have been simultaneously measured.

    Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic children

    – pD

  9. Roger April 9, 2009 at 18:06 #

    Can you post some links in regards to dendrite spines in autism and/or immunological interactions?
    – pD

    pD,it’s “dendritic,dear.

    Actually there’s quite a bit of findings out there about this.Here are a couple of the top results from Google:

    Shelley Halpain, Ph.D., and Research Associate Barbara Calabrese, Ph.D., describe how a protein called MARCKS affects the shape of neurons, particularly the part of the neurons known as dendritic spines, which are essential for learning and memory.

    Because dendritic spines are so central to mental functioning, it’s no surprise they are associated with neurological and psychiatric diseases. In mental retardation and autism, for instance, the shape of the dendritic spines are different. Under a microscope, the dendritic spines of many mentally retarded people are longer and appear more immature. In recent years, scientists have become increasingly aware of the possibility that a number of psychiatric and neurodegenerative diseases like Alzheimer’s are also affected by synaptic changes brought about by spine morphology. The brains of schizophrenic patients or people suffering from mood disorders also show a reduced number of dendritic spines i

    Because dendritic spines are so central to mental functioning, it’s no surprise they are associated with neurological and psychiatric diseases. In mental retardation and autism, for instance, the shape of the dendritic spines are different. Under a microscope, the dendritic spines of many mentally retarded people are longer and appear more immature. In recent years, scientists have become increasingly aware of the possibility that a number of psychiatric and neurodegenerative diseases like Alzheimer’s are also affected by synaptic changes brought about by spine morphology.

    http://www.scripps.edu/philanthropy/autism.html

    Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1.
    Hung AY, Futai K, Sala C, Valtschanoff JG, Ryu J, Woodworth MA, Kidd FL, Sung CC, Miyakawa T, Bear MF, Weinberg RJ, Sheng M.

    The Institute of Physical and Chemical Research (RIKEN)-Massachusetts Institute of Technology Neuroscience Research Center, Cambridge, Massachusetts 02139, USA.

    Experience-dependent changes in the structure of dendritic spines may contribute to learning and memory. Encoded by three genes, the Shank family of postsynaptic scaffold proteins are abundant and enriched in the postsynaptic density (PSD) of central excitatory synapses. When expressed in cultured hippocampal neurons, Shank promotes the maturation and enlargement of dendritic spines. Recently, Shank3 has been genetically implicated in human autism, suggesting an important role for Shank proteins in normal cognitive development. Here, we report the phenotype of Shank1 knock-out mice. Shank1 mutants showed altered PSD protein composition; reduced size of dendritic spines; smaller, thinner PSDs; and weaker basal synaptic transmission. Standard measures of synaptic plasticity were normal. Behaviorally, they had increased anxiety-related behavior and impaired contextual fear memory. Remarkably, Shank1-deficient mice displayed enhanced performance in a spatial learning task; however, their long-term memory retention in this task was impaired. These results affirm the importance of Shank1 for synapse structure and function in vivo, and they highlight a differential role for Shank1 in specific cognitive processes, a feature that may be relevant to human autism spectrum disorders.

    PMID: 18272690 [PubMed – indexed for MEDLINE]

    http://www.ncbi.nlm.nih.gov/pubmed/18272690

    Current genetic evidence links autism with defects in signaling between neurons, particularly at specialized regions of the cells known as synapses. Bernardo Sabatini and his colleagues at Harvard Medical School plan to study how neuron activity affects synapse formation, focusing on the role of three autism-associated proteins in this pathway.

    To create a synapse, a cytoplasmic extension from one neuron, known as dendritic spine, makes contact with the axon of a nearby cell. Once the synapse is formed, electrical activation in the axon causes release of neurotransmitter from the axon, inducing an electrical and chemical pulse in the spine. Activity in both cells is necessary to stabilize the connection and strengthen the synapse. This process occurs both during normal development and during learning, but some evidence suggests it is impaired in autism. Dendritic spines are abnormal in mouse models of the disorder, as they are in models of the related disorders Fragile X Syndrome and Tuberous Sclerosis Complex. Three of the known autism-associated genes, including members of the Shank, neurexin and neuregulin families, also produce proteins that are found in the synapse and that probably form a complex. Preliminary data from the Sabatini team suggest that, after neurotransmitter is detected in the spine, one of these Shank proteins travels out the active dendritic spine. The protein’s role in the spine and why activity causes it to leave the spine remains unclear.

    Sabatini and colleagues plan to study synapse formation in neurons deficient for these autism-associated genes, specifically looking for defects in the activity-dependent final steps. Using a combination of optics and chemistry, the researchers plan to carefully control the release of the neurotransmitter glutamate sensed by a dendritic spine. This technique will mimic the release of glutamate from the axon and trigger the electrochemical pulses that would normally be induced in the spine. The researchers then plan to look for changes in the number of synapses and in the morphology and composition of the dendritic spines. Based on their hypothesis that autism-related proteins assist in synapse formation, the researchers expect that loss of the proteins will cause consistent defects in these structures and in their signaling strength, which may underlie the learning and social impairments seen in people with autism.

    http://sfari.org/grants/name/perturbed-activity-dependent-plasticity-mechanisms-in-autism

    Lots more,but this should get you started.

  10. passionlessDrone April 10, 2009 at 00:39 #

    Hi Roger –

    Great stuff, and very much appreciated! Thank you!

    – pD

  11. me.yahoo.com/a/TuRz.joYnfzpKUWMPSYwTtN6HTLFunmLzPblUMkn April 10, 2009 at 18:18 #

    Mental retardation is associated with the absence of short thick spines.

    “Golgi studies reveal abnormally long, thin spines and the absence of short, thick spines on dendrites of cortical neurons in retarded children with normal karyotypes. The degree of dendritic spine loss and abnormality appears to be related to age and the severity of developmental retardation. Dendritic spine “dysgenesis” is a common feature of the microstructural pathology that occurs in profound mental retardation of unknown etiology”.
    http://www.sciencemag.org/cgi/content/abstract/186/4169/1126

    As the immune system is becoming more implicated in autism the term autistic dendritis i.e. inflammation of dendrites rather than dysgenesis may be a more useful model.
    Dendrite structural changes are related to their function i.e. dendrite firing rates and the clinical features of autism. Increasing dendrite firing rates in fragile X syndrome with gene therapy improved the autistic features of frgile X syndrome.
    http://www.pnas.org/content/104/27/11489.abstract?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Susumu+Tonegawa&searchid=1&FIRSTINDEX=0&sortspec=date&resourcetype=HWCIT

    Here is some more food for thought:
    http://www.associatedcontent.com/article/1625648/autistic_dendritis.html?cat=70
    http://www.associatedcontent.com/article/1122668/psychiatric_disease_another_approach.html?cat=72

  12. me.yahoo.com/a/TuRz.joYnfzpKUWMPSYwTtN6HTLFunmLzPblUMkn April 10, 2009 at 23:06 #

    The dendrite spines or dendritic spines whatever are short and thick in diseases ssociated with mental retardation.

    “Golgi studies reveal abnormally long, thin spines and the absence of short, thick spines on dendrites of cortical neurons in retarded children with normal karyotypes. The degree of dendritic spine loss and abnormality appears to be related to age and the severity of developmental retardation. Dendritic spine “dysgenesis” is a common feature of the microstructural pathology that occurs in profound mental retardation of unknown etiology”.
    http://www.sciencemag.org/cgi/content/abstract/186/4169/1126

    As it appears that immunological abnormalities are increasingly associated with psychiatric diseases including autism the term “autistic dendritis” rather than dysgenesis may be a more appropriate description.

  13. passionlessDrone April 14, 2009 at 14:12 #

    Hi Roger and Dr. Treg –

    A friend of mine forwarded me this link this morning:

    http://www.webmd.com/brain/news/20090413/how-pcbs-may-hurt-the-brain

    Specific to this conversation, alterations to dendrite plasticity are mentioned as a result of PCB exposure.

    Generalizing out to autism as a whole, these studies would tend to have some rather bleak implications regarding the question as to if we are observing a real increase in the number of children with developmental disabilities, as well as the oft repeated mantra that ‘the poison is in the dose’.

    – pD

  14. Matt April 16, 2009 at 01:57 #

    pD, a new study came out today related to your question above. You can find it at the following site. Not sure how to drop in a hyperlink on this page. http://news.yahoo.com/s/nm/20090415/hl_nm/us_asperger_cortisol_1

    According to the article, it reports that children with Asperger’s Syndrome show a flat marginal cortisol response to the stress of transitioning from sleep to wakefulness and getting up in the morning. This is additive to the literature on cortisol abnormalities in autism.

  15. passionlessDrone April 20, 2009 at 17:29 #

    Hello friends –

    Is anyone still following this thread? I doubt it. Anyways, here is a link to a paper that indicates that an inflammatory process initiated by lps administration is able to affect dendritic length and density, and significantly increase oxidative damage as measured by isoprostane measurements; even though the inflammation levels were not sufficient to produce the more tell tale signs of neurodegeneration. Unsurprizingly, a pre-treatment regiment of some types of anti inflammatories were sufficient to amerliorate these symptoms. This approach was taken after a vareity of knockout mice incapable of generating an innate immune response via TLR4 were found not to suffer effects from LPS injection.

    As noted by the authors, a limitation here is that this was an acute state of neuroinflammation, as opposed to a chronic condition. None the less, if our broader question is whether or not we have evidence that inflammation is capable of affecting causing physiological changes consistent with autism without more obvious signs of pathology; the answer seems to be yes.

    Neuronal oxidative damage and dendritic degeneration following activation of CD14-dependent innate immune response in vivo

    – pD

  16. Roger Kulp February 12, 2016 at 22:22 #

    I am glad this thread is still open.This is a discussion we need to be having.And it is is a discussion we would be having more of,if more autistic children were to undergo whole exome sequencing,like I did a few months ago.I am especially thinking of all these children with both a diagnosis of autism,and many complex medical issues,and regressions.Children whose parents claim were “vaccine damaged”,who would benefit the most from such testing.But the same can be said of children with autism and intellectual disability of otherwise unexplained causes.

    I am guessing that there is no black and white delineation between autism,and features of autism,it’s all shades of grey,where biomarkers play a big part.So where do we draw the line?This has been a moral dilemma to for me ever since I got my WES results,that showed I had a unique,and unknown,variant of a very rare genetic disease called ataxia telangiectasia like disorder.MRE11 mutations.There is supposedly only 25 other known cases of this disease in the world,none previously known to exist with autism or autistic features.I have a more complex version of the cellular immune deficiency,very different types of vision and vascular problems,but very little of the mobility problems usually seen in A-T and related disorders.The cerebrovascular problems may have been a contributing factor to my seizures all these years.

    It became clear to me as soon as I learned about what A-T and ATLD were,and my family history,that the cerebral folate deficiency that was responsible for my “autism” was due to an inherited immune condition,just as Dr. Ramaekers in Belgium said in his original articles.

    I can understand now why people would want to stick to an autism diagnosis,or even saying their child was “vaccine damaged” without wanting to look for an underlying cause.Both claims give you a sense of community,and belonging.As well as a sense of false security and certainty.While a diagnosis of a very rare genetic disease can put you in exactly the opposite situation.

    I don’t expect anything to come of this post,but I just thought I would throw this out there,in case some parent sometime in the future,finds that their child on the spectrum gets diagnosed with one of the diseases in the A-T family,and finds this post through an internet search.

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