A Call for New Studies on Autism

Forgive me if this is posted elsewhere, but i have heard/read mention of there being anywhere from sixteen to twenty or so well conducted peer-reviewed studies that have discredited the whole vaccination/autism idea. ...

A list of papers on the MMR causing autism:
http://www.immunize.org/catg.d/p4026.pdf

(3 papers saying it does, with one that was retracted versus 25 saying is does not)

Another list on thimerosal (unfortunately not a side by side comparison):
http://www.immunize.org/journalarticles/conc_thim.asp

And the full autism list;
http://www.immunize.org/autism/
 
{snip} I still wonder why this seems to be some excuse to not study autism to some greater depth. {snip}
You lost me there. I did not detect any suggestion that research on autism is less important.

However, based on the cited study, an enhanced search for environmental causes (as a major problem) is not warranted. In other words, while the possibility of environmental causes must be born in mind, there is not yet reason to redirect significant, precious resources to focus primarily on that avenue of inquiry.
 
The big point on this is that the decision was made to pay out in this particular case, rather than spend a lot of time and effort splitting hairs in court. The court did NOT decide that vaccines were responsible for the girl's problem. It was sort of the equivalent of a...mental blank, starts with an "H", plea -- in which you say, "I'm not admitting guilt, but I think a jury might find me guilty," or of a plea-bargain.

The anti-vaccine crowd are anxious to spin the case as being "proof" that They (the conspiracy of CDC/big Pharma/the AMA) know they can't afford to let the evidence come up in court--which is bogus. The big anti-vax line has been disproved by innumerable studies. Mercury preservative and the vaccines themselves have not been the "cause" of autism. They have not been the trigger of autism.

I think people will spin the story either way depending on many factors, which is indeed consistent with how polarized the debate over a vaccine-autism link has played out, and continues to... If one takes the middle road and concentrates on objectivity, then, in my opinion, investigating physiological mechanisms(always being cognizant of interindividual variation) would be of utmost importance in determining the validity of the proposed link to vaccine administration. (note: I would not assert that vaccines are a singular cause). Epidimiological studies play an important role in generating new hypotheses and identifying patterns, which can be further studied from a physiological standpoint, but it seems they are inadequate for categorically confirming or refuting causation, in ASD regression. This inadequacey stems from the high degree of heterogeneity among individuals afflicted with Autism, often having a number of potential factors playing part in the etiology, and therefore making it more difficult to adequately design epidemiological studies. For example, an imaginary epidemiological study of 100 ASD diagnosed individuals reveals that regression has no link to vaccines. This could be an entirely valid study with sound methodology, BUT that doesn't equate to categorical certainty that all instances of ASD have no connection to vaccine administration. Whereas, en epidemiological study of 100 people who became plagued by a pathogenic bacterial outbreak, can with reasonable certainty pinpoint its etiology.

A relevant Journal article to the Hannah Poling case is here

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003815

http://content.nejm.org/cgi/content/full/358/20/2089 -- an article by Paul Offit regarding Hannah .

http://content.nejm.org/cgi/content/full/359/6/655 --A response from Jon Poling(Hannah's Dad) who is a neurologist.

Here are some salient points from the results/discussion section:

In one case, the timing of regression coincided with a recent vaccination.
Recently, there has been increased concern regarding a possible causative role of vaccinations in autistic children with an underlying mitochondrial cytopathy [35], [36]. For one of our 25 patients, the child's autism/neurodevelopmental deterioration appeared to follow vaccination [12], [36]. Although there may have been a temporal relationship of the events in this case, such timing does not prove causation. That said, there might be no difference between the inflammatory or catabolic stress of vaccinations and that of common childhood diseases, which are known precipitants of mitochondrial regression [37]. Large, population-based studies will be needed to identify a possible relationship of vaccination with autistic regression in persons with mitochondrial cytopathies.
This indicates to me that we are still in the unknown phase of linking vaccination to triggering autism, let me know what you think.

From a biochemical perspective, patients' blood and urine laboratory data revealed marked interindividual variation that did not appear to correspond with specific ETC defects or clinical phenotypes. Significant intraindividual variation was also noted for determinations of blood lactate and pyruvate levels, plasma alanine levels, serum transaminases and CPK, and urinary organic acids, with intermittent normal levels in most cases.
Because of the variability of phenotypes associated with these putative mutations, it is possible that there are important environmental or genetic factors in addition to the mtDNA mutation that contribute to the development of autism in a child with one of these mtDNA mutations. The mutations noted here are different from those described in prior case reports of children with autism and mitochondrial disease
For most individuals with defects of oxidative phosphorylation, the diagnosis is made through ETC determination but an underlying nuclear or mitochondrial mutation usually cannot be identified [43], [48], [49]. The biochemical assessment of mitochondrial disorders, especially ETC enzyme assay, is complex and subject to limitations [49], [50]. Even a clear-cut deficiency of one or more ETC activities in vitro does not prove a genetic defect of oxidative phosphorylation because ETC deficiencies can be secondary to other conditions

So the questions arise: are all mitochondrial disorders that may predispose an individual to autism rare inherited genetic defects? Why couldn't a dysbiosis in the gut lead to impaired nutrient digestion and assimilation, which could impact oxidative phosphorylation? Do some individuals that have minor instances of energy impairment(i.e. not show up as genetic defect) also have other predispositions which make them at risk for a regression into ASD upon substantial triggering?

A couple other hypothesis regarding the proposed MMR vaccine autism link, and I can't seem to find any peer reviewed studies looking at these aspects but here they are:

One: It has been documented that the MMR vaccine elicits a prolonged endogenous pulse of interferon gamma, which is a cytokine that modulates various immune responses. This cytokine is also implicated in increasing the permeability of both the gut epithelial lining and the blood brain barrier, two membrames which normally tightly control the flow of molecules across their path. Obvious implications here are the translocation of viral pathogens into sterile sites as well as the translocation of activated immune complexes into unwanted areas. Both of which could play an etiologic role in the gut problems and regression into Autism, which has been amply documented in the anecdotes of parents.

Two: In addition the the endogenous production of Interferon gamma and resulting increased permeability, the measles virus as well as the attenuated virus used in the MMR vaccine suppress the host immune system, this is just part of the normal virulence of Measles. This immunosuppression could allow translocated viral pathogens to replicate with less inhibition from the immune system.

Lastly, Interferon gamma increases the host cell presentation of MHC I molecules. These are the molecules which when presented alert the circulating immune system to step in and initiate apoptosis. Now, if the individual had a latent CNS infection by one of many viral pathogens, which have an affinity for hiding out in neural cells(various herpes simplex viruses, CMV, epstein barr virus) and also can be congenitally passed on and the individual can be asymptomatic,then this increase in MHC I presentation could be a possible etiologic clue. By, increasing presentation of viral peptides by MHC I molecules on neuronal cells, the immune system would target these cells and initiate cell death.

To me these are interesting hypotheses and if any one would like to read more here is the link: (note the hypotheses are supported by a plethora of peer reviewed journals, which support every step of the rationale)

http://members.jorsm.com/~binstock/index.htm


Exactly because this child's medical condition is so rare, and has so few knowns, and produces autism-like symptoms, it would be difficult to disprove the idea that vaccines contributed to, or exacerbate, her symptoms. Given the the court was willing to hear it, it's prudent to go for a pay-out without a decision of cause, and argue the point on a clearer case.

This above statement is inconsistence with the evidence.

When she was 19 months old, Hannah, the daughter of Jon and Terry Poling, received five vaccines — diphtheria–tetanus–acellular pertussis, Haemophilus influenzae type b (Hib), measles–mumps–rubella (MMR), varicella, and inactivated polio. At the time, Hannah was interactive, playful, and communicative. Two days later, she was lethargic, irritable, and febrile. Ten days after vaccination, she developed a rash consistent with vaccine-induced varicella.
Months later, with delays in neurologic and psychological development, Hannah was diagnosed with encephalopathy caused by a mitochondrial enzyme deficit. Hannah's signs included problems with language, communication, and behavior — all features of autism spectrum disorder. Although it is not unusual for children with mitochondrial enzyme deficiencies to develop neurologic signs between their first and second years of life, Hannah's parents believed that vaccines had triggered her encephalopathy. They sued the Department of Health and Human Services (DHHS) for compensation under the Vaccine Injury Compensation Program (VICP) and won.

To win a VICP award, the claimant does not need to prove everything that is required to hold a vaccine maker liable in a product liability lawsuit. But a causal connection must be shown. If medical records show that a child had one of several listed adverse effects within a short period after vaccination, the VICP presumes that it was caused by the vaccine (although the government can seek to prove otherwise). An advisory committee helps to amend the list of adverse effects as the consensus view changes with the availability of new studies. If families claim that a vaccine caused an adverse effect that is not on the list, the burden of proof rests with them. Autism is not on the list for any vaccine, and the VICP has rejected about 300 such claims outright.

So, as you can see in this case the burden of proof rested on the Poling's and they had to show a causal connection.
Are you not intrigued of the possibility of a vaccine-autism link by the sequence of events in Hannah's case?

My heart goes out to families going through this; and it's a horrible thing to face. But the American worldview seems to now include something akin to, "A bad thing has happened! Someone else now needs to pay for it!" That's simply invalid.

What is invalid? As far as the "American worldview" goes, yes, there is a gravitation towards "sue happiness" but that is more a consequence of the social justice system we have all been raised and accustomed to. I personally, don't hold the belief system that accidents always have to be compesated for monetarily, but in the case of Hannah, a series of vaccines administered in close temporal succession was too much stress for her particular biochemistry and triggered a regression into autism. The choice was available to either not pursue legal recourse against the state for damages incurred or to sue for compensation, which would include continued care for her autistic disorder. However, this doesn't have any particular significance as to whether there exists a vaccine autism link in this case.

Speaking to another comment on whether or not research is going on, lots of research is going on. It's just going on in areas where there's some strong evidence suggesting that research will be fruitful.

Agreed, in fact the research for the next five years is being determined by a conglomerate of individuals and groups,in an effort to appeal to the concerns of the public. This, IMO, is a comendable approach, and pretty much nullifies any idea that there is a huge conspiracy trying to cover evidence.

On April 11, 2008, the National Vaccine Advisory Committee took an unusual step: in the name of transparency, trust, and collaboration, it asked members of the public to help set its vaccine-safety research agenda for the next 5 years.

Right now, we have such a bewildering array of things included in "autism spectrum disorders" that what really needs to happen is to have Autism defined, and delineated, to a particular set of neural processing issues. That condition seems to have a very strong genetic component. When you get into "pervasive developmental disability" and such, though, you're overlapping with a lot of prior work on other forms of learning disability, and we don't have a clear path to work on. Unfortunately, the publicity and indignation--as well as the sensational fear-mongering--of the Enraged Parents has pushed the clamor for research well ahead of the clear path for research.

I don't agree with the above statements. First of all trying to obtain a nice neat classification of Autism is what I see as applying the outmoded paradigm of disease<->diagnosis to a disorder that has roots in the differences of individuals. Although there are overlapping and common symptoms of this disorder, I don't think that defining autism to a particular set of neural processing issues is going to facilitate the understanding of etiology, rather, I would contend that this type of "boxing in" will only prove detrimental to further research. I would also contend that this won't happen because of the increasing understanding of the importance of individual heterogeneity in the etiology of ASD.

It's not easy to screen for environmental factors when you don't even know, reliably, who is and is not affected by a "disease". Untangling the increase in diagnosis from any possible increase in occurance is the logical first step; as is, in parallel, looking at concurrent medical problems, as has been posited for gut issues.

Gut issues are my particular interest, as the potential of the microbiome of the gut to influence the host, both negatively and positively is not completely understood. The avenues of reasearch into the ecology of the GI tract and its impact on the immune system, nutritional digestion and assimilation, causitive role in inflammatory disorders, and the important connections between the state of the gut and the state of the brain are beyond intriguing to me. And warrant an exhaustive approach to researching these intricacies.

Again, the challenge is separating anecdote from evidence, and the very organizations that one would expect would want to lead the charge are encouraging obfuscation. It makes me very sad. It made me stop giving money to my preferred Autism charity, which merged with Autism Speaks (which is on record saying it will "not accept" any study that the CDC is involved with)
.

I personally think it is the exact opposite, I think the challenge is going to be integrating anecdote with evidence, in fact the avant garde of ASD treatment is trying to establish a new approach to understanding called narrativomics. I think that we have to realize that the basic relationship of patient/doctor is predicated upon the anecdote and the cummulative history of the patient. Therefore, anecdote should and will be considered an important piece of the puzzle, in unravelling the mysteries surrounding ASD.
 
I ...To me these are interesting hypotheses and if any one would like to read more here is the link: (note the hypotheses are supported by a plethora of peer reviewed journals, which support every step of the rationale)

http://members.jorsm.com/~binstock/index.htm



.....

What peer reviewed journals and papers? The link only has stuff written by Teresa Binstock over eight years ago, and she has on the page:
[SIZE=-1]My writings do not constitute medical
advice.[/SIZE]


[SIZE=-1]Instead, they represent seeking to understand
autism-spectrum disorders[/SIZE]


[SIZE=-1]and their causes and associated
traits.[/SIZE]

She has not really been published in a peer reviewed journal (mostly in Medical Hypothesis, which even though it is indexed at www.pubmed.gov it is a "pay us and we will print whatever you write" type of journal, no peer review involved.).

A few years ago there was some discussion on the folks who were pushing the "mercury in vaccines cause autism" hypothesis, and her qualifications were discussed. It was surmised that at best she had an undergraduate degree in math, and no further studies. See here:
http://photoninthedarkness.blogspot.com/2005/07/mercury-nostalgia.html#112130671850395142 ... where someone volunteered (so be skeptical) that she...
Teresa Binstock has a bachelors in Math and has been playing scientist for some years now. Her main type of "research" now is monitoring parents' listservs and noting what they say about their children and mercury poisoning and how they respond to stuff like cilantro, red wine and saunas (chelation therapies). She has a "foundation" or something with a goofy name and which consists of her, alone.

Binstock has a paper where she says that upset intestines are connected to a part of the brain that controls some aspect of speech. She thinks that the upset intestines cause speech problems, either that or viruses are travelling up the neurons from the intestines to the brain, where they do some unspecified damage. She gets at this by reading various research and combining what she learns from the papers.

I wondered what she was up to lately, and found her blog with one entry:
http://ravenintellections.typepad.c...eresa_b/2007/12/vaccination-pol.html#comments ... and it has been spammed by a guy who will diagnose a person from photographs and video (I kid you not!).

Anyway, if you post papers in the future, could you list its PubMed index number please?

Something like this, the link to the paper is:
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003140 and the PMID: 18769550 ... Which helps us find the abstract and related articles by using that number like this:
http://www.ncbi.nlm.nih.gov/pubmed/18769550

Thank you.
 
You lost me there. I did not detect any suggestion that research on autism is less important.

However, based on the cited study, an enhanced search for environmental causes (as a major problem) is not warranted. In other words, while the possibility of environmental causes must be born in mind, there is not yet reason to redirect significant, precious resources to focus primarily on that avenue of inquiry.

I meant research on the approaches that prompted the article. Perhaps you are right and those approaches aren't worthy; I simply don't know, this is not my field.
 
But I didn't think Hannah Poling had autism. I thought she had a pre-existing mitochondrial disorder with features similar to autism. What am I missing?
 
But I didn't think Hannah Poling had autism. I thought she had a pre-existing mitochondrial disorder with features similar to autism. What am I missing?
You are missing the fact that anti-vaxxers are trying to misappropriate Poling to support their claims.
 
Second, although a California study claimed to show that these diagnostic expansions didn't contribute to the increased number of diagnosed California cases from the 1980s to the 1990s, the authors of the Current Directions in Psychological Science article identified a serious flaw in the unpublished California study's reasoning.

http://www.eurekalert.org/pub_releases/2005-06/bpl-trn062905.php

I find it kind of weird that they figure a statistical jump to 0 in one area of diagnosis, but an equal jump in ASD diagnosese isn't much of a factor. It seems "researchers" in California are under the microscope in this area, and have been before.

Two conditions on the milder end of the autistic spectrum--Asperger's syndrome and the awkwardly named PDD-NOS (pervasive developmental disorder, not otherwise specified)--were added to the DSM in 1994 and 1987, respectively. Grinker and others say 50% to 75% of the increase in diagnoses is coming in these milder categories.
http://www.time.com/time/printout/0,8816,1576829,00.html

It seems this new study is also ignoring that more new cases are coming from areas with increased services to allow for a diagnosis, when those areas weren't covered before. Also, the population has gone up.
More than 3,000 new cases of autism were reported in California in 2006, compared with 205 in 1990.

Let's say the population (and this is purely out of thin air at the moment, but I'm trying to make a point) was 34 million in 1990, but only 5 million of those people had access to professionals who could give a diagnosis for their children. So, only 205 get diagnosed, but now they are basing that on the 34 million people instead of just the 2 million with access. In 2006 there are millions of more people, but they all have access to services, so all children are now getting diagnosed. So out of 37 million people, 3000 kids who are new on the scene, and/or not previously diagnosed in areas before, are now getting diagnosed.

205 is out of what population base with access to services compared to 2006? What was the population in 1990? What was the criteria in 1990, and what are those variables now. We need percentages, not just the figures (which look hugely different without the variables to show the reasons for the "huge" difference). A LOT has changed in those 16 years.

205 kids out of 34 million is 0.0006%

3000 kids out of 37 million is
0.008%

IN 2008 there are 38 million californians. How many kids are going to get diagnosed this year? 3000 again? How many were diagnosed in 2004, 2005, and 2007? Why are we comparing 1990 to 2006 when the criteria has changed, as well as access to people who can diagnose (only a psychiatrist can diagnose ASD, not psychologists, not MDs, not anyone else) There was a criteria change in 1994. I could only get a diagnosis for my child in one of two big cities in province in 1999. I couldn't get a diagnosis for him in my area. I had to travel 2 hours to reach someone who had that "power". There was 2 year waiting list as well, I had to "move" my son to that city and travel 4 days a week (4 hours both ways) 4 times a week for 6 months straight to get a diagnosis before he was 7. Things have changed now.

Until we see the actual study and the variables used, and they propose an environmental factor that actually causes a large cases of ASD (as criteriad at the moment), then I have wonder why this presented in the media and stirring up parents AGAIN like this.


What about access to services? What about school requirement changes?

This from the article:
Some issues related to whether the increase is merely a reporting artifact remain unresolved. There could be other, unknown issues involving diagnosis and reporting, scientists say.

Uh. Yeah. Also, tell us what in pet flea shampoo (mentioned in the article) could change the brain development in fetuses, or something at least plausible to get funding for looking at environment causes. Researchers need a plausible hypothesis to get their funding (most of the time, unless it has to do with altie stuff, then you can waste funding to try to see why altie people say vitamin c might cure cancer without saying one reason how, and get more funding even when previous studies came up negative). Right now there is plenty of plausible hypothese in genetics, and that is why there is funding.
 
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Hannah has a mitochondrial disorder. The same thing would have happened to her if she had gotten the disease, but she got the vaccine first. So, in the courts, technically they can blame the vaccine in her case (since she got them at 3 months of age, but any illness afterward also aggravates and worsens her symptoms). She would have had to live in a bubble to not have had any effects from stress, diseases, or the vaccine.

http://scienceblogs.com/insolence/2008/03/the_hannah_poling_case_and_the_rebrandin.php

Mitochondrial disorders of the sort suffered by Hannah are genetic in nature and rare, an estimated 5.7 individuals per 100,000 worldwide, and, as described well in this New Scientist article, the subset of these disorders that cause autism-like symptoms is even more rare. It is also known that children with mitochondrial disorders are prone to develop an encephalopathy in response to stress or fever that can cause them to regress. The source of this stress is often an infection, such as a cold or normal childhood illness, that results in a fever. The reason is that the mitochondria are the "batteries" or energy sources of the cell, and mitochondrial diseases can lead a child to be "energy challenged," so to speak. Because neurons have such a high constant resting energy requirement, stressors like fever can in these children result depletion of cellular energy.
 
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Also keep in mind, that less people still get autism than get schizophrenia. STILL. Even if autism rates rose to 1/200 instead of the oft quoted 1/300, twice to three times as many people get schizophrenia (1/100).

They get schizophrenia most often between 16 - 25 years old (depending on whether the person is male or female if they get it earlier or later). Why don't we see cries to look at environmental factors for the brain development stage at that time in life?

Um, cuz the criteria didn't change all of a sudden in the 1990s. Instead people started getting diagnosed more decades ago, before the media could start reporting on every "surge" in the amount of people suddenly diagnosed compared to 16 years previously.

Once the dust settles, and diagnosese are the same percent per population (it is sooo dumb to look at how many people are diagnosed per year, it makes far more sense to look at how many people are diagnosed overall), then people can stop looking to blame "causes" and accept that a certain amount of people with get ASD type symptoms, just like they now accept that one percent of all people will get schizophrenia no matter what is going on.

Treatment should be the focus, not cause. But... people wanna sue someone. Fund treatment and care already. Families need help, not something to just point a finger at. What good does that do? They still haven't found a way to decrease the impact of schizophrenia on people who end up getting it. Most schizophrenics are left suffering medicine effects, or in one in a few million case... go chop someone's head off. More will hurt themselves more than someone else though. Most street people have schizophrenia or more "adult" forms of neurological disorders. They can't care for themselves (I and my siblings keep a relative employed and therefore housed), and their relatives get little sympathy.

Yeah, I'm kind of jealous at the attention ASD gets compared to schizophrenia cases. One affects toddlers though, and I guess toddlers are just cuter than teens and young adults. argh.
 
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