Messages posted by: RAJ

Hi Connie;

Very interesting article, the first with autism Ian collaboration, congratulations.

I do have one question that Dr. Law may be able to answer, if the parent(s) in the majority of cases (low risk cases) do not possess the mutation themselves, how does the theory explain the broad autism phenotype findings in first degree relatives.

Also listened to Pod cast, again very interesting especially the number of twins in the database.

Keep up the good work.

Thanks for wading through the complexity of the report. I have my answer, no, the study did not control for the confounding variable of mental retardation.

One of the disappointing findings from the study is that they were not able to replicate the consistent findings of regions of chromosome 7 as a candidate gene for autism.

There is now troubling evidence that many of the authors of this study may have an inherent bias on funding in this area since many of principal investigators have in fact taken out patents on various 'autism susceptibility' genes.

Joseph Buxbaum, one of the principle investigators is listed as the 'inventor' of an autism susceptibility gene:

http://patents1.ic.gc.ca/details?patent_number=2548590

I never realized that anyone could actually patent a gene but apparently that is the fact. I guess there is nothing wrong for them to take out patents since they should be rewarded for drug treatments that could be developed if the suspect gene eventually turns out to have a risk for autism, no matter how small the risk, but it certainly suggests an inherent bias.

Thanks again for providing me with the answer I requested.

Connie (IAN Staff) wrote:

Hi RAJ!

I have the article you refer to in hand, but realize that I am going to need some help answering your question, as I am not a geneticist and these topics get very complex, very quickly. I'll investigate and get back to you!

Thanks, all I am looking for is a simple yes or no. As parents, we are entitled to get the basic information of what was actually found in these studies without the inevitable conjecturing and extrapolating a finding to explain all of autism.

When this study was published the Consortium's PR machine went into a full court press with appearances on Good Morning America, CNN and the evening TV newscasts with the inevitable breathless 'Autism Gene Discovered!

Another study published a few months later also reported variants in the same two chromosomes ( 2 and 11) reported in the consortium's study published in Nature. The authors of that study didn't hold worldwide press conferences in fact the study was barely noticed anywhere.

That paper reported genetic variations on chromosome 2 and chromosome 11 were identified as susceptibility genes for adverse vaccine reactions.

http://news.biocompare.com/newsstory.asp?id=186110

Hi Connie;

Several months ago the Autism Genome Project Consortium reported on two findings from their genome wide scan involving app 3,000 persons from multiple incidence families. The findings were massively hyped by the authors in the media as 'breakthroughs'. Reading some of what I could find without access to the total report, apparently the findings were located in chromosome 11p12-p13 and a deletion of a neurexin gene.

http://www.nature.com/ng/journal/v39/n3/abs/ng1985.html

Apparently the neurexin gene was in found in exactly two cases (out of some 3,000) and the cases were from the same family and they were sisters. The chromosome 11p12-p13 was a 'hot spot that contains some 160 genes and the findings were merely suggestive.

Unusual chromosome arrangements in autism have been reported for decades usually involving a handful of cases in each case and they are almost exclusively found in mental retardation syndromes with those afflicted carrying a second diagnosis within the PDD's.

There are other single gene disorders (Tuberous Sclerosis, PKU, Fragile 'X', Rhett Syndrome) that are mental retardation syndromes with a subset of those afflicted meeting criteria for a diagnosis of autism secondary to the mental retardation.

My question , which one of your scientific advisors might be able to answer, is does that report segregate the genetic findings by IQ? If not how can anyone segregate the confounding variable of mental retardation from autism and it is possible that these genome wide scans may identify a previously unrecognized mental retardation syndrome rather than an autism susceptibility gene.

missbennet wrote:

RAJ, Once again we differ ! Regarding your comment that "polygenic theorists would have you believe that autism is genetic...", I take issue with what I consider to be your oversimplification of those people like myself who feel that there is a probable genetic component to autism.

Where did I ever claim to speak for anyone but myself? As far as the polygenic theorists are concerned, you bet I will criticize them, they claim autism is genetic with no environmental component. In fact, there is a genetic component in most conditions where the cause(s) are not known.

I am a parent whose child recovered and was actively involved in interest in autism research. I also was an occasional contributor to the Journal of Autism and Developmental Disorders in the early 1990's.

Go to PUBMED and enter 'autism Jensen RA'. From the titles you can tell where my interest in autism is.

I lost all interest in autism research in the mid 1990's with my daughters recovery and the direction of autism research. My interest has returned with early retirement and I am in the process of preparing an article tentatively titled ' Evidence for gene environment interactions in idiopathic autism'.

So you can see, I agree with you that there is a strong genetic component in autism just as there is a strong genetic component in leprosy. What I object to most strenuously is the negative stereotyping of parents by those who claim autism is a genetic disorder.

Two more recent reports on prematurity and autism.

The first is from the mother of twin boys both eventually diagnosed with PDD-NOS. The polygenic theorists would have you believe that autism is genetic and the story of these twin boys had nothing to do with their eventual diagnosis

http://www.prematurity.org/research/not-catchingup.html

The second is an abstract published last January.

(Note from Connie, the moderator: I had to remove this link, as it was so long it broke the forum formatting. You can find this article abstract by going to www.pubmed.gov and searching on the title "Prenatal and birth complications in autism" and/or the authors, Brimacombe, Ming, and Lamendola.)

One alternative that we used with our daughter was enrolling her in religious schools. When she had improved enough to be mainstreamed in the local public school we soon found out it was not for her. She attended a Lutheran middle school and then we enrolled her in the local Catholic High School.

Our family is secular, never attend church, but we found out that smaller class size in religious schools and a staff that did not tolerate 'bullying', 'teasing' or 'insulting' other children was the perfect mainstreaming option for her.

We, or rather my wife tried home schooling but it was too much to handle which is why we went to the religious school option. The cost was 500.00 per month which was well worth the expense.

I'm surprised the mainstreaming in a religious school was not listed as one of the alternatives to public schools.

missbennet wrote:

Could you specify in the context of this study, which controls were incorrect and tell me what they should have used in order to show what you surmised, that is, that these findings are not specific to autism and are not accurate conclusions to be drawn here. I would really appreciate you taking a moment to answer that!

The NIH used randomly selected normal controls. The correct controls would be to use other handicapping conditions to see if a finding is specific to autism. The Michigan study found that autism and ADHD both have 'large heads' in a small subgroup and found that autistic kids with 'large heads' have a higher rate of 'hyperactivity' and 'impulsiveness' than autistic kids who do not have 'large heads'.

Here is the abstract comparing Autistic kids and ADHD kids with respect to 'head size':

Several recent reports have described the presence of increased head circumference (megalencephaly) in patients with autism. Although some studies have described reports of megalencephaly in other disorders such as schizophrenia in adults, few such studies have been performed in children and adolescents. In the present study, the authors compared 20 subjects with autism/ pervasive developmental disorder (DSM-IV; all males; mean age = 10.9 years) with 20 controls with attention deficit hyperactivity disorder (DSM-IV; all males; mean age = 11.1 years). Four subjects and five controls had evidence of megalencephaly. In addition to their core symptoms, the autistic subjects with megalencephaly were hyperactive and impulsive. These findings suggest that megalencephaly may not be specific to autism, and when present, it may index the presence of additional symptoms such as hyperactivity and impulsivity.

Connie (IAN Staff) wrote:

An update to my last post!
"In the analysis, we accounted for appetite stimulating medications such as Risperdal in two ways. First, within our case group, we compared children being treated with such meds to those who were not treated and found no differences between them on height, weight, or Body Mass Index (BMI). However, BMI was, on average, higher in children with autism than in the controls, so we included BMI as a co-variate in the analyses to be sure the case-control differences we were seeing were not just because the kids with autism were bigger."

So, the answer is YES. The researchers did take into account meds that can lead to weight gain in their analysis.

The study also supported the notion that autistic boys have larger head sizes than controls.

High BMI is also reported in ADHD as is large head size. Neither of these findings appear to be specific to autism but leads the research community into making links and associations that are not there.

References
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BMC Pediatr. 2005 Dec 21;5:48.
Prevalence of overweight in children and adolescents with attention deficit hyperactivity disorder and autism spectrum disorders: a chart review.

Curtin C, Bandini LG, Perrin EC, Tybor DJ, Must A.
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J Intellect Disabil Res. 1999 Aug;43 ( Pt 4):279-82.
Is megalencephaly specific to autism?
Ghaziuddin M, Zaccagnini J, Tsai L, Elardo S.

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Connie (IAN Staff) wrote:

There are cautionary words in RAJ's post that we should all note, especially as we try to think critically about ASDs. This applies especially to us parents --and, as many of you know, I am one of those, too. Basically...we need to acknowledge that we might tend to "see ASD everywhere" because it is such a vivid and dominant part of our own lives. The same might be said of therapists who treat it all day!

I myself try to be critical about what I think of as "broad autism phenotype" versus simply "eccentric," for example. On the other hand, I think many of us do become adept at "knowing it when we see it." There is a definite quality to the social disconnect that is part of ASD.

Here is an example of 'sofa-side' diagnosis that may explain in part the so-called 'autism explosion'.

http://www.latimes.com/features/health/la-he-myturn18jun18,1,3911699.story?coll=la-headlines-health

Here's one of the first reports (1979) associating prematurity with autism. The case report also shows how you cannot assume a genetic cause in twins just because they are identical. All identical twins possess the same strong, mild or nil liability to the consequences of the same intrauterine environment.

1: J Autism Dev Disord. 1979 Mar;9(1):105-9.Links
Early infantile autism in monozygotic twins.
Eshkevari HS.

A pair of male monozygotic twins concordant for autism is reported. During pregnancy the mother suffered from severe toxemia, and delivery occurred 2 months before term. Although there may have been a genetic influence, it appears that gestational damage was the main etiological factor for the autism in both children.

Connie (IAN Staff) wrote:

Thank you, missbennet, and I think you make a good point here, as far as genetics and our families. One thing I hope an understanding of autism and genetics will give people is a deeper understanding of, and empathy for, others in their family (or maybe even themselves) who have autistic-like traits associated with the "broad autism phenotype." By this, I mean things like social anxiety, a detail-oriented/see the trees not the forest processing mode, an obsessive special topic, etc.

Research groups in the US and the UK have over the last few years began to publish results from investigating the prevelance of the 'broad autism phenotype' in the general population. Constantino and Todd have found that autistic-traits in the general population are quite common and widely distributed throughout the general population. They used large samples taken from the Missouri Twin Registry and found that autistic-like traits are mederatly to highly heritable. But that says nothing about autism pre se being heritable. Happe, Ronald and Plomin (2006) in the UK also reported results from a large sample (thousands of twin pairs) who were objectively scored for 'autistic-like traits'. They found that 10% of the total sample possessed one or more autistic-like traits.

The entire concept of the broad autism phenotype was introduced by child psychiatrists who specialize in autism and have observed certain 'traits' in parents that appear to occur commonly within thwir clinics. What they do not see is how common and widespread these traits are in the general population and they may have misinterpreted the actual magnitude of the genetic component in autism.

Connie (IAN Staff) wrote:

Hi missbennett.

To read more on Autism and genetics in general, go here:
http://www.iancommunity.org/cs/understanding_research/insights_from_genetics

Interpretations of genetic data where the cause(s) are unknown are inappropriate when they are labelled as 'genetic'. A better understanding of how twin data can be misinterpreted is to compare the genetic data reported in autism to the genetic data in other conditions where the cause(s) are completly understood.

The 'cause' of leprosy is exposure to Myobacterium Laprae but the genetic data in leprosy is a mirror image of the genetic data published in autism over many decades. Twin studies in India have shown the magnitude of the genetic compnent with very high concordance rates reported in monozygotic twins ( 60 -85%

and a rapid fallof in concordance rates in dyzygotic twins ( 5 - 20%

. The sib risk ratio is 2.4, the same as reported by Folstein and Rutter as well as Pickles. Multiplex leproy families have been recruited and genome wide scans for leprosy suscetability genes have been underway for many years with just as many candidate genes identified as there are in autism. There is also the same unexplained high male to female ratio ( 3:1 in leprosy)that has perplexed autism geneticists

http://www.nature.com/ng/journal/v27/n4/full/ng0401_439.html

Its all in interpretation of data isn't it. As a parent myself and an occasional contributor to the Journal of Autism and Developmental Disorders back in the early 1990's before my daughter recovered, my view is that parents must question everything they are told, unsparingly.

I see the response of the autism research community to the perplexing problem of autism to be based entirely on whatever the current thinking in child psychiatry happens to be.

The dark ages of when a refrigerator mother happened to defrost long enough to have inflicted psychological damage in their child has been replaced by the new paradigm where refrigerator parents have defrosted long enough to have induced genetic damage in the child.

BTW when is Kennedy Krieger going to segregate concordance of their MZ twins by chorionic status?