Messages posted by: RAJ

A December report in the medical Journal 'Neurology' has reported a strong link between exposure to the anti-convulsant drug valproate acid and the later diagnosis of Autism:

http://www.medscape.com/viewarticle/584582?src=mp&spon=30&uac=126881ET

The study followed 632 children.

The prevelance of ASD in childen exposed to valproate acid in utero was 6.3%

The prevelance of ASD in children not exposed to calproat acid in utero was 0.9%

A correction of typos in my original post.

"A new study that hasn't yet been published but the abstact is available and showed an association between extreme low birth rate and the later development of ASD".

Should read 'extreme low birth weight' not 'extreme low birth rate'

The control group was children born with normal birth weight.

A new study that hasn't yet been published but the abstact is available and showed an association between extreme low birth rate and the later development of ASD.

http://www.ncbi.nlm.nih.gov/pubmed/19322106?
The Lead Author did inform me that 219 low birth weight babies were followed up at age 5 - 8 and 8 were described as having a pervasive developmental disorder (Autism or Asperger Syndrome). The study had a control group of typically developing children. 1 case out of 179 of typically developing children were described as having a pervasive developmental disorder.

Our experience was a disaster. We were asked to include our then 4 year old daughter to particpate in a 'social skills' group started by the local pediatric clinic where she was receiving speech therapy.

After three sessions the only social 'skill' she acquired was in copying one of the boys in the group who spent most of the sessions waving his hands in front of his face.

We had to withdraw her from further participation and her acquired 'skill' disappeared.

To be fair, it was a very young group ( 3 and 4 year olds) and they varied extremely in terms of severity of symptoms.

I would suggest that any parent who is invited to enroll their child in such a group be allowed to observe the group before considering placing their child in the group.

A new study published by Deborah Fein has reported that up to 25% of children diagnosed with an ASD lose their diagnosis and recover:

http://www.ncbi.nlm.nih.gov/pubmed/19009353?

An interesting study, but one which does not explain at least two other observations related to autism.
The authors wrote:

"More importantly, it strongly supports the emerging idea that autism stems from disruptions in the brain's ability to form new connections in response to experience - consistent with autism's onset during the first year of life, when many of these connections are normally made"

Autism is more than just a problem with postnatal brain connections, there are structural defects, usually prenatal in origin, that have been consistently shown to be present at autopsy:

http://www.ncbi.nlm.nih.gov/pubmed/15329353?

The authors also state:

"In addition, since people with autism tend not to have children, most of the genes identified thus far aren't inherited from a parent, but instead are mutated during embryonic development, making them hard to track through traditional linkage studies in families"

Once again there is the notion that the parents don't pass on genetic liability to autism, they are spontaneous genetic mutations in the child, an idea previously proposed by Wigler earlier this year where he claimed that 90% of the cases of autism are denovo mutations and the parents are therefore unaffected.

What then does one make of the entire concept of the "Broad Autism Phenotype"? It seem that an interesting debate should be forthcoming between molecular geneticists and child psychiatrists over the very existence of the concept of the 'Broad Autism Phenotype".

To date, no gene specific to autism has ever been identified (most are also reported in mental retardation with or without autism'.

There is a real problem in autism research related to the perplexing problem in of heterogeneity and lack of specificity in both the genetic and environmental components of autism.

Professor Rutter has recently given a talk on the problem of the glacial pace in finding find any any genetic defect apecific to autism:

http://www.youtube.com/watch?v=0MVLH4B0tEU&feature=related

Thanks Connie for the NIH link on the prevelance of schizophrenia in the US (1.1). Actually my math was wrong regarding the article on mental illnness in parents of autistic people. The actual lifetime prevelance cited in the article was less than 1%, .667% (Fifteen parents out of over 2400 biological parents).

Ironically, if you use the NIH prevelance of 1.1 it could be reasonbly argued that the prevelance of schizophrenia in the parents of autistic people (.667) represents a biological resistance, rather than susceptability, for parenting an autistic child.

Thanks for linking to the Pediatrics free online entire article. Reading the abstract and the commentary on science websites one gets the impression that shizophrenia is rampant among parents of autistic children. A full reading of the entire article (thanks again)gives an entire different impression, especially to those who take any major autism announcement with a large grain of salt.

Thee rate of schizophrenia reported (7 mothers and 8 fathers) represent 1% of the entire sample of nearly 2500 parents of the autistic people. It has been known and accepted for decades that the prevelance of schizophrenia in the general population is 1%... Where's the linkage? It would be expected that 1% of any group would have a parent who was diagnosed with schizophrenia from everyone with red hair to everyone who is right-handed.

The control group, randomly selected, did have a lower prevelance of schizophrenia than did the autistic group, but the autistic group did not have a higher prevelance that the universally accepted rate of 1%.

In political preference polls this is known as an outlier where 7 polls have candidate A with an 8-12 point lead and one poll has Candidate B with an 10 point lead.

For example,this study was based on patient registries in Sweden, but in next door neighbor Finland, another study of (twins) found the prevelance of schizophrenia to be 2%, twice as high as the 1% general population prevelance.

http://archpsyc.ama-assn.org/cgi/content/abstract/55/1/67

The myth that schizophrenia is linked to autism has been dispelled by many of the most distinguished researchers in the field from Eric Schopler to Michael Rutter.

It is important for parents to simply not accept at face value any study that receives widespread media attention without raising reasonable critiques of the information being promulgated to the media.

I read your article on a mouse model for autism (front page) based on a genetic mutation in mice that disrupts early brain development and the effected mice displaying 'autistic-type' behaviors.

IAN readers should be aware that for every genetic mouse model for autism there are also environmentally induced mouse models for autism

Environmental animal models for autism:

Anticonvulsant drugs
http://www.ncbi.nlm.nih.gov/pubmed/6822256

http://www.ncbi.nlm.nih.gov/pubmed/2790086

http://www.ncbi.nlm.nih.gov/pubmed/10840175

Infections:

http://www.ncbi.nlm.nih.gov/pubmed/18248790

http://www.ncbi.nlm.nih.gov/pubmed/16860408

Debate and argument over diagnostic issues in autism has gone on for decades. The following link lists the APA's set of diagnotic criteria for 'autism' over many decades:

http://www.unstrange.com/dsm1.html

In my view the important dates for concepts in autism diagnosis are with the publication of DSM-III-R in 1984 and the publication of DSM-IV in 1994.

Fred Volkmar published the results of a trial of DSM-III-R and reported an overdiagnosis of autism. Volkmar was appointed to head the APA's study group on autism whose charge was to redefine the diagnostic criteria for autism.

The APA published the revisions in DSM-IV in 1994 and it had the opposite effect, not only did the new criteria result in vastly overdiagnosing autism, at least with respect to DSM-III, it may be entirely responsible for the so-called autism epidemic.

The most significant an completly overlooked change was to remove Kanner's highly specific diagnostic criteria "indifference to the existence of other people, including parents". In its place was the ambigous 'deficits in social reciprocity' which might apply to very large numbers of the general population with or without a disability of any kind.

I read your article written by Professor Hagermann on the association between Fragile X mental retardation Syndrome and autism. Not all researchers agree with the concept of relationship between Fragile X and Autism.

What frustrates me as a parent is that there is no debate and argument about what 'autism' actually is.

The definition of 'autism' remains elusive and since Kanner's publication in 1943, the paper that first recognized infantile autism as a specific disorder, prevelance rates have swung widely depending on definition and diagnostic tools used to make a diagnosis.

In 1965 Kanner published a paper in Behavioral Science on the brief two decade history of 'autism'.

http://neurodiversity.com/library_kanner_1965.html

Here is what Kanner wrote in 1965:
"This sage advice was not heeded by many authors. While the majority of the Europeans were satisfied with a sharp delineation of infantile autism as an illness sui generis, there was a tendency in this country to view it as a developmental anomaly ascribed exclusively to maternal emotional determinants. Moreover, it became a habit to dilute the original concept of infantile autism by diagnosing it in many disparate conditions which show one or another isolated symptom found as a part feature of the overall syndrome. Almost overnight, the country seemed to be populated by a multitude of autistic children, and somehow this trend became noticeable overseas as well. Mentally defective children who displayed bizarre behavior were promptly labeled autistic and, in accordance with preconceived notions, both parents were urged to undergo protracted psychotherapy in addition to treatment directed toward the defective child's own supposedly underlying emotional problem.

By 1953, van Krevelen rightly became impatient with the confused and confusing use of the term infantile autism as a slogan indiscriminately applied with cavalier abandonment of the criteria outlined rather succinctly and unmistakably from the beginning. He warned against the prevailing "abuse of the diagnosis of autism," declaring that it "threatens to become a fashion." A little slower to anger, I waited until 1957 before I made a similar plea for the acknowledgment of the specificity of the illness and for adherence to the established criteria".

The startling prevelance rates began to rise with the introduction of DSM-III-R and ICD-10 in 1987. Diagnostic 'Gold Standard' tools ADOS, ARI-R emerged shortly based on the DSM-III-R and ICD-10 diagnostic criteria. All of these tools are checklists in the form of a Chinese Restaurant Menu.. Two from column A... one from column B... If enough items on the checklist are marked off, the child qualifies for an 'autism' label even if the child does not show the core defining feature of what Kanner called 'infantile autism'.

The problem is that as the number of what Kanner called 'isolated symptoms that are part features' of the overall syndrome carry the same weight as the core defining feature of what he described as the 'sui generis' of infantile autism. As the number of isolated feature parts of the overall syndrome began to expand, none of which are specific to autism, the prevelance rates began to dramatically rise.

In my opinion, the autism epidemic is a myth. There is nothing inherently wrong with over diagnosing since, as Schopler has stated, it has become a passkey to special education services. The problem is that in research no one can possibly know whether the sample of 'autistic' people participating in research projects actually meet the original concept of what autism is, leading psychiatrists and behavioral geneticists to making false assumptions and drawing misleading conclusions.

Hi Connie,

I read the articles on your home page about the recent report on microscopic variants found on chromosome 16P.11. The article includes one of the most repeated statements in genetic studies of autism, 'Autism is 90% heritable'. That heritability estimate is based on the Gold Standard twin study published by Bailey et al in 1995.

The new finding also noted that the majority of cases where genetic variants reported in chromosome 16P.11 were spontaneous mutations that were not found in the parent(s). Wigler et al earlier this year published his 'Unified Theory of Autism' based in part on Ian data. In Science Daily, Wigler suggested that 90% of autism cases were sporadic, new mutations in the affected child that were not present in the parent(s).

If the majority of autism cases are sporadic, 'caused' by a de novo mutation in the affected child but the mutation is not present in the parent(s) then there exists two models of autism that are incompatible with each other, the 90% conundrum.

By inference, since the parents do not possess the genetic variant, they are unaffected, which raises important questions about the validity of the Broad Autism Phenotype and the entire polygenic hypothesis.

My question is, how does IAN's editorial board respond to this important question which relates to two competing theories which are incompatible to each other.

Perhaps you might ask Dr. Zimmerman who commented on the article you posted on the home page of IAn.

Thanks

Michael Rutter has often reminded autism researchers of the importance of comparing autism to other conditions. It seems that every few months there is a new unifying theory that attempts to explain all of autism, the latest being the mirror neuron theory. Disruption of the mirror neuron system has been invoked to explain everything from autism to schizophrenia.

Has scientific research become so overly specialized that researchers interpret every grand theory through the prism of their own specialty?

Search PubMed (the medical lit database) at www.pubmed.gov to see an example. ("An intersubjective perspective on negative symptoms of schizophrenia: implications of simulation theory," appearing in Cognitive Neuropsychiatry, 2007, 12(2), pgs. 144-164, by Salvatore and colleagues.)

(Sorry, RAJ, I removed your direct link because most links from PubMed stretch the forums beyond the screen -- they're too long. --Connie)

Hi Connie;
Here's a new study that may shed light on the original study about the theory for sporadic and inherited autism.

http://richarddawkins.net/article,1601,n,n

An entire genome scan of a single individual has been completed and reported that half of the subjects 23,224 genes contained variations or mutations.

The theory is based on a previous study published by Cold Spring Harbor that found 12 out of 129 (10%) of persons with an ASD from single incidence families had a copy number variation, but none of the CNV's were specific to a single gene or even chromosome. The study says nothing about what the CNV's actually do to 'cause' autism. The best researched report of CNV's associated with a specific gene comes from HIV research. CNV's in a specific gene was associated with resistance to infection after exposure to the HIV virus.

http://www.wellcome.ac.uk/doc_WTX034711.html

More problematic is that if the majority of cases are sporadic, with parents unaffected, the entire concept of the 'broad autism phenotype' would be discredited