Study Suggests Post-Natal, Environmental Causes of Autism

"Our results suggest that FKPB12 regulates neuron signaling that curbs the manifestation of traits observed in several neurological disorders including autism, obsessive-compulsive disorder and schizophrenia.These disorders are widely believed to be "determined in utero by genetic hormonal and environmental factors. Because our study indicates that postnatal release of mTOR activity can result in certain perseverative behaviors, it challenges the idea that some aspects of these conditions are developmentally predetermined."

- AFP, NYU neuroscientist Dr. Eric Klann

Autism clearly has a strong genetic component. Some believe it is entirely genetic with no environmental causes or factors. Those who subscribe to the "entirely genetic" belief find it easy to believe that the astonishing rise in the numbers of autism disorder diagnoses is due entirely to diagnostic definition changes, enhanced public awareness and other social factors. If they are wrong in their beliefs, and if scientific researchers and health authorities refuse to investigate potential environmental causes or triggers of autism then possible treatments, cures or enhancements of the lives of autistic people will be sacrificed on the alter of such unwarranted certainty.

From the erroneous and harmful "Refrigerator Mother" beliefs of Bettelheim to the belief that autism arises solely from genetic factors our popular understanding of, and ability to treat and cure, autism disorders have been restricted by simplistic, single factor explanations of the complex group of pervasive developmental, or autism spectrum, disorders. Recently though there has begun an autism research paradigm shift based on the view that:

"autism is not a rare disorder with a constant rate but frequent condition with a rising incidence. It is a combination of environmental influence and genetic vulnerabilities. It is both preventable and treatable, not by any one method but by a combination of behavioral and biomedical approaches. Autistic kids are not defective, they are sick but otherwise normal kids, and thus, recoverable."

A significant example of the autism research paradigm shift can be seen in the recent study authored by researchers at New York University's Center for Neural Science and the Baylor College of Medicine and published in Neuron,Volume 60, Issue 5, 832-845, 10 December 2008. The researchers studied the effects on mice of removal of the FK506-binding protein 12 (FKBP12) which regulates an enzyme (mTOR) involved in learning and memorization. mTOR affects the the ability to change behavior and regulates connections between neurons thereby playing a key role in learning and memorization.

As stated on AFP News, removal of FKBP12 from the brains of mice late in development reduced the mice's capacity to analyze, respond and adapt to new situations. In one example the FKBP12 removed mice, once they learned a path through a maze, had difficulty learning how to travel through a different version of the maze. The AFP article describes this phenomenon as "enhanced perseveration, or pathological repetition, ... often observed in individuals suffering from autism or other neurological disorders".

The Autism Research Paradigm Shift is a central component of the Autism Knowledge Revolution now taking place. Hopefully, that revolution in learning and understanding autism disorders will not be derailed or slowed by the world's current economic crisis ... or by ideologies, agendas and simplistic views of autism disorders.

autism

The CDC and the Autism Research Paradigm Shift

David Kirby has published, at the Age of Autism, a letter from an official in the Office of CDC Director Dr. Julie Gerberding in which it is stated that:

While it is important to understand if autism is affecting any group of children disproportionately, it is also important to keep in mind that there are likely multiple causes of the autism spectrum of disorders. Most scientists agree that today's research will show that a person's genetic profile may make them more or less susceptible to ASDs as a result of any number of factors such as infections, the physical environment, chemical exposures, or psychosocial components.

It is not clear from Mr. Kirby's article who the official in the office of Dr. Gerberding was that sent the email or whether that official's view represents the official view of the CDC. But it seems consistent with the autism research paradigm shift proposed by the University of Minnesota:

Autism research is poised for another paradigm shift, from an irreversible condition to a treatable disease. In the revolutionary paradigm, autism is not a rare disorder with a constant rate but frequent condition with a rising incidence. It is a combination of environmental influence and genetic vulnerabilities. It is both preventable and treatable, not by any one method but by a combination of behavioral and biomedical approaches. Autistic kids are not defective, they are sick but otherwise normal kids, and thus, recoverable.

Creating a premier center for effective treatment of autism is not as simple as adding a new wing on a hospital, purchasing the latest medical technology or creating another diagnostic center.

What is needed is a revolutionary clinical effort premised on the paradigm that autism may well be a treatable and preventable disease.

The Autism Knowledge Revolution has been marked by dramatic advances in our understanding of the structural and genetic bases of autism. The autism research paradigm shift, a shift toward investigation of the interaction of genetic susceptibility and environmental triggers may well speed the pace of that knowledge revolution.

Reactionary bloggers at the Autism Hub and Neurodiversity ideological movements will not be happy with the autism research paradigm shift but the maturing of scientific inquiry into autism, the movement past official defensiveness, may someday result in more effective treatment and cures. And those are autism realities that will be happily embraced by most parents of autistic children.

autism

"MARBLES" - Rare Study Examines Environmental Factors In Autism Disorders

MARBLES, Markers of Autism Risk in Babies - Learning Early Signs, is a rarity. The study being conducted by UC Davis researcher Irva Hertz-Picciotto is looking at possible environmental triggers for autism.

The Autism Knowledge Revolution advances almost daily with announcements of genetic studies and breakthroughs in understanding genetic causes or bases for autism spectrum disorders. But there seem to be fewer studies focusing on possible environmental factors.

The News10/KXTV report quotes Ms. Hertz-Picciotto:

"Autism is very clearly not a single cause type of condition. It's got to be multiple factors," said Hertz-Picciotto, who hopes her study will reveal environmental factors that combined with genetics can trigger autism.

"We expect to find a number of different exposures that affect neurodevelopment and may be related to autism mildly, small increments of risk, for each exposure, but there may be multiple exposures," said Hertz-Picciotto.

To date the study involves 100 women and 59 babies who are being followed for a three year period. Blood samples will be withdrawn at regular periods.

autism

Autism and Nicotine Addiction - The Neurexin Connection

Science Daily reports on findings presented by Rene Anand, associate professor of pharmacology in Ohio State University’s College of Medicine and principal investigator of research presented today at the at the Society for Neuroscience meeting in Washington, D.C. The findings identified a relationship between two proteins in the brain that have links to both nicotine addiction and autism suggesting a possible drug therapy to alleviate some symptoms of autism.

The neurexin-1 gene produces a protein which lures another protein "a specific type of nicotinic acetylcholine receptor, to the synapses, where the receptor then has a role in helping neurons communicate signals among themselves and to the rest of the body." Persons with autism have previously been found to have a shortage of nicotinic receptors in their brains while people who are addicted to nicotine have too many.

There is some speculation that drugs known as cholinergic agents, used to counter nicotine addiction, could be adjusted for use in autistic children in an effort to increase the level of neurexin-1 beta protein in their brains. It is hoped that more neurexin would alleviate some of the symptoms of autism by encouraging the presence of more nicotinic acetylcholine receptors and number of other proteins important for the proper formation and maturation of synapses.

These cholinergic agents already exist so presumably they will be adjusted for autism as described and their effectiveness tested in the near future.

The Autism Knowledge Revolution continues.

autism

FMR4 - New Gene Link to Fragile X and Autism

The Autism Knowledge Revolution is continuing at such an explosive pace that it barely makes the news when an important new research development provides new insights into the biological structures and process of autism disorder. More of the genes associated with autism and related conditions, Fragile X, in the report that follows, are becoming known. At times it seems on a daily basis.

PLoS ONE has published a report - A Novel RNA Transcript with Antiapoptotic Function Is Silenced in Fragile X Syndrome of a study by researchers Ahmad M. Khalil, Mohammad Ali Faghihi, Farzaneh Modarresi, Shaun P. Brothers, Claes Wahlestedt of the Molecular and Integrative Neurosciences Department (MIND), The Scripps Research Institute, Jupiter, Florida which identifies a new gene FMR4 involved with Fragile X syndrome and potentially many cases of autism.

In New Gene Linked To Fragile X Syndrome -- Suggests Potential Targets For Autism And Other Neurological Disorders Science Daily translates from science into layperson the article published in PLoS ONE :

ScienceDaily (Jan. 30, 2008) — Scientists at The Scripps Research Institute have discovered a new gene involved in fragile X syndrome, a condition that often shares many symptoms of autism. The discovery may lead to new tests or treatments for several neurological disorders.

...

Fragile X syndrome affects thousands of patients worldwide with severe learning disabilities, often accompanied by anxiety disorders, obsessive-compulsive behavior, and attention deficit hyperactivity disorder. There are currently no therapeutic treatments available for fragile X syndrome. Approximately one-third of all children diagnosed with fragile X syndrome also have some degree of autism, according to The National Fragile X Foundation, including such behaviors as social anxiety, poor eye contact, and hand biting.

More than 16 years ago, scientists linked fragile X syndrome to inactivation of FMR1 gene expression, leading to the lack of a protein known as the fragile X mental retardation protein, now considered to be critical for neuronal function. Until the current study, no other functional gene other than FMR1 had been shown to be inactivated in the disorder.

However, Wahlestedt knew the FMR1 gene locus-a specific point on a chromosome-was not well mapped. Wahlestedt and his colleagues hypothesized that unknown regulatory genes might be transcribed from the region.

The new study shows at least one other functional gene-FMR4-from this genetic region is linked to fragile X syndrome, although the gene's exact role in the intact brain remains uncharacterized.......

For anyone wondering, as I was, what the term anti-apoptic means, it relates to apoptosis for which I found some definitions on-line:

MedicineNet.com:

Apoptosis:

A form of cell death in which a programmed sequence of events leads to the elimination of cells without releasing harmful substances into the surrounding area. Apoptosis plays a crucial role in developing and maintaining health by eliminating old cells, unnecessary cells, and unhealthy cells. The human body replaces perhaps a million cells a second. Too little or too much apoptosis plays a role in a great many diseases. When programmed cell death does not work right, cells that should be eliminated may hang around and become immortal. For example, in cancer and leukemia. When apoptosis works overly well, it kills too many cells and inflicts grave tissue damage. This is the case in strokes and neurodegenerative disorders such as Alzheimer, Huntington and Parkinson diseases. Apoptosis is also called programmed cell death or cell suicide. Strictly speaking, the term apoptosis refers only to the structural changes cells go through, and programmed cell death refers to the complete underlying process, but the terms are often used interchangeably.

Merriam-Webster OnLine

apoptosis

Main Entry:

ap·o·pto·sis

Pronunciation:

\ˌa-pəp-ˈtō-səs, -pə-ˈtō-\

Function:

noun

Inflected Form(s):

plural ap·o·pto·ses \-ˌsēz\

Etymology:

New Latin, from Greek apoptōsis a falling off, from apopiptein to fall off, from apo- + piptein to fall — more at feather

Date:

1972

: a genetically directed process of cell self-destruction that is marked by the fragmentation of nuclear DNA, is activated either by the presence of a stimulus or removal of a suppressing agent or stimulus, and is a normal physiological process eliminating DNA-damaged, superfluous, or unwanted cells —called also programmed cell death

— ap·o·pto·tic \-ˈtä-tik\ adjective

autism

Autism, Genetics and Environment - Study Finds Autism Immune System Link

A study reported in the January 2008 issue of Genomics, Gene expression changes in children with autism, has found that a group of genes with known links to natural-killer cells, that attack viruses, bacteria and malignancies, are expressed at high levels in the blood of children with autism when compared to children without the disorder. The study also found gene expression distinctions in children with early onset and regressive autism. The study is summarized in a digestible format on the UC Newsroom article Researchers identify gene expression profile distinctions in children with autism. Comments by the senior researcher Frank Sharp M.D. clinical neurologist, neuroscientist, and professor, department of neurology, school of medicine, indicate that the findings suggest a possible environmental role in the development of autism disorders:

"What we found were 11 specific genes with expression levels that were significantly higher in the blood of children with autism when compared to the blood of typically developing children," said Frank Sharp, senior author of the study and professor of neurology with the M.I.N.D. Institute.

"Those 11 genes are all known to be expressed by natural-killer cells, which are cells in the immune system necessary for mounting a defense against infected cells. We were surprised by our results because we were not looking for these particular genes. And while a number of studies have shown immune system dysregulation to be an important factor in autism, ours is one of the first to implicate these particular cells."

...

"What we are seeing can reflect something in the environment that is triggering the activation of these genes or something genetic that the children have from the time they were conceived," Sharp explained. "Such an immune response could be caused by exposure to a virus, another infectious agent or even a toxin.

Another possibility is that these changes represent a genetic susceptibility factor that predisposes children to autism when they are exposed to some environmental factor." He added that the current study also does not identify whether or not the natural-killer cells are functioning abnormally, which further work by M.I.N.D. Institute immunologists will reveal. "If the natural-killer cells are dysfunctional, this might mean that they cannot rid a pregnant mother, fetus or newborn of an infection, which could contribute to autism."

The study is also featured in an article by Carrie Peyton Dahlberg at sacbee.com which features several interesting comments by Dr. Jeffrey Gregg, director of molecular diagnostics for the UC Davis Medical Center who was also involved in the study. It is pointed out that both similarities and differences were found between the early onset and regression autism cases:

Children with that "regressive" autism had nearly 500 genes that were activated differently than children with "early onset" autism, Gregg and his colleagues found after examining blood samples from 61 children.

"That would suggest that those two groups are very different … and may have totally different underlying pathology," Gregg said.

Both groups, though, as well as other children with a range of symptoms called autism spectrum disorder, shared the 11 strongly expressed genes that control natural killer immune cells.

Dr. David Amaral, the UC Davis MIND Institute's research director suggested that much remains to be learned about how the genetic and environmental factors giving rise to autism interact:

It is still unclear how early those differences emerge, but other MIND Institute researchers are looking at immune differences in mothers' bloodstreams that might be predictive for having a child with autism, said Dr. David Amaral, the institute's research director.

"Things are moving really, really fast now," Amaral said, with scientists around the country working to understand the relationship of genetic and environmental factors that may underlie autism.

It seems clear from this study that environmental factors can not be ruled out in trying to understand the causes -- and potential treatments for autism. Some of the rhetoric which dismisses all genetic or all environmental factors appears to be ill founded. The Autism Knowledge Revolution is being carried out by researchers and scientists in relevant medical fields and the knowledge they are gaining appears to point to both genetics and environment as being involved in the development of autism.

autism

Facing Autism in New Brunswick Nominated For A 2007 Canadian Blog Award

Facing Autism in New Brunswick has been nominated for recognition in the Best Personal Blog category of the Canadian Blog Awards 2007 . It really is an honour and I thank Scott Tribe for the nomination. There are a number of excellent blogs nominated in the Personal Blog category and I feel good about just being included in that list.

I am happy to see that some people appreciate the realistic approach that I have taken in describing Autism Disorders and my son's life as a person with Autism Disorder and profound developmental delays. There are many blog sites on the internet which paint a rosy picture, a joyful picture of autism. Some of these sites are hosted by people who condemn any attempt to describe autism realistically.

I have always believed that I would be doing a great disservice to Conor by bowing to pressure to paint autism as something other than what it is for him and so many other autistic persons - a debilitating neurological disorder which severely limits their life prospects. I include happy stories, and happy pictures, of life with Conor on this site. He is my buddy. And he makes me very happy. But daily life with Conor's autism is a real challenge and sometimes he hurts himself and others. His long term prospects - after his mom and dad have departed as we all must do - are not pretty. I feel obligated to tell the world the complete truth, good and bad, about Autism Disorder.

For now there is little in the way of evidence based treatments or interventions available to help autistic children. Applied Behavior Analysis, ABA, is the only intervention which has consistently, based on decades of research, been found to be effective in making gains in all domains for autistic children but even ABA is not a cure.

There is, however, an incredible explosion of research now taking place in various areas of autism. The neurological structures and processes of autism, causes and possible treatments are all being explored. We truly are living in the era of the Autism Knowledge Revolution. Hope for treatments to improve the lives for autistic persons is more realistic today than ever before.

Long live the revolution. Long live the Autism Knowledge Revolution.

autism

CNTNAP2 Gene And The Unravelling Of Autism Spectrum Disorders

If anyone doubted that we are living in the era of the Autism Knowledge Revolution they should doubt no longer. The January 10 2008 edition of the American Journal of Human Genetics includes reports of three studies which separately validate the March 2006 study led by Dr. Dietrich A. Stephan, that identified a gene called CNTNAP2 which, when mutated, suggested a predisposition to autism. In Unravelling Autism Dr. Stephan comments on the three studies and states:

In this issue of AJHG, Alarcón et al.,¹ Arking et al.,² and Bakkaloglu et al.³ identify a series of functional variants in the CNTNAP2 gene that unequivocally implicate this gene as causing Type 1 autism in the general population. ...... The modern technologies and strategies derived from the Human Genome Project, coupled with the elegant sample banking, phenotyping, and data dissemination resources of groups like AGRE, are resulting, finally, in the unraveling of Autism Spectrum Disorder.

Dr. Stephan offers characteristics of Type 1 autism which many parents will recognize in their autistic children:

The three studies herein^{1, 2, 3} have moderate sample overlap and use different strategies to narrow the phenotype of the ASD cohorts to relative homogeneity before performing genotyping/resequencing across the CNTNAP2 gene locus. Nevertheless, the three studies together identify a set of common and rare variants that provide unequivocal evidence that the CNTNAP2 gene, when disrupted, leads to a subtype of ASD. This genetic subtype can be clinically characterized by ADOS/ADI-R-defined autism with language deficits and potential gender bias and parent-of-origin effects. Type 1 autism may also be associated with seizures.

The gender bias referred to by Dr. Stephan is the male gender bias associated with autism which sees from 3 to 1 to 4 to 1 male to female ratios amongst persons with autism. On the practical side Dr. Stephan indicates that the CNTNAP2 information might be of assistance in early detection and intervention in the 12 to 24 month period.

autism

Autism, Chromosome 16p11.2 and De Novo Gene Mutations

As the father of a son with Autism Disorder I have been following closely the incredible explosion of research into the nature, causes and possible treatments for autism, what I describe as the Autism Knowledge Revolution. As someone who is not a scientist or researcher I try to read the original journal articles publishing these findings but usually have to resort to other sources to translate the language and concepts downward to my own level of understanding which is basically plain English.

It is exciting to see new reports like the Association between Microdeletion and Microduplication at 16p11.2 and Autism published in the New England Journal of Medicine which identifies a Chromosome involved in 1% of autism cases. I try to read and understand the original articles but I also like to consult layman's interpretations offered by credible sources for help and certainty that I truly understand the nature of the research and the possible implications of any findings. I also check other autism bloggers but do so with the knowledge that autism bloggers have a tendency to try and cram any new studies into their own ideological take on the major autism fault lines such as the genetics versus environment causal debates.


My own view for many years based on little more than the "twins" studies and my own son's pre and post natal history was that genetics was probably more significant than environment in causing autism. But I never ruled out environmental possibilities and it is not clear to me that a truly scientific, or at least a truly open minded approach ever rules any possible factor, or set of factors, out on an absolute basis. It is with that mindset that I have read the Chromosome 16p11.2 report and various news commentaries on the report and its findings.


Any finding of a genetic basis to autism gives many of us an automatic knee-jerk thought that autism is an inherited condition, a simple "like father like son", causal relationship. But as I read the article, with my layman's limitations, I was struck by the reference to "de novo mutations" and it was difficult for me to see a simple direct inheritance relationship in what the authors were saying, although admittedly I might have misunderstood:

The abstract published in the NEJM states:

Methods As a first component of a genomewide association study of families from the Autism Genetic Resource Exchange (AGRE), we used two novel algorithms to search for recurrent copy-number variations in genotype data from 751 multiplex families with autism. Specific recurrent de novo events were further evaluated in clinical-testing data from Children's Hospital Boston and in a large population study in Iceland.

Results Among the AGRE families, we observed five instances of a de novo deletion of 593 kb on chromosome 16p11.2. Using comparative genomic hybridization, we observed the identical deletion in 5 of 512 children referred to Children's Hospital Boston for developmental delay, mental retardation, or suspected autism spectrum disorder, as well as in 3 of 299 persons with autism in an Icelandic population; the deletion was also carried by 2 of 18,834 unscreened Icelandic control subjects. The reciprocal duplication of this region occurred in 7 affected persons in AGRE families and 4 of the 512 children from Children's Hospital Boston. The duplication also appeared to be a high-penetrance risk factor.

Conclusions We have identified a novel, recurrent microdeletion and a reciprocal microduplication that carry substantial susceptibility to autism and appear to account for approximately 1% of cases. We did not identify other regions with similar aggregations of large de novo mutations.

As a practicing lawyer I am familiar, in the legal context, with the expression "de novo". In some Canadian legal processes an appeal can be done by way of "trial de novo", essentially a new trial before a higher tribunal, rather than an appeal of specific issues from the original trial. I wasn't sure what "de novo" meant in describing genes.

In What is a gene mutation and how do mutations occur? the NIMH states:

A gene mutation is a permanent change in the DNA sequence that makes up a gene. Mutations range in size from a single DNA building block (DNA base) to a large segment of a chromosome.

Gene mutations occur in two ways: they can be inherited from a parent or acquired during a person’s lifetime. Mutations that are passed from parent to child are called hereditary mutations or germline mutations (because they are present in the egg and sperm cells, which are also called germ cells). This type of mutation is present throughout a person’s life in virtually every cell in the body.

Mutations that occur only in an egg or sperm cell, or those that occur just after fertilization, are called new (de novo) mutations. De novo mutations may explain genetic disorders in which an affected child has a mutation in every cell, but has no family history of the disorder.

Acquired (or somatic) mutations occur in the DNA of individual cells at some time during a person’s life. These changes can be caused by environmental factors such as ultraviolet radiation from the sun, or can occur if a mistake is made as DNA copies itself during cell division. Acquired mutations in somatic cells (cells other than sperm and egg cells) cannot be passed on to the next generation.

Every step forward in understanding autism is in itself a positive development. And popular comment on the Chromosome 16p11.2 findings argue that the findings may help lead toward development of drugs which could be aimed at treating or curing some cases of autism. I hope so.

In the meantime though I also remain curious about the nature of the de novo gene muations involved and the extent to which they are caused by environmental factors.

autism

Autism Predictions 2008

These are my autism predictions for 2008. Some are wildly speculative; some are ho hum continuations of existing trends. Like all attempts to "predict" the future they are inherently futile but I will make them anyway.

1. The Autism Knowledge Revolution will continue to expand and add to our real knowledge of autism disorders. 2007 saw a breathtaking explosion of research into the neurolgoical bases and structures of autism disorders. That trend will continue and the public will be informed less and less by prejudice and ideology and more and more by actual knowledge of what autism disorders are and how they can be treated. Research will also continue into possible environmental contributors to the rise of autism diagnoses.

2. In Canada the federal government of Prime Minister Stephen Harper will continue to ignore, thereby contributing to the worsening of , Canada's autism crisis just as it has helped sabotage international efforts to address the global warming crisis. (No this years return of a traditional Canadian winter does not offset the measurable reality that the polar ice caps are shrinking. In the North the warming is wrecking havoc on the Arctic environment and impairing the traditional Inuit way of life). Canada's National Autism Strategy will remain a joke as long as Stephen Harper remains as Prime Minister of Canada.

3. The stigma attached to intellectually impaired autistic persons will continue. Intellectually impaired autistic persons will remain invisible to the eyes of Dr. Sanjay Gupta, CNN and other major media organizations and stars who seek out autistic persons to portray for public consumption. And the Neurodiversity bloggers who like to portray historical geniuses such as Einstein as autistic will continue to deny the existence of the the many intellectually impaired autistic persons.

4. Ignorance about autism will continue. Autistic children in both Canada and the United States will still be sent home from public schools because "educators" are not educated about the realities of autism disorders. And some autistic youths will continue to be charged as criminals for behavior resulting from their autism disorders.

5. Autism reality will assert itself daily as lower functioning persons with autism move from the care of their families to residential and institutional settings where they will begin their lives in the care of strangers.

6. Some autistic persons such as Dr. Temple Grandin will continue to shine as role models for persons with Aspergers and High Functioning Autism.

7. Parents will continue to fight for their children with Autism Disorders. They will continue to educate, treat and care for their autistic children while hoping that the Autism Knowledge Revolution soon finds a cure for their children's Disorders. They will do so because they love their children - not their children's neurological disorders.

Autism and the Fever Effect

Is there a fever effect in children with autism? Can a fever temporarily offer some temporary improvement to autistic children? Some parents have thought they actually noticed such a beneficial effect from fever when their autistic children were young. I know in the past I thought I saw such an effect from fever with Conor but I thought it was just my imagination. Now, a study published in Pediatrics, suggests there may in fact be something to it; a fever may have a beneficial effect on autistic children.

In Behaviors Associated With Fever in Children With Autism Spectrum Disorders Laura K. Curran, Craig J. Newschaffer, Li-Ching Lee, Stephen O. Crawford, Michael V. Johnston, and Andrew W. Zimmerman studies 30 autistic children aged 2-18 during and after an episode of fever and documented improvements in behavior. The researchers found less "aberrant" behavior in terms of irritability, hyperactivity, stereotypy and inappropriate speech. The study authors are careful to point out several limitations in the study including possible information bias arising from data collection by parent reports and possible selection bias resulting from participation by a small fraction of eligible families from recruitment sources and make suggestions for reducing these possible biases in future studies. They clearly indicate that further study is needed to prove conclusively that the improvements are fever-specific effects. The study offers several possible biological mechanism explanations for the effects involving immunologic and neurobiological pathways, intracellular signaling, and synaptic plasticityL:

(1) neurobiological effects of selected proinflammatory16 and/or antiinflammatory cytokines, which have been found to be increased in cerebrospinal fluid (in the absence of fever) and postmortem brain tissue of individuals with autism17 and may be generated during different phases of responses to fever, (2) modification of neuronal and synaptic function secondary to variations in body temperature that influence neural conduction velocities or synaptic transmission,18 (3) modification of dynamic neural networks as a result of changes in cellular signal transduction and gene transcription that regulate synapse formation and function,19 (4) increased production of other stress-related proteins, such as heat-shock proteins, during fever that might modify energy consumption and mitochondrial activity,20 and (5) stimulation of the hypothalamic-pituitary-adrenal axis leading to modifications of neurotransmitter production and interaction.

The Fever Effect may or may not be confirmed in future studies but it is another interesting new development in the Autism Knowledge Revolution.

autism

Autism Awareness Month - 1 in 150

In Canada, October is Autism Awareness Month.

Since October 2006 there have been many important developments in autism awareness. The Autism Knowledge Revolution has picked up steam with almost each new day bringing news of an important new scientific study on the causes of, or potential treatments for, autism. A Unified Autism Theory was advanced. There is a renewed focus on the study and development of bio-medical treatments. The CDC estimate of 1 in 166 persons having an autism disorder which had stood since 2004 was replaced in February 2007 by a prevalence rate of 1 in 150.

The 1 in 150 estimate by the CDC in the US is not necessarily the end of the story. In the UK the generally accepted estimate is 1 in 100. Debates continue to rage, as all debates on autism issues seem to do, over whether the newer prevalence rates actually reflect increases in autism cases, changes in diagnostic criteria and public awareness or some combination of these factors.

At the end of the day though the reality remains that autism specific services are needed in great number. Many autistic children pre-school or school age, require Applied Behavior Analysis intervention as a health treatment and as an educational interventions. And many autistic adults are not capable of living independent lives. SOME require residential care and treatment and some require full institutional care.

These are hard realities that many would rather avoid. We do so at peril, not to ourselves, but to the autistic persons we care about. During Autism Awareness month we should celebrate the joy that our autistic loved ones being to our lives but, if we truly care,we should also help them face the challenges ahead. We must ensure that autism specific services are available for them across the life span.

Yes, Autism Should Be Cured

Autism should be cured.

Most parents of severely autistic children will answer that question as I have just done. There are some high functioning autistic persons who argue that autism should not be cured. There are some parents of high functioning autistic persons and professionals who work with them who argue that autism should not be cured. Some simply ask whether we should seek to cure autism. The answer to any such question is yes, yes, yes, we should.

We should seek to cure autism so that severely autistic people can be cured and their lives enhanced. That is really all there is to it. This is not to suggest that the higher functioning autistic people who push their views on the internet should be forced to be cured. Absolutely not. But for severely autistic children, whose parents, legally, morally and practically speak for them, the answer is yes they should be given the chance to be cured. What other medical condition do we not seek to cure, or at least to give people the choice of being cured if they are capable of making the choice; or of having their care givers or guardians make the choice if they are not capable?

My son Conor is 11 1/2 and did not have access to 40 hours of ABA between the ages of 2 and 5. He has received ABA as much as possible though particularly since trained UNB-CEL Autism Training Intervention Program began graduating Autism Support Workers; some of whom now work in the school system. With ABA we are able to communicate at a basic level with Conor and he has learned some reading, writing and math skills. (He loves Dr. Seuss and Pinky Dinky Doo) We have also been able to moderate his self aggressive behaviour using ABA and knowledge of what environmental factors are likely to prompt frustration and self aggression.

Would we accept a cure for Conor if one were available and did not involve serious risk to his safety? Yes, if I could cure Conor's autism with the wave of my hand I would stop typing this commentary and do it now before finishing this sentence. I know that Conor is more than his autism; that his personality, his identity, are not dictated by his autism, that Conor would still be Conor. With one major difference. His opportunities to experience and enjoy life would be enhanced immeasurably.

The high functioning autistic persons who oppose curing autism have every right to decide not to be cured of their autism - for themselves. They have absolutely no right to do so for my son and other severely autistic children. They can argue until the sun ceases to shine but they will never convince me, nor most parents of severely autisic children, that we should not cure our children of their autism, that we should not enhance our childrens' lives as parents have strived to do since the beginning of human existence.

Yes, autism should be cured. And the Autism Knowledge Revolution which jumps almost daily onto our internet pages holds out great promise of doing exactly that.

Reseach Based Autism Understanding and Hope for Treatment

Children and adults with autism and their families have been cursed by ignorance. Ignorance of what autism is, what causes it and what treatments are suitable. From Bettleheim, to his heirs in the Neurodiversity movement today, parents have been scapegoated for the challenges faced by autistic children, children who become adults and in some cases face greater challenges alone, without family. A variety of quack treatments have defrauded families of time, money and hope.

Early intensive intervention with Applied Behavior Analysis has been demonstrated and proven effective in helping many autistic persons to overcome their autism deficits or improve their abilities to function and understand the world. But ABA is expensive and time consuming and governments and other service providers have resisted the introduction and proper provision of ABA services. They have been aided in their resistance by ideologues with personal agendas who argue against ABA on any ground they can and who will use distorted caricatures of ABA to advance their agendas.

Today research into the causes of autism and possible biomedical treatments is exploding. An Autism Knowledge Revolution is taking place. The paradigm for researching and understanding autism has shifted to a combined genetic/environmental perspective withtreatments encompassing combined biomedical/behavioral approaches. Each days headlines bring new reports of important developments. With this research is coming greater understanding of autism, its genetic roots and its environmental triggers. And hope for treatments that will help all autistic persons grows.

http://www.newsday.com/news/local/nassau/

Researchers: New understanding of autism is near

Last month, the Cold Spring Harbor team developed a grand unification theory that stitched together previous notions about the genetics of autism and demonstrated how DNA variants - often transmitted from mothers to sons but not exclusively so - may lie at the disorder's roots. Boys are three times more likely than girls to develop autism, Wigler said. He's calling on the CDC to use laboratory techniques similar to the ones he and his Cold Spring Harbor collaborators have developed to assess the prevalence of autism-related mutations in the U.S. population. Screening would help provide guidance on the rate of autism's growth in the population, he said.

...

Based on his work to date, Wigler surmises a clear genetic understanding of the numerous ways in which autism manifests may be tantalizingly close: "I expect that we'll have a very good bead on a number of the [genetic] causes," of autism in the not-too-distant future, Wigler said. "And I suspect there will be a way to treat children to lessen the symptoms." With his Cold Spring Harbor collaborators, Jonathan Sebat and Lakshmi Muthuswamy, Wigler has found that spontaneous mutations specific to autism occur with a relative degree of frequency in the human genome. These random strikes are technically known as copy number variants, or CNVs. The Cold Spring Harbor team defines these mutating hits as a major cause of autism.

...

Alison Singer, executive director of Autism Speaks, a national advocacy organization, said the Cold Spring Harbor studies are destined to have a strong impact on how parents understand autism.

"We want them to pursue the science wherever it leads," Singer said. "But we don't want to get into a situation where we blame the parents. When some parents read stories about older fathers or older mothers, they can become very sensitive."

Singer said what's missing in Wigler's work is the mechanism that causes genes to mutate. Susceptibility genes, she said, often need an outside stimulus to set off a genetic chain of events. Perhaps parents may be correct who think vaccination underlies autism, said Singer, whose daughter and brother are autistic.

"In the 1960s, when my brother was diagnosed, there was the theory of the 'refrigerator mother,' the mother who was too cold," Singer said. "They were essentially telling my mother that she wasn't interacting and bonding with her child. But, of course, we found out that autism is not the fault of bad parenting."

Wigler thinks his work will yield practical information that aids the lay and scientific understanding of autism. It is even possible that knowing which genes are affected can lead to medications that block the function of variant DNA.

A Unified Theory of Autism?

The Autism Knowledge Revolution is picking up pace and seems at times to be adding to our knowledge of autism on a daily basis. A new study offers a genetic mutation model of autism acquisition which the scientists involved suggest may help unify some of the current disparate theories of autism. The theory involves mothers acquiring and passing on autism related genetic mutations to their children. The mutations are spontaneous, arising from assaults to chromosomes. The assaults can arise from a wide range of unspecified environmental facts including naturally occurring cosmic rays and environmental toxins and contaminants. In addition to maternal transmission of the autism related genetic mutation older moms are indicated as being more likely to have an autistic child according to this study by geneticists at Cold Spring Harbor Laboratory. Scientists from the Kennedy Krieger Institute and the Albert Einstein College of Medicine in the Bronx collaborated in the study. The data network developed by iancommunity.org also assisted the reasearchers in the study. This purported Unified Theory of Autism seems to fit with the autism research paradigm shift mentioned in an earlier post. Environment versus genetics as competing and conflicting theories of autism causation seems to be giving way to environment and genetics as a unified theory of autism develops.

From Newsday.com:

http://tinyurl.com/2mc92b

A new model for understanding how autism is acquired and passed from one generation to the next is being offered as a grand unification theory that links other theories and illustrates how women play a key role in transmitting the disorder, scientists reported yesterday.

Geneticists at Cold Spring Harbor Laboratory have been on a genome-wide hunt to pinpoint the genes that cause autism, a brain disorder that usually appears within the first three years of life and can result in difficulties in learning, language and social interaction.

As part of their search, geneticists at the laboratory have collaborated with scientists at Albert Einstein College of Medicine in the Bronx and crafted a working theory of the disorder to aid not only scientists, but also physicians and families coping with autistic children.

"We're really unifying a field that people didn't realize needed unification," said Cold Spring Harbor molecular geneticist Michael Wigler, who, along with his colleagues report results of their research in the Proceedings of the National Academy of Sciences.

What Wigler and his team found is a previously unrecognized pattern: Mothers, they say, acquire genetic mutations spontaneously that are specific to autism, which can be passed to their children. The mothers do not themselves exhibit traits of the disorder, but they have a 50 percent chance of transmitting the trait.

Wigler describes spontaneous mutations as significant assaults to chromosomes that alter the function of genes. In addition to mothers playing a key role transmitting the autism-related mutations, Wigler said older mothers are more likely than younger ones to have an autistic child.

Genes can be damaged, he said, by cosmic rays that occur naturally, toxins and a vast array of environmental contaminants that have yet to be identified.

"There's very definitely a male/female disparity in autism," Wigler said, but there is still isn't strong evidence explaining why boys are more affected than girls. Boys are three times more likely than girls to develop the condition, Wigler said.

Paul Law of the Kennedy Krieger Institute in Baltimore, a collaborator on the project and the father of an autistic son, said hunting down genetic clues to autism will offer clarity in the face of a mystifying condition.

He and his wife, Kiely, developed iancommunity.org, a database that not only helps families but also aided Wigler in the study reported today. The database includes information on autism from families throughout the United States. "This demonstrates the power of the families, that they are a valuable source of information and that's really the building block," Law said.

Autism Research Paradigm Shift

The Autism Knowledge Revolution is taking shape before our eyes on the inter-net with reports on a regular basis of new breakthroughs in autism research. At the University of Minnesota it is hoped that a new autism research center will be accompanied by a paradigm shift in how autism is viewed. In an opinion article, TwinCities.com reviews the shift from Bettelheim's "refrigerator mom" theory which viewed autism as arising from personal interaction, or lack thereof, between mother and infant child to a genetic model which viewed autism as irreversible with the only viable treatment being behavior therapy promising only the possibility of limited improvements. The new paradigm views autism as both preventable and treatable by a combination of behavioral and biomedical approaches and autistic children as recoverable:

Autism research is poised for another paradigm shift, from an irreversible condition to a treatable disease. In the revolutionary paradigm, autism is not a rare disorder with a constant rate but frequent condition with a rising incidence. It is a combination of environmental influence and genetic vulnerabilities. It is both preventable and treatable, not by any one method but by a combination of behavioral and biomedical approaches. Autistic kids are not defective, they are sick but otherwise normal kids, and thus, recoverable.

Creating a premier center for effective treatment of autism is not as simple as adding a new wing on a hospital, purchasing the latest medical technology or creating another diagnostic center.

What is needed is a revolutionary clinical effort premised on the paradigm that autism may well be a treatable and preventable disease.

I believe the University of Minnesota's proposed paradigm shift is in fact amongst the forefront of a shift that is already taking place in the Autism Knowledge Revolution; one that is happening in front of our eyes. With the inter-net's ability to make scientific research quickly and readily available and understandable by the unwashed masses, and with parents' desperately seeking to help their autistic children, all eyes will be upon the University of Minnesota and other research centers that have embraced the paradigm shift. Of course there will be those who will cling to older paradigms, including some high functioning autistic persons, some parents who have surrendered to the sweet appeal of defeat dressed as acceptance, and researchers who simply will not be able to let go of old paradigms which have served as the foundations on which their careers have been built.

http://www.twincities.com/opinion/ci_6374763

Applied Autism Research & Education - ABA Most Effective for Teaching Autistic Individuals

There is a real explosion in research taking place today; an Autism Knowledge Revolution is happening as we type our blogs and read our daily news. Much of the research is directed towards causes and cures and some of the promising recent developments offer hope for treatments and cures for autism. In the meantime though autistic children need interventions that work, that will help them learn and grow. Applied research is the term used by Alan Harchik to describe research into effective autism interventions. Alan Harchik Ph.D., is senior vice president of the May Institute, which operates schools for children and adolescents with autism and other developmental disabilities in Arlington, Braintree, Chatham and West Springfield. Mr. Harchik comments on the current state of applied autism research in an article in The Republican.

We already know that the principles and procedures of applied behavior analysis provide us with the most effective and most evidence-based methods for teaching individuals with autism. However, there is still much for us to learn about behavior analysis, and a great deal of research is being conducted in this area that looks at the intricacies of an instructional session. It is the type of research that has caught the attention of U.S. senators Hillary Clinton and Wayne Allard. Their "Expanding the Promise for Individuals with Autism Act" focuses on treatment provision and determining the most effective interventions.

Similarly, the Organization for Autism Research www.researchautism.org is a group that provides funding solely for the conduct of "applied" research that examines, in a scientific manner, effective interventions for children with autism. Applied research means that the procedures and findings are directly applied to real-world situations. Typically, the research is conducted in natural settings and includes children who directly benefit from their participation in the research.

One line of applied research has examined the details of discrete-trial, one-to-one teaching during which the instructor works on simple tasks, such as imitation of movements or verbal sounds, matching pictures, identifying common everyday objects, making requests, or following simple instructions. In these interactions, the instructor establishes attention and eye contact with the child, gives the instruction, and provides praise and a reward for a correct answer. If an incorrect answer occurs, the instructor provides some sort of assistance. This assistance is called a "prompt."

Applied research is being conducted all over the country to explore the best ways to provide a prompt when a child needs assistance. For example, my colleagues at the May Center in West Springfield and in Kansas, Texas, and Wisconsin are examining the differences that occur when we provide a prompt (a) immediately as compared to waiting a few seconds; (b) before as compared to after a child answers; and (c) paired with saying "no."

Typically, we present a child with the different types of prompts during instruction on different skills and then make comparisons. We are finding that all of these methods are usually effective, but that some children learn better with one type of prompt compared to another.

A next task for us is to determine which method is most effective for each child. This example of intervention research shows the importance of examining even the smallest aspects of instruction. It is research that builds our knowledge over time and can be used today by parents and teachers who work with children and adults with autism.


http://www.masslive.com/metroeastplus/republican/index.ssf?/base/news-3/1183447612315370.xml&coll=1

Mr. Harchik's expertise and authority to speak about autism, aba and applied autism research is not based on an ideological perspective or on obsessive deconstruction of one or two leading ABA studies. His knowledge and opinions are solidly rooted in an impressive clinical and professional background as set out in his profile on the May Institute web site:

Clinical Leadership

Alan Harchik, Ph.D., BCBA
Chief Operating Officer

Alan Harchik, Ph.D., BCBA, is Chief Operating Officer of May Institute. He is responsible for the operation of the Institute’s service programs in autism, mental retardation, brain injury, and mental health. Dr. Harchik is a licensed psychologist, a board certified behavior analyst, and a certified teacher of children with moderate and severe special needs.

Dr. Harchik’s experience at the May Institute began in 1983 when he was a live-in group home parent and residential direct-care staff member. As May’s Senior Vice-President for Autism and Developmental Disabilities Services in Western Massachusetts and Connecticut, he later developed and managed programs for children and adults with disabilities, including a specialized day school, home-based early intervention services, outreach consultation to public schools, community group homes and apartments, and employment services.

Dr. Harchik has expertise in the areas of autism and developmental disabilities, applied behavior analysis, organizational behavior management, staff training and supervision, severe challenging behavior, choice making, self-management, and skill development.

Dr. Harchik earned his Ph.D. in psychology from the University of Kansas after graduating magna cum laude from Boston University with a degree in special education. He holds active teaching appointments at the University of Massachusetts at Amherst and Westfield State College, and is an adjunct faculty member at the University of Kansas, Northeastern University, and Fitchburg State College.

He has published in a variety of professional journals and presented at numerous conferences across the United States. He writes a monthly column on autism and disabilities for the Springfield Republican newspaper and serves as an expert consultant for the Civil Rights Division of the United States Department of Justice.

http://www.mayinstitute.org/about_may/leadership/bio_alan_harchik.asp

Revving Up the Autism Knowledge Revolution

We are living in a revolutionary era. The hardware era is giving away to the software age, and as a result, the economic and social landscape of the world is undergoing seismic changes.

The Knowledge Revolution, Noel M. Tichy, Ph.D., 2002

On March 18 2007 in "The Autism Knowledge Revolution" I commented on the revolution in autism knowledge currently taking place. As impressive as the Autism Knowledge Revolution, the "AKR" appeared just 3 short months ago it appears that the AKR is proceeding at an even more explosive pace then I had thought at that time. Since that post the world has been made aware of the protein/neuroligin study by Davide Comoletti1, Alexander Grishaev, Andrew E. Whitten, Igor Tsigelny, Palmer Taylor and Jill Trewhella published in a recent issues of Structure in which the authors "developed structural models that delineate the spatial arrangements of different neuroligin domains and their partnering molecules. As mutations of neurexin and neuroligin genes appear to be linked to autism, these models provide a structural framework for understanding altered recognition by these proteins in neurodevelopmental disorders."

Just this week Hayashi et al reported in their study that "FXS is tied to a mutated X chromosome gene called the fragile X mental retardation 1 ( FMR1) gene. When this gene is mutated, it can cause mild learning disabilities to severe autism.

"Our study suggests that inhibiting a certain enzyme in the brain could be an effective therapy for countering the debilitating symptoms of FXS in children, and possibly in autistic kids as well". One of the study's authors, Tonegawara, even offered the possibility of reversal of symptoms after the symptoms are pronounced. "Notably, due to an elegant genetic manipulation of method employed by the Picower Institute researchers, PAK inhibition in the FXS mice did not take place until a few weeks after appearance of disease symptoms. This implies that future treatment may still be effective even after symptoms are already pronounced,"

At present there is no cure for autism. Nor is there a biomedical treatment for reversing the symptoms of autism. The Autism Knowledge Revolution, and the breathtaking pace at which it is proceeding, is increasingly offering hope that cures and treatments for autism may not be as far off as once thought. As a father of an autistic 11 year old boy with Autism Disorder with pronounced developmental delays I hope that some of that knowledge will be converted into treatments which will help my son with his serious autism deficits. But if that does not happen, I still hope that other autistic children, will some day soon benefit directly from the Autism Knowledge Revolution.

The Autism Knowledge Revolution

We are living in a revolutionary era. The hardware era is giving away to the software age, and as a result, the economic and social landscape of the world is undergoing seismic changes. The Knowledge Revolution, Noel M. Tichy, Ph.D., 2002

The world is awakening now to another knowledge based revolution - the revolutionary explosion in our knowledge of autism disorders. Like other revolutions the Autism Knowledge Revolution also promises to be seismic in its impact. Recent autism reports have brought news of the Autism Genome Project with studies providing new information about the genetic bases of autism disorders. Gene mutations are being identified as the cause of some instances of autism. A new study suggests that the amygdala, a part of the brain associated with emotional learning and fear, shrinks in people with autism, as a result of chronic stress caused by social fear in childhood.


Like other revolutions there are those who fear the onset of the Autism Knowledge Revolution and its impact. They stand on principle and cloak their fears in the mantle of human rights. Fear mongering is already spreading in relation to genetic research in autism with wild speculation about what the purveyors of such fear describe as a eugenics program similar to some of history's worst atrocities. Others express a more practical fear; that our rapidly increasing knowledge in the genetics of autism will be of no value to older autistic children and adults. As the father of a severely autistic 11 year old boy I understand that particular fear but I do not believe that genetic research will yield only clues to prevention of autism occurrence or education of the very young. It is quite possible that our knowledge of autism disorders will assist in understanding how autism works in all individuals with an autism disorder and that may lead to new ways of understanding autistic persons and how to enhance their lives.

Hopefully one result of the Autism Knowledge Revolution will be the end of some of the needless hostility surrounding the vaccine/mercury autism debate. The believers in the Mercury Theory have clung to their theory with almost no scientific support and have resorted in desperation to belief in a world wide conspiracy involving "big pharma", big government and a "bought and paid for" world science community doing the bidding of Big Pharma. Some opponents of the Mercury Theory have been just as virulent and would censor any reference to autism as a disorder, disease or medical condition by any term. More research, more knowledge, may well show some environmental factors in the onset of autism, mercury based or otherwise. Or it may disprove conclusively any such connections.

The future holds promise but never provides promises or guarantees. Some of the research currently under way may lead to dead ends; part of the scientific process of elimination. But the increase in knowledge of autism will undoubtedly increase our uderstanding of autism. Surely a good thing in and of itself.

The autism knowledge revolution does provide hope, hope of a cure for those who seek it for themselves or their loved ones. It is a hope based not on resignation or "acceptance of autism". It is a hope based on solid scientific research as most of our advances of the last 300 years have been. There are no limits at this time on where this knowledge might lead. While concern that it will not assist older autistic persons is understandable it does not automatically follow that such research will be of no benefit to them and all autistic persons, regardless of age.

Those of us who are not ourselves scientists, and do not imagine ourselves to be scientists, can still assist by involvement in organizations, such as Autism Speaks, and CAIRN (Canadian Association Intervention Research Network), which have been such powerful positive forces in the advancement of autism research.

We can all lobby, create public awareness and raise funds.

We can all join the Autism Knowledge Revolution.