Discussion continues about autism legislation, and is going to continue here in the US under a new administration. One piece of federal autism legislation that has been passed here is the 2006 Combating Autism Act (CAA), under which the Interagency Autism Coordinating Committee (IACC) was charged to create a Strategic Plan for research in autism spectrum disorders. (Regarding how the CAA was voted on and passed, and on its unfortunate name, go here.)

Over the past year-plus, the IACC has been developing a draft of the Strategic Plan. This draft was reviewed at the IACC’s November 21st meeting and, as review of the plan was not completed, the IACC met again on December 12th to continue review of the draft Strategic Plan and, per the agenda, to discuss cost estimates.

The IACC will be meeting next on January 14th (and go here for how to listen in virtually, via the web or conference call). This meeting will be to continue the review of the draft Strategic Plan, and to make budget recommendations and finalize the plan.  There’s a report about the December 12th meeting on the Autism Speaks website which notes that 38 research initiatives were approved, and that the budget for these will exceed the amounts authorized by the CAA in a certain period of years. The IACC Strategic Plan recommends that more than $1 billion be spent on research objectives.

I was able to listen to some but not to all of the December 12th meeting. Autism Speaks lists 10 of the 38 research objectives, which include (with my commentary on some initiatives and some emphases in italics)

Develop at least one new diagnostic instrument (briefer, less time intensive); [Interesting I think, recalling the two-day-plus process---ordeal---of having Charlie evaluated by a diagnostic team in Minneapolis; might something get missed, though, if the process is hurried up too much?]

Validate a panel of biomarkers that separately, or in combination of behavioral measures, accurately identify, one or more subtypes of children at risk for developing ASD; [At the November 21st and December 12th meetings, some members of the IACC brought up the need for such "biomarkers" repeatedly, as well as the notion of "subtypes" of children who be "at risk" or susceptible to being diagnosed with autism.]

Establish an international network of brain and other tissue acquisition sites with standardized protocols;

Complete a large-scale, multi-disciplinary, collaborative project that longitudinally and comprehensively examines how the biological, clinical and developmental profiles of children, youths and adults with ASD change over time compared to typically developing individuals by 2020;

Coordinate and implement the inclusion of approximately 20,000 subjects for genome-wide association studies, as well as a sample of 1,200 sequencing studies to examine more than 50 candidate genes by 2011;

Study the effect of vaccines, vaccine components and multiple vaccine administration in autism causation and severity through a variety of approaches including cell and animal studies and understand whether and how certain subpopulations in humans may be more susceptible to adverse effects of vaccines; [Again, the mention of "subtypes" of individuals with certain susceptibilities, such as the so-to-speak "subpopulation of mitochondrial autism."]

Determine design and feasibility of addressing different health outcomes in vaccinated, unvaccinated and alternatively-vaccinated groups; [Yes, another mention of vaccines; this study being the long-called for study of various "health outcomes" in vaccinated vs. unvaccinated, and not "alternatively-vaccinated groups"---those vaccinated under an "alternate schedule"?]

Conduct a multi-site study of the subsequent pregnancies of 1000 women with a child with ASD to assess the impact of environmental factors by 2014; [Sounds like the UC Davis M.I.N.D. Institute MARBLES study.]

Standardize and validate at least 20 robust model systems (cellular and/or animal) that replicate features of ASD and will allow identification of specific molecular targets or neural circuits amenable to existing or new interventions; [But are "features of ASD" as seen in an animal (such as a mouse) model equivalent to features of ASD in human?]

Test the efficacy of 11 evidence-based services for people with ASD in community settings by 2015.[Would like to know about the what and where of these.]

And if the full $1 billion worth of research initiatives are not funded, what studies might be the first to be tabled…………….

A potentially double-good plan involves (1) preserving one of the last strips of undeveloped land within Dubuque’s city limits and (2) creating a residential facility with an on-site farm for autistic adults: Today’s THOnline tells more about an effort to preserve green space and provide a place to live, and to work, for autistic adults. $985,000 has to be raised to purchase the property and the whole project could cost some $2million, so there’s a lot more to do. Says Craig Beytien, whose autistic son is 15 years old, “‘We’ve got the passion and some ability, but does the economic model support it?’”Goes without saying—hoping that it can, and will. 

MARBLES stands for Markers of Autism Risk in Babies—Learning Early Signs. The study investigates “biological and environmental triggers that children are exposed to prenatally and post-partum”: Some 100 women who have a biological autistic child and who are pregnant, or who are planning on becoming pregnant, are participating in MARBLES, which began in 2006. Researchers from the UC Davis-M.I.N.D. Institute are collecting blood, urine, hair, saliva, and breast milk (if the mother is breast feeding), as well as dust from participants’ houses, and mothers are interviewed and medical records examined. It’s noted that MARBLES is “unique” because

follows mothers before, during, and after their pregnancies, allowing us to obtain information about the pre-natal and post-natal environment to which the baby is exposed.? By gathering information in real-time we increase the accuracy of the information collected and will be able to better understand and observe the biological and behavioral changes that may occur in the mother and/or baby throughout the pregnancy and early childhood period.

The November 22nd InsideBayArea opens by suggesting that people’s homes “might reveal clues for solving one of the biggest mysteries of modern medicine: the cause of a rapid rise in autistic children.” Besides collecting dust with a “special vaccuum,” researchers are also noting what household cleaners soaps, beauty products, electronics, and types of paint, each family uses. And, when Danielle Bell of Danville—whose almost 4-year-old son Jake is autistic—had her now 8-month-old daughter, Layla, researchers were present and “took for laboratory analysis the umbilical cord, a portion of the placenta and what is known as meconium, or the baby’s first bowel movement.”

In the search for a cause, for some of us, it could be said that our homes indeed contain “clues” about autism, in our very selves, in our genes, and not so much is to be revealed by analyzin the dust or the types household cleaning products.

Aside from discovering our housekeeping habits……..

An article in the September 10th New England Journal of Medicine entitled Recurrent Rearrangements of Chromosome 1q21.1 and Variable Pediatric Phenotypes describes the associations between a microdeletion at 1q21.1 and impairments including mental retardation associated with microcephaly, cardiac abnormalities, or cataracts. A microdeletion at 16p11.2 is associated with susceptibility to mental retardation or autism and was discussed in the NEJM in February. In an editorial accompanying the new NEJM study, David H. Ledbetter, Ph.D., of the Department of Human Genetics, Emory University, Atlanta, notes that a “technologic revolution in human cytogenetics” has made these discoveries possible, thanks to “genomewide assessment of copy-number alterations (deletions and duplications)” that are performed “by means of high-density array technologies, hereafter referred to as cytogenetic arrays.”

That is, new technologies are enabling us to discover “new syndromes caused by deletion of genomic segments of 500 kb to 2 Mb in size” and Ledbetter concludes that pediatricians and clinicians “like researchers, can now shift to a ‘genotype first’ model of diagnosis for children with unexplained developmental abnormalities”—-doctors now have more tools at their hands to help make and/or confirm a diagnosis in a child with developmental delays.

The study’s authors note that 1q21.1 rearrangements are associated with a “broad spectrum of disorders” and further they “dispel the notion that such rearrangements will necessarily follow the one-gene, one-disease model.” As PhysOrg notes,

The authors recognize that the diversity of disorders and the lack of a distinct syndrome accompanying 1q21.1 rearrangements will complicate genetic diagnosing and counseling. They suggest that clinicians caring for patients who have unexplained developmental abnormalities consider the identification of a 1q21.1 rearrangement in a patient a significant clinical finding and probably an influential genetic factor contributing to the patient’s disorder. Evaluating the patient’s family members may reveal apparently unaffected or mildly affected relatives carrying the same rearrangement. Keeping in mind the many possible repercussions of having this rearrangement in the chromosome, the authors suggest that young carriers should be monitored over the long term for the emergence of learning disabilities, autism, schizophrenia, or other neuropsychiatric disorders.

This study, the authors said, adds 1q21.1 as a chromosomal locus to the growing list of structural variants that might eventually be included in genetic screening panels for people with developmental delays or neuropsychiatric diagnoses.

“Clinical diagnosis in patients with these lesions may be most readily achieved on the basis of genotype rather than phenotype,” as the study’s authors conclude. The study both shows the “importance of rare structural variants in human disease” and also reveals some of the challenges, namely:

First, large samples of patients and controls are required to show that a specific variant is pathogenic. Although there have been several reports of patients with 1q21.1 deletions in studies of specific diseases, our study shows that recurrent 1q21.1 microdeletions are significantly associated with pediatric disease, through systematic comparison of the frequency of rearrangements in affected and unaffected persons. Second, detailed clinical evaluations of affected persons disclosed a much broader spectrum of phenotypes than anticipated, dispelling any notion of syndromic disease. While this article was being reviewed before publication, two groups reported enrichment of 1q21.1 deletions in persons with schizophrenia; they report deletions in 0.26% of patients with schizophrenia, as compared with our finding of deletions in 0.5% of persons with developmental abnormalities. These results confirm the association of 1q21.1 rearrangements with a broad spectrum of phenotypes but also further dispel the notion that rare copy-number variants will necessarily follow the one gene (or one rearrangement)–one disease model.

Researchers hope that such findings will lead to more accurate diagnosis (via genetic testing), and also “‘more effective treatments,’” as Professor Ledbetter is quoted (in HealthScout).

The new study further attests to the complexity of autism genetics, and to deep-running variance from individual to individual—there’s no one “autism gene” to be found.

Darn, I thought it was my own state of New Jersey that does: According to the most recent figures released by the Centers for Disease Control and Prevention in 2007, about 1 in 150 8-year-old children in multiple areas of the United States had an ASD, and New Jersey has the highest prevalence rate, 1 in 94. An article in the August 20th CityPages in Minnesota suggests that it’s rather the North Star state that has the highest rate, 1 in 81.

The CityPages article mentions a 2001 CDC study but not the more recent one in 2007, though it does cite the 1 in 150 figure. For the 1 in 81 figure, the article relies on a chart made up from data from public school districts around the country. (You can see the chart here via a parent’s website.) The parent of an autistic child, Dan Hollenbeck, arrived at this figure by finding the number of cases of autism services provided by each state’s public schools and then dividing this by the number of children enrolled. The figures that Hollenbeck arrived at provide an idea of how many children who are classified under the code of autism are receiving services in school districts across the US. But, it should be noted that school districts around the country vary in how they classify children as needing to receive services for autism, and services and programs for autistic children in public school vary widely from state to state (and within states—that’s certainly the case here in New Jersey–between rich and poor school districts, for instance). More than a few children classified under the autism code wouldn’t be diagnosed with autism if a full diagnostic assessment was done.

Further, Hollenbeck is the Director of Technology at Thoughtful House, an Austin-based center which is “fighting for the recovery of children with developmental disorders through the unique combination of medical care, education, and research.” Dr. Andrew Wakefield (the figure at the center of the MMR-autism controversy) is on the research staff of Thoughtful House, which says that we are “in the midst of an epidemic of developmental disorders that includes autism, Asperger’s Syndrome, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), pervasive development disorder (PDD), and nonverbal learning disorder (NLD). And, Hollenbeck and his wife, Laura Hewiston (the researcher behind a certain infamous poster presentation on monkeys and vaccines) are listed as litigants (see #437) in the Autism Omnibus proceedings in which some 4800 families are claiming that vaccines injured their children and causes them to become autistic.

In other words, there is some motivation for Hollenbeck to offer data that suggest that the rates of autism have risen “epidemically,” and especially due to vaccines or something in vaccines. (And, CityPages needs to make a few clarifications about the data that it is using.)

The 1 in 81 figure suggests that educators in Minnesota are very aware about autism and about providing services for children. And that’s certainly also the case in New Jersey which, according to Hollenbeck’s figures, has 1 in 115 children with autism, which is rather counter to the CDC’s 2007 figures, and rather counter to what the “Jerseyan in the street” would tell you about autism here. Down here at the shore on Tuesday morning, my son Charlie got over-stimulated in a bakery—chock full of vacationers and display cases—-and someone who is probably the owner appeared from the back; he has an autistic grandson. (We’d always noted a collection jar for autism events on the counter.) Last week, there was a young autistic man in the waves with his father every day, and this week there’s a boy a bit older than Charlie. And there’s Charlie himself; when we tell the lifeguards about why it’s so hard for him to understand about “swimming flag to flag,” saying “autism” is pretty much all that needs to be said. Back home, there’s our school district which has a quite high rate of autistic students compared to the overall total of students—-because it’s a district with a very strong autism program and also special education services, and many families (like us) have moved to it for that reason.

No discussion of autism rates among students (and no discussion of the so-called “autism epidemic“) is complete without keeping in mind Washington University Paul Shattuck’s 2006 article on The Contribution of Diagnostic Substitution to the Growing Administrative Prevalence of Autism in US Special Education,” in which he found that, as the rates of the autism diagnosis increased from 1994 to 2003, the rates of diagnoses of mental retardation and learning disabilities decreased. George Washington University anthropologist Roy Richard Grinker’s 2007 book Unstrange Minds: Remapping the World of Autism further explains how historical and cultural factors have led many to feel and even to believe that there is an epidemic of autism, in no small part due to our better understanding of autism, broadened and refined diagnostic criteria, and a huge increase in public awareness. There’s more and more research going on about the causes of autism: The August 19th KQED has a report on northern California researchers who are studying the causes, especially environmental ones , of autism. A blog details a video report, which can be seen here. Researchers are studying seemingly everything from dirty diapers to carpet dust in an effort to find if there are any “risk factors” that an expecting mother might encounter, that might be linked to her having an autistic child.

Having gone from Minnesota back to Jersey by way of California in this post, I have to note that we’ve connections to all three of these states. Charlie was diagnosed in Minnesota, has receive most of his school education in New Jersey (Jim’s native state), and I’m California born and bred, and there’s no question that, in all of those states (and in Missouri, where Charlie was born), we’ve encountered many autistic children. But then the chicken or egg question arises: Is the increase in autism is due to something specific that can be pointed to, something external and in the environment; or is it because of our being able to better detect and diagnose autism, significant changes in the diagnostic criteria for autism, the steady rise in public awareness about autism, and the increase in services, schools, therapies for autism (and college students)?

We’ve got the technology to measure Michael Phelps winning his seventh gold medal by .001 of a second—surely we’re better able to count cases of autism?

In the ongoing chicken and egg type debate over what the causes of autism might be, how often have you it said that it’s believed that a child may have a “genetic predisposition” to autism, but that it’s an “environmental trigger”—-it’s something in the environment—-that leads to a child “having autism”?

An August 13th post on Mind Hacks on a letter to Nature on psychiatric genetics offers something to reflect on. From the letter:

Your News Feature ‘The brains of the family’ (Nature 454, 154–157; 2008) and accompanying Editorial ‘An unnecessary battle’ (Nature 454, 137–138; 2008) highlight the need to adopt a more integrated perspective when trying to unravel the biological complexity of neuropsychiatric disorders such as schizophrenia and depression. But the ‘battle’ between genetics and neuroscience, despite being well funded, may be missing the point.

The full version is only available via subscription; Mind Hacks quotes more:

Napoleon Bonaparte advised: “Never interrupt your enemy when he is making a mistake.” Those of us who assess the contribution of non-heritable risk factors to neuropsychiatric illness would like to politely interrupt this battle to remind opponents that environmental risk factors have now overtaken genetic factors with respect to both effect size and the proportion of the population that is affected.

For schizophrenia, for example, factors relating to urban birth, cannabis use and migrant status are well replicated and have relatively large effects — in contrast to the scant evidence that remains after decades of genetics research. Although the ‘heritability index’ for schizophrenia is large (about 85%), this metric encompasses the neglected contribution of gene–environment interactions, as well as the high-profile genetic component. This key point is largely forgotten in the heat of the battle.

Mind Hacks explains” gene-environment interactions” as “where exactly the same genes can produce different heritability depending on the environment.” So, if we all lived in a “virtually identical environment” and had “almost exactly the same life experiences,” genetics alone would have to account for our differences; whereas, if “environment was widely different for everyone, much more of the difference would come from experience.” It’s been noted that studies into the genetics of autism only relate to a small number of cases: If (as suggested in a recent study), different (and many different) genetic mutations lead to autism in different individuals, what other factors might be coming into play, it’s wondered?

Granted, when people talk about “environmental factors” that might “trigger” autism, factors such as “urban birth, cannabis use and migrant status”aren’t what they mean, but rather something more like pollution and vaccines or something in vaccines…….

Autism incidents rising, is the headline for an August 9th story in the Grand Rapids Herald-Review. Two different school districts report having 35 and 52 students diagnosed with autism, versus five and maybe two students ten years ago: It’s been the past ten years that have seen the results of changes in the diagnostic criteria for autism spectrum disorders and a concurrent rise in diagnoses.

Though, isn’t it “autism incidence” that is meant in the headline for that Grand Rapids Herald-Review article?

“It’s the media’s fault.”

How often do you hear that, or even say it to yourself, on hearing some tired myth or piece of misinformation about autism stated yet again? Michael Savage’s over-the-top “99% of kids are no autistic but brats” comments is but one example.

An article by a team of bioethicists and available online August 6th in Neurology examines media coverage in America about the Terry Schiavo case. In 1990, Schiavo had a cardiac arrest that led to irreversible brain damage and a “persistent vegetative state” diagnosis. From Science Daily:

“In the course of our research, we were surprised by the amount of medical inaccuracies that these newspapers had published, said Dr. ÉricRacine [of the Institut de recherches cliniques de Montréal (IRCM)]. Some journalists even wrote about Mrs. Schiavo’s reactions to specific words or expressions supposedly showing that she was conscious.” More than scientific and medical information, the legal, political and ethical dimensions made the headlines.[my empahsis]

Only 1% of the articles examined gave a definition of the “persistent vegetative state,” an essential concept to understand the issues at stake. The persistent vegetative state is an established neurological condition characterized by severe lesions to the cerebral cortex, which eliminate higher functions: inability to communicate, absence of memory, absence of pain, etc.

However, the brain stem responsible for vital functions is not damaged, which accounts for the patients’ reflexes and their ability to breathe and swallow independently. Despite the fact that Terri Schiavo’s medical condition did not allow any reasonable hope of recovery, a fifth of all articles (21%) contained statements according to which her condition would improve. “Our observations show that the press capitalized on the controversy to a large extent, and selling copies mattered more than delivering scientific information [my empahsis]. Media coverage sustained myths and false hopes,” explains Éric Racine.

More than scientific and medical information, the legal, political and ethical dimensions made the headlines.

….[T]he press capitalized on the controversy to a large extent, and selling copies mattered more than delivering scientific information….

Apply these sentences to coverage of autism in the mass media (calling on some recent reports in CBS…..), and of the hypothetical vaccine-autism link in particular, and certain things resonate.

Controversy sells.

Tomorrow, August 7th, from 11 am to 3 pm EST, there will be a meeting of the Meeting of the Interagency Autism Coordinating Committee (IACC) Autism Strategic Plan Implementation Workgroup. The purpose of the meeting is to discuss budgetary requirements for the IACC Strategic Plan for Autism Spectrum Disorders (ASD) Research; workgroup findings will be forwarded to the IACC for consideration and discussion at the next committee meeting on November 21, 2008. You can listen in to the workgroup meeting through a conference call phone number and a web presentation tool on the Internet.

Click this link to join the Webinar:
https://www1.gotomeeting.com/register/921061447 [(Please note this information has been corrected, thanks to Regan]

Or, call this conference call phone number: (888) 455-2920
Access code: 3857872.

As a parent, when I see the phrase “nature-nurture,” I get a bit stuck on the “nurture” word, as any suggestion that we didn’t provide the right emotional, social, and so forth “environment” for Charlie and did not provide enough “nurture” can lead a parent to think of the discredited “refrigerator mother” theory of autism. Neuroscientists at MIT’s Picower Institute for Learning and Memory are using the phrase “nature-nurture” to describe new findings about genes, the brain’s development, and autism. The researchers have found a set of genes—calcium sensor called cardiac Troponin C, or cTropC—that are

…..particularly sensitive to a critical period of development. The lack of proteins from these genes during a key phase of development could be one of the culprits in developing autism.

The study shows how autism “can be genetic and yet be dependent on the environment,” as co-author Mriganka Sur, Sherman Fairchild Professor of Neuroscience at the Picower Institute and chair of MIT’s brain and cognitive sciences department, says in Science Daily:

“Many genes require activity to be expressed and make their assigned proteins. They alter their expression when activity is altered. Thus, we reveal an important mechanism of brain development that should open up a window into the mechanisms and treatment of brain disorders such as autism.”

In the brain, some genes are only expressed, or turned on, in response to stimulus from the outside world. Like a panel of switches that turn lights on and off, genes that don’t receive electricity don’t “turn on” and express their particular proteins.

Scientists are trying to figure out the correlation between “nature”—the genes—-and “nurture”—the external environment. By identifying “which genes are particularly apt to switch their expression patterns in response to ‘nurture,’” they hope to detect the genes that are implicated in developmental disorders.

The study is published in the July 8th Proceedings of the National Academy of Sciences.