Guanfacine (Tenex) for ADHD - more good news

These results are gratifying, but not surprising ...

Guanfacine Extended Release in Children and Adoles...[J Am Acad Child Adolesc Psychiatry. 2008] - PubMed Result

.... Guanfacine extended-release was effective in reducing symptoms of ADHD. Adverse events were mild to moderate, did not interfere with improvements in attention, and rarely led to discontinuation....

Guanfacine is a curious and perhaps powerful drug, so we need to treat it with cautious appreciation. The value comes because it's complementary to methylphenidate (Ritalin); it works by different mechanisms and the two seem to mesh well. Although Ritalin is exceedingly safe, it has some street value and can be problematic with adolescents. Ritalin can also exacerbate OCD symptoms and tics; Guanfacine doesn't seem to.

Even more interestingly, many believe Guanfacine can reduce "explosive" type behaviors.

Overall, good news.

Provigil and ADHD

This is old news (2006) but recent enthusiasm for using Provigil (modafinil) as a productivity enhancement for scientists brought it to mind:

Use of Drug to Treat ADHD in Children Opposed - washingtonpost.com

... A Food and Drug Administration advisory committee voted 12 to 1 against recommending modafinil as safe for children with ADHD. Earlier, the psychopharmacologic drugs panel unanimously agreed that modafinil works as a treatment for ADHD...

... The committee recommended that Cephalon Inc. undertake a 3,000-patient trial to determine the risk modafinil may pose for Stevens-Johnson syndrome...

... one out of 900 children involved in earlier studies of the drug developed the disease. He and Cephalon spokeswoman Jenifer Antonacci said the agency and the company will discuss the committee's recommendation ...

Please note that the enthusiasm for Provigil use by healthy people is occurring at the same time as a series of studies showing accelerated aging associated with lack of sleep.

A new drug for ADHD would be interesting, but it's hard to beat the incredible safety record of Ritalin. Provigil would have to have some really unique or complementary effect to be worth serious consideration.

Software for disabled persons

Hmm. I wonder if they'd consider doing an iPhone version of the Jaeggi working memory trainer ...

Entrepreneurial Edge - Software That Opens Worlds to the Disabled - NYTimes.com

ONE computer program would allow vision-impaired shoppers to point their cellphones at supermarket shelves and hear descriptions of products and prices. Another would allow a physically disabled person to guide a computer mouse using brain waves and eye movements.

The two programs were among those created by eight groups of volunteers at a two-day software-writing competition this fall. The goal of the competition, sponsored by a nonprofit corporation, is to encourage new computer programs that help disabled people expand their capabilities.

The corporation, set up by computer science students and graduates at the University of Southern California, is named Project:Possibility. It grew out of an idea two years ago by Christopher Leung, then a master’s degree candidate in computer science and engineering at the university, who was working on a project at NASA’s Jet Propulsion Laboratory in Pasadena....

I don't know what will come of this effort, but it's encouraging that many people are thinking (again) of how software can help people "be the best they can be".

Fragile X and memory

Pretty far from human application, but noteworthy ...

Fruit Flies, Fragile X and Foolery: Scientific American Podcast:

University of Alberta researcher Francois Bolduc keeps 300,000 fruit flies in a basement laboratory. He discovered that disrupting one gene known as FMR1 in the flies’ brains can wipe out their long-term memory. What’s interesting for us is that damage to that gene in people is associated with learning and memory problems, epilepsy and autism. That constellation of traits is known as fragile X syndrome. Bolduc then worked on curing his forgetful flies—he found a class of drugs that reduces the activity of the FMR1 gene. And the insects were able to regain their memory...

Working memory and COMT inhibitors - the nicotine example

Obviously, I'm not considering smoking as an aide to my son's limited short term memory. It is interesting, however, to note how substances associated with smoking act on the brain ...

FuturePundit: Gene Variant Makes Nicotine Withdrawal Harder

....

Spurred by their previous findings that carriers of the catechol-O-methyltransferase (COMT) val gene variant are more susceptible to smoking relapse, the Penn researchers set out to learn if smokers with this genetic background would be more likely to exhibit altered brain function and cognitive deficits during periods of abstinence from smoking.

...Results showed that smokers with the COMT val/val genotype suffered greater deficits in working memory and brain function when they had refrained from smoking for 14 or more hours, compared to their performance on this task when they had been smoking as usual....

... Inhibitors of this COMT enzyme might work to ease withdrawal from nicotine. Inhibitors of COMT already are known to increase working memory...

One method may be to offer carriers of this gene targeted therapies with drugs like COMT inhibitors, some of which have been shown to increase working memory in healthy volunteers.

The researchers were trying to understand why some people have a much harder time stopping smoking that others. It seems at least some of these persistent smokers experience brain dysfunction when they stop. The article does not tell us whether these people are experiencing a return to baseline cognition or whether they're experiencing a transient impairment. I assume the latter.

Even as smoking has become mercifully unusual in wealthier parts of North America, there's been more interest in the pharmacologic action of chemicals produced by the nicotine plant.

This related ticle on COMT inhibitors and executive function is interesting. Tolcapone is used to treat Parkinson's Disease (emphases mine):

Tolcapone improves cognition and cortical information processing in normal human subjects....

Prefrontal cortical dopamine (DA) regulates various executive cognitive functions, including attention and working memory. Efforts to enhance prefrontal-related cognition, which have focused on catecholaminergic stimulant drugs, have been unsatisfactory. Recently, the demonstration that a functional polymorphism in the catecholamine-O-methyltransferase (COMT) gene impacts prefrontal cognition raises the possibility of a novel pharmacological approach for the treatment of prefrontal lobe executive dysfunction.

To explore in a proof of concept study the effects of tolcapone, a CNS penetrant specific COMT inhibitor, we performed a randomized, double blind, placebo controlled, and crossover design of this drug in normal subjects stratified by COMT (val158met) genotype. COMT enzyme activity was determined in peripheral blood.

Forty-seven normal volunteers with no family history of psychiatric disorders underwent neuropsychological testing and 34 of those subjects underwent physiological measurement of prefrontal information processing assessed by blood oxygen level-dependent functional magnetic resonance imaging (fMRI).

We found significant drug effects on measures of executive function and verbal episodic memory and a significant drug by genotype interaction on the latter, such that individuals with val/val genotypes improved, whereas individuals with met/met genotypes worsened on tolcapone. fMRI revealed a significant tolcapone-induced improvement in the efficiency of information processing in prefrontal cortex during a working memory test. This study demonstrates enhancement of prefrontal cortical function in normal human subjects with a nonstimulant drug having COMT inhibitory activity. Our results are consistent with data from animal studies and from computational models of the effects of selective enhancement of DA signaling in the prefrontal cortex.

Please note that some people got worse on Tolcapone. I think we're a long way (20 years) from a safe medicine that can improve working memory, but this will be an interesting thread to follow.

Improving working memory in low IQ children

Working memory, sometimes called short-term memory, is currently thought to be closely related to IQ test results (for example) and perhaps to the cognitive performance that IQ tests try to measure.

It's also generally assumed that IQ cannot be improved, that individual capacity is determined almost entirely by genetics, intrauterine life, and perhaps the first few months of postnatal life. [1]. On the other hand, there's some evidence that working memory can be improved by training, though we don't know if the training effects persist.

That's roughly where the published science seems to be, but we're always free to draw some speculative (ok, breathtaking) inferences.

Wild speculation number one is that for most professionals under 50 it's not worth investing a lot of effort into training or improving working memory. My hypothesis is that in healthy brains things are pretty much aligned and that there aren't huge differences in subsystem performance. In other words, there aren't big performance bottlenecks. Improving working memory by, say, 10%, might only boost cognitive performance by 1%. Physical exercise is likely a far better investment than short-term memory practice. (I'm amazed by how important physical exercise seems to be to memory preservation, I never expected that.)

Once you get past 50 or so the rules change. I think the majority of us have some subsystem failure by then, so gains might be larger. I won't explore this one, however, as my major interest now is younger persons.

Consider the child, or young adult, with mental retardation (old term), cognitive disability (newer term), pervasive developmental delay (somewhat meaningless term), autism-spectrum disorders, severe ADHD and the like [2]. They often have patchy cognitive function. Some subsystems might work pretty well, while others, like working memory, might be pretty much shot.

This brings us to wild speculation #2. Imagine that IQ was the measured result of interactions between working memory, processing speed and, "rhubarb". (For this discussion "rhubarb" doesn't matter.) If "rhubarb" was working at 80% efficiency, and working memory at 10%, then working memory would be a performance bottleneck.

In this case a 10% improvement in working memory might become a 7-8% improvement in overall cognitive performance. That's a pretty significant improvement for someone who's on the borderline of social or quasi-independent function.

Now, that's an awful lot of speculation, but it's not hard to imagine how to test the hypotheses. We'd identify a set of children with low IQs, and work on short-term memory training...

Oh. Wait. It's been done. It worked. There are similar articles, including a review of the topic published in the PNAS that pointed out this is only the start of a long research agenda.

In the meantime, what about those low IQ children we know of today?

Well, when I wrote about this topic a few months ago Martin Walker of MindEvolve mentioned he's developed a software program to apply Jaeggi et al's techniques at home [5]. I've also previously written about games for improving focal cognitive weaknesses, and there's a real cottage industry of brain training exercises, including for working memory [3]. On my iPhone there are games like "Garf" [3] and "Matches".

I'm going to think about this a bit more. There might be a way to work this into our regular homework times for one child in particular ...

[1] In the interests of simplicity I'll assume IQ tests are a good approximation to IQ. It also obvious that IQ can be lowered by poor nutrition, head injuries, infection, seizures, trauma and so on.
[2] One of my pet peeves is the futility of classifying cognitive disorders given our limited knowledge of the underlying pathophysiology. Don't get me started on "reactive attachment disorder".
[3] As I wrote above though, I suspect those will have limited effects on the average "balanced" brain.
[4] My wife is very good at this. I am astoundingly bad at it. Hmmm.
[5] Windows only, $50, no trial version. The price is reasonable, but we don't have much Windows left in our home, and it's hard to spend the money without testing it first.

Why I will be flexible even if I am old

We all become less flexible as we age.

I will be more flexible than most.

How can I boast that?

It is a small benefit of parenting some very inflexible children. In middle-age my wife and I have been given a graduate level extended boot camp style program in enhanced flexibility.

Our natural bounds have been shattered.

Assuming a normal decay curve from our artificially elevated heights, we may expect a twenty year flexibility bonus.

It's good to have something to offset the accelerated aging associated with parenting special needs children.

Warner on Risperdal use in children

The NYT's Judith Warner meant well with a recent blog post about Risperdal use in children with "bipolar disorder" but she was ill-served by the research psychiatrists she interviewed.

Here are some excerpts of her writing, with the less sensible parts removed ...

Tough Choices for Tough Children - Judith Warner Blog - NYTimes.com

It was disturbing to read in The Times this week that the “atypical” antipsychotic Risperdal, a tranquilizing whopper of a drug with serious, sometimes deadly side effects, is now being widely prescribed to children with attention deficit hyperactivity disorder.

.. why, according to new Food and Drug Administration data on doctors’ prescribing practices, were 16 percent of the pediatric users of Risperdal over the past three years children with A.D.H.D.?

... The biggest controversy in the controversial field of psychiatry these days ... is the issue of pediatric bipolar disorder... a group of children who are really difficult: chronically irritable, extremely aggressive, prone to explosive outbursts and out-of-control rages.

Many doctors, influenced by the work of Dr. Joseph Biederman at Harvard Medical School (whose ties to industry were detailed in The Times in June), say these symptoms are signs of mania, and call these children bipolar. Others label them with “extreme A.D.H.D.” or Oppositional Defiant Disorder or “severe mood dysregulation,” ...

... This will not satisfy the critics of today’s biological psychiatry for whom no drug use is good drug use, nor the critics of today’s culture of parenting who are sure that all the aggression, irritability and out-of-control behavior that psychiatrists call mental illness is actually nothing more than a state of “toddlerhood in perpetuity” caused by ineffective parenting practices, as the conservative family psychologist and writer John Rosemond and his coauthor have asserted in his new book, “The Diseasing of America’s Children.”

And here's what I wrote as a comment (edited) ...

It was a noble effort, but I think you were led astray by your psychiatrist colleagues.

The best writing, by far, on the problem of the "explosive child" is by Ross Greene. For a discussion of Greene, Kazdin and the NYT's own Amy Sutherland see my blog posting.[1]

Greene's book is still in print, still sells well at Amazon, and has a 4.5 star rating.[2]. that's incredible for a book that's aimed at parents with children chronically on the edge of disaster.

You know Greene's book is for real, because not all his case study children do well. Some do horribly. That makes him believable. People who need Greene already know that not all endings are happy.

I'm an expert. Honest. An MD, MS, years of experience, and a child straight out of Greene. He's on two meds and I can easily see how he might have ended up on Risperdal, but, thus far, he's holding. We owe a lot to Greene and Kazdin and our helpers.

I'm also, interestingly, a world-class expert in nosologies and classifications (yeah, it's true).

So I can tell you that every classification we can invent for these children is merely a convenience. We don't know enough about the brain and this class of brain disorders to classify them the way we do heart failure or renal failure. Pediatric brain failure isn't well suited to classification.

One of Greenes many strengths is that he realizes this, and is humble about how much the diagnostic categories like 'childhood bipolar' or ODD or ADHD or PDD or autism really mean. They're better than nothing, but not enormously better. New classifications, in the absence of new science, won't change practice.

There's a vast amount we can do to bring basic behavioral messages (extinction, reinforcement) and teachings like Greenes to psychiatrists (who know very little about this domain). We'll still need to put a significant number of these children on drugs like Risperdal though. These are children facing terrible outcomes, and if the drugs are shown to help the terrible risks are worth bearing.

I didn't bother saying anything about oxygen-sucking dolts like Rosemond. People like him are a canker sore on the parents of troubled children [1]. Enough said.

Update 11/26/08: [1] On reflection, I have an idea where Rosemond and the like get their ideas. One of our children gets more "timeouts" (really calm-down intervals generally lasting under 30 seconds, but we call them "timeouts") on a sub-average day than another child has had in her entire life -- and will probably ever have. That's not an order of magnitude difference, it's a 2-3 order of magnitude difference. A 100 to 1000 times increase in parenting challenges.

Now, both these children are abnormal -- they're just abnormal at different ends of a broad scale. If all we knew was the easier child, we might also have astoundingly stupid ideas about parenting.

Altering brain chemistry through dietary means: implications from Alzheimer’s research

A BBC Science article on the animal Alzheimer studies caught my attention because of the reference to altering brain function through dietary changes. Emphases mine …

BBC NEWS | Health | Fatty acids clue to Alzheimer's

Controlling the level of a fatty acid in the brain could help treat Alzheimer's disease, an American study has suggested.

Tests on mice showed that reducing excess levels of the acid lessened animals' memory problems and behavioural changes.

Writing in Nature Neuroscience, the team said fatty acid levels could be controlled through diet or drugs…

… Scientists from Gladstone Institute of Neurological Disease and the University of California looked at fatty acids in the brains of normal mice and compared them with those in mice genetically engineered to have an Alzheimer's-like condition.

They identified raised levels of a fatty acid called arachidonic acid in the brains of the Alzheimer's mice …

… Its release is controlled by the PLA2 enzyme.

The scientists again used genetic engineering to lower PLA2 levels in the animals, and found that even a partial reduction halted memory deterioration and other impairments.

Dr Rene Sanchez-Mejia, who worked on the study, said: "The most striking change we discovered in the Alzheimer's mice was an increase in arachidonic acid and related metabolites [products] in the hippocampus, a memory centre that is affected early and severely by Alzheimer's disease."

He suggested too much arachidonic acid might over-stimulate brain cells, and that lowering levels allowed them to function normally…

I doubt this will end up being all that important for Alzheimer’s prevention, but it’s interesting as another hint that we might be able to alter behavior in children and adults with cognitive and behavior disorders through dietary interventions.

I tried looking for more discussions on this general topic, but I found very little. Seems far fetched for now, but I’ll keep an eye open.

Diary of a Special Ed Teacher

Just found this one through a NYT essay "Miss Dennis" wrote - Your Mama's Mad Tedious: Diary of a Special Ed Teacher. I'll be reading the back posts and subscribing to the feed.

I hope to do a post on her NYT article, she does repeat the article in her blog.

OpenOffice for OS X: touts accessibility

I'm impressed that their accessibility support is a touted feature: www: OpenOffice.org 3.0 New Features: "OpenOffice.org integrates well with the Mac OS X accessibility APIs, and thus offers better accessibility support than many other Mac OS X applications."

Accessibility solutions for OS X

Apple has long been a distant 2nd when it comes to accessibility solutions. Microsoft has put more effort into a reasonable foundation, and 3rd party vendors have built on top of Microsoft's base.

Recently, though, Apple has tried a bit harder. Legal threats from several states and fears of being shut out of the education market may have provided valuable motivation. (See: section 508.)

For example, OS X 10.5 has an improved screen reader, though Apple still has a long way to go. On the other hand persons with joint and motor disorders want robust voice commands and speech-to-text recognition -- but OS X provides only the feeble and under-developed "Speech Commands" tool.

In addition to the improved OS X accessibility page (still heavy on the marketing) Apple now has a 3rd party OS X accessibility page. Unfortunately, some of the solutions are only mildly related to accessibility and a few are basically web services that work on any reasonably browser.

There's a general accessibility page for all Apple products with some links I'll explore, such as the lioncourt blog.

At the moment I'm focusing on things I can do with for my mother, but the combination of poor vision, bad joint disease and limited sensation puts things beyond what Apple can do. Now if she had a way to say "open mail" and "read messages" and then listen to the messages ...

Harcourt family learning series - useful

We've been using the Harcourt Family Learning Complete Curriculum books with our kids, including one child who's disabilities make reading and math pretty darned hard.

I'm happy with them. Amazon.com has a pretty good list of the books. The books were published by "Spark Publishing" (Flash Kids), but their web site is gone. I suspect they're no more. I can't find any evidence anyone else is publishing these.

The reading and math exercises are interesting enough and quite polished. The Grade 3 level readings are reasonably interesting to our 11 yo boy; it's tough to find that kind of age interesting/readable combination anywhere else.

Recommended if you can find 'em! We have the "complete curriculum" for grades 1, 3 and 4.

Controlling nerve cell connectivity - more developments

A day or two ago my post on Fragile X and autism research included a discussion of a general theme in current autism research ...

... Bear and other scientists have also identified several drugs that seem to correct the problem. The drugs don't replace the missing brakes in the brain. Instead, they limit acceleration by reducing the activity of a group of receptors on brain cells known as mGluR5 receptors.

The drugs have reversed most of the effects of Fragile X in mice. They are now being tried in humans. And at least one small study found that a single dose of a drug had an effect....

The idea is that neuronal connectivity is a delicate, dynamic, balance. Too much connectivity, or too little, can both prevent cognition from working correctly.

So now there's research on modulating neuronal interconnectivity. If they worked safely these drugs would inevitably be used on "normal" brains, probably illegally, but they could be of enormous benefit to persons with impaired cognition.

Note in this review the implication that autism and schizophrenia may be, in a simplistic sense, two sides of one coin.

A Switch to Turn Off Autism?: Scientific American

Scientists say they have pinpointed a gene in the brain that can calm nerve cells that become too jumpy, potentially paving the way for new therapies to treat autism and other neurological disorders...

... The brain is continually trying to strike a balance between too much and too little nerve cell activity. Neurologists believe that when the balance tips, disorders such as autism and schizophrenia may occur. They are not sure why neurons (nerve cells) go berserk. But Greenberg says he and his colleagues located a gene in mice and rats that helps keep neural activity in check—and may one day be manipulated to prevent or reverse neurological problems.

Researchers report in Nature that they discovered a gene called Npas4 churns out a protein that keeps neurons from becoming overexcited when they fire (communicate with one another through connections known as synapses). When scientists blocked the protein, the nerve cells fired or sent out more signals than normal; when they beefed up production, the neurons quieted down...

As scientists learn more about how brain cells stay balanced, Greenberg says they will be able to identify people who are genetically at risk for neurological disorders and develop new drugs to prevent and treat them. He notes that some of the other genes that Npas4 affects also have been linked to autism...

Drugs to treat these disorders are years away from common use -- if ever. In the near term understanding the protein products of these genes may help us better classify and organize brain disorders, though we can also expect that prenatal testing will lead to more abortions.

These developments may also increase the value of doing genetic testing on persons with cognitive disorders, so that if appropriate trials are available one might, very carefully, consider enrolling.

Minnesota Special Hockey Oct 11th open skate

Our family has enjoyed MN Special Hockey four about 2.5 seasons. We joined up in a pre-launch test, back when we skated with sled hockey. We're starting a new season with a free open skate the University of Minnesota's Mariucci arena (pdf flyer, see directions).

If you have a friend or family member in the Twin Cities region with a cognitive or social/behavioral disability, please invite them to our open skate - or check out our contact list.

MN Special Hockey has worked well for us. It's kind of a milder version of pond hockey, except that we play in good settings with great volunteers and coaches. We even have cheerleaders for the special games.

We get support from very generous donors like Section 108, Hockey Docs, 21 for kids and the Dasburg's -- so everyone can play. (Our family doesn't need financial support, but even without support it's not bad.) Games/practices are weekly, so it's not a burden.

We have three teams that roughly surround the Minneapolis St. Paul metro area, so there's a team in a reasonable drive for the entire metro area.

We're a fairly pale bunch, but not entirely white. Otherwise we're pretty diverse, aged 4 through 50+. Most players are more or less cognitively impaired, but a few are higher IQ Asperger's or varying degrees of autism.

When we started almost nobody skated, but after a few years some do pretty well. Some play in a private world, some are getting good enough to out skate me.

So regardless of age or skating ability, MN special hockey is worth a look! Come by the skate -- parking is easy and it's free.

Our media links and front page have some additional background.

Congress Passes Mental Health Parity Bill

Bush says he'll sign. This is a big step forward for all children and adults with special needs, though the primary focus is on the adult psychiatric disorders ...

Health Blog : Congress Passes Mental Health Parity Bill

The long fight over putting the coverage of mental health on par with other health conditions is nearly over.

Both houses of Congress yesterday passed bills that would prohibit employers who offer mental health coverage from doing things like charging higher co-pays for mental health services than for other kinds of health care. That’s long been a common practice...

.... Kennedy, who has battled substance abuse, is a Rhode Island Dem. and a sponsor of the bill. His dad, Sen. Ted Kennedy, now battling brain cancer, has been a champion of the legislation in the Senate.

The legislation exempts businesses with fewer than 50 employees. That’s one of several compromises that won the bill broad support from the business community and the Bush administration.

The House passed the language as a stand-alone bill (online here), while the Senate included it in another measure. So they’ll have to come to a joint agreement about what form the measure will take to be sent off to the White House for the president’s signature.

People who suffer from chronic depression will pay much less for health care, but those who do not will pay slightly more. That's the way insurance works, it's a good thing.

Bill Clinton on heatlhcare coverage for autistic children

It's hard to remember the glory days of Bill Clinton's administration.

Here's a side comment on an interview he recently had ...

Clinton on the bail-out — Crooked Timber:

.... He didn’t talk about healthcare in great detail, but it was clearly on his mind. He said that when he had been stumping for Hillary, he had heard tragic stories about people with no or insufficient health insurance in every town that he had visited. He had been particularly struck by the lack of help for families with autistic kids. He didn’t talk at all about the policy responses – but this was clearly something that he saw as a priority....

NPR series on autism: Hope for Fragile X, autism in college and more.

Public radio has been running a series on cognitive disorders. You can read summaries and listen to audio on the npr web site. I assembled this list by visiting a few and checking out related links. It covers most of the programs over the past two years, the more recent ones are first.

• Drugs Hint At Potential Reversal Of Autism (see below)
• An Autistic Student's Journey To College
• Confronting 'That Autism Thing'
• Autism: Helping Children Connect
• How To Avoid Being Bankrupted By Autism
• Why Can't Doctors Diagnose Autism?
• Autism Chronicles: Single With An Autistic Child
• Finding Support For Autism
• Autistic and Proud: A Movement Takes Hold
• Autism: The Unlikely New Campaign Issue
• Pediatrician: What Parents Should Know About Autism
• A Mother Inspired, Not Defeated, by Autism
• Autism Study Lends Credence to 'Fever Effect'
• Parents Fight for Autism Insurance Coverage
• Autism Poses Extra Obstacles for Blacks
• Neuroscientists Focus on Autism

Like millions of other NPR donors, I wish NPR provided downloadable MP3s rather than streaming audio. I must remember that the next time they hit me up for money.

I heard the most recent program on my commute this morning. It was on of those stories about parents, the Tranfaglia-Clapps in this case, who create a foundation and hound scientists to accelerate progress in their disorder. Alas, I’m no saint. These stories annoy me. Should I feel bad because I haven’t created a foundation for my kids?

Rationally, it’s not a good bet. Ironically, the Tranfaglia-Clapps were inspired by the movie “Lorenzo’s Oil”, but that was a movie. In reality the “oil” was a bust; the time and energy largely wasted except insofar as they supported new studies and research directions. That’s the hard thing about science and clinical research – there are lots of “busts”. There are many ways to spend one’s limited time and energy with special needs children, and time spent on developing a foundation has to be subtracted from competing priorities.

Even bad bets have winners though, and in this case the family’s small foundation made a starter grant to a neuroscientist casting around for money. Maybe Dr. Bear would have found his starter grant elsewhere, but chances are his work, at least, would have moved slower and taken longer. His initial results worked, and he was able to raise NIH funds….

Drugs Hint At Potential Reversal Of Autism : NPR

… every now and then, a basic scientist makes a discovery that changes human lives.

Mark Bear, who directs the Picower Institute for Learning and Memory at MIT, is one of those basic scientists. He's discovered a system in the brain that could change the lives of thousands of people with the genetic disorder known as Fragile X Syndrome.

Fragile X is a mutation on the X chromosome that can cause mental retardation and autism. Until now, there has been no treatment.

But Bear discovered that the mutation responsible for Fragile X appears to disrupt a system in the brain that regulates synapses — the connections between brain cells. He says the system works a bit like a car.

"You really need both the accelerator and the brake to properly function," Bear says. "In the case of Fragile X, it's like the brakes are missing. So even tapping the accelerator can have the car careening out of control."

Bear and other scientists have also identified several drugs that seem to correct the problem. The drugs don't replace the missing brakes in the brain. Instead, they limit acceleration by reducing the activity of a group of receptors on brain cells known as mGluR5 receptors.

The drugs have reversed most of the effects of Fragile X in mice. They are now being tried in humans. And at least one small study found that a single dose of a drug had an effect.

The implications for people with Fragile X are huge. If the drugs work, people with the disorder could see their IQs rise and their autism diminish.

"It's a dream come true to think that we have the prospect of having gone from really basic science discovery to a potential treatment," Bear says.

Bear's research was funded in part by a group called FRAXA. Katie Clapp and her husband, Michael Tranfaglia, started the group in the early 1990s as a way to help their son Andy, who has Fragile X Syndrome.

Clapp says she now has reason to hope that Andy, who is now 19, can get better.

"We're not expecting a miracle, or to make up for his 19 years of development," she says. "But if we can watch improvement happen, that's a dream."

We can cure damn near anything in mice, so the animal studies are just interesting.

There are lots of hits on mGluR5 and autism, including a 2007 TIME article. Here’s a 2005 review synopsis:

Purpose of review: This review will describe recent developments in the neurobiology of fragile X syndrome (FXS), the association between FXS and autism, and involvement in premutation carriers.

Recent findings: Metabotropic glutamate receptor 5 (mGluR5)-coupled pathways are dysregulated in individuals with FXS and this is thought to relate to the FXS phenotype. The mGluR5 model suggests that mGluR5 antagonists, including downstream effectors such as lithium, could be useful for treating FXS. Two forms of clinical involvement associated with the fragile X mental retardation 1 (FMR1) gene, autism and fragile X-associated tremor/ataxia syndrome (FXTAS), have received additional attention during the past year. One study has found that approximately 30% of individuals with FXS have autism; those with autism have lowered cognitive abilities, language problems, and behavioral difficulties compared to those with FXS alone. Furthermore, evidence is mounting that autism also occurs in some young males who have premutation alleles. Finally, males and occasional females with premutation alleles may develop a neurological syndrome with aging that consists of tremor, ataxia, peripheral neuropathy, and cognitive deficits. Significant brain atrophy and white-matter disease is usually seen. This new disorder (FXTAS) is thought to be related to elevated levels of abnormal FMR1 mRNA.

Summary: Full-mutation forms of the gene (> 200 repeats) can cause autism, learning disabilities, anxiety disorders, and mental retardation. Disorders associated with premutation forms of the gene (55-200 repeats) include, in addition to autism, FXTAS in older males and females, and premature ovarian failure.

My sense is that this sounds like a step along a road, but it might be a dead end. Progress, nonetheless.

I’ll take a look at the other programs over time and I’ll blog on any that are worthwhile. The next time NPR asks you for money, tell ‘em you’re going to hold back until they start providing MP3 downloads …

The rise and fall of autism vaccine theories

Salon features a book review by a physician journalist that traces the rise and fall of theories relating autism to vaccines. These theories are as dead as phlogiston, but strong supporters persist. Some of those supporters have financial motivations, but for others the belief has come to resemble religious devotion.

Most of the story was familiar to me, though I recall far more early skepticism than Dr. Parikh mentions. I think there was more early support among UK scientists, but US physicians were more suspicious. Those suspicions were justified, Lancet retracted the original article and the primary author is now suspected of fraud (emphases mine):

Salon.com Books | Inside the vaccine-and-autism scare

By Rahul Parikh

Sep. 22, 2008 | ... Dr. Paul A. Offit's new book, "Autism's False Prophets: Bad Science, Risky Medicine, and the Search for a Cure,

... Offit begins by tracing the history of the anti-vaccine movement to its roots in England in 1998: That's where a young, charismatic and ambitious researcher named Andrew Wakefield held a news conference to reveal he had discovered that the measles-mumps-rubella (MMR) vaccine causes autism. The prestigious medical journal Lancet subsequently published his paper. Soon, headlines warning parents about "child jabs" appeared on the front page of newspapers all over the U.K., and droves of parents began refusing the MMR vaccine. Despite the resurgence of measles in the U.K. as a result, Wakefield was hailed as a muckraker. The BBC even made a biopic about his fight against the establishment.

... Among the resulting press were Robert F. Kennedy Jr.'s "Deadly Immunity," published simultaneously in Rolling Stone and Salon, and David Kirby's blockbuster book, "Evidence of Harm," a damning account of the link between autism and vaccines and of our government's efforts to cover up a link between the two...

... it wasn't until 2004 that Brian Deer, an investigative reporter for London's Sunday Times, discovered damaging evidence against him. Despite what Wakefield claimed in his paper, his hospital's ethics committee never approved his experiments to put children to sleep under general anesthesia, do spinal taps on them, take biopsies of their intestines (one of the children was hospitalized after his colon perforated in several places) and take volumes of blood from their veins. Deer also discovered serious conflicts of interest: Wakefield's research was secretly bankrolled by a personal injury lawyer whose clients were suing MMR makers. Wakefield himself was given close to a million dollars to prove that the MMR caused autism. He had filed a patent for a new MMR vaccine at the same time he was doing his research. Upon learning this, Lancet retracted his paper, and he was charged with professional misconduct in 2005. If he is found guilty of misconduct, he will never practice medicine in the U.K. again.

The last nail in the coffin came in 2007 during an "autism omnibus proceeding" in the United States. (This is a federal hearing for several thousand parents who claim their children developed autism because of vaccines. Those parents are seeking compensation from the federal government.) Wakefield's former research assistant testified that his discovery about the MMR vaccine was, in reality, the result of contaminated lab equipment and that Wakefield knew this about but ignored it. In other words, as Offit writes, "Wakefield had crossed the line from ill-conceived, poorly performed science to fraud."

Eleven studies now show that the MMR vaccine doesn't cause autism (the most recent just came out). Six have shown that thimerosal doesn't cause autism; three have shown thimerosal doesn't cause neurological problems. Studies showing the opposite, like Wakefield's, use flawed methods, have serious conflicts of interest or have been conducted in animals whose results can't be extrapolated to humans.

... the father-and-son team of Mark and David Geier, one a doctor and the other with a college degree in biology. The elder, Mark, opened a homemade lab in his basement, where, under the patronage of anti-vaccine advocates, he works on his theories. They include prescribing Lupron to autistic children, a drug that several states use to chemically castrate sex offenders. The son, David, runs a medical-legal consulting firm, where he offers up expert witnesses for vaccine-injury trials. The two work hand in hand to make money both selling treatments and testifying as expert witnesses in vaccine-autism cases...

In addition to the obvious harm caused by falls in vaccination rates, these 17 research studies were a necessary but huge waste of time, money, and talent. I'd rather one of them had been spent on strategies for helping autistic children learn more effectively ...

Kindle reader - not ready for visually or cognitively impaired

It's a little disappointing that the Kindle is not quite ready for people with visual impairment ...

Amazon.com: Vision Impaired - Can a Kindle help? - kindle swindle Discussion Forum

A family member has been having a signifificant problem with her vision. I liked the idea of the magnification provided by a Kindle. I have several questions ...

Reviewing the responses I learn that the Kindle allows several font sizes, but even the largest is only comparable to a large text book. The contrast doesn't work as well for persons with macular degeneration as a backlit device.

Of course there's no screen reader integration - yet.

The good news is that there are no technical problems with increasing the font sizes, and even the screen reader abilities can't be too far away.

I hope Amazon will provide more support for the visually impaired in Kindle 2.0.

Palin cut special needs funding by 62%

She made these cuts while Alaska's oil revenue was booming.

Grasping Reality with Both Hands: The Semi-Daily Journal Economist Brad DeLong

[Palin]:

To the families of special-needs children all across this country, I have a message: For years, you sought to make America a more welcoming place for your sons and daughters. I pledge to you that if we are elected, you will have a friend and advocate in the White House.

But then you read:

However, a comment here notes that Palin actually slashed funding for schools for special needs kids by 62%. Budgets: FY 2007 (pre-Palin), 2008, 2009 (all pdfs).

This is consistent with her political record and ideology.

We already know McCain's dismal attitude towards support for disabled persons, and Obama's strong policy position.

A vote for McCain/Palin is a vote against our children and loved ones.

Technology for special needs

It's hard for corporations to invest in solutions for special needs adults with cognitive disabilities. The market seems too small.

On the other hand, it's easy to justify solutions for aging Americans with pre-dementia -- that's a large and growing market that will hopefully include me one day. (Live long enough, your brain will go.)

The cognitive state of a pre-demented 75 yo overlaps with that of a young person with cognitive impairment. So all of the solutions described in this article are applicable to our loved ones (emphases mine) ...

Basics - For the Advanced in Age, Easy-to-Use Technology - NYTimes.com

...“The new market is old age,” said Joseph F. Coughlin, director of the Age Lab at M.I.T. ...

The companies that are successfully marketing new technologies to older people are not those that have created high-tech ways for seniors to open jars. Rather, they are the ones that have learned to create products that span generations, providing style and utility to a range of age groups...

... Consumers with less-nimble fingers find the large knobs in Honda’s boxy Element easy to manipulate...

The rash of accident avoidance technologies — like blind spot detection, lane departure warning and adaptive cruise control (which slows your vehicle down if you get too close to another car) — cross age boundaries in their appeal...

Here are some current technology products created for aging consumers:

... The Jitterbug clamshell phone (www.jitterbug.com), made by Samsung ($147, not including a service plan), does not reveal itself as a phone for older people until it is opened, displaying oversize buttons and large type on the screen. One-touch buttons enable easy dialing of 911 and other emergency numbers. The carrier markets the phone to the elderly with ads that explain that consumers can either dial numbers or ask a Jitterbug operator to do it for them. The company says 30 percent chose an operator’s help.

Phone numbers can be manually entered into the Jitterbug or the company can do it for consumers. Full text-messaging will be available next year.

... The Pantech Breeze ($50 with contract), by AT&T, and the Coupe ($30 with contract), by Verizon, are a bit more subtle in that they look more like standard cellphones. They are simplified flip phones with somewhat large buttons, oversize type and three one-touch buttons for emergencies. The Breeze includes Bluetooth capability and a pedometer.

... Later this year, iRobot will market the ConnectR, its “virtual visiting robot,” which will allow people to remotely view and speak to others. With its activities managed from a Web site at a remote location, the robot can be told to travel around a house to make sure that its occupants are safe, to read a story to a child...

TAKE YOUR MEDICINE Another problem of aging is forgetfulness. A number of automated pill dispensers that verbally alert users when to take their medication are available. From Timex, the Daily Medication Manager (www.timexhealthcare.com) holds medication and can alert a user to take dosages up to four times a day.

Med-Time, from the American Medical Alert Corporation (www.age-in-place.com), can be programmed to dispense as many as 15 pills, each up to 28 dosages a day. When the unit beeps, the user turns the device over to release the pills.

The simple moments of forgetfulness may not be able to be eliminated, but their effects can be mitigated.

For those who misplace items, the Loc8tor (www.loc8tor.com), starting at about $100, can find up to seven items. A small tag is attached to an object, which is then registered on the Loc8tor’s main unit using radio frequency. When an item is misplaced up to 600 feet away, the user chooses the item from the list and a series of tones points the user in the correct direction.

Of course, if the main unit is lost, you may never find your keys. In which case, several lock manufacturers offer keyless home entry locks that use fingerprint recognition technology to open a door. Available from such companies as Kwikset and 1Touch, the units, which start at around $200, can authorize 50 or more users depending on the model...

Public response to autistic behaviors - living in a small world

Dave Kolpack's editorial on public responses to disruptive children begins with the phrase "politically incorrect". That's best read as "truth that offends the weak minded". He gets a little better, but not much better.

Emphases mine.

Disruptive behavior by autistic children stirs debate, brings forth conflicted feelings
By DAVE KOLPACK , Associated Press
August 13, 2008

FARGO, N.D. - When a 13-year-old Minnesota boy was banned from church after parishioners complained about his behavior, it exposed a painful truth so politically incorrect that some people feel guilty just saying it out loud: Some autistic children can be annoying and disruptive in public.

The case of Adam Race and others like him has laid bare conflicted feelings — among both parents of these children and other people — over autistic youngsters in public places. And it has stirred debate over how much consideration one side owes the other.

In the case of Adam Race, a judge agreed with a priest in Bertha, Minn., who said the 225-pound teenager was disruptive and dangerous, and upheld a restraining order barring him from services. The priest said Adam spit, wet his pants, made loud noises and nearly ran over people while bolting from the church after services.

Carol Race, Adam's mother, said the congregation's claims were exaggerated. But in a letter to the Star Tribune of Minneapolis, JoAnn Brinda of Crystal, Minn., said the Race family should have shown more consideration for others.

"I don't understand why families that have a challenged child who becomes loud and abusive remain at a service where all participants are quiet and contemplative most of the time," Brinda wrote....

...Similar cases involving people with autism have played out in public recently. A California man was kicked out of a health club for screaming. A North Carolina boy was taken off a plane before takeoff after having a meltdown. A South Carolina girl was ordered out of a restaurant by the town's police chief for crying.

Syndicated radio talk show host Michael Savage added to the furor last month when he charged that doctors and drug companies are overdiagnosing autism, and said, "I'll tell you what autism is: In 99 percent of the cases, it's a brat who hasn't been told to cut the act out." Several major companies pulled their advertising from Savage's show.

Lisa Jo Rudy, who is the mother of an autistic child and writes and consults on autism, said Savage's words were "truly nasty and hurtful." At the same time, Rudy said the talk show host has raised awareness of some of the frustrations of parents of autistic children and the wider public, too.

Rudy said there are times when parents should not put their children in situations where they may be disruptive. "Some of these stories really are the ones where the general public can absolutely identify with the other side of the story," Rudy said.

Jason Goldtrap of Davenport, Fla., said too many people diagnosed with autism are out and about in public because of political correctness. Goldtrap, 40, has two nephews, ages 3 and 21, with autism, and said the older one has become so violent at times that the police have been called.

"I certainly sympathize with all the families who are in this situation," Goldtrap said. "But when we got away from the concept of institutionalization in America, we lost an important element of trying to maintain civility. There is a place for mental institutions."

Goldtrap added: "If it were up to me, he would be in an institution. My brother doesn't agree, and that's his prerogative." He declined to identify his brother, saying, "I don't want to start another argument."

.... Many parents say that their autistic children are largely misunderstood, that they can't help it when they act up, and that they need interaction with the public...

Asperger's tends to run in genetically related families, and it's associated with categorical rigidity and intolerance of disruption. I wonder if Mr. Goldtrap might carry a diagnosis he's unaware of.

I think what we're seeing here is the graying of America. The boomer's are now over in their 50s and 60s, and they're pretty removed from their child rearing days. Now they have little tolerance for normal children, and less for children with disabilities.

Sure it's hypocritical and selfish, but these are primates we're talking about.

As usual, there are no simple answers. Today, while visiting a coffee shop on a regular outing with one of my sons, a staff person pulled me aside. She and a colleague were compelled to tell me how much they loved my son's calm manners, his smile and his quiet charm. They have no idea of his disabilities, it was genuine praise for a "well behaved child" that I gratefully accepted.

They've never seen him meltdown. Probably they never will -- the setting works for him. If they did, then maybe they'd put him in the disruptive autistic-keep-indoors child category. He's still the same person of course.

Another child is often praised for his charm and behavior; but at home he routinely pushes our extreme parenting skills to new limits of invention. I still remember, at a thankfully much younger age, a spectacular meltdown on an airplane ...

Of course I also remember our quite normal daughter awakening after a flight when Mum had left to get a cart -- her shrieks could be heard on incoming flights.

Life's complicated. If you retreat indoors, the children don't get any practice with the real world. You'll never discover that seemingly utterly insane road trips work inexpicably well for one set of kids.

On the other hand, if your child hits the wall in a public setting, you may have to explain to the nice officer why you're physically restraining a screaming child. This is even more fun if an adopted child doesn't actually resemble their parent; mercifully we've somehow missed this experience so far. In the days that sort of thing happened to me people were slower to call the police than I'd have expected.

We don't go to church. We never did find a place that would accept both me (effectively an atheist) and our kids. The intellectual churches tend to have gray haired parishioners who like things quiet, the loud and tolerant churches can't deal with an atheistic snake in the grass.

It's a small world, and getting smaller all the time. Do your best, and if your son or daughter goes ballistic near me you'll have at least one sympathetic bystander.

The Tropic Thunder boycott

Here's the email from the Down Syndrome of MN executive director:

By now you may be aware that Tropic Thunder, a film which depicts people with developmental disabilities in a derogatory and disrespectful manner, will open in our area tomorrow evening.

Despite aggressive attempts to get Dreamworks-Paramount to modify the offensive content, the film with its offensive and hurtful stereotypes about people with disabilities has debuted intact. The Down Syndrome Association of Minnesota, therefore, joins the National Down Syndrome Congress, National Down Syndrome Society, Special Olympics and Arc of the United States and other disability organizations in calling for a boycott. One of the best ways to send a message to Hollywood is to cut into their ticket sales.

Considering what we ask, we must be completely honest. While trusted members of our community were allowed to preview the complete film, all that is available generally is a promotional trailer. That brief glimpse leaves a nasty taste, but to be fair is not the full movie.

We have elected to trust our colleagues who have seen the full film. You can read the reaction of one, journalist Patricia Bauer, on her blog at www.patriciaebauer.com Based on what Patricia says and the reports of other leaders in both the Down syndrome and larger disabilities community, we reiterate our call for a boycott of TropicThunder.

Special Olympics USA has taken a bold lead on this issue calling for the elimination of the term "retard” ­ or the R-word as they put it ­from popular language. Language is a powerful tool. Individuals with developmental disabilities are not "retards"; they are our sons, daughters, friends, employees, neighbors, classmates; people deserving respect.

It is quite easy to avoid the film, however, if you agree we need to make a loud and clear statement ­ about Tropic Thunder and the larger issue of disrespectful, prejudicial language ­we urge you to both join the boycott and spread the word among your friends, neighbors and co-workers.

Finally, I would direct your attention to a short video produced by Will Schermerhorn of [Blueberry Shoes Productions]. This very short video was put together for the Arc of Northern Virginia. It is a beautiful counterpoint to “Tropic Thunder”.

Kathleen Forney
Executive Director
Down Syndrome Association of Minnesota

Patricia Bauer has a good sample of responses to the movie, both those defending it as a parody of Hollywood and those offended by the "R" word.

Probably the best comparison is the use of the "N" word in film -- a matter of debate when used by black directors; offensive when used by white directors. By that metric the movie is at best gratuitously offensive, at worst cruel.

Schizophrenia revelations - implications for autism

Following close on the heels of findings that major gene scramblings are common in "normal" brains comes more startling news about brain disorders:

Gene-Hunters Find Hope and Hurdles in Schizophrenia Studies - NYTimes.com

... The variants discovered by the two groups, one led by Dr. Kari Stefansson of Decode Genetics in Iceland and the other by Dr. Pamela Sklar of Massachusetts General Hospital, are rare. They substantially increase the risk of schizophrenia but account for a tiny fraction of the total number of cases.

This finding, coupled with the general lack of success so far in finding common variants for schizophrenia, raises the possibility that the genetic component of the disease is due to a large number of variants, each of which is very rare, rather than to a handful of common variants...

... The new focus on rare mutations suggests that natural selection is highly efficient at removing schizophrenia-causing genes from the population. Despite selection against the disease, according to this new idea, schizophrenia continues to appear because it is driven by a spate of new mutations that occur all the time in the population....

“This may be the case in other brain diseases, too,” Dr. Goldstein said, “because successful cognitive functioning is a highly complex system and there are many independent ways to take it down.”

The search for common variants in schizophrenia, however, has not been very successful so far, though not for want of trying. There have been more than a thousand studies, implicating 3,608 genetic variants.

But when all the data are pooled, only 24 of those variants turn out to be statistically significant, according to an analysis in the current issue of Nature Genetics by a group led by Dr. Lars Bertram of Massachusetts General Hospital...

I read this as consistent with recent literature telling us that the human brain has been undergoing rapid evolution for a few thousand years, perhaps with an unusually accelerated mutation rage and high selection pressures.

Rapidly evolving organs are often fragile things -- like a car slapped together in a rush. Thousands of thousands of things can go wrong. Some are manageable, others produce schizophrenia and perhaps autism.

The bad news is we were hoping gene studies would identify common genetic mechanisms; we could then use these to characterize disease subtypes, better evaluate therapies, and identify new drug targets. Now that door seems to have shut. We have to look further up the bioinformatics chain for common functions that meds could act on, and we may fear that they'll be hard to find.

Autism and ADHD are not so different after all

More evidence that our current categorization of early onset cognitive disorders needs a rewrite.

Evidence for overlapping genetic influences on aut...[J Child Psychol Psychiatry. 2008] - PubMed Result

BACKGROUND: High levels of clinical comorbidity have been reported between autistic spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD). This study takes an individual differences approach to determine the degree of phenotypic and aetiological overlap between autistic traits and ADHD behaviours in the general population.

METHODS: The Twins Early Development Study is a community sample born in England and Wales. Families with twins born in 1994-6 were invited to join; 6,771 families participated in the study when the twins were 8 years old. Parents completed the Childhood Asperger Syndrome Test and the Conners' DSM-IV subscales....

RESULTS: Significant correlations were found between autistic and ADHD traits in the general population (.54 for parent data, .51 for teacher data). In the bivariate models, all genetic correlations were >.50, indicating a moderate degree of overlap in genetic influences on autistic and ADHD traits...

CONCLUSIONS: These results suggest there are some common genetic influences operating across autistic traits and ADHD behaviours throughout normal variation and at the extreme. This is relevant for molecular genetic research, as well as for psychiatrists and psychologists, who may have assumed these two sets of behaviours are independent.

I suspect all clinicians with significant experience with autism are accustomed to children who have features of both ADHD and autism. So no surprises there. Unfortunately, most studies of ADHD or autism focus on "pure" subjects, so they exclude children who have features of both.

That means there's very little research about children with both ADHD and autism spectrum disorder -- we don't know what medications, behavioral or educational interventions are most effective.

These results may justify research on the large number of children and adults who aren't "pure" examples.

Please don't feed the nasty man

Imagine there exists a nasty man of limited insight who's income depends on national attention.

Isn't giving him attention like feeding a bear with a bad tooth? He'll just come back for more.

Lessons from gene deletions affecting learning and autism both

On the one hand, this article annoyed me. It demonstrates the usual confusion between association and causation, and it extrapolates from an exotic genetic disorder to the much larger group of children labeled as "autistic".

The reasoning errors, incidentally are not the journalist's. They come from the researchers. Researchers are as prone to this fallacy as anyone else.

On the other hand, it has some interesting hints. So I'll delete the worst parts, and focus on the interesting hints.

Autism Genes That Control Early Learning: Scientific American

A new genetic analysis of large, inbred Middle Eastern families... pinpointed six new genes that may contribute to autism ....

They report in Science that all of the linked genes are involved in forming new and stronger connections, called synapses, between nerve cells in the brain, which is the biological basis of learning and memory formation...

The researchers studied 88 families in which one or more children had been diagnosed with autism, and the parents of each autistic child were cousins. Marrying second and third—and even first cousins—is not uncommon in the Middle East...s

The team found a total of six mutations affecting genes that had previously not been linked to autism. The mutations came in the form of deletions, where part or all of both copies of the genes were missing in a child with the disorder. All of the genes are known to be involved in parts of the same process: creating and strengthening synapses...

...Walsh says the team believes these deletions—which in most cases found here only remove some, but not all, of the DNA that makes up a gene—may mean that the genes can regain some of their normal function. In fact, some of these genes may just be switched off. "This presents the possibility that in some kids we could get the gene going again without necessarily having to put it back in the brain," he says...

...Walsh notes that many children diagnosed with autism tend to show vast improvement when they are placed in environments that allow them to practice learning repetitively. He says that these activities essentially train the neurons to make up for their lost function.

From a science perspective it's another advance in studying neurodiversity, and it fits in the context that large numbers of "normal" people have significant neuro gene deletions.

From a parent's perspective, I was struck by the idea that these neurons can form connections, but they take a lot of persistence to form. In particular, highly repetive learning.

It's hard to do that kind of teaching in a conventional classroom. It bores most students and teachers to tears. This fits with our experience in trying to teach reading however ...

Guanfacine for ADHD in children with autism -- and a recent literature report

Guanfacine in Children with Autism and/or Intellec...[J Dev Behav Pediatr. 2008] is basically reassuring. Guanfacine substantially improves ADHD behaviors in children with autism and similar cognitive disorders. It doesn't have other behavior score benefits. Side-effects were as expected.

I have a standing PubMed search on Guanfacine because it's a long used medication that was recently found to be an "alpha 2A adrenoceptor". That's making it the subject of extensive research, such as:

• changes in neuronal connectivity
• extended release works well in children and adolescents
• strengthening working memory networks (?)
• better prefrontal cortical regulation of behavior in aging animals (?)
  

Guanfacine (Tenex) is not FDA approved for use in ADHD, but the recent crop of articles expect approval shortly. It has been widely used for several years. Our son has taken it for about 2 years.

The challenge is that this medication will be taken for a very long time by very large numbers of children, often in combination with Ritalin. There are sure to be surprises, both good and bad. We don't know it nearly as well as we do Ritalin.

Games for focal abilities: Set and visual perception

Last week I wrote about focal abilities in the context of cognitive disability, and implications for employment in a distributed world. I was partly inspired by a friend who knew of an autistic child who was very good at the card game "Set":

Be the Best You can Be: Employment for special needs persons – hints from the classification of galaxies

...These [larger] disabilities are often offset by domains of relative, and even, absolute, strength, such as rapid pattern recognition in the card game “Set”, or rapid discrimination of large amounts of visual data. Tasks similar to the Galaxy Zoo classification, but with payment attached, might become an option – in time...

Since Child A has almost savant abilities to locate family members in a crowd, Andrew suggested I try him with "Set" -- a "game of visual perception".

The directions seem complex at first. Players choose groups of 3 cards from a larger set of 12 in which each of four attributes (color, shape, shading, number) are either identical or unique. I wasn't sure my son would get the game.

He saw me practicing as I thought about how to teach this, walked over, and started stamping out sets.

I guess he's played this before.

I'm not sure he's brilliant at Set, but for now he's much better than I am. Unsurprisingly, given his ADHD, he doesn't have much patience for the rules. He prefers to lay out all the cards, and pick out sets without keeping score.

It's great to have a game he can excel at, even though we'll need to be flexible with the rules.

Employment for special needs persons – hints from the classification of galaxies

The  Galaxy Zoo uses humans as “computers”. We’re very good at grouping things by resemblance, so hobbyists are used to group images of galaxies into “types”

... With your help, we've been able to collect millions of classifications, with which to do science faster than we ever thought possible...

…If you're already familiar with basic Galaxy Zoo analysis, click here to read the instructions and click here to take part. Galaxy Zoo 2 will go live in the near future featuring a much more detailed classification system, while further off we plan GalaxyZoo 3 with lots of exciting new data...

One amateur astronomer made an important original discovery.

Some persons on the autism spectrum with a personal interest in astronomy might be interested in the Galaxy Zoo today, but from a special needs perspective I’m mostly interested in where things might go in the future.

There will likely be tasks that humans do much better than computers for at least a few years. A few decades, I hope.

Some of these tasks will be open to people with focal cognitive disability. These disabilities are often offset by domains of relative, and even, absolute, strength, such as rapid pattern recognition in the card game “Set”, or rapid discrimination of large amounts of visual data. Tasks similar to the Galaxy Zoo classification, but with payment attached, might become an option – in time.

Incidentally, the first “computers” were humans. Even into WW II men and women did computational tasks by hand and were known as “computers”. (Engineers, of course, used slide rules until the late 1970s, but they weren’t called “computers”.) So this is a “back to the future” story.

See also:

• Outsourcing your crowd sourcing
• Distributed transcription using Amazon’s Amazing Turk

Does Ritalin specifically target the prefrontal cortex?

I've long been impressed by the unexpected safety of Ritalin (methylphenidate). It's rare for a medication to both alter brain function and have low toxicity, yet many years of use have given us little bad news.

Now FP reports on a study that suggests why Ritalin is both safe and effective for ADHD. It might not the drug we thought it was ...

FuturePundit: Research On Ritalin Mechanism Of Action

... In a paper publishing online this week in Biological Psychiatry, University of Wisconsin-Madison psychology researchers David Devilbiss and Craig Berridge report that Ritalin fine-tunes the functioning of neurons in the prefrontal cortex (PFC) - a brain region involved in attention, decision-making and impulse control - while having few effects outside it.

... Mounting behavioral and neurochemical evidence suggests that clinically relevant doses of Ritalin primarily target the PFC, without affecting brain centers linked to over-arousal and addiction. In other words, Ritalin at low doses doesn't appear to act like a stimulant at all.

Ritalin at lower doses appears to cause the prefrontal cortex (PFC) to be more sensitive to signals coming in from the hippocampus.

When they listened to individual PFC neurons, the scientists found that while cognition-enhancing doses of Ritalin had little effect on spontaneous activity, the neurons' sensitivity to signals coming from the hippocampus increased dramatically. Under higher, stimulatory doses, on the other hand, PFC neurons stopped responding to incoming information. "This suggests that the therapeutic effects of Ritalin likely stem from this fine-tuning of PFC sensitivity," says Berridge. "You're improving the ability of these neurons to respond to behaviorally relevant signals, and that translates into better cognition, attention and working memory." Higher doses associated with drug abuse and cognitive impairment, in contrast, impair functioning of the PFC...

I wonder if this will change thoughts about optimal dosing of Ritalin. I would very much like to see animal models studied to look for tolerance of Ritalin's alleged PFC effects.

When ADHD is an adaptive advantage ...

First, the news article (excerpt from FuturePundit: Hyperactivity Gene Helps Nomadic Tribesmen?). Then the anecdote ...

.... Kenyan nomads do better with an ADHD gene whereas those who have converted to settled living do worse with this same version of the DRD4 gene.

A propensity for attention deficit hyperactivity disorder (ADHD) might be beneficial to a group of Kenyan nomads, according to new research published in the open access journal BMC Evolutionary Biology. Scientists have shown that an ADHD-associated version of the gene DRD4 is associated with better health in nomadic tribesmen, and yet may cause malnourishment in their settled cousins....

... A study led by Dan Eisenberg, an anthropology graduate student from Northwestern University in the US, analyzed the correlates of body mass index (BMI) and height with two genetic polymorphisms in dopamine receptor genes, in particular the 48 base pair (bp) repeat polymorphism in the dopamine receptor D4 (DRD4) gene.

The DRD4 gene codes for a receptor for dopamine, one of the chemical messengers used in the brain. According to Eisenberg "this gene is likely to be involved in impulsivity, reward anticipation and addiction". One version of the DRD4 gene, the '7R allele', is believed to be associated with food craving as well as ADHD. By studying adult men of the Ariaal of Kenya, some of whom still live as nomads while others have recently settled, the research team investigated whether this association would have the same implications in different environments. 

While those with the DRD4/7R allele were better nourished in the nomadic population, they were less well-nourished in the settled population...  

...It is possible that in the nomadic setting, a boy with this allele might be able to more effectively defend livestock against raiders or locate food and water sources, but that the same tendencies might not be as beneficial in settled pursuits such as focusing in school, farming or selling goods...

There's a personal connection. 

Today we couldn't find child B at the pool. Since he has the classic Aspie tendency to wander, we became a bit anxious. 

We recruited child A, who, among other traits, has pretty severe ADHD. He also has a weird visual talent. He can pick things or people he's interested in out of a very large amount of visual input -- almost instantaneously. 

I told him we needed his "laser eyes" to find his brother, and I walked behind him. Zip. In 1-3 seconds he says "B is not in the big pool". He walks to where I can barely make out people in the diving pool. Zip. "B is by the climbing wall." A few minutes later I was able to spot Child B where Child A said he was.

In our society Child A is disabled. In a hunter gatherer society, at a slightly older age, he'd walk to high ground, spot game across the veldt, then head home to await delivery of the finest cuts of meat and play with his many children. I, in the same society, would be long dead. 

Adaptation is local.


Update: See also an earlier post on the same theme.

Update 7/5/08: The Economist has a more detailed review.

Road vacations: better options than you might think

Vacations with special needs children can be less than restful.

We have gone with long van-bound hotel-staying road trips for years. The first years, when the children were young and our techniques were less advanced, were like hang gliding around a tornado.

We did complex real-time calculations around video length, gasoline levels, food levels, drug levels, bladder volume, local geography, local facility expectations, weather and much more.

Now it's more like base jumping -- risky, but fairly predictable.

Here's a quick (very quick) post on advantages and recommendations for our family. The reality varies from trip-to-trip as we all age and change.

On the last trip we took our dog. That odyssey also involved a very politically challenging 50th anniversary parent celebration and several different family reunions at multiple sites. It spanned two nations, maybe 2,000 miles or so. My back blew out and I needed an ambulance ride to an ED about 60% through, then spent 3 days flat on the floor of the van until I invented a rig that allowed me to sit and drive.

And yet, and yet ... the children thought the trip went well.

Which is to say that if the vacation can work for the children under these circumstances, then the arrangement is more robust than even we expected.

Vacation for us? That was a funny one. Actually, if not for my back, I'd have had fun. I think my wife actually had a good time, and even I will remember the trip fondly after a few more weeks of forgetfulness.

Advantages and advice follow. I'll ask my wife to review and expand so this may develop further.

Advantages

1. In a moving van, no-one can hear your child scream.
2. Variety (external)
3. Consistency and predictability (internal)
4. They'll never see you again
5. You can stop the van, you can't stop the plane.
6. Flexibility

Tips

1. Small town parks, usually by schools.
2. Picnic, not restaurant
3. McDonald's drive through. (Same everywhere)
4. Avoid the big interstate (rest areas on I 90)
5. Avoid poor/destitute/hyper-urban areas (need breaks, need space)
6. Audio CDs ("books on tape") - superb. Little House in the Big Woods, Hank the Cow Dog
7. Activity bags: small toys, coloring books"Yu-Gi-Oh" cards and "duel disks".
8. iPod Playlists.
9. Movie in pm
10. Rituals: breakfast in room.
11. Gas station BID: bathroom, snacks
12. Swim in AM and PM
13. Ideally stay with one or two hotel chains (Baymont, AmericInn, Residence Inn)
14. Try to maintain your usual behavioral management regiment (ours fell apart on our last trip, no doubt)

Canadian revolution in mental health understanding ...

This Canadian Globe and Mail series focuses on common disorders with onset in adolescence and adulthood, but it's entirely relevant to cognitive disorders that present in childhood and at birth.

Gordon's Notes: An astounding series on mental health disorders

... astounded by their special series on mental health: Breakdown: Canada's Mental Health Crisis.

The title is misleading, there's nothing particularly Canadian about the stories. The portrayal of schizophrenia (let us honor the Bigelow family) and David Golbloom's review of the mission of the Mental Health Commission of Canada are among the best writings on mental health I've seen anywhere...

... Canada evolved the endless commission as an alternative to civil war. So the Mental Health commission may have an impact both in Canada and the US...

Canada is often 5-10 years more advanced than the US, so this is a strong indicator of cultural change that's likely to occur here -- sooner with Obama, later with McCain, but still on the way.

Autism spectrum disorders as disability vs different ability – a recent debate

Writing in the Britannica blog,  John Pitney replies to a Stanley Fish article …

Stanley Fish and Autism –John Pitney - Britannica Blog

In an entry on his New York Times blog, Stanley Fish wonders whether autism is just another “difference” like race or sexual orientation….

… Fish hints that autism may be a superior form of existence.  “A genetic difference is often adaptive and can be regarded as an advance in the evolutionary process…

… Apparently Fish gets his knowledge of autism from another movie, Rain Man.  (If you haven’t seen the picture, it portrays Dustin Hoffman as an autistic adult who can perform amazing feats of memory.) In real life, few autistic people have savant skills.  Among those who do, a large portion have severe problems with other areas of life such as toilet training.  It’s ridiculous to compare them to the X-Men.

Fish takes his cue from the “neurodiversity” movement, which questions whether we should see autism as a disease or disability.   Like adherents of this movement, he fails to make the crucial distinction between autistic people and the condition itself…

… That is reckless.  Autism is not a personality quirk.  It is a complicated neurological disorder that involves the entire brain.  It affects speech, language, body movement, memory, and emotion.  It comes in many varieties and degrees of severity, but even the “mildest” forms are life-shaping disasters. 

Fish might still object that the “disorder” label stigmatizes something that is merely a “difference.”  To say that autism is just a difference is like saying lung cancer is just a different form of cell growth and that painful wheezing is just a different form of respiration.

In his play Professional Foul, Tom Stoppard writes that “you can persuade a man to believe almost anything, provided he is clever enough.”  Stanley Fish is a very clever man, and other clever people will derive fleeting amusement from his comparison of autism to mutant superpowers.  He will now move on, and apply his drive-by cleverness to other topics. 

Meanwhile, he has done real harm by trivializing the struggles of autistic people, including my little boy.

During the 1970s there was a populist “revolt” against psychiatry. Schizophrenics weren’t mentally ill, the rebels claimed, they simply “thought differently”. They should not be strongly encouraged, much less forced, to seek treatment.

To put it mildly, this did great harm. The dark side of this meme persists in Scientology today.

Fish is so wrong on so many levels, not the least of which is a profound ignorance of how natural selection works. I think, though, as with the “don’t treat schizophrenia” movement, there’s an element of truth among the mire.

I’ve written previously about the legitimate scientific foundations for thinking about diverse minds, the fuzziness of our diagnostic categories, the astonishing prevalence of major genetic defects in seemingly neurotypical brains, and (elsewhere) about visualizing neurodiversity.

So for me Fish is mostly wrong, and Pitney is mostly right. In our world and in most conceivable worlds, the diverse disorders we crudely categorize as “autism” are severely disabling a source of sorrow and suffering for autistic person and their families. And yet, even so, there are people (electrical engineers, software engineers, etc) with traits that are highly adaptive in the modern world, even when these traits overlap to a certain extent with high IQ Asperger’s, which in turn overlaps with the most functional end of the so-called-autism spectrum disorder.

If we could “remove the autism” entirely from our children, they would be different people. Lung cancer, to use Pitney’s example, is not a part of a person. Heck, lungs aren’t a part of a person – not really. Aspects of a mind are the person, including disabling aspects. It’s not so easy to separate autistic persons from their disorder.

So if I had magical powers I’d “fix” some of the afflictions my children have – no doubt – but I would not want them to be different people. Some of the traits would have to remain – parts of the people I love – things they would not abandon lest they lose themselves.