NPR’s Asperger’s FAIL

NPR’s “All Things Considered” ran a piece today on the difficulties in defining “mental disorders.” Based on what is posted on their site regarding the piece, they essentially report the opinion of one man, Allen Frances, who has taken it upon himself to do two selfish things. The first is that he blames himself for what he calls the “Asperger’s epidemic.” The second is that he felt compelled to discuss some unfounded–or at least, unsupported–assumptions about Asperger’s diagnoses on NPR.

Frances, former chief of psychiatry at Duke University Medical Center, was the editor of the previous edition of the “mental disorders” bible, the Diagnostic and Statistical Manual of Mental Disorders. We’re coming up on the fifth version of this hefty tome. From my personal experience, by the time it comes out, research will be about five years ahead of much of what it contains. But never mind that. Frances’ issue with IV was that it contained Asperger’s as a diagnostic category (he has other issues not addressed in the NPR piece). He describes having acquiesced in its inclusion based on needs expressed by professionals who were seeing children with autism-like behaviors that weren’t as severe as the disorder known as autism.

Now he regrets that. Why? Because so many children are now being diagnosed with Asperger’s. As the parent of a child with autism, as the friend of many families with parents or children with autism, as the acquaintance of many grown people with autism–including Asperger’s–I can say that many of us would perceive that increase as a good thing. Why? Because that means more people with autism are able to recognize what makes them tick, and it helps them to know that yes, in a world where many of us feel like Temple Grandin’s aptly described “anthropologist on Mars,” there are a lot of other like-minded anthropologists out there.

That’s not Frances’ take. Based on a study done at the time IV was formulated, Asperger’s was “vanishingly rare.” That’s not too shocking given that for most professionals, it didn’t exist yet. The explanation that he offers for the increase in Asperger’s cases isn’t that there is now a diagnostic category for it, but that people–parents, presumably–seek the diagnosis so that their children can get services at school. This part is worth quoting from the piece:

“And so kids who previously might have been considered on the boundary, eccentric, socially shy, but bright and doing well in school would mainstream [into] regular classes,” Frances says. “Now if they get the diagnosis of Asperger’s disorder, [they] get into a special program where they may get $50,000 a year worth of educational services.”

The clear inference to draw from this is that there are hundreds of medical professionals out there deliberately stretching the diagnostic checklist for Asperger’s to cover children who are “doing well in school” and who are “socially shy” (what other kind of shy is there?). I have a few problems with this scenario.

First, if your child is doing well in school, you don’t get services. Services are for academic support. Period. There aren’t “special programs.” A child may have academic supports from almost nothing to a full-time aide in an integrated classroom to exclusion in a resource classroom. There is no one “special program.” That’s one reason they call those things INDIVIDUAL education plans. Regardless, if you’re doing well academically, you don’t get these supports. If you have speech or motor deficits, you receive appropriate therapies. But the deficits have to be there–they’re not something you just make up.

Second, if your child is doing well in school, parents and schools and medical professionals don’t generally go looking for a label to slap on the child. Parents seek help because their child has a problem or problems. The gold standard for calling something a disorder is if it interferes regularly with the general processes of daily life. Doing well in school but being “shy” doesn’t meet that standard. With autism, with Asperger’s, we’re talking about debilitating, meltdown-inducing, terror-filling anxiety. There is a difference.

Third, I don’t have a clue where he got the monetary value from, and NPR provides no balance for that statement. It’s just sitting there, making any family with a child receiving any services look like a faking money suck. Nice.

The piece as presented on the NPR Website provides nothing in the way of confirmation from objective sources. No studies indicating overdiagnosis. No input from experts in autism confirming what Frances says. His off-the-cuff commentary, his self blame, his stirring the pot all just sit there, unchallenged. Even the apparent effort at “balance” at the end of the story is almost a non-sequitur, part of a story with no real core. It’s as though they can’t make up their minds about whether the piece is about difficulties of diagnosis in general, the blurred lines between disorder and merely discombobulated, or that Asperger’s in particular is an overdiagnosed condition.

They don’t even provide Frances’ qualifications to speak to autism in particular. Not all doctors are oncologists, and not all psychiatrists have a deep understanding of developmental disorders.

All in all, a shoddy presentation that is already making its way around the Twitterverse, with parents once again feeling as though they have to defend their child’s diagnosis of a developmental difference that often goes unseen. Here’s the deal: The diagnostic criteria are clear, and a child who’s merely eccentric and doing well in school does not fit those criteria. If there is some modicum of overdiagnosis, it’s certainly not because of parents overseeking a label so they can have their child be stigmatized at school by receiving services. Look to the diagnosticians to blame. Or, in the complete absence of any evidence from Frances himself or NPR, do what Frances asks and blame him. Given his focus on his regrets over IV, he clearly seems to have something to expiate. And so does NPR. I’ll turn to D.H. Lawrence and say that thing is…a pettiness.

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Autism, SHANK, and busy highways

Two autism studies in the news. I’ve summarized them at the Thinking Person’s Guide to Autism here. Let’s just say that the headlines, stories, and news releases have hyped yet again. Indeed, the title of this post should’ve been: “Headlines hype, news releases overpromise again in autism research.”

The worst offender is easily, “Proximity to freeways increases autism risk, study finds.” Um, no. The study found that autism rates are higher among people living within 309 meters of freeways. That in no way means that living close to a freeway increases autism risk. It’s a common, basic overinterpretation of correlation and epidemiological conclusions, but it’s really starting to get old. You can read more about the fuzzy definition of “freeway” and “major road” here.

Mitochondrial dysfunction and autism

Beautiful pic of mitochondria

Mitochondria are the powerhouses of the cell, the biology teachers will tell you. These organelles also happen to be likely former bacteria that once were independently living cells, capable of dividing on their own to make new mitochondria. Indeed, they continue to divide by a kind of binary fission as our cells divide, ensuring that a double dose is available for partitioning into the two new cells that result from cell division.

To achieve these feats, mitochondria have their own DNA, their own proteins, and their own protein-making machinery. That means that they also have the potential to undergo genetic mutations that affect the sequence of the proteins their genes encode. Because most of the proteins in mitochondria are mission critical and must function exactly right, the persistence of such mutations is relatively rare. But they do happen, causing disease. One question that has arisen in the study of the causes of autism is whether or not such changes might underlie at least a portion of the cases of this developmental difference.

The high-profile Hannah Poling case

Certainly lending a high profile to this question was the case of Hannah Poling, whose mitochondrial disorder appeared to be linked to her autism symptoms and may have interacted with a bolus of vaccine doses she received, followed by a high fever. Fevers can tax our cellular powerhouses, and if mitochondrial function is already compromised, the high temperatures and extra burden may result in chronic negative outcomes.

Poling’s case brought to the forefront the question of whether or not people with autism might have mitochondrial dysfunction at greater rates. A recent study in the Journal of the American Medical Association (which steadfastly keeps its articles unavailable behind a paywall) has sought to address that question by measuring markers of mitochondrial dysfunction in children with autism and comparing these endpoints with outcomes in children without autism.

Study specifics: “Full-syndrome autism”

The autistic group in the study had what the researchers called “full syndrome autism,” which I take to mean intense symptoms of autism. They used the Autism Diagnostic Inventory-Revised

(ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) to confirm this diagnosis and to ensure as uniform a population among their autistic group as possible. Ultimately, the study included 10 children in this group, recruited consecutively in the clinic based on their fulfillment of the selection criteria. This study was essentially case control, meaning that the control group consisted of 10 non-autistic children, selected to match as closely as possible the demographic characteristics of the autistic group.

The authors report that while only one child among the 10 who were autistic fulfilled the definitive criteria for a mitochondrial respiratory chain disorder, the children with autism were more likely to have indicators of mitochondrial dysfunction.

A problem with pyruvate dehydrogenase (break out your Krebs notes, folks)

Specifically, six out of ten showed lowered levels of activity for one parameter, while eight out of ten showed higher levels than controls for another metabolic endpoint, and two of ten showed higher levels than controls of a third metabolic endpoint. Overall, the results indicated low activity of a mitochondria-specific enzyme, pyruvate dehydrogenase, which is involved in one of the first steps of carbohydrate metabolism that takes place in the mitochondria. Reduced activity of an enzyme anywhere in this process will result in changes in the enzyme’s own products and products further down the pathway and throw off mitochondrial function. Further, half of the autistic group exhibited higher levels of DNA replication, an indicator of cellular stress, more frequently than controls and also had more deletions in their DNA than controls. Statistical analysis suggested that all of these differences were significant.

What does it mean for autism?

Do these findings mean that all or most people with autism have mitochondrial dysfunction? No. The study results do not support that conclusion. Further, the authors themselves list six limitations of the study. These include the possibility that some findings of statistical significance could be in error because of sample size or confounders within the sample and that there were changes in some of the endpoints in the autistic group in both directions. In other words, some autistic children had much higher values than controls, while some had lower values, muddying the meaning of the statistics. The authors note that a study like this one does not allow anyone to draw conclusions about a cause-and-effect association between autism and mitochondria, and they urge caution with regard to generalizing the findings to a larger population.

If there is an association, questions arise from that conclusion. Does mitochondrial dysfunction underlie autism, producing autistic-like symptoms, as some argued in the Hannah Poling case? Or, do autistic manifestations such as anxiety or high stress or some other autism-related factor influence the mitochondria?

Chickens, eggs, MRI, mitochondria, autism

As interesting as both of these recent autism-related studies are, we still have the “Which came first” question to deal with. Did autism cause the brain or mitochondrial differences, or did the brain or mitochondrial differences trigger the autism? Right now, these chicken-and-egg questions may not matter as much as the findings do for helping to identify autism more specifically and addressing some of its negative aspects. Regardless of your stance on neurodiversity or vaccine or acceptance or cure or the in-betweens where most of us fall, it would be difficult to argue that a mitochondrial dysfunction shouldn’t be identified and ameliorated or that an awareness of brain structure differences won’t lead to useful information about what drives autism behaviors.

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Note: More lay-accessible versions of this post and the previous post are available at BlogHer.

MRI, brain differences, and autism

MRI: Sagittal view of the brain. Photo courtesy of Wikipedia commons.

You may have read the news reports blaring the finding of an “autism test” that could lead to early and definitive diagnosis of autism. The new evaluation, which has proved worthy of its own name, the Lange-Lainhart test, uses magnetic resonance imaging (MRI) techniques to image brain areas to detect changes associated with autism.

I’ve been unable to find the complete paper, reported to have been published in Autism Research on Nov. 29; the journal has only papers through October available on its Website as of this writing. According to reports, however, the authors state that the new test was 94% accurate in identifying who was autistic and who wasn’t among 60 males tested. The participants in the study were ages  8 to 26; 30 were diagnosed with what the researchers call “high-functioning autism,” and 30 were typically developing.

The imaging technique the authors used involves tracing water diffusion along axons, the long connectors that link neurons to other neurons or tissues. This diffusion tensor imaging process yields an image that can highlight variations in the patterns of these connective pathways in different areas of the brain. This study focused on six brain areas associated with language, social, and emotional functioning, all of which are traditionally considered to be problematic among people with autism.

In the brains of non-autistic participants, the flow patterns were organized in a typical way that indicated connectivity among the brain regions. In the participants diagnosed with high-functioning autism, the flow was disorganized in a pattern common to the autistic group, indicating less connectivity and interaction and thus less exchange of information in the network. The researchers repeated the test on another, smaller set of participants, 12 with autism and 7 without, and produced similar results.

These findings imply that autistic brains may operate like a set of computer hardware components that cannot communicate very well with each other while still functioning perfectly well separately. There may be camera that captures a visual image without trouble or a microphone that captures a voice clearly, but the system lacks the network necessary to integrate the two inputs into a unified perception.

The news reports I’ve read on the study make a big deal out the prospect that this imaging breakthrough could lead to earlier diagnosis of autism, something that most experts believe is key to ameliorating some of its negative manifestations. But experts also urge the standard cautious optimism, and rightfully so.

For one thing, the participants in this study were ages 8 to 26, not within the time frame for early diagnosis of autism, and all of them were male. The study findings can’t tell us whether their brains present with these differences as a result of developing with autism, or whether they have autism because their brains are built this way. Before there can be talk of “early diagnosis” and linking these changes to manifestations of autism, we’d need studies showing these differences in much younger children. Further, given the frequent findings of differences between males and females on the spectrum, investigations involving autistic girls and women are necessary.

This study is not the first to use imaging to identify distinctions between autistic and non-autistic people. Other studies have also done so, finding pattern variations in the neuronal tracts of children with autism compared to children without it, in critical areas relevant to the clinical symptoms of autism.

While I find these results intriguing, I note one thing that no one seems to have commented on. In the reports I’ve read about this study, the researchers observe that currently, the only way to diagnose autism is based on a symptom checklist, questionnaires, screenings, and so on—any autism parents reading this will know that drill—and the ultimate call relies on the expertise of the medical professional conducting the evaluations. The implication of these comments is that we need some better, more unequivocal, less-subjective methods of identifying autistic people.

Yet, presumably the autistic boys and men they used for this study were diagnosed using just such subjective evaluation, and their autism diagnoses appear to have been confirmed in 94% of cases by similarities of MRI findings. In my mind, this outcome suggests that the process of subjective evaluation seems to be working pretty well. Of course, we’re a visual species and like our decisions to be given literally in black and white. Such MRI results may fulfill a need that has less to do with correct outcomes than it does with a dose of visual confirmation–and satisfaction.

Sexual selection: Do females follow fads?

Is this male attired in the fashionable look of the season? Based on the reaction of the female in the background, perhaps not. Source: Wikimedia Commons

Timeline, 2008: Sexual selection is a mechanism of evolution that sometimes butts heads with natural selection. Under the tenets of natural selection, nature chooses based on characteristics that confer a competitive edge in a given environment. Under this construct, environment is “the decider.” But in sexual selection, either competition between the same sex or a choice made by the opposite sex determines the traits that persist. Sometimes, such traits aren’t so useful when it comes to the everyday ho-hum activities like foraging for food or avoiding predators, but they can be quite successful at catching the eye of an interested female.

Those female opinions have long been considered unchanging. In the widowbird, for example, having long, flowing black tailfeathers is a great way to attract the lady widow birds. But perhaps they don’t call them widowbirds for nothing: if those male tailfeathers get too long, the bird can’t escape easily from predators and ends up a meal instead of a mate. In these cases, natural selection pushes the tailfeather trait in one direction—shorter—while sexual selection urges it the other way—longer. The upshot is a middling area for tailfeathers length.

This kind of intersexual selection occurs throughout the animal kingdom. Probably the most well-recognized pair that engages in it is the peacock and peahen. Everyone has seen the multicolored baggage any peacock worth his plumage drags around behind him. A peacock will fan out those feathers in an impressive demonstration, strutting back and forth and waving its tail in the wind, showing off for all he’s worth. It’s a successful tactic as long as nothing is around that wants to eat him.

Frogs hoping for a mate find themselves elbow deep in the “paradox of the lek.” The lek is the breeding roundup for frogs, where they all assemble in a sort of amphibian prom. For the males, it’s a tough call, literally. They must call loudly enough to show the females how beautifully androgenized they are—androgens determine the power of their larynx—while at the same time not standing out enough to attract one of the many predators inevitably drawn to a gathering of hundreds of croaking frogs. Trapped in this paradox, the frog does his best, but natural selection and sexual selection again end up stabilizing the trait within expected grooves.

This status quo has become the expectation for many biologists who study sexual selection: natural selection may alter its choices with a shifting environment, but what’s hot to the females stays hot, environmental changes notwithstanding. But the biologists had never taken a close look at the lark bunting.

A male lark bunting has a few traits that may attract females: when it shakes off its drab winter plumage and takes on the glossy black of mating season, the male bird also sports white patches on its wings that flash through the sky and sings a song intended to draw in the ladies. But the ladies appear to be slaves to fashion, not consistently choosing large patches over small, or large bodies over lighter ones. Instead, female lark buntings change their choices with the seasons, selecting a large male one year, a dark-colored male with little in the way of patches the next, and a small-bodied male the next. Lark buntings select a new mate each year, and the choice appears to be linked to how well the male will aid in parenting duties, which both parents share. It may be that a big body is useful in a year of many predators, but a small body might work out better when food supplies are low.

The researchers who uncovered this secret of lark bunting female fickleness watched the birds for five years and based their findings on statistical correlations only. For this reason, they don’t know exactly what drives the females’ annually varying choices, but they speculate that environmental factors play a role. Thus, sexual selection steps away from the realm of the static and becomes more like—possibly almost indistinguishable from—natural selection.

Note: This blog post has been submitted for the ScienceOnline 2011 Travel Award Contest sponsored by NESCent, the National Evolutionary Synthesis Center. Here’s hoping that the judges find sexual selection to be this year’s travel award fad.

Beethoven died of lead poisoning–or did he?

Did lead kill Beethoven?

Timeline, 2005 and 2010: Literary folk have often noted the passion and emotion of Ludwig van Beethoven’s works. Lucy Honeychurch, the heroine of E.M. Forster’s A Room with a View, became “peevish” after playing Beethoven, and of course there’s the famous hooligan Alex from A Clockwork Orange, who was roused to stunning displays of violence after hearing “Ludwig van.” Given Beethoven’s own behavior, which was punctuated by violent rages, frequent sudden outbursts, and wandering the streets humming loudly, it’s not surprising that his music would communicate his passion.

A heavy metal influence?

A study in 2005 (news release here) yielded results that suggested that much of his anger, however, was attributable to the effects of heavy metal…specifically, lead. Beethoven became sick in his 20s (he also went deaf in his 20s), and suffered until his death at the age of 56 from a variety of illnesses, including chronic diarrhea and other stomach ailments. His death was lingering and painful, and some people thought that he had suffered from syphilis. Yet now many of his symptoms fit the classic description of slow lead poisoning. Among the effects of lead poisoning are irritability, aggressive behavior, headaches, and abdominal pain and cramping, all of which Beethoven experienced.

Doctor to businessmen to Sotheby’s to science

Some samples of the great composer’s hair and skull are available today for sophisticated testing for metals. A Viennese doctor apparently snagged a few fragments of his skull 142 years ago and the pieces eventually made their way through the family to a California businessman. The hairs were cut by a student soon after Beethoven died and ended up at a Sotheby’s auction. A few years ago, tests on the hairs suggested that Beethoven’s body harbored high levels of lead—hair accumulates and retains such toxins better than any other tissue—but because the testing method destroyed the hair, further tests were not completed.

Wobbling electrons solve the mystery?

Since that time, a powerful new X-ray technique has become available. The Department of Energy’s Argonne National Laboratory owns the X-ray. In the facility, subatomic particles fly through a tubular tunnel almost at the speed of light, emitting as they travel X-rays 100 times brighter than the sun’s surface. These X-rays can bounce off of the surface of even a tiny sample. As they bounce off of the sample, electrons wobble out of place, releasing energy in a pattern that is specific to the atom being bombarded.

Researchers were interested in Beethoven’s hair and skull pieces. The team that evaluated the samples actually works on developing bacteria that can take up heavy metals and render them relatively harmless; such organisms would be useful in environmental detoxification. They placed Beethoven’s hair in their high-powered X-ray. The electrons wobbled and the pattern indicated that Beethoven was simply full of lead. In fact, they reported that the poor man had about 60 parts per million of lead in his body, which is 100 times normal levels. It certainly was enough to make a person manifest the various symptoms that characterized most of Beethoven’s life.

The team also looked for a pattern that arsenic would emit, and they found none. This result seemed to exonerate Beethoven from having had syphilis, since arsenic would have been the treatment of choice for such an ailment.

Not so fast

At the time the study results were revealed, ideas about how did Beethoven built up so much lead abounded. Some suggested that  his body was less able than normal to rid itself of the heavy metal, through which he’d have been exposed by many channels. His stomach problems and temperament led him to consume much wine, and the vessels for drinking wine contained lead. In addition, his medicines probably were stored in lead-lined bottles or vials, and he may well have visited spas—for his health, ironically—at which he consumed or swam in mineral water containing lead. In one report, Beethoven’s poor doctor was identified as the likely culprit in his demise.

Fast-forward five years to 2010. A deeper analysis (news release here) of the bone fragments from Beethoven’s school indicated that his lead levels were not that spectacular. The bone is the reservoir for most of the lead the body takes up, and Beethoven’s bones simply didn’t have enough to have caused his various physical ailments. While the experts seemed to be in agreement that the results point away from lead, a new heavy metal mystery arose from the results. One skull fragment they tested had about 13 mcg of lead per gram of bone, nothing to write home about, while another sample turned up with 48 micrograms per gram, a much higher level. Nevertheless, we must look elsewhere for what killed one of the world’s greatest western composers. Ideas being tossed around include lupus and heart disease. What we do know is that he lived in terrible pain, both from his maladies and from the treatments designed to help, including pouring hot oil in his ears, according to one Beethoven scholar quoted in the New York Times.

Another wrongly accused suspect

Heavy metals have featured in other historical whodunits. For example, Napoleon reportedly died of stomach cancer during his exile on Elba, but one analysis showed that he actually died of slow arsenic poisoning, suggested to have been at the hand of his closest assistant. Then, much like Beethoven’s story, a later study showed that arsenic likely played no role in the great general’s death.

No legal limit for bats?

  • A bat in the hand

    Timeline, 2010: People with a blood alcohol level of 0.3 percent are undeniably kneewalking, dangerously drunk. In fact, in all 50 states in the US, the cutoff for official intoxication while driving is 0.08, almost a quarter of that amount. But what has people staggering and driving deadly appears to have no effect whatsoever on some bat species.

Why, you may be wondering, would anyone ask this question about bats in the first place? Bats are not notorious alcoholics. But the bat species that dine on fruit or nectar frequently encounter food of the fermented sort, meaning that with every meal, they may also imbibe a martini or two worth of ethanol.

Batty sobriety testing

Recognizing this exposure, researchers hypothesized that the bats would suffer impairments similar to those that humans experience when they overindulge. To test this, they selected 106 bats representing six bat species in northern Belize. Some of the bats got a simple sugar-water treat, but the other bats drank up enough ethanol to produce a blood alcohol level of more than 0.3 percent. Then, the bats got the batty version of a field sobriety test.

Bats navigate by echolocation, bouncing sound waves off of nearby objects to identify their location. To determine if the alcohol affected the bats’ navigation skills and jammed the sonar, the researchers festooned a ceiling with dangling plastic chains. The test was to see if the animals could maneuver around the chains while under the influence of a great deal of alcohol. To their surprise, the scientists found that the drunk bats did just as well as the sober ones.

Some bats hold their drink better than others

Interestingly, the bats did show a human-like variation in their alcohol tolerance, with some bats showing higher levels of intoxication than others. But one question that arises from these results is, Why would bats have such an enormous alcohol tolerance?

As it turns out, not all of them do. These New World bats could, it seems, drink their Old World cousins under the table. Previous research with Old World bats from Egypt found that those animals weren’t so great at holding their drink. Thus, it seems that different bat species have different capacities for handling—and functioning under the influence of—alcohol.

One potential explanation the investigators offer for this difference is the availability of the food itself. In some areas, fruit is widely available at all times, meaning that the bats that live there are continually exposed to ethanol in their diet. Since they can’t exactly stop eating, there may have been some selection for those bats who could get drunk but still manage to fly their way home or to more food. In other bat-inhabited areas, however, the food sources vary, and these animals may not experience a daily exposure to intoxication-inducing foods.

Alcohol driving speciation?

This study may be one of the first to identify a potential role for alcohol in the speciation of a taxon. Bats as a group underwent a broad adaptive radiation, meaning that there was a burst of speciation as different bat species evolved in different niches. Factors driving this burst are thought to have included different types of fruit; for example, tough fruits require different bat dentition features compared to soft fruits. Now, it seems that alcohol availability may also have played a role in geographical variation of alcohol tolerance in bats. Bats with greater tolerance would have been able to exploit a readily available supply of alcohol-laden foods.

What’s next in drunk-animal research? The investigators who made this unexpected bat discovery have a new animal target—flying foxes, which aren’t really foxes at all but yet another species of bat that lives in West Africa. We’ll have to wait and see how these Old World bats compare to the New World varieties when it comes to holding their liquor.

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