Preventing schizophrenia: not yet

A study testing whether schizophrenia in teenagers could be prevented has failed. It didn't tell us the treatments don't work, it did tell us the approach is not practical today.

We need better ways to identify young people with incipient schizophrenia, and safer drugs with fewer side-effects, before we can try this again.

I don't know what makes pyschiatrists think early treatment would prevent development of symptomatic schizophrenia. Maybe it's entirely too early for this sort of study. Do we really know enough about the disorder?

What science tells us about treating autism and ADHD

Alas, not very much.

John Hawks Anthropology Weblog : Evidence-based medicine and education

...At the Cambridge conference, prominent neuroscientists working in areas such as literacy, numeracy, IQ, learning, social cognition and ADHD spoke directly to teachers about the scientific evidence being gathered in scientists' laboratories. The teachers were amazed by how little was known. Although there was enthusiasm for and appreciation of getting first-hand information, this was coupled with frustration at hearing that many of the brain-based programmes currently in schools had no scientific basis. The frustration arose because the neuroscientists were not telling the teachers 'what works instead'. One delegate said that the conference "Left teachers feeling [that] they had lots stripped away from them and nothing put in [its] place".

Years ago I reviewed the ADHD literature, including some state-of-the-art reviews. Bottom line: we knew very little. Things aren't much better.

It's just as bad in autism. We don't even know what we're studying -- the terms "autism" and "ADHD" and the associated DSM-IV criteria may confuse more than they help. It's very hard to study something you can't even properly name.

There's a lot of great science happening now. In twenty years we may have new words, new diagnostic tests, maybe even evidence-based therapy. For now we're walking in very dim light. Recently I had a psychiatrist suggest the benefits of omega fatty acides in autism -- only to admit that the first trial that might give us a hint of a clue is barely starting.

Dim light indeed! Parents and therapists have to work with the data we have, but, for now, we must treat each intervention as an experiment that should be monitored. Continue it it helps, stop if it doesn't, try to measure outcomes objectively.

Most of all, clinicians should be humble. We don't really know what's going on and what helps or hurts.

PS. There are some topics, however, where there is decent evidence of a "dead end". It's really time to put the vaccine preservative and dental mercury stuff way in back of the back burner. There are so many better places to put resources now.

The genetics of neuropsychiatric disorders: Neuregulin

Neuregulin dysregulation may be related to schizophrenia.

This class of gene has also been theorized to play a role in autism, possibly related to a disorder in normal post-natal brain development around the time of language expression.

Autism: probably not increasing - whatever it is

A research paper claims that the apparent increase in autism prevalence is primarily the reclassification of mental retardation as autism...

Respectful Insolence: Evidence against an "autism epidemic"

... Shattuck analyzes special education figures that are being used to bolster claims of an autism "epidemic" and finds them wanting. In essence, diagnostic substitution can explain nearly all of the apparent increase of autism as recorded by the number of children receiving special education services. What that means is that children that would have been diagnosed with something else 15-20 years ago are now being diagnosed with autism. Dr. Shattuck starts with an example from a different condition, mental retardation as one of his reasons for suspecting diagnostic substitution as a cause of the perceived "epidemic":

...Second, prior research has established a precedent of diagnostic substitution in special education enrollment. From 1976 to 1992 the number of children in the mental retardation (MR) category decreased by 41%, whereas the number in the learning disabilities (LD) category increased 198%. There is considerable evidence that suggests this was because of a growing likelihood that schools would use the LD label for children with mild MR, presumably because a label of LD was increasingly seen as carrying less stigma than MR. Finally, a recent epidemiological study depicted a downward deflection in the incidence trend of other developmental disorders just as the trend for autism made a sharp upturn in the early 1990s, again suggesting the possibility of diagnostic substitution.

RI goes on to quote from an editorial arguing that the data is not sufficient to rule out some increase, even if it is not as enormous as initially thought.

I tend to believe the increase is relatively small, and perhaps due to the "silicon valley effect" (mating engineers). I have personal knowledge of two children who have both "educational" and "clinical" (different worlds) diagnoses of autism spectrum disorder. They are remarkably different people with very different IQs and abilities. In some ways they are almost perfect opposites, though they share a few common traits.

This is a superb mess. Much of its driven by an astoundingly boneheaded decision; "mental retardation" does not quality for educational services in most states, "learning disability" or "autism" do. I think the reasoning is supposed to be that "MR" can't be helped by special services, but an assymetric defect or autism can. Not surprisingly psychologists, physicians, teachers, and parents serve the needs of children best by conspiring to make the diagnosis of "mental retardation" relatively rare. Duh.

Other than the "mental retardation services" debacle, the autism classification confusion is perpetuated by our almost complete lack of understanding of what's happening, why it happens, and how it happens in the brains of these children and adults. It's very hard to classify something you truly don't understand. "Dropsy" in the 19th century became everything from venous insufficiency to renal failure to heart failure in the 20th century.

We're gradually moving to an anatomic-functional-genetic classification of brain development disorders. With luck both "autism" and "schizophrenia" will join "dropsy" in the garbage heap of abandoned ontologies. One day we'll be able to make meaningful assignments of individual brains to useful classifications, and then the real research will begin.

Autism: a deeper understanding of the "face" problem

It's not a surprising breakthrough, but it's an interesting study that is consistent with an emerging picture. They studied ASD persons with above average IQ. I know someone like that.

BBC NEWS | Health | Weak brain links 'explain autism'

...Dr Geoff Bird, at the UCL Institute of Cognitive Neuroscience, who led the research, said: 'The standard view of social problems in ASD is that there is a problem in the part of the brain that processes faces.

'Our research suggests that this is not the real problem - it seems to be that paying attention to faces doesn't lead to the normal increase in brain activity.

'This is because the face-processing areas of the brain are not well connected to those parts of the brain that control attention - such as the frontal and parietal regions.

So persons with autism can indeed process facial data well, but the data doesn't connect up with anything. It gets handled like any other visual input, it doesn't benefit from special networks that facilitate social interaction. Presumably those networks involve "mirror neurons". My personal wild guess is that the motor neuron network is sacrificed during early development to compensate for other brain injuries.

In time we may understand how to create electronic aides, "cognitive prostheses", to compensate for some of this ...

Siblings of disabled children

The NYT has a brief review on the experiences of siblings of disabled children. There's nothing new, but it's noteworthy that there's more discussion. Some do well with increased responsibilities, others are burdened. There were no evidence-based recommendations on how to mitigate harm done to siblings.

The developing brain: some big surprises

This is quite surprising. The human brain changes extensively between birth and adolescence (that we knew), but what's interesting is that it the pattern of changes is highly variable. Not everyone's brain follows the same developmental path.

Science & Technology at Scientific American.com: Smart Kids Found to Undergo Delayed Brain Development

... Rapoport and her colleagues at NIMH and McGill University followed 307 children of varying ages as they grew up, scanning them with an MRI machine periodically. They then compared such measures as brain volume with the results of a standard IQ test. Contrary to popular perception, the brightest kids did not necessarily have the largest brains.

They did, however, exhibit a distinctive pattern of brain development. Whereas an average child's cortex thickness peaked around age eight, the smartest children experienced thickening of the cortex until early adolescence. In all of the subjects, the cortex waned during adolescence, perhaps due to the pruning of neurons as the brain becomes more efficient, the researchers speculate.

Complicating the picture, however, relatively intelligent children--smarter than average but not the smartest--followed roughly the same development pattern as their more typical peers. And in the smartest kids the cortex shrank more than most during adolescence, in some cases dropping them below their relatively intelligent peers.

Although such intelligence seems to be genetic, the child-rearing environment may play an even more critical role, the researchers stress. Studies in rats have shown that their cortex thickness depends on richness of experience. [jf: I think this is misleading. The experimental rats they refer to had very limited environments, any reasonably decent human environment may be more than rich enough to make genetics the rate limiting step.]

It will be very interesting to see the results of similar studies performed in autistic children, particularly if we study not only pre-adolescents but also changes extending into the 20s. I have long wondered what the true natural history of so-called "high functioning autism" really is ...

Redefining mental retardation and autism - the revolution ahead

I've been known to protest that medical progress is much slower than popularly imagined. It's been over seven years since I was in active practice, yet current textbooks are often very familiar. Some of the meds are new, but the newest ones don't always last. Much of the therapy is basically unchanged.

But there are revolutions brewing.

The intersection of high resolution neuro-imaging and genetic analysis is dramatically changing our understanding of disorders sometimes known as 'mental retardation':

A developmental and genetic classification for malformations of cortical development -- Barkovich et al. 65 (12): 1873 -- Neurology

Increasing recognition of malformations of cortical development and continuing improvements in imaging techniques, molecular biologic techniques, and knowledge of mechanisms of brain development have resulted in continual improvement of the understanding of these disorders. The authors propose a revised classification based on the stage of development (cell proliferation, neuronal migration, cortical organization) at which cortical development was first affected. The categories are based on known developmental steps, known pathologic features, known genetics (when possible), and, when necessary, neuroimaging features. In those cases in which the precise developmental and genetic features are uncertain, classification is based on known relationships among the genetics, pathologic features, and neuroimaging features. The major change since the prior classification has been a shift to using genotype, rather than phenotype, as the basis for classifying disorders wherever the genotype–phenotype relationship is adequately understood. Other substantial changes include more detailed classification of congenital microcephalies, particularly those in which the genes have been mapped or identified, and revised classification of congenital muscular dystrophies and polymicrogyrias. Information on genetic testing is also included. This classification allows a better conceptual understanding of the disorders, and the use of neuroimaging characteristics allows it to be applied to all patients without necessitating brain biopsy, as in pathology-based classifications.

This very specialized article is not for the layperson; it's really written for the pediatric neurologist. Beneath the jargon, however, are some tectonic shifts in the definition of developmental disorders. It's a migration from external appearances (pre-1990 and still the world in which most of us live) beyond imaging studies (1990-2001, cutting edge yet) to the intersection of genes and environment (2005 and beyond).

The word "autism" doesn't appear in the paper, but that's only a matter of time. We are about to change the way we think of disorders of the developing mind and brain, and many of our labels are going to go away. In the new world we'll begin to make sensible statements about prognosis and to design studies of therapy that can be truly meaningful. This is good.

PS. See also: Asperger's a vague diagnostic concept.

When ADHD is not a disorder: the adaptive advantages of spontaneity

We have often thought our son would have done well laboring on a farm, or scouting ahead of a tribe spying for enemies, predators, and prey. Alas, his superior visual processing and restless activity are ill-suited to today's world. In our world his ADHD and other traits mean he is profoundly disabled.

Paul Steinberg writes about how a set of traits that are adaptive in on setting, can be maladaptive in another...

Attention Surplus? Re-examining a Disorder - New York Times:
March 7, 2006
By PAUL STEINBERG, M.D.

... Every generation likes to believe that it is witnessing the most dramatic epoch in history. In the case of the current Western world, that belief may indeed be accurate, particularly in light of the striking changes of the last 30 years.

As the business writer and consultant Peter Drucker pointed out, most people in the United States, Japan and parts of Europe are "knowledge workers." We live in an information age, in a knowledge-based economy.

For those of us who have "attention-surplus disorder" — a term coined by Dr. Ned Hallowell, a psychiatrist in Boston who has A.D.H.D. — this knowledge-based economy has been a godsend. We thrive.

But attention disorder cases, up to 5 to 15 percent of the population, are at a distinct disadvantage. What once conferred certain advantages in a hunter-gatherer era, in an agrarian age or even in an industrial age is now a potentially horrific character flaw, making people feel stupid or lazy and irresponsible, when in fact neither description is apt.

The term attention-deficit disorder turns out to be a misnomer. Most people who have it actually have remarkably good attention spans as long as they are doing activities that they enjoy or find stimulating. As Martha B. Denckla of the Kennedy Krieger Institute in Baltimore has noted, we should probably be calling the condition something like "intention-inhibition disorder," because it is a condition in which one's best intentions — say, reading 50 pages in a dense textbook or writing a 10-page paper in a timely fashion — go awry.

Essentially, A.D.H.D. is a problem dealing with the menial work of daily life, the tedium involved in many school situations and 9-to-5 jobs.

Another hallmark, impulsivity, or its more positive variant, spontaneity, appears to be a vestige from lower animals forced to survive in the wild. Wild animals cannot survive without an extraordinary ability to react. If predators lurk, they need to act quickly...

... For those with attention disorder who wish to be full participants in a knowledge-based world, medications equalize their opportunities. The drugs should and can be used only as needed in the context of dealing with the tedium of school or the drab paperwork of some jobs.

Cardiologists, biostatisticians and consumer advocates may clamor, appropriately or inappropriately, to reduce the use of the medications. But unless we go back to the caveman world, some people will find the drugs increasingly necessary to succeed as knowledge workers in a drastically transformed modern world.

Paul Steinberg is a psychiatrist and writer in Washington.

Paul's primary agenda is to justify the use of Ritalin despite its new 'black box warning'. Even so, it's nice to see some attention given to how a set of traits can become a disorder -- depending on the context.

As to that black-box warning, it should focus minds prior to prescribing stimulant meds of all classes. That's not bad, even though I rather suspect we'll find caffeine has similar problems. In our case, however, we didn't blink an eye. When you're receiving incoming fire, sometimes you drive without a seat belt.

No more adwords

The Google Adword links that have been showing up lately have been largely for sites that exploit vulnerable families with false claims and toxic treatments.

They're gone.