Tuesday, November 27, 2007

It's Not Another Shot in the Ritalin Wars

A few weeks ago a neuroimaging study was published in the Proceedings of the National Academy of Sciences. Normally, many such studies are published in various journals in science and medicine without a whole lot of fanfare. But this one had a magic phrase in the title. The phrase was one that gets ideologues everywhere very excited. The title of the study is:

Attention deficit/hyperactivity disorder is characterized by a delay in cortical maturation

The magic phrase? Attention Deficit/Hyperactivity Disorder.
In the weeks since the study was published, the press and blog worlds have been having a great deal of fun making the conclusions into another shot in the ideological "Ritalin Wars."
Some writers have claimed that AD/HD does not exist. Others have used it to claim that AD/HD is an artifact of poor diet, bad parenting, and/or curriculum reform in the public schools. Some have actually come to the conclusion that the title might suggest, that AD/HD is definitively a form of developmental delay. As we shall see, though, despite the way you might read the title, that is not the conclusion of the study.

Being a scientist myself, I decided that I would not weigh in on the conclusions until I had the chance to actually read the study. Today, as I procrastinate on a research paper I am writing, seemed like the ideal time to do so. So I went to the NY Times article from a few weeks ago and got the journal title for the article, as well as the name of the first author. Then I connected to my university library system -the joys of technology are without number!--and in five minutes I had used the e-journal finder to navigate to Highwire Press and download a pdf file copy of the study.

You can try this at home, but you may have to pay a fee to download the study. Most journals are made available to students and researchers via institutional subscriptions to publishers and databases. The article was published earlier this month in the PNAS. It is in the current issue.
The citation is:
Shaw, P. et. al. (2007). Attention deficit/hyperactivity disorder is characterized by a delay in cortical maturation. Proceedings of the National Academy of Sciences, 104 (49) 19649 - 19654.

It is a very good study. The methodology was good, the number of subjects was impressive--446 human subjects--and the conclusions made matched the data that was published. This study overall is an excellent advance in tracking brain anatomy differences between subjects that carry the diagnosis of AD/HD and those that do not.

In the abstract the researchers say:
There is controversy over the nature of the disturbance in brain development that underpins attention-deficit/hyperactivity disorder (ADHD). In particular, it is unclear whether the disorder results from a delay in brain maturation or whether it represents a complete deviation from the template of typical development.

They are telling us the purpose of the study: to get evidence that might solve the controversy in the field. But pay attention to the wording. The controversy is not whether or not the disorder results from a delay in brain maturation, but whether or not it "represents a complete deviation from the template of typical development." The question they is whether or not AD/HD can result partly from a delay in brain maturation.

The authors repeat this in different words in the introductory paragraph:
Since its earliest descriptions, there has been debate as to whether the disorder is a consequence partly of delay in brain maturation or as a complete deviation from the template of typical development.

As I have said above, the data from their work does support their hypothesis that AD/HD is "a consequence partly of delay in brain maturation." That means they have done a good study. But one study does not an etiology make. It is important for the non-scientist to get it that one does not prove or disprove a hypothesis from one study, even one so well constructed as this one. Good scientists know this, and in the discussion section of any well-written scientific report, they will report caveats and weaknesses and any possible confounding variables. This is so that, when future studies are done, they (or others) can try to fill in the gaps for the study. That's usually done by fiddling with the methodology.

This study was a well-written study by good scientists and they do point out weaknesses that might be fixed in future work. In the very beginning they point out that many studies using physiological data (this study uses anatomical data)--that is how the brain is actually working--support their hypothesis, but there are also many other studies that find "a quantitatively distinct neurophysiology, with unique architecture of the (EEG) and some highly anomylous findings in functional imaging studies, more in keeping with ADHD as a deviation from typical development." This is interesting. When I first heard of the study and heard that it was done using anatomical imaging, I wondered about what functional imaging would show. If I want, I can check it out.

Geek Alert! A question I now have is this: fMRI studies require the use of fluorescent dyes or other ways of getting the signal above ground. These are not usually done on children (for obvious reasons). So I wonder if these confounding studies are targeting an adult population with ADHD? If so, it could be that we are dealing with two very different populations. After all, adults with ADHD would be the children who did not grow out of it.

Another issue: The study was done using anatomical imaging and not functional imaging. The researchers used very good techniques to get at the maturational rate of various parts of the brain, but ultimately they were still measuing gray matter (neuron cell bodies) cortical thickness. Two questions: Are there differences between the two populations in the percentage of gray matter v. white matter (glia and myelenation)? And what about physiological differences? Do the brains work differently? I saw an fMRI study just this morning that showed differences in activation in the pre-frontal cortex (Brodman 9) for adults with ADHD (little to no activation) and typical adults.

In other words, anatomy is not the whole story here.
And to be fair, it was not the authors who claimed that it was.
That would be the press and pundits and ideologues. In other words, those who either did not bother to read the study carefully or those who have an axe to grind when it comes to issues about AD/HD.

So what did we find out from this study? We found out that part of the difference between kids with a diagnosis of ADHD and those without, is in the rate of brain maturation. Kids with AD/HD diagnoses (it was a mixed group of kids with primarily hyperactive, primarily inattentive and combined types) have brains in which the cortices mature more slowly, delayed by approximately 3 years, with a very significant p value. And we found out that in these kids, the brain development trajectory was the same for kids with and without ADHD.

But the researchers also analyzed the data for specific brain areas. And these tests showed that the trajectory of the brain development for all cortical areas was not identical. The kids with ADHD tended to have faster motor area maturation than those without. And they had slower executive function (frontal lobes!) maturation.
What does James Webb say of gifted kids? Farrari motor and dune buggy driver! It looks like the same developmental pattern is true for kids with ADHD.

This is very useful information. It is particularly useful for people who treat kids with ADHD as well as for people who teach them. It is very helpful in planning interventions to help these kids learn academically and function socially to know that their executive function maturity may be more than three years behind the average kid. As a teacher, as a researcher, and as a parent, I find this information to be extremely helpful and very interesting.

But it is not another shot in the Ritalin wars.

The authors did not say that ADHD does not exist. In fact, in their first paragraph, they define it as a neurological disorder. They describe the delayed maturation of the cortices of the brain as a "characterizing" ADHD. It is, then, a characteristic that could be used to differentiate people who have ADHD and people with other psychiatric diagnoses.

They did not say that children with ADHD should not be treated with stimulants like Ritalin. In fact, one possible confounding variable they mention is that 80% of the clinical population in the study (clinical = those with ADHD diagnoses) were being treated with stimulant medication. They do say that stimulant medication can be an effective short-acting treatment.

Finally, by calling the maturational delay a characteristic, the authors imply that there is another, more ultimate cause. They discuss this further in the last part of the discussion. The differences cannot be attibuted to intelligence or sociocultural factors because these were controlled in the design of the study. There is definite evidence that the differences are partly due to genetics because brain growth and development is controlled by molecules called neurotrophins and "polymorphisms within the brain-derived neurotrophic factor and
nerve growth-factor 3 genes have already been tentatively linked with ADHD."

A polymorphism is a difference in DNA base sequences from one individual to another.

A claim that genetics is involved in causing a neurological disorder does not mean that environment does not play a role. It is likely that something as complicated as differences in brain development is controlled by quite a few genes, that is, it is polygenic. It is also likely that some of those genes effect a number of different systems, that is, they are pleiotrophic. And of course, environment does affect gene expression--that is what proteins the genes make and when they are activated.

So that's it, folks. It is a very good study. It was done well, and as in most well-done scientific studies, it raises more questions for future work.

And the findings do not provide fuel for the ideologues among us.


Angela said...

This is fascinating stuff, and I truly appreciate your explanation of the findings for the non-scientists in the crowd!

Courtney said...

Thank you for your post. I am not a scientist but was an art education major. In school I did a paper/presentation on ADHD and found that during the research, I really enjoyed trying to pick apart studies (play devil's advocate) and try to determine what was really being said. So, a long-winded way of saying - I enjoyed your post.

christinemm said...

Thanks for your wonderful analysis and for sharing it with us. I know if it were not for blogging you still would have researched that but you would not have had a platform to share it with the rest of us.

I had not heard of the study so I am glad I heard your analysis first.

I am going to link to your post on my blog. Thanks again.

christinemm said...

Oh and I meant to say did you read my post a couple of weeks ago about the best college class I took? It focused on media reporting in science versus what the studies really say.


momof3feistykids said...

Excellent post!

Rebecca said...

Wow, thank you! There was a blurb about this study in the current issue of The Week (news magazine) which I was planning to post on my blog -- but now I'll do so with a link to you.

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