20 October 2003
A short while ago, I was involved in a discussion at an online forum about claims that were being made by a certain
doctor who shall remain nameless in the matter of the 'diagnosis' of so-called 'ADHD' through the use of brain
scans - claims that were, in my opinion, wholly unsubstantiated.
Subsequently, I received an email from a Professor Jonathan Leo, of the Western University of Health Sciences, together
with a copy of a paper he had co-authored which reviews the most recent research related to brain scans and the
diagnosis of 'ADHD' (and coincidentally makes a reference to the doctor in question).
"Broken Brains or Flawed Studies? A Critical Review of ADHD Neuroimaging Research", by Jonathan Leo, Western University
of Health Sciences, and David Cohen, Florida International University, was published last month in The Journal of
Mind and Behavior, Winter 2003, Volume 24, Number 1.
This is its opening statement:
"A review of over thirty neuroimaging studies on children diagnosed with Attention Deficit/Hyperactivity Disorder
(ADD, ADHD) by Giedd, Blumenthal, Molloy, and Castellanos (2001) is organized around tables listing the main findings
of studies using different types of neuroimaging. Like most researchers in this field, Giedd et al. conclude that the
evidence supports the involvement of right frontal-striatal circuitry with cerebellar modulation in ADHD. However,
Giedd et al. do not report on a confounding variable of crucial interest in this field of research - whether
subjects had been previously treated with stimulants or other psychotropic drugs. In the present paper, we have
redone five of the tables from the Giedd et al. review, adding information on the subjects' prior medication
exposure, as reported in the individual studies included in the review. We found that most subjects diagnosed with ADD
or ADHD had prior medication use, often for several months or years. This substantial confound invalidates any
suggestion of ADHD-specific neuropathology. Moreover, the few recent studies using unmedicated ADHD subjects have
inexplicably avoided making straightforward comparisons of these subjects with controls."
Note the words "inexplicably avoided".
The complete paper is fascinating to read, a tale of years of work and millions of dollars spent on producing
ultimately inconclusive results.
You can read the paper in its entirety here:
The following is an overview of "Broken Brains or Flawed Studies?" from Insight Magazine:
In ADHD Studies, Pictures May Lie
by Kelly Patricia O'Meara
It has been two decades since researchers first began to explore the use of brain imaging for the purpose of
diagnosing attention-deficit/hyperactivity disorder (ADHD), the alleged mental disorder affecting an estimated 5 million
children. And two decades later, despite widely accepted beliefs, there still are no confirming data to support the
use of any brain-imaging modalities in the diagnosis of ADHD.
A recent review by Jonathan Leo, professor of anatomy at the Western University of Health Sciences in Pomona, Calif., and
professor David Cohen of the School of Social Work at Florida International University in Miami, dispels the myth
of brain imaging as a way to diagnose ADHD. And it finds that the majority of studies dating back to 1978 failed,
unaccountably, to consider a major variable - the use of psychotropic drugs by participants in the studies.
Leo and Cohen's review, entitled "Broken Brains or Flawed Studies? A Critical Review of ADHD Neuroimaging Research,"
was published last month in the Journal of Mind and Behavior and looked at 33 of the most recent studies using
computerized topography, magnetic resonance imaging (MRI), single photon emission computerized topography or positron
emission topography on ADHD-diagnosed subjects. The researchers were stunned: According to Leo, "Dr. Cohen and I
pulled the studies that had been done on brain imaging and ADHD and what jumped out at us was that every single study
used medicated kids, subjects who had been on stimulants or some other drugs that we don't know because that information
wasn't made part of the study."
Leo explains, "The general public sees a picture of a brain, and one brain looks a little brighter than the 'normal'
brain, but how do you know if you're not looking at something like 'this is your brain' and 'this is your brain
on drugs'? We found that most subjects with ADD [attention-deficit disorder] or ADHD had prior medication use, often
for several months or years. So the major conclusion of our review of these studies is to ask ourselves what are these
researchers doing? You have to wonder if they're really doing research or trying to come up with a marketing
Cohen tells Insight that "there were a number of problems with these studies, but the fact that the kids were either
on drugs or stopped taking them within days of the study was not an outstanding issue when we first got into the studies.
In other words, this wasn't something that we were looking for." He notes, "Only in about one or two of the studies is
mention even made about medications and that's as far as it went - a mention. But this is a major variable and it's
important because drugs influence the brain. That's why we give drugs in the first place. It's not an abstract issue,
and we do cite a number of studies on animals and kids that show that stimulant drugs cause very persistent changes in
Cohen explains, "You want to be able to rule out these changes, so you would want to use kids that aren't on drugs
or just recently taken off of them when you're scanning them. At the very least what you want to do is report the
medication status. What we found was that only 19 of the 33 studies reported the medication status, some of the 19
reported in an unclear manner and a single study made something out of the fact that most subjects were on
According to the researchers, 93 percent of the subjects in the ADHD diagnosed group were either on drugs, just off
drugs or had been medicated for years. This is a major confound, but it wasn't a major issue among the researchers
reviewing the ADHD studies. Perhaps the most troubling issue came when professors Leo and Cohen reviewed the widely
touted 2001 study conducted by some of the most renowned scientists of the National Institute of Mental Health
(NIMH), entitled Developmental Trajectories of Brain Volume Abnormalities in Children and Adolescents with Attention-
Although 14 scientists contributed to the study, it is generally referred to as the "Castellanos study" after the
lead scientist, child psychiatrist F. Xavier Castellanos. Ten years in the making and unknown millions spent,
Castellanos and his team conducted 544 MRI scans of 291 subjects - 152 ADHD-diagnosed patients and 139 control
subjects (normal). The Castellanos results were that "on initial scan, patients with ADHD had significantly smaller
brain volumes in all regions, even after adjustment for significant covariates."
The celebrated doctor further concluded that "developmental trajectories for all structures, except caudate, remain
roughly parallel for patients and controls during childhood and adolescence, suggesting that genetic and/or early
environmental influences on brain development in ADHD are fixed, not progressive and unrelated to stimulant
treatment." In other words, kids diagnosed with ADHD had smaller brains than those kids in the "normal" control
group, and brain size isn't due to drug use.
Leo and Cohen are not only disturbed by the conclusion, but surprised that the Castellanos study received such strong
public attention given that even the NIMH doctor was not using matched groups. According to Cohen, "Castellanos
essentially is the first-ever study using un-medicated kids. So we say finally here comes a study from a very experienced
researcher - who has done four or five of these brain-imaging studies - and what do we get? The control group is
completely inappropriate for these ADHD-diagnosed kids. Castellanos picked a control group of kids that are more
than two years older than the unmedicated ADHD kids and he finds that the unmedicated ADHD kids have smaller brains?
That's obvious because the control group is two years older and significantly heavier and taller."
Cohen says, "What is surprising is that the Castellanos review is saying that a major difference with ADHD and
normal kids is brain size. But brain size is typically correlated with head size, and I really doubt that with all
these kids on Ritalin it all boils down to head size. That's a stretch. But another way of looking at it is that for 30
years researchers have had trouble getting appropriate subjects for these studies. So with the NIMH review it
finally has a group of non-medicated ADHD kids but now the problem is getting a control group - undiagnosed kids?"
Castellanos, now with the Child Studies Center of New York University, tells Insight that he accounted for the age
difference in subgroups and "the control group is age-matched for the ADHD group as a whole and unmedicated
children with ADHD were significantly younger. That's because by the time kids get older they've been medicated.
It is very difficult to find kids that are unmedicated. This is the nature of the condition. It is very difficult to find
very hyperactive children who have not been medicated who are older. We included all of the children in one analyses
and in another analyses we limited ourselves to age-matched subgroups."
Leo argues that NIMH "still can do a legitimate study and take their unmedicated ADHD kids and compare them to a
normal control group - same age, size, etc. But they haven't done it and the question is why? In a landmark 10-year study
the NIMH didn't use a normal control group - what's the hang up?"
Cohen agrees. "The study that needs to be done is so simple: Just compare ADHD-diagnosed kids who haven't been medicated
with a similar age group of 'normal' kids who haven't been diagnosed. It's the only study that needs to be done, and
there isn't a single study that compares these two groups of kids. In essence what you've got here is a large body of
studies that cannot support the notion that there is some brain pathology specific to ADHD because of the confound of
prior or current medication used during the studies. And until they do the appropriate study, this won't change."
Finally, says Leo, "Given all the problems with the ADHD imaging research, parents who are contemplating medicating
their children should not be told that this research suggests that there is a biological basis for ADHD."
Because the Leo-Cohen review is newly published, no critiques have been posted to date about the validity of the
review. NIMH has not responded to Insight's questions about the Castellanos review nor the cost of the 10-year study.
This, by the way, is the concluding statement of Jonathan Leo's and David Cohen's paper "Broken Brains or Flawed
"... after twenty-five years, and thirty-five studies, there is not a single straightforward experiment comparing typical
unmedicated children with an ADHD diagnosis to typical controls. We are perplexed."
It seems, then, that the proponents of biopsychiatry who claim 'ADHD' to be a 'neurological disorder' or 'brain
disease' have had their opportunities to resolve the debate over the validity of their dubious 'diagnosis' once and for
all, but they have failed to take advantage of those opportunities - in Professor Cohen's words, "The study that
needs to be done is so simple: Just compare ADHD-diagnosed kids who haven't been medicated with a similar age group of
'normal' kids who haven't been diagnosed."
Then we'd know for sure, wouldn't we?
Could it be that the reason the proponents of biopsychiatry will not make that obvious and simple comparison is that
they DARE NOT RISK IT?