In ADHD Studies, Pictures May Lie; Researchers contend brain-imaging studies relied on by doctors for the last 20 years to diagnose attention-deficit/hyperactivity disorder are based on flawed data

Insight on the News, August 19, 2003 by Kelly Patricia O'Meara

Byline: Kelly Patricia O'Meara, INSIGHT

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 slogan."

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 the brain."

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 medications."

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-Deficit/Hyperactivity Disorder.

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.