Broken Brains or Flawed Studies?

Broken Brains or Flawed Studies?

Thu, 24 Jul 2003

Broken Brains or Flawed Studies? A critical review of ADHD imaging studies by Jonathan Leo, Ph.D and David Cohen, Ph.D methodically demonstrates how scientifically flawed methodology undermines the integrity and claimed findings of over 30 imaging studies that are the basis for psychiatry’s claims that children with ADHD have brain abnormalities.

The essential confounding variable that these studies don’t address is that most of the ADHD children in the imaging studies had been exposed to psychostimulant and other psychotropic drugs before their brains were scanned. Why does that matter? Because prior exposure to psychotropic drugs has been proven to cause brain alterations—differences in brain structure or function cannot, therefore, be attributed to ADHD.

Indeed, Dr. Leo and Dr. Cohen state a fact that is not even in dispute among neuroscientists: “an astronomical number of experimental and clinical studies on animals and humans find that almost every studied psychotropic drug has been consistently shown to produce subtle or gross, transient or persistent effects on the functioning and structure of the central nervous system.”

One such study was headed by Dr. Nora Volkow (then) a senior scientist at Brookhaven Laboratories. She and her team of scientists compared the effects on the brain of addictive drugs– Ritalin and cocaine. They found “direct evidence” that “therapeutic doses [0.5 mg] of oral methylphenidate [Ritalin] significantly increases extracellular dopamine concentration in the human brain.”

See: Volkow, et al in The Journal of Neuroscience, 2001, Vol 21, RC121, pp. 1-5]

Indeed (as discussed by Sharav), Dr. Volkow told the Journal of the American Medical Association that the Brookhaven team was shocked to find that “instead of being a less potent transport inhibitor than cocaine, methylphenidate [Ritalin] was more potent.” Dr. Volkow told JAMA: “the data clearly show that the notion that Ritalin is a weak stimulant is completely incorrect.”

See: Sharav, VH, Children in Clinical Research: A Conflict of Moral Values, American Journal of Bioethics. 2003, Vol 3: InFocus online at:

Dr. Volkow is the new Director of the National Institute of Drug Addiction (NIDA).

Prior exposure to psychotropic drugs is a crucial confounding variable in ADHD (and other psychiatric) imaging studies that psychiatrists have disregarded. Since they have not ruled out drug-induced abnormalities, what is the verifiable basis upon which psychiatrists make claims about “evidence” of brain abnormalities in those “diagnosed” with one or another psychiatric disorder? In fact, no one has found scientific evidence of any brain abnormality in people with a psychiatric diagnosis.

The authors report that some ADHD children were used repeatedly by different investigators in studies that exposed them to Ritalin and (in some cases) to dextroamphetamine)–essentially reducing them to lab rats.

A study by Teicher et al, published in Nature Medicine, 2000, pp 470-473 is one of the trials criticized by Drs. Leo and Cohen:

11 children with ADHD were compared with 6 normal controls. The ADHD children were randomized to one of four groups: placebo, or methylphenidate (Ritalin) at 0.5, 0.8, or 1.5 mg/kg. All ADHD children were cycled in all four groups, but the order was different. Their brains were scanned by functional MRI relaxometry after placebo–which for some children occurred after they had been on Ritalin for 3 weeks–and compared to the controls.

Is that method of comparison scientifically sound?

As the authors point out: “A child randomized to placebo and then scanned is not comparable to a child administered three weeks of the drug followed by placebo and then scanned. Teicher and colleagues grouped children who NEVER received drug treatment with children experiencing withdrawal from drug treatment.” [p. 43]

Neuroscientists who examine the effects of psychotropic drugs on the brain and central nervous system, have been reporting adverse effects–such as drug-induced brain abnormalities, addiction, and withdrawal symptoms among others. Psychopharmacologists who have financial ties to drug manufacturers conduct clinical trials designed NOT to detect adverse effects. Furthermore, they proclaim positive findings that they invariably attribute to the drugs.

The ADHD / Ritalin promoters–including psychopharmacologists at the National Institute of Mental Health (NIMH) and the pharmaceutical industry–skew clinical trials to get “favorable” results which are then broadcast as "breakthrough revelations."

A 1996 NIMH press release announced: “Subtle Brain Circuit Abnormalities Confirmed in ADHD” Dr. Xavier Castellanos, Chief ADHD Research Unit Child Psychiatry Branch at NIMH, claimed to have “found that the entire right cerebral hemispheres in boys with ADHD were, on average, 5.2% smaller than those of controls. The right side of the brain is normally larger than the left. Hence, the ADHD children, as a group, had abnormally symmetrical brains.”

In 2002, another NIMH Press Release made an even bolder pronouncement: “Brain Shrinkage in ADHD Not Caused by Medications” Dr. Castellanos declared: “There is no evidence that medication harms the brain,” said Dr. Castellanos, who conducted the study at NIMH before joining New York University. “It’s possible that medication may promote brain maturation.” See:

Novartis, the manufacturer of Ritalin was more modest in its May 2003 Press Release than NIMH and did not claim that Ritalin promoted “brain maturation”: ” Study Shows Ritalin® LA Provides Statistically Greater ADHD Symptom Management Over Concerta® Across the School Day”

The basis for the NIMH “brain maturation” claim was a study conducted by Dr. Castellanos et al which has much in common with phrenology studies that compared skull size to establish racial superiority of Germans by comparing head size to Italians, Jews, French. Dr. Castellanos and his NIMH team tested three groups of children: 49 children (average age 8.3 years) were diagnosed with ADHD but never before medicated; 139 controls (boys aged 10 years and girls 10.9); and 103 ADHD-diagnosed medicated children.

Dr. Castellanos et al made their “brain maturation” claim by comparing the brain size of never medicated 8 year olds with healthy controls who were two years older! Whether brain size is an indication of ADHJD is highly questionable. However, if there was an established correlation, a proper comparison would surely have required that the children be of the same age and same size. Frankly, we find it astounding that such confounding variables were not recognized by these national ADHD experts.

These unsubstantiated, unscientific NIMH pronouncements encourage the media to air misleading reports about the safety of these drugs–thereby ensuring that doctors will misguidedly increase prescribing these drugs to young children. Based on Dr. Castellanos claims in an interview The New York Times headline on October 9, 2002 proclaimed: “Brain Size Tied to Attention Deficit Hyperactivity Disorder.

This false claim was then further inflated in an article that reported “Ritalin is Safe and It Works: Research Dispels Fears That Drug Hurts Kids, and Finds That It Actually Helps Brains Grow.” See: Kurth The Detroit Free Press, Dec 12, 2002

David Cohen is a board member and secretary of AHRP.

Broken Brains of Flawed Studies? was published in the Journal of Mind and Behavior, Winter 2003, Vol 24, pp 29-56 is available online at: