Dopamine & ADHD

thinkingm4  The Journal of the American Medical Association (JAMA. 2009;302(10):1084-1091) recently published work by Dr. Nora D. Volkow, MD, et al regarding evaluation of the biological bases that may reveal a reward/motivational deficit present in the brains of persons with ADHD.

Volkow and her colleagues theorized that ADHD may be connected to reward-motivation deficits. Volkow investigated whether lack of motivation and its relationship to reward could be traced to depression of dopamine in various areas of the brain.

To determine whether dopamine was depressed in ADHD persons, the researchers used positron emission tomography (PET scans) to measure dopamine levels in 53 nonmedicated ADHD adults and 44 healthy non ADHD adults between 2001-2009.

Since the biological mechanisms of ADHD are unknown, studies of this type have become the holy grails of research. While Volkow’s credentials are quite impressive (NIH, NIDA, etc.) this research is not new or conclusive. The theory that dopamine dysfunction/depression may be involved with ADHD symptoms has been researched for many years.

Furthermore, Volkow’s  small sample size consisted only of adults and therefore should not be extrapolated to include the child population. The small sample size alone should prevent it from being generalized to the entire adult ADHD population. One has a problem of antecedence here; is ADHD caused by dopamine depression in the brain? Or is the dopamine depression the result of ADHD that was acquired by other biological means? This research cannot answer that question.

What does the research tell us? It tells us that for some adults, dopamine may play a role in ADHD. For those adults, taking a stimulant medication may increase dopaminergic activity thus increasing reward/motivation responses and thus increasing attention to task. That might be a stretch.

On the downside, persons with depressed dopamine levels would probably greatly enjoy using stimulants. Study participants reported this. This may contribute to the frequent incidences of substance abuse among ADHD persons.

The authors write,"Despite decades of research, the specific neurobiological mechanisms underlying this disorder still remain unclear. Genetic, clinical and imaging studies point to a disruption of the brain dopamine system, which is corroborated by the clinical effectiveness of stimulant drugs (methylphenidate hydrochloride and amphetamine), which increase extracellular dopamine in the brain."

Unfortunately, the study leaves us with more questions than answers. Does it tell us what happens long term? Does it tell us of side effects?  Does it tell us if this actually applies to children? Can we conclusively determine a causal relationship between reward/motivation and ADHD? Does it solve the problem of antecedence? Do we know anything conclusively about all ADHD adults. No. There’s still a long road ahead.

ADHD Medications: Mayo Clinic Study Contradicts MTA Study

As I wrote earlier, the longest study actually performed while following live children was the MTA and its 3-Year Follow-up of the NIMH MTA (multi-modal treatment) recently published in the journal of the American Academy of Child and Adolescent Psychiatry.

Co-author, Professor William Pelham, of the University at Buffalo, says: “The children had a substantial decrease in their rate of growth so they weren’t growing as much as other kids both in terms of their height and in terms of their weight. And the second was that there were no beneficial effects – none.”

Pelham adds, “In the short run [medication] will help the child behave better, in the long run it won’t. And that information should be made very clear to parents.”

Here’s the most telling observation of the study: “I think that we exaggerated the beneficial impact of medication in the first study. We had thought that children medicated longer would have better outcomes. That didn’t happen to be the case. There’s no indication that medication’s better than nothing in the long run.”

It’s obvious that this information was not good for the pharmaceutical industry. As is now common practice, a study will be launched to counter this kind of negative press. So, it was no surprise that the respected Mayo Clinic released a study two months later that “…reveals that compared to children without AD/HD, children with ADHD are at risk for poor long-term school outcomes such as low achievement in reading, absenteeism, repeating a grade, and dropping out of school. Both studies appear in the current edition of the Journal of Development & Behavioral Pediatrics, (”

“In this study, treatment with stimulant medication during childhood was associated with more favorable long-term school outcomes,” explains William Barbaresi, M.D., Mayo Clinic pediatrician and lead author of the reports.

The MTA study focused on real families in real-time. The researchers were able to observe family dynamics, environment, pharmacological interventions and their relationships to academic and behavioral outcomes. This, of course, takes a significant amount of time and field researchers.

According to the Mayo Clinic Press Release, “The two Mayo Clinic studies are the first population-based, long-term studies to investigate links between ADHD, school performance and factors that modify long-term school performance of children with ADHD.”

Here’s how research like this works: researchers are given access to school files and medical records. They select and review data from files to draw their conclusions. This is becoming more popular than live research because it is less expensive, doesn’t require a significant number of field researchers, and can be done in less time. Unlike real-time research like the MTA, the Mayo study’s limitations are significant; it doesn’t allow real-time access to families or teachers to gain information regarding environment, family issues, etc; to interpret information; or to clarify written information. So the researchers are fairly limited to test scores and medical records. While this makes it easy to prepare and select data, it falls far short the information gather by a real-time study.

The Mayo study press release summarizes the research:

Dr. Barbaresi believes that both studies provide the first solid evidence of the long-term negative academic performance associated with untreated ADHD – as well as evidence for the best way to manage this problem. Dr. Barbaresi says, “The finding that treatment with stimulant medications is associated with long-term improvement in school outcomes is significant. Previously, there was evidence that treatment with stimulant medications improved short-term academic performance, but there was no good evidence that long-term outcomes are better with stimulant treatment. Our data can guide clinicians in their efforts to help children with ADHD succeed in school.”

Note that no mention is made of height and weight loss of children in the Mayo Clinic study as was found by the MTA. Furthermore it also directly contradicts information released by the MTA. Here’s the rub, funding for the Mayo study was contributed by grants from the U.S. Public Health Service; National Institutes of Health; Mayo Clinic Foundation for Biomedical Research; and McNeil Consumer and Specialty Pharmaceuticals.

Obviously the one extraordinary contributor was McNeil Consumer and Specialty Pharmaceuticals. McNeil is the producer of Concerta, a stimulant medication for ADHD. Is it likely that McNeil would contribute to a study that would indicate weight loss and stunted growth from use of its product? Not likely.

Would McNeil contribute to a study whose researchers said, “I think that we exaggerated the beneficial impact of medication in the first study. We had thought that children medicated longer would have better outcomes. That didn’t happen to be the case. There’s no indication that medication’s better than nothing in the long run.” Not likely.

It is a direct conflict of interest for a pharmaceutical company to participate in research with universities, hospitals, or other entities. I’ve never seen negative information released from a study performed by a pharmaceutical company on their own drug. Strange, isn’t it?