'Brain chemical link' to ADHD

Wednesday September 9 2009

The Daily Mail reported today that a brain chemical has been found that "could spell an end to ADHD". Attention deficit hyperactivity disorder is associated with attention and behavioural problems in young children, particularly boys, and can sometimes persist through adolescence and into adulthood.

The newspaper said that studies of brain scans have shown that children with ADHD have a lack of dopamine, a chemical messenger in the brain.

This study found that the brains of people with ADHD had fewer receptors and transporters (which transmit signals between nerve cells in the brain) available for the nerve-signalling chemical dopamine than people without the condition.

The finding supports previous studies suggesting that dopamine is involved in ADHD. However, this study only included a relatively small number of adults with the condition, and the reason for this relationship is uncertain and will require further research. ADHD is a complex disorder that has no single identified cause. This research furthers knowledge of the condition, but it is far too early to conclude that it “could spell an end to ADHD”.

Where did the story come from?

The research was carried out by Dr Nora D Volkow from the National Institute on Drug Abuse in Maryland, US, and colleagues from other US institutions.

The study received financial support from the Intramural Research Program of the National Institutes of Health (NIH), the National Institute of Mental Health, and infrastructure support from the Department of Energy. Individual authors also received research support and consulting fees from various pharmaceutical companies.

The study was published in the peer-reviewed Journal of the American Medical Association .

What kind of scientific study was this?

In this case-control study, brain scans of adults with ADHD were compared with healthy controls to see whether there were biological differences involving the chemical dopamine. Previous studies have indicated that problems in dopamine signalling have a role in ADHD, and it has been suggested these problems may cause the short attention span and impulsive behaviour that are a symptom of ADHD.

The researchers say that children with ADHD are also thought to have “reward and motivation deficits”, as they do not show typical behaviour when rewarded or punished. As dopamine transmission is thought to be involved in reward and motivation behaviour, this could be explained by a deficit of the chemical.

The researchers enrolled 53 adults with ADHD who had never received any medication for the condition (average age 32), and 44 healthy controls (average age 31), between 2001 and 2009. Those with ADHD were clinically referred to the study and met validated diagnostic criteria for ADHD. The controls were recruited through newspaper adverts.

The researchers excluded anyone with a history of substance abuse or antipsychotic medication use, diagnosed psychiatric disorders, neurological disease medical conditions that may affect brain function (including cardiovascular disease), or a history of severe head trauma.

The participants received PET brain imaging (position emission tomography, a detailed scan that shows both structure and current functioning of body tissues). This scan examined the dopamine transporter and receptor proteins found at the synapses (junctions between nerve cells). These proteins allow dopamine to transmit signals from one nerve cell to another, and remove dopamine from the junction between the nerves, stopping the signal once it has been sent.

The researchers assessed the function of these proteins by injecting the participants with radioactively labelled chemicals (markers) that bind to the receptors and transporters. They then used PET to see which parts of the brain the chemicals bound to, and how much of the chemicals bound. All participants were assessed using various scales assessing ADHD symptoms (including inattention and hyperactivity) and overall impairment.

What were the results of the study?

People with ADHD had significantly less of the marker chemicals binding in the left side of the brain than controls. This area of the brain is believed to be involved in the reward pathway.

Controls without ADHD had significantly higher availability of the dopamine receptors and transporters in four different regions of the brain (nucleus accumbens, midbrain, caudate and hypothalamic regions).

Ratings of attention symptoms were significantly correlated with the availability of the dopamine receptor in all brain regions and with the dopamine transporter in one region. This indicated that individuals with more attention problems had lower receptor availability. No relationship was found between levels of activity or reflectivity and receptor or transporter availability.

What interpretations did the researchers draw from these results?

The researchers conclude that in participants with ADHD a reduction in the dopamine transporters and receptors in the area of the brain involved in the reward pathway was associated with inattention symptoms.

What does the NHS Knowledge Service make of this study?

This study found that people with ADHD had a lower availability of dopamine receptors and transporters at the junctions between nerve cells. The researchers suggest that this dopamine deficit contributes to ADHD, and could be involved in the attention and hyperactivity problems typical of ADHD.

However, this is early research in a relatively small number of adults with ADHD. Not all children diagnosed with ADHD will continue to have it in adulthood and so these adult participants may have certain characteristics that differ from childhood ADHD. The results are made more robust by the researchers’ stringent attempts to exclude anyone with medical or psychiatric conditions that could interfere with the results. They also only included people who had never taken medication for ADHD, such as Ritalin, which avoids the possibility that the treatment could be responsible for any findings.

At this point, it is not possible to tell whether the people developed ADHD because of dopamine pathway deficits or whether the deficits are a result of having the condition. In addition, as the researchers say, the low levels of binding at dopamine receptors in people with ADHD could either reflect low receptor levels or the presence of high levels of dopamine competing with the labelling chemicals for binding to the receptors, or a combination of these.

Finally, associations were only observed between brain scan results and attention symptoms and not with hyperactive symptoms, and hence the findings do not explain the whole spectrum of the ADHD disorder.

These are promising findings but they will need further research in other population groups before more definite conclusions can be made. It is too early to conclude that this finding “could spell an end to ADHD”. ADHD is a complex disorder and its causes remain uncertain but potentially include various genetic and environmental factors.

Analysis by Bazian
Edited by NHS Choices