Our ADHD researchers in the media – Explaining the biology and treatment of ADHD

A short while ago, three of our professors were in the media, featuring an article and a TV-documentary about ADHD. Professor Andreas Reif wrote an elegant piece for the Frankfurter Algemeine – a German national newspaper – explaining the biology of ADHD and the need for treatment [see also this recent post on Andreas Reif’s recent appearances in German Media]. Around the same time, professors Barbara Franke and Phillip Asherson appeared in a documentary in which Britisch comedian Rory Bremner went on a personal mission to discover the science of ADHD. As not everyone can read German, and the BBC show is unfortunately only viewable inside the UK, I’ll tell you about the highlights of both pieces.

Fidgety Philip

Do you know the stories by Heinrich Hoffman (1845)? The psychiatrist who wrote a children’s book about naughty children. One of the stories is about Fidgety Philip – or Zappelphilip in German – a boy who can’t sit still and as a result pulls down the tablecloth including everything that’s on top of it, smashing all the table’s contents on the floor. Both Andreas Reif and Rory Bremner mention Fidgety Philip, as the characteristics of this boy resemble several symptoms of ADHD: fidgetiness, restlessness and impulsivity. This example illustrates that ADHD is not a new or modern day phenomenon.

Busy brains

Interestingly, it’s not just the behaviour of people with ADHD that is restless. As Rory Bremner describes it “the music in my brain is [..] pounding and rapid and switching”. This ‘busy brain’ is often described by people with ADHD. And this makes it logical to expect that you should be able to see this with an MRI-scanner – a machine that allows researchers to measure brain activity. Unfortunately, reality is not so simple. Despite a lot of research on people with ADHD and their brain activity, we still can’t diagnose ADHD by using a brain scan. As professor Katya Rubia explains to Rory Bremner, differences in the brains of people with ADHD, compared to those without ADHD, can be seen when you average over large groups (see figure below). For instance, children with ADHD have smaller brain structures in the frontal parts and in deeper areas of the brain (the basal ganglia). These regions are also known to be less activated in children with ADHD, when they need to inhibit a response. As an example, in the documentary Rory Bremner finds it very difficult to inhibit his comments about Katya Rubia’s accent and beauty. This could be due to under activation of his frontal brain and basal ganglia. However, the MRI findings are only based on averages, and can be very different for individual people. Just like that you can’t tell if someone is a man or a women just by measuring their length – even though men on average are taller than women – you can’t tell if someone has ADHD by just looking at their brains.

Meta-analysis of structural MRI studies in ADHD
Differences in brain structure between children with ADHD and children without ADHD. Results are averages from a meta-analysis of 27 studies. Yellow areas indicate decreased volumes in ADHD children compared to children without ADHD. From the study by Norman and colleagues, in JAMA psychiatry, 2016.

 

Fruit flies and ginger bread men

So why does someone have ADHD? Are you born with ADHD? Is it the fault of your parents? Or should we blame society? Extensive research has shown that there is a strong genetic component to ADHD. This means that you inherit the risk for developing ADHD from your parents – even when they don’t raise you, as for instance in the case of adoption. Professor Andreas Reif describes that there are hundreds or even thousands of genes that can contribute to ADHD. Each single gene by itself will not cause ADHD, but together they contribute to the risk for ADHD. The situation with the genes is therefore similar as to that of the brain scans: no gene test can prove that you have ADHD as there is too much variation between individuals. So why should we put time and money in investigating the genetics of ADHD?

For one thing, if we understand which combination of genes contributes to a high risk for developing ADHD, screening could help in early detection of those at risk. For instance, ADHD is known to often co-occur with other disorders, such as depression, substance abuse or obesity. If we know who is at risk of developing such a secondary disorder, the person can be informed about the importance of behavioural adaptations that reduce this risk, such as regular exercise in the case of obesity. Another reason is that better understanding of causal mechanisms can aid in developing new treatments for ADHD.

In order to study these causal mechanisms, professor Barbara Franke uses fruit flies (drosophila melanogaster). With these flies she can investigate which gene is associated with which specific aspect of ADHD, such as hyperactivity or inattention. In the documentary Barbara Franke shows Rory Bremner how she releases fruit flies in a specially designed maze. At the end of the maze, the fruit flies can find food. The more often they go through the maze, the better they learn the route. But while the flies go through the maze, they are being distracted by a light which they should ignore. For this experiment, some fruit flies have undergone modifications of genes that we suspect to pose risk for ADHD. And it turns out that the ADHD-like flies are more distracted by the lights than the ‘normal’ flies. In this way, we can find out which genes cause increased distractibility.

But it’s not just genes that contribute to ADHD. Although genes explain about 80% of ADHD, environmental influences, such as preterm birth or toxins during pregnancy also contribute to the risk for ADHD [i.e. see this recent post by Stephen Faraone)]. In the documentary, Peter Hill shows Rory Bremner how genetic and environmental factors can contribute to slightly different appearances – also called phenotypes – by baking gingerbread men. Peter and Rory bake several of these cookies, but with slight differences in the ingredients and procedure. One gingerbread man for instance is baked less long, which translates to environmental. The other gingerbread men lack eggs, contain less flour, or have no ginger. These are exemplary of the genetic influences of ADHD. All in all, the gingerbread men still look like gingerbread men – and probably are just as tasty – but knowledge about what happened in the preparation and baking process can help understand why they are different.

Medication & treatment

As mentioned earlier, ultimately we hope that a better understanding of ADHD enables better treatment. At the moment, psychostimulant medication, such as Ritalin and Concerta, is the most widely used form of treatment. As Andreas Reif explains, methylphenidate (which is the active substance in Ritalin) increases the availability of dopamine and noradrenaline in the brain. These two substances are necessary for a wide range of cognitive tasks, including learning, paying attention and inhibiting responses. In people with ADHD there seems to be too little dopamine available, which is why they benefit from this medication. Rory Bremner tries it for the first time in the documentary, just before he gives a comedy show. He describes the effect as “It’s a bit like someone switched my brain from techno radio 1 to classic fm”. However, as professor Phillip Asherson tell us, although this medication can help you to focus, some people will feel more nervous or restless. In that case, the medication doesn’t work for them.

Alternative forms of treatment are also being tested, such as neurofeedback. Friederike Blume from Tübingen shows Rory Bremner how she uses EEG (measuring electric signals in the brain by using a device that looks like a swim cap) combined with virtual reality in order to train people to improve their neural signals. Similar to going to the gym, regular neurofeedback training may help to improve brain functioning and hence reduce symptoms.

And what happens when ADHD is left untreated? In some cases, not so much. Rory Bremner was never diagnosed with ADHD, even though in the documentary he finds out that he does have all the symptoms of ADHD. For a comedian as himself, an impulsive and associative mind is very beneficial. However, for others, untreated ADHD can cause big problems. About 30% of the offenders in prison has ADHD, and most of them have not received treatment. As most of these offences concern impulsive offences, such as spraying graffiti, medication can help to prevent such behaviour.

So, what have we learned?

All in all, both the documentary and the newspaper article give us an idea of what the research on ADHD is all about: from fruit flies to brain scans, researchers are trying to discover the biology of ADHD. As Andreas Reif puts it, better knowledge and diagnostics of ADHD, in all stages of life, can greatly improve detecting and treating ADHD. And this can greatly improve quality of life of those with ADHD. That’s what inspires us to do the research.

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