Unpacking ADHD

One of the many lessons we learned from the COVID 19 pandemic is the importance of having sufficient ventilators and other breathing aids to save the lives of people in hypoxic respiratory failure - where they are not getting enough oxygen into their blood to survive. Now, a group of scientists have taken inspiration from the aquatic world of sea cucumbers, freshwater fish called loaches, and the so called bum-breathing turtles, to develop a new approach. Termed ‘Enteral ventilation via anus’, the technique uses either a steady oxygen flow or the injection of a highly-oxygenated liquid into the anus, with remarkable, life-saving results in mice, rats, and even pigs. Takanori Takebe of Tokyo Medical and Dental University and Cincinnati Children’s Hospital, and lead author on the study, spoke to Eva Higginbotham…

Eva - Although it might seem strange to us, breathing through your backside has some advantages for the animals that do it. For example, the Fitzroy River turtle in Australia, sometimes affectionately called the bum breathing turtle, can stay underwater for up to three weeks at a time, thanks to this ability. And thanks to new research out of Tokyo's Medical and Dental University and Cincinnati's Children's Hospital, intestinal breathing might soon be something we humans are getting comfortable with.

Takanori - We started looking more carefully about the interanus application of oxygen, which turned out to be very effective.

Eva - That's Takanori Takebe. He and his team have devised two new approaches for getting oxygen into the blood of mice, rats, and pigs, and both take advantage of the fact that the mammalian rectum, that's the last bit of the large intestine before the anus, is both supplied with loads of blood vessels and has a fairly permeable membrane for gases to cross over, making it an excellent part of the body to adapt as another site to breathe from.

Takanori - One is a very intuitive approach we just intubated, from the anus, just to provide oxygen gas continuously. This oxygen delivery is really able to persist survival in lethal conditions. Even up to 60 minutes or even longer.

Eva - 60 minutes of breathing through the rectum just by pumping in oxygen. Sounds amazing, but also like you could get a bit uncomfortable. The more clinically relevant approach uses a liquid that's very good at dissolving oxygen, perfluorocarbon or PFC. This liquid is already used by doctors during some ice surgeries and sometimes as a type of synthetic blood for transfusions. So we already know that it's safe for humans.

Takanori - So that liquid ventilation approach is also having greater impacts on oxygenation. So as to really rescue those fatal hypoxic conditions in the mouse, rats, and pig model system.

Eva - Incredibly, Takanori showed that when just less than a pint of this PFC was injected into the anus of pigs, they would stay happily oxygenated for up to 20 minutes when in respiratory failure. And they didn't stop there, by re-injecting every 20 minutes or so they could keep the pigs going for hours, or even more. Importantly though, when we breathe in and out using our lungs, we aren't just taking in oxygen. We're getting rid of carbon dioxide and other waste products too.

Takanori在th -e experiments. We are quite surprised to see that carbon dioxide is actually eliminated from the body. So this observation is supporting the idea that oxygen is sucked up into the circulatory system. And whereas carbon dioxide is eliminated from the body as if perfluorocarbon is working as a breathing or gas exchange in the rectrum regions.

Eva - Takanori imagines that this new technology could be life-saving if deployed in ambulances for people being rushed to hospital, unable to breathe, or in hospitals for COVID patients who require extra oxygen or where there are limited mechanical ventilators. And he's also been approached by some other characters.

Takanori - Yeah. We actually had a discussion with an astronaut yesterday, and he is really excited to apply to space applications, particularly in emergency conditions. So there are a number of potential scenarios. We can envision the application of the intestine breathing approach, not just for medicine, but also for more broader context. So that was really exciting to me

Eva - Who knows, perhaps in the future, you'll be scuba diving without a gas canister to lug around with you. And instead with a more subtle breathing apparatus to keep you going.

For cricket lovers, there’s nothing more satisfying than the sound of leather on willow. But scientists say the sport should be swapping out its willow bats…for bamboo! Ben Tinkler-Davies from the University of Cambridge and his colleagues have been testing out a bamboo prototype, and they say it performs just as well, if not better. And it improves performance in the materials lab, at the wicket, and even ecologically. Adam Murphy spoke with Ben about the bats...

Ben - So willow's been used for about 200 years for cricket bats, and what you're looking for is a stiff, light material. And we decided to look at bamboo as a more sustainable alternative. So we ran a lot of computer simulations and material testing, and we found that in almost all capacities that bamboo outperformed the willow. So it's both stiffer, more flexible and harder. So this means that when you hit the ball as a player, the ball is going to fly off the bat at a lot higher speed. Which is obviously much more advantageous. And the major benefit is that it's grown close to where the bats are manufactured. Instead of having to ship the willow from England to India, it's grown very close to the facilities to make the bats. So from an environmental point of view, we're cutting down a lot on the carbon emissions from the process.

Adam - And then how do you go about actually turning a stalk into a bat? It's not like you can carve it out from a single bamboo strip.

Ben - Exactly. So the traditional willow bats are all, you cut down a Willow tree and you cut it into the shape straight away, but the bamboo column, or what you see going from the ground is hollow. So what you've got to do is cut it into thin ply. So you split it along the length, and then you glue all these plys together. So you really form a laminate material. And from that, you can cut that to the right shape and then use material processes to finish it into the desired shape of the bamboo bat.

Adam - You mentioned, because it's stiffer it leaves the bat quicker, but what about other kinds of performance? What about for the cricketer picking this thing up? How's it going to go? How's it going to perform?

Ben - The first prototype that we've made is approximately 40% heavier than a traditional willow bat. And this is something we expected because although you see a bamboo column and it's very light, when you process it into its engineered form, it's quite dense. So from a weight perspective, the bat is heavier, but this also means that if you do manage to find the middle of a bat, it travels a lot faster. So when we performed a lot of computer simulations, we found that the sweet spot, or the middle of the bat where you really want to hit it is longer and wider than a willow bat. So this means you've got more room for error when you're timing your shots.

Adam - That all comes into the “sounding too good to be true” end of things. So are there any downsides to how this bat works?

本,所以,就像我之前说的,我认为主要的做wnside is the weight of the bat. and it's something that we're going to look to build some lighter prototypes, which we can then see how that works. But what a lot of people have said is that, you know, they love the traditional sound of leather on Willow. So we tested that, took it to the nets and people said, okay, we can't tell the difference. So we took it into the lab and we said, okay, can we tell the difference here? And it came out that the frequencies, or how it sounds, is very similar, so although we've got a heavier bat, which we're going to look to optimise and make lighter for the purists of the game, who loved that sound of leather on willow, you're not going to lose that. You're just going to have to be getting used to the fact it's leather on bamboo. So the main difference really is the aesthetics and what the bat looks like. But from a materials point of view, and from an ecological point of view, we think we found a more sustainable solution to the problems faced with willow in cricket.

For the people who have it, ADHD, attention deficit hyperactivity disorder, can potentially be a tough thing to deal with. But how do they find out they have it in the first place? What does the diagnostic process look like for ADHD? Chris Smith spoke to Tony Lloyd, Chief Executive of the ADHD Foundation...

Tony - Well in children, what we tend to look at is three core characteristics, which are: inattention (poor memory, inability to maintain concentration, forgetfulness, mind wandering), impulsivity, and sometimes, but not always, hyperactivity. Now these are natural characteristics that appear in all children, aren't they? What constitutes a diagnosis of ADHD is when these characteristics appear in a more extreme form. But increasingly clinicians also look at two other things, which are: low emotional resilience, that inclines towards anxiety and depression; and also what we call 'poor executive functioning skills', which is the ability to manage distractibility and maintain focus in terms of organising your thoughts, emotions, and how you might factor all those things in with how you choose to respond to your environment or not. So with children, we use a whole range of rating scales, but increasingly we're using computer-based cognitive functioning tests such as QB tests, which are over 80% reliable. And they tell us about cognitive functioning, whereas the behavioural rating scales tell us about what the observable presentation is, and that can differ according to context. We know that obviously children with ADHD are going to struggle much more in a school classroom than they are playing out on the playground. So context and environment are really important in terms of how we discern how ADHD is actually impacting on the child.

Chris - And what about when someone presents later in their life? We've been hearing about Adam's experience - would you use the same sorts of criteria? Or do you tend to approach this differently in adults?

Tony - No, we approach with the same rigorous criteria. We use QB testing, and my understanding is that it is going to be implemented by NHS England across the country as part of a national strategy within a couple of years, because it provides that quantitative, objective measure of cognitive functioning. I think what we've got to remember here is that ADHD is significantly underdiagnosed in the UK. The World Health Organisation says that prevalence should be in the region of about 5.26%, but we know in the UK that diagnostic rates are well below 3% and that use of medication is actually below 1%. We are seeing an increasing number of adults coming forward now because ADHD is less stigmatised, people have a better understanding of it, it's not some stereotypical idea about 'naughty children', which is incredibly unhelpful. And people don't understand that ADHD also correlates - undiagnosed or unmanaged ADHD - with anxiety, depression, eating disorders, obsessive compulsive disorder, things like that. So we see people presenting with other mental health conditions, and that's when often we arrive at ADHD as an underlying cause.

Chris - And that could be a giveaway. Yes, indeed. Now given how common this is - I mean, 5% is a lot of people - is it actually becoming more common, or are we just better at picking it up? Where previously we may have ignored it, or not put people in a position where it would have manifested itself the way it is. Or is something else changing?

Tony - One - we're much better at picking it up, and there's less stigma attached to it. And also we're seeing research now that's suggesting that every graduate with ADHD is twice as likely to start their own business; that over 30% of business owners have either ADHD or dyslexia or both. I think we need to understand ADHD in the context of a neurodiverse paradigm: where you have dyslexia, which affects approximately one in ten people; autism, approximately one in fifty; dyspraxia, approximately one in twenty; and ADHD, one in 20; but these things rarely travel alone.

Chris - You mentioned there's a genetic link there. So does this mean if you see a child manifesting this, one perhaps ought to consider the parents as well? Because they may well also have this, and be like Adam and not realise, and may be able to explain some aspects of their lives on the basis of that.

Tony - Yes, ADHD is over 80% genetic - we're certain. We know that traumatic brain injury, which can be caused by premature birth for example, or traumatic birth, or head injury, can be a cause of ADHD. But for the most part it's genetic, so there's usually some family history. But that doesn't mean to say that either or both parents might have ADHD. We do know that there is an increased prevalence of ADHD with parents who conceive children in their late thirties, or an increased prevalence where parents have had children who've been born preterm; but yes, there's usually a family history of some neurodevelopmental condition, whether it's dyslexia, autism spectrum, ADHD, or dyspraxia.

After making a diagnosis of ADHD, attention deficit hyperactivity disortder, inevitably thoughts turn to managing the condition. But what does treatment look like? Max Davie is a consultant paediatrician and works with ADHD UK, and he took Chris Smith through the treatment options...

Max - Broadly speaking, the two sorts of intervention that I think are most useful are - one, environmental modification. And then secondly, medication. In children, the first one comes first, the environmental modification. So we would look at how people understand the condition around the child, we'd look at the child's brain health - so essentially that's exercise, sleep and mood. We would support the family at home, and this could be anything from a parenting intervention, to just helping them to sort out their housing - that can be a really crucial element. We need to support them in school, and for an older person into employment or training, make sure everyone understands and that they get the reasonable adjustments that are required within schools to help them through. And then medication at the end, generally, in children, when those things have been sorted out as far as we're able. That's the kind of structure of the interventions anyway.

Chris - What sorts of things in the environment tend to be bad triggers for people that will disclose more ADHD type negative effects?

Max - Yeah. I think you've put that really well actually in that they don't cause ADHD, but they make the ADHD more troublesome. So I mean there's so many of them, but I think a harsh and negative either school or parenting environment will make things worse. Poor sleep is a really big trigger and you can get into a real vicious cycle of sleeping worse, so therefore your behaviour is worse, then your mood is worse. And therefore as any parent will know an irritable and sleep deprived child is often actually harder to get to sleep subsequently. So you can really get into a big problem there. So I think those are two really big ones for me.

Chris - I know you're a paediatrician, but presumably a lot of what you've just said also applies to adults.

Max - Yeah, a hundred percent. I think there is a distinction to an extent in that medications are offered earlier for adults, but the principles are exactly the same. I think that's really important to emphasise.

Chris - Now there's going to be something of a tension because people don't like taking medicines if they can avoid it. And we see this with a whole spectrum of different diseases, whether it's high blood pressure or say depression. People prefer not to have to take medications. But there's an additional element when it comes to children, isn't there, because people are concerned. Medicating children has a whole range of different sorts of manifestations and negative associations, but one of them is people are concerned that because the young brain is still developing, perhaps that could alter its development in unforeseen or perhaps negative ways. Is there any truth to that?

Max - I think the evidence so far is that giving medication to a child who has ADHD, and you've made a proper diagnosis, is probably a benefit to their cognitive development because it gives them more positive experiences. Everything that we do, everything that we put into our bodies or experience, changes our brains. I think that if you give the right medication at the right dose to the right child, it will actually, by giving them vastly more positive experiences going forward, will positively impact their brain development. So I'm not worried about that really.

Chris - And the medications that we use, what are they and how do they work?

Max - Basically they're stimulants, which broadly speaking will stimulate those parts of your brain which supervise the rest of the brain. And they are things like methylphenidate. They are very effective, but they do have some side effects. And then there are non-stimulants, which tend to be a little bit less likely to be effective, but they are a little bit gentler, take a bit longer to work, and they sort of alter the kind of balance of the brain. And they kind of alter the way that these supervisory elements can communicate with the rest of the brain. So two different classes of drugs that work in slightly different ways and can work together quite nicely. So we have a few kind of tricks up our sleeves, even if the first thing we try doesn't work.

Chris - And is that an indefinite thing? People then are almost, I don't want to use the word condemned, but it almost is like that, you have to continue to use these medications indefinitely in order to continue to get that effect?

Max - It's not a life sentence. I suppose my experience is mainly with children and very often what I will say to people, quite often the children are starting this at sort of age seven or eight, and the parents will rightly ask me, is this going to be forever? And I suppose my answer is if it works and they tolerate it, we're probably in for a stretch up until secondary school. And then, frankly, the young person will tell you whether or not they want to carry on with it. And you know they're very clear about that very often. And if they want to carry on with it then they can.

Chris - And do most people elect to carry on?

Max - I mean, well, it's really interesting. My experience in clinical practice is that most people do, but actually, if you look at some of the data on following people up with medication, there is really quite a high dropout rate. But it's just not something that I experienced personally, so I've never quite squared that circle if I'm completely honest.

Chris - And do we have any data on people who do go on medication versus people who don't, is there a sort of a clear direction from beneficial outcomes as to what the best choice is?

Max - So the best data comes from Scandinavian birth registries, as it often does when you're looking at chronic conditions. The comparators that are treatment versus non treatment. So it's not non-pharmacological versus pharmacological treatment. So it's not drug versus non-drug, it's treatment versus non-treatment, but the benefits of treating these conditions over not doing so are absolutely legion. The most striking, the most eye-popping, is that if you treat ADHD, your chances of getting involved in the criminal justice system are halved.

Chris - That's a staggering difference.

Max - It is really staggering. I mean, it's a fairly low number already, but it really is a big big difference. Advantages in employment, education, relationships, all the way through, treating ADHD is better than not treating it. It's not quite the same as saying "the medications do this". And there's a bit of an unanswered question about to what extent medication versus these other environmental modifications or supporting the person's mental health are the crucial elements, but certainly going to seek treatment, getting a diagnosis where it's appropriate, is unequivocally a good thing.