Professor Edmund Sonuga-Barke So,  for a long time at the journal,   we’ve been planning a major review of  ADHD as part of our Annual Research   Review issues, for a number of years.  And in thinking about that, I’ve been   very aware that the ADHD field is in a period  of transition in some ways, a period of flux,   as established ways of thinking about the  condition are being revised in the light of   scientific evidence that’s coming out, or at least  being challenged in the light of that evidence. And I’ve been banging on about this for a few  years now, this notion of a paradigm shift,   or challenging the traditional paradigm, at least,  and I thought rather than me just writing about   it, it would be amazing if we could get some  of the leading Scientists, in the ADHD field,   to reflect on the – our understanding of  ADHD in the light of science to, kind of,   inform that debate and that discussion  as we go forward. And so, what I did,   as I reached out to colleagues and friends,  each one of them really the top of the tree   in their particular specialism, and asked them  to answer, really, three questions. One is, what   did they “consider settled science currently?”  The second one being, what did they think were   “the most recent exciting new developments” in  their particular area? And the third one being,   what did they think was “the crucial unanswered  questions that the field needs to address?” And so, there were eight colleagues who  were invited to do this, and they covered   issues around the causes of ADHD, but also the  conceptualisation of ADHD, as well, and the   presentation of ADHD. And so, you know, so, pretty  broad and comprehensive coverage. My role in the   whole thing, really, was as a bit of a ringmaster  and a little bit of a nag, as well, keeping things   in – keeping momentum moving forward, you know,  supporting the writing and helping making sure   that everybody was writing to a similar format,  addressing the questions. But also, you know,   to place the whole reviewing context,  historical context, philosophical context,   and als – as well as, kind of, draw out some more  general themes that I think are illustrated by   these eight different parts of the review, by  one of my eminent colleagues who prepared them. So, it’s, kind of, very unusual and to a –  to act – to allow people the scope to say,   “This is what I think,” rather than having a very  systematic approach. So, clearly, as you – if you,   you know, if you get to reading the article,  you’ll see it’s evidence-based and science driven,   without a doubt. I don’t know how many references  there are, but it must be getting up for 300,   but it still makes clear that there’s a big  deal of interpretation, by the various authors,   in terms of what they consider we’ve achieved and  what they consider the future holds for the field. Yeah, so, obviously, we had to decide on what  the key divisions within the review would be.   We couldn’t cover everything, but clearly, there  are some major areas that we had no choice but to   cover. In terms of the causes of ADHD, we looked  at genetic factors and we looked at environmental   factors. So, there’s Barbara Franke and Joel Nigg  covered those areas. We also looked, obviously,   at neuroscience and Jeff Newcorn and Xavier  Castellanos worked together on that section,   focusing on brain structure and  function, but also on neurochemistry. Now, quite clearly, those are – those four  areas are at the core of causal models of ADHD   and within the neuroscience, of course,  there was mention of neuropsychology,   as well, which is also essential. And if we think  about translational science, that is applying   scientific evidence to improve clinical practice,  these three areas are key in that, and also,   they’re also three areas where our thinking about  the nature of ADHD is changing most radically,   I suppose, in some ways, in the light  of research over the last ten years,   in particular, which we can –  I can talk about that later. In terms of the presentation of the condition, how  it presents, there were areas on the developmental   course of ADHD, there were – was a section on  the structure of ADHD in terms of, kind of,   a broader phenotype, what might be  include over and above inattention,   hyperactivity and impulsivity. And that focused  on things like emotion regulation, sleep and so   forth, as well as comorbidities, so-called  comorbidities or co-occurring conditions,   like emotional problems, depression, anxiety,  conduct problems, so forth and so on,   and actually including autism as well, which is a  major area of research, over the last ten years. So, yeah, so it’s been a – it’s a pretty  comprehensive and broad-based review that   tries to address all these different areas in  terms, as I say, in terms of what we consider   established fact, ‘fact’ and what we  consider the most important questions   that we need to answer going forward.  So, yeah, so, in terms of those areas,   Luis Rohde did the developmental pathways and  then, Emily Simonoff and Stephen Becker did the   overlapping conditions, and sorry, I forgot the  final one, which is this whole issue of stigma,   quality of life, stigma, wellbeing and Sven  Bölte covered those really important areas. Now, those areas might not have been included.  This is – in a way, this is how the field is   being shaped. Those areas, in an equivalent  review ten years ago, the areas around stigma,   quality of life and so forth, might not have  been included, because – but the focus is very   much more, you know, on the personal experience  of people with ADHD in the research field now,   very much being considered, you know,  centrally in terms of core research questions. So, I, basically, trusted my colleagues.  I also, obviously, reviewed – I mean,   these are people you can trust. I also reviewed,  obviously, very carefully and multiple drafts. So,   it wasn’t just like, “Go away and write  2,000/3,000 words on genetics of ADHD.”   There was many, many iterations and, of course,  it wasn’t just myself working on each section   with the relevant – particular colleague, but of  course, they were circulated to the whole group,   so that we looked not only at the content  of each section, but we looked at synergies   between the sections and so forth. Making  sure that there was a consistency even where   there might be some disagreement, you  know, in the views of the individual. Yeah, no, it’s a very different approach,  because of course, we are pushed more and   more to a much more standardised approach. But  I think it’s – in a way, that’s a bit spurious,   because I think sometimes, the so-called  standardised approach still hides a lot of   opinion and at least here, it’s explicit.  You might even say that it’s unabashed   eminence-based science. But I think, you  know – that’s supposed to be a bad thing,   but I think on certain occasions it’s a –  rather a good thing when you’re dealing with   people who have such knowledge and expertise. And  taking – and as long as one is open about the,   you know, the – and transparent about  that, I think it’s a good thing, yeah. So, the process was fascinating. Took a long  time, as you can imagine, but chiselling away   at the different sections, developing some degree  of similarity of style and having a common focus,   foci or focuses, across the different  sections was really important. So,   it’s been an amazing experience, actually,  working with all of these wonderful colleagues,   on this particular – and we hope that,  you know, people in the field will enjoy   reading it. I did notice already we’ve had  over six – I think over 6,000 downloads of   the article, so that suggests people  are, hopefully, finding it useful. So, yeah, I think the development of a, kind of,  formal diagnostic system that’s focused on the   observable characteristics, they call it  ‘phenomenological approach’ to diagnosis,   has been absolutely essential in terms of progress  in the treatment of ADHD, but also in linking it   to the science of A – the research on ADHD. As its  expressed in the DSM, the Diagnostic, Statistical   Manual of the American Psychiatric Association, or  in the World Health Organization’s International   Classification of Diseases, it is explicitly open  to being updated in light of evidence. And so,   as listeners will know, there have been a series  of versions of these diagnostic manuals and   the ADHD diagnosis, although at its core it’s  remained pretty much the same over – you know,   since the DSM-III-R, so, kind of, first – the  first, kind of, manifestation, or closest to the   current manifesta – current characterisation,  you know, it’s pretty – it’s remained pretty   much the same since then in terms of the core  inattention, impulsiveness and hyperactivity. Of course, now, history goes a long – a lot  further back than that, right the way back   to George Still, with his concept of “Moral  lack of – lack of moral control,” you know,   way back in the early 20th Century,  right at the start of the 20th Century,   so the long historical progression of the ADHD  construct. But the most recent phenomenological   approaches, from a scientific point of view,  have provided the framework to make explicit   the definition of ADHD and therefore, to allow its  research in a kind of, a standardised and coherent   way of building a coherent body of knowledge  about an identifiable and definable phenomena. However, as with all concepts, there are multiple  levels of significance and this who – the whole   notion of ADHD, attention deficit hyperactivity  disorder, is very firmly grounded in a medical   model of neurodevelopmental diversity, if you  put it – call it that if you like. So, that at   the core of that model is the notion that ADHD  is a category that’s distinct from normal – the,   kind of, normal range of expressions of  attention, impulsivity and hyperactivity,   or levels of activity, impulse control and so  forth in the general population, so it’s distinct.   The boundaries between it and other conditions are  clear and identifiable, that the underlying causal   structure is unitary, that there is really –  it’s a kind of, a unitary biological entity.   Cau – the causes may be complex, but they’re,  kind of, common to the condition. There’s one   unitary entity, it’s a category, it’s easily  – it’s distinguishable from other conditions. And so, you know, that – some people call that,  kind of like, a disease model or a medical model,   and crucially, within that position  – perspective, the causes lie within   the individual and particularly within the  brains of the individual. And so, of course,   that has a big impact on the science that  we’ve done, because the obvious scientific   question there is, you know, from a  translational point of view, you want   to know which bit of the brain isn’t working,  what is the unitary cause of this categorical   condition? And so, of course, that focuses on  some very particular research questions that   we might answer by neuroscience, or we might  answer by genetics and so forth and so on. However, despite the many benefits of this  system of definition and categorisation,   the science that’s been done over the last  – particularly the last ten to 20 years,   has started to actually question, or lead to the  questioning of some of these assumptions that I   just mentioned. So, in a way, the – wouldn’t  say the seeds of the destruction of this model,   but they lie, actually, in the model  itself. So all the benefits we’ve had,   moving the field forwards, actually have  led us to then question the assumptions of   the model. So, it’s a wonderful, kind of,  philosophy of science paradox, in a way. I mean, so, for instance, we can think about  whether it’s a category, is ADHD a category?   Are there clear boundaries between normality and  disorder? Well, there aren’t. I think we can say,   without fear of correction now, that it’s a  dimension. There are no clearcut differences   in the underlying causes of ADHD behaviours as you  become – as it becomes more severe. You see what I   mean? So, there’s no, sort of, step change around  any boundary that would suggest it’s a separate   entity from normality. They call that a taxon.  So, there’s no evidence for a taxon of ADHD,   and that comes from genetic studies, from  epidemiological studies, neurosci – you know,   across the board, there’s simply not  one study that supports it’s a category. So, what does that mean, yeah? That starts  to challenge the underlying assumptions of   the current system. What about the boundaries  between, say, ADHD and other conditions? Well,   they’re very fuzzy. You know, we know now  that ADHD shares genetic influences with   a whole range of other conditions.  I’m sure Barbara spoke about that;   she wrote about it in the review, of course.  So, that there are shared genes with autism,   there are shared genes with depression,  etc., etc., we can go on and on. There   are shared neuropsychological aspects and  neuroscientific aspects with other conditions,   so the boundaries aren’t clear in terms of ADHD,  either. So, that’s interesting and challenging. Is there a single biological entity, is  it one thing? Well, probably not. So,   the most popular causal model, previously, in  terms of brain processes, was the so-called   executive dysfunction model and this was the idea  that ADHD was caused by deficits within the system   of executive control, which is underpinned  by so-called frontostriatal brain networks,   particularly dorsal frontostriatal brain  networks that link the basal ganglia with   the frontal and prefrontal cortex. And  this was popularised by Russell Barkley,   the brilliant – probably the most influential  ADHD Researcher that we’ve ever had. So,   his idea was that ADHD was essentially a disorder  of executive function, nice and simple and,   of course, then, you say, “Well, if it’s an  exhau – a disorder of executive dys – function,   then what you do is, of course, try and treat the  executive dysfunction to improve the ADHD.” So,   it’s a very nice translational, simple, quite  linear model from genes, to brains, to behaviour. However, what we know now, from psychological –  neuropsychological testing, from brain imaging   studies, is that in fact, there isn’t a single  cause, underlying cause of ADHD. That you can   manifest ADHD in a same – similar way that ten  people might have a very similar clinical profile,   but actually, if you look at  their neuropsychological profile,   it might be very, very different. So,  some of them might have an executive   problem and others might have a problem,  for instance, in motivational features. So, we introduced a – I introduced a concept,  a delay aversion, quite a few years ago now,   and what we showed was that there were people  with ADHD who had no executive function   deficits at all, but really struggled with  handling delay in waiting for things. So,   that was more core than the executive control and  in fact, these things were totally dissociable;   they weren’t correlated. So, it, kind  of, supports the notion that there are   neural or neuropsychological subtypes  within the broader ADHD grouping. So, you can see all of those three things  challenge the simple diagnostic system that   we’ve got. The problem is that the simple  diagnostic system works pretty well. And so,   there’s again, a bit of a paradox here that  while it’s probably not been good for science,   that system, because it’s built on the wrong  assumptions, so we’ve often asked the wrong   questions, I call it a scientific red herring  because we’re distracted by asking about only   executive function, when it’s actually not a  problem for quite a few people with ADHD. So,   you know, you’re looking at the heterogeneity  rather than this, kind of, unitary model. So, it’s pushed us towards asking the wrong  questions, towards asking what I think,   very often, the wrong questions, and  it’s played, for instance, it’s really   played down the role of the environment in  ADHD, which I think has been unfortunate.   And, you know, I think the evidence is – and  as Joel talk – wrote about in his section,   you know, there is growing evidence for the  role of the environment in its interplay   with genetic factors. But also, within  studies that we’ve done in – of severe   institutional deprivation as a primary cause of  ADHD, potentially. So, you know, that’s another   consequence of the model  that we’ve been working with. So, scientifically, it’s probably not been a  good thing. It’s been a good steppingstone,   perhaps, brought some order, reliability and  system, but it’s actually, scientifically,   probably, isn’t supported by the evidence that  we’re finding now. But clinically, it seems to   still have great value. Now, how could that be the  case if it’s not actually a good scien – if it’s   not grounded on the science that’s developing?  And that’s something I’ve tried to address. I wrote a commentary recently in  our sister journal, JCPP Advances,   in response to a paper by Ben Lahey and  colleagues arguing for the complete overhaul   of the dimen – of the categorical  model towards a dimensional model. Now, given what I’ve just said, you  think you’d support that, but actually,   I argued against it. In fact, I – that the  commentary is entitled “If It Don’t Fit,   Don’t Force It,” which some of you may remember  was an incredible soul record of the 1970s. But,   basically, saying it’s – to force a dimensional  model would be so disruptive to the clinical   practice and without any clear evidence of  exactly what are the key dimensions and how   it would impact decision-making. Which is the  key thing here, make – ability to make decisions   about who needs intervention and who doesn’t need  intervention, and which sort of intervention they   need. It would be a big experiment that would be  incredibly costly, I don’t just mean financially,   with a big risk that it would be a  total failure. So, I argued against it. And I think the reason categorical  systems are probably not going anywhere,   in terms of clinical practice, is  that Clinicians are human beings and   human beings think categorically. They make  categorical decisions all the time, that is,   should I do this, or should I do that?  And so, that categorical thinking – sorry,   the diagnostic system needs to cut  with the grain of human cognition,   which is categorical. It’s also trait-based. We  also do think about people’s individual behaviour   as belonging to them, you know. This just – this  is just a natural way human beings think and so,   that really constrains what can be an effective  clinical diagnostic system for the Clinician. So, we’re caught – I feel we’re caught  in a very interesting tension, actually,   and it’s not clear to me what the solution  is. Some people have argued for a sort of,   a hybrid system where you keep the categorical  definitions, you refine them, to some degree,   but you overlap them with more dimensional systems  focusing on underlying causes, perhaps. And that’s   very much linked to the, so-called RDoC approach  that was developed by the National Institute   of Health – Mental – the National Institute of  Mental Health in – Tom Insel – in the States, and   is providing the basis for quite a lot of research  struc – you know, the framework for quite a lot of   research, with the goal of identing what – to find  what are the core underlying cause of dimensions. So, you could overlay that on the categorical  model, so you get information both about the   categories, you know, who fits in which –  you know, who is defined in which category,   even though the boundaries are arbitrary, to  some degree, they seem to work, and overlap it   with issues about underlying causes. And that’s  quite important clinically as we go forward,   because it may be the case that you  need to treat the symptoms of ADHD,   but you also need to treat  the underlying difficulties. So, for instance, if a person with ADHD also has  working memory problems, then the treatment for   ADHD may not improve the working memory problems,  but it might improve the symptoms. So, then,   you need to target the underlying working memory  problems, which can also cause great impairment,   as well. So, I think it’s – it will be good  to have measures of, you know, the neural,   the neuropsychological, neurobiological profile,  alongside the clinical categories. I guess that’s   how I’ve been thinking about it, anyway, at  least. But it is a very interesting, and I think   we call it conundrum, so very interesting  conundrum, this tension between the two,   the scientific use of the diagnostic categories  and the clinical use of the diagnostic categories. And it’s essential that we have Clinicians and  at the same time, I should say, it’s essential   that we have Clinicians and Scientists  being able to talk to each other,   so using a common set of concepts. You know,  we can’t have one going – ‘cause without that,   then there’ll be no translational research at all. So, it’s a very long answer to your question, but  I hope it – I hope you think it was clear, anyhow. I think a hybrid system is a – is the most  likely to bear fruit, yeah. It’s a – but it’s   an interesting situation we find ourselves in,  I think, and it’s not just ADHD, of course, it’s   nearly – the other neurodevelopmental conditions,  as well as the other mental health conditions,   you know. So, yeah, but apart from those – so, in  a way, you can challenge a, you know, a paradigm,   a diagnostic paradigm, you know, in terms of  scientific credibility, which I’ve been talking   about, but you can also challenge it in terms  of whether it actually delivers on its promise   to improve treatment, ‘cause that’s the whole  point of what we do. If peo – if the people with   ADHD aren’t going to benefit from the research  we do, then we may as well just stop doing it,   you know. This isn’t – I mean, it’s great, it’s  very enjoyable, fascinating intellectually,   but actually, ultimately, it’s supposed  to improve the lives of people with ADHD. And I think there is a great frustration in  the field that the actual science of ADHD,   I don’t mean the science of pharmacology  or, you know, whatever, the actual science   of ADHD has not delivered translational  benefits or therapeutic innovation for   the people with ADHD so far. And we’ve got  to think about what’s the barrier to that,   as well, and it may be the categorical  system is a barrier to that. So, again,   another little complexity in thinking about  the relationship between science and practice. But then, the third one, the third reason  to challenge a paradigm, you might call not   scientific credibility, not therapeutic value,  but something like a cultural critique. So,   people are starting to challenge the notion  that ADHD – that divergence, inattention,   impulse control and activity levels constitute  a disorder, and that disorder is a result of   brain dysfunction. They’re challenging  that concept. They’re not saying it on   scientific grounds. They’re saying it – that  this is oppressive to neurodivergent people,   and this is a so-called neurodiversity movement  and, in a way, it’s the biggest challenge.   It’s the most radical challenge, it’s not  maybe the biggest, it’s the most radical   challenge to the whole of ADHD and autism, you  know, spectrum disorder and whatever concepts. And it’s the notion that in and of itself,  patterns of neurodivergence don’t constitute   disorder and don’t necessarily have a negative  impact on the lives of individuals who have   ADHD. And that impact depends, and the  status of that neurodivergence depends,   on the environment in which they live and  the environment in which they’re – as the   ac – as activists, you know, neurodiversity  activists would say, the environment in which   is imposed on them by neurotypical people.  So, I mean, the whole movement, I think,   is – it’s been very prominent in the autism  area, but it’s been – logically, you know,   there’s no reason not to extend it, the same  arguments to the ADHD area, although, you know,   the advocates of it, you know, there’s fewer  in the ADHD field than in the autism field. But, you know, there are some interesting  implications of this position, and I wrote a   little bit about that in the Annual Research  Review, but I’ve written at greater length,   in various commentaries, about, you  know, how does this impact science?   ‘Cause I – just remind everybody, I’m not a Sci  – I’m not a Clinician. I am just a Scientist,   so I really focus on the scientific implications  of a neurodiversity movement. And I think in –   what it really does is it makes you  focus much more on the environment. So, I think we’re at a fascinating stage in the  science of ADHD and we definitely need to explore   alternative paradigms, I think, given the lack of  progress in terms of the therapeutic developments,   therapeutic innovations. You know, it makes  us think, you know, what is a ADHD positive   environment? What would it look like, you  know? How would we restructure it? How   would we introduce reasonable adjustments  to a classroom environment, for instance,   that would mean that people with ADHD wouldn’t  struggle in those environments in the way that   they do now? And how could we introduce that, all  that, without disrupting the education of other   people in the cla – other kids in the class? So,  it’s fas – some fascinating questions, I think,   that it raises, which we address in – to some  extent, in the Annual Research Review paper. So, the – I think the one final thing that  I’d like to focus on is the whole issue of   ADHD in girls and young women. It seems to me  that this is one of the most important areas,   clinically and scientifically, in our  field, which has been, to a large extent,   overlooked. Now, because ADHD’s been sidered  as – considered as a male condition, largely,   and the ratios between men – males and  females vary, you know, between one to three   or one to four, in the general population,  perhaps one to eight, even, in the clinic. So, far fewer females seem to display ADHD and  even fewer of them seem to get referred for help,   and what it looks like is that the main issue  is the age at which the diagnosis is made. So,   when you move into adolescence, the ratio is  much closer. So, girls seem to be being diagnosed   later than males, than boys, you know, females  later than males, and when you get to adulthood,   it’s pretty much 50-50, it’s one-to-one, you know.  And many, many women get diagnosed in adulthood,   but look back over their lives and  recognise that they were displaying,   you know, all the difficulties that somebody  with ADHD might experience. You know,   so they might get diagnosed at 25 or 30, but  look back and think my golly, even when I was,   you know, five and six, I was pretty much  the same person, but nobody spotted it. And so, I think we should consider, and I know  it’s a very controversial statement, but given all   the data and given all the differences, both in  age of the diagnosis, age of onset, perhaps even,   might be a later onset in females, the pattern  of symptomatology. Don’t forget, you know, the   DSM 18 symptoms was, basically, built initially  on clinical experience, which of course, in a   circular way, was mainly with boys. And so, we’re  exploring, with my PhD student, Anna Maria, she’s   working on talking to women with ADHD and trying  to get them to talk about their condition and   their experiences to try and identify other areas  of behaviours, other behaviours, other symptoms,   that might be key for women, that men – but not so  key for men. So, she’s working on that, so she’s   been doing an amazing job, and I think other  people, you know, are working on exactly that. So, maybe their phenotype is different, the  age of onset is different and, of course,   some of the factors are crucially different, as  well. So, the whole role of the menstrual cycle   in ADHD and the role of oestrogen and hormones  more generally, and the fluctuations in symptoms   over the – both over the, you know, timescale of  a month, but also over the timescale of a life,   you know, in menopause and so forth, and also  puberty being particularly important. So,   it may be that the causal structure  is – the causal factors are different,   it may be that the presentation is different  and certainly, the age of onset is different,   which all – course, all means that there may  be very important differences in the treatment   that’s needed, as well, the therapy  or the interventions that are needed. So, I definitely think this is an area of real  great importance for the field, and one of the   things that I allowed myself in that – in pulling  together these incredible sections that were   written in the review, is to ask each person to  think about the issue of sex differences in ADHD,   as it related to their particular topic. And that  was really, really helpful and interesting. So,   I do think this is a really important  area, going forward, for the field.