‘ADHD, autism, and the elevated risk of later depression’ In conversation with Professor Anita Thapar

In this podcast we talk to Professor Anita Thapar, Professor, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University. A researcher and a clinician, Anita is also on the board of the UK national neurodiversity charity ADHD Foundation.

Anita talks about the relationship between disorders, such as, ADHD and autism, the elevated risk of later depression, and what is known about the mechanisms behind this association.

Anita also looks at what factors may be protective in terms of mitigating the association between neurodevelopmental disorders and youth depression, and how research can impact, or change, the trajectory, from childhood neurodevelopmental disorder, to youth depression.

Please subscribe and rate our podcast from your preferred streaming platform, including: SoundCloud, iTunes, Spotify, CastBox, Deezer, Google Podcasts and Radio.com (not available in the EU).

I am a clinician scientist. My primary interests are in child neurodevelopmental disorders and depression. I was Lead Editor (Joint) of the 6th Edition of Rutter’s Child and Adolescent Psychiatry-the leading textbook for clinicians and scientists.

I head the academic Child and Adolescent Psychiatry Section in the Division of Psychological Medicine and Clinical Neurosciences and the developmental disorders group within the MRC Centre for Neuropsychiatric Genetics and Genomics and Division. I also have honorary NHS consultant contracts with Cwm Taf and Cardiff and Vale UHBs.

My wider roles include:

• Teaching/training of medical and psychology/biomedical students and trainee NHS clinicians
• NHS liaison
• Translation of our research into policy including Welsh Government Together for Children and Young Peoples Programme on child and adolescent mental health (neurodevelopmental and early help and enhanced support work streams).

Bio and image via Cardiff University

Transcript

Interviewer: Hello, welcome to the In Conversation podcast series for the Association for Child and Adolescent Mental Health, or ACAMH for short. I’m Jo Carlowe, a freelance journalist with a specialism in psychology. Today, I’m interviewing child psychiatrist Professor Anita Thapar of the Division of Psychological Medicine and Clinical Neurosciences at Cardiff University. Anita also directs a Developmental Disorder Group with the MRC Centre for Neuropsychiatric Genetics and Genomics. Anita’s research focuses on the origins, development and complications of child neurodevelopmental disorders, and adolescent depression. If you’re a fan of our In Conversation series, please subscribe on iTunes, or your preferred streaming platform. Let us know how we did with a rating, or review, and do share with friends and colleagues. Anita, welcome. Thank you for joining me. Can you start by introducing yourself?

Professor Anita Thapar: Thanks Jo. My name’s Anita Thapar. I’m a Professor of Child and Adolescent Psychiatry, at Cardiff. And I have two roles. As you mentioned, I direct the science in the Child and Adolescent Psychiatry section, the academic section at Cardiff University. But I’m also a clinician. So I have an honorary NHS contract. That’s really quite important to me that I have both roles, because I feel passionately about those.

Interviewer: And how did you come to be interested in the field of child and adolescent mental health?

Professor Anita Thapar: I first became interested, through the clinical route. So when I was a medical student, doing my pediatrics / child health block, I got to spend some time with a child and adolescent psychiatrist who was seeing children, and young people, on the pediatrics ward. And I became really interested then. I had thought, until then, that I would, perhaps, do pediatrics. But then I got really interested in child and adolescent mental health. And so, I think it was quite unusual; by the time I left medical school, I knew I wanted to do child and adolescent psychiatry. So my first route was actually doing the clinical training in psychiatry, and then child, and adolescent, psychiatry.

In my day, we didn’t get much exposure to research. And I think that’s quite different for students now. So I came to research later, really, after I’d done quite a lot of my clinical training. And I think that influences me in the sense that, for me, the clinical is really important, as well as the research.

Interviewer: Your research focuses on youth depression and neurodevelopmental disorders? Can you say something about the relationship between disorders, such as, ADHD and autism, and the elevated risk of later depression?

Professor Anita Thapar: We’ve known for some time that individuals with ADHD, and autism, quite often they will have co-occurring depression. Any clinician, particularly, perhaps, who sees adolescents with ADHD and autism, or young adults, will recognise that. We, and other people, have found  through doing longitudinal studies that ADHD, and autism, seem to behave like risk factors, for future depression.

And I think that the important message for practitioners is that today’s ADHD, and autism, could become tomorrow’s depression. ADHD and autism, of course, typically manifest early in development, whereas depression typically manifests after adolescence. So I think those links are really important to recognise.

Interviewer: And what is known about the mechanisms behind this association?

Professor Anita Thapar: Well, this is something that we’re really interested in. Because there are several potential explanations as to why they’re going together. So first, ADHD, ASD, could go together with depression because we know that they share the same sorts of risk factors.

For example, family, twin, and recent molecular genetic studies show that genetic risks that confer susceptibility to ADHD and ASD also influence depression. So you’ve got this shared genetic risk. So that’s why they might go together. The second explanation is that having ADHD or ASD may cause later depression. One of the things that’s really challenging in research and that’s not just in mental health, but across lots of other areas is it’s really hard to show whether something causes something.

So the way that we, approach that, because it’s not usually possible to do randomised control trials for everything, is you use different study designs, and see if the results all converge on something similar.

In a study where we followed up children, it was a longitudinal data analysis, that suggested ADHD, and ASD, were linked to later depression. We also used an approach called Mendelian randomisation, which is, basically, using genetics, as a way of testing potential causal mechanisms. I won’t go into an explanation on Mendelian randomisation. But that also suggested, at least for ADHD, there may be likely causal links with depression.

And another approach altogether was used by colleagues in Sweden. They used registry, and prescription, data, and found lower rates of depression in people with ADHD when their ADHD was being treated with medication. So each of these designs, you can see flaws in them, but they also have different strengths. But they all are suggesting the same. So that does suggest that it may be that the ADHD, ASD, link with depression, it could, in part, be because they have causal effects.

But the second issue, is “OK, well, that’s all very well, but how might that happen?” Actually, we don’t really know, for sure, how that happens. There are several possibilities. So one possibility is through social stresses. Because we know social stresses can lead to depression. We also know, from research that I’ve conducted, and my team have conducted, and other people have conducted, that ADHD, and ASD, can lead to increased stressors.

So just to give a concrete example. In a study using an adoption design, we looked at children who had been adopted away. So this work was conducted with my colleague, Professor Gordon Harold, at Cambridge, and colleagues in the United States. We looked at children who had been adopted at birth. And we found that ADHD symptoms in the children predicted maternal hostility in the adoptive mother, which suggests that ADHD can lead to stressors. We also know that ADHD, and ASD, can also lead to stressors, such as, being bullied, friendship difficulties, being excluded from school, or academic failure.

So all these social stressors could account for the link between ADHD, ASD, and later depression. A paper, I think, that you picked up on, Jo, which was conducted by one of the PhD students in our group, found that peer difficulties and academic strain may account for part of the link, but only part. So we do need to find out a bit more about those mechanisms. Another really interesting finding is around irritability, anger, in those with neurodevelopmental disorders. People with ADHD, and, also, autism show much higher rates of severe irritability and repeated angry outbursts.

Work carried out by Dr Olga Eyre, in my group, and others, elsewhere, have shown that irritability, like, repeated outbursts of anger, seems to account for quite a lot of the link between ADHD, ASD, and later depression. So this gives us a really strong clue who’s at greatest risk, and also highlights the importance of recognising irritability, in children with neurodevelopmental disorders.

Interviewer: What factors may be protective in terms of mitigating the association between neurodevelopmental disorders and youth depression? You have talked a bit about people having access to the right treatments?

Professor Anita Thapar: This is a really important question. Because so much more work needs to be done to see what factors might mitigate that link. And most scientists, and ourselves, included, are focused on risks. And actually, at the moment, we’re focused on gaining funding, to look exactly at this.

But we can make some predictions. The first one is, is that, at least for ADHD, the evidence, so far, suggests that, where possible, really effective treatment of ADHD symptoms may be important, as a protective factor. We don’t have definitive evidence, but this is, from the observational evidence, so far. I mean, it’s interesting because I’m trained in medicine. We actually do that for diabetes, and high blood pressure, which are continuous traits, like ADHD, to prevent adverse outcomes.

But, we don’t necessarily always have the resources to do that for ADHD. And I think it’s really important for ADHD, and ASD, that we do think about depression prevention, because otherwise it will further add to impairments. The other way that we may be able to mitigate it- as I said, this is inferred from findings, rather than there being direct research showing it-,is that we know, from observational studies, that parents of children with ADHD, or ASD, neurodevelopmental disorders, have higher rates of depression.

We also know from studies of adult depression, and looking at offspring, that the treatment of parent depression has been found to be helpful in preventing depression in their offspring. So you may infer that it’s possible that treating parent depression in the families of children with ADHD, and ASD, may be helpful. But, as I said, we just don’t have that direct research. The other way we could think about mitigating risk for depression is reducing stressors.

We know stressors are a potent risk factor for depression. So I think this is an important message for schools, in relation to bullying, friendships, and academic stressors, for young people with ADHD, or ASD. So there does need to be greater school, community, and public, awareness, around the stressors that young people with neurodevelopmental difficulties face. And also, for those interfacing, with families, to consider family stress. The other issue is irritability. And, at present, we really don’t know how best to treat this, because it’s not a diagnosis.

The UK will typically consider this as an aspect of oppositional defiant disorder and use parenting interventions, which reduces the oppositional behaviour. But we don’t know whether that will then disrupt the link between irritability and later depression.

Interviewer: Anita, how can research, such as yours, impact, or change, the trajectory, from childhood neurodevelopmental disorder, to youth depression? So, in other words, how do you translate your findings into clinical practice, and how do you use them to influence policy and training?

Professor Anita Thapar: I think one of the most important things, and I see this repeatedly amongst clinicians, services, policymakers, and scientists, is that ADHD or ASD is looked at by one group and depression is looked at by another group. And I think it’s really important to recognise that today’s ADHD, or ASD, or neurodevelopmental problem, could become tomorrow’s depression.

Again, work carried out by one of our team, Olga Eyre, she found that almost 50% of early onset depression, in early adolescence, was preceded by neurodevelopmental problems. So it is really important for those who work with young people with neuro developmental disorders, so, this could be families, schools, higher education, child health, psychiatry in the NHS, or social care, people need to be aware that neurodevelopmental disorders are a risk factor for depression, so they need to recognise the depression.

So, for example, if a person with a neurodevelopmental disorder suddenly becomes much more withdrawn, shows more difficult behaviour, refuses to go to school, stops attending university, that’s really important to recognise. So that has implications for training of staff. You could think that if somebody is working with people with neurodevelopmental problems, they need to be trained in neurodevelopmental difficulties. But are they trained to recognise depression, before it becomes established? So I think the training in recognition, is really important.

Interviewer: Anita, I want to turn now to a paper that was published in the Journal of Child Psychology and Psychiatry, the JCPP, in July 2020, with the title Investigating Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder Traits in the General Population, What Happens in Adult Life? What was the main aim of the study, what did you find, and why is it important to focus on young adults, given that ADHD, and ASD, are generally considered early onset disorders?

Professor Anita Thapar: I came at this, really, with a clinical, and research, hat. So, as a clinician, and every clinician will know, that the transition from children’s services, to adult services, for people with neurodevelopmental problems, is really challenging. And then, we’d been conducting, for many years, a large study of children with ADHD. And we did a follow up after age 18. And so many in the research had been lost to services. I felt really conscious that we’d seen this in our research.

And so, I set up a clinical transition service, for 15 to 25 years old. I have the luxury of flexibility, because I’m an academic, and I’m funded by the University. And the reason I wanted to do that is so I would have the opportunity of linking with adult mental health services around neurodevelopmental problems. So when I was doing this clinic, I started seeing 22 year olds with ADHD. Sometimes they’d come with their parents, sometimes with their partner.

And I noticed, having had years of seeing children, then adolescents, the difference in how they were presenting the predominant symptoms. The types of impairments that they were experiencing, at that age, were really quite different. And it made me realise that I actually don’t know much about what’s typical in the population, in terms of ADHD like symptoms, after the age of 18. So basically, I  then turned to look at the UK population based cohort, which we do a lot of work with, the ALSPAC cohort, based in Bristol. And it was really interesting because it has been brilliantly assessed, in that cohort, for ADHD, and ASD, right from early childhood, up to age to 18.

And at the time I looked at data, they were 23. And basically no-one had looked at ADHD, and ASD, after 18. And so I talk to my colleague in Bristol, I said, “Why hasn’t anyone looked at it?” And they said, “We had better get funding and you’d better do it.” So basically, we put in for funding, this was myself, our colleagues in Cardiff, and colleagues in Bristol, to the Wellcome Trust, to look at neurodevelopmental problems at age 25.

I was really interested, because we get parents still coming to clinic, after 18. So, in ALSPAC, we went back to the parents and asked them to report, as well as, of course, asking the 25 year olds. And we found that both raters- parents of the 25 year olds and the 25 year olds-themselves, their  ratings of ADHD, and ASD, had similar characteristics to the childhood ADHD, and ASD. But there were much stronger links with communication, and cognitive difficulties, for the parent reported symptoms. We also looked at genetic risk scores which is like a composite measure of common gene variants, associated with ADHD, and autism.

And both parent and self reports of ADHD were associated with that composite ADHD genetic risk score. From a clinical perspective, it looked like at age 25, parents are really still very good informants, especially around ADHD. And I thought, well, the main clinical message from, at least, our first data analysis, and that JCPP paper, is that it’s worth , if you can, getting the parents along to clinic. And actually, I did find it quite helpful when they did come to clinic.

And so, now my team is looking at what symptoms are most impairing at age 25? Is that different to what’s impairing at younger ages?

Interviewer: Can you say anything more about those differences?

Professor Anita Thapar: Well, that paper isn’t out yet. I can tell you there were some symptoms that were  equally impairing across all ages, whereas there were other symptoms that were much more impairing at age 25. So, I won’t give the details, because, you know, we do have to check that. But, I think, the important clinical message, which I think anyone who works in child and adolescent services will be really familiar with, is to make developmental allowances. So the, sorts of, symptoms, and impairment, that are there at five, we know they’re not the same as they are at 15.

Well, equally, at 25, we need to be conscious that there’s further developmental change. And I think it’s quite interesting. From a service perspective, something magical happens at 18. Now anyone with children over the age of 18 will realise that nothing magical does actually happen at 18. And so, I think this, kind of, continuity of how we think, particularly, say, for 16 to 25, how we link with, adults, if it’s an adult service dealing with the over 18s, or perhaps you have a 16 to 25 year old service, I think is quite important. Because you do have this continuity, and yet developmental change.

Interviewer: Anita, you also, recently, co-authored a paper, What Has Happened to Children’s Wellbeing in the UK? That was published in The Lancet Psychiatry in January of this year. Can you share some of the overarching themes that emerged from this work?

Professor Anita Thapar: This was a requested piece, rather than original research. And basically, The Lancet Psychiatry, asked me to write something, a topical piece, on child and adolescent mental health from 2020. They wanted something which was a bit different from COVID. And I focused on the 2020 Good Childhood Report. Because I found it really interesting. What that report showed is a decline in children’s wellbeing, in recent years, and they did a comparison across different countries, and the UK seemed to be doing especially poorly.

So, I was immediately struck by that. This was, of course, around measures of wellbeing, which we don’t use, in clinical services. But it struck me with, you know, how this seemed to be matched with increased referrals to services. And, more importantly, from a research perspective, I was struck that it mirrors the findings from England’s young people’s mental health surveys, that had shown a sharp increase in the prevalence of adolescent mental health disorders in 2020.

I wanted to focus, on this report, because it examined well-being. And, in psychiatry, we tend to focus on mental health disorders. It’s a construct we don’t usually use. And I was struck, because I work, quite a lot, with my colleagues, in social sciences, and I work quite a lot with government, that colleagues in government, and social sciences, use well-being, and they don’t use the, sorts of, measures, of mental health disorder, the type we use in research, or in the NHS specialist services. I had to  learn about well-being.

And so, I wanted to highlight the key issues about the different measurements around mental health, in the piece, and how we need in the future, to understand how they link up better so that the different types of research around mental health could link up better.

Interviewer: And can you say anything about why the UK seems to be doing so badly? It’s a really huge question, I know that.

Professor Anita Thapar: I know. Well .the Good Childhood Report was observational. So they couldn’t really infer causality. But, according to that report, it didn’t seem to be due to, social media, and, digital use, but ..at least in terms of looking at it, from observational data, what they did find, was to do with child poverty. So the two things were to do with child poverty, and fear of failure. That’s important because it relates to sectors where there have been changes in government policy, e.g. austerity, schooling, the new curriculum, exam changes. So I think we can’t be conclusive. But these give clues on what we should look at. And I think it’s very powerful looking at differences between different countries where you may have different policies as well as using other types of. research designs ..because at the end of that paper, we suggested that, approach as  it’s really difficult to do randomised control trials for everything.

But, I think, if you can move beyond observation, to actually try and identify why well-being has deteriorated, and using different research approaches, which show the same thing, this might give you a bit more confidence about what has caused the decline in well-being.

Interviewer: How do you hope that paper might be used, to inform policy?

Professor Anita Thapar: I would hope that it will make policymakers aware that there are these different definitions, around mental health, and that different groups use different definitions. So we will use disorder perhaps, and…or mental health problem. And our social science colleagues may use wellbeing. So I think, first of all, we need an awareness that these different terms are used. I think it’s interesting for policymakers..and important for them to note the decline in wellbeing and the increase in mental health disorders.

And, if you’re putting in policy changes, build in evaluation, at the same time, so, work with scientists. And I think the third message would be for scientists, is that, right, we’ve got all this observational data now, on mental health disorders, and wellbeing. Let’s move to actually now doing research, using designs that can actually start telling us a little bit about potential causal mechanisms.

Interviewer: Anita, what are you working on currently? Are there any particular research projects, or recent findings, that you can share with us?

Professor Anita Thapar: So actually, one of our main tasks in the academic Child and Adolescent Psychiatry section at Cardiff University is setting up and launching the Wolfson Centre for Young People’s Mental Health, later this year. And that’s going to focus on young people’s depression, and anxiety. But, as I’ve already said, this will be very much linked with the other work that we’re doing on neurodevelopmental problems. My immediate focus is really to do with ADHD, ASD, and neurodevelopmental problems, including its links with depression. Because that research is ongoing, it’s being funded by the Wellcome Trust.

What we’re starting to find, like other people, so, we’re not the only group that found this, is that, ADHD, and ASD, at the moment, we define them as having their onset, their origins, in early development. And what we’re finding is that for ADHD, and ASD, that isn’t necessarily the case. And so, we’ve got some interesting findings, that tell us about what these later onset groups might represent? Because there’s a lot of hypotheses about what it could be. Is it actually a neurodevelopmental problem, or is it something different?

So we’re working quite a lot on that. The other related work, which, again, is part of this Wellcome Trust, neurodevelopmental grant, is looking at ADHD, ASD symptoms, across different ages, and across different countries. So, we’re looking across five different countries. So again, this is work that is being conducted in partnership with colleagues at Bristol at the MRC IEU.

One of my priorities is to make sure that we help the next generation of scientists, and clinicians, who are really interested in child and adolescent mental health. So we have quite a few people who are putting in for different fellowships, including around neurodevelopmental problems, irritability, and what might help these difficulties.

Interviewer: Anita, is there anything else, in the pipeline, that you’d like to mention?

Professor Anita Thapar: Well, what we do next, like all researchers, will depend, to a large extent, on what gets funded. But, I mean, it’s interesting you ask this question. I do hope that what we do get funded, is research on factors that actually modify adverse mental health outcomes, including depression in young people, with neurodevelopmental difficulties. There is another plan that’s in the pipeline, but again, you know, it depends on funding.

I’m really struck. in more recent years, although we’ve done a lot of clinical research, based on young people, who’ve come from clinics, it’s getting really hard to do large scale research, of that type. And so, we’ve had to rely a lot on population cohorts, which are really useful, but they don’t include many of the, sorts of, people that we would see, in clinic. So despite the expected difficulties faced by people with neurodevelopmental difficulties, the, subsequent mental health problems, the personal, and societal, costs, I’m really struck that there just isn’t commensurate funding for services and research.

And I think the only way we’re going to address that is to raise awareness about it, and try and look at solutions. So I’m hoping that we can persuade funders that in the UK, the only way we can do this is to conduct really large-scale clinical research on people with neurodevelopmental difficulties, beyond just population cohorts. We need to really pool our resources, across the UK, to develop a really large cohort of people, in clinical services, with neurodevelopmental difficulties.

Interviewer: Finally, Anita, what is your takeaway message for those listening to our conversation today?

Professor Anita Thapar: So I hope from this podcast, and, reading other studies, that you’ll realise that all these different disorders show such strong overlaps And we all recognise this, when you see somebody in clinic, it’s messy, they don’t just have one thing. So, I guess, my take home message is that diagnoses are helpful, I use them in practice and the reason that they’re helpful in clinical practice, and specialist services, is to implement evidence based interventions. So, for example, we wouldn’t treat depression with stimulant medication. But my take home message is don’t get fixated on them. Our diagnoses don’t carve nature at its joints. Because these different neurodevelopmental disorders strongly overlap with each other, and they overlap with different mental health disorders. So I’m not saying dispense with diagnosis, but it is just a tool. For example, for specialist treatment decision making. I don’t think we should lose sight of the actual problems with daily functioning. And it shouldn’t be a barrier for young people, and families, to access help, or, necessarily, the preferred way of allocating resources. So I think getting hung up on making the perfect diagnosis is a problem, there has to be a balance.

Interviewer: Okay. Anita, thank you ever so much. For more details on Professor Anita Thapar, please visit the ACAMH website www.acamh.org and Twitter at ACAMH, ACAMH is spelt ACAMH. And don’t forget to follow us on iTunes, or your preferred streaming platform. Let us know if you enjoy the podcast with a rating, or review, and do share with friends and colleagues