Neurodevelopmental Dimensional Assessment and Genomic Risk of Neuropsychiatric Conditions

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In this Papers Podcast, Dr. Sam Chawner discusses his JCPP Advances paper ‘Neurodevelopmental dimensional assessment of young children at high genomic risk of neuropsychiatric conditions’ ( Sam is the first author of the paper.

There is an overview of the paper, methodology, key findings, and implications for practice.

Discussion points include:

  • What are copy-number variants (CNVs) and how they impact child development.
  • Insight into what 22q11.2 deletion syndrome is, how it is typically diagnosed, and how it is associated with psychiatric risk.
  • Implications for clinicians and CAMH professionals.
  • Whether there are adequate interventions targeted at early age groups.
  • Recommendations for prevention, detection, and the targeting of interventions.

In this series, we speak to authors of papers published in one of ACAMH’s three journals. These are The Journal of Child Psychology and Psychiatry (JCPP)The Child and Adolescent Mental Health (CAMH) journal; and JCPP Advances.

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Dr. Sam Chawner
Dr. Sam Chawner

Dr. Samuel Chawner is a Medical Research Foundation Fellow at the Division of Psychological Medicine & Clinical Neurosciences at Cardiff University School of Medicine. His research focuses on the impact of genomics on child neurodevelopment and mental health, with the goal of providing new insights into the emergence of psychiatric problems in children and young people.


[00:00:01.360] Jo Carlowe: Hello, welcome to the Papers 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. In this series, we speak to authors of papers published in one of ACAMH’s three journals. These are the Journal of Child Psychology and Psychiatry, commonly known as JCPP, the Child and Adolescent Mental Health, known as CAMH, and JCPP Advances.

Today, I’m interviewing Dr. Sam Chawner, Medical Research Foundation Fellow, at the Division of Psychological Medicine and Clinical Neurosciences at Cardiff University. Sam is the first author of the paper, “Neurodevelopmental Dimensional Assessment of Young Children at High Genomic Risk of Neuropsychiatric Conditions,” recently published in JCPP Advances. This paper will be the focus of today’s podcast. If you’re a fan of our Papers Podcast series, please subscribe on your preferred streaming platform, let you know how we did, with a rating or review, and do share with friends and colleagues.

Sam, welcome, thank you for joining me. Can you start with an introduction about who you are and what you do?

[00:01:17.740] Dr. Sam Chawner: Yeah, thank you for the invitation, Jo. I’m a Medical Research Foundation Fellow at Cardiff University, and within the Division I’m based at the Centre for Neuropsychiatric Genetics and Genomics. And my research really focuses on how genetics shapes child development and how genetics also influences the development of psychiatric problems across the lifespan.

[00:01:41.020] Jo Carlowe: Thank you. Sam, in your research, you focus on a class of genetic conditions known as ‘copy number variants’. With the layperson in mind, can you tell us what we need to know about copy number variants, and how they impact child development?

[00:01:56.470] Dr. Sam Chawner: Good question, and when I first started at Cardiff University, I hadn’t come across copy number variants before. A brief, sort of, intro, we all have 23 pairs of chromosomes, and excluding the sex chromosomes, that means we have two copies of each gene. A copy number variant is when there’s a large section of a chromosome that’s either missing, or we could call that deleted, so then there’s one less copy, or there can be a duplication, so there’s an extra copy. And sometimes we shorten copy number variant to CNV. Most people will have a CNV, but most of them are benign, but there are a certain copy number variants that if they hit certain genes, they impact human health and development. In some cases these get diagnosed via NHS medical genetic clinics, following a referral.

We now know that there’s a range of CNVs that impact child development, and large-scale studies have compared the genetics of individuals with certain health conditions to controls who don’t have that health condition. And through these studies, CNVs have been linked to learning difficulties, neurodevelopmental problems, a range of psychiatric problems, and also neurological conditions, such as epilepsy. And there’s other physical health conditions, but those are, kind of, the main ones surrounding child development.

[00:03:17.920] Jo Carlowe: Yeah, that’s really helpful, thank you, very clear. In your work, you combined psychiatric genetics and developmental psychology, to investigate the early developmental origins of psychiatric risk. Can you give us an overview of some of your projects, and how these dovetail with the research in the JCPP Advances paper that we’re going to explore today?

[00:03:39.640] Dr. Sam Chawner: I’ve always been interested in overlaps between biology and psychology, and even for my undergraduate degree, I did, sort of, a combined course, looking at psychology and genetics, and then my PhD focused on neuropsychiatric genetics. And, in fact, for this paper, it was a collaboration between the School of Medicine and the School of Psychology, and I think it’s important to highlight how much can be gained by working across disciplines. My PhD focused on a genetic condition called 22q1.2 deletion syndrome, and this is known as one of the strongest genetic risk factors for schizophrenia. It’s a condition with low awareness in the UK, that affects approximately one in 4,000 births.

And as part of my PhD, I followed up children with this condition into their teenage years, and looked at cognitive changes linked to the development of early psychotic symptoms. And I guess it’s an example of how we can use measures of cognitive development, and this can be combined with genetics, to understand the emergence of psychiatric conditions.

After that, I worked on a project as part of my postdoctoral work in the nationwide IMAGINE ID study. And this was looking at a wider range of genetic conditions that have been linked to high risk of psychiatric outcomes. And we looked at a range of domains across childhood development, including language, sleep, social functioning, anxiety and motor issues, and found that children with these risk genetic conditions struggled across all these domains, compared to control children.

And to me, this just highlighted the wide impact genetic risk factor’s already having in childhood. The average age of children in the study was ten, and this, kind of, raised the question, “So how early do these problems start? How does psychiatric risk present in a very young child?” And that’s, kind of, what led to the work we’re going to discuss more today.

[00:05:45.560] Jo Carlowe: Great, thank you. In the JCPP Advances paper, so this is “Neurodevelopmental Dimensional Assessment of Young Children at a High Genomic Risk of Neuropsychiatric Conditions,” you do talk about deletion syndrome, and you alluded to this before, so this is 22q deletion syndrome, which is identified as one of the strongest risk factors for neurodevelopmental conditions. Can you just tell us a little more about 22q deletion syndrome, and how it is typically diagnosed, and how it’s associated with psychiatric risk?

[00:06:16.500] Dr. Sam Chawner: 22q1.2 deletion syndrome means that the individual has a deletion on chromosome 22, specifically in the chromosome region q11.2. In the past, it was also known as DiGeorge syndrome, and velo-cardio-facial syndrome, and, in fact, some hospitals still use that terminology. But within research, there’s a focus now to call the syndrome based on the genetic location.

It’s typically diagnosed in early childhood, following referral to medical genetics, usually made by a Paediatrician or a Cardiologist or a Speech and Language Therapist who may be concerned about a child’s development. Though I have met many individuals with the syndrome who were missed in childhood and not diagnosed until adulthood, and it’s very likely that there are many individuals in the population who go undiagnosed their whole lives. That is because the clinical presentation is very variable, so some individuals may have subtle symptoms, and then never get that referral.

[00:07:21.340] Jo Carlowe: What would be the typical presentations then?

[00:07:23.950] Dr. Sam Chawner: In early childhood, often signs could be a cardiac abnormality, so there could be congenital heart issues, immune system problems, there can be cleft palate issues, and then there can also be delay in speech development and other developmental delays. But the pattern of symptoms is different for every individual, and over 180 symptoms have been linked to the condition. So, it’s very complex and variable, and then it changes across the life course as well.

[00:07:56.840] Jo Carlowe: And there appears to be an association with psychiatric risk linked?

[00:08:00.229] Dr. Sam Chawner: Yeah, so early studies found that one in four adults with 22q deletion syndrome developed schizophrenia, and since then, the condition has also been linked to ADHD, autism and anxiety. And, also, for many years, we’ve known the condition is linked to intellectual disability, but the degree of intellectual impairment, again, is very variable. IQ can range from 50 up to 130, in individuals. But on average, the IQ’s around 30 IQ points below the general population.

Interestingly, more recent population studies, although they find 22q deletion syndrome still is a strong risk factor for psychiatric outcomes, the magnitude of risk is lower than some of the more historical, clinical studies. And this is, kind of, a new area and over time we’ll get improved estimates of psychiatric risk, by, sort of, using these different methodologies. But, nonetheless, 22q deletion syndrome still remains one of the strongest risk factors we know.

[00:09:06.570] Jo Carlowe: Staying with your paper, Sam, can you give us a more general overview of what you looked at, and why?

[00:09:12.390] Dr. Sam Chawner: Yeah, so the paper focuses on characterising the behaviour of two to five-year-olds with 22q1.2 deletion syndrome. And for families with a child with this condition, there’s very little information out there on this developmental period, most of the research is focused on older children. So, there’s, kind of, a real need to document this to provide information for families and Clinicians. But, also, as the condition is often diagnosed in the first few years of life, and this provided, sort of, a rare research opportunity to investigate how genetic risk for psychiatric outcomes influences early child’s development.

[00:09:55.610] Jo Carlowe: And can you tell us a little about the methodology that you used for this study?

[00:10:00.620] Dr. Sam Chawner: In terms of designing the assessments we did with the young children with 22q deletion syndrome, we used the Research Domain Criteria framework, which moves away from our traditional, categorical psychiatric diagnostic approaches, and focuses on dimensional approaches to capturing behaviour. And this is particularly important when assessing young children. At this age, it’s often many years before psychiatric problems typically onset, so traditional psychiatric measures for older children would not work. But, also, we had to make assessments fun and accessible to children with varying communication needs.

So, we examined sleep functioning, cognition, motor, reward valuation, and social processes, and these were, sort of, some of the main domains within the Research Domain Criteria framework. And then within these, we looked at, sort of, various subdomains. But for the cognitive assessments, we had to keep them quite playful, and we used approaches that were very interactive with the child, and it wasn’t a formal testing environment.

[00:11:05.881] Jo Carlowe: And what about the findings? What key findings from the paper would you like to highlight?

[00:11:11.350] Dr. Sam Chawner: I think the main finding was, although these children were very young, at age two to five, and it’s, you know, many years before psychiatric problems may develop later in life, they’re already experiencing a wide range of difficulties across all the developmental domains we looked at. And we compared this to sibling controls, so individuals within the same family who were age two to five, who didn’t have the genetic condition. And they were already scoring high on some of the liability measures for neurodevelopmental and psychiatric traits, using some of the questionnaires we included.

Another important finding was that we did cluster analysis, and this revealed a subgroup of children with 22q deletion syndrome, who – neurodevelopmental and psychiatric liability was particularly increased, and they were starting to diverge from other children with 22q deletion syndrome and the controls. So, at this early age, we could potentially identify this, sort of, high risk subgroup. And then finally, early motor and sleep impairment seemed to index those children who were showing greater liability for neurodevelopmental and psychiatric outcomes.

[00:12:28.660] Jo Carlowe: So, what are the implications of this for…

[00:12:32.380] Dr. Sam Chawner: Hmmm.

[00:12:33.380] Jo Carlowe: …Clinicians and CAMH professionals?

[00:12:34.760] Dr. Sam Chawner: The work highlights that genetic risk for psychiatric outcomes manifests very early, and, to me, this really indicates that interventions are likely to be needed very early on in development. For example, currently, early intervention for psychosis focuses on late adolescence, when teenagers may first start experiencing psychotic symptoms, but this could already be actually a late stage to intervene. And I guess these findings support the increased awareness of the role of CAMHS in providing early years support, you know, services for supporting children below age five are growing rapidly. And if support can be provided early, this could have lifelong effects on development, and possibly prevent symptom onset of later mental health conditions.

[00:13:25.790] Jo Carlowe: But do you think there are adequate interventions actually targeted at such a young age group?

[00:13:31.519] Dr. Sam Chawner: This is a really difficult area, that, at the moment, I don’t think we could develop an intervention, say, for the early years that’s focusing on, you know, a specific psychiatric condition such as, say, psychosis later in development. And then, also, it would be very difficult, at the moment, to identify who’s at risk, and then would that even be ethical? There’s so many important questions and dilemmas.

But I think the idea of services that are promoting wellbeing in development in early years, that is going to have a general lifelong effect. But I think with increased research, we may understand which groups in society may benefit more from this support, and then we also may understand, you know, if there’s different groups which are at risk for different outcomes, can we tailor early intervention support?

[00:14:23.070] Jo Carlowe: Given that, from your findings, Sam, what recommendations do you have, in terms of prevention, detection, and the targeting of interventions for children at high genomic risk of neuropsychiatric conditions?

[00:14:37.880] Dr. Sam Chawner: Yeah, I think it’s really important when we’re talking about genetics and prevention and intervention to recognise there are lots of important ethical issues this raises. And we have to be very careful, when making clinical recommendations, you know, it could be very stigmatising for a young child to have the label of “being at psychiatric risk,” when indeed, many won’t develop psychiatric problems, even though they are at increased risk. At the same time, if we know a child has a certain genetic diagnosis, this does provide an opportunity to implement early monitoring and support, that you could argue it would be unethical not to provide that, knowing that we know these conditions are risk factors.

I currently work with Psychiatrists from the Cardiff and London 22q deletion syndrome clinics. In their services they provide advice to parents about the psychiatric presentation that can be associated with 22q deletion syndrome, and then they may offer screening or monitoring of psychiatric problems in early adolescence. So, I think this is one example of how increased links between psychiatric and genetic services can lead to more personalised approaches to medicine.

And regarding thinking about how to, sort of, tackle these, sort of, ethical issues in the future, I think genetic counselling will become increasingly important in this area. And Cardiff is trialling an innovative new service that brings together Genetic Counselling Experts from the All Wales Medical Genomics Service with child and adult psychiatric expertise.

[00:16:19.190] Jo Carlowe: Is there anything else in the paper that you would like to highlight?

[00:16:22.649] Dr. Sam Chawner: I guess I’d like to thank all the children and families who took part, and their generosity and time. It, you know, involved them coming to Cardiff for the day and doing all sorts of unusual test with us. But, you know, it was great to meet the families, and I think the children also enjoyed the day, and we did things like a teddy bears’ picnic, as well as some of the more, sort of, language and shape-based test assessments.

I’d also like to thank the charity Max Appeal, who provide support to families affected by 22q1.2 deletion syndrome. They very much helped putting us in touch with families, but they also provide a great service and support to families who have received a diagnosis, but then also in later years, when families may be struggling with different issues. And a special moment of this research was when the BBC Breakfast crew visited the department, and together with Max Appeal, we were able to highlight this research project for 22q11.2 Awareness Day.

[00:17:30.000] Jo Carlowe: Are you planning any follow-up research, or is there anything else in the pipeline that you’d like to share with us?

[00:17:35.980] Dr. Sam Chawner: I guess, funding permitting, this work needs replicating on a larger scale and across different countries. And we’ve seen this happen for studies of 22q deletion syndrome at later developmental stages, so in, sort of, late childhood and adolescence. But, also, I’m starting to work with large-scale population cohorts, including those from Scandinavia, where it’s possible to link genetics and early life health and behaviour data, so we can look at the impact of genetics on early child development at a population scale.

[00:18:11.830] Jo Carlowe: Great, well, sounds exciting. And, finally, Sam, what is your take home message for our listeners?

[00:18:17.370] Dr. Sam Chawner: I guess we often think the impact of genetics on clinical practice in CAMHS is many years in the future. I’d argue for the families I see through my research, genetics is already changing lives, and 22q deletion syndrome is an example where families are in high clinical need and the diagnosis could lead to tailored support and early intervention for mental health problems. However, the current reality for many families with this condition is that they struggle to access support, despite their children being at high risk, and there’s low awareness of the condition in the UK. But I hope the development of multidisciplinary services for 22q deletion syndrome, and greater integration between Genetics and Psychiatry, is starting to change that.

[00:19:06.460] Jo Carlowe: Brilliant, Sam, thank you ever so much. For more details on Dr. Sam Chawner, please visit the ACAMH website,, and Twitter @acamh. ACAMH is spelt A-C-A-M-H, and don’t forget to follow us on your preferred streaming platform, let us know if you enjoy the podcast, with a rating or review, and do share with friends and colleagues.

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