TY - JOUR
T1 - Neuropsychiatric risk in children with intellectual disability of genetic origin
T2 - IMAGINE, a UK national cohort study
AU - Wolstencroft, Jeanne
AU - Wicks, Francesca
AU - Srinivasan, Ramya
AU - Wynn, Sarah
AU - Ford, Tamsin
AU - Baker, Kate
AU - Chawner, Samuel J.R.A.
AU - Hall, Jeremy
AU - van den Bree, Marianne B.M.
AU - Owen, Michael J.
AU - Erwood, Marie
AU - Lafont, Amy
AU - Timur, Husne
AU - Ye, Zheng
AU - Walker, Neil
AU - Wallwork, Sarah
AU - Skuse, David
AU - Denaxas, Spiros
AU - Mandy, William
AU - Davies, Sarah
AU - Juj, Manoj
AU - Kerry, Eleanor
AU - Lucock, Anna
AU - Printzlau, Frida
AU - Walker, Susan
AU - Watkins, Alice
AU - Coscini, Nadia
AU - Fatih, Nasrtullah
AU - Lahiri, Nayana
AU - Denyer, Hayley
AU - Andrews, Sophie
AU - Cuthbert, Andrew
AU - Challenger, Aimee
AU - Lewis, Nicola
AU - Ray, Sinead
AU - Sopp, Matthew
AU - Moss, Hayley
AU - Holmans, Peter
AU - Bowen, Samantha
AU - Bradley, Karen
AU - Birch, Philippa
AU - Tong, Molly
AU - Searle, Beverley
AU - Robertson, Lisa
AU - Berg, Jonathan
AU - Lampe, Anne
AU - Joss, Shelagh
AU - Brennan, Paul
AU - Kraus, Alison
AU - Weber, Astrid
AU - Rawson, Myfanwy
AU - Quarrell, Oliver
AU - Vasudevan, Pradeep
AU - Harrison, Rachel
AU - Williams, Denise
AU - Maher, Eamonn R.
AU - Kini, Usha
AU - Clowes, Virginia E.
AU - Van Dijk, Fleur
AU - Gurasashvilli , Jana
AU - Mansour, Sahar
AU - Holder-Espinasse, Muriel
AU - Watford , Amy
AU - Rankin, Julia
AU - Baralle, Diana
AU - Procter, Annie
AU - Dewhurst, Eleanor
AU - Raymond, F Lucy
N1 - Publisher Copyright:
© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
PY - 2022/9
Y1 - 2022/9
N2 - Background: Children with intellectual disability frequently have multiple co-morbid neuropsychiatric conditions and poor physical health. Genomic testing is increasingly recommended as a first-line investigation for these children. We aim to determine the effect of genomics, inheritance, and socioeconomic deprivation on neuropsychiatric risk in children with intellectual disability of genetic origin as compared with the general population. Methods: IMAGINE is a prospective cohort study using online mental health and medical assessments in a cohort of 3407 UK participants with intellectual disability and pathogenic genomic variants as identified by the UK's National Health Service (NHS). Our study is on a subset of these participants, including all children aged 4–19 years. We collected diagnostic genomic reports from NHS records and asked primary caregivers to provide an assessment of their child using the Development and Well-Being Assessment (DAWBA), the Strengths and Difficulties Questionnaire (SDQ), the Adaptive Behaviour Assessment System 3 (ABAS-3), and a medical history questionnaire. Each child was assigned a rank based on their postcode using the index of multiple deprivation (IMD). We compared the IMAGINE cohort with the 2017 National Survey of Children's Mental Health in England. The main outcomes of interest were mental health and neurodevelopment according to the DAWBA and SDQ. Findings: We recruited 2770 children from the IMAGINE study between Oct 1, 2014 and June 30, 2019, of whom 2397 (86·5%) had a basic assessment of their mental health completed by their families and 1277 (46·1%) completed a medical history questionnaire. The mean age of participants was 9·2 years (SD 3·9); 1339 (55·9%) were boys and 1058 (44·1%) were girls. 355 (27·8%) of 1277 reported a seizure disorder and 814 (63·7%) reported movement or co-ordination problems. 1771 (73·9%) of 2397 participants had a pathogenic copy number variant (CNV) and 626 (26·1%) had a pathogenic single nucleotide variant (SNV). Participants were representative of the socioeconomic spectrum of the UK general population. The relative risk (RR) of co-occurring neuropsychiatric diagnoses, compared with the English national population, was high: autism spectrum disorder RR 29·2 (95% CI 23·9–36·5), ADHD RR 13·5 (95% CI 11·1–16·3). In children with a CNV, those with a familial variant tended to live in more socioeconomically deprived areas than those with a de novo variant. Both inheritance and socioeconomic deprivation contributed to neuropsychiatric risk in those with a CNV.Interpretation: Children with genomic variants and intellectual disability are at an increased risk of neuropsychiatric difficulties. CNV variant inheritance and socioeconomic deprivation also contribute to the risk. Early genomic investigations of children with intellectual disability could facilitate the identification of the most vulnerable children. Additionally, harnessing parental expertise using online DAWBA assessments could rapidly identify children with exceptional needs to child mental health services. Funding: UK Medical Research Council and Medical Research Foundation.
AB - Background: Children with intellectual disability frequently have multiple co-morbid neuropsychiatric conditions and poor physical health. Genomic testing is increasingly recommended as a first-line investigation for these children. We aim to determine the effect of genomics, inheritance, and socioeconomic deprivation on neuropsychiatric risk in children with intellectual disability of genetic origin as compared with the general population. Methods: IMAGINE is a prospective cohort study using online mental health and medical assessments in a cohort of 3407 UK participants with intellectual disability and pathogenic genomic variants as identified by the UK's National Health Service (NHS). Our study is on a subset of these participants, including all children aged 4–19 years. We collected diagnostic genomic reports from NHS records and asked primary caregivers to provide an assessment of their child using the Development and Well-Being Assessment (DAWBA), the Strengths and Difficulties Questionnaire (SDQ), the Adaptive Behaviour Assessment System 3 (ABAS-3), and a medical history questionnaire. Each child was assigned a rank based on their postcode using the index of multiple deprivation (IMD). We compared the IMAGINE cohort with the 2017 National Survey of Children's Mental Health in England. The main outcomes of interest were mental health and neurodevelopment according to the DAWBA and SDQ. Findings: We recruited 2770 children from the IMAGINE study between Oct 1, 2014 and June 30, 2019, of whom 2397 (86·5%) had a basic assessment of their mental health completed by their families and 1277 (46·1%) completed a medical history questionnaire. The mean age of participants was 9·2 years (SD 3·9); 1339 (55·9%) were boys and 1058 (44·1%) were girls. 355 (27·8%) of 1277 reported a seizure disorder and 814 (63·7%) reported movement or co-ordination problems. 1771 (73·9%) of 2397 participants had a pathogenic copy number variant (CNV) and 626 (26·1%) had a pathogenic single nucleotide variant (SNV). Participants were representative of the socioeconomic spectrum of the UK general population. The relative risk (RR) of co-occurring neuropsychiatric diagnoses, compared with the English national population, was high: autism spectrum disorder RR 29·2 (95% CI 23·9–36·5), ADHD RR 13·5 (95% CI 11·1–16·3). In children with a CNV, those with a familial variant tended to live in more socioeconomically deprived areas than those with a de novo variant. Both inheritance and socioeconomic deprivation contributed to neuropsychiatric risk in those with a CNV.Interpretation: Children with genomic variants and intellectual disability are at an increased risk of neuropsychiatric difficulties. CNV variant inheritance and socioeconomic deprivation also contribute to the risk. Early genomic investigations of children with intellectual disability could facilitate the identification of the most vulnerable children. Additionally, harnessing parental expertise using online DAWBA assessments could rapidly identify children with exceptional needs to child mental health services. Funding: UK Medical Research Council and Medical Research Foundation.
UR - http://www.scopus.com/inward/record.url?scp=85135928260&partnerID=8YFLogxK
U2 - 10.1016/S2215-0366(22)00207-3
DO - 10.1016/S2215-0366(22)00207-3
M3 - Article
C2 - 35932790
AN - SCOPUS:85135928260
SN - 2215-0366
VL - 9
SP - 715
EP - 724
JO - The Lancet Psychiatry
JF - The Lancet Psychiatry
IS - 9
ER -