Early-Life Injuries and the Development of Attention-Deficit/Hyperactivity Disorder

Theresa Wimberley; Isabell Brikell; Emil M. Pedersen; Esben Agerbo; Bjarni J. Vilhjálmsson; Clara Albiñana; Florian Privé; Anita Thapar; Kate Langley; Lucy Riglin; Marianne Simonsen; Helena S. Nielsen; Anders D. Børglum; Merete Nordentoft; Preben B. Mortensen; Søren Dalsgaard

doi:10.4088/JCP.21m14033

Early-Life Injuries and the Development of Attention-Deficit/Hyperactivity Disorder

Theresa Wimberley^*, Isabell Brikell, Emil M. Pedersen, Esben Agerbo, Bjarni J. Vilhjálmsson, Clara Albiñana, Florian Privé, Anita Thapar, Kate Langley, Lucy Riglin, Marianne Simonsen, Helena S. Nielsen, Anders D. Børglum, Merete Nordentoft, Preben B. Mortensen, Søren Dalsgaard

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

1 Citationer (Scopus)

Abstract

Objective: To estimate phenotypic and familial association between early-life injuries and attention-deficit/hyperactivity disorder (ADHD) and the genetic contribution to the association using polygenic risk score for ADHD (PRS-ADHD) and genetic correlation analyses. Methods: Children born in Denmark between 1995–2010 (n = 786,543) were followed from age 5 years until a median age of 14 years (interquartile range: 10–18 years). Using ICD-10 diagnoses, we estimated hazard ratios (HRs) and absolute risks of ADHD by number of hospital/emergency ward–treated injuries by age 5. In a subset of ADHD cases and controls born 1995 to 2005 who had genetic data available (n = 16,580), we estimated incidence rate ratios (IRRs) for the association between PRS-ADHD and number of injuries before age 5 and the genetic correlation between ADHD and any injury before age 5. Results: Injuries were associated with ADHD (HR = 1.61; 95% CI, 1.55–1.66) in males (HR = 1.59; 1.53–1.65) and females (HR = 1.65; 1.54–1.77), with a dose-response relationship with number of injuries. The absolute ADHD risk by age 15 was 8.4% (3+ injuries) vs 3.1% (no injuries). ADHD was also associated with injuries in relatives, with a stronger association in first- than second-degree relatives. PRS-ADHD was marginally associated with the number of injuries in the general population (IRR = 1.06; 1.00–1.14), with a genetic correlation of 0.53 (0.21–0.85). Conclusions: Early-life injuries in individuals and their relatives were associated with a diagnosis of ADHD. However, even in children with the most injuries, more than 90% were not diagnosed with ADHD by age 15. Despite a low positive predictive value and that the impact of unmeasured factors such as parental behavior remains unclear, results indicate that the association is partly explained by genetics, suggesting that early-life injuries may represent or herald early behavioral manifestations of ADHD.

Originalsprog	Engelsk
Artikelnummer	21m14033
Tidsskrift	Journal of Clinical Psychiatry
Vol/bind	83
Udgave nummer	1
Antal sider	19
ISSN	0160-6689
DOI	https://doi.org/10.4088/JCP.21m14033
Status	Udgivet - 2022

Bibliografisk note

Funding Information:
Submitted: April 9, 2021; accepted September 7, 2021. Published online: January 4, 2022. Potential conflicts of interest: None. Funding/support: This study was funded by grants from Novo Nordisk Foundation (NNF16OC0022018), the Lundbeck Foundation (iPSYCH grant R248-2017-2003), and the Stanley Medical Research Institute and supported by CIRRAU. Dr Dalsgaard’s research is further supported by grants from National Institutes of Health (R01, grant ES026993), the European Commission (Horizon 2020, grant 667302), Helsefonden (grant 19-8-0260), and the European Union’s Horizon 2020 research and innovation programme under grant agreement 847879. The Wellcome Trust provided additional funding for Drs Riglin and Thapar (204895/Z/16/Z). Data handling and analysis on the GenomeDK HPC facility were supported by National Institute of Mental Health (1U01MH109514-01 to Dr Børglum) and Center for Genomics and Personalized Medicine (grant to Dr Børglum). Dr Børglum’s research was further supported by the European Community Horizon 2020 Programme (grant 667302). Role of the sponsor: The supporting sources had no role in the design, conduct, and reporting of the study. Supplementary material: Available at PSYCHIATRIST.COM

Publisher Copyright:
© Copyright 2022 Physicians Postgraduate Press, Inc.

Adgang til dokumentet

10.4088/JCP.21m14033

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7612325/pdf/EMS140872.pdfLicens: CC BY

Citationsformater

Wimberley, T., Brikell, I., Pedersen, E. M., Agerbo, E., Vilhjálmsson, B. J., Albiñana, C., Privé, F., Thapar, A., Langley, K., Riglin, L., Simonsen, M., Nielsen, H. S., Børglum, A. D., Nordentoft, M., Mortensen, P. B., & Dalsgaard, S. (2022). Early-Life Injuries and the Development of Attention-Deficit/Hyperactivity Disorder. Journal of Clinical Psychiatry, 83(1), [21m14033]. https://doi.org/10.4088/JCP.21m14033

Early-Life Injuries and the Development of Attention-Deficit/Hyperactivity Disorder. / Wimberley, Theresa; Brikell, Isabell; Pedersen, Emil M.; Agerbo, Esben; Vilhjálmsson, Bjarni J.; Albiñana, Clara; Privé, Florian; Thapar, Anita; Langley, Kate; Riglin, Lucy; Simonsen, Marianne; Nielsen, Helena S.; Børglum, Anders D.; Nordentoft, Merete; Mortensen, Preben B.; Dalsgaard, Søren.

I: Journal of Clinical Psychiatry, Bind 83, Nr. 1, 21m14033, 2022.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Wimberley, T, Brikell, I, Pedersen, EM, Agerbo, E, Vilhjálmsson, BJ, Albiñana, C, Privé, F, Thapar, A, Langley, K, Riglin, L, Simonsen, M, Nielsen, HS, Børglum, AD, Nordentoft, M, Mortensen, PB & Dalsgaard, S 2022, 'Early-Life Injuries and the Development of Attention-Deficit/Hyperactivity Disorder', Journal of Clinical Psychiatry, bind 83, nr. 1, 21m14033. https://doi.org/10.4088/JCP.21m14033

Wimberley, Theresa ; Brikell, Isabell ; Pedersen, Emil M. ; Agerbo, Esben ; Vilhjálmsson, Bjarni J. ; Albiñana, Clara ; Privé, Florian ; Thapar, Anita ; Langley, Kate ; Riglin, Lucy ; Simonsen, Marianne ; Nielsen, Helena S. ; Børglum, Anders D. ; Nordentoft, Merete ; Mortensen, Preben B. ; Dalsgaard, Søren. / Early-Life Injuries and the Development of Attention-Deficit/Hyperactivity Disorder. I: Journal of Clinical Psychiatry. 2022 ; Bind 83, Nr. 1.

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abstract = "Objective: To estimate phenotypic and familial association between early-life injuries and attention-deficit/hyperactivity disorder (ADHD) and the genetic contribution to the association using polygenic risk score for ADHD (PRS-ADHD) and genetic correlation analyses. Methods: Children born in Denmark between 1995–2010 (n = 786,543) were followed from age 5 years until a median age of 14 years (interquartile range: 10–18 years). Using ICD-10 diagnoses, we estimated hazard ratios (HRs) and absolute risks of ADHD by number of hospital/emergency ward–treated injuries by age 5. In a subset of ADHD cases and controls born 1995 to 2005 who had genetic data available (n = 16,580), we estimated incidence rate ratios (IRRs) for the association between PRS-ADHD and number of injuries before age 5 and the genetic correlation between ADHD and any injury before age 5. Results: Injuries were associated with ADHD (HR = 1.61; 95% CI, 1.55–1.66) in males (HR = 1.59; 1.53–1.65) and females (HR = 1.65; 1.54–1.77), with a dose-response relationship with number of injuries. The absolute ADHD risk by age 15 was 8.4% (3+ injuries) vs 3.1% (no injuries). ADHD was also associated with injuries in relatives, with a stronger association in first- than second-degree relatives. PRS-ADHD was marginally associated with the number of injuries in the general population (IRR = 1.06; 1.00–1.14), with a genetic correlation of 0.53 (0.21–0.85). Conclusions: Early-life injuries in individuals and their relatives were associated with a diagnosis of ADHD. However, even in children with the most injuries, more than 90% were not diagnosed with ADHD by age 15. Despite a low positive predictive value and that the impact of unmeasured factors such as parental behavior remains unclear, results indicate that the association is partly explained by genetics, suggesting that early-life injuries may represent or herald early behavioral manifestations of ADHD.",

author = "Theresa Wimberley and Isabell Brikell and Pedersen, {Emil M.} and Esben Agerbo and Vilhj{\'a}lmsson, {Bjarni J.} and Clara Albi{\~n}ana and Florian Priv{\'e} and Anita Thapar and Kate Langley and Lucy Riglin and Marianne Simonsen and Nielsen, {Helena S.} and B{\o}rglum, {Anders D.} and Merete Nordentoft and Mortensen, {Preben B.} and S{\o}ren Dalsgaard",

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T1 - Early-Life Injuries and the Development of Attention-Deficit/Hyperactivity Disorder

AU - Wimberley, Theresa

AU - Brikell, Isabell

AU - Pedersen, Emil M.

AU - Agerbo, Esben

AU - Vilhjálmsson, Bjarni J.

AU - Albiñana, Clara

AU - Privé, Florian

AU - Thapar, Anita

AU - Langley, Kate

AU - Riglin, Lucy

AU - Simonsen, Marianne

AU - Nielsen, Helena S.

AU - Børglum, Anders D.

AU - Nordentoft, Merete

AU - Mortensen, Preben B.

AU - Dalsgaard, Søren

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Y1 - 2022

N2 - Objective: To estimate phenotypic and familial association between early-life injuries and attention-deficit/hyperactivity disorder (ADHD) and the genetic contribution to the association using polygenic risk score for ADHD (PRS-ADHD) and genetic correlation analyses. Methods: Children born in Denmark between 1995–2010 (n = 786,543) were followed from age 5 years until a median age of 14 years (interquartile range: 10–18 years). Using ICD-10 diagnoses, we estimated hazard ratios (HRs) and absolute risks of ADHD by number of hospital/emergency ward–treated injuries by age 5. In a subset of ADHD cases and controls born 1995 to 2005 who had genetic data available (n = 16,580), we estimated incidence rate ratios (IRRs) for the association between PRS-ADHD and number of injuries before age 5 and the genetic correlation between ADHD and any injury before age 5. Results: Injuries were associated with ADHD (HR = 1.61; 95% CI, 1.55–1.66) in males (HR = 1.59; 1.53–1.65) and females (HR = 1.65; 1.54–1.77), with a dose-response relationship with number of injuries. The absolute ADHD risk by age 15 was 8.4% (3+ injuries) vs 3.1% (no injuries). ADHD was also associated with injuries in relatives, with a stronger association in first- than second-degree relatives. PRS-ADHD was marginally associated with the number of injuries in the general population (IRR = 1.06; 1.00–1.14), with a genetic correlation of 0.53 (0.21–0.85). Conclusions: Early-life injuries in individuals and their relatives were associated with a diagnosis of ADHD. However, even in children with the most injuries, more than 90% were not diagnosed with ADHD by age 15. Despite a low positive predictive value and that the impact of unmeasured factors such as parental behavior remains unclear, results indicate that the association is partly explained by genetics, suggesting that early-life injuries may represent or herald early behavioral manifestations of ADHD.

AB - Objective: To estimate phenotypic and familial association between early-life injuries and attention-deficit/hyperactivity disorder (ADHD) and the genetic contribution to the association using polygenic risk score for ADHD (PRS-ADHD) and genetic correlation analyses. Methods: Children born in Denmark between 1995–2010 (n = 786,543) were followed from age 5 years until a median age of 14 years (interquartile range: 10–18 years). Using ICD-10 diagnoses, we estimated hazard ratios (HRs) and absolute risks of ADHD by number of hospital/emergency ward–treated injuries by age 5. In a subset of ADHD cases and controls born 1995 to 2005 who had genetic data available (n = 16,580), we estimated incidence rate ratios (IRRs) for the association between PRS-ADHD and number of injuries before age 5 and the genetic correlation between ADHD and any injury before age 5. Results: Injuries were associated with ADHD (HR = 1.61; 95% CI, 1.55–1.66) in males (HR = 1.59; 1.53–1.65) and females (HR = 1.65; 1.54–1.77), with a dose-response relationship with number of injuries. The absolute ADHD risk by age 15 was 8.4% (3+ injuries) vs 3.1% (no injuries). ADHD was also associated with injuries in relatives, with a stronger association in first- than second-degree relatives. PRS-ADHD was marginally associated with the number of injuries in the general population (IRR = 1.06; 1.00–1.14), with a genetic correlation of 0.53 (0.21–0.85). Conclusions: Early-life injuries in individuals and their relatives were associated with a diagnosis of ADHD. However, even in children with the most injuries, more than 90% were not diagnosed with ADHD by age 15. Despite a low positive predictive value and that the impact of unmeasured factors such as parental behavior remains unclear, results indicate that the association is partly explained by genetics, suggesting that early-life injuries may represent or herald early behavioral manifestations of ADHD.

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DO - 10.4088/JCP.21m14033

M3 - Journal article

C2 - 34985833

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