Neurocognitive markers of late-onset ADHD: a 6-year longitudinal study

Shahrzad Ilbegi; Jan K. Buitelaar; Pieter J. Hoekstra; Catharina A. Hartman; Barbara Franke; Stephen V. Faraone; Jaap Oosterlaan; Marjolein Luman; Marloes van Lieshout; Nanda N.J. Rommelse

doi:10.1111/jcpp.13272

Neurocognitive markers of late-onset ADHD: a 6-year longitudinal study

Shahrzad Ilbegi^*
, Jan K. Buitelaar
, Pieter J. Hoekstra
, Catharina A. Hartman
, Barbara Franke
, Stephen V. Faraone
, Jaap Oosterlaan
, Marjolein Luman
, Marloes van Lieshout
, Nanda N.J. Rommelse

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

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Abstract

Background: There is an increased interest in ‘late-onset’ attention-deficit/hyperactivity disorder (ADHD), referring to the onset of clinically significant ADHD symptoms after the age of 12 years. This study aimed to examine whether unaffected siblings with late-onset ADHD could be differentiated from stable unaffected siblings by their neurocognitive functioning in childhood. Methods: We report findings from a 6-year prospective, longitudinal study of the Dutch part of the International Multicenter ADHD Genetics (IMAGE) study, including individuals with childhood-onset (persistent) ADHD (n = 193), their siblings with late-onset ADHD (n = 34), their stable unaffected siblings (n = 111) and healthy controls (n = 186). At study entry (mean age: 11.3) and follow-up (mean age: 17.01), participants were assessed for ADHD by structured psychiatric interviews and multi-informant questionnaires. Several neurocognitive functions were assessed at baseline and after 6 years, including time reproduction, timing variability (reaction time variability and time production variability), reaction time speed, motor control and working memory; intelligence was taken as a measure of overall neurocognitive functioning. Results: Siblings with late-onset ADHD were similar to individuals with childhood-onset ADHD in showing longer reaction times and/or higher error rates on all neurocognitive measures at baseline and follow-up, when compared to healthy controls. They differed from stable unaffected siblings (who were similar to healthy controls) by greater reaction time variability and timing production variability at baseline. No significant group by time interaction was found for any of the tasks. Conclusions: For unaffected siblings of individuals with ADHD, reaction time variability and timing production variability may serve as neurocognitive marker for late-onset ADHD.

Original language	English
Pages (from-to)	244-252
Number of pages	9
Journal	Journal of Child Psychology and Psychiatry and Allied Disciplines
Volume	62
Issue number	2
Early online date	12 Jul 2020
DOIs	https://doi.org/10.1111/jcpp.13272
Publication status	Published - Feb 2021

Bibliographical note

Publisher Copyright:
© 2020 Association for Child and Adolescent Mental Health

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Funding

This work was supported by National Institute of Health (NIH) Grant R01MH62873, the Netherlands Organization for Scientific Research (NWO) Large Investment Grant 1750102007010, ZonMW Grant 60‐60600‐97‐193 and grants from Radboud University Medical Center, University Medical Center Groningen and Accare, and VU University Amsterdam. B.F. is supported by a Vici grant (016.130.669) from NWO, and she and J.K.B. received funding from the European Commission Framework 7 Program under grant number 602450 (IMAGEMEND). This work was supported by National Institute of Health (NIH) Grant R01MH62873, the Netherlands Organization for Scientific Research (NWO) Large Investment Grant 1750102007010, ZonMW Grant 60-60600-97-193 and grants from Radboud University Medical Center, University Medical Center Groningen and Accare, and VU University Amsterdam. B.F. is supported by a Vici grant (016.130.669) from NWO, and she and J.K.B. received funding from the European Commission Framework 7 Program under grant number 602450 (IMAGEMEND). All participants gave informed consent, and the study was approved by ethical committees of University Medical Centre Utrecht and Arnhem-Nijmegen. Reference numbers are as follows: 97/268, 2008/163 and 2012/542. The authors thank all the families and teachers who took part in this study and all students for their assistance in data collection. This study was presented as an oral presentation at the 7th World Congress on ADHD, Lisbon, Portugal, 27 April 2019. J.K.B. has been in the past 3?years a consultant to / member of advisory board of / and/or speaker for Janssen Cilag BV, Eli Lilly, Lundbeck, Shire, Roche, Medice, Novartis and Servier. He has received research support from Roche and Vifor. J.K.B. has been in the past 3 years a consultant to / member of advisory board of / and/or speaker for Janssen Cilag BV, Eli Lilly, Lundbeck, Shire, Roche, Medice, Novartis and Servier. He has received research support from Roche and Vifor. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents and royalties. P.J.H. has been paid member of an advisory board of Takeda. B.F.’s work is supported by a personal Vici grant from the Netherlands Organization for Scientific Research (NWO; grant 016‐130‐669). The remaining authors have declared that they have no competing or potential conflicts of interests. Key points

Funders	Funder number
National Institutes of Health
European Commission
Vifor
Vrije Universiteit Amsterdam
University Medical Centre Utrecht
Roche
Seventh Framework Programme	602450
Arnhem-Nijmegen	97/268, 2012/542, 2008/163
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	1750102007010, 016.130.669
National Institute of Mental Health	R01MH062873
ZonMw	60‐60600‐97‐193

Keywords

Late-onset ADHD
neurocognitive markers
unaffected siblings

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10.1111/jcpp.13272

Child Psychology Psychiatry - 2020 - Ilbegi - Neurocognitive markers of late‐onset ADHD a 6‐year longitudinal studyFinal published version, 278 KBLicence: Article 25fa Dutch Copyright Act

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Cite this

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title = "Neurocognitive markers of late-onset ADHD: a 6-year longitudinal study",

abstract = "Background: There is an increased interest in {\textquoteleft}late-onset{\textquoteright} attention-deficit/hyperactivity disorder (ADHD), referring to the onset of clinically significant ADHD symptoms after the age of 12 years. This study aimed to examine whether unaffected siblings with late-onset ADHD could be differentiated from stable unaffected siblings by their neurocognitive functioning in childhood. Methods: We report findings from a 6-year prospective, longitudinal study of the Dutch part of the International Multicenter ADHD Genetics (IMAGE) study, including individuals with childhood-onset (persistent) ADHD (n = 193), their siblings with late-onset ADHD (n = 34), their stable unaffected siblings (n = 111) and healthy controls (n = 186). At study entry (mean age: 11.3) and follow-up (mean age: 17.01), participants were assessed for ADHD by structured psychiatric interviews and multi-informant questionnaires. Several neurocognitive functions were assessed at baseline and after 6 years, including time reproduction, timing variability (reaction time variability and time production variability), reaction time speed, motor control and working memory; intelligence was taken as a measure of overall neurocognitive functioning. Results: Siblings with late-onset ADHD were similar to individuals with childhood-onset ADHD in showing longer reaction times and/or higher error rates on all neurocognitive measures at baseline and follow-up, when compared to healthy controls. They differed from stable unaffected siblings (who were similar to healthy controls) by greater reaction time variability and timing production variability at baseline. No significant group by time interaction was found for any of the tasks. Conclusions: For unaffected siblings of individuals with ADHD, reaction time variability and timing production variability may serve as neurocognitive marker for late-onset ADHD.",

keywords = "Late-onset ADHD, neurocognitive markers, unaffected siblings",

author = "Shahrzad Ilbegi and Buitelaar, \{Jan K.\} and Hoekstra, \{Pieter J.\} and Hartman, \{Catharina A.\} and Barbara Franke and Faraone, \{Stephen V.\} and Jaap Oosterlaan and Marjolein Luman and \{van Lieshout\}, Marloes and Rommelse, \{Nanda N.J.\}",

year = "2021",

month = feb,

doi = "10.1111/jcpp.13272",

language = "English",

volume = "62",

pages = "244--252",

journal = "Journal of Child Psychology and Psychiatry and Allied Disciplines",

issn = "0021-9630",

publisher = "Wiley-Blackwell Publishing Ltd",

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TY - JOUR

T1 - Neurocognitive markers of late-onset ADHD

T2 - a 6-year longitudinal study

AU - Ilbegi, Shahrzad

AU - Buitelaar, Jan K.

AU - Hoekstra, Pieter J.

AU - Hartman, Catharina A.

AU - Franke, Barbara

AU - Faraone, Stephen V.

AU - Oosterlaan, Jaap

AU - Luman, Marjolein

AU - van Lieshout, Marloes

AU - Rommelse, Nanda N.J.

PY - 2021/2

Y1 - 2021/2

N2 - Background: There is an increased interest in ‘late-onset’ attention-deficit/hyperactivity disorder (ADHD), referring to the onset of clinically significant ADHD symptoms after the age of 12 years. This study aimed to examine whether unaffected siblings with late-onset ADHD could be differentiated from stable unaffected siblings by their neurocognitive functioning in childhood. Methods: We report findings from a 6-year prospective, longitudinal study of the Dutch part of the International Multicenter ADHD Genetics (IMAGE) study, including individuals with childhood-onset (persistent) ADHD (n = 193), their siblings with late-onset ADHD (n = 34), their stable unaffected siblings (n = 111) and healthy controls (n = 186). At study entry (mean age: 11.3) and follow-up (mean age: 17.01), participants were assessed for ADHD by structured psychiatric interviews and multi-informant questionnaires. Several neurocognitive functions were assessed at baseline and after 6 years, including time reproduction, timing variability (reaction time variability and time production variability), reaction time speed, motor control and working memory; intelligence was taken as a measure of overall neurocognitive functioning. Results: Siblings with late-onset ADHD were similar to individuals with childhood-onset ADHD in showing longer reaction times and/or higher error rates on all neurocognitive measures at baseline and follow-up, when compared to healthy controls. They differed from stable unaffected siblings (who were similar to healthy controls) by greater reaction time variability and timing production variability at baseline. No significant group by time interaction was found for any of the tasks. Conclusions: For unaffected siblings of individuals with ADHD, reaction time variability and timing production variability may serve as neurocognitive marker for late-onset ADHD.

AB - Background: There is an increased interest in ‘late-onset’ attention-deficit/hyperactivity disorder (ADHD), referring to the onset of clinically significant ADHD symptoms after the age of 12 years. This study aimed to examine whether unaffected siblings with late-onset ADHD could be differentiated from stable unaffected siblings by their neurocognitive functioning in childhood. Methods: We report findings from a 6-year prospective, longitudinal study of the Dutch part of the International Multicenter ADHD Genetics (IMAGE) study, including individuals with childhood-onset (persistent) ADHD (n = 193), their siblings with late-onset ADHD (n = 34), their stable unaffected siblings (n = 111) and healthy controls (n = 186). At study entry (mean age: 11.3) and follow-up (mean age: 17.01), participants were assessed for ADHD by structured psychiatric interviews and multi-informant questionnaires. Several neurocognitive functions were assessed at baseline and after 6 years, including time reproduction, timing variability (reaction time variability and time production variability), reaction time speed, motor control and working memory; intelligence was taken as a measure of overall neurocognitive functioning. Results: Siblings with late-onset ADHD were similar to individuals with childhood-onset ADHD in showing longer reaction times and/or higher error rates on all neurocognitive measures at baseline and follow-up, when compared to healthy controls. They differed from stable unaffected siblings (who were similar to healthy controls) by greater reaction time variability and timing production variability at baseline. No significant group by time interaction was found for any of the tasks. Conclusions: For unaffected siblings of individuals with ADHD, reaction time variability and timing production variability may serve as neurocognitive marker for late-onset ADHD.

KW - Late-onset ADHD

KW - neurocognitive markers

KW - unaffected siblings

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AN - SCOPUS:85087682072

SN - 0021-9630

VL - 62

SP - 244

EP - 252

JO - Journal of Child Psychology and Psychiatry and Allied Disciplines

JF - Journal of Child Psychology and Psychiatry and Allied Disciplines

IS - 2

ER -

Neurocognitive markers of late-onset ADHD: a 6-year longitudinal study

Abstract

Bibliographical note

Funding

Keywords

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Cite this