Structural brain alterations and their association with cognitive function and symptoms in Attention-deficit/Hyperactivity Disorder families

Wenhao Jiang; Kuaikuai Duan; Kelly Rootes-Murdy; Pieter J. Hoekstra; Catharina A. Hartman; Jaap Oosterlaan; Dirk Heslenfeld; Barbara Franke; Jan Buitelaar; Alejandro Arias-Vasquez; Jingyu Liu; Jessica A. Turner

doi:10.1016/j.nicl.2020.102273

Structural brain alterations and their association with cognitive function and symptoms in Attention-deficit/Hyperactivity Disorder families

Wenhao Jiang, Kuaikuai Duan, Kelly Rootes-Murdy, Pieter J. Hoekstra, Catharina A. Hartman, Jaap Oosterlaan, Dirk Heslenfeld, Barbara Franke, Jan Buitelaar, Alejandro Arias-Vasquez, Jingyu Liu, Jessica A. Turner^*

^*Corresponding author for this work

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

Abstract

Gray matter disruptions have been found consistently in Attention-deficit/Hyperactivity Disorder (ADHD). The organization of these alterations into brain structural networks remains largely unexplored. We investigated 508 participants (281 males) with ADHD (N = 210), their unaffected siblings (N = 108), individuals with subthreshold ADHD (N = 49), and unrelated healthy controls (N = 141) with an age range from 7 to 18 years old from 336 families in the Dutch NeuroIMAGE project. Source based morphometry was used to examine structural brain network alterations and their association with symptoms and cognitive performance. Two networks showed significant reductions in individuals with ADHD compared to unrelated healthy controls after False Discovery Rate correction. Component A, mainly located in bilateral Crus I, showed a ADHD/typically developing difference with subthreshold cases being intermediate between ADHD and typically developing controls. The unaffected siblings were similar to controls. After correcting for IQ and medication status, component A showed a negative correlation with inattention symptoms across the entire sample. Component B included a maximum cluster in the bilateral insula, where unaffected siblings, similar to individuals with ADHD, showed significantly reduced loadings compared to controls; but no relationship with individual symptoms or cognitive measures was found for component B. This multivariate approach suggests that areas reflecting genetic liability within ADHD are partly separate from those areas modulating symptom severity.

Original language	English
Article number	102273
Pages (from-to)	1-8
Number of pages	8
Journal	NeuroImage: Clinical
Volume	27
Early online date	23 Apr 2020
DOIs	https://doi.org/10.1016/j.nicl.2020.102273
Publication status	Published - 2020

Funding

This study was supported by the National Institutes of Health and The National Institute of Mental Health through the grant 1R01MH106655 . This NeuroIMAGE study was supported by NIH Grant R01MH62873 , NWO Large Investment Grant 1750102007010 and grants from Radboud University Medical Center , University Medical Center Groningen and Accare , and VU University Amsterdam . This work was also supported by grants from NWO Brain & Cognition ( 433-09-242 and 056-13-015 ) and from ZonMW ( 60-60600-97-193 ). Further support was received from the European Union’s FP7 program under grant agreement no. 278948 (TACTICS), no. 602450 (IMAGEMEND), no. 602805 (Aggressotype), and from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 667302 (CoCA) and no. 728018 (Eat2beNICE). Barbara Franke receives funding from a personal Vici grant (to Barbara Franke) of the Netherlands Organization for Scientific Research ( NWO , grant numbers 433-09-229 and 016-130-669 ) and a pilot grant of the Dutch National Research Agenda for the NeuroLabNL project.

Funders	Funder number
Dutch National Research Agenda
European Union's FP7
European Union's Horizon 2020 research and innovation program
European Union’s FP7	602805, 602450, 278948
Netherlands Organization for Scientific Research
National Institutes of Health	R01MH62873
National Institute of Mental Health	R01MH106655
Horizon 2020 Framework Programme	667302
Chiropractic and Osteopathic College of Australasia	728018
ZonMw	60-60600-97-193
Vrije Universiteit Amsterdam	433-09-242, 056-13-015
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	016-130-669, 1750102007010, 433-09-229

Keywords

ADHD
Cerebellum
Inattention
Independent component analysis
Insula

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Jiang, W., Duan, K., Rootes-Murdy, K., Hoekstra, P. J., Hartman, C. A., Oosterlaan, J., Heslenfeld, D., Franke, B., Buitelaar, J., Arias-Vasquez, A., Liu, J., & Turner, J. A. (2020). Structural brain alterations and their association with cognitive function and symptoms in Attention-deficit/Hyperactivity Disorder families. NeuroImage: Clinical, 27, 1-8. Article 102273. https://doi.org/10.1016/j.nicl.2020.102273

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title = "Structural brain alterations and their association with cognitive function and symptoms in Attention-deficit/Hyperactivity Disorder families",

abstract = "Gray matter disruptions have been found consistently in Attention-deficit/Hyperactivity Disorder (ADHD). The organization of these alterations into brain structural networks remains largely unexplored. We investigated 508 participants (281 males) with ADHD (N = 210), their unaffected siblings (N = 108), individuals with subthreshold ADHD (N = 49), and unrelated healthy controls (N = 141) with an age range from 7 to 18 years old from 336 families in the Dutch NeuroIMAGE project. Source based morphometry was used to examine structural brain network alterations and their association with symptoms and cognitive performance. Two networks showed significant reductions in individuals with ADHD compared to unrelated healthy controls after False Discovery Rate correction. Component A, mainly located in bilateral Crus I, showed a ADHD/typically developing difference with subthreshold cases being intermediate between ADHD and typically developing controls. The unaffected siblings were similar to controls. After correcting for IQ and medication status, component A showed a negative correlation with inattention symptoms across the entire sample. Component B included a maximum cluster in the bilateral insula, where unaffected siblings, similar to individuals with ADHD, showed significantly reduced loadings compared to controls; but no relationship with individual symptoms or cognitive measures was found for component B. This multivariate approach suggests that areas reflecting genetic liability within ADHD are partly separate from those areas modulating symptom severity.",

keywords = "ADHD, Cerebellum, Inattention, Independent component analysis, Insula",

author = "Wenhao Jiang and Kuaikuai Duan and Kelly Rootes-Murdy and Hoekstra, \{Pieter J.\} and Hartman, \{Catharina A.\} and Jaap Oosterlaan and Dirk Heslenfeld and Barbara Franke and Jan Buitelaar and Alejandro Arias-Vasquez and Jingyu Liu and Turner, \{Jessica A.\}",

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Jiang, W, Duan, K, Rootes-Murdy, K, Hoekstra, PJ, Hartman, CA, Oosterlaan, J, Heslenfeld, D, Franke, B, Buitelaar, J, Arias-Vasquez, A, Liu, J & Turner, JA 2020, 'Structural brain alterations and their association with cognitive function and symptoms in Attention-deficit/Hyperactivity Disorder families', NeuroImage: Clinical, vol. 27, 102273, pp. 1-8. https://doi.org/10.1016/j.nicl.2020.102273

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T1 - Structural brain alterations and their association with cognitive function and symptoms in Attention-deficit/Hyperactivity Disorder families

AU - Jiang, Wenhao

AU - Duan, Kuaikuai

AU - Rootes-Murdy, Kelly

AU - Hoekstra, Pieter J.

AU - Hartman, Catharina A.

AU - Oosterlaan, Jaap

AU - Heslenfeld, Dirk

AU - Franke, Barbara

AU - Buitelaar, Jan

AU - Arias-Vasquez, Alejandro

AU - Liu, Jingyu

AU - Turner, Jessica A.

PY - 2020

Y1 - 2020

N2 - Gray matter disruptions have been found consistently in Attention-deficit/Hyperactivity Disorder (ADHD). The organization of these alterations into brain structural networks remains largely unexplored. We investigated 508 participants (281 males) with ADHD (N = 210), their unaffected siblings (N = 108), individuals with subthreshold ADHD (N = 49), and unrelated healthy controls (N = 141) with an age range from 7 to 18 years old from 336 families in the Dutch NeuroIMAGE project. Source based morphometry was used to examine structural brain network alterations and their association with symptoms and cognitive performance. Two networks showed significant reductions in individuals with ADHD compared to unrelated healthy controls after False Discovery Rate correction. Component A, mainly located in bilateral Crus I, showed a ADHD/typically developing difference with subthreshold cases being intermediate between ADHD and typically developing controls. The unaffected siblings were similar to controls. After correcting for IQ and medication status, component A showed a negative correlation with inattention symptoms across the entire sample. Component B included a maximum cluster in the bilateral insula, where unaffected siblings, similar to individuals with ADHD, showed significantly reduced loadings compared to controls; but no relationship with individual symptoms or cognitive measures was found for component B. This multivariate approach suggests that areas reflecting genetic liability within ADHD are partly separate from those areas modulating symptom severity.

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KW - Cerebellum

KW - Inattention

KW - Independent component analysis

KW - Insula

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JF - NeuroImage: Clinical

M1 - 102273

ER -

Structural brain alterations and their association with cognitive function and symptoms in Attention-deficit/Hyperactivity Disorder families

Abstract

Funding

Keywords

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