Structural Brain Abnormalities of Attention-Deficit/Hyperactivity Disorder With Oppositional Defiant Disorder

Siri D. S. Noordermeer; Marjolein Luman; Corina U. Greven; Kim Veroude; Stephen V. Faraone; Catharina A. Hartman; Pieter J. Hoekstra; Barbara Franke; Jan K. Buitelaar; Dirk J. Heslenfeld; Jaap Oosterlaan

doi:10.1016/j.biopsych.2017.07.008

Structural Brain Abnormalities of Attention-Deficit/Hyperactivity Disorder With Oppositional Defiant Disorder

Siri D. S. Noordermeer, Marjolein Luman, Corina U. Greven, Kim Veroude, Stephen V. Faraone, Catharina A. Hartman, Pieter J. Hoekstra, Barbara Franke, Jan K. Buitelaar, Dirk J. Heslenfeld, Jaap Oosterlaan

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Abstract

Background Attention-deficit/hyperactivity disorder (ADHD) is associated with structural abnormalities in total gray matter, basal ganglia, and cerebellum. Findings of structural abnormalities in frontal and temporal lobes, amygdala, and insula are less consistent. Remarkably, the impact of comorbid oppositional defiant disorder (ODD) (comorbidity rates up to 60%) on these neuroanatomical differences is scarcely studied, while ODD (in combination with conduct disorder) has been associated with structural abnormalities of the frontal lobe, amygdala, and insula. The aim of this study was to investigate the effect of comorbid ODD on cerebral volume and cortical thickness in ADHD. Methods Three groups, 16 ± 3.5 years of age (mean ± SD; range 7–29 years), were studied on volumetric and cortical thickness characteristics using structural magnetic resonance imaging (surface-based morphometry): ADHD+ODD (n = 67), ADHD-only (n = 243), and control subjects (n = 233). Analyses included the moderators age, gender, IQ, and scan site. Results ADHD+ODD and ADHD-only showed volumetric reductions in total gray matter and (mainly) frontal brain areas. Stepwise volumetric reductions (ADHD+ODD < ADHD-only < control subjects) were found for mainly frontal regions, and ADHD+ODD was uniquely associated with reductions in several structures (e.g., the precuneus). In general, findings remained significant after accounting for ADHD symptom severity. There were no group differences in cortical thickness. Exploratory voxelwise analyses showed no group differences. Conclusions ADHD+ODD and ADHD-only were associated with volumetric reductions in brain areas crucial for attention, (working) memory, and decision-making. Volumetric reductions of frontal lobes were largest in the ADHD+ODD group, possibly underlying observed larger impairments in neurocognitive functions. Previously reported striatal abnormalities in ADHD may be caused by comorbid conduct disorder rather than ODD.

Original language	English
Pages (from-to)	642-650
Number of pages	9
Journal	Biological Psychiatry
Volume	82
Issue number	9
DOIs	https://doi.org/10.1016/j.biopsych.2017.07.008
Publication status	Published - 1 Nov 2017

Funding

This work was supported by National Institutes of Health Grant Nos. R01MH62873 and R13MH059126 and National Institute of Mental Health Grant No. R01MH094469 (to SVF), Netherlands Organization for Scientific Research Large Investment Grant No. 1750102007010 and Netherlands Organization for Scientific Research Brain and Cognition Grant No. 056-24-011 (to JKB), European Union Seventh Framework Programs AGGRESSOTYPE (Grant No. 602805 to BF) and MATRICS (Grant No. 603016 to PJH and CAH), and by grants from Radboud University Medical Center (to JKB), University Medical Center Groningen and Accare (to PJH and CAH), and Vrije Universiteit Amsterdam (to JO). BF is supported by a Vici grant from the Netherlands Organization for Scientific Research (016-310-669).

Funders	Funder number
European Union Seventh Framework Programs AGGRESSOTYPE	602805, 603016
Netherlands Organization for Scientific Research Brain and Cognition	056-24-011
Netherlands Organization for Scientific Research Large Investment	1750102007010
University Medical Center Groningen and Accare
National Institutes of Health	R01MH62873, R13MH059126
National Institute of Mental Health	R01MH094469
Vrije Universiteit Amsterdam
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	016-310-669
Radboud Universitair Medisch Centrum

Keywords

ADHD
Comorbidity
Cortical thickness
ODD
SBM
Structural MRI

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Noordermeer, S. D. S., Luman, M., Greven, C. U., Veroude, K., Faraone, S. V., Hartman, C. A., Hoekstra, P. J., Franke, B., Buitelaar, J. K., Heslenfeld, D. J., & Oosterlaan, J. (2017). Structural Brain Abnormalities of Attention-Deficit/Hyperactivity Disorder With Oppositional Defiant Disorder. Biological Psychiatry, 82(9), 642-650. https://doi.org/10.1016/j.biopsych.2017.07.008

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abstract = "Background Attention-deficit/hyperactivity disorder (ADHD) is associated with structural abnormalities in total gray matter, basal ganglia, and cerebellum. Findings of structural abnormalities in frontal and temporal lobes, amygdala, and insula are less consistent. Remarkably, the impact of comorbid oppositional defiant disorder (ODD) (comorbidity rates up to 60%) on these neuroanatomical differences is scarcely studied, while ODD (in combination with conduct disorder) has been associated with structural abnormalities of the frontal lobe, amygdala, and insula. The aim of this study was to investigate the effect of comorbid ODD on cerebral volume and cortical thickness in ADHD. Methods Three groups, 16 ± 3.5 years of age (mean ± SD; range 7–29 years), were studied on volumetric and cortical thickness characteristics using structural magnetic resonance imaging (surface-based morphometry): ADHD+ODD (n = 67), ADHD-only (n = 243), and control subjects (n = 233). Analyses included the moderators age, gender, IQ, and scan site. Results ADHD+ODD and ADHD-only showed volumetric reductions in total gray matter and (mainly) frontal brain areas. Stepwise volumetric reductions (ADHD+ODD < ADHD-only < control subjects) were found for mainly frontal regions, and ADHD+ODD was uniquely associated with reductions in several structures (e.g., the precuneus). In general, findings remained significant after accounting for ADHD symptom severity. There were no group differences in cortical thickness. Exploratory voxelwise analyses showed no group differences. Conclusions ADHD+ODD and ADHD-only were associated with volumetric reductions in brain areas crucial for attention, (working) memory, and decision-making. Volumetric reductions of frontal lobes were largest in the ADHD+ODD group, possibly underlying observed larger impairments in neurocognitive functions. Previously reported striatal abnormalities in ADHD may be caused by comorbid conduct disorder rather than ODD.",

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AU - Veroude, Kim

AU - Faraone, Stephen V.

AU - Hartman, Catharina A.

AU - Hoekstra, Pieter J.

AU - Franke, Barbara

AU - Buitelaar, Jan K.

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AU - Oosterlaan, Jaap

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Structural Brain Abnormalities of Attention-Deficit/Hyperactivity Disorder With Oppositional Defiant Disorder

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