Cortical morphology as a shared neurobiological substrate of attention-deficit/hyperactivity symptoms and executive functioning: a population-based pediatric neuroimaging study.
Attention-deficit/hyperactivity symptoms have repeatedly been associated with poor cognitive functioning. Genetic studies have demonstrated a shared etiology of attention-deficit/hyperactivity disorder (ADHD) and cognitive ability, suggesting a common underlying neurobiology of ADHD and cognition. Further, neuroimaging studies suggest that altered cortical development is related to ADHD. In a large population-based sample we investigated whether cortical morphology, as a potential neurobiological substrate, underlies the association between attention-deficit/hyperactivity symptoms and cognitive problems.



The sample consisted of school-aged children with data on attention-deficit/hyperactivity symptoms, cognitive functioning and structural imaging. First, we investigated the association between attention-deficit/ hyperactivity symptoms and different domains of cognition. Next, we identified cortical correlates of attention-deficit/hyperactivity symptoms and related cognitive domains. Finally, we studied the role of cortical thickness and gyrification in the behaviour-cognition associations.



We included 776 children in our analyses. We found that attention-deficit/hyperactivity symptoms were associated specifically with problems in attention and executive functioning (EF; b = -0.041, 95% confidence interval [CI] -0.07 to -0.01,p= 0.004). Cortical thickness and gyrification were associated with both attention-deficit/hyperactivity symptoms and EF in brain regions that have been previously implicated in ADHD. This partly explained the association between attention-deficit/hyperactivity symptoms and EF (bindirect= -0.008, bias-corrected 95% CI -0.018 to -0.001).



The nature of our study did not allow us to draw inferences regarding temporal associations; longitudinal studies are needed for clarification.



In a large, population-based sample of children, we identified a shared cortical morphology underlying attention-deficit/hyperactivity symptoms and EF.
From the The Generation R Study Group, Erasmus MC, Rotterdam, The Netherlands (Mous, Muetzel, El Marroun, Jaddoe); the Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia, Rotterdam, The Netherlands (Mous, White, Muetzel, El Marroun, Verhulst, Posthuma, Tiemeier); the Department of Radiology, Erasmus MC, Rotterdam, The Netherlands (White); the Centre for Child and Family Studies, Leiden University, Leiden, The Netherlands (Rijlaarsdam); the Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research (CNCR), VU University, Amsterdam, The Netherlands (Polderman, Posthuma); the Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands (Jaddoe, Tiemeier); the Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (Jaddoe); the Department of Clinical Genetics, VU MC, Amsterdam, The Netherlands (Posthuma); and the Department of Psychiatry, Erasmus MC, Rotterdam,The Netherlands (Tiemeier).
Sabine E
SE
Mous
From the The Generation R Study Group, Erasmus MC, Rotterdam, The Netherlands (Mous, Muetzel, El Marroun, Jaddoe); the Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia, Rotterdam, The Netherlands (Mous, White, Muetzel, El Marroun, Verhulst, Posthuma, Tiemeier); the Department of Radiology, Erasmus MC, Rotterdam, The Netherlands (White); the Centre for Child and Family Studies, Leiden University, Leiden, The Netherlands (Rijlaarsdam); the Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research (CNCR), VU University, Amsterdam, The Netherlands (Polderman, Posthuma); the Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands (Jaddoe, Tiemeier); the Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (Jaddoe); the Department of Clinical Genetics, VU MC, Amsterdam, The Netherlands (Posthuma); and the Department of Psychiatry, Erasmus MC, Rotterdam,The Netherlands (Tiemeier).
Tonya
T
White
From the The Generation R Study Group, Erasmus MC, Rotterdam, The Netherlands (Mous, Muetzel, El Marroun, Jaddoe); the Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia, Rotterdam, The Netherlands (Mous, White, Muetzel, El Marroun, Verhulst, Posthuma, Tiemeier); the Department of Radiology, Erasmus MC, Rotterdam, The Netherlands (White); the Centre for Child and Family Studies, Leiden University, Leiden, The Netherlands (Rijlaarsdam); the Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research (CNCR), VU University, Amsterdam, The Netherlands (Polderman, Posthuma); the Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands (Jaddoe, Tiemeier); the Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (Jaddoe); the Department of Clinical Genetics, VU MC, Amsterdam, The Netherlands (Posthuma); and the Department of Psychiatry, Erasmus MC, Rotterdam,The Netherlands (Tiemeier).
Ryan L
RL
Muetzel
From the The Generation R Study Group, Erasmus MC, Rotterdam, The Netherlands (Mous, Muetzel, El Marroun, Jaddoe); the Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia, Rotterdam, The Netherlands (Mous, White, Muetzel, El Marroun, Verhulst, Posthuma, Tiemeier); the Department of Radiology, Erasmus MC, Rotterdam, The Netherlands (White); the Centre for Child and Family Studies, Leiden University, Leiden, The Netherlands (Rijlaarsdam); the Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research (CNCR), VU University, Amsterdam, The Netherlands (Polderman, Posthuma); the Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands (Jaddoe, Tiemeier); the Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (Jaddoe); the Department of Clinical Genetics, VU MC, Amsterdam, The Netherlands (Posthuma); and the Department of Psychiatry, Erasmus MC, Rotterdam,The Netherlands (Tiemeier).
Hanan
H
El Marroun
From the The Generation R Study Group, Erasmus MC, Rotterdam, The Netherlands (Mous, Muetzel, El Marroun, Jaddoe); the Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia, Rotterdam, The Netherlands (Mous, White, Muetzel, El Marroun, Verhulst, Posthuma, Tiemeier); the Department of Radiology, Erasmus MC, Rotterdam, The Netherlands (White); the Centre for Child and Family Studies, Leiden University, Leiden, The Netherlands (Rijlaarsdam); the Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research (CNCR), VU University, Amsterdam, The Netherlands (Polderman, Posthuma); the Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands (Jaddoe, Tiemeier); the Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (Jaddoe); the Department of Clinical Genetics, VU MC, Amsterdam, The Netherlands (Posthuma); and the Department of Psychiatry, Erasmus MC, Rotterdam,The Netherlands (Tiemeier).
Jolien
J
Rijlaarsdam
From the The Generation R Study Group, Erasmus MC, Rotterdam, The Netherlands (Mous, Muetzel, El Marroun, Jaddoe); the Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia, Rotterdam, The Netherlands (Mous, White, Muetzel, El Marroun, Verhulst, Posthuma, Tiemeier); the Department of Radiology, Erasmus MC, Rotterdam, The Netherlands (White); the Centre for Child and Family Studies, Leiden University, Leiden, The Netherlands (Rijlaarsdam); the Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research (CNCR), VU University, Amsterdam, The Netherlands (Polderman, Posthuma); the Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands (Jaddoe, Tiemeier); the Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (Jaddoe); the Department of Clinical Genetics, VU MC, Amsterdam, The Netherlands (Posthuma); and the Department of Psychiatry, Erasmus MC, Rotterdam,The Netherlands (Tiemeier).
Tinca J C
TJ
Polderman
From the The Generation R Study Group, Erasmus MC, Rotterdam, The Netherlands (Mous, Muetzel, El Marroun, Jaddoe); the Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia, Rotterdam, The Netherlands (Mous, White, Muetzel, El Marroun, Verhulst, Posthuma, Tiemeier); the Department of Radiology, Erasmus MC, Rotterdam, The Netherlands (White); the Centre for Child and Family Studies, Leiden University, Leiden, The Netherlands (Rijlaarsdam); the Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research (CNCR), VU University, Amsterdam, The Netherlands (Polderman, Posthuma); the Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands (Jaddoe, Tiemeier); the Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (Jaddoe); the Department of Clinical Genetics, VU MC, Amsterdam, The Netherlands (Posthuma); and the Department of Psychiatry, Erasmus MC, Rotterdam,The Netherlands (Tiemeier).
Vincent W
VW
Jaddoe
From the The Generation R Study Group, Erasmus MC, Rotterdam, The Netherlands (Mous, Muetzel, El Marroun, Jaddoe); the Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia, Rotterdam, The Netherlands (Mous, White, Muetzel, El Marroun, Verhulst, Posthuma, Tiemeier); the Department of Radiology, Erasmus MC, Rotterdam, The Netherlands (White); the Centre for Child and Family Studies, Leiden University, Leiden, The Netherlands (Rijlaarsdam); the Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research (CNCR), VU University, Amsterdam, The Netherlands (Polderman, Posthuma); the Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands (Jaddoe, Tiemeier); the Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (Jaddoe); the Department of Clinical Genetics, VU MC, Amsterdam, The Netherlands (Posthuma); and the Department of Psychiatry, Erasmus MC, Rotterdam,The Netherlands (Tiemeier).
Frank C
FC
Verhulst
From the The Generation R Study Group, Erasmus MC, Rotterdam, The Netherlands (Mous, Muetzel, El Marroun, Jaddoe); the Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia, Rotterdam, The Netherlands (Mous, White, Muetzel, El Marroun, Verhulst, Posthuma, Tiemeier); the Department of Radiology, Erasmus MC, Rotterdam, The Netherlands (White); the Centre for Child and Family Studies, Leiden University, Leiden, The Netherlands (Rijlaarsdam); the Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research (CNCR), VU University, Amsterdam, The Netherlands (Polderman, Posthuma); the Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands (Jaddoe, Tiemeier); the Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (Jaddoe); the Department of Clinical Genetics, VU MC, Amsterdam, The Netherlands (Posthuma); and the Department of Psychiatry, Erasmus MC, Rotterdam,The Netherlands (Tiemeier).
Danielle
D
Posthuma
From the The Generation R Study Group, Erasmus MC, Rotterdam, The Netherlands (Mous, Muetzel, El Marroun, Jaddoe); the Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC-Sophia, Rotterdam, The Netherlands (Mous, White, Muetzel, El Marroun, Verhulst, Posthuma, Tiemeier); the Department of Radiology, Erasmus MC, Rotterdam, The Netherlands (White); the Centre for Child and Family Studies, Leiden University, Leiden, The Netherlands (Rijlaarsdam); the Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research (CNCR), VU University, Amsterdam, The Netherlands (Polderman, Posthuma); the Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands (Jaddoe, Tiemeier); the Department of Pediatrics, Erasmus MC-Sophia, Rotterdam, The Netherlands (Jaddoe); the Department of Clinical Genetics, VU MC, Amsterdam, The Netherlands (Posthuma); and the Department of Psychiatry, Erasmus MC, Rotterdam,The Netherlands (Tiemeier).
Henning
H
Tiemeier
D001288:Attention; D001289:Attention Deficit Disorder with Hyperactivity / Q000000981:diagnostic imaging* / Q000523:psychology; D001921:Brain / Q000000981:diagnostic imaging*; D002648:Child; D003071:Cognition; D015331:Cohort Studies; D056344:Executive Function; D005260:Female; D006801:Humans; D008297:Male; D059906:Neuroimaging; D009483:Neuropsychological Tests; D009929:Organ Size; D012044:Regression Analysis; D012727:Sex Characteristics
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