Cortical morphology as a shared neurobiological substrate of attention-deficit/hyperactivity symptoms and executive functioning: a population-based pediatric neuroimaging study

Cortical morphology as a shared neurobiological substrate of attention-deficit/hyperactivity symptoms and executive functioning: a population-based pediatric neuroimaging study

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J Psychiatry Neurosci 2017;42(2):103-112

Sabine E. Mous, PhD; Tonya White, MD, PhD; Ryan L. Muetzel, MSc; Hanan El Marroun, PhD; Jolien Rijlaarsdam, PhD; Tinca J.C. Polderman, PhD; Vincent W. Jaddoe, MD, PhD; Frank C. Verhulst, MD, PhD; Danielle Posthuma, PhD; Henning Tiemeier, MD, PhD

Abstract

Background: 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.

Methods: 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.

Results: 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).

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

Conclusion: In a large, population-based sample of children, we identified a shared cortical morphology underlying attention-deficit/hyperactivity symptoms and EF.


Submitted Dec. 9, 2015; Revised Mar. 22, 2016; Accepted Apr. 27, 2016; Early-released Sept. 27, 2016

Acknowledgements:The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR-MDC), Rotterdam. We gratefully acknowledge the contribution of children and parents, general practitioners, hospitals, midwives and pharmacies in Rotterdam. The general design of Generation R Study is made possible by financial support from the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development (ZonMw), the Netherlands Organisation for Scientific Research (NWO), the Ministry of Health, Welfare and Sport and the Ministry of Youth and Families. In addition, this study is financially supported through NWO ZonMw (TOP project number 91211021); and the NWO Brain & Cognition (project number 433-09-228).

Affiliations: 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).

Competing interests: F.C. Verhulst is head of the Department of Child and Adolescent Psychiatry/Psychology at the Erasmus Medical Center, which publishes the Achenbach System of Empirically Based Assessment (ASEBA) and from which he receives remuneration. No other competing interests declared.

Contributors: S. Mous, T. White and H. Tiemeier designed the study. S. Mous, T. White, R. Muetzel, H. El Marroun, V. Jaddoe, F. Verhulst, D. Posthuma and H. Tiemeier acquired the data, which S. Mous, T. White, J. Rijlaarsdam, T. Polderman and H. Tiemeier analyzed. S. Mous wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.150371

Correspondence to: H. Tiemeier, Erasmus MC, Department of Epidemiology, room Na-2818, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands; h.tiemeier@erasmusmc.nl