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Aging-dependent genetic effects associated to ADHD predict longitudinal changes of ventricular volumes in adulthood

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dc.contributor.author Vilor Tejedor, Natàlia, 1988-
dc.contributor.author Ikram, Mohammad Arfan
dc.contributor.author Roshchupkin, Gennady V.
dc.contributor.author Vinke, Elisabeth J.
dc.contributor.author Vernooij, Meike W.
dc.contributor.author Adams, Hieab H.
dc.date.accessioned 2020-10-21T06:39:50Z
dc.date.available 2020-10-21T06:39:50Z
dc.date.issued 2020
dc.identifier.citation Vilor-Tejedor N, Ikram MA, Roshchupkin G, Vinke EJ, Vernooij MW, Adams HHH. Aging-dependent genetic effects associated to ADHD predict longitudinal changes of ventricular volumes in adulthood. Front Psychiatry. 2020; 11:574. DOI: 10.3389/fpsyt.2020.00574
dc.identifier.issn 1664-0640
dc.identifier.uri http://hdl.handle.net/10230/45536
dc.description.abstract Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood-onset disorder that can persist into adult life. Most genetic studies have focused on investigating biological mechanisms of ADHD during childhood. However, little is known about whether genetic variants associated with ADHD influence structural brain changes throughout adulthood. Methods: Participant of the study were drawn from a population-based sample of 3,220 healthy individuals drawn from the Rotterdam Study, with at least two magnetic resonance imaging (MRI)-scans (8,468 scans) obtained every 3-4 years. We investigate associations of genetic single nucleotide polymorphisms (SNPs) that have previously been identified in genome-wide association studies for ADHD, and trajectories of global and subcortical brain structures in an adult population (aged 50 years and older), acquired through MRI. We also evaluated the existence of age-dependent effects of these genetic variants on trajectories of brain structures. These analyses were reproduced among individuals 70 years of age or older to further explore aging-dependent mechanisms. We additionally tested baseline associations using the first MRI-scan of the 3,220 individuals. Results: We observed significant age-dependent effects on the rs212178 in trajectories of ventricular size (lateral ventricles, P= 4E-05; inferior lateral ventricles, P=3.8E-03; third ventricle, P=2.5E-03; fourth ventricle, P=5.5E-03). Specifically, carriers of the G allele, which was reported as protective for ADHD, had a smaller increase of ventricular size compared with homozygotes for the A allele in elder stages. Post hoc analysis on the subset of individuals older than 70 years of age reinforced these results (lateral ventricles, P=7.3E-05). In addition, the rs4916723, and the rs281324 displayed nominal significant age-dependent effects in trajectories of the amygdala volume (P=1.4E-03), and caudate volume (P=1.8E-03), respectively. Conclusions: To the best of our knowledge, this is the first study suggesting the involvement of protective genetic variants for ADHD on prevention of brain atrophy during adulthood.
dc.description.sponsorship The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. This research is supported by the Dutch Technology Foundation STW (12723), which is part of the NWO, and which is partly funded by the Ministry of Economic Affairs. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (project: ORACLE, grant agreement No: 678543).
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Frontiers
dc.relation.ispartof Front Psychiatry. 2020; 11:574
dc.rights © 2020 Vilor-Tejedor, Ikram, Roshchupkin, Vinke, Vernooij and Adams. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Aging-dependent genetic effects associated to ADHD predict longitudinal changes of ventricular volumes in adulthood
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.3389/fpsyt.2020.00574
dc.subject.keyword Adulthood
dc.subject.keyword Aging
dc.subject.keyword Brain atrophy
dc.subject.keyword Brain trajectories
dc.subject.keyword Neurogenetics
dc.subject.keyword rs212178
dc.subject.keyword Ventricle size
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/678543
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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