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VNTR-DAT1 and COMTVal158Met Genotypes Modulate Mental Flexibility and Adaptive Behavior Skills in Down Syndrome

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dc.contributor.author Del Hoyo Soriano, Laura
dc.contributor.author Xicota Vila, Laura, 1987-
dc.contributor.author Langohr, Klaus
dc.contributor.author Sánchez Benavides, Gonzalo
dc.contributor.author Sola Llopis, Susana de
dc.contributor.author Cuenca Royo, Aida Ma, 1981-
dc.contributor.author Rodríguez, Joan
dc.contributor.author Rodríguez-Morató, Jose, 1987-
dc.contributor.author Farré Albaladejo, Magí
dc.contributor.author Dierssen, Mara
dc.contributor.author Torre Fornell, Rafael de la
dc.contributor.author The TESDAD Study Group
dc.date.accessioned 2017-01-18T08:39:09Z
dc.date.available 2017-01-18T08:39:09Z
dc.date.issued 2016
dc.identifier.citation Del Hoyo Soriano L, Xicota Vila L, Langohr K, Sánchez Benavides G, Sola Llopis S de, Cuenca Royo AM, Rodríguez J, Rodríguez-Morató J, Farré Albaladejo M, Dierssen M, Torre Fornell R de la, The TESDAD Study Group. VNTR-DAT1 and COMTVal158Met Genotypes Modulate Mental Flexibility and Adaptive Behavior Skills in Down Syndrome. Frontiers in Behavioral Neuroscience. 2016; 10: 193. DOI: 10.3389/fnbeh.2016.00193
dc.identifier.issn 1662-5153
dc.identifier.uri http://hdl.handle.net/10230/27921
dc.description.abstract Down syndrome (DS) is an aneuploidy syndrome that is caused by trisomy for human chromosome 21 resulting in a characteristic cognitive and behavioral phenotype, which includes executive functioning and adaptive behavior difficulties possibly due to prefrontal cortex (PFC) deficits. DS also present a high risk for early onset of Alzheimer Disease-like dementia. The dopamine (DA) system plays a neuromodulatory role in the activity of the PFC. Several studies have implicated trait differences in DA signaling on executive functioning based on genetic polymorphisms in the genes encoding for the catechol-O-methyltransferase (COMTVal158Met) and the dopamine transporter (VNTR-DAT1). Since it is known that the phenotypic consequences of genetic variants are modulated by the genetic background in which they occur, we here explore whether these polymorphisms variants interact with the trisomic genetic background to influence gene expression, and how this in turn mediates DS phenotype variability regarding PFC cognition. We genotyped 69 young adults of both genders with DS, and found that VNTR-DAT1 was in Hardy-Weinberg equilibrium but COMTVal158Met had a reduced frequency of Met allele homozygotes. In our population, genotypes conferring higher DA availability, such as Met allele carriers and VNTR-DAT1 10-repeat allele homozygotes, resulted in improved performance in executive function tasks that require mental flexibility. Met allele carriers showed worse adaptive social skills and self-direction, and increased scores in the social subscale of the Dementia Questionnaire for People with Intellectual Disabilities than Val allele homozygotes. The VNTR-DAT1 was not involved in adaptive behavior or early dementia symptoms. Our results suggest that genetic variants of COMTVal158Met and VNTR-DAT1 may contribute to PFC-dependent cognition, while only COMTVal158Met is involved in behavioral phenotypes of DS, similar to euploid population.
dc.description.sponsorship This work was supported by grants, donations and agreements from Fondation Jérôme Lejeune (Paris, France), Instituto de Salud Carlos III FEDER, (PI11/00744), MINECO (SAF2010-19434 and SAF2013-49129-C2-1-R), EU (Era Net Neuron PCIN-2013-060), DIUE de la Generalitat de Catalunya (SGR 2009/1450, 2014SGR 680, 2014 SGR 464, SGR 2009/718, and SGR 2014/1125). LdH is recipient of a pre-doctoral fellowship from ISCIII [FI12/00319]. CRG is Center of Excellence Severo Ochoa SEV-2012-0208.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Frontiers
dc.relation.ispartof Frontiers in Behavioral Neuroscience. 2016; 10: 193
dc.rights © 2016 del Hoyo, Xicota, Langohr, Sánchez-Benavides, de Sola, Cuenca-Royo, Rodriguez, Rodríguez-Morató, Farré, Dierssen, de la Torre and the TESDAD Study Group. 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) or licensor 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 https://creativecommons.org/licenses/by/4.0/
dc.title VNTR-DAT1 and COMTVal158Met Genotypes Modulate Mental Flexibility and Adaptive Behavior Skills in Down Syndrome
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.3389/fnbeh.2016.00193
dc.subject.keyword Down syndrome
dc.subject.keyword PFC-dependent cognition
dc.subject.keyword Dopamine
dc.subject.keyword COMTVal158Met
dc.subject.keyword VNTR-DAT1
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SEV2012-0208
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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