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FOXP2 expression and gray matter density in the male brains of patients with schizophrenia

Common genetic variants of FOXP2 may contribute to schizophrenia vulnerability, but controversial results have been reported for this proposal. Here we evaluated the potential impact of the common FOXP2 rs2396753 polymorphism in schizophrenia. It was previously reported to be part of a risk haplotyp...

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Autores principales: Sanjuán, Julio, Castro-Martínez, Xochitl Helga, García-Martí, Gracián, González-Fernández, Javier, Sanz-Requena, Roberto, Haro, Josep María, Meana, J. Javier, Martí-Bonmatí, Luis, Nacher, Juan, Sebastiá-Ortega, Noelia, Gilabert-Juan, Javier, Moltó, María Dolores
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286223/
https://www.ncbi.nlm.nih.gov/pubmed/32734433
http://dx.doi.org/10.1007/s11682-020-00339-x
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author Sanjuán, Julio
Castro-Martínez, Xochitl Helga
García-Martí, Gracián
González-Fernández, Javier
Sanz-Requena, Roberto
Haro, Josep María
Meana, J. Javier
Martí-Bonmatí, Luis
Nacher, Juan
Sebastiá-Ortega, Noelia
Gilabert-Juan, Javier
Moltó, María Dolores
author_facet Sanjuán, Julio
Castro-Martínez, Xochitl Helga
García-Martí, Gracián
González-Fernández, Javier
Sanz-Requena, Roberto
Haro, Josep María
Meana, J. Javier
Martí-Bonmatí, Luis
Nacher, Juan
Sebastiá-Ortega, Noelia
Gilabert-Juan, Javier
Moltó, María Dolores
author_sort Sanjuán, Julio
collection PubMed
description Common genetic variants of FOXP2 may contribute to schizophrenia vulnerability, but controversial results have been reported for this proposal. Here we evaluated the potential impact of the common FOXP2 rs2396753 polymorphism in schizophrenia. It was previously reported to be part of a risk haplotype for this disease and to have significant effects on gray matter concentration in the patients. We undertook the first examination into whether rs2396753 affects the brain expression of FOXP2 and a replication study of earlier neuroimaging findings of the influence of this genetic variant on brain structure. FOXP2 expression levels were measured in postmortem prefrontal cortex samples of 84 male subjects (48 patients and 36 controls) from the CIBERSAM Brain and the Stanley Foundation Array Collections. High-resolution anatomical magnetic resonance imaging was performed on 79 male subjects (61 patients, 18 controls) using optimized voxel-based morphometry. We found differences in FOXP2 expression and brain morphometry depending on the rs2396753, relating low FOXP2 mRNA levels with reduction of gray matter density. We detected an interaction between rs2396753 and the clinical groups, showing that heterozygous patients for this polymorphism have gray matter density decrease and low FOXP2 expression comparing with the heterozygous controls. This study shows the importance of independent replication of neuroimaging genetic studies of FOXP2 as a candidate gene in schizophrenia. Furthermore, our results suggest that the FOXP2 rs2396753 affects mRNA levels, thus providing new knowledge about its significance as a potential susceptibility polymorphism in schizophrenia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11682-020-00339-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-82862232021-07-20 FOXP2 expression and gray matter density in the male brains of patients with schizophrenia Sanjuán, Julio Castro-Martínez, Xochitl Helga García-Martí, Gracián González-Fernández, Javier Sanz-Requena, Roberto Haro, Josep María Meana, J. Javier Martí-Bonmatí, Luis Nacher, Juan Sebastiá-Ortega, Noelia Gilabert-Juan, Javier Moltó, María Dolores Brain Imaging Behav Original Research Common genetic variants of FOXP2 may contribute to schizophrenia vulnerability, but controversial results have been reported for this proposal. Here we evaluated the potential impact of the common FOXP2 rs2396753 polymorphism in schizophrenia. It was previously reported to be part of a risk haplotype for this disease and to have significant effects on gray matter concentration in the patients. We undertook the first examination into whether rs2396753 affects the brain expression of FOXP2 and a replication study of earlier neuroimaging findings of the influence of this genetic variant on brain structure. FOXP2 expression levels were measured in postmortem prefrontal cortex samples of 84 male subjects (48 patients and 36 controls) from the CIBERSAM Brain and the Stanley Foundation Array Collections. High-resolution anatomical magnetic resonance imaging was performed on 79 male subjects (61 patients, 18 controls) using optimized voxel-based morphometry. We found differences in FOXP2 expression and brain morphometry depending on the rs2396753, relating low FOXP2 mRNA levels with reduction of gray matter density. We detected an interaction between rs2396753 and the clinical groups, showing that heterozygous patients for this polymorphism have gray matter density decrease and low FOXP2 expression comparing with the heterozygous controls. This study shows the importance of independent replication of neuroimaging genetic studies of FOXP2 as a candidate gene in schizophrenia. Furthermore, our results suggest that the FOXP2 rs2396753 affects mRNA levels, thus providing new knowledge about its significance as a potential susceptibility polymorphism in schizophrenia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11682-020-00339-x) contains supplementary material, which is available to authorized users. Springer US 2020-07-30 2021 /pmc/articles/PMC8286223/ /pubmed/32734433 http://dx.doi.org/10.1007/s11682-020-00339-x Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Research
Sanjuán, Julio
Castro-Martínez, Xochitl Helga
García-Martí, Gracián
González-Fernández, Javier
Sanz-Requena, Roberto
Haro, Josep María
Meana, J. Javier
Martí-Bonmatí, Luis
Nacher, Juan
Sebastiá-Ortega, Noelia
Gilabert-Juan, Javier
Moltó, María Dolores
FOXP2 expression and gray matter density in the male brains of patients with schizophrenia
title FOXP2 expression and gray matter density in the male brains of patients with schizophrenia
title_full FOXP2 expression and gray matter density in the male brains of patients with schizophrenia
title_fullStr FOXP2 expression and gray matter density in the male brains of patients with schizophrenia
title_full_unstemmed FOXP2 expression and gray matter density in the male brains of patients with schizophrenia
title_short FOXP2 expression and gray matter density in the male brains of patients with schizophrenia
title_sort foxp2 expression and gray matter density in the male brains of patients with schizophrenia
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286223/
https://www.ncbi.nlm.nih.gov/pubmed/32734433
http://dx.doi.org/10.1007/s11682-020-00339-x
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