Brain structural and functional substrates of ADGRL3 (latrophilin 3) haplotype in attention-deficit/hyperactivity disorder

Abstract Previous studies have shown that the gene encoding the adhesion G protein-coupled receptor L3 (ADGRL3; formerly latrophilin 3, LPHN3) is associated with Attention-Deficit/Hyperactivity Disorder (ADHD). Conversely, no studies have investigated the anatomical or functional brain substrates of...

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Autores principales:	Ana Moreno-Alcázar, Josep A. Ramos-Quiroga, Marta Ribases, Cristina Sánchez-Mora, Gloria Palomar, Rosa Bosch, Josep Salavert, Lydia Fortea, Gemma C. Monté-Rubio, Erick J. Canales-Rodríguez, Michael P. Milham, F. Xavier Castellanos, Miquel Casas, Edith Pomarol-Clotet, Joaquim Radua
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d6a7a4f2ed7241499062980a6f50f247
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spelling	oai:doaj.org-article:d6a7a4f2ed7241499062980a6f50f2472021-12-02T13:57:26ZBrain structural and functional substrates of ADGRL3 (latrophilin 3) haplotype in attention-deficit/hyperactivity disorder10.1038/s41598-021-81915-z2045-2322https://doaj.org/article/d6a7a4f2ed7241499062980a6f50f2472021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81915-zhttps://doaj.org/toc/2045-2322Abstract Previous studies have shown that the gene encoding the adhesion G protein-coupled receptor L3 (ADGRL3; formerly latrophilin 3, LPHN3) is associated with Attention-Deficit/Hyperactivity Disorder (ADHD). Conversely, no studies have investigated the anatomical or functional brain substrates of ADGRL3 risk variants. We examined here whether individuals with different ADGRL3 haplotypes, including both patients with ADHD and healthy controls, showed differences in brain anatomy and function. We recruited and genotyped adult patients with combined type ADHD and healthy controls to achieve a sample balanced for age, sex, premorbid IQ, and three ADGRL3 haplotype groups (risk, protective, and others). The final sample (n = 128) underwent structural and functional brain imaging (voxel-based morphometry and n-back working memory fMRI). We analyzed the brain structural and functional effects of ADHD, haplotypes, and their interaction, covarying for age, sex, and medication. Individuals (patients or controls) with the protective haplotype showed strong, widespread hypo-activation in the frontal cortex extending to inferior temporal and fusiform gyri. Individuals (patients or controls) with the risk haplotype also showed hypo-activation, more focused in the right temporal cortex. Patients showed parietal hyper-activation. Disorder-haplotype interactions, as well as structural findings, were not statistically significant. To sum up, both protective and risk ADGRL3 haplotypes are associated with substantial brain hypo-activation during working memory tasks, stressing this gene’s relevance in cognitive brain function. Conversely, we did not find brain effects of the interactions between adult ADHD and ADGRL3 haplotypes.Ana Moreno-AlcázarJosep A. Ramos-QuirogaMarta RibasesCristina Sánchez-MoraGloria PalomarRosa BoschJosep SalavertLydia ForteaGemma C. Monté-RubioErick J. Canales-RodríguezMichael P. MilhamF. Xavier CastellanosMiquel CasasEdith Pomarol-ClotetJoaquim RaduaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ana Moreno-Alcázar Josep A. Ramos-Quiroga Marta Ribases Cristina Sánchez-Mora Gloria Palomar Rosa Bosch Josep Salavert Lydia Fortea Gemma C. Monté-Rubio Erick J. Canales-Rodríguez Michael P. Milham F. Xavier Castellanos Miquel Casas Edith Pomarol-Clotet Joaquim Radua Brain structural and functional substrates of ADGRL3 (latrophilin 3) haplotype in attention-deficit/hyperactivity disorder
description	Abstract Previous studies have shown that the gene encoding the adhesion G protein-coupled receptor L3 (ADGRL3; formerly latrophilin 3, LPHN3) is associated with Attention-Deficit/Hyperactivity Disorder (ADHD). Conversely, no studies have investigated the anatomical or functional brain substrates of ADGRL3 risk variants. We examined here whether individuals with different ADGRL3 haplotypes, including both patients with ADHD and healthy controls, showed differences in brain anatomy and function. We recruited and genotyped adult patients with combined type ADHD and healthy controls to achieve a sample balanced for age, sex, premorbid IQ, and three ADGRL3 haplotype groups (risk, protective, and others). The final sample (n = 128) underwent structural and functional brain imaging (voxel-based morphometry and n-back working memory fMRI). We analyzed the brain structural and functional effects of ADHD, haplotypes, and their interaction, covarying for age, sex, and medication. Individuals (patients or controls) with the protective haplotype showed strong, widespread hypo-activation in the frontal cortex extending to inferior temporal and fusiform gyri. Individuals (patients or controls) with the risk haplotype also showed hypo-activation, more focused in the right temporal cortex. Patients showed parietal hyper-activation. Disorder-haplotype interactions, as well as structural findings, were not statistically significant. To sum up, both protective and risk ADGRL3 haplotypes are associated with substantial brain hypo-activation during working memory tasks, stressing this gene’s relevance in cognitive brain function. Conversely, we did not find brain effects of the interactions between adult ADHD and ADGRL3 haplotypes.
format	article
author	Ana Moreno-Alcázar Josep A. Ramos-Quiroga Marta Ribases Cristina Sánchez-Mora Gloria Palomar Rosa Bosch Josep Salavert Lydia Fortea Gemma C. Monté-Rubio Erick J. Canales-Rodríguez Michael P. Milham F. Xavier Castellanos Miquel Casas Edith Pomarol-Clotet Joaquim Radua
author_facet	Ana Moreno-Alcázar Josep A. Ramos-Quiroga Marta Ribases Cristina Sánchez-Mora Gloria Palomar Rosa Bosch Josep Salavert Lydia Fortea Gemma C. Monté-Rubio Erick J. Canales-Rodríguez Michael P. Milham F. Xavier Castellanos Miquel Casas Edith Pomarol-Clotet Joaquim Radua
author_sort	Ana Moreno-Alcázar
title	Brain structural and functional substrates of ADGRL3 (latrophilin 3) haplotype in attention-deficit/hyperactivity disorder
title_short	Brain structural and functional substrates of ADGRL3 (latrophilin 3) haplotype in attention-deficit/hyperactivity disorder
title_full	Brain structural and functional substrates of ADGRL3 (latrophilin 3) haplotype in attention-deficit/hyperactivity disorder
title_fullStr	Brain structural and functional substrates of ADGRL3 (latrophilin 3) haplotype in attention-deficit/hyperactivity disorder
title_full_unstemmed	Brain structural and functional substrates of ADGRL3 (latrophilin 3) haplotype in attention-deficit/hyperactivity disorder
title_sort	brain structural and functional substrates of adgrl3 (latrophilin 3) haplotype in attention-deficit/hyperactivity disorder
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d6a7a4f2ed7241499062980a6f50f247
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Brain structural and functional substrates of ADGRL3 (latrophilin 3) haplotype in attention-deficit/hyperactivity disorder

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