Brain structural and functional substrates of ADGRL3 (latrophilin 3) haplotype in attention-deficit/hyperactivity disorder
Moreno Alcázar, Ana (Centro de Investigación Biomédica en Red de Salud Mental)
Ramos-Quiroga, Josep Antoni (Universitat de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Ribasés Haro, Marta (Universitat de Barcelona. Departament de Genètica, Microbiologia i Estadística)
Sánchez-Mora, Cristina (Universitat de Barcelona. Departament de Genètica, Microbiologia i Estadística)
Palomar, Gloria (Hospital Universitari Vall d'Hebron)
Bosch, Rosa (Hospital Universitari Vall d'Hebron)
Salavert, Josep (Hospita Sant Rafael (Barcelona))
Fortea, Lydia (Universitat de Barcelona)
Monté-Rubio, Gemma C. (Universitat de Barcelona)
Canales-Rodriguez, Erick Jorge (École Polytechnique Fédérale de Lausanne)
Milham, Michael P. (Child Mind Institute. Center for the Developing Brain)
Castellanos, Francisco X (Hassenfeld Children's Hospital at NYU Langone)
Casas Brugué, Miquel (Hospital Universitari Vall d'Hebron)
Pomarol-Clotet, Edith (Centro de Investigación Biomédica en Red de Salud Mental)
Radua, Joaquim (King's College London)

Data:	2021
Resum:	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.
Ajuts:	Ministerio de Ciencia e Innovación CP09/00119 Ministerio de Economía y Competitividad CD15/00199 Ministerio de Ciencia e Innovación CP10/00596 Ministerio de Ciencia e Innovación PI11/01766
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Functional magnetic resonance imaging ; Magnetic resonance imaging ; Genotyping and haplotyping ; ADHD
Publicat a:	Scientific reports, Vol. 11 (january 2021) , ISSN 2045-2322

DOI: 10.1038/s41598-021-81915-z
PMID: 33504901

12 p, 1.6 MB

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