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Brain structural and functional substrates of ADGRL3 (latrophilin 3) haplotype in attention-deficit/hyperactivity disorder.
- Source :
-
Scientific reports [Sci Rep] 2021 Jan 27; Vol. 11 (1), pp. 2373. Date of Electronic Publication: 2021 Jan 27. - Publication Year :
- 2021
-
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.
- Subjects :
- Adult
Case-Control Studies
Female
Functional Neuroimaging
Genetic Association Studies
Genetic Predisposition to Disease
Genotype
Haplotypes
Humans
Image Processing, Computer-Assisted
Male
Middle Aged
Young Adult
Attention Deficit Disorder with Hyperactivity diagnosis
Attention Deficit Disorder with Hyperactivity genetics
Brain metabolism
Brain physiopathology
Receptors, G-Protein-Coupled genetics
Receptors, Peptide genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 33504901
- Full Text :
- https://doi.org/10.1038/s41598-021-81915-z