Developmental trajectories of neuroanatomical alterations associated with the 16p11.2 copy number variations
Open accessAbstract
Most of human genome is present in two copies (maternal and paternal). However, segments of the genome can be deleted or duplicated, and many of these genomic variations (known as Copy Number Variants) are associated with psychiatric disorders. 16p11.2 copy number variants (breakpoint 4-5) confer high risk for neurodevelopmental disorders and are associated with structural brain alterations of large effect-size. Methods used in previous studies were unable to investigate the onset of these alterations and whether they evolve with age. In this study, we aim at characterizing age-related effects of 16p11.2 copy number variants by analyzing a group with a broad age range including younger individuals. A large normative developmental dataset was used to accurately adjust for effects of age. We normalized volumes of segmented brain regions as well as volumes of each voxel defined by tensor-based morphometry. Results show that the total intracranial volumes, the global gray and white matter volumes are respectively higher and lower in deletion and duplication carriers compared to control subjects at 4.5 years of age. These differences remain stable through childhood, adolescence and adulthood until 23 years of age (range: 0.5 to 1.0 Z-score). Voxel-based results are consistent with previous findings in 16p11.2 copy number variant carriers, including increased volume in the calcarine cortex and insula in deletions, compared to controls, with an inverse effect in duplication carriers (1.0 Z-score). All large effect-size voxel-based differences are present at 4.5 years and seem to remain stable until the age of 23. Our results highlight the stability of a neuroimaging endophenotype over 2 decades during which neurodevelopmental symptoms evolve at a rapid pace.
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16p11.2 duplications have reduced cortical thickness, reduced hippocampal volume, and enlarged ventricles.
“16p11.2 duplications also have the reduced cortical thickness [14, 23], reduced hippocampal volume [49] and enlarged ventricles [50, 53, 55].”
From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [50]
MRI studies show reciprocal brain volume changes, with increased gray/white matter in 16p11.2 deletions and decreased gray/white matter in 16p11.2 duplications.
“MRI studies show reciprocal brain volume changes, with increased gray/white matter in 16p11.2 deletions, and decreased gray/white matter in 16p11.2 duplications [14, 23, 49, 50].”
From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [50]
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- Authors
- Cárdenas-de-la-Parra, A., Martin-Brevet, S., Moreau, C., Rodriguez-Herreros, B., Fonov, V. S., Maillard, A. M., Zürcher, N. R., Addor, M.-C., Andrieux, J., Arveiler, B., Baujatm, G., Sloan-Bénan, F., Belfiore, M., Bonneau, D., Bouquillon, S., Boute, O., Brusco, A., Busa, T., Caberg, J.-H., Campion, D., Colombert, V., Cordier, M.-P., David, A., Debray, F.-G., Delrue, M.-A., Doco-Fenzy, M., Dunkhase-Heinl, U., Edery, P., Fagerberg, C., Faivre, L., Forzano, F., Genevieve, D., Gérard, M., Giachino, D., Guichet, A., Guillin, O., Héron, D., Isidor, B., Jacquette, A., Jaillard, S., Journel, H., Keren, B., Lacombe, D., Lebon, S., Le Caignec, C., Lemaître, M.-P., Lespinasse, J., Mathieu-Dramart, M., Mercier, S., Mignot, C., Missirian, C., Petit, F., Pilekær Sørensen, K., Pinson, L., Plessis, G., Prieur, F., Rooryck-Thambo, C., Rossi, M., Sanlaville, D., Schlott Kristiansen, B., Schluth-Bolard, C., Till, M., Van Haelst, M., Van Maldergem, L., Hadjikhani, N., Beckmann, J. S., Reymond, A., Draganski, B., Jacquemont, S., & Collins, D. L.
- Affiliations
- CHU Sainte-Justine Research Center (CA)
- Montreal Neurological Institute and Hospital (CA)
- Centre Hospitalier Universitaire Vaudois (CH)
- Harvard University (US)
- Centre Hospitalier Universitaire de Lille (FR)
- Centre Hospitalier Universitaire de Bordeaux (FR)
- Hôpital Necker-Enfants Malades (FR)
- University Hospital of Geneva (CH)
- Centre Hospitalier Universitaire d'Angers (FR)
- Hôpital Jeanne de Flandre (FR)
- University of Turin (IT)
- Hôpital de la Timone (FR)
- Centre Hospitalier Universitaire de Liège (BE)
- École Nationale Vétérinaire de Toulouse (FR)
- Institut de Recherche en Santé, Environnement et Travail (FR)
- University of Lausanne (CH)
- ORCID
- Moreau, Clara
- Fonov, Vladimir S.
- Maillard, Anne M.
- Zürcher, Nicole R.
- Addor, Marie-Claude
- Bonneau, Dominique
- Brusco, Alfredo
- Busa, Tiffany
- Caberg, Jean-Hubert
- Campion, Dominique
- Delrue, Marie-Ange
- Edery, Patrick
- Fagerberg, Christina
- Faivre, Laurence
- Forzano, Francesca
- Gérard, Marion
- Giachino, Daniela
- Héron, Delphine
- Isidor, Bertrand
- Jacquette, Aurélia
- Jaillard, Sylvie
- Keren, Boris
- Lacombe, Didier
- Lebon, Sébastien
- Mercier, Sandra
- Mignot, Cyril
- Missirian, Chantal
- Petit, Florence
- Prieur, Fabienne
- Rossi, Massimiliano
- Sanlaville, Damien
- Hadjikhani, Nouchine
- Beckmann, Jacques S.
- Reymond, Alexandre
- Draganski, Bogdan
- Jacquemont, Sébastien
- Collins, D. Louis
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2019-12
- Volume
- 203
- Pages
- 116155
- ISSN
- 1053-8119 (ISSN-L)
- OpenAlex
- W2971528011
- Cited by
- 14
- References
- 32
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 2 · 2021: 5 · 2020: 2
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- NeuroImage (acceptedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- HAL (submittedVersion)
- IRIS (submittedVersion)
- ORBi (University of Liège) (submittedVersion, other-oa)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- Compute Canada
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A_160203, 31003A_182632)
- National Institute of Mental Health
- National Institute on Drug Abuse
- National Institute of Child Health and Human Development
- Horizon 2020 (692145)
- Fondation Leenaards
- National Institute of Neurological Disorders and Stroke (−2317, N01-HD02-3343, N01-NS-9-2314, N01-MH9-0002)
- Fondation Jean-Louis Lévesque
- Canadian Institutes of Health Research (MOP-111169)
- Fonds de recherche du Québec â Nature et technologies
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
- Keywords
- neurodevelopmental disorders, brain structure, brain volume, calcarine cortex, insula, intracranial volume, gray and white matter volume, developmental trajectories, mental illness
- MeSH terms
- Adolescent, Adult, Brain, Child, Child, Preschool, Chromosome Deletion, Chromosomes, Human, Pair 16, Humans, Young Adult, DNA Copy Number Variations, Chromosome Duplication
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