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Altered white matter microstructure in 22q11.2 deletion syndrome: a multi-site diffusion tensor imaging study

Villalon-Reina, Julio, Martinez, Kenia, Qu, Xiaoping, Ching, Christopher, Nir, Talia, Kothapalli, Deydeep, Corbin, Conor, Dagiang, Sun, Lin, Amy, Forsyth, Jennifer, Kushan, Lelia, Vajdi, Ariana, Jalbrzikowski, Maria, Hansen, Laura, Jonas, Rachel, van Amelsvoort, Therese, Bakker, Geor, Kates, Wendy, Antshel, Kevin, Fremont, Wanda, Campbell, Linda, McCable, Kathryn, Daly, Eileen, Gudbrandsen, Maria, Murphy, Clodagh, Murphy, Declan, Craig, Michael, Emanual, Beverly, McDonna-McGinn, Donna, Vorstman, Jacob, Fiksinski, Ania, Koops, Sanne, Ruparel, Kosha, Roalf, David, Raquel, Gur, Eric, Schmitt, Simon, Tony, Goodrich-Hunsaker, Naomi, Durdle, Courtney, Doherty, Joanne, Cunningham, Adam, Van Den Bree, Marianne ORCID:, Linden, David, Owen, Michael ORCID:, Moss, Hayley, Kelly, Sinead, Donohoe, Gary, Murphy, Kieran, Arango, Celso, Jahanshad, Neda, Thompson, Paul and Bearden, Carrie 2020. Altered white matter microstructure in 22q11.2 deletion syndrome: a multi-site diffusion tensor imaging study. Molecular Psychiatry 25 , pp. 2818-2831. 10.1038/s41380-019-0450-0

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22q11.2 deletion syndrome (22q11DS)—a neurodevelopmental condition caused by a hemizygous deletion on chromosome 22—is associated with an elevated risk of psychosis and other developmental brain disorders. Prior single-site diffusion magnetic resonance imaging (dMRI) studies have reported altered white matter (WM) microstructure in 22q11DS, but small samples and variable methods have led to contradictory results. Here we present the largest study ever conducted of dMRI-derived measures of WM microstructure in 22q11DS (334 22q11.2 deletion carriers and 260 healthy age- and sex-matched controls; age range 6–52 years). Using harmonization protocols developed by the ENIGMA-DTI working group, we identified widespread reductions in mean, axial and radial diffusivities in 22q11DS, most pronounced in regions with major cortico-cortical and cortico-thalamic fibers: the corona radiata, corpus callosum, superior longitudinal fasciculus, posterior thalamic radiations, and sagittal stratum (Cohen’s d’s ranging from −0.9 to −1.3). Only the posterior limb of the internal capsule (IC), comprised primarily of corticofugal fibers, showed higher axial diffusivity in 22q11DS. 22q11DS patients showed higher mean fractional anisotropy (FA) in callosal and projection fibers (IC and corona radiata) relative to controls, but lower FA than controls in regions with predominantly association fibers. Psychotic illness in 22q11DS was associated with more substantial diffusivity reductions in multiple regions. Overall, these findings indicate large effects of the 22q11.2 deletion on WM microstructure, especially in major cortico-cortical connections. Taken together with findings from animal models, this pattern of abnormalities may reflect disrupted neurogenesis of projection neurons in outer cortical layers.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Cardiff University Brain Research Imaging Centre (CUBRIC)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Springer Nature
ISSN: 1359-4184
Date of First Compliant Deposit: 24 June 2019
Date of Acceptance: 3 April 2019
Last Modified: 08 May 2023 17:30

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