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

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Julio E Villalon-Reina, Kenia Martínez, Xiaoping Qu, Christopher R K Ching, Talia Nir, Deydeep Kothapalli, Conor Corbin, Daqiang Sun, Amy Lin, Jennifer K. Forsyth, Leila Kushan, Ariana Vajdi, Maria Jalbrzikowski, Laura Hansen, Rachel K. Jonas, Therese Van Amelsvoort, Geor Bakker, Wendy R. Kates, Kevin M. Antshel, Wanda Fremont & 33 more Linda E. Campbell, Kathryn L. McCabe, Christina Maria Gudbrandsen, Eileen M Daly, Christina Maria Gudbrandsen, Clodagh Murphy, Declan G Murphy, Michael Craig, Beverly S. Emanuel, Donna M. McDonald-McGinn, Jacob A. S. Vorstman, Ania Fiksinski, Sanne Koops, Kosha Ruparel, David R. Roalf, Raquel E. Gur, J. Eric Schmitt, Tony J. Simon, Naomi J. Goodrich-hunsaker, Courtney A. Durdle, Joanne Doherty, Adam C Cunningham, Marianne van den Bree, David E. J. Linden, Michael J. Owen, Hayley Moss, Sinead Kelly, Gary Donohoe, Kieran C. Murphy, Celso Arango, Neda Jahanshad, Paul M. Thompson, Carrie E. Bearden

Original languageEnglish
JournalMolecular Psychiatry
Early online date29 Jul 2019
Publication statusPublished - 2019


King's Authors


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.

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