@article{0236bcbe688648c5ba4f510d0bf9f825,
title = "Altered white matter microstructure in 22q11.2 deletion syndrome: a multisite diffusion tensor imaging study",
abstract = "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.",
keywords = "CARDIO-FACIAL SYNDROME, VELOCARDIOFACIAL SYNDROME, CORPUS-CALLOSUM, BRAIN, ABNORMALITIES, ANISOTROPY, AXON, CHILDREN, MODEL, SCHIZOPHRENIA",
author = "Villal{\'o}n-Reina, {Julio E} and Kenia Mart{\'i}nez and Xiaoping Qu and Ching, {Christopher R K} and Nir, {Talia M} and Deydeep Kothapalli and Conor Corbin and Daqiang Sun and Amy Lin and Forsyth, {Jennifer K} and Leila Kushan and Ariana Vajdi and Maria Jalbrzikowski and Laura Hansen and Jonas, {Rachel K} and {van Amelsvoort}, Therese and Geor Bakker and Kates, {Wendy R} and Antshel, {Kevin M} and Wanda Fremont and Campbell, {Linda E} and McCabe, {Kathryn L} and Eileen Daly and Maria Gudbrandsen and Murphy, {Clodagh M} and Declan Murphy and Michael Craig and Beverly Emanuel and McDonald-McGinn, {Donna M} and Vorstman, {Jacob A S} and Fiksinski, {Ania M} and Sanne Koops and Kosha Ruparel and David Roalf and Gur, {Raquel E} and {Eric Schmitt}, J and Simon, {Tony J} and Goodrich-Hunsaker, {Naomi J} and Durdle, {Courtney A} and Doherty, {Joanne L} and Cunningham, {Adam C} and {van den Bree}, Marianne and Linden, {David E J} and Michael Owen and Hayley Moss and Sinead Kelly and Gary Donohoe and Murphy, {Kieran C} and Celso Arango and Neda Jahanshad and Thompson, {Paul M} and Bearden, {Carrie E}",
note = "Funding Information: Acknowledgements The ENIGMA-22q working group gratefully acknowledges support from the NIH Big Data to Knowledge (BD2K) award (U54 EB020403 to PMT). This manuscript was also supported by grants from the National Institute of Mental Health: RO1 MH085953 and R01MH100900 to CEB, R01MH116147 to PMT, R01MH117601 to NJ, 1UO1-MH191719 to DMcD, 5UO1MH101724 to MvdB and MO, 5U01MH101722-02 to JASV, 5U01MH101723-02 to REG, R01 MH064824 to WRK; the Miller Family Endowed Term Chair at the UCLA Brain Research Institute (CEB); Neurobehavioral Genetics Predoctoral Training Grant 5T32MH073526 to CRKC and AL; National Institutes of Health grants: IH U01 MH087626, U01MH101719, and MH089983 to REG, and U01 MH087636 to BE and DMcD. The Wellcome Trust Institutional Strategic Support Fund (ISSF to MvdB), the Waterloo Foundation (WF 918-1234 to MvdB), the Baily Thomas Charitable Fund (2315/1 to MvdB), Wellcome Trust (102003/Z/13/Z to JD), National Institute on Aging (NIA T32AG058507 to CRKC and TMN), Wellcome Trust (100202/Z/12/Z to MO). We thank the participants and their families for being a part of our research. We also thank the ENIGMA-Schizophrenia Working Group for sharing their data for comparative analyses. Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2020",
month = nov,
doi = "10.1038/s41380-019-0450-0",
language = "English",
volume = "25",
pages = "2818--2831",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "11",
}