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

• Published in: Molecular psychiatry Vol. 25; no. 11; pp. 2818 - 2831
• Main Authors: Villalón-Reina, Julio E., Martínez, Kenia, Qu, Xiaoping, Ching, Christopher R. K., Nir, Talia M., Kothapalli, Deydeep, Corbin, Conor, Sun, Daqiang, Lin, Amy, Forsyth, Jennifer K., Kushan, Leila, Vajdi, Ariana, Jalbrzikowski, Maria, Hansen, Laura, Jonas, Rachel K., van Amelsvoort, Therese, Bakker, Geor, Kates, Wendy R., Antshel, Kevin M., Fremont, Wanda, Campbell, Linda E., McCabe, Kathryn L., Daly, Eileen, Gudbrandsen, Maria, Murphy, Clodagh M., Murphy, Declan, Craig, Michael, Emanuel, Beverly, McDonald-McGinn, Donna M., Vorstman, Jacob A.S., Fiksinski, Ania M., Koops, Sanne, Ruparel, Kosha, Roalf, David, Gur, Raquel E., Eric Schmitt, J., Simon, Tony J., Goodrich-Hunsaker, Naomi J., Durdle, Courtney A., Doherty, Joanne L., Cunningham, Adam C., van den Bree, Marianne, Linden, David E. J., Owen, Michael, Moss, Hayley, Kelly, Sinead, Donohoe, Gary, Murphy, Kieran C., Arango, Celso, Jahanshad, Neda, Thompson, Paul M., Bearden, Carrie E.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2020; Nature Publishing Group
• Subjects: 59/57; 631/208; 631/378; 692/53/2421; 692/699/476/1799; Adolescent; Adult; Age; Animal models; Anisotropy; Behavioral Sciences; Biological Psychology; Child; Chromosome 22; Chromosome deletion; Complications and side effects; Corpus callosum; Development and progression; Diffusion Magnetic Resonance Imaging; DiGeorge syndrome; DiGeorge Syndrome - diagnostic imaging; DiGeorge Syndrome - genetics; DiGeorge Syndrome - pathology; Female; Gene deletion; Genetic aspects; Humans; Magnetic resonance imaging; Male; Medicine; Medicine & Public Health; Middle Aged; Neurodevelopmental disorders; Neurogenesis; Neuroimaging; Neurosciences; Pharmacotherapy; Psychiatry; Psychoses; Psychosis; Risk factors; Schizophrenia; Substantia alba; Thalamus; White Matter - diagnostic imaging; White Matter - pathology; Working groups; Young Adult; Spain
• DOI: 10.1038/s41380-019-0450-0
• ISSN: 1359-4184

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.