Source‐based morphometry reveals structural brain pattern abnormalities in 22q11.2 deletion syndrome
Authors: Ge Ruiyang , Ching Christopher R. K. , Bassett Anne S. , Kushan Leila , Antshel Kevin M. , van Amelsvoort Therese , Bakker Geor , Butcher Nancy J. , Campbell Linda E. , Chow Eva W. C. , Craig Michael , Crossley Nicolas A. , Cunningham Adam , Daly Eileen , Doherty Joanne L. , Durdle Courtney A. , Emanuel Beverly S. , Fiksinski Ania , Forsyth Jennifer K. , Fremont Wanda , Goodrich‐Hunsaker Naomi J. , Gudbrandsen Maria , Gur Raquel E. , Jalbrzikowski Maria , Kates Wendy R. , Lin Amy , Linden David E. J. , McCabe Kathryn L. , McDonald‐McGinn Donna , Moss Hayley , Murphy Declan G. , Murphy Kieran C. , Owen Michael J. , Villalon‐Reina Julio E. , Repetto Gabriela M. , Roalf David R. , Ruparel Kosha , Schmitt J. Eric , Schuite‐Koops Sanne , Angkustsiri Kathleen , Sun Daqiang , Vajdi Ariana , van den Bree Marianne , Vorstman Jacob , Thompson Paul M. , Vila‐Rodriguez Fidel , Bearden Carrie E. 
Published: January 2024

Abstract22q11.2 deletion syndrome (22q11DS) is the most frequently occurring microdeletion in humans. It is associated with a significant impact on brain structure, including prominent reductions in gray matter volume (GMV), and neuropsychiatric manifestations, including cognitive impairment and psychosis. It is unclear whether GMV alterations in 22q11DS occur according to distinct structural patterns. Then, 783 participants (470 with 22q11DS: 51% females, mean age [SD] 18.2 [9.2]; and 313 typically developing [TD] controls: 46% females, mean age 18.0 [8.6]) from 13 datasets were included in the present study. We segmented structural T1‐weighted brain MRI scans and extracted GMV images, which were then utilized in a novel source‐based morphometry (SBM) pipeline (SS‐Detect) to generate structural brain patterns (SBPs) that capture co‐varying GMV. We investigated the impact of the 22q11.2 deletion, deletion size, intelligence quotient, and psychosis on the SBPs. Seventeen GMV‐SBPs were derived, which provided spatial patterns of GMV covariance associated with a quantitative metric (i.e., loading score) for analysis. Patterns of topographically widespread differences in GMV covariance, including the cerebellum, discriminated individuals with 22q11DS from healthy controls. The spatial extents of the SBPs that revealed disparities between individuals with 22q11DS and controls were consistent with the findings of the univariate voxel‐based morphometry analysis. Larger deletion size was associated with significantly lower GMV in frontal and occipital SBPs; however, history of psychosis did not show a strong relationship with these covariance patterns. 22q11DS is associated with distinct structural abnormalities captured by topographical GMV covariance patterns that include the cerebellum. Findings indicate that structural anomalies in 22q11DS manifest in a nonrandom manner and in distinct covarying anatomical patterns, rather than a diffuse global process. These SBP abnormalities converge with previously reported cortical surface area abnormalities, suggesting disturbances of early neurodevelopment as the most likely underlying mechanism.