These consistent cross-site findings highlight the homogeneity of this single genetic etiology, and support the suitability of 22q11DS as a biological model of schizophrenia. Psychotic illness in this highly penetrant deletion was associated with similar neuroanatomic abnormalities to idiopathic schizophrenia. We found a robust neuroanatomic signature of 22q11DS, and the first evidence that deletion size impacts brain structure. Finally, cortical SA was significantly greater in 22q11DS cases with smaller 1.5 Mb deletions, relative to those with typical 3 Mb deletions. Comparison of 22q11DS-psychosis to idiopathic schizophrenia (ENIGMA-Schizophrenia Working Group) revealed significant convergence of affected brain regions, particularly in fronto-temporal cortex. controls were classified with 93.8% accuracy based on these neuroanatomic patterns. Cortical surface area (SA), however, showed pervasive reductions in 22q11DS (left/right hemispheres: d = −1.01/−1.02). Compared to controls, 22q11DS individuals showed thicker cortical gray matter overall (left/right hemispheres: Cohen’s d = 0.61/0.65), but focal thickness reduction in temporal and cingulate cortex. The imaging data were collected from 10 centers worldwide, including 474 subjects with 22q11DS (age = 18.2 ± 8.6 46.9% female) and 315 typically developing, matched controls (age = 18.0 ± 9.2 45.9% female). To address these issues, we developed the ENIGMA (Enhancing Neuro Imaging Genetics Through Meta-Analysis) 22q11.2 Working Group, representing the largest analysis of brain structural alterations in 22q11DS to date. Prior studies reported widespread cortical changes in 22q11DS, but were generally underpowered to characterize neuroanatomic abnormalities associated with psychosis in 22q11DS, and/or neuroanatomic effects of variability in deletion size. The 22q11.2 deletion (22q11DS) is a common chromosomal microdeletion and a potent risk factor for psychotic illness. McDonald-McGinn, 28, 29, 30 Beverly Emanuel, 29, 30 Theo G. Butcher, 16, 18 Fidel Vila-Rodriguez, 25 Joanne Doherty, 26 Adam Cunningham, 26 Marianne B.M. Murphy, 13, 14 Declan Murphy, 13, 14 Michael Craig, 13, 15 Jacob Vorstman, 16, 17, 19 Ania Fiksinski, 16, 18, 19, 20, 21 Sanne Koops, 17 Kosha Ruparel, 22 David R. McCabe, 11, 23 Eileen Daly, 13 Maria Gudbrandsen, 13 Clodagh M. Jonas, 1, 4 Therese van Amelsvoort, 7 Geor Bakker, 7 Wendy R. Villalon-Reina, 3 Xiaoping Qu, 3 Rachel K. Forsyth, 1, 5 Leila Kushan, 1 Ariana Vajdi, 1 Maria Jalbrzikowski, 6 Laura Hansen, 1 Julio E.
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