TY - JOUR
T1 - Large-scale mapping of cortical alterations in 22q11.2 deletion syndrome
T2 - Convergence with idiopathic psychosis and effects of deletion size
AU - Sun, Daqiang
AU - Ching, Christopher R.K.
AU - Lin, Amy
AU - Forsyth, Jennifer K.
AU - Kushan, Leila
AU - Vajdi, Ariana
AU - Jalbrzikowski, Maria
AU - Hansen, Laura
AU - Villalon-Reina, Julio E.
AU - Qu, Xiaoping
AU - Jonas, Rachel K.
AU - van Amelsvoort, Therese
AU - Bakker, Geor
AU - Kates, Wendy R.
AU - Antshel, Kevin M.
AU - Fremont, Wanda
AU - Campbell, Linda E.
AU - McCabe, Kathryn L.
AU - Daly, Eileen
AU - Gudbrandsen, Maria
AU - Murphy, Clodagh M.
AU - Murphy, Declan
AU - Craig, Michael
AU - Vorstman, Jacob
AU - Fiksinski, Ania
AU - Koops, Sanne
AU - Ruparel, Kosha
AU - Roalf, David R.
AU - Gur, Raquel E.
AU - Schmitt, J. Eric
AU - Simon, Tony J.
AU - Goodrich-Hunsaker, Naomi J.
AU - Durdle, Courtney A.
AU - Bassett, Anne S.
AU - Chow, Eva W.C.
AU - Butcher, Nancy J.
AU - Vila-Rodriguez, Fidel
AU - Doherty, Joanne
AU - Cunningham, Adam
AU - van den Bree, Marianne B.M.
AU - Linden, David E.J.
AU - Moss, Hayley
AU - Owen, Michael J.
AU - Murphy, Kieran C.
AU - McDonald-McGinn, Donna M.
AU - Emanuel, Beverly
AU - van Erp, Theo G.M.
AU - Turner, Jessica A.
AU - Thompson, Paul M.
AU - Bearden, Carrie E.
N1 - Publisher Copyright: © 2018, The Author(s).
PY - 2020/8/1
Y1 - 2020/8/1
N2 - The 22q11.2 deletion (22q11DS) is a common chromosomal microdeletion and a potent risk factor for psychotic illness. 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. 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. 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). 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. Cortical surface area (SA), however, showed pervasive reductions in 22q11DS (left/right hemispheres: d = −1.01/−1.02). 22q11DS cases vs. controls were classified with 93.8% accuracy based on these neuroanatomic patterns. Comparison of 22q11DS-psychosis to idiopathic schizophrenia (ENIGMA-Schizophrenia Working Group) revealed significant convergence of affected brain regions, particularly in fronto-temporal cortex. Finally, cortical SA was significantly greater in 22q11DS cases with smaller 1.5 Mb deletions, relative to those with typical 3 Mb deletions. We found a robust neuroanatomic signature of 22q11DS, and the first evidence that deletion size impacts brain structure. Psychotic illness in this highly penetrant deletion was associated with similar neuroanatomic abnormalities to idiopathic schizophrenia. 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.
AB - The 22q11.2 deletion (22q11DS) is a common chromosomal microdeletion and a potent risk factor for psychotic illness. 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. 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. 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). 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. Cortical surface area (SA), however, showed pervasive reductions in 22q11DS (left/right hemispheres: d = −1.01/−1.02). 22q11DS cases vs. controls were classified with 93.8% accuracy based on these neuroanatomic patterns. Comparison of 22q11DS-psychosis to idiopathic schizophrenia (ENIGMA-Schizophrenia Working Group) revealed significant convergence of affected brain regions, particularly in fronto-temporal cortex. Finally, cortical SA was significantly greater in 22q11DS cases with smaller 1.5 Mb deletions, relative to those with typical 3 Mb deletions. We found a robust neuroanatomic signature of 22q11DS, and the first evidence that deletion size impacts brain structure. Psychotic illness in this highly penetrant deletion was associated with similar neuroanatomic abnormalities to idiopathic schizophrenia. 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.
UR - https://www.scopus.com/pages/publications/85048359856
U2 - 10.1038/s41380-018-0078-5
DO - 10.1038/s41380-018-0078-5
M3 - Article
C2 - 29895892
SN - 1359-4184
VL - 25
SP - 1822
EP - 1834
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 8
ER -