Large-scale mapping of cortical alterations in 22q11.2 deletion syndrome: Convergence with idiopathic psychosis and effects of deletion size

Sun, Daqiang, Ching, Christopher R. K., Lin, Amy, Forsyth, Jennifer K., Kushan, Leila, Vajdi, Ariana, Jalbrzikowski, Maria, Hansen, Laura, Villalon-Reina, Julio E., Qu, Xiaoping, 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, Vorstman, Jacob, Fiksinski, Ania, Koops, Sanne, Ruparel, Kosha, Roalf, David R., Gur, Raquel E., Schmitt, J. Eric, Simon, Tony J., Goodrich-Hunsaker, Naomi J., Durdle, Courtney A., Bassett, Anne S., Chow, Eva W. C., Butcher, Nancy J., Vila-Rodriguez, Fidel, Doherty, Joanne, Cunningham, Adam, Van Den Bree, Marianne B M. ORCID: https://orcid.org/0000-0002-4426-3254, Linden, David E. J. ORCID: https://orcid.org/0000-0002-5638-9292, Moss, Hayley, Owen, Michael J. ORCID: https://orcid.org/0000-0003-4798-0862, Murphy, Kieran C., McDonald-McGinn, Donna M., Emanuel, Beverly, van Erp, Theo G. M., Turner, Jessica A., Thompson, Paul M. and Bearden, Carrie E. 2020. Large-scale mapping of cortical alterations in 22q11.2 deletion syndrome: Convergence with idiopathic psychosis and effects of deletion size. Molecular Psychiatry 25 , pp. 1822-1834. 10.1038/s41380-018-0078-5

Preview

PDF - Published Version Available under License Creative Commons Attribution Non-commercial. Download (3MB) | Preview

Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Springer Nature
ISSN:	1359-4184
Date of First Compliant Deposit:	28 June 2018
Date of Acceptance:	23 April 2018
Last Modified:	11 Oct 2023 19:32
URI:	https://orca.cardiff.ac.uk/id/eprint/112773

Citation Data

Cited 66 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item