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

Daqiang Sun, Christopher R.K. Ching, Amy Lin, Jennifer K. Forsyth, Leila Kushan, Ariana Vajdi, Maria Jalbrzikowski, Laura Hansen, Julio E. Villalon-Reina, Xiaoping Qu, Rachel K. Jonas, Therese van Amelsvoort, Geor Bakker, Wendy R. Kates, Kevin M. Antshel, Wanda Fremont, Linda E. Campbell, Kathryn L. McCabe, Eileen Daly, Maria GudbrandsenClodagh M. Murphy, Declan Murphy, Michael Craig, Jacob Vorstman, Ania Fiksinski, Sanne Koops, Kosha Ruparel, David R. Roalf, Raquel E. Gur, J. Eric Schmitt, Tony J. Simon, Naomi J. Goodrich-Hunsaker, Courtney A. Durdle, Anne S. Bassett, Eva W.C. Chow, N. J. Butcher, Fidel Vila-Rodriguez, Joanne Doherty, Adam Cunningham, M. B.M. van Den Bree, David E.J. Linden, Hayley Moss, Michael J. Owen, Kieran C. Murphy, D. M. McDonald-McGinn, Beverly Emanuel, Theo G.M. van Erp, Jessica A. Turner, Paul M. Thompson, Carrie E. Bearden

Research output: Contribution to journalArticle

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalMolecular Psychiatry
DOIs
StateAccepted/In press - Jun 13 2018

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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    Sun, D., Ching, C. R. K., Lin, A., Forsyth, J. K., Kushan, L., Vajdi, A., Jalbrzikowski, M., Hansen, L., Villalon-Reina, J. E., Qu, X., Jonas, R. K., van Amelsvoort, T., Bakker, G., Kates, W. R., Antshel, K. M., Fremont, W., Campbell, L. E., McCabe, K. L., Daly, E., ... Bearden, C. E. (Accepted/In press). Large-scale mapping of cortical alterations in 22q11.2 deletion syndrome: Convergence with idiopathic psychosis and effects of deletion size. Molecular Psychiatry, 1-13. https://doi.org/10.1038/s41380-018-0078-5