Large-scale mapping of cortical alterations in 22q11.2 deletion syndrome: Convergence with idiopathic psychosis and effects of deletion size.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
08
08
2017
accepted:
23
04
2018
revised:
15
04
2018
pubmed:
14
6
2018
medline:
23
3
2021
entrez:
14
6
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 29895892
doi: 10.1038/s41380-018-0078-5
pii: 10.1038/s41380-018-0078-5
pmc: PMC6292748
mid: NIHMS962497
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1822-1834Subventions
Organisme : NIMH NIH HHS
ID : U01 MH087626
Pays : United States
Organisme : NIMH NIH HHS
ID : T32 MH073526
Pays : United States
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 100202/Z/12/Z
Pays : United Kingdom
Organisme : CIHR
ID : MOP 74631
Pays : Canada
Organisme : NIMH NIH HHS
ID : U01 MH101723
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH101719
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD087101
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH085953
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD105354
Pays : United States
Organisme : NIBIB NIH HHS
ID : U54 EB020403
Pays : United States
Organisme : CIHR
ID : MOP 79518
Pays : Canada
Organisme : CIHR
ID : MOP 89066
Pays : Canada
Organisme : CIHR
ID : MOP 111238
Pays : Canada
Organisme : Medical Research Council
ID : MR/N026063/1
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : R01 MH100900
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD086984
Pays : United States
Organisme : CIHR
ID : MOP 97800
Pays : Canada
Organisme : NIMH NIH HHS
ID : U01 MH101724
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : K01 MH112774
Pays : United States
Organisme : Wellcome Trust
ID : 102003/Z/13/Z
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : U01 MH087636
Pays : United States
Organisme : NIMH NIH HHS
ID : RC2 MH089983
Pays : United States
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