Dataset Information

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

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.

SUBMITTER: Sun D

PROVIDER: S-EPMC6292748 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Sun Daqiang D Ching Christopher R K CRK Lin Amy A Forsyth Jennifer K JK Kushan Leila L Vajdi Ariana A Jalbrzikowski Maria M Hansen Laura L Villalon-Reina Julio E JE Qu Xiaoping X Jonas Rachel K RK van Amelsvoort Therese T Bakker Geor G Kates Wendy R WR Antshel Kevin M KM Fremont Wanda W Campbell Linda E LE McCabe Kathryn L KL Daly Eileen E Gudbrandsen Maria M Murphy Clodagh M CM Murphy Declan D Craig Michael M Vorstman Jacob J Fiksinski Ania A Koops Sanne S Ruparel Kosha K Roalf David R DR Gur Raquel E RE Schmitt J Eric JE Simon Tony J TJ Goodrich-Hunsaker Naomi J NJ Durdle Courtney A CA Bassett Anne S AS Chow Eva W C EWC Butcher Nancy J NJ Vila-Rodriguez Fidel F Doherty Joanne J Cunningham Adam A van den Bree Marianne B M MBM Linden David E J DEJ Moss Hayley H Owen Michael J MJ Murphy Kieran C KC McDonald-McGinn Donna M DM Emanuel Beverly B van Erp Theo G M TGM Turner Jessica A JA Thompson Paul M PM Bearden Carrie E CE

Molecular psychiatry 20180613 8

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 th ...[more]

PMID: 29895892

Similar Datasets

Project description:Objective22q11.2 deletion syndrome (22q11DS) is among the strongest known genetic risk factors for schizophrenia. Previous studies have reported variable alterations in subcortical brain structures in 22q11DS. To better characterize subcortical alterations in 22q11DS, including modulating effects of clinical and genetic heterogeneity, the authors studied a large multicenter neuroimaging cohort from the ENIGMA 22q11.2 Deletion Syndrome Working Group.MethodsSubcortical structures were measured using harmonized protocols for gross volume and subcortical shape morphometry in 533 individuals with 22q11DS and 330 matched healthy control subjects (age range, 6-56 years; 49% female).ResultsCompared with the control group, the 22q11DS group showed lower intracranial volume (ICV) and thalamus, putamen, hippocampus, and amygdala volumes and greater lateral ventricle, caudate, and accumbens volumes (Cohen's d values, -0.90 to 0.93). Shape analysis revealed complex differences in the 22q11DS group across all structures. The larger A-D deletion was associated with more extensive shape alterations compared with the smaller A-B deletion. Participants with 22q11DS with psychosis showed lower ICV and hippocampus, amygdala, and thalamus volumes (Cohen's d values, -0.91 to 0.53) compared with participants with 22q11DS without psychosis. Shape analysis revealed lower thickness and surface area across subregions of these structures. Compared with subcortical findings from other neuropsychiatric disorders studied by the ENIGMA consortium, significant convergence was observed between participants with 22q11DS with psychosis and participants with schizophrenia, bipolar disorder, major depressive disorder, and obsessive-compulsive disorder.ConclusionsIn the largest neuroimaging study of 22q11DS to date, the authors found widespread alterations to subcortical brain structures, which were affected by deletion size and psychotic illness. Findings indicate significant overlap between 22q11DS-associated psychosis, idiopathic schizophrenia, and other severe neuropsychiatric illnesses.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets