期刊
AMERICAN JOURNAL OF PSYCHIATRY
卷 177, 期 7, 页码 589-600出版社
AMER PSYCHIATRIC PUBLISHING, INC
DOI: 10.1176/appi.ajp.2019.19060583
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资金
- National Institute on Aging (NIA) [T32AG058507]
- NIMH [5T32MH073526, RO1 MH085953, R01MH100900, U01MH101719, U01MH101719-04S1, R01MH116147, R01MH111671, MH064824, R01 MH119185, R01 MH087636-01A1, U01MH101723-01(3/5)]
- NIH/National Institute of Biomedical Imaging and Bioengineering (NIBIB) from the BigData to Knowledge (BD2K) Program [U54EB020403]
- NIH/NIBIB grant [U54EB020403]
- NIBIB [P41 EB015922]
- NIA [R56AG058854]
- National Institute for Health Research Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London
- EU-AIMS (European Autism Interventions)/EU AIMS-2TRIALS, a European Innovative Medicines Initiative [115300, 777394]
- NARSAD Young Investigators Award
- Life Span Brain Institute (University of Pennsylvania School of Medicine)
- Life Span Brain Institute (Children's Hospital of Philadelphia)
- National Institute of Child Health and Human Development (NICHD) [PO1-HD070454]
- NIH [UO1-MH191719]
- National Institute of General Medical Sciences grant [R01 GM125757]
- NICHD [PO1-HD070454]
- NIH grant [UO1-MH191719, R01MH107108, R01HD042794, HDU54079125]
- Dalglish Family Chair in 22q11.2 Deletion Syndrome
- Canadian Institutes of Health Research (CIHR) [MOP-79518, MOP-89066, MOP97800, MOP-111238]
- CIHR [MOP-74631]
- Michael Smith Foundation for Health Research
- Seedlings Foundation
- Wellcome Trust [102003/Z/13/Z, 100202/Z/12/Z]
- MRC Centre grant [MR/L010305/1]
- FONDECYT [1160736]
- Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT), Chile [PIA ACT192064]
- National Institute for Health Research Maudsley Biomedical Research Centre at South London Maudsley Foundation Trust and King's College London
- Biogen
- Shire
- Brain Canada
- Canadian Institutes of Health Research
- Vancouver Coastal Health Research Institute
- Takeda
- FONDECYT Chile [1171014]
- MRC [MR/N026063/1] Funding Source: UKRI
- Wellcome Trust [102003/Z/13/Z] Funding Source: Wellcome Trust
Objective: 22q11.2 deletion syndrome (22q11DS) is among the strongest known genetic risk factors for schizophrenia. Previous studies have reported variable alterations in sub-cortical 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. Methods: Subcortical structures were measured using harmonized protocols for gross volume and subcortical shape morphometry in 533 individualswith 22q11DS and 330matched healthy control subjects (age range, 6-56 years; 49% female). Results: Compared 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, 20.90 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, 20.91 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. Conclusions: In 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.
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