In vivo evidence of microstructural hypo-connectivity of brain white matter in 22q11.2 deletion syndrome
Year: 2023
Type: article
Study design: Observational Study
Abstract: 22q11.2 deletion syndrome, or 22q11.2DS, is a genetic syndrome associated with high rates of schizophrenia and autism spectrum disorders, in addition to widespread structural and functional abnormalities throughout the brain. Experimental animal models have identified neuronal connectivity deficits, e.g., decreased axonal length and complexity of axonal branching, as a primary mechanism underlying atypical brain development in 22q11.2DS. However, it is still unclear whether deficits in axonal morphology can also be observed in people with 22q11.2DS. Here, we provide an unparalleled in vivo characterization of white matter microstructure in participants with 22q11.2DS (12-15 years) and those undergoing typical development (8-18 years) using a customized magnetic resonance imaging scanner which is sensitive to axonal morphology. A rich array of diffusion MRI metrics are extracted to present microstructural profiles of typical and atypical white matter development, and provide new evidence of connectivity differences in individuals with 22q11.2DS. A recent, large-scale consortium study of 22q11.2DS identified higher diffusion anisotropy and reduced overall diffusion mobility of water as hallmark microstructural alterations of white matter in individuals across a wide age range (6-52 years). We observed similar findings across the white matter tracts included in this study, in addition to identifying deficits in axonal morphology. This, in combination with reduced tract volume measurements, supports the hypothesis that abnormal microstructural connectivity in 22q11.2DS may be mediated by densely packed axons with disproportionately small diameters. Our findings provide insight into the in vivo white matter phenotype of 22q11.2DS, and promote the continued investigation of shared features in neurodevelopmental and psychiatric disorders.
Source: Molecular Psychiatry
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,990
Funders: U.S. Department of Health and Human Services, Wellcome Trust, International Seafood Sustainability Foundation, Research Councils UK, Wolfson Foundation, National Institutes of Health, Medical Research Council, Engineering and Physical Sciences Research Council, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Excitatory-inhibitory balance in adolescents at high genetic risk of mental disorder: a study of cortical gamma oscillations and GABA concentrations in 22q11.2 deletion syndrome., G1407313830, Multi-scale and multi-modal assessment of coupling in the healthy and diseased brain., G221132721, Multi-scale and multi-modal assessment of coupling in the healthy and diseased brain., G3452322270, G3594153814, G3600827044, Cardiff University-Equipment Account, Tractometry., 1/9: Dissecting the effects of genomic variants on nenriched for neuropsychiatric disorderseurobehavioral dimensions in CNVs , G4337960835, G4682386035, Longitudinal Characterization of Postnatal Brain Maturation after Fetal Zika Infection, G5391219585, G5542938584, MRC Centre for Neuropsychiatric Genetics and Genomics, G5824453992, National Facility for In Vivo MR Imaging of Human Tissue Microstructure, G6467904493, G6831410772, G7035699760, Mesoscopic Biomarkers of Neurodegeneration and Inflammation with Diffusion MRI, Tractometry., G8259417765, IMAGINE-2: Stratifying Genomic Causes of Intellectual Disability by Mental Health Outcomes in Childhood and Adolescence, Center for Advanced Imaging Innovation and Research (CAI2R)
OpenAlex ID: W4385272347