In vivo evidence of microstructural hypo-connectivity of brain white matter in 22q11.2 deletion syndrome [post]

Erika Raven, Jelle Veraart, Rogier Kievit, Sila Genc, Isobel Ward, Adam Cunningham, Joanne Doherty, Marianne van den Bree, Derek Jones
2020 unpublished
22q11.2 Deletion Syndrome, or 22q11.2DS, is a genetic syndrome associated with high rates of schizophrenia, autism, and attention deficit hyperactivity disorder, 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
more » ... er deficits in axonal morphology can also be observed in people with 22q11.2DS. Here, we provide an unparalleled in vivo characterisation of white matter microstructure in both typically-developing children and children with 22q11.2DS using a dedicated magnetic resonance imaging scanner which is sensitive to axonal morphology. By extracting a rich array of diffusion metrics, we present microstructural profiles of typical and atypical white matter development, and provide new evidence of connectivity differences between typically-developing and 22q11.2DS children. A recent, large-scale consortium study identified higher diffusion anisotropy and reduced overall mobility of water as hallmark microstructural alterations of white matter in 22q11.2DS, in particular for commissural fibers. We observed similar findings across all white matter tracts in this study, in addition to identifying deficits in axonal morphology. This, in combination with reduced tract volume measurements, supports the hypothesis that microstructural connectivity in 22q11.2DS is mediated by densely packed axons with disproportionately small diameters. Our findings provide insight into the in vivo mechanistic features of 22q11.2DS, and promote further investigation of shared features in neurodevelopmental and psychiatric disorders.
doi:10.21203/ fatcat:xsyz7prlsfa2nh25juyc6sjuou