Structural deviations of the posterior fossa and the cerebellum and their cognitive links in a neurodevelopmental deletion syndrome.

Autor: Sefik E; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.; Department of Psychology, Emory University, Atlanta, GA, USA., Duan K; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.; Tri-institutional Center for Translational Research in Neuroimaging and Data Science, Georgia State University, Georgia Institute of Technology, Emory University, Atlanta, GA, USA., Li Y; Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA., Sholar B; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.; Marcus Autism Center, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA, USA., Evans L; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.; Marcus Autism Center, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA, USA., Pincus J; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.; Marcus Autism Center, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA, USA., Ammar Z; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.; Marcus Autism Center, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA, USA., Murphy MM; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA., Klaiman C; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.; Marcus Autism Center, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA, USA., Saulnier CA; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.; Neurodevelopmental Assessment & Consulting Services, Atlanta, GA, USA., Pulver SL; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.; Marcus Autism Center, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA, USA., Goldman-Yassen AE; Department of Radiology, Children's Healthcare of Atlanta, Atlanta, GA, USA.; Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA., Guo Y; Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA., Walker EF; Department of Psychology, Emory University, Atlanta, GA, USA., Li L; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.; Marcus Autism Center, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA, USA., Mulle JG; Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA. jennifer.mulle@rutgers.edu., Shultz S; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA. sarah.shultz@emory.edu.; Marcus Autism Center, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA, USA. sarah.shultz@emory.edu.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2024 Nov; Vol. 29 (11), pp. 3395-3411. Date of Electronic Publication: 2024 May 14.
DOI: 10.1038/s41380-024-02584-8
Abstrakt: High-impact genetic variants associated with neurodevelopmental disorders provide biologically-defined entry points for mechanistic investigation. The 3q29 deletion (3q29Del) is one such variant, conferring a 40-100-fold increased risk for schizophrenia, as well as high risk for autism and intellectual disability. However, the mechanisms leading to neurodevelopmental disability remain largely unknown. Here, we report the first in vivo quantitative neuroimaging study in individuals with 3q29Del (N = 24) and neurotypical controls (N = 1608) using structural MRI. Given prior radiology reports of posterior fossa abnormalities in 3q29Del, we focused our investigation on the cerebellum and its tissue-types and lobules. Additionally, we compared the prevalence of cystic/cyst-like malformations of the posterior fossa between 3q29Del and controls and examined the association between neuroanatomical findings and quantitative traits to probe gene-brain-behavior relationships. 3q29Del participants had smaller cerebellar cortex volumes than controls, before and after correction for intracranial volume (ICV). An anterior-posterior gradient emerged in finer grained lobule-based and voxel-wise analyses. 3q29Del participants also had larger cerebellar white matter volumes than controls following ICV-correction and displayed elevated rates of posterior fossa arachnoid cysts and mega cisterna magna findings independent of cerebellar volume. Cerebellar white matter and subregional gray matter volumes were associated with visual-perception and visual-motor integration skills as well as IQ, while cystic/cyst-like malformations yielded no behavioral link. In summary, we find that abnormal development of cerebellar structures may represent neuroimaging-based biomarkers of cognitive and sensorimotor function in 3q29Del, adding to the growing evidence identifying cerebellar pathology as an intersection point between syndromic and idiopathic forms of neurodevelopmental disabilities.
(© 2024. The Author(s).)
Databáze: MEDLINE
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