title: Topological methods reveal high and low functioning neuro-phenotypes within fragile X syndrome.
abstract: Fragile X syndrome (FXS), due to mutations of the FMR1 gene, is the most common known inherited cause of developmental disability as well as the most common single-gene risk factor for autism. Our goal was to examine variation in brain structure in FXS with topological data analysis (TDA), and to assess how such variation is associated with measures of IQ and autism-related behaviors. To this end, we analyzed imaging and behavioral data from young boys (n = 52; aged 1.57-4.15 years) diagnosed with FXS. Application of topological methods to structural MRI data revealed two large subgroups within the study population. Comparison of these subgroups showed significant between-subgroup neuroanatomical differences similar to those previously reported to distinguish children with FXS from typically developing controls (e.g., enlarged caudate). In addition to neuroanatomy, the groups showed significant differences in IQ and autism severity scores. These results suggest that despite arising from a single gene mutation, FXS may encompass two biologically, and clinically separable phenotypes. In addition, these findings underscore the potential of TDA as a powerful tool in the search for biological phenotypes of neuropsychiatric disorders.
authors.affiliation: Center for Interdisciplinary Brain Sciences Research, Stanford University Medical School, Stanford, California.
authors.forename: David
authors.initials: D
authors.lastname: Romano
authors.forename: Monica
authors.initials: M
authors.lastname: Nicolau
authors.forename: Eve-Marie
authors.initials: EM
authors.lastname: Quintin
authors.forename: Paul K
authors.initials: PK
authors.lastname: Mazaika
authors.forename: Amy A
authors.initials: AA
authors.lastname: Lightbody
authors.forename: Heather
authors.initials: H
authors.lastname: Cody Hazlett
authors.forename: Joseph
authors.initials: J
authors.lastname: Piven
authors.forename: Gunnar
authors.initials: G
authors.lastname: Carlsson
authors.forename: Allan L
authors.initials: AL
authors.lastname: Reiss
mesh_terms: D001321:Autistic Disorder / Q000175:diagnosis / Q000523:psychology; D001921:Brain / Q000254:growth & development / Q000473:pathology*; D002675:Child, Preschool; D005600:Fragile X Syndrome / Q000469:parasitology* / Q000473:pathology*; D066128:Gray Matter / Q000254:growth & development / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D007223:Infant; D007360:Intelligence; D007361:Intelligence Tests; D008279:Magnetic Resonance Imaging; D008297:Male; D055361:Multilevel Analysis; D010641:Phenotype; D011569:Psychiatric Status Rating Scales; D066127:White Matter / Q000254:growth & development / Q000473:pathology
keywords: MRI; autism spectrum behavior; multivariate pattern analysis; topological data analysis; voxel-based morphometry
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