Open AccessTopological methods reveal high and low functioning neuro‐phenotypes within fragile X syndrome
Author(s) -
Romano David,
Nicolau Monica,
Quintin EveMarie,
Mazaika Paul K.,
Lightbody Amy A.,
Cody Hazlett Heather,
Piven Joseph,
Carlsson Gunnar,
Reiss Allan L.
Publication year - 2014
Publication title -
human brain mapping
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.005
H-Index - 191
eISSN - 1097-0193
pISSN - 1065-9471
DOI - 10.1002/hbm.22521
Subject(s) - fragile x syndrome , autism , fmr1 , phenotype , neuroanatomy , topological data analysis , typically developing , fragile x , intellectual disability , autism spectrum disorder , psychology , population , neuroscience , gene , biology , genetics , medicine , developmental psychology , environmental health , algorithm , computer science
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. Hum Brain Mapp 35:4904–4915, 2014 . © 2014 Wiley Periodicals, Inc.