Topological methods reveal high and low functioning neuro-phenotypes within fragile X syndrome
Article first published online: 15 APR 2014
Copyright © 2014 Wiley Periodicals, Inc.
Human Brain Mapping
Volume 35, Issue 9, pages 4904–4915, September 2014
How to Cite
Romano, D., Nicolau, M., Quintin, E.-M., Mazaika, P. K., Lightbody, A. A., Cody Hazlett, H., Piven, J., Carlsson, G. and Reiss, A. L. (2014), Topological methods reveal high and low functioning neuro-phenotypes within fragile X syndrome. Hum. Brain Mapp., 35: 4904–4915. doi: 10.1002/hbm.22521
- Issue published online: 18 JUL 2014
- Article first published online: 15 APR 2014
- Manuscript Accepted: 20 MAR 2014
- Manuscript Revised: 24 FEB 2014
- Manuscript Received: 12 NOV 2013
- National Institute of Mental Health . Grant Numbers: R01MH050047 , R01MH064708 , R01MH064580 , MH061696 , 5T32MH019908
- National Institute of Child Health and Human Development . Grant Number: P30HD003110
- the Canel Family Fund.
- autism spectrum behavior;
- topological data analysis;
- multivariate pattern analysis;
- voxel-based morphometry
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.