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Specific effect of the fragile-X mental retardation-1 gene (FMR1) on white matter microstructure
Tamar Green1, Naama Barnea-Goraly1, Mira Raman1
1Tamar Green, MD, Center for Interdisciplinary Brain Sciences Research, Stanford University School of Medicine, Stanford, California, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv; Naama Barnea-Goraly, MD, Mira Raman, MS, Scott S. Hall, PhD, Amy A. Lightbody, PhD, Jennifer L. Bruno, PhD, Eve-Marie Quintin, PhD, Center for Interdisciplinary Brain Sciences Research, Stanford University School of Medicine, Stanford, California; Allan L. Reiss, MD, Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, and Department of Radiology, Stanford University School of Medicine, Stanford, California.
Background:
Fragile-X syndrome (FXS) is a neurodevelopmental disorder associated with intellectual disability and neurobiological abnormalities including white matter microstructural differences. White matter differences have been found relative to neurotypical individuals.
Aims:
To examine whether FXS white matter differences are related specifically to FXS or more generally to the presence of intellectual disability.
Method:
We used voxel-based and tract-based analytic approaches to compare individuals with FXS (n = 40) with gender- and IQ-matched controls (n = 30).
Results:
Individuals with FXS had increased fractional anisotropy and decreased radial diffusivity values compared with IQ-matched controls in the inferior longitudinal, inferior fronto-occipital and uncinate fasciculi.
Conclusions:
The genetic variation associated with FXS affects white matter microstructure independently of overall IQ. White matter differences, found in FXS relative to IQ-matched controls, are distinct from reported differences relative to neurotypical controls. This underscores the need to consider cognitive ability differences when investigating white matter microstructure in neurodevelopmental disorders.
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