title: Profiles of aberrant white matter microstructure in fragile X syndrome.
abstract: Previous studies attempting to quantify white matter (WM) microstructure in individuals with fragile X syndrome (FXS) have produced inconsistent findings, most likely due to the various control groups employed, differing analysis methods, and failure to examine for potential motion artifact. In addition, analyses have heretofore lacked sufficient specificity to provide regional information. In this study, we used Automated Fiber-tract Quantification (AFQ) to identify specific regions of aberrant WM microstructure along WM tracts in patients with FXS that differed from controls who were matched on age, IQ and degree of autistic symptoms. Participants were 20 patients with FXS, aged 10 to 23 years, and 20 matched controls. Using Automated Fiber-tract Quantification (AFQ), we created Tract Profiles of fractional anisotropy and mean diffusivity along 18 major WM fascicles. We found that fractional anisotropy was significantly increased in the left and right inferior longitudinal fasciculus (ILF), right uncinate fasciculus, and left cingulum hippocampus in individuals with FXS compared to controls. Conversely, mean diffusivity was significantly decreased in the right ILF in patients with FXS compared to controls. Age was significantly negatively associated with MD values across both groups in 11 tracts. Taken together, these findings indicate that FXS results in abnormal WM microstructure in specific regions of the ILF and uncinate fasciculus, most likely caused by inefficient synaptic pruning as a result of decreased or absent Fragile X Mental Retardation Protein (FMRP). Longitudinal studies are needed to confirm these findings.
authors.affiliation: Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States. Electronic address: hallss@stanford.edu.
authors.forename: Scott S
authors.initials: SS
authors.lastname: Hall
authors.affiliation: Center for Neurobiological Imaging (CNI), Stanford University, Stanford, CA, United States.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Dougherty
authors.affiliation: Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, United States.
authors.forename: Allan L
authors.initials: AL
authors.lastname: Reiss
mesh_terms: D000293:Adolescent; D000328:Adult; D016880:Anisotropy; D002648:Child; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D056324:Diffusion Tensor Imaging / Q000379:methods; D005260:Female; D005600:Fragile X Syndrome / Q000000981:diagnostic imaging*; D006801:Humans; D008297:Male; D009415:Nerve Net; D066127:White Matter / Q000000981:diagnostic imaging*; D055815:Young Adult
keywords: Autism; Diffusion tensor imaging; FMR1 gene; Fragile X syndrome; White matter microstructure