title: White matter microstructure correlates with autism trait severity in a combined clinical-control sample of high-functioning adults.
abstract: Diffusion tensor imaging (DTI) studies have demonstrated white matter (WM) abnormalities in tracts involved in emotion processing in autism spectrum disorder (ASD), but little is known regarding the nature and distribution of WM anomalies in relation to ASD trait severity in adults. Increasing evidence suggests that ASD occurs at the extreme of a distribution of social abilities. We aimed to examine WM microstructure as a potential marker for ASD symptom severity in a combined clinical-neurotypical population. SIENAX was used to estimate whole brain volume. Tract-based spatial statistics (TBSS) was used to provide a voxel-wise comparison of WM microstructure in 50 high-functioning young adults: 25 ASD and 25 neurotypical. The severity of ASD traits was measured by autism quotient (AQ); we examined regressions between DTI markers of WM microstructure and ASD trait severity. Cognitive abilities, measured by intelligence quotient, were well-matched between the groups and were controlled in all analyses. There were no significant group differences in whole brain volume. TBSS showed widespread regions of significantly reduced fractional anisotropy (FA) and increased mean diffusivity (MD) and radial diffusivity (RD) in ASD compared with controls. Linear regression analyses in the combined sample showed that average whole WM skeleton FA was negatively influenced by AQ (p = 0.004), whilst MD and RD were positively related to AQ (p = 0.002; p = 0.001). Regression slopes were similar within both groups and strongest for AQ social, communication and attention switching scores. In conclusion, similar regression characteristics were found between WM microstructure and ASD trait severity in a combined sample of ASD and neurotypical adults. WM anomalies were relatively more severe in the clinically diagnosed sample. Both findings suggest that there is a dimensional relationship between WM microstructure and severity of ASD traits from neurotypical subjects through to clinical ASD, with reduced coherence of WM associated with greater ASD symptoms. General cognitive abilities were independent of the relationship between WM indices and ASD traits.
authors.affiliation: Imaging and Biophysics Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: Clare R
authors.initials: CR
authors.lastname: Gibbard
authors.forename: Juejing
authors.initials: J
authors.lastname: Ren
authors.forename: Kiran K
authors.initials: KK
authors.lastname: Seunarine
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Clayden
authors.forename: David H
authors.initials: DH
authors.lastname: Skuse
authors.forename: Chris A
authors.initials: CA
authors.lastname: Clark
keywords: Autism quotient; Autism spectrum disorder; Diffusion tensor imaging; Tract-based spatial statistics; White matter