White Matter Abnormalities in Autism and Unaffected Siblings

Abstract

This study was conducted to identify a potential neuroendophenotype for autism using diffusion tensor imaging. Whole-brain, voxel-based analysis of fractional anisotropy was conducted in 50 children: 19 with autism, 20 unaffected siblings, and 11 controls. Relative to controls, participants with autism exhibited bilateral reductions in fractional anisotropy across association, commissure, and projection fibers. The most severely affected tracts included the uncinate fasciculus, forceps minor, and inferior fronto-occipital fasciculus. Unaffected siblings also exhibited reductions in fractional anisotropy, albeit less severe with fewer affected tracts, sparing the uncinate fasciculus and forceps minor. These results suggest the presence of a neuroendophenotype for autism.

White matter endophenotypes and correlates for the clinical diagnosis of autism spectrum disorder

“…Our novel approach revealed that the left stria terminalis was related to the development of an ASD diagnosis. On the other hand, the results of conventional approaches in this study were consistent with the results of prior studies (Barnea-Goraly et al , 2010; Jou et al , 2016; Chien et al , 2017). Specifically, comparisons between adult males with ASD and their unaffected brothers did not show any significant differences in white matter organization, regardless of whether a voxel- or cluster-level approach was used.…”

“…Indeed, prior DTI studies have revealed that individuals with ASD share alterations with their unaffected siblings (Barnea-Goraly et al , 2010; Jou et al , 2016; Chien et al , 2017), supporting the existence of a white matter ASD endophenotype. Intriguingly, no differences in any DTI parameters were observed between individuals with ASD and their unaffected siblings (Barnea-Goraly et al , 2010; Jou et al , 2016; Chien et al , 2017), leaving the neural correlates for the development of ASD among individuals with endophenotypes undetermined. However, identifying the neural basis for the development of a clinical diagnosis of ASD according to endophenotypes is informative because it may provide a clue to understanding the mechanism of the development of ASD among people with endophenotypes.…”

Reduced tract integrity of the model for social communication is a neural substrate of social communication deficits in autism spectrum disorder

“…In neuroimaging studies, social communication deficits in ASD have been associated with specific brain regions, such as the prefrontal cortex, temporal lobe, and temporal‐parietal regions (Anderson et al., ; Hesling et al., ; Tesink et al., ). Recent tractography studies on ASD have shown altered white matter integrity in the inferior longitudinal fasciculus (ILF; Koldewyn et al., ; Pryweller et al., ), inferior frontal‐occipital fasciculus (IFOF; Raznahan et al., ; Verly et al., ), arcuate fasciculus (AF; Lo et al., ; Roberts et al., ), superior longitudinal fasciculus (SLF; Fletcher et al., ; Poustka et al., ), and uncinate fasciculus (UF; Jou et al., ; Lo et al., ; Poustka et al., ; Verly et al., ). These white matter tracts pass through specific brain regions relevant to the social communication functions, and so they are possibly responsible for social communication deficits.…”

“…These white matter tracts pass through specific brain regions relevant to the social communication functions, and so they are possibly responsible for social communication deficits. Although information gathered from previous imaging studies inferred that alterations of white matter tracts might affect social language skills in ASD (Courchesne et al., ; Groen, Zwiers, Van Der Gaag, & Buitelaar, ; Jou et al., ; Koldewyn et al., ; Pina‐Camacho et al., ; Poustka et al., ; Pryweller et al., ; Verhoeven, De Cock, Lagae, & Sunaert, ; Verly et al., ), identification of specific white matter tracts and their involvement in social communication deficits in ASD are still lacking.…”

Cortical surface architecture endophenotype and correlates of clinical diagnosis of autism spectrum disorder

“…As genetic traits contribute to variation in brain anatomy, shared alterations in brain morphology between siblings discordant for an ASD diagnosis can serve as the endophenotype. Indeed, to identify an ASD endophenotype, prior neuroimaging studies enrolled three groups (i.e., individuals with ASD, their biological siblings without the diagnosis, and typically developing [TD] individuals) . These studies compared three groups in magnetic resonance imaging (MRI) parameters and regarded the atypical findings shared by the individuals with ASD and their siblings without the diagnosis as an ASD endophenotype.…”