Altered frontal aslant tracts as a heritable neural basis of social communication deficits in autism spectrum disorder: A sibling study using tract‐based automatic analysis

Abstract

Investigating social behaviors and brain structural alterations in unaffected siblings of individuals with autism spectrum disorder (ASD) may help identify intermediate phenotypes of social communication deficits in ASD. This study hypothesized that such intermediate phenotypes could be identified in white matter tracts of the social communication model that exhibited reduced tract integrity and associations with social communication deficits. Boys with ASD (N = 30), unaffected male siblings (N = 27), and typically developing (TD) boys (N = 30) underwent clinical evaluation and MRI scanning. Group differences in generalized fractional anisotropy (GFA) values, a white matter integrity index derived from diffusion MRI data, and the relationships of GFA with the Social Responsiveness Scale (SRS) scores and the Child Behavior Checklist (CBCL/4–18) scores were investigated. Significant differences were found in the GFA values of the frontal aslant tract (FAT) among the three groups, with the decreasing order of GFA from TD to siblings to ASD. The GFA values of the FAT were associated with the social communication scores (on the SRS) in the sibling group, and those of the superior longitudinal fasciculus III were associated with the social problems scores (on the CBCL/4–18) in the boys with ASD. Due to the altered tract integrity and association with social communication deficits in the unaffected siblings of individuals with ASD, the FAT might be a heritable neural basis for social communication deficits of ASD. Autism Res 2019, 12: 225–238 © 2018 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Autism spectrum disorder (ASD) is a group of highly heritable disorders with social communication deficits as one of the core symptoms. This study aimed to identify a neural trait of social communication deficits in individuals with ASD. We investigated brain structural alterations and their associations with social communication scores in unaffected siblings of individuals with ASD. The siblings' frontal aslant tract was found to be impaired, and this tract showed a significant association with the social communication scores. Our findings support that the frontal aslant tract might be a potential neural trait of social communication deficits in ASD.

Microstructural differences in white matter tracts across middle to late adulthood: a diffusion MRI study on 7167 UK Biobank participants

“…We recently developed a tract-based automatic analysis (TBAA) technique and established a complete processing pipeline for dMRI data . Thus far, the TBAA technique and processing pipeline have been applied in clinical studies on various neurological or psychiatric diseases (Chen et al, 2018;Chien et al, 2017;Huang et al, 2018;Lo et al, 2019;Tsai et al, 2019;Wu et al, 2015). By using massive dMRI data provided by the UK Biobank and our automatic analysis pipeline, we aimed to characterize heterogeneous patterns of age-related differences in dMRI-derived tract properties in healthy individuals aged 47-76 years.…”

Suicidality in Children with Elevated Autistic Traits

“…The SRS-C has been widely used in epidemiological [Y. L. Chen, Chen, & Gau, 2015;Y. L. Chen, Shen, et al, 2017] and clinical [Lo et al, 2019] studies. High scores indicate severe autistic traits.…”

“…The responses are arranged according to a 4‐point Likert scale as follows: 1, not true ; 2, somewhat true ; 3, often true ; and 4, almost always true . The SRS‐C has been widely used in epidemiological [Y. L. Chen, Chen, & Gau, 2015; Y. L. Chen, Shen, et al, 2017] and clinical [Lo et al, 2019] studies. High scores indicate severe autistic traits.…”

Altered cingulate structures and the associations with social awareness deficits and CNTNAP2 gene in autism spectrum disorder

“…Still, it is better conceptualized as a one-factor model ( Gau et al, 2013 ). The Chinese SRS has been widely used in ASD research from children to young adults in Taiwan, e.g., ( Chen et al, 2017 , Hsiao et al, 2013 , Lau et al, 2014 , Lo et al, 2019 ), that covered the age range of our ASD sample. High internal consistency was found for the four subscales (Cronbach's alpha, 0.94–0.95) and the total scale (Cronbach's alpha, 0.95).…”