Fronto-occipital Structural Disconnectivity as an Endophenotype of ASD

Abstract

Introduction Autism spectrum disorders (ASD) are characterized by deficits in social interaction and behavioral impairments. Several studies have reported differences in white matter generalized Fractional Anisotropy (gFA) in ASD. Objectives We studied white matter microstructural integrity in individuals with ASD. Aims We conducted the first DWI-based whole brain tractography study to compare gFA in 22 deep white matter tracts in first-degree relatives of individuals with ASD to controls and individuals with ASD. Futhermore, we replicated our significants results in an independant sample. Methods Fifty-one first-degree relatives of individuals with ASD, 29 controls and 14 individuals with ASD participated. We performed q-ball imaging whole-brain tractography based on 1.5 T diffusion weighted MRI over 32 non-colinear directions. Then, we computed mean gFA along 22 main deep white matter tracts. A linear mixed model using group, gender, age and IQ as fixed effects and family as a random effect was used and Bonferroni correction applied. We also recruited a replication sample comprising 23 individuals with ASD and 32 controls. Results We demonstrated a significantly reduced mean gFA along the left IFOF in first-degree relatives of individuals with ASD and individuals with ASD compared with controls and replicated this finding in an independant sample of patients. A decrease in mean gFA was also observed in the left CST when we compared first-degree relatives of individuals with ASD to controls (no such decrease was present in patients). Conclusion Our work suggests that structural fronto-occipital disconnectivity may be an endophenotype of ASD.