19836
Impaired White Matter Integrity in Unaffected Siblings of Probands with Autism Spcectrum Disorders
Increased head circumstances were noted between probands with autism spectrum disorders (ASD) and their unaffected siblings. Siblings, like their probands, revealed significantly reduced amygdala volume, as well as aberrant white matter integrity in the frontal, parietal and temporal lobes on structural MRI. However, considering the heterogeneity of ASD brains, using the whole tract to compare between siblings and controls may under-estimate the difference between siblings and controls.
Objectives:
This study aimed to investigate white matter integrity between unaffected siblings of ASD probands by using a segment-based analysis, and examined the clinical correlates.
Methods:
Forty unaffected siblings of probands with ASD (mean age 15.5±5.9 yrs; male n=29, 72.5%) were recruited with thirty-nine age-, sex-matched typically developing controls (14.7±6.3 yrs; male n=26, 66.7%). Using a clustering method for the diffusion spectrum images, we searched for the largest segment of each tract with the largest difference compared to controls.
Results:
Compared to matched controls, unaffected siblings showed reduced mean generalized fraction anisotropy (mGFA) on nine tracts, including bilateral frontal-aslent tracts, right superior longitudinal tract 2, right CST toe, frontostriatal tracts (left ventrolateral, right ventrolateral), thalamic radiation (left ventral, right dorsal), corpus callosum (splenium) and increased mGFA of precuneus. Among the ten tracts, reduced right SLF2 was associated with more stereotyped behaviors and overall social responsiveness deficits in the siblings. Besides, impaired frontostriatal tracts, thalamic radiation and splenium were associated with higher agitated, destructive behaviors, internalizing and externalizing symptoms. Moreover, several tracts in siblings were associated visual memory deficits, spatial working memory, and planning deficits.
Conclusions:
The unaffected siblings of ASD probands showed aberrant white matter integrity which were correlated with clinical autistic traits and executive dysfunction. The abnormal tract integrity could serve as a potential endophenotype for ASD research.