Convergent microstructural brain changes across genetic models of autism spectrum disorder-A pilot study

Autism spectrum disorder (ASD) is a complex and genetically heterogeneous neuropsychiatric disease affecting as many as 1 in 68 children. Large scale genetic sequencing of individuals along the autism spectrum has uncovered several genetic risk factors for ASD; however, understanding how, and to what extent, individual genes contribute to the overall disease phenotype remains unclear. Neuroimaging studies of ASD have revealed a wide spectrum of structural and functional perturbations that are thought to reflect, in part, the complex genetic heterogeneity underpinning ASD. These perturbations, in both preclinical models and clinical patients, were identified in preclinical genetic models and ASD patients when compared to control populations; however, few studies have directly explored intrinsic differences between the models themselves. To better understand the degree and extent to which individual genes associated with ASD differ in their contribution to global measures of white matter microstructure, diffusion tensor imaging (DTI) was acquired from three novel rat genetic models of ASD (Fmr1, Nrxn1, and Pten) and DTI parameters of fractional anisotropy, mean, axial, and radial diffusivity were measured. Subsequent whole-brain voxel-wise analysis comparing each genetic model to each other (Fmr1:Nrxn1; Fmr1:Pten; Nrxn1:Pten) identified no significant differences in any comparison for all diffusion parameters assessed (FA, AD, MD, RD).