Abstract
BackgroundAutism spectrum disorder (ASD) is a genetically and phenotypically heterogeneous disorder. Promising initiatives utilizing interdisciplinary characterization of ASD suggest phenotypic subtypes related to specific likely gene-disrupting mutations (LGDMs). However, the role of functionally associated LGDMs in the neural social phenotype is unknown.MethodsIn this study of 26 children with ASD (n = 13 with an LGDM) and 13 control children, we characterized patterns of mu attenuation and habituation as children watched videos containing social and nonsocial motions during electroencephalography acquisition.ResultsDiagnostic comparisons were consistent with prior work suggesting aberrant mu attenuation in ASD within the upper mu band (10–12 Hz), but typical patterns within the lower mu band (8–10 Hz). Preliminary exploration indicated distinct social sensitization patterns (i.e., increasing mu attenuation for social motion) for children with an LGDM that is primarily expressed during embryonic development. In contrast, children with an LGDM primarily expressed post-embryonic development exhibited stable typical patterns of lower mu attenuation. Neural social indices were associated with social responsiveness, but not cognition.ConclusionsThese findings suggest unique neurophysiological profiles for certain genetic etiologies of ASD, further clarifying possible genetic functional subtypes of ASD and providing insight into mechanisms for targeted treatment approaches.
Highlights
Autism spectrum disorder (ASD) is a genetically and phenotypically heterogeneous disorder
Per Iossifov and colleagues [5, 18], likely gene-disrupting mutations (LGDMs) consisted of five genes primarily expressed in embryonic development (ADNP [44], DYRK1A, n = 3 [8], MED13L [5], SETBP1 [45], and SETD2, n = 2 [46]) and four genes primarily expressed post-embryonic development (CHD8, n = 2 [7], DSCAM [42], GRIN2B [47], and SCN2A [48])
Diagnostic comparisons (TYP and ASD) We first examined mu attenuation related to social discrimination using a diagnostic comparison of typical development and ASD
Summary
Autism spectrum disorder (ASD) is a genetically and phenotypically heterogeneous disorder. Promising initiatives utilizing interdisciplinary characterization of ASD suggest phenotypic subtypes related to specific likely gene-disrupting mutations (LGDMs). The role of functionally associated LGDMs in the neural social phenotype is unknown. The significant etiologic and phenotypic heterogeneity of autism spectrum disorder (ASD) [1] has made it challenging to target underlying mechanisms of ASD pathology. Considering that more than 1000 genes have been implicated in ASD [1, 2], recent initiatives have targeted genetic pathways [3, 4] and rare de novo likely gene-disrupting mutations (LGDMs) [5]. The relevant contribution of genetic risk to aspects of the ASD phenotype (i.e., social communicative impairments) is poorly understood, especially for low-functioning individuals with ASD. The neural indices have been targeted in relation to copy number variations, such as the 16p11.2 locus [16, 17], little is known about neural patterns associated with LGDMs, likely due to the wide
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