1. Chang J, Gilman SR, Chiang AH, Sanders SJ, Vitkup D. {{Genotype to phenotype relationships in autism spectrum disorders}}. {Nat Neurosci}. 2014.
Autism spectrum disorders (ASDs) are characterized by phenotypic and genetic heterogeneity. Our analysis of functional networks perturbed in ASD suggests that both truncating and nontruncating de novo mutations contribute to autism, with a bias against truncating mutations in early embryonic development. We find that functional mutations are preferentially observed in genes likely to be haploinsufficient. Multiple cell types and brain areas are affected, but the impact of ASD mutations appears to be strongest in cortical interneurons, pyramidal neurons and the medium spiny neurons of the striatum, implicating cortical and corticostriatal brain circuits. In females, truncating ASD mutations on average affect genes with 50-100% higher brain expression than in males. Our results also suggest that truncating de novo mutations play a smaller role in the etiology of high-functioning ASD cases. Overall, we find that stronger functional insults usually lead to more severe intellectual, social and behavioral ASD phenotypes.
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2. Daluwatte C, Miles JH, Sun J, Yao G. {{Association between pupillary light reflex and sensory behaviors in children with autism spectrum disorders}}. {Res Dev Disabil}. 2014; 37C: 209-15.
Atypical pupillary light reflexes (PLR) has been observed in children with autism spectrum disorders (ASD), which suggests potential autonomic nervous system (ANS) dysfunction in ASD. ANS is also involved in modulating sensory processing and sensory dysfunction has been widely reported in children with ASD. However, the potential association between physiological measurements of PLR and behavioral observations (e.g. sensory behaviors) has not been examined extensively in literature. In this study, we investigated the potential correlation between PLR and frequently observed sensory behaviors in children with ASD. We found a significant association between PLR constriction amplitude and a set of sensory behaviors in the ASD group but not in typically developing children. Children with ASD who showed more atypical sensory behaviors also had smaller PLR constriction amplitudes. A smaller PLR constriction amplitude suggests lower parasympathetic modulation. This observation implies that some atypical sensory behaviors in children with ASD could be associated with decreased parasympathetic modulation.
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3. Martinez-Cerdeno V, Camacho J, Fox E, Miller E, Ariza J, Kienzle D, Plank K, Noctor SC, Van de Water J. {{Prenatal Exposure to Autism-Specific Maternal Autoantibodies Alters Proliferation of Cortical Neural Precursor Cells, Enlarges Brain, and Increases Neuronal Size in Adult Animals}}. {Cereb Cortex}. 2014.
Autism spectrum disorders (ASDs) affect up to 1 in 68 children. Autism-specific autoantibodies directed against fetal brain proteins have been found exclusively in a subpopulation of mothers whose children were diagnosed with ASD or maternal autoantibody-related autism. We tested the impact of autoantibodies on brain development in mice by transferring human antigen-specific IgG directly into the cerebral ventricles of embryonic mice during cortical neurogenesis. We show that autoantibodies recognize radial glial cells during development. We also show that prenatal exposure to autism-specific maternal autoantibodies increased cellular proliferation in the subventricular zone (SVZ) of the embryonic neocortex, increased adult brain size also and weight, and increased the size of adult cortical neurons. We propose that prenatal exposure to autism-specific maternal autoantibodies directly affects radial glial cell development and presents a viable pathologic mechanism for the maternal autoantibody-related prenatal ASD risk factor.
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4. Nicolle A, Ropar D, Beck SR. {{Regret and disappointment in autism spectrum disorders: The matter of thinking versus feeling}}. {Cortex}. 2014.
