1. Barua S, Kuizon S, Ted Brown W, Junaid MA. {{High Gestational Folic Acid Supplementation Alters Expression of Imprinted and Candidate Autism Susceptibility Genes in a sex-Specific Manner in Mouse Offspring}}. {J Mol Neurosci};2015 (Nov 7)
Maternal nutrients play critical roles in modulating epigenetic events and exert long-term influences on the progeny’s health. Folic acid (FA) supplementation during pregnancy has decreased the incidence of neural tube defects in newborns, but the influence of high doses of maternal FA supplementation on infants’ brain development is unclear. The present study was aimed at investigating the effects of a high dose of gestational FA on the expression of genes in the cerebral hemispheres (CHs) of 1-day-old pups. One week prior to mating and throughout the entire period of gestation, female C57BL/6J mice were fed a diet, containing FA at either 2 mg/kg (control diet (CD)) or 20 mg/kg (high maternal folic acid (HMFA)). At postnatal day 1, pups from different dams were sacrificed and CH tissues were collected. Quantitative RT-PCR and Western blot analysis confirmed sex-specific alterations in the expression of several genes that modulate various cellular functions (P < 0.05) in pups from the HMFA group. Genomic DNA methylation analysis showed no difference in the level of overall methylation in pups from the HMFA group. These findings demonstrate that HMFA supplementation alters offsprings' CH gene expression in a sex-specific manner. These changes may influence infants' brain development.
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2. Chita-Tegmark M. {{Social attention in ASD: A review and meta-analysis of eye-tracking studies}}. {Res Dev Disabil};2015 (Nov 5);48:79-93.
Determining whether social attention is reduced in Autism Spectrum Disorder (ASD) and what factors influence social attention is important to our theoretical understanding of developmental trajectories of ASD and to designing targeted interventions for ASD. This meta-analysis examines data from 38 articles that used eye-tracking methods to compare individuals with ASD and TD controls. In this paper, the impact of eight factors on the size of the effect for the difference in social attention between these two groups are evaluated: age, non-verbal IQ matching, verbal IQ matching, motion, social content, ecological validity, audio input and attention bids. Results show that individuals with ASD spend less time attending to social stimuli than typically developing (TD) controls, with a mean effect size of 0.55. Social attention in ASD was most impacted when stimuli had a high social content (showed more than one person). This meta-analysis provides an opportunity to survey the eye-tracking research on social attention in ASD and to outline potential future research directions, more specifically research of social attention in the context of stimuli with high social content.
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3. Cummings JR, Lynch FL, Rust KC, Coleman KJ, Madden JM, Owen-Smith AA, Yau VM, Qian Y, Pearson KA, Crawford PM, Massolo ML, Quinn VP, Croen LA. {{Health Services Utilization Among Children With and Without Autism Spectrum Disorders}}. {J Autism Dev Disord};2015 (Nov 7)
Using data from multiple health systems (2009-2010) and the largest sample to date, this study compares health services use among youth with and without an autism spectrum disorder (ASD)-including preventive services not previously studied. To examine these differences, we estimated logistic and count data models, controlling for demographic characteristics, comorbid physical health, and mental health conditions. Results indicated that youth with an ASD had greater health care use in many categories, but were less likely to receive important preventive services including flu shots and other vaccinations. An improved understanding of the overall patterns of health care use among this population could enable health systems to facilitate the receipt of appropriate and effective health care.
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4. Grayson DR, Guidotti A. {{Merging data from genetic and epigenetic approaches to better understand autistic spectrum disorder}}. {Epigenomics};2015 (Nov 9)
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that is characterized by a wide range of cognitive and behavioral abnormalities. Genetic research has identified large numbers of genes that contribute to ASD phenotypes. There is compelling evidence that environmental factors contribute to ASD through influences that differentially impact the brain through epigenetic mechanisms. Both genetic mutations and epigenetic influences alter gene expression in different cell types of the brain. Mutations impact the expression of large numbers of genes and also have downstream consequences depending on specific pathways associated with the mutation. Environmental factors impact the expression of sets of genes by altering methylation/hydroxymethylation patterns, local histone modification patterns and chromatin remodeling. Herein, we discuss recent developments in the research of ASD with a focus on epigenetic pathways as a complement to current genetic screening.
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5. Kissine M, Cano-Chervel J, Carlier S, De Brabanter P, Ducenne L, Pairon MC, Deconinck N, Delvenne V, Leybaert J. {{Children with Autism Understand Indirect Speech Acts: Evidence from a Semi-Structured Act-Out Task}}. {PLoS One};2015;10(11):e0142191.
Children with Autism Spectrum Disorder are often said to present a global pragmatic impairment. However, there is some observational evidence that context-based comprehension of indirect requests may be preserved in autism. In order to provide experimental confirmation to this hypothesis, indirect speech act comprehension was tested in a group of 15 children with autism between 7 and 12 years and a group of 20 typically developing children between 2:7 and 3:6 years. The aim of the study was to determine whether children with autism can display genuinely contextual understanding of indirect requests. The experiment consisted of a three-pronged semi-structured task involving Mr Potato Head. In the first phase a declarative sentence was uttered by one adult as an instruction to put a garment on a Mr Potato Head toy; in the second the same sentence was uttered as a comment on a picture by another speaker; in the third phase the same sentence was uttered as a comment on a picture by the first speaker. Children with autism complied with the indirect request in the first phase and demonstrated the capacity to inhibit the directive interpretation in phases 2 and 3. TD children had some difficulty in understanding the indirect instruction in phase 1. These results call for a more nuanced view of pragmatic dysfunction in autism.
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6. Luo SY, Wu LQ, Duan RH. {{Molecular medicine of fragile X syndrome: based on known molecular mechanisms}}. {World J Pediatr};2015 (Nov 7)
BACKGROUND: Extensive research on fragile X mental retardation gene knockout mice and mutant Drosophila models has largely expanded our knowledge on mechanism-based treatment of fragile X syndrome (FXS). In light of these findings, several clinical trials are now underway for therapeutic translation to humans. DATA SOURCES: Electronic literature searches were conducted using the PubMed database and ClinicalTrials.gov. The search terms included « fragile X syndrome », « FXS and medication », « FXS and therapeutics » and « FXS and treatment ». Based on the publications identified in this search, we reviewed the neuroanatomical abnormalities in FXS patients and the potential pathogenic mechanisms to monitor the progress of FXS research, from basic studies to clinical trials. RESULTS: The pathological mechanisms of FXS were categorized on the basis of neuroanatomy, synaptic structure, synaptic transmission and fragile X mental retardation protein (FMRP) loss of function. The neuroanatomical abnormalities in FXS were described to motivate extensive research into the region-specific pathologies in the brain responsible for FXS behavioural manifestations. Mechanism-directed molecular medicines were classified according to their target pathological mechanisms, and the most recent progress in clinical trials was discussed. CONCLUSIONS: Current mechanism-based studies and clinical trials have greatly contributed to the development of FXS pharmacological therapeutics. Research examining the extent to which these treatments provided a rescue effect or FMRP compensation for the developmental impairments in FXS patients may help to improve the efficacy of treatments.
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7. Maekawa M, Iwayama Y, Ohnishi T, Toyoshima M, Shimamoto C, Hisano Y, Toyota T, Balan S, Matsuzaki H, Iwata Y, Takagai S, Yamada K, Ota M, Fukuchi S, Okada Y, Akamatsu W, Tsujii M, Kojima N, Owada Y, Okano H, Mori N, Yoshikawa T. {{Investigation of the fatty acid transporter-encoding genes SLC27A3 and SLC27A4 in autism}}. {Sci Rep};2015;5:16239.
The solute carrier 27A (SLC27A) gene family encodes fatty acid transport proteins (FATPs) and includes 6 members. During fetal and postnatal periods of development, the growing brain requires a reliable supply of fatty acids. Because autism spectrum disorders (ASD) are now recognized as disorders caused by impaired early brain development, it is possible that functional abnormalities of SLC27A genes may contribute to the pathogenesis of ASD. Here, we confirmed the expression of SLC27A3 and SLC27A4 in human neural stem cells derived from human induced pluripotent stem cells, which suggested their involvement in the developmental stage of the central nervous system. Additionally, we resequenced the SLC27A3 and SLC27A4 genes using 267 ASD patient and 1140 control samples and detected 47 (44 novel and 29 nonsynonymous) and 30 (17 novel and 14 nonsynonymous) variants for the SLC27A3 and SLC27A4, respectively, revealing that they are highly polymorphic with multiple rare variants. The SLC27A4 Ser209 allele was more frequently represented in ASD samples. Furthermore, we showed that a SLC27A4 Ser209 mutant resulted in significantly higher fluorescently-labeled fatty acid uptake into bEnd3 cells, a mouse brain capillary-derived endothelial cell line, compared with SLC27A4 Gly209, suggesting that the functional change may contribute to ASD pathophysiology.
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8. Sanders SJ. {{First glimpses of the neurobiology of autism spectrum disorder}}. {Curr Opin Genet Dev};2015 (Nov 5);33:80-92.
Rapid progress in identifying the genes underlying autism spectrum disorder (ASD) has provided the substrate for a first wave of analyses into the underlying neurobiology. This review describes the consensus across these diverse analyses, highlighting two distinct sets of genes: 1) Genes that regulate chromatin and transcription, especially in cortical projection neurons and striatal medium spiny neurons during mid-fetal development; and 2) Genes involved in synapse development and function, especially during infancy and early childhood, and differentially expressed in the post mortem ASD brain. Both gene sets are also regulatory targets of the ASD genes CHD8 and FMRP. It remains to be seen whether these represent two independent paths to the ASD phenotype or two components of a common path.
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9. Tirado MJ, Saldana D. {{Readers with Autism Can Produce Inferences, but they Cannot Answer Inferential Questions}}. {J Autism Dev Disord};2015 (Nov 7)
Readers with autism (ASD), poor comprehension (PC), and typical development (TD) took part in three reading experiments requiring the production of inferences. In Experiments 1 and 2 reading times for target phrases-placed immediately after text implicitly indicating the emotion of a protagonist or after a number of filler sentences, respectively-were used as measures of inferencing. In Experiment 3, participants were explicitly asked to identify the protagonist’s emotion. There were no significant differences among groups in Experiment 1. Compared to TD readers, the PC group performed poorly in Experiments 2 and 3. ASD readers performed worse than PC participants only in the explicit-question task. Although ASD readers can produce inferences, they respond to questions about them with difficulty.
