1. Arunachalam S, Luyster RJ. {{The integrity of lexical acquisition mechanisms in autism spectrum disorders: A research review}}. {Autism research : official journal of the International Society for Autism Research}. 2015 Dec 21.
Research on autism spectrum disorders (ASD) has rapidly expanded in recent years, yielding important developments in both theory and practice. While we have gained important insights into how children with ASD differ from typically developing (TD) children in terms of phenotypic features, less has been learned about if and how development in ASD differs from typical development in terms of underlying mechanisms of change. This article aims to provide a review of processes subserving lexical development in ASD, with the goal of identifying contributing factors to the heterogeneity of language outcomes in ASD. The focus is on available evidence of the integrity or disruption of these mechanisms in ASD, as well as their significance for vocabulary development; topics include early speech perception and preference, speech segmentation, word learning, and category formation. Significant gaps in the literature are identified and future directions are suggested. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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2. Bedford R, Pickles A, Lord C. {{Early gross motor skills predict the subsequent development of language in children with autism spectrum disorder}}. {Autism research : official journal of the International Society for Autism Research}. 2015 Dec 22.
BACKGROUND: Motor milestones such as the onset of walking are important developmental markers, not only for later motor skills but also for more widespread social-cognitive development. The aim of the current study was to test whether gross motor abilities, specifically the onset of walking, predicted the subsequent rate of language development in a large cohort of children with autism spectrum disorder (ASD). METHODS: We ran growth curve models for expressive and receptive language measured at 2, 3, 5 and 9 years in 209 autistic children. Measures of gross motor, visual reception and autism symptoms were collected at the 2 year visit. In Model 1, walking onset was included as a predictor of the slope of language development. Model 2 included a measure of non-verbal IQ and autism symptom severity as covariates. The final model, Model 3, additionally covaried for gross motor ability. RESULTS: In the first model, parent-reported age of walking onset significantly predicted the subsequent rate of language development although the relationship became non-significant when gross motor skill, non-verbal ability and autism severity scores were included (Models 2 & 3). Gross motor score, however, did remain a significant predictor of both expressive and receptive language development. CONCLUSIONS: Taken together, the model results provide some evidence that early motor abilities in young children with ASD can have longitudinal cross-domain influences, potentially contributing, in part, to the linguistic difficulties that characterise ASD. Autism Res 2015. (c) 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.
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3. Begeer S, Bernstein DM, Assfalg A, Azdad H, Glasbergen T, Wierda M, Koot HM. {{Equal egocentric bias in school-aged children with and without autism spectrum disorders}}. {Journal of experimental child psychology}. 2015 Dec 11;144:15-26.
Egocentric bias is a core feature of autism. This phenomenon has been studied using the false belief task. However, typically developing children who pass categorical (pass or fail) false belief tasks may still show subtle egocentric bias. We examined 7- to 13-year-old children with autism spectrum disorder (ASD; n=76) or typical development (n=113) using tasks with a continuous response scale: a modified false belief task and a visual hindsight bias task. All children showed robust egocentric bias on both tasks, but no group effects were found. Our large sample size, coupled with our sensitive tasks and resoundingly null group effects, indicate that children with and without ASD possess more similar egocentric tendencies than previously reported.
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4. Brian JA, Smith IM, Zwaigenbaum L, Roberts W, Bryson SE. {{The Social ABCs caregiver-mediated intervention for toddlers with autism spectrum disorder: Feasibility, acceptability, and evidence of promise from a multisite study}}. {Autism research : official journal of the International Society for Autism Research}. 2015 Dec 21.
The Social ABCs is a parent-mediated intervention for toddlers with suspected or confirmed autism spectrum disorder (ASD). We undertook a multi-site pilot study to evaluate feasibility and acceptability, and to identify trends in child and parent behavior to inform future research using a larger sample and a rigorous research design. The program involved 12 weeks of parent coaching, followed by 12 weeks’ implementation, and 3-month follow-up assessment for 20 parent-toddler dyads (age range: 12-32 months). Parents successfully learned the techniques and rated the intervention as highly acceptable. Paired samples t-tests revealed significant gains in children’s functional communication (responsivity, initiations), and language gains (age-equivalents on standardized measures) commensurate with typical developmental rates. Significant increases in shared smiling and social orienting also emerged, but were attenuated at follow-up. Parents’ fidelity was positively associated with child responsivity. Training parents as mediators is a feasible and highly acceptable approach that provides a potentially cost-effective opportunity for intensive intervention at a very young age at the first signs of ASD risk. Child and parent gains in several key variables demonstrate the promise of this intervention. Autism Res 2015. (c) 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.
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5. Chandrasekara CH, Wijesundera WS, Perera HN, Chong SS, Rajan-Babu IS. {{Cascade Screening for Fragile X Syndrome/CGG Repeat Expansions in Children Attending Special Education in Sri Lanka}}. {PloS one}. 2015;10(12):e0145537.
Fragile X syndrome (FXS) is the commonest cause of inherited mental retardation and clinically presents with learning, emotional and behaviour problems. FXS is caused by expansion of cytosine-guanine-guanine (CGG) repeats present in the 5′ untranslated region of the FMR1 gene. The aim of this study was to screen children attending special education institutions in Sri Lanka to estimate the prevalence of CGG repeat expansions. The study population comprised a representative national sample of 850 children (540 males, 310 females) with 5 to 18 years of age from moderate to severe mental retardation of wide ranging aetiology. Screening for CGG repeat expansion was carried out on DNA extracted from buccal cells using 3′ direct triplet primed PCR followed by melting curve analysis. To identify the expanded status of screened positive samples, capillary electrophoresis, methylation specific PCR and Southern hybridization were carried out using venous blood samples. Prevalence of CGG repeat expansions was 2.2%. Further classification of the positive samples into FXS full mutation, pre-mutation and grey zone gave prevalence of 1.3%, 0.8% and 0.1% respectively. All positive cases were male. No females with FXS were detected in our study may have been due to the small sample size.
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6. Chen YW, Bundy A, Cordier R, Chien YL, Einfeld S. {{The Experience of Social Participation in Everyday Contexts Among Individuals with Autism Spectrum Disorders: An Experience Sampling Study}}. {Journal of autism and developmental disorders}. 2015 Dec 21.
This study explored the everyday life experiences of individuals with an autism spectrum disorder (ASD). Fourteen Australians and 16 Taiwanese (aged 16-45 years) with Asperger syndrome/high functioning autism recorded what they were doing, level of interest/involvement, emotional reactions and preference for being alone 7 times/day for 7 days. Multilevel analyses showed that ‘solitary/parallel leisure’ and ‘social activities’ were positively associated with interest and involvement. Engaging in these two activities and interacting with friends were positively associated with enjoyment. However, engaging in ‘social activities’ and having less severe ASD symptoms were associated with in-the-moment anxiety. Severity of ASD and social anxiety moderated experience in social situations. The findings highlight the importance of considering the in-the-moment experience of people with ASD.
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7. Epstein A, Leonard H, Davis E, Williams K, Reddihough D, Murphy N, Whitehouse A, Downs E. {{Conceptualizing a quality of life framework for girls with Rett syndrome using qualitative methods}}. {American journal of medical genetics Part A}. 2015 Dec 21.
Rett syndrome is a neurodevelopmental disorder mainly affecting females and associated with a mutation on the MECP2 gene. There has been no systematic evaluation of the domains of quality of life (QOL) in Rett syndrome. The aims of this study were to explore QOL in school-aged children with Rett syndrome and compare domains with those identified in other available QOL scales. The sample comprised 21 families registered with the Australian Rett Syndrome Database whose daughter with Rett syndrome was aged 6-18 years. Semi-structured telephone interviews were conducted with each parent caregiver (19 mothers, 2 fathers) to investigate aspects of their daughter’s life that were satisfying or challenging to her. Qualitative thematic analysis using a grounded theory framework was conducted, and emerging domains compared with those in two generic and three disability parent-report child QOL measures. Ten domains were identified: physical health, body pain, and discomfort, behavioral and emotional well-being, communication skills, movement and mobility, social connectedness, variety of activities, provision of targeted services, stability of daily routines, and the natural environment. The two latter domains were newly identified and each domain contained elements not represented in the comparison measures. Our data articulated important aspects of life beyond the genetic diagnosis. Existing QOL scales for children in the general population or with other disabilities did not capture the QOL of children with Rett syndrome. Our findings support the construction of a new parent-report measure to enable measurement of QOL in this group. (c) 2015 Wiley Periodicals, Inc.
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8. Glerean E, Pan RK, Salmi J, Kujala R, Lahnakoski JM, Roine U, Nummenmaa L, Leppamaki S, Nieminen-von Wendt T, Tani P, Saramaki J, Sams M, Jaaskelainen IP. {{Reorganization of functionally connected brain subnetworks in high-functioning autism}}. {Human brain mapping}. 2015 Dec 21.
Previous functional connectivity studies have found both hypo- and hyper-connectivity in brains of individuals having autism spectrum disorder (ASD). Here we studied abnormalities in functional brain subnetworks in high-functioning individuals with ASD during free viewing of a movie containing social cues and interactions. Twenty-six subjects (13 with ASD) watched a 68-min movie during functional magnetic resonance imaging. For each subject, we computed Pearson’s correlation between haemodynamic time-courses of each pair of 6-mm isotropic voxels. From the whole-brain functional networks, we derived individual and group-level subnetworks using graph theory. Scaled inclusivity was then calculated between all subject pairs to estimate intersubject similarity of connectivity structure of each subnetwork. Additional 54 individuals (27 with ASD) from the ABIDE resting-state database were included to test the reproducibility of the results. Between-group differences were observed in the composition of default-mode and ventro-temporal-limbic (VTL) subnetworks. The VTL subnetwork included amygdala, striatum, thalamus, parahippocampal, fusiform, and inferior temporal gyri. Further, VTL subnetwork similarity between subject pairs correlated significantly with similarity of symptom gravity measured with autism quotient. This correlation was observed also within the controls, and in the reproducibility dataset with ADI-R and ADOS scores. Our results highlight how the reorganization of functional subnetworks in individuals with ASD clarifies the mixture of hypo- and hyper-connectivity findings. Importantly, only the functional organization of the VTL subnetwork emerges as a marker of inter-individual similarities that co-vary with behavioral measures across all participants. These findings suggest a pivotal role of ventro-temporal and limbic systems in autism. Hum Brain Mapp, 2015. (c) 2015 Wiley Periodicals, Inc.
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9. Kim KC, Rhee J, Park JE, Lee DK, Choi CS, Kim JW, Lee HW, Song MR, Yoo HJ, Chung C, Shin CY. {{Overexpression of Telomerase Reverse Transcriptase Induces Autism-like Excitatory Phenotypes in Mice}}. {Molecular neurobiology}. 2015 Dec 22.
In addition to its classical role as a regulator of telomere length, recent reports suggest that telomerase reverse transcriptase (TERT) plays a role in the transcriptional regulation of gene expression such as beta-catenin-responsive pathways. Silencing or over-expression of TERT in cultured NPCs demonstrated that TERT induced glutamatergic neuronal differentiation. During embryonic brain development, expression of transcription factors involved in glutamatergic neuronal differentiation was increased in mice over-expressing TERT (TERT-tg mice). We observed increased expression of NMDA receptor subunits and phosphorylation of alpha-CaMKII in TERT-tg mice. TERT-tg mice showed autism spectrum disorder (ASD)-like behavioral phenotypes as well as lowered threshold against electrically induced seizure. Interestingly, the NMDA receptor antagonist memantine restored behavioral abnormalities in TERT-tg mice. Consistent with the alteration in excitatory/inhibitory (E/I) ratio, TERT-tg mice showed autism-like behaviors, abnormal synaptic organization, and function in mPFC suggesting the role of altered TERT activity in the manifestation of ASD, which is further supported by the significant association of certain SNPs in Korean ASD patients.
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10. Lee JA, Damianov A, Lin CH, Fontes M, Parikshak NN, Anderson ES, Geschwind DH, Black DL, Martin KC. {{Cytoplasmic Rbfox1 Regulates the Expression of Synaptic and Autism-Related Genes}}. {Neuron}. 2015 Dec 10.
Human genetic studies have identified the neuronal RNA binding protein, Rbfox1, as a candidate gene for autism spectrum disorders. While Rbfox1 functions as a splicing regulator in the nucleus, it is also alternatively spliced to produce cytoplasmic isoforms. To investigate the function of cytoplasmic Rbfox1, we knocked down Rbfox proteins in mouse neurons and rescued with cytoplasmic or nuclear Rbfox1. Transcriptome profiling showed that nuclear Rbfox1 rescued splicing changes, whereas cytoplasmic Rbfox1 rescued changes in mRNA levels. iCLIP-seq of subcellular fractions revealed that Rbfox1 bound predominantly to introns in nascent RNA, while cytoplasmic Rbox1 bound to 3′ UTRs. Cytoplasmic Rbfox1 binding increased target mRNA stability and translation, and Rbfox1 and miRNA binding sites overlapped significantly. Cytoplasmic Rbfox1 target mRNAs were enriched in genes involved in cortical development and autism. Our results uncover a new Rbfox1 regulatory network and highlight the importance of cytoplasmic RNA metabolism to cortical development and disease.
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11. Liew Z, Ritz B, Virk J, Olsen J. {{Maternal use of acetaminophen during pregnancy and risk of autism spectrum disorders in childhood: A Danish national birth cohort study}}. {Autism research : official journal of the International Society for Autism Research}. 2015 Dec 21.
Acetaminophen (paracetamol) is the most commonly used pain and fever medication during pregnancy. Previously, a positive ecological correlation between acetaminophen use and autism spectrum disorders (ASD) has been reported but evidence from larger studies based on prospective data is lacking. We followed 64,322 children and mothers enrolled in the Danish National Birth Cohort (DNBC; 1996-2002) for average 12.7 years to investigate whether acetaminophen use in pregnancy is associated with increased risk of ASD in the offspring. Information on acetaminophen use was collected prospectively from three computer-assisted telephone interviews. We used records from the Danish hospital and psychiatric registries to identify diagnoses of ASD. At the end of follow up, 1,027 (1.6%) children were diagnosed with ASD, 345 (0.5%) with infantile autism. We found that 31% of ASD (26% of infantile autism) have also been diagnosed with hyperkinetic disorders. More than 50% women reported ever using acetaminophen in pregnancy. We used Cox proportional hazards model to estimate hazard ratio (HR) and 95% confident interval (CI). Prenatal use of acetaminophen was associated with an increased risk of ASD accompanied by hyperkinetic symptoms (HR = 1.51 95% CI 1.19-1.92), but not with other ASD cases (HR = 1.06 95% CI 0.92-1.24). Longer duration of use (i.e., use for >20 weeks in gestation) increased the risk of ASD or infantile autism with hyperkinetic symptoms almost twofold. Maternal use of acetaminophen in pregnancy was associated with ASD with hyperkinetic symptoms only, suggesting acetaminophen exposure early in fetal life may specifically impact this hyperactive behavioral phenotype. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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12. Perez E, Ponce SD, Piccinini DJ, Lopez N, Valentinuzzi ME. {{Autism: Historic View and a Current Biomedical Engineering Approach}}. {IEEE pulse}. 2015 Sep-Oct;6(5):40-6.
13. Zhao S, Uono S, Yoshimura S, Toichi M. {{Is impaired joint attention present in non-clinical individuals with high autistic traits?}}. {Molecular autism}. 2015;6:67.
BACKGROUND: Joint attention skills are impaired in individuals with autism spectrum disorder (ASD). Recently, varying degrees of autistic social attention deficit have been detected in the general population. We investigated gaze-triggered attention in individuals with high and low levels of autistic traits under visual-auditory cross-modal conditions, which are more sensitive to social attention deficits than unimodal paradigms. METHODS: Sixty-six typically developing adults were divided into low- and high-autistic-trait groups according to scores on the autism-spectrum quotient (AQ) questionnaire. We examined gaze-triggered attention under visual-auditory cross-modal conditions. Two sounds (a social voice and a non-social tone) were manipulated as targets to infer the relationship between the cue and the target. Two types of stimulus onset asynchrony (SOA) conditions (a shorter 200-ms SOA and a longer 800-ms SOA) were used to directly test the effect of gaze cues on the detection of a sound target across different temporal intervals. RESULTS: Individuals with high autistic traits (high-AQ group) did not differ from those with low autistic traits (low-AQ group) with respect to gaze-triggered attention when voices or tones were used as targets under the shorter SOA condition. In contrast, under the longer SOA condition, gaze-triggered attention was not observed in response to tonal targets among individuals in the high-AQ group, whereas it was observed among individuals in the low-AQ group. The results demonstrated that cross-modal gaze-triggered attention is short-lived in individuals with high autistic traits. CONCLUSIONS: This finding provides insight into the cross-modal joint attention function among individuals along the autism spectrum from low autistic traits to ASD and may further our understanding of social behaviours among individuals at different places along the autistic trait continuum.
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14. Zhou Y, Kaiser T, Monteiro P, Zhang X, Van der Goes MS, Wang D, Barak B, Zeng M, Li C, Lu C, Wells M, Amaya A, Nguyen S, Lewis M, Sanjana N, Zhou Y, Zhang M, Zhang F, Fu Z, Feng G. {{Mice with Shank3 Mutations Associated with ASD and Schizophrenia Display Both Shared and Distinct Defects}}. {Neuron}. 2015 Dec 10.
Genetic studies have revealed significant overlaps of risk genes among psychiatric disorders. However, it is not clear how different mutations of the same gene contribute to different disorders. We characterized two lines of mutant mice with Shank3 mutations linked to ASD and schizophrenia. We found both shared and distinct synaptic and behavioral phenotypes. Mice with the ASD-linked InsG3680 mutation manifest striatal synaptic transmission defects before weaning age and impaired juvenile social interaction, coinciding with the early onset of ASD symptoms. On the other hand, adult mice carrying the schizophrenia-linked R1117X mutation show profound synaptic defects in prefrontal cortex and social dominance behavior. Furthermore, we found differential Shank3 mRNA stability and SHANK1/2 upregulation in these two lines. These data demonstrate that different alleles of the same gene may have distinct phenotypes at molecular, synaptic, and circuit levels in mice, which may inform exploration of these relationships in human patients.
