1. Baribeau DA, Anagnostou E. {{A Comparison of Neuroimaging Findings in Childhood Onset Schizophrenia and Autism Spectrum Disorder: A Review of the Literature}}. {Frontiers in psychiatry}. 2013;4:175.
Background: Autism spectrum disorder (ASD) and childhood onset schizophrenia (COS) are pediatric neurodevelopmental disorders associated with significant morbidity. Both conditions are thought to share an underlying genetic architecture. A comparison of neuroimaging findings across ASD and COS with a focus on altered neurodevelopmental trajectories can shed light on potential clinical biomarkers and may highlight an underlying etiopathogenesis. Methods: A comprehensive review of the medical literature was conducted to summarize neuroimaging data with respect to both conditions in terms of structural imaging (including volumetric analysis, cortical thickness and morphology, and region of interest studies), white matter analysis (include volumetric analysis and diffusion tensor imaging) and functional connectivity. Results: In ASD, a pattern of early brain overgrowth in the first few years of life is followed by dysmaturation in adolescence. Functional analyses have suggested impaired long-range connectivity as well as increased local and/or subcortical connectivity in this condition. In COS, deficits in cerebral volume, cortical thickness, and white matter maturation seem most pronounced in childhood and adolescence, and may level off in adulthood. Deficits in local connectivity, with increased long-range connectivity have been proposed, in keeping with exaggerated cortical thinning. Conclusion: The neuroimaging literature supports a neurodevelopmental origin of both ASD and COS and provides evidence for dynamic changes in both conditions that vary across space and time in the developing brain. Looking forward, imaging studies which capture the early post natal period, which are longitudinal and prospective, and which maximize the signal to noise ratio across heterogeneous conditions will be required to translate research findings into a clinical environment.
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2. Bryson SA, Ostmeyer KF. {{Increasing the Effectiveness of Community Mental Health Center Social Skills Groups for Children with Autism Spectrum Disorder: A Training and Consultation Example}}. {Administration and policy in mental health}. 2014 Jan 4.
The goal of this collaboration between a university and two community mental health (CMH) centers was to increase capacity among staff serving children with autism spectrum disorder (ASD) in usual care social skills groups. University researchers observed two usual care social skills groups in two sites; identified needs and strengths; delivered tailored trainings on behavioral management principles; and provided follow-up coaching. After training and coaching, CMH staff demonstrated significant gains in self-reported and observed behavioral management skills. Foundational education in behavior management may benefit successful implementation of ASD-specific evidence based practices in community settings.
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3. Chmielnicki E. {{Autism: Bacterial link to autistic behaviors}}. {Nature medicine}. 2014 Jan 7;20(1):28.
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4. Cuddapah VA, Pillai RB, Shekar KV, Lane JB, Motil KJ, Skinner SA, Tarquinio DC, Glaze DG, McGwin G, Kaufmann WE, Percy AK, Neul JL, Olsen ML. {{Methyl-CpG-binding protein 2 (MECP2) mutation type is associated with disease severity in Rett syndrome}}. {Journal of medical genetics}. 2014 Jan 7.
BACKGROUND: Rett syndrome (RTT), a neurodevelopmental disorder that primarily affects girls, is characterised by a period of apparently normal development until 6-18 months of age when motor and communication abilities regress. More than 95% of individuals with RTT have mutations in methyl-CpG-binding protein 2 (MECP2), whose protein product modulates gene transcription. Surprisingly, although the disorder is caused by mutations in a single gene, disease severity in affected individuals can be quite variable. To explore the source of this phenotypic variability, we propose that specific MECP2 mutations lead to different degrees of disease severity. METHODS: Using a database of 1052 participants assessed over 4940 unique visits, the largest cohort of both typical and atypical RTT patients studied to date, we examined the relationship between MECP2 mutation status and various phenotypic measures over time. RESULTS: In general agreement with previous studies, we found that particular mutations, such as p.Arg133Cys, p.Arg294X, p.Arg306Cys, 3 degrees truncations and other point mutations, were relatively less severe in both typical and atypical RTT. In contrast, p.Arg106Trp, p.Arg168X, p.Arg255X, p.Arg270X, splice sites, deletions, insertions and deletions were significantly more severe. We also demonstrated that, for most mutation types, clinical severity increases with age. Furthermore, of the clinical features of RTT, ambulation, hand use and age at onset of stereotypies are strongly linked to overall disease severity. CONCLUSIONS: We have confirmed that MECP2 mutation type is a strong predictor of disease severity. These data also indicate that clinical severity continues to become progressively worse regardless of initial severity. These findings will allow clinicians and families to anticipate and prepare better for the needs of individuals with RTT.
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5. Ionita-Laza I, Xu B, Makarov V, Buxbaum JD, Roos JL, Gogos JA, Karayiorgou M. {{Scan statistic-based analysis of exome sequencing data identifies FAN1 at 15q13.3 as a susceptibility gene for schizophrenia and autism}}. {Proceedings of the National Academy of Sciences of the United States of America}. 2014 Jan 7;111(1):343-8.
We used a family-based cluster detection approach designed to localize significant rare disease-risk variants clusters within a region of interest to systematically search for schizophrenia (SCZ) susceptibility genes within 49 genomic loci previously implicated by de novo copy number variants. Using two independent whole-exome sequencing family datasets and a follow-up autism spectrum disorder (ASD) case/control whole-exome sequencing dataset, we identified variants in one gene, Fanconi-associated nuclease 1 (FAN1), as being associated with both SCZ and ASD. FAN1 is located in a region on chromosome 15q13.3 implicated by a recurrent copy number variant, which predisposes to an array of psychiatric and neurodevelopmental phenotypes. In both SCZ and ASD datasets, rare nonsynonymous risk variants cluster significantly in affected individuals within a 20-kb window that spans several key functional domains of the gene. Our finding suggests that FAN1 is a key driver in the 15q13.3 locus for the associated psychiatric and neurodevelopmental phenotypes. FAN1 encodes a DNA repair enzyme, thus implicating abnormalities in DNA repair in the susceptibility to SCZ or ASD.
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6. Isong IA, Rao SR, Holifield C, Iannuzzi D, Hanson E, Ware J, Nelson LP. {{Addressing Dental Fear in Children With Autism Spectrum Disorders: A Randomized Controlled Pilot Study Using Electronic Screen Media}}. {Clinical pediatrics}. 2014 Jan 3.
Background. Dental care is a significant unmet health care need for children with autism spectrum disorders (ASD). Many children with ASD do not receive dental care because of fear associated with dental procedures; oftentimes they require general anesthesia for regular dental procedures, placing them at risk of associated complications. Many children with ASD have a strong preference for visual stimuli, particularly electronic screen media. The use of visual teaching materials is a fundamental principle in designing educational programs for children with ASD. Purpose. To determine if an innovative strategy using 2 types of electronic screen media was feasible and beneficial in reducing fear and uncooperative behaviors in children with ASD undergoing dental visits. Methods. We conducted a randomized controlled trial at Boston Children’s Hospital dental clinic. Eighty (80) children aged 7 to 17 years with a known diagnosis of ASD and history of dental fear were enrolled in the study. Each child completed 2 preventive dental visits that were scheduled 6 months apart (visit 1 and visit 2). After visit 1, subjects were randomly assigned to 1 of 4 groups: (1) group A, control (usual care); (2) group B, treatment (video peer modeling that involved watching a DVD recording of a typically developing child undergoing a dental visit); (3) group C, treatment (video goggles that involved watching a favorite movie during the dental visit using sunglass-style video eyewear); and (4) group D, treatment (video peer modeling plus video goggles). Subjects who refused or were unable to wear the goggles watched the movie using a handheld portable DVD player. During both visits, the subject’s level of anxiety and behavior were measured using the Venham Anxiety and Behavior Scales. Analyses of variance and Fisher’s exact tests compared baseline characteristics across groups. Using intention to treat approach, repeated measures analyses were employed to test whether the outcomes differed significantly: (1) between visits 1 and 2 within each group and (2) between each intervention group and the control group over time (an interaction). Results. Between visits 1 and 2, mean anxiety and behavior scores decreased significantly by 0.8 points (P = .03) for subjects within groups C and D. Significant changes were not observed within groups A and B. Mean anxiety and behavior scores did not differ significantly between groups over time, although group A versus C pairwise comparisons showed a trend toward significance (P = .06). Conclusion. These findings suggest that certain electronic screen media technologies may be useful tools for reducing fear and uncooperative behaviors among children with ASD undergoing dental visits. Further studies are needed to assess the efficacy of these strategies using larger sample sizes. Findings from future studies could be relevant for nondental providers who care for children with ASD in other medical settings.
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7. Kamio Y, Moriwaki A, Inada N. {{Utility of teacher-report assessments of autistic severity in Japanese school children}}. {Autism research and treatment}. 2013;2013:373240.
Recent studies suggest that many children with milder autism spectrum disorder (ASD) are undiagnosed, untreated, and being educated in mainstream classes without support and that school teachers might be the best persons to identify a child’s social deviance. At present, only a few screening measures using teacher ratings of ASD have been validated. The aim of this study was to examine the utility of teacher ratings on the Social Responsiveness Scale (SRS), a quantitative measure of ASD. We recruited 130 participants aged 4 to 17 years from local schools or local pediatric outpatient clinics specializing in neurodevelopmental disorders that included 70 children with ASD. We found that the teacher-report SRS can be reliably and validly applied to children as a screening tool or for other research purposes, and it also has cross-cultural comparability. Although parent-teacher agreement was satisfactory overall, a discrepancy existed for children with ASD, especially for girls with ASD. To improve sensitivity in children at higher risk, especially girls, we cannot overstate the importance of using standardized norms specific to gender, informant, and culture.
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8. Krumm N, O’Roak BJ, Shendure J, Eichler EE. {{A de novo convergence of autism genetics and molecular neuroscience}}. {Trends in neurosciences}. 2013 Dec 30.
Autism spectrum disorder (ASD) and intellectual disability (ID) are neurodevelopmental disorders with large genetic components, but identification of pathogenic genes has proceeded slowly because hundreds of loci are involved. New exome sequencing technology has identified novel rare variants and has found that sporadic cases of ASD/ID are enriched for disruptive de novo mutations. Targeted large-scale resequencing studies have confirmed the significance of specific loci, including chromodomain helicase DNA binding protein 8 (CHD8), sodium channel, voltage-gated, type II, alpha subunit (SCN2A), dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), and catenin (cadherin-associated protein), beta 1, 88kDa (CTNNB1, beta-catenin). We review recent studies and suggest that they have led to a convergence on three functional pathways: (i) chromatin remodeling; (ii) wnt signaling during development; and (iii) synaptic function. These pathways and genes significantly expand the neurobiological targets for study, and suggest a path for future genetic and functional studies.
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9. Ma Y, Wang C, Li B, Qin L, Su J, Yang M, He S. {{Bcl-2-associated transcription factor 1 interacts with fragile X-related protein 1}}. {Acta biochimica et biophysica Sinica}. 2014 Jan 3.
The absence of fragile X mental retardation protein (FMRP) causes fragile X syndrome (FXS), which is the leading cause of hereditary mental retardation. Fragile X-related protein 1 (FXR1P), which plays an important role in normal muscle development, is one of the two autosomal paralogs of FMRP. To understand the functions of FXR1P, we screened FXR1P-interacting proteins by using a yeast two-hybrid system. The fragile X-related gene 1 (FXR1) was fused to pGBKT7 and then used as the bait to screen the human fetal brain cDNA library. The screening results revealed 10 FXR1P-interacting proteins including Bcl-2-associated transcription factor 1 (BTF). The interaction between FXR1P and BTF was confirmed by using both beta-galactosidase assay and growth test in selective media. Co-immunoprecipitation assay in mammalian cells was also carried out to confirm the FXR1P/BTF interaction. Moreover, we confirmed that BTF co-localized with FXR1P in the cytoplasm around the nucleus in rat vascular smooth muscle cells by using confocal fluorescence microscopy. These results provide clues to elucidate the relationship between FXR1P and FXS.
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10. Piras I, Haapanen L, Napolioni V, Sacco R, Van de Water J, Persico A. {{Anti-brain antibodies are associated with more severe cognitive and behavioral profiles in Italian children with Autism Spectrum Disorder}}. {Brain, behavior, and immunity}. 2014 Jan 2.
Circulating 45 and 62 kDa antibodies targeting the cerebellum were previously associated with Autism Spectrum Disorder (ASD), lower adaptive/cognitive function and aberrant behaviors. Moreover, 37, 39 and 73 kDa maternal antibodies (mAb) targeting the fetal brain were previously correlated with broad autism spectrum, irritability, abnormal brain enlargement and impaired expressive language. The present study aims towards clinically characterizing individuals with brain-targeted IgG and/or exposed to maternal antibrain antibodies in a large sample of Italian autistic children (N = 355), their unaffected siblings (N = 142) and mothers (N=333). The presence of patient- and mother-produced anti-brain antibodies does not confer increased risk of autism within the same sibship. However, the 45 and 62 kDa antibodies are correlated with autism severity: the 45 kDa Ab is associated with cognitive impairment and lower scores at the Vineland Adaptive Behavior Scales, the 62 kDa Ab with motor stereotypies, while both correlate with larger head circumference (all P<0.05). On the other hand, maternal 37, 39 and 73 kDa antibrain antibodies, either alone or in combination, are correlated with impaired verbal and non-verbal language development, neurodevelopmental delay and sleep/wake cycle disturbances in their autistic children (P<0.05). Presence of the 62 kDa autoAb in the child is significantly associated with presence of the 39 and/or 73 kDa antibodies in his/her mother. Our results confirm and extend previous observations in an ethnically distinct sample, providing further evidence of a pathomorphic role for anti-brain antibodies in autism while demonstrating their familial clustering.
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11. Samms-Vaughan ME. {{The status of early identification and early intervention in autism spectrum disorders in lower- and middle-income countries}}. {International journal of speech-language pathology}. 2014 Jan 7.
There is limited information on autism spectrum disorders from lower- and middle-income countries (LMIC). This paper reviews the status of early identification and early intervention for autism spectrum disorders in response to the article by Camarata (2014) . The PubMed database was searched to identify relevant epidemiological studies from LMIC. Seven studies from five countries were identified: Colombia, India, Jamaica, Jordan, and Mexico. The mean age of parental concern, at 21-24 months, and mean age of diagnosis, at 45-57 months, were similar in LMIC, but later than in high-income countries. Both country groups reported language disorder to be the symptom of initial concern. Similarities in biological aspects of the disorders were noted across LMIC and high-income countries. Comparable ages of identification and diagnosis across vastly different LMIC suggest limited resources to be the underlying contributory factor. Recommendations for improving early identification and intervention made by researchers in the LMIC are reported.
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12. Thiemann-Bourque K. {{Peer-Mediated AAC Instruction for Young Children with Autism and other Developmental Disabilities}}. {Perspectives on augmentative and alternative communication}. 2012 Dec;21(4).
Many young children with developmental disabilities (DD) have significant delays in social, communication, and play skills. For those children learning to use augmentative and alternative communication (.AAC% successful social interactions with peers will require explicit instruction on the same system for both communication partners. Peer-mediated (PM) interventions are recommended best practice based on more than 30 years of research with young children with autism and other DDs. Integrating direct AAC instruction within PM programs to advance social reciprocity in typical preschool routines is a necessary and important next step for young AAC users. In this article, I will summarize the design and outcomes of two PM AAC studies documenting positive social outcomes for preschool children with severe autism. I will also teach} peer partners how to use AAC highlight strategies to recruit peers without disabilities systems (e.g., Picture Exchange Communication System [PECS], Speech Generating Devices [SGDs]), and engineer the preschool classroom for successful AAC communication. I will describe data collection procedures for measuring changes in reciprocal child and peer social communication interactions.
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13. Thiemann-Bourque KS. {{Instruction using the Picture Exchange Communication Systems (PECS) appears to enhance generalization of communication skills among children with autism in comparison to Responsive Education and Prelinguistic Milieu Teaching (RPMT)}}. {Evidence-based communication assessment and intervention}. 2010;4(4).
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14. Tomlinson M, Yasamy MT, Emerson E, Officer A, Richler D, Saxena S. {{Setting global research priorities for developmental disabilities, including intellectual disabilities and autism}}. {Journal of intellectual disability research : JIDR}. 2014 Jan 7.
OBJECTIVES: The prevalence of intellectual disabilities (ID) has been estimated at 10.4/1000 worldwide with higher rates among children and adolescents in lower income countries. The objective of this paper is to address research priorities for development disabilities, notably ID and autism, at the global level and to propose the more rational use of scarce funds in addressing this under-investigated area. METHODS: An expert group was identified and invited to systematically list and score research questions. They applied the priority setting methodology of the Child Health and Nutrition Research Initiative (CHNRI) to generate research questions and to evaluate them using a set of five criteria: answerability, feasibility, applicability and impact, support within the context and equity. FINDINGS: The results of this process clearly indicated that the important priorities for future research related to the need for effective and efficient approaches to early intervention, empowerment of families supporting a person with developmental disability and to address preventable causes of poor health in people with ID and autism. CONCLUSIONS: For the public health and other systems to become more effective in delivering appropriate support to persons with developmental disabilities, greater (and more targeted) investment in research is required to produce evidence of what works consistent with international human rights standards.
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15. Waterhouse L, Gillberg C. {{Why Autism Must be Taken Apart}}. {J Autism Dev Disord}. 2014 Jan 4.
Although accumulated evidence has demonstrated that autism is found with many varied brain dysfunctions, researchers have tried to find a single brain dysfunction that would provide neurobiological validity for autism. However, unitary models of autism brain dysfunction have not adequately addressed conflicting evidence, and efforts to find a single unifying brain dysfunction have led the field away from research to explore individual variation and micro-subgroups. Autism must be taken apart in order to find neurobiological treatment targets. Three research changes are needed. The belief that there is a single defining autism spectrum disorder brain dysfunction must be relinquished. The noise caused by the thorny brain-symptom inference problem must be reduced. Researchers must explore individual variation in brain measures within autism.
