1. Tabet R, Moutin E, Becker JA, Heintz D, Fouillen L, Flatter E, Krezel W, Alunni V, Koebel P, Dembele D, Tassone F, Bardoni B, Mandel JL, Vitale N, Muller D, Le Merrer J, Moine H. {{Fragile X Mental Retardation Protein (FMRP) controls diacylglycerol kinase activity in neurons}}. {Proc Natl Acad Sci U S A};2016 (May 27)
Fragile X syndrome (FXS) is caused by the absence of the Fragile X Mental Retardation Protein (FMRP) in neurons. In the mouse, the lack of FMRP is associated with an excessive translation of hundreds of neuronal proteins, notably including postsynaptic proteins. This local protein synthesis deregulation is proposed to underlie the observed defects of glutamatergic synapse maturation and function and to affect preferentially the hundreds of mRNA species that were reported to bind to FMRP. How FMRP impacts synaptic protein translation and which mRNAs are most important for the pathology remain unclear. Here we show by cross-linking immunoprecipitation in cortical neurons that FMRP is mostly associated with one unique mRNA: diacylglycerol kinase kappa (Dgkkappa), a master regulator that controls the switch between diacylglycerol and phosphatidic acid signaling pathways. The absence of FMRP in neurons abolishes group 1 metabotropic glutamate receptor-dependent DGK activity combined with a loss of Dgkkappa expression. The reduction of Dgkkappa in neurons is sufficient to cause dendritic spine abnormalities, synaptic plasticity alterations, and behavior disorders similar to those observed in the FXS mouse model. Overexpression of Dgkkappa in neurons is able to rescue the dendritic spine defects of the Fragile X Mental Retardation 1 gene KO neurons. Together, these data suggest that Dgkkappa deregulation contributes to FXS pathology and support a model where FMRP, by controlling the translation of Dgkkappa, indirectly controls synaptic proteins translation and membrane properties by impacting lipid signaling in dendritic spine.
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2. Rapp JT, Gunby K. {{Task interspersal for individuals with autism and other neurodevelopmental disorders}}. {J Appl Behav Anal};2016 (May 27)
This paper reviews recent studies on task interspersal (TI) for increasing skill acquisition in children who have been diagnosed with autism spectrum disorders and other neurodevelopmental disorders. We highlight some limitations of these studies and provide specific recommendations for future research on TI procedures.
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3. Parletta N, Niyonsenga T, Duff J. {{Omega-3 and Omega-6 Polyunsaturated Fatty Acid Levels and Correlations with Symptoms in Children with Attention Deficit Hyperactivity Disorder, Autistic Spectrum Disorder and Typically Developing Controls}}. {PLoS One};2016;11(5):e0156432.
BACKGROUND: There is evidence that children with Attention Deficit Hyperactivity Disorder (ADHD) and Autistic Spectrum Disorder (ASD) have lower omega-3 polyunsaturated fatty acid (n-3 PUFA) levels compared with controls and conflicting evidence regarding omega-6 (n-6) PUFA levels. OBJECTIVES: This study investigated whether erythrocyte n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were lower and n-6 PUFA arachidonic acid (AA) higher in children with ADHD, ASD and controls, and whether lower n-3 and higher n-6 PUFAs correlated with poorer scores on the Australian Twin Behaviour Rating Scale (ATBRS; ADHD symptoms) and Test of Variable Attention (TOVA) in children with ADHD, and Childhood Autism Rating Scale (CARS) in children with ASD. METHODS: Assessments and blood samples of 565 children aged 3-17 years with ADHD (n = 401), ASD (n = 85) or controls (n = 79) were analysed. One-way ANOVAs with Tukey’s post-hoc analysis investigated differences in PUFA levels between groups and Pearson’s correlations investigated correlations between PUFA levels and ATBRS, TOVA and CARS scores. RESULTS: Children with ADHD and ASD had lower DHA, EPA and AA, higher AA/EPA ratio and lower n-3/n-6 than controls (P<0.001 except AA between ADHD and controls: P = 0.047). Children with ASD had lower DHA, EPA and AA than children with ADHD (P<0.001 for all comparisons). ATBRS scores correlated negatively with EPA (r = -.294, P<0.001), DHA (r = -.424, P<0.001), n-3/n-6 (r = -.477, P<0.001) and positively with AA/EPA (r = .222, P <.01). TOVA scores correlated positively with DHA (r = .610, P<0.001), EPA (r = .418, P<0.001) AA (r = .199, P<0.001), and n-3/n-6 (r = .509, P<0.001) and negatively with AA/EPA (r = -.243, P<0.001). CARS scores correlated significantly with DHA (r = .328, P = 0.002), EPA (r = -.225, P = 0.038) and AA (r = .251, P = 0.021). CONCLUSIONS: Children with ADHD and ASD had low levels of EPA, DHA and AA and high ratio of n-6/n-3 PUFAs and these correlated significantly with symptoms. Future research should further investigate abnormal fatty acid metabolism in these disorders. Lien vers le texte intégral (Open Access ou abonnement)
4. Mevel K, Fransson P. {{The functional brain connectome of the child and autism spectrum disorders}}. {Acta Paediatr};2016 (May 26)
Brain connectomics is a relatively new field of research that maps the brain’s large-scale structural and functional networks at rest. The connectome of the human brain develops progressively from early infancy to late adolescence and this review describes the theory behind the concept and its applicability to studying the development and dynamics of brain networks through graph-theoretical metrics. We also describe how the brain connectome concept could further our understanding of autism spectrum disorders (ASD). CONCLUSION: Further research into the functional child brain connectome concept could enhance our understanding of atypical brain connectivity patterns presumed to be linked to ASD. This article is protected by copyright. All rights reserved.
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5. Manor-Binyamini I, Nator M. {{Parental coping with adolescent developmental disabilities in terms of stress, sense of coherence and hope within the Druze community of Israel}}. {Res Dev Disabil};2016 (May 23);55:358-367.
BACKGROUND: Many studies have examined the coping resources of parents of children with disabilities but most have involved Western families and only a few refer to unique and traditional cultures. AIM: This study sought to compare Druze parents of adolescents with and without developmental disabilities (DD) in the context of Druze traditions and beliefs and whether they may lead to better coping by parents of a child with DD. The study used the measures of stress; sense of coherence (SOC) – an orientation towards the world which reflects an ongoing confidence that things fall into place in a logical and meaningful way; and hope. METHODS AND PROCEDURES: The sample group consisted of 99 Druze parents of adolescents with and without DD enrolled in regular and special schools in Israel. The parents were asked to complete four questionnaires on demography, stress, SOC (Sense of coherence) and hope. OUTCOMES AND RESULTS: The research findings indicate a higher sense of parental stress and a lower overall SOC, particularly meaningfulness, and hope among parents of adolescents with DD. There was no difference between the two groups of parents with respect to marital, economic and overall stress or in the other two components of SOC. CONCLUSIONS AND IMPLICATIONS: The results of the study partly contradict the assumption in the limited literature about Druze that they may cope better with life stressors as a result of their traditions and beliefs. The results also indicate the need for further research and culturally-based intervention programs.
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6. Lee JS, Yoo Y, Lim BC, Kim KJ, Song J, Choi M, Chae JH. {{GM3 synthase deficiency due to ST3GAL5 variants in two Korean female siblings: Masquerading as Rett syndrome-like phenotype}}. {Am J Med Genet A};2016 (May 27)
There have been a few reports of GM3 synthase deficiency since the disease of the ganglioside biosynthetic pathway was first reported in 2004. It is characterized by infantile-onset epilepsy with severe intellectual disability, blindness, cutaneous dyspigmentation, and choreoathetosis. Here we report the cases of two Korean female siblings with ST3GAL5 variants, who presented with a Rett-like phenotype. They had delayed speech, hand stereotypies with a loss of purposeful hand movements, and choreoathetosis, but no clinical seizures. One of them had microcephaly, while the other had small head circumference less than 10th centile. There were no abnormal laboratory findings with the exception of a high lactate level. MECP2/CDKL5/FOXG1 genetic tests with an array comparative genomic hybridization revealed no molecular defects. Through whole-exome sequencing of the proband, we found compound heterozygous ST3GAL5 variants (p.Gly201Arg and p.Cys195Ser), both of which were novel. The siblings were the same compound heterozygotes and their unaffected parents were heterozygous carriers of each variant. Liquid chromatography-mass spectrometry analysis confirmed a low level of GM3 and its downstream metabolites, indicating GM3 synthase deficiency. These cases expanded the clinical and genetic spectrum of the ultra-rare disease, GM3 synthase deficiency with ST3GAL5 variants. (c) 2016 Wiley Periodicals, Inc.
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7. Koski S, Gabriels RL, Beresford C. {{Interventions for paediatric surgery patients with comorbid autism spectrum disorder: a systematic literature review}}. {Arch Dis Child};2016 (May 25)
AIMS: To survey perioperative management practices for paediatric patients diagnosed with autism spectrum disorder (ASD). METHODS: A systematic review was carried out of empirical studies and case reports published in peer-reviewed journals of current best practices and behavioural interventions for paediatric patients with ASD who had undergone surgery. RESULTS: The final sample included 11 articles published between 1997 and 2016 that met broad inclusion criteria of surveying perioperative interventions for the ASD population. There is broad endorsement across the scant publications on this topic of the following practices: increased attention to individual patient needs, rehearsal and other desensitisation efforts, departure from a sole focus on sedation or restraint of the combative or uncooperative patient and engaging caregivers in tuning perioperative management to individual needs. CONCLUSIONS: This review supports the need for an individualised structure and approach to the perioperative care of these unique patients.
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8. Kilincaslan A, Mutluer TD, Pasabeyoglu B, Tutkunkardas MD, Mukaddes NM. {{Effects of Atomoxetine in Individuals with Attention-Deficit/Hyperactivity Disorder and Low-Functioning Autism Spectrum Disorder}}. {J Child Adolesc Psychopharmacol};2016 (May 26)
OBJECTIVES: This naturalistic, retrospective study investigated the effects of atomoxetine (ATX) on attention-deficit/hyperactivity disorder (ADHD) symptoms and autistic features in children with autism spectrum disorders (ASDs) and intellectual disability (ID). METHODS: Participants (n = 37, age range 6-17 years, mean: 10.16 +/- 3.60) were assessed at baseline, 4th and 12th weeks using Clinical Global Impressions (CGI) scales, DSM-IV-based ADHD-rating scale (ADHD-RS), and amended Turkish version of Aberrant Behavior Checklist (ABC). The primary outcome measure was a treatment response defined by a CGI-improvement score of 1 or 2 together with a decrease of at least 25% in the parent-rated ADHD-RS total score at the end of 12th week. RESULTS: Five patients (13.5%) stopped medication at 4 weeks due to ineffectivity (2) and intolerable side effects (increased motor activity and talkativeness [n = 1], irritability [n = 2], temper outbursts [n = 2], and increased blood pressure [n = 1]). Sixteen patients (43.2%) were judged to be responders according to primary outcome measure. Improvement rate on CGI scale was 48.8%. On ADHD-RS, there were significant reductions between baseline and 4th week and between baseline and 12th week in both hyperactivity and inattention, and between baseline and 12th week in impulsivity scores. Decrease was significant in hyperactivity and social withdrawal subscales of the parent-reported ABC. Responders based on primary outcome measure were not significantly different from nonresponders in terms of sociodemographic features or clinical parameters, including intellectual, language, autism symptom, and ADHD symptom levels. CONCLUSION: In this chart review, ATX appears to be safe and effective for social withdrawal and ADHD symptoms in children with ASD and ID.
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9. Dougherty CC, Evans DW, Katuwal GJ, Michael AM. {{Asymmetry of fusiform structure in autism spectrum disorder: trajectory and association with symptom severity}}. {Mol Autism};2016;7:28.
BACKGROUND: While asymmetry in the fusiform gyrus (FFG) has been reported in functional and structural studies in typically developing controls (TDC), few studies have examined FFG asymmetry in autism spectrum disorder (ASD) subjects and those studies are limited by small sample sizes, and confounded by cognitive ability or handedness. No previous work has examined FFG surface area or cortical thickness asymmetry in ASD; nor do we understand the trajectory of FFG asymmetry over time. Finally, it is not known how FFG structural asymmetry relates to ASD symptom severity. METHODS: In this study, we examined FFG volume, surface area, and cortical thickness asymmetry, as well as their cross-sectional trajectories in a large sample of right-handed males aged 7 to 25 years with 128 ASD and 127 TDC subjects using general linear models. In addition, we examined the relationship between FFG asymmetry and ASD severity using the Autism Diagnostic Observation Schedule (ADOS) and Gotham autism severity scores. RESULTS: Findings revealed that while group differences were evident with mean leftward asymmetry in ASD and mean near symmetry in TDC volume and surface area, asymmetry for both groups existed on a spectrum encompassing leftward and rightward asymmetry. In ASD subjects, volume asymmetry was negatively associated with ADOS and autism severity score symptom measures, with a subset of rightward asymmetric patients being most severely affected. We also observed differential trajectory of surface area asymmetry: ASD subjects exhibited a change from leftward asymmetry toward symmetry from age 7 to 25, whereas TDCs exhibited the reverse trend with a change from near symmetry toward leftward symmetry over the observed age range. CONCLUSIONS: Abnormalities in FFG structural asymmetry are related to symptom severity in ASD and show differential developmental trajectory compared to TDC. This study is the first to note these findings. These results may have important implications for understanding the role of FFG asymmetry in ASD.
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10. Cariveau T, Kodak T, Campbell V. {{The effects of intertrial interval and instructional format on skill acquisition and maintenance for children with autism spectrum disorders}}. {J Appl Behav Anal};2016 (May 26)
We replicated and extended the study by Koegel, Dunlap, and Dyer (1980) by examining the effects of 3 intertrial-interval (ITI) durations on skill acquisition in 2 children with autism spectrum disorders. Specifically, we compared the effect of short (2 s), progressive (2 s to 20 s), and long (20 s) ITIs on participants’ mastery of tacts or intraverbals presented in massed-trial and varied-trial instructional formats. We also measured (a) stereotypic and problem behavior during the ITI, (b) maintenance of skills, and (c) responding to novel adults and settings. Results showed that short ITIs in a varied-trial format produced the most efficient acquisition of skills; however, most ITI durations produced more efficient skill acquisition in a varied format compared to a massed format. The trial format and ITI duration associated with the lowest levels of stereotypic and problem behavior during the ITI and responding during maintenance and novel adult and setting probes differed across participants.
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11. Bourke J, de Klerk N, Smith T, Leonard H. {{Population-Based Prevalence of Intellectual Disability and Autism Spectrum Disorders in Western Australia: A Comparison With Previous Estimates}}. {Medicine (Baltimore)};2016 (May);95(21):e3737.
To investigate the prevalence of intellectual disability (ID) and/or autism spectrum disorders (ASDs) in Western Australia (WA).A cohort of children born from 1983 to 2010 in WA with an ID and/or ASD were identified using the population-based IDEA (Intellectual Disability Exploring Answers) database, which ascertains cases through the Disability Services Commission (DSC) as well as education sources. Information on race, gender, mother’s residence at birth and deaths was obtained through linkage to the Midwives Notification System and the Mortality Register. Diagnostic information on the cause of ID was obtained through review of medical records where available and children were classified as biomedical cause, ASD, or unknown cause.An overall prevalence of ID of 17.0/1000 livebirths (95% CI: 16.7, 17.4) showed an increase from the 10-year previous prevalence of 14.3/1000. The prevalence for mild or moderate ID was 15.0 (95% CI: 14.6, 15.3), severe ID was 1.2 (95% CI: 1.1, 1.3), and unknown level of ID was 0.9 (95% CI: 0.8, 1.0)/1000 livebirths. The prevalence for Aboriginal children was 39.0/1000 compared with 15.7/1000 for non-Aboriginal children, giving a prevalence ratio of 2.5 (95% CI: 2.4, 2.6). Prevalence of all ASD was 5.1/1000 of which 3.8/1000 had ASD and ID.The prevalence of ID has risen in WA over the last 10 years with most of this increase due to mild or moderate ID. Whilst the prevalence of ASD has also increased over this time this does not fully explain the observed increase. Aboriginal children are at a 2.5-fold risk of ID but are less likely to be accessing disability services.
