1. Begeer S, Fink E, van der Meijden S, Goossens F, Olthof T. {{Bullying-related behaviour in a mainstream high school versus a high school for autism: Self-report and peer-report}}. {Autism};2015 (Aug 3)
This study examined the frequency of bullying, victimisation and defending behaviours among children with autism spectrum disorder and normal intelligence, using both self-report and peer-report information. Peer-report and self-report data were collected on a single classroom of 26 early adolescent boys attending a special school for children with autism and compared with 23 typically developing boys attending a single mainstream secondary school. Results showed that self- and peer-reported bully and victimisation rates did not differ between boys with autism spectrum disorder and typically developing boys. However, self-reported defending behaviour was less likely to be reported by boys in the autism spectrum disorder school compared to boys in the mainstream school, although there was no such difference for peer-reported defending.
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2. Burket JA, Benson AD, Green TL, Rook JM, Lindsley CW, Conn PJ, Deutsch SI. {{Effects of VU0410120, a novel GlyT1 inhibitor, on measures of sociability, cognition and stereotypic behaviors in a mouse model of autism}}. {Prog Neuropsychopharmacol Biol Psychiatry};2015 (Aug 3);61:10-17.
The NMDA receptor is a highly regulated glutamate-gated cationic channel receptor that has an important role in the regulation of sociability and cognition. The genetically-inbred Balb/c mouse has altered endogenous tone of NMDA receptor-mediated neurotransmission and is a model of impaired sociability, relevant to Autism Spectrum Disorders (ASDs). Because glycine is an obligatory co-agonist that works cooperatively with glutamate to promote opening of the ion channel, one prominent strategy to promote NMDA receptor-mediated neurotransmission involves inhibition of the glycine type 1 transporter (GlyT1). The current study evaluated the dose-dependent effects of VU0410120, a selective, high-affinity competitive GlyT1 inhibitor, on measures of sociability, cognition and stereotypic behaviors in Balb/c and Swiss Webster mice. The data show that doses of VU0410120 (i.e., 18 and 30mg/kg) that improve measures of sociability and spatial working memory in the Balb/c mouse strain elicit intense stereotypic behaviors in the Swiss Webster comparator strain (i.e., burrowing and jumping). Furthermore, the data suggest that selective GlyT1 inhibition improves sociability and spatial working memory at doses that do not worsen or elicit stereotypic behaviors in a social situation in the Balb/c strain. However, the elicitation of stereotypic behaviors in the Swiss Webster comparator strain at therapeutically relevant doses of VU0410120 suggest that genetic factors (i.e., mouse strain differences) influence sensitivity to GlyT1-elicited stereotypic behaviors, and emergence of intense stereotypic behaviors may be dose-limiting side effects of this interventional strategy.
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3. Divan G, Hamdani SU, Vajartkar V, Minhas A, Taylor C, Aldred C, Leadbitter K, Rahman A, Green J, Patel V. {{Adapting an evidence-based intervention for autism spectrum disorder for scaling up in resource-constrained settings: the development of the PASS intervention in South Asia}}. {Glob Health Action};2015;8:27278.
BACKGROUND: Evidence-based interventions for autism spectrum disorders evaluated in high-income countries typically require highly specialised manpower, which is a scarce resource in most low- and middle-income settings. This resource limitation results in most children not having access to evidence-based interventions. OBJECTIVE: This paper reports on the systematic adaptation of an evidence-based intervention, the Preschool Autism Communication Therapy (PACT) evaluated in a large trial in the United Kingdom for delivery in a low-resource setting through the process of task-shifting. DESIGN: The adaptation process used the Medical Research Council framework for the development and adaptation of complex interventions, focusing on qualitative methods and case series and was conducted simultaneously in India and Pakistan. RESULTS: The original intervention delivered by speech and language therapists in a high-resource setting required adaptation in some aspects of its content and delivery to enhance contextual acceptability and to enable the intervention to be delivered by non-specialists. CONCLUSIONS: The resulting intervention, the Parent-mediated intervention for Autism Spectrum Disorder in South Asia (PASS), shares the core theoretical foundations of the original PACT but is adapted in several respects to enhance its acceptability, feasibility, and scalability in low-resource settings.
4. Dyer O. {{Rise in US autism cases is mostly due to changes in diagnosis, study claims}}. {BMJ};2015;351:h4209.
5. Krishnan N, Krishnan K, Connors CR, Choy MS, Page R, Peti W, Van Aelst L, Shea SD, Tonks NK. {{PTP1B inhibition suggests a therapeutic strategy for Rett syndrome}}. {J Clin Invest};2015 (Aug 3);125(8):3163-3177.
The X-linked neurological disorder Rett syndrome (RTT) presents with autistic features and is caused primarily by mutations in a transcriptional regulator, methyl CpG-binding protein 2 (MECP2). Current treatment options for RTT are limited to alleviating some neurological symptoms; hence, more effective therapeutic strategies are needed. We identified the protein tyrosine phosphatase PTP1B as a therapeutic candidate for treatment of RTT. We demonstrated that the PTPN1 gene, which encodes PTP1B, was a target of MECP2 and that disruption of MECP2 function was associated with increased levels of PTP1B in RTT models. Pharmacological inhibition of PTP1B ameliorated the effects of MECP2 disruption in mouse models of RTT, including improved survival in young male (Mecp2-/y) mice and improved behavior in female heterozygous (Mecp2-/+) mice. We demonstrated that PTP1B was a negative regulator of tyrosine phosphorylation of the tyrosine kinase TRKB, the receptor for brain-derived neurotrophic factor (BDNF). Therefore, the elevated PTP1B that accompanies disruption of MECP2 function in RTT represents a barrier to BDNF signaling. Inhibition of PTP1B led to increased tyrosine phosphorylation of TRKB in the brain, which would augment BDNF signaling. This study presents PTP1B as a mechanism-based therapeutic target for RTT, validating a unique strategy for treating the disease by modifying signal transduction pathways with small-molecule drugs.
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6. Small DM, Pelphrey KA. {{Autism Spectrum Disorder: Sniffing Out a New Biomarker}}. {Curr Biol};2015 (Aug 3);25(15):R674-676.
Early intervention improves prognosis in autism spectrum disorder, yet diagnosis is very difficult in preverbal children. A new study demonstrates that the automatic adjustments in sniffing patterns to pleasant and unpleasant odors may provide a window into early diagnosis.
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7. Tautz L. {{PTP1B: a new therapeutic target for Rett syndrome}}. {J Clin Invest};2015 (Aug 3);125(8):2931-2934.
Rett syndrome (RTT) is an X-linked neurodevelopmental disorder that is characterized by successive loss of acquired cognitive, social, and motor skills and development of autistic behavior. RTT affects approximately 1 in 10,000 live female births and is the second most common cause of severe mental retardation in females, after Down syndrome. Currently, there is no cure or effective therapy for RTT. Approved treatment regimens are presently limited to supportive management of specific physical and mental disabilities. In this issue, Krishnan and colleagues reveal that the protein tyrosine phosphatase PTP1B is upregulated in patients with RTT and in murine models and provide strong evidence that targeting PTP1B has potential as a viable therapeutic strategy for the treatment of RTT.
