1. Akechi H, Kikuchi Y, Tojo Y, Osanai H, Hasegawa T. {{Brief Report: Pointing Cues Facilitate Word Learning in Children with Autism Spectrum Disorder}}. {J Autism Dev Disord};2012 (May 30)
Children with autism spectrum disorder (ASD) reportedly have difficulty associating novel words to an object via the speaker’s gaze. It has also been suggested that their performance is related to their gaze duration on the object and improves when the object moves and becomes more salient. However, there is a possibility that they have only relied on the object’s movement and have not referenced the speaker’s cue (i.e. gaze direction). The current study with children with ASD and typically developing children aged 6-11 years demonstrated that adding another speaker’s cue (i.e. pointing) improves the performance of children with ASD. This suggests that additional speaker’s cues may help referential word learning in children with ASD.
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2. Liu J, Koscielska KA, Cao Z, Hulsizer S, Grace N, Mitchell G, Nacey C, Githinji J, McGee J, Garcia-Arocena D, Hagerman RJ, Nolta J, Pessah IN, Hagerman PJ. {{Signaling defects in iPSC-derived fragile X premutation neurons}}. {Hum Mol Genet};2012 (May 28)
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a leading monogenic, neurodegenerative disorder affecting premutation carriers of the fragile X (FMR1) gene. To investigate the underlying cellular neuropathology, we produced iPSC-derived neurons from isogenic subclones of primary fibroblasts of a female premutation carrier; with each subclone bearing exclusively either the normal or the expanded (premutation) form of the FMR1 gene as the active allele. We show that neurons harboring the stably-active, expanded allele (EX-Xa) have reduced PSD95 protein expression, reduced synaptic puncta density, and reduced neurite length. Importantly, such neurons are also functionally abnormal, with calcium transients of higher amplitude and increased frequency than for neurons harboring the normal-active allele. Moreover, sustained calcium elevation was found in the EX-Xa neurons after glutamate application. By excluding the individual genetic background variation, we have demonstrated neuronal phenotypes directly linked to the FMR1 premutation. Our approach represents a unique isogenic, X-chromosomal epigenetic model to aid the development of targeted therapeutics for FXTAS, and more broadly as a model for the study of common neurodevelopmental (e.g., autism) and neurodegenerative (e.g., Parkinsonism; dementias) disorders.
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3. Ruble L, Birdwhistell J, Toland MD, McGrew JH. {{Analysis of Parent, Teacher, and Consultant Speech Exchanges and Educational Outcomes of Students With Autism During COMPASS Consultation}}. {J Educ Psychol Consult};2011;21(4):259-283.
The significant increase in the numbers of students with autism combined with the need for better trained teachers (National Research Council, 2001) call for research on the effectiveness of alternative methods, such as consultation, that have the potential to improve service delivery. Data from 2 randomized controlled single-blind trials indicate that an autism-specific consultation planning framework known as the collaborative model for promoting competence and success (COMPASS) is effective in increasing child Individual Education Programs (IEP) outcomes (Ruble, Dal-rymple, & McGrew, 2010; Ruble, McGrew, & Toland, 2011). In this study, we describe the verbal interactions, defined as speech acts and speech act exchanges that take place during COMPASS consultation, and examine the associations between speech exchanges and child outcomes. We applied the Psychosocial Processes Coding Scheme (Leaper, 1991) to code speech acts. Speech act exchanges were overwhelmingly affiliative, failed to show statistically significant relationships with child IEP outcomes and teacher adherence, but did correlate positively with IEP quality.
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4. Wong JD, Seltzer MM, Greenberg JS, Hong J, Almeida DM, Coe CL. {{Stressful life events and daily stressors affect awakening cortisol level in midlife mothers of individuals with autism spectrum disorders}}. {Aging Ment Health};2012 (May 29)
Objectives: The current study examines the awakening cortisol level in midlife mothers (M = 51.4 years old, SD = 8.4) of individuals (M = 22.1 years old, SD = 7.1) with autism spectrum disorders (ASD) under stressful conditions that are not specific to their son or daughter’s ASD symptoms. Methods: In addition to completing a set of questionnaires and in-home interviews, 82 mothers from the Adolescents and Adults with Autism Study (AAA) participated in a Daily Diary Study. Results: Findings from the multilevel models indicated that mothers who previously were exposed to no negative life events in the previous period had an increased awakening cortisol level on days following a greater number and more severe stressors, a normative stress response. In contrast, we observed a flatter cortisol level of daily stressors in mothers who experienced a greater number of negative life events in the previous period. Conclusion: These findings highlight the sustained toll that global and everyday stressors have on awakening cortisol level of midlife and aging mothers of individuals with ASD.
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5. Xu ZH, Yang Q, Feng B, Liu SB, Zhang N, Xing JH, Li XQ, Wu YM, Gao GD, Zhao MG. {{Group I mGluR antagonist rescues the deficit of D1- induced LTP in a mouse model of fragile X syndrome}}. {Mol Neurodegener};2012 (May 28);7(1):24.
ABSTRACT: BACKGROUND: Fragile X syndrome (FXS) is caused by the absence of the mRNA-binding protein Fragile X mental retardation protein (FMRP), encoded by the Fmr1 gene. Overactive signaling by group 1 metabotropic glutamate receptor (Grp1 mGluR) could contribute to slowed synaptic development and other symptoms of FXS. Our previous study has identified that facilitation of synaptic long-term potentiation (LTP) by D1 receptor is impaired in Fmr1 knockout (KO) mice. However, the contribution of Grp1 mGluR to the facilitation of synaptic plasticity by D1 receptor stimulation in the prefrontal cortex has been less extensively studied. RESULTS: Here we demonstrated that DL-AP3, a Grp1 mGluR antagonist, rescued LTP facilitation by D1 receptor agonist SKF81297 in Fmr1KO mice. Grp1 mGluR inhibition restored the GluR1-subtype AMPA receptors surface insertion by D1 activation in the cultured Fmr1KO neurons. Simultaneous treatment of Grp1 mGluR antagonist with D1 agonist recovered the D1 receptor signaling by reversing the subcellular redistribution of G protein-coupled receptor kinase 2 (GRK2) in the Fmr1KO neurons. Treatment of SKF81297 alone failed to increase the phosphorylation of NR2B-containing N-methyl D-aspartate receptors (NMDARs) at Tyr-1472 (p-NR2B-Tyr1472) in the cultures from KO mice. However, simultaneous treatment of DL-AP3 could rescue the level of p-NR2B-Tyr1472 by SKF81297 in the cultures from KO mice. Furthermore, behavioral tests indicated that simultaneous treatment of Grp1 mGluR antagonist with D1 agonist inhibited hyperactivity and improved the learning ability in the Fmr1KO mice. CONCLUSION: The findings demonstrate that mGluR1 inhibition is a useful strategy to recover D1 receptor signaling in the Fmr1KO mice, and combination of Grp1 mGluR antagonist and D1 agonist is a potential drug therapy for the FXS.
