1. Doll CA, Broadie K. {{Neuron class-specific requirements for Fragile X Mental Retardation Protein in critical period development of calcium signaling in learning and memory circuitry}}. {Neurobiol Dis};2016 (Feb 3)
Neural circuit optimization occurs through sensory activity-dependent mechanisms that refine synaptic connectivity and information processing during early-use developmental critical periods. Fragile X Mental Retardation Protein (FMRP), the gene product lost in Fragile X syndrome (FXS), acts as an activity sensor during critical period development, both as an RNA-binding translation regulator and channel-binding excitability regulator. Here, we employ a Drosophila FXS disease model to assay calcium signaling dynamics with a targeted transgenic GCaMP reporter during critical period development of the mushroom body (MB) learning/memory circuit. We find FMRP regulates depolarization-induced calcium signaling in a neuron-specific manner within this circuit, suppressing activity-dependent calcium transients in excitatory cholinergic MB input projection neurons and enhancing calcium signals in inhibitory GABAergic MB output neurons. Both changes are restricted to the developmental critical period and rectified at maturity. Importantly, conditional genetic (dfmr1) rescue of null mutants during the critical period corrects calcium signaling defects in both neuron classes, indicating a temporally restricted FMRP requirement. Likewise, conditional dfmr1 knockdown (RNAi) during the critical period replicates constitutive null mutant defects in both neuron classes, confirming cell-autonomous requirements for FMRP in developmental regulation of calcium signaling dynamics. Optogenetic stimulation during the critical period enhances depolarization-induced calcium signaling in both neuron classes, but this developmental change is eliminated in dfmr1 null mutants, indicating the activity-dependent regulation requires FMRP. These results show FMRP shapes neuron class-specific calcium signaling in excitatory vs. inhibitory neurons in developing learning/memory circuitry, and that FMRP mediates activity-dependent regulation of calcium signaling specifically during the early-use critical period.
Lien vers le texte intégral (Open Access ou abonnement)
2. Houwen S, Visser L, van der Putten A, Vlaskamp C. {{The interrelationships between motor, cognitive, and language development in children with and without intellectual and developmental disabilities}}. {Res Dev Disabil};2016 (Feb 3);53-54:19-31.
It is generally agreed that cognitive and language development are dependent on the emergence of motor skills. As the literature on this issue concerning children with developmental disabilities is scarce, we examined the interrelationships between motor, cognitive, and language development in children with intellectual and developmental disabilities (IDD) and compared them to those in children without IDD. In addition, we investigated whether these relationships differ between children with different levels of cognitive delay. Seventy-seven children with IDD (calendar age between 1;0 and 9;10 years; mean developmental age: 1;8 years) and 130 typically developing children (calendar age between 0;3 and 3;6 years; mean developmental age: 1;10 years) were tested with the Dutch Bayley Scales of Infant and Toddler Development, Third Edition, which assesses development across three domains using five subscales: fine motor development, gross motor development (motor), cognition (cognitive), receptive communication, and expressive communication (language). Results showed that correlations between the motor, cognitive, and language domains were strong, namely .61 to .94 in children with IDD and weak to strong, namely .24 to .56 in children without IDD. Furthermore, the correlations showed a tendency to increase with the severity of IDD. It can be concluded that both fine and gross motor development are more strongly associated with cognition, and consequently language, in children with IDD than in children without IDD. The findings of this study emphasize the importance of early interventions that boost both motor and cognitive development, and suggest that such interventions will also enhance language development.
Lien vers le texte intégral (Open Access ou abonnement)
3. Jiang L, Li G, Hao L, Guo R, Yang C, Du Y. {{[Epidemiological investigation on autism spectrum disorders among preschool children in Shanghai]}}. {Zhonghua Liu Xing Bing Xue Za Zhi};2015 (Dec);36(12):1365-1368.
OBJECTIVE: To investigate the prevalence of autism spectrum disorders (ASD) of children aged 4-6 years in public kindergartens in Shanghai. METHODS: Songjiang district and Xuhui district were selected randomly as the representative sample. By means of « Clancy Autism Behavior Scale », « Social Communication Questionnaire » and « high-functioning Autism Spectrum Screening Questionnaire », all of the 33 public kindergartens in chosen area, which contained 10 385 children aged 4-6 years, were surveyed. Those who were screened as suspected cases would be further diagnosed by « Autism Diagnostic Interview-Revised » and « Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ». RESULTS: Among 9 665 valid questionnaires, 9 children were diagnosed with ASD. The ratio of male to female was 8:1, the point prevalence rate was 0.93 per thousand. The results of ADI-R corresponded with that of DSM-5. There were two children who never had medical records. For others, « language » problem was the most likely reason for their parents to seek medical help, while « deficits in social communication » was the main symptom of patients. CONCLUSION: The prevalence of ASD was lower than those recorded in literature, home and abroad which might be related to some patients not going to public kindergartens.
4. Lovelace JW, Wen TH, Reinhard S, Hsu MS, Sidhu H, Ethell IM, Binder DK, Razak KA. {{Matrix metalloproteinase-9 deletion rescues auditory evoked potential habituation deficit in a mouse model of Fragile X Syndrome}}. {Neurobiol Dis};2016 (Feb 2)
Sensory processing deficits are common in autism spectrum disorders, but the underlying mechanisms are unclear. Fragile X Syndrome (FXS) is a leading genetic cause of intellectual disability and autism. Electrophysiological responses in humans with FXS show reduced habituation with sound repetition and this deficit may underlie auditory hypersensitivity in FXS. Our previous study in Fmr1 knockout (KO) mice revealed an unusually long state of increased sound-driven excitability in auditory cortical neurons suggesting that cortical responses to repeated sounds may exhibit abnormal habituation as in humans with FXS. Here, we tested this prediction by comparing cortical event related potentials (ERP) recorded from wildtype (WT) and Fmr1 KO mice. We report a repetition-rate dependent reduction in habituation of N1 amplitude in Fmr1 KO mice and show that matrix metalloproteinase-9 (MMP-9), one of the known FMRP targets, contributes to the reduced ERP habituation. Our studies demonstrate a significant up-regulation of MMP-9 levels in the auditory cortex of adult Fmr1 KO mice, whereas a genetic deletion of Mmp-9 reverses ERP habituation deficits in Fmr1 KO mice. Although the N1 amplitude of Mmp-9/Fmr1 DKO recordings was larger than WT and KO recordings, the habituation of ERPs in Mmp-9/Fmr1 DKO mice is similar to WT mice implicating MMP-9 as a potential target for reversing sensory processing deficits in FXS. Together these data establish ERP habituation as a translation relevant, physiological pre-clinical marker of auditory processing deficits in FXS and suggest that abnormal MMP-9 regulation is a mechanism underlying auditory hypersensitivity in FXS. SIGNIFICANCE: Fragile X Syndrome (FXS) is the leading known genetic cause of autism spectrum disorders. Individuals with FXS show symptoms of auditory hypersensitivity. These symptoms may arise due to sustained neural responses to repeated sounds, but the underlying mechanisms remain unclear. For the first time, this study shows deficits in habituation of neural responses to repeated sounds in the Fmr1 KO mice as seen in humans with FXS. We also report an abnormally high level of matrix metalloprotease-9 (MMP-9) in the auditory cortex of Fmr1 KO mice and that deletion of Mmp-9 from Fmr1 KO mice reverses habituation deficits. These data provide a translation relevant electrophysiological biomarker for sensory deficits in FXS and implicate MMP-9 as a target for drug discovery.
Lien vers le texte intégral (Open Access ou abonnement)
5. Muskat B, Greenblatt A, Nicholas DB, Ratnapalan S, Cohen-Silver J, Newton AS, Craig WR, Kilmer C, Zwaigenbaum L. {{Parent and health care provider perspectives related to disclosure of autism spectrum disorder in pediatric emergency departments}}. {Autism};2016 (Feb 5)
Children and youth with autism spectrum disorder presenting in emergency departments face potential cognitive, sensory, and behavioral challenges, and it is crucial for providers to be aware of their unique needs. However, disclosure of a child’s autism spectrum disorder can be complex for parental caregivers and is not well understood. This qualitative study utilized a grounded theory approach and analyzed data from 28 parents and 16 health care providers related to autism spectrum disorder disclosure within two Canadian pediatric emergency departments. Study results indicated that participants identified benefits and risks of disclosure. Encouraging understanding, expediting service, and preparing health care providers for working with children with autism spectrum disorder were identified as benefits of disclosure. Risks related to disclosure included potential negative attributions toward the children and parental discomfort in disclosing a diagnosis in front of the children. Parents discussed the health care encounters they experienced following disclosure and provided recommendations for improving the disclosure process in the emergency department. It is recommended that future research explore the experiences of parents who choose not to disclose their child’s autism spectrum disorder. Greater awareness of the disclosure experience and the development of resources and tools to support communication between parents and health care providers are also recommended.
Lien vers le texte intégral (Open Access ou abonnement)
6. Peckett H, MacCallum F, Knibbs J. {{Maternal experience of Lego Therapy in families with children with autism spectrum conditions: What is the impact on family relationships?}}. {Autism};2016 (Feb 5)
This study aimed to explore mothers’ experience of implementing Lego Therapy at home within the family. Following a Lego Therapy training session, mothers carried out hourly sessions with their child with an autism spectrum condition and the child’s sibling, once a week, for 6 weeks. Mothers were interviewed following the intervention, and the data were analysed using interpretative phenomenological analysis. Themes emerged around improved family relationships, a positive impact on the child as an individual, and changed maternal, sibling and child perspectives. Challenging and facilitative aspects also emerged, as did some ambivalence about the impact of the intervention in the wider context. The findings are supportive of previous Lego Therapy studies and have implications for strengths-based service provision.
Lien vers le texte intégral (Open Access ou abonnement)
7. Pruitt MM, Willis K, Timmons L, Ekas NV. {{The impact of maternal, child, and family characteristics on the daily well-being and parenting experiences of mothers of children with autism spectrum disorder}}. {Autism};2016 (Feb 5)
This study utilized a daily diaries method to explore the global factors that impact daily general affect and daily parenting interactions of mothers of children with autism spectrum disorder. Eighty-three mothers of a child with autism spectrum disorder between the ages of 3 and 13 years completed global assessments of maternal depressive symptoms, child autism spectrum disorder symptom severity, and family functioning. Mothers then reported on their daily negative and positive affect as well as their daily positive and frustrating parenting interactions for 14 consecutive days. The results indicated that higher levels of maternal depressive symptoms were related to decreased daily positive affect, whereas greater child social motivation impairments were related to increased daily positive affect. Only maternal depressive symptoms were associated with increased daily negative affect. Furthermore, higher levels of family cohesion were related to increased daily positive parenting interactions. Finally, higher maternal depressive symptoms as well as family rigidity were related to increased daily frustrating parenting interactions. Implications for interventions focused on the family system are discussed.
Lien vers le texte intégral (Open Access ou abonnement)
8. Radley KC, Hanglein J, Arak M. {{School-based social skills training for preschool-age children with autism spectrum disorder}}. {Autism};2016 (Feb 5)
Individuals with autism spectrum disorder display impairments in social interactions and communication that appear at early ages and result in short- and long-term negative outcomes. As such, there is a need for effective social skills training programs for young children with autism spectrum disorder-particularly interventions capable of being delivered in educational settings. The study evaluated the effects of the Superheroes Social Skills program on accurate demonstration of social skills in young children with autism spectrum disorder. Two preschool-age children with autism spectrum disorder participated in a weekly social skills intervention. A multiple probe design across skills was used to determine the effects of the intervention. Both participants demonstrated substantial improvements in skill accuracy. Social skills checklists also indicated improvements in social functioning over baseline levels.
Lien vers le texte intégral (Open Access ou abonnement)
9. Rosa M, Puig O, Lazaro L, Calvo R. {{Socioeconomic status and intelligence quotient as predictors of psychiatric disorders in children and adolescents with high-functioning autism spectrum disorder and in their siblings}}. {Autism};2016 (Feb 5)
Previous studies have shown high rates of comorbid disorders in children and adolescents with autism spectrum disorder, but failed to compare them with general population and few of them have identified predictors of comorbidity. This study compared the rates of psychiatric disorders in 50 children and adolescents with autism spectrum disorder, 24 of their siblings, 32 controls from general population and 22 of their siblings. Children and adolescent with autism spectrum disorder and their siblings had higher rates of attention deficit and hyperactivity disorder compared to controls. Lower socioeconomic status and intelligence quotient were the main risk factors. The contribution of socioeconomic status and intelligence quotient to increase the risk of developing comorbidity in autism spectrum disorder and psychopathology in their siblings deserves further study.
Lien vers le texte intégral (Open Access ou abonnement)
10. Vanvuchelen M, Van Schuerbeeck L, Braeken MA. {{Screening accuracy of the parent-completed Ages and Stages Questionnaires – second edition as a broadband screener for motor problems in preschoolers with autism spectrum disorders}}. {Autism};2016 (Feb 5)
Children with autism spectrum disorders are at risk for motor problems. However, this area is often overlooked in the developmental evaluation in autism diagnostic clinics. An alternative can be to identify children who should receive intensive motor assessment by using a parent-based screener. The aim of this study was to examine whether the Ages and Stages Questionnaires – second edition may be used to identify gross and fine motor problems in children. High-functioning children with autism spectrum disorder (n = 43, 22-54 m) participated in this study. Sensitivity, specificity, predictive values and areas under the receiver operating characteristic curve were calculated by comparing the Ages and Stages Questionnaires – second edition scores to the developmental evaluation of the Peabody Developmental Motor Scale – second edition. The results revealed that both the Ages and Stages Questionnaires – second edition gross and fine motor domain may be used to identify children without motor problems. In contrast, sensitivity analyses revealed the likelihood of under screening motor problems in this population. The Ages and Stages Questionnaires – second edition met only the criteria of a fair to good accuracy to identify poor gross motor (sensitivity = 100%) and below-average fine motor development (sensitivity = 71%) in this sample. Hence, the capacity of the Ages and Stages Questionnaires – second edition to identify motor problems in preschoolers with autism spectrum disorder appears to be limited. It is recommended to include a formal standardized motor test in the diagnostic procedure for all children with autism spectrum disorder.
