1. Etherton M, Foldy C, Sharma M, Tabuchi K, Liu X, Shamloo M, Malenka RC, Sudhof TC. {{Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function}}. {Proc Natl Acad Sci U S A};2011 (Aug 1)
Multiple independent mutations in neuroligin genes were identified in patients with familial autism, including the R451C substitution in neuroligin-3 (NL3). Previous studies showed that NL3(R451C) knock-in mice exhibited modestly impaired social behaviors, enhanced water maze learning abilities, and increased synaptic inhibition in the somatosensory cortex, and they suggested that the behavioral changes in these mice may be caused by a general shift of synaptic transmission to inhibition. Here, we confirm that NL3(R451C) mutant mice behaviorally exhibit social interaction deficits and electrophysiologically display increased synaptic inhibition in the somatosensory cortex. Unexpectedly, however, we find that the NL3(R451C) mutation produced a strikingly different phenotype in the hippocampus. Specifically, in the hippocampal CA1 region, the NL3(R451C) mutation caused an approximately 1.5-fold increase in AMPA receptor-mediated excitatory synaptic transmission, dramatically altered the kinetics of NMDA receptor-mediated synaptic responses, induced an approximately twofold up-regulation of NMDA receptors containing NR2B subunits, and enhanced long-term potentiation almost twofold. NL3 KO mice did not exhibit any of these changes. Quantitative light microscopy and EM revealed that the NL3(R451C) mutation increased dendritic branching and altered the structure of synapses in the stratum radiatum of the hippocampus. Thus, in NL3(R451C) mutant mice, a single point mutation in a synaptic cell adhesion molecule causes context-dependent changes in synaptic transmission; these changes are consistent with the broad impact of this mutation on murine and human behaviors, suggesting that NL3 controls excitatory and inhibitory synapse properties in a region- and circuit-specific manner.
Lien vers le texte intégral (Open Access ou abonnement)
2. Faucz FR, Souza J, Filho AB, Sotomaior VS, Frantz E, Antoniuk S, Rosenfeld JA, Raskin S. {{Mosaic partial trisomy 19p12-q13.11 due to a small supernumerary marker chromosome: A locus associated with Asperger syndrome?}}. {Am J Med Genet A};2011 (Aug 3)
In the neurodevelopmentally impaired population the frequency of small supernumerary marker chromosomes (sSMC) is about 0.3%. To find the origin of a sSMC in a 4-year-old boy with Asperger syndrome (AS) a microarray-based comparative genomic hybridization (aCGH), using a 135K-feature whole-genome microarray, and Metaphase FISH analysis, was performed. The sSMC was characterized as being composed of 18.4 Mb from 19p12q13.11. Based on the size and genic content, it is expected that the partial trisomy detected is responsible for the characteristics observed in the patient. In that case it could be an indication of a novel locus associated with AS. (c) 2011 Wiley-Liss, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
3. Gerber F, Bessero S, Robbiani B, Courvoisier DS, Baud MA, Traore MC, Blanco P, Giroud M, Galli Carminati G. {{Comparing residential programmes for adults with autism spectrum disorders and intellectual disability: outcomes of challenging behaviour and quality of life}}. {J Intellect Disabil Res};2011 (Aug 1)
Background Owing to methodological issues, little research has been conducted to examine quality of life (QoL) as a treatment outcome in autism spectrum disorders (ASD) and intellectual disabilities (ID). This study was conducted to combine QoL measures and objective observations of challenging behaviours (CB) in order to evaluate changes over time in adults with ASD and ID who were treated in two different residential programmes; we hypothesised that a decrease in CB would be related to an improved QoL. Method In a longitudinal study (45 months), we followed 31 adults with ASD and ID who had been integrated into two residential programmes [Autism Programme with a Structured Method (PAMS) vs. traditional programme for ID (No-PAMS)] for 2-19 years. QoL [Quality of Life Inventory in a Residential Environment (IQVMR)] and severity of autistic features (Childhood Autism Rating Scales) were evaluated annually. CB, as measured by the Aberrant Behaviour Checklist (ABC), including stereotypic behaviour and inappropriate speech, were repeatedly assessed every 3 months. Results Observed separately, the groups’ results were different. In the PAMS programme, stereotypic behaviour and inappropriate speech (ABC scores) significantly decreased, and the IQVMR total score increased; in contrast, in the comparison group, ABC scores did not change and the IQVMR total score decreased. In all, three mixed-effect ANCOVAs partially confirmed that the PAMS programme had an effect on CB and that QoL improvement did not directly depend on the type of programme but on reducing CB as measured by the ABC. Conclusion The PAMS programme has a positive and indirect influence on QoL by reducing CB.
Lien vers le texte intégral (Open Access ou abonnement)
4. Goodrich-Hunsaker NJ, Wong LM, McLennan Y, Tassone F, Harvey D, Rivera SM, Simon TJ. {{Adult Female Fragile X Premutation Carriers Exhibit Age- and CGG Repeat Length-Related Impairments on an Attentionally Based Enumeration Task}}. {Front Hum Neurosci};2011;5:63.
The high frequency of the fragile X premutation in the general population and its emerging neurocognitive implications highlight the need to investigate the effects of the premutation on lifespan cognitive development. Until recently, cognitive function in fragile X premutation carriers (fXPCs) was presumed to be unaffected by the mutation. Although as a group fXPCs did not differ from healthy controls (HCs), we show that young adult female fXPCs show subtle age- and significant fragile X mental retardation 1 (FMR1) gene mutation-modulated cognitive function as tested by a basic numerical enumeration task. These results indicate that older women with the premutation and fXPCs with greater CGG repeat lengths were at higher risk for difficulties in the deployment of volitional attention required to count 5-8 items, but spared performance when spatial shifts of attention were minimized to subitize a few (1-3). Results from the current study add to a growing body of evidence that suggests the premutation allele is associated with a subtle phenotype and implies that the cognitive demands necessary for counting are less effectively deployed in female fXPCs compared to HCs.
Lien vers le texte intégral (Open Access ou abonnement)
5. Kim KY, Hysolli E, Park IH. {{Neuronal maturation defect in induced pluripotent stem cells from patients with Rett syndrome}}. {Proc Natl Acad Sci U S A};2011 (Aug 1)
Rett syndrome (RTT) is one of the most prevalent female neurodevelopmental disorders that cause severe mental retardation. Mutations in methyl CpG binding protein 2 (MeCP2) are mainly responsible for RTT. Patients with classical RTT exhibit normal development until age 6-18 mo, at which point they become symptomatic and display loss of language and motor skills, purposeful hand movements, and normal head growth. Murine genetic models and postmortem human brains have been used to study the disease and enable the molecular dissection of RTT. In this work, we applied a recently developed reprogramming approach to generate a novel in vitro human RTT model. Induced pluripotent stem cells (iPSCs) were derived from RTT fibroblasts by overexpressing the reprogramming factors OCT4, SOX2, KLF4, and MYC. Intriguingly, whereas some iPSCs maintained X chromosome inactivation, in others the X chromosome was reactivated. Thus, iPSCs were isolated that retained a single active X chromosome expressing either mutant or WT MeCP2, as well as iPSCs with reactivated X chromosomes expressing both mutant and WT MeCP2. When these cells underwent neuronal differentiation, the mutant monoallelic or biallelelic RTT-iPSCs displayed a defect in neuronal maturation consistent with RTT phenotypes. Our in vitro model of RTT is an important tool allowing the further investigation of the pathophysiology of RTT and the development of the curative therapeutics.
Lien vers le texte intégral (Open Access ou abonnement)
6. Lunsky Y, Lin E, Balogh R, Klein-Geltink J. {{Datapoints: diabetes prevalence among persons with serious mental illness and developmental disability}}. {Psychiatr Serv};2011 (Aug);62(8):830.
Lien vers le texte intégral (Open Access ou abonnement)
7. Narendorf SC, Shattuck PT, Sterzing PR. {{Mental health service use among adolescents with an autism spectrum disorder}}. {Psychiatr Serv};2011 (Aug);62(8):975-978.
Objective: This study examined prevalence and correlates of mental health service use among adolescents with an autism spectrum disorder. Methods: Data from the National Longitudinal Transition Study-2 were used to examine mental health service use among 920 youths with this disorder. Estimatesare nationally representative ofstudents enrolled in the special education autism category. Regression models examined the association of predisposing, enabling, and need factors with service use overall and with a focus on receiving these services at school. Results: Overall, 46% (weighted) of the youths had used a mental health service in the past year. Of those who had, 49% (weighted) had received it at school. Need variables were the strongest correlates of service use. African-American youths and youths from lower-income families were more likely to receive school-based services. Conclusions: Schools played a key role in providing services, especially for vulnerable populations. Focused attention on youths with an autism spectrum disorder is needed to ensure continuity of care as youths leave high school. (Psychiatric Services 62:975-978, 2011).
