1. Adams C, Lockton E, Freed J, Gaile J, Earl G, McBean K, Nash M, Green J, Vail A, Law J. {{The Social Communication Intervention Project: a randomized controlled trial of the effectiveness of speech and language therapy for school-age children who have pragmatic and social communication problems with or without autism spectrum disorder}}. {Int J Lang Commun Disord};2012 (May);47(3):233-244.
Background: Children who show disproportionate difficulty with the pragmatic as compared with the structural aspects of language are described as having pragmatic language impairment (PLI) or social communication disorder (SCD). Some children who have PLI also show mild social impairments associated with high-functioning autism or autism spectrum disorder (ASD). There is little robust evidence of effectiveness of speech-language interventions which target the language, pragmatic or social communication needs of these children. Aims: To evaluate the effectiveness of an intensive manualized social communication intervention (SCIP) for children who have PLI with or without features of ASD. Methods & Procedures: In a single-blind RCT design, 88 children with pragmatic and social communication needs aged 5;11-10;8, recruited from UK speech and language therapy services, were randomly assigned in a 2:1 ratio to SCIP or to treatment-as-usual. Children in the SCIP condition received up to 20 sessions of direct intervention from a specialist research speech and language therapist working with supervised assistants. All therapy content and methodology was derived from an intervention manual. A primary outcome measure of structural language and secondary outcome measures of narrative, parent-reported pragmatic functioning and social communication, blind-rated perceptions of conversational competence and teacher-reported ratings of classroom learning skills were taken pre-intervention, immediately post-intervention and at 6-month follow-up. Analysis was by intention to treat. Outcomes & Results: No significant treatment effect was found for the primary outcome measure of structural language ability or for a measure of narrative ability. Significant treatment effects were found for blind-rated perceptions of conversational competence, for parent-reported measures of pragmatic functioning and social communication, and for teacher-reported ratings of classroom learning skills. Conclusions & Implications: There is some evidence of an intervention effect on blind and parent/teacher-reported communication outcomes, but not standardized language assessment outcomes, for 6-11-year-old children who have pragmatic and social communication needs. These findings are discussed in the context of the increasingly central role of service user outcomes in providing evidence for an intervention. The substantial overlap between the presence of PLI and ASD (75%) across the whole cohort suggests that the intervention may also be applicable to some verbally able children with ASD who have pragmatic communication needs.
Lien vers le texte intégral (Open Access ou abonnement)
2. Callan MA, Clements N, Ahrendt N, Zarnescu DC. {{Fragile X Protein is required for inhibition of insulin signaling and regulates glial-dependent neuroblast reactivation in the developing brain}}. {Brain Res};2012 (Mar 27)
Fragile X syndrome (FXS) is the most common form of inherited mental disability and known cause of autism. It is caused by loss of function for the RNA binding protein FMRP, which has been demonstrated to regulate several aspects of RNA metabolism including transport, stability and translation at synapses. Recently, FMRP has been implicated in neural stem cell proliferation and differentiation both in cultured neurospheres as well as in vivo mouse and fly models of FXS. We have previously shown that FMRP deficient Drosophila neuroblasts upregulate Cyclin E, prematurely exit quiescence, and overproliferate to generate on average 16% more neurons. Here we further investigate FMRP’s role during early development using the Drosophila larval brain as a model. Using tissue specific RNAi we find that FMRP is required sequentially, first in neuroblasts and then in glia, to regulate exit from quiescence as measured by Cyclin E expression in the brain. Furthermore, we tested the hypothesis that FMRP controls brain development by regulating the insulin signaling pathway, which has been recently shown to regulate neuroblast exit from quiescence. Our data indicate that phosphoAkt, a readout of insulin signaling, is upregulated in dFmr1 brains at the time when FMRP is required in glia for neuroblast reactivation. In addition, dFmr1 interacts genetically with dFoxO, a transcriptional regulator of insulin signaling. Our results provide the first evidence that FMRP is required in vivo, in glia for neuroblast reactivation and suggest that it may do so by regulating the output of the insulin signaling pathway. This article is part of a Special Issue entitled: RNA-Binding Proteins.
Lien vers le texte intégral (Open Access ou abonnement)
3. Hobson RP, Hobson JA, Garcia-Perez R, Du Bois J. {{Dialogic Linkage and Resonance in Autism}}. {J Autism Dev Disord};2012 (Apr 20)
We evaluated how children with autism make linguistic adjustments when talking with someone else. We devised two novel measures to assess (a) overall conversational linkage and (b) utterance-by-utterance resonance within dialogue between an adult and matched participants with and without autism (n = 12 per group). Participants with autism were less able to establish ‘cognitive linkage’ with an interlocutor. As predicted, only among children with autism was there a positive correlation between the ability to link in with speaker’s meanings and ratings of emotional connectedness with the conversational partner. Participants with autism were not less likely to show a basic form of dialogic resonance across successive utterances (the ‘frame grab’), but more often elaborated their responses in an atypical manner.
Lien vers le texte intégral (Open Access ou abonnement)
4. Itoh M, Tahimic CG, Ide S, Otsuki A, Sasaoka T, Noguchi S, Oshimura M, Goto Y, Kurimasa A. {{Methyl CpG-binding Protein Isoform MeCP2_e2 Is Dispensable for Rett Syndrome Phenotypes but Essential for Embryo Viability and Placenta Development}}. {J Biol Chem};2012 (Apr 20);287(17):13859-13867.
Methyl CpG-binding protein 2 gene (MeCP2) mutations are implicated in Rett syndrome (RTT), one of the common causes of female mental retardation. Two MeCP2 isoforms have been reported: MeCP2_e2 (splicing of all four exons) and MeCP2_e1 (alternative splicing of exons 1, 3, and 4). Their relative expression levels vary among tissues, with MeCP2_e1 being more dominant in adult brain, whereas MeCP2_e2 is expressed more abundantly in placenta, liver, and skeletal muscle. In this study, we performed specific disruption of the MeCP2_e2-defining exon 2 using the Cre-loxP system and examined the consequences of selective loss of MeCP2_e2 function in vivo. We performed behavior evaluation, gene expression analysis, using RT-PCR and real-time quantitative PCR, and histological analysis. We demonstrate that selective deletion of MeCP2_e2 does not result in RTT-associated neurological phenotypes but confers a survival disadvantage to embryos carrying a MeCP2_e2 null allele of maternal origin. In addition, we reveal a specific requirement for MeCP2_e2 function in extraembryonic tissue, where selective loss of MeCP2_e2 results in placenta defects and up-regulation of peg-1, as determined by the parental origin of the mutant allele. Taken together, our findings suggest a novel role for MeCP2 in normal placenta development and illustrate how paternal X chromosome inactivation in extraembryonic tissues confers a survival disadvantage for carriers of a mutant maternal MeCP2_e2 allele. Moreover, our findings provide an explanation for the absence of reports on MeCP2_e2-specific exon 2 mutations in RTT. MeCP2_e2 mutations in humans may result in a phenotype that evades a diagnosis of RTT.
Lien vers le texte intégral (Open Access ou abonnement)
5. Kocovska E, Fernell E, Billstedt E, Minnis H, Gillberg C. {{Vitamin D and autism: Clinical review}}. {Res Dev Disabil};2012 (Apr 20);33(5):1541-1550.
BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with multiple genetic and environmental risk factors. The interplay between genetic and environmental factors has become the subject of intensified research in the last several years. Vitamin D deficiency has recently been proposed as a possible environmental risk factor for ASD. OBJECTIVE: The aim of the current paper is to systematically review the research regarding the possible connection between ASD and vitamin D, and to provide a narrative review of the literature regarding the role of vitamin D in various biological processes in order to generate hypotheses for future research. RESULTS: Systematic data obtained by different research groups provide some, albeit very limited, support for the possible role of vitamin D deficiency in the pathogenesis of ASD. There are two main areas of involvement of vitamin D in the human body that could potentially have direct impact on the development of ASD: (1) the brain (its homeostasis, immune system and neurodevelopment) and (2) gene regulation. CONCLUSION: Vitamin D deficiency – either during pregnancy or early childhood – may be an environmental trigger for ASD in individuals genetically predisposed for the broad phenotype of autism. On the basis of the results of the present review, we argue for the recognition of this possibly important role of vitamin D in ASD, and for urgent research in the field.
Lien vers le texte intégral (Open Access ou abonnement)
6. Kumar M, Kim S, Pickup S, Chen R, Fairless AH, Ittyerah R, Abel T, Brodkin ES, Poptani H. {{Longitudinal in-vivo diffusion tensor imaging for assessing brain developmental changes in BALB/cJ mice, a model of reduced sociability relevant to autism}}. {Brain Res};2012 (Mar 25)
Diffusion tensor imaging (DTI) is highly sensitive in detecting brain structure and connectivity phenotypes in autism spectrum disorders (ASD). Since one of the core symptoms of ASD is reduced sociability (reduced tendency to seek social interaction), we hypothesized that DTI will be sensitive in detecting neural phenotypes that correlate with decreased sociability in mouse models. Relative to C57BL/6J (B6) mice, juvenile BALB/cJ mice show reduced sociability. We performed social approach test in a three-chambered apparatus and in-vivo longitudinal DTI at post-natal days 30, 50 and 70days-of-age in BALB/cJ (n=32) and B6 (n=15) mice to assess the correlation between DTI and sociability and to evaluate differences in DTI parameters between these two strains. Fractional anisotropy (FA) and mean diffusivity (MD) values from in-vivo DTI data were analyzed from white matter (corpus callosum, internal and external capsule) and gray matter (cerebral cortex, frontal motor cortex, hippocampus, thalamus and amygdaloid) regions based on their relevance to ASD. A moderate but significant (p<0.05) negative correlation between sociability and FA in hippocampus and frontal motor cortex was noted for BALB/cJ mice at 30days-of-age. Significant differences in FA and MD values between BALB/cJ and B6 mice were observed in most white and gray matter areas at all three time points. Significant differences in developmental trajectories of FA and MD values from thalamus and frontal motor cortex were also observed between BALB/cJ and B6, indicating relative under-connectivity in BALB/cJ mice. These results indicate that DTI may be used as an in-vivo, non-invasive imaging method to assess developmental trajectories of brain connectivity in mouse models of neurodevelopmental and behavioral disorders.
Lien vers le texte intégral (Open Access ou abonnement)
7. Memari A, Ziaee V, Mirfazeli F, Kordi R. {{Investigation of Autism Comorbidities and Associations in a School-Based Community Sample}}. {J Child Adolesc Psychiatr Nurs};2012 (May);25(2):84-90.
PROBLEM: Individuals with autism spectrum disorders (ASDs) have at least as many comorbidities as individuals with typical development may show, but sometimes with different presentations. METHODS: The study used a school-based health survey related to children diagnosed with ASD in Tehran to determine the possibility of comorbid conditions. Ninety-one children and adolescents with ASD between the ages of 6 and 14 years were included in the study, all from five schools of different districts of the city, using stratified random sampling. All of the subjects had received a clinical diagnosis of ASD (autism, Asperger, and pervasive developmental disorder-not otherwise specified) by a child neurologist or psychiatrist. All of the schools had registered the subjects and were restricted to those with high-functioning forms of ASD, and none were identified with co-occurring mental retardation. FINDINGS: Results indicated that 72.5% had at least one comorbid condition. There was a trend of higher severity in autism symptoms in subjects with comorbidity. Results showed that attention-deficit/hyperactivity disorder and epileptic disorders were the leading comorbidity in respective categories. CONCLUSION: Autistic individuals should be monitored regarding their comorbid profiles, with an emphasis on female subjects and those with more severe symptoms. Clinically, the current study has implications for school healthcare providers, including nurses, in addition to researchers and practitioners working with children diagnosed with ASDs.
Lien vers le texte intégral (Open Access ou abonnement)
8. Okabe Y, Takahashi T, Mitsumasu C, Kosai K, Tanaka E, Matsuishi T. {{Alterations of Gene Expression and Glutamate Clearance in Astrocytes Derived from an MeCP2-Null Mouse Model of Rett Syndrome}}. {PLoS One};2012;7(4):e35354.
Rett syndrome (RTT) is a neurodevelopmetal disorder associated with mutations in the methyl-CpG-binding protein 2 (MeCP2) gene. MeCP2-deficient mice recapitulate the neurological degeneration observed in RTT patients. Recent studies indicated a role of not only neurons but also glial cells in neuronal dysfunction in RTT. We cultured astrocytes from MeCP2-null mouse brain and examined astroglial gene expression, growth rate, cytotoxic effects, and glutamate (Glu) clearance. Semi-quantitative RT-PCR analysis revealed that expression of astroglial marker genes, including GFAP and S100beta, was significantly higher in MeCP2-null astrocytes than in control astrocytes. Loss of MeCP2 did not affect astroglial cell morphology, growth, or cytotoxic effects, but did alter Glu clearance in astrocytes. When high extracellular Glu was added to the astrocyte cultures and incubated, a time-dependent decrease of extracellular Glu concentration occurred due to Glu clearance by astrocytes. Although the shapes of the profiles of Glu concentration versus time for each strain of astrocytes were grossly similar, Glu concentration in the medium of MeCP2-null astrocytes were lower than those of control astrocytes at 12 and 18 h. In addition, MeCP2 deficiency impaired downregulation of excitatory amino acid transporter 1 and 2 (EAAT1/2) transcripts, but not induction of glutamine synthetase (GS) transcripts, upon high Glu exposure. In contrast, GS protein was significantly higher in MeCP2-null astrocytes than in control astrocytes. These findings suggest that MeCP2 affects astroglial genes expression in cultured astrocytes, and that abnormal Glu clearance in MeCP2-deficient astrocytes may influence the onset and progression of RTT.
Lien vers le texte intégral (Open Access ou abonnement)
9. Osada H, Tachimori H, Koyama T, Kurita H. {{Longitudinal Developmental Courses in Japanese Children with Autism Spectrum Disorder}}. {Child Psychiatry Hum Dev};2012 (Apr 20)
We followed up 67 children with autistic disorder (AD) and 31 children with pervasive developmental disorder not otherwise specified (PDDNOS) for more than 10 years by reviewing medical records at a clinic for children with developmental disabilities. The participants’ data were collected between their first visit to the clinic and the visit at which they applied for basic disability benefits. The standardized IQ scores and autistic symptoms were examined as measures of the children’s personal functioning. For environmental factors, we examined the participants’ educational placements and work and residential status. Using structural equation modeling, we examined the longitudinal developmental courses of AD and PDDNOS. Participants diagnosed with AD consistently showed lower IQ and more severe autistic symptoms than those diagnosed with PDDNOS. Relationships between personal functioning and environmental factors differed between the two groups. AD and PDDNOS are heterogeneous, so they must be treated differently to improve children’s prognoses.
Lien vers le texte intégral (Open Access ou abonnement)
10. Rai K, Hegde AM, Jose N. {{Salivary antioxidants and oral health in children with autism}}. {Arch Oral Biol};2012 (Apr 20)
Individuals with autism vary widely in abilities, intelligence, and behaviours. Autistic children have preferences for soft and sweetened food making them susceptible to caries. A wide spectrum of medical and behavioural symptoms is exhibited by children with autism, which makes routine dental care very difficult in them. Mental retardation is evident in approximately 70% of individuals with autism and most psychiatric disorders including autism are associated with increased oxidative stress. OBJECTIVES: To evaluate the oral health status of children with autism and to determine the salivary pH and total salivary antioxidant concentration (TAC). MATERIALS AND METHODS: 101 subjects with autism between age group of 6 and 12 year were part of the study and 50 normal healthy siblings of same age group were taken as control group. Oral health status was analysed using oral hygiene index-simplified and dentition status index. The salivary total anti-oxidant level was estimated using phosphomolybdic acid using spectrophotometric method and the salivary pH using the pH indicating paper. The results were statistically analyzed using Mann-Whitney U test. RESULTS: A statistically very highly significant difference was seen in the mean oral hygiene index scores (autistic group – 1.2 and control group – 1, P<0.001) and the mean salivary total antioxidant concentration (autistic group – 5.7mug/ml and control group – 38mug/ml, P<0.001). No statistical significant difference was observed in the dental caries status and the salivary pH of autistic group and the control group. CONCLUSIONS: Similar dental caries status was observed in children with autism and their healthy normal siblings. Oral hygiene was poor in children with autism whereas the Salivary TAC was significantly reduced in autistic children.
Lien vers le texte intégral (Open Access ou abonnement)
11. Ramisch J. {{Marriage and family therapists working with couples who have children with autism}}. {J Marital Fam Ther};2012 (Apr);38(2):305-316.
Current research about families and couples who have children with autism is discussed using the Double ABCX model as a guide. A case study is presented along with recommendations for therapists who work with couples who have children with autism. Marriage and family therapists are encouraged to use the Double ABCX model as both an assessment tool as well as for intervention. More research and effective therapists in this area are needed in order to keep up with the rising rates of families that include children diagnosed with autism.
Lien vers le texte intégral (Open Access ou abonnement)
12. Shih CH. {{A finger-pressing position detector for assisting people with developmental disabilities to control their environmental stimulation through fine motor activities with a standard keyboard}}. {Res Dev Disabil};2012 (Apr 20);33(5):1360-1365.
This study used a standard keyboard with a newly developed finger-pressing position detection program (FPPDP), i.e. a new software program, which turns a standard keyboard into a finger-pressing position detector, to evaluate whether two people with developmental disabilities would be able to actively perform fine motor activities to control their preferred environmental stimulation. An ABAB design was adopted in this study. The data showed that both participants’ target responses (i.e. fine motor activities) significantly increased (i.e. they performed more fine motor activities to activate the environmental stimulation) during the intervention phases. The practical and developmental implications of the findings are discussed.
Lien vers le texte intégral (Open Access ou abonnement)
13. Tabet AC, Pilorge M, Delorme R, Amsellem F, Pinard JM, Leboyer M, Verloes A, Benzacken B, Betancur C. {{Autism multiplex family with 16p11.2p12.2 microduplication syndrome in monozygotic twins and distal 16p11.2 deletion in their brother}}. {Eur J Hum Genet};2012 (May);20(5):594.
Lien vers le texte intégral (Open Access ou abonnement)
14. Uno Y, Uchiyama T, Kurosawa M, Aleksic B, Ozaki N. {{The combined measles, mumps, and rubella vaccines and the total number of vaccines are not associated with development of autism spectrum disorder: The first case-control study in Asia}}. {Vaccine};2012 (Apr 20)
OBJECTIVE: The aim of this study was to investigate the relationship between autism spectrum disorder (ASD) and general vaccinations, including measles-mumps-rubella (MMR) vaccine, in Japanese subjects, a population with high genetic homogeneity. PATIENTS AND METHODS: A case-control study was performed. Cases (n=189) were diagnosed with ASD, while controls (n=224) were volunteers from general schools, matched by sex and birth year to cases. Vaccination history and prenatal, perinatal, and neonatal factors from the Maternal and Child Health handbook, which was part of each subject’s file, were examined. To determine the relationship between potential risk factors and ASD, crude odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated, and the differences in mean values of the quantitative variables between cases and controls were analyzed using an unpaired t-test. Moreover, MMR vaccination and the effect of the number of vaccine injections were investigated using a conditional multiple regression model. RESULTS: For MMR vaccination, the OR was 1.04 (95% CI, 0.65-1.68), and no significant differences were found for the other vaccines. For all of the prenatal, perinatal and neonatal factors, there were no significant differences between cases and controls. Furthermore, regarding the presence of ASD, MMR vaccination and the number of vaccine injections had ORs of 1.10 (95% CI, 0.64-1.90) and 1.10 (95% CI, 0.95-1.26), respectively, in the conditional multiple regression model; no significant differences were found. CONCLUSIONS: In this study, there were not any convincing evidences that MMR vaccination and increasing the number of vaccine injections were associated with an increased risk of ASD in a genetically homogeneous population. Therefore, these findings indicate that there is no basis for avoiding vaccination out of concern for ASD.
Lien vers le texte intégral (Open Access ou abonnement)
15. Williams K, Wray JA, Wheeler DM. {{Intravenous secretin for autism spectrum disorders (ASD)}}. {Cochrane Database Syst Rev};2012;4:CD003495.
BACKGROUND: In 1998 secretin, a gastrointestinal hormone, was suggested as an effective treatment for autism spectrum disorders (ASD) based on anecdotal evidence. OBJECTIVES: To assess whether intravenous secretin improves the core features of ASD, other aspects of behaviour or function such as self-injurious behaviour, and the quality of life of affected individuals and their carers. We also assessed whether secretin causes harm. This is an updated version of our review of this topic originally published in 2005. SEARCH METHODS: We searched CENTRAL (2010 Issue 1), MEDLINE (1950 to January 2010) , EMBASE (1980 to 2010 Week 2), PsycINFO (1806 to 2010 Week 2), CINAHL (1938 to January 2010), ERIC (1966 to January 2010), Sociological Abstracts (1952 to January 2010). Sociofile and HealthStar were searched in March 2005 when this review was first published, but were not available for this update. Records were limited to studies published since 1998 as this is when secretin was first proposed as a possible treatment for ASD. We searched reference lists of trials and reviews; we also contacted experts and trialists to find unpublished studies. SELECTION CRITERIA: Randomised controlled trials of intravenous secretin compared to a placebo treatment in children or adults diagnosed with ASD, where at least one standardised outcome measure was reported. DATA COLLECTION AND ANALYSIS: Sixteen studies met the inclusion criteria but for two of these, conducted by Repligen, the only available multisite data were reported in press releases. All outcome data from the other 14 trials were continuous. Where trials used cross-over designs, we conducted analysis on results from the first treatment phase. Where mean change from baseline was reported, we used this in preference to post-treatment scores for meta-analyses or forest plots. Meta-analysis was able to be attempted for only one outcome (Childhood Autism Rating Scale). Insufficient data were available to conduct sensitivity or subgroup analyses to assess the impact of study quality, clinical differences in the intervention or clinically relevant differences between groups, such as age or presence of gastrointestinal symptoms. MAIN RESULTS: Over 900 children were recruited for the secretin trials. Twenty-five established standardised outcome measures were reported to assess core features of ASD, communication, behaviour, visuospatial skills, affect and adverse events. One standardised measure of global impression was also used. No more than four studies used any one outcome measure similarly. When duration from the start of the intervention to outcome assessment was known, outcomes were reported at between three and six weeks. Meta-analysis of data was not possible but there is now consistency of findings, with RCTs of the efficacy of secretin in autism not showing improvements for core features of ASD. AUTHORS’ CONCLUSIONS: There is no evidence that single or multiple dose intravenous secretin is effective and as such currently it should not be recommended or administered as a treatment for ASD. Further experimental assessment of secretin’s effectiveness for ASD can only be justified if there is new high-quality and replicated scientific evidence that either finds that secretin has a role in neurotransmission in a way that could benefit all children with ASD or identifies important subgroups of children with ASD who could benefit from secretin because of a proven link between the action of secretin and the known cause of their ASD, or the type of problems they are experiencing.
