1. {{Autistic children have better social interaction, thanks to theatre programme}}. {Nurs Stand};2015 (Oct 14);30(7):15.
Participating in theatre-based programmes can significantly improve the social abilities of children with autism, according to a North American study.
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2. Campbell JE, Morgan M, Barnett V, Spreat S. {{Handheld Devices and Video Modeling to Enhance the Learning of Self-Help Skills in Adolescents With Autism Spectrum Disorder}}. {OTJR (Thorofare N J)};2015 (Apr);35(2):95-100.
The viewing of videos is a much-studied intervention to teach self-help, social, and vocational skills. Many of the studies to date looked at video modeling using televisions, computers, and other large screens. This study looked at the use of video modeling on portable handheld devices to teach hand washing to three adolescent students with an autism spectrum disorder. Three students participated in this 4-week study conducted by occupational therapists. Baseline data were obtained for the first student for 1 week, the second for 2 weeks, and the third for 3 weeks; videos were introduced when the participants each finished the baseline phase. Given the cognitive and motor needs of the participants, the occupational therapist set the player so that the participants only had to press the play button to start the video playing. The participants were able to hold the players and view at distances that were most appropriate for their individual needs and preferences. The results suggest that video modeling on a handheld device improves the acquisition of self-help skills.
3. Cederlof M, Pettersson E, Sariaslan A, Larsson H, Ostberg P, Kelleher I, Langstrom N, Gumpert CH, Lundstrom S, Lichtenstein P. {{The association between childhood autistic traits and adolescent psychotic experiences is explained by general neuropsychiatric problems}}. {Am J Med Genet B Neuropsychiatr Genet};2015 (Oct 13)
Studies suggest associations between childhood autistic traits and adolescent psychotic experiences. However, recent research suggests that a general neuropsychiatric problems factor predicts adverse outcomes better than specific diagnostic entities. To examine if the alleged association between autistic traits and psychotic experiences could rather be explained by a general neuropsychiatric problems factor comprising symptoms of ADHD, tic disorder, developmental coordination disorder, and learning disorder, we conducted a prospective cohort study based on the Child and Adolescent Twin Study in Sweden. In addition, we examined the genetic and environmental influences on the associations. A total of 9,282 twins with data on childhood autistic traits and other neuropsychiatric problems, and follow-up data on psychotic experiences at ages 15 and/or 18 years were included. First, psychotic experiences were regressed on autistic traits and second, the general neuropsychiatric problems factor was added to the model. Auditory hallucinations were analyzed separately from the other psychotic experiences. Finally, twin analyses were employed to disentangle genetic from environmental influences in the observed associations. Replicating prior research, significant associations were found between autistic traits in childhood and auditory hallucinations at ages 15 and 18. However, after controlling for the general neuropsychiatric problems factor, the associations between autistic traits and auditory hallucinations disappeared, whereas the association between the general neuropsychiatric problems factor and auditory hallucinations persisted after controlling for autistic traits. Twin analyses revealed that the association between the general neuropsychiatric problems factor and auditory hallucinations was driven by shared genetic influences. (c) 2015 Wiley Periodicals, Inc.
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4. Cobb SR. {{Cognitive disorders: Deep brain stimulation for Rett syndrome}}. {Nature};2015 (Oct 15);526(7573):331-332.
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5. Crawford S. {{On the origins of autism: The Quantitative Threshold Exposure hypothesis}}. {Med Hypotheses};2015 (Oct 16)
The Quantitative Threshold Exposure (QTE) hypothesis is a multifactorial threshold model that accounts for the cumulative effects of risk factor exposure in both the causation of autism spectrum disorder (ASD) and its dramatic increase over the past 30years. The QTE hypothesis proposes that ASD is triggered by the cumulative effects of high-level exposure to endogenous and environmental factors that act as antigens to impair normal immune system (IS) and associated central nervous system (CNS) functions during critical developmental stages. The quantitative threshold parameters that comprise a cumulative risk for the development of ASD are identified by the assessment of documented epidemiological factors that, in sum, determine the likelihood that ASD will occur as a result of their effects on critically integrated IS and CNS pathways active during prenatal, neo-natal and early childhood brain maturation. The model proposes an explanation for the relationship between critical developmental stages of brain/immune system development in conjunction with the quantitative effects of genetic and environmental risk factors that may interface with these critical developmental windows. This model may be useful even when the individual contributions of specific risk factors cannot be quantified, as it proposes that the combined quantitative level of exposure to risk factors for ASD rather than exposure to any one risk factor per se defines threshold occurrence rates.
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6. Endreffy I, Bjorklund G, Dicso F, Urbina MA, Endreffy E. {{Acid glycosaminoglycan (aGAG) excretion is increased in children with autism spectrum disorder, and it can be controlled by diet}}. {Metab Brain Dis};2015 (Oct 14)
Autism research continues to receive considerable attention as the options for successful management are limited. The understanding of the autism spectrum disorder (ASD) etiology has now progressed to encompass genetic, epigenetic, neurological, hormonal, and environmental factors that affect outcomes for patients with ASD. Glycosaminoglycans (GAGs) are a family of linear, sulfated polysaccharides that are associated with central nervous system (CNS) development, maintenance, and disorders. Proteoglycans (PG) regulate diverse functions in the central nervous system. Heparan sulfate (HS) and chondroitin sulfate (CS) are two major GAGs present in the PGs of the CNS. As neuroscience advances, biochemical treatments to correct brain chemistry become better defined. Nutrient therapy can be very potent and has minimal to no side effects, since no molecules foreign to the body are needed. Given GAGs are involved in several neurological functions, and that its level can be somewhat modulated by the diet, the present study aimed to evaluate the role of GAGs levels in ASD symptoms. Both tGAG and its different fractions were evaluated in the urine of ASD and healthy control childrens. As levels differed between groups, a second trial was conduted evaluating if diet could reduce tGAG levels and if this in turn decrease ASD symptoms. The present study found that tGAG concentration was significantly higher in the urine of children with ASD compared to healthy control children and this was also evident in all GAG fractions. Within groups (controls and ASD), no gender differences in GAG excretion were found. The use of a 90 days elimination diet (casein-free, special carbohydrates, multivitamin/mineral supplement), had major effects in reducing urinary tGAG excretion in children with ASD.
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7. Gao L, Xi QQ, Wu J, Han Y, Dai W, Su YY, Zhang X. {{Association between Prenatal Environmental Factors and Child Autism: A Case Control Study in Tianjin, China}}. {Biomed Environ Sci};2015 (Sep);28(9):642-650.
OBJECTIVE: To investigate the association between autism and prenatal environmental risk factors. METHODS: A case-control study was conducted among 193 children with autism from the special educational schools and 733 typical development controls matched by age and gender by using questionnaire in Tianjin from 2007 to 2012. Statistical analysis included quick unbiased efficient statistical tree (QUEST) and logistic regression in SPSS 20.0. RESULTS: There were four predictors by QUEST and the logistic regression analysis, maternal air conditioner use during pregnancy (OR=0.316, 95% CI: 0.215-0.463) was the single first-level node (chi2=50.994, P=0.000); newborn complications (OR=4.277, 95% CI: 2.314-7.908) and paternal consumption of freshwater fish (OR=0.383, 95% CI: 0.256-0.573) were second-layer predictors (chi2=45.248, P=0.000; chi2=24.212, P=0.000); and maternal depression (OR=4.822, 95% CI: 3.047-7.631) was the single third-level predictor (chi2=23.835, P=0.000). The prediction accuracy of the tree was 89.2%. CONCLUSION: The air conditioner use during pregnancy and paternal freshwater fish diet might be beneficial for the prevention of autism, while newborn complications and maternal depression might be the risk factors.
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8. Ghanizadeh A, Tordjman S, Jaafari N. {{Aripiprazole for treating irritability in children & adolescents with autism: A systematic review}}. {Indian J Med Res};2015 (Sep);142(3):269-275.
BACKGROUND & OBJECTIVES: No clear therapeutic benefits of antipsychotics have been reported for the treatment of behavioural symptoms in autism. This systematic review provides an assessment of evidence for treating irritability in autism by aripiprazole. METHODS: The databases of MEDLINE/PubMed and Google Scholar were searched for relevant articles about the effect of aripiprazole in children with autism. The articles were searched according to the inclusion and exclusion criteria specifed for this review. All the double-blind, controlled, randomized, clinical trials examining the efficacy of aripiprazole for treating children and adolescents with autism were included. RESULTS: From the 93 titles identified, 26 were irrelevant and 58 were evaluated for more details. Only five articles met the inclusive criteria. The evidence from precise randomized double blind clinical trials of aripiprazole for the treatment of autism in children and adolescents was convincing enough to recommend aripiprazole. Adverse effects were not very common and were usually mild. INTERPRETATION & CONCLUSIONS: Current evidence suggests that aripiprazole is as effective and safe as risperidone for treating irritability in autism. However, further studies with larger sample size and longer duration are required.
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9. Hao S, Tang B, Wu Z, Ure K, Sun Y, Tao H, Gao Y, Patel AJ, Curry DJ, Samaco RC, Zoghbi HY, Tang J. {{Forniceal deep brain stimulation rescues hippocampal memory in Rett syndrome mice}}. {Nature};2015 (Oct 15);526(7573):430-434.
Deep brain stimulation (DBS) has improved the prospects for many individuals with diseases affecting motor control, and recently it has shown promise for improving cognitive function as well. Several studies in individuals with Alzheimer disease and in amnesic rats have demonstrated that DBS targeted to the fimbria-fornix, the region that appears to regulate hippocampal activity, can mitigate defects in hippocampus-dependent memory. Despite these promising results, DBS has not been tested for its ability to improve cognition in any childhood intellectual disability disorder. Such disorders are a pressing concern: they affect as much as 3% of the population and involve hundreds of different genes. We proposed that stimulating the neural circuits that underlie learning and memory might provide a more promising route to treating these otherwise intractable disorders than seeking to adjust levels of one molecule at a time. We therefore studied the effects of forniceal DBS in a well-characterized mouse model of Rett syndrome (RTT), which is a leading cause of intellectual disability in females. Caused by mutations that impair the function of MeCP2 (ref. 6), RTT appears by the second year of life in humans, causing profound impairment in cognitive, motor and social skills, along with an array of neurological features. RTT mice, which reproduce the broad phenotype of this disorder, also show clear deficits in hippocampus-dependent learning and memory and hippocampal synaptic plasticity. Here we show that forniceal DBS in RTT mice rescues contextual fear memory as well as spatial learning and memory. In parallel, forniceal DBS restores in vivo hippocampal long-term potentiation and hippocampal neurogenesis. These results indicate that forniceal DBS might mitigate cognitive dysfunction in RTT.
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10. Huber KM, Klann E, Costa-Mattioli M, Zukin RS. {{Dysregulation of Mammalian Target of Rapamycin Signaling in Mouse Models of Autism}}. {J Neurosci};2015 (Oct 14);35(41):13836-13842.
The mammalian target of rapamycin (mTOR) is a central regulator of a diverse array of cellular processes, including cell growth, proliferation, autophagy, translation, and actin polymerization. Components of the mTOR cascade are present at synapses and influence synaptic plasticity and spine morphogenesis. A prevailing view is that the study of mTOR and its role in autism spectrum disorders (ASDs) will elucidate the molecular mechanisms by which mTOR regulates neuronal function under physiological and pathological conditions. Although many ASDs arise as a result of mutations in genes with multiple molecular functions, they appear to converge on common biological pathways that give rise to autism-relevant behaviors. Dysregulation of mTOR signaling has been identified as a phenotypic feature common to fragile X syndrome, tuberous sclerosis complex 1 and 2, neurofibromatosis 1, phosphatase and tensin homolog, and potentially Rett syndrome. Below are a summary of topics covered in a symposium that presents dysregulation of mTOR as a unifying theme in a subset of ASDs.
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11. Leno VC, Naples A, Cox A, Rutherford H, McPartland J. {{Common and Distinct Modulation of Electrophysiological Indices of Feedback Processing by Autistic and Psychopathic Traits}}. {Soc Neurosci};2015 (Oct 16)
Both autism spectrum disorder (ASD) and psychopathy are primarily characterized by social dysfunction; overlapping phenotypic features may reflect altered function in common brain mechanisms. The current study examined the degree to which neural response to social and non-social feedback is modulated by autistic versus psychopathic traits in a sample of typically-developing adults (N=31, 11 males, 18-52 years). Event-related potentials were recorded whilst participants completed a behavioral task and received feedback on task performance. Both autistic and psychopathic traits were associated with alterations in the neural correlates of feedback processing. Sensitivity to specific forms of feedback (social, non-social, positively-valenced, negatively-valenced) differed between the two traits. Autistic traits were associated with decreased sensitivity to social feedback. In contrast, the antisocial domain of psychopathic traits was associated with an overall decrease in sensitivity to feedback, and the interpersonal manipulation domain was associated with preserved processing of positively-valenced feedback. Results suggest distinct alterations within specific mechanisms of feedback processing may underlie similar difficulties in social behavior.
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12. McGrane IR, Loveland JG, Zaluski HJ, Foster KD. {{Serum Quetiapine Concentration Changes with Concomitant Oxcarbazepine Therapy in a Boy with Autism Spectrum Disorder}}. {J Child Adolesc Psychopharmacol};2015 (Oct 15)
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13. McKinlay CJ, Alsweiler JM, Ansell JM, Anstice NS, Chase JG, Gamble GD, Harris DL, Jacobs RJ, Jiang Y, Paudel N, Signal M, Thompson B, Wouldes TA, Yu TY, Harding JE. {{Neonatal Glycemia and Neurodevelopmental Outcomes at 2 Years}}. {N Engl J Med};2015 (Oct 15);373(16):1507-1518.
BACKGROUND: Neonatal hypoglycemia is common and can cause neurologic impairment, but evidence supporting thresholds for intervention is limited. METHODS: We performed a prospective cohort study involving 528 neonates with a gestational age of at least 35 weeks who were considered to be at risk for hypoglycemia; all were treated to maintain a blood glucose concentration of at least 47 mg per deciliter (2.6 mmol per liter). We intermittently measured blood glucose for up to 7 days. We continuously monitored interstitial glucose concentrations, which were masked to clinical staff. Assessment at 2 years included Bayley Scales of Infant Development III and tests of executive and visual function. RESULTS: Of 614 children, 528 were eligible, and 404 (77% of eligible children) were assessed; 216 children (53%) had neonatal hypoglycemia (blood glucose concentration, <47 mg per deciliter). Hypoglycemia, when treated to maintain a blood glucose concentration of at least 47 mg per deciliter, was not associated with an increased risk of the primary outcomes of neurosensory impairment (risk ratio, 0.95; 95% confidence interval [CI], 0.75 to 1.20; P=0.67) and processing difficulty, defined as an executive-function score or motion coherence threshold that was more than 1.5 SD from the mean (risk ratio, 0.92; 95% CI, 0.56 to 1.51; P=0.74). Risks were not increased among children with unrecognized hypoglycemia (a low interstitial glucose concentration only). The lowest blood glucose concentration, number of hypoglycemic episodes and events, and negative interstitial increment (area above the interstitial glucose concentration curve and below 47 mg per deciliter) also did not predict the outcome. CONCLUSIONS: In this cohort, neonatal hypoglycemia was not associated with an adverse neurologic outcome when treatment was provided to maintain a blood glucose concentration of at least 47 mg per deciliter. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.).
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14. Mittal K, Dadhania D, Dey AK, Gadewar R, Hira P. {{Unruptured Noncoronary Sinus of Valsalva Aneurysm Associated with Atrial Septal Defect (ASD)}}. {J Clin Diagn Res};2015 (Aug);9(8):TD01-02.
Sinus of Valsalva aneurysms are rare cardiac anomalies. Incidence of this anomaly is higher in Asian population with male preponderance. Our case highlights a rare association between unruptured sinus of Valsalva aneurysm and atrial septal defect (ASD). Rarely diagnosis of sinus of Valsalva aneurysm is missed on two dimensional echocardiography. Multi slice CT scan is done to confirm echocardiographic findings and to detect any missed complications, other cardiac abnormalities and anatomy for a precise surgical approach.
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15. Murray AL, McKenzie K, Kuenssberg R, Booth T. {{Do the Autism Spectrum Quotient (AQ) and Autism Spectrum Quotient Short Form (AQ-S) Primarily Reflect General ASD Traits or Specific ASD Traits? A Bi-Factor Analysis}}. {Assessment};2015 (Oct 16)
In the current study, we fit confirmatory bi-factor models to the items of the Autism Spectrum Quotient (AQ) and Autism Spectrum Quotient Short Form (AQ-S) in order to assess the extents to which the items of each reflect general versus specific factors. The models were fit in a combined sample of individuals with and without a clinical diagnosis of autism spectrum disorders. Results indicated that, with the exception of the Attention to Details factor in the AQ and the Numbers/Patterns factors in the AQ-S, items primarily reflected a general factor. This suggests that when attempting to estimate an association between a specific symptom measured by the AQ or AQ-S and some criterion, associations will be confounded by the general factor. To resolve this, we recommend using a bi-factor measurement model or factor scores from a bi-factor measurement whenever hypotheses about specific symptoms are being assessed.
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16. Mutluer T, Karakoc Demirkaya S, Abali O. {{Assessment of sleep problems and related risk factors observed in Turkish children with Autism spectrum disorders}}. {Autism Res};2015 (Oct 13)
Sleep problems are common and difficult to manage in children with autism spectrum disorders (ASD). Another major adverse impact of sleep problems is that they exacerbate behavioral problems. To assess sleep problems and possible behavioral risk factors in detail, we aimed to compare sleep habits of children with ASD, with healthy children. The relationship between sleep difficulties and concomitant behavioral problems such as repetitive behaviors, hyperactivity, and social withdrawal were also examined. Hundred and seventeen children and adolescents including 64 with the diagnosis of ASD and 53 healthy subjects were enrolled in the study. Diagnostic Interview for ASD was performed according to DSM-IV-TR. Socio-demographical data form and childhood autism rating scale were filled by researchers. Aberrant behavior checklist (ABC), child behavior checklist and pediatric sleep questionnaire (PSQ) were completed by the parents of the children. Children with ASD had higher frequency of sleep problems, snoring, breathing problems, behavioral problems compared with healthy children (for all parameters; P < 0.001). A positive correlation was identified between the total score of PSQ and the total score of ABC (P < 0.05, Spearman correlation coefficient: 0.347). Sleep latency was prolonged in children with ASD compared with healthy subjects (P < 0.001). In accordance with the current literature, children with ASD were subject to sleep problems significantly more than the control group. Identified risk factors for sleep problems in ASD children were behavioral factors such as stereotypies, self-mutilation, hyperactivity, and social withdrawal. Autism Res 2015. (c) 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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17. Namasivayam AK, Yan T, Wong WY, van Lieshout P. {{Quality of statistical reporting in developmental disability journals}}. {Int J Rehabil Res};2015 (Oct 16)
Null hypothesis significance testing (NHST) dominates quantitative data analysis, but its use is controversial and has been heavily criticized. The American Psychological Association has advocated the reporting of effect sizes (ES), confidence intervals (CIs), and statistical power analysis to complement NHST results to provide a more comprehensive understanding of research findings. The aim of this paper is to carry out a sample survey of statistical reporting practices in two journals with the highest h5-index scores in the areas of developmental disability and rehabilitation. Using a checklist that includes critical recommendations by American Psychological Association, we examined 100 randomly selected articles out of 456 articles reporting inferential statistics in the year 2013 in the Journal of Autism and Developmental Disorders (JADD) and Research in Developmental Disabilities (RDD). The results showed that for both journals, ES were reported only half the time (JADD 59.3%; RDD 55.87%). These findings are similar to psychology journals, but are in stark contrast to ES reporting in educational journals (73%). Furthermore, a priori power and sample size determination (JADD 10%; RDD 6%), along with reporting and interpreting precision measures (CI: JADD 13.33%; RDD 16.67%), were the least reported metrics in these journals, but not dissimilar to journals in other disciplines. To advance the science in developmental disability and rehabilitation and to bridge the research-to-practice divide, reforms in statistical reporting, such as providing supplemental measures to NHST, are clearly needed.
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18. Oerlemans AM, Burmanje MJ, Franke B, Buitelaar JK, Hartman CA, Rommelse NN. {{Identifying Unique Versus Shared Pre- and Perinatal Risk Factors for ASD and ADHD Using a Simplex-Multiplex Stratification}}. {J Abnorm Child Psychol};2015 (Oct 14)
Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur. Besides shared genetic factors, pre- and perinatal risk factors (PPFs) may determine if ASD, ADHD, or the combination of both disorders becomes manifest. This study aimed to test shared and unique involvement of PPFs for ASD and ADHD, using an approach that stratifies the sample into affected/unaffected offspring and single-incidence (SPX) versus multi-incidence (MPX) families. Pre- perinatal data based on retrospective parent-report were collected in 288 children (71 % males) from 31 SPX and 59 MPX ASD families, 476 children (65 % males) from 31 SPX and 171 MPX ADHD families, and 408 control children (42 % males). Except for large family size and more firstborns amongst affected offspring, no shared PFFs were identified for ASD and ADHD. PPFs predominantly related to ASD (maternal infections and suboptimal condition at birth) were more often reported in affected than unaffected siblings. PPFs associated with ADHD (low parental age, maternal diseases, smoking and stress) were shared between affected and unaffected siblings. Firstborn-ship was more frequent in SPX than MPX ASD probands. Our results suggest that the co-morbidity of ASD and ADHD is not likely explained by shared PPFs. Instead, PPFs might play a crucial role in the developmental pathways leading up to either disorder. PPFs in ADHD appear to index an increased shared risk, whereas in ASD PPFs possibly have a more determining role in the disorder. SPX-MPX stratification detected possible etiological differences in ASD families, but provided no deeper insight in the role of PPFs in ADHD.
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19. Pintaudi M, Veneselli E, Voci A, Vignoli A, Castiglione D, Calevo MG, Grasselli E, Ragazzoni M, Cogliati F, Calzari L, Scornavacca GF, Russo S, Vergani L. {{Blood oxidative stress and metallothionein expression in Rett syndrome: Probing for markers}}. {World J Biol Psychiatry};2015 (Oct 15):1-12.
OBJECTIVES: Oxidative stress seems to be involved in Rett syndrome (RTT). The aim of this study was to assess the antioxidant status in RTT children with MECP2 gene mutations with respect to healthy controls, and to explore novel blood antioxidant markers for RTT severity. METHODS: In erythrocytes from RTT females aged 2-14 years (n = 27) and age-matched controls (n = 27), we measured the levels of malonaldehyde and the activity of two antioxidant enzymes, Cu/Zn-superoxide dismutase and catalase, by spectrophotometric assays. In leukocytes, the expression of metallothioneins, the main non-enzymatic antioxidants, was assessed by real-time RT-PCR. In nine selected RTT children, methylome analysis was also performed. RESULTS: Blood of RTT patients showed increased lipid peroxidation and a dysregulated pattern of MT expression, while enzymatic activities did not change significantly with respect to controls. Moreover, we observed no epigenetic dysregulation in CpG-enriched promoter regions of the analysed genes but significant hypomethylation in the random loci. CONCLUSIONS: As the haematic level of MT-1A directly correlates with the phenotype severity, this metallothionein can represent a marker for RTT severity. Moreover, the attempt to link the level of blood oxidative stress with MECP2 mutation and specific clinical features led us to draw some interesting conclusions.
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20. Scott M, Falkmer M, Girdler S, Falkmer T. {{Viewpoints on Factors for Successful Employment for Adults with Autism Spectrum Disorder}}. {PLoS One};2015;10(10):e0139281.
This article explores the key factors for successful employment from the viewpoints of adults with autism spectrum disorder (ASD) and employers. Two groups of individuals participated in this study, 40 adults with ASD and 35 employers. Q method was used to understand and contrast the viewpoints of the two groups. Data were analysed using by-person varimax rotation factor analysis. Results showed that although both groups appear committed to the employment process, the difference in their understanding regarding the type of workplace support required, job expectations and productivity requirements continues to hinder successful employment. These results highlight the need to facilitate communication between employees and employers to ensure a clear understanding of the needs of both groups are met. The use of an ASD-specific workplace tool may assist in facilitating the necessary communication between these two groups.
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21. Simmons R, Stanley C. {{Neonatal Hypoglycemia Studies–Is There a Sweet Story of Success Yet?}}. {N Engl J Med};2015 (Oct 15);373(16):1567-1569.
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22. Sobotka SA, Francis A, Vander Ploeg Booth K. {{Associations of family characteristics with perceptions of care among parents of children with autism}}. {Child Care Health Dev};2015 (Oct 16)
BACKGROUND: Although autism spectrum disorder (ASD) is an increasingly common chronic disability, primary care provider (PCPs) report deficits in providing primary care for children with ASD, and parents report lapses in receipt of medical home services. In this study, we describe parental experiences with specific medical home components for their children with ASD. METHODS: We analysed data from all children within the National Survey of Children with Special Health Care Needs database with ASD and a usual place for care (n = 2859). We evaluated the receipt of core medical home components: accessible, comprehensive, coordinated, family centred and compassionate and culturally sensitive care. RESULTS: Children were mean age 10.1 years, and respondents were 75% mothers and 95% reported having a primary care provider (PCP). Seventy-one percent reported care to be usually comprehensive, over three-fourths of respondents reported care to be family centred and compassionate and 87% reported care to be culturally sensitive. Of the parents who reported a need for care coordination (n = 1049), only 14% of parents reported usually getting the help they needed. More educated, English-speaking, non-Hispanic White mothers of older children supported by private insurance were more likely to report never getting as much help coordinating care as desired. Coordination with education services are especially important for children with ASD, yet 27% of parents reported dissatisfaction with PCPs’ communication with schools or early intervention. CONCLUSION: Although parents report a high level of access to PCPs and places for care as well as receiving most core components of the medical home, care coordination activities are lacking for children with ASD. More resourced families are particularly likely to report unmet needs.
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23. Solomon O, Heritage J, Yin L, Maynard DW, Bauman ML. {{‘What Brings Him Here Today?’: Medical Problem Presentation Involving Children with Autism Spectrum Disorders and Typically Developing Children}}. {J Autism Dev Disord};2015 (Oct 13)
Conversation and discourse analyses were used to examine medical problem presentation in pediatric care. Healthcare visits involving children with ASD and typically developing children were analyzed. We examined how children’s communicative and epistemic capabilities, and their opportunities to be socialized into a competent patient role are interactionally achieved. We found that medical problem presentation is designed to contain a ‘pre-visit’ account of the interactional and epistemic work that children and caregivers carry out at home to identify the child’s health problems; and that the intersubjective accessibility of children’s experiences that becomes disrupted by ASD presents a dilemma to all participants in the visit. The article examines interactional roots of unmet healthcare needs and foregone medical care of people with ASD.
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24. Speed HE, Masiulis I, Gibson JR, Powell CM. {{Increased Cortical Inhibition in Autism-Linked Neuroligin-3R451C Mice Is Due in Part to Loss of Endocannabinoid Signaling}}. {PLoS One};2015;10(10):e0140638.
A single, maternally inherited, X-linked point mutation leading to an arginine to cysteine substitution at amino acid 451 (R451C) of Neuroligin 3 (NLGN3R451C) is a likely cause of autism in two brothers. Knockin mice expressing the Nlgn3R451C mutation in place of wild-type Nlgn3 demonstrate increased inhibitory synaptic strength in somatosensory cortex, resulting in an excitatory/inhibitory (E/I) imbalance that is potentially relevant for autism-associated behavioral deficits characteristic of these mice. We have replicated the increase in evoked inhibitory postsynaptic currents (eIPSCs) onto layer II/III cortical pyramidal neurons. We also find that increased frequency of spontaneous mIPSCs in Nlgn3R451C mice occurs in the absence of action potential-driven transmission. This suggests the E/I imbalance is due to changes at the synapse level, as opposed to the network level. Next, we use paired whole-cell recordings in an attempt to identify specific interneuron subtypes affected by the Nlgn3R451C mutation. Curiously, we observe no change in the amplitude of cell-to-cell, unitary IPSCs (uIPSCs) from parvalbumin-positive (PV) or somatostatin-positive (SOM) interneurons onto pyramidal neurons. We also observe no change in the number or density of PV and SOM interneurons in LII/III of somatosensory cortex. This effectively rules out a role for these particular interneurons in the increased inhibitory synaptic transmission, pointing to perhaps alternative interneuron subtypes. Lastly, impaired endocannabinoid signaling has been implicated in hippocampal synaptic dysfunction in Nlgn3R451C mice, but has not been investigated at cortical synapses. We find that bath application of the CB1 antagonist, AM 251 in WT mice eliminates the Nlgn3R451C increase in eIPSC amplitude and mIPSC frequency, indicating that increased inhibitory transmission in mutant mice is due, at least in part, to a loss of endocannabinoid signaling through CB1 receptors likely acting at interneurons other than PV or SOM.
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25. Uzunova G, Pallanti S, Hollander E. {{Excitatory/inhibitory imbalance in autism spectrum disorders: Implications for interventions and therapeutics}}. {World J Biol Psychiatry};2015 (Oct 15):1-13.
OBJECTIVES: Imbalance between excitation and inhibition and increased excitatory-inhibitory (E-I) ratio is a common mechanism in autism spectrum disorders (ASD) that is responsible for the learning and memory, cognitive, sensory, motor deficits, and seizures occurring in these disorders. ASD are very heterogeneous and better understanding of E-I imbalance in brain will lead to better diagnosis and treatments. METHODS: We perform a critical literature review of the causes and presentations of E-I imbalance in ASD. RESULTS: E-I imbalance in ASD is due primarily to abnormal glutamatergic and GABAergic neurotransmission in key brain regions such as neocortex, hippocampus, amygdala, and cerebellum. Other causes are due to dysfunction of neuropeptides (oxytocin), synaptic proteins (neuroligins), and immune system molecules (cytokines). At the neuropathological level E-I imbalance in ASD is presented as a « minicolumnopathy ». E-I imbalance alters the manner by which the brain processes information and regulates behaviour. New developments for investigating E-I imbalance such as optogenetics and transcranial magnetic stimulation (TMS) are presented. Non-invasive brain stimulation methods such as TMS for treatment of the core symptoms of ASD are discussed. CONCLUSIONS: Understanding E-I imbalance has important implications for developing better pharmacological and behavioural treatments for ASD, including TMS, new drugs, biomarkers and patient stratification.
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26. Valacchi G, Sticozzi C, Belmonte G, Cervellati F, Pecorelli A, Signorini C, Leoncini S, Ciccoli L, De Felice C, Della Ragione F, Scalabri F, Marracino F, Madonna M, M DE, Joussef H, Stefania F. {{Scavenger Receptor B1 oxidative post-translational modifications are responsible for its loss in Rett syndrome}}. {Free Radic Biol Med};2014 (Oct);75 Suppl 1:S10-S11.
The modulation of the HDL receptor scavenger receptor B1 (SRB1) was evaluated in skin fibroblasts isolated from Rett syndrome (RTT) patients, a rare neurodevelopmental disorder affecting almost exclusively females associated in up to 95% of cases to de novo loss-of-function mutations in the X-chromosome-linked gene encoding the methyl-CpG-binding protein 2 (MeCP2). Patients showed an altered plasma lipid profile, while their skin fibroblasts showed a dramatic reduction in SRB1 (immunogold, Western blot and immunohistochemistry). The decreased SRB1 levels were demonstrated to be the consequence of its binding with 4-hydroxy-2-nonenal (4HNE), a product of lipid peroxidation, and its increased ubiquitination. Therefore the loss of SRB1 in RTT cells is a consequence of the chronic oxidative stress status present in RTT. In addition RTT fibroblast presented high intracellular levels of H2O2 and 4HNE protein adducts. This finding was correlated with the constitutive activation of NADPH oxidase (NOX) and was reverted by DPI (NOX inhibitor) or Desferal (Iron chelator) pre-treatment. To confirm the alteration of status redox in RTT cells, the activity of several enzymes involved in protecting the cell from OS was also evaluated. Glutathione peroxidase (GPx), Supeoxide dismutase and Glucose-6-phosphate dehydrogenase (G6PDH) activity were decreased respect to control. These data paralleled with a constitutive activation of NRF2 and elevated gene expression of Heme oxigenase-1 (HO-1) and NAD(P)H dehydrogenase quinone 1 (NQO-1). Of note, when NRF2 pathway was stimulated via exogenous oxidants, RTT fibroblast did not respond as the control cells.
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27. Wink LK, Pedapati EV, Horn PS, McDougle CJ, Erickson CA. {{Multiple Antipsychotic Medication Use in Autism Spectrum Disorder}}. {J Child Adolesc Psychopharmacol};2015 (Oct 14)
OBJECTIVE: The purpose of this study was to explore the use of multiple antipsychotic medications in patients with autism spectrum disorder (ASD) by reviewing the longitudinal medication management of 1100 patients consecutively treated for behavioral symptoms associated with ASD at a tertiary care specialty clinic. METHODS: We identified all patients with ASD treated with daily doses of two or more antipsychotics for at least two visits at our clinic. For each patient meeting inclusion criteria, diagnostic and demographic data were collected. To evaluate clinical need and effectiveness of antipsychotic medications in this sample, we reviewed symptoms targeted with each antipsychotic medication and concomitant medications prescribed. Clinical Global Impressions-Severity (CGI-S) and Clinical Global Impressions-Improvement (CGI-I) scale ratings had been completed at the time of each visit, and the duration of treatment with antipsychotic medications was determined. To evaluate the safety and tolerability of antipsychotic medication use in ASD, we reviewed reported adverse effects and calculated body mass index (BMI) change with treatment. RESULTS: Seventy patients met the inclusion criteria (6.4% of our sample). The majority of patients were moderately to severely ill Caucasian males, as determined by baseline mean CGI-S of 4.7 (SD = 0.8), and were diagnosed with autistic disorder and comorbid intellectual disability. The mean age was 15.1 years (SD = 10.9), the primary targeted symptoms were agitation/irritability, physical aggression, and self-injury. The majority of patients remained on two or more antipsychotics for >1 year. In this population, patients demonstrated greater symptomatic improvement and generally tolerated treatment without significant adverse effects. CONCLUSIONS: The use of two or more antipsychotic medications may be increasingly common in patients with ASD. This retrospective study demonstrates that this treatment approach may be of some clinical benefit, and is generally well tolerated. Prospective studies focusing on the efficacy and safety of concomitant antipsychotic medication usage in ASD should be considered.
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28. Zhang Z, Cao M, Chang CW, Wang C, Shi X, Zhan X, Birnbaum SG, Bezprozvanny I, Huber K, Wu JI. {{Autism-Associated Chromatin Regulator Brg1/SmarcA4 is Required for Synapse Development and MEF2-mediated Synapse Remodeling}}. {Mol Cell Biol};2015 (Oct 12)
Synapse development requires normal neuronal activities and the precise expression of synapse-related genes. Dysregulation of synaptic genes results in neurological diseases such as autism spectrum disorders (ASD). Mutations in genes encoding chromatin remodeling factor Brg1/SmarcA4 and its associated proteins are the genetic causes of several developmental diseases with neurological defects and autistic symptoms. Recent large-scale genomic studies predicted Brg1/SmarcA4 as one of the key nodes of the ASD gene network. We report that Brg1 deletion in early postnatal hippocampal neurons led to reduced dendritic spine density and maturation and impaired synapse activities. In developing mice, neuronal Brg1 deletion caused severe neurological defects. Gene expression analyses indicated that Brg1 regulates a significant number of genes known to be involved in synapse function and implicated in ASD. We found that Brg1 is required for dendritic spine/synapse elimination mediated by the ASD-associated transcription factor MEF2 and that Brg1 regulates the activity-induced expression of a specific subset of genes that overlap significantly with the targets of MEF2. Our analyses showed that Brg1 interacts with MEF2 and that MEF2 is required for Brg1 recruitment to target genes in response to neuron activation. Thus, Brg1 plays important roles both in synapse development/maturation and in MEF2-mediated synapse remodeling. Our study reveals specific functions of the epigenetic regulator Brg1 in synapse development and provides insights into its role in neurological diseases such as ASD.
