1. Adams R, Taylor J, Duncan A, Bishop S. {{Peer Victimization and Educational Outcomes in Mainstreamed Adolescents with Autism Spectrum Disorder (ASD)}}. {J Autism Dev Disord}. 2016.
The majority of adolescents with ASD spend a significant amount of the school day in general education settings; yet, many of these students exhibit problems at school. The current manuscript examined whether specific types of peer victimization were associated with a range of educational outcomes. Participants from study 1 included parents of 1221 adolescents from the Interactive Autism Network. Study 2 included 54 adolescent males and one of their parents that were recruited from a clinic registry. Both studies found that all types of victimization were associated with educational outcomes. These findings indicate that, in addition to improving overall well-being of students with ASD, reducing peer victimization could have positive effects on educational performance of these students.
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2. Arnevik EA, Helverschou SB. {{Autism Spectrum Disorder and Co-occurring Substance Use Disorder – A Systematic Review}}. {Subst Abuse}. 2016; 10: 69-75.
OBJECTIVE: Patients with co-occurring autism spectrum disorders (ASD) and substance use disorder (SUD) require special attention from clinical services. Screening for this co-occurrence is not generally an integral part of routine clinical assessments, and failure to identify and understand this group of patients may contribute to a worsening of their symptoms and/or an increase in drug abuse. Thus, there is a need to review the evidence base on patients with co-occurring ASD and SUD in order to enhance clinical practice and future research. METHODS: We reviewed all identified papers on patients with co-occurring ASD and SUD. The focus of the review was on epidemiology, patient characteristics, function of drug use, and the effect of current interventions. RESULTS: A total of 18 papers were included in the analysis. Eleven papers were based on epidemiological studies, although only one study reported the prevalence of ASD in an SUD population. Two papers explored the role of personality, three papers studied subgroups of individuals serving prison for violent or sexual crimes, and one paper explored the function of drugs in the ASD patient group. There were no studies testing specific treatment interventions. CONCLUSIONS: In most of the treatment settings studied, there were relatively few patients with co-occurring ASD and SUD, but due to differences in study samples it was difficult to establish a general prevalence rate. The one consistent finding was the lack of focused treatment studies. There is clearly a need for research on interventions that take account of the special needs of this patient group.
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3. Cantiani C, Choudhury NA, Yu YH, Shafer VL, Schwartz RG, Benasich AA. {{From Sensory Perception to Lexical-Semantic Processing: An ERP Study in Non-Verbal Children with Autism}}. {PLoS One}. 2016; 11(8): e0161637.
This study examines electrocortical activity associated with visual and auditory sensory perception and lexical-semantic processing in nonverbal (NV) or minimally-verbal (MV) children with Autism Spectrum Disorder (ASD). Currently, there is no agreement on whether these children comprehend incoming linguistic information and whether their perception is comparable to that of typically developing children. Event-related potentials (ERPs) of 10 NV/MV children with ASD and 10 neurotypical children were recorded during a picture-word matching paradigm. Atypical ERP responses were evident at all levels of processing in children with ASD. Basic perceptual processing was delayed in both visual and auditory domains but overall was similar in amplitude to typically-developing children. However, significant differences between groups were found at the lexical-semantic level, suggesting more atypical higher-order processes. The results suggest that although basic perception is relatively preserved in NV/MV children with ASD, higher levels of processing, including lexical- semantic functions, are impaired. The use of passive ERP paradigms that do not require active participant response shows significant potential for assessment of non-compliant populations such as NV/MV children with ASD.
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4. Grainger C, Williams DM, Lind SE. {{Judgment of Learning Accuracy in High-functioning Adolescents and Adults with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2016.
This study explored whether adults and adolescents with autism spectrum disorder (ASD) demonstrate difficulties making metacognitive judgments, specifically judgments of learning. Across two experiments, the study examined whether individuals with ASD could accurately judge whether they had learnt a piece of information (in this case word pairs). In Experiment 1, adults with ASD demonstrated typical accuracy on a standard ‘cue-alone’ judgment of learning (JOL) task, compared to age- and IQ-matched neurotypical adults. Additionally, in Experiment 2, adolescents with ASD demonstrated typical accuracy on both a standard ‘cue-alone’ JOL task, and a ‘cue-target’ JOL task. These results suggest that JOL accuracy is unimpaired in ASD. These results have important implications for both theories of metacognition in ASD and educational practise.
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5. Greiss Hess L, Fitzpatrick SE, Nguyen DV, Chen Y, Gaul KN, Schneider A, Lemons Chitwood K, Eldeeb MA, Polussa J, Hessl D, Rivera S, Hagerman RJ. {{A Randomized, Double-Blind, Placebo-Controlled Trial of Low-Dose Sertraline in Young Children With Fragile X Syndrome}}. {J Dev Behav Pediatr}. 2016.
OBJECTIVE: Observational studies and anecdotal reports suggest that sertraline, a selective serotonin reuptake inhibitor, may improve language development in young children with fragile X syndrome (FXS). METHODS: The authors evaluated the efficacy of 6 months of treatment with low-dose sertraline in a randomized, double-blind, placebo-controlled trial in 52 children with FXS aged 2 to 6 years. RESULTS: Eighty-one subjects were screened for eligibility, and 57 were randomized to sertraline (27) or placebo (30). Two subjects from the sertraline arm and 3 from the placebo arm discontinued. Intent-to-treat analysis showed no difference from placebo on the primary outcomes: the Mullen Scales of Early Learning (MSEL) expressive language (EL) age equivalent and Clinical Global Impression Scale-Improvement. However, analyses of secondary measures showed significant improvements, particularly in motor and visual perceptual abilities and social participation. Sertraline was well tolerated, with no difference in side effects between sertraline and placebo groups. No serious adverse events occurred. CONCLUSION: This randomized controlled trial of 6 months of sertraline treatment showed no primary benefit with respect to early EL development and global clinical improvement. However, in secondary exploratory analyses, there were significant improvements seen on motor and visual perceptual subtests, the cognitive T score sum on the MSEL, and on one measure of social participation on the Sensory Processing Measure-Preschool. Furthermore, post hoc analysis found significant improvement in early EL development as measured by the MSEL among children with autism spectrum disorder on sertraline. Treatment appears safe for this 6-month period in young children with FXS, but the authors do not know the long-term side effects of this treatment. These results warrant further studies of sertraline in young children with FXS using refined outcome measures as well as longer term follow-up studies to address long-term side effects of low-dose sertraline in early childhood.
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6. Hannant P, Tavassoli T, Cassidy S. {{The Role of Sensorimotor Difficulties in Autism Spectrum Conditions}}. {Front Neurol}. 2016; 7: 124.
In addition to difficulties in social communication, current diagnostic criteria for autism spectrum conditions (ASC) also incorporate sensorimotor difficulties, repetitive motor movements, and atypical reactivity to sensory input (1). This paper explores whether sensorimotor difficulties are associated with the development and maintenance of symptoms in ASC. First, studies have shown difficulties coordinating sensory input into planning and executing movement effectively in ASC. Second, studies have shown associations between sensory reactivity and motor coordination with core ASC symptoms, suggesting these areas each strongly influence the development of social and communication skills. Third, studies have begun to demonstrate that sensorimotor difficulties in ASC could account for reduced social attention early in development, with a cascading effect on later social, communicative and emotional development. These results suggest that sensorimotor difficulties not only contribute to non-social difficulties such as narrow circumscribed interests, but also to the development of social behaviors such as effectively coordinating eye contact with speech and gesture, interpreting others’ behavior, and responding appropriately. Further research is needed to explore the link between sensory and motor difficulties in ASC and their contribution to the development and maintenance of ASC.
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7. Hashemi E, Ariza J, Lechpammer M, Noctor SC, Martinez-Cerdeno V. {{Abnormal white matter tracts resembling pencil fibers involving prefrontal cortex (Brodmann area 47) in autism: a case report}}. {J Med Case Rep}. 2016; 10(1): 237.
BACKGROUND: Autism is not correlated with any neuropathological hallmark as the brain of autistic individuals lack defined lesions. However, previous investigations have reported cortical heterotopias and local distortion of the cytoarchitecture of the neocortex in some cases of autism. CASE PRESENTATION: Our patient was a 40-year-old white woman diagnosed at an early age with autism and mental retardation. Pencil fibers were present within the prefrontal cortex (Brodmann area 47) and its composition resembled that of the underlying white matter region. Pencil fibers encompassed most of the extent of the cortical grey matter and were populated by oligodendrocytes, astrocytes, and microglial cells, but not by neurons. CONCLUSIONS: Here we report a new cytoarchitectural abnormality that has not been previously described in autism. Future pathological examinations should keep in mind the potential presence of pencil fibers within the prefrontal cortex of cases with autism.
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8. Liu CX, Peng XL, Hu CC, Li CY, Li Q, Xu X. {{Developmental profiling of ASD-related shank3 transcripts and their differential regulation by valproic acid in zebrafish}}. {Dev Genes Evol}. 2016.
SHANK3 is a scaffolding protein that binds to various synaptic proteins at the postsynaptic density (PSD) of excitatory glutamatergic synapses. SHANK3 is not only strongly implicated in autism spectrum disorders (ASD) but also plays a critical role in human Phelan-McDermid syndrome (22q13.3 deletion syndrome). Accumulated experimental evidence demonstrates that the zebrafish model system is useful for studying the functions of ASD-related gene during early development. However, many basic features of shank3 transcript expression in zebrafish remain poorly understood. Here, we investigated temporal, spatial, and isoform-specific expression patterns of shank3 during zebrafish development on the basis of previous researches and the differential effects of each shank3 transcript expression after exposure to valproic acid (VPA), an ASD-associated drug. At first, we observed that both shank3a and shank3b were barely expressed at very early ages (before 24 h post-fertilization (hpf)), whereas their expression levels were increased and mainly enriched in the nervous system after 24 hpf. Secondly, all of the six shank3 transcripts gradually increased during the first 7 hpf and then decreased. Subsequently, they exhibited a second increasing peak between 1 month post-fertilization (mpf) and adulthood. Thirdly, VPA treatment affected the isoform-specific expression of zebrafish shank3. In particular, the mRNA expression levels of those isoforms that contain a SAM domain were significantly increased, whereas the mRNA expression level of those which contained an ANK domain but without a SAM domain was decreased. To conclude, our findings support the molecular diversity of shank3 in zebrafish and provide a molecular framework to understand the isoform-specific function of shank3 in zebrafish.
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9. Olexova L, Stefanik P, Krskova L. {{Increased anxiety-like behaviour and altered GABAergic system in the amygdala and cerebellum of VPA rats – An animal model of autism}}. {Neurosci Lett}. 2016; 629: 9-14.
Anxiety is one of the associated symptoms of autism spectrum disorder. According to the literature, increases in anxiety are accompanied by GABAergic system deregulation. The aim of our study, performed using an animal model of autism in the form of rats prenatally treated with valproic acid (VPA rats), was to investigate changes in anxiety-like behaviour and the gene expression of molecules that control levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain. Anxiety-like behaviours were investigated using zone preferences in the open field test. The levels of the 65 and 67kDa enzymes of l-glutamic acid decarboxylase (GAD) mRNAs and type 1 GABA transporter (GAT1) were evaluated in the amygdala, as well as GABA producing enzymes in the cortex layer of the cerebellum. Our research showed that adult VPA rats spent less time in the inner zone of the testing chamber and more time in the outer zone of the testing chamber in the open field test. We also found that adult VPA rats had increased expression of GAT1 in the amygdala, as well as decreased levels of GAD65 and GAD67 mRNA in the cerebellum compared to control animals. These findings support the existence of a relationship between increased anxiety-like behaviour and changes in the regulation of the GABAergic system in VPA rats.
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10. Olincy A, Blakeley-Smith A, Johnson L, Kem WR, Freedman R. {{Brief Report: Initial Trial of Alpha7-Nicotinic Receptor Stimulation in Two Adult Patients with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2016.
Abnormalities in CHRNA7, the alpha7-nicotinic receptor gene, have been reported in autism spectrum disorder. These genetic abnormalities potentially decrease the receptor’s expression and diminish its functional role. This double-blind, placebo-controlled crossover study in two adult patients investigated whether an investigational receptor-specific partial agonist drug would increase the inhibitory functions of the gene and thereby increase patients’ attention. An electrophysiological biomarker, P50 inhibition, verified the intended neurobiological effect of the agonist, and neuropsychological testing verified a primary cognitive effect. Both patients perceived increased attention in their self-ratings. Alpha7-nicotinic receptor agonists, currently the target of drug development in schizophrenia and Alzheimer Disease, may also have positive clinical effects in autism spectrum disorder.
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11. Pedersen AL, Pettygrove S, Lu Z, Andrews J, Meaney FJ, Kurzius-Spencer M, Lee LC, Durkin MS, Cunniff C. {{DSM Criteria that Best Differentiate Intellectual Disability from Autism Spectrum Disorder}}. {Child Psychiatry Hum Dev}. 2016.
Clinical characteristics of autism spectrum disorder (ASD) and intellectual disability (ID) overlap, creating potential for diagnostic confusion. Diagnostic and statistical manual of mental disorders (DSM) criteria that best differentiate children with ID and some ASD features from those with comorbid ID and ASD were identified. Records-based surveillance of ASD among 8-year-old children across 14 US populations ascertained 2816 children with ID, with or without ASD. Area under the curve (AUC) was conducted to determine discriminatory power of DSM criteria. AUC analyses indicated that restricted interests or repetitive behaviors best differentiated between the two groups. A subset of 6 criteria focused on social interactions and stereotyped behaviors was most effective at differentiating the two groups (AUC of 0.923), while communication-related criteria were least discriminatory. Matching children with appropriate treatments requires differentiation between ID and ASD. Shifting to DSM-5 may improve differentiation with decreased emphasis on language-related behaviors.
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12. Soke GN, Rosenberg SA, Hamman RF, Fingerlin T, Robinson C, Carpenter L, Giarelli E, Lee LC, Wiggins LD, Durkin MS, DiGuiseppi C. {{Brief Report: Prevalence of Self-injurious Behaviors among Children with Autism Spectrum Disorder-A Population-Based Study}}. {J Autism Dev Disord}. 2016.
Self-injurious behaviors (SIB) have been reported in more than 30 % of children with an autism spectrum disorder (ASD) in clinic-based studies. This study estimated the prevalence of SIB in a large population-based sample of children with ASD in the United States. A total of 8065 children who met the surveillance case definition for ASD in the Autism and Developmental Disabilities Monitoring (ADDM) Network during the 2000, 2006, and 2008 surveillance years were included. The presence of SIB was reported from available health and/or educational records by an expert clinician in ADDM Network. SIB prevalence averaged 27.7 % across all sites and surveillance years, with some variation between sites. Clinicians should inquire about SIB during assessments of children with ASD.
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13. Stahlhut M, Downs J, Leonard H, Bisgaard AM, Nordmark E. {{Building the repertoire of measures of walking in Rett syndrome}}. {Disabil Rehabil}. 2016: 1-6.
BACKGROUND: The repertoire of measures of walking in Rett syndrome is limited. This study aimed to determine measurement properties of a modified two-minute walk test (2MWT) and a modified Rett syndrome-specific functional mobility scale (FMS-RS) in Rett syndrome. METHODS: Forty-two girls and women with Rett syndrome (median 18.4 years, range 2.4-60.9 years) were assessed for clinical severity, gross motor skills, and mobility. To measure walking capacity, 27 of this group completed a 2MWT twice on two different assessment days. To assess walking performance, the FMS-RS was administered to the total sample of parents (n = 42) on two occasions approximately one week apart. RESULTS: There were negative correlations between clinical severity and 2MWT (r = -0.48) and FMS-RS (r = -0.60-0.66). There were positive correlations between gross motor skills and mobility and 2MWT (r = 0.51, 0.43) and FMS-RS (r = 0.71-0.93, 0.74-0.94), respectively. Test-retest reliability for the 2MWT was good with high intraday and interday correlations (ICC = 0.86-0.98). For the 2MWT, the standard error of measurement was 13.8 m and we would be 95% confident that changes greater than 38 m would be greater than within subject error. There was good test-retest reliability for all three distances on the FMS-RS (ICC = 0.94-0.99). CONCLUSIONS: Walking capacity as measured by the 2MWT showed expected but limited relationships with measures of different constructs, providing some support for concurrent validity. Walking performance as measured with the FMS-RS was more strongly consistent with other clinical measures supporting its concurrent validity. Test-retest reliability was good for both the FMS-RS and the 2MWT. Therefore, these measures have the potential to be used in clinical practice and research. Implications for Rehabilitation Walking is one of the commonest daily physical activities in ambulant girls and women with RTT. Comprehensive knowledge about the walking abilities in this population is limited. Evidence of validity and test-retest reliability have been demonstrated for the modified two-minute walk test (2MWT) and the Rett syndrome-specific functional mobility scale (FMS-RS). The 2MWT and FMS-RS offer detailed information of the capacity and performance of walking, respectively, in girls and women with RTT.
