1. Bishop SL, Hus V, Duncan A, Huerta M, Gotham K, Pickles A, Kreiger A, Buja A, Lund S, Lord C. {{Subcategories of Restricted and Repetitive Behaviors in Children with Autism Spectrum Disorders}}. {J Autism Dev Disord};2012 (Oct 14)
Research suggests that restricted and repetitive behaviors (RRBs) can be subdivided into Repetitive Sensory Motor (RSM) and Insistence on Sameness (IS) behaviors. However, because the majority of previous studies have used the Autism Diagnostic Interview-Revised (ADI-R), it is not clear whether these subcategories reflect the actual organization of RRBs in ASD. Using data from the Simons Simplex Collection (n = 1,825), we examined the association between scores on the ADI-R and the Repetitive Behavior Scale-Revised. Analyses supported the construct validity of RSM and IS subcategories. As in previous studies, IS behaviors showed no relationship with IQ. These findings support the continued use of RRB subcategories, particularly IS behaviors, as a means of creating more behaviorally homogeneous subgroups of children with ASD.
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2. Breece E, Paciotti B, Nordahl CW, Ozonoff S, Van de Water JA, Rogers SJ, Amaral D, Ashwood P. {{Myeloid dendritic cells frequencies are increased in children with autism spectrum disorder and associated with amygdala volume and repetitive behaviors}}. {Brain Behav Immun};2012 (Oct 10)
The pathophysiology of Autism Spectrum Disorder (ASD) is not yet known; however, studies suggest that dysfunction of the immune system affects many children with ASD. Increasing evidence points to dysfunction of the innate immune system including activation of microglia and perivascular macrophages, increases in inflammatory cytokines/chemokines in brain tissue and CSF, and abnormal peripheral monocyte cell function. Dendritic cells are major players in innate immunity and have important functions in the phagocytosis of pathogens or debris, antigen presentation, activation of naive T cells, induction of tolerance and cytokine/chemokine production. In this study, we assessed circulating frequencies of myeloid dendritic cells (defined as Lin-1(-)BDCA1(+)CD11c(+) and Lin-1(-)BDCA3(+)CD123(-)) and plasmacytoid dendritic cells (Lin-1(-)BDCA2(+)CD123(+) or Lin-1(-)BDCA4(+) CD11c(-)) in 57 children with ASD, and 29 typically developing controls of the same age, all of who were enrolled as part of the Autism Phenome Project (APP). The frequencies of dendritic cells and associations with behavioral assessment and MRI measurements of amygdala volume were compared in the same participants. The frequencies of myeloid dendritic cells were significantly increased in children with ASD compared to typically developing controls (p < 0.03). Elevated frequencies of myeloid dendritic cells were positively associated with abnormal right and left amygdala enlargement, severity of gastrointestinal symptoms and increased repetitive behaviors. The frequencies of plasmacytoid dendritic cells were also associated with amygdala volumes as well as developmental regression in children with ASD. Dendritic cells play key roles in modulating immune responses and differences in frequencies or functions of these cells may result in immune dysfunction in children with ASD. These data further implicate innate immune cells in the complex pathophysiology of ASD.
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3. Essa MM, Braidy N, Vijayan KR, Subash S, Guillemin GJ. {{Excitotoxicity in the Pathogenesis of Autism}}. {Neurotox Res};2012 (Oct 13)
Autism is a debilitating neurodevelopment disorder characterised by stereotyped interests and behaviours, and abnormalities in verbal and non-verbal communication. It is a multifactorial disorder resulting from interactions between genetic, environmental and immunological factors. Excitotoxicity and oxidative stress are potential mechanisms, which are likely to serve as a converging point to these risk factors. Substantial evidence suggests that excitotoxicity, oxidative stress and impaired mitochondrial function are the leading cause of neuronal dysfunction in autistic patients. Glutamate is the primary excitatory neurotransmitter produced in the CNS, and overactivity of glutamate and its receptors leads to excitotoxicity. The over excitatory action of glutamate, and the glutamatergic receptors NMDA and AMPA, leads to activation of enzymes that damage cellular structure, membrane permeability and electrochemical gradients. The role of excitotoxicity and the mechanism behind its action in autistic subjects is delineated in this review.
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4. Ghanizadeh A, Berk M, Farrashbandi H, Alavi Shoushtari A, Villagonzalo KA. {{Targeting the mitochondrial electron transport chain in autism, a systematic review and synthesis of a novel therapeutic approach}}. {Mitochondrion};2012 (Oct 9)
Autism is a complex developmental disorder with an unknown etiology and without any curative treatment. The mitochondrial electron transfer chains play a major role in the production of ATP, and the generation and management of reactive oxidative stress (ROS). This paper is a systematic review of the role of the mitochondrial electron transport chain in autism, and a consequent hypothesis for treating autism is synthesized. An electronic search with pre-specified inclusion criteria was conducted in order to retrieve all the published articles about the mitochondrial electron transport chain in autism. The two databases of PUBMED and Google Scholar were searched. From one hundred twenty five retrieved titles, 12 (three case control study and 9 case reports) articles met inclusion criteria. All of the included studies indicated dysfunction of electron transport chain in autism. The mitochondrial electron transfer chain seems impaired in some children with autism and ROS production is additionally enhanced. It is hypothesized that interventions involving alternative electron shuttling may improve autism through lowering the production of ROS. In addition, it is expected that this alternative electron shuttling to cytochrome c might enhance the production of ATP which is impaired in the disorder.
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5. Hanson E, Cerban BM, Slater CM, Caccamo LM, Bacic J, Chan E. {{Brief Report: Prevalence of Attention Deficit/Hyperactivity Disorder Among Individuals with an Autism Spectrum Disorder}}. {J Autism Dev Disord};2012 (Oct 13)
Currently, both the DSM-IV-TR and ICD-10 preclude the diagnosis of Attention Deficit/Hyperactivity Disorder (ADHD) in cases that present with an Autism Spectrum Disorder (ASD). This criterion will be removed in the upcoming DSM-V, but the relationship between ASD and ADHD, and in particular the prevalence of ADHD among the ASD population, remains controversial. Previous studies have reported clinically significant ADHD symptoms in one-third to three-quarters of ASD-affected individuals (probands). In our sample of 1,838 simplex children and adolescents with ASD, we found that less than 16 % met clinically significant levels of ADHD symptoms, per parent report. When both parent and teacher reports were considered, the comorbidity rate was even lower, at 2 %.
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6. Puffenberger EG, Jinks RN, Wang H, Xin B, Fiorentini C, Sherman EA, Degrazio D, Shaw C, Sougnez C, Cibulskis K, Gabriel S, Kelley RI, Morton DH, Strauss KA. {{A Homozygous Missense Mutation in HERC2 Associated with Global Developmental Delay and Autism Spectrum Disorder}}. {Hum Mutat};2012 (Oct 15)
We studied a unique phenotype of cognitive delay, autistic behavior, and gait instability segregating in three separate sibships. We initiated genome-wide mapping in two sibships using Affymetrix 10K SNP Mapping Arrays and identified a homozygous 8.2 Mb region on chromosome 15 common to five affected children. We used exome sequencing of two affected children to assess coding sequence variants within the mapped interval. Four novel homozygous exome variants were shared between the two patients; however, only two variants localized to the mapped interval on chromosome 15. A third sibship in an Ohio Amish deme narrowed the mapped interval to 2.6 Mb and excluded one of the two novel homozygous exome variants. The remaining variant, a missense change in HERC2 (c.1781C>T, p.Pro594Leu), occurs in a highly conserved proline residue within an RCC1-like functional domain. Functional studies of truncated HERC2 in ARPE cells suggest that the p.Pro594Leu variant induces protein aggregation and leads to decreased HERC2 abundance. The phenotypic correlation with the mouse Herc1 and Herc2 mutants as well as the phenotypic overlap with Angelman syndrome provide further evidence that pathogenic changes in HERC2 are associated with non-syndromic intellectual disability, autism, and gait disturbance.
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7. Reed SR, Stahmer AC, Suhrheinrich J, Schreibman L. {{Stimulus Overselectivity in Typical Development: Implications for Teaching Children with Autism}}. {J Autism Dev Disord};2012 (Oct 13)
Stimulus overselectivity is widely accepted as a stimulus control abnormality in autism spectrum disorders and subsets of other populations. Previous research has demonstrated a link between both chronological and mental age and overselectivity in typical development. However, the age at which children are developmentally ready to respond to discriminations involving simultaneous multiple cues has not been established. Thirty-seven typically developing preschoolers completed a task requiring response to simultaneous cues (color and shape) to establish the age at which typically developing children can successfully respond to multiple cues. Results demonstrate that typically developing children under 36 months of age have difficulty responding to multiple cues. Implications for behavioral treatment for autism are discussed.
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8. Sandiford GA, Mainess KJ, Daher NS. {{A Pilot Study on the Efficacy of Melodic Based Communication Therapy for Eliciting Speech in Nonverbal Children with Autism}}. {J Autism Dev Disord};2012 (Oct 14)
The purpose of this study was to compare the efficacy of Melodic Based Communication Therapy (MBCT) to traditional speech and language therapy for eliciting speech in nonverbal children with autism. Participants were 12 nonverbal children with autism ages 5 through 7 randomly assigned to either treatment group. Both groups made significant progress after treatment. The MBCT group progressed significantly in number of verbal attempts after weeks 1 through 4 and number of correct words after weeks 1 and 3, while the traditional group progressed significantly after weeks 4 and 5. No significant differences in number of verbal attempts or number of correct words were noted between groups following treatment. A significant number of new words were heard in the home environment for the MBCT group (p = .04). Participants in the MBCT group had more imitative attempts (p = .03). MBCT appears to be a valid form of intervention for children with autism.
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9. Spencer MD, Holt RJ, Chura LR, Calder AJ, Suckling J, Bullmore ET, Baron-Cohen S. {{Atypical activation during the Embedded Figures Task as a functional magnetic resonance imaging endophenotype of autism}}. {Brain};2012 (Oct 11)
Atypical activation during the Embedded Figures Task has been demonstrated in autism, but has not been investigated in siblings or related to measures of clinical severity. We identified atypical activation during the Embedded Figures Task in participants with autism and unaffected siblings compared with control subjects in a number of temporal and frontal brain regions. Autism and sibling groups, however, did not differ in terms of activation during this task. This suggests that the pattern of atypical activation identified may represent a functional endophenotype of autism, related to familial risk for the condition shared between individuals with autism and their siblings. We also found that reduced activation in autism relative to control subjects in regions including associative visual and face processing areas was strongly correlated with the clinical severity of impairments in reciprocal social interaction. Behavioural performance was intact in autism and sibling groups. Results are discussed in terms of atypical information processing styles or of increased activation in temporal and frontal regions in autism and the broader phenotype. By separating the aspects of atypical activation as markers of familial risk for the condition from those that are autism-specific, our findings offer new insight into the factors that might cause the expression of autism in families, affecting some children but not others.
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10. Whitehouse AJ, Holt BJ, Serralha M, Holt PG, Hart PH, Kusel MM. {{Maternal Vitamin D Levels and the Autism Phenotype Among Offspring}}. {J Autism Dev Disord};2012 (Oct 16)
We tested whether maternal vitamin D insufficiency during pregnancy is related to the autism phenotype. Serum 25(OH)-vitamin D concentrations of 929 women were measured at 18 weeks’ pregnancy. The mothers of the three children with a clinical diagnosis of autism spectrum disorder had 25(OH)-vitamin D concentrations above the population mean. The offspring of 406 women completed the Autism-Spectrum Quotient in early adulthood. Maternal 25(OH)-vitamin D concentrations were unrelated to offspring scores on the majority of scales. However, offspring of mothers with low 25(OH)-vitamin D concentrations (<49 nmol/L) were at increased risk for ‘high’ scores (>/=2SD above mean) on the Attention Switching subscale (odds ratio: 5.46, 95 % confidence interval: 1.29, 23.05). The involvement of maternal vitamin D during pregnancy in autism requires continued investigation.
