1. Hodgson NW, Waly MI, Al-Farsi YM, Al-Sharbati MM, Al-Farsi O, Ali A, Ouhtit A, Zang T, Zhou ZS, Deth RC. {{Decreased glutathione and elevated hair mercury levels are associated with nutritional deficiency-based autism in Oman}}. {Exp Biol Med (Maywood)}. 2014.
Genetic, nutrition, and environmental factors have each been implicated as sources of risk for autism. Oxidative stress, including low plasma levels of the antioxidant glutathione, has been reported by numerous autism studies, which can disrupt methylation-dependent epigenetic regulation of gene expression with neurodevelopmental consequences. We investigated the status of redox and methylation metabolites, as well as the level of protein homocysteinylation and hair mercury levels, in autistic and neurotypical control Omani children, who were previously shown to exhibit significant nutritional deficiencies in serum folate and vitamin B12. The serum level of glutathione in autistic subjects was significantly below control levels, while levels of homocysteine and S-adenosylhomocysteine were elevated, indicative of oxidative stress and decreased methionine synthase activity. Autistic males had lower glutathione and higher homocysteine levels than females, while homocysteinylation of serum proteins was increased in autistic males but not females. Mercury levels were markedly elevated in the hair of autistic subjects vs. control subjects, consistent with the importance of glutathione for its elimination. Thus, autism in Oman is associated with decreased antioxidant resources and decreased methylation capacity, in conjunction with elevated hair levels of mercury.
Lien vers le texte intégral (Open Access ou abonnement)
2. Koegel RL, Kim S, Koegel LK. {{Training Paraprofessionals to Improve Socialization in Students with ASD}}. {J Autism Dev Disord}. 2014.
An important line of research relates to whether school personnel, such as paraprofessionals, who are present during unstructured social periods, such as lunch-recess, could successfully implement interventions to improve socialization between students with ASD and their typical peers in a group setting. Therefore, within the context of a multiple baseline across participants design, we assessed whether training paraprofessionals to provide social interventions would enhance social development in students with ASD in a group setting. Results showed that paraprofessionals who were not providing any social opportunities during baseline were able to meet fidelity of implementation following a brief training. Consequently, the children with ASD increased their levels of engagement and rates of initiation with typically developing peers following intervention. Implications for training paraprofessionals to implement effective social interventions for students with ASD are discussed.
Lien vers le texte intégral (Open Access ou abonnement)
3. Kovac J, Podkrajsek KT, Luksic MM, Battelino T. {{Weak association of glyoxalase 1 (GLO1) variants with autism spectrum disorder}}. {Eur Child Adolesc Psychiatry}. 2014.
The prevalence of the autism spectrum disorder (ASD) was recently estimated to 1 in 88 children by the CDC MMWR. In up to 25 % of the cases, the genetic cause can be identified. Past studies identified increased level of advanced glycation end products (AGE) in the brain samples of ASD patients. The methylglyoxal (MG) is one of the main precursors for AGE formation. Humans developed effective mechanism of the MG metabolism involving two enzymes glyoxalase 1 (GLO1) and hydroxyacylglutathione hydrolase (HAGH). Our aim was to analyse genetic variants of GLO1 and HAGH in population of 143 paediatric participants with ASD. We detected 7 genetic variants in GLO1 and 16 variants in HAGH using high-resolution melting (HRM) analysis. A novel association between variant rs1049346 and ASD [OR (allele C)] = 1.5; 95 % CI = 1.1-2.2 and p < 0.05) was identified, and weak association between ASD and variant rs2736654 [OR (allele A)] = 2.2; 95 % CI = 0.99-4.9; p = 0.045) was confirmed. Additionally, a novel genetic variant (GLO1 c.484G > A, p.Ala161Thr) with predicted potentially damaging effect on the activity of the glyoxalase 1 that may contribute to the aetiology of ASD was identified in one participant with ASD. No association between genetic variants of the HAGH gene and ASD was found. Increased level of MG and, consequently, AGEs can induce oxidative stress, mitochondrial dysfunction and inflammation all of which have been implicated to act in the aetiology of the ASD. Our results indicate potential importance of MG metabolism in ASD. However, these results must be interpreted with caution until a causative relation is demonstrated.
Lien vers le texte intégral (Open Access ou abonnement)
4. Murphy JW, Foxe JJ, Peters JB, Molholm S. {{Susceptibility to Distraction in Autism Spectrum Disorder: Probing the Integrity of Oscillatory Alpha-Band Suppression Mechanisms}}. {Autism Res}. 2014.
When attention is directed to one information stream over another, the brain can be configured in advance to selectively process the relevant stream and suppress potentially distracting inputs. One key mechanism of suppression is through the deployment of anticipatory alpha-band ( approximately 10 Hz) oscillatory activity, with greater alpha-band power observed in cortical regions that will ultimately process the distracting stream. Atypical attention has been implicated in autism spectrum disorder (ASD), including greater interference by distracting task-irrelevant inputs. Here we tested the integrity of these alpha-band mechanisms in ASD using an intersensory attention task. Electroencephalography (EEG) was recorded while participants were cued on a trial-by-trial basis to selectively deploy attention to the visual or auditory modality in anticipation of a target within the cued modality. Whereas typically developing (TD) children showed the predicted alpha-band modulation, with increased alpha-band power over parieto-occipital scalp when attention was deployed to the auditory compared with the visual modality, this differential pattern was entirely absent at the group level in the ASD cohort. Further, only the ASD group showed impaired performance due to the presence of task-irrelevant sensory information. These data suggest that impaired modulation of alpha-band activity plays a role in increased distraction from extraneous sensory inputs in ASD. Autism Res 2014, : -. (c) 2014 International Society for Autism Research, Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
5. Stoner R, Chow ML, Boyle MP, Sunkin SM, Mouton PR, Roy S, Wynshaw-Boris A, Colamarino SA, Lein ES, Courchesne E. {{Patches of disorganization in the neocortex of children with autism}}. {N Engl J Med}. 2014; 370(13): 1209-19.
BACKGROUND: Autism involves early brain overgrowth and dysfunction, which is most strongly evident in the prefrontal cortex. As assessed on pathological analysis, an excess of neurons in the prefrontal cortex among children with autism signals a disturbance in prenatal development and may be concomitant with abnormal cell type and laminar development. METHODS: To systematically examine neocortical architecture during the early years after the onset of autism, we used RNA in situ hybridization with a panel of layer- and cell-type-specific molecular markers to phenotype cortical microstructure. We assayed markers for neurons and glia, along with genes that have been implicated in the risk of autism, in prefrontal, temporal, and occipital neocortical tissue from postmortem samples obtained from children with autism and unaffected children between the ages of 2 and 15 years. RESULTS: We observed focal patches of abnormal laminar cytoarchitecture and cortical disorganization of neurons, but not glia, in prefrontal and temporal cortical tissue from 10 of 11 children with autism and from 1 of 11 unaffected children. We observed heterogeneity between cases with respect to cell types that were most abnormal in the patches and the layers that were most affected by the pathological features. No cortical layer was uniformly spared, with the clearest signs of abnormal expression in layers 4 and 5. Three-dimensional reconstruction of layer markers confirmed the focal geometry and size of patches. CONCLUSIONS: In this small, explorative study, we found focal disruption of cortical laminar architecture in the cortexes of a majority of young children with autism. Our data support a probable dysregulation of layer formation and layer-specific neuronal differentiation at prenatal developmental stages. (Funded by the Simons Foundation and others.).
Lien vers le texte intégral (Open Access ou abonnement)
6. Wood JJ, Fujii C, Renno P, Van Dyke M. {{Impact of Cognitive Behavioral Therapy on Observed Autism Symptom Severity During School Recess: A Preliminary Randomized, Controlled Trial}}. {J Autism Dev Disord}. 2014.
This study compared cognitive behavioral therapy (CBT) and treatment-as-usual (TAU) in terms of effects on observed social communication-related autism symptom severity during unstructured play time at school for children with autism spectrum disorders (ASD). Thirteen children with ASD (7-11 years old) were randomly assigned to 32 sessions of CBT or community-based psychosocial treatment (TAU) for 16 weeks. The CBT program is based on the memory retrieval competition model and emphasizes the development of perspective-taking through guided behavioral experimentation supplemented with reflective Socratic discussion and supported by parent training and school consultation to promote generalization of social communication and emotion regulation skills. Trained observers blind to treatment condition observed each child during recess on two separate days at baseline and again at posttreatment, using a structured behavioral observation system that generates frequency scores for observed social communication-related autism symptoms. CBT outperformed TAU at posttreatment on the frequency of self-isolation, the proportion of time spent with peers, the frequency of positive or appropriate interaction with peers, and the frequency of positive or appropriate peer responses to the target child (d effect size range 1.34-1.62). On average, children in CBT were engaged in positive or appropriate social interaction with peers in 68.6 % of observed intervals at posttreatment, compared to 25 % of intervals for children in TAU. Further investigation of this intervention modality with larger samples and follow-up assessments is warranted.
