1. {{Divorce among parents of children with autism: dispelling urban legends}}. {Autism};2013 (Nov);17(6):643-644.
2. de Theije CG, Koelink PJ, Korte-Bouws GA, da Silva SL, Mechiel Korte S, Olivier B, Garssen J, Kraneveld AD. {{Intestinal inflammation in a murine model of autism spectrum disorders}}. {Brain Behav Immun};2013 (Dec 7)
Autism spectrum disorder (ASD) is a cluster of neurodevelopmental disorders characterized by impairments in communication, social interest and stereotypical behaviour. Dysfunction of the intestinal tract is reported in patients with ASD and implicated in the development and severity of ASD symptoms. However, more research is required to investigate the association of intestinal problems with ASD and the potential underlying mechanisms. The purpose of this study was to investigate comorbid symptoms of intestinal inflammation in a murine model of ASD induced by prenatal exposure to valproic acid (VPA). Pregnant BALB/c females were treated subcutaneously with 600mg/kg VPA or phosphate buffered saline on gestational day 11. Offspring were housed with their mother until weaning on postnatal day 21 (P21). All pups were exposed to a social behaviour test on P28. Inflammatory correlates and activity of the serotonergic system were measured in brain and intestinal tissue. Here we demonstrate, in addition to reduced social behaviour and increased expression of neuroinflammatory markers in the brain, that VPA in utero- exposed male offspring showed epithelial cell loss and neutrophil infiltration in the intestinal tract. Furthermore, reduced levels of serotonin were not only observed the prefrontal cortex and amygdala of VPA in utero- exposed males, but also in the small intestine. Overall, we demonstrate that gender-specific inflammatory conditions are present in the small intestines of VPA in utero- exposed mice and are accompanied by a disturbed serotonergic system in the brain as well as in the intestinal tract.
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3. Doshi-Velez F, Ge Y, Kohane I. {{Comorbidity Clusters in Autism Spectrum Disorders: An Electronic Health Record Time-Series Analysis}}. {Pediatrics};2013 (Dec 9)
OBJECTIVE:The distinct trajectories of patients with autism spectrum disorders (ASDs) have not been extensively studied, particularly regarding clinical manifestations beyond the neurobehavioral criteria from the Diagnostic and Statistical Manual of Mental Disorders. The objective of this study was to investigate the patterns of co-occurrence of medical comorbidities in ASDs.METHODS:International Classification of Diseases, Ninth Revision codes from patients aged at least 15 years and a diagnosis of ASD were obtained from electronic medical records. These codes were aggregated by using phenotype-wide association studies categories and processed into 1350-dimensional vectors describing the counts of the most common categories in 6-month blocks between the ages of 0 to 15. Hierarchical clustering was used to identify subgroups with distinct courses.RESULTS:Four subgroups were identified. The first was characterized by seizures (n = 120, subgroup prevalence 77.5%). The second (n = 197) was characterized by multisystem disorders including gastrointestinal disorders (prevalence 24.3%) and auditory disorders and infections (prevalence 87.8%), and the third was characterized by psychiatric disorders (n = 212, prevalence 33.0%). The last group (n = 4316) could not be further resolved. The prevalence of psychiatric disorders was uncorrelated with seizure activity (P = .17), but a significant correlation existed between gastrointestinal disorders and seizures (P < .001). The correlation results were replicated by using a second sample of 496 individuals from a different geographic region.CONCLUSIONS:Three distinct patterns of medical trajectories were identified by unsupervised clustering of electronic health record diagnoses. These may point to distinct etiologies with different genetic and environmental contributions. Additional clinical and molecular characterizations will be required to further delineate these subgroups.
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4. Eriksson JM, Andersen LM, Bejerot S. {{RAADS-14 Screen: validity of a screening tool for autism spectrum disorder in an adult psychiatric population}}. {Mol Autism};2013 (Dec 9);4(1):49.
BACKGROUND: Autism spectrum disorder (ASD) can be difficult to distinguish from other psychiatric disorders. The clinical assessment of ASD is lengthy, and has to be performed by a specialized clinician. Therefore, a screening instrument to aid in the identification of patients who may have undiagnosed ASD should be useful. The purpose of this study was to develop such a screening instrument. METHODS: Based on the 80 item Ritvo Autism and Asperger Diagnostic Scale-Revised (RAADS-R), we developed a 14 item self-evaluation questionnaire, the RAADS-14 Screen. In total, 135 adults with ASD and 508 psychiatric controls completed the abridged version of the RAADS-R. RESULTS: The RAADS-14 Screen score was significantly higher in the ASD group than in the control samples, with a median score of 32 for ASD, 15 for attention deficit hyperactivity disorder, and 11 for other psychiatric disorders (P < 0.001). A cut-off score of 14 or above reached a sensitivity of 97% and a specificity of 46 to 64%. A factor analysis identified three factors consistent with mentalizing deficits, social anxiety, and sensory reactivity relevant for the diagnosis of ASD. The psychometric properties of RAADS-14 Screen were shown to be satisfactory. CONCLUSIONS: The results of this study indicate that RAADS-14 Screen is a promising measure in screening for ASD in adult psychiatric outpatients.
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5. Gandhi RM, Kogan CS, Messier C, Macleod LS. {{Visual-spatial learning impairments are associated with hippocampal PSD-95 protein dysregulation in a mouse model of fragile X syndrome}}. {Neuroreport};2013 (Dec 7)
Fragile X syndrome is the most common cause of inherited intellectual disability and is caused by the lack of fragile X mental retardation protein (FMRP) expression. In-vitro findings in mice and post-mortem autopsies in humans are characterized by dendritic spine abnormalities in the absence of Fmrp/FMRP. Biochemical and electrophysiological studies have identified postsynaptic density protein (PSD)-95 as having an established role in dendritic morphology as well as a molecular target of Fmrp. How Fmrp affects the expression of PSD-95 following behavioral learning is unknown. In the current study, wild-type controls and Fmr1 knockout mice were trained in a subset of the Hebb-Williams (H-W) mazes. Dorsal hippocampal PSD-95 protein levels relative to a stable cytoskeleton protein (beta-tubulin) were measured. We report a significant upregulation of PSD-95 protein levels in wild-type mice, whereas training-related protein increases were blunted in Fmr1 knockout mice. In addition, there was a significant negative correlation between mean total errors on the mazes and PSD-95 protein levels. The coefficient of determination indicated that the mean total errors on the H-W mazes accounted for 35% of the variance in PSD-95 protein levels. These novel findings suggest that reduced PSD-95-associated postsynaptic plasticity may contribute to the learning and memory deficits observed in human fragile X syndrome patients.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivitives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.
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6. Liratni M, Blanchet C, Pry R. {{[Place of socialization/communication learning groups in autism with moderate mental retardation.]}}. {Arch Pediatr};2013 (Dec 6)
Studies based on social skills training groups for people with autism always target people without mental retardation and the subjects are more often teenagers and adults than children. Quantitative and standardized psychometrics are not routinely studied. OBJECTIVES: Describing the changes in symptoms and social communication skills of five children with autism and moderate mental retardation, who participated in 20 sessions in a social skills training group appropriate to their developmental level. METHOD: Standardized scales to develop the target skills and applied behavioral analysis and structured techniques were implemented in these sessions. To measure changes, we assessed the children before and after the 20 sessions (Vineland Adaptative Behavior Scale and Autism Diagnostic Observation Schedule) and we noted whether or not of the target skills were achieved. RESULTS: The scores showed a significant improvement in autistic symptoms and social communication skills. CONCLUSION: The results show that this type of educational experience appears relevant to meeting objectives in social and communication skills. However, any conclusions as to a significant impact of the intervention are strongly limited by the absence of a control group.
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7. Sundaram S, Huq A, Hsia T, Chugani H. {{Exome sequencing and diffusion tensor imaging in developmental disabilities}}. {Pediatr Res};2013 (Dec 6)
Background:We had previously shown that arcuate fasciculus is poorly developed in patients with intellectual and developmental disabilities (IDD) using diffusion tensor imaging (DTI). In the present study, we used exome sequencing to identify the candidate variants in IDD patients with and without DTI abnormalities.Methods:Eighteen children with IDD (age: 67+/-36 months, 9 females) were included in the present study. The DTI was used to determine the integrity of arcuate fasciculus. The next generation sequencing was performed on the Solid 4 platform. A novel, analytical strategy was developed to identify a set of candidate genes of interest. Novel, nonsynonymous variants in the patients were then looked for within this subset of genes and in known IDD genes.Results:Seven novel, nonsynonymous (all of them were heterozygous, missense) variants belonged to ultra-conserved genes that are known to cause abnormal brain morphology in mutant mice. Similarly, 3 novel, nonsynonymous (all of them were heterozygous, missense) variants belonged to known IDD genes. Two patients with underdeveloped arcuate fasciculus contained novel, nonsynonymous variants in genes (MID1 and EN2) regulating axon guidance pathway.Conclusions:Exome sequencing identified several new the genetic causes of IDD.Pediatric Research (2013); doi:10.1038/pr.2013.234.
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8. Wang M, Reid D. {{Using the virtual reality-cognitive rehabilitation approach to improve contextual processing in children with autism}}. {ScientificWorldJournal};2013;2013:716890.
Background. This pilot study investigated the efficacy of a novel virtual reality-cognitive rehabilitation (VR-CR) intervention to improve contextual processing of objects in children with autism. Previous research supports that children with autism show deficits in contextual processing, as well as deficits in its elementary components: abstraction and cognitive flexibility. Methods. Four children with autism participated in a multiple-baseline, single-subject study. The children were taught how to see objects in context by reinforcing attention to pivotal contextual information. Results. All children demonstrated statistically significant improvements in contextual processing and cognitive flexibility. Mixed results were found on the control test and changes in context-related behaviours. Conclusions. Larger-scale studies are warranted to determine the effectiveness and usability in comprehensive educational programs.
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9. Warrier V, Baron-Cohen S, Chakrabarti B. {{Genetic variation in GABRB3 is associated with Asperger syndrome and multiple endophenotypes relevant to autism}}. {Mol Autism};2013 (Dec 9);4(1):48.
BACKGROUND: Autism spectrum conditions (ASC) are associated with deficits in social interaction and communication, alongside repetitive, restricted, and stereotyped behavior. ASC is highly heritable. The gamma-aminobutyric acid (GABA)-ergic system has been associated consistently with atypicalities in autism, in both genetic association and expression studies. A key component of the GABA-ergic system is encoded by the GABRB3 gene, which has been previously implicated both in ASC and in individual differences in empathy. METHODS: In this study, 45 genotyped single nucleotide polymorphisms (SNPs) within GABRB3 were tested for association with Asperger syndrome (AS), and related quantitative traits measured through the following tests: the Empathy Quotient (EQ), the Autism Spectrum Quotient (AQ), the Systemizing Quotient-Revised (SQ-R), the Embedded Figures Test (EFT), the Reading the Mind in the Eyes Test (RMET), and the Mental Rotation Test (MRT). Two-loci, three-loci, four-loci haplotype analyses, and one seven-loci haplotype analysis were also performed in the AS case–control sample. RESULTS: Three SNPs (rs7180158, rs7165604, rs12593579) were significantly associated with AS, and two SNPs (rs9806546, rs11636966) were significantly associated with EQ. Two SNP-SNP pairs, rs12438141-rs1035751 and rs12438141-rs7179514, showed significant association with variation in the EFT scores. One SNP-SNP pair, rs7174437-rs1863455, was significantly associated with variation in the MRT scores. Additionally, a few haplotypes, including a 19 kb genomic region that formed a linkage disequilibrium (LD) block in our sample and contained several nominally significant SNPs, were found to be significantly associated with AS. CONCLUSION: The current study confirms the role of GABRB3 as an important candidate gene in both ASC and normative variation in related endophenotypes.
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10. Zurcher NR, Rogier O, Boshyan J, Hippolyte L, Russo B, Gillberg N, Helles A, Ruest T, Lemonnier E, Gillberg C, Hadjikhani N. {{Perception of social cues of danger in autism spectrum disorders}}. {PLoS One};2013;8(12):e81206.
Intuitive grasping of the meaning of subtle social cues is particularly affected in autism spectrum disorders (ASD). Despite their relevance in social communication, the effect of averted gaze in fearful faces in conveying a signal of environmental threat has not been investigated using real face stimuli in adults with ASD. Here, using functional MRI, we show that briefly presented fearful faces with averted gaze, previously shown to be a strong communicative signal of environmental danger, produce different patterns of brain activation than fearful faces with direct gaze in a group of 26 normally intelligent adults with ASD compared with 26 matched controls. While implicit cue of threat produces brain activation in attention, emotion processing and mental state attribution networks in controls, this effect is absent in individuals with ASD. Instead, individuals with ASD show activation in the subcortical face-processing system in response to direct eye contact. An effect of differences in looking behavior was excluded in a separate eye tracking experiment. Our data suggest that individuals with ASD are more sensitive to direct eye contact than to social signals of danger conveyed by averted fearful gaze.
